@article {pmid39361354,
year = {2024},
author = {Hazelwood, E and Lopez Manzano, C and Vincent, EE and Albanes, D and Bishop, DT and Le Marchand, L and Ulrich, CM and Peters, U and Murphy, G and Samadder, NJ and Anderson, L and Gunter, MJ and Murphy, N and Van Guelpen, B and Papadimitriou, N},
title = {Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-0926},
pmid = {39361354},
issn = {1538-7755},
abstract = {BACKGROUND: Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis.

METHODS: Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied.

RESULTS: We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC.

CONCLUSIONS: Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk.

IMPACT: This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.},
}

@article {pmid39361286,
year = {2024},
author = {Pizzo, A and Leisenring, WM and Stratton, KL and Lamoureux, É and Flynn, JS and Alschuler, K and Krull, KR and Jibb, LA and Nathan, PC and Olgin, JE and Stinson, JN and Armstrong, GT and Alberts, NM},
title = {Fear of Cancer Recurrence in Adult Survivors of Childhood Cancer.},
journal = {JAMA network open},
volume = {7},
number = {10},
pages = {e2436144},
doi = {10.1001/jamanetworkopen.2024.36144},
pmid = {39361286},
issn = {2574-3805},
mesh = {Humans ; *Cancer Survivors/psychology/statistics & numerical data ; Female ; Male ; *Fear/psychology ; Adult ; Cross-Sectional Studies ; *Neoplasm Recurrence, Local/psychology/epidemiology ; Retrospective Studies ; Neoplasms/psychology/epidemiology ; Risk Factors ; Middle Aged ; Prevalence ; Child ; },
abstract = {IMPORTANCE: Fear of cancer recurrence is common among survivors of adult-onset cancer and associated with increased distress, functional impairment, and health care utilization. However, little is known about the prevalence and risk factors of fear of cancer recurrence among adult survivors of childhood cancer who are also at high risk for subsequent malignant neoplasms.

OBJECTIVE: To characterize the prevalence of and risk factors for clinically significant fear of cancer recurrence in adult survivors of childhood cancer.

This cross-sectional investigation included participants recruited from the Childhood Cancer Survivor Study, a retrospective cohort study of long-term childhood cancer survivors treated at 31 institutions between 1970 and 1999 across North America. Participants were recruited and completed psychosocial measures via online survey between October 2018 and April 2019. Cancer and treatment-related variables were abstracted from medical records. Data were analyzed from May 2023 to July 2024.

MAIN OUTCOMES AND MEASURES: Clinically significant fear of cancer recurrence was assessed via the Fear of Cancer Recurrence Inventory-Short Form. Poisson regression models estimated prevalence ratios (PRs) with 95% CIs adjusted for age and sex to examine the associations of demographic, disease, treatment, and psychosocial variables with fear of cancer recurrence.

RESULTS: The final sample included 229 adult survivors of childhood cancer (115 female [50.2%]; mean [SD] age, 39.6 [9.9] years; mean [SD] time since diagnosis, 31.7 [8.4] years). Among survivors, 38 (16.6%; 95% CI, 11.6%-21.6%) reported clinically significant fear of cancer recurrence, and an additional 36 (15.7%) reported high fear of cancer recurrence. Clinically significant fear of cancer recurrence was associated with unemployment (PR, 2.5; 95% CI, 1.3-4.8), presence of neurologic chronic health conditions (PR, 3.3; 95% CI, 1.8-6.1), treatment with pelvic radiation (PR, 2.9; 95% CI, 1.5-5.6), and amputation or limb sparing surgery (PR, 2.4; 95% CI, 1.2-4.9). Higher risk of clinically significant fear of cancer recurrence was also associated with having either elevated anxiety or depression (PR, 2.6; 95% CI, 1.2-5.9), having both elevated (PR, 3.2; 95% CI, 1.2-8.4), and perceived poor health status (PR, 3.0; 95% CI, 3.1-9.7).

CONCLUSIONS AND RELEVANCE: Decades following treatment, one-third of childhood cancer survivors in this study reported elevated fear their cancer will recur or a subsequent malignant neoplasm will develop. Findings suggest that fear of cancer recurrence should be routinely screened, and clinically significant symptoms intervened upon as a part of survivorship care.},
}

Humans
*Cancer Survivors/psychology/statistics & numerical data
Female
Male
*Fear/psychology
Adult
Cross-Sectional Studies
*Neoplasm Recurrence, Local/psychology/epidemiology
Retrospective Studies
Neoplasms/psychology/epidemiology
Risk Factors
Middle Aged
Prevalence
Child

@article {pmid39361281,
year = {2024},
author = {Gjesvik, J and Moshina, N and Lee, CI and Miglioretti, DL and Hofvind, S},
title = {Artificial Intelligence Algorithm for Subclinical Breast Cancer Detection.},
journal = {JAMA network open},
volume = {7},
number = {10},
pages = {e2437402},
doi = {10.1001/jamanetworkopen.2024.37402},
pmid = {39361281},
issn = {2574-3805},
mesh = {Humans ; *Breast Neoplasms/diagnosis/diagnostic imaging ; Female ; Middle Aged ; *Artificial Intelligence ; *Algorithms ; Aged ; Retrospective Studies ; *Early Detection of Cancer/methods ; *Mammography/methods/statistics & numerical data ; Norway/epidemiology ; },
abstract = {IMPORTANCE: Early breast cancer detection is associated with lower morbidity and mortality.

OBJECTIVE: To examine whether a commercial artificial intelligence (AI) algorithm for breast cancer detection could estimate the development of future cancer.

This retrospective cohort study of 116 495 women aged 50 to 69 years with no prior history of breast cancer before they underwent at least 3 consecutive biennial screening examinations used scores from an AI algorithm (INSIGHT MMG, version 1.1.7.2; Lunit Inc; used September 28, 2022, to April 5, 2023) for breast cancer detection and screening data from multiple, consecutive rounds of mammography performed from September 13, 2004, to December 21, 2018, at 9 breast centers in Norway. The statistical analyses were performed from September 2023 to August 2024.

EXPOSURE: Artificial intelligence algorithm score indicating suspicion for the presence of breast cancer. The algorithm provided a continuous cancer detection score for each examination ranging from 0 to 100, with increasing values indicating a higher likelihood of cancer being present on the current mammogram.

MAIN OUTCOMES AND MEASURES: Maximum AI algorithm score for cancer detection and absolute difference in score among breasts of women developing screening-detected cancer, women with interval cancer, and women who screened negative.

RESULTS: The mean (SD) age at the first study round was 58.5 (4.5) years for 1265 women with screening-detected cancer in the third round, 57.4 (4.6) years for 342 women with interval cancer after 3 negative screening rounds, and 56.4 (4.9) years for 116 495 women without breast cancer all 3 screening rounds. The mean (SD) absolute differences in AI scores among breasts of women developing screening-detected cancer were 21.3 (28.1) at the first study round, 30.7 (32.5) at the second study round, and 79.0 (28.9) at the third study round. The mean (SD) differences prior to interval cancer were 19.7 (27.0) at the first study round, 21.0 (27.7) at the second study round, and 34.0 (33.6) at the third study round. The mean (SD) differences among women who did not develop breast cancer were 9.9 (17.5) at the first study round, 9.6 (17.4) at the second study round, and 9.3 (17.3) at the third study round. Areas under the receiver operating characteristic curve for the absolute difference were 0.63 (95% CI, 0.61-0.65) at the first study round, 0.72 (95% CI, 0.71-0.74) at the second study round, and 0.96 (95% CI, 0.95-0.96) at the third study round for screening-detected cancer and 0.64 (95% CI, 0.61-0.67) at the first study round, 0.65 (95% CI, 0.62-0.68) at the second study round, and 0.77 (95% CI, 0.74-0.79) at the third study round for interval cancers.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of women undergoing screening mammography, mean absolute AI scores were higher for breasts developing vs not developing cancer 4 to 6 years before their eventual detection. These findings suggest that commercial AI algorithms developed for breast cancer detection may identify women at high risk of a future breast cancer, offering a pathway for personalized screening approaches that can lead to earlier cancer diagnosis.},
}

Humans
*Breast Neoplasms/diagnosis/diagnostic imaging
Female
Middle Aged
*Artificial Intelligence
*Algorithms
Aged
Retrospective Studies
*Early Detection of Cancer/methods
*Mammography/methods/statistics & numerical data
Norway/epidemiology

@article {pmid39361275,
year = {2024},
author = {Kampouri, E and Reynolds, G and Teh, BW and Hill, JA},
title = {Chimeric antigen receptor-T-cell therapies going viral: latent and incidental viral infections.},
journal = {Current opinion in infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1097/QCO.0000000000001066},
pmid = {39361275},
issn = {1473-6527},
abstract = {PURPOSE OF REVIEW: Infections are the leading cause of non-relapse mortality following chimeric antigen receptor (CAR)-T-cell therapy, with viral infections being frequent both in the early and late phases post-infusion. We review the epidemiology of viral infections and discuss critical approaches to prevention and management strategies in this setting.

RECENT FINDINGS: Herpesviruses dominate the early period. herpes simplex virus and varicella zoster virus infections are rare due to widespread antiviral prophylaxis, but cytomegalovirus (CMV) reactivation is increasingly observed, particularly in high-risk groups including B cell maturation antigen (BCMA)-CAR-T-cell therapy recipients and patients receiving corticosteroids. While CMV end-organ disease is rare, CMV is associated with increased mortality, emphasizing the need to evaluate the broader impact of CMV on long-term hematological, infection, and survival outcomes. Human herpesvirus-6 (HHV-6) has also emerged as a concern, with its diagnosis complicated by overlapping symptoms with neurotoxicity, underscoring the importance of considering viral encephalitis in differential diagnoses. Respiratory viruses are the most common late infections with a higher incidence after BCMA CAR-T-cell therapy. Vaccination remains a critical preventive measure against respiratory viruses but may be less immunogenic following CAR-T-cell therapy. The optimal timing, type of vaccine, and dosing schedule require further investigation.

SUMMARY: A better understanding of viral epidemiology and preventive trials are needed to improve infection prevention practices and outcomes following CAR-T-cell therapies.},
}

@article {pmid39359003,
year = {2024},
author = {Halloran, ME and Struchiner, CJ},
title = {Invited Commentary: Thirty-five Years of Leaky Vaccines.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwae379},
pmid = {39359003},
issn = {1476-6256},
abstract = {Over the past 35 years, the term "leaky vaccine" has gained widespread use in both mathematical modeling and epidemiologic methods for evaluating vaccines. Here we present a short history as we recall it of how the term was coined in the context of the history of sporozoite malaria vaccines that were thought to be possibly leaky in the 1980s. We draw a contrast with the all-or-none vaccine mechanism and review a few consequences for study design and population level effects. We invite readers to contribute information covering the time period preceding our memories in the 1980s as we may have overlooked something.},
}

@article {pmid39357788,
year = {2024},
author = {Wisdom, AJ and Yeap, BY and Michalski, JM and Horick, NK and Zietman, AL and Christodouleas, JP and Kamran, SC and Parikh, RR and Vapiwala, N and Mihalcik, S and Miyamoto, DT and Zeng, J and Gay, HA and Pisansky, TM and Mishra, MV and Spratt, DE and Mendenhall, NP and Soffen, EM and Bekelman, JE and Efstathiou, JA},
title = {Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy vs. IMRT for Localized Prostate Cancer.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2024.09.043},
pmid = {39357788},
issn = {1879-355X},
abstract = {PURPOSE/OBJECTIVES: Men with localized prostate cancer may receive either photon-based intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). The XXXXX trial (NCT01617161), demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT to PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials.

MATERIALS/METHODS: Patients with low- or intermediate-risk prostate cancer were randomized to either PBT or IMRT with stratification by institution, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs. moderate hypofractionation: 70.0 Gy in 28 fractions). The primary endpoint is a change from baseline bowel health using the EPIC score 24 months after radiotherapy. Secondary objectives include treatment-related differences in urinary and erectile functions, adverse events, and efficacy endpoints.

RESULTS: Between 07/2012 and 11/2021, 450 patients were successfully accrued. Patients were randomized to either PBT (N=226) or to IMRT (N=224); 13 were ineligible or withdrew prior to treatment. The median age of 437 analyzed patients was 68 years (range 46-89). 41% of patients had low-risk and 59% had intermediate-risk disease. 49% of patients were treated with conventional fractionation and 51% with moderately hypofractionation. For patients receiving PBT, 48% used a rectal balloon, 44% a rectal spacer, and 5% both. For patients receiving IMRT, 46% used a rectal balloon, 42% a rectal spacer, and 5% both. PBT and IMRT arms were balanced for baseline variables.

CONCLUSIONS: Despite significant challenges, the XXXXX trial demonstrated that, with targeted recruitment approaches, multicenter collaboration, payer engagement, and protocol updates to incorporate contemporary techniques, it is feasible to perform a large phase III randomized clinical trial to assess whether PBT improves outcomes. We will separately report primary results and continue to monitor participants for longer followup and secondary endpoints.},
}

@article {pmid39357459,
year = {2024},
author = {Chappidi, MR and Iravani, A and Stambler, N and Baskaran, S and DiPippo, VA and Denes, BS and Lin, DW},
title = {Impact of Baseline Renal Insufficiency on Piflufolastat F-18 Performance and Investigation of Changes in Renal Function Following Piflufolastat F-18 Administration: Results From the OSPREY Trial.},
journal = {Clinical genitourinary cancer},
volume = {22},
number = {6},
pages = {102223},
doi = {10.1016/j.clgc.2024.102223},
pmid = {39357459},
issn = {1938-0682},
abstract = {INTRODUCTION: Piflufolastat F-18, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, is predominantly eliminated via urinary excretion, and the kidneys have one of the highest absorbed doses. Therefore, this subgroup analysis aimed to investigate the impact of piflufolastat F-18 on renal function and its diagnostic performance in patients stratified by baseline renal function.

PATIENTS AND METHODS: The OSPREY clinical trial enrolled 2 cohorts: A-high-risk patients undergoing radical prostatectomy with pelvic lymphadenectomy, and B-patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Baseline estimated glomerular filtration rates were calculated, and patients were stratified by baseline chronic kidney disease (CKD) stage. Changes in serum creatinine within 28 days postdose and diagnostic performance of piflufolastat F-18 were assessed for each CKD stage group in both cohorts.

RESULTS: 385 patients (cohort A, n = 268; cohort B, n = 117) underwent piflufolastat F-18-PET/CT. Baseline and postpiflufolastat F-18 median creatinine levels (mg/dL) were similar for patients in cohort A (0.95 [n = 264] vs. 0.95 [n = 252], respectively) and cohort B (0.93 [n = 116] vs. 0.96 [n = 84], respectively). Among 332 men (cohort A, n = 249; cohort B, n = 83) with baseline and postpiflufolastat creatinine measurements, there were minimal changes in creatinine across all baseline CKD stage groups (median change ranged from -0.02 to 0.023 in groups with >1 patient). The diagnostic performance of piflufolastat F-18 showed no meaningful differences when stratified by baseline CKD stage.

CONCLUSION: Piflufolastat F-18 appears to be safe and effective for imaging prostate cancer, including men with mild/moderate renal insufficiency.},
}

@article {pmid39353277,
year = {2024},
author = {Irajizad, E and Fahrmann, JF and Toumazis, I and Vykoukal, J and Dennison, JB and Shen, Y and Do, KA and Ostrin, EJ and Feng, Z and Hanash, S},
title = {Biomarker trajectory for earlier detection of lung cancer.},
journal = {EBioMedicine},
volume = {108},
number = {},
pages = {105377},
doi = {10.1016/j.ebiom.2024.105377},
pmid = {39353277},
issn = {2352-3964},
abstract = {BACKGROUND: To determine whether an algorithm based on repeated measurements of a panel of four circulating protein biomarkers (4 MP) for lung cancer risk assessment results in improved performance over a single time measurement.

METHODS: We conducted data analysis of the 4 MP consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in pre-diagnostic sera from 2483 ever-smoker participants (389 cases and 2094 randomly selected non-cases) in the Prostate, Lung, Colorectal, Ovarian (PLCO) Study who had at least two sequential blood collections over 6 years. A parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history at each time point, was compared to a single-threshold (ST) method.

FINDINGS: Among ever-smoker participants, the PEB approach yielded an additional 4% improvement in the AUC compared to the ST approach (P-value: 0.009). When considering an ≥10 PY smoking history and at a fixing the specificity corresponding to 1% 6-year lung cancer risk, PEB resulted in significant improvement in the sensitivity (SenPEB:96.3% vs SenST:91.0%; P-value: 6.7e-3). The PEB algorithm identified 17 of the 35 cases that remained ST negative, at an average of 1.26 years before diagnosis. Ten case individuals who were positive based on ST at an average of 1.03 years prior to diagnosis were identified earlier by PEB, at an average of 2.70 years.

INTERPRETATION: An algorithm based on repeated measurements of the 4 MP improves sensitivity and results in an earlier detection of lung cancer compared to a single-threshold method.

FUNDING: This study was supported by NIH Grant Nos. U01CA271888, U01CA194733, U01CA213285, NCI EDRN U01 CA200468, P30CA016672, and U24CA086368; the Cancer Prevention & Research Institute of Texas RP180505 and RP160693; the SPORE P50CA140388; the CCTS TR000371; and the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program and the Lyda Hill Foundation.},
}

@article {pmid39356983,
year = {2024},
author = {Lurain, K and Ramaswami, R and Ekwede, I and Eulo, V and Goyal, G and Menon, M and Odeny, TA and Sharon, E and Wagner, MJ and Wang, CJ and Bhardwaj, N and Friedlander, PA and Abdul-Hay, M and Cornejo Castro, EM and Labo, N and Marshall, VA and Miley, W and Moore, K and Roshan, R and Whitby, D and Kask, AS and Kaiser, J and Han, E and Wright, A and Yarchoan, R and Fling, SP and Uldrick, TS},
title = {Cancer Immunotherapy Trials Network 12: Pembrolizumab in HIV-Associated Kaposi Sarcoma.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2400640},
doi = {10.1200/JCO.24.00640},
pmid = {39356983},
issn = {1527-7755},
abstract = {PURPOSE: Cancer Immunotherapy Trials Network 12 demonstrated safety of pembrolizumab in treating advanced cancer in people with HIV. Here, we report results of the Kaposi sarcoma (KS) cohort.

METHODS: In this multicenter phase I trial, we enrolled participants with HIV-associated KS on antiretroviral therapy with CD4[+] ≥50 cells/μL and HIV plasma RNA <200 copies/mL. Pembrolizumab 200 mg intravenously was administered once every 3 weeks for up to 35 cycles. The primary end point was safety, and the secondary end point was KS response by modified AIDS Clinical Trials Group Criteria.

RESULTS: Thirty-two cisgender men enrolled with baseline median CD4[+] T-cell count of 274 cells/µL. All but nine participants had received previous systemic KS therapy. Participants received a median of 11 cycles of pembrolizumab (range, 1-35). Sixty-six percent had grade ≥1 treatment-emergent adverse events, including one death from polyclonal KS herpesvirus-related B-cell lymphoproliferation. Thirty-one percent had ≥one immune-mediated AEs (imAEs) with 25% requiring systemic steroids. In 29 participants with evaluable KS, the overall response rate (ORR) was 62.1% (95% CI, 42.3 to 79.3) and did not differ by CD4[+] T-cell count. ORR in the eight participants with evaluable disease without previous KS therapy was 87.5% (95% CI, 47.3 to 99.7). Median duration of response (DOR) was not reached, and the Kaplan-Meier estimate of DOR of ≥12 months was 92.3% (95% CI, 56.6 to 98.8). Median progression-free survival was 28.2 months (95% CI, 4.2 to noncalculable).

CONCLUSION: Pembrolizumab yielded a high rate of durable responses in HIV-associated KS. imAEs were successfully managed with standard guidelines.},
}

@article {pmid39354185,
year = {2024},
author = {Armstrong, AJ and Taylor, A and Haffner, MC and Abida, W and Bryce, AH and Karsh, LI and Tagawa, ST and Twardowski, P and Serritella, AV and Lang, JM},
title = {Germline and somatic testing for homologous repair deficiency in patients with prostate cancer (part 1 of 2).},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {39354185},
issn = {1476-5608},
abstract = {BACKGROUND/OBJECTIVES: Unfortunately, not all metastatic castration resistant prostate cancer (mCRPC) patients receive available life-prolonging systemic therapies, emphasizing the need to optimize mCRPC treatment selections. Better guidelines are necessary to determine genetic testing in prostate cancer.

SUBJECTS/METHODS: In this two-part expert opinion-based guide, we provide an expert consensus opinion on the utilization of germline and somatic testing to detect HRR alterations in patients with mCRPC. This guide was developed by a multidisciplinary expert panel that convened in 2023-2024, including representatives from medical oncology, urology, radiation oncology, pathology, medical genomics, and basic science.

RESULTS/CONCLUSION: We argue for the widespread adoption of germline testing in all patients with prostate cancer and for somatic mutations testing in patients at the time of recurrent/metastatic disease. In this first part, we review how genomic testing is performed. We also review how to overcome certain barriers to integrate genetic and biomarker testing into clinical practice.},
}

@article {pmid39354095,
year = {2024},
author = {Zhao, LP and Papadopoulos, GK and Skyler, JS and Pugliese, A and Parikh, HM and Kwok, WW and Lybrand, TP and Bondinas, GP and Moustakas, AK and Wang, R and Pyo, CW and Nelson, WC and Geraghty, DE and Lernmark, Å},
title = {Progression to type 1 diabetes in the DPT-1 and TN07 clinical trials is critically associated with specific residues in HLA-DQA1-B1 heterodimers.},
journal = {Diabetologia},
volume = {},
number = {},
pages = {},
pmid = {39354095},
issn = {1432-0428},
support = {R01 DK132406/DK/NIDDK NIH HHS/United States ; },
abstract = {AIMS/HYPOTHESIS: The aim of this work was to explore molecular amino acids (AAs) and related structures of HLA-DQA1-DQB1 that underlie its contribution to the progression from stages 1 or 2 to stage 3 type 1 diabetes.

METHODS: Using high-resolution DQA1 and DQB1 genotypes from 1216 participants in the Diabetes Prevention Trial-Type 1 and the Diabetes Prevention Trial, we applied hierarchically organised haplotype association analysis (HOH) to decipher which AAs contributed to the associations of DQ with disease and their structural properties. HOH relied on the Cox regression to quantify the association of DQ with time-to-onset of type 1 diabetes.

RESULTS: By numerating all possible DQ heterodimers of α- and β-chains, we showed that the heterodimerisation increases genetic diversity at the cellular level from 43 empirically observed haplotypes to 186 possible heterodimers. Heterodimerisation turned several neutral haplotypes (DQ2.2, DQ2.3 and DQ4.4) to risk haplotypes (DQ2.2/2.3-DQ4.4 and DQ4.4-DQ2.2). HOH uncovered eight AAs on the α-chain (-16α, -13α, -6α, α22, α23, α44, α72, α157) and six AAs on the β-chain (-18β, β9, β13, β26, β57, β135) that contributed to the association of DQ with progression of type 1 diabetes. The specific AAs concerned the signal peptide (minus sign, possible linkage to expression levels), pockets 1, 4 and 9 in the antigen-binding groove of the α1β1 domain, and the putative homodimerisation of the αβ heterodimers.

CONCLUSIONS/INTERPRETATION: These results unveil the contribution made by DQ to type 1 diabetes progression at individual residues and related protein structures, shedding light on its immunological mechanisms and providing new leads for developing treatment strategies.

DATA AVAILABILITY: Clinical trial data and biospecimen samples are available through the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository portal (https://repository.niddk.nih.gov/studies).},
}

@article {pmid38985835,
year = {2024},
author = {Jiang, D and Houck, KL and Murdiyarso, L and Higgins, H and Rhoads, N and Romero, SK and Kozar, R and Nascimbene, A and Gernsheimer, TB and Sanchez, ZAC and Ramasubramanian, AK and Adili, R and Dong, JF},
title = {RBCs regulate platelet function and hemostasis under shear conditions through biophysical and biochemical means.},
journal = {Blood},
volume = {144},
number = {14},
pages = {1521-1531},
doi = {10.1182/blood.2024023887},
pmid = {38985835},
issn = {1528-0020},
mesh = {Animals ; *Hemostasis/physiology ; *Blood Platelets/metabolism ; *Erythrocytes/metabolism/cytology ; Mice ; Adenosine Diphosphate/metabolism ; Platelet Aggregation ; Humans ; Mice, Inbred C57BL ; Thrombocytopenia/pathology/blood ; Erythrocyte Transfusion ; },
abstract = {Red blood cells (RBCs) have been hypothesized to support hemostasis by facilitating platelet margination and releasing platelet-activating factors such as adenosine 5'-diphosphate (ADP). Significant knowledge gaps remain regarding how RBCs influence platelet function, especially in (patho)physiologically relevant hemodynamic conditions. Here, we present results showing how RBCs affect platelet function and hemostasis in conditions of anemia, thrombocytopenia, and pancytopenia and how the biochemical and biophysical properties of RBCs regulate platelet function at the blood and vessel wall interface and in the fluid phase under flow conditions. We found that RBCs promoted platelet deposition to collagen under flow conditions in moderate (50 × 103/μL) but not severe (10 × 103/μL) thrombocytopenia in vitro. Reduction in hematocrit by 45% increased bleeding in mice with hemolytic anemia. In contrast, bleeding diathesis was observed in mice with a 90% but not with a 60% reduction in platelet counts. RBC transfusion improved hemostasis by enhancing fibrin clot formation at the site of vascular injury in mice with severe pancytopenia induced by total body irradiation. Altering membrane deformability changed the ability of RBCs to promote shear-induced platelet aggregation. RBC-derived ADP contributed to platelet activation and aggregation in vitro under pathologically high shear stresses, as observed in patients supported by left ventricular assist devices. These findings demonstrate that RBCs support platelet function and hemostasis through multiple mechanisms, both at the blood and vessel wall interface and in the fluidic phase of circulation.},
}

Animals
*Hemostasis/physiology
*Blood Platelets/metabolism
*Erythrocytes/metabolism/cytology
Mice
Adenosine Diphosphate/metabolism
Platelet Aggregation
Humans
Mice, Inbred C57BL
Thrombocytopenia/pathology/blood
Erythrocyte Transfusion

@article {pmid39352173,
year = {2024},
author = {Weinstock, LM and Bishop, TM and Bauer, MS and Benware, J and Bossarte, RM and Bradley, J and Dobscha, SK and Gibbs, J and Gildea, SM and Graves, H and Haas, G and House, S and Kennedy, CJ and Landes, SJ and Liu, H and Luedtke, A and Marx, BP and Miller, A and Nock, MK and Owen, RR and Pigeon, WR and Sampson, NA and Santiago-Colon, A and Shivakumar, G and Urosevic, S and Kessler, RC},
title = {Design of a multicenter randomized controlled trial of a post-discharge suicide prevention intervention for high-risk psychiatric inpatients: The Veterans Coordinated Community Care Study.},
journal = {International journal of methods in psychiatric research},
volume = {33},
number = {4},
pages = {e70003},
pmid = {39352173},
issn = {1557-0657},
support = {EBP 22-104//Department of Veterans Affairs Quality Enhancement Research Initiative/ ; PII 18-195//Department of Veterans Affairs Quality Enhancement Research Initiative/ ; QUE 20-026//Department of Veterans Affairs Quality Enhancement Research Initiative/ ; //Warren Alpert Foundation/ ; 36C24122P0883//National Center for PTSD, U.S. Department of Veterans Affairs/ ; 36C24122P0883//VA Boston Healthcare System/ ; UL1 TR003107/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Suicide Prevention ; *Veterans ; United States ; *Patient Discharge ; *Inpatients ; Mental Disorders/prevention & control/therapy ; United States Department of Veterans Affairs ; Adult ; Female ; Male ; Middle Aged ; Follow-Up Studies ; },
abstract = {BACKGROUND: The period after psychiatric hospital discharge is one of elevated risk for suicide-related behaviors (SRBs). Post-discharge clinical outreach, although potentially effective in preventing SRBs, would be more cost-effective if targeted at high-risk patients. To this end, a machine learning model was developed to predict post-discharge suicides among Veterans Health Administration (VHA) psychiatric inpatients and target a high-risk preventive intervention.

METHODS: The Veterans Coordinated Community Care (3C) Study is a multicenter randomized controlled trial using this model to identify high-risk VHA psychiatric inpatients (n = 850) randomized with equal allocation to either the Coping Long Term with Active Suicide Program (CLASP) post-discharge clinical outreach intervention or treatment-as-usual (TAU). The primary outcome is SRBs over a 6-month follow-up. We will estimate average treatment effects adjusted for loss to follow-up and investigate the possibility of heterogeneity of treatment effects.

RESULTS: Recruitment is underway and will end September 2024. Six-month follow-up will end and analysis will begin in Summer 2025.

CONCLUSION: Results will provide information about the effectiveness of CLASP versus TAU in reducing post-discharge SRBs and provide guidance to VHA clinicians and policymakers about the implications of targeted use of CLASP among high-risk psychiatric inpatients in the months after hospital discharge.

CLINICAL TRIALS REGISTRATION: ClinicalTrials.Gov identifier: NCT05272176 (https://www.

CLINICALTRIALS: gov/ct2/show/NCT05272176).},
}

Humans
*Suicide Prevention
*Veterans
United States
*Patient Discharge
*Inpatients
Mental Disorders/prevention & control/therapy
United States Department of Veterans Affairs
Adult
Female
Male
Middle Aged
Follow-Up Studies

@article {pmid39352001,
year = {2024},
author = {Shadman, M and Salkar, M and Srivastava, B and Karve, S and Emond, B and Gogna, P and Manceur, AM and Lafeuille, MH and Rava, A and Sun, H and Howarth, A and Tomicki, S and Agatep, B and Jones, B and Franceschini, E and Saifan, C and Bacchus, S and Roeker, L and Stephens, DM},
title = {Real-world outcomes following ibrutinib dose reduction in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.},
journal = {Leukemia & lymphoma},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/10428194.2024.2402814},
pmid = {39352001},
issn = {1029-2403},
abstract = {This study used real-world data from three separate United States (US) databases to evaluate dosing patterns and time to next treatment (TTNT) following the first-incident adverse event (AE) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treated with first-line ibrutinib with and without dose reduction (DR). Median TTNT or death in patients with and without a DR following an AE in each database was as follows: Optum Clinformatics Data Mart (CDM): 59.5 and 30.6 months; ConcertAI: 27.1 and 18.0 months; and Medicare Fee-for-Service (FFS): 49.8 and 22.0 months, respectively. Median TTNT or death in patients with cardiac AEs, with and without a DR, was: Optum CDM: 44.4 and 22.9 months; ConcertAI: 29.9 and 18.3 months; and Medicare FFS: 49.6 and 14.0 months, respectively. Ibrutinib DR was associated with fewer outpatient visits and lower CLL/SLL-related medical costs. These findings suggest that utilizing ibrutinib DR may effectively manage tolerability without compromising clinical efficacy.},
}

@article {pmid39349773,
year = {2024},
author = {Liu, S and Zhu, J and Zhong, H and Wu, C and Xue, H and Darst, BF and Guo, X and Durda, P and Tracy, RP and Liu, Y and Johnson, WC and Taylor, KD and Manichaikul, AW and Goodarzi, MO and Gerszten, RE and Clish, CB and Chen, YI and Highland, H and Haiman, CA and Gignoux, CR and Lange, L and Conti, DV and Raffield, LM and Wilkens, L and Marchand, LL and North, KE and Young, KL and Loos, RJ and Buyske, S and Matise, T and Peters, U and Kooperberg, C and Reiner, AP and Yu, B and Boerwinkle, E and Sun, Q and Rooney, MR and Echouffo-Tcheugui, JB and Daviglus, ML and Qi, Q and Mancuso, N and Li, C and Deng, Y and Manning, A and Meigs, JB and Rich, SS and Rotter, JI and Wu, L},
title = {Identification of proteins associated with type 2 diabetes risk in diverse racial and ethnic populations.},
journal = {Diabetologia},
volume = {},
number = {},
pages = {},
pmid = {39349773},
issn = {1432-0428},
support = {R01CA263494/BC/NCI NIH HHS/United States ; U54HG013243//NHGRI/NIMHD/ ; },
abstract = {AIMS/HYPOTHESIS: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.

METHODS: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were applied to genome-wide association study summary statistics of 250,127 type 2 diabetes cases and 1,222,941 controls from different racial and ethnic populations.

RESULTS: We identified three, 44 and one protein associated with type 2 diabetes risk in Asian, European and Hispanic/Latino populations, respectively. Meta-analysis identified 40 proteins associated with type 2 diabetes risk across the populations, including well-established as well as novel proteins not yet implicated in type 2 diabetes development.

CONCLUSIONS/INTERPRETATION: Our study improves our understanding of the aetiology of type 2 diabetes in diverse populations.

DATA AVAILABILITY: The summary statistics of multi-ethnic type 2 diabetes GWAS of MVP, DIAMANTE, Biobank Japan and other studies are available from The database of Genotypes and Phenotypes (dbGaP) under accession number phs001672.v3.p1. MESA genetic, proteome and covariate data can be accessed through dbGaP under phs000209.v13.p3. All code is available on GitHub (https://github.com/Arthur1021/MESA-1K-PWAS).},
}

@article {pmid39348623,
year = {2024},
author = {Sankaran, S and Banerjee, R},
title = {Smartwatch Biometrics in the Electronic Medical Record: Time for a New Vital Sign?.},
journal = {JCO clinical cancer informatics},
volume = {8},
number = {},
pages = {e2400161},
doi = {10.1200/CCI-24-00161},
pmid = {39348623},
issn = {2473-4276},
mesh = {Humans ; *Electronic Health Records ; *Biometry/methods ; *Smartphone ; Vital Signs ; },
abstract = {Smartphone biometrics in the EMR: is the 5th vital sign here? @JCOCCI_ASCO commentary by Sankaran and @RahulBanerjeeMD here.},
}

Humans
*Electronic Health Records
*Biometry/methods
*Smartphone
Vital Signs

@article {pmid39348095,
year = {2024},
author = {Harris, HR and Saboda, K and Thomson, CA and Saquib, N and Shadyab, AH and Schnatz, PF and Robles-Morales, R and Qi, L and Roe, DJ and Farland, LV},
title = {History of infertility and risk of endometrial cancer in the Women's Health Initiative.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-0717},
pmid = {39348095},
issn = {1538-7755},
abstract = {BACKGROUND: Several studies have suggested an association between infertility and risk of endometrial cancer. However, most studies have evaluated this relationship in premenopausal people, yet the mean age of endometrial cancer is 60 years old, after the average age of menopause.

METHODS: Our study included Women's Health Initiative participants who self-reported whether they had a history of infertility. Cox proportional hazards models were used to examine the association between infertility and incident endometrial cancer. Given that all infertility diagnoses occurred prior to study enrollment, we conducted secondary analyses using logistic regression examining prevalent endometrial cancer cases diagnosed before study baseline.

RESULTS: Approximately 18% of participants reported a history of infertility. No statistically significant association was observed between infertility and risk of incident endometrial cancer overall (incident cases=1622; hazard ratio [HR]=1.12; 95% confidence interval [CI]=0.99-1.26). While point estimates suggested an increase in risk of endometrial cancer among women with BMI ≥25 (HR=1.15; 95% CI=0.99-1.33), none of the associations were statistically significant. There was an association between history of infertility and prevalent endometrial cancer cases (odds ratio [OR]=1.19; 95% CI=1.06-1.34), with the strongest association for infertility diagnosis due to endometriosis (OR=2.42; 95% CI=1.83-3.19).

CONCLUSIONS: In a population of postmenopausal participants, we observed a modest, but not statistically significant, association between overall infertility and incident endometrial cancer, with the suggestion of a higher risk among those with a BMI ≥25.

IMPACT: Our findings highlight, as observed in previous studies, that risk factors for endometrial cancer may vary by body mass index.},
}

@article {pmid39018351,
year = {2024},
author = {Hammermeister Suger, A and Harrison, TA and Henning, B and Turman, C and Kraft, P and Lindström, S},
title = {Nonadditive Effects of Common Genetic Variants Have a Negligent Contribution to Cancer Heritability.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {33},
number = {10},
pages = {1383-1388},
pmid = {39018351},
issn = {1538-7755},
support = {R01 CA194393/CA/NCI NIH HHS/United States ; CA194393//National Cancer Institute (NCI)/ ; T32CA09168//National Cancer Institute (NCI)/ ; },
mesh = {Humans ; *Neoplasms/genetics ; *Genome-Wide Association Study ; *Genetic Predisposition to Disease ; Genetic Variation ; Female ; Male ; Polymorphism, Single Nucleotide ; Case-Control Studies ; },
abstract = {BACKGROUND: Contribution of dominance effects to cancer heritability is unknown. We leveraged existing genome-wide association data for seven cancers to estimate the contribution of dominance effects to the heritability of individual cancer types.

METHODS: We estimated the proportion of phenotypic variation caused by dominance genetic effects using genome-wide association data for seven cancers (breast, colorectal, lung, melanoma, nonmelanoma skin, ovarian, and prostate) in a total of 166,772 cases and 284,824 controls.

RESULTS: We observed no evidence of a meaningful contribution of dominance effects to cancer heritability. By contrast, additive effects ranged between 0.11 and 0.34.

CONCLUSIONS: In line with studies of other human traits, the dominance effects of common genetic variants play a minimal role in cancer etiology.

IMPACT: These results support the assumption of an additive inheritance model when conducting cancer association studies with common genetic variants.},
}

Humans
*Neoplasms/genetics
*Genome-Wide Association Study
*Genetic Predisposition to Disease
Genetic Variation
Female
Male
Polymorphism, Single Nucleotide
Case-Control Studies

@article {pmid39346961,
year = {2024},
author = {Zeller, MA and Chang, J and Trevisan, G and Main, RG and Gauger, PC and Zhang, J},
title = {Rapid PRRSV-2 ORF5-based lineage classification using Nextclade.},
journal = {Frontiers in veterinary science},
volume = {11},
number = {},
pages = {1419340},
pmid = {39346961},
issn = {2297-1769},
abstract = {Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a global challenge for swine health. Yim-Im et al. 2023 provides a standard genetic nomenclature, extending previously published works to better characterize PRRSV-2 ORF5-based genetic lineages on a global scale. To facilitate the use of this nomenclature, scaffold sequences, including historical and contemporary vaccines, were synthesized into a dataset designed for Nextclade v3.0. Metadata from the scaffold sequences representing year, country, and RFLP typing of the sequence were incorporated into the dataset. These scaffold sequences were processed through the Augur pipeline using DQ478308.1 as a reference strain for rooting and comparison. The resultant classifier can be accessed through the Nextclade website (https://clades.nextstrain.org/) or a link on the PRRSView homepage (https://prrsv.vdl.iastate.edu/). The resultant classifier functions the same as other classifiers hosted by the Nextclade core group and can provide phylogenetic-based PRRSV-2 ORF5 classifications on demand. Nextclade provides additional sequence metrics such as classification quality and notable mutations relative to the reference. The submitted sequences are grafted to the reference tree using phylogenetic placement, allowing for comparison to nearby sequences of reference viruses and vaccine strains. Additional comparisons between sequences can be made with metadata incorporated in the dataset. Although Nextclade is hosted as a webtool, the sequences are not uploaded to a server, and all analysis stay strictly confidential to the user. This work provides a standardized, trivial workflow facilitated by Nextclade to rapidly assign lineage classifications to PRRSV-2, identify mutations of interest, and compare contemporary strains to relevant vaccines.},
}

@article {pmid39345789,
year = {2024},
author = {Parraga-Leo, A and Oskotsky, TT and Oskotsky, B and Wibrand, C and Roldan, A and Tang, AS and Ha, CWY and Wong, RJ and Minot, SS and Andreoletti, G and Kosti, I and Theis, KR and Ng, S and Lee, YS and Diaz-Gimeno, P and Bennett, PR and MacIntyre, DA and Lynch, SV and Romero, R and Tarca, AL and Stevenson, DK and Aghaeepour, N and Golob, JL and Sirota, M},
title = {VMAP: Vaginal Microbiome Atlas during Pregnancy.},
journal = {JAMIA open},
volume = {7},
number = {3},
pages = {ooae099},
pmid = {39345789},
issn = {2574-2531},
abstract = {OBJECTIVES: To enable interactive visualization of the vaginal microbiome across the pregnancy and facilitate discovery of novel insights and generation of new hypotheses.

MATERIAL AND METHODS: Vaginal Microbiome Atlas during Pregnancy (VMAP) was created with R shiny to generate visualizations of structured vaginal microbiome data from multiple studies.

RESULTS: VMAP (http://vmapapp.org) visualizes 3880 vaginal microbiome samples of 1402 pregnant individuals from 11 studies, aggregated via open-source tool MaLiAmPi. Visualized features include diversity measures, VALENCIA community state types, and composition (phylotypes, taxonomy) that can be filtered by various categories.

DISCUSSION: This work represents one of the largest and most geographically diverse aggregations of the vaginal microbiome in pregnancy to date and serves as a user-friendly resource to further analyze vaginal microbiome data and better understand pregnancies and associated outcomes.

CONCLUSION: VMAP can be obtained from https://github.com/msirota/vmap.git and is currently deployed as an online app for non-R users.},
}

@article {pmid39343510,
year = {2024},
author = {Chae, YK and Othus, M and Patel, S and Powers, B and Hsueh, CT and Govindarajan, R and Bucur, S and Kim, HS and Chung, LI and McLeod, C and Chen, HX and Sharon, E and Streicher, H and Ryan, CW and Blanke, C and Kurzrock, R},
title = {Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the desmoid tumors.},
journal = {Journal for immunotherapy of cancer},
volume = {12},
number = {9},
pages = {},
pmid = {39343510},
issn = {2051-1426},
mesh = {Humans ; Male ; Female ; Middle Aged ; Adult ; *CTLA-4 Antigen/antagonists & inhibitors ; *Fibromatosis, Aggressive/drug therapy ; Aged ; Young Adult ; Prospective Studies ; Ipilimumab/therapeutic use/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology/adverse effects ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Nivolumab/therapeutic use/pharmacology ; Adolescent ; },
abstract = {BACKGROUND: Dual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors are ultrarare soft-tissue tumors, traditionally treated with surgery. This study reviews the first results of using ipilimumab and nivolumab in the desmoid tumor cohort of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial.

METHODS: DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) that opened at 1,016 US sites. The primary endpoint included overall response rate (ORR) defined as confirmed complete (CR) and partial responses (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; stable disease (SD) ≥6 months plus CR and PR) and toxicity.

RESULTS: Sixteen evaluable patients (median age: 37) with desmoid tumors and a median of 1.5 prior therapies (with no prior exposure to immunotherapy) were analyzed. The tumors varied in location (eight abdomen, three lower limb, two upper limb, two pelvis, and one neck). ORR was 18.8% (3/16; 3 confirmed PR): 40% regression (PFS 30+ months), 83% regression (PFS 16 months) and 71% regression (PFS 8.4 months). Seven additional patients (43.8%) had prolonged SD over 6 months (PFS: 16.5, 22.4+, 22.6, 30.1, 38.2+, 48.3+ and 60.7+ months). Overall CBR was 62.5% (10/16). Median PFS was 19.4 months, with 6-month PFS of 73% and 1-year PFS of 67%. All patients were alive at 1 year; median OS was not assessable, as 13 patients were alive at analysis. Common adverse events included fatigue, nausea and hypothyroidism, with 50% experiencing grade 3-4 events. There were no grade 5 events.

CONCLUSION: Treatment with ipilimumab and nivolumab in desmoid tumors yielded an ORR of 18.8% and a CBR of 62.5% with durable responses seen. This is the first prospective study exploring the efficacy of this combination in this rare disease. Ongoing studies aim to identify markers for response and resistance. Expanded trials are necessary.

TRIAL REGISTRATION NUMBER: NCT02834013.},
}

Humans
Male
Female
Middle Aged
Adult
*CTLA-4 Antigen/antagonists & inhibitors
*Fibromatosis, Aggressive/drug therapy
Aged
Young Adult
Prospective Studies
Ipilimumab/therapeutic use/pharmacology
Immune Checkpoint Inhibitors/therapeutic use/pharmacology/adverse effects
Programmed Cell Death 1 Receptor/antagonists & inhibitors
Nivolumab/therapeutic use/pharmacology
Adolescent

@article {pmid39341639,
year = {2024},
author = {Butler, CD and Combs Bowles, D and Hanigan, IC and Harmer, A and Potter, JD},
title = {The Lancet Countdown on health and climate change: competing interests and optimism bias.},
journal = {Lancet (London, England)},
volume = {404},
number = {10459},
pages = {1196-1197},
doi = {10.1016/S0140-6736(24)01491-0},
pmid = {39341639},
issn = {1474-547X},
mesh = {Humans ; Bias ; *Climate Change ; *Global Health ; *Optimism ; },
}

Humans
Bias
*Climate Change
*Global Health
*Optimism

@article {pmid39339842,
year = {2024},
author = {Huang, Y and Alam, S and Andersen-Nissen, E and Carpp, LN and Dintwe, OB and Flach, BS and Grunenberg, N and Laher, F and De Rosa, SC and Ferrari, G and Innes, C and Bekker, LG and Kublin, JG and McElrath, MJ and Tomaras, GD and Gray, GE and Gilbert, PB},
title = {Non-HIV Vaccine-Induced Immune Responses as Potential Baseline Immunogenicity Predictors of ALVAC-HIV and AIDSVAX B/E-Induced Immune Responses.},
journal = {Viruses},
volume = {16},
number = {9},
pages = {},
pmid = {39339842},
issn = {1999-4915},
support = {UM1AI068635//National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH)/ ; R37AI054165//National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH)/ ; R01CA277133//National Cancer Institute of the NIH/ ; },
mesh = {Humans ; *AIDS Vaccines/immunology/administration & dosage ; *HIV Infections/immunology/prevention & control ; *Immunoglobulin G/blood/immunology ; *CD4-Positive T-Lymphocytes/immunology ; Male ; Female ; Adult ; Tetanus Toxoid/immunology/administration & dosage ; Immunogenicity, Vaccine ; HIV Antibodies/blood/immunology ; Hepatitis B Vaccines/immunology/administration & dosage ; HIV-1/immunology ; Young Adult ; Antibodies, Viral/blood/immunology ; Viral Vaccines ; },
abstract = {Identifying correlations between immune responses elicited via HIV and non-HIV vaccines could aid the search for correlates of HIV protection and increase statistical power in HIV vaccine-efficacy trial designs. An exploratory objective of the HVTN 097 phase 1b trial was to assess whether immune responses [focusing on those supported as correlates of risk (CoR) of HIV acquisition] induced via the RV144 pox-prime HIV vaccine regimen correlated with those induced via tetanus toxoid (TT) and/or hepatitis B virus (HBV) vaccines. We measured TT-specific and HBV-specific IgG-binding antibody responses and TT-specific and HBV-specific CD4+ T-cell responses at multiple time points in HVTN 097 participants, and we assessed their correlations at peak time points with HIV vaccine (ALVAC-HIV and AIDSVAX B/E)-induced responses. Four correlations were significant [false discovery rate-adjusted p-value (FDR) ≤ 0.2]. Three of these four were with IgG-binding antibody responses to TT measured one month after TT receipt, with the strongest and most significant correlation [rho = 0.368 (95% CI: 0.096, 0.588; p = 0.008; FDR = 0.137)] being with IgG-binding antibody responses to MN gp120 gDneg (B protein boost) measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. The fourth significant correlation [(rho = 0.361; 95% CI: 0.049, 0.609; p = 0.021; FDR = 0.137)] was between CD4+ T-cell responses to a hepatitis B surface antigen peptide pool, measured 2 weeks after the third HBV vaccination, and IgG-binding antibody responses to gp70BCaseAV1V2 (B V1V2 immune correlate), measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. These moderate correlations imply that either vaccine, TT or HBV, could potentially provide a moderately useful immunogenicity predictor for the ALVAC-HIV and AIDSVAX B/E HIV vaccine regimen.},
}

Humans
*AIDS Vaccines/immunology/administration & dosage
*HIV Infections/immunology/prevention & control
*Immunoglobulin G/blood/immunology
*CD4-Positive T-Lymphocytes/immunology
Male
Female
Adult
Tetanus Toxoid/immunology/administration & dosage
Immunogenicity, Vaccine
HIV Antibodies/blood/immunology
Hepatitis B Vaccines/immunology/administration & dosage
HIV-1/immunology
Young Adult
Antibodies, Viral/blood/immunology
Viral Vaccines

@article {pmid39334347,
year = {2024},
author = {Michel, AM and Yi, H and Amenta, J and Collins, N and Vaynrub, A and Umakanth, S and Anderson, G and Arnold, K and Law, C and Pruthi, S and Sandoval-Leon, A and Shirley, R and Perdekamp, MG and Colonna, S and Krisher, S and King, T and Yee, LD and Ballinger, TJ and Braun-Inglis, C and Mangino, DA and Wisinski, K and DeYoung, CA and Ross, M and Floyd, J and Kaster, A and VanderWalde, L and Saphner, TJ and Zarwan, C and Lo, S and Graham, C and Conlin, A and Yost, K and Agnese, D and Jernigan, C and Hershman, DL and Neuhouser, ML and Arun, B and Crew, KD and Kukafka, R},
title = {Use of web-based decision support to improve informed choice for chemoprevention: a qualitative analysis of pre-implementation interviews (SWOG S1904).},
journal = {BMC medical informatics and decision making},
volume = {24},
number = {1},
pages = {272},
pmid = {39334347},
issn = {1472-6947},
mesh = {Humans ; Female ; *Chemoprevention ; *Qualitative Research ; *Breast Neoplasms/prevention & control ; Middle Aged ; Adult ; Internet ; Male ; Decision Support Techniques ; Interviews as Topic ; },
abstract = {BACKGROUND: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.

METHODS: The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. Interviews sought to understand attitudes/beliefs and barriers/facilitators to chemoprevention.

RESULTS: Interviews with 25 providers (18 physicians and 7 advanced practice providers) were included. Providers were predominantly female (84%), white (72%), and non-Hispanic (88%). Nearly all providers (96%) had prescribed chemoprevention for eligible patients. Three themes emerged in qualitative analysis. The first theme describes providers' confidence in chemoprevention and the utility of decision support tools. The second theme elucidates barriers to chemoprevention, including time constraints, risk communication and perceptions of patients' fear of side effects and anxiety. The third theme is the need for early implementation of decision support tools.

CONCLUSIONS: This qualitative study suggests that providers were interested in the early inclusion of decision aids (DA) in their chemoprevention discussion workflow. The DAs may help overcome certain barriers which were elucidated in these interviews, including patient level concerns about side effects, clinic time constraints and difficulty communicating risk. A multi-faceted intervention with a DA as one active component may be needed.

TRIAL REGISTRATION: This trial was registered with the NIH clinical trial registry, clinicaltrials.gov, NCT04496739.},
}

Humans
Female
*Chemoprevention
*Qualitative Research
*Breast Neoplasms/prevention & control
Middle Aged
Adult
Internet
Male
Decision Support Techniques
Interviews as Topic

@article {pmid39314963,
year = {2024},
author = {Huddleston, J and Bedford, T},
title = {Timely vaccine strain selection and genomic surveillance improves evolutionary forecast accuracy of seasonal influenza A/H3N2.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39314963},
support = {R01 AI165821/AI/NIAID NIH HHS/United States ; },
abstract = {For the last decade, evolutionary forecasting models have influenced seasonal influenza vaccine design. These models attempt to predict which genetic variants circulating at the time of vaccine strain selection will be dominant 12 months later in the influenza season targeted by vaccination campaign. Forecasting models depend on hemagglutinin (HA) sequences from the WHO's Global Influenza Surveillance and Response System to identify currently circulating groups of related strains (clades) and estimate clade fitness for forecasts. However, the average lag between collection of a clinical sample and the submission of its sequence to the Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu database is ~3 months. Submission lags complicate the already difficult 12-month forecasting problem by reducing understanding of current clade frequencies at the time of forecasting. These constraints of a 12-month forecast horizon and 3-month average submission lags create an upper bound on the accuracy of any long-term forecasting model. The global response to the SARS-CoV-2 pandemic revealed that modern vaccine technology like mRNA vaccines can reduce how far we need to forecast into the future to 6 months or less and that expanded support for sequencing can reduce submission lags to GISAID to 1 month on average. To determine whether these recent advances could also improve long-term forecasts for seasonal influenza, we quantified the effects of reducing forecast horizons and submission lags on the accuracy of forecasts for A/H3N2 populations. We found that reducing forecast horizons from 12 months to 6 or 3 months reduced average absolute forecasting errors to 25% and 50% of the 12-month average, respectively. Reducing submission lags provided little improvement to forecasting accuracy but decreased the uncertainty in current clade frequencies by 50%. These results show the potential to substantially improve the accuracy of existing influenza forecasting models by modernizing influenza vaccine development and increasing global sequencing capacity.},
}

@article {pmid39314956,
year = {2024},
author = {Burns, AC and Zellers, S and Windred, DP and Daghlas, I and Sinnott-Armstrong, N and Rutter, M and Hublin, C and Friligkou, E and Polimanti, R and Phillips, AJK and Cain, SW and Kaprio, J and Ollila, HM and Saxena, R and Lane, JM},
title = {Sleep inertia drives the association of evening chronotype with psychiatric disorders: epidemiological and genetic evidence.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39314956},
support = {R01 HG012810/HG/NHGRI NIH HHS/United States ; },
abstract = {Evening chronotypes (a.k.a. "night-owls") are held to be at greater risk for psychiatric disorders. This is postulated to be due to delayed circadian timing increasing the likelihood of circadian misalignment in an early-oriented society. Circadian misalignment is known to heighten sleep inertia, the difficulty transitioning from sleep to wake characterized by low arousal and cognitive impairment, and evening chronotypes experience greater sleep inertia. Therefore, difficulty awakening may explain the relationship between evening chronotype and psychiatric disorders by acting as a biomarker of circadian misalignment. In analyzing the longitudinal incidence of psychiatric disorders in the UK Biobank (n = 496,820), we found that evening chronotype predicted increased incidence of major depressive disorder, schizophrenia, generalized anxiety disorder and bipolar disorder. Crucially, this effect was dependent on sleep inertia, which was a much stronger predictor of these disorders, such that evening types without sleep inertia were at no higher risk as compared to morning types. Longitudinal analyses of suicide and depressed mood (CES-D score) in the Older Finnish Twin Cohort (n = 23,854) replicated this pattern of results. Twin and genome-wide association analyses of difficulty awakening identified the trait to be heritable (Twin H [2] = 0.40; SNP h [2] = 0.08), enriched for circadian rhythms genes and have substantial shared genetic architecture with chronotype. Marginal and conditional Mendelian randomization analyses mirrored the epidemiological results, such that the causal effect of evening chronotype on psychiatric disorders was driven by shared genetic architecture with difficulty awakening. In contrast, difficult awakening was strongly causally associated with psychiatric disorders independently of chronotype. Psychiatric disorders were only weakly reverse causally linked to difficult awakening. Collectively, these results challenge the notion that evening chronotype is a risk factor for psychiatric disorders per se, suggesting instead that evening types are at greater risk for psychiatric disorders due to circadian misalignment, for which sleep inertia may be acting as a biomarker.},
}

@article {pmid39334118,
year = {2024},
author = {Ko, LK and Jang, SH and Rodriguez, E and Buta, M and Ibarra, G and Reuland, D},
title = {Dissemination of colorectal cancer information among Hispanic patients and their social network.},
journal = {BMC public health},
volume = {24},
number = {1},
pages = {2616},
pmid = {39334118},
issn = {1471-2458},
mesh = {Humans ; *Colorectal Neoplasms/ethnology/diagnosis ; *Hispanic or Latino/psychology/statistics & numerical data ; Female ; Male ; Middle Aged ; *Early Detection of Cancer/psychology/statistics & numerical data ; Aged ; *Information Dissemination ; Washington ; Decision Support Techniques ; Social Support ; Adult ; },
abstract = {BACKGROUND: Colorectal cancer (CRC) screening decision aids can inform patients about CRC screening benefits, costs, and procedures. Patients who receive the decision aid report wanting to share the information with their families and friends. We evaluated a CRC screening decision aid on Hispanic patients' communication to their alters and whether patient-alter communication leads to alters' CRC screening intention.

METHODS: We conducted a one-arm pre/post study of Hispanic patients and their alters; patients (n = 42) and their alters (n = 19) were recruited from a clinic site in Yakima County, Washington State. Patients viewed a CRC screening decision aid at the clinic site. Survey data from patients and alters were collected via telephone including patients' communication with their alters about CRC screening after viewing the decision aid and alters' intention to be screened for CRC after talking to the patient.

RESULTS: Most participants reported sharing CRC information with their alters after viewing the decision aid, and most alters confirmed they had received CRC information from participants (68%). The decision aid was associated with participants' own intention to undergo CRC screening and with alters' intention to be screened for CRC using a fecal occult blood test (p = 0.014) and sigmoidoscopy (p = 0.011).

CONCLUSIONS: Patient decision aids have the potential to increase CRC screening behavior beyond the decision aid recipients to their social network.

TRIAL REGISTRATION: Trials Registration Number: NCT04444232 "Retrospectively registered."},
}

Humans
*Colorectal Neoplasms/ethnology/diagnosis
*Hispanic or Latino/psychology/statistics & numerical data
Female
Male
Middle Aged
*Early Detection of Cancer/psychology/statistics & numerical data
Aged
*Information Dissemination
Washington
Decision Support Techniques
Social Support
Adult

@article {pmid39333696,
year = {2024},
author = {Serritella, AV and Taylor, A and Haffner, MC and Abida, W and Bryce, A and Karsh, LI and Tagawa, ST and Twardowski, P and Armstrong, AJ and Lang, JM},
title = {Therapeutic implications of homologous repair deficiency testing in patients with prostate cancer (Part 2 of 2).},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {39333696},
issn = {1476-5608},
abstract = {BACKGROUND/OBJECTIVES: Unfortunately, not all metastatic castration-resistant prostate cancer (mCRPC) patients receive available life-prolonging systemic therapies, emphasizing the need to optimize mCRPC treatment selections. Better guidelines are necessary to determine genetic testing for prostate cancer.

SUBJECTS/METHODS: In this two-part expert opinion-based guide, we provide an expert consensus opinion on the utilization of germline and somatic testing to detect HRR alterations in patients with mCRPC. This guide was developed by a multidisciplinary expert panel that convened in 2023-2024, including representatives from medical oncology, urology, radiation oncology, pathology, medical genomics, and basic science.

RESULTS/CONCLUSIONS: In this second part, we highlight how genetic testing can lead to improved, life-prolonging mCRPC therapeutic strategies based on a review of the recent phase III trials and subsequent regulatory approvals for PARP inhibitors in mCRPC.},
}

@article {pmid39333103,
year = {2024},
author = {Fiorenza, S and Zheng, Y and Purushe, J and Bock, TJ and Sarthy, J and Janssens, DH and Sheih, AS and Kimble, EL and Kirchmeier, D and Phi, TD and Gauthier, J and Hirayama, AV and Riddell, SR and Wu, Q and Gottardo, R and Maloney, DG and Yang, JYH and Henikoff, S and Turtle, CJ},
title = {Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {8309},
pmid = {39333103},
issn = {2041-1723},
support = {Clinical Fellowship Grant//Haematology Society of Australia and New Zealand (HSANZ)/ ; },
mesh = {Humans ; *Receptors, Chimeric Antigen/metabolism/genetics/immunology ; *Immunotherapy, Adoptive/methods ; *Histone Code ; *CD8-Positive T-Lymphocytes/immunology/metabolism ; Kruppel-Like Transcription Factors/metabolism/genetics ; Transcription Factors/metabolism/genetics ; Histones/metabolism ; Lymphoma/genetics/metabolism/therapy ; Cell Proliferation/genetics ; T-Lymphocyte Subsets/immunology/metabolism ; Immunologic Memory ; },
abstract = {Chimeric antigen receptor-modified T cell (CAR-T) immunotherapy has revolutionised blood cancer treatment. Parsing the genetic underpinnings of T cell quality and CAR-T efficacy is challenging. Transcriptomics inform CAR-T state, but the nature of dynamic transcription during activation hinders identification of transiently or minimally expressed genes, such as transcription factors, and over-emphasises effector and metabolism genes. Here we explore whether analyses of transcriptionally repressive and permissive histone methylation marks describe CAR-T cell functional states and therapeutic potential beyond transcriptomic analyses. Histone mark analyses improve identification of differences between naïve, central memory, and effector memory CD8 + T cell subsets of human origin, and CAR-T derived from these subsets. We find important differences between CAR-T manufactured from central memory cells of healthy donors and of patients. By examining CAR-T products from a clinical trial in lymphoma (NCT01865617), we find a novel association between the activity of the transcription factor KLF7 with in vivo CAR-T accumulation in patients and demonstrate that over-expression of KLF7 increases in vitro CAR-T proliferation and IL-2 production. In conclusion, histone marks provide a rich dataset for identification of functionally relevant genes not apparent by transcriptomics.},
}

Humans
*Receptors, Chimeric Antigen/metabolism/genetics/immunology
*Immunotherapy, Adoptive/methods
*Histone Code
*CD8-Positive T-Lymphocytes/immunology/metabolism
Kruppel-Like Transcription Factors/metabolism/genetics
Transcription Factors/metabolism/genetics
Histones/metabolism
Lymphoma/genetics/metabolism/therapy
Cell Proliferation/genetics
T-Lymphocyte Subsets/immunology/metabolism
Immunologic Memory

@article {pmid39332809,
year = {2024},
author = {Amonoo, HL and Guo, M and Keane, EP and Boardman, AC and Song, MT and Wolfe, ED and Cutler, C and Jim, HS and Lee, SJ and Huffman, JC and El-Jawahri, A},
title = {A Peer Support Intervention in Patients with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation (HSCT): The STEPP Proof-of-Concept Trial.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.09.022},
pmid = {39332809},
issn = {2666-6367},
abstract = {BACKGROUND: Although peer support interventions are associated with improved patient-reported outcomes in diverse cancer populations, structured peer support programs tailored to the needs of patients undergoing hematopoietic stem cell transplantation (HSCT) are lacking.

OBJECTIVE: This single-arm, proof-of-concept trial aimed to refine the Supporting Transplant Experiences with Peer Program (STEPP), a structured, five-session, manualized, phone-delivered peer support intervention for patients undergoing HSCT, informed by qualitative feedback from patients.

STUDY DESIGN: Adult patients with hematologic malignancies scheduled to undergo allogeneic or autologous HSCT were eligible to participate in the study approximately two weeks prior to their HSCT hospitalization. Participants received the STEPP intervention, which focused on providing informational, emotional, and practical support. To refine the intervention, we conducted semi-structured qualitative exit interviews to gather feedback on the content of STEPP and to identify facilitators and barriers to engagement. Transcribed interviews were analyzed using rapid analytic methods by two coders.

RESULTS: Of the 37 eligible patients, 25 enrolled in the study, 20 completed all intervention sessions and 20 completed exit interviews. Participants highlighted that discussions with peer mentors/STEPP interventionists about the transplant journey and processing information provided by the clinical team were the most valuable aspects of STEPP. Positive experiences during the first intervention session facilitated patient engagement with the program. Potential barriers to engagement included logistical challenges in connecting with interventionists while experiencing physical symptoms during inpatient hospitalization and being paired with an interventionist who had a different cancer diagnosis and/or type of transplant.

CONCLUSIONS: Patients undergoing HSCT reported positive experiences with the structured five-session, phone-delivered peer support intervention administered before and during the HSCT hospitalization. Patients' descriptions of barriers and facilitators to engagement with the STEPP intervention underscore the importance of patient input and programmatic structure in peer support interventions for this population. Insights from this proof-of-concept trial will be incorporated into future trials of STEPP to improve outcomes in HSCT recipients.},
}

@article {pmid39332390,
year = {2024},
author = {Drain, PK and Niu, X and Shapiro, AE and Magcaba, ZP and Ngcobo, Z and Ngwane, MW and Thomas, KK and Dalmat, RR and Morton, JF and Budiawan, E and Pinter, A and Cantera, J and Anderson, C and Buchmann, R and Wilson, D and Grant, B and , },
title = {Real-world diagnostic accuracy of lipoarabinomannan in three non-sputum biospecimens for pulmonary tuberculosis disease.},
journal = {EBioMedicine},
volume = {108},
number = {},
pages = {105353},
doi = {10.1016/j.ebiom.2024.105353},
pmid = {39332390},
issn = {2352-3964},
abstract = {BACKGROUND: Development of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV.

METHODS: We conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4-20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard.

FINDINGS: Urine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4-20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells <200 cells/mm[3]. Urine LAM by S4-20 achieved diagnostic sensitivity of 62% (95% CI: 53%-70%) and specificity of 99% (95% CI: 96%-100%). Plasma and serum LAM by FIND 28 showed similar sensitivity (70%, 95% CI: 62%-78%) and comparable specificities (90%, 95% CI: 82%-97%; 94%, 95% CI: 88%-99%). Diagnostic sensitivity of urine LAM by S4-20 was higher among participants without HIV (41%, 95% CI: 24%-61%) compared to HIV-positive participants with CD4 ≥200 cells/mm[3] (20%, 95% CI: 8%-39%).

INTERPRETATION: Detection of LAM was achievable in non-sputum specimens for pulmonary TB, but additional analyte concentration or signal amplification may be required to achieve diagnostic accuracy targets.

FUNDING: Bill and Melinda Gates Foundation.},
}

@article {pmid39331724,
year = {2024},
author = {Badros, AZ and Foster, L and Anderson, LD and Chaulagain, CP and Pettijohn, EM and Cowan, AJ and Costello, CL and Larson, S and Sborov, DW and Shain, KH and Silbermann, R and Shah, N and Chung, A and Krevvata, M and Pei, H and Patel, S and Khare, V and Cortoos, A and Carson, R and Lin, T and Voorhees, PM},
title = {Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025746},
pmid = {39331724},
issn = {1528-0020},
abstract = {No randomized trial has directly compared daratumumab and lenalidomide (D-R) maintenance therapy versus standard-of-care lenalidomide (R) alone post-transplant. Here, we report the primary results of the phase 3 AURIGA study evaluating D-R versus R maintenance in NDMM patients who were in ≥very good partial response, minimal residual disease (MRD; threshold 10-5) positive, and anti-CD38 naïve post-transplant. Patients were randomized 1:1 to D-R or R maintenance for up to 36 cycles. Two hundred patients were randomized (D-R, n=99; R, n=101). The primary endpoint, MRD-negative (10-5) conversion rate by 12 months from start of maintenance, was significantly higher for D-R versus R (50.5% vs 18.8%; odds ratio [OR], 4.51; 95% confidence interval [CI], 2.37-8.57; P<0.0001). MRD-negative (10-6) conversion rate was similarly higher with D-R (23.2% vs 5.0%; OR, 5.97; 95% CI, 2.15-16.58; P=0.0002). At 32.3 months' median follow-up, D-R achieved a higher overall MRD-negative (10-5) conversion rate (D-R, 60.6% vs R, 27.7%; OR, 4.12; 95% CI, 2.26-7.52; P<0.0001) and ≥complete response rate (75.8% vs 61.4%; OR, 2.00; 95% CI, 1.08-3.69; P=0.0255) versus R alone. Progression-free survival (PFS) favored D-R versus R (hazard ratio, 0.53; 95% CI, 0.29-0.97); estimated 30-month PFS rates were 82.7% for D-R and 66.4% for R. Incidences of grade 3/4 cytopenias (54.2% vs 46.9%) and infections (18.8% vs 13.3%) were slightly higher with D-R versus R. In conclusion, D-R maintenance achieved a higher MRD-negative conversion rate and improved PFS post-transplant versus R alone, with no new safety concerns. This trial was registered at www.ClinicalTrials.gov: #NCT03901963.},
}

@article {pmid39331494,
year = {2024},
author = {Unger, JM and Xiao, H and Vaidya, R and LeBlanc, M},
title = {Patient Enrollment to Industry-Sponsored Versus Federally Sponsored Cancer Clinical Trials.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2400843},
doi = {10.1200/JCO.24.00843},
pmid = {39331494},
issn = {1527-7755},
abstract = {PURPOSEThe conduct of cancer clinical research in the United States is supported by both private and public sponsors. Industry aims to obtain new drug approvals. Federally sponsored trials examine a broad set of research questions that are not typically addressed by industry; these trials, which are also more commonly conducted in diverse populations, were recently shown to have contributed to gains of 14 million life-years for patients with cancer. Despite the different mandates, the proportion of patients who might participate in industry-sponsored versus federally sponsored cancer studies is unknown.METHODSWe evaluated trial enrollment patterns from 2008 to 2022 using ClinicalTrials.gov data. The ratio of enrollments attributable to industry versus federal sponsors was estimated. A large set of estimates on the basis of different combinations of study characteristics were generated. Point estimates were determined as the mean of combinations and confidence limits by the IQR. Five-year intervals were examined to smooth annual variation.RESULTSIn total, N = 26,080 studies were examined. The estimated enrollment ratio from 2018 to 2022 for all industry-sponsored versus federally sponsored trials was 8.1 (IQR, 6.2-9.9). For adult trials, the ratio increased from 4.8 (IQR, 4.4-5.3) during 2008-2012 to 9.6 (IQR, 7.4-11.8) during 2018-2022; for trials in children, the ratio increased from 0.7 (IQR, 0.6-0.7) to 2.3 (IQR, 1.8-2.7). Despite increasing cancer incidence, enrollment counts for federally sponsored trials were flat over the study period.CONCLUSIONIn the United States, there is a growing reliance on industry to conduct cancer clinical research. Underinvestment in federally sponsored research comes at a cost for both patients and researchers, with lost opportunities for scientific, clinical, and population advances.},
}

@article {pmid39326063,
year = {2024},
author = {Gritti, I and Wan, J and Weeresekara, V and Vaz, JM and Tarantino, G and Bryde, TH and Vijay, V and Kammula, AV and Kattel, P and Zhu, S and Vu, P and Chan, M and Wu, MJ and Gordan, JD and Patra, KC and Silveira, VS and Manguso, RT and Wein, MN and Ott, CJ and Qi, J and Liu, D and Sakamoto, K and Gujral, TS and Bardeesy, N},
title = {DNAJB1-PRKACA fusion drives fibrolamellar liver cancer through impaired SIK signaling and CRTC2/p300-mediated transcriptional reprogramming.},
journal = {Cancer discovery},
volume = {},
number = {},
pages = {},
doi = {10.1158/2159-8290.CD-24-0634},
pmid = {39326063},
issn = {2159-8290},
abstract = {Fibrolamellar carcinoma (FLC) is a liver cancer of adolescents and young adults characterized by fusions of the genes encoding the protein kinase A catalytic subunit, PRKACA, and heat shock protein, DNAJB1. The chimeric DNAJB1-PRKACA protein has increased kinase activity and is essential for FLC xenograft growth. Here, we explore the critical oncogenic pathways controlled by DNAJB1-PRKACA using patient-derived FLC models, engineered systems, and patient samples. We show that a core function of DNAJB1-PRKACA is the phosphorylation and inactivation of Salt-inducible kinases (SIKs). This leads to deregulation of the CRTC2 transcriptional co-activator and p300 acetyltransferase, resulting in transcriptional reprogramming and increased global histone acetylation, driving malignant growth. Our studies establish a central oncogenic mechanism of DNAJB1-PRKACA and suggest the potential of targeting CRTC2/p300 in FLC. Notably, these findings link this rare cancer's signature fusion oncoprotein to more common cancer gene alterations involving STK11 and GNAS, which also function via SIK suppression.},
}

@article {pmid39325616,
year = {2024},
author = {Kaneko, T and Boulanger-Weill, J and Isabella, AJ and Moens, CB},
title = {Position-independent functional refinement within the vagus motor topographic map.},
journal = {Cell reports},
volume = {43},
number = {10},
pages = {114740},
doi = {10.1016/j.celrep.2024.114740},
pmid = {39325616},
issn = {2211-1247},
abstract = {Motor neurons in the central nervous system often lie in a continuous topographic map, where neurons that innervate different body parts are spatially intermingled. This is the case for the efferent neurons of the vagus nerve, which innervate diverse muscle and organ targets in the head and viscera for brain-body communication. It remains elusive how neighboring motor neurons with different fixed peripheral axon targets develop the separate somatodendritic (input) connectivity they need to generate spatially precise body control. Here, we show that vagus motor neurons in the zebrafish indeed generate spatially appropriate peripheral responses to focal sensory stimulation even when they are transplanted into ectopic positions within the topographic map, indicating that circuit refinement occurs after the establishment of coarse topography. Refinement depends on motor neuron synaptic transmission, suggesting that an experience-dependent periphery-to-brain feedback mechanism establishes specific input connectivity among intermingled motor populations.},
}

@article {pmid39325506,
year = {2024},
author = {Fong, Y and Dang, L and Zhang, B and Fintzi, J and Chen, S and Wang, J and Rouphael, NG and Branche, AR and Diemert, DJ and Falsey, AR and Losada, C and Baden, LR and Frey, SE and Whitaker, JA and Little, SJ and Kamidani, S and Walter, EB and Novak, RM and Rupp, R and Jackson, LA and Yu, C and Magaret, CA and Molitor, C and Borate, B and Babu, TM and Kottkamp, AC and Luetkemeyer, AF and Immergluck, LC and Presti, RM and Bäcker, M and Winokur, PL and Mahgoub, SM and Goepfert, PA and Fusco, DN and Atmar, RL and Posavad, CM and Mu, J and Makowski, M and Makhene, MK and Nayak, SU and Roberts, PC and Follmann, D and Gilbert, PB and , },
title = {Neutralizing Antibody Immune Correlates for a Recombinant Protein Vaccine in the COVAIL Trial.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciae465},
pmid = {39325506},
issn = {1537-6591},
abstract = {For COVAIL recipients of a COVID-19 Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.},
}

@article {pmid39324163,
year = {2024},
author = {McGowan, M and Wairimu, N and Reedy, AM and Mogere, P and Culquichicon, C and Njeru, I and Malen, RC and Jahn, A and Bärnighausen, T and Roche, SD and Ngure, K and Ortblad, KF},
title = {Formalized peer referral to HIV pre-exposure prophylaxis supported with self-testing: a mixed-methods pilot study among young Kenyan women.},
journal = {Frontiers in public health},
volume = {12},
number = {},
pages = {1428609},
pmid = {39324163},
issn = {2296-2565},
mesh = {Humans ; Female ; Kenya ; *Pre-Exposure Prophylaxis ; Pilot Projects ; *HIV Infections/prevention & control/diagnosis ; *Peer Group ; Adolescent ; *Referral and Consultation ; Young Adult ; *Self-Testing ; Anti-HIV Agents/therapeutic use/administration & dosage ; },
abstract = {BACKGROUND: The uptake of daily oral HIV pre-exposure prophylaxis (PrEP)-a highly effective intervention-remains low among African adolescent girls and young women (AGYW) who could benefit. AGYW who initiate PrEP often do so through informal peer referral, which may be enhanced with formalized peer referral and peer-delivered HIV self-testing (HIVST). To understand the feasibility of this PrEP referral model among AGYW, we conducted a pilot study in Kenya.

METHOD: From March to May 2022, we recruited AGYW (≥16-24 years) using PrEP (i.e., "peer providers") from public healthcare clinics in Kiambu County and trained them on HIV prevention, HIVST use, and peer-supported linkage to clinic-based HIV services. Following training, peer providers received eight HIVST kits and were encouraged to refer four peers (i.e., "peer clients") to PrEP. We completed surveys with peer providers and clients one month following intervention delivery to assess PrEP initiation among peer clients. Later, we conducted focus group discussions (FGDs) with peer providers and clients to identify factors that facilitated or challenged intervention outcomes.

RESULTS: We trained 16 peer providers (median age: 23 years, IQR 21-24) who reported delivering the intervention to 56 peer clients; 30 peer clients (median age: 21 years, IQR 19-22) contacted the study team and were enrolled. Most of the enrolled peer clients reported behaviors associated with HIV risk (e.g., condomless sex; 80%, 24/30) and were PrEP-naïve (87%, 26/30). At one-month, PrEP initiation among eligible PrEP-naïve peer clients was high, as reported by providers (78%, 43/55) and clients (85%, 22/26); recent HIVST use was also high among peer clients (provider report: 95%, 53/56; client report: 97%, 29/30). In the FGDs, participants reported that intervention outcomes were facilitated by close preexisting relationships, HIVST assistance, and being escorted to clinic-based HIV services by peer providers; intervention barriers included conflicting priorities and limited HIVST experience.

CONCLUSION: A formalized model of peer referral with HIVST delivery supported PrEP initiation among Kenyan AGYW. These findings demonstrate the potential for peer-delivered interventions to engage AGYW in HIV prevention services; however, more research is needed on the effectiveness and sustainability of this approach at scale.},
}

Humans
Female
Kenya
*Pre-Exposure Prophylaxis
Pilot Projects
*HIV Infections/prevention & control/diagnosis
*Peer Group
Adolescent
*Referral and Consultation
Young Adult
*Self-Testing
Anti-HIV Agents/therapeutic use/administration & dosage

@article {pmid39322372,
year = {2024},
author = {Issaka, RB and Bell-Brown, A and Jewell, T and Jackson, SL and Weiner, BJ},
title = {Interventions to Increase Follow-Up of Abnormal Stool-Based Colorectal Cancer Screening Tests in Safety Net Settings: A Systematic Review.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {22},
number = {10},
pages = {1967-1974.e3},
doi = {10.1016/j.cgh.2024.07.001},
pmid = {39322372},
issn = {1542-7714},
mesh = {Humans ; *Colorectal Neoplasms/diagnosis ; *Early Detection of Cancer/methods ; Feces/chemistry ; Safety-net Providers ; Occult Blood ; },
}

Humans
*Colorectal Neoplasms/diagnosis
*Early Detection of Cancer/methods
Feces/chemistry
Safety-net Providers
Occult Blood

@article {pmid39321924,
year = {2024},
author = {Rosen, EA and Liu, C},
title = {Author Response to: "COVID-19 Outcomes Among Hematopoietic Cell Transplant and Chimeric Antigen Receptor T-cell Recipients: Correspondence".},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.09.019},
pmid = {39321924},
issn = {2666-6367},
}

@article {pmid39321347,
year = {2024},
author = {Banerjee, R and Sexton, R and Cowan, AJ and Rosenberg, AS and Ailawadhi, S and Rajkumar, SV and Kumar, SK and Dispenzieri, A and Lonial, S and Durie, BGM and Richardson, PG and Usmani, SZ and Hoering, A and Orlowski, RZ},
title = {Dexamethasone dose intensity does not impact outcomes in newly diagnosed multiple myeloma: a secondary SWOG analysis.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025939},
pmid = {39321347},
issn = {1528-0020},
abstract = {Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM) despite common toxicities including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 milligrams (mg) once weekly was associated with lower mortality than higher doses of dexamethasone. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM have not been fully characterized. We conducted a secondary pooled analysis of the S0777 and S1211 SWOG studies of NDMM, which employed lenalidomide-dexamethasone (Rd) alone with or without bortezomib (VRd) and with or without elotuzumab (Elo-VRd). Planned dexamethasone intensity was 40-60 mg weekly in all arms. Patients were categorized into FD-DEX (full-dose dexamethasone maintained throughout induction) or LD-DEX (lowered-dose dexamethasone or discontinuation; only permitted for Grade 3+ toxicities per both study protocols). Of 541 evaluated patients, the LD-DEX group comprised 373 patients (69%). There was no difference in PFS or OS between the FD-DEX or LD-DEX groups, which were balanced in terms of age, stage, and performance status. Predictors of PFS and OS in multivariate models were treatment arm, age ≥70, and thrombocytopenia; FD-DEX did not significantly improve either outcome. Our study suggests that dexamethasone dose reductions are common in multiple myeloma, even within clinical trials. Given dexamethasone's many toxicities and unclear benefit in the era of modern treatment regimens, dexamethasone dose reduction during NDMM induction warrants further prospective study. NCT00644228, NCT01668719.},
}

@article {pmid39320863,
year = {2024},
author = {Kennedy, CJ and Kearns, JC and Geraci, JC and Gildea, SM and Hwang, IH and King, AJ and Liu, H and Luedtke, A and Marx, BP and Papini, S and Petukhova, MV and Sampson, NA and Smoller, JW and Wolock, CJ and Zainal, NH and Stein, MB and Ursano, RJ and Wagner, JR and Kessler, RC},
title = {Predicting Suicides Among US Army Soldiers After Leaving Active Service.},
journal = {JAMA psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamapsychiatry.2024.2744},
pmid = {39320863},
issn = {2168-6238},
abstract = {IMPORTANCE: The suicide rate of military servicemembers increases sharply after returning to civilian life. Identifying high-risk servicemembers before they leave service could help target preventive interventions.

OBJECTIVE: To develop a model based on administrative data for regular US Army soldiers that can predict suicides 1 to 120 months after leaving active service.

In this prognostic study, a consolidated administrative database was created for all regular US Army soldiers who left service from 2010 through 2019. Machine learning models were trained to predict suicides over the next 1 to 120 months in a random 70% training sample. Validation was implemented in the remaining 30%. Data were analyzed from March 2023 through March 2024.

MAIN OUTCOME AND MEASURES: The outcome was suicide in the National Death Index. Predictors came from administrative records available before leaving service on sociodemographics, Army career characteristics, psychopathologic risk factors, indicators of physical health, social networks and supports, and stressors.

RESULTS: Of the 800 579 soldiers in the cohort (84.9% male; median [IQR] age at discharge, 26 [23-33] years), 2084 suicides had occurred as of December 31, 2019 (51.6 per 100 000 person-years). A lasso model assuming consistent slopes over time discriminated as well over all but the shortest risk horizons as more complex stacked generalization ensemble machine learning models. Test sample area under the receiver operating characteristic curve ranged from 0.87 (SE = 0.06) for suicides in the first month after leaving service to 0.72 (SE = 0.003) for suicides over 120 months. The 10% of soldiers with highest predicted risk accounted for between 30.7% (SE = 1.8) and 46.6% (SE = 6.6) of all suicides across horizons. Calibration was for the most part better for the lasso model than the super learner model (both estimated over 120-month horizons.) Net benefit of a model-informed prevention strategy was positive compared with intervene-with-all or intervene-with-none strategies over a range of plausible intervention thresholds. Sociodemographics, Army career characteristics, and psychopathologic risk factors were the most important classes of predictors.

CONCLUSIONS AND RELEVANCE: These results demonstrated that a model based on administrative variables available at the time of leaving active Army service can predict suicides with meaningful accuracy over the subsequent decade. However, final determination of cost-effectiveness would require information beyond the scope of this report about intervention content, costs, and effects over relevant horizons in relation to the monetary value placed on preventing suicides.},
}

@article {pmid39320295,
year = {2024},
author = {Oved, JH and Russell, A and DeZern, A and Prockop, SE and Bonfim, C and Sharma, A and Purtill, D and Lakkaraja, M and Bidgoli, A and Bhoopalan, SV and Soni, S and Boelens, JJ and Abraham, A},
title = {The role of the conditioning regimen for autologous and ex vivo genetically modified hematopoietic stem cell-based therapies: recommendations from the ISCT stem cell engineering committee.},
journal = {Cytotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcyt.2024.09.001},
pmid = {39320295},
issn = {1477-2566},
abstract = {BACKGROUND: The advent of autologous gene modified cell therapies to treat monogenic disorders has been a major step forward for the field of hematopoietic stem cell transplantation (HCT) and cellular therapies. The need for disease-specific conditioning to enable these products to provide a potential cure has required extrapolation from experience in myeloablative and non-myeloablative HCT for these disorders.

METHODS: In this manuscript, we review the current datasets and clinical experience using different conditioning regimens for autologous gene therapies in hemoglobinopathies, metabolic and lysosomal disorders, inborn errors of immunity (IEI) and bone marrow failure (BMF) syndromes.

RESULTS: The disease specific and unique conditioning requirements of each disorder are considered in order to achieve maximal benefit while minimizing associated toxicities.

CONCLUSIONS: Standardized recommendations based on these data are made for each set of disorders to harmonize treatment. Future directions and the possibility of non-genotoxic conditioning regimens for autologous gene therapies are also discussed. Ethical Statement: The authors followed all relevant ethical considerations in writing this manuscript.},
}

@article {pmid39319780,
year = {2024},
author = {Perofsky, AC and Huddleston, J and Hansen, CL and Barnes, JR and Rowe, T and Xu, X and Kondor, R and Wentworth, DE and Lewis, N and Whittaker, L and Ermetal, B and Harvey, R and Galiano, M and Daniels, RS and McCauley, JW and Fujisaki, S and Nakamura, K and Kishida, N and Watanabe, S and Hasegawa, H and Sullivan, SG and Barr, IG and Subbarao, K and Krammer, F and Bedford, T and Viboud, C},
title = {Antigenic drift and subtype interference shape A(H3N2) epidemic dynamics in the United States.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
doi = {10.7554/eLife.91849},
pmid = {39319780},
issn = {2050-084X},
support = {1354890//National Science Foundation/ ; F31 AI140714/NH/NIH HHS/United States ; R01 AI165821/NH/NIH HHS/United States ; FC001030/CRUK_/Cancer Research UK/United Kingdom ; FC001030/MRC_/Medical Research Council/United Kingdom ; FC001030/WT_/Wellcome Trust/United Kingdom ; 10110400//Ministry of Health, Labour and Welfare/ ; 10111800//Ministry of Health, Labour and Welfare/ ; JP22fk0108118//Japan Agency for Medical Research and Development/ ; JP23fk0108662//Japan Agency for Medical Research and Development/ ; HHSN272201400008C/NH/NIH HHS/United States ; 75N93021C00014/NH/NIH HHS/United States ; 75N93019C00051/NH/NIH HHS/United States ; R35 GM119774/NH/NIH HHS/United States ; R01 AI127893/NH/NIH HHS/United States ; },
mesh = {*Influenza A Virus, H3N2 Subtype/genetics/immunology ; United States/epidemiology ; *Influenza, Human/epidemiology/virology/immunology ; Humans ; *Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology ; *Epidemics ; *Antigenic Drift and Shift/genetics ; Child ; Adult ; Neuraminidase/genetics/immunology ; Adolescent ; Child, Preschool ; Antigens, Viral/immunology/genetics ; Young Adult ; Evolution, Molecular ; Seasons ; Middle Aged ; },
abstract = {Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.},
}

*Influenza A Virus, H3N2 Subtype/genetics/immunology
United States/epidemiology
*Influenza, Human/epidemiology/virology/immunology
Humans
*Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology
*Epidemics
*Antigenic Drift and Shift/genetics
Child
Adult
Neuraminidase/genetics/immunology
Adolescent
Child, Preschool
Antigens, Viral/immunology/genetics
Young Adult
Evolution, Molecular
Seasons
Middle Aged

@article {pmid39319420,
year = {2024},
author = {Boyle, GE and Sitko, K and Galloway, JG and Haddox, HK and Bianchi, AH and Dixon, A and Wheelock, MK and Vandi, AJ and Wang, ZR and Thomson, RES and Garge, RK and Rettie, AE and Rubin, AF and Geck, RC and Gillam, EMJ and DeWitt, WS and Matsen, FA and Fowler, DM},
title = {Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff.},
journal = {Genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/genetics/iyae156},
pmid = {39319420},
issn = {1943-2631},
abstract = {The Cytochrome P450s (CYPs) enzyme family metabolizes ∼80% of small molecule drugs. Variants in CYPs can substantially alter drug metabolism, leading to improper dosing and severe adverse drug reactions. Due to low sequence conservation, predicting variant effects across CYPs is challenging. Even closely related CYPs like CYP2C9 and CYP2C19, which share 92% amino acid sequence identity, display distinct phenotypic properties. Using Variant Abundance by Massively Parallel sequencing (VAMP-seq), we measured the steady-state protein abundance of 7,660 single amino acid variants in CYP2C19 expressed in cultured human cells. Our findings confirmed critical positions and structural features essential for CYP function and revealed how variants at conserved positions influence abundance. We jointly analyzed 4,670 variants whose abundance was measured in both CYP2C19 and CYP2C9, finding that the homologs have different variant abundances in substrate recognition sites within the hydrophobic core. We also measured the abundance of all single and some multiple WT amino acid exchanges between CYP2C19 and CYP2C9. While most exchanges had no effect, substitutions in substrate recognition site 4 (SRS4) reduced abundance in CYP2C19. Double and triple mutants showed distinct interactions, highlighting a region that points to differing thermodynamic properties between the two homologs. These positions are known contributors to substrate specificity, suggesting an evolutionary tradeoff between stability and enzymatic function. Finally, we analyzed 368 previously unannotated human variants, finding that 43% had decreased abundance. By comparing variant effects between these homologs, we uncovered regions underlying their functional differences, advancing our understanding of this versatile family of enzymes.},
}

@article {pmid39318685,
year = {2024},
author = {Tereshchenko, LG and Haq, KT and Howell, SJ and Mitchell, EC and Martínez, J and Hyde, J and Briceno, G and Pena, J and Pocius, E and Khan, A and Soliman, EZ and Lima, JAC and Kapadia, SR and Misra-Hebert, AD and Kattan, MW and Kansal, MM and Daviglus, ML and Kaplan, R},
title = {Latent profiles of global electrical heterogeneity: the Hispanic Community Health Study/Study of Latinos.},
journal = {European heart journal. Digital health},
volume = {5},
number = {5},
pages = {611-621},
pmid = {39318685},
issn = {2634-3916},
abstract = {AIMS: Despite the highest prevalence of stroke, obesity, and diabetes across races/ethnicities, paradoxically, Hispanic/Latino populations have the lowest prevalence of atrial fibrillation and major Minnesota code-defined ECG abnormalities. We aimed to use Latent Profile Analysis in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) population to obtain insight into epidemiological discrepancies.

METHODS AND RESULTS: We conducted a cross-sectional analysis of baseline HCHS/SOL visit. Global electrical heterogeneity (GEH) was measured as spatial QRS-T angle (QRSTa), spatial ventricular gradient azimuth (SVGaz), elevation (SVGel), magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). Statistical analysis accounted for the stratified two-stage area probability sample design. We fitted a multivariate latent profile generalized structural equation model adjusted for age, sex, ethnic background, education, hypertension, diabetes, smoking, dyslipidaemia, obesity, chronic kidney disease, physical activity, diet quality, average RR' interval, median beat type, and cardiovascular disease (CVD) to gain insight into the GEH profiles. Among 15 684 participants (age 41 years; 53% females; 6% known CVD), 17% had an increased probability of likely abnormal GEH profile (QRSTa 80 ± 27°, SVGaz -4 ± 21°, SVGel 72 ± 12°, SVGmag 45 ± 12 mVms, and SAIQRST 120 ± 23 mVms). There was a 23% probability for a participant of being in Class 1 with a narrow QRSTa (40.0 ± 10.2°) and large SVG (SVGmag 108.3 ± 22.6 mVms; SAIQRST 203.4 ± 39.1 mVms) and a 60% probability of being in intermediate Class 2.

CONCLUSION: A substantial proportion (17%) in the Hispanic/Latino population had an increased probability of altered, likely abnormal GEH profile, whereas 83% of the population was resilient to harmful risk factors exposures.},
}

@article {pmid38685481,
year = {2024},
author = {Rowell, S and Meier, EN and Hoyos Gomez, T and Fleming, M and Jui, J and Morrison, L and Bulger, E and Sopko, G and Weisfeldt, M and Christenson, J and Klotz, P and McMullan, J and Callum, J and Sheehan, K and Tibbs, B and Aufderheide, T and Cotton, B and Gandhi, R and Idris, A and Frascone, RJ and Ferrara, M and Richmond, N and Kannas, D and Schlamp, R and Robinson, B and Dries, D and Tallon, J and Hendrickson, A and Gamber, M and Garrett, J and Simonson, R and McKinley, WI and Schreiber, M},
title = {The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: A subgroup analysis from the prehospital TXA for TBI trial.},
journal = {The journal of trauma and acute care surgery},
volume = {97},
number = {4},
pages = {572-580},
doi = {10.1097/TA.0000000000004354},
pmid = {38685481},
issn = {2163-0763},
mesh = {Humans ; Male ; Female ; *Tranexamic Acid/administration & dosage/therapeutic use ; Middle Aged ; *Intracranial Hemorrhage, Traumatic/drug therapy/mortality ; *Antifibrinolytic Agents/administration & dosage/therapeutic use ; Adult ; *Emergency Medical Services/methods ; *Glasgow Coma Scale ; *Tomography, X-Ray Computed ; Brain Injuries, Traumatic/mortality/complications/drug therapy ; Treatment Outcome ; },
abstract = {BACKGROUND: In the prehospital tranexamic acid (TXA) for traumatic brain injury (TBI) trial, TXA administered within 2 hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT).

METHODS: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale score < 13) and systolic blood pressure ≥ 90 mm Hg within 2 hours of injury to a 2-g out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-g out-of-hospital TXA bolus/1-g in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) ≤ 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors.

RESULTS: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-g TXA bolus group (17%) compared with the other two groups (1-g bolus/1-g infusion 26%, placebo 27%). The estimated adjusted difference between the 2-g bolus and placebo groups was -8·5 percentage points (95% confidence interval [CI], -15.9 to -1.0) and between the 2-g bolus and 1-g bolus/1-g infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). Disability Rating Scale at 6 months was lower in the 2-g TXA bolus group than the 1-g bolus/1-g infusion (estimated difference - 2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups.

CONCLUSION: A 2-g out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing.

LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.},
}

Humans
Male
Female
*Tranexamic Acid/administration & dosage/therapeutic use
Middle Aged
*Intracranial Hemorrhage, Traumatic/drug therapy/mortality
*Antifibrinolytic Agents/administration & dosage/therapeutic use
Adult
*Emergency Medical Services/methods
*Glasgow Coma Scale
*Tomography, X-Ray Computed
Brain Injuries, Traumatic/mortality/complications/drug therapy
Treatment Outcome

@article {pmid39317093,
year = {2024},
author = {Jones, SMW and Guthrie, KA and Arnold, K and Krouse, R},
title = {The bowel function instrument for rectal cancer survivors with anastomosis and ostomy.},
journal = {Journal of psychosomatic research},
volume = {187},
number = {},
pages = {111931},
doi = {10.1016/j.jpsychores.2024.111931},
pmid = {39317093},
issn = {1879-1360},
abstract = {OBJECTIVE: Rectal cancer is often treated with surgery such as ostomy or anastomosis. The Bowel Function Instrument (BFI) is a valid and reliable 18-item measure of physical bowel symptoms. Some items on the BFI do not apply to those with ostomies. We reanalyzed data from a previous validation study to inform the best method for scoring the BFI for both people with ostomies and anastomosis.

METHODS: People (n = 575) with rectal cancer treated with ostomy (n = 181, 31 %) or anastomosis (n = 394, 69 %) completed the BFI and Short Form 12 (SF12) measure on a mailed survey. The full BFI has three subscales and a total score based on 14 items: soilage/urgency (4 items); frequency of bowel movements (6 items); and dietary changes (4 items). We used confirmatory factor analysis (CFA) to examine two versions (8-item, 11-item) of the BFI adapted for use with both ostomy and anastomosis. We also examined reliability and validity of the version supported by the CFA.

RESULTS: CFA results supported the 8-item BFI that included only the soilage/urgency items and dietary changes items but not the frequency items. The 8-item BFI was reliable (Cronbach's alpha of 0.788). The 8-item BFI score significantly correlated with all SF12 subscales with Pearson correlations ranging from 0.115 (Vitality) to 0.318 (social function).

CONCLUSIONS: The 8-item version of the BFI was valid and reliable as a total score for people with ostomy or anastomosis. The 8-item BFI may be useful for monitoring bowel function during and after treatment for rectal cancer.},
}

@article {pmid39316822,
year = {2024},
author = {Thomas, CE and Lin, Y and Kim, M and Kawaguchi, ES and Qu, C and Um, CY and Lynch, BM and Van Guelpen, B and Tsilidis, K and Carreras-Torres, R and van Duijnhoven, FJ and Sakoda, LC and Campbell, PT and Tian, Y and Chang-Claude, J and Bézieau, S and Budiarto, A and Palmer, JR and Newcomb, PA and Casey, G and Le Marchand, L and Giannakis, M and Li, CI and Gsur, A and Newton, C and Obón-Santacana, M and Moreno, V and Vodicka, P and Brenner, H and Hoffmeister, M and Pellatt, AJ and Schoen, RE and Dimou, N and Murphy, N and Gunter, MJ and Castellví-Bel, S and Figueiredo, JC and Chan, AT and Song, M and Li, L and Bishop, DT and Gruber, SB and Baurley, JW and Bien, SA and Conti, DV and Huyghe, JR and Kundaje, A and Su, YR and Wang, J and Keku, TO and Woods, MO and Berndt, SI and Chanock, SJ and Tangen, CM and Wolk, A and Burnett-Hartman, A and Wu, AH and White, E and Devall, MA and Díez-Obrero, V and Drew, DA and Giovannucci, E and Hidaka, A and Kim, AE and Lewinger, JP and Morrison, J and Ose, J and Papadimitriou, N and Pardamean, B and Peoples, AR and Ruiz-Narvaez, EA and Shcherbina, A and Stern, MC and Chen, X and Thomas, DC and Platz, EA and Gauderman, WJ and Peters, U and Hsu, L},
title = {Characterization of additive gene-environment interactions for colorectal cancer risk.},
journal = {Epidemiology (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/EDE.0000000000001795},
pmid = {39316822},
issn = {1531-5487},
abstract = {BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure.

METHODS: Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk.

RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility.

CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.},
}

@article {pmid39316666,
year = {2024},
author = {Brown, JR and Eichhorst, B and Lamanna, N and O'Brien, SM and Tam, CS and Qiu, L and Jurczak, W and Zhou, K and Šimkovič, M and Mayer, J and Gillespie-Twardy, A and Ferrajoli, A and Ganly, PS and Weinkove, R and Grosicki, S and Mital, A and Robak, T and Osterborg, A and Yimer, HA and Wang, MY and Salmi, T and Wang, L and Li, J and Wu, K and Cohen, AC and Shadman, M},
title = {Sustained Benefit of Zanubrutinib vs Ibrutinib in Patients With R/R CLL/SLL: Final Comparative Analysis of ALPINE.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024024667},
pmid = {39316666},
issn = {1528-0020},
abstract = {ALPINE (NCT03734016) established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL); here we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n=327) or ibrutinib (n=325). At an overall median follow-up of 42.5 months, progression-free survival benefit with zanubrutinib vs ibrutinib was sustained (HR: 0.68 [95% CI, 0.54-0.84]), including in patients with del(17p)/TP53 mutation (HR: 0.51 [95% CI, 0.33-0.78]) and across multiple sensitivity analyses. Overall response rate remained higher with zanubrutinib compared with ibrutinib (85.6% vs 75.4%); responses deepened over time with complete response/complete response with incomplete bone marrow recovery rates of 11.6% (zanubrutinib) and 7.7% (ibrutinib). While median overall survival has not been reached in either treatment group, fewer zanubrutinib patients have died than ibrutinib patients (HR: 0.77 [95% CI, 0.55-1.06]). With median exposure time of 41.2 and 37.8 months in zanubrutinib and ibrutinib arms, respectively, the most common non-hematologic adverse events included COVID-19-related infection (46.0% vs 33.3%), diarrhea (18.8% vs 25.6%), upper respiratory tract infection (29.3% vs 19.8%), and hypertension (27.2% vs 25.3%). Cardiac events were lower with zanubrutinib (25.9% vs 35.5%) despite similar rates of hypertension. Incidence of atrial fibrillation/flutter was lower with zanubrutinib vs ibrutinib (7.1% vs 17.0%); no cardiac deaths were reported with zanubrutinib vs six cardiac deaths with ibrutinib. This analysis, at 42.5 months median follow-up, demonstrates that zanubrutinib remains more efficacious than ibrutinib with an improved overall safety/tolerability profile.},
}

@article {pmid39315857,
year = {2024},
author = {Ortiz Romero, PL and Kim, YH and Molloy, K and Quaglino, P and Scarisbrick, J and Thornton, S and Sandilands, K and Dent, JE and Nixon, A and Williams, A and Shinohara, MM},
title = {Health-related quality of life in cutaneous T-cell lymphoma: A post hoc analysis of a phase 3 trial in mycosis fungoides and Sézary syndrome.},
journal = {Journal of the European Academy of Dermatology and Venereology : JEADV},
volume = {},
number = {},
pages = {},
doi = {10.1111/jdv.20357},
pmid = {39315857},
issn = {1468-3083},
support = {TD1 1QH//Kyowa Kirin Services Ltd, Galabank Business Park, Galashiels, Scotland/ ; },
abstract = {BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are common subtypes of cutaneous T-cell lymphoma that primarily affect the skin but may spread to the lymph nodes, viscera and blood. The symptom burden may compromise health-related quality of life (HRQL). The phase 3 MAVORIC study (ClinicalTrials.gov identifier NCT01728805) in patients with relapsed/refractory MF/SS reported improved HRQL with mogamulizumab compared with vorinostat.

OBJECTIVES: Use baseline (pre-treatment) data from the MAVORIC study to describe the symptom burden of MF/SS and identify characteristics associated with worse HRQL.

METHODS: Data were from 372 adults with stage IB-IVB histologically confirmed relapsed/ refractory MF or SS. Associations between demographic and medical history variables and worse HRQL (Skindex-29, ItchyQol and Functional Assessment of Cancer Therapy - General [FACT-G]) were determined by regression models.

RESULTS: In the cohort of 372 adults, 70% were white; 42% were female; mean age was 63 (SD 13.0) years. Fifty-five per cent had MF and 45% had SS; 77% had advanced (stage IIB-IV) disease, involving the skin in all patients and the blood and/or nodes in 66%. HRQL scores showed impairment versus normative means (where available), with the greatest impact on Symptoms and Emotions in the Skindex-29, Functioning in the ItchyQol, and Functional Wellbeing in the FACT-G. In regression analysis, worse HRQL across all domains and total score was associated with being female and younger, worse mSWAT score and worse itch for the Skindex-29 (n = 352), and being female, younger, Black/African American, worse performance status and worse itch for the ItchyQol (n = 369). Associations across domains and total score were not found for the FACT-G. Associations between domains and demographic/medical history were seen for all instruments.

CONCLUSIONS: The symptoms of advanced MF/SS compromise all HRQL domains. Treatment goals and therapeutic choice should be informed by individual patients' disease burden.},
}

@article {pmid39315814,
year = {2024},
author = {Loes, AN and Tarabi, RAL and Huddleston, J and Touyon, L and Wong, SS and Cheng, SMS and Leung, NHL and Hannon, WW and Bedford, T and Cobey, S and Cowling, BJ and Bloom, JD},
title = {High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0068924},
doi = {10.1128/jvi.00689-24},
pmid = {39315814},
issn = {1098-5514},
abstract = {UNLABELLED: The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes using a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify the infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately 1 month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year-although the titers 6 months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. We provide an experimental protocol (dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1) and computational pipeline (https://github.com/jbloomlab/seqneut-pipeline) for the sequencing-based neutralization assays to facilitate the use of this method by others.

IMPORTANCE: We describe a new approach that can rapidly measure how the antibodies in human serum inhibit infection by many different influenza strains. This new approach is useful for understanding how viral evolution affects antibody immunity. We apply the approach to study the effect of repeated influenza vaccination.},
}

@article {pmid39315598,
year = {2024},
author = {Kwendakwema, CN and Hopkins, T and Bell-Brown, A and Simianu, VV and Shankaran, V and Issaka, RB},
title = {Clinician perceptions on barriers and facilitators to 1-year surveillance colonoscopy completion in survivors of colorectal cancer.},
journal = {Cancer medicine},
volume = {13},
number = {18},
pages = {e70244},
doi = {10.1002/cam4.70244},
pmid = {39315598},
issn = {2045-7634},
support = {T32CA009515/CA/NCI NIH HHS/United States ; K08CA241296/RC/CCR NIH HHS/United States ; P30 CA015704/RC/CCR NIH HHS/United States ; },
mesh = {Humans ; *Colorectal Neoplasms/psychology/surgery ; *Colonoscopy/psychology ; *Cancer Survivors/psychology ; Male ; Female ; Middle Aged ; Attitude of Health Personnel ; Early Detection of Cancer/psychology ; Health Services Accessibility ; },
abstract = {INTRODUCTION: Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Surveillance colonoscopy is recommended 1-year after surgical resection for patients with stage I-III CRC; however, only 18%-61% of CRC survivors complete this test. This study describes clinician-identified barriers and facilitators to surveillance colonoscopy among CRC survivors.

METHODS: We conducted semi-structured interviews with clinicians until thematic saturation was achieved. Interviews were analyzed using the social cognitive theory.

RESULTS: Thirteen clinicians were interviewed, and all identified health system-level barriers to surveillance colonoscopy completion; the most common being fragmented care due to patients receiving care across many health systems. Clinicians also identified social determinants of health barriers (e.g., geographical distance between patients and health systems) to 1-year surveillance colonoscopy completion.

CONCLUSIONS: Clinicians identified several potentially modifiable barriers to 1-year surveillance colonoscopy completion which, if addressed, could improve post-treatment care and outcomes among stage I-III CRC survivors.},
}

Humans
*Colorectal Neoplasms/psychology/surgery
*Colonoscopy/psychology
*Cancer Survivors/psychology
Male
Female
Middle Aged
Attitude of Health Personnel
Early Detection of Cancer/psychology
Health Services Accessibility

@article {pmid39315597,
year = {2024},
author = {Rosenthal, EA and Hsu, L and Thomas, M and Peters, U and Kachulis, C and Patterson, K and Jarvik, GP},
title = {Comparing Ancestry Standardization Approaches for a Transancestry Colorectal Cancer Polygenic Risk Score.},
journal = {Genetic epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1002/gepi.22590},
pmid = {39315597},
issn = {1098-2272},
support = {//This work was funded by the Office of the Director at the National Institute of Health, under award notice 1OT2OD002748-01 and by the NHGRI through the grant U01HG008657./ ; },
abstract = {Colorectal cancer (CRC) is a complex disease with monogenic, polygenic and environmental risk factors. Polygenic risk scores (PRSs) aim to identify high polygenic risk individuals. Due to differences in genetic background, PRS distributions vary by ancestry, necessitating standardization. We compared four post-hoc methods using the All of Us Research Program Whole Genome Sequence data for a transancestry CRC PRS. We contrasted results from linear models trained on A. the entire data or an ancestrally diverse subset AND B. covariates including principal components of ancestry or admixture. Standardization with the training subset also adjusted the variance. All methods performed similarly within ancestry, OR (95% C.I.) per s.d. change in PRS: African 1.5 (1.02, 2.08), Admixed American 2.2 (1.27, 3.85), European 1.6 (1.43, 1.89), and Middle Eastern 1.1 (0.71, 1.63). Using admixture and an ancestrally diverse training set provided distributions closest to standard Normal. Training a model on ancestrally diverse participants, adjusting both the mean and variance using admixture as covariates, created standard Normal z-scores, which can be used to identify patients at high polygenic risk. These scores can be incorporated into comprehensive risk calculation including other known risk factors, allowing for more precise risk estimates.},
}

@article {pmid39311908,
year = {2024},
author = {Wang, L and Chao, M and Han, RR and Li, L and Dong, L and Chen, F and Jin, MZ and Gao, L and Wang, Y and Feng, DY and Zhu, G and Guo, W and Zhao, WJ and Jin, SJ and Wei, DP and Sun, W and Dai, JX and Jin, WL},
title = {Single-cell map of diverse immune phenotypes in the metastatic brain tumor microenvironment of non-small-cell lung cancer.},
journal = {International journal of surgery (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/JS9.0000000000002088},
pmid = {39311908},
issn = {1743-9159},
}

@article {pmid39311597,
year = {2024},
author = {Marzinke, MA and Han, K and Hanscom, B and Guo, X and Piwowar-Manning, E and Hendrix, CW and Rose, S and Spooner, E and Mathew, C and Innes, S and Sekabira, R and Mutambanengwe, M and Rooney, JF and Rinehart, AR and Adeyeye, A and Cohen, MS and Hosseinipour, M and Ford, SL and Delany-Moretlwe, S},
title = {Pharmacologic evaluation of delayed long-acting cabotegravir administration among cisgender women in HPTN 084.},
journal = {Antimicrobial agents and chemotherapy},
volume = {},
number = {},
pages = {e0099424},
doi = {10.1128/aac.00994-24},
pmid = {39311597},
issn = {1098-6596},
abstract = {UNLABELLED: HPTN 084 demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with daily oral tenofovir disoproxil fumarate-emtricitabine (F/TDF) for HIV prevention in women. CAB-LA (600 mg) or placebo injections were administered 4 weeks after an initial dose (loading dose) and every 2 months (Q2M) thereafter; this is the approved regimen. Participants experienced both loading dose and Q2M delays during the trial. CAB concentrations were evaluated before a delay, at the visit associated with the delay, and the visit after a delayed injection was administered. During the blinded phase of the trial, 194 participants randomized to CAB-LA experienced at least one injection delay. Plasma CAB concentrations were maintained above the 4× protein adjusted 90% inhibitory concentration (4× PA-IC90; protocol-specific threshold) for all loading dose and 98% of Q2M delays when injections were administered up to 6 weeks late. The feasibility of shifting to an every 3-month (Q3M) regimen in females was interrogated via simulation studies using a population pharmacokinetic model. Q3M injections in both CAB-naïve (with a loading dose) and previously CAB-exposed females were predicted to yield higher steady-state exposures than in males on the approved Q2M regimen. Although there is observed forgiveness following an isolated delayed CAB-LA injection and simulations suggest acceptable CAB-LA exposures in women with a 600 mg CAB-LA Q3M regimen, empirical efficacy of this regimen has not been established, and transitioning to this dosing schema is not recommended. Future pharmacokinetic bridging studies are aimed at evaluating higher dose CAB-LA formulations administered less frequently.

CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT03164564.},
}

@article {pmid39308420,
year = {2024},
author = {Damerell, V and Klaassen-Dekker, N and Brezina, S and Ose, J and Ulvik, A and van Roekel, EH and Holowatyj, AN and Baierl, A and Böhm, J and Bours, MJL and Brenner, H and de Wilt, JHW and Grady, WM and Habermann, N and Hoffmeister, M and Keski-Rahkonen, P and Lin, T and Schirmacher, P and Schrotz-King, P and Ulrich, AB and van Duijnhoven, FJB and Warby, CA and Shibata, D and Toriola, AT and Figueiredo, JC and Siegel, EM and Li, CI and Gsur, A and Kampman, E and Schneider, M and Ueland, PM and Weijenberg, MP and Ulrich, CM and Kok, DE and Gigic, B and , },
title = {Circulating tryptophan-kynurenine pathway metabolites are associated with all-cause mortality among patients with stage I-III colorectal cancer.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.35183},
pmid = {39308420},
issn = {1097-0215},
support = {//Netherlands Organization for Health Research and Development/ ; 2014/1179//Wereld Kanker Onderzoek Fonds/ ; 2016/1620//Wereld Kanker Onderzoek Fonds/ ; //Research Council Norway/Norwegian Cancer Society/ ; API02104FW//Austrian Science Fund/ ; UW2014-6877//Dutch Cancer Society/ ; UM 2012-5653//Dutch Cancer Society/ ; UW 2013-5927//Dutch Cancer Society/ ; UW 2015-7//Dutch Cancer Society/ ; //Cottrell Family Fund/ ; //Rodger C. Haggitt Endowed Chair/ ; FOCUS I2104-B26//Transcan/ ; MetaboCCC I 1578-B19//Transcan/ ; 01KT1503//Bundesministerium für Bildung und Forschung/ ; 01KD2101D//Bundesministerium für Bildung und Forschung/ ; //Huntsman Cancer Foundation/ ; P30 CA15704//National Insitutes of Health/ ; U01 CA152756/CA/NCI NIH HHS/United States ; R01 CA194663/CA/NCI NIH HHS/United States ; R01 CA220//National Insitutes of Health/ ; R01 CA207371/CA/NCI NIH HHS/United States ; U01 CA20//NIH/NCI/ ; T32 HG008962/HG/NHGRI NIH HHS/United States ; //VLAG Graduate School/ ; //Stiftung LebensBlicke/ ; R01 CA189184/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; //Matthias-Lackas Foundations/ ; //Rahel-Goitein-Straus-Program, Medical Faculty, Heidelberg University/ ; //Heidelberger Stiftung Chirurgie/ ; //Stichting Alpe d'HuZes/ ; 00005739//Health Foundation Limburg/ ; //Seattle Translational Tumor Research program/ ; //Fred Hutchinson Cancer Center/ ; //Listwin Family Foundation/ ; //R.A.C.E. Charities/ ; },
abstract = {Alterations within the tryptophan-kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan-kynurenine pathway metabolites and all-cause mortality among CRC patients. This study utilizes data from 2102 stage I-III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (HK), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography-tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above-mentioned metabolites with all-cause mortality, adjusted for potential confounders. During a median follow-up of 3.2 years (interquartile range: 2.2-4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all-cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine-to-tryptophan ratio, a marker of cell-mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan-kynurenine pathway metabolites may be prognostic markers of survival in CRC patients.},
}

@article {pmid39282444,
year = {2024},
author = {Zych, MG and Contreras, M and Vashisth, M and Mammel, AE and Ha, G and Hatch, EM},
title = {RCC1 depletion drives protein transport defects and rupture in micronuclei.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39282444},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R35 GM124766/GM/NIGMS NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; DP2 CA280624/CA/NCI NIH HHS/United States ; T32 CA009657/CA/NCI NIH HHS/United States ; },
abstract = {Micronuclei (MN) are a commonly used marker of chromosome instability that form when missegregated chromatin recruits its own nuclear envelope (NE) after mitosis. MN frequently rupture, which results in genome instability, upregulation of metastatic genes, and increased immune signaling. MN rupture is linked to NE defects, but the cause of these defects is poorly understood. Previous work from our lab found that chromosome identity correlates with rupture timing for small MN, i.e. MN containing a short chromosome, with more euchromatic chromosomes forming more stable MN with fewer nuclear lamina gaps. Here we demonstrate that histone methylation promotes rupture and nuclear lamina defects in small MN. This correlates with increased MN size, and we go on to find that all MN have a constitutive nuclear export defect that drives MN growth and nuclear lamina gap expansion, making the MN susceptible to rupture. We demonstrate that these export defects arise from decreased RCC1 levels in MN and that additional loss of RCC1 caused by low histone methylation in small euchromatic MN results in additional import defects that suppress nuclear lamina gaps and MN rupture. Through analysis of mutational signatures associated with early and late rupturing chromosomes in the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset, we identify an enrichment of APOBEC and DNA polymerase E hypermutation signatures in chromothripsis events on early and mid rupturing chromosomes, respectively, suggesting that MN rupture timing could determine the landscape of structural variation in chromothripsis. Our study defines a new model of MN rupture where increased MN growth, caused by defects in protein export, drives gaps in nuclear lamina organization that make the MN susceptible to membrane rupture with long-lasting effects on genome architecture.},
}

@article {pmid39282381,
year = {2024},
author = {Shinde, P and Willemsen, L and Anderson, M and Aoki, M and Basu, S and Burel, JG and Cheng, P and Dastidar, SG and Dunleavy, A and Einav, T and Forschmiedt, J and Fourati, S and Garcia, J and Gibson, W and Greenbaum, JA and Guan, L and Guan, W and Gygi, JP and Ha, B and Hou, J and Hsiao, J and Huang, Y and Jansen, R and Kakoty, B and Kang, Z and Kobie, JJ and Kojima, M and Konstorum, A and Lee, J and Lewis, SA and Li, A and Lock, EF and Mahita, J and Mendes, M and Meng, H and Neher, A and Nili, S and Olsen, LR and Orfield, S and Overton, JA and Pai, N and Parker, C and Qian, B and Rasmussen, M and Reyna, J and Richardson, E and Safo, S and Sorenson, J and Srinivasan, A and Thrupp, N and Tippalagama, R and Trevizani, R and Ventz, S and Wang, J and Wu, CC and Ay, F and Grant, B and Kleinstein, SH and Peters, B},
title = {Putting computational models of immunity to the test - an invited challenge to predict B. pertussis vaccination outcomes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39282381},
issn = {2692-8205},
support = {U01 AI141995/AI/NIAID NIH HHS/United States ; U01 AI150753/AI/NIAID NIH HHS/United States ; U19 AI142742/AI/NIAID NIH HHS/United States ; },
abstract = {Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting B. pertussis booster responses and generate experimental data for the explicit purpose of model evaluation. We here describe our second computational prediction challenge using this resource, where we benchmarked 49 algorithms from 53 scientists. We found that the most successful models stood out in their handling of nonlinearities, reducing large feature sets to representative subsets, and advanced data preprocessing. In contrast, we found that models adopted from literature that were developed to predict vaccine antibody responses in other settings performed poorly, reinforcing the need for purpose-built models. Overall, this demonstrates the value of purpose-generated datasets for rigorous and open model evaluations to identify features that improve the reliability and applicability of computational models in vaccine response prediction.},
}

@article {pmid39307421,
year = {2024},
author = {Iftikhar, R and DeFilipp, Z and DeZern, AE and Pulsipher, MA and Bejanyan, N and Burroughs, LM and Kharfan-Dabaja, MA and Arai, S and Kassim, A and Nakamura, R and Saldaña, BJD and Aljurf, M and Hamadani, M and Carpenter, PA and Antin, JH},
title = {Allogeneic Hematopoietic Cell Transplantation for the Treatment of Severe Aplastic Anemia: Evidence-Based Guidelines from the American Society for Transplantation and Cellular Therapy.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.09.017},
pmid = {39307421},
issn = {2666-6367},
abstract = {Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe aplastic anemia (SAA). Existing guidance about HCT in SAA is primarily derived from expert reviews, registry data and societal guidelines; however, transplant-specific guidelines for SAA are lacking. A panel of SAA experts, both pediatric and adult transplant physicians, developed consensus recommendations using Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology employing a GRADE guideline development tool. The panel agrees with previous recommendations for the preferential use of bone marrow as a graft source and the use of rabbit over horse antithymocyte globulin (ATG) for HCT conditioning. Fludarabine containing regimens are preferred for patients at high risk of graft failure and those receiving matched unrelated or haploidentical donor transplant. Given advancements in HCT, the panel does not endorse the historical 40-year age cut-off for considering upfront HCT in adults, acknowledging that fit older patients may also benefit from HCT. The panel also endorses increased utilization of HCT by prioritizing matched unrelated or haploidentical donor HCT over immunosuppressive therapy in children and adults who lack a matched related donor. Finally, the panel suggests either calcineurin inhibitor plus methotrexate or post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis for matched related or matched unrelated donor recipients. These recommendations reflect a significant advancement in transplant strategies for SAA and highlight the importance of ongoing and further research to revisit current evidence in terms of donor choice, conditioning chemotherapy, GVHD prophylaxis and post-transplant immunosuppression.},
}

@article {pmid39298209,
year = {2024},
author = {Langer, SL and Romano, JM and Todd, M and Keefe, FJ and Syrjala, KL and Bricker, JB and Burns, J and Bolger, N and Porter, LS},
title = {Couple communication in cancer: A tale of two conceptual models.},
journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association},
volume = {},
number = {},
pages = {},
doi = {10.1037/hea0001396},
pmid = {39298209},
issn = {1930-7810},
support = {/CA/NCI NIH HHS/United States ; },
abstract = {UNLABELLED: Cancer poses significant challenges for patients and caregiving partners. Avoidant communication has been linked to poorer psychosocial adjustment to cancer. Two conceptual models have been proposed to account for this linkage: the social-cognitive processing and relationship intimacy models.

OBJECTIVE: To examine the utility of these models in explaining patient and partner psychological and relationship adjustment on a day-to-day basis using ecological momentary assessment.

METHOD: Patients with breast, colorectal, or lung cancer and their partners (286 dyads) were prompted twice daily for 14 days via smartphone to answer questions about communication with their partner, adjustment (psychological distress and relationship satisfaction), and hypothesized mediators (avoidant thoughts and intimacy). Data were collected from 2017 to 2020.

RESULTS: Participants responded to 92% of prompts and completed 91%. Results supported the relationship intimacy but not the social-cognitive processing model. On afternoons when participants (both patients and caregivers) held back or perceived avoidance or criticism from their partner, they reported less intimacy, as did their partners; this lowered intimacy, in turn, led to participants' (both patients' and caregivers') own lowered relationship satisfaction that evening and to patients' lowered relationship satisfaction through caregivers' lowered intimacy (one-tailed Bayesian ps < .025). When distress was the criterion, patients' holding back or perceived avoidance/criticism led to their own increased distress through their own decreased intimacy, and caregivers' holding back or perceived avoidance/criticism led to patients' increased distress through patients' lowered intimacy (one-tailed Bayesian ps < .005).

CONCLUSIONS: Findings offer implications for interventions designed to improve communication and enhance closeness. (PsycInfo Database Record (c) 2024 APA, all rights reserved).},
}

@article {pmid39297845,
year = {2024},
author = {McGraw, KE and Schilling, K and Glabonjat, RA and Galvez-Fernandez, M and Domingo-Relloso, A and Martinez-Morata, I and Jones, MR and Nigra, A and Post, WS and Kaufman, J and Tellez-Plaza, M and Valeri, L and Brown, ER and Kronmal, RA and Barr, RG and Shea, S and Navas-Acien, A and Sanchez, TR},
title = {Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis.},
journal = {Journal of the American College of Cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacc.2024.07.020},
pmid = {39297845},
issn = {1558-3597},
abstract = {BACKGROUND: Exposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression.

OBJECTIVES: The authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis).

METHODS: We analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (μg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors.

RESULTS: At baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%-74%) higher at baseline and 75% (95% CI: 47%-107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%-71%), 39% (95% CI: 17%-64%), and 47% (95% CI: 25%-74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors.

CONCLUSIONS: Exposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression.},
}

@article {pmid39297750,
year = {2024},
author = {Kopmar, NE and Qu, X and Liu, Y and Gooley, TA and Ghiuzeli, CM and Mawad, R and Percival, MM and Fang, M and Cassaday, RD},
title = {Prognostic significance of chromosomal genomic array testing in adults with newly-diagnosed acute lymphoblastic leukemia.},
journal = {Leukemia & lymphoma},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/10428194.2024.2404959},
pmid = {39297750},
issn = {1029-2403},
}

@article {pmid39306478,
year = {2024},
author = {Francini, E and Agarwal, N and Castro, E and Cheng, HH and Chi, KN and Clarke, N and Mateo, J and Rathkopf, D and Saad, F and Tombal, B},
title = {Intensification Approaches and Treatment Sequencing in Metastatic Castration-resistant Prostate Cancer: A Systematic Review.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2024.09.008},
pmid = {39306478},
issn = {1873-7560},
abstract = {BACKGROUND AND OBJECTIVE: Recently, research on treatment intensification has gathered momentum, and three novel therapy combinations were approved for metastatic castration-resistant prostate cancer (mCRPC). This systematic review summarizes the current and emerging evidence around intensified strategies for mCRPC and provides guidance for an ideal therapeutic sequencing.

METHODS: Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines were followed to perform this review. PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials.gov, and major international societies' online proceedings were searched comprehensively until May 15, 2024, for terms related to treatment intensification and sequencing for mCRPC.

KEY FINDINGS AND LIMITATIONS: Overall, 28 clinical trials and 24 ongoing studies of intensification treatments were included in this review. Algorithms of optimal sequencing of approved treatments for mCRPC were outlined according to the use of androgen receptor pathway inhibitors (ARPIs) with or without docetaxel for earlier disease states. In first line, poly(ADP-ribose) polymerase inhibitor + ARPI combinations improve radiographical progression-free survival (rPFS), particularly for those with BRCA1/2 alterations. The AKT inhibitor combination of ipatasertib + abiraterone extends rPFS in those with PTEN loss or PIK3CA/AKT1/PTEN alterations. In those with two or more risk factors for early progression on enzalutamide, radionuclide 177-Lu-PSMA-617 + enzalutamide prolongs progression-free survival. Ongoing research of intensified approaches for mCRPC, and available and potential predictive and prognostic biomarkers are discussed.

Recent approvals and ongoing investigations of single agents and intensification approaches will keep transforming the mCRPC treatment landscape. Improvement of patient profiling applying recognized genomic, molecular, and clinical predictive and prognostic indicators is fundamental to optimize sequential use of available therapies.},
}

@article {pmid39306373,
year = {2024},
author = {Issaka, RB and Bell-Brown, A and Jewell, T and Jackson, SL and Weiner, BJ},
title = {Interventions to Increase Follow-Up of Abnormal Stool-Based Colorectal Cancer Screening Tests in Safety Net Settings: A Systematic Review.},
journal = {Gastroenterology},
volume = {167},
number = {5},
pages = {826-833.e3},
doi = {10.1053/j.gastro.2024.08.002},
pmid = {39306373},
issn = {1528-0012},
mesh = {Humans ; *Colorectal Neoplasms/diagnosis ; *Early Detection of Cancer/methods ; *Occult Blood ; *Safety-net Providers ; Feces/chemistry ; Colonoscopy ; Mass Screening/methods ; },
}

Humans
*Colorectal Neoplasms/diagnosis
*Early Detection of Cancer/methods
*Occult Blood
*Safety-net Providers
Feces/chemistry
Colonoscopy
Mass Screening/methods

@article {pmid39305480,
year = {2024},
author = {Chen, JG and Kensler, TW and Zhu, J and Zhu, YR and Wang, JB and Lu, JH and Muñoz, A and Groopman, JD},
title = {Profound primary prevention of liver cancer following a natural experiment in China: A 50-year perspective and public health implications.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.35198},
pmid = {39305480},
issn = {1097-0215},
support = {MS22019008//Science and Technology Project of Nantong City/ ; P30 CA006973/CA/NCI NIH HHS/United States ; R35 CA197222/CA/NCI NIH HHS/United States ; 2008ZX10002-015//Chinese National Key Projects/ ; 2008ZX10002-017//Chinese National Key Projects/ ; 2012ZX10002009//Chinese National Key Projects/ ; BRA2019030//Project 333 of Jiangsu Province/ ; },
abstract = {Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8-fold the risk of liver cancer relative to HBV alone. Using the population-based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin-specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age-standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases. A natural experiment of economic reform in the 1980s drove a rapid switch from consumption of heavily contaminated corn to minimally, if any, contaminated rice and subsequent dietary diversity. Aflatoxin consumption appears to accelerate the time to liver cancer diagnosis; lowering exposure to this carcinogen adds years of life before a cancer diagnosis. Thus, in 1990 the median age of diagnosis was 48 years, while increasing to 67 years by 2021. These findings have important translational public health implications since up to 5 billion people worldwide might be routinely exposed to dietary aflatoxin, especially in societies using corn as the staple food. Interventions against aflatoxin are an achievable outcome leading to a reduction in liver cancer incidence and years of delay of its nearly always fatal diagnosis.},
}

@article {pmid39304265,
year = {2024},
author = {, },
title = {Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.},
journal = {The Lancet. Neurology},
volume = {23},
number = {10},
pages = {973-1003},
doi = {10.1016/S1474-4422(24)00369-7},
pmid = {39304265},
issn = {1474-4465},
mesh = {Humans ; *Global Burden of Disease ; Risk Factors ; *Stroke/epidemiology ; *Global Health ; Disability-Adjusted Life Years ; Incidence ; Prevalence ; Quality-Adjusted Life Years ; Male ; Female ; },
abstract = {BACKGROUND: Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990-2021.

METHODS: We estimated incidence, prevalence, death, and disability-adjusted life-year (DALY) counts and age-standardised rates per 100 000 people per year for overall stroke, ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage, for 204 countries and territories from 1990 to 2021. We also calculated burden of stroke attributable to 23 risk factors and six risk clusters (air pollution, tobacco smoking, behavioural, dietary, environmental, and metabolic risks) at the global and regional levels (21 GBD regions and Socio-demographic Index [SDI] quintiles), using the standard GBD methodology. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline.

FINDINGS: In 2021, stroke was the third most common GBD level 3 cause of death (7·3 million [95% UI 6·6-7·8] deaths; 10·7% [9·8-11·3] of all deaths) after ischaemic heart disease and COVID-19, and the fourth most common cause of DALYs (160·5 million [147·8-171·6] DALYs; 5·6% [5·0-6·1] of all DALYs). In 2021, there were 93·8 million (89·0-99·3) prevalent and 11·9 million (10·7-13·2) incident strokes. We found disparities in stroke burden and risk factors by GBD region, country or territory, and SDI, as well as a stagnation in the reduction of incidence from 2015 onwards, and even some increases in the stroke incidence, death, prevalence, and DALY rates in southeast Asia, east Asia, and Oceania, countries with lower SDI, and people younger than 70 years. Globally, ischaemic stroke constituted 65·3% (62·4-67·7), intracerebral haemorrhage constituted 28·8% (28·3-28·8), and subarachnoid haemorrhage constituted 5·8% (5·7-6·0) of incident strokes. There were substantial increases in DALYs attributable to high BMI (88·2% [53·4-117·7]), high ambient temperature (72·4% [51·1 to 179·5]), high fasting plasma glucose (32·1% [26·7-38·1]), diet high in sugar-sweetened beverages (23·4% [12·7-35·7]), low physical activity (11·3% [1·8-34·9]), high systolic blood pressure (6·7% [2·5-11·6]), lead exposure (6·5% [4·5-11·2]), and diet low in omega-6 polyunsaturated fatty acids (5·3% [0·5-10·5]).

INTERPRETATION: Stroke burden has increased from 1990 to 2021, and the contribution of several risk factors has also increased. Effective, accessible, and affordable measures to improve stroke surveillance, prevention (with the emphasis on blood pressure, lifestyle, and environmental factors), acute care, and rehabilitation need to be urgently implemented across all countries to reduce stroke burden.

FUNDING: Bill & Melinda Gates Foundation.},
}

Humans
*Global Burden of Disease
Risk Factors
*Stroke/epidemiology
*Global Health
Disability-Adjusted Life Years
Incidence
Prevalence
Quality-Adjusted Life Years
Male
Female

@article {pmid39303988,
year = {2024},
author = {Taylor, MR and Cole, SW and Bradford, MC and Zhou, C and Fladeboe, KM and Knight, JM and Baker, KS and Yi-Frazier, JP and Rosenberg, AR},
title = {Resilience intervention improves stress-related gene expression in adolescent and young adult HCT recipients.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.09.014},
pmid = {39303988},
issn = {2666-6367},
abstract = {BACKGROUND: Overactivation of the stress response can influence cancer outcomes through immune-related pathways. Adolescents and young adults (AYAs) undergoing hematopoietic cell transplantation (HCT) are at risk for poor outcomes, yet there are limited behavioral interventions and no psychosocial biomarker data for this population. The Conserved Transcriptional Response to Adversity (CTRA) is an inflammation-related pattern observed in conditions of heightened stress and is associated with HCT outcomes.

OBJECTIVE: The objective of the current study was to explore the CTRA gene regulatory impact of the PRISM intervention among AYAs receiving HCT. We hypothesized that patients who received the intervention would have favorable gene expression signatures compared to those in the control arm.

STUDY DESIGN: This was an ancillary study within a randomized trial testing the Promoting Resilience in Stress Management (PRISM) intervention on psychosocial outcomes among AYAs aged 12-24 years receiving HCT (NCT03640325). CTRA was quantified through genome-wide transcriptional profiles obtained from whole blood collected at baseline, 1-, and 3-months post HCT. Group differences in CTRA gene expression were estimated using mixed effect linear models.

RESULTS: There were no baseline group differences in CTRA expression, but PRISM participants showed a greater decline in CTRA at 1 month compared to controls (β -0.301 ± SE 0.114, p = 0.016), even when controlling for demographic (Group x Time interaction: F(2, 18) = 7.41, p = 0.004; β -0.386 ± 0.127, p = 0.007) and clinical covariates (Group x Time interaction: F(2, 20) = 7.03, p = 0.005; β -0.480 ± 0.144, p = 0.003). These differences were not detectable at 3 months (β -0.147 ± SE 0.120, p=0.235).

CONCLUSIONS: There was a change in stress-related gene expression among AYAs randomized to a psychosocial intervention. The stress-inflammation axis may be a targetable pathway in the AYA HCT population.},
}

@article {pmid39303986,
year = {2024},
author = {Wickline, MM and Carpenter, PA and Harris, JR and Iribarren, SJ and Reding, KW and Pike, KC and Lee, SJ and Lee, CJ and Oshima, MU and Vo, PT and Berry, DL},
title = {Associations between demographic factors, clinical variables, social determinants of health, vaccine hesitancy, vaccine behavior, and revaccination status: A survey of adult HCT survivors in the United States.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.09.012},
pmid = {39303986},
issn = {2666-6367},
abstract = {BACKGROUND: Comprehensive survivorship care after hematopoietic cell transplantation (HCT) includes revaccination to restore immunity to vaccine-preventable diseases (VPDs). There is complexity to revaccination in this setting, and revaccination rates are sub-optimal. HCT survivors are at high-risk for morbidity and mortality from infections including VPDs, underscoring the importance of interventions to improve revaccination rates among survivors. Determining associations between survivor characteristics and revaccination uptake may guide interventions.

OBJECTIVES: The overall study objective was to advance our understanding of factors influencing revaccination uptake among adult HCT survivors living in the U.S. The specific study aims were to: 1) determine the prevalence of adult survivors who are completely, partially, or not revaccinated at 2-8 years after HCT and 2) examine associations between demographic variables, social determinants of health, clinical variables, past vaccination behaviors, vaccine hesitancy (Vaccination Confidence Scale), and revaccination status in adult HCT survivors.

STUDY DESIGN: This study employed a one-time cross-sectional revaccination survey of adults who were surviving 2-8 years after HCT and living in the U.S. The survey was sent to eligible survivors in the Fred Hutchinson Cancer Center Long-term Follow-up research cohort. The point prevalence of revaccination outcomes was determined from all the respondents (n=338), differences in intent to revaccinate for people not yet fully revaccinated were explored using Fisher's exact test (n=126), and associations were examined between revaccination outcomes and predictors using multivariable logistic regression (n=292).

RESULTS: Survey response rate was 30%. Among respondents, 62% were completely revaccinated, 33% were partially revaccinated, and 4% were not revaccinated. Most respondents (77%) who were not yet fully revaccinated planned to complete the revaccination protocol. However, fewer not-revaccinated respondents than partially revaccinated respondents planned to complete revaccination (50% vs 80%, p=0.032). Factors associated with incomplete revaccination were shorter time from HCT, inadequate immune reconstitution, and not having received all childhood vaccines as a child.

CONCLUSIONS: Our analysis has identified multiple variables associated with revaccination outcomes, indicating the potential for interventions to enhance post-HCT revaccination rates. Since many survivors cannot be revaccinated promptly due to delayed immune recovery, clinicians should iteratively re-evaluate for revaccination readiness as long as it takes to ensure eventual revaccination. Broader efforts by the healthcare community to increase childhood vaccine uptake might eventually support revaccination uptake. Future research that builds on these findings should focus on intervention testing.},
}

@article {pmid39303435,
year = {2024},
author = {Boyd, DT and Jones, KV and Quinn, CR and Hill, M and Nelson, LE and Beauchamp, G and Emel, L and Hightow-Weidman, L and Shoptaw, S and Magnus, M and Piwowar-Manning, E and Mayer, KH and Fields, SD and Wheeler, DP and Dyer, TV and Wilton, L},
title = {Ethnic identity and social support as mediators between childhood sexual abuse and depression among black men who have sex with men.},
journal = {Child abuse & neglect},
volume = {157},
number = {},
pages = {107064},
doi = {10.1016/j.chiabu.2024.107064},
pmid = {39303435},
issn = {1873-7757},
abstract = {BACKGROUND: Survivors of childhood sexual abuse (CSA) often experience long-term adverse mental health effects, a trend that has been observed in research focusing on men who have sex with men (MSM), especially Black MSM.

OBJECTIVE: The aim of this study was to investigate the direct and indirect effects of childhood sexual abuse on depression symptoms among Black MSM through early sexual debut, histories of incarceration, ethnic identity, and social support. In addition, we examine the role of social support and ethnic identity as mediators of depression symptoms.

PARTICIPANTS AND SETTING: The HPTN 073 study enrolled and followed 226 HIV-uninfected Black MSM in three US cities (Los Angeles; Washington, DC; and Chapel Hill, North Carolina) from February 2013 to September 2015. Study participants were offered once-daily oral emtricitabine/tenofovir preexposure prophylaxis combined with counseling and followed for 52 weeks.

METHODS: A path analysis was used to examine direct and indirect effects of CSA experiences on depression symptoms through incarceration, early sexual debut ethnic identity, and social support, and to see whether social support and ethnic identity mediated the relationship between incarceration and depression symptoms.

RESULTS: Our results indicate that childhood sexual abuse was direct and positively associated with early sexual debut (β = 0.21, p < .001). Both ethnic identity (β = -0.14, p < .001) and social support (β = -0.82, p < .001) were direct and negatively associated with depressive symptoms.

CONCLUSION: Our research underscores the significant impact of CSA factors on the life trajectories of some Black MSM, including experiences such as incarceration, sexual debut, and depression symptoms.},
}

@article {pmid39302970,
year = {2024},
author = {Cole, JM and Scott, CB and Johnson, MM and Golightly, PR and Carlson, J and Ming, MJ and Harpak, A and Kirkpatrick, M},
title = {The battle of the sexes in humans is highly polygenic.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {39},
pages = {e2412315121},
doi = {10.1073/pnas.2412315121},
pmid = {39302970},
issn = {1091-6490},
support = {GM116853//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; GM151108//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
mesh = {Humans ; Male ; Female ; *Multifactorial Inheritance/genetics ; *Fertility/genetics ; Selection, Genetic ; Haplotypes ; Alleles ; Sex Characteristics ; Genome-Wide Association Study ; Genome, Human ; },
abstract = {Sex-differential selection (SDS), which occurs when the fitness effects of alleles differ between males and females, can have profound impacts on the maintenance of genetic variation, disease risk, and other key aspects of natural populations. Because the sexes mix their autosomal genomes each generation, quantifying SDS is not possible using conventional population genetic approaches. Here, we introduce a method that exploits subtle sex differences in haplotype frequencies resulting from SDS acting in the current generation. Using data from 300K individuals in the UK Biobank, we estimate the strength of SDS throughout the genome. While only a handful of loci under SDS are individually significant, we uncover highly polygenic signals of genome-wide SDS for both viability and fecundity. Selection coefficients of [Formula: see text] may be typical. Despite its ubiquity, SDS may impose a mortality load of less than 1%. An interesting life-history tradeoff emerges: Alleles that increase viability more strongly in females than males tend to increase fecundity more strongly in males than in females. Finally, we find marginal evidence of SDS on fecundity acting on alleles affecting arm fat-free mass. Taken together, our findings connect the long-standing evidence of SDS acting on human phenotypes with its impact on the genome.},
}

Humans
Male
Female
*Multifactorial Inheritance/genetics
*Fertility/genetics
Selection, Genetic
Haplotypes
Alleles
Sex Characteristics
Genome-Wide Association Study
Genome, Human

@article {pmid39302924,
year = {2024},
author = {Naicker, V and Laher, F and Bekker, LG and Seaton, KE and Allen, M and De Rosa, S and Yates, NL and Mkhize, NN and Saunders, K and Heptinstall, J and Malahleha, M and Mngadi, K and Daniels, B and Innes, C and Yu, C and Modise, T and Bekker, V and Grunenberg, N and Furch, B and Miner, MD and Phogat, S and Diazgranados, CA and Gurunathan, S and Koutsoukos, M and Van Der Meeren, O and Roxby, AC and Ferrari, G and Morris, L and Montefiori, D and McElrath, MJ and Tomaras, GD and Moodie, Z},
title = {Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1-2 randomized double-blind placebo-controlled trial.},
journal = {PLOS global public health},
volume = {4},
number = {9},
pages = {e0003319},
doi = {10.1371/journal.pgph.0003319},
pmid = {39302924},
issn = {2767-3375},
abstract = {Induction of broad, durable immune responses is a challenge in HIV vaccine development. HVTN 100 Part A administered subtype C-containing ALVAC-HIV at months 0 and 1, and ALVAC-HIV with bivalent subtype C gp120/MF59 at months 3, 6 and 12. As IgG binding antibody and T-cell responses were similar or greater at month 12.5 vs. month 6.5, but waned by month 18, we investigated vaccine-elicited immune responses after a month 30 boost in this study, HVTN 100 Part B. From 13 September 2017 to 7 August 2018, a subgroup of vaccinees was randomized to receive intramuscular injections of ALVAC+gp120/MF59 (n = 32) or gp120/MF59 alone (n = 31) and a subgroup of placebo recipients was administered placebo (n = 7) at month 30. Primary outcomes were safety, IgG binding antibodies (bAbs) to vaccine-specific and V1V2 Env proteins and vaccine-specific CD4+ T cells at month 30.5. Secondary outcomes included neutralizing and antibody dependent cellular cytotoxicity functions and durability at months 30 and 36. Both vaccine groups had an acceptable safety profile. There were no statistically significant differences in the occurrence or level of IgG bAbs between the vaccine boost groups for any vaccine-specific or V1V2 antigens. IgG responses were higher to vaccine-matched gp120 than to V1V2. The booster vaccination restored the magnitude-breadth IgG bAb response to V1V2 antigens at month 30.5. However, it rapidly waned by month 36. CD4+ T-cell response rates to the 3 vaccine-matched Env antigens for the combined vaccine groups ranged from 37% at month 30, boosted to as high as 91% at month 30.5, and waned by month 36 to as low as 44%, with no significant differences between the vaccine boost groups. Because these responses waned after 6 months, additional strategies may be needed to maintain the durability of prime-boost vaccine regimens and to generate these or other immune responses that confer protection. Trial registration: South African National Clinical Trials Register (SANCTR number: DOH-27-0215-4796) and ClinicalTrials.gov (NCT02404311).},
}

@article {pmid39302431,
year = {2024},
author = {Smith, JR and Arellano, AA and Avgousti, DC},
title = {Viral imitation is the sincerest form of epigenetic flattery.},
journal = {Molecular biology of the cell},
volume = {35},
number = {10},
pages = {pe3},
doi = {10.1091/mbc.E23-04-0147},
pmid = {39302431},
issn = {1939-4586},
mesh = {*Epigenesis, Genetic ; Humans ; *SARS-CoV-2/physiology ; *Histones/metabolism ; Influenza A virus/genetics/physiology ; Chromatin/metabolism ; COVID-19/virology ; Immune Evasion ; Animals ; Host-Pathogen Interactions ; },
abstract = {Viruses use multiple strategies to successfully generate progeny and overcome host defenses. In recent years, it has become increasingly evident that epigenetic mechanisms of host gene regulation are vulnerable to viral manipulation. In the form of histone mimicry, viral invasion of host chromatin is a striking example of how viruses have evolved to invade every aspect of cellular function for viral benefit. In this perspective, we will review how three viruses-influenza A, SARS-CoV-2, and Cotesia plutellae bracovirus-use histone mimicry to promote viral success through immune evasion. These examples highlight the importance of this burgeoning field and point toward the wealth of knowledge we have yet to uncover.},
}

*Epigenesis, Genetic
Humans
*SARS-CoV-2/physiology
*Histones/metabolism
Influenza A virus/genetics/physiology
Chromatin/metabolism
COVID-19/virology
Immune Evasion
Animals
Host-Pathogen Interactions

@article {pmid39302139,
year = {2024},
author = {Zhu, K and Zhao, YQ and Zheng, Y},
title = {Designing cancer screening trials for reduction in late-stage cancer incidence.},
journal = {Biometrics},
volume = {80},
number = {3},
pages = {},
doi = {10.1093/biomtc/ujae097},
pmid = {39302139},
issn = {1541-0420},
support = {R01 CA236558/NH/NIH HHS/United States ; },
mesh = {Humans ; *Early Detection of Cancer/methods/statistics & numerical data ; Incidence ; *Neoplasms/diagnosis ; Randomized Controlled Trials as Topic ; Models, Statistical ; Research Design ; Biomarkers, Tumor/blood ; Mass Screening/methods/statistics & numerical data ; Computer Simulation ; Biometry/methods ; Sensitivity and Specificity ; },
abstract = {Before implementing a biomarker test for early cancer detection into routine clinical care, the test must demonstrate clinical utility, that is, the test results should lead to clinical actions that positively affect patient-relevant outcomes. Unlike therapeutical trials for patients diagnosed with cancer, designing a randomized controlled trial (RCT) to demonstrate the clinical utility of an early detection biomarker with mortality and related endpoints poses unique challenges. The hurdles stem from the prolonged natural progression of the disease and the lack of information regarding the time-varying screening effect on the target asymptomatic population. To facilitate the study design of screening trials, we propose using a generic multistate disease history model and derive model-based effect sizes. The model links key performance metrics of the test, such as sensitivity, to primary endpoints like the incidence of late-stage cancer. It also incorporates the practical implementation of the biomarker-testing program in real-world scenarios. Based on the chronological time scale aligned with RCT, our method allows the assessment of study powers based on key features of the new program, including the test sensitivity, the length of follow-up, and the number and frequency of repeated tests. The calculation tool from the proposed method will enable practitioners to perform realistic and quick evaluations when strategizing screening trials for specific diseases. We use numerical examples based on the National Lung Screening Trial to demonstrate the method.},
}

Humans
*Early Detection of Cancer/methods/statistics & numerical data
Incidence
*Neoplasms/diagnosis
Randomized Controlled Trials as Topic
Models, Statistical
Research Design
Biomarkers, Tumor/blood
Mass Screening/methods/statistics & numerical data
Computer Simulation
Biometry/methods
Sensitivity and Specificity

@article {pmid39301523,
year = {2022},
author = {Nelson, LE and Wilton, L and Whitfield, DL and Williams, GC and Mayer, KH and Komárek, A and Boyd, DT and Beauchamp, G and Fields, SD and Wheeler, DP and , },
title = {Client-Centered Care Coordination (C4[™]) for HIV/STI Prevention: a Theoretical, Conceptual, and Methodological Overview-HIV Prevention Trials Network (HPTN) 073.},
journal = {Sexuality research & social policy : journal of NSRC : SR & SP},
volume = {19},
number = {3},
pages = {1365-1382},
pmid = {39301523},
issn = {1868-9884},
abstract = {INTRODUCTION: There are few culturally informed, theory-driven evidence-based strategies to support PrEP use among Black MSM. This paper describes the theoretical foundation and conceptual development of C4[™] to support the prevention of HIV and other STIs.

METHODS: C4[™] integrates self-determination theory with comprehensive risk counseling and services using an integrative anti-racism lens. C4[™] was implemented in a 52-week HIV prevention demonstration project to facilitate PrEP use and adherence among Black MSM (N=225) in three US cities from 2014-2017.

RESULTS: PrEP use was 79%, with 91% of PrEP users starting within 30-days. 12-month retention in C4[™] was 92%. Care coordination encounters focused primarily on clients' needs related to PrEP adherence (43%) and sexual health (19%). Over the 12-month period, a substantial proportion of the men made progress towards their PrEP adherence goals at the 8-week (83%), 26-week (75%) and 52-week (81%) study visits.

CONCLUSIONS: C4[™] is a multi-level, multi-component intervention that dually targets individual-level motivations and capacities of Black MSM and the healthcare facility-level attitudes, behaviors and processes that characterize the climates where Black MSM receive services.

POLICY IMPLICATIONS: Public health policy efforts to scale-up PrEP may consider C4[™] as a tool to optimize the use of PrEP and PrEP program retention with Black MSM. C4[™] is also a tool for healthcare facilities to transform their models of service delivery towards improving the implementation PrEP services, including ensuring racial equity in the prevention impact of novel PrEP formulations such as long-acting injectable and potential future long-acting oral regimens.},
}

@article {pmid39282263,
year = {2024},
author = {Banjoko, AW and Ng'uni, T and Naidoo, N and Ramsuran, V and Hyrien, O and Ndhlovu, ZM},
title = {High Resolution Class I HLA -A, -B, and -C Diversity in Eastern and Southern African Populations.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39282263},
issn = {2692-8205},
abstract = {Africa remains significantly underrepresented in high-resolution Human Leukocyte Antigen (HLA) data, despite being one of the most genetically diverse regions in the world. This critical gap in genetic information poses a substantial barrier to HLA-based research on the continent. In this study, Class I HLA data from Eastern and Southern African populations were analysed to assess genetic diversity across the region. We examined allele and haplotype frequency distributions, deviations from Hardy-Weinberg Equilibrium (HWE), linkage disequilibrium (LD), and conducted neutrality tests of homozygosity across various populations. Additionally, the African HLA data were compared to those of Caucasian and African American populations using the Jaccard index and multidimensional scaling (MDS) methods. The study revealed that South African populations exhibited 50.4% more genetic diversity within the Class I HLA region compared to other African populations. Zambia showed an estimated 36.5% genetic diversity, with Kenya, Rwanda and Uganda showing 35.7%, 34.2%, and 31.1%, respectively. Furthermore, an analysis of in-country diversity among different tribes indicated an average Class I HLA diversity of 25.7% in Kenya, 17% in Rwanda, 2.8% in South Africa, 13.6% in Uganda, and 6.5% in Zambia. The study also highlighted the genetic distinctness of Caucasian and African American populations compared to African populations. Notably, the differential frequencies of disease-promoting and disease-preventing HLA alleles across these populations emphasize the urgent need to generate high-quality HLA data for all regions of Africa and its major ethnic groups. Such efforts will be crucial in enhancing healthcare outcomes across the continent.},
}

@article {pmid39281752,
year = {2024},
author = {Zanti, M and O'Mahony, DG and Parsons, MT and Dorling, L and Dennis, J and Boddicker, NJ and Chen, W and Hu, C and Naven, M and Yiangou, K and Ahearn, TU and Ambrosone, CB and Andrulis, IL and Antoniou, AC and Auer, PL and Baynes, C and Bodelon, C and Bogdanova, NV and Bojesen, SE and Bolla, MK and Brantley, KD and Camp, NJ and Campbell, A and Castelao, JE and Cessna, MH and Chang-Claude, J and Chen, F and Chenevix-Trench, G and , and Conroy, DM and Czene, K and De Nicolo, A and Domchek, SM and Dörk, T and Dunning, AM and Eliassen, AH and Evans, DG and Fasching, PA and Figueroa, JD and Flyger, H and Gago-Dominguez, M and García-Closas, M and Glendon, G and González-Neira, A and Grassmann, F and Hadjisavvas, A and Haiman, CA and Hamann, U and Hart, SN and Hartman, MBA and Ho, WK and Hodge, JM and Hoppe, R and Howell, SJ and , and Jakubowska, A and Khusnutdinova, EK and Ko, YD and Kraft, P and Kristensen, VN and Lacey, JV and Li, J and Lim, GH and Lindström, S and Lophatananon, A and Luccarini, C and Mannermaa, A and Martinez, ME and Mavroudis, D and Milne, RL and Muir, K and Nathanson, KL and Nuñez-Torres, R and Obi, N and Olson, JE and Palmer, JR and Panayiotidis, MI and Patel, AV and Pharoah, PDP and Polley, EC and Rashid, MU and Ruddy, KJ and Saloustros, E and Sawyer, EJ and Schmidt, MK and Southey, MC and Tan, VK and Teo, SH and Teras, LR and Torres, D and Trentham-Dietz, A and Truong, T and Vachon, CM and Wang, Q and Weitzel, JN and Yadav, S and Yao, S and Zirpoli, GR and Cline, MS and Devilee, P and Tavtigian, SV and Goldgar, DE and Couch, FJ and Easton, DF and Spurdle, AB and Michailidou, K},
title = {Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39281752},
abstract = {Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS, and previous findings indicate that case-control likelihood ratios (LRs) outperform odds ratios for variant classification. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyzed germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 303,925 unaffected controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observed 11,227 BRCA1 and BRCA2 variants, with 6,921 being coding, covering 23.4% of BRCA1 and BRCA2 VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control LR evidence was highly consistent with ClinVar assertions for (likely) benign or pathogenic variants; exhibiting 99.1% sensitivity and 95.4% specificity for BRCA1 and 92.2% sensitivity and 86.6% specificity for BRCA2. This approach provides case-control evidence for 785 unclassified variants, that can serve as a valuable element for clinical classification.},
}

@article {pmid39228737,
year = {2024},
author = {Weinstock, JS and Chaudhry, SA and Ioannou, M and Viskadourou, M and Reventun, P and Jakubek, YA and Liggett, LA and Laurie, C and Broome, JG and Khan, A and Taylor, KD and Guo, X and Peyser, PA and Boerwinkle, E and Chami, N and Kenny, EE and Loos, RJ and Psaty, BM and Russell, TP and Brody, JA and Yun, JH and Cho, MH and Vasan, RS and Kardia, SL and Smith, JA and Raffield, LM and Bidulescu, A and O'Brien, E and de Andrade, M and Rotter, JI and Rich, SS and Tracy, RP and Chen, YI and Gu, CC and Hsiung, CA and Kooperberg, C and Haring, B and Nassir, R and Mathias, R and Reiner, A and Sankaran, V and Lowenstein, CJ and Blackwell, TW and Abecasis, GR and Smith, AV and Kang, HM and Natarajan, P and Jaiswal, S and Bick, A and Post, WS and Scheet, P and Auer, P and Karantanos, T and Battle, A and Arvanitis, M},
title = {The Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39228737},
abstract = {Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we used 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. We quantified CH by estimating the total mutation burden. Because estimating somatic mutation burden without a paired-tissue sample is challenging, we developed a novel statistical method, the Genomic and Epigenomic informed Mutation (GEM) rate, that uses external genomic and epigenomic data sources to distinguish artifactual signals from true somatic mutations. We performed a genome-wide association study of GEM to discover the germline determinants of CH-LPMneg. After fine-mapping and variant-to-gene analyses, we identified seven genes associated with CH-LPMneg (TCL1A, TERT, SMC4, NRIP1, PRDM16, MSRA, SCARB1), and one locus associated with a sex-associated mutation pathway (SRGAP2C). We performed a secondary analysis excluding individuals with mCAs, finding that the genetic architecture was largely unaffected by their inclusion. Functional analyses of SMC4 and NRIP1 implicated altered HSC self-renewal and proliferation as the primary mediator of mutation burden in blood. We then performed comprehensive multi-tissue transcriptomic analyses, finding that the expression levels of 404 genes are associated with GEM. Finally, we performed phenotypic association meta-analyses across four cohorts, finding that GEM is associated with increased white blood cell count and increased risk for incident peripheral artery disease, but is not significantly associated with incident stroke or coronary disease events. Overall, we develop GEM for quantifying mutation burden from WGS without a paired-tissue sample and use GEM to discover the genetic, genomic, and phenotypic correlates of CH-LPMneg.},
}

@article {pmid39298738,
year = {2024},
author = {Gyurkocza, B and Nath, R and Seropian, S and Choe, H and Litzow, MR and Abboud, C and Koshy, N and Stiff, P and Tomlinson, B and Abhyankar, S and Foran, J and Hari, P and Chen, G and Al-Kadhimi, Z and Kebriaei, P and Sabloff, M and Orozco, JJ and Jamieson, K and Silverman, M and Van Besien, K and Schuster, M and Law, AD and Larkin, K and Pandit-Taskar, N and Rowley, SD and Munshi, P and Cook, R and Levy, MY and Lazarus, HM and Sandmaier, BM and Pagel, JM and Reddy, V and MacDougall, J and McNamara, K and Spross, J and Haeuber, E and Vusirikala, M and Nahar, A and Desai, A and Giralt, S},
title = {Randomized Phase III SIERRA Trial of [131]I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2302018},
doi = {10.1200/JCO.23.02018},
pmid = {39298738},
issn = {1527-7755},
abstract = {PURPOSE: Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate [131]I-apamistamab with conventional care.

METHODS: SIERRA (ClinicalTrials.gov identifier: NCT02665065) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an [131]I-apamistamab-led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the [131]I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive [131]I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population.

RESULTS: The ITT population included 153 patients ([131]I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received [131]I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with [131]I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring [131]I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the [131]I-apamistamab and conventional care groups, respectively.

CONCLUSION: The [131]I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. [131]I-apamistamab was well tolerated and could address an unmet need in this population.},
}

@article {pmid39298390,
year = {2024},
author = {Kwan, ML and Pimentel, N and Izano, M and Iribarren, C and Rana, JS and Nguyen-Huynh, M and Cheng, R and Laurent, CA and Lee, VS and Roh, JM and Rillamas-Sun, E and Hershman, DL and Kushi, LH and Greenlee, H and Neugebauer, R},
title = {Adherence to cardiovascular medications and risk of cardiovascular disease in breast cancer patients: A causal inference approach in the Pathways Heart Study.},
journal = {PloS one},
volume = {19},
number = {9},
pages = {e0310531},
doi = {10.1371/journal.pone.0310531},
pmid = {39298390},
issn = {1932-6203},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/epidemiology ; *Medication Adherence/statistics & numerical data ; Middle Aged ; *Cardiovascular Diseases/drug therapy/epidemiology ; Aged ; Prospective Studies ; Cardiovascular Agents/therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Risk Factors ; Heart Failure/drug therapy/epidemiology ; },
abstract = {PURPOSE: Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005-2013.

METHODS: Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA<100% versus CAA = 100% (ref), 2) CAA<80% versus CAA≥80% (ref) and 3) CAA<80% versus 80%≤CAA<100% versus CAA = 100%.

RESULTS: Poor statin adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA<100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD.

CONCLUSIONS: Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.},
}

Humans
Female
*Breast Neoplasms/drug therapy/epidemiology
*Medication Adherence/statistics & numerical data
Middle Aged
*Cardiovascular Diseases/drug therapy/epidemiology
Aged
Prospective Studies
Cardiovascular Agents/therapeutic use
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Risk Factors
Heart Failure/drug therapy/epidemiology

@article {pmid39297068,
year = {2024},
author = {Guinigundo, A and Baek, G},
title = {Staying Abreast of New Biomarkers in Hematology/Oncology.},
journal = {Journal of the advanced practitioner in oncology},
volume = {15},
number = {3},
pages = {164-169},
pmid = {39297068},
issn = {2150-0878},
abstract = {There has been an increasing number of approvals for targeted therapies in oncology in the past decade, changing the treatment paradigm for many solid tumors and hematologic malignancies. At JADPRO Live 2023, presenters provided an in-depth review of cancer biomarkers, including testing methodology, recommended therapies, and how advanced practitioners can integrate results into clinical decision-making.},
}

@article {pmid39289368,
year = {2024},
author = {Walter, M and Haick, AK and Riley, R and Massa, PA and Strongin, DE and Klouser, LM and Loprieno, MA and Stensland, L and Santo, TK and Roychoudhury, P and Aubert, M and Taylor, MP and Jerome, KR and Verdin, E},
title = {Viral gene drive spread during herpes simplex virus 1 infection in mice.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {8161},
pmid = {39289368},
issn = {2041-1723},
support = {R21AI178255//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {Animals ; *Herpesvirus 1, Human/genetics/physiology ; Mice ; *Herpes Simplex/virology/genetics ; Humans ; Coinfection/virology ; Gene Drive Technology/methods ; Female ; Vero Cells ; Chlorocebus aethiops ; Encephalitis, Herpes Simplex/genetics/virology ; Mice, Inbred C57BL ; Recombination, Genetic/genetics ; Genes, Viral/genetics ; },
abstract = {Gene drives are genetic modifications designed to propagate efficiently through a population. Most applications rely on homologous recombination during sexual reproduction in diploid organisms such as insects, but we recently developed a gene drive in herpesviruses that relies on co-infection of cells by wild-type and engineered viruses. Here, we report on a viral gene drive against human herpes simplex virus 1 (HSV-1) and show that it propagates efficiently in cell culture and during HSV-1 infection in mice. We describe high levels of co-infection and gene drive-mediated recombination in neuronal tissues during herpes encephalitis as the infection progresses from the site of inoculation to the peripheral and central nervous systems. In addition, we show evidence that a superinfecting gene drive virus could recombine with wild-type viruses during latent infection. These findings indicate that HSV-1 achieves high rates of co-infection and recombination during viral infection, a phenomenon that is currently underappreciated. Overall, this study shows that a viral gene drive could spread in vivo during HSV-1 infection, paving the way toward therapeutic applications.},
}

Animals
*Herpesvirus 1, Human/genetics/physiology
Mice
*Herpes Simplex/virology/genetics
Humans
Coinfection/virology
Gene Drive Technology/methods
Female
Vero Cells
Chlorocebus aethiops
Encephalitis, Herpes Simplex/genetics/virology
Mice, Inbred C57BL
Recombination, Genetic/genetics
Genes, Viral/genetics

@article {pmid39257746,
year = {2024},
author = {Owens, K and Rahman, A and Bozic, I},
title = {Spatiotemporal dynamics of tumor - CAR T-cell interaction following local administration in solid cancers.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39257746},
issn = {2692-8205},
abstract = {The success of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic malignancies has generated widespread interest in translating this technology to solid cancers. However, issues like tumor infiltration, the immunosuppressive tumor microenvironment, and tumor heterogeneity limit its efficacy in the solid tumor setting. Recent experimental and clinical studies propose local administration directly into the tumor or at the tumor site to increase CAR T-cell infiltration and improve treatment outcomes. Characteristics of the types of solid tumors that may be the most receptive to this treatment approach remain unclear. In this work, we develop a spatiotemporal model for CAR T-cell treatment of solid tumors, and use numerical simulations to compare the effect of introducing CAR T cells via intratumoral injection versus intracavitary administration in diverse cancer types. We demonstrate that the model can recapitulate tumor and CAR T-cell data from imaging studies of local administration of CAR T cells in mouse models. Our results suggest that locally administered CAR T cells will be most successful against slowly proliferating, highly diffusive tumors, which have the lowest average tumor cell density. These findings affirm the clinical observation that CAR T cells will not perform equally across different types of solid tumors, and suggest that measuring tumor density may be helpful when considering the feasibility of CAR T-cell therapy and planning dosages for a particular patient. We additionally find that local delivery of CAR T cells can result in deep tumor responses, provided that the initial CAR T-cell dose does not contain a significant fraction of exhausted cells.},
}

@article {pmid39294476,
year = {2024},
author = {Luo, K and Zhang, Y and Kaplan, RC and Qi, Q},
title = {Reply to: Milk intake, lactase non-persistence and type 2 diabetes risk in Chinese adults.},
journal = {Nature metabolism},
volume = {},
number = {},
pages = {},
pmid = {39294476},
issn = {2522-5812},
support = {R01-DK119268//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01-DK126698//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 23POST1020455//American Heart Association (American Heart Association, Inc.)/ ; R01-MD011389//U.S. Department of Health & Human Services | NIH | National Institute on Minority Health and Health Disparities (NIMHD)/ ; },
}

@article {pmid39294453,
year = {2024},
author = {Duggan, C and Carosso, E and Ibarra, G and Neuhouser, ML and Thompson, B},
title = {Developing a Dietary Questionnaire for Rural Mexican Americans.},
journal = {Journal of immigrant and minority health},
volume = {},
number = {},
pages = {},
pmid = {39294453},
issn = {1557-1920},
support = {P30 CA015704-39/NH/NIH HHS/United States ; },
abstract = {Latinos form the largest ethnic population in the United States (18.5%), and the majority are Mexican Americans (61.4%). Many Mexican Americans have unique dietary behaviors, yet few food frequency questionnaires explicitly define Mexican American diets. The objective of this work was to engage with a population of rural Mexican Americans to develop a Mexican American food frequency questionnaire. Because acculturation is linked to dietary intake, we also examined acculturation by diet. We used mixed methods with three phases: (1) a qualitative phase in which a sample of rural Mexican-Americans (N = 15) identified and provided rich data about foods they ate; (2) a developmental phase in which 4 day food records were completed sequentially by two new and different samples of Mexican Americans (N = 19); and 3) a preliminary assessment phase where a new sample of Mexican Americans (N = 49) completed the final food frequency questionnaire. The final questionnaire included many traditional Mexican foods and beverages identified by study participants as part of their typical diet. Traditional Mexican foods and beverages were consumed regularly; little variation in diet was seen by level of acculturation. Respondents perceived diets containing commercial sugar-sweetened beverages as unhealthful, but not those with traditional Mexican drinks, which may represent an unappreciated source of added sugar in the diet. Future work includes studies examining dietary patterns in other urban and rural communities with traditional Mexican diets.},
}

@article {pmid39294153,
year = {2024},
author = {Wagner, C and Kistler, KE and Perchetti, GA and Baker, N and Frisbie, LA and Torres, LM and Aragona, F and Yun, C and Figgins, M and Greninger, AL and Cox, A and Oltean, HN and Roychoudhury, P and Bedford, T},
title = {Author Correction: Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {8199},
doi = {10.1038/s41467-024-52571-4},
pmid = {39294153},
issn = {2041-1723},
}

@article {pmid39293548,
year = {2024},
author = {Marsh, TL and Parikh, ND and Roberts, LR and Schwartz, ME and Nguyen, MH and Befeler, A and Page-Lester, S and Tayob, N and Srivastava, S and Rinaudo, JA and Singal, AG and Reddy, KR and Marrero, JA},
title = {A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2024.09.008},
pmid = {39293548},
issn = {1528-0012},
abstract = {BACKGROUND & AIMS: Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score [Gender, Age, AFP-L3, AFP, and Des-carboxy-prothrombin] has been shown to have excellent sensitivity and specificity for HCC in phase two studies. We performed a phase three biomarker validation study to compare GALAD with AFP in detecting HCC.

METHODS: This is a prospective study of patients with cirrhosis enrolled at seven centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per AASLD guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and DCP (des-gamma carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months prior to the clinical diagnosis. All analyses were conducted by an unblinded statistician in the EDRN data management and coordinating center.

RESULTS: A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage) with an annual incident rate of 2.4%. The AUC for AFP and GALAD within 12 months prior to HCC 0.66 and 0.78 (p<0.001), respectively. Using cutoff for GALAD of -1.36, the specificity was 82% and sensitivity at 12 months prior to HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months prior to HCC diagnosis (p=0.001).

CONCLUSION: GALAD score, compared to AFP, improves the detection of HCC within 12 months prior to the actual diagnosis.},
}

@article {pmid39293545,
year = {2024},
author = {Matsumoto, MM and Lee, CI},
title = {Realizing the potential for opportunistic early detection of abnormalities on medical imaging using artificial intelligence.},
journal = {Journal of the American College of Radiology : JACR},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacr.2024.09.003},
pmid = {39293545},
issn = {1558-349X},
}

@article {pmid39293515,
year = {2024},
author = {Rathkopf, D and Patel, MR and Choudhury, AD and Rasco, D and Lakhani, N and Hawley, JE and Srinivas, S and Aparicio, A and Narayan, V and Runcie, KD and Emamekhoo, H and Reichert, ZR and Nguyen, MH and Wells, AL and Kandimalla, R and Liu, C and Suryawanshi, S and Han, J and Wu, J and Arora, VK and Pourdehnad, M and Armstrong, AJ},
title = {Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2024.09.005},
pmid = {39293515},
issn = {1569-8041},
abstract = {BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase 1 multicenter study of BMS-986365 in patients with progressive mCRPC.

PATIENTS AND METHODS: Patients who progressed on androgen deprivation therapy, ≥ 1 ARPI, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (Part A) and expansion (Part B) of BMS-986365 up to 900 mg twice daily (BID). Primary objectives were safety, tolerability, and to define maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Key secondary endpoints included decline in prostate-specific antigen ≥50% (PSA50) and radiographic progression-free survival (rPFS).

RESULTS: Parts A and B enrolled 27 and 68 patients, respectively. In Part B, the median number of prior therapies was 4 (range 2-11). The most common treatment-related adverse events (TRAEs) were asymptomatic prolonged corrected QT interval (47%) and bradycardia (34%). Part A MTD was not reached and RP2D selection is ongoing. Across Part B three highest doses (400-900 mg BID, n = 60), PSA50 was 32% (n = 19), including 50% (n = 10/20) at 900 mg; median rPFS (95% CI) was 6.3 months (5.3-12.6), including 8.3 months (3.8-16.6) at 900 mg; and rPFS was longer in patients without versus with prior chemotherapy: 16.5 months (5.5-not evaluable) versus 5.5 months (2.7-8.3), respectively. Efficacy was observed in patients with AR ligand binding domain (LBD) WT or with AR LBD mutations.

CONCLUSIONS: BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with potentially higher benefit in chemotherapy-naïve patients. These data show BMS-986365's potential to overcome resistance to current ARPIs, regardless of AR LBD mutation status.},
}

@article {pmid39292927,
year = {2024},
author = {Wolff, D and Cutler, C and Lee, SJ and Pusic, I and Bittencourt, H and White, J and Hamadani, M and Arai, S and Salhotra, A and Perez-Simon, JA and Alousi, A and Choe, H and Kwon, M and Bermúdez, A and Kim, I and Socié, G and Chhabra, S and Radojcic, V and O'Toole, T and Tian, C and Ordentlich, P and DeFilipp, Z and Kitko, CL and , },
title = {Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease.},
journal = {The New England journal of medicine},
volume = {391},
number = {11},
pages = {1002-1014},
doi = {10.1056/NEJMoa2401537},
pmid = {39292927},
issn = {1533-4406},
mesh = {Humans ; *Graft vs Host Disease ; Female ; Male ; Middle Aged ; Adult ; Chronic Disease ; *Recurrence ; Aged ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects/administration & dosage ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors ; Young Adult ; Dose-Response Relationship, Drug ; Adolescent ; Bronchiolitis Obliterans Syndrome ; },
abstract = {BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-dependent monocytes and macrophages are key mediators of chronic graft-versus-host disease (GVHD), a major long-term complication of allogeneic hematopoietic stem-cell transplantation. The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD.

METHODS: In this phase 2, multinational, pivotal, randomized study, we evaluated axatilimab at three different doses in patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg per kilogram of body weight every 2 weeks (0.3-mg dose group), at a dose of 1 mg per kilogram every 2 weeks (1-mg dose group), or at a dose of 3 mg per kilogram every 4 weeks (3-mg dose group). The primary end point was overall response (complete or partial response) in the first six cycles; the key secondary end point was a patient-reported decrease in chronic GVHD symptom burden, as assessed by a reduction of more than 5 points on the modified Lee Symptom Scale (range, 0 to 100, with higher scores indicating worse symptoms). The primary end point would be met if the lower bound of the 95% confidence interval exceeded 30%.

RESULTS: A total of 241 patients were enrolled (80 patients in the 0.3-mg dose group, 81 in the 1-mg dose group, and 80 in the 3-mg dose group). The primary end point was met in all the groups; an overall response was observed in 74% (95% confidence interval [CI], 63 to 83) of the patients in the 0.3-mg dose group, 67% (95% CI, 55 to 77) of the patients in the 1-mg dose group, and 50% (95% CI, 39 to 61) of the patients in the 3-mg dose group. A reduction of more than 5 points on the modified Lee Symptom Scale was reported in 60%, 69%, and 41% of the patients in the three dose groups, respectively. The most common adverse events were dose-dependent transient laboratory abnormalities related to CSF1R blockade. Adverse events leading to discontinuation of axatilimab occurred in 6% of the patients in the 0.3-mg dose group, 22% in the 1-mg dose group, and 18% in the 3-mg dose group.

CONCLUSIONS: Targeting CSF1R-dependent monocytes and macrophages with axatilimab resulted in a high incidence of response among patients with recurrent or refractory chronic GVHD. (Funded by Syndax Pharmaceuticals and Incyte; AGAVE-201 ClinicalTrials.gov number, NCT04710576.).},
}

Humans
*Graft vs Host Disease
Female
Male
Middle Aged
Adult
Chronic Disease
*Recurrence
Aged
*Hematopoietic Stem Cell Transplantation/adverse effects
*Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects/administration & dosage
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors
Young Adult
Dose-Response Relationship, Drug
Adolescent
Bronchiolitis Obliterans Syndrome

@article {pmid39292670,
year = {2024},
author = {Earnest, JT and Kirstein, OD and Mendoza, AC and Barrera-Fuentes, GA and Puerta-Guardo, H and Parra-Cardeña, M and Yam-Trujillo, K and Collins, MH and Pavia-Ruz, N and Ayora-Talavera, G and Gonzalez-Olvera, G and Medina-Barreiro, A and Bibiano-Marin, W and Lenhart, A and Halloran, ME and Longini, I and Dean, N and Waller, LA and Crisp, AM and Correa-Morales, F and Palacio-Vargas, J and Granja-Perez, P and Villanueva, S and Delfın-Gonzalez, H and Gomez-Dantes, H and Manrique-Saide, P and Vazquez-Prokopec, GM},
title = {The TIRS trial: Enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiologic impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico.},
journal = {PloS one},
volume = {19},
number = {9},
pages = {e0310480},
doi = {10.1371/journal.pone.0310480},
pmid = {39292670},
issn = {1932-6203},
mesh = {Humans ; Child ; *Aedes/virology ; Animals ; Mexico/epidemiology ; Adolescent ; Child, Preschool ; Female ; *Mosquito Control/methods ; Male ; *Mosquito Vectors/virology ; *Dengue/epidemiology/prevention & control/virology ; *Insecticides ; Seroepidemiologic Studies ; Zika Virus Infection/epidemiology/prevention & control ; Zika Virus/immunology/isolation & purification ; Chikungunya Fever/epidemiology/prevention & control ; Dengue Virus/immunology/isolation & purification ; Chikungunya virus/immunology ; },
abstract = {Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks.},
}

Humans
Child
*Aedes/virology
Animals
Mexico/epidemiology
Adolescent
Child, Preschool
Female
*Mosquito Control/methods
Male
*Mosquito Vectors/virology
*Dengue/epidemiology/prevention & control/virology
*Insecticides
Seroepidemiologic Studies
Zika Virus Infection/epidemiology/prevention & control
Zika Virus/immunology/isolation & purification
Chikungunya Fever/epidemiology/prevention & control
Dengue Virus/immunology/isolation & purification
Chikungunya virus/immunology

@article {pmid39291745,
year = {2024},
author = {Nagana Gowda, GA and Pascua, V and Hill, L and Djukovic, D and Wang, D and Raftery, D},
title = {Discovery of Hypoxanthine and Inosine as Robust Biomarkers for Predicting the Preanalytical Quality of Human Plasma and Serum for Metabolomics.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.4c03719},
pmid = {39291745},
issn = {1520-6882},
abstract = {In cold human blood, the anomalous dynamics of adenosine triphosphate (ATP) result in the progressive accumulation of adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, and hypoxanthine. While the ATP, ADP, AMP, and IMP are confined to red blood cells (RBCs), inosine and hypoxanthine are excreted into plasma/serum. The plasma/serum levels of inosine and hypoxanthine depend on the temperature of blood and the plasma/serum contact time with the RBCs, and hence they represent robust biomarkers for evaluating the preanalytical quality of plasma/serum. These biomarkers are highly specific since they are generally absent or at very low levels in fresh plasma/serum and are highly sensitive since they are derived from ATP, one of the most abundant metabolites in blood. Further, whether blood was kept at room temperature or on ice could be predicted based on inosine levels. An analysis of >2000 plasma/serum samples processed for metabolomics-centric analyses showed alarmingly high levels of inosine and hypoxanthine. The results highlight the gravity of sample quality challenges with high risk of grossly inaccurate measurements and incorrect study outcomes. The discovery of these robust biomarkers provides new ways to address the longstanding and underappreciated preanalytical sample quality challenges in the blood metabolomics field.},
}

@article {pmid39290875,
year = {2024},
author = {Crotty, EE and Paulson, VA and Ronsley, R and Vitanza, NA and Lee, A and Hauptman, J and Goldstein, HE and Lockwood, CM and Leary, SES and Cole, BL},
title = {Cerebrospinal fluid liquid biopsy by low-pass whole genome sequencing for clinical disease monitoring in pediatric embryonal tumors.},
journal = {Neuro-oncology advances},
volume = {6},
number = {1},
pages = {vdae126},
pmid = {39290875},
issn = {2632-2498},
abstract = {BACKGROUND: Liquid biopsy assays that detect cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) are a promising tool for disease monitoring in pediatric patients with primary central nervous system (CNS) tumors. As a compliment to tissue-derived molecular analyses, CSF liquid biopsy has the potential to transform risk stratification, prognostication, and precision medicine approaches.

METHODS: In this pilot study, we evaluated a clinical pipeline to determine feasibility and sensitivity of low-pass whole genome sequencing (LP-WGS) of CSF-derived cfDNA from patients with CNS embryonal tumors. Thirty-two longitudinal CSF samples collected from 17 patients with molecularly characterized medulloblastoma (12), embryonal tumor with multilayered rosettes (2), CNS embryonal tumor, not elsewhere classified (NEC) (2), and atypical teratoid/rhabdoid tumor (1) were analyzed.

RESULTS: Adequate CSF-derived cfDNA for LP-WGS analysis was obtained in 94% of samples (30/32). Copy number variants compatible with neoplasia were detected in 90% (27/30) and included key alterations, such as isodicentric ch17, monosomy 6, and MYCN amplification, among others. Compared to tissue specimens, LP-WGS detected additional aberrations in CSF not previously identified in corresponding primary tumor specimens, suggesting a more comprehensive profile of tumor heterogeneity or evolution of cfDNA profiles over time. Among the 12 CSF samples obtained at initial staging, only 2 (17%) were cytologically positive, compared to 11 (92%) that were copy number positive by LP-WGS.

CONCLUSIONS: LP-WGS of CSF-derived cfDNA is feasible using a clinical platform, with greater sensitivity for tumor detection compared to conventional CSF cytologic analysis at initial staging. Large prospective studies are needed to further evaluate LP-WGS as a predictive biomarker.},
}

@article {pmid39290639,
year = {2024},
author = {Eapen, M and Antin, JH and Tolar, J and Arai, S and Horwitz, ME and Kou, J and Leifer, E and McCarty, JM and Nakamura, R and Pulsipher, MA and Rowley, SD and Horowitz, MM and Deeg, HJ},
title = {Long-term survival after unrelated donor marrow transplantation for aplastic anaemia after optimized conditioning regimen: a retrospective multicentre cohort study.},
journal = {EClinicalMedicine},
volume = {76},
number = {},
pages = {102819},
pmid = {39290639},
issn = {2589-5370},
abstract = {BACKGROUND: Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50 mg/kg (150, 100, 50, 0 mg/kg) in combination with total body irradiation (TBI) 2 Gy, anti-thymocyte globulin (ATG) and fludarabine.

METHODS: Ninety-six patients with severe aplastic anaemia aged ≤65 years with adequate organ function enrolled on a trial of human leukocyte antigen (HLA)-matched or 1 HLA-locus mismatched unrelated donor marrow transplantation conducted between 02/2006 and 12/2013 in the United States (NCT00326417). Exclusion criteria were Karnofsky performance status of less than 60, clonal cytogenetic abnormalities and inherited marrow failure syndormes. The primary outcome was day-100 engraftment (achievement of absolute neutrophil recovery to at least 0.5 × 10[9]/L without subsequent decline) and day-100 survival. The trial determined the lowest effective Cy dose as 50 mg/kg (n = 38) for day-100 engraftment and survival. Cy dose 100 mg/kg (n = 41) was also acceptable. Accrual to Cy doses 150 mg/kg (n = 15) and 0 mg/kg (n = 3) was terminated early for toxicities. The current study is an extended follow up of patients enrolled on the trial (NCT00326477) and includes 76 of 96 patients alive ≥1 year after transplantation. There were 20 deaths in the first year after transplantation (Cy 0 mg/kg [n = 2], Cy 50 mg/kg [n = 1], Cy 100 mg/kg [n = 10], Cy 150 mg/kg [n = 7]). Patients were followed prospectively from transplantation and data reported using standardized data collection forms until death, loss to follow up or last contact through November 2023. The incidence of graft failure was calculated using the cumulative incidence estimator and the probability of survival using the Kaplan-Meier estimator.

FINDINGS: The median follow up of the cohort is 8.02 (IQR) 5.16-10.12) years. With Cy 50 mg/kg, there was one graft failure and five deaths ≥1 year after transplantation. With Cy 100 mg/kg there was only one late death and no graft failure. The 8-year probabilities of survival were 85.0% (95% CI 67.3-93.5) and 75.6% (95% CI 59.4-86.1) after Cy 50 mg/kg and 100 mg/kg, respectively, P = 0.31. With Cy 0 mg/kg and 150 mg/kg, there were no graft failures or death ≥1 year after transplantation. Regardless of Cy dose 12 of 15 patients aged ≥50 years died.

INTERPRETATION: Cy 50 mg/kg or 100 mg/kg with TBI 2 Gy, ATG and fludarabine are effective conditioning regimens for unrelated donor marrow transplants for aplastic anaemia. Identification of an optimized transplantation approach for patients aged ≥50 years is needed.

FUNDING: US National Institutes of Health.},
}

@article {pmid39290356,
year = {2024},
author = {Thomson, TJ and Hu, XJ and Nosyk, B},
title = {Estimating effects of time-varying exposures on mortality risk.},
journal = {Journal of applied statistics},
volume = {51},
number = {13},
pages = {2652-2671},
pmid = {39290356},
issn = {0266-4763},
abstract = {Administrative databases have become an increasingly popular data source for population-based health research. We explore how mortality risk is associated with some health service utilization process via linked administrative data. A generalized Cox regression model is proposed using a time-dependent stratification variable to summarize lifetime service utilization. Recognizing the service utilization over time as an internal covariate in the survival analysis, conventional likelihood methods are inapplicable. We present an estimating function based procedure for estimating model parameters, and provide a testing procedure for updating the stratification levels. The proposed approach is examined both asymptotically and numerically via simulation. We motivate and illustrate the proposed approach using an on-going program pertaining to opioid agonist treatment (OAT) management for individuals identified with opioid use disorders. Our analysis of the OAT data indicates that the OAT effect on mortality risk decreases in successive OAT attempts, in which two risk classes based on an individual's treatment episode number are established: one with 1-3 OAT episodes, and the other with 4+ OAT episodes.},
}

@article {pmid39290203,
year = {2024},
author = {Raychaudhuri, S and Dong, ZM and Knowles, S and Graf, S},
title = {EBV-Positive Classic Hodgkin Lymphoma and Primary Nodal T-Cell/NK-Cell Lymphoma Arising in the Background of Follicular Lymphoma.},
journal = {Case reports in hematology},
volume = {2024},
number = {},
pages = {8810646},
pmid = {39290203},
issn = {2090-6560},
abstract = {EBV-positive primary nodal T-cell/NK cell lymphoma (TNKL) is a rare diagnosis with a poor prognosis. No relationship with follicular lymphoma (FL), classic Hodgkin lymphoma (cHL), or other non-Hodgkin lymphomas is established. We describe a case of Epstein-Barr virus (EBV)-positive cHL and EBV-positive primary nodal TNKL in the background of an antecedent FL, with all 3 subtypes identified in a single lymph node biopsy from an immunocompetent patient. Intensive frontline therapy achieved only a temporary response, with subsequent rapid progression associated with hemophagocytic lymphohistiocytosis (HLH). We discuss the relationship of the three lymphoma subtypes and the potential roles of EBV and immune dysregulation as contributing factors to this previously undescribed composite lymphoma.},
}

@article {pmid39257755,
year = {2024},
author = {Gray, CN and Ashokkumar, M and Janssens, DH and Kirchherr, J and Allard, B and Hsieh, E and Hafer, TL and Archin, NM and Browne, EP and Emerman, M},
title = {Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39257755},
issn = {2692-8205},
support = {DP1 DA051110/DA/NIDA NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R56 AI170226/AI/NIAID NIH HHS/United States ; R61 DA047023/DA/NIDA NIH HHS/United States ; R01 AI143381/AI/NIAID NIH HHS/United States ; T32 AI083203/AI/NIAID NIH HHS/United States ; },
abstract = {The latent HIV reservoir is a major barrier to HIV cure. Combining latency reversal agents (LRAs) with differing mechanisms of action such as AZD5582, a non-canonical NF-kB activator, and I-BET151, a bromodomain inhibitor is appealing towards inducing HIV-1 reactivation. However, even this LRA combination needs improvement as it is inefficient at activating proviruses in cells from people living with HIV (PLWH). We performed a CRISPR screen in conjunction with AZD5582 & I-BET151 and identified a member of the Integrator complex as a target to improve this LRA combination, specifically Integrator complex subunit 12 (INTS12). Integrator functions as a genome-wide attenuator of transcription that acts on elongation through its RNA cleavage and phosphatase modules. Knockout of INTS12 improved latency reactivation at the transcriptional level and is more specific to the HIV-1 provirus than AZD5582 & I-BET151 treatment alone. We found that INTS12 is present on chromatin at the promoter of HIV and therefore its effect on HIV may be direct. Additionally, we observed more RNAPII in the gene body of HIV only with the combination of INTS12 knockout with AZD5582 & I-BET151, indicating that INTS12 induces a transcriptional elongation block to viral reactivation. Moreover, knockout of INTS12 increased HIV-1 reactivation in CD4 T cells from virally suppressed PLWH ex vivo. We also detected viral RNA in the supernatant from CD4 T cells of all three virally suppressed PLWH tested upon INTS12 knockout suggesting that INTS12 prevents full-length HIV RNA production in primary T cells.},
}

@article {pmid39253641,
year = {2024},
author = {Brusselmans, M and Carvalho, LM and Hong, SL and Gao, J and Matsen, FA and Rambaut, A and Lemey, P and Suchard, MA and Dudas, G and Baele, G},
title = {On the importance of assessing topological convergence in Bayesian phylogenetic inference.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {39253641},
issn = {2331-8422},
support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI153044/AI/NIAID NIH HHS/United States ; R01 AI162611/AI/NIAID NIH HHS/United States ; },
abstract = {Modern phylogenetics research is often performed within a Bayesian framework, using sampling algorithms such as Markov chain Monte Carlo (MCMC) to approximate the posterior distribution. These algorithms require careful evaluation of the quality of the generated samples. Within the field of phylogenetics, one frequently adopted diagnostic approach is to evaluate the effective sample size (ESS) and to investigate trace graphs of the sampled parameters. A major limitation of these approaches is that they are developed for continuous parameters and therefore incompatible with a crucial parameter in these inferences: the tree topology. Several recent advancements have aimed at extending these diagnostics to topological space. In this reflection paper, we present two case studies - one on Ebola virus and one on HIV - illustrating how these topological diagnostics can contain information not found in standard diagnostics, and how decisions regarding which of these diagnostics to compute can impact inferences regarding MCMC convergence and mixing. Our results show the importance of running multiple replicate analyses and of carefully assessing topological convergence using the output of these replicate analyses. To this end, we illustrate different ways of assessing and visualizing the topological convergence of these replicates. Given the major importance of detecting convergence and mixing issues in Bayesian phylogenetic analyses, the lack of a unified approach to this problem warrants further action, especially now that additional tools are becoming available to researchers.},
}

@article {pmid39289635,
year = {2024},
author = {Leader, AE and Rebbeck, TR and Oh, WK and Patel, AV and Winer, EP and Bailey, LO and Gomella, LG and Lumpkins, CY and Garraway, IP and Aiello, LB and Baskin, ML and Cheng, HH and Cooney, KA and Ganzak, A and George, DJ and Halabi, S and Hathaway, F and Healy, C and Kim, JW and Leapman, MS and Loeb, S and Maxwell, KN and McNair, C and Morgan, TM and Prindeville, B and Soule, HR and Steward, WL and Suttiratana, SC and Taplin, ME and Yamoah, K and Fortune, T and Bennett, K and Blanding-Godbolt, J and Gross, L and Giri, VN},
title = {Adaptation of the socioecological model to address disparities in engagement of Black men in prostate cancer genetic testing.},
journal = {BMC public health},
volume = {24},
number = {1},
pages = {2533},
pmid = {39289635},
issn = {1471-2458},
abstract = {BACKGROUND: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT.

METHODS: Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement.

RESULTS: All societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65-4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00).

CONCLUSION: The SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families.},
}

@article {pmid39288406,
year = {2024},
author = {Chen, X and Soma, L and Murphy, C and Tretiakova, M and Naresh, KN and Fromm, JR},
title = {Utility of CCR7 to differentiate classic Hodgkin lymphoma and other B-cell lymphomas by flow cytometry and immunohistochemistry.},
journal = {American journal of clinical pathology},
volume = {},
number = {},
pages = {},
doi = {10.1093/ajcp/aqae119},
pmid = {39288406},
issn = {1943-7722},
abstract = {OBJECTIVES: Classic Hodgkin lymphoma (CHL) is characterized by infrequent neoplastic Hodgkin and Reed-Sternberg (HRS) cells in an inflammatory background. The diagnostic utility of CC-chemokine receptor 7 (CCR7) in CHL was explored using flow cytometry and immunohistochemistry (IHC).

METHODS: Neoplastic specimens and non-neoplastic lymph nodes were immunophenotyped and CCR7 expression was measured semiquantitatively by flow cytometry (clone 3D12) and IHC (clone 150503).

RESULTS: Our results showed that CCR7 was expressed on HRS cells in the vast majority of CHL cases (45/48 by flow cytometry, 57/59 by IHC) but rarely expressed in neoplastic cells in diffuse large B-cell lymphoma, not otherwise specified (1/25 by flow cytometry, 2/40 by IHC) and nodular lymphocyte predominant Hodgkin lymphoma (0/4 by flow cytometry, 1/13 by IHC). Primary mediastinal large B-cell lymphoma (PMLBCL) revealed weak CCR7 expression by flow cytometry in most cases (8/10) but only occasionally by IHC (2/12). Both cases (2/2) of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) also showed CCR7 expression detected by flow cytometry compared with IHC (0/7). The HRS cells demonstrated a greater percentage of positive cells and greater antigen intensity than the other B-cell lymphomas by IHC. The expression identified by flow cytometry in PMLBCL and THRLBCL but not by IHC suggests that there may be differences in the detection capabilities of the 2 techniques or the 2 CCR7 clones used.

CONCLUSIONS: The expression of CCR7 in HRS cells suggests its potential utility in differentiating CHL from other B-cell lymphomas. Incorporating CCR7 into flow cytometry and IHC panels may further enhance the diagnostic sensitivity of CHL.},
}

@article {pmid39287821,
year = {2024},
author = {Morgensztern, D and Ready, N and Johnson, ML and Dowlati, A and Choudhury, N and Carbone, DP and Schaefer, E and Arnold, SM and Puri, S and Piotrowska, Z and Hegde, A and Chiang, AC and Iams, W and Tolcher, A and Nosaki, K and Kozuki, T and Li, T and Santana-Davila, R and Akamatsu, H and Murakami, H and Yokouchi, H and Wang, S and Zha, J and Li, R and Robinson, RR and Hingorani, P and Jeng, EE and Furqan, M},
title = {A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, in Patients With Small Cell Lung Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-24-1547},
pmid = {39287821},
issn = {1557-3265},
abstract = {PURPOSE: Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy.

PATIENTS AND METHODS: ABBV-011 was administered intravenously once every 3 weeks (Q3W) during dose escalation (0.3-2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by immunohistochemistry) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated.

RESULTS: As of August 2022, 99 patients received ABBV-011 monotherapy (dose escalation, n=36; Japanese dose evaluation, n=3; dose expansion, n=60 [1 mg/kg, n=40]); median age was 63 years (range, 41-79). Thirty-two percent, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. Most common treatment-emergent adverse events (TEAEs) were fatigue (50%), nausea (42%), and thrombocytopenia (41%). Most common hepatic TEAEs were increased aspartate aminotransferase (22%), increased g-glutamyltransferase (21%), and hyperbilirubinemia (17%); 2 patients experienced veno-occlusive liver disease. Objective response rate (ORR) was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n=40), ORR was 25%; median response duration was 4.2 months (95% CI, 2.6-6.7) and median progression-free survival was 3.5 months (95% CI, 1.5-4.2).

CONCLUSIONS: ABBV-011 1.0 mg/kg Q3W monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.},
}