@article {pmid39031841,
year = {2024},
author = {Rosenberg, AR and Taylor, MR and Fladeboe, KM and Zhou, C and Levine, DR and Johnston, EE and Freyer, DR and Comiskey, L and Junkins, CC and Bradford, M and Odom, JN and Baker, KS and Yi-Frazier, JP},
title = {Resilience and distress among adolescents and young adults receiving hematopoietic cell transplantation: The Promoting Resilience in Stress Management randomized trial.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35440},
pmid = {39031841},
issn = {1097-0142},
support = {R01 CA225629/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Adolescents and young adults (AYAs) receiving hematopoietic cell transplantation (HCT) are at high risk of poor psychosocial health. This study aimed to determine whether the Promoting Resilience in Stress Management (PRISM) intervention mitigated these risks during the first 6 months posttransplant.

METHODS: This multisite, parallel, randomized trial was conducted from April 2019 to March 2023. Eligible AYAs were aged 12-24 years, English speaking, and within 1 month of HCT for cancer or cancer predisposition syndrome. They were assigned 1:1 to PRISM (a brief, skills-based intervention targeting "resilience resources" [stress management, goal setting, cognitive reframing, and meaning making]) or usual care (UC). Outcomes included total symptoms of depression and anxiety (Hospital Anxiety and Depression Scale; primary outcome), hope (Snyder Hope Scale), resilience (10-item Connor-Davidson Resilience Scale), and health-related quality of life (HRQOL; Pediatric Quality of Life Inventory Cancer Module). Analyses leveraged multivariable linear regressions; exploratory analyses assessed the influence of baseline depression or anxiety.

RESULTS: Of 94 enrolled and randomized AYAs, the mean age was 16.7 years (SD, 4.2); 43 (46%) were female, 56 (60%) were non-Hispanic White, 22 (23%) were Hispanic, and nine (10%) were Black. Most (77%) had leukemia. Of n = 50 randomized to PRISM and n = 44 to UC, 37 (74%) and 33 (73%) completed all study procedures, respectively. In intention-to-treat analyses, PRISM did not affect 6-month depression and anxiety (β = -1.1; 95% CI, -3.7 to 1.5), hope (β = 0.83; 95% CI, -3.3 to 4.9), resilience (β = -0.01; 95% CI, -3.0 to 3.0), or HRQOL (β = 1.5; 95% CI, -4.7 to 7.9). Among AYAs with preexisting anxiety or depression, PRISM recipients reported greater 6-month improvements in hope (score change, +3.71; SD, 6.9) versus UC recipients (score change, -2.76; SD, 6.5) (p = .04).

CONCLUSIONS: Resilience coaching did not influence outcomes in this sample. Exploratory findings suggest it may be more effective when directed toward those with concurrent distress.},
}

@article {pmid39029743,
year = {2024},
author = {Cuthbertson, CC and Evenson, KR and Wen, F and Moore, CC and Howard, AG and Di, C and Parada, H and Matthews, CE and Manson, JE and Buring, J and Shiroma, EJ and LaCroix, AZ and Lee, IM},
title = {Associations of steps per day and step intensity with the risk of cancer: Findings from the Women's Health Accelerometry Collaboration cohort.},
journal = {Preventive medicine},
volume = {186},
number = {},
pages = {108070},
doi = {10.1016/j.ypmed.2024.108070},
pmid = {39029743},
issn = {1096-0260},
abstract = {OBJECTIVE: Accumulating more steps/day is associated with a lower risk of cancer mortality and composite cancer outcomes. However, less is known about the relationship of steps/day with the risk of multiple site-specific cancers.

METHODS: This study included >22,000 women from the Women's Health Accelerometry Collaboration Cohort (2011-2022), comprised of women from the Women's Health Study and Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study. Steps/day and step intensity were collected with accelerometry. Incident cancer cases and deaths were adjudicated. Stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of steps/day and step intensity with incident breast, colon, endometrial, lung, and ovarian cancers, a composite of 13 physical activity-related cancers, total invasive cancer, and fatal cancer.

RESULTS: On average, women were 73.4 years old, accumulated 4993 steps/day, and had 7.9 years of follow-up. There were small nonsignificant inverse associations with the risks of colon cancer (HR = 0.94, 95% CI: 0.83, 1.05), endometrial cancer (HR = 0.91, 95% CI: 0.82, 1.01), and fatal cancer (HR = 0.95 95% CI: 0.90, 1.00) per 1000 steps/day. More minutes at ≥40 steps/min and a faster peak 10- and 30-min step cadence were associated with a lower risk of endometrial cancer, but findings were attenuated after adjustment for body mass index and steps/day.

CONCLUSIONS: Among women 62-97 years, there were small nonsignificant inverse associations of colon, endometrial, and fatal cancer with more steps/day. Epidemiologic studies with longer follow-up and updated assessments are needed to further explore these associations.},
}

@article {pmid39028918,
year = {2024},
author = {Chlebowski, RT and Aragaki, AK and Pan, K and Luo, J and Rohan, TE and Johnson, KC and Wactawski-Wende, J and Jung, SY and Xiao, Q and Lavasani, S and Manson, JE and Simon, MS},
title = {Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2302092},
doi = {10.1200/JCO.23.02092},
pmid = {39028918},
issn = {1527-7755},
abstract = {Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report long-term colorectal cancer findings from the Women's Health Initiative trial where 16,608 postmenopausal women with a uterus were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg, plus medroxyprogesterone acetate (MPA) 2.5 mg, or placebo. When intervention ended after 5.6 years, although there were 44% fewer colorectal cancers in the intervention group (43 v 72, P = .003), the cancers were more commonly lymph node-positive (59.0% v 29.4%, P = .003). Now after cumulative 24-year follow-up, with 431 colorectal cancers, CEE plus MPA no longer influenced colorectal cancer incidence (215 [0.15, annualized rate %] v 216 [0.15], hazard ratio [HR], 0.95 [95% CI, 0.79 to 1.15]). Although not statistically significant, there were more colorectal cancer deaths with CEE plus MPA (87 [0.049] v 69 [0.041] deaths, HR, 1.20 [95% CI, 0.87 to 1.65], P = .26). Vaginal bleeding (54.1% v 5.2% at 6 months) and breast changes were more frequent in the intervention group. After adjusting for postrandomization vaginal bleeding and breast changes, bowel examinations were significantly delayed in intervention group participants (P = .005), potentially contributing to diagnostic delay. Taken together, the findings suggest no clinically meaningful benefit for about 5 years of CEE plus MPA use on colorectal cancer outcome.},
}

@article {pmid39028203,
year = {2024},
author = {Hsu, VP and Pergam, SA and Shenoy, ES and Banach, DB and Jones Batshon, L and Branch-Elliman, W and Dumyati, G and Haessler, S and Jump, RLP and Malani, AN and Mathew, TA and Murthy, RK and Weber, DJ},
title = {SHEA position statement on pandemic preparedness for policymakers: emerging infectious threats.},
journal = {Infection control and hospital epidemiology},
volume = {},
number = {},
pages = {1-3},
doi = {10.1017/ice.2024.64},
pmid = {39028203},
issn = {1559-6834},
}

@article {pmid39026837,
year = {2024},
author = {Grosely, R and Alvarado, C and Ivanov, IP and Nicholson, OB and Puglisi, JD and Dever, TE and Lapointe, CP},
title = {eIF1 and eIF5 dynamically control translation start site fidelity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39026837},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R35 GM145306/GM/NIGMS NIH HHS/United States ; R00 GM144678/GM/NIGMS NIH HHS/United States ; RF1 AG064690/AG/NIA NIH HHS/United States ; R01 AG064690/AG/NIA NIH HHS/United States ; },
abstract = {Translation initiation defines the identity of a synthesized protein through selection of a translation start site on a messenger RNA. This process is essential to well-controlled protein synthesis, modulated by stress responses, and dysregulated in many human diseases. The eukaryotic initiation factors eIF1 and eIF5 interact with the initiator methionyl-tRNAi [Met] on the 40S ribosomal subunit to coordinate start site selection. Here, using single-molecule analysis of in vitro reconstituted human initiation combined with translation assays in cells, we examine eIF1 and eIF5 function. During translation initiation on a panel of RNAs, we monitored both proteins directly and in real time using single-molecule fluorescence. As expected, eIF1 loaded onto mRNAs as a component of the 43S initiation complex. Rapid (~ 2 s) eIF1 departure required a translation start site and was delayed by alternative start sites and a longer 5' untranslated region (5'UTR). After its initial departure, eIF1 rapidly and transiently sampled initiation complexes, with more prolonged sampling events on alternative start sites. By contrast, eIF5 only transiently bound initiation complexes late in initiation immediately prior to association of eIF5B, which allowed joining of the 60S ribosomal subunit. eIF5 association required the presence of a translation start site and was inhibited and destabilized by alternative start sites. Using both knockdown and overexpression experiments in human cells, we validated that eIF1 and eIF5 have opposing roles during initiation. Collectively, our findings demonstrate how multiple eIF1 and eIF5 binding events control start-site selection fidelity throughout initiation, which is tuned in response to changes in the levels of both proteins.},
}

@article {pmid39026820,
year = {2024},
author = {Krishnamoorthy, GP and Glover, AR and Untch, BR and Sigcha-Coello, N and Xu, B and Vukel, D and Liu, Y and Tiedje, V and Berman, K and Tamarapu, PP and Acuña-Ruiz, A and Saqcena, M and de Stanchina, E and Boucai, L and Ghossein, RA and Knauf, JA and Abdel-Wahab, O and Bradley, RK and Fagin, JA},
title = {RBM10 loss induces aberrant splicing of cytoskeletal and extracellular matrix mRNAs and promotes metastatic fitness.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39026820},
issn = {2692-8205},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA050706/CA/NCI NIH HHS/United States ; R01 CA249663/CA/NCI NIH HHS/United States ; R01 CA255211/CA/NCI NIH HHS/United States ; },
abstract = {RBM10 modulates transcriptome-wide cassette exon splicing. Loss-of-function RBM10 mutations are enriched in thyroid cancers with distant metastases. Analysis of transcriptomes and genes mis-spliced by RBM10 loss showed pro-migratory and RHO/RAC signaling signatures. RBM10 loss increases cell velocity. Cytoskeletal and ECM transcripts subject to exon-inclusion events included vinculin (VCL), tenascin C (TNC) and CD44. Knockdown of the VCL exon inclusion transcript in RBM10-null cells reduced cell velocity, whereas knockdown of TNC and CD44 exon-inclusion isoforms reduced invasiveness. RAC1-GTP levels were increased in RBM10-null cells. Mouse Hras [G12V] /Rbm1O [KO] thyrocytes develop metastases that are reversed by RBM10 or by combined knockdown of VCL, CD44 and TNC inclusion isoforms. Thus, RBM10 loss generates exon inclusions in transcripts regulating ECM-cytoskeletal interactions, leading to RAC1 activation and metastatic competency. Moreover, a CRISPR-Cas9 screen for synthetic lethality with RBM10 loss identified NFkB effectors as central to viability, providing a therapeutic target for these lethal thyroid cancers.},
}

@article {pmid39026080,
year = {2024},
author = {Nagle, CM and Ibiebele, TI and Bandera, EV and Cramer, D and Doherty, JA and Giles, GG and Goodman, MT and Hanley, GE and Harris, HR and Jensen, A and Kjaer, SK and Lee, AW and Milne, RL and Qin, B and Richardson, J and Sasamoto, N and Sieh, W and Terry, KL and Titus, L and Trabert, B and Wentzensen, N and Wu, AH and Berchuck, A and Pike, M and Pearce, CL and Webb, PM},
title = {Pre-diagnosis tea and coffee consumption and survival after a diagnosis of ovarian cancer: results from the Ovarian Cancer Association Consortium.},
journal = {British journal of cancer},
volume = {},
number = {},
pages = {},
pmid = {39026080},
issn = {1532-1827},
support = {NIH-K07-CA095666, R01-CA83918, NIH-K22-CA138563, P30-CA072720//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-CA54419, P50-CA105009//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-CA112523, R01-CA87538//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-CA58598, N01-CN-55424, N01-PC-67001//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-CA61107//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-CA61107//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-CA54419, P50-CA105009//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P01-CA17054, P30-CA14089, R01-CA61132, N01-PC67010, R03-CA113148, R03-CA115195, N01-CN025403//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; //Rutgers Cancer Institute of New Jersey (Cancer Institute of New Jersey)/ ; W81XWH-10-1-02802//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH-10-1-02802//U.S. Department of Defense (United States Department of Defense)/ ; 209057, 396414, 1074383//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 209057, 396414, 1074383//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Intramural Research Program//U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)/ ; W81XSH-16-2-0010//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; },
abstract = {BACKGROUND: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain.

METHODS: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).

RESULTS: Compared with women who did not drink any green tea, consumption of one or more cups/day was associated with better overall survival (aHR = 0.84, 95% CI 0.71-1.00, p-trend = 0.04). A similar association was seen for ovarian cancer-specific survival in five studies with this information (aHR = 0.81, 0.66-0.99, p-trend = 0.045). There was no consistent variation between subgroups defined by clinical or lifestyle characteristics and adjustment for other aspects of lifestyle did not appreciably alter the estimates. We found no evidence of an association between coffee, black or herbal tea, or caffeine intake and survival.

CONCLUSION: The observed association with green tea consumption before diagnosis raises the possibility that consumption after diagnosis might improve patient outcomes.},
}

@article {pmid39025648,
year = {2024},
author = {Frost, SHL and Orozco, JJ and Bäck, TA and Miller, BW and Santos, EB and Kenoyer, A and Knoblaugh, SE and Hamlin, DK and Wilbur, DS and Sandmaier, BM},
title = {[211]At-Labeled Anti-CD45 Antibody as a Nonmyeloablative Conditioning for Canine DLA-Haploidentical Stem Cell Transplantation.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.124.267540},
pmid = {39025648},
issn = {1535-5667},
abstract = {The α-emitter [211]At deposits a high amount of energy within a few cell diameters, resulting in irreparable DNA double-strand breaks while minimizing off-target toxicity. We investigated the use of the [211]At-labeled anti-CD45 monoclonal antibody (mAb) [211]At-CD45-B10 as a nonmyeloablative conditioning regimen for dog-leukocyte-antigen-haploidentical hematopoietic cell transplantation. Methods: Seventeen healthy dogs were injected with either a 0.50 (n = 14) or 0.75 (n = 3) mg/kg dose of anti-CD45 mAb labeled with [211]At (8.436-23.199 MBq [0.228-0.627 mCi/kg]) on day -3. Peripheral blood stem cells from dog-leukocyte-antigen-haploidentical donors were given on day 0. Peripheral blood chimerism was calculated by polymerase chain reaction assays, and blood clearance of the radioimmunoconjugate was studied using enzyme-linked immunosorbent assay and radioactivity measurements of serial blood samples. Results: All dogs achieved donor chimerism by day 28 (range, 27%-100%). The hematopoietic engraftment rate was 100%, though engraftment durability was variable. No difference in absorbed dose to blood was seen for the 2 mAb dosing levels studied. Neutropenia (0-29 cells/μL), lymphocytopenia (36-130 cells/μL), and thrombocytopenia (1.5-9 × 10[3]/μL) with prompt recovery were observed. The main adverse nonhematologic event related to [211]At-CD45-B10 was mild reversible transaminitis. Graft-versus-host disease was not seen. Twelve of the 17 dogs survived over 30 d, with donor chimerism ranging from 3% to 99%. Conclusion: The results suggest that nonmyeloablative conditioning with [211]At-CD45-B10 could be used in haploidentical hematopoietic cell transplantation though with variable engraftment.},
}

@article {pmid39025327,
year = {2024},
author = {Aglago, EK and Qu, C and Harlid, S and Phipps, AI and Steinfelder, RS and Ogino, S and Thomas, CE and Hsu, L and Toland, AE and Brenner, H and Berndt, SI and Buchanan, DD and Campbell, PT and Cao, Y and Chan, AT and Drew, DA and Figueiredo, JC and French, AJ and Gallinger, S and Georgeson, P and Giannakis, M and Goode, EL and Gruber, SB and Gunter, MJ and Harrison, TA and Hoffmeister, M and Huang, WY and Hullar, MA and Huyghe, JR and Jenkins, MA and Lynch, BM and Moreno, V and Murphy, N and Newton, CC and Nowak, JA and Obón-Santacana, M and Sun, W and Ugai, T and Um, CY and Zaidi, SH and Tsilidis, KK and van Guelpen, B and Peters, U},
title = {Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2024.07.012},
pmid = {39025327},
issn = {1938-3207},
abstract = {BACKGROUND: Folate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer.

OBJECTIVE: We examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to somatic mutations in genes linked to CRC using targeted sequencing.

DESIGN: Participants within two large CRC consortia with available information on dietary folate, supplemental folic acid, and total folate intake were included. Colorectal tumor samples from cases were sequenced for the presence of non-silent mutations in 105 genes and 6 signaling pathways (IGF2/PI3K, MMR, RTK/RAS, TGF-β, WNT, TP53/ATM). Multinomial logistic regression models were run comparing mutated/non-mutated CRC cases to controls to compute multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (CI). Heterogeneity of associations of mutated versus non-mutated CRC cases was tested in case-only analyses using logistic regression. Analyses were performed separately in hypermutated and non-hypermutated tumors, as they exhibit different clinical behaviors.

RESULTS: We included 4,339 CRC cases (702 hypermutated tumors, 16.2%) and 11,767 controls. Total folate intake was inversely associated with CRC risk (OR=0.93, 95%CI=0.90-0.96). Among hypermutated tumors, 12 genes (AXIN2, B2M, BCOR, CHD1, DOCK3, FBLN2, MAP3K21, POLD1, RYR1, TET2, UTP20, ZNF521) showed nominal statistical significance (P<0.05) for heterogeneity by mutation status, but none remained significant after multiple testing correction. Among these genetic subtypes, the associations between folate variables and CRC were mostly inverse or towards the null, except for tumors mutated for DOCK3 (supplemental folic acid), CHD1 (total folate), and ZNF521 (dietary folate) that showed positive associations. We did not observe differential associations in analyses among non-hypermutated tumors, or according to the signaling pathways.

CONCLUSIONS: Folate intake was not differentially associated with CRC risk according to mutations in the genes explored. The nominally significant differential mutation effects observed in a few genes warrants further investigation.},
}

@article {pmid39024224,
year = {2024},
author = {Wilkens, LR and Castelfranco, AM and Monroe, KR and Kristal, BS and Cheng, I and Maskarinec, G and Hullar, MA and Lampe, JW and Shepherd, JA and Franke, AA and Ernst, T and Le Marchand, L and Lim, U},
title = {Prediction of future visceral adiposity and application to cancer research: The Multiethnic Cohort Study.},
journal = {PloS one},
volume = {19},
number = {7},
pages = {e0306606},
pmid = {39024224},
issn = {1932-6203},
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Adiposity ; Body Mass Index ; Case-Control Studies ; Cohort Studies ; Ethnicity ; *Intra-Abdominal Fat/diagnostic imaging ; Magnetic Resonance Imaging ; Neoplasms/diagnostic imaging ; Racial Groups ; },
abstract = {BACKGROUND: We previously developed a prediction score for MRI-quantified abdominal visceral adipose tissue (VAT) based on concurrent measurements of height, body mass index (BMI), and nine blood biomarkers, for optimal performance in five racial/ethnic groups. Here we evaluated the VAT score for prediction of future VAT and examined if enhancement with additional biomarkers, lifestyle behavior information, and medical history improves the prediction.

METHODS: We examined 500 participants from the Multiethnic Cohort (MEC) with detailed data (age 50-66) collected 10 years prior to their MRI assessment of VAT. We generated three forecasted VAT prediction models: first by applying the original VAT equation to the past data on the predictors ("original"), second by refitting the past data on anthropometry and biomarkers ("refit"), and third by building a new prediction model based on the past data enhanced with lifestyle and medical history ("enhanced"). We compared the forecasted prediction scores to future VAT using the coefficient of determination (R2). In independent nested case-control data in MEC, we applied the concurrent and forecasted VAT models to assess association of the scores with subsequent incident breast cancer (950 pairs) and colorectal cancer (831 pairs).

RESULTS: Compared to the VAT prediction by the concurrent VAT score (R2 = 0.70 in men, 0.68 in women), the forecasted original VAT score (R2 = 0.54, 0.48) performed better than past anthropometry alone (R2 = 0.47, 0.40) or two published scores (VAI, METS-VF). The forecasted refit (R2 = 0.61, 0.51) and enhanced (R2 = 0.62, 0.55) VAT scores each showed slight improvements. Similar to the concurrent VAT score, the forecasted VAT scores were associated with breast cancer, but not colorectal cancer. Both the refit score (adjusted OR for tertile 3 vs. 1 = 1.27; 95% CI: 1.00-1.62) and enhanced score (1.27; 0.99-1.62) were associated with breast cancer independently of BMI.

CONCLUSIONS: Predicted VAT from midlife data can be used as a surrogate to assess the effect of VAT on incident diseases associated with obesity, as illustrated for postmenopausal breast cancer.},
}

Aged
Female
Humans
Male
Middle Aged
*Adiposity
Body Mass Index
Case-Control Studies
Cohort Studies
Ethnicity
*Intra-Abdominal Fat/diagnostic imaging
Magnetic Resonance Imaging
Neoplasms/diagnostic imaging
Racial Groups

@article {pmid39023913,
year = {2024},
author = {Neuhouser, ML and Schenk, JM and Wright, JL},
title = {Exercise for Prostate Cancer-Worthy Goals but Suboptimal Trial Designs.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2024.2057},
pmid = {39023913},
issn = {2374-2445},
}

@article {pmid39023869,
year = {2024},
author = {Radich, J},
title = {Transplant, MRD, and predicting relapse in AML.},
journal = {Blood},
volume = {144},
number = {3},
pages = {245-247},
doi = {10.1182/blood.2024024870},
pmid = {39023869},
issn = {1528-0020},
mesh = {Humans ; *Leukemia, Myeloid, Acute/pathology/diagnosis ; *Neoplasm, Residual/diagnosis ; *Hematopoietic Stem Cell Transplantation ; Recurrence ; Prognosis ; Male ; },
}

Humans
*Leukemia, Myeloid, Acute/pathology/diagnosis
*Neoplasm, Residual/diagnosis
*Hematopoietic Stem Cell Transplantation
Recurrence
Prognosis
Male

@article {pmid39022903,
year = {2024},
author = {Rosen, EA and Stohs, EJ},
title = {Changing the culture of blood cultures: Opportunities for diagnostic stewardship in febrile neutropenia.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e14346},
doi = {10.1111/tid.14346},
pmid = {39022903},
issn = {1399-3062},
support = {T32AI118690//National Institute of Allergy and Infectious Diseases of the National Institutes of Health/ ; /NH/NIH HHS/United States ; },
}

@article {pmid39021245,
year = {2024},
author = {Zang, PD and Seylani, A and Yu, EY and Dorff, TB},
title = {PROTAC'ing the androgen receptor and other emerging therapeutics in prostate cancer.},
journal = {Expert review of anticancer therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14737140.2024.2379913},
pmid = {39021245},
issn = {1744-8328},
abstract = {INTRODUCTION: The androgen receptor (AR) is a critical driver of prostate cancer progression and the advent of androgen receptor pathway inhibitors (ARPIs) has transformed the treatment landscape of metastatic prostate cancer. However, resistance to ARPIs eventually develops via mutations in AR, AR overexpression, and alternative AR signaling which have required novel approaches to target effectively.

AREAS COVERED: The mechanism of action and early clinical results of proteolysis targeting chimera (PROTAC) agents targeting AR are reviewed. Preclinical and early clinical data for other emerging AR-targeting therapeutics, including dual anti-androgen receptor inhibitors (DAARIs) and anitens that target the N-terminal domain (NTD) of AR, were also identified through literature search for agents which may circumvent resistance through AR splice variants and AR LBD mutations. The literature search utilized PubMed to identify articles that were relevant to this review from 2000 - 2024.

EXPERT OPINION: PROTACs, DAARIs, and anitens represent novel and promising AR-targeting therapeutics that may become an important part of prostate cancer treatment in the future. Elucidating mechanisms of resistance, including ability of these agents to target full length AR, may yield further insights into maximal therapeutic efficacy aimed at silencing AR signaling.},
}

@article {pmid39020019,
year = {2024},
author = {Gjærde, LK and Brück, O and Gagelmann, N and Gavriilaki, E and Inngjerdingen, M and Keranen, M and Kisch, A and Myhre, AE and Olivieri, A and Perez-Simon, JA and Perovic, D and Perovic, V and Piekarska, A and Pulanic, D and Rathje, K and Van Veen, S and Dachy, G and Moiseev, I and Penack, O and Peric, Z and Greinix, H and Lee, SJ and Wolff, D and Schoemans, H},
title = {Standardized translations of the Lee Chronic GvHD Symptom Scale to 12 European languages: an EU COST Action cGvHD Eurograft project.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {39020019},
issn = {1476-5365},
}

@article {pmid39019980,
year = {2024},
author = {Broderick, A and Pan, E and Li, J and Chu, A and Hwang, C and Barata, PC and Cackowski, FC and Labriola, M and Ghose, A and Bilen, MA and Kilari, D and Thapa, B and Piero, M and Graham, L and Tripathi, A and Garje, R and Koshkin, VS and Hernandez, E and Dorff, TB and Schweizer, MT and Alva, AS and McKay, RR and Armstrong, AJ},
title = {Clinical implications of Wnt pathway genetic alterations in men with advanced prostate cancer.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {39019980},
issn = {1476-5608},
support = {R01 1R01CA233585//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {BACKGROUND: Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models but the impact of genetic alterations in Wnt signaling genes in men with advanced prostate cancer is unknown.

METHODS: We utilized the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database for this retrospective analysis. Patients with activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 were defined as Wnt-altered, while those lacking such alterations were defined as Wnt non-altered. We compared patient characteristics and clinical outcomes as well as co-occurring genetic alterations according to Wnt alteration status.

RESULTS: Of the 1498 patients included, 193 (12.9%) were Wnt-altered. These men had a statistically significant 2-fold increased prevalence of liver and lung metastases as compared with Wnt non-altered patients at the time of initial diagnosis, (4.66% v 2.15% ; 6.22% v 3.07%), first metastatic disease diagnosis (10.88% v 5.29%; 13.99% v 6.21%), and CRPC development (11.40% v 6.36%; 12.95% v 5.29%). Wnt alterations were associated with more co-occurring alterations in RB1 (10.4% v 6.2%), AR (38.9% vs 25.7%), SPOP (13.5% vs 4.1%), FOXA1 (6.7% vs 2.8%), and PIK3CA (10.9% vs 5.1%). We found no significant differences in overall survival or other clinical outcomes from initial diagnosis, first metastatic disease, diagnosis of CRPC, or with AR inhibition for mCRPC between the Wnt groups.

CONCLUSIONS: Wnt-altered patients with prostate cancer have a higher prevalence of visceral metastases and are enriched in RB1, AR, SPOP, FOXA1, and PIK3CA alterations. Despite these associations, Wnt alterations were not associated with worse survival or treatment outcomes in men with advanced prostate cancer.},
}

@article {pmid39019209,
year = {2024},
author = {Barbour, AB and Upadhyay, R and Anderson, AC and Kutuk, T and Kumar, R and Wang, SJ and Psutka, SP and Fekrmandi, F and Skalina, KA and Bruynzeel, AME and Correa, RJM and Pra, AD and Biancia, CD and Hannan, R and Louie, A and Singh, AK and Swaminath, A and Tang, C and Teh, BS and Zaorsky, NG and Lo, SS and Siva, S},
title = {Stereotactic Body Radiotherapy for Primary Renal Cell Carcinoma: A Case-Based Radiosurgery Society Practice Guide.},
journal = {Practical radiation oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.prro.2024.06.012},
pmid = {39019209},
issn = {1879-8519},
abstract = {Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiotherapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of an expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by three cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques like MRI-guided SBRT, and SBRT response assessment.},
}

@article {pmid39019058,
year = {2024},
author = {Gradishar, WJ and Moran, MS and Abraham, J and Abramson, V and Aft, R and Agnese, D and Allison, KH and Anderson, B and Bailey, J and Burstein, HJ and Chen, N and Chew, H and Dang, C and Elias, AD and Giordano, SH and Goetz, MP and Jankowitz, RC and Javid, SH and Krishnamurthy, J and Leitch, AM and Lyons, J and McCloskey, S and McShane, M and Mortimer, J and Patel, SA and Rosenberger, LH and Rugo, HS and Santa-Maria, C and Schneider, BP and Smith, ML and Soliman, H and Stringer-Reasor, EM and Telli, ML and Wei, M and Wisinski, KB and Yeung, KT and Young, JS and Schonfeld, R and Kumar, R},
title = {Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {22},
number = {5},
pages = {331-357},
doi = {10.6004/jnccn.2024.0035},
pmid = {39019058},
issn = {1540-1413},
mesh = {Humans ; *Breast Neoplasms/therapy/diagnosis/pathology ; Female ; Medical Oncology/standards/methods ; Combined Modality Therapy/standards ; },
abstract = {Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.},
}

Humans
*Breast Neoplasms/therapy/diagnosis/pathology
Female
Medical Oncology/standards/methods
Combined Modality Therapy/standards

@article {pmid39005374,
year = {2024},
author = {Wu, P and Becker, FB and Ogelman, R and Camci, ED and Linbo, TH and Simon, JA and Rubel, EW and Raible, DW},
title = {Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39005374},
issn = {2692-8205},
support = {R01 DC005987/DC/NIDCD NIH HHS/United States ; },
abstract = {Mechanosensory hair cells of the inner ears and lateral line of vertebrates display heightened vulnerability to environmental insult, with damage resulting in hearing and balance disorders. An important example is hair cell loss due to exposure to toxic agents including therapeutic drugs such as the aminoglycoside antibiotics such as neomycin and gentamicin and antineoplastic agents. We describe two distinct cellular pathways for aminoglycoside-induced hair cell death in zebrafish lateral line hair cells. Neomycin exposure results in death from acute exposure with most cells dying within 1 hour of exposure. By contrast, exposure to gentamicin results primarily in delayed hair cell death, taking up to 24 hours for maximal effect. Washout experiments demonstrate that delayed death does not require continuous exposure, demonstrating two mechanisms where downstream responses differ in their timing. Acute damage is associated with mitochondrial calcium fluxes and can be alleviated by the mitochondrially-targeted antioxidant mitoTEMPO, while delayed death is independent of these factors. Conversely delayed death is associated with lysosomal accumulation and is reduced by altering endolysosomal function, while acute death is not sensitive to lysosomal manipulations. These experiments reveal the complexity of responses of hair cells to closely related compounds, suggesting that intervention focusing on early events rather than specific death pathways may be a successful therapeutic strategy.},
}

@article {pmid39005354,
year = {2024},
author = {MacLean, F and Tsegaye, AT and Graham, JB and Swarts, JL and Vick, SC and Potchen, N and Talavera, IC and Warrier, L and Dubrulle, J and Schroeder, LK and Mar, C and Thomas, KK and Mack, M and Sabo, MC and Chohan, BH and Ngure, K and Mugo, N and Lingappa, JR and Lund, JM and , },
title = {Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39005354},
issn = {2692-8205},
support = {T32 AI007509/AI/NIAID NIH HHS/United States ; T32 AI007140/AI/NIAID NIH HHS/United States ; R01 AI131914/AI/NIAID NIH HHS/United States ; R01 AI141435/AI/NIAID NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; T32 AI083203/AI/NIAID NIH HHS/United States ; R01 AI129715/AI/NIAID NIH HHS/United States ; },
abstract = {Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent in reproductive-age women worldwide. Adverse outcomes associated with BV include an increased risk of sexually acquired Human Immunodeficiency Virus (HIV), yet the immunological mechanisms underlying this association are not well understood. To investigate BV driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and peripheral blood mononuclear cells (PBMC). Immunofluorescence analysis of genital mucosal tissues revealed a reduced density of CD3[+]CD4[+]CCR5[+] cells in the VT lamina propria of individuals with compared to those without BV (median 243.8 cells/mm[2] BV- vs 106.9 cells/mm[2] BV+, p=0.043). High-parameter flow cytometry of VT biopsies revealed an increased frequency in individuals with compared to those without BV of dysfunctional CD39[+] conventional CD4[+] T cells (Tconv) (median frequency 15% BV- vs 30% BV+, padj=0.0331) and tissue-resident CD69+CD103[+] Tconv (median frequency 24% BV- vs 38% BV+, padj=0.0061), previously reported to be implicated in HIV acquisition and replication. Our data suggests that BV elicits diverse and complex VT T cell alterations and expands on potential immunological mechanisms that may promote adverse outcomes including HIV susceptibility.},
}

@article {pmid39019054,
year = {2024},
author = {Swetter, SM and Johnson, D and Albertini, MR and Barker, CA and Bateni, S and Baumgartner, J and Bhatia, S and Bichakjian, C and Boland, G and Chandra, S and Chmielowski, B and DiMaio, D and Dronca, R and Fields, RC and Fleming, MD and Galan, A and Guild, S and Hyngstrom, J and Karakousis, G and Kendra, K and Kiuru, M and Lange, JR and Lanning, R and Logan, T and Olson, D and Olszanski, AJ and Ott, PA and Ross, MI and Rothermel, L and Salama, AK and Sharma, R and Skitzki, J and Smith, E and Tsai, K and Wuthrick, E and Xing, Y and McMillian, N and Espinosa, S},
title = {NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {22},
number = {5},
pages = {290-298},
doi = {10.6004/jnccn.2024.0036},
pmid = {39019054},
issn = {1540-1413},
mesh = {Humans ; *Melanoma/therapy/diagnosis/pathology ; *Skin Neoplasms/therapy/diagnosis/pathology ; Neoplasm Staging ; Medical Oncology/standards/methods ; },
abstract = {The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.},
}

Humans
*Melanoma/therapy/diagnosis/pathology
*Skin Neoplasms/therapy/diagnosis/pathology
Neoplasm Staging
Medical Oncology/standards/methods

@article {pmid39018074,
year = {2024},
author = {Shen, MJ and Stokes, T and Yarborough, S and Harrison, J},
title = {Improving Pain Self-Management Among Rural Older Adults With Cancer.},
journal = {JAMA network open},
volume = {7},
number = {7},
pages = {e2421298},
pmid = {39018074},
issn = {2574-3805},
mesh = {Humans ; Aged ; Female ; Male ; *Self-Management/methods ; *Rural Population/statistics & numerical data ; *Pain Management/methods ; *Neoplasms/complications/psychology/therapy ; Cancer Pain/therapy/psychology ; Tennessee ; Aged, 80 and over ; Feasibility Studies ; Patient Education as Topic/methods ; },
abstract = {IMPORTANCE: Undertreated cancer pain is a major public health concern among older adults in rural communities. Interventions to improve pain management among this vulnerable population are needed.

OBJECTIVE: To test the feasibility, acceptability, and changes in pain outcomes from exposure to an adapted intervention, Cancer Health Empowerment for Living without Pain (CA-HELP), to improve patients' communication about pain to their clinicians.

Older adults with cancer (aged ≥65 years) who were residing in a noninstitutional rural setting and receiving outpatient care at a rural-based clinic in Tennessee were enrolled in the study, in which everyone received the intervention, in May 2022. All patients were given assessments at baseline and 1 week after intervention. Mean score differences were analyzed using 1-tailed paired sample t tests (α = .05). Data were analyzed in June 2022.

EXPOSURE: The adapted version of CA-HELP included an 18-page patient-facing workbook and a 30-minute telephone coaching call with a registered nurse to coach patients on pain education and communication techniques to discuss pain with their medical team.

MAIN OUTCOMES AND MEASURES: Feasibility was examined through accrual and completion rates. Acceptability was measured by helpfulness, difficulty, and satisfaction with the intervention. Changes in outcomes were measured using mean score differences from pre-post assessments of pain self-management, self-efficacy for communicating with clinicians about pain, patient-reported pain, and misconceptions about pain.

RESULTS: Among the 30 total participants, the mean (SD) age was 73.0 (5.1) years; 17 participants (56.7%) were female, 5 (16.7%) were Black or African American, 30 (100%) were non-Hispanic or non-Latino, 24 (80.0%) were White, 16 (53.3%) had less than a high school education, and 15 (50.0%) reported income less than $21 000 per year. Based on accrual and completion rates of 100%, this intervention was highly feasible. Fidelity rates for delivering intervention components (100%) and communication competence (27 participants [90%]) were also high. Regarding acceptability, all patients rated the intervention as helpful, with the majority (24 participants [80%]) rating it as "very helpful." Most patients rated the intervention as "not at all difficult" (27 participants [90%]), enjoyed participating (21 participants [70%]), and reported being "very satisfied" (25 participants [83.3%]). Pre-post changes in outcomes suggested significant improvements in pain self-management and self-efficacy for communicating with clinicians about pain, as well as significant reductions in patient-reported pain and pain misconceptions.

CONCLUSIONS AND RELEVANCE: In this case-series study of CA-HELP, results suggested the adapted version of CA-HELP was feasible and acceptable and showed changes in pain-related outcome measures among older adults with cancer in a rural setting.},
}

Humans
Aged
Female
Male
*Self-Management/methods
*Rural Population/statistics & numerical data
*Pain Management/methods
*Neoplasms/complications/psychology/therapy
Cancer Pain/therapy/psychology
Tennessee
Aged, 80 and over
Feasibility Studies
Patient Education as Topic/methods

@article {pmid39017661,
year = {2024},
author = {Rashidi, A and Pidala, J and Hamilton, BK and Pavletic, SZ and Kim, K and Zevin, A and Mays, JW and Lee, SJ},
title = {Oral and gut microbiome alterations in oral chronic graft-versus-host disease: results from Close Assessment and Testing for Chronic GVHD (CATCH study).},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-24-0875},
pmid = {39017661},
issn = {1557-3265},
abstract = {PURPOSE: Whether and how the oral microbiome and its changes in allogeneic hematopoietic cell transplantation (alloHCT) recipients may contribute to oral chronic graft-versus-host disease (cGVHD) pathogenesis is unknown. In addition, while the oral and colonic microbiota are distinct in healthy adults, whether oral microbes may ectopically colonize the gut in alloHCT patients is unknown.

EXPERIMENTAL DESIGN: To address these knowledge gaps, longitudinal oral and fecal samples were collected prospectively in the multicenter CATCH Study (Close Assessment and Testing for Chronic GVHD; NCT04188912). Through shotgun metagenomic sequencing of the samples collected at baseline, oral cGVHD onset, first post-cGVHD onset visit, and 1-year post-HCT timepoints in patients with oral cGVHD (cases; N = 29) or without any cGVHD (controls; N = 51), we examined whether (i) oral and/or gut microbiomes and their longitudinal trajectories differ between cases and controls, and (ii) oral and gut microbiomes overlap in alloHCT recipients, especially those developing cGVHD.

RESULTS: A total of 195 samples were analyzed. The onset of oral cGVHD was characterized by an expansion of Streptococcus salivarius and Veillonella parvula in the oral microbiome. High levels of oral/gut microbiota overlap were observed, particularly in patients with oral cGVHD, suggesting ectopic colonization of the gut by oral bacteria.

CONCLUSIONS: The unusual coalescence of two distant niches in these patients may have short- or long-term consequences for the host, a novel avenue for future research. In addition, this study suggests a contribution of the oral microbiome to oral cGVHD pathogenesis.},
}

@article {pmid39014324,
year = {2024},
author = {Huo, Y and Yang, Y and Halloran, ME and Longini, IM and Dean, NE},
title = {Hypothesis testing and sample size considerations for the test-negative design.},
journal = {BMC medical research methodology},
volume = {24},
number = {1},
pages = {151},
pmid = {39014324},
issn = {1471-2288},
mesh = {Humans ; Sample Size ; Case-Control Studies ; *Research Design ; Vaccine Efficacy/statistics & numerical data ; Logistic Models ; Computer Simulation ; Odds Ratio ; Vaccination/statistics & numerical data ; Observational Studies as Topic/methods/statistics & numerical data ; },
abstract = {The test-negative design (TND) is an observational study design to evaluate vaccine effectiveness (VE) that enrolls individuals receiving diagnostic testing for a target disease as part of routine care. VE is estimated as one minus the adjusted odds ratio of testing positive versus negative comparing vaccinated and unvaccinated patients. Although the TND is related to case-control studies, it is distinct in that the ratio of test-positive cases to test-negative controls is not typically pre-specified. For both types of studies, sparse cells are common when vaccines are highly effective. We consider the implications of these features on power for the TND. We use simulation studies to explore three hypothesis-testing procedures and associated sample size calculations for case-control and TND studies. These tests, all based on a simple logistic regression model, are a standard Wald test, a continuity-corrected Wald test, and a score test. The Wald test performs poorly in both case-control and TND when VE is high because the number of vaccinated test-positive cases can be low or zero. Continuity corrections help to stabilize the variance but induce bias. We observe superior performance with the score test as the variance is pooled under the null hypothesis of no group differences. We recommend using a score-based approach to design and analyze both case-control and TND. We propose a modification to the TND score sample size to account for additional variability in the ratio of controls over cases. This work enhances our understanding of the data generating mechanism in a test-negative design (TND) and how it is distinct from that of a case-control study due to its passive recruitment of controls.},
}

Humans
Sample Size
Case-Control Studies
*Research Design
Vaccine Efficacy/statistics & numerical data
Logistic Models
Computer Simulation
Odds Ratio
Vaccination/statistics & numerical data
Observational Studies as Topic/methods/statistics & numerical data

@article {pmid39013466,
year = {2024},
author = {Carr, CR and Crawford, KHD and Murphy, M and Galloway, JG and Haddox, HK and Matsen, FA and Andersen, KG and King, NP and Bloom, JD},
title = {Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2024.06.013},
pmid = {39013466},
issn = {1097-4180},
abstract = {Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of the Lassa virus's glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we used pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affected cell entry and antibody neutralization. Our experiments defined functional constraints throughout GPC. We quantified how GPC mutations affected neutralization with a panel of monoclonal antibodies. All antibodies tested were escaped by mutations that existed among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid the design of therapeutics and vaccines.},
}

@article {pmid39012906,
year = {2024},
author = {Desai, P and Zhou, Y and Grenet, J and Handelman, SK and Crispino, CM and Tarbay, LN and Whitsel, EA and Roboz, G and Barac, A and Honigberg, M and Bick, A and Anderson, G and Wactawski-Wende, J and Jakubek Swartzlander, YA and Bacon, J and Wong, J and Ma, X and Scheet, P and Li, Z and Kasi, P and Prentice, R and Auer, P and Manson, JE and Reiner, A and Simon, M},
title = {Association of clonal hematopoiesis and mosaic chromosomal alterations with solid malignancy incidence and mortality.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35455},
pmid = {39012906},
issn = {1097-0142},
support = {1 R01 CA248747-01A1/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways.

METHODS: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers.

RESULTS: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or lung cancer (p = .32). CHIP carriers who developed colorectal cancer also had a greater risk for advanced-stage (p = .01), but this was not seen in breast or lung cancer. CHIP was associated with increased colorectal cancer mortality both with (HR, 3.99; 95% CI, 2.41-6.62; p < .001) and without adjustment (HR, 2.50; 95% CI, 1.32-4.72; p = .004) for advanced-stage and a borderline higher breast cancer mortality (HR, 1.53; 95% CI, 0.98-2.41; p = .06). Conversely, mCA (cell fraction [CF] >3%) did not correlate with cancer risk. With higher CFs (mCA >5%), autosomal mCA was associated with increased breast cancer risk (HR, 1.39; 95% CI, 1.06-1.83; p = .01). There was no association of mCA (>3%) with breast, colorectal, or lung mortality except higher colon cancer mortality (HR, 2.19; 95% CI, 1.11-4.3; p = .02) with mCA >5%.

CONCLUSIONS: CHIP and mCA (CF >5%) were associated with higher breast cancer risk and colorectal cancer mortality individually. These data could inform on novel pathways that impact cancer risk and lead to better risk stratification.},
}

@article {pmid39010324,
year = {2024},
author = {Fischer, MD and Green, ML and Selke, S and Limaye, AP and Wald, A and Boeckh, MJ and Phipps, AI and Pergam, SA and Johnston, C},
title = {Evaluation of oral herpes simplex virus shedding among solid organ transplant recipients: A pilot study.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e14335},
doi = {10.1111/tid.14335},
pmid = {39010324},
issn = {1399-3062},
support = {T32 AI 007044//National Institute of Allergy and Infectious Diseases/ ; K-23AI097234//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {BACKGROUND: Herpes simplex viruses (HSVs) frequently reactivate during immunosuppression and may be a risk factor for adverse outcomes after solid organ transplant (SOT). While suppressive antiviral therapy reduces the risk of symptomatic HSV reactivation, the kinetics of asymptomatic viral shedding with chronic immunosuppression after transplant are not well understood. We report the characteristics of oral HSV shedding among 15 HSV-1 seropositive SOT recipients (n = 8 liver, n = 7 kidney, median age 58.5 years, median 20 months post-transplant) who were not taking daily antiviral suppressive therapy.

METHODS: Participants self-collected oral swabs three times daily for 6 weeks for HSV quantification and recorded the presence of oral symptoms or lesions in a diary.

RESULTS: Sample collection adherence was high (median 122 swabs/person, range: 85.7%-101.6% of expected swabs). Most participants (n = 12, 80%) experienced at least one shedding episode, with a median shedding rate of 8.9% (range: 0%-33.6%). There were 32 total shedding episodes, 24 (75%) of which occurred without symptoms or lesions. For episodes of known duration, the median length was 21.8 hrs (interquartile range: 10.8-46.1 hrs).

CONCLUSION: Most shedding episodes (78.1%) lasted >12 hrs, suggesting that twice-daily sampling may be sufficient to detect most episodes. These data show that self-collection of oral swabs is feasible for patients who have undergone SOTs and can provide insight into the frequency of oral HSV reactivation, which can be used to design future studies in this population.},
}

@article {pmid39010279,
year = {2024},
author = {Becktell, K and Chen, Y and Yasui, Y and Phelan, R and Armstrong, GT and Link, M and Oeffinger, K and Snyder, C and Daw, N and Weil, B and Weldon, C and Chow, EJ and Schwartz, CL},
title = {Long-term outcomes among survivors of childhood osteosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e31189},
doi = {10.1002/pbc.31189},
pmid = {39010279},
issn = {1545-5017},
support = {U24 CA055727/CA/NCI NIH HHS/United States ; //American Lebanese-Syrian Associated Charities/ ; P30 CA021765/CA/NCI NIH HHS/United States ; CA55727/CA/NCI NIH HHS/United States ; CA21765//Cancer Center Support/ ; },
abstract = {PURPOSE: Treatment strategies for osteosarcoma evolving between 1970 and 1999 improved 5-year survival and continue as standard of care today. This report evaluates the impact of these evolving therapies on long-term health outcomes.

METHODS: Five-year survivors of childhood osteosarcoma in CCSS treated from 1970 to 1999 were evaluated for late (>5 years from diagnosis) mortality, chronic health conditions (CHCs), and health status using piecewise-exponential and logistical models. Comparisons were made between survivors and siblings without cancer, and among survivors examining historical and current standard chemotherapies (e.g., methotrexate/doxorubicin/cisplatin [MAP] vs. others), specific chemotherapy agents and surgical approaches (amputation vs. limb salvage [LS]). Models were evaluated adjusting for attained age, sex, race, ethnicity, and age at diagnosis.

RESULTS: A total of 1257 survivors of osteosarcoma were followed on average for 24.4 years. Twenty-year all-cause late mortality was 13.3% (95% confidence interval [CI]: 11.7%-14.9%) overall and 11.7% (95% CI: 6.9%-16.5%) for the subset treated with MAP plus LS. Survivors were at higher risk of CHCs (rate ratio [RR] 3.7, 95% CI: 3.2-4.3) than the sibling cohort, most notably having more serious cardiac, musculoskeletal, and hearing CHCs. Within the survivor cohort, the risk of severe CHCs was twice as high with MAP versus no chemotherapy (RR 2.1, 95% CI: 1.3-3.4). Compared with primary amputation, serious musculoskeletal CHCs were higher after LS (RR 6.6, 95% CI: 3.6-13.4), without discernable differences in health status.

CONCLUSION: Contemporary osteosarcoma therapy with MAP plus LS, while improving 5-year disease-free survival, continues to be associated with a high burden of late mortality, CHCs, and health status limitations.},
}

@article {pmid39009580,
year = {2024},
author = {Wacker, JN and Woods, JJ and Rupert, PB and Peterson, A and Allaire, M and Lukens, WW and Gaiser, AN and Minasian, SG and Strong, RK and Abergel, RJ},
title = {Actinium chelation and crystallization in a macromolecular scaffold.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {5741},
pmid = {39009580},
issn = {2041-1723},
support = {P30 GM124169/GM/NIGMS NIH HHS/United States ; DE-AC02-05CH11231//U.S. Department of Energy (DOE)/ ; },
mesh = {*Actinium/chemistry ; *Chelating Agents/chemistry ; Crystallization ; Radiopharmaceuticals/chemistry ; Humans ; Ligands ; },
abstract = {Targeted alpha therapy (TAT) pairs the specificity of antigen targeting with the lethality of alpha particles to eradicate cancerous cells. Actinium-225 [[225]Ac; t1/2 = 9.920(3) days] is an alpha-emitting radioisotope driving the next generation of TAT radiopharmaceuticals. Despite promising clinical results, a fundamental understanding of Ac coordination chemistry lags behind the rest of the Periodic Table due to its limited availability, lack of stable isotopes, and inadequate systems poised to probe the chemical behavior of this radionuclide. In this work, we demonstrate a platform that combines an 8-coordinate synthetic ligand and a mammalian protein to characterize the solution and solid-state behavior of the longest-lived Ac isotope, [227]Ac [t1/2 = 21.772(3) years]. We expect these results to direct renewed efforts for [225]Ac-TAT development, aid in understanding Ac coordination behavior relative to other +3 lanthanides and actinides, and more broadly inform this element's position on the Periodic Table.},
}

*Actinium/chemistry
*Chelating Agents/chemistry
Crystallization
Radiopharmaceuticals/chemistry
Humans
Ligands

@article {pmid39005399,
year = {2024},
author = {Briney, CA and Henriksen, JC and Lin, C and Jones, LA and Benner, L and Rains, AB and Gutierrez, R and Gafken, PR and Rissland, OS},
title = {Muskelin acts as a substrate receptor of the highly regulated Drosophila CTLH E3 ligase during the maternal-to-zygotic transition.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39005399},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R35 GM128680/GM/NIGMS NIH HHS/United States ; P40 OD010949/OD/NIH HHS/United States ; T32 GM141742/GM/NIGMS NIH HHS/United States ; T32 GM136444/GM/NIGMS NIH HHS/United States ; S10 OD030225/OD/NIH HHS/United States ; },
abstract = {The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that in Drosophila the deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch (TRAL) are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies. In particular, Drosophila lacks an identifiable substrate adaptor, and the mechanisms restricting degradation of ME31B and its cofactors to the MZT are unknown. Here, we show that the developmental specificity of the CTLH complex is mediated by multipronged regulation, including transcriptional control by the transcription factor OVO and autoinhibition of the E3 ligase. One major regulatory target is the subunit Muskelin, which we demonstrate acts as a substrate adaptor for the Drosophila CTLH complex. Although conserved, Muskelin has structural roles in other species, suggesting a surprising functional plasticity. Finally, we find that Muskelin has few targets beyond the three known RNA binding proteins, showing exquisite target specificity. Thus, multiple levels of integrated regulation restrict the activity of the embryonic CTLH complex to early embryogenesis, seemingly with the goal of regulating three important RNA binding proteins.},
}

@article {pmid39009417,
year = {2024},
author = {Arends, T and Hamm, DC and van der Maarel, S and Tapscott, SJ},
title = {Facioscapulohumeral Dystrophy: Molecular Basis and Therapeutic Opportunities.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041492},
pmid = {39009417},
issn = {1943-0264},
abstract = {Facioscapulohumeral dystrophy (FSHD) is caused by misexpression of the early embryonic transcription factor Double Homeobox Protein 4 (DUX4) in skeletal muscle. DUX4 is normally expressed at the 4-cell stage of the human embryo and initiates a portion of the first wave of embryonic gene expression that establishes the totipotent cells of the embryo. Following brief expression, the DUX4 locus is suppressed by epigenetic silencing and remains silenced in nearly all somatic cells. Mutations that cause FSHD decrease the efficiency of epigenetic silencing of the DUX4 locus and result in aberrant expression of this transcription factor in skeletal muscles. DUX4 expression in these skeletal muscles reactivates part of the early totipotent program and suppresses the muscle program-resulting in a progressive muscular dystrophy that affects some muscles earlier than others. These advances in understanding the cause of FSHD have led to multiple therapeutic strategies that are now entering clinical trials.},
}

@article {pmid39009001,
year = {2024},
author = {Donnell, D},
title = {Reassuring long-term safety, resistance, and efficacy data for two daily formulations of PrEP.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(24)00158-9},
pmid = {39009001},
issn = {2352-3018},
}

@article {pmid39008818,
year = {2024},
author = {Pidala, JA and Gooley, TA and Luznik, L and Blazar, BR},
title = {Chronic graft-versus-host disease: Unresolved complication or ancient history?.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2023022735},
pmid = {39008818},
issn = {1528-0020},
abstract = {Chronic graft-vs.-host disease (GVHD) is associated with morbidity, mortality, impaired quality of life, prolonged immunosuppressive (IS) therapy, and infection risk after allogeneic hematopoietic cell transplantation (HCT). Major strides have occurred in the understanding of chronic GVHD biology, NIH Consensus meetings have refined rigorous approaches to diagnosis, staging and response criteria, major interventional trials have established standard benchmarks for treatment outcome, and three agents to date have been FDA-approved for treating steroid-refractory chronic GVHD. Promising results from several recent trials have led some but not others to conclude that the risk of developing chronic GVHD is sufficiently low to by-and-large be considered a major post-HCT complication of the past. We propose that it is time to critically examine the results of contemporary GVHD prophylaxis regimens and discuss the state-of-the-science and associated controversies in spectrum of conclusions reached as to the risk of chronic GVHD. With these data, the current chronic GVHD incidence can be most precisely determined, and the present and future burden of chronic GVHD-affected patients be accurately modeled. Through review of existing evidence, we highlight unresolved needs and opportunities to refine best GVHD prophylaxis or preemptive therapy approaches, optimize established chronic GVHD therapy, and make the argument that support of preclinical and clinical research is critical in improving patient outcomes.},
}

@article {pmid39008789,
year = {2024},
author = {Leonard, S and Helstrom, E and Correa, A and Sindhani, M and Uzzo, N and Jia, AY and Kutikov, A and Uzzo, R and Psutka, SP and Calaway, A and Klaassen, Z and Staehler, M and Smaldone, M and Wallis, CJD and Bukavina, L},
title = {Financial Distress in Genitourinary Cancer: Insights From CDC National Health Interview Survey.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2300733},
doi = {10.1200/OP.23.00733},
pmid = {39008789},
issn = {2688-1535},
abstract = {PURPOSE: This study leverages CDC National Health Interview Survey data to examine Financial Distress (FD) among genitourinary (GU) cancer survivors, specifically prostate cancer (PC), kidney cancer (KC), and bladder cancer (BC). It investigates the economic impacts faced by these patients, especially in relation to disparities in insurance coverage and its effects on material, psychological, and behavioral aspects of FD.

METHODS: We retrospectively analyzed responses from GU cancer survivors, stratifying by cancer status and age (18-64 years, ≥65 years). Medical financial hardship was divided into three domains: material, psychological, and behavioral. Associations between cancer history, hardship, and clinical factors were assessed using generalized ordinal logistic regressions.

RESULTS: Significant health care access disparities were found, particularly for mental health services, with 25% of younger BC survivors and 4.7% of younger KC survivors reporting affordability issues, in contrast to 2.7% of noncancer individuals. Dental care was also problematic, with higher avoidance rates among younger BC (27%) and KC (15%) survivors compared with the general population. Surprisingly, noncancer individuals reported more difficulty in affording prescriptions than BC survivors across both age groups. PC survivors, however, showed lower FD across all domains versus noncancer controls, indicating fewer concerns about medical bills and a lesser tendency to forgo care.

CONCLUSION: The study underscores significant gaps in the financial support system for GU cancer survivors, with urgent needs in mental and dental health care access. Policy interventions, including comprehensive insurance reforms, are imperative to alleviate the financial burdens on these individuals.},
}

@article {pmid39008717,
year = {2024},
author = {Mehta, RS and Petersdorf, EW and Wang, T and Spellman, SR and Lee, SJ},
title = {Interplay between donor age and HLA-DP matching in 10/10 HLA-matched unrelated donor HCT.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024013677},
pmid = {39008717},
issn = {2473-9537},
abstract = {In 10/10 HLA-matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) with calcineurin-inhibitor (CNI)-based prophylaxis, T-cell epitope DP-matched and permissive mismatched donors are associated with similar overall survival (OS) while donors with non-permissive mismatches should be avoided. Younger unrelated donors are also favored over older donors. We explored outcomes associated with different combinations of DP-matching and donor age (dichotomized at 35 years) to further guide donor selection. Using a Center for International Blood and Marrow Transplant Research dataset, we categorized 10,783 patients into six groups: DP-matched/younger donor (n=1591), DP-matched/older donor (n=526), permissive-mismatched/younger donor (n=3845), permissive-mismatched/older donor (n=1184), non-permissive mismatched/younger donor (n=2659), non-permissive mismatched/older donor (n=978). We noted that younger donor age, rather than DP-matching, was associated with better OS. Younger donors with permissive mismatches were associated with improved OS compared to older matched donors. Furthermore, younger donors with non-permissive mismatches were associated with improved OS compared to older donors with permissive mismatches. Our study adds further information about the association of DP-matching and donor age with HCT outcomes. Donor age should be prioritized over DP-matching in patients undergoing 10/10 HLA-MUD with CNI prophylaxis. Among those with younger donors, permissive-mismatched or DP-matched donors are preferred over non-permissive mismatched donors.},
}

@article {pmid39008559,
year = {2024},
author = {Wang, Y and Chen, GC and Wang, Z and Luo, K and Zhang, Y and Li, Y and McClain, AC and Jankowska, MM and Perreira, KM and Mattei, J and Isasi, CR and Llabre, MM and Thyagarajan, B and Daviglus, ML and Van Horn, L and Goldsztajn Farelo, D and Maldonado, LE and Levine, SR and Yu, B and Boerwinkle, E and Knight, R and Burk, RD and Kaplan, RC and Qi, Q and Peters, BA},
title = {Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, and Cardiovascular Disease Risk in US Hispanics and Latinos: Results From HCHS/SOL.},
journal = {Circulation},
volume = {150},
number = {3},
pages = {215-229},
doi = {10.1161/CIRCULATIONAHA.124.069824},
pmid = {39008559},
issn = {1524-4539},
mesh = {Humans ; *Gastrointestinal Microbiome ; Male ; Female ; *Acculturation ; *Cardiovascular Diseases/blood/ethnology ; *Hispanic or Latino ; Middle Aged ; United States/epidemiology ; Adult ; *Diet/adverse effects ; Risk Factors ; Incidence ; },
abstract = {BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults.

METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD.

RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001).

CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.},
}

Humans
*Gastrointestinal Microbiome
Male
Female
*Acculturation
*Cardiovascular Diseases/blood/ethnology
*Hispanic or Latino
Middle Aged
United States/epidemiology
Adult
*Diet/adverse effects
Risk Factors
Incidence

@article {pmid39007490,
year = {2024},
author = {Kumar, A and Rara, M and Yu, M and Wen, KW and Grady, WM and Chak, A and Iyer, PG and Rustgi, AK and Wang, TC and Rubenstein, JH and Liu, Y and Kresty, L and Westerhoff, M and Kwon, RS and Wamsteker, E and Wang, T and Berry, L and Canto, MI and Shaheen, NJ and Wang, KK and Abrams, JA and Stachler, MD},
title = {Molecular analysis of persistent and recurrent Barrett's esophagus in the setting of endoscopic therapy.},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000000751},
pmid = {39007490},
issn = {2155-384X},
support = {U54CA163004/CA/NCI NIH HHS/United States ; U54CA163059/CA/NCI NIH HHS/United States ; U54CA163060/CA/NCI NIH HHS/United States ; U24CA163056/CA/NCI NIH HHS/United States ; R37CA269649/CA/NCI NIH HHS/United States ; Clinician Scientist Development Award/DDCF/Doris Duke Charitable Foundation/United States ; R01CA238433/CA/NCI NIH HHS/United States ; R01CA255298/CA/NCI NIH HHS/United States ; R01CA272898/CA/NCI NIH HHS/United States ; P30DK132710/DK/NIDDK NIH HHS/United States ; Professorship Fund//Russ and Kathy Van Cleve/ ; },
abstract = {INTRODUCTION: Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. While effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease.

METHODS: We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre- and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups.

RESULTS: The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway (p=0.01), amplifications of oncogenes (p=0.01), and deletions of tumor suppressor genes (p=0.02). These associations were no longer significant after adjusting for patient age and BE length. Over half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre- and post-treatment samples that shared at least 50% of their driver mutations.

CONCLUSION: Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. While it was expected to find shared driver mutations in pre- and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.},
}

@article {pmid39006423,
year = {2024},
author = {Asano, Y and Veatch, J and McAfee, M and Bakhtiari, J and Lee, B and Martin, L and Zhang, S and Mazziotta, F and Paulson, KG and Schmitt, TM and Munkbhat, A and Young, C and Seaton, B and Hunter, D and Horst, N and Lindberg, M and Miller, N and Stone, M and Bielas, J and Koelle, D and Voillet, V and Gottardo, R and Gooley, T and Oda, S and Greenberg, PD and Nghiem, P and Chapuis, AG},
title = {Tumor Regression Following Engineered Polyomavirus-Specific T Cell Therapy in Immune Checkpoint Inhibitor-Refractory Merkel Cell Carcinoma.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39006423},
support = {P01 CA225517/CA/NCI NIH HHS/United States ; },
abstract = {Although immune check-point inhibitors (CPIs) revolutionized treatment of Merkel cell carcinoma (MCC), patients with CPI-refractory MCC lack effective therapy. More than 80% of MCC express T-antigens encoded by Merkel cell polyomavirus, which is an ideal target for T-cell receptor (TCR)-based immunotherapy. However, MCC often repress HLA expression, requiring additional strategies to reverse the downregulation for allowing T cells to recognize their targets. We identified TCRMCC1 that recognizes a T-antigen epitope restricted to human leukocyte antigen (HLA)-A*02:01. Seven CPI-refractory metastatic MCC patients received CD4 and CD8 T cells transduced with TCRMCC1 (TTCR-MCC1) preceded either by lymphodepleting chemotherapy or an HLA-upregulating regimen (single-fraction radiation therapy (SFRT) or systemic interferon gamma (IFNγ)) with concurrent avelumab. Two patients who received preceding SFRT and IFNγ respectively experienced tumor regression. One experienced regression of 13/14 subcutaneous lesions with 1 'escape' lesion and the other had delayed tumor regression in all lesions after initial progression. Although TTCR-MCC1 cells with an activated phenotype infiltrated tumors including the 'escape' lesion, all progressing lesions transcriptionally lacked HLA expression. While SFRT/IFNγ did not immediately upregulate tumor HLA expression, a secondary endogenous antigen-specific T cell infiltrate was detected in one of the regressing tumors and associated with HLA upregulation, indicating in situ immune responses have the potential to reverse HLA downregulation. Indeed, supplying a strong co-stimulatory signal via a CD200R-CD28 switch receptor allows TTCR-MCC1 cells to control HLA-downregulated MCC cells in a xenograft mouse model, upregulating HLA expression. Our results demonstrate the potential of TCR gene therapy for metastatic MCC and propose a next strategy for overcoming epigenetic downregulation of HLA in MCC.},
}

@article {pmid39003390,
year = {2024},
author = {Cox, ER and Summers, C and Milano, F and Dahlberg, A and Bleakley, M and Sandmaier, BM and Thakar, MS},
title = {Outcomes of patients undergoing third hematopoietic cell transplantation for hematologic malignancies.},
journal = {Annals of hematology},
volume = {},
number = {},
pages = {},
pmid = {39003390},
issn = {1432-0584},
abstract = {With advancements in novel therapeutics, it is unclear whether third hematopoietic cell transplantation (HCT3) has a place in the treatment of recurrent hematopoietic malignancies. We evaluated patients with hematologic malignancies who underwent HCT3 between 2000-2020. Nine patients, with a median age of 18 (9-68) years at HCT3 with acute myelogenous leukemia (n = 5), acute lymphoblastic leukemia (n = 2), myelodysplastic syndrome (n = 1), or undifferentiated acute leukemia (n = 1), were identified. The median time between first HCT and HCT3 was 3.9 (0.7-13.6) years. Indication for HCT3 was relapse (n = 8) or graft failure (n = 1) after second HCT. At HCT3, seven of nine patients were in complete remission by flow cytometry. All experienced robust donor engraftment by one month after HCT3 (≥ 90% CD3) while one died at day + 24 of multi-organ failure and was not evaluable for chimerism. In total, eight patients died from relapse (n = 4), non-relapse, (n = 3) or unknown (n = 1) causes at a median of 0.6 (range, 0.1 - 9.9) years after HCT3. After HCT3, estimated overall survival at 6 months, 1 year, and 5 years was 88%, 63%, and 22%, respectively. In this highly selected group, HCT3 provided a treatment option although long-term survival was still dismal.},
}

@article {pmid39003201,
year = {2024},
author = {Plimack, ER and Tangen, C and Plets, M and Kokate, R and Xiu, J and Nabhan, C and Ross, EA and Grundy, E and Choi, W and Dinney, CPN and Lee, IC and Fong, M and Scott Lucia, M and Daneshmand, S and Theodorescu, D and Goldkorn, A and Lerner, SP and Flaig, TW and McConkey, DJ},
title = {Correlative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2024.06.018},
pmid = {39003201},
issn = {1873-7560},
abstract = {We previously reported that tumors harboring any one of four gene mutations (ATM, RB1, FANCC, or ERCC2) were likely to respond to neoadjuvant cisplatin-based chemotherapy (NAC), resulting in cancer-free surgical specimens at the time of cystectomy (pT0). Here, we report our validation of this finding. Using the CARIS 592 Gene Panel (Caris Life Sciences, Phoenix, AZ, USA), we analyzed 105 pre-NAC tumor specimens from a large multicenter trial (S1314) of either neoadjuvant gemcitabine and cisplatin (GC), or dose-dense methotrexate, vinblastine, Adriamycin, and cisplatin (DDMVAC). We found that a mutation in any one of these four genes predicted for pT0 at surgery (odds ratio = 5.36; 95% confidence interval [CI] 2.05, 14.02; two-sided p = 0.0006). The biomarker was better at predicting the presence of disease (negative predictive value for pT0 86%; 95% CI 73%, 94%) than the absence of disease (positive predictive value for pT0 48%; 95% CI 35%, 62%). There was no evidence of an interaction between the treatment arm (DDMVAC vs GC) and the genetic variant in terms of pT0. When combined with clinical assessment, these findings help inform patient selection for bladder preservation after cisplatin-based chemotherapy. PATIENT SUMMARY: A common standard of care for patients with muscle-invasive bladder cancer is neoadjuvant chemotherapy (NAC) followed by cystectomy to achieve cure. We previously discovered that specific DNA mutations in tumor samples collected at initial biopsy (transurethral resection of a bladder tumor) were predictive of a complete response to NAC. In other words, patients with these mutations were more likely to have a bladder found to be cancer free after surgery. In this study, we analyzed a larger set of tumor samples from a national clinical trial of chemotherapy followed by cystectomy to validate these earlier findings. We conclude that this biomarker test, when combined with careful clinical assessment, can be used to allocate patients to careful bladder surveillance instead of surgery. This hypothesis has been tested in the RETAIN trial presented previously (NCT02710734).},
}

@article {pmid39001544,
year = {2024},
author = {Foley, GR and Marthick, JR and Lucas, SE and Raspin, K and Banks, A and Stanford, JL and Ostrander, EA and FitzGerald, LM and Dickinson, JL},
title = {Germline Sequencing of DNA Damage Repair Genes in Two Hereditary Prostate Cancer Cohorts Reveals New Disease Risk-Associated Gene Variants.},
journal = {Cancers},
volume = {16},
number = {13},
pages = {},
pmid = {39001544},
issn = {2072-6694},
support = {NA//Cancer Council Tasmania/ ; IPAP20210253//IMPACT Perpetual Trustees/ ; NA//Royal Hobart Hospital Research Foundation/ ; NA//Cancer Australia/ ; NA//The Mazda Foundation/ ; NA//Max Bruce Trust/ ; NA//The Estate of Dr RA Parker/ ; NA//Tasmanian Community Fund/ ; NA//Robert Malcom Familial Prostate Cancer Bequest/ ; P30 CA015704/CA/NCI NIH HHS/United States ; NA//Institute for Prostate Cancer Research of the University of Washington Medicine and Fred Hutchinson Cancer Center/ ; },
abstract = {Rare, inherited variants in DNA damage repair (DDR) genes have a recognised role in prostate cancer (PrCa) susceptibility. In addition, these genes are therapeutically targetable. While rare variants are informing clinical management in other common cancers, defining the rare disease-associated variants in PrCa has been challenging. Here, whole-genome and -exome sequencing data from two independent, high-risk Australian and North American familial PrCa datasets were interrogated for novel DDR risk variants. Rare DDR gene variants (predicted to be damaging and present in two or more family members) were identified and subsequently genotyped in 1963 individuals (700 familial and 459 sporadic PrCa cases, 482 unaffected relatives, and 322 screened controls), and association analyses accounting for relatedness (MQLS) undertaken. In the combined datasets, rare ERCC3 (rs145201970, p = 2.57 × 10[-4]) and BRIP1 (rs4988345, p = 0.025) variants were significantly associated with PrCa risk. A PARP2 (rs200603922, p = 0.028) variant in the Australian dataset and a MUTYH (rs36053993, p = 0.031) variant in the North American dataset were also associated with risk. Evaluation of clinicopathological characteristics provided no evidence for a younger age or higher-grade disease at diagnosis in variant carriers, which should be taken into consideration when determining genetic screening eligibility criteria for targeted, gene-based treatments in the future. This study adds valuable knowledge to our understanding of PrCa-associated DDR genes, which will underpin effective clinical screening and treatment strategies.},
}

@article {pmid39001542,
year = {2024},
author = {Alam, R and Fan, X and Hippe, DS and Tachiki, LM and Gong, E and Huynh, E and Nghiem, P and Park, SY},
title = {Lack of Clinically Significant Relationships of Age or Body Mass Index with Merkel Cell Carcinoma Immunotherapy Outcomes.},
journal = {Cancers},
volume = {16},
number = {13},
pages = {},
pmid = {39001542},
issn = {2072-6694},
support = {P01 CA225517/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; Kelsey Dickson Team Science Courage Research Award//Prostate Cancer Foundation/ ; MCC Gift Fund//University of Washington/ ; },
abstract = {Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a high risk of metastasis. The development of anti-PD-1/PD-L1 immunotherapy has improved outcomes for advanced MCC, yet about 50% of such patients do not achieve durable responses. This study analyzed the effects of age and body mass index (BMI) on immunotherapy response in 183 advanced MCC patients from a single-center longitudinal database. Using Fine-Gray or Cox regression models, treatment response, progression-free survival (PFS), MCC-specific survival, and overall survival (OS) were evaluated. Age showed a significant non-linear relationship with treatment response (p = 0.04), with patients much older or younger than 70 years less likely to respond. However, age was not significantly associated with PFS (p = 0.21), MCC-specific survival (p = 0.72), or OS (p = 0.36). Similarly, BMI was not significantly correlated with treatment response (p = 0.41), PFS (p = 0.52), MCC-specific survival (p = 0.78), or OS (p = 0.71). Unlike previous studies suggesting that obesity and advanced age improve outcomes in other cancers, these associations were not observed in MCC. These findings suggest that age and BMI should not influence eligibility for immunotherapy in MCC patients, emphasizing the importance of unbiased patient selection for this treatment.},
}

@article {pmid38997299,
year = {2024},
author = {Koester, ST and Chow, A and Pepper-Tunick, E and Lee, P and Eckert, M and Brenchley, L and Gardner, P and Song, HJ and Li, N and Schiffenbauer, A and Volochayev, R and Bayat, N and McLean, JS and Rider, LG and Shenoi, S and Stevens, AM and Dey, N},
title = {Familial clustering of dysbiotic oral and fecal microbiomes in juvenile dermatomyositis.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {16158},
pmid = {38997299},
issn = {2045-2322},
support = {HHSN2732016000021/ES/NIEHS NIH HHS/United States ; ZIAES101074/NH/NIH HHS/United States ; DK111941/DK/NIDDK NIH HHS/United States ; },
mesh = {Humans ; *Feces/microbiology ; *Dermatomyositis/microbiology/genetics ; Female ; Male ; Child ; *Mouth/microbiology ; *RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome/genetics ; Prospective Studies ; Dysbiosis/microbiology ; Microbiota/genetics ; Child, Preschool ; Adolescent ; Saliva/microbiology ; Adult ; },
abstract = {Juvenile dermatomyositis (JDM) is a rare immune-mediated disease of childhood with putative links to microbial exposures. In this multi-center, prospective, observational cohort study, we evaluated whether JDM is associated with discrete oral and gut microbiome signatures. We generated 16S rRNA sequencing data from fecal, saliva, supragingival, and subgingival plaque samples from JDM probands (n = 28). To control for genetic and environmental determinants of microbiome community structure, we also profiled microbiomes of unaffected family members (n = 27 siblings, n = 26 mothers, and n = 17 fathers). Sample type (oral-vs-fecal) and nuclear family unit were the predominant variables explaining variance in microbiome diversity, more so than having a diagnosis of JDM. The oral and gut microbiomes of JDM probands were more similar to their own unaffected siblings than they were to the microbiomes of other JDM probands. In a sibling-paired within-family analysis, several potentially immunomodulatory bacterial taxa were differentially abundant in the microbiomes of JDM probands compared to their unaffected siblings, including Faecalibacterium (gut) and Streptococcus (oral cavity). While microbiome features of JDM are often shared by unaffected family members, the loss or gain of specific fecal and oral bacteria may play a role in disease pathogenesis or be secondary to immune dysfunction in susceptible individuals.},
}

Humans
*Feces/microbiology
*Dermatomyositis/microbiology/genetics
Female
Male
Child
*Mouth/microbiology
*RNA, Ribosomal, 16S/genetics
*Gastrointestinal Microbiome/genetics
Prospective Studies
Dysbiosis/microbiology
Microbiota/genetics
Child, Preschool
Adolescent
Saliva/microbiology
Adult

@article {pmid38996457,
year = {2024},
author = {Sokolov, D and Sullivan, LB},
title = {Thrifty tissues prefer recycled purines over new-cleotides.},
journal = {Molecular cell},
volume = {84},
number = {13},
pages = {2407-2409},
doi = {10.1016/j.molcel.2024.06.015},
pmid = {38996457},
issn = {1097-4164},
mesh = {*Purines/metabolism ; Humans ; Animals ; Neoplasms/metabolism/genetics/pathology ; Purine Nucleotides/metabolism ; },
abstract = {In two recent studies appearing in Cell[1] and Cell Metabolism,[2] Tran et al. and Wu et al. describe underappreciated nuance in organismal and cellular purine nucleotide salvage pathways and identify purine salvage as a metabolic limitation for tumor growth.},
}

*Purines/metabolism
Humans
Animals
Neoplasms/metabolism/genetics/pathology
Purine Nucleotides/metabolism

@article {pmid38996210,
year = {2024},
author = {Xie, Z and Komrokji, RS and Al-Ali, N and Regelson, A and Geyer, S and Patel, AA and Saygin, C and Zeidan, AM and Bewersdorf, JP and Mendez, LM and Kishtagari, A and Zeidner, JF and Coombs, CC and Madanat, YF and Chung, SS and Badar, T and Foran, JM and Desai, P and Tsai, C and Griffiths, EA and Al Malki, MM and Amanam, I and Lai, C and Deeg, HJ and Ades, L and Arana-Yi, C and Osman, AE and Dinner, SN and Abaza, Y and Taylor, J and Chandhok, NS and Soong, D and Brunner, AM and Carraway, HE and Singh, A and Elena, C and Ferrari, J and Galli, A and Pozzi, S and Padron, E and Patnaik, MM and Malcovati, L and Savona, MR and Al-Kali, A},
title = {Risk Prediction for Clonal Cytopenia: Multicenter Real-World Evidence.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024024756},
pmid = {38996210},
issn = {1528-0020},
abstract = {Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 CCUS patients investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count <100×109/L (score = 2.5), and ≥2 mutations (score = 3). Variable scores were based on the coefficients from the Cox proportional hazards model. This led to the development of the Clonal Cytopenia Risk Score (CCRS), which stratified patients into low- (score <2.5 points), intermediate- (score 2.5-<5), and high-risk (score ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high- (37.2%) risk groups, respectively, by Gray's test (P <.0001). We further validated the CCRS by applying it to an independent CCUS cohort of 104 patients, demonstrating a c-index of 0.64 (P =.005) in stratifying the cumulative incidence of MN. Our study underscores the importance of integrating clinical and molecular data to assess the risk of CCUS progression, making the CCRS a valuable tool that is practical and easily calculable. These findings are clinically relevant, shaping the management strategies for CCUS and informing future clinical trial designs.},
}

@article {pmid38992469,
year = {2024},
author = {Mehta, RS and Petersdorf, EW and Wang, T and Lee, SJ},
title = {Haploidentical versus mismatched unrelated donor HCT: HLA-factors and donor age considerations.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.07.005},
pmid = {38992469},
issn = {2666-6367},
abstract = {HLA-mismatched unrelated donors and haploidentical related donors are suitable stem cell sources for hematopoietic cell transplantation (HCT) when patients lack HLA-matched donors. Clinical outcome after mismatched HCT is influenced by HLA factors including the similarity of peptide-binding motifs (PBMs) between the patient and unrelated donor, and of the HLA-B leader in unrelated and haploidentical donors. Whether these factors can aid in the selection between mismatched unrelated and haploidentical donors is not known. To address this question, we investigated outcomes between the two donor types defined by matching for the PBM and leader peptide. We compared PBM-matched (n=614) and mismatched (n=958) MMUDs with calcineurin-inhibitor-based prophylaxis to four haploidentical groups that received post-transplant cyclophosphamide (PTCy)-based prophylaxis. The haploidentical groups were B-leader matched/DRB1-mismatched (n=722), B-leader matched/DRB1-matched (n=154), B-leader mismatched/DRB1-mismatched (n=493), and B-leader mismatched/DRB1-matched (n=63). Multivariate analysis showed that the B-leader matched/DRB1-mismatched haploidentical group had the best overall survival (OS) compared to the PBM-matched MMUD, while other haploidentical groups had comparable OS. The PBM-mismatched MMUD showed the poorest outcomes, similar to the B-leader mismatched/DRB1-matched haploidentical group. Among non-HLA factors, donor age was the most significant predictor of OS. These results suggest that a B-leader matched/DRB1 mismatched haploidentical donor might be the preferred choice among donors of similar age. If such a donor is not available, the youngest donor from either PBM-matched unrelated or other haploidentical groups could be a beneficial choice. These findings need validation with both donor groups receiving PTCy-based GVHD prophylaxis.},
}

@article {pmid38994535,
year = {2021},
author = {Grivas, P and Kiedrowski, LA and Sonpavde, GP and Gupta, SV and Thomas, RA and Gourdin, TS and Hardin, AI and Hamann, KM and Faltas, BM and Vogelzang, NJ},
title = {Spectrum of FGFR2/3 Alterations in Cell-Free DNA of Patients with Advanced Urothelial Carcinoma.},
journal = {Bladder cancer (Amsterdam, Netherlands)},
volume = {7},
number = {2},
pages = {143-148},
pmid = {38994535},
issn = {2352-3735},
abstract = {Detecting genomic alterations (GAs) in advanced urothelial carcinoma (aUC) can expand treatment options by identifying candidates for targeted therapies. Erdafitinib is FDA-approved for patients with platinum-refractory aUC with activating mutation or fusion in FGFR2/3. We explored the prevalence and spectrum of FGFR2/3 GAs identified with plasma cfDNA NGS testing (Guardant360) in 997 patients with aUC. FGFR2/3 GAs were detected in 201 patients (20%) with characterized activating GAs in 141 (14%). Our results indicate the Guardant360-based FGFR2/3 GA detection rate is similar to those described from previous studies employing tumor tissue testing, suggesting that plasma-based cfDNA NGS may non-invasively identify candidates for anti-FGFR targeted therapies.},
}

@article {pmid38993215,
year = {2021},
author = {Nelson, AA and Cronk, RJ and Lemke, EA and Szabo, A and Khaki, AR and Diamantopoulos, LN and Grivas, P and Nezami, BG and MacLennan, GT and Zhang, T and Hoimes, CJ},
title = {Early Bone Metastases are Associated with Worse Outcomes in Metastatic Urothelial Carcinoma.},
journal = {Bladder cancer (Amsterdam, Netherlands)},
volume = {7},
number = {1},
pages = {33-42},
pmid = {38993215},
issn = {2352-3735},
abstract = {BACKGROUND: Outcomes of patients with metastatic urothelial carcinoma (mUC) with early bone metastases (eBM) vs no early bone metastases (nBM) have not thoroughly been described in the age of immuno-oncology.

OBJECTIVE: To compare survival and other clinical outcomes in patients with eBM and nBM.

METHODS: We used a multi-institutional database of patients with mUC treated with systemic therapy. Demographic, metastatic site, treatment patterns, and clinical outcomes were recorded. Wilcoxon rank-sum, chi-square tests were performed. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed.

RESULTS: We identified 270 pts, 67% men, mean age 69±11 years. At metastatic diagnosis, 27% had≥1 eBM and were more likely to have de novo vs. recurrent metastases (42% vs 19%, p < 0.001). Patients with eBM had shorter overall survival (OS) vs. those with nBM, (6.1 vs 13.7 months, p < 0.0001). On multivariable analysis, eBM independently associated with higher risk of death, HR = 2.52 (95% CI: 1.75-3.63, p < 0.0001). OS was shorter for patients with eBM who received initial immune checkpoint inhibitor vs platinum-based chemotherapy, (1.6 vs 9.1 months, p = 0.02). Patients with eBM received higher opioid analgesic doses compared to patients with nBM and received quantitatively more palliative radiation.

CONCLUSIONS: Patients with mUC and eBM have poorer outcomes, may benefit less from anti-PD-1/PD-L1 therapy and represent an unmet need for novel therapeutic interventions. Dedicated clinical trials, biomarker validation to assist in patient selection, as well as consensus on reporting of non-measurable disease are required.},
}

@article {pmid38991829,
year = {2024},
author = {Cicero, KI and Dlamini, X and Mavengere, Y and Justman, J and Nuwagaba-Biribonwoha, H and Dlamini, S and Dlamini, M and Ngwenyama, S and Ngcamphalala, C and Low, A and Philip, NM and El-Sadr, WM and Sahabo, R and Abreha, T and Temesgen, S and Mahlalela, N and Chiuzan, C and Chen, Y and Pan, SS and Lentzsch, S and Neugut, AI},
title = {Prevalence of monoclonal gammopathy of undetermined significance in eswatini: a Population-Based study in africa.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkae056},
pmid = {38991829},
issn = {2515-5091},
abstract = {PURPOSE: Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiologic studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, USA study.

METHODS: Between 2016 and 2017, 13,339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally-representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared to that of Olmsted County. Additionally, demographic and HIV-related associations with MGUS were assessed.

RESULTS: Of the 515 samples randomly selected, the median age was 50 years (range 35-80) and 60% were female; 38.6% were HIV-positive, of whom 82.4% were on antiretroviral therapy. We found that 68 had evidence of MGUS for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (OR, 1.05; 95%CI, 0.62-1.77), but among HIV-positive individuals, MGUS was less frequent for those on antiretroviral therapy (adjusted OR, 0.31; 95%CI, 0.11-0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2-3.4%), while light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%).

CONCLUSION: Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection.},
}

@article {pmid38991631,
year = {2024},
author = {Vinayak, S and Cecil, DL and Disis, ML},
title = {Vaccines for breast cancer prevention: Are we there yet?.},
journal = {Molecular aspects of medicine},
volume = {98},
number = {},
pages = {101292},
doi = {10.1016/j.mam.2024.101292},
pmid = {38991631},
issn = {1872-9452},
}

@article {pmid38991590,
year = {2024},
author = {Plender, EG and Prodanov, T and Hsieh, P and Nizamis, E and Harvey, WT and Sulovari, A and Munson, KM and Kaufman, EJ and O'Neal, WK and Valdmanis, PN and Marschall, T and Bloom, JD and Eichler, EE},
title = {Structural and genetic diversity in the secreted mucins MUC5AC and MUC5B.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2024.06.007},
pmid = {38991590},
issn = {1537-6605},
support = {R01 HG002385/HG/NHGRI NIH HHS/United States ; R01 HG010169/HG/NHGRI NIH HHS/United States ; U24 HG007497/HG/NHGRI NIH HHS/United States ; },
abstract = {The secreted mucins MUC5AC and MUC5B are large glycoproteins that play critical defensive roles in pathogen entrapment and mucociliary clearance. Their respective genes contain polymorphic and degenerate protein-coding variable number tandem repeats (VNTRs) that make the loci difficult to investigate with short reads. We characterize the structural diversity of MUC5AC and MUC5B by long-read sequencing and assembly of 206 human and 20 nonhuman primate (NHP) haplotypes. We find that human MUC5B is largely invariant (5,761-5,762 amino acids [aa]); however, seven haplotypes have expanded VNTRs (6,291-7,019 aa). In contrast, 30 allelic variants of MUC5AC encode 16 distinct proteins (5,249-6,325 aa) with cysteine-rich domain and VNTR copy-number variation. We group MUC5AC alleles into three phylogenetic clades: H1 (46%, ∼5,654 aa), H2 (33%, ∼5,742 aa), and H3 (7%, ∼6,325 aa). The two most common human MUC5AC variants are smaller than NHP gene models, suggesting a reduction in protein length during recent human evolution. Linkage disequilibrium and Tajima's D analyses reveal that East Asians carry exceptionally large blocks with an excess of rare variation (p < 0.05) at MUC5AC. To validate this result, we use Locityper for genotyping MUC5AC haplogroups in 2,600 unrelated samples from the 1000 Genomes Project. We observe a signature of positive selection in H1 among East Asians and a depletion of the likely ancestral haplogroup (H3). In Europeans, H3 alleles show an excess of common variation and deviate from Hardy-Weinberg equilibrium (p < 0.05), consistent with heterozygote advantage and balancing selection. This study provides a generalizable strategy to characterize complex protein-coding VNTRs for improved disease associations.},
}

@article {pmid38991198,
year = {2024},
author = {Vonhoff, F and Ko'omoa-Lange, DL and Davis, JS and Termini, CM and Martínez-Montemayor, MM},
title = {Maximizing Access to Cell Biology for PEERS: Retracting the term minority in favor of a more inclusive lexicon.},
journal = {Molecular biology of the cell},
volume = {35},
number = {8},
pages = {vo1},
doi = {10.1091/mbc.E24-04-0156},
pmid = {38991198},
issn = {1939-4586},
mesh = {Humans ; *Cell Biology ; *Minority Groups ; Societies, Scientific ; United States ; Peer Group ; Terminology as Topic ; },
abstract = {The word minority, when used incorrectly, is a condescending term that segregates, inaccurately represents groups as being smaller or less important, and fuels microaggressions. Scientific societies and other institutions have normalized using the word minority, or the "M word," to refer to members of underrepresented groups in Science, Technology, Engineering, and Mathematics (STEM). The message put forth using the term minority often directly conflicts with the inclusive agenda these societies seek to enact. More inclusive acronyms such as PEER (Persons Excluded because of their Ethnicity or Race) have been created to more accurately reflect the active process of exclusion by institutions. Here, we detail the rationale behind the decision to eradicate the word minority from the name of a prominent committee within the American Society for Cell Biology (ASCB). The ASCB Minority Affairs Committee changed its name to the Maximizing Access to Cell Biology for PEERS Committee. Herein, we emphasize the basis for the name change and highlight the contradictions intrinsic to the word minority in this context. We highlight why swift action is required for this rewording within the context of a committee dedicated to supporting the inclusion of PEERs in the scientific community.},
}

Humans
*Cell Biology
*Minority Groups
Societies, Scientific
United States
Peer Group
Terminology as Topic

@article {pmid38991033,
year = {2024},
author = {Yanagi, KS and Jochim, B and Kunjo, SO and Breen, P and Ruvkun, G and Lehrbach, N},
title = {Mutations in nucleotide metabolism genes bypass proteasome defects in png-1/NGLY1-deficient Caenorhabditis elegans.},
journal = {PLoS biology},
volume = {22},
number = {7},
pages = {e3002720},
doi = {10.1371/journal.pbio.3002720},
pmid = {38991033},
issn = {1545-7885},
abstract = {The conserved SKN-1A/Nrf1 transcription factor regulates the expression of proteasome subunit genes and is essential for maintenance of adequate proteasome function in animal development, aging, and stress responses. Unusual among transcription factors, SKN-1A/Nrf1 is a glycoprotein synthesized in the endoplasmic reticulum (ER). N-glycosylated SKN-1A/Nrf1 exits the ER and is deglycosylated in the cytosol by the PNG-1/NGLY1 peptide:N-glycanase. Deglycosylation edits the protein sequence of SKN-1A/Nrf1 by converting N-glycosylated asparagine residues to aspartate, which is necessary for SKN-1A/Nrf1 transcriptional activation of proteasome subunit genes. Homozygous loss-of-function mutations in the peptide:N-glycanase (NGLY1) gene cause NGLY1 deficiency, a congenital disorder of deglycosylation. There are no effective treatments for NGLY1 deficiency. Since SKN-1A/Nrf1 is a major client of NGLY1, the resulting proteasome deficit contributes to NGLY1 disease. We sought to identify targets for mitigation of proteasome dysfunction in NGLY1 deficiency that might indicate new avenues for treatment. We isolated mutations that suppress the sensitivity to proteasome inhibitors caused by inactivation of the NGLY1 ortholog PNG-1 in Caenorhabditis elegans. We identified multiple suppressor mutations affecting 3 conserved genes: rsks-1, tald-1, and ent-4. We show that the suppressors act through a SKN-1/Nrf-independent mechanism and confer proteostasis benefits consistent with amelioration of proteasome dysfunction. ent-4 encodes an intestinal nucleoside/nucleotide transporter, and we show that restriction of nucleotide availability is beneficial, whereas a nucleotide-rich diet exacerbates proteasome dysfunction in PNG-1/NGLY1-deficient C. elegans. Our findings suggest that dietary or pharmacological interventions altering nucleotide availability have the potential to mitigate proteasome insufficiency in NGLY1 deficiency and other diseases associated with proteasome dysfunction.},
}

@article {pmid38990255,
year = {2024},
author = {Dickerson, LK and Lipson, TA and Chauhan, SSB and Allen, GI and Young, B and Park, JO and Pillarisetty, VG and O'Connell, KM and Sham, JG},
title = {Evaluating surgeon communication of pancreatic cancer prognosis using the VitalTalk ADAPT framework.},
journal = {Journal of surgical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jso.27777},
pmid = {38990255},
issn = {1096-9098},
support = {//The Donald E. Bocek Endowed Research Development Award in Pancreatic Cancer/ ; },
abstract = {BACKGROUND AND OBJECTIVES: Few data exist to guide optimal communication practices for surgical oncologists. VitalTalk, an evidence-based communication skills training model for clinicians, offers the five-step ADAPT tool for discussing prognosis. This study aimed to characterize surgeon communication of pancreatic cancer prognosis using VitalTalk's ADAPT framework.

METHODS: Contemporaneous audio recordings from 12 initial surgeon-patient encounters for borderline resectable pancreatic cancer were transcribed. Directed qualitative content analysis based on ADAPT (Ask, Discover, Anticipate, Provide, and Track) was used to deductively code transcripts.

RESULTS: All encounters contained at least one ADAPT step while only one (8%) incorporated four or five steps. Surgeons provided prognostic information (Provide) in all but one encounter (92%); most was qualitative and clustered into themes: serious illness, surgical candidacy, prognostic ambiguity, and cancer recurrence. Surgeons elicited understanding (Ask), requested information preferences (Discover), anticipated ambivalence (Anticipate), and responded to emotion (Track) in a minority of encounters (25%-42%); of 15 patient emotional cues, six were not addressed by surgeons.

CONCLUSIONS: During an initial encounter for pancreatic cancer, surgeons focus heavily on providing information but omit critical prognostic communication steps. Future studies are needed to investigate if surgeon training in palliative care-based communication is feasible and impacts patient-perceived quality of communication.},
}

@article {pmid38988271,
year = {2024},
author = {Rashidi, A and Liang, L and Gooley, T and Hujoel, PP and Zevin, A and Rothen, M and Hagstrom, MK and Cutler, C and Lee, SJ and Dean, DR and Sroussi, HY and Treister, NS},
title = {Microbiota signature of oral chronic graft-versus-host disease 6+ years after transplantation.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.285650},
pmid = {38988271},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid38987855,
year = {2024},
author = {Middeldorp, ME and Manson, JE and Aragaki, AK and Clar, A and Sesso, HD and Albert, CM},
title = {Cocoa flavanol supplementation and incident atrial fibrillation in the COSMOS trial.},
journal = {European journal of preventive cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/eurjpc/zwae229},
pmid = {38987855},
issn = {2047-4881},
}

@article {pmid38985302,
year = {2024},
author = {Pophali, PA and Fein, JA and Ahn, KW and Allbee-Johnson, M and Ahmed, N and Awan, FT and Farhan, S and Grover, NS and Hilal, T and Iqbal, M and Maakaron, J and Modi, D and Nasrollahi, E and Schachter, L and Sauter, CS and Hamadani, M and Herrera, AF and Shouval, R and Shadman, M},
title = {CD19-directed CART Therapy for T cell/Histiocyte Rich Large B-cell Lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024013863},
pmid = {38985302},
issn = {2473-9537},
abstract = {T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the CIBMTR registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART between 2018-2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range: 1-7) prior therapies and were treated with Axicabtagene ciloleucel (69%). At median follow-up of 23 months post-CART, 2-year overall and progression-free survival were 42% (95% CI: 27-57) and 29% (95% CI: 17-43), respectively. In univariable analysis, poor performance status pre-CART was associated with higher mortality (HR 2.35, 95%CI 1.02-5.5). The 2-year cumulative incidences of relapse/progression and non-relapse mortality were 69% and 2%, respectively. Grade ≥3 CRS and ICANS occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART for R/R THRLBCL, approximately 30% of patients were alive and progression-free 2 years post-CART. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CART.},
}

@article {pmid38984364,
year = {2024},
author = {Singh, SN and Wininger, M and Raitt, M and Adabag, S and Moore, H and Rottman, JN and Scrymgeour, A and Zhang, J and Zheng, K and Guarino, P and Kyriakides, TC and , and Johnson, G and Williams, A and Beed, A and MacMurdy, K and Saavedra, P},
title = {Efficacy and safety of implantable cardioverter-defibrillator implantation in the elderly-The I-70 Study: A randomized clinical trial.},
journal = {Heart rhythm O2},
volume = {5},
number = {6},
pages = {365-373},
pmid = {38984364},
issn = {2666-5018},
abstract = {BACKGROUND: There is conflicting evidence on the efficacy of primary prevention implantable cardioverter-defibrillator (ICD) implantation in the elderly.

OBJECTIVE: The purpose of this study was to determine the efficacy and safety of ICD implantation in patients 70 years and older.

METHODS: Patients (n = 167) aged 70 years or older and eligible for ICD implantation were randomly assigned (1:1) to receive either optimal medical therapy (OMT) (n = 85) or OMT plus ICD (n = 82).

RESULTS: Of the 167 participants (mean age 76.4 years; 165 men), 144 completed the study protocol according to their assigned treatment. Average participant follow-up was 31.5 months. Mortality was similar between the 2 groups: 27 deaths in OMT vs 26 death in ICD (unadjusted hazard ratio 0.92; 95% confidence interval 0.53-1.57), but there was a trend favoring the ICD over the first 36 months of follow-up. Rates of sudden death (7 vs 5; P = .81) and all-cause hospitalization (2.65 events per participant in OMT vs 3.09 in ICD; P = .31) were not statistically significantly different. Eleven participants randomized to ICD received appropriate therapy. Five participants received an inappropriate therapy that included at least 1 ICD shock.

CONCLUSION: The study did not recruit to target sample size, and accumulated data did not show benefit of ICD therapy in patients 70 years or older. Future studies similar in design might be feasible but will need to contend with patient treatment preference given the large number of patients who do not want an ICD implanted. Further research is needed to determine whether the ICD is effective in prolonging life among elderly device candidates.},
}

@article {pmid38983599,
year = {2024},
author = {Cadiou, G and Beauvais, T and Marotte, L and Lambot, S and Deleine, C and Vignes, C and Gantier, M and Hussong, M and Rulli, S and Jarry, A and Simon, S and Malissen, B and Labarriere, N},
title = {Differential impact of genetic deletion of TIGIT or PD-1 on melanoma-specific T-lymphocytes.},
journal = {Oncoimmunology},
volume = {13},
number = {1},
pages = {2376782},
pmid = {38983599},
issn = {2162-402X},
mesh = {Animals ; Mice ; *Programmed Cell Death 1 Receptor/genetics/metabolism ; *Receptors, Immunologic/genetics/metabolism ; *Melanoma/immunology/genetics/pathology/therapy ; Gene Deletion ; Tumor Microenvironment/immunology ; Mice, Knockout ; Mice, Inbred C57BL ; T-Lymphocytes/immunology/metabolism ; Cell Line, Tumor ; Humans ; Lymphocyte Activation/immunology ; },
abstract = {Immune checkpoint (IC) blockade and adoptive transfer of tumor-specific T-cells (ACT) are two major strategies to treat metastatic melanoma. Their combination can potentiate T-cell activation in the suppressive tumor microenvironment, but the autoimmune adverse effects associated with systemic injection of IC blockers persist with this strategy. ACT of tumor-reactive T-cells defective for IC expression would overcome this issue. For this purpose, PD-1 and TIGIT appear to be relevant candidates, because their co-expression on highly tumor-reactive lymphocytes limits their therapeutic efficacy within the tumor microenvironme,nt. Our study compares the consequences of PDCD1 or TIGIT genetic deletion on anti-tumor properties and T-cell fitness of melanoma-specific T lymphocytes. Transcriptomic analyses revealed down-regulation of cell cycle-related genes in PD-1[KO] T-cells, consistent with biological observations, whereas proliferative pathways were preserved in TIGIT[KO] T-cells. Functional analyses showed that PD-1[KO] and TIGIT[KO] T-cells displayed superior antitumor reactivity than their wild-type counterpart in vitro and in a preclinical melanoma model using immunodeficient mice. Interestingly, it appears that TIGIT[KO] T-cells were more effective at inhibiting tumor cell proliferation in vivo, and persist longer within tumors than PD-1[KO] T-cells, consistent with the absence of impact of TIGIT deletion on T-cell fitness. Taken together, these results suggest that TIGIT deletion, over PD-1 deletion, in melanoma-specific T-cells is a compelling option for future immunotherapeutic strategies.},
}

Animals
Mice
*Programmed Cell Death 1 Receptor/genetics/metabolism
*Receptors, Immunologic/genetics/metabolism
*Melanoma/immunology/genetics/pathology/therapy
Gene Deletion
Tumor Microenvironment/immunology
Mice, Knockout
Mice, Inbred C57BL
T-Lymphocytes/immunology/metabolism
Cell Line, Tumor
Humans
Lymphocyte Activation/immunology

@article {pmid38982075,
year = {2024},
author = {Hurvitz, SA and Bardia, A and Punie, K and Kalinsky, K and Carey, LA and Rugo, HS and Diéras, V and Phan, S and Delaney, R and Zhu, Y and Tolaney, SM},
title = {Author Correction: Subgroup analyses from the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer.},
journal = {NPJ breast cancer},
volume = {10},
number = {1},
pages = {55},
doi = {10.1038/s41523-024-00666-y},
pmid = {38982075},
issn = {2374-4677},
}

@article {pmid38981645,
year = {2024},
author = {Manyara, AM and Davies, P and Stewart, D and Weir, CJ and Young, AE and Blazeby, J and Butcher, NJ and Bujkiewicz, S and Chan, AW and Dawoud, D and Offringa, M and Ouwens, M and Hróbjartssson, A and Amstutz, A and Bertolaccini, L and Bruno, VD and Devane, D and Faria, CDCM and Gilbert, PB and Harris, R and Lassere, M and Marinelli, L and Markham, S and Powers, JH and Rezaei, Y and Richert, L and Schwendicke, F and Tereshchenko, LG and Thoma, A and Turan, A and Worrall, A and Christensen, R and Collins, GS and Ross, JS and Taylor, RS and Ciani, O},
title = {Reporting of surrogate endpoints in randomised controlled trial reports (CONSORT-Surrogate): extension checklist with explanation and elaboration.},
journal = {BMJ (Clinical research ed.)},
volume = {386},
number = {},
pages = {e078524},
pmid = {38981645},
issn = {1756-1833},
mesh = {*Checklist ; Humans ; *Randomized Controlled Trials as Topic/standards ; *Biomarkers/blood ; Research Design/standards ; },
abstract = {Randomised controlled trials commonly use surrogate endpoints to substitute for a target outcome (outcome of direct interest and relevance to trial participants, clinicians, and other stakeholders—eg, all cause mortality) to improve their efficiency (through shorter trial duration, reduced sample size, and thus lower research costs), or for ethical or practical reasons. But reliance on surrogate endpoints can increase the uncertainty of an intervention’s treatment effect and potential failure to provide adequate information on intervention harms, which has led to calls for improved reporting of trials using surrogate endpoints. This report presents a consensus driven reporting guideline for trials using surrogate endpoints as the primary outcomes—the CONSORT (Consolidated Standards of Reporting Trials) extension checklist: CONSORT-Surrogate. The extension includes nine items modified from the CONSORT 2010 checklist and two new items. Examples and explanations for each item are provided. We recommend that all stakeholders (including trial investigators and sponsors, journal editors and peer reviewers, research ethics reviewers, and funders) use this extension in reporting trial reports using surrogate endpoints. Use of this checklist will improve transparency, interpretation, and usefulness of trial findings, and ultimately reduce research waste.},
}

*Checklist
Humans
*Randomized Controlled Trials as Topic/standards
*Biomarkers/blood
Research Design/standards

@article {pmid38981624,
year = {2024},
author = {Manyara, AM and Davies, P and Stewart, D and Weir, CJ and Young, AE and Blazeby, J and Butcher, NJ and Bujkiewicz, S and Chan, AW and Dawoud, D and Offringa, M and Ouwens, M and Hróbjartssson, A and Amstutz, A and Bertolaccini, L and Bruno, VD and Devane, D and Faria, CDCM and Gilbert, PB and Harris, R and Lassere, M and Marinelli, L and Markham, S and Powers, JH and Rezaei, Y and Richert, L and Schwendicke, F and Tereshchenko, LG and Thoma, A and Turan, A and Worrall, A and Christensen, R and Collins, GS and Ross, JS and Taylor, RS and Ciani, O},
title = {Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration.},
journal = {BMJ (Clinical research ed.)},
volume = {386},
number = {},
pages = {e078525},
pmid = {38981624},
issn = {1756-1833},
mesh = {*Checklist ; Humans ; *Randomized Controlled Trials as Topic/methods/standards ; *Biomarkers/blood ; Research Design/standards ; Clinical Trial Protocols as Topic ; },
abstract = {Randomised controlled trials often use surrogate endpoints to substitute for a target outcome (an outcome of direct interest and relevance to trial participants, clinicians, and other stakeholders—eg, all cause mortality) to improve efficiency (through shortened duration of follow-up, reduced sample size, and lower research costs), and for ethical or practical reasons. However, their use has a fundamental limitation in terms of uncertainty of the intervention effect on the target outcome and limited information on potential intervention harms. There have been increasing calls for improved reporting of trial protocols that use surrogate endpoints. This report presents the SPIRIT-Surrogate, an extension of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist, a consensus driven reporting guideline designed for trial protocols using surrogate endpoints as the primary outcome(s). The SPIRIT-Surrogate extension includes nine items modified from the SPIRIT 2013 checklist. The guideline provides examples and explanations for each item. We recommend that all stakeholders (including trial investigators and sponsors, research ethics reviewers, funders, journal editors, and peer reviewers) use this extension in reporting trial protocols that use surrogate endpoints. Its use will allow for improved design of such trials, improved transparency, and interpretation of findings when trials are completed, and ultimately reduced research waste.},
}

*Checklist
Humans
*Randomized Controlled Trials as Topic/methods/standards
*Biomarkers/blood
Research Design/standards
Clinical Trial Protocols as Topic

@article {pmid38981590,
year = {2024},
author = {Duan, C and Liu, Q and Wang, J and Tong, Q and Bai, F and Han, J and Wang, S and Hippe, DS and Zeng, J and Bowen, SR},
title = {GWO+RuleFit: rule-based explainable machine-learning combined with heuristics to predict mid-treatment FDG PET response to chemoradiation for locally advanced non-small cell lung cancer.},
journal = {Physics in medicine and biology},
volume = {},
number = {},
pages = {},
doi = {10.1088/1361-6560/ad6118},
pmid = {38981590},
issn = {1361-6560},
abstract = {Vital rules learned from FDG-PET radiomics of tumor subregional response can provide clinical decision support for precise treatment adaptation. We combined a rule-based machine learning (ML) model (RuleFit) with a heuristic algorithm (Gray Wolf Optimizer, GWO) for mid-chemoradiation FDG-PET response prediction in patients with locally advanced non-small cell lung cancer. Approach: Tumors subregions were identified using K-means clustering. GWO+RuleFit consists of three main parts: (i) a random forest is constructed based on conventional features or radiomic features extracted from tumor regions or subregions in FDG-PET images, from which the initial rules are generated; (ii) GWO is used for iterative rule selection; (iii) the selected rules are fit to a linear model to make predictions about the target variable. Two target variables were considered: a binary response measure (∆SUVmean⩾20% decline) for classification and a continuous response measure (∆SUVmean) for regression. GWO+RuleFit was benchmarked against common ML algorithms and RuleFit, with leave-one-out cross-validated performance evaluated by the area under the receiver operating characteristic curve (AUC) in classification and root-mean-square error (RMSE) in regression. Main results: GWO+RuleFit selected 15 rules from the radiomic feature dataset of 23 patients. For treatment response classification, GWO+RuleFit attained numerically better cross-validated performance than RuleFit across tumor regions and sets of features (AUC:0.58-0.86 vs. 0.52-0.78, p=0.170-0.925). GWO+Rulefit also had the best or second-best performance numerically compared to all other algorithms for all conditions. For treatment response regression prediction, GWO+RuleFit (RMSE:0.162-0.192) performed better numerically for low-dimensional models (p=0.097-0.614) and significantly better for high-dimensional models across all tumor regions except one (RMSE:0.189-0.219, p<0.004). Significance: The GWO+RuleFit selected rules were interpretable, highlighting distinct radiomic phenotypes that modulated treatment response. GWO+Rulefit achieved parsimonious models while maintaining utility for treatment response prediction, which can aid clinical decisions for patient risk stratification, treatment selection, and biologically driven adaptation. Clinical trial: NCT02773238.},
}

@article {pmid38981364,
year = {2024},
author = {Ng, ZX and Koh, ES and Lee, SF and Tan, CL and Teo, K and Wong, A and Lo, SS and Vellayappan, B},
title = {A systematic review and meta-analysis informing the role of adjuvant radiotherapy (RT) in Grade 2 and 3 oligodendroglioma.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {126},
number = {},
pages = {247-255},
doi = {10.1016/j.jocn.2024.06.020},
pmid = {38981364},
issn = {1532-2653},
abstract = {BACKGROUND AND PURPOSE: Evidence and clinical guidelines support the use of adjuvant RT in high-risk low-grade gliomas. However, patients with oligodendroglioma have a more indolent disease course and delaying or avoiding RT is often considered to reduce treatment-related toxicities. As the optimal adjuvant management for oligodendroglioma is unclear, we aimed to assess the effect of adjuvant RT on overall survival (OS) and progression-free survival (PFS).

METHODS: MEDLINE, EMBASE, CENTRAL and CINAHL were searched from January 1990 to February 2023 for studies comparing adjuvant RT versus no adjuvant RT for patients with oligodendroglioma.

RESULTS: This review found 17 eligible studies including 14 comparative retrospective studies and 3 randomized controlled trials. Using random-effects model, the results suggested that adjuvant RT improved OS by 28 % (HR 0.72, 95 % CI (0.56-0.93), I[2] = 86 %), and PFS by 48 % (HR 0.52, (95 % CI 0.40-0.66), I[2] = 48 %) compared to patients without adjuvant RT. Subgroup analysis showed that upfront adjuvant RT improved OS and PFS compared to salvage RT. There were no significant differences in OS and PFS between adjuvant RT versus adjuvant chemotherapy. There was improvement in PFS but not OS for adjuvant chemoradiotherapy versus adjuvant chemotherapy alone. Adjuvant RT improved OS in WHO Grade 3 but not WHO Grade 2 oligodendroglioma.

CONCLUSION: Overall, adjuvant RT improved OS and PFS in patients with oligodendroglioma. In patients with low-risk features (e.g. Grade 2, gross total resection), alternative approaches and individualization of management such as adjuvant chemotherapy alone may be reasonable considering the lack of survival benefit. Future efforts should prospectively investigate these treatment regimens on molecularly-classified oligodendroglioma patients (defined by presence of IDH mutation and 1p/19q co-deletion), balancing between maximizing survival outcomes and reducing RT-related toxicities.},
}

@article {pmid38981063,
year = {2024},
author = {Alberts, NM and Leisenring, W and Whitton, J and Stratton, K and Jibb, L and Flynn, J and Pizzo, A and Brinkman, TM and Birnie, K and Gibson, TM and McDonald, A and Ford, J and Olgin, JE and Nathan, PC and Stinson, JN and Armstrong, GT},
title = {Characterization of chronic pain, pain interference, and daily pain experiences in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.},
journal = {Pain},
volume = {},
number = {},
pages = {},
doi = {10.1097/j.pain.0000000000003284},
pmid = {38981063},
issn = {1872-6623},
support = {CA55727//National Cancer Institute (NCI)/ ; N/A//Childhood Cancer Survivor Study (CCSS)/ ; N/A//Canada Research Chairs/ ; U2CEB021881//National Institutes of Health (NIH)/ ; },
abstract = {Although survivors of childhood cancer are at an increased risk, little is known about the prevalence of chronic pain, associated interference, and daily pain experiences. Survivors (N = 233; mean age = 40.8 years, range 22-64 years; mean time since diagnosis = 32.7 years) from the Childhood Cancer Survivor Study completed pain and psychosocial measures. Survivors with chronic pain completed 2-week, daily measures assessing pain and psychological symptoms using mHealth-based ecological momentary assessment. Multivariable-modified Poisson and linear regression models estimated prevalence ratio estimates (PR) and mean effects with 95% confidence intervals (CI) for associations of key risk factors with chronic pain and pain interference, respectively. Multilevel mixed models examined outcomes of daily pain and pain interference with prior day symptoms. Ninety-six survivors (41%) reported chronic pain, of whom 23 (24%) had severe interference. Chronic pain was associated with previous intravenous methotrexate treatment (PR = 1.6, 95% CI 1.1-2.3), respiratory (PR = 1.8, 95% CI 1.2-2.5), gastrointestinal (PR = 1.6, 95% CI 11.0-2.3), and neurological (PR = 1.5, 95% CI 1.0-2.1) chronic health conditions, unemployment (PR = 1.4, 95% CI 1.0-1.9) and clinically significant depression and anxiety (PR = 2.9, 95% CI 2.0-4.2), as well as a diagnosis of childhood Ewing sarcoma or osteosarcoma (PR = 1.9, 95% CI 1.0-3.5). Higher pain interference was associated with cardiovascular and neurological conditions, unemployment and clinical levels of depression and/or anxiety, and fear of cancer recurrence. For male, but not female survivors, low sleep quality, elevated anxiety, and elevated depression predicted high pain intensity and interference the next day. A substantial proportion of childhood cancer survivors experience chronic pain and significant associated interference. Chronic pain should be routinely evaluated, and interventions are needed.},
}

@article {pmid38980855,
year = {2024},
author = {Kazmirak, C and Tollefson, D and Lankowski, A and Sanchez, H and Gonzales, I and Espinoza, D and Duerr, A},
title = {Practices and preferences for HIV testing and treatment services amongst partners of transgender women in Lima, Peru: An exploratory, mixed methods study.},
journal = {PloS one},
volume = {19},
number = {7},
pages = {e0306852},
pmid = {38980855},
issn = {1932-6203},
mesh = {Humans ; *Transgender Persons/psychology ; Female ; Peru/epidemiology ; *HIV Infections/diagnosis/epidemiology/psychology ; Adult ; Male ; Cross-Sectional Studies ; *Sexual Partners/psychology ; *HIV Testing ; Middle Aged ; Young Adult ; Adolescent ; Surveys and Questionnaires ; Patient Preference/statistics & numerical data ; },
abstract = {BACKGROUND: In Peru, one-third of transgender women (TW) are estimated to be living with HIV. While TW are recognized as a priority population, their sexual partners are an at-risk hidden population with unmet needs for HIV services. We conducted a study examining the practices and preferences for HIV services among partners of transgender women (PTW), as compared to TW, to better understand the needs of PTW and inform HIV service delivery for them in Peru.

METHODS: Between July-October 2022 we conducted a cross-sectional mixed methods study among PTW and TW in Lima, Peru. Using an explanatory sequential design, we administered online surveys to PTW (n = 165) and TW (n = 69), then interviewed a subset of participants (n = 20: 16 PTW, 4 TW). We quantitatively and qualitatively described PTW practices/perspectives on HIV testing and treatment and compared them to TW practices/preferences; we also compared practices/preferences among PTW based on their relationship with TW.

RESULTS: Overall, PTW and TW shared similar experiences and preferences for HIV testing/treatment, but fewer PTW reported accessing non-traditional HIV testing options and PTW expressed less strong preferences for HIV services. PTW practices/preferences varied by type of relationship with TWs. Surveys and interviews highlighted a need to prioritize efficiency for HIV testing, eliminate gender/sexuality-based discrimination in healthcare settings, increase privacy when delivering HIV services, and increase awareness of pre-exposure prophylaxis.

CONCLUSION: PTW identified many aspects related to the location, convenience, and privacy of HIV services as important. Next steps could include a discrete choice experiment to further clarify priorities for HIV services for PTW in Peru.},
}

Humans
*Transgender Persons/psychology
Female
Peru/epidemiology
*HIV Infections/diagnosis/epidemiology/psychology
Adult
Male
Cross-Sectional Studies
*Sexual Partners/psychology
*HIV Testing
Middle Aged
Young Adult
Adolescent
Surveys and Questionnaires
Patient Preference/statistics & numerical data

@article {pmid38980676,
year = {2024},
author = {Gebrael, G and Jo, Y and Swami, U and Plets, M and Hage Chehade, C and Narang, A and Gupta, S and Myint, ZW and Sayegh, N and Tangen, CM and Hussain, M and Dorff, T and Lara, PN and Lerner, SP and Thompson, I and Agarwal, N},
title = {Bone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG-1216 Trial.},
journal = {JAMA network open},
volume = {7},
number = {7},
pages = {e2419966},
pmid = {38980676},
issn = {2574-3805},
mesh = {Humans ; Male ; Aged ; *Androgen Antagonists/therapeutic use ; Middle Aged ; *Prostatic Neoplasms/mortality/drug therapy/complications/pathology ; *Bone Neoplasms/secondary/mortality/complications/drug therapy ; Nitriles/therapeutic use ; Prospective Studies ; Cancer Pain/drug therapy ; Anilides/therapeutic use ; Tosyl Compounds/therapeutic use/adverse effects ; Androstenes/therapeutic use ; Pain/drug therapy/etiology ; },
abstract = {IMPORTANCE: The presence of bone pain is significantly associated with worse overall survival (OS) in patients with castration-resistant prostate cancer. However, there are few data regarding bone pain and survival outcomes in the context of metastatic, hormone-sensitive prostate cancer (MHSPC).

OBJECTIVE: To compare survival outcomes among patients with MHSPC by presence or absence of baseline bone pain at diagnosis.

This post hoc secondary analysis, conducted from September 1 to December 31, 2023, used patient-level data from SWOG-1216, a phase 3, prospective randomized clinical trial that enrolled patients with newly diagnosed MHSPC from 248 academic and community centers across the US from March 1, 2013, to July 15, 2017. All patients in the intention-to-treat population who had available bone pain status were eligible and included in this secondary analysis.

INTERVENTIONS: In the SWOG-1216 trial, patients were randomized (1:1) to receive either androgen deprivation therapy (ADT) with orteronel, 300 mg orally twice daily (experimental group), or ADT with bicalutamide, 50 mg orally daily (control group), until disease progression, unacceptable toxic effects, or patient withdrawal.

MAIN OUTCOMES AND MEASURES: Overall survival was the primary end point; progression-free survival (PFS) and prostate-specific antigen (PSA) response were secondary end points. Cox proportional hazards regression models were used for both univariable and multivariable analyses adjusting for age, treatment type, Gleason score, disease volume, Zubrod performance status, and PSA level.

RESULTS: Of the 1279 male study participants, 301 (23.5%) had baseline bone pain at MHSPC diagnosis and 896 (70.1%) did not. Bone pain status was unavailable in 82 patients (6.4%). The median age of the 1197 patients eligible and included in this secondary analysis was 67.6 years (IQR, 61.8-73.6 years). Compared with patients who did not experience bone pain, those with baseline bone pain were younger (median age, 66.0 [IQR, 60.1-73.4] years vs 68.2 [IQR, 62.4-73.7] years; P = .02) and had a higher incidence of high-volume disease (212 [70.4%] vs 373 [41.6%]; P < .001). After adjustment, bone pain was associated with shorter PFS and OS. At a median follow-up of 4.0 years (IQR, 2.5-5.4 years), patients with bone pain had median PFS of 1.3 years (95% CI, 1.1-1.7 years) vs 3.7 years (95% CI, 3.3-4.2 years) in patients without initial bone pain (adjusted hazard ratio [AHR], 1.46; 95% CI, 1.22-1.74; P < .001) and OS of 3.9 years (95% CI, 3.3-4.8 years) vs not reached (NR) (95% CI, 6.6 years to NR) in patients without initial bone pain (AHR, 1.66; 95% CI, 1.34-2.05; P < .001).

CONCLUSIONS AND RELEVANCE: In this post hoc secondary analysis of the SWOG-1216 randomized clinical trial, patients with baseline bone pain at MHSPC diagnosis had worse survival outcomes than those without bone pain. These data suggest prioritizing these patients for enrollment in clinical trials, may aid patient counseling, and indicate that the inclusion of bone pain in prognostic models of MHSPC may be warranted.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01809691.},
}

Humans
Male
Aged
*Androgen Antagonists/therapeutic use
Middle Aged
*Prostatic Neoplasms/mortality/drug therapy/complications/pathology
*Bone Neoplasms/secondary/mortality/complications/drug therapy
Nitriles/therapeutic use
Prospective Studies
Cancer Pain/drug therapy
Anilides/therapeutic use
Tosyl Compounds/therapeutic use/adverse effects
Androstenes/therapeutic use
Pain/drug therapy/etiology

@article {pmid38980027,
year = {2024},
author = {Fogel, JM and Piwowar-Manning, E and Moser, A and Hill, T and Ahmed, S and Cummings, V and Mostafa, HH and Wang, Z and Jennings, A and Gallardo-Cartagena, JA and Figueroa, MI and St Clair, M and Rinehart, AR and Adeyeye, A and Rooney, JF and Cohen, MS and Grinsztejn, B and Landovitz, RJ and Eshleman, SH and , },
title = {Evaluation of Xpert point-of-care assays for detection of HIV infection in persons using long-acting cabotegravir for pre-exposure prophylaxis.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0030724},
doi = {10.1128/spectrum.00307-24},
pmid = {38980027},
issn = {2165-0497},
abstract = {UNLABELLED: Detection of HIV infection may be challenging in persons using long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) due to viral suppression and reduced/delayed antibody production. We evaluated two point-of-care tests for detecting HIV infection in persons who received CAB-LA in the HPTN 083 trial. Samples were obtained from 12 participants who received CAB-LA and had delayed detection of HIV infection using HIV rapid tests and an antigen/antibody test (52 plasma samples; 18 dried blood spot [DBS] samples). Plasma samples were tested with the Xpert HIV-1 Viral Load XC test (Xpert VL-XC); DBS samples were tested with the total nucleic acid Xpert HIV-1 Qual XC test (Xpert Qual-XC). Results from these assays were compared to results from three reference, laboratory-based, plasma RNA assays (Aptima HIV-1 Qualitative assay [Aptima Qual]; Aptima HIV-1 Quant DX Assay [Aptima Quant]; cobas HIV-1/HIV-2 Qualitative Test [cobas]). HIV RNA was detected with all four plasma assays for all samples with viral loads (VLs) ≥ 200 copies/mL; the number of samples with VLs < 200 copies/mL with HIV RNA detected was: Xpert VL-XC: 19/26 (73.1%); Aptima Qual: 17/26 (65.4%); Aptima Quant: 17/26 (65.4%); and cobas: 12/21 (57.1%). The Xpert Qual-XC assay was positive for all DBS samples with VLs ≥ 200 copies/mL and 1/10 DBS with VLs < 200 copies/mL. The performance of the Xpert VL-XC assay was comparable to the reference assays for detecting HIV infection in these cases. The Xpert Qual-XC assay was less sensitive than plasma-based HIV RNA assays for detecting HIV in the setting of CAB-LA PrEP.

IMPORTANCE: HIV RNA assays can detect HIV infections earlier than HIV rapid tests or Ag/Ab tests in persons using CAB-LA PrEP. Earlier HIV diagnosis could allow for earlier treatment initiation and reduced risk of INSTI resistance. POC tests may help detect HIV infection before CAB-LA administration and may be more accessible than laboratory-based assays in some settings. In this study, the POC Xpert VL-XC assay detected HIV RNA in most samples from individuals who received CAB-LA PrEP and had delayed detection of HIV infection with HIV rapid tests and an Ag/Ab test. The performance of this assay was similar to laboratory-based HIV RNA assays in this cohort. The POC Xpert Qual-XC assay detects both HIV RNA and DNA, with a higher viral load cutoff for RNA detection. This assay was negative for most lower viral load samples and did not offer an advantage for HIV screening in persons using CAB-LA PrEP.},
}

@article {pmid38977707,
year = {2024},
author = {Chari, A and Kaufman, JL and Laubach, J and Sborov, DW and Reeves, B and Rodriguez, C and Silbermann, R and Costa, LJ and Anderson, LD and Nathwani, N and Shah, N and Bumma, N and Holstein, SA and Costello, C and Jakubowiak, A and Wildes, TM and Orlowski, RZ and Shain, KH and Cowan, AJ and Pei, H and Cortoos, A and Patel, S and Lin, TS and Voorhees, PM and Usmani, SZ and Richardson, PG},
title = {Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN.},
journal = {Blood cancer journal},
volume = {14},
number = {1},
pages = {107},
pmid = {38977707},
issn = {2044-5385},
mesh = {Humans ; *Multiple Myeloma/drug therapy/mortality/therapy/diagnosis ; Aged ; Female ; Male ; Middle Aged ; *Antibodies, Monoclonal/therapeutic use/administration & dosage ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Adult ; Dexamethasone/administration & dosage/therapeutic use ; Bortezomib/therapeutic use/administration & dosage ; Lenalidomide/therapeutic use/administration & dosage ; },
abstract = {The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease-negativity (10[-5]) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a trend toward improved progression-free survival versus RVd (hazard ratio [95% confidence interval]) in patients ≥ 65 years (0.29 [0.06-1.48]), with HRCAs (0.38 [0.14-1.01]), and with gain/amp(1q21) (0.42 [0.14-1.27]). In the functional high-risk subgroup (not MRD negative at the end of consolidation), the hazard ratio was 0.82 (0.35-1.89). Among patients ≥ 65 years, grade 3/4 treatment-emergent adverse event (TEAE) rates were higher for D-RVd versus RVd (88.9% vs 77.8%), as were TEAEs leading to discontinuation of ≥ 1 treatment component (37.0% vs 25.9%). One D-RVd patient died due to an unrelated TEAE. These results support the addition of daratumumab to RVd in transplant-eligible patients with high-risk NDMM. Video Abstract.},
}

Humans
*Multiple Myeloma/drug therapy/mortality/therapy/diagnosis
Aged
Female
Male
Middle Aged
*Antibodies, Monoclonal/therapeutic use/administration & dosage
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Adult
Dexamethasone/administration & dosage/therapeutic use
Bortezomib/therapeutic use/administration & dosage
Lenalidomide/therapeutic use/administration & dosage

@article {pmid38977682,
year = {2024},
author = {Shadman, M and Ahn, KW and Kaur, M and Lekakis, L and Beitinjaneh, A and Iqbal, M and Ahmed, N and Hill, B and Hossain, NM and Riedell, P and Gopal, AK and Grover, N and Frigault, M and Brammer, J and Ghosh, N and Merryman, R and Lazaryan, A and Ram, R and Hertzberg, M and Savani, B and Awan, F and Khimani, F and Ahmed, S and Kenkre, VP and Ulrickson, M and Shah, N and Kharfan-Dabaja, MA and Herrera, A and Sauter, C and Hamadani, M},
title = {Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission.},
journal = {Blood cancer journal},
volume = {14},
number = {1},
pages = {108},
pmid = {38977682},
issn = {2044-5385},
support = {27305C0011/ES/NIEHS NIH HHS/United States ; 27307C0011/ES/NIEHS NIH HHS/United States ; 27398C0011/ES/NIEHS NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Lymphoma, Large B-Cell, Diffuse/therapy/mortality ; Middle Aged ; Female ; Male ; Adult ; *Transplantation, Autologous ; Retrospective Studies ; Aged ; *Hematopoietic Stem Cell Transplantation/methods ; *Immunotherapy, Adoptive/methods ; Young Adult ; Remission Induction ; Adolescent ; Treatment Outcome ; Pathologic Complete Response ; },
abstract = {In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015-2021) vs. CAR-T (2018-2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT (n = 281) or commercial CAR-T (n = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.},
}

Humans
*Lymphoma, Large B-Cell, Diffuse/therapy/mortality
Middle Aged
Female
Male
Adult
*Transplantation, Autologous
Retrospective Studies
Aged
*Hematopoietic Stem Cell Transplantation/methods
*Immunotherapy, Adoptive/methods
Young Adult
Remission Induction
Adolescent
Treatment Outcome
Pathologic Complete Response

@article {pmid38976877,
year = {2024},
author = {Vedula, RS and Karp, HQ and Koob, J and Lim, F and Garcia, JS and Winer, ES and Luskin, MR and Ghiaur, G and Kim, AS and Beppu, LW and Sala-Torra, O and Radich, JP and Gootenberg, JS and Abudayyeh, O and Zhang, F and Lindsley, RC},
title = {CRISPR-based rapid molecular diagnostic tests for fusion-driven leukemias.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2023022908},
pmid = {38976877},
issn = {1528-0020},
abstract = {Fusion oncogenes can be cancer-defining molecular alterations that are essential for diagnosis and therapy selection.1,2 Rapid and accessible molecular diagnostics for fusion-driven leukemias such as acute promyelocytic leukemia (APL), Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and chronic myeloid leukemia (CML) are unavailable, creating a barrier to timely diagnosis and effective targeted therapy in many healthcare settings, including community hospitals and low-resource environments. We developed CRISPR-based RNA-fusion transcript detection assays using SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the diagnosis of fusion-driven leukemias. We validated these assays using diagnostic APL and CML patient samples from academic centers and dried blood spots from low-resource environments, demonstrating 100% sensitivity and specificity. We identified assay optimizations to enable the use of these tests outside of tertiary cancer centers and clinical laboratories, enhancing the potential impact of this technology. Rapid point-of-care diagnostics can improve outcomes in cancer patients by expanding access to therapies for highly treatable diseases that would otherwise lead to serious adverse outcomes due to delayed or missed diagnoses.},
}

@article {pmid38976697,
year = {2024},
author = {Kosmider, E and Wallner, J and Gervassi, A and Bender Ignacio, RA and Pinto-Santini, D and Gornalusse, G and Pandey, U and Hladik, F and Edlefsen, PT and Lama, JR and Duerr, AC and Frenkel, LM},
title = {Observational study of effects of HIV acquisition and antiretroviral treatment on biomarkers of systemic immune activation.},
journal = {PloS one},
volume = {19},
number = {7},
pages = {e0288895},
pmid = {38976697},
issn = {1932-6203},
mesh = {Humans ; *HIV Infections/drug therapy/immunology/blood ; Male ; *Biomarkers/blood ; Female ; Adult ; Retrospective Studies ; Inflammation/blood ; Middle Aged ; Acute-Phase Proteins/metabolism ; C-Reactive Protein/metabolism/analysis ; Anti-HIV Agents/therapeutic use ; Transgender Persons ; Carrier Proteins ; Membrane Glycoproteins ; },
abstract = {To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants' specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery. When evaluating systematic variation in these markers over time, we found that multiple biomarkers consistently varied across participants' two pre-infection or two post-ART-suppression specimens. Additionally, we compared changes in biomarkers after vs before HIV acquisition. Across 47 participants, the levels of C-reactive protein (CRP), monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein (LBP) significantly decreased following HIV infection. Randomization to deferred-ART initiation was associated with greater increases in CRP and no decrease in LBP. Acquisition of HIV appeared to induce systemic inflammation, with elevation of biomarkers previously associated with infections and cardiovascular disease. Initiation of ART during the early weeks of infection tempered the increase in pro-inflammatory biomarkers compared to delaying ART for ~24 weeks after HIV diagnosis. These findings provide insight into potential mediators by which immediate-ART initiation improves health outcomes, perhaps because immediate-ART limits the size of the HIV reservoir or limits immune dysregulation that in turn trigger systemic inflammation.},
}

Humans
*HIV Infections/drug therapy/immunology/blood
Male
*Biomarkers/blood
Female
Adult
Retrospective Studies
Inflammation/blood
Middle Aged
Acute-Phase Proteins/metabolism
C-Reactive Protein/metabolism/analysis
Anti-HIV Agents/therapeutic use
Transgender Persons
Carrier Proteins
Membrane Glycoproteins

@article {pmid38976321,
year = {2024},
author = {McClure, JB and Heffner, JL and Krakauer, C and Mun, S and Catz, SL},
title = {A Novel mHealth App for Smokers Living With HIV Who Are Ambivalent About Quitting Smoking: Formative Research and Randomized Feasibility Study.},
journal = {JMIR formative research},
volume = {8},
number = {},
pages = {e58063},
doi = {10.2196/58063},
pmid = {38976321},
issn = {2561-326X},
abstract = {BACKGROUND: More people who smoke and are living with HIV now die from tobacco-related diseases than HIV itself. Most people are ambivalent about quitting smoking and want to quit someday but not yet. Scalable, effective interventions are needed to motivate and support smoking cessation among people ambivalent about quitting smoking (PAQS) who are living with HIV.

OBJECTIVE: This study aims to develop an app-based intervention for PAQS who are living with HIV and assess its feasibility, acceptability, and potential impact. Results of this study will inform plans for future research and development.

METHODS: In phase 1, PAQS living with HIV (n=8) participated in user-centered design interviews to inform the final intervention app design and recruitment plan for a subsequent randomized pilot study. In phase 2, PAQS living with HIV were randomized to either a standard care control app or a similar experimental app with additional content tailored for PAQS and those with HIV. Participants were followed for 3 months. Feasibility focused on recruitment, retention, and participants' willingness to install the app. The study was not powered for statistical significance. Indices of acceptability (satisfaction and use) and impact (smoking behavior change and treatment uptake) were assessed via automated data and self-report among those who installed and used the app (n=19).

RESULTS: Recruitment for both study phases was a challenge, particularly via web-based and social media platforms. Enrollment success was greater among people living with HIV recruited from a health care provider and research registry. Once enrolled, retention for the phase 2 randomized study was good; 74% (14/19) of the participants completed the 3-month follow-up. Phase 1 findings suggested that PAQS living with HIV were receptive to using an app-based intervention to help them decide whether, when, and how to stop smoking, despite not being ready to quit smoking. Phase 2 findings further supported this conclusion based on feedback from people who agreed to use an app, but group differences were observed. Indices of acceptability favored the experimental arm, including a descriptively higher mean number of sessions and utilization badges. Similarly, indices of potential impact were descriptively higher in the experimental arm (proportion reducing smoking, making a quit attempt, or calling free tobacco quitline). No participants in either arm quit smoking at the 3-month follow-up.

CONCLUSIONS: On the basis of this formative work, PAQS living with HIV may be receptive to using a mobile health-based app intervention to help them decide whether, when, or how to stop using tobacco. Indices of acceptability and impact indicate that additional research and development are warranted.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05339659; https://clinicaltrials.gov/study/NCT05339659.},
}

@article {pmid38974349,
year = {2024},
author = {Liu, Y and Lawler, T and Liu, Z and Thuruthumaly, C and Vajaranant, T and Wallace, R and Tinker, L and Nalbandyan, M and Mares, J},
title = {Low Macular Pigment Optical Density Is Associated with Manifest Primary Open-Angle Glaucoma in Older Women.},
journal = {Current developments in nutrition},
volume = {8},
number = {6},
pages = {103789},
pmid = {38974349},
issn = {2475-2991},
abstract = {BACKGROUND: Lower density of carotenoids lutein and zeaxanthin (L/Z) in the macula (i.e., macular pigment) has been linked to greater risk for age-related eye disease.

OBJECTIVES: We evaluated whether macular pigment optical density (MPOD) was associated with manifest primary open-angle glaucoma (POAG) among older women in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2).

METHODS: MPOD was measured with customized heterochromatic flicker photometry in women who attended CAREDS2 (2016-2019) and CAREDS1 (2001-2004) study visits. Manifest POAG at CAREDS2 was assessed using visual fields, disc photos, optical coherence tomography, and medical records. Age-adjusted linear and logistic regression models were used to investigate the cross-sectional association between POAG and MPOD at CAREDS2, and MPOD measured 15 years earlier at CAREDS1.

RESULTS: Among 426 CAREDS2 participants (mean age: 80 y; range: 69-98 y), 26 eyes with manifest POAG from 26 participants were identified. Glaucomatous eyes had 25% lower MPOD compared to nonglaucomatous eyes [mean (SE): 0.40 (0.05) compared with 0.53 (0.01)] optical density units (ODU), respectively (P = 0.01). Compared with MPOD quartile 1, odds for POAG were lower for women in quartiles 2-4 (P-trend = 0.01). After excluding eyes with age-related macular degeneration, associations were similar but not statistically significant (P-trend = 0.16). Results were similar for MPOD measured at CAREDS1.

CONCLUSIONS: Our results add to growing evidence that low MPOD may be a novel glaucoma risk factor and support further studies to assess the utility of dietary interventions for glaucoma prevention.},
}

@article {pmid38973806,
year = {2024},
author = {Sofer, T and Granot-Hershkovitz, E and Tarraf, W and Filigrana, P and Isasi, CR and Suglia, SF and Kaplan, R and Taylor, K and Daviglus, ML and Testai, FD and Zeng, D and Cai, J and Fornage, M and González, HM and DeCarli, C},
title = {Intracranial Volume Is Driven by Both Genetics and Early Life Exposures: The SOL-INCA-MRI Study.},
journal = {Ethnicity & disease},
volume = {34},
number = {2},
pages = {103-112},
pmid = {38973806},
issn = {1945-0826},
support = {N01HC65236/HL/NHLBI NIH HHS/United States ; N01HC65235/HL/NHLBI NIH HHS/United States ; R01 AG080598/AG/NIA NIH HHS/United States ; N01HC65233/HL/NHLBI NIH HHS/United States ; RF1 AG077639/AG/NIA NIH HHS/United States ; R01 AG075758/AG/NIA NIH HHS/United States ; R01 AG048642/AG/NIA NIH HHS/United States ; RF1 AG061022/AG/NIA NIH HHS/United States ; RF1 AG054548/AG/NIA NIH HHS/United States ; N01HC65234/HL/NHLBI NIH HHS/United States ; N01HC65237/HL/NHLBI NIH HHS/United States ; R21 AG070644/AG/NIA NIH HHS/United States ; R21 AG056952/AG/NIA NIH HHS/United States ; P30 AG072972/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Magnetic Resonance Imaging ; Female ; Male ; *Hispanic or Latino ; *Brain/diagnostic imaging ; Adult ; Middle Aged ; United States ; Organ Size ; Aged ; Child ; },
abstract = {Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging - MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm[3] in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm[3] smaller ICV (95% CI, -39.97 to -8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm[3] greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development.},
}

Humans
*Magnetic Resonance Imaging
Female
Male
*Hispanic or Latino
*Brain/diagnostic imaging
Adult
Middle Aged
United States
Organ Size
Aged
Child

@article {pmid38972511,
year = {2024},
author = {Iqbal, M and Kumar, A and Dreger, P and Chavez, J and Sauter, CS and Sureda, AM and Bachanova, V and Maziarz, RT and Dreyling, M and Smith, SM and Jacobson, C and Glass, B and Casulo, C and Oluwole, OO and Montoto, S and Advani, R and Cohen, J and Salles, G and Hamad, N and Kuruvilla, J and Kahl, BS and Shadman, M and Kanate, AS and Budde, LE and Kamdar, M and Flowers, C and Hamadani, M and Kharfan-Dabaja, MA},
title = {Clinical Practice Recommendations for Hematopoietic Cell Transplantation and Cellular Therapies in Follicular Lymphoma: A Collaborative Effort on behalf of The American Society of Transplantation and Cellular Therapy and the European Society of Blood and Marrow Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.06.025},
pmid = {38972511},
issn = {2666-6367},
abstract = {Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL), accounting for nearly one-third of all NHL. The therapeutic landscape for patients with FL has significantly expanded over the past decade, but the disease continues to be considered incurable. Hematopoietic cell transplantation (HCT) is potentially curative in some cases. Recently, the emergence of chimeric antigen receptor T-cell therapy (CAR-T) for patients with relapsed/refractory (R/R) FL has yielded impressive response rates and long-term remissions, but definitive statement on the curative potential of CAR-T is currently not possible due to limited patient numbers and relatively short follow up. A consensus on the contemporary role, optimal timing, and sequencing of HCT (autologous or allogeneic) and cellular therapies in FL is needed. As a result, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines endorsed this effort to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 15 consensus statements/recommendations. Of note, the use of bispecific antibodies in R/R FL was not in the scope of this project. Key statements/recommendations are as follows: 1) Autologous HCT is recommended as an option for consolidation therapy in patients with progression of untransformed disease within 24 months of front line chemoimmunotherapy and upon achieving a complete (CR) or partial response (PR) to salvage second line therapies; 2) CAR-T is considered as a treatment option for patients who did not achieve CR or PR after second or subsequent lines of therapies; 3) Allogeneic HCT is considered as consolidative treatment in relapsed FL patients with chemosensitive disease who have received 3 or more lines of systemic therapy and are the following clinical scenarios: post CAR-T failure; lack of access to CAR-T or have therapy related myeloid neoplasm. These clinical practice recommendations will help guide clinicians managing patients with FL.},
}

@article {pmid38971667,
year = {2024},
author = {Chauhan, SSB and Vierra, B and Park, JO and Pillarisetty, VG and Davidson, GH and Sham, JG},
title = {Prophylactic somatostatin analogs for postoperative pancreatic fistulas: a cross-sectional survey of AHPBA surgeons.},
journal = {HPB : the official journal of the International Hepato Pancreato Biliary Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.hpb.2024.06.002},
pmid = {38971667},
issn = {1477-2574},
abstract = {BACKGROUND: Postoperative pancreatic fistulas lead to substantially increased morbidity, mortality, and healthcare costs after pancreatectomy. Studies have reported conflicting data on the role of prophylactic somatostatin analogs in the reduction of postoperative pancreatic fistula. Current practice patterns, surgeon beliefs, and barriers to using these drugs in the Americas is not known.

METHODS: An online 26-question cross-sectional survey was distributed via email to the members of the Americas Hepato-Pancreato-Biliary Association in April 2023.

RESULTS: One hundred and two surgeons responded in spring 2023. 48.0% of respondents reported using prophylactic SSAs during their surgical training, however, only 29.4% do so in their current practice, most commonly when performing Whipple procedures. Octreotide was the most frequently used SSA (34.3%), followed by octreotide LAR (12.7%) and pasireotide (11.8%). Reasons for not prescribing included a lack of high-quality data (62.7%), perception of limited efficacy (34.3%) and high cost (30.4%).

CONCLUSION: These results highlight key areas for future study including understanding surgeon rationale for patient and drug selection. Variable practice patterns amongst surgeons also underscore the importance of generalizability in the design of future clinical trials in order to maximize impact.},
}

@article {pmid38971327,
year = {2024},
author = {Wang, J and Zhang, W and Xu, X and Buglioni, A and Li, P and Chen, X and Liu, Y and Xu, M and Herrick, JL and Horna, P and Zhang, X and Song, J and Jevremovic, D and He, R and Shi, M and Yuan, J},
title = {Clinicopathologic Features and Outcomes of Acute Leukemia Harboring PICALM::MLLT10 Fusion.},
journal = {Human pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.humpath.2024.07.003},
pmid = {38971327},
issn = {1532-8392},
abstract = {The PICALM::MLLT10 fusion is a rare but recurrent cytogenetic abnormality in acute leukemia, with limited clinicopathologic and outcome data available. Herein, we analyzed 156 acute leukemia patients with PICALM::MLLT10 fusion, including 12 patients from our institutions and 144 patients from the literature. The PICALM::MLLT10 fusion preferentially manifested in pediatric and young adult patients, with a median age of 24 years. T-lymphoblastic leukemia/lymphoma (T-ALL) constituted 65% of cases, acute myeloid leukemia (AML) 27%, and acute leukemia of ambiguous lineage (ALAL) 8%. About half of T-ALL were classified as an early T-precursor (ETP)-ALL. In our institutions' cohort, mediastinum was the most common extramedullary site of involvement. Eight of 12 patients were diagnosed with T-ALL exhibiting a pro-/pre-T stage phenotype (CD4/CD8-double negative, CD7-positive), and frequent CD79a expression. NGS revealed pathogenic mutations in 5 of 6 tested cases, including NOTCH1, and genes in RAS and JAK-STAT pathways and epigenetic modifiers. Of 138 cases with follow-up, pediatric patients (<18 years) had 5-year overall survival (OS) of 71%, significantly better than adults at 33%. The 5-year OS for AML patients was 25%, notably shorter than T-ALL patients at 54%; this distinction was observed in both pediatric and adult populations. Furthermore, adult but not pediatric ETP-ALL patients demonstrated inferior survival compared to non-ETP-ALL patients. Neither karyotype complexity nor transplant status had a discernible impact on OS. In conclusion, PICALM::MLLT10 fusion is most commonly seen in T-ALL patients, particularly those with an ETP phenotype. AML and adult ETP-ALL patients had adverse prognosis. PICALM::MLTT10 fusion testing should be considered in T-ALL, AML, and ALAL patients.},
}

@article {pmid38969253,
year = {2024},
author = {Lee, JM and Ichikawa, L and Kerlikowske, K and Buist, DSM and Lee, CI and Sprague, BL and Henderson, LM and Onega, T and Wernli, KJ and Lowry, KP and Stout, NK and Tosteson, ANA and Miglioretti, DL},
title = {Relative timing of mammography and MRI for breast cancer screening: Impact on performance evaluation.},
journal = {Journal of the American College of Radiology : JACR},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacr.2024.06.020},
pmid = {38969253},
issn = {1558-349X},
abstract = {OBJECTIVE: Mammography and MRI screening typically occur in combination or in alternating sequence. We compared multimodality screening performance accounting for the relative timing of mammography and MRI and overlapping follow-up periods.

METHODS: We identified 8,260 screening mammograms performed 2005-2017 in the Breast Cancer Surveillance Consortium, paired with screening MRIs within +/- 90 days (combined screening) or 91-270 days (alternating screening). Performance for combined screening [cancer detection rate (CDR) per 1000 examinations and sensitivity] was calculated with one-year follow-up for each modality, and with a single follow-up period treating the two tests as a single test. Alternating screening performance was calculated with one-year follow-up for each modality and also with follow-up ending at the next screen if within one year (truncated follow-up).

RESULTS: For 3,810 combined screening pairs, CDR per 1000 screens was 6.8 (95%CI: 4.6-10.0) for mammography and 12.3 (95%CI: 9.3-16.4) for MRI as separate tests compared to 13.1 (95%CI: 10.0-17.3) as a single combined test. Sensitivity of each test was 48.1% (35.0%-61.5%) for mammography and 79.7% (95%CI: 67.7-88.0%) for MRI compared to 96.2% (95%CI: 85.9-99.0%) for combined screening. For 4,450 alternating screening pairs, mammography CDR per 1000 screens changed from 3.6 (95%CI: 2.2-5.9) to zero with truncated follow-up; sensitivity was incalculable (denominator=0). MRI CDR per 1000 screens changed from 12.1 (95%CI 9.3-15.8) to 11.7 (95%CI: 8.9-15.3) with truncated follow-up; sensitivity changed from 75.0% (95%CI 63.8-83.6%) to 86.7% (95%CI 75.5-93.2%).

DISCUSSION: Updating auditing approaches to account for combined and alternating screening sequencing and to address outcome attribution issues arising from overlapping follow-up periods can improve the accuracy of multimodality screening performance evaluation.},
}

@article {pmid38968146,
year = {2024},
author = {Fingrut, WB and Troyer, J and Russell, E and Aviles, MM and Della-Moretta, S and Dobson, D and Hasanali, ZS and Hu, B and Lapite, A and Pillai, PM and Schramm, J and Villagomez, L and Vo, P and Wang'ondu, R and Yui, JC and Weyand, AC},
title = {The American Society of Hematology Health Equity Compendium: examining health equity across the Blood Journals.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024013633},
pmid = {38968146},
issn = {2473-9537},
}

@article {pmid38968122,
year = {2024},
author = {Zaidi, S and Park, J and Chan, JM and Roudier, MP and Zhao, JL and Gopalan, A and Wadosky, KM and Patel, RA and Sayar, E and Karthaus, WR and Kates, DH and Chaudhary, O and Xu, T and Masilionis, I and Mazutis, L and Chaligné, R and Obradovic, A and Linkov, I and Barlas, A and Jungbluth, AA and Rekhtman, N and Silber, J and Manova-Todorova, K and Watson, PA and True, LD and Morrissey, C and Scher, HI and Rathkopf, DE and Morris, MJ and Goodrich, DW and Choi, J and Nelson, PS and Haffner, MC and Sawyers, CL},
title = {Single-cell analysis of treatment-resistant prostate cancer: Implications of cell state changes for cell surface antigen-targeted therapies.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {28},
pages = {e2322203121},
doi = {10.1073/pnas.2322203121},
pmid = {38968122},
issn = {1091-6490},
support = {NA//Howard Hughes Medical Institute (HHMI)/ ; CA155169//HHS | NIH | National Cancer Institute (NCI)/ ; },
mesh = {Male ; Humans ; *Single-Cell Analysis/methods ; Animals ; Mice ; Prostatic Neoplasms/genetics/metabolism/pathology/drug therapy ; Antigens, Surface/metabolism/genetics ; Antigens, Neoplasm/metabolism/genetics/immunology ; Biomarkers, Tumor/metabolism/genetics ; Adenocarcinoma/genetics/pathology/metabolism/drug therapy ; Carcinoma, Neuroendocrine/genetics/pathology/metabolism/drug therapy ; Gene Expression Regulation, Neoplastic ; Prostatic Neoplasms, Castration-Resistant/metabolism/pathology/genetics/drug therapy ; },
abstract = {Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)-a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival. To understand how lineage markers vary across the evolution of lineage plasticity in prostate cancer, we applied single-cell analyses to 21 human prostate tumor biopsies and two genetically engineered mouse models, together with tissue microarray analysis on 131 tumor samples. Not only did we observe a higher degree of phenotypic heterogeneity in castrate-resistant PRAD and NEPC than previously anticipated but also found that the expression of molecules targeted therapeutically, namely PSMA, STEAP1, STEAP2, TROP2, CEACAM5, and DLL3, varied within a subset of gene-regulatory networks (GRNs). We also noted that NEPC and small cell lung cancer subtypes shared a set of GRNs, indicative of conserved biologic pathways that may be exploited therapeutically across tumor types. While this extreme level of transcriptional heterogeneity, particularly in cell surface marker expression, may mitigate the durability of clinical responses to current and future antigen-directed therapies, its delineation may yield signatures for patient selection in clinical trials, potentially across distinct cancer types.},
}

Male
Humans
*Single-Cell Analysis/methods
Animals
Mice
Prostatic Neoplasms/genetics/metabolism/pathology/drug therapy
Antigens, Surface/metabolism/genetics
Antigens, Neoplasm/metabolism/genetics/immunology
Biomarkers, Tumor/metabolism/genetics
Adenocarcinoma/genetics/pathology/metabolism/drug therapy
Carcinoma, Neuroendocrine/genetics/pathology/metabolism/drug therapy
Gene Expression Regulation, Neoplastic
Prostatic Neoplasms, Castration-Resistant/metabolism/pathology/genetics/drug therapy

@article {pmid38965267,
year = {2024},
author = {Riem, L and DuCharme, O and Cousins, M and Feng, X and Kenney, A and Morris, J and Tapscott, SJ and Tawil, R and Statland, J and Shaw, D and Wang, L and Walker, M and Lewis, L and Jacobs, MA and Leung, DG and Friedman, SD and Blemker, SS},
title = {AI driven analysis of MRI to measure health and disease progression in FSHD.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {15462},
pmid = {38965267},
issn = {2045-2322},
support = {K23 NS091379/NS/NINDS NIH HHS/United States ; P50 AR065139/AR/NIAMS NIH HHS/United States ; 1K23NS091379/GF/NIH HHS/United States ; },
mesh = {Humans ; *Muscular Dystrophy, Facioscapulohumeral/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; *Disease Progression ; *Artificial Intelligence ; Male ; Female ; Middle Aged ; Adult ; Muscle, Skeletal/diagnostic imaging/pathology ; Image Processing, Computer-Assisted/methods ; },
abstract = {Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers.},
}

Humans
*Muscular Dystrophy, Facioscapulohumeral/diagnostic imaging/pathology
*Magnetic Resonance Imaging/methods
*Disease Progression
*Artificial Intelligence
Male
Female
Middle Aged
Adult
Muscle, Skeletal/diagnostic imaging/pathology
Image Processing, Computer-Assisted/methods

@article {pmid38964333,
year = {2024},
author = {Wang, H and Yao, Z and Kang, K and Zhou, L and Xiu, W and Sun, J and Xie, C and Yu, M and Li, Y and Zhang, Y and Zheng, Y and Lin, G and Pan, X and Wu, Y and Luo, R and Wang, L and Tang, M and Liao, S and Zhu, J and Zhou, X and Zhang, X and Xu, Y and Liu, Y and Peng, F and Wang, J and Xiang, L and Yin, L and Deng, L and Huang, M and Gong, Y and Zou, B and Wang, H and Wu, L and Yuan, Z and Bi, N and Fan, M and Xu, Y and Tong, R and Yi, L and Gan, L and Xue, J and Mo, X and Chen, C and Na, F and Lu, Y},
title = {Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.},
journal = {Med (New York, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.medj.2024.06.002},
pmid = {38964333},
issn = {2666-6340},
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.

METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety.

FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1[+] PD-1[+] CD8[+] stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3).

CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation.

FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).},
}

@article {pmid38963827,
year = {2024},
author = {Goya, S and Wendm, ST and Xie, H and Nguyen, TV and Barnes, S and Shankar, RR and Sereewit, J and Cruz, K and Pérez-Osorio, AC and Mills, MG and Greninger, AL},
title = {Genomic epidemiology and evolution of rhinovirus in western Washington State, 2021-22.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiae347},
pmid = {38963827},
issn = {1537-6613},
abstract = {BACKGROUND: Human rhinoviruses (RV) primarily cause the common cold, but infection outcomes vary from subclinical to severe cases, including asthma exacerbations and fatal pneumonia in immunocompromised individuals. To date, therapeutic strategies have been hindered by the high diversity of serotypes. Global surveillance efforts have traditionally focused on sequencing VP1 or VP2/VP4 genetic regions, leaving gaps in our understanding of RV genomic diversity.

METHODS: We sequenced 1,078 RV genomes from nasal swabs of symptomatic and asymptomatic individuals to explore viral evolution during two epidemiologically distinct periods in Washington State: when the COVID-19 pandemic affected the circulation of other seasonal respiratory viruses except for RV (February - July 2021), and when the seasonal viruses reemerged with the severe RSV and influenza outbreak (November-December 2022). We constructed maximum likelihood and BEAST-phylodynamic trees to characterize intra-genotype evolution.

RESULTS: We detected 99 of 168 known genotypes and observed inter-genotypic recombination and genotype cluster swapping from 2021 to 2022. We found a significant association between the presence of symptoms and viral load, but not with RV species or genotype. Phylodynamic trees, polyprotein selection pressure, and Shannon entropy revealed co-circulation of divergent clades within genotypes with high amino acid constraints throughout polyprotein.

DISCUSSION: Our study underscores the dynamic nature of RV genomic epidemiology within a localized geographic region, as more than 20% of existing genotypes within each RV species co-circulated each studied month. Our findings also emphasize the importance of investigating correlations between rhinovirus genotypes and serotypes to understand long-term immunity and cross-protection.},
}

@article {pmid38963825,
year = {2024},
author = {Papini, C and Mirzaei S, S and Xing, M and Tonning Olsson, I and Salloum, R and de Blank, PMK and Lange, KR and King, TZ and Srivastava, D and Leisenring, WM and Howell, RM and Oeffinger, KC and Robison, LL and Armstrong, GT and Krull, KR and Brinkman, TM},
title = {Neurocognitive outcomes and functional independence in adult survivors of childhood medulloblastoma diagnosed over three decades.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noae119},
pmid = {38963825},
issn = {1523-5866},
support = {P30 CA021765/CA/NCI NIH HHS/United States ; T32 CA250803/CA/NCI NIH HHS/United States ; U24 CA055727/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown.

METHODS: Adult survivors of childhood medulloblastoma (n=505; median[minimum-maximum] age, 29[18-46] years) and sibling controls (n=727; 32[18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI]≥30 Gy, no chemotherapy), standard-risk (CSI>0 to <30 Gy +chemotherapy) and high-risk (CSI≥30 Gy +chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver's license, marital/partner status. Multivariable models estimated risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence.

RESULTS: Survivors in each treatment exposure group had 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval [CI] 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems and seizures were associated with 33%-34%, 25-26% and 21%-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with non-independence.

CONCLUSIONS: Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.},
}

@article {pmid38963280,
year = {2024},
author = {Lyman, GH and Kuderer, NM},
title = {Artificial Intelligence and Cancer Clinical Research: III Risk Prediction Models for Febrile Neutropenia in Patients Receiving Cancer Chemotherapy.},
journal = {Cancer investigation},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/07357907.2024.2370692},
pmid = {38963280},
issn = {1532-4192},
}

@article {pmid38574299,
year = {2024},
author = {Ledergor, G and Fan, Z and Wu, K and McCarthy, E and Hyrenius-Wittsten, A and Starzinski, A and Chang, H and Bridge, M and Kwek, S and Cheung, A and Bylsma, S and Hansen, E and Wolf, J and Wong, S and Shah, N and Roybal, KT and Martin, T and Ye, CJ and Fong, L},
title = {CD4+ CAR T-cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR T-cell therapy.},
journal = {Blood advances},
volume = {8},
number = {13},
pages = {3562-3575},
doi = {10.1182/bloodadvances.2023012416},
pmid = {38574299},
issn = {2473-9537},
support = {R35 CA253175/CA/NCI NIH HHS/United States ; },
mesh = {*Multiple Myeloma/therapy/immunology ; Humans ; *B-Cell Maturation Antigen/metabolism/immunology ; *Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/immunology/metabolism ; *CD4-Positive T-Lymphocytes/immunology/metabolism ; Recurrence ; Male ; Female ; T-Cell Exhaustion ; },
abstract = {Multiple myeloma is characterized by frequent clinical relapses after conventional therapy. Recently, chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA) has been established as a treatment option for patients with relapsed or refractory disease. However, although >70% of patients initially respond to this treatment, clinical relapse and disease progression occur in most cases. Recent studies showed persistent expression of BCMA at the time of relapse, indicating that immune-intrinsic mechanisms may contribute to this resistance. Although there were no preexisting T-cell features associated with clinical outcomes, we found that patients with a durable response to CAR T-cell treatment had greater persistence of their CAR T cells than patients with transient clinical responses. They also possessed a significantly higher proportion of CD8+ T-effector memory cells. In contrast, patients with short-lived responses to treatment have increased frequencies of cytotoxic CD4+ CAR T cells. These cells expand in vivo early after infusion but express exhaustion markers (hepatitis A virus cellular receptor 2 [HAVCR2] and T-cell immunoglobulin and mucin domain-containing-3 [TIGIT]) and remain polyclonal. Finally, we demonstrate that nonclassical monocytes are enriched in the myeloma niche and may induce CAR T-cell dysfunction through mechanisms that include transforming growth factor β. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR T-cell therapy.},
}

*Multiple Myeloma/therapy/immunology
Humans
*B-Cell Maturation Antigen/metabolism/immunology
*Immunotherapy, Adoptive/methods
*Receptors, Chimeric Antigen/immunology/metabolism
*CD4-Positive T-Lymphocytes/immunology/metabolism
Recurrence
Male
Female
T-Cell Exhaustion

@article {pmid38961298,
year = {2024},
author = {Dadonaite, B and Brown, J and McMahon, TE and Farrell, AG and Figgins, MD and Asarnow, D and Stewart, C and Lee, J and Logue, J and Bedford, T and Murrell, B and Chu, HY and Veesler, D and Bloom, JD},
title = {Spike deep mutational scanning helps predict success of SARS-CoV-2 clades.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {38961298},
issn = {1476-4687},
abstract = {SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion[1] and affect other properties that contribute to viral fitness, such as ACE2 receptor binding and cell entry[2,3]. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning[4] to measure how more than 9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully affected ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456 and 473; however, the antigenic effects of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however, many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.},
}

@article {pmid38955177,
year = {2024},
author = {Madan, A and Kelly, KP and Bahk, P and Sullivan, CE and Poling, ME and Brent, AE and Alassaf, M and Dubrulle, J and Rajan, A},
title = {Atg8/LC3 controls systemic nutrient surplus signaling in flies and humans.},
journal = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2024.06.005},
pmid = {38955177},
issn = {1879-0445},
abstract = {Organisms experience constant nutritional flux. Mechanisms at the interface of opposing nutritional states-scarcity and surplus-enable organismal energy homeostasis. Contingent on nutritional stores, adipocytes secrete adipokines, such as the fat hormone leptin, to signal nutrient status to the central brain. Increased leptin secretion underlies metabolic dysregulation during common obesity, but the molecular mechanisms regulating leptin secretion from human adipocytes are poorly understood. Here, we report that Atg8/LC3 family proteins, best known for their role in autophagy during nutrient scarcity, play an evolutionarily conserved role during nutrient surplus by promoting adipokine secretion. We show that in a well-fed state, Atg8/LC3 promotes the secretion of the Drosophila functional leptin ortholog unpaired 2 (Upd2) and leptin from human adipocytes. Proteomic analyses reveal that LC3 directs leptin to a secretory pathway in human cells. We identified LC3-dependent extracellular vesicle (EV) loading and secretion (LDELS) as a required step for leptin release, highlighting a unique secretory route adopted by leptin in human adipocytes. In Drosophila, mutations to Upd2's Atg8 interaction motif (AIM) result in constitutive adipokine retention. Atg8-mediated Upd2 retention alters lipid storage and hunger response and rewires the bulk organismal transcriptome in a manner conducive to starvation survival. Thus, Atg8/LC3's bidirectional role in nutrient sensing-conveying nutrient surplus and responding to nutrient deprivation-enables organisms to manage nutrient flux effectively. We posit that decoding how bidirectional molecular switches-such as Atg8/LC3-operate at the nexus of nutritional scarcity and surplus will inform therapeutic strategies to tackle chronic metabolic disorders.},
}

@article {pmid38954235,
year = {2024},
author = {Marín-Chollom, AM and Rillamas-Sun, E and Koch, PA and Contento, IR and Gaffney, AO and Ulanday, KT and Hershman, DL and Greenlee, H},
title = {Social Support, Diet, and Physical Activity among Latina/Hispanic Women Breast Cancer Survivors.},
journal = {Journal of immigrant and minority health},
volume = {},
number = {},
pages = {},
pmid = {38954235},
issn = {1557-1920},
support = {R01 CA186080-01A1/CA/NCI NIH HHS/United States ; UL1TR00040/TR/NCATS NIH HHS/United States ; Avon Pilot Study//Herbert Irving comprehensive cancer center, Columbia University/ ; },
abstract = {Diet and physical activity guidelines for cancer survivorship are less likely to be followed by populations of minority cancer survivors, such as Latina/Hispanic women, compared to non-Hispanic White women. It is important to understand psychosocial mechanisms that may increase adherence to healthy lifestyle habits, especially in populations at risk for poorer cancer outcomes. This cross-sectional study examined the relationships between overall social support (SS) and SS from three sources (family, friends, and significant other) with diet (fruit and vegetables, fat, energy density, and diet quality), and moderate-to-vigorous physical activity (MVPA) behaviors in Latina/Hispanic women with a history of breast cancer (n = 85; M age = 55.2; SD = 9.2). Linear regression models and odds ratios were used to examine associations and adjusted for age, income, and acculturation. Family, significant other, and total SS were positively related to total fruit and vegetable intake but SS from friends was not. Higher levels of SS from all sources were each related to a low energy density diet. A higher quality diet was only related to SS from family. SS was not related to fat intake or MVPA. Higher SS from family and a significant other were associated with higher odds of meeting the fruit/vegetable guidelines; (family, OR = 3.72, 95% CI [1.21, 11.39]; significant other, OR = 3.32, 95% CI [1.08, 10.30]). Having more SS from family or a significant other may contribute to Latina/Hispanic women breast cancer survivors meeting national guidelines for a diet high in fruits and vegetables and low in energy density.},
}

@article {pmid38953656,
year = {2024},
author = {Rudd, PA and Kher, G and Tame, JRH and Irie, H and Haselhorst, T and von Itzstein, M and Pancera, M and Hansman, GS},
title = {Human milk oligosaccharide 2'-fucosyllactose guards norovirus histo-blood group antigen co-factor binding site.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0086524},
doi = {10.1128/jvi.00865-24},
pmid = {38953656},
issn = {1098-5514},
}

@article {pmid38953655,
year = {2024},
author = {Hansman, GS and Kher, G and Svirina, AD and Tame, JRH and Hartley-Tassell, L and Irie, H and Haselhorst, T and von Itzstein, M and Rudd, PA and Pancera, M},
title = {Development of a broad-spectrum therapeutic Fc-nanobody for human noroviruses.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0070724},
doi = {10.1128/jvi.00707-24},
pmid = {38953655},
issn = {1098-5514},
abstract = {Human norovirus was discovered more than five decades ago and is a widespread cause of outbreaks of acute gastroenteritis. There are no approved vaccines or antivirals currently available. However, norovirus inhibitors, including capsid-specific monoclonal antibodies (Mabs) and nanobodies, have recently shown promising results. Several Mabs and nanobodies were found to inhibit norovirus replication using a human intestinal enteroid (HIE) culture system and/or could block norovirus attachment to histo-blood group antigen (HBGA) co-factors. In our pursuit to develop a single broad-spectrum norovirus therapeutic, we continued our analysis and development of a cross-reactive and HBGA interfering nanobody (NB26). To improve NB26 binding capacity and therapeutic potential, we conjugated NB26 onto a human IgG Fc domain (Fc-NB26). We confirmed that Fc-NB26 cross-reacts with genetically diverse GII genotype capsid protruding (P) domains (GII.8, GII.14, GII.17, GII.24, GII.26, and GII.NA1) using a direct enzyme-linked immunosorbent assay. Furthermore, X-ray crystallography structures of these P domains and structures of other GII genotypes reveal that the NB26 binding site is largely conserved, validating its broad reactivity. We showed that Fc-NB26 has ~100-fold higher affinity toward the norovirus P domain compared to native NB26. We also found that both NB26 and Fc-NB26 neutralize human norovirus replication in the HIE culture system. Furthermore, the mode of inhibition confirmed that like NB26, Fc-NB26 caused norovirus particle disassembly and aggregation. Overall, these new findings demonstrate that structural modifications to nanobodies can improve their therapeutic potential.IMPORTANCEDeveloping vaccines and antivirals against norovirus remains a challenge, mainly due to the constant genetic and antigenic evolution. Moreover, re-infection with genetically related and/or antigenic variants is not uncommon. We further developed our leading norovirus nanobody (NB26) that indirectly interfered with norovirus binding to HBGAs, by converting NB26 into a dimeric Fc-linked Nanobody (Fc-NB26). We found that Fc-NB26 had improved binding affinity and neutralization capacity compared with native NB26. Using X-ray crystallography, we showed this nanobody engaged highly conserved capsid residues among genetically diverse noroviruses. Development of such broadly reactive potent therapeutic nanobodies delivered as a slow-releasing prophylactic could be of exceptional value for norovirus outbreaks, especially for the prevention or treatment of severe acute gastroenteritis in high-risk groups such as the young, elderly, and immunocompromised.},
}

@article {pmid38950184,
year = {2024},
author = {Samorodnitsky, S and Campbell, K and Ribas, A and C Wu, M},
title = {A Spatial Omnibus Test (SPOT) for Spatial Proteomic Data.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btae425},
pmid = {38950184},
issn = {1367-4811},
abstract = {MOTIVATION: Spatial proteomics can reveal the spatial organization of immune cells in the tumor immune microenvironment. Relating measures of spatial clustering, such as Ripley's K or Besag's L, to patient outcomes may offer important clinical insights. However, these measures require pre-specifying a radius in which to quantify clustering, yet no consensus exists on the optimal radius which may be context-specific.

RESULTS: We propose a SPatial Omnibus Test (SPOT) which conducts this analysis across a range of candidate radii. At each radius, SPOT evaluates the association between the spatial summary and outcome, adjusting for confounders. SPOT then aggregates results across radii using the Cauchy combination test, yielding an omnibus p-value characterizing the overall degree of association. Using simulations, we verify that the type I error rate is controlled and show SPOT can be more powerful than alternatives. We also apply SPOT to an ovarian and lung cancer study.

AVAILABILITY: An R package and tutorial is provided at https://github.com/sarahsamorodnitsky/SPOT.},
}

@article {pmid38950175,
year = {2024},
author = {Li, M and Hua, X and Li, S and Wu, MC and Zhao, N},
title = {A multi-bin rarefying method for evaluating alpha diversities in TCR sequencing data.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btae431},
pmid = {38950175},
issn = {1367-4811},
abstract = {MOTIVATION: T cell receptors (TCRs) constitute a major component of our adaptive immune system, governing the recognition and response to internal and external antigens. Studying the TCR diversity via sequencing technology is critical for a deeper understanding of immune dynamics. However, library sizes differ substantially across samples, hindering the accurate estimation/comparisons of alpha diversities. To address this, researchers frequently use an overall rarefying approach in which all samples are sub-sampled to an even depth. Despite its pervasive application, its efficacy has never been rigorously assessed.

RESULTS: In this paper, we develop an innovative "multi-bin" rarefying approach that partitions samples into multiple bins according to their library sizes, conducts rarefying within each bin for alpha diversity calculations, and performs meta-analysis across bins. Extensive simulations using real-world data highlight the inadequacy of the overall rarefying approach in controlling the confounding effect of library size. Our method proves robust in addressing library size confounding, outperforming competing normalization strategies by achieving better-controlled type-I error rates and enhanced statistical power in association tests.

The code is available at https://github.com/mli171/MultibinAlpha. The datasets are freely available at https://doi.org/10.21417/B7001Z and https://doi.org/10.21417/AR2019NC.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}

@article {pmid38949847,
year = {2024},
author = {Zhao, LP and Papadopoulos, GK and Skyler, JS and Parikh, HM and Kwok, WW and Bondinas, GP and Moustakas, AK and Wang, R and Pyo, CW and Nelson, WC and Geraghty, DE and Lernmark, Å},
title = {Oral Insulin Delay of Stage 3 Type 1 Diabetes Revisited in HLA DR4-DQ8 Participants in the TrialNet Oral Insulin Prevention Trial (TN07).},
journal = {Diabetes care},
volume = {},
number = {},
pages = {},
doi = {10.2337/dc24-0573},
pmid = {38949847},
issn = {1935-5548},
support = {RO1 DK132406//Division of Diabetes, Endocrinology, and Metabolic Diseases/ ; },
abstract = {OBJECTIVE: To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1/2 who carry HLA DR4-DQ8 and/or have elevated levels of IA-2 autoantibodies (IA-2As).

RESEARCH AND METHODS: Next-generation targeted sequencing technology was used to genotype eight HLA class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants in the TrialNet oral insulin preventative trial (TN07). Baseline levels of autoantibodies against insulin (IAA), GAD65 (GADA), and IA-2A were determined prior to treatment assignment. Available clinical and demographic covariables from TN07 were used in this post hoc analysis with the Cox regression model to quantify the preventive efficacy of oral insulin.

RESULTS: Oral insulin reduced the frequency of T1D onset among participants with elevated IA-2A levels (HR 0.62; P = 0.012) but had no preventive effect among those with low IA-2A levels (HR 1.03; P = 0.91). High IA-2A levels were positively associated with the HLA DR4-DQ8 haplotype (OR 1.63; P = 6.37 × 10-6) and negatively associated with the HLA DR7-containing DRB1*07:01-DRB4*01:01-DQA1*02:01-DQB1*02:02 extended haplotype (OR 0.49; P = 0.037). Among DR4-DQ8 carriers, oral insulin delayed the progression toward stage 3 T1D onset (HR 0.59; P = 0.027), especially if participants also had high IA-2A level (HR 0.50; P = 0.028).

CONCLUSIONS: These results suggest the presence of a T1D endotype characterized by HLA DR4-DQ8 and/or elevated IA-2A levels; for those patients with stage 1/2 disease with such an endotype, oral insulin delays the clinical T1D onset.},
}

@article {pmid38949435,
year = {2024},
author = {McClelland, RS and Lokken, EM and Kinuthia, J and Srinivasan, S and Richardson, BA and Jaoko, W and Lannon, S and Pulei, A and Fiedler, TL and Munch, MM and Proll, S and John-Stewart, G and Fredricks, DN},
title = {A prospective cohort study examining the association between the periconceptual vaginal microbiota and first-trimester miscarriage in Kenyan women.},
journal = {Paediatric and perinatal epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ppe.13099},
pmid = {38949435},
issn = {1365-3016},
support = {//United States National Institutes of Health/ ; T32 AI07140/AI/NIAID NIH HHS/United States ; R01 HD87346-RSM/HD/NICHD NIH HHS/United States ; F32 HD100202/HD/NICHD NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Studies evaluating the association between the vaginal microbiota and miscarriage have produced variable results.

OBJECTIVE: This study evaluated the association between periconceptual and first-trimester vaginal microbiota and women's risk for miscarriage.

METHODS: At monthly preconception visits and at 9-12 weeks gestation, women collected vaginal swabs for molecular characterisation of the vaginal microbiota. Participants who became pregnant were followed to identify miscarriage versus pregnancy continuing to at least 20 weeks gestation.

RESULTS: Forty-five women experienced miscarriage and 144 had pregnancies continuing to ≥20 weeks. A principal component analysis of periconceptual and first-trimester vaginal bacteria identified by 16S rRNA gene PCR with next-generation sequencing did not identify distinct bacterial communities with miscarriage versus continuing pregnancy. Using taxon-directed quantitative PCR assays, increasing concentrations of Megasphaera hutchinsoni, Mageeibacillus indolicus, Mobiluncus mulieris and Sneathia sanguinegens/vaginalis were not associated with miscarriage. In exploratory analyses, these data were examined as a binary exposure to allow for multivariable modelling. Detection of Mobiluncus mulieris in first-trimester samples was associated with miscarriage (adjusted relative risk [aRR] 2.14, 95% confidence interval [CI] 1.08, 4.22). Additional analyses compared women with early first-trimester miscarriage (range 4.7-7.3 weeks) to women with continuing pregnancies. Mobiluncus mulieris was detected in all eight (100%) first-trimester samples from women with early first-trimester miscarriage compared to 101/192 (52.6%) samples from women with continuing pregnancy (model did not converge). Detection of Mageeibacillus indolicus in first-trimester samples was also associated with early first-trimester miscarriage (aRR 4.10, 95% CI 1.17, 14.31).

CONCLUSIONS: The primary analyses in this study demonstrated no association between periconceptual or first-trimester vaginal microbiota and miscarriage. Exploratory analyses showing strong associations between first-trimester detection of Mobiluncus mulieris and Mageeibacillus indolicus and early first-trimester miscarriage suggest the need for future studies to determine if these findings are reproducible.},
}

@article {pmid38947062,
year = {2024},
author = {Scherer, M and Nandi, V and Sobieszczyk, ME and Laeyendecker, O and Karuna, S and Andrasik, M and Janes, HE and Brown, EE and Tieu, HV},
title = {Incidence and prevalence of hepatitis C and B infections among men who have sex with men and transgender women enrolled in a United States HIV vaccine trial.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {38947062},
issn = {2693-5015},
support = {UM1 AI069424/AI/NIAID NIH HHS/United States ; UM1 AI069534/AI/NIAID NIH HHS/United States ; UM1 AI069439/AI/NIAID NIH HHS/United States ; UM1 AI069481/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; HHSN272200800014C/AI/NIAID NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; UM1 AI069418/AI/NIAID NIH HHS/United States ; UM1 AI069501/AI/NIAID NIH HHS/United States ; P30 AI050409/AI/NIAID NIH HHS/United States ; UM1 AI069554/AI/NIAID NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; UM1 AI069412/AI/NIAID NIH HHS/United States ; UM1 AI069470/AI/NIAID NIH HHS/United States ; UM1 AI068614/AI/NIAID NIH HHS/United States ; UL1 TR000451/TR/NCATS NIH HHS/United States ; UM1 AI069452/AI/NIAID NIH HHS/United States ; UM1 AI069496/AI/NIAID NIH HHS/United States ; UM1 AI069511/AI/NIAID NIH HHS/United States ; P30 AI036219/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Rising hepatitis C and B virus (HCV and HBV) rates have been reported in men who have sex with men (MSM) and transgender women (TGW). This study characterizes HCV and HBV infections longitudinally among 2,496 MSM/TGW aged 18-50 years and at risk for HIV acquisition enrolled in an HIV-1 vaccine trial in 18 U.S. cities between 2009-2013.

METHODS: Participants completed behavioral surveys, HIV testing, and blood collection over 24 months. Of the 2,397 participants who consented for future testing, 1,792 (74.8%) had available paired stored blood samples at baseline and a later timepoint (Month 24 [N = 999]; if unavailable, M12 [N = 775] or M15 [N = 18]).

RESULTS: Among 1,792 participants, 98.1% were MSM, 0.8% were TGW, and the median age was 30 years (IQR 24, 40). Participants reported a median number of 3 male sex partners (IQR 1,5) within the past 3 months. Condomless insertive anal sex was reported by 55.8% and condomless receptive anal sex by 46.7%.1.3% reported injection drug use. During follow-up, 1.4% reported pre-exposure prophylaxis (PrEP) use. At baseline 11/1792 (0.61%) participants had HCV infection (HCV AB positive, RNA detectable), with all having persistent detectable RNA and chronic HCV infection at follow-up. Phylogenetic analysis showed no clusters of HCV infection. 8 participants had HCV AB positive, RNA undetectable at baseline and follow-up, representing past HCV infection with clearance; only 2 acquired HCV, which cleared over 12-24 months. At baseline, 2 participants (2/1792 = 0.11%) had positive HBsAg, indicating chronic HBV infection. Over 12-24 months, 4 (4/1790, 0.22%) developed HBsAg positivity; these participants had HBcAB positivity at baseline, thereby likely representing reactivation. There were no new HBV infections during follow-up.

CONCLUSION: Among 1,792 men who have sex with men and transgender women aged 18-50 years and at risk for HIV acquisition enrolled in a U.S. HIV-1 vaccine trial, incident hepatitis C infection rates were extremely low, with no cases of incident hepatitis B infection. These rates of incident HCV infection and HBSAg positivity are lower than previously reported among MSM/TGW.},
}

@article {pmid38947282,
year = {2024},
author = {Samorodnitsky, S and Wendt, CH and Lock, EF},
title = {Bayesian Simultaneous Factorization and Prediction Using Multi-Omic Data.},
journal = {Computational statistics & data analysis},
volume = {197},
number = {},
pages = {},
pmid = {38947282},
issn = {0167-9473},
support = {R01 GM130622/GM/NIGMS NIH HHS/United States ; R01 HL140971/HL/NHLBI NIH HHS/United States ; R21 CA231214/CA/NCI NIH HHS/United States ; },
abstract = {Integrative factorization methods for multi-omic data estimate factors explaining biological variation. Factors can be treated as covariates to predict an outcome and the factorization can be used to impute missing values. However, no available methods provide a comprehensive framework for statistical inference and uncertainty quantification for these tasks. A novel framework, Bayesian Simultaneous Factorization (BSF), is proposed to decompose multi-omics variation into joint and individual structures simultaneously within a probabilistic framework. BSF uses conjugate normal priors and the posterior mode of this model can be estimated by solving a structured nuclear norm-penalized objective that also achieves rank selection and motivates the choice of hyperparameters. BSF is then extended to simultaneously predict a continuous or binary phenotype while estimating latent factors, termed Bayesian Simultaneous Factorization and Prediction (BSFP). BSF and BSFP accommodate concurrent imputation, i.e., imputation during the model-fitting process, and full posterior inference for missing data, including "blockwise" missingness. It is shown via simulation that BSFP is competitive in recovering latent variation structure, and demonstrate the importance of accounting for uncertainty in the estimated factorization within the predictive model. The imputation performance of BSF is examined via simulation under missing-at-random and missing-not-at-random assumptions. Finally, BSFP is used to predict lung function based on the bronchoalveolar lavage metabolome and proteome from a study of HIV-associated obstructive lung disease, revealing multi-omic patterns related to lung function decline and a cluster of patients with obstructive lung disease driven by shared metabolomic and proteomic abundance patterns.},
}

@article {pmid38947011,
year = {2024},
author = {Abernethy, NF and McCloskey, K and Trahey, M and Rinn, L and Broder, GB and Andrasik, M and Laborde, R and McGhan, D and Spendolini, S and Marimuthu, S and Kanzmeier, A and Hanes, J and Kublin, J},
title = {Rapid Development of a Registry to Accelerate COVID-19 Vaccine Clinical Trials.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {38947011},
issn = {2693-5015},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: The unprecedented scientific response to the SARS-Cov-2 pandemic in 2020 required the rapid development and activation of extensive clinical trial networks to study vaccines and therapeutics. The COVID-19 Prevention Network (CoVPN) coordinated hundreds of sites conducting phase 2 and 3 clinical trials of vaccines and antibody therapeutics. To facilitate these clinical trials, the CoVPN Volunteer Screening Registry (VSR) was created to collect volunteer information at scale, identify volunteers at risk of COVID-19 who met enrollment criteria, distribute candidates across clinical trial sites, and enable monitoring of volunteering and enrollment progress.

METHODS: We developed a secure database to support three primary web-based interfaces: a national volunteer questionnaire intake form, a clinical trial site portal, and an Administrative Portal. The Site Portal supported filters based on volunteer attributes, visual analytics, enrollment status tracking, geographic search, and clinical risk prediction. The Administrative Portal supported oversight and development with pre-specified reports aggregated by geography, trial, and trial site; charts of volunteer rates over time; volunteer risk score calculation; and dynamic, user-defined reports.

FINDINGS: Over 650,000 volunteers joined the VSR, and 1094 users were trained to utilize the system. The VSR played a key role in recruitment for the Moderna, Oxford-AstraZeneca, Janssen, and Novavax vaccine clinical trials, provided support to the Pfizer and Sanofi vaccine and prophylactic antibody clinical trials, and enhanced the diversity of trial participants. Clinical trial sites selected 166,729 volunteer records for follow-up screening, and of these 47·7% represented groups prioritized for increased enrollment. Despite the unprecedented urgency of its development, the system maintained 99·99% uptime.

INTERPRETATION: The success of the VSR demonstrates that information tools can be rapidly yet safely developed through a public-private partnership and integrated into a distributed and accelerated clinical trial setting. We further summarize the requirements, design, and development of the system, and discuss lessons learned for future pandemic preparedness.},
}

@article {pmid38946649,
year = {2024},
author = {Woolston, DW and Lee, ND and Shadman, M and Latorre-Esteves, E and Tee, XR and Fredrickson, J and Kohrn, BF and Ujjani, C and Eckel, A and Till, B and Fang, M and Radich, J and Bozic, I and Risques, RA and Yeung, CCS},
title = {Erratum to: Ultra-deep mutational landscape in chronic lymphocytic leukemia uncovers dynamics of resistance to targeted therapies.},
journal = {Haematologica},
volume = {109},
number = {7},
pages = {2378},
pmid = {38946649},
issn = {1592-8721},
mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/genetics/drug therapy/mortality ; *Mutation ; *Drug Resistance, Neoplasm/genetics ; *Molecular Targeted Therapy ; High-Throughput Nucleotide Sequencing ; },
}

Humans
*Leukemia, Lymphocytic, Chronic, B-Cell/genetics/drug therapy/mortality
*Mutation
*Drug Resistance, Neoplasm/genetics
*Molecular Targeted Therapy
High-Throughput Nucleotide Sequencing