@article {pmid39177120,
year = {2024},
author = {Higano, CS and Cheng, H},
title = {Editorial Comment.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000004212},
doi = {10.1097/JU.0000000000004212},
pmid = {39177120},
issn = {1527-3792},
}

@article {pmid39175935,
year = {2024},
author = {Wolock, CJ and Gilbert, PB and Simon, N and Carone, M},
title = {A framework for leveraging machine learning tools to estimate personalized survival curves.},
journal = {Journal of computational and graphical statistics : a joint publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America},
volume = {33},
number = {3},
pages = {1098-1108},
pmid = {39175935},
issn = {1061-8600},
support = {R01 HL137808/HL/NHLBI NIH HHS/United States ; R37 AI029168/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {The conditional survival function of a time-to-event outcome subject to censoring and truncation is a common target of estimation in survival analysis. This parameter may be of scientific interest and also often appears as a nuisance in nonparametric and semiparametric problems. In addition to classical parametric and semiparametric methods (e.g., based on the Cox proportional hazards model), flexible machine learning approaches have been developed to estimate the conditional survival function. However, many of these methods are either implicitly or explicitly targeted toward risk stratification rather than overall survival function estimation. Others apply only to discrete-time settings or require inverse probability of censoring weights, which can be as difficult to estimate as the outcome survival function itself. Here, we employ a decomposition of the conditional survival function in terms of observable regression models in which censoring and truncation play no role. This allows application of an array of flexible regression and classification methods rather than only approaches that explicitly handle the complexities inherent to survival data. We outline estimation procedures based on this decomposition, empirically assess their performance, and demonstrate their use on data from an HIV vaccine trial. Supplementary materials for this article are available online.},
}

@article {pmid39173097,
year = {2024},
author = {Varco-Merth, B and Chaunzwa, M and Duell, DM and Marenco, A and Goodwin, W and Dannay, R and Nekorchuk, M and Shao, D and Busman-Sahay, K and Fennessey, CM and Silipino, L and Hull, M and Bosche, WJ and Fast, R and Oswald, K and Shoemaker, R and Bochart, R and MacAllister, R and Labriola, CS and Smedley, JV and Axthelm, MK and Davenport, MP and Edlefsen, PT and Estes, JD and Keele, BF and Lifson, JD and Lewin, SR and Picker, LJ and Okoye, AA},
title = {Impact of alemtuzumab-mediated lymphocyte depletion on SIV reservoir establishment and persistence.},
journal = {PLoS pathogens},
volume = {20},
number = {8},
pages = {e1012496},
doi = {10.1371/journal.ppat.1012496},
pmid = {39173097},
issn = {1553-7374},
abstract = {Persistence of the rebound-competent viral reservoir (RCVR) within the CD4+ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected rhesus macaques (RM) receiving antiretroviral therapy (ART). Alemtuzumab administered during chronic ART or at the time of ART initiation induced >95% depletion of circulating CD4+ T cells in peripheral blood and substantial CD4+ T cell depletion in lymph nodes. However, treatment was followed by proliferation and reconstitution of CD4+ T cells in blood, and despite ongoing ART, levels of cell-associated SIV DNA in blood and lymphoid tissues were not substantially different between alemtuzumab-treated and control RM after immune cell reconstitution, irrespective of the time of alemtuzumab treatment. Upon ART cessation, 19 of 22 alemtuzumab-treated RM and 13 of 13 controls rebounded in <28 days with no difference in the time to rebound between treatment groups. Time to rebound and reactivation rate was associated with plasma viral loads (pVLs) at time of ART initiation, suggesting lymphocyte depletion had no durable impact on the RCVR. However, 3 alemtuzumab-treated RM that had lowest levels of pre-ART viremia, failed to rebound after ART withdrawal, in contrast to controls with similar levels of SIV replication. These observations suggest that alemtuzumab therapy has little to no ability to reduce well-established RCVRs but may facilitate RCVR destabilization when pre-ART virus levels are particularly low.},
}

@article {pmid39173088,
year = {2024},
author = {Chlebowski, RT and Aragaki, AK and Pan, K and Haque, R and Rohan, TE and Song, M and Wactawski-Wende, J and Lane, DS and Harris, HR and Strickler, H and Kauntiz, AM and Runowicz, CD},
title = {Menopausal Hormone Therapy and Ovarian and Endometrial Cancers: Long-Term Follow-Up of the Women's Health Initiative Randomized Trials.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2301918},
doi = {10.1200/JCO.23.01918},
pmid = {39173088},
issn = {1527-7755},
abstract = {PURPOSE: Menopausal hormone therapy's influence on ovarian and endometrial cancers remains unsettled. Therefore, we assessed the long-term influence of conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) and CEE-alone on ovarian and endometrial cancer incidence and mortality in the Women's Health Initiative randomized, placebo-controlled clinical trials.

MATERIALS AND METHODS: Postmenopausal women, age 50-79 years, were entered on two randomized clinical trials evaluating different menopausal hormone therapy regimens. In 16,608 women with a uterus, 8,506 were randomly assigned to once daily 0.625 mg of CEE plus 2.5 mg once daily of MPA and 8,102 placebo. In 10,739 women with previous hysterectomy, 5,310 were randomly assigned to once daily 0.625 mg of CEE-alone and 5,429 placebo. Intervention was stopped for cause before planned 8.5-year intervention after 5.6 years (CEE plus MPA) and after 7.2 years (CEE-alone). Outcomes include incidence and mortality from ovarian and endometrial cancers and deaths after these cancers.

RESULTS: After 20-year follow-up, CEE-alone, versus placebo, significantly increased ovarian cancer incidence (35 cases [0.041%] v 17 [0.020%]; hazard ratio [HR], 2.04 [95% CI, 1.14 to 3.65]; P = .014) and ovarian cancer mortality (P = .006). By contrast, CEE plus MPA, versus placebo, did not increase ovarian cancer incidence (75 cases [0.051%] v 63 [0.045%]; HR, 1.14 [95% CI, 0.82 to 1.59]; P = .44) or ovarian cancer mortality but did significantly lower endometrial cancer incidence (106 cases [0.073%] v 140 [0.10%]; HR, 0.72 [95% CI, 0.56 to 0.92]; P = .01).

CONCLUSION: In randomized clinical trials, CEE-alone increased ovarian cancer incidence and ovarian cancer mortality, while CEE plus MPA did not. By contrast, CEE plus MPA significantly reduced endometrial cancer incidence.},
}

@article {pmid39172451,
year = {2024},
author = {Onyeaka, HK and Chido-Amajuoyi, OG and Sokale, I and Ajayi, KV and Evins, AE and Amonoo, HL and Shete, S},
title = {Disparities in Exposure to Tobacco on Television or Streaming Platforms.},
journal = {JAMA network open},
volume = {7},
number = {8},
pages = {e2427781},
pmid = {39172451},
issn = {2574-3805},
mesh = {Humans ; Female ; Male ; *Television/statistics & numerical data ; Cross-Sectional Studies ; Adult ; Middle Aged ; *Advertising/statistics & numerical data ; United States/epidemiology ; Tobacco Products/statistics & numerical data ; Adolescent ; Young Adult ; Marketing ; Aged ; Tobacco Industry ; },
abstract = {IMPORTANCE: With the rise in popularity of streaming platforms concerns about exposure to tobacco advertising and promotion have emerged. While tobacco marketing and promotion through traditional television (TV) media channels has been extensively studied, less is known about exposure to tobacco through TV or streaming platforms and its associated factors.

OBJECTIVE: To examine the prevalence and factors associated with exposure to tobacco products advertised, marketed, or promoted on TV or streaming platforms among US adults.

This cross-sectional study used data from the National Cancer Institute's Health Information National Trends Survey (HINTS 6), conducted from March 7 to November 8, 2022. The nationally representative survey included noninstitutionalized civilian US adults.

MAIN OUTCOMES AND MEASURES: The primary outcome was self-reported exposure to tobacco advertisements, marketing, or promotion on TV or streaming platforms in the past 3 months. Factors associated with exposure were explored using multivariable survey logistic regression.

RESULTS: The study included 5775 participants (3415 females [weighted percentage, 50.5%], 970 Hispanic individuals [weighted percentage, 16.9%], 872 non-Hispanic Black or African American individuals [11.1%], 3144 non-White individuals [61.5%], and 632 individuals who currently smoke [12.0%]). The estimated exposure to tobacco advertisements, marketing, or promotion on television or streaming platforms was 12.4% (95% CI, 10.8%-14.2%). Multivariable logistic regression analysis revealed that exposure odds were higher among those who had a level of education of high school or less (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), individuals who currently smoke (aOR, 1.85; 95% CI, 1.06-3.25), non-Hispanic Black or African American respondents (aOR, 2.20; 95% CI, 1.40-3.45) and Hispanic respondents (aOR, 1.58; 95% CI, 1.04-2.42).

CONCLUSIONS AND RELEVANCE: In this study of the prevalence of exposure to tobacco advertisements on TV or streaming platforms among US adults, disparities in exposure by race or ethnicity, education level, and smoking status were identified. These findings underscore the need for targeted public health interventions and regulation to address these disparities and reduce the impact of tobacco advertisements on vulnerable populations.},
}

Humans
Female
Male
*Television/statistics & numerical data
Cross-Sectional Studies
Adult
Middle Aged
*Advertising/statistics & numerical data
United States/epidemiology
Tobacco Products/statistics & numerical data
Adolescent
Young Adult
Marketing
Aged
Tobacco Industry

@article {pmid39169220,
year = {2024},
author = {Wang, JZ and Patil, V and Landry, AP and Gui, C and Ajisebutu, A and Liu, J and Saarela, O and Pugh, SL and Won, M and Patel, Z and Yakubov, R and Kaloti, R and Wilson, C and Cohen-Gadol, A and Zaazoue, MA and Tabatabai, G and Tatagiba, M and Behling, F and Almiron Bonnin, DA and Holland, EC and Kruser, TJ and Barnholtz-Sloan, JS and Sloan, AE and Horbinski, C and Chotai, S and Chambless, LB and Gao, A and Rebchuk, AD and Makarenko, S and Yip, S and Sahm, F and Maas, SLN and Tsang, DS and , and Rogers, CL and Aldape, K and Nassiri, F and Zadeh, G},
title = {Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {39169220},
issn = {1546-170X},
abstract = {Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.},
}

@article {pmid39169114,
year = {2024},
author = {Rodríguez-Arbolí, E and Othus, M and Freeman, SD and Buccisano, F and Ngai, LL and Thomas, I and Palmieri, R and Cloos, J and Johnson, S and Meddi, E and Russell, NH and Venditti, A and Gradowska, P and Ossenkoppele, GJ and Löwenberg, B and Walter, RB},
title = {Optimal prognostic threshold for measurable residual disease positivity by multiparameter flow cytometry in acute myeloid leukemia (AML).},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {39169114},
issn = {1476-5551},
support = {P01-CA078902//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P01-CA018029//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30-CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
}

@article {pmid39167805,
year = {2024},
author = {Carpenter, PA and Gooley, TA and Boiko, JR and Lee, CJ and Burroughs, L and Mehta, RS and Salit, RB and Bhatt, NS and Krakow, EF and Dahlberg, A and Yeh, AC and Summers, C and Ueda Oshima, M and Petersdorf, EW and Vo, PT and Connelly-Smith, L and Lee, SJ},
title = {Decreasing Chronic Graft-Versus-Host Disease rates in all populations.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024012722},
pmid = {39167805},
issn = {2473-9537},
abstract = {Since 2005 there has been steady decline in chronic graft-versus-host disease (cGVHD) at Fred Hutchinson Cancer Center (FHCC). To better understand this phenomenon, we studied the risk of cGVHD requiring systemic immunosuppression (cGVHD-IS) as a function of hematopoietic cell transplantation (HCT)-date in 3066 survivors from 2005 through 2019. Cox regression models were fit to assess associations of HCT-date (as a continuous linear variable) with cause-specific hazards of cGVHD, using unadjusted and adjusted models. Median follow-up for study subjects was 7.0 years (range, 1.0-17.2). Two-year probabilities of cGVHD-IS declined among all survivors from 45-52% (2005-2007) to approximately 40% (2008-2012) and then further to ~26% by 2017. A decline was also observed when the analysis was restricted to 502 pediatric survivors, with cGVHD-IS probabilities being <10% since 2013. Among 305 adult and pediatric survivors who were transplanted for nonmalignant diseases, cGVHD rates showed greater fluctuation but remained <20% after 2016. Each 5-year increase in HCT-date was associated with a 27% decrease in the cause-specific hazard of cGVHD (unadjusted hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.68-0.78, p<.0001); the HR was 0.81 (95% CI 0.75-0.87, p<.0001) even after adjusting for various factors (age, donor/stem-cell source, race, sex, conditioning intensity, GVHD prophylaxis, among others) that could lead to cGVHD reduction. The decline in cGVHD was not fully explained by demographic shifts and greater use of HCT approaches generally associated with lower cGVHD rates. This observation underscores that single-cohort cGVHD-prevention studies should use contemporaneous and not historical controls for comparisons.},
}

@article {pmid39167766,
year = {2024},
author = {Hamilton, BK and Pandya, BJ and Ivanescu, C and Elsouda, D and Hamadani, M and Chen, YB and Levis, MJ and Ueda Oshima, M and Litzow, MR and Soiffer, RJ and Ustun, C and Perl, AE and Singh, AK and Geller, NL and Hasabou, N and Rosales, M and Cella, D and Corredoira, L and Pestana, C and Horowitz, MM and Logan, BR},
title = {Health-Related Quality of Life with Gilteritinib versus Placebo Post-Transplant for FLT3-ITD+ Acute Myeloid Leukemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024013746},
pmid = {39167766},
issn = {2473-9537},
abstract = {BMT CTN 1506 was a phase III randomized trial comparing gilteritinib versus placebo after allogeneic HCT for FLT3-ITD-positive AML. The primary analysis comparing relapse-free survival (RFS) was not statistically significant, however, patients with detectable FLT3-ITD MRD peri-HCT had significantly longer RFS with gilteritinib. The aim of this analysis is to describe the effect of post-HCT gilteritinib versus placebo on health-related quality of life (HRQOL). HRQOL was measured using the Functional Assessment of Cancer Therapy (FACT)-BMT, FACT-Leukemia (-Leu), and EQ-5D-5L at post-HCT randomization, day 29, month 3, 6, 12, 18, 24, and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. Between 8/2017 and 7/2020, 356 patients were randomized. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in FACT-BMT, FACT-Leu, or EQ-5D-5L scores at any time point between cohorts. There was an increase in scores over time, indicating improvement in HRQOL post-HCT. Clinically meaningful improvement and time to improvement in HRQOL was similar in both arms. Despite higher TEAEs with gilteritinib, response to the question of being "bothered by side effects of treatment" did not differ between groups. Subgroup analysis of MRD detectable and negative patients demonstrated no differences in HRQOL between arms. For FLT3-ITD+ AML patients undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. Trial Registration: NCT02997202.},
}

@article {pmid39167765,
year = {2024},
author = {Mehta, RS and Ramdial, JL and Kebriaei, P and Champlin, RE and Popat, UR and Rezvani, K and Shpall, EJ},
title = {Haploidentical versus HLA-matched sibling donor HCT with PTCy prophylaxis: HLA factors and donor age considerations.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024013853},
pmid = {39167765},
issn = {2473-9537},
abstract = {HLA-matched sibling donors (MSDs) are preferred for hematopoietic cell transplantation (HCT). However, the use of alternative donors, especially haploidentical, is increasing, as is our understanding of the impact of HLA factors such as B-leader and DRB1-matching on its outcomes. Yet, data comparing these donor types, particularly considering these HLA factors, is lacking. Herein, we compared haploidentical-HCT (n=1052) to MSD-HCT (n=400), both with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis. The haploidentical group included older patients (median 49 vs. 46 years) with younger donors (39 vs. 45 years) compared to MSD recipients. Other characteristics were similar. In multivariate analysis, haploidentical group had similar overall survival (OS) [hazard ratio (HR), [95% confidence interval] 0.94, [0.78-1.14], p=.54], non-relapse mortality (HR 0.98 [0.72-1.32], p=.87) and relapse (HR 0.87, [0.70-1.08], p=.20) as the MSD group. Younger donors age was a significant predictor of improved OS. Next, we directly compared the outcomes of 'younger' haploidentical (donor age <35 years, n=347) versus an 'older' MSD (donor age >=50 years, n=143) in 'older' recipients (patient age >=50 years). Patients with 'younger' haploidentical B-leader matched donors had significantly superior OS (HR 0.65, [0.48-0.90], p=.009) compared to 'older' MSD group. Additionally, patients with 'younger' DRB1-mismatched haploidentical donors (HR 0.63 [0.46-0.87], p=.004) had significantly lower risk of relapse than 'older' MSDs. Our study suggests that haploidentical-HCT may offer comparable outcomes to MSD-PTCy HCT. Moreover, among 'older' patients, a 'younger' haploidentical B-leader matched donor might be preferable to an 'older' MSD. These findings need validation in larger datasets.},
}

@article {pmid39164488,
year = {2024},
author = {Hamazaki, N and Yang, W and Kubo, CA and Qiu, C and Martin, BK and Garge, RK and Regalado, SG and Nichols, EK and Pendyala, S and Bradley, N and Fowler, DM and Lee, C and Daza, RM and Srivatsan, S and Shendure, J},
title = {Retinoic acid induces human gastruloids with posterior embryo-like structures.},
journal = {Nature cell biology},
volume = {},
number = {},
pages = {},
pmid = {39164488},
issn = {1476-4679},
support = {UM1HG011586//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; },
abstract = {Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed of all three germ layers, human gastruloids do not morphologically resemble post-implantation human embryos. Here we show that an early pulse of retinoic acid (RA), together with later Matrigel, robustly induces human gastruloids with posterior embryo-like morphological structures, including a neural tube flanked by segmented somites and diverse cell types, including neural crest, neural progenitors, renal progenitors and myocytes. Through in silico staging based on single-cell RNA sequencing, we find that human RA-gastruloids progress further than other human or mouse embryo models, aligning to E9.5 mouse and CS11 cynomolgus monkey embryos. We leverage chemical and genetic perturbations of RA-gastruloids to confirm that WNT and BMP signalling regulate somite formation and neural tube length in the human context, while transcription factors TBX6 and PAX3 underpin presomitic mesoderm and neural crest, respectively. Looking forward, RA-gastruloids are a robust, scalable model for decoding early human embryogenesis.},
}

@article {pmid39164407,
year = {2024},
author = {Gambacorti-Passerini, C and Brümmendorf, TH and Abruzzese, E and Kelly, KR and Oehler, VG and García-Gutiérrez, V and Hjorth-Hansen, H and Ernst, T and Leip, E and Purcell, S and Luscan, G and Viqueira, A and Giles, FJ and Hochhaus, A},
title = {Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {39164407},
issn = {1476-5551},
abstract = {This final analysis from the phase 4 BYOND trial reports outcomes with bosutinib in patients with previously treated chronic myeloid leukemia (CML); 163 patients with CML resistant/intolerant to previous tyrosine kinase inhibitors received bosutinib (starting dose: 500 mg QD). At study completion (median follow-up, 47.8 months), 48.1% (n = 75/156) of patients with Philadelphia chromosome-positive chronic phase CML were still receiving treatment. Among evaluable patients, 71.8% (95% CI, 63.9-78.9) and 59.7% (95% CI, 51.4-67.7) attained or maintained major molecular response (MMR) and molecular response (MR)[4], respectively, at any time on treatment. The majority of patients achieved a deeper molecular response relative to baseline while on bosutinib. Kaplan-Meier probabilities (95% CI) of maintaining MMR and MR[4] at 36 months were 87.2% (78.0-92.7) and 80.7% (69.4-88.1), respectively. At 48 months, the Kaplan-Meier overall survival rate was 88.3% (95% CI, 81.8-92.6); there were 17 deaths, including 2 that were considered CML related. Long-term adverse events (AEs) were consistent with the known safety profile of bosutinib, and no new safety issues were identified. The management of AEs through dose reduction maintained efficacy while improving tolerability. These results support the use of bosutinib in patients with previously treated CML.ClinicalTrials.gov, NCT02228382.},
}

@article {pmid39163750,
year = {2024},
author = {Suzuki, Y and Chen, L and Matsuo, K and Ferris, JS and Elkin, EB and Melamed, A and Kong, CY and Bickell, N and Myers, ER and Havrilesky, LJ and Xu, X and Blank, SV and Hazelton, WD and Hershman, DL and Wright, JD},
title = {Weight-loss therapy in patients with obesity with endometrial intraepithelial neoplasia and uterine cancer.},
journal = {Gynecologic oncology},
volume = {190},
number = {},
pages = {78-83},
doi = {10.1016/j.ygyno.2024.08.003},
pmid = {39163750},
issn = {1095-6859},
abstract = {OBJECTIVE: Although obesity is an important risk factor for endometrial intraepithelial neoplasia (EIN) and uterine cancer, little is known about the trends in use of weight-loss therapy for patients with obesity with EIN and uterine cancer. We examined the use of weight-loss therapy among patients with obesity with EIN and uterine cancer.

METHODS: The Merative MarketScan Database was used to identify patients aged 18-70 years who were obese and diagnosed with EIN or uterine cancer. The primary treatment for EIN or uterine cancer was categorized as either primary hysterectomy or hormonal therapy. Nutrition counseling, bariatric surgeries, and weight-management medications were identified as weight-loss therapy. We analyzed trends in the use of any weight-loss therapies with Cochran-Armitage tests. A multivariable logistic regression model was developed to examine factors associated with weight-loss therapy use.

RESULTS: Overall, 15,374 patients were identified, including 5561 (36.2%) patients with EIN and obesity, and 9813 (63.8%) patients with uterine cancer and obesity. Weight-loss therapy was utilized within 1 year after diagnosis in 480 (8.6%) patients with EIN and in 802 (8.2%) patients with uterine cancer. Use of any weight-loss therapy after diagnosis of EIN increased from 4.1% in 2009 to 12.6% in 2020 (P < .001), and the use of any weight-loss therapy after diagnosis of uterine cancer increased from 4.9% in 2009 to 11.4% in 2020 (P < .001). In a multivariable regression model, younger age and patients with high comorbidity score were associated with a higher likelihood of using any weight-loss therapy.

CONCLUSIONS: Use of weight-loss therapy has increased, however there is still a significant underuse of this adjunctive therapy in patients with obesity with EIN or uterine cancer.},
}

@article {pmid39163616,
year = {2024},
author = {Sharifi, H and Bertini, CD and Alkhunaizi, M and Hernandez, MP and Musa, Z and Borges, C and Turk, I and Bashoura, L and Dickey, BF and Cheng, GS and Yanik, GA and Galban, C and Guo, HH and Godoy, M and Reinhardt, J and Hoffman, E and Castro, M and Rondon, G and Alousi, A and Champlin, RE and Shpall, EJ and Lu, Y and Peterson, SW and Datta, K and Nicolls, M and Hsu, JL and Sheshadri, A},
title = {CT strain metrics allow for earlier diagnosis of bronchiolitis obliterans syndrome after hematopoietic cell transplant.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024013748},
pmid = {39163616},
issn = {2473-9537},
abstract = {Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative CT (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using Pulmonary Function Tests (PFT) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from two large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS. Patients with transient impairment or healthy lungs were included for comparison. PFT were done at month 0, 6, and 12. Analysis was performed with association statistics, principal component analysis, conditional inference trees (CIT), and machine learning (ML) classifier models. Our cohort included 84 allogeneic HCT recipients -- 66 BOS (NIH-defined, early, or mixed) and 18 without BOS. All qCT metrics had moderate correlation with Forced Expiratory Volume in 1 second, and each qCT metric differentiated BOS from those without BOS (non-BOS) (P < 0.0001). CIT's distinguished 94% of participants with BOS versus non-BOS, 85% early BOS versus non-BOS, 92% early BOS versus NIH-BOS. ML models diagnosed BOS with area under the curve (AUC) 0.84 (95% confidence interval [CI] 0.74-0.94) and early BOS with AUC 0.84 (95% CI 0.69 - 0.97). Quantitative CT metrics can identify individuals with early BOS, paving the way for closer monitoring and earlier treatment in this vulnerable population.},
}

@article {pmid39163531,
year = {2024},
author = {Hatashima, A and Shadman, M},
title = {BTK inhibitors: moving the needle on the treatment of chronic lymphocytic leukemia.},
journal = {Expert review of hematology},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17474086.2024.2391097},
pmid = {39163531},
issn = {1747-4094},
abstract = {INTRODUCTION: Bruton's tyrosine kinaseinhibitors (BTKis) changed the trajectory of upfront and relapsed/refractory chronic lymphocytic leukemia (CLL) treatment. However, BTKis are plagued by a spectrum of toxicities. Zanubrutinib was developed to circumvent challenges with prolonged tolerability by increasing BTK selectivity and maximizing efficacy through pharmacokinetic/pharmacodynamic optimization. However, with the availability of ibrutinib, acalabrutinib, and zanubrutinib, limited data exists to guide sequencing of BTKi therapy in the relapsed/refractory setting.

AREAS COVERED: We review the first head-to-head trial (ALPINE) of zanubrutinib versus ibrutinib for the treatment of relapsed/refractory CLL and compare zanubrutinib's clinical efficacy and toxicities, including in patients with del(17p) and/or TP53 mutations to ibrutinib and acalabrutinib.

EXPERT OPINION: Zanubrutinibrepresents one of the new standards of care for relapsed/refractory CLL based on superior progression-free survival and response rates over ibrutinib. Whilezanubrutinib is associated with fewer cardiac toxicities, similar rates of neutropenia and hypertension are noted. Ongoing studies are pushing the envelope, utilizing targeted drug combinations and minimal residual disease markers as well as receptor tyrosine kinase-like orphan receptor 1 inhibitors, chimeric antigen receptor T-cells, and novel BTK degraders. However, zanubrutinibrepresents a strong contender in the arsenal of treatment options for relapsed/refractory CLL.},
}

@article {pmid39161959,
year = {2024},
author = {Riley, AK and Grant, M and Snell, A and Cromwell, E and Vichas, A and Moorthi, S and Rominger, C and Modukuri, SP and Urisman, A and Castel, P and Wan, L and Berger, AH},
title = {The deubiquitinase USP9X regulates RIT1 protein abundance and oncogenic phenotypes.},
journal = {iScience},
volume = {27},
number = {8},
pages = {110499},
pmid = {39161959},
issn = {2589-0042},
abstract = {RIT1 is a rare and understudied oncogene in lung cancer. Despite structural similarity to other RAS GTPase proteins such as KRAS, oncogenic RIT1 activity does not appear to be tightly regulated by nucleotide exchange or hydrolysis. Instead, there is a growing understanding that the protein abundance of RIT1 is important for its regulation and function. We previously identified the deubiquitinase USP9X as a RIT1 dependency in RIT1-mutant cells. Here, we demonstrate that both wild-type and mutant forms of RIT1 are substrates of USP9X. Depletion of USP9X leads to decreased RIT1 protein stability and abundance and resensitizes cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in vitro and in vivo. Our work expands upon the current understanding of RIT1 protein regulation and presents USP9X as a key regulator of RIT1-driven oncogenic phenotypes.},
}

@article {pmid39159422,
year = {2024},
author = {García-Albéniz, X and Hsu, J and Etzioni, R and Chan, JM and Shi, J and Dickerman, B and Hernán, MA},
title = {Prostate-Specific Antigen Screening and Prostate Cancer Mortality: An Emulation of Target Trials in US Medicare.},
journal = {JCO clinical cancer informatics},
volume = {8},
number = {},
pages = {e2400094},
doi = {10.1200/CCI.24.00094},
pmid = {39159422},
issn = {2473-4276},
mesh = {Humans ; Male ; Aged ; *Prostate-Specific Antigen/blood ; United States/epidemiology ; *Prostatic Neoplasms/mortality/diagnosis ; *Medicare ; Aged, 80 and over ; *Early Detection of Cancer/methods ; Mass Screening/methods ; Incidence ; },
abstract = {PURPOSE: No consensus about the effectiveness of prostate-specific antigen (PSA) screening exists among clinical guidelines, especially for the elderly. Randomized trials of PSA screening have yielded different results, partly because of variations in adherence, and it is unlikely that new trials will be conducted. Our objective was to estimate the effect of annual PSA screening on prostate cancer (PC) mortality in Medicare beneficiaries age 67-84 years.

METHODS: This is a large-scale, population-based, observational study of two screening strategies: annual PSA screening and no screening. We used data from 537,599 US Medicare (2001-2008) beneficiaries age 67-84 years who had a good life expectancy, no previous PC, and no PSA test in the 2 years before baseline. We estimated the 8-year PC mortality and incidence, treatments for PC, and treatment complications of PSA screening.

RESULTS: In men age 67-74 years, the estimated difference in 8-year risk of PC death between PSA screening and no screening was -2.3 (95% CI, -4.1 to -1.1) deaths per 1,000 men (a negative risk difference favors screening). Treatment complications were more frequent under PSA screening than under no screening. In men age 75-84 years, risk difference estimates were closer to zero.

CONCLUSION: Our estimates suggest that under conventional statistical criteria, annual PSA screening for 8 years is highly compatible with reductions of PC mortality from four to one fewer PC deaths per 1,000 screened men age 67-74 years. As with any study using real-world data, the estimates could be affected by residual confounding.},
}

Humans
Male
Aged
*Prostate-Specific Antigen/blood
United States/epidemiology
*Prostatic Neoplasms/mortality/diagnosis
*Medicare
Aged, 80 and over
*Early Detection of Cancer/methods
Mass Screening/methods
Incidence

@article {pmid39158801,
year = {2024},
author = {Husnik, MJ and Heffron, R and Hughes, JP and Richardson, B and van der Straten, A and Palanee-Phillips, T and Soto-Torres, L and Singh, D and Mirembe, BG and Livant, E and Gaffoor, Z and Mansoor, LE and Siva, SS and Dadabhai, S and Kiweewa, FM and Baeten, JM and , },
title = {Efficacy of the Dapivirine Vaginal Ring Accounting for Imperfect Adherence.},
journal = {AIDS and behavior},
volume = {},
number = {},
pages = {},
pmid = {39158801},
issn = {1573-3254},
support = {UM1AI068633//Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases/ ; UM1AI068615//Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases/ ; UM1AI106707//Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases/ ; },
abstract = {Product adherence is critical to obtaining objective estimates of efficacy of pre-exposure prophylactic interventions against HIV-1 infection. With imperfect adherence, intention-to-treat analyses assess the collective effects of complete, sub-optimal and non-adherence, providing a biased and attenuated estimate of the average causal effect of an intervention. Using data from the MTN-020/ASPIRE phase III trial evaluating HIV-1 efficacy of the dapivirine vaginal ring, we conducted per-protocol, and adherence-adjusted causal inference analyses using principal stratification and marginal structural models. We constructed two adherence cut offs of ≥ 0.9 mg (low cutoff) and > 4.0 mg (high cutoff) that represent drug released from the ring over a 28-day period. The HIV-1 efficacy estimate (95% CI) was 30.8% (3.6%, 50.3%) (P = 0.03) from the per-protocol analysis, and 53.6% (16.5%, 74.3%) (P = 0.01) among the highest predicted adherers from principal stratification analyses using the low cutoff. Marginal structural models produced efficacy estimates (95% CIs) ranging from 48.8 (21.8, 66.4) (P = 0.0019) to 56.5% (32.8%, 71.9%) (P = 0.0002). Application of adherence-adjusted causal inference methods are useful in interpreting HIV-1 efficacy in secondary analyses of PrEP clinical trials.},
}

@article {pmid39158464,
year = {2024},
author = {Mukand, NH and Chirikova, E and Lichtensztajn, D and Negoita, S and Aboushwareb, T and Bennett, J and Brooks, JD and Leppert, JT and Chung, BI and Li, C and Schwartz, SM and Gershman, ST and Insaf, T and Morawski, BM and Stroup, A and Wu, XC and Doherty, JA and Petkov, VI and Zambon, JP and Gomez, SL and Cheng, I},
title = {Assessing sociodemographic and regional disparities in Oncotype DX Genomic Prostate Score uptake.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35511},
pmid = {39158464},
issn = {1097-0142},
support = {HHSN261201800032I/CA/NCI NIH HHS/United States ; 5NU58DP006344//Centers for Disease Control and Prevention's National Program of Cancer Registries/ ; HHSN261201800015I/CA/NCI NIH HHS/United States ; HHSN261201800009I/CA/NCI NIH HHS/United States ; T32AG049663//National Institute on Aging of the National Institutes of Health/ ; T32MD015070/MD/NIMHD NIH HHS/United States ; },
abstract = {BACKGROUND: The Oncotype DX Genomic Prostate Score (ODX-GPS) is a gene expression assay that predicts disease aggressiveness. The objective of this study was to identify sociodemographic and regional factors associated with ODX-GPS uptake.

METHODS: Data from Surveillance Epidemiology and End Results registries on men with localized prostate cancer with a Gleason score of 3 + 3 or 3 + 4, PSA ≤20 ng/mL, and stage T1c to T2c disease from 2013 through 2017 were linked with ODX-GPS data. Census-tract level neighborhood socioeconomic status (nSES) quintiles were constructed using a composite socioeconomic score. Multivariable logistic regression was used to estimate the associations of ODX-GPS uptake with age at diagnosis, race and ethnicity, nSES, geographic region, insurance type, and marital status, accounting for National Comprehensive Cancer Network risk group, year of diagnosis, and clustering by census tract.

RESULTS: Among 111,434 eligible men, 5.5% had ODX-GPS test uptake. Of these, 78.3% were non-Hispanic White, 9.6% were Black, 6.7% were Hispanic, and 3.6% were Asian American. Black men had the lowest odds of ODX-GPS uptake (odds ratio, 0.70; 95% confidence interval [CI], 0.63-0.76). Those in the highest versus lowest quintile of nSES were 1.64 times more likely (95% CI, 1.38-2.94) to have ODX-GPS uptake. The odds of ODX-GPS uptake were statistically significantly higher among men residing in the Northeast, West, and Midwest compared to the South.

CONCLUSIONS: Disparities in ODX-GPS uptake by race, ethnicity, nSES, and geographical region were identified. Concerted efforts should be made to ensure that this clinical test is equitably available.},
}

@article {pmid39158404,
year = {2024},
author = {Liss, MA and Zeltser, N and Zheng, Y and Lopez, C and Liu, M and Patel, Y and Yamaguchi, TN and Eng, SE and Tian, M and Semmes, OJ and Lin, DW and Brooks, JD and Wei, JT and Klein, EA and Tewari, AK and Mosquera, JM and Khani, F and Robinson, BD and Asad, M and Troyer, DA and Kagan, J and Sanda, MG and Thompson, IM and Boutros, PC and Leach, RJ},
title = {Upgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort.},
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-24-0326},
pmid = {39158404},
issn = {1538-7755},
abstract = {BACKGROUND: Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower-grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery.

METHODS: We established a prospective, multi-institutional cohort of men with Grade Group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantify ancestry, pathogenic variants in DNA damage response genes and polygenic risk.

RESULTS: Of 285 men, 67% upgraded at surgery. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores were significantly associated with upgrading. No assessed genetic risk factor was predictive of upgrading, including polygenic risk scores for prostate cancer diagnosis.

CONCLUSIONS: In a cohort of low-grade prostate cancer patients, a majority upgraded at radical prostatectomy. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores portended the presence of higher-grade disease, while germline genetics was not informative in this setting. Patients with low-risk prostate cancer, but elevated PSA density or percent cancer in positive biopsy cores, may benefit from repeat biopsy, additional imaging or other approaches to complement active surveillance.

IMPACT: Further risk stratification of patients with low-risk prostate cancer may provide useful context for active surveillance decision-making.},
}

@article {pmid39158354,
year = {2024},
author = {Triplette, M and Giustini, N and Anderson, N and Go, T and Scout, NFN and Heffner, JL},
title = {A Multistakeholder Qualitative Study to Inform Sexual Orientation and Gender Identity Data Collection in the Cancer Care Setting.},
journal = {LGBT health},
volume = {},
number = {},
pages = {},
doi = {10.1089/lgbt.2024.0065},
pmid = {39158354},
issn = {2325-8306},
abstract = {Purpose: Sexual and gender minoritized (SGM) populations face health disparities along the cancer care continuum, although attempts to define these disparities are limited by a lack of comprehensive sexual orientation and gender identity (SOGI) data collection. The objective of this study was to interview a diverse group of stakeholders to understand attitudes, barriers, and facilitators to inform data collection approaches in a cancer care setting. Methods: This was a qualitative study conducted from March to July 2023 with paired surveys of stakeholders including patients, caregivers, providers, and cancer registry staff. Twenty participants across these categories, including half who identified as SGM, completed surveys and interviews. Qualitative data were reduced to themes with exemplar quotations using rapid qualitative analysis methods and compared to survey data. Results: Themes revealed general support for SOGI data collection as part of holistic cancer care, and all participants acknowledged that specific SOGI-related information, particularly correct pronoun usage, was essential to inform patient-centered care. Themes revealed tensions around optimal SOGI data collection methods, mixed opinions on the relevance of sexual orientation, experiences of discrimination and discomfort related to SOGI, and limited acknowledgment of population benefits of SOGI data collection. Conclusion: Themes demonstrated overall support for SOGI data collection but also revealed several barriers, such as a lack of recognition of population benefits and experiences of discrimination and discomfort, that will need to be addressed to comprehensively collect these data. Based on diverse preferences and limitations of all methods of collection, a multimodal approach may be needed to optimize completion.},
}

@article {pmid39149278,
year = {2024},
author = {Langley, CA and Dietzen, PA and Emerman, M and Tenthorey, JL and Malik, HS},
title = {Antiviral Mx proteins have an ancient origin and widespread distribution among eukaryotes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39149278},
issn = {2692-8205},
support = {T32 GM007270/GM/NIGMS NIH HHS/United States ; U54 AI170792/AI/NIAID NIH HHS/United States ; },
abstract = {First identified in mammals, Mx proteins are potent antivirals against a broad swathe of viruses. Mx proteins arose within the Dynamin superfamily of proteins (DSP), mediating critical cellular processes, such as endocytosis and mitochondrial, plastid, and peroxisomal dynamics. And yet, the evolutionary origins of Mx proteins are poorly understood. Using a series of phylogenomic analyses with stepwise increments in taxonomic coverage, we show that Mx proteins predate the interferon signaling system in vertebrates. Our analyses find an ancient monophyletic DSP lineage in eukaryotes that groups vertebrate and invertebrate Mx proteins with previously undescribed fungal MxF proteins, the relatively uncharacterized plant and algal Dynamin 4A/4C proteins, and representatives from several early-branching eukaryotic lineages. Thus, Mx-like proteins date back close to the origin of Eukarya. Our phylogenetic analyses also reveal that host-encoded and NCLDV (nucleocytoplasmic large DNA viruses)-encoded DSPs are interspersed in four distinct DSP lineages, indicating recurrent viral theft of host DSPs. Our analyses thus reveal an ancient history of viral and antiviral functions encoded by the Dynamin superfamily in eukaryotes.},
}

@article {pmid39149271,
year = {2024},
author = {Liao, H and Kottapalli, S and Huang, Y and Chaw, M and Gehring, J and Waltner, O and Phung-Rojas, M and Daza, RM and Matsen, FA and Trapnell, C and Shendure, J and Srivatsan, S},
title = {Optics-free reconstruction of 2D images via DNA barcode proximity graphs.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39149271},
issn = {2692-8205},
support = {R01 AI146028/AI/NIAID NIH HHS/United States ; R01 HG010632/HG/NHGRI NIH HHS/United States ; },
abstract = {Spatial genomic technologies include imaging- and sequencing-based methods (1-3). An emerging subcategory of sequencing-based methods relies on a surface coated with coordinate-associated DNA barcodes, which are leveraged to tag endogenous nucleic acids or cells in an overlaid tissue section (4-7). However, the physical registration of DNA barcodes to spatial coordinates is challenging, necessitating either high density printing of coordinate-specific oligonucleotides or in situ sequencing/probing of randomly deposited, oligonucleotide-bearing beads. As a consequence, the surface areas available to sequencing-based spatial genomic methods are constrained by the time, labor, cost, and instrumentation required to either print, synthesize or decode a coordinate-tagged surface. To address this challenge, we developed SCOPE (Spatial reConstruction via Oligonucleotide Proximity Encoding), an optics-free, DNA microscopy (8) inspired method. With SCOPE, the relative positions of randomly deposited beads on a 2D surface are inferred from the ex situ sequencing of chimeric molecules formed from diffusing "sender" and tethered "receiver" oligonucleotides. As a first proof-of-concept, we apply SCOPE to reconstruct an asymmetric "swoosh" shape resembling the Nike logo (16.75 × 9.25 mm). Next, we use a microarray printer to encode a "color" version of the Snellen eye chart for visual acuity (17.18 × 40.97 mm), and apply SCOPE to achieve optics-free reconstruction of individual letters. Although these are early demonstrations of the concept and much work remains to be done, we envision that the optics-free, sequencing-based quantitation of the molecular proximities of DNA barcodes will enable spatial genomics in constant experimental time, across fields of view and at resolutions that are determined by sequencing depth, bead size, and diffusion kinetics, rather than the limitations of optical instruments or microarray printers.},
}

@article {pmid39149252,
year = {2024},
author = {Sui, Z and Li, Z and Sun, W},
title = {Exploit Spatially Resolved Transcriptomic Data to Infer Cellular Features from Pathology Imaging Data.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39149252},
issn = {2692-8205},
support = {R01 GM105785/GM/NIGMS NIH HHS/United States ; },
abstract = {Digital pathology is a rapidly advancing field where deep learning methods can be employed to extract meaningful imaging features. However, the efficacy of training deep learning models is often hindered by the scarcity of annotated pathology images, particularly images with detailed annotations for small image patches or tiles. To overcome this challenge, we propose an innovative approach that leverages paired spatially resolved transcriptomic data to annotate pathology images. We demonstrate the feasibility of this approach and introduce a novel transfer-learning neural network model, STpath (Spatial Transcriptomics and pathology images), designed to predict cell type proportions or classify tumor microenvironments. Our findings reveal that the features from pre-trained deep learning models are associated with cell type identities in pathology image patches. Evaluating STpath using three distinct breast cancer datasets, we observe its promising performance despite the limited training data. STpath excels in samples with variable cell type proportions and high-resolution pathology images. As the influx of spatially resolved transcriptomic data continues, we anticipate ongoing updates to STpath, evolving it into an invaluable AI tool for assisting pathologists in various diagnostic tasks.},
}

@article {pmid39158218,
year = {2024},
author = {Garderet, L and Gras, L and Koster, L and Baaij, L and Hamad, N and Dsouza, A and Estrada-Merly, N and Hari, P and Saber, W and Cowan, AJ and Iida, M and Okamoto, S and Takamatsu, H and Mizuno, S and Kawamura, K and Kodera, Y and Ko, BS and Liam, C and Ho, KW and Goh, AS and Tan, SK and Elhaddad, AM and Bazarbachi, A and Chaudhry, QUN and Alfar, R and Bekadja, MA and Benakli, M and Ortiz, CAF and Riva, E and Galeano, S and Bass, F and Mian, HS and McCurdy, A and Wang, FR and Meng, L and Neumann, D and Koh, M and Snowden, JA and Schönland, S and McLornan, DP and Hayden, PJ and Sureda, A and Greinix, HT and Aljurf, M and Atsuta, Y and Niederwieser, D},
title = {Global characteristics and outcomes of autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma: A study of the worldwide network for blood and marrow transplantation (WBMT).},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.27451},
pmid = {39158218},
issn = {1096-8652},
abstract = {Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.},
}

@article {pmid39157608,
year = {2024},
author = {Gajzer, DC and Chen, X and Sabath, DE and Poh, C and Naresh, KN},
title = {Does a subset of mature T-cell leukemias with features akin to T-cell prolymphocytic leukemia but lacking rearrangement of the TCL1 represent peripheral T-cell lymphoma, NOS in a leukemic phase?.},
journal = {EJHaem},
volume = {5},
number = {4},
pages = {900-904},
pmid = {39157608},
issn = {2688-6146},
abstract = {In the current WHO classification, a T-cell prolymphocytic leukemia (T-PLL) diagnosis requires lymphocytosis of >5 × 109/L, evidence of monoclonality, and TCL1A or MTCP1 rearrangement. However, the 2019 consensus document suggested that in the absence of rearrangement of TCL1-family, the presence of abnormalities involving chromosome 11 (11q22.3; ATM), chromosome 8 (idic(8)(p11), t(8;8), trisomy 8q), 5, 12, 13, 22, or a complex karyotype, as well as involvement specific sites (e.g., splenomegaly, effusions) would suffice for a diagnosis of T-PLL. We present a patient diagnosed with T-PLL with MTCP1 rearrangement who was successfully treated with alemtuzumab followed by consolidative allogeneic unrelated donor stem cell transplantation. Eight years later, the patient presented with inguinal lymphadenopathy with features more akin to peripheral T-cell lymphoma, NOS (PTCL, NOS) of the GATA3 subtype, and there was no evidence of peripheral blood involvement. However, the lymphoma cells were clonally related to those at presentation. Currently, literature on T-PLL-like cases lacking the rearrangement of TCL1A is limited, and the possibility of whether a proportion of such cases could represent PTCL, NOS (with leukemic involvement) needs consideration.},
}

@article {pmid39157604,
year = {2024},
author = {Kannan, A and Zhuo, Y and Banerjee, R},
title = {Dramatically elevated plasma vascular endothelial growth factor levels from influenza A infection in polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome: A case report.},
journal = {EJHaem},
volume = {5},
number = {4},
pages = {842-844},
pmid = {39157604},
issn = {2688-6146},
abstract = {We present a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome who had a dramatic and sustained elevation in plasma vascular endothelial growth factor (VEGF) levels from 182 to 740 pg/mL while on lenalidomide-dexamethasone therapy. Given his biochemical evidence of progression, second-line daratumumab was added. In hindsight, a concurrent influenza A infection was the likely driver of his VEGF elevation rather than his underlying POEMS syndrome. Given the importance of longitudinal VEGF monitoring and the infectious risks of plasma cell therapies, our case highlights the need for caution with POEMS response assessments in the setting of a respiratory viral infection.},
}

@article {pmid39155578,
year = {2024},
author = {Boothby, A and Hegerova, L and Fletcher, SN and Shadman, M and Johnsen, JM},
title = {Successful treatment of acquired von Willebrand syndrome secondary to low-grade CLL with rituximab and venetoclax.},
journal = {Leukemia & lymphoma},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/10428194.2024.2392813},
pmid = {39155578},
issn = {1029-2403},
}

@article {pmid39154703,
year = {2024},
author = {Gu, T and Vasilatos, SN and Yin, J and Qin, Y and Zhang, L and Davidson, NE and Huang, Y},
title = {Restoration of TFPI2 by LSD1 Inhibition Suppresses Tumor Progression and Potentiates Antitumor Immunity in Breast Cancer.},
journal = {Cancer letters},
volume = {},
number = {},
pages = {217182},
doi = {10.1016/j.canlet.2024.217182},
pmid = {39154703},
issn = {1872-7980},
abstract = {Histone lysine-specific demethylase 1 (LSD1) is frequently overexpressed in triple negative breast cancer (TNBC), which is associated with worse clinical outcome in TNBC patients. However, the underlying mechanisms by which LSD1 promotes TNBC progression remain to be identified. We recently established a genetically engineered murine model by crossing mammary gland conditional LSD1 knockout mice with Brca1-deficient mice to explore the role of LSD1 in TNBC pathogenesis. Cre-mediated Brca1 loss led to higher incidence of tumor formation in mouse mammary glands, which was hindered by concurrent depletion of LSD1, indicating a critical role of LSD1 in promoting Brca1-deficient tumors. We also demonstrated that the silencing of a tumor suppressor gene, Tissue Factor Pathway Inhibitor 2 (TFPI2), is functionally associated with LSD1-mediated TNBC progression. Mouse Brca1-deficient tumors exhibited elevated LSD1 expression and decreased TFPI2 level compared to normal mammary tissues. Analysis of TCGA database revealed that TFPI2 expression is significantly lower in aggressive ER-negative or basal-like BC. Restoration of TFPI2 through LSD1 inhibition increased H3K4me2 enrichment at the TFPI2 promoter, suppressed tumor progression, and enhanced antitumor efficacy of chemotherapeutic agent. Induction of TFPI2 by LSD1 ablation downregulates activity of matrix metalloproteinases (MMPs) that in turn increases the level of cytotoxic T lymphocyte attracting chemokines in tumor environment, leading to enhanced tumor infiltration of CD8+ T cells. Moreover, induction of TFPI2 potentiates antitumor effect of LSD1 inhibitor and immune checkpoint blockade in poorly immunogenic TNBC. Together, our study identifies previously unrecognized roles of TFPI2 in LSD1-mediated TNBC progression, therapeutic response, and immunogenic effects.},
}

@article {pmid39154228,
year = {2024},
author = {Snyder, C and Smith, KC and Leisenring, WM and Stratton, KL and Boyd, CM and Choi, Y and Dean, LT and Hudson, MM and Chow, EJ and Oeffinger, KC and Park, ER and McDonald, AJ and Armstrong, GT and Nathan, PC},
title = {Continuity and coordination of care for childhood cancer survivors with multiple chronic conditions: Results from the Childhood Cancer Survivor Study.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35522},
pmid = {39154228},
issn = {1097-0142},
support = {CA21765/CA/NCI NIH HHS/United States ; P30CA006973/CA/NCI NIH HHS/United States ; P30 CA021765/CA/NCI NIH HHS/United States ; CA55727/CA/NCI NIH HHS/United States ; U24 CA055727/CA/NCI NIH HHS/United States ; K24AG056578/AG/NIA NIH HHS/United States ; },
abstract = {INTRODUCTION: Continuity and coordination-of-care for childhood cancer survivors with multiple chronic conditions are understudied but critical for appropriate follow-up care.

METHODS: From April through June 2022, 800 Childhood Cancer Survivor Study participants with two or more chronic conditions (one or more severe/life-threatening/disabling) were emailed the "Patient Perceived Continuity-of-Care from Multiple Clinicians" survey. The survey asked about survivors' main (takes care of most health care) and coordinating (ensures follow-up) provider, produced three care-coordination summary scores (main provider, across multiple providers, patient-provider partnership), and included six discontinuity indicators (e.g., having to organize own care). Discontinuity (yes/no) was defined as poor care on one or more discontinuity item. Chi-square tests assessed associations between discontinuity and sociodemographics. Modified Poisson regression models estimated prevalence ratios (PRs) for discontinuity risk associated with the specialty and number of years seeing the main and coordinating provider, and PRs associated with better scores on the three care-coordination summary measures. Inverse probability weights adjusted for survey non-participation.

RESULTS: A total of 377 (47%) survivors responded (mean age 48 years, 68% female, 89% non-Hispanic White, 78% privately insured, 74% ≥college graduate); 147/373 (39%) reported discontinuity. Younger survivors were more likely to report discontinuity (chi-square p = .02). Seeing the main provider ≤3 years was associated with more prevalent discontinuity (PR; 95%CI) (1.17; 1.02-1.34 vs ≥ 10 years). Cancer specialist main providers were associated with less prevalent discontinuity (0.81; 0.66-0.99 vs. primary care). Better scores on all three care-coordination summary measures were associated with less prevalent discontinuity: main provider (0.73; 0.64-0.83), across multiple providers (0.81; 0.78-0.83), patient-provider partnership (0.85; 0.80-0.89).

CONCLUSIONS: Care discontinuity among childhood cancer survivors is prevalent and requires intervention.},
}

@article {pmid39151729,
year = {2024},
author = {Sajulga, RW and Bolon, YT and Maiers, MJ and Petersdorf, EW},
title = {A Tool for the Assessment of HLA-DQ Heterodimer Variation in Hematopoietic Cell Transplantation: HLA-DQ Heterodimers Tool.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.08.006},
pmid = {39151729},
issn = {2666-6367},
abstract = {BACKGROUND: When optimizing transplants, clinical decision-makers consider HLA-A, -B, -C, -DRB1 (8 matched alleles out of 8), and sometimes HLA-DQB1 (10 out of 10) matching between the patient and donor. HLA-DQ is a heterodimer formed by the β chain product of HLA-DQB1 and an α chain product of HLA-DQA1. In addition to molecules defined by the parentally-inherited cis haplotypes, α-β trans-dimerization is possible between certain alleles, leading to unique molecules and a potential source of mismatched molecules. Recently, researchers uncovered that clinical outcome after HLA-DQB1-mismatched unrelated donor HCT depends on the total number of HLA-DQ molecule mismatches and the specific α-β heterodimer mismatch.

OBJECTIVE: Our objective in this study is to develop an automated tool for analyzing HLA-DQ heterodimer data and validating it through numerous datasets and analyses. By doing so, we provide an HLA-DQ heterodimer tool for DQα-DQβ trans-heterodimer evaluation, HLA-DQ imputation, and HLA-DQ-featured source selection to the transplant field.

STUDY DESIGN: In our study, we leverage 352,148 high-confidence, statistically-phased (via a modified expectation-maximization algorithm) HLA-DRB1∼DQA1∼DQB1 haplotypes, 1,052 pedigree-phased HLA-DQA1∼DQB1 haplotypes, and 13,663 historical transplants to characterize HLA-DQ heterodimers data.

RESULTS: Using our developed QLASSy (HLA-DQA1 and HLA-DQB1 Heterodimers Assessment) tool, we first assessed the data quality of HLA-DQ heterodimers in our data for trans-dimers, missing HLA-DQA1 typing, and unexpected HLA-DQA1 and HLA-DQB1 combinations. Since trans-dimers enable up to four unique HLA-DQ molecules in individuals, we provide in-silico validations for 99.7% of 275 unique trans-dimers generated by 176,074 U.S. donors with HLA-DQA1 and HLA-DQB1 data. Many individuals lack HLA-DQA1 typing, so we developed and validated high-confidence HLA-DQ annotation imputation via HLA-DRB1 with >99% correct predictions in 23,698 individuals. A select few individuals displayed unexpected HLA-DQ combinations. We revisited the typing of 61 donors with unexpected HLA-DQ combinations based on their HLA-DQA1 and HLA-DQB1 typing and corrected 22 out of 61 (36%) cases of donors through data review or retyping and used imputation to resolve unexpected combinations. After verifying the data quality of our datasets, we analyzed our datasets further: we explored the frequencies of observed HLA-DQ combinations to compare HLA-DQ across populations (for instance, we found more high-risk molecules in Asian/Pacific Islander and Black/African American populations), demonstrated the effect of HLA-DQA1 and HLA-DQB1 mismatching on HLA-DQ molecular mismatches, and highlighted where donor selections could be improved at the time of search for historical transplants with this new HLA-DQ information (where 51.9% of G2-mismatched transplants had lower-risk, G2-matched alternatives).

CONCLUSION: We encapsulated our findings into a tool that imputes missing HLA-DQA1 as needed, annotates HLA-DQ (mis)matches, and highlights other important HLA-DQ data to consider for the present and future. Altogether, these valuable datasets, analyses, and a culminating tool serve as actionable resources to enhance donor selection and improve patient outcomes.},
}

@article {pmid39149486,
year = {2024},
author = {Stanton, S and Schmitz, F and Copeland, W and DellAringa, J and Newhall, K and Disis, M},
title = {Populations of triple negative and hormone receptor positive HER2 negative breast tumors share immune gene profiles.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {39149486},
issn = {2693-5015},
support = {KL2 TR000421/TR/NCATS NIH HHS/United States ; },
abstract = {In breast cancer, triple negative (TN) breast cancer has most responses to immune checkpoint inhibitor (ICI) therapy. Lymphocyte infiltrate does not impact prognosis in Hormone receptor positive HER2 negative (HR + HER2-) breast tumors and few HR + HER2- tumors respond to ICI. We contrasted immune-associated gene expression between 119 TN and 475 HR + HER2- breast tumors from The Cancer Genome Atlas (TCGA) and confirmed our findings in 299 TN and 1369 HR + HER2- breast tumors in the METABRIC database. TN and HR+ HER2- tumors grouped into immune-high or -low tumors, both subtypes were represented in the immune-high group. The largest difference between the immune-high TN and HR + HER2- tumors was TN tumors had more abundant Th1 and Th2 CD4[+] T cells while HR + HER2- tumors had more abundant fibroblasts (log2FC > 0.3; p < 10×10[-10]). This suggests an immune-high signature is not dictated by breast cancer subtype, but fibroblast subsets associated with worse outcome were higher in the immune-high HR + HER2- tumors.},
}

@article {pmid39151455,
year = {2024},
author = {Bagatell, R and Park, JR and Acharya, S and Aldrink, J and Allison, J and Alva, E and Arndt, C and Benedetti, D and Brown, E and Cho, S and Church, A and Davidoff, A and Desai, A and DuBois, S and Fair, D and Farinhas, J and Harrison, D and Huang, F and Iskander, P and Kreissman, S and Macy, M and Na, B and Pashankar, F and Pendyala, P and Pinto, N and Polites, S and Rabah, R and Shimada, H and Slatnick, L and Sokol, E and Twist, C and Vo, K and Watt, T and Wolden, S and Zage, P and Schonfeld, R and Hang, L},
title = {Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {22},
number = {6},
pages = {413-433},
doi = {10.6004/jnccn.2024.0040},
pmid = {39151455},
issn = {1540-1413},
mesh = {Humans ; *Neuroblastoma/therapy/diagnosis/pathology ; *Medical Oncology/standards/methods ; Child ; Neoplasm Staging ; },
abstract = {Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.},
}

Humans
*Neuroblastoma/therapy/diagnosis/pathology
*Medical Oncology/standards/methods
Child
Neoplasm Staging

@article {pmid39151454,
year = {2024},
author = {Benson, AB and Venook, AP and Adam, M and Chang, G and Chen, YJ and Ciombor, KK and Cohen, SA and Cooper, HS and Deming, D and Garrido-Laguna, I and Grem, JL and Haste, P and Hecht, JR and Hoffe, S and Hunt, S and Hussan, H and Johung, KL and Joseph, N and Kirilcuk, N and Krishnamurthi, S and Malla, M and Maratt, JK and Messersmith, WA and Meyerhardt, J and Miller, ED and Mulcahy, MF and Nurkin, S and Parikh, A and Patel, H and Pedersen, K and Saltz, L and Schneider, C and Shibata, D and Shogan, B and Skibber, JM and Sofocleous, CT and Tavakkoli, A and Willett, CG and Wu, C and Jones, F and Gurski, L},
title = {NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {22},
number = {6},
pages = {366-375},
doi = {10.6004/jnccn.2024.0041},
pmid = {39151454},
issn = {1540-1413},
mesh = {Humans ; *Rectal Neoplasms/therapy/diagnosis/pathology ; Neoadjuvant Therapy/methods/standards ; Combined Modality Therapy/methods ; Neoplasm Staging ; Medical Oncology/standards/methods ; },
abstract = {The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy.},
}

Humans
*Rectal Neoplasms/therapy/diagnosis/pathology
Neoadjuvant Therapy/methods/standards
Combined Modality Therapy/methods
Neoplasm Staging
Medical Oncology/standards/methods

@article {pmid39151112,
year = {2024},
author = {Bhatt, VR and Shostrom, VK and Choe, HK and Hamilton, BK and Gundabolu, K and Maness, LJ and Kumar, V and Mahato, RI and Smith, LM and Nishihori, T and Lee, SJ},
title = {A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2400205},
doi = {10.1200/JCO.24.00205},
pmid = {39151112},
issn = {1527-7755},
abstract = {PURPOSE: Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD.

PATIENTS AND METHODS: In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria.

RESULTS: Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals.

CONCLUSION: The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.},
}

@article {pmid39151108,
year = {2024},
author = {Cigliola, A and Basnet, A and Jacob, JM and Mercinelli, C and Tateo, V and Patanè, DA and Bratslavsky, G and Cheng, L and Grivas, P and Kamat, AM and Spiess, PE and Pavlick, DC and Lin, DI and Ross, JS and Necchi, A},
title = {Urachal and Nonurachal Adenocarcinomas of the Urinary Bladder: A Comprehensive Genomic Profiling Study.},
journal = {JCO precision oncology},
volume = {8},
number = {},
pages = {e2400200},
doi = {10.1200/PO.24.00200},
pmid = {39151108},
issn = {2473-4284},
mesh = {Humans ; *Urinary Bladder Neoplasms/genetics/pathology ; *Adenocarcinoma/genetics/pathology ; Female ; Male ; Middle Aged ; Aged ; Adult ; Genomics ; Aged, 80 and over ; Gene Expression Profiling ; },
abstract = {PURPOSE: Although both urachal (U) and nonurachal (NU) bladder adenocarcinomas (adenoCas) share several histologic similarities, they differ in location and sometimes in therapeutic options. We analyzed the differences in genomic alterations (GAs) between these tumor entities, with the aim of identifying potential therapeutic targets for clinical trials.

MATERIALS AND METHODS: Overall, 133 U and 328 NU adenoCas were analyzed. Hybrid capture-based comprehensive genomic profiling (CGP) was performed to evaluate all classes of GA. Germline status of GA was predicted using a validated somatic-germline computational method. CGP was performed using the FoundationOne and FoundationOne CDx assays (Foundation Medicine, Inc).

RESULTS: The most frequent GA in both U and NU cohorts included TP53 (86.5% v 81.1%) and KRAS (34.6% v 27.7%). GAs characteristic of colorectal adenoCa, such as SMAD4 (P = .069) and GNAS (P = .071), were more common in U versus NU. Conversely, TERT (P < .01) and RB1 (P = .071) were more prevalent in NU adenoCa. Notably, both U and NU adenoCas exhibited possibly targetable GA in PIK3CA (7.5% v 7.9%) and ERBB2 (6.8% v 7.6%). Biomarkers associated with potential benefit from anti-PD-1/L1 were infrequent. Median tumor mutational burden was 2.6 and 3.5 mutations per megabase for U and NU, respectively, and PD-L1 expression >1% was rare. Genomic ancestry and genomic signature distribution were similar in both tumor types. GAs were most commonly of somatic nature. Limitations include lack of clinical data, tumor heterogeneity, and retrospective nature.

CONCLUSION: U and NU adenoCAs revealed differences in GA, with PIK3CA and ERBB2 being identified as putative therapeutic targets. Biomarkers of response to anti-PD-(L)1 were uncommon. Results highlight the potential of CGP to personalize treatment options of bladder adenoCa and inform clinical trial designs.},
}

Humans
*Urinary Bladder Neoplasms/genetics/pathology
*Adenocarcinoma/genetics/pathology
Female
Male
Middle Aged
Aged
Adult
Genomics
Aged, 80 and over
Gene Expression Profiling

@article {pmid39150991,
year = {2024},
author = {Belleville, AE and Thomas, JD and Tonnies, J and Gabel, AM and Borrero Rossi, A and Singh, P and Queitsch, C and Bradley, RK},
title = {An autoregulatory poison exon in Smndc1 is conserved across kingdoms and influences organism growth.},
journal = {PLoS genetics},
volume = {20},
number = {8},
pages = {e1011363},
doi = {10.1371/journal.pgen.1011363},
pmid = {39150991},
issn = {1553-7404},
abstract = {Many of the most highly conserved elements in the human genome are "poison exons," alternatively spliced exons that contain premature termination codons and permit post-transcriptional regulation of mRNA abundance through induction of nonsense-mediated mRNA decay (NMD). Poison exons are widely assumed to be highly conserved due to their presumed importance for organismal fitness, but this functional importance has never been tested in the context of a whole organism. Here, we report that a poison exon in Smndc1 is conserved across mammals and plants and plays a molecular autoregulatory function in both kingdoms. We generated mouse and A. thaliana models lacking this poison exon to find its loss leads to deregulation of SMNDC1 protein levels, pervasive alterations in mRNA processing, and organismal size restriction. Together, these models demonstrate the importance of poison exons for both molecular and organismal phenotypes that likely explain their extraordinary conservation.},
}

@article {pmid39150988,
year = {2024},
author = {Byrne, CM and Márquez, AC and Cai, B and Coombs, D and Gantt, S},
title = {Spatial kinetics and immune control of murine cytomegalovirus infection in the salivary glands.},
journal = {PLoS computational biology},
volume = {20},
number = {8},
pages = {e1011940},
doi = {10.1371/journal.pcbi.1011940},
pmid = {39150988},
issn = {1553-7358},
abstract = {Human cytomegalovirus (HCMV) is the most common congenital infection. Several HCMV vaccines are in development, but none have yet been approved. An understanding of the kinetics of CMV replication and transmission may inform the rational design of vaccines to prevent this infection. The salivary glands (SG) are an important site of sustained CMV replication following primary infection and during viral reactivation from latency. As such, the strength of the immune response in the SG likely influences viral dissemination within and between hosts. To study the relationship between the immune response and viral replication in the SG, and viral dissemination from the SG to other tissues, mice were infected with low doses of murine CMV (MCMV). Following intra-SG inoculation, we characterized the viral and immunological dynamics in the SG, blood, and spleen, and identified organ-specific immune correlates of protection. Using these data, we constructed compartmental mathematical models of MCMV infection. Model fitting to data and analysis indicate the importance of cellular immune responses in different organs and point to a threshold of infection within the SG necessary for the establishment and spread of infection.},
}

@article {pmid39150951,
year = {2024},
author = {Donzella, SM and Masters, M and Phipps, AI and Patel, AV and Zhong, C},
title = {Validity of self-reported sleep duration in the Cancer Prevention Study- 3.},
journal = {PloS one},
volume = {19},
number = {8},
pages = {e0307409},
pmid = {39150951},
issn = {1932-6203},
mesh = {Female ; Humans ; Male ; *Neoplasms/prevention & control ; Reproducibility of Results ; *Self Report/statistics & numerical data ; *Sleep Duration ; Time Factors ; },
abstract = {PURPOSE: We examined the one-year test re-test reliability and validity criterion of survey-assessed sleep duration collected from two separate questions.

METHODS: The Activity Validation Sub Study included 751 participants of the Cancer Prevention Study-3 study to further investigate rest/activity cycles. Sleep duration was collected using three methods: survey, Daysimeter device, and sleep diary. Survey-assessed sleep duration was collected using 2 different questions, each with different response options (categorical and continuous). Selected participants (n = 170) were asked to wear a Daysimeter device for seven consecutive days for two non-consecutive quarters. Participants were excluded from the current study due to incomplete/implausible survey or device data or reported working night shift. We calculated reliability of pre- and post-survey sleep duration for both survey question using Spearman correlation. We used the method of triads to estimate the validity coefficient (VC) between the three sleep duration measurements in the present study and the "true" latent sleep duration measure, and bootstrapping methods to calculate the 95% confidence intervals (95%CI).

RESULTS: Of 119 participants included in the study (52.10% male), test-retest correlation showed strong and moderate correlations for sleep duration collected continuously and categorically, respectively. The VC for survey-assessed continuous sleep duration was 0.82 (95%CI 0.71, 0.90) for weekday and 0.68 (95%CI 0.46, 0.83) for weekend. Performance of the VC was slightly weaker for survey-assessed categorical sleep duration (weekday VC = 0.57 95%CI 0.42, 0.71; weekend VC = 0.47 95%CI 0.29, 0.62).

CONCLUSION: The two survey-assessed sleep duration questions used in the AVSS and CPS-3 cohorts are valid approximations of sleep duration.},
}

Female
Humans
Male
*Neoplasms/prevention & control
Reproducibility of Results
*Self Report/statistics & numerical data
*Sleep Duration
Time Factors

@article {pmid39150133,
year = {2024},
author = {Corey, L},
title = {Reflections on Progress in Genital Herpes Therapy and Prevention 1997 to 2024.},
journal = {Sexually transmitted diseases},
volume = {51},
number = {9},
pages = {614-615},
doi = {10.1097/OLQ.0000000000002030},
pmid = {39150133},
issn = {1537-4521},
mesh = {Humans ; *Herpes Genitalis/drug therapy/prevention & control ; *Antiviral Agents/therapeutic use ; Female ; Male ; },
}

Humans
*Herpes Genitalis/drug therapy/prevention & control
*Antiviral Agents/therapeutic use
Female
Male

@article {pmid39149908,
year = {2024},
author = {Vermulst, M and Paskvan, SL and Chung, CS and Franke, K and Clegg, N and Minot, S and Madeoy, J and Long, AS and Gout, JF and Bielas, JH},
title = {MADDD-seq, a novel massively parallel sequencing tool for simultaneous detection of DNA damage and mutations.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae632},
pmid = {39149908},
issn = {1362-4962},
support = {R01AG054641/AG/NIA NIH HHS/United States ; R01CA204894/CA/NCI NIH HHS/United States ; R01ES026222/ES/NIEHS NIH HHS/United States ; //University of Southern California/ ; },
abstract = {Our genome is exposed to a wide variety of DNA-damaging agents. If left unrepaired, this damage can be converted into mutations that promote carcinogenesis or the development of genetically inherited diseases. As a result, researchers and clinicians require tools that can detect DNA damage and mutations with exceptional sensitivity. In this study, we describe a massively parallel sequencing tool termed Mutation And DNA Damage Detection-seq (MADDD-seq) that is capable of detecting O6-methyl guanine lesions and mutations simultaneously, with a single assay. To illustrate the dual capabilities of MADDD-seq, we treated WT and DNA repair deficient yeast cells with the DNA-damaging agent MNNG and tracked DNA lesions and mutations over a 24-h time period. This approach allowed us to identify thousands of DNA adducts and mutations in a single sequencing run and gain deep insight into the kinetics of DNA repair and mutagenesis.},
}

@article {pmid39147634,
year = {2024},
author = {Chahine, SY and Alkhatib, KY and Arakelyan, G and Buxton, C and Giannarini, G and Hamilton, RJ and Holt, SK and Bernhard, JC and Jiang, DM and Lin, D and Liu, JJ and Manley, B and Master, VA and Matveev, V and Necchi, A and Packiam, VT and Patel, SH and Peak, T and Peyton, CC and Pierorazio, PM and Prakash, G and Salari, K and Sexton, WJ and Singla, N and Spiess, PE and Psutka, SP},
title = {Testicular Germ Cell Tumors with Venous Tumor Thrombus: Prevalence, Presentation, and Management.},
journal = {European urology focus},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euf.2024.07.017},
pmid = {39147634},
issn = {2405-4569},
abstract = {BACKGROUND AND OBJECTIVE: There are limited data on the prevalence and management of testicular germ cell tumor (TGCT) cases presenting with venous tumor thrombus (VTT). Our objectives were to describe the prevalence of TGCT with VTT, to identify a multicenter retrospective cohort, and to ascertain expert opinion regarding optimal management of this entity.

METHODS: Using the IBM Marketscan database, we identified men with testicular cancer who underwent retroperitoneal lymph node dissection (RPLND) with concurrent VTT or inferior vena cava (IVC) tumor thrombectomy to estimate the prevalence of VTT in TGCT. To identify a multicenter retrospective cohort of patients, we surveyed surgeons and described the presentation, management, and outcomes for the cohort.

KEY FINDINGS AND LIMITATIONS: The prevalence of TGCT with VTT in the IBM Marketscan database was 0.3% (n = 7/2517) when using stringent criteria and 3.1% (n = 79/2517) when using broad criteria. In response to our survey, 16 surgeons from ten centers contributed data for 34 patients. Most patients (n = 29, 85%) presented with nonseminomatous germ cell tumor. Surgical management was used for 93.9% (n = 31), including postchemotherapy tumor thrombectomy with primary cavorrhaphy in 63%. The Marketscan analysis was limited to insured individuals and did not include clinicopathological details, and use of billing codes may have included patients with stromal tumors. In addition, lack of responses to the anonymous survey limited data capture, and the RedCap survey did not address symptoms specific to IVC obstruction or allow central review of the imaging leading to VTT diagnosis.

VTT among males with TGCT is rare and requires complex multidisciplinary management, including venous tumor thrombectomy at the time of postchemotherapy RPLND.

PATIENT SUMMARY: Using a medical database, we estimated that the frequency of testicular cancer cases in which the tumor extends into a blood vessel (called venous tumor thrombus, VTT) is just 0.3-3.1%. We carried out a survey of surgeons with experience of this condition. Our results indicate that although testicular cancers respond well to chemotherapy, VTT is less responsive and complex surgery is necessary for this rare condition.},
}

@article {pmid39146495,
year = {2024},
author = {Jones, SMW and Ohlsen, TJD and Karvonen, KA and Sorror, ML},
title = {Addressing Financial Hardship in Malignant Hematology and Hematopoietic Cell Transplant: A Team Approach.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024012998},
pmid = {39146495},
issn = {2473-9537},
abstract = {Financial hardship is a common experience for patients and their families after the diagnosis of a hematologic malignancy and is associated with worse outcomes. Healthcare costs, increased costs of living, income poverty, and inadequate wealth contribute to financial hardship following diagnosis and treatment of a hematologic malignancy and/or hematopoietic cell transplant. Given the multidimensional nature of financial hardship, a multidisciplinary team-based approach is needed to address this public health hazard. Hematologists and oncologists may mitigate the impact of financial hardship by matching treatment options with patient goals of care and reducing symptom burden disruptive to employment. Social workers and financial navigators can assist with screening and resource deployment. Policymakers and researchers can identify structural and policy changes to prevent financial hardship. By alleviating this major healthcare burden from patients, care teams may improve survival and quality of life for patients with hematologic malignancies.},
}

@article {pmid39146390,
year = {2024},
author = {Yuan, AE and Shou, W},
title = {A rigorous and versatile statistical test for correlations between stationary time series.},
journal = {PLoS biology},
volume = {22},
number = {8},
pages = {e3002758},
doi = {10.1371/journal.pbio.3002758},
pmid = {39146390},
issn = {1545-7885},
abstract = {In disciplines from biology to climate science, a routine task is to compute a correlation between a pair of time series and determine whether the correlation is statistically significant (i.e., unlikely under the null hypothesis that the time series are independent). This problem is challenging because time series typically exhibit autocorrelation and thus cannot be properly analyzed with the standard iid-oriented statistical tests. Although there are well-known parametric tests for time series, these are designed for linear correlation statistics and thus not suitable for the increasingly popular nonlinear correlation statistics. There are also nonparametric tests that can be used with any correlation statistic, but for these, the conditions that guarantee correct false positive rates are either restrictive or unclear. Here, we describe the truncated time-shift (TTS) test, a nonparametric procedure to test for dependence between 2 time series. We prove that this test correctly controls the false positive rate as long as one of the time series is stationary, a minimally restrictive requirement among current tests. The TTS test is versatile because it can be used with any correlation statistic. Using synthetic data, we demonstrate that this test performs correctly even while other tests suffer high false positive rates. In simulation examples, simple guidelines for parameter choices allow high statistical power to be achieved with sufficient data. We apply the test to datasets from climatology, animal behavior, and microbiome science, verifying previously discovered dependence relationships and detecting additional relationships.},
}

@article {pmid39148929,
year = {2023},
author = {Koester, ST and Li, N and Dey, N},
title = {RET is a sex-biased regulator of intestinal tumorigenesis.},
journal = {Frontiers in gastroenterology (Lausanne, Switzerland)},
volume = {2},
number = {},
pages = {},
pmid = {39148929},
issn = {2813-1169},
support = {K08 DK111941/DK/NIDDK NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; U54 CA274374/CA/NCI NIH HHS/United States ; },
abstract = {Ret is implicated in colorectal cancer (CRC) as both a proto-oncogene and a tumor suppressor. We asked whether RET signaling regulates tumorigenesis in an Apc-deficient preclinical model of CRC. We observed a sex-biased phenotype: Apc [Min/+] Ret+/- females had significantly greater tumor burden than Apc [Min/+]Ret+/- males, a phenomenon not seen in Apc [Min/+] mice, which had equal distributions by sex. Dysfunctional RET signaling was associated with gene expression changes in diverse tumor signaling pathways in tumors and normal-appearing colon. Sex-biased gene expression differences mirroring tumor phenotypes were seen in 26 genes, including the Apc tumor suppressor gene. Ret and Tlr4 expression were significantly correlated in tumor samples from female but not male Apc [Min/+] Ret+/- mice. Antibiotics resulted in reduction of tumor burden, inverting the sex-biased phenotype such that microbiota-depleted Apc [Min/+] Ret+/- males had significantly more tumors than female littermates. Reconstitution of the microbiome rescued the sex-biased phenotype. Our findings suggest that RET represents a sexually dimorphic microbiome-mediated "switch" for regulation of tumorigenesis.},
}

@article {pmid39145953,
year = {2024},
author = {O'Regan, RM and Zhang, Y and Fleming, GF and Francis, PA and Kammler, R and Viale, G and Dell'Orto, P and Lang, I and Bellet, M and Bonnefoi, HR and Tondini, C and Villa, F and Bernardo, A and Ciruelos, EM and Neven, P and Karlsson, P and Müller, B and Jochum, W and Zaman, K and Martino, S and Geyer, CE and Jerzak, KJ and Davidson, NE and Coleman, RE and Ingle, JN and van Mackelenbergh, MT and Loi, S and Colleoni, M and Schnabel, CA and Treuner, K and Regan, MM},
title = {Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {39145953},
issn = {2374-2445},
abstract = {IMPORTANCE: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.

OBJECTIVE: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.

This prospective-retrospective translational study used all available tumor tissue samples from female patients from the Suppression of Ovarian Function Trial (SOFT). These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. BCI testing was performed blinded to clinical data and outcome. The a priori hypothesis was that BCI HOXB13/IL17BR ratio (BCI[H/I])-high tumors would benefit more from OFS and high BCI portended poorer prognosis in this population. Settings spanned multiple centers internationally. Participants included premenopausal female patients with HR+ early breast cancer with specimens in the International Breast Cancer Study Group tumor repository available for RNA extraction. Data were collected from December 2003 to April 2021 and were analyzed from May 2022 to October 2022.

MAIN OUTCOMES AND MEASURES: Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses.

RESULTS: Tumor specimens were available for 1718 of the 3047 female patients in the SOFT intention-to-treat population. The 1687 patients (98.2%) who had specimens that yielded sufficient RNA for BCI testing represented the parent trial population. The median (IQR) follow-up time was 12 (10.5-13.4) years, and 512 patients (30.3%) were younger than 40 years. Tumors were BCI(H/I)-low for 972 patients (57.6%) and BCI(H/I)-high for 715 patients (42.4%). Patients with tumors classified as BCI(H/I)-low exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48 [95% CI, 0.33-0.71]) and an absolute benefit of 7.3% from tamoxifen plus OFS (HR, 0.69 [95% CI, 0.48-0.97]) relative to tamoxifen alone. In contrast, patients with BCI(H/I)-high tumors did not benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03 [95% CI, 0.70-1.53]; P for interaction = .006) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05 [95% CI, 0.72-1.54]; P for interaction = .11) compared with tamoxifen alone. BCI continuous index was significantly prognostic in the N0 subgroup for DRFI (n = 1110; P = .004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk N0 cancers, respectively.

CONCLUSIONS AND RELEVANCE: In this prospective-retrospective translational study of patients enrolled in SOFT, BCI was confirmed as prognostic in premenopausal women with HR+ breast cancer. The benefit from OFS-containing adjuvant endocrine therapy was greater for patients with BCI(H/I)-low tumors than BCI(H/I)-high tumors. BCI(H/I)-low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.},
}

@article {pmid39143224,
year = {2024},
author = {Pölönen, P and Di Giacomo, D and Seffernick, AE and Elsayed, A and Kimura, S and Benini, F and Montefiori, LE and Wood, BL and Xu, J and Chen, C and Cheng, Z and Newman, H and Myers, J and Iacobucci, I and Li, E and Sussman, J and Hedges, D and Hui, Y and Diorio, C and Uppuluri, L and Frank, D and Fan, Y and Chang, Y and Meshinchi, S and Ries, R and Shraim, R and Li, A and Bernt, KM and Devidas, M and Winter, SS and Dunsmore, KP and Inaba, H and Carroll, WL and Ramirez, NC and Phillips, AH and Kriwacki, RW and Yang, JJ and Vincent, TL and Zhao, Y and Ghate, PS and Wang, J and Reilly, C and Zhou, X and Sanders, MA and Takita, J and Kato, M and Takasugi, N and Chang, BH and Press, RD and Loh, M and Rampersaud, E and Raetz, E and Hunger, SP and Tan, K and Chang, TC and Wu, G and Pounds, SB and Mullighan, CG and Teachey, DT},
title = {The genomic basis of childhood T-lineage acute lymphoblastic leukaemia.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {39143224},
issn = {1476-4687},
abstract = {T-lineage acute lymphoblastic leukaemia (T-ALL) is a high-risk tumour[1] that has eluded comprehensive genomic characterization, which is partly due to the high frequency of noncoding genomic alterations that result in oncogene deregulation[2,3]. Here we report an integrated analysis of genome and transcriptome sequencing of tumour and remission samples from more than 1,300 uniformly treated children with T-ALL, coupled with epigenomic and single-cell analyses of malignant and normal T cell precursors. This approach identified 15 subtypes with distinct genomic drivers, gene expression patterns, developmental states and outcomes. Analyses of chromatin topology revealed multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific manner, thereby demonstrating widespread involvement of the noncoding genome. We show that the immunophenotypically described, high-risk entity of early T cell precursor ALL is superseded by a broader category of 'early T cell precursor-like' leukaemia. This category has a variable immunophenotype and diverse genomic alterations of a core set of genes that encode regulators of hematopoietic stem cell development. Using multivariable outcome models, we show that genetic subtypes, driver and concomitant genetic alterations independently predict treatment failure and survival. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.},
}

@article {pmid39142704,
year = {2024},
author = {Wright, NC and Follis, S and Larson, JC and Crandall, CJ and Stefanick, ML and Ing, SW and Cauley, JA},
title = {Fractures by race and ethnicity in a diverse sample of postmenopausal women: a current evaluation among Hispanic and Asian origin groups.},
journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbmr/zjae117},
pmid = {39142704},
issn = {1523-4681},
support = {/HL/NHLBI NIH HHS/United States ; /NH/NIH HHS/United States ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; 1R01AR080868-01A1/AR/NIAMS NIH HHS/United States ; },
abstract = {Using 1998-2022 Women's Health Initiative (WHI) data, our study provides contemporary fracture data by race and ethnicity, specifically focusing on Hispanic and Asian women. Fractures of interest included any clinical, hip, and major osteoporotic fractures (MOFs). We utilized the updated race and ethnicity information collected in 2003, which included seven Asian and five Hispanic origin groups. We computed crude and age-standardized fracture incidence rates per 10 000 woman-years across race and ethnic categories and by Asian and Hispanic origin. We used Cox proportional hazards model, adjusting for age and WHI clinical trial arm, to evaluate the risk of fracture (1) by race compared to White women, (2) Asian origin compared to White women, (3) Hispanic compared to non-Hispanic women, and (4) Asian and Hispanic origins compared the most prevalent origin group. Over a median (interquartile range) follow-up of 19.4 (9.2-24.2) years, 44.2% of the 160 824 women experienced any clinical fracture, including 36 278 MOFs and 8962 hip fractures. Compared to White women, Black, Pacific Islander, Asian, and multiracial women had significantly lower risk of any clinical and MOFs, while only Black and Asian women had significantly lower hip fracture risk. Within Asian women, Filipina women had 24% lower risk of any clinical fracture compared to Japanese women. Hispanic women had significantly lower risk of any clinical, hip, and MOF fractures compared to non-Hispanic women, with no differences in fracture risk observed within Hispanic origin groups. In this diverse sample of postmenopausal women, we confirmed racial and ethnic differences in fracture rates and risk, with novel findings among within Asian and Hispanic subgroups. These data can aid in future longitudinal studies evaluate contributors to racial and ethnic differences in fractures.},
}

@article {pmid39142660,
year = {2024},
author = {Huang, Y and Follmann, D},
title = {Exposure proximal immune correlates analysis.},
journal = {Biostatistics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/biostatistics/kxae031},
pmid = {39142660},
issn = {1468-4357},
support = {R01CA277133/GF/NIH HHS/United States ; },
abstract = {Immune response decays over time, and vaccine-induced protection often wanes. Understanding how vaccine efficacy changes over time is critical to guiding the development and application of vaccines in preventing infectious diseases. The objective of this article is to develop statistical methods that assess the effect of decaying immune responses on the risk of disease and on vaccine efficacy, within the context of Cox regression with sparse sampling of immune responses, in a baseline-naive population. We aim to further disentangle the various aspects of the time-varying vaccine effect, whether direct on disease or mediated through immune responses. Based on time-to-event data from a vaccine efficacy trial and sparse sampling of longitudinal immune responses, we propose a weighted estimated induced likelihood approach that models the longitudinal immune response trajectory and the time to event separately. This approach assesses the effects of the decaying immune response, the peak immune response, and/or the waning vaccine effect on the risk of disease. The proposed method is applicable not only to standard randomized trial designs but also to augmented vaccine trial designs that re-vaccinate uninfected placebo recipients at the end of the standard trial period. We conducted simulation studies to evaluate the performance of our method and applied the method to analyze immune correlates from a phase III SARS-CoV-2 vaccine trial.},
}

@article {pmid39142425,
year = {2024},
author = {Neuhouser, ML and Butt, HI and Hu, C and Shadyab, AH and Garcia, L and Follis, S and Mouton, C and Harris, HR and Wactawski-Wende, J and Gower, EW and Vitolins, M and Von Ah, D and Nassir, R and Karanth, S and Ng, T and Paskett, E and Manson, JE and Chen, Z},
title = {Risk factors for long COVID syndrome in postmenopausal women with previously reported diagnosis of COVID-19.},
journal = {Annals of epidemiology},
volume = {98},
number = {},
pages = {36-43},
doi = {10.1016/j.annepidem.2024.08.003},
pmid = {39142425},
issn = {1873-2585},
abstract = {PURPOSE: Long COVID-19 syndrome occurs in 10-20 % of people after a confirmed/probable SARS-COV-2 infection; new symptoms begin within three months of COVID-19 diagnosis and last > 8 weeks. Little is known about risk factors for long COVID, particularly in older people who are at greater risk of COVID complications.

METHODS: Data are from Women's Health Initiative (WHI) postmenopausal women who completed COVID surveys that included questions on whether they had ever been diagnosed with COVID and length and nature of symptoms. Long COVID was classified using standard consensus criteria. Using WHI demographic and health data collected at study enrollment (1993-98) through the present day, machine learning identified the top 20 risk factors for long COVID. These variables were tested in logistic regression models.

RESULTS: Of n = 37,280 survey respondents, 1237 (mean age = 83 years) reported a positive COVID-19 test and 425 (30 %) reported long COVID. Symptoms included an array of neurological, cardio-pulmonary, musculoskeletal, and general fatigue, and malaise symptoms. Long COVID risk factors included weight loss, physical and mobility limitations, and specific heath conditions (e.g., history of heart valve procedure, rheumatoid arthritis).

CONCLUSIONS: Knowledge of risk factors for long COVID may be the first step in understanding the etiology of this complex disease.},
}

@article {pmid39142284,
year = {2024},
author = {Tervi, A and Ramste, M and Abner, E and Cheng, P and Lane, JM and Maher, M and Valliere, J and Lammi, V and Strausz, S and Riikonen, J and Nguyen, T and Martyn, GE and Sheth, MU and Xia, F and Docampo, ML and Gu, W and , and Esko, T and Saxena, R and Pirinen, M and Palotie, A and Ripatti, S and Sinnott-Armstrong, N and Daly, M and Engreitz, JM and Rabinovitch, M and Heckman, CA and Quertermous, T and Jones, SE and Ollila, HM},
title = {Genetic and functional analysis of Raynaud's syndrome implicates loci in vasculature and immunity.},
journal = {Cell genomics},
volume = {},
number = {},
pages = {100630},
doi = {10.1016/j.xgen.2024.100630},
pmid = {39142284},
issn = {2666-979X},
abstract = {Raynaud's syndrome is a dysautonomia where exposure to cold causes vasoconstriction and hypoxia, particularly in the extremities. We performed meta-analysis in four cohorts and discovered eight loci (ADRA2A, IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, and RAB6C) where ADRA2A, ACVR2A, NOS3, TMEM51, and IRX1 co-localized with expression quantitative trait loci (eQTLs), particularly in distal arteries. CRISPR gene editing further showed that ADRA2A and NOS3 loci modified gene expression and in situ RNAscope clarified the specificity of ADRA2A in small vessels and IRX1 around small capillaries in the skin. A functional contraction assay in the cold showed lower contraction in ADRA2A-deficient and higher contraction in ADRA2A-overexpressing smooth muscle cells. Overall, our study highlights the power of genome-wide association testing with functional follow-up as a method to understand complex diseases. The results indicate temperature-dependent adrenergic signaling through ADRA2A, effects at the microvasculature by IRX1, endothelial signaling by NOS3, and immune mechanisms by the HLA locus in Raynaud's syndrome.},
}

@article {pmid39141666,
year = {2024},
author = {Smith, SK and Manschot, C and Kuhn, E and Laber, E and Somers, TJ and Syrjala, KL and Applebaum, AJ},
title = {Assessing the utility of the PC-PTSD-5 as a screening tool among a cancer survivor sample.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35504},
pmid = {39141666},
issn = {1097-0142},
support = {CA244172/CA/NCI NIH HHS/United States ; },
abstract = {INTRODUCTION: Hematopoietic stem cell transplantation (HCT) is an intensive and invasive procedure used in cancer treatment that can lead to posttraumatic stress disorder (PTSD) symptoms. These symptoms are frequently overlooked in oncology and general health care settings. The suitability and utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) within the cancer population remains uncertain. This study aims to evaluate its performance as a brief (five-item) case-finding screening alternative to the longer (20-item) PTSD Checklist for DSM-5 (PCL-5) in survivors who received an HCT 1 to 5 years ago.

METHODS: A total of 817 cancer survivors completed the PC-PTSD-5 and PCL-5 during recruitment for a randomized clinical trial. Optimal cut scores for identifying probable PTSD and item performance were determined using indices correcting for chance and item response theory analyses.

RESULTS: Of the HCT sample, 10.4% screened as positive for probable DSM-5 PTSD using the PCL-5. The PC-PTSD-5 exhibited strong internal consistency and significant associations with PCL-5 scores (total, r = .82; items, rs = .56-.61). A cutoff score of 2 provided optimal sensitivity for screening (κ[Se] = .95), whereas a cut score of 4 demonstrated the highest efficiency for detecting a probable DSM-5 PTSD diagnosis on the PCL-5 (κ[Eff] = .39). Item response theory analyses indicated that item 4 (numbing) of the PC-PTSD-5 yielded the most informative data, with other items potentially lacking incremental utility.

CONCLUSION: Although not an instrument validation study, these findings offer efficient evidence for using the PC-PTSD-5 as a succinct screening tool among cancer survivors in a clinical context.

TRIALS REGISTRATION: ClinicalTrials.gov, NCT04058795, registered 8/16/2019.},
}

@article {pmid39141407,
year = {2024},
author = {Johnston, C and Wald, A},
title = {Genital Herpes.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2024.12743},
pmid = {39141407},
issn = {1538-3598},
}

@article {pmid39141346,
year = {2024},
author = {Salisbury, NJH and Amonkar, S and Landazuri Vinueza, J and Carter, JJ and Roman, A and Galloway, DA},
title = {Polyomavirus ALTOs, but not MTs, downregulate viral early gene expression by activating the NF-κB pathway.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {34},
pages = {e2403133121},
doi = {10.1073/pnas.2403133121},
pmid = {39141346},
issn = {1091-6490},
support = {R35 CA209979/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *NF-kappa B/metabolism ; *Gene Expression Regulation, Viral ; *Signal Transduction ; Antigens, Viral, Tumor/genetics/metabolism ; Merkel cell polyomavirus/genetics ; Polyomavirus Infections/virology/genetics/metabolism ; Carcinoma, Merkel Cell/virology/genetics/metabolism ; Open Reading Frames/genetics ; Cell Line, Tumor ; Down-Regulation ; Alternative Splicing ; },
abstract = {Polyomaviruses are small, circular dsDNA viruses that can cause cancer. Alternative splicing of polyomavirus early transcripts generates large and small tumor antigens (LT, ST) that play essential roles in viral replication and tumorigenesis. Some polyomaviruses also express middle tumor antigens (MTs) or alternate LT open reading frames (ALTOs), which are evolutionarily related but have distinct gene structures. MTs are a splice variant of the early transcript whereas ALTOs are overprinted on the second exon of the LT transcript in an alternate reading frame and are translated via an alternative start codon. Merkel cell polyomavirus (MCPyV), the only human polyomavirus that causes cancer, encodes an ALTO but its role in the viral lifecycle and tumorigenesis has remained elusive. Here, we show MCPyV ALTO acts as a tumor suppressor and is silenced in Merkel cell carcinoma (MCC). Rescuing ALTO in MCC cells induces growth arrest and activates NF-κB signaling. ALTO activates NF-κB by binding SQSTM1 and TRAF2&3 via two N-Terminal Activating Regions (NTAR1+2), resembling Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1). Following activation, NF-κB dimers bind the MCPyV noncoding control region (NCCR) and downregulate early transcription. Beyond MCPyV, NTAR motifs are conserved in other polyomavirus ALTOs, which activate NF-κB signaling, but are lacking in MTs that do not. Furthermore, polyomavirus ALTOs downregulate their respective viral early transcription in an NF-κB- and NTAR-dependent manner. Our findings suggest that ALTOs evolved to suppress viral replication and promote viral latency and that MCPyV ALTO must be silenced for MCC to develop.},
}

Humans
*NF-kappa B/metabolism
*Gene Expression Regulation, Viral
*Signal Transduction
Antigens, Viral, Tumor/genetics/metabolism
Merkel cell polyomavirus/genetics
Polyomavirus Infections/virology/genetics/metabolism
Carcinoma, Merkel Cell/virology/genetics/metabolism
Open Reading Frames/genetics
Cell Line, Tumor
Down-Regulation
Alternative Splicing

@article {pmid39005367,
year = {2024},
author = {Gao, Y and Feder, AF},
title = {Detecting branching rate heterogeneity in multifurcating trees with applications in lineage tracing data.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39005367},
issn = {2692-8205},
support = {DP2 CA280623/CA/NCI NIH HHS/United States ; },
abstract = {Understanding cellular birth rate differences is crucial for predicting cancer progression and interpreting tumor-derived genetic data. Lineage tracing experiments enable detailed reconstruction of cellular genealogies, offering new opportunities to measure branching rate heterogeneity. However, the lineage tracing process can introduce complex tree features that complicate this effort. Here, we examine tree characteristics in lineage tracing-derived genealogies and find that editing window placement leads to multifurcations at a tree's root or tips. We propose several ways in which existing tree topology-based metrics can be extended to test for rate heterogeneity on trees even in the presence of lineage-tracing associated distortions. Although these methods vary in power and robustness, a test based on the J 1 statistic effectively detects branching rate heterogeneity in simulated lineage tracing data. Tests based on other common statistics (s ^ and the Sackin index) show interior performance to J 1 . We apply our validated methods to xenograft experimental data and find widespread rate heterogeneity across multiple study systems. Our results demonstrate the potential of tree topology statistics in analyzing lineage tracing data, and highlight the challenges associated with adapting phylogenetic methods to these systems.},
}

@article {pmid32511329,
year = {2020},
author = {Gordon, DE and Jang, GM and Bouhaddou, M and Xu, J and Obernier, K and O'Meara, MJ and Guo, JZ and Swaney, DL and Tummino, TA and Huettenhain, R and Kaake, RM and Richards, AL and Tutuncuoglu, B and Foussard, H and Batra, J and Haas, K and Modak, M and Kim, M and Haas, P and Polacco, BJ and Braberg, H and Fabius, JM and Eckhardt, M and Soucheray, M and Bennett, MJ and Cakir, M and McGregor, MJ and Li, Q and Naing, ZZC and Zhou, Y and Peng, S and Kirby, IT and Melnyk, JE and Chorba, JS and Lou, K and Dai, SA and Shen, W and Shi, Y and Zhang, Z and Barrio-Hernandez, I and Memon, D and Hernandez-Armenta, C and Mathy, CJP and Perica, T and Pilla, KB and Ganesan, SJ and Saltzberg, DJ and Ramachandran, R and Liu, X and Rosenthal, SB and Calviello, L and Venkataramanan, S and Liboy-Lugo, J and Lin, Y and Wankowicz, SA and Bohn, M and Sharp, PP and Trenker, R and Young, JM and Cavero, DA and Hiatt, J and Roth, TL and Rathore, U and Subramanian, A and Noack, J and Hubert, M and Roesch, F and Vallet, T and Meyer, B and White, KM and Miorin, L and Rosenberg, OS and Verba, KA and Agard, D and Ott, M and Emerman, M and Ruggero, D and García-Sastre, A and Jura, N and von Zastrow, M and Taunton, J and Ashworth, A and Schwartz, O and Vignuzzi, M and d'Enfert, C and Mukherjee, S and Jacobson, M and Malik, HS and Fujimori, DG and Ideker, T and Craik, CS and Floor, S and Fraser, JS and Gross, J and Sali, A and Kortemme, T and Beltrao, P and Shokat, K and Shoichet, BK and Krogan, NJ},
title = {A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {32511329},
issn = {2692-8205},
support = {U19 AI135990/AI/NIAID NIH HHS/United States ; R01 AI122747/AI/NIAID NIH HHS/United States ; R01 CA221969/CA/NCI NIH HHS/United States ; R01 CA244550/CA/NCI NIH HHS/United States ; K08 HL124068/HL/NHLBI NIH HHS/United States ; R35 GM122481/GM/NIGMS NIH HHS/United States ; P01 AI063302/AI/NIAID NIH HHS/United States ; P50 AI150476/AI/NIAID NIH HHS/United States ; R01 AI143292/AI/NIAID NIH HHS/United States ; F32 CA236347/CA/NCI NIH HHS/United States ; R01 AI120694/AI/NIAID NIH HHS/United States ; T32 GM008284/GM/NIGMS NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; R01 HG009979/HG/NHGRI NIH HHS/United States ; P01 AI120943/AI/NIAID NIH HHS/United States ; U19 AI135972/AI/NIAID NIH HHS/United States ; T32 GM064337/GM/NIGMS NIH HHS/United States ; },
abstract = {An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption[1,2]. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 67 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.},
}

@article {pmid39140467,
year = {2024},
author = {Kim, J and Xu, S and Jung, SR and Nguyen, A and Cheng, Y and Zhao, M and Fujimoto, BS and Nelson, W and Schiro, P and Franklin, JL and Higginbotham, JN and Coffey, RJ and Shi, M and Vojtech, LN and Hladik, F and Tewari, M and Tigges, J and Ghiran, I and Jovanovic-Talisman, T and Laurent, LC and Das, S and Gololobova, O and Witwer, KW and Xu, T and Charest, A and Jensen, KVK and Raffai, RL and Jones, JC and Welsh, JA and Nolan, JP and Chiu, DT},
title = {Comparison of EV characterization by commercial high-sensitivity flow cytometers and a custom single-molecule flow cytometer.},
journal = {Journal of extracellular vesicles},
volume = {13},
number = {8},
pages = {e12498},
pmid = {39140467},
issn = {2001-3078},
support = {P50 CA095103/CA/NCI NIH HHS/United States ; R35 CA197570/CA/NCI NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; UG3 CA241685/CA/NCI NIH HHS/United States ; //National Institute of Health/ ; UH3 CA241685/CA/NCI NIH HHS/United States ; //VA Merit grant/ ; },
mesh = {*Flow Cytometry/methods/instrumentation ; Humans ; *Extracellular Vesicles/metabolism ; Colorectal Neoplasms/diagnosis ; Cell Line, Tumor ; Single Molecule Imaging/methods/instrumentation ; },
abstract = {High-sensitivity flow cytometers have been developed for multi-parameter characterization of single extracellular vesicles (EVs), but performance varies among instruments and calibration methods. Here we compare the characterization of identical (split) EV samples derived from human colorectal cancer (DiFi) cells by three high-sensitivity flow cytometers, two commercial instruments, CytoFLEX/CellStream, and a custom single-molecule flow cytometer (SMFC). DiFi EVs were stained with the membrane dye di-8-ANEPPS and with PE-conjugated anti-EGFR or anti-tetraspanin (CD9/CD63/CD81) antibodies for estimation of EV size and surface protein copy numbers. The limits of detection (LODs) for immunofluorescence and vesicle size based on calibration using cross-calibrated, hard-dyed beads were ∼10 PE/∼80 nm EV diameter for CytoFLEX and ∼10 PEs/∼67 nm for CellStream. For the SMFC, the LOD for immunofluorescence was 1 PE and ≤ 35 nm for size. The population of EVs detected by each system (di-8-ANEPPS[+]/PE[+] particles) differed widely depending on the LOD of the system; for example, CellStream/CytoFLEX detected only 5.7% and 1.5% of the tetraspanin-labelled EVs detected by SMFC, respectively, and median EV diameter and antibody copy numbers were much larger for CellStream/CytoFLEX than for SMFC as measured and validated using super-resolution/single-molecule TIRF microscopy. To obtain a dataset representing a common EV population analysed by all three platforms, we filtered out SMFC and CellStream measurements for EVs below the CytoFLEX LODs as determined by bead calibration (10 PE/80 nm). The inter-platform agreement using this filtered dataset was significantly better than for the unfiltered dataset, but even better concordance between results was obtained by applying higher cutoffs (21 PE/120 nm) determined by threshold analysis using the SMFC data. The results demonstrate the impact of specifying LODs to define the EV population analysed on inter-instrument reproducibility in EV flow cytometry studies, and the utility of threshold analysis of SMFC data for providing semi-quantitative LOD values for other flow cytometers.},
}

*Flow Cytometry/methods/instrumentation
Humans
*Extracellular Vesicles/metabolism
Colorectal Neoplasms/diagnosis
Cell Line, Tumor
Single Molecule Imaging/methods/instrumentation

@article {pmid39137832,
year = {2024},
author = {D'Souza, A and Stowe, HB and Green, OL and Schiff, J and Hugo, GD and Ginn, J and Maraghechi, B and Kang, KH and Kim, H and Badiyan, SN and Samson, P and Robinson, CG and Price, A and Henke, LE},
title = {Dosimetric predictors of acute and late gastrointestinal toxicities in stereotactic online adaptive magnetic resonance-guided radiotherapy (SMART) for locally advanced pancreatic adenocarcinoma.},
journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology},
volume = {},
number = {},
pages = {110473},
doi = {10.1016/j.radonc.2024.110473},
pmid = {39137832},
issn = {1879-0887},
abstract = {BACKGROUND AND PURPOSE: A retrospective evaluation of dosimetric predictors and leveraged dose-volume data for gastrointestinal (GI) toxicities for locally-advanced pancreatic cancer (LAPC) treated with daily stereotactic MRI-guided online-adaptive radiotherapy (SMART).

MATERIALS AND METHODS: 147 patients with LAPC were treated with SMART at our institution between 2018 and 2021. Patients were evaluated using CTCAE V5.0 for RT-related acute (≤3 months) and late (>3 months) toxicities. Each organ at risk (OAR) was matched to a ≥ grade 2 (Gr2+) toxicity endpoint composite group. A least absolute shrinkage selector operator regression model was constructed by dose-volumes per OAR to account for OAR multicollinearity. A receiver operator curve (ROC) analysis was performed for the combined averages of significant toxicity groups to identify critical volumes per dose levels.

RESULTS: 18 of 147 patients experienced Gr2+ GI toxicity. 17 Gr2+ duodenal toxicities were seen; the most significant predictor was a V33Gy odds ratio (OR) of 1.69 per cc (95 % CI 1.14-2.88). 17 Gr2+ small bowel (SB) toxicities were seen; the most significant predictor was a V33Gy OR of 1.60 per cc (95 % CI 1.01-2.53). The AUC was 0.72 for duodenum and SB. The optimal duodenal cut-point was 1.00 cc (true positive (TP): 17.8 %; true negative (TN); 94.9 %). The SB cut-point was 1.75 cc (TP: 16.7 %; TN: 94.3 %). No stomach or large bowel dose toxicity predictors were identified.

CONCLUSIONS: For LAPC treated with SMART, the dose-volume threshold of V33Gy for duodenum and SB was associated with Gr2+ toxicities. These metrics can be utilized to guide future dose-volume constraints for patients undergoing upper abdominal SBRT.},
}

@article {pmid39136970,
year = {2024},
author = {Appelbaum, JS and Appelbaum, FR and Percival, ME},
title = {Second chances for secondary AML.},
journal = {Blood advances},
volume = {8},
number = {15},
pages = {4221-4222},
doi = {10.1182/bloodadvances.2024013318},
pmid = {39136970},
issn = {2473-9537},
mesh = {Humans ; *Leukemia, Myeloid, Acute/therapy/diagnosis ; Neoplasms, Second Primary/etiology/diagnosis ; },
}

Humans
*Leukemia, Myeloid, Acute/therapy/diagnosis
Neoplasms, Second Primary/etiology/diagnosis

@article {pmid39136016,
year = {2024},
author = {Barreto, BC and Neves, MVGD and Cardoso, CMA and Meira, CS and Daltro, PS and Figueira, CP and Santos, GC and Silva, DN and Távora, F and Neto, JDS and Macambira, SG and Lampe, PD and Coutinho, KCDS and Kasai Brunswick, TH and Ribeiro Dos Santos, R and Campos de Carvalho, AC and Soares, MBP},
title = {The effects of inflammation on connexin 43 in chronic Chagas disease cardiomyopathy.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1440662},
pmid = {39136016},
issn = {1664-3224},
mesh = {*Connexin 43/metabolism/genetics ; Animals ; *Chagas Cardiomyopathy/metabolism/pathology/immunology/parasitology ; Humans ; Mice ; *Myocytes, Cardiac/metabolism/parasitology/pathology ; *Mice, Inbred C57BL ; Inflammation/metabolism ; Phosphorylation ; Male ; Chronic Disease ; Trypanosoma cruzi ; Disease Models, Animal ; Cell Line ; Cytokines/metabolism ; Arrhythmias, Cardiac/metabolism/parasitology/immunology ; Female ; },
abstract = {BACKGROUND: Cardiac arrhythmias are the main cause of sudden death due to Chronic Chagasic Cardiomyopathy (CCC). Here we investigated alterations in connexin 43 (Cx43) expression and phosphorylation in cardiomyocytes as well as associations with cardiac arrhythmias in CCC.

METHODS: C57Bl/6 mice infected with Trypanosoma cruzi underwent cardiac evaluations at 6 and 12 months after infection via treadmill testing and EKG. Histopathology, cytokine gene expression, and distribution of total Cx43 and its phosphorylated forms Cx43[S368] and Cx43[S325/328/330] were investigated. Human heart samples obtained from subjects with CCC were submitted to immunofluorescence analysis. In vitro simulation of a pro-inflammatory microenvironment (IL-1β, TNF, and IFN-γ) was performed in H9c2 cells and iPSC-derived cardiomyocytes to evaluate Cx43 distribution, action potential duration, and Lucifer Yellow dye transfer.

RESULTS: Mice chronically infected with T. cruzi exhibited impaired cardiac function associated with increased inflammation, fibrosis and upregulated IL-1β, TNF, and IFN-γ gene expression. Confocal microscopy revealed altered total Cx43, Cx43[S368] and Cx43[S325/328/330] localization and phosphorylation patterns in CCC, with dispersed staining outside the intercalated disc areas, i.e., in lateral membranes and the cytoplasm. Reduced co-localization of total Cx43 and N-cadherin was observed in the intercalated discs of CCC mouse hearts compared to controls. Similar results were obtained in human CCC heart samples, which showed Cx43 distribution outside the intercalated discs. Stimulation of human iPSC-derived cardiomyocytes or H9c2 cells with IL-1β, TNF, and IFN-γ induced alterations in Cx43 localization, reduced action potential duration and dye transfer between adjacent cells.

CONCLUSION: Heart inflammation in CCC affects the distribution and phosphorylation pattern of Cx43, which may contribute to the generation of conduction disturbances in Chagas disease.},
}

*Connexin 43/metabolism/genetics
Animals
*Chagas Cardiomyopathy/metabolism/pathology/immunology/parasitology
Humans
Mice
*Myocytes, Cardiac/metabolism/parasitology/pathology
*Mice, Inbred C57BL
Inflammation/metabolism
Phosphorylation
Male
Chronic Disease
Trypanosoma cruzi
Disease Models, Animal
Cell Line
Cytokines/metabolism
Arrhythmias, Cardiac/metabolism/parasitology/immunology
Female

@article {pmid39134575,
year = {2024},
author = {Lin, HY and Mazumder, H and Sarkar, I and Huang, PY and Eeles, RA and Kote-Jarai, Z and Muir, KR and , and Schleutker, J and Pashayan, N and Batra, J and , and Neal, DE and Nielsen, SF and Nordestgaard, BG and Grönberg, H and Wiklund, F and MacInnis, RJ and Haiman, CA and Travis, RC and Stanford, JL and Kibel, AS and Cybulski, C and Khaw, KT and Maier, C and Thibodeau, SN and Teixeira, MR and Cannon-Albright, L and Brenner, H and Kaneva, R and Pandha, H and , and Park, JY},
title = {Cluster effect for SNP-SNP interaction pairs for predicting complex traits.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {18677},
pmid = {39134575},
issn = {2045-2322},
support = {PC220560//U.S. Department of Defense/ ; },
mesh = {*Polymorphism, Single Nucleotide ; Humans ; *Multifactorial Inheritance/genetics ; Gene Frequency ; Genome-Wide Association Study/methods ; Cluster Analysis ; Models, Genetic ; Epistasis, Genetic ; },
abstract = {Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP-SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP-SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP-SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP-SNP interaction detection accuracy.},
}

*Polymorphism, Single Nucleotide
Humans
*Multifactorial Inheritance/genetics
Gene Frequency
Genome-Wide Association Study/methods
Cluster Analysis
Models, Genetic
Epistasis, Genetic

@article {pmid39134521,
year = {2024},
author = {Gagne, M and Flynn, BJ and Honeycutt, CC and Flebbe, DR and Andrew, SF and Provost, SJ and McCormick, L and Van Ry, A and McCarthy, E and Todd, JM and Bao, S and Teng, IT and Marciano, S and Rudich, Y and Li, C and Jain, S and Wali, B and Pessaint, L and Dodson, A and Cook, A and Lewis, MG and Andersen, H and Zahradník, J and Suthar, MS and Nason, MC and Foulds, KE and Kwong, PD and Roederer, M and Schreiber, G and Seder, RA and Douek, DC},
title = {Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {6894},
pmid = {39134521},
issn = {2041-1723},
support = {75N93021C00017/AI/NIAID NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; 3814/19//Israel Science Foundation (ISF)/ ; P51 OD011132/CD/ODCDC CDC HHS/United States ; },
mesh = {Animals ; *SARS-CoV-2/drug effects/physiology/immunology ; *Angiotensin-Converting Enzyme 2/metabolism ; *Macaca mulatta ; *Virus Replication/drug effects ; Male ; *COVID-19/virology/immunology/prevention & control ; Humans ; *Antiviral Agents/pharmacology ; COVID-19 Drug Treatment ; Spike Glycoprotein, Coronavirus/metabolism/genetics/immunology ; Disease Models, Animal ; Vero Cells ; Chlorocebus aethiops ; },
abstract = {SARS-CoV-2 has the capacity to evolve mutations that escape vaccine- and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool that would maintain its efficacy despite the ongoing emergence of new variants. Here, we challenge male rhesus macaques with SARS-CoV-2 Delta-the most pathogenic variant in a highly susceptible animal model. At the time of challenge, we also treat the macaques with aerosolized RBD-62, a protein developed through multiple rounds of in vitro evolution of SARS-CoV-2 RBD to acquire 1000-fold enhanced ACE2 binding affinity. RBD-62 treatment equivalently suppresses virus replication in both upper and lower airways, a phenomenon not previously observed with clinically approved vaccines. Importantly, RBD-62 does not block the development of virus-specific T- and B-cell responses and does not elicit anti-drug immunity. These data provide proof-of-concept that RBD-62 can prevent severe disease from a highly virulent variant.},
}

Animals
*SARS-CoV-2/drug effects/physiology/immunology
*Angiotensin-Converting Enzyme 2/metabolism
*Macaca mulatta
*Virus Replication/drug effects
Male
*COVID-19/virology/immunology/prevention & control
Humans
*Antiviral Agents/pharmacology
COVID-19 Drug Treatment
Spike Glycoprotein, Coronavirus/metabolism/genetics/immunology
Disease Models, Animal
Vero Cells
Chlorocebus aethiops

@article {pmid39133932,
year = {2024},
author = {Döhner, H and DiNardo, CD and Wei, AH and Löwenberg, B and Appelbaum, F and Craddock, C and Dombret, H and Ebert, BL and Fenaux, P and Godley, LA and Hasserjian, RP and Larson, RA and Levine, RL and Miyazaki, Y and Niederwieser, D and Ossenkoppele, GJ and Röllig, C and Sierra, J and Stein, EM and Tallman, MS and Tien, HF and Wang, J and Wierzbowska, A},
title = {Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025409},
pmid = {39133932},
issn = {1528-0020},
abstract = {The European LeukemiaNet (ELN) genetic risk classifications were developed based on data from younger adults receiving intensive chemotherapy. Emerging analyses from patients receiving less-intensive therapies prompted a proposal for an ELN genetic risk classification specifically for this patient population.},
}

@article {pmid39133891,
year = {2024},
author = {Annesley, C and Lamble, AJ and Summers, C and Pulsipher, MA and Wayne, AS and Rivers, J and Huang, W and Wilson, A and Wu, Q and Seidel, KD and Mgebroff, S and Brown, CT and Lindgren, C and Park, JR and Jensen, MC and Gardner, RA},
title = {Feasibility and Favorable Responses Following Investigational CAR T-Cell Therapy for Relapsed and Refractory Infant ALL.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024012638},
pmid = {39133891},
issn = {2473-9537},
abstract = {Infants with B-cell acute lymphoblastic leukemia (B-ALL) continue to have significantly worse outcomes compared to older children with B-ALL, and those with relapsed or refractory (R/R) infant ALL have especially dismal outcomes with conventional treatment. CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in the treatment of R/R childhood B-ALL, though the majority of reports have been in non-infant patients. Barriers to the successful implementation of CAR T-cell therapy in infant B-ALL include challenges related to apheresis, product manufacturing and disease-specific considerations such as lineage switch. We describe our experience utilizing two experimental CD19-CAR T-cell products, SCRI-CAR19 or SCRI-CAR19x22, for 19 patients with R/R infant B-ALL enrolled on three clinical trials. CAR T-cell products were successfully manufactured in 18/19 (94.7%) patients, with a median age of 22.5 months at enrollment (range, 14.5-40.1 months). Sixteen of 17 (94.1%) treated patients achieved a complete remission without detectable minimal residual disease. The 1-year leukemia free survival was 75% and 1-year overall survival was 76.5%, with a median follow up time of 35.8 months (range, 1.7-83.6 months). Cytokine release syndrome (CRS) occurred in 14/17 (82.4%) patients, with only 1 patient experiencing Grade 3 CRS. Neurotoxicity occurred in 2/17 (11.8%) patients with all events ≤ Grade 2. With the successful early clinical experience of CAR T-cell therapy in this population, more systematic evaluation specific to infant ALL is warranted.},
}

@article {pmid39133650,
year = {2024},
author = {Ford, ES and Li, AZ and Laing, KJ and Dong, L and Diem, K and Jing, L and Mayer-Blackwell, K and Basu, K and Ott, M and Tartaglia, J and Gurunathan, S and Reid, JL and Ecsedi, M and Chapuis, AG and Huang, ML and Magaret, AS and Johnston, C and Zhu, J and Koelle, DM and Corey, L},
title = {Expansion of the HSV-2-specific T cell repertoire in skin after immunotherapeutic HSV-2 vaccine.},
journal = {JCI insight},
volume = {9},
number = {14},
pages = {},
doi = {10.1172/jci.insight.179010},
pmid = {39133650},
issn = {2379-3708},
mesh = {Humans ; *Herpesvirus 2, Human/immunology ; *Skin/immunology/virology ; *Herpes Genitalis/immunology/prevention & control/virology ; *CD4-Positive T-Lymphocytes/immunology ; Female ; Receptors, Antigen, T-Cell, alpha-beta/immunology/genetics ; Male ; Adult ; Vaccination ; Middle Aged ; },
abstract = {The skin at the site of HSV-2 reactivation is enriched for HSV-2-specific T cells. To evaluate whether an immunotherapeutic vaccine could elicit skin-based memory T cells, we studied skin biopsies and HSV-2-reactive CD4+ T cells from PBMCs by T cell receptor (TCR) β chain (TRB) sequencing before and after vaccination with a replication-incompetent whole-virus HSV-2 vaccine candidate (HSV529). The representation of HSV-2-reactive CD4+ TRB sequences from PBMCs in the skin TRB repertoire increased after the first vaccine dose. We found sustained expansion after vaccination of unique, skin-based T cell clonotypes that were not detected in HSV-2-reactive CD4+ T cells isolated from PBMCs. In one participant, a switch in immunodominance occurred with the emergence of a TCR αβ pair after vaccination that was not detected in blood. This TCRαβ was shown to be HSV-2 reactive by expression of a synthetic TCR in a Jurkat-based NR4A1 reporter system. The skin in areas of HSV-2 reactivation possessed an oligoclonal TRB repertoire that was distinct from the circulation. Defining the influence of therapeutic vaccination on the HSV-2-specific TRB repertoire requires tissue-based evaluation.},
}

Humans
*Herpesvirus 2, Human/immunology
*Skin/immunology/virology
*Herpes Genitalis/immunology/prevention & control/virology
*CD4-Positive T-Lymphocytes/immunology
Female
Receptors, Antigen, T-Cell, alpha-beta/immunology/genetics
Male
Adult
Vaccination
Middle Aged

@article {pmid39133444,
year = {2024},
author = {Jones, SMW and Briant, KJ and Doody, DR and Iachan, R and Mendoza, JA},
title = {A person-reported cumulative social risk measure does not show bias by income and education.},
journal = {Journal of patient-reported outcomes},
volume = {8},
number = {1},
pages = {90},
pmid = {39133444},
issn = {2509-8020},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P30CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; *Educational Status ; *Income ; Middle Aged ; Adult ; *Social Determinants of Health ; Bias ; Aged ; Racism ; Self Report ; },
abstract = {BACKGROUND: Social risk such as housing instability, trouble affording medical care and food insecurity are a downstream effect of social determinants of health (SDOHs) and are frequently associated with worse health. SDOHs include experiences of racism, sexism and other discrimination as well as differences in income and education. The collective effects of each social risk a person reports are called cumulative social risk. Cumulative social risk has traditionally been measured through counts or sum scores that treat each social risk as equivalent. We have proposed to use item response theory (IRT) as an alternative measure of person-reported cumulative social risk as IRT accounts for the severity in each risk and allows for more efficient screening with computerized adaptive testing.

METHODS: We conducted a differential item functioning (DIF) analysis comparing IRT-based person-reported cumulative social risk scores by income and education in a population-based sample (n = 2122). Six social risk items were analyzed using the two-parameter logistic model and graded response model.

RESULTS: Analyses showed no DIF on an IRT-based cumulative social risk score by education level for the six items examined. Statistically significant DIF was found on three items by income level but the ultimate effect on the scores was negligible.

CONCLUSIONS: Results suggest an IRT-based cumulative social risk score is not biased by education and income level and can be used for comparisons between groups. An IRT-based cumulative social risk score will be useful for combining datasets to examine policy factors affecting social risk and for more efficient screening of patients for social risk using computerized adaptive testing.},
}

Humans
Female
Male
*Educational Status
*Income
Middle Aged
Adult
*Social Determinants of Health
Bias
Aged
Racism
Self Report

@article {pmid39132937,
year = {2024},
author = {Brown, JR and Eichhorst, B and Hillmen, P and Jurczak, W and Kaźmierczak, M and Lamanna, N and O'Brien, SM and Tam, CS and Qiu, L and Zhou, K and Simkovic, 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 Salmi, T and Wang, MD and Fu, L and Li, J and Wu, K and Cohen, A and Shadman, M},
title = {Plain language summary of zanubrutinib or ibrutinib in chronic lymphocytic leukemia that is resistant to treatment or has come back after treatment.},
journal = {Future oncology (London, England)},
volume = {20},
number = {12},
pages = {717-726},
doi = {10.2217/fon-2023-0849},
pmid = {39132937},
issn = {1744-8301},
mesh = {Humans ; *Piperidines/therapeutic use ; *Adenine/analogs & derivatives/therapeutic use ; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; *Pyrimidines/therapeutic use ; *Pyrazoles/therapeutic use ; *Drug Resistance, Neoplasm ; *Protein Kinase Inhibitors/therapeutic use/adverse effects ; Antineoplastic Agents/therapeutic use ; Pyrazines/therapeutic use ; Thiazoles/therapeutic use ; Treatment Outcome ; },
}

Humans
*Piperidines/therapeutic use
*Adenine/analogs & derivatives/therapeutic use
*Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy
*Pyrimidines/therapeutic use
*Pyrazoles/therapeutic use
*Drug Resistance, Neoplasm
*Protein Kinase Inhibitors/therapeutic use/adverse effects
Antineoplastic Agents/therapeutic use
Pyrazines/therapeutic use
Thiazoles/therapeutic use
Treatment Outcome

@article {pmid39132880,
year = {2024},
author = {Simpson, S and Yu, K and Bell-Brown, A and Kimura, A and Meisner, A and Issaka, RB},
title = {Factors associated with mailed fecal immunochemical test (FIT) completion in an integrated academic-community healthcare system.},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000000757},
pmid = {39132880},
issn = {2155-384X},
support = {K08 CA241296/CA/NCI NIH HHS/United States ; },
abstract = {INTRODUCTION: Mailed fecal immunochemical test (FIT) outreach is an effective strategy to increase colorectal cancer (CRC) screening. This study aimed to determine the patient-, clinic-, and geographical-level factors associated with CRC screening completion in a mailed FIT outreach program.

METHODS: This retrospective cohort study was conducted in UW Medicine's integrated healthcare system, and included patients 50-75 years old, who were due for CRC screening, and had a primary care encounter in the past 3 years. Eligible patients received mailed outreach that included a letter with information about CRC screening, FIT kit, and a pre-paid return envelope. CRC screening and factors associated with completion were obtained from electronic health records and the CRC screening program database.

RESULTS: Of the 9,719 patients who received mailed outreach, 29.6% completed FIT mailed outreach. The median FIT return time was 27 days (IQR 14 - 54). On multivariate analysis, individuals with a higher area deprivation index, insured through Medicaid, living without a partner, and whose last primary care visit was >12 months ago were less likely to complete a FIT compared to their counterparts. Over a 12-month period, overall CRC screening across the health system increased by 2 percentage points (68% to 70%).

DISCUSSION: Mailed FIT outreach in an integrated academic-community practice was feasible, with 32% of invited patients completing CRC screening by FIT or colonoscopy, on par with published literature. Patient and geographic-level factors were associated with CRC screening completion. These data will inform additional interventions aimed to increase CRC screening participation in this population.},
}

@article {pmid39129757,
year = {2023},
author = {Bloom, JD},
title = {Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market.},
journal = {Virus evolution},
volume = {9},
number = {2},
pages = {vead050},
pmid = {39129757},
issn = {2057-1577},
abstract = {The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10[8] total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.},
}

@article {pmid39128225,
year = {2024},
author = {Morrish, F and Gingras, H and Noonan, J and Huang, L and Sweet, IR and Kuok, IT and Knoblaugh, SE and Hockenbery, DM},
title = {Mitochondrial diabetes in mice expressing a dominant-negative allele of nuclear respiratory factor-1 (Nrf1) in pancreatic β-cells.},
journal = {Biochemical and biophysical research communications},
volume = {737},
number = {},
pages = {150478},
doi = {10.1016/j.bbrc.2024.150478},
pmid = {39128225},
issn = {1090-2104},
abstract = {Genetic polymorphisms in nuclear respiratory factor-1 (Nrf1), a key transcriptional regulator of nuclear-encoded mitochondrial proteins, have been linked to diabetes. Homozygous deletion of Nrf1 is embryonic lethal in mice. Our goal was to generate mice with β-cell-specific reduction in NRF1 function to investigate the relationship between NRF1 and diabetes. We report the generation of mice expressing a dominant-negative allele of Nrf1 (DNNRF1) in pancreatic β-cells. Heterozygous transgenic mice had high fed blood glucose levels detected at 3 wks of age, which persisted through adulthood. Plasma insulin levels in DNNRF1 transgenic mice were reduced, while insulin sensitivity remained intact in young animals. Islet size was reduced with increased numbers of apoptotic cells, and insulin content in islets by immunohistochemistry was low. Glucose-stimulated insulin secretion in isolated islets was reduced in DNNRF1-mice, but partially rescued by KCl, suggesting that decreased mitochondrial function contributed to the insulin secretory defect. Electron micrographs demonstrated abnormal mitochondrial morphology in β-cells. Expression of NRF1 target genes Tfam, Tfb1m and Tfb2m, and islet cytochrome c oxidase and succinate dehydrogenase activities were reduced in DNNRF1-mice. Rescue of mitochondrial function with low level activation of transgenic c-Myc in β-cells was sufficient to restore β-cell mass and prevent diabetes. This study demonstrates that reduced NRF1 function can lead to loss of β-cell function and establishes a model to study the interplay between regulators of bi-genomic gene transcription in diabetes.},
}

@article {pmid39127048,
year = {2024},
author = {Barrero, DJ and Wijeratne, SS and Zhao, X and Cunningham, GF and Yan, R and Nelson, CR and Arimura, Y and Funabiki, H and Asbury, CL and Yu, Z and Subramanian, R and Biggins, S},
title = {Architecture of native kinetochores revealed by structural studies utilizing a thermophilic yeast.},
journal = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2024.07.036},
pmid = {39127048},
issn = {1879-0445},
abstract = {Eukaryotic chromosome segregation requires kinetochores, multi-megadalton protein machines that assemble on the centromeres of chromosomes and mediate attachments to dynamic spindle microtubules. Kinetochores are built from numerous complexes, and there has been progress in structural studies on recombinant subassemblies. However, there is limited structural information on native kinetochore architecture. To address this, we purified functional, native kinetochores from the thermophilic yeast Kluyveromyces marxianus and examined them by electron microscopy (EM), cryoelectron tomography (cryo-ET), and atomic force microscopy (AFM). The kinetochores are extremely large, flexible assemblies that exhibit features consistent with prior models. We assigned kinetochore polarity by visualizing their interactions with microtubules and locating the microtubule binder, Ndc80c. This work shows that isolated kinetochores are more dynamic and complex than what might be anticipated based on the known structures of recombinant subassemblies and provides the foundation to study the global architecture and functions of kinetochores at a structural level.},
}

@article {pmid38669315,
year = {2024},
author = {Holtzman, NG and Curtis, LM and Salit, RB and Shaffer, BC and Pirsl, F and Ostojic, A and Steinberg, SM and Schulz, E and Wilder, JS and Hughes, TE and Rose, J and Memon, S and Korngold, R and Gea-Banacloche, JC and Fowler, DH and Hakim, FT and Gress, RE and Bishop, MR and Pavletic, SZ},
title = {High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention.},
journal = {Blood advances},
volume = {8},
number = {16},
pages = {4294-4310},
doi = {10.1182/bloodadvances.2023010973},
pmid = {38669315},
issn = {2473-9537},
mesh = {Humans ; *Graft vs Host Disease/prevention & control/etiology ; *Alemtuzumab/therapeutic use/administration & dosage ; Female ; Male ; Middle Aged ; Adult ; *Methotrexate/therapeutic use/administration & dosage ; *Tacrolimus/therapeutic use ; *Sirolimus/therapeutic use ; *Cyclosporine/therapeutic use/administration & dosage ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Aged ; Immunosuppressive Agents/therapeutic use ; Chronic Disease ; Transplantation Conditioning/methods ; Transplantation, Homologous ; Young Adult ; Hematologic Neoplasms/therapy ; Bronchiolitis Obliterans Syndrome ; },
abstract = {Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P = .0002), as well as any grade (P = .003) and moderate-severe (P < .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P = .003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted naïve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130.},
}

Humans
*Graft vs Host Disease/prevention & control/etiology
*Alemtuzumab/therapeutic use/administration & dosage
Female
Male
Middle Aged
Adult
*Methotrexate/therapeutic use/administration & dosage
*Tacrolimus/therapeutic use
*Sirolimus/therapeutic use
*Cyclosporine/therapeutic use/administration & dosage
*Hematopoietic Stem Cell Transplantation/adverse effects
Aged
Immunosuppressive Agents/therapeutic use
Chronic Disease
Transplantation Conditioning/methods
Transplantation, Homologous
Young Adult
Hematologic Neoplasms/therapy
Bronchiolitis Obliterans Syndrome

@article {pmid39126374,
year = {2024},
author = {Felker, J and Bjornard, K and Close, A and Chavez, J and Chow, EJ and Meacham, LR and Burns, K},
title = {Fertility preservation in pediatric central nervous system tumors: A report from the Children's Oncology Group.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e31246},
doi = {10.1002/pbc.31246},
pmid = {39126374},
issn = {1545-5017},
support = {//St. Baldrick's Foundation/ ; U10CA098543/NH/NIH HHS/United States ; UG1CA189955/NH/NIH HHS/United States ; U10CA180886/NH/NIH HHS/United States ; U10CA18099/NH/NIH HHS/United States ; U10CA098413/NH/NIH HHS/United States ; U10 CA180899/CA/NCI NIH HHS/United States ; //Children's Oncology Group/ ; },
abstract = {The Oncofertility Consortium Pediatric Initiative Network has published recommendations about the risks of infertility due to gonadotoxic therapy. We abstracted gonadotoxic therapies from central nervous system (CNS) Children's Oncology Group (COG) protocols between 2000 and 2022. We assigned them as unknown, minimal, significant, or high levels of increased risk for gonadal dysfunction/infertility. Seven of 11 CNS protocols placed patients at a high level of risk in at least one treatment arm. Males (7/11) were most commonly at a high level of risk, followed by pubertal females (6/11) and prepubertal females (5/11), highlighting the importance of pre-treatment counseling regarding fertility preservation interventions in this population.},
}

@article {pmid39125034,
year = {2024},
author = {Promsong, A and Chuerduangphui, J and Levy, CN and Hladik, F and Satthakarn, S and Nittayananta, W},
title = {Effects of Ellagic Acid on Vaginal Innate Immune Mediators and HPV16 Infection In Vitro.},
journal = {Molecules (Basel, Switzerland)},
volume = {29},
number = {15},
pages = {},
pmid = {39125034},
issn = {1420-3049},
mesh = {Humans ; Female ; *Ellagic Acid/pharmacology ; *Immunity, Innate/drug effects ; *Vagina/virology/immunology/drug effects ; *Human papillomavirus 16 ; *Papillomavirus Infections/immunology/virology/drug therapy ; Cytokines/metabolism ; Epithelial Cells/drug effects/virology/metabolism/immunology ; beta-Defensins/metabolism ; HEK293 Cells ; },
abstract = {Ellagic acid (EA) is a phenolic phytochemical found in many plants and their fruits. Vaginal epithelial cells are the first line of defense against pathogen invasion in the female reproductive tract and express antimicrobial peptides, including hBD2 and SLPI. This study investigated the in vitro effects of EA (1) on vaginal innate immunity using human vaginal epithelial cells, and (2) on HPV16 pseudovirus infection. Vaginal cells were cultured in the presence or absence of EA, and the expression of hBD2 and SLPI was determined at both transcriptional and translational levels. In addition, secretion of various cytokines and chemokines was measured. Cytotoxicity of EA was determined by CellTiter-blue and MTT assays. To investigate the ability of EA to inhibit HPV16 infection, EA was used to treat HEK-293FT cells in pre-attachment and adsorption steps. We found significant increases in both hBD2 mRNA (mean 2.9-fold at 12.5 µM EA, p < 0.001) and protein (mean 7.1-fold at 12.5 µM EA, p = 0.002) in response to EA. SLPI mRNA also increased significantly (mean 1.4-fold at 25 µM EA, p = 0.01), but SLPI protein did not. Secretion of IL-2 but not of other cytokines/chemokines was induced by EA in a dose-dependent manner. EA was not cytotoxic. At the pre-attachment step, EA at CC20 and CC50 showed a slight trend towards inhibiting HPV16 pseudovirus, but this was not significant. In summary, vaginal epithelial cells can respond to EA by producing innate immune factors, and at tested concentrations, EA is not cytotoxic. Thus, plant-derived EA could be useful as an immunomodulatory agent to improve vaginal health.},
}

Humans
Female
*Ellagic Acid/pharmacology
*Immunity, Innate/drug effects
*Vagina/virology/immunology/drug effects
*Human papillomavirus 16
*Papillomavirus Infections/immunology/virology/drug therapy
Cytokines/metabolism
Epithelial Cells/drug effects/virology/metabolism/immunology
beta-Defensins/metabolism
HEK293 Cells

@article {pmid39123464,
year = {2024},
author = {Ebadi, M and Pankuch, M and Boyer, S and Chang, J and Stevens, C and Hall, MD and Hasan, S and Bates, JE and Flampouri, S and Kole, AJ and Mohindra, P and Rossi, C and Sanghvi, P and McGee, L and Rana, Z and Tseng, YD},
title = {Proton Pencil Beam Scanning Facilitates the Safe Treatment of Extended Radiation Targets for Hodgkin Lymphoma: A Report from the Proton Collaborative Group Registry.},
journal = {Cancers},
volume = {16},
number = {15},
pages = {},
pmid = {39123464},
issn = {2072-6694},
abstract = {Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT.},
}

@article {pmid39122670,
year = {2024},
author = {Rachid Zaim, S and Pebworth, MP and McGrath, I and Okada, L and Weiss, M and Reading, J and Czartoski, JL and Torgerson, TR and McElrath, MJ and Bumol, TF and Skene, PJ and Li, XJ},
title = {MOCHA's advanced statistical modeling of scATAC-seq data enables functional genomic inference in large human cohorts.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {6828},
pmid = {39122670},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/genetics/virology ; *Models, Statistical ; *Single-Cell Analysis/methods ; *Gene Regulatory Networks ; *Genomics/methods ; *Chromatin/genetics/metabolism ; SARS-CoV-2/genetics ; Transposases/metabolism/genetics ; Chromatin Immunoprecipitation Sequencing/methods ; Cohort Studies ; Gene Expression Regulation ; },
abstract = {Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) is being increasingly used to study gene regulation. However, major analytical gaps limit its utility in studying gene regulatory programs in complex diseases. In response, MOCHA (Model-based single cell Open CHromatin Analysis) presents major advances over existing analysis tools, including: 1) improving identification of sample-specific open chromatin, 2) statistical modeling of technical drop-out with zero-inflated methods, 3) mitigation of false positives in single cell analysis, 4) identification of alternative transcription-starting-site regulation, and 5) modules for inferring temporal gene regulatory networks from longitudinal data. These advances, in addition to open chromatin analyses, provide a robust framework after quality control and cell labeling to study gene regulatory programs in human disease. We benchmark MOCHA with four state-of-the-art tools to demonstrate its advances. We also construct cross-sectional and longitudinal gene regulatory networks, identifying potential mechanisms of COVID-19 response. MOCHA provides researchers with a robust analytical tool for functional genomic inference from scATAC-seq data.},
}

Humans
*COVID-19/genetics/virology
*Models, Statistical
*Single-Cell Analysis/methods
*Gene Regulatory Networks
*Genomics/methods
*Chromatin/genetics/metabolism
SARS-CoV-2/genetics
Transposases/metabolism/genetics
Chromatin Immunoprecipitation Sequencing/methods
Cohort Studies
Gene Expression Regulation

@article {pmid39119980,
year = {2024},
author = {Filigrana, P and Moon, JY and Gallo, LC and Fernández-Rhodes, L and Perreira, KM and Daviglus, ML and Thyagarajan, B and Garcia-Bedoya, OL and Cai, J and Xue, X and Kaplan, RC and Suglia, S and Isasi, CR},
title = {LifeCourse Socioeconomic Position and Ideal Cardiovascular Health in Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos.},
journal = {Journal of the American Heart Association},
volume = {},
number = {},
pages = {e035503},
doi = {10.1161/JAHA.124.035503},
pmid = {39119980},
issn = {2047-9980},
abstract = {BACKGROUND: The Hispanic/Latino population experiences socioeconomic disadvantages across the lifespan. Yet, little is known about the role of these disadvantages in cardiovascular health (CVH). We assessed the association of lifecourse socioeconomic position (SEP) with ideal CVH and change in Hispanic/Latino adults.

METHODS AND RESULTS: We used longitudinal data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Childhood SEP was determined using parental educational attainment. Adult SEP was determined through an index combining participants' education, occupation, income, and assets at baseline. We classified participants into 4 socioeconomic mobility categories (eg, stable low or high SEP, upward or downward mobility). Using the 4 health factors of the American Heart Association "Life's Essential 8," we built a score of ideal CVH at baseline and the 6-year follow-up. Linear mixed-effects models using inverse probability weighting were fitted to assess the main associations. Higher childhood SEP was associated with higher ideal CVH at baseline (β for high school versus high school versus
CONCLUSIONS: Although high childhood and adult SEP and socioeconomic mobility were associated with higher levels of ideal CVH, they were not associated with change in ideal-CVH.},
}

@article {pmid39119731,
year = {2024},
author = {Issaka, RB and Ibekwe, LN and Todd, KW and Burnett-Hartman, AN and Clark, CR and Del Vecchio, NJ and Kamineni, A and Neslund-Dudas, C and Chubak, J and Corley, DA and Haas, JS and Honda, SA and Li, CI and Winer, RL and Pruitt, SL},
title = {Association between racial residential segregation and screening uptake for colorectal and cervical cancer among Black and White patients in five US health care systems.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35514},
pmid = {39119731},
issn = {1097-0142},
support = {K08CA241296//Division of Cancer Prevention, National Cancer Institute/ ; UM1CA221939//Division of Cancer Prevention, National Cancer Institute/ ; UM1CA221940//Division of Cancer Prevention, National Cancer Institute/ ; UM1CA222035//Division of Cancer Prevention, National Cancer Institute/ ; },
abstract = {BACKGROUND: Despite increased recognition that structural racism contributes to poorer health outcomes for racial and ethnic minorities, there are knowledge gaps about how current patterns of racial residential segregation are associated with cancer screening uptake. The authors examined associations between Black residential segregation and screening for colorectal cancer (CRC) and cervical cancer among non-Hispanic Black and non-Hispanic White adults.

METHODS: This was a retrospective study of CRC and cervical cancer screening-eligible adults from five health care systems within the Population-Based Research to Optimize the Screening Process (PROSPR II) Consortium (cohort entry, 2010-2012). Residential segregation was measured using site-specific quartiles of the Black local isolation score (LIS). The outcome was receipt of CRC or cervical cancer screening within 3 years of cohort entry (2010-2015). Logistic regression was used to calculate associations between the LIS and screening completion, adjusting for patient-level covariates.

RESULTS: Among CRC (n = 642,661) and cervical cancer (n = 163,340) screening-eligible patients, 456,526 (71.0%) and 106,124 (65.0%), respectively, received screening. Across PROSPR sites, living in neighborhoods with higher LIS tended to be associated with lower odds of CRC screening (Kaiser Permanente Northern California: adjusted odds ratio [aOR] LIS trend in Black patients, 0.95 [p < .001]; aOR LIS trend in White patients, 0.98 [p < .001]; Kaiser Permanente Southern California: aOR LIS trend in Black patients, 0.98 [p = .026]; aOR LIS trend in White patients, 1.01 [p = .023]; Kaiser Permanente Washington: aOR LIS trend in White patients, 0.97 [p = .002]. However, for cervical cancer screening, associations with the LIS varied by site and race (Kaiser Permanente Washington: aOR LIS trend in White patients, 0.95 [p < .001]; Mass General Brigham: aOR LIS trend in Black patients, 1.12 [p < .001]; aOR LIS trend in White patients, 1.03 [p < .001]).

CONCLUSIONS: Across five diverse health care systems, the direction of the association between Black residential segregation and screening varied by PROSPR site, race, and screening type. Additional research, including studies that examine multiple dimensions of segregation and structural racism using intersectional approaches, are needed to further disentangle these relationships.},
}

@article {pmid39118035,
year = {2024},
author = {Sun, V and Guthrie, KA and Arnold, KB and Antonoff, M and Erhunmwunsee, L and Borondy-Kitts, A and Johnson, J and Jones, L and Ramirez, M and Tong, BC and Moremen, JR and Yang, CJ and Ng, T and Kim, SS and Brown, LM and Blasberg, JD and Lui, NS and Kneuertz, PJ and Toloza, EM and Kim, JY and Raz, DJ},
title = {Comparative effectiveness of perioperative physical activity in older adults with lung cancer and their family caregivers: design of a multicenter pragmatic randomized trial.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {976},
pmid = {39118035},
issn = {1471-2407},
support = {HA-2021C3-24773/PCORI/Patient-Centered Outcomes Research Institute/United States ; HA-2021C3-24773/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
mesh = {Humans ; *Caregivers ; Aged ; *Lung Neoplasms/surgery ; *Quality of Life ; *Exercise ; Male ; Female ; Telephone ; Perioperative Care/methods ; },
abstract = {BACKGROUND: With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs.

METHODS: In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed.

DISCUSSION: The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06196008.},
}

Humans
*Caregivers
Aged
*Lung Neoplasms/surgery
*Quality of Life
*Exercise
Male
Female
Telephone
Perioperative Care/methods

@article {pmid39115975,
year = {2024},
author = {Wong, JS and Uno, H and Tramontano, AC and Fisher, L and Pellegrini, CV and Abel, GA and Burstein, HJ and Chun, YS and King, TA and Schrag, D and Winer, E and Bellon, JR and Cheney, MD and Hardenbergh, P and Ho, A and Horst, KC and Kim, JN and Leonard, KL and Moran, MS and Park, CC and Recht, A and Soto, DE and Shiloh, RY and Stinson, SF and Snyder, KM and Taghian, AG and Warren, LE and Wright, JL and Punglia, RS},
title = {Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction: A Randomized Clinical Trial.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {39115975},
issn = {2374-2445},
abstract = {IMPORTANCE: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined.

OBJECTIVE: To compare HF and CF PMRT outcomes after implant-based reconstruction.

This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023.

INTERVENTIONS: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event.

MAIN OUTCOMES AND MEASURES: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence.

RESULTS: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03422003.},
}

@article {pmid39115548,
year = {2024},
author = {Moghaddam, SJ and Savai, R and Salehi-Rad, R and Sengupta, S and Kammer, MN and Massion, P and Beane, JE and Ostrin, EJ and Priolo, C and Tennis, MA and Stabile, LP and Bauer, AK and Sears, CR and Szabo, E and Rivera, MP and Powell, CA and Kadara, H and Jenkins, BJ and Dubinett, SM and Houghton, AM and Kim, CF and Keith, RL},
title = {Premalignant Progression in the Lung: Knowledge Gaps and Novel Opportunities for Interception of Non-Small Cell Lung Cancer. An Official American Thoracic Society Research Statement.},
journal = {American journal of respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
doi = {10.1164/rccm.202406-1168ST},
pmid = {39115548},
issn = {1535-4970},
support = {I01 BX005353/BX/BLRD VA/United States ; },
abstract = {RATIONALE: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing for timely and effective intervention before cancer development.

OBJECTIVES: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung.

METHODS: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the transformation of premalignant lung lesions to advanced lung cancer.

RESULTS: This research statement identifies significant gaps in knowledge and proposes potential research questions aimed at expanding our understanding of the mechanisms underlying the progression of premalignant lung lesions to lung cancer in an effort to explore potential innovative modalities to intercept lung cancer at its nascent stages.

CONCLUSIONS: The identified gaps in knowledge about the biological mechanisms of premalignant progression in the lung, along with ongoing challenges in screening, detection, and early intervention, highlight the critical need to prioritize research in this domain. Such focused investigations are essential to devise effective preventive strategies that may ultimately decrease lung cancer incidence and improve patient outcomes.},
}

@article {pmid39115391,
year = {2024},
author = {Di, M and Potnis, KC and Long, JB and Isufi, I and Foss, F and Seropian, S and Gross, CP and Huntington, SF},
title = {Costs of care during chimeric antigen receptor T-cell therapy in relapsed/refractory B cell lymphomas.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkae059},
pmid = {39115391},
issn = {2515-5091},
abstract = {High upfront cost may be a barrier to adopting chimeric antigen receptor T-cell therapy (CAR-T) for relapsed/refractory B cell lymphoma (BCL). Data on the real-world costs are limited. Using the Blue Cross Blue Shield Axis database, we evaluated 271 commercially insured patients who received CAR-T for BCL (median age: 58 years, men: 68%, diffuse large BCL: 87%, inpatient CAR-T: 85%). Our peri-CAR-T period of interest comprised -41 to + 154 days from CAR-T index, divided into seven 28-day intervals. Median total costs were $608,100 (interquartile range: $534,100-$732,800); 8.5% of patients had total costs >$1,000,000. Median cost of CAR-T products was $402,500, and median out-of-pocket copayment was $510. Monthly costs were highest during the month of CAR-T administration (median: $521,500), with median costs <$25,000 in all other 28-day intervals. Costs of CAR-T use were substantial, largely driven by product acquisition. Future studies should examine the relation between costs, access, and financial outcomes.},
}

@article {pmid39115038,
year = {2024},
author = {Grillová, L and Romeis, E and Lieberman, NAP and Tantalo, LC and Xu, LH and Molini, B and Trejos, AT and Lacey, G and Goulding, D and Thomson, NR and Greninger, AL and Giacani, L},
title = {Bright New Resources for Syphilis Research: Genetically Encoded Fluorescent Tags for Treponema pallidum and Sf1Ep Cells.},
journal = {Molecular microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1111/mmi.15304},
pmid = {39115038},
issn = {1365-2958},
support = {8394150//Open Philanthropy Project/ ; U19AI144133//National Institute of Allergy and Infectious Diseases/ ; BB/010589/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 206194/WT_/Wellcome Trust/United Kingdom ; INV-051483//the Bill & Melinda Gates Foundation/ ; },
abstract = {The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. pallidum (T. pallidum) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance of controlled studies to assess differential treponemal gene expression, and generation of loss-of-function mutants to evaluate the contribution of specific genetic loci to T. pallidum virulence. Building on this progress, we engineered the T. pallidum SS14 strain to express a red-shifted green fluorescent protein (GFP) and Sf1Ep cells to express mCherry and blue fluorescent protein (BFP) for enhanced visualization. These new resources improve microscopy- and cell sorting-based applications for T. pallidum, better capturing the physical interaction between the host and pathogen, among other possibilities. Continued efforts to develop and share new tools and resources are required to help our overall knowledge of T. pallidum biology and syphilis pathogenesis reach that of other bacterial pathogens, including spirochetes.},
}

@article {pmid39115010,
year = {2024},
author = {Peter, J and Takalani, A and Meyer, J and Semete-Makokotlela, B and Collie, S and Seocharan, I and Goga, A and Garrett, N and Gail-Bekker, L and Gray, G},
title = {Vaccine pharmacovigilance in South Africa: successes and limitations of current approaches.},
journal = {Expert opinion on drug safety},
volume = {},
number = {},
pages = {},
doi = {10.1080/14740338.2024.2387322},
pmid = {39115010},
issn = {1744-764X},
abstract = {INTRODUCTION: Despite the public health success of vaccination, there is an ongoing need to build public confidence in vaccines and improve systems to monitor safety while maintaining data security and patient privacy. African countries face multiple challenges in establishing systems for vaccine pharmacovigilance as was demonstrated during COVID-19 mass vaccination. We provide a framework for the development of pharmacovigilance using the COVID-19 vaccination roll-out as an exemplar.

AREAS COVERED: We describe the pre-COVID-19 vaccine pharmacovigilance systems in Southern Africa and propose improvements based on our experience of COVID-19 vaccine roll-out in South Africa where we implemented systems to evaluate real-world safety and effectiveness of COVID-19 vaccinations. By conducting a pubmed review of the literature on pharmacovigilance with a focus on Africa and from guidance emanating from the World Health Organisation (WHO), we evaluate challenges and opportunities to improve pharmacovigilance in our setting.

EXPERT OPINION: There are ongoing efforts to improve pharmacovigilance on the African continent with improved coordination at a national level with the support of WHO, the national regulatory authorities, and national departments of health. COVID-19 vaccine roll-out provided an opportunity to improve pharmacovigilance by integrating national vaccine platforms with active and passive surveillance including hospital and death registries.},
}

@article {pmid39113782,
year = {2024},
author = {Wang, CY and Hwang, WH and Song, X},
title = {Biomarker data with measurement error in medical research: A literature review.},
journal = {Wiley interdisciplinary reviews. Computational statistics},
volume = {16},
number = {1},
pages = {},
pmid = {39113782},
issn = {1939-5108},
support = {R21 AI176947/AI/NIAID NIH HHS/United States ; R21 CA239168/CA/NCI NIH HHS/United States ; R01 HL130483/HL/NHLBI NIH HHS/United States ; R21 CA201207/CA/NCI NIH HHS/United States ; R01 AG085616/AG/NIA NIH HHS/United States ; R03 CA235122/CA/NCI NIH HHS/United States ; },
abstract = {A biomarker is a measurable indicator of the severity or presence of a disease or medical condition in biomedical or epidemiological research. Biomarkers may help in early diagnosis and prevention of diseases. Several biomarkers have been identified for many diseases such as carbohydrate antigen 19-9 for pancreatic cancer. However, biomarkers may be measured with errors due to many reasons such as specimen collection or day-to-day within-subject variability of the biomarker, among others. Measurement error in the biomarker leads to bias in the regression parameter estimation for the association of the biomarker with disease in epidemiological studies. In addition, measurement error in the biomarkers may affect standard diagnostic measures to evaluate the performance of biomarkers such as the receiver operating characteristic (ROC) curve, area under the ROC curve, sensitivity, and specificity. Measurement error may also have an effect on how to combine multiple cancer biomarkers as a composite predictor for disease diagnosis. In follow-up studies, biomarkers are often collected intermittently at examination times, which may be sparse and typically biomarkers are not observed at the event times. Joint modeling of longitudinal and time-to-event data is a valid approach to account for measurement error in the analysis of repeatedly measured biomarkers and time-to-event outcomes. In this article, we provide a literature review on existing methods to correct for estimation in regression analysis, diagnostic measures, and joint modeling of longitudinal biomarkers and survival outcomes when the biomarkers are measured with errors. This article is categorized under: Statistical and Graphical Methods of Data Analysis > Robust MethodsStatistical and Graphical Methods of Data Analysis > EM AlgorithmStatistical Models > Survival Models.},
}

@article {pmid39113729,
year = {2024},
author = {Hirayama, AV and Wright, JH and Smythe, KS and Fiorenza, S and Shaw, AN and Gauthier, J and Maloney, DG and Naresh, KN and Yeung, CCS and Turtle, CJ},
title = {PD-L1[+] macrophage and tumor cell abundance and proximity to T cells in the pretreatment large B-cell lymphoma microenvironment impact CD19 CAR-T cell immunotherapy efficacy.},
journal = {HemaSphere},
volume = {8},
number = {8},
pages = {e142},
pmid = {39113729},
issn = {2572-9241},
abstract = {CD19-targeted chimeric antigen receptor T-cell (CAR-T) immunotherapy has transformed the management of relapsed/refractory large B-cell lymphoma (LBCL), yet durable remissions are observed in less than half of treated patients. The tumor microenvironment (TME) is a key and understudied factor impacting CD19 CAR-T therapy outcomes. Using NanoString nCounter transcriptome profiling (n = 24) and multiplex immunohistochemistry (mIHC, n = 15), we studied the TME in pretreatment biopsies from patients with LBCL undergoing CD19 CAR-T therapy. Patients who achieved complete response (CR) after CAR-T therapy demonstrated higher expression of genes associated with T-cell trafficking and function, whereas those who did not achieve CR had higher expression of genes associated with macrophages and T-cell dysfunction. Distinct patterns of immune infiltration and fibrosis in the TME were associated with CAR-T therapy outcomes, and these findings were corroborated using artificial intelligence-assisted image analyses. Patients who achieved CR had a lower proportion of the biopsy occupied by an interspersed immune infiltrate and a higher proportion of hypocellular/fibrotic regions. Furthermore, mIHC revealed lower density of CD4[+] T cells and higher densities of both macrophages and tumor cells expressing PD-L1 in non-CR patients. Spatial analysis revealed that PD-1[+] T cells were in close proximity to PD-L1[+] macrophages or PD-L1[+] tumor cells in patients who did not compared to those who did achieve CR after CAR-T therapy. These findings suggest that morphologic patterns in the TME and engagement of the PD-1/PD-L1 axis in pretreatment biopsies may impact CD19 CAR-T immunotherapy response in patients with LBCL.},
}

@article {pmid39112630,
year = {2024},
author = {Kousa, AI and Jahn, L and Zhao, K and Flores, AE and Acenas, D and Lederer, E and Argyropoulos, KV and Lemarquis, AL and Granadier, D and Cooper, K and D'Andrea, M and Sheridan, JM and Tsai, J and Sikkema, L and Lazrak, A and Nichols, K and Lee, N and Ghale, R and Malard, F and Andrlova, H and Velardi, E and Youssef, S and Burgos da Silva, M and Docampo, M and Sharma, R and Mazutis, L and Wimmer, VC and Rogers, KL and DeWolf, S and Gipson, B and Gomes, ALC and Setty, M and Pe'er, D and Hale, L and Manley, NR and Gray, DHD and van den Brink, MRM and Dudakov, JA},
title = {Age-related epithelial defects limit thymic function and regeneration.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {39112630},
issn = {1529-2916},
support = {R35-HL-171556//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL145276//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL165673//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; F30-HL165761//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL123340//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL147584//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-AI70035//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; P30-CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01-CA228308//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30 CA008748/CA/NCI NIH HHS/United States ; P01-AG052359//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; ALTF-431-2017//European Molecular Biology Organization (EMBO)/ ; 1090236//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1158024//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1078763//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1121325//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1187367//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1146518//Cancer Council Victoria/ ; 1102104//Cancer Council Victoria/ ; T32-GM007270//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.},
}

@article {pmid38885329,
year = {2024},
author = {Simpson, J and Starke, CE and Ortiz, AM and Ransier, A and Darko, S and Llewellyn-Lacey, S and Fennessey, CM and Keele, BF and Douek, DC and Price, DA and Brenchley, JM},
title = {Immunotoxin-mediated depletion of Gag-specific CD8+ T cells undermines natural control of SIV.},
journal = {JCI insight},
volume = {9},
number = {14},
pages = {},
doi = {10.1172/jci.insight.174168},
pmid = {38885329},
issn = {2379-3708},
mesh = {Animals ; *CD8-Positive T-Lymphocytes/immunology ; *Simian Immunodeficiency Virus/immunology ; *Simian Acquired Immunodeficiency Syndrome/immunology ; *Macaca mulatta ; *Immunotoxins/immunology/pharmacology ; Gene Products, gag/immunology ; Virus Replication/immunology/drug effects ; Lymphocyte Depletion/methods ; },
abstract = {Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is potentially confounded by several factors, including reactive CD4+ T cell proliferation, and provides no information on epitope specificity, a likely determinant of CD8+ T cell efficacy. We circumvented these limitations by selectively depleting CD8+ T cells specific for the Gag epitope CTPYDINQM (CM9) via the administration of immunotoxin-conjugated tetrameric complexes of CM9/Mamu-A*01. Immunotoxin administration effectively depleted circulating but not tissue-localized CM9-specific CD8+ T cells, akin to the bulk depletion pattern observed with antibodies directed against CD8. However, we found no evidence to indicate that circulating CM9-specific CD8+ T cells suppressed viral replication in Mamu-A*01+ rhesus macaques during acute or chronic progressive infection with a pathogenic strain of SIV. This observation extended to macaques with established infection during and after continuous antiretroviral therapy. In contrast, natural controller macaques experienced dramatic increases in plasma viremia after immunotoxin administration, highlighting the importance of CD8+ T cell-mediated immunity against CM9. Collectively, these data showed that CM9-specific CD8+ T cells were necessary but not sufficient for robust immune control of SIV in a nonhuman primate model and, more generally, validated an approach that could inform the design of next-generation vaccines against HIV-1.},
}

Animals
*CD8-Positive T-Lymphocytes/immunology
*Simian Immunodeficiency Virus/immunology
*Simian Acquired Immunodeficiency Syndrome/immunology
*Macaca mulatta
*Immunotoxins/immunology/pharmacology
Gene Products, gag/immunology
Virus Replication/immunology/drug effects
Lymphocyte Depletion/methods

@article {pmid39112401,
year = {2023},
author = {Siddiqi, T and Maloney, DG and Kenderian, SS and Brander, DM and Dorritie, K and Soumerai, J and Riedell, PA and Shah, NN and Nath, R and Fakhri, B and Stephens, DM and Ma, S and Feldman, T and Solomon, SR and Schuster, SJ and Perna, SK and Tuazon, S and Ou, S and Papp, E and Chen, Y and Wierda, W},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {60-62},
doi = {10.1002/hon.3163_26},
pmid = {39112401},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39112400,
year = {2023},
author = {Alig, SK and Esfahani, MS and Garofalo, A and Li, MY and Rossi, C and Adams, R and Binkley, MS and Jin, MC and Olsen, M and Telenius, A and Mutter, J and Sworder, BJ and Schroers-Martin, J and King, DA and Schultz, A and Bögeholz, J and Su, S and Kathuria, KR and Kang, X and Liu, CL and Spina, V and Tousseyn, T and Buedts, L and Flerlage, T and Flerlage, JE and Castellino, SM and Advani, R and Rossi, D and Lynch, R and Ghesquières, H and Casasnovas, O and Kurtz, DM and Marks, LJ and Link, MP and André, M and Vandenberghe, P and Steidl, C and Diehn, M and Alizadeh, AA},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {96-98},
doi = {10.1002/hon.3163_60},
pmid = {39112400},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39112366,
year = {2023},
author = {Shadman, M and Yeung, C and Redman, M and Lee, SY and Lee, DH and Qian, DH and Ra, S and Ujjani, CS and Dezube, BJ and Warren, EH and Chapuis, AG and Green, DJ and Cowan, AJ and Cassaday, RD and Kiem, H and Poh, C and Smith, SD and Milano, F and Gauthier, J and Hirayama, AV and Turtle, CJ and Lynch, RC and Gopal, AK and Maloney, DG and Till, BG},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {87-88},
doi = {10.1002/hon.3163_49},
pmid = {39112366},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39112270,
year = {2023},
author = {Amengual, JE and Reagan, P and Li, H and Saeed, H and Vaidya, R and Unger, JM and Danilov, A and LeBlanc, M and Friedberg, JW and Smith, SM},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {842-843},
doi = {10.1002/hon.3166_OT22},
pmid = {39112270},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39112252,
year = {2023},
author = {Westin, J and Jacobson, CA and Chavez, JC and Sureda, A and Morschhauser, F and Glaß, B and Dickinson, M and Davies, A and Flinn, IW and Maloney, DG and Chamuleau, M and Tees, M and Xue, A and Shahani, S and Nikolajeva, O and Kang, J and Kaplan, A and Schupp, M and Miao, H and Rich, ES},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {171-173},
doi = {10.1002/hon.3163_T06},
pmid = {39112252},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39112204,
year = {2023},
author = {Lynch, RC and Poh, C and Shadman, M and Till, BG and Smith, SD and Ujjani, C and Ottemiller, S and Verni, K and Fessel, M and Joy, B and Gausman, D and Rasmussen, H and Vandermeer, J and Voutsinas, J and Gopal, AK},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {577-578},
doi = {10.1002/hon.3164_432},
pmid = {39112204},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39112201,
year = {2023},
author = {Phillips, T and Wang, M and Robak, T and Gallinson, D and Stevens, D and Patel, K and Ramadan, S and Wun, C and Jurczak, W and Smith, SD},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {586-587},
doi = {10.1002/hon.3164_439},
pmid = {39112201},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39111731,
year = {2024},
author = {Kozono, D and Hua, X and Wu, MC and Tolba, KA and Waqar, SN and Dragnev, KH and Cheng, H and Hirsch, FR and Mack, PC and Gray, JE and Kelly, K and Borghaei, H and Herbst, RS and Gandara, DR and Redman, MW},
title = {Lung-MAP Next Generation Sequencing Analysis of Advanced Squamous Cell Lung Cancers (SWOG S1400).},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtho.2024.07.024},
pmid = {39111731},
issn = {1556-1380},
abstract = {INTRODUCTION: Squamous cell cancer (SqCC) is a lung cancer subtype with few targeted therapy options. Molecular characterization, i.e., by next generation sequencing (NGS), is needed to identify potential targets. Lung-MAP SWOG S1400 enrolled patients with previously treated stage IV or recurrent SqCC to assess NGS biomarkers for therapeutic substudies.

METHODS: Tumors underwent NGS using Foundation Medicine's FoundationOne research platform, which sequenced the exons and/or introns of 313 cancer-related genes. Mutually Exclusive Gene Set Analysis (MEGSA) and Selected Events Linked by Evolutionary Conditions across human Tumors (SELECT) were performed to identify mutually exclusive and co-occurring gene alterations. Comparisons were performed with data on 495 lung SqCC downloaded from The Cancer Genome Atlas. Cox proportional hazards models were used to examine associations between genetic variants and survival.

RESULTS: NGS data are reported for 1672 patients enrolled on S1400 between 2014 and 2019. MEGSA identified two non-overlapping sets of mutually exclusive alterations with a false discovery rate < 15%: NFE2L2, KEAP1 and PARP4; and CDKN2A and RB1. PARP4, a relatively uncharacterized gene, showed three frequent mutations suggesting functional significance: 3116T>C (I1039T), 3176A>G (Q1059R) and 3509C>T (T1170I). NFE2L2 and KEAP1 alterations when taken together were associated with poorer survival.

CONCLUSIONS: As the largest dataset to-date of lung SqCC profiled on a clinical trial, the S1400 NGS dataset establishes a rich resource for biomarker discovery. Mutual exclusivity of PARP4 and NFE2L2 or KEAP1 alterations suggests that PARP4 may have an uncharacterized role in a key pathway known to impact oxidative stress response and treatment resistance.},
}

@article {pmid39110181,
year = {2024},
author = {Le Bihan, D and Iima, M and Partridge, SC},
title = {Fat-signal suppression in breast diffusion-weighted imaging: the Good, the Bad, and the Ugly.},
journal = {European radiology},
volume = {},
number = {},
pages = {},
pmid = {39110181},
issn = {1432-1084},
abstract = {OBJECTIVES: Fat-signal suppression is essential for breast diffusion magnetic resonance imaging (or diffusion-weighted MRI, DWI) as the very low diffusion coefficient of fat tends to decrease absolute diffusion coefficient (ADC) values. Among several methods, the STIR (short-tau inversion recovery) method is a popular approach, but signal suppression/attenuation is not specific to fat contrary to other methods such as SPAIR (spectral adiabatic (or attenuated) inversion recovery). This article focuses on those two techniques to illustrate the importance of appropriate fat suppression in breast DWI, briefly presenting the pros and cons of both approaches.

METHODS AND RESULTS: We show here through simulation and data acquired in a dedicated breast DWI phantom made of vials with water and various concentrations of polyvinylpyrrolidone (PVP) how ADC values obtained with STIR DWI may be biased toward tissue components with the longest T1 values: ADC values obtained with STIR fat suppression may be over/underestimated depending on the T1 and ADC profile within tissues. This bias is also illustrated in two clinical examples.

CONCLUSION: Fat-specific methods should be preferred over STIR for fat-signal suppression in breast DWI, such as SPAIR which also provides a higher sensitivity than STIR for lesion detection. One should remain aware, however, that efficient fat-signal suppression with SPAIR requires good B0 shimming to avoid ADC underestimation from residual fat contamination.

CLINICAL RELEVANCE STATEMENT: The spectral adiabatic (or attenuated) inversion recovery (SPAIR) method should be preferred over short-tau inversion recovery (STIR) for fat suppression in breast DWI.

KEY POINTS: Fat-signal suppression is essential for breast DWI; the SPAIR method is recommended. Short-tau inversion recovery (STIR) is not specific to fat; as a result, SNR is decreased and ADC values may be over- or underestimated. The STIR fat-suppression method must not be used after the injection of gadolinium-based contrast agents.},
}

@article {pmid39112187,
year = {2023},
author = {Brown, JR and Eichorst, B and Ghia, P and Jurczak, W and Kahl, BS and Lamanna, N and Robak, T and Shadman, M and Tam, CS and Qiu, L and Cohen, A and Zhang, M and Salmi, T and Paik, J and Wang, L and Zhang, J and Ma, H and Tedeschi, A},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {459-461},
doi = {10.1002/hon.3164_339},
pmid = {39112187},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39112177,
year = {2023},
author = {Shadman, M and Burke, JM and Zafar, SF and Misleh, J and Rao, SS and Farber, CM and Cohen, A and Crescenzo, R and By, K and Flinn, IW and Sharman, JP},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {469-471},
doi = {10.1002/hon.3164_345},
pmid = {39112177},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic

@article {pmid39112167,
year = {2023},
author = {Pinto, AA and Bosch, F and Bisneto, JCV and Sanz, RG and Garcia, CG and Smith, SD and Wallace, DS and Arcaini, L and Merryman, R and Marolleau, J and De Filippi, R and Chêne, L and Bonny, C and Fagerberg, J and Friedberg, JW and Ansel, S and Armand, P and Zinzani, PL},
title = {17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.},
journal = {Hematological oncology},
volume = {41 Suppl 2},
number = {},
pages = {581-582},
doi = {10.1002/hon.3164_435},
pmid = {39112167},
issn = {1099-1069},
mesh = {Humans ; *Lymphoma/therapy ; Switzerland ; Congresses as Topic ; },
}

Humans
*Lymphoma/therapy
Switzerland
Congresses as Topic