tbuckley/cabot-search huggingface dataset:
Adrenal-Permissive Germline <i>HSD3B1</i> Allele and Prostate Cancer Outcomes
Authors: Rana R. McKay, Tyler J. Nelson, Meghana S. Pagadala, Craig C. Teerlink, Anthony Gao, Alex K. Bryant, Fatai Y. Agiri, Kripa Guram, Reid F. Thompson, Kathryn M. Pridgen, Tyler M. Seibert, Kyung Min Lee, Hannah Carter, Julie A. Lynch, Richard L. Hauger, Brent S. Rose
Journal: JAMA Network Open (2024)

Importance The adrenal androgen–metabolizing 3β-hydroxysteroid dehydrogenase-1 enzyme, encoded by the HSD3B1 gene, catalyzes the rate-limiting step necessary for synthesizing nontesticular testosterone and dihydrotestosterone production. The common adrenal-permissive HSD3B1 (1245C) allele is responsible for encoding the 3β-HSD1 protein with decreased susceptibility to degradation resulting in higher extragonadal androgen synthesis. Retrospective studies have suggested an association of the HSD3B1 adrenal-permissive homozygous genotype with androgen deprivation therapy resistance in prostate cancer. Objective To evaluate differences in mortality outcomes by HSD3B1 genetic status among men with prostate cancer. Design, Setting, and Participants This cohort study of patients with prostate cancer who were enrolled in the Million Veteran Program within the Veterans Health Administration (VHA) system between 2011 and 2023 collected genotyping and phenotyping information. Exposure HSD3B1 genotype status was categorized as AA (homozygous adrenal-restrictive), AC (heterozygous adrenal-restrictive), or CC (homozygous adrenal-permissive). Main Outcomes and Measures The primary outcome of this study was prostate cancer–specific mortality (PCSM), defined as the time from diagnosis to death from prostate cancer, censored at the date of last VHA follow-up. Secondary outcomes included incidence of metastases and PCSM in predefined subgroups. Results Of the 5287 participants (median [IQR] age, 69 [64-74] years), 402 (7.6%) had the CC genotype, 1970 (37.3%) had the AC genotype, and 2915 (55.1%) had the AA genotype. Overall, the primary cause of death for 91 patients (1.7%) was prostate cancer. Cumulative incidence of PCSM at 5 years after prostate cancer diagnosis was higher among men with the CC genotype (4.0%; 95% CI, 1.7%-6.2%) compared with the AC genotype (2.1%; 95% CI, 1.3%-2.8%) and AA genotype (1.9%; 95% CI, 1.3%-2.4%) ( P = .02). In the 619 patients who developed metastatic disease at any time, the cumulative incidence of PCSM at 5 years was higher among patients with the CC genotype (36.0%; 95% CI, 16.7%-50.8%) compared with the AC genotype (17.9%; 95% CI, 10.5%-24.7%) and AA genotype (18.5%; 95% CI, 12.0%-24.6%) ( P = .01). Conclusions and Relevance In this cohort study of US veterans undergoing treatment for prostate cancer at the VHA, the HSD3B1 CC genotype was associated with inferior outcomes. The HSD3B1 biomarker may help identify patients who may benefit from therapeutic targeting of 3β-hydroxysteroid dehydrogenase-1 and the androgen-signaling axis.
Strides in Racial Bias Training—A Step Closer to Health Equity
Authors: Monique Jindal, Nao Hagiwara
Journal: JAMA Network Open (2024)

Cristina M. Gonzalez, MD, MEd; Tavinder K. Ark, PhD; Marla R. Fisher, MD; Paul R. Marantz, MD, MPH; Diana J. Burgess, PhD; Felise Milan, MD; Malika T. Samuel, BFA; Monica L. Lypson, MD, MHPE; Carlos J. Rodriguez, MD, MPH; Adina L. Kalet, MD, MPH
Consolidating NRMP Fellowship Matches to Enhance the Applicant Experience
Authors: Jeanette L. Calli, Laurie S. Curtin
Journal: JAMA Cardiology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Racial and Ethnic Concordance Between National Health Service Corps Clinicians and Underserved Populations
Authors: Olesya Baker, Marcela Horvitz-Lennon, Hao Yu
Journal: JAMA Network Open (2024)

Importance Despite the widely recognized importance of racial and ethnic concordance between patients and clinicians, there is a lack of studies on clinician diversity in medically underserved areas and whether it aligns with the changing demographic landscape. Objective To assess trends in National Health Services Corps (NHSC) clinician diversity and racial and ethnic concordance between NHSC clinicians and the populations in underserved areas from before to after the 2009 NHSC expansion. Design, Setting, and Participants This cross-sectional, population-based study compared trends in the diversity of NHSC clinicians practicing in health professional shortage areas (HPSAs) and the HPSA populations during 2003 to 2019 using the Health Resources and Services Administration’s NHSC Field Strength Database and Area Health Resources Files. The analysis was performed from February through May 2023. Main Outcomes and Measures Concordance was measured with an annual community representativeness ratio defined as the ratio of the proportions of same race or ethnicity NHSC clinicians to HPSA population. Results There were a total of 41 180 clinicians practicing in HPSAs from 2003 to 2019; the median (IQR) age was 34 (30-41) years. Among 38 569 NHSC clinicians who reported gender, 28 444 (73.7%) identified as female and 10 125 (26.3%) identified as male. The average annual number of NHSC clinicians increased from 3357 in 2003 to 2008 to 9592 in 2009 to 2019. Before 2009, 1076 clinicians (5.3%) identified as Black, 9780 (48.6%) as Hispanic, 908 (4.5%) as other, and 8380 (41.6%) as White. During this period, concordance was low among non-Hispanic White and Black individuals due to clinician underrepresentation relative to the population, yet Hispanic clinicians were overrepresented. Following the 2009 NHSC expansion, the main change was the sharp decline in the proportion of Hispanic clinicians, to 1601 (13%) by 2019; while concordance was achieved for non-Hispanic White and Black individuals, Hispanic clinicians became underrepresented relative to population. The results held across 3 specialties: primary care, mental health care, and dental care. Conclusions and Relevance This cross-sectional study of trends in racial and ethnic concordance found that while the NHSC expansion starting in 2009 improved clinician-population concordance for non-Hispanic White and Black individuals, it reversed a prior trend for Hispanic individuals among whom clinicians became underrepresented relative to the population. Targeted NHSC clinician recruitment efforts are needed to improve concordance for Hispanic individuals in underserved areas, especially given Hispanics’ projected growth in the US.
Modifier 22 Use in Fee-for-Service Medicare
Authors: Christopher P. Childers, Naveen V. Manisundaram, Chung-Yuan Hu, George J. Chang
Journal: JAMA Surgery (2024)

Importance Modifier 22 is a mechanism designed for surgeons to identify cases that are more complex than their Current Procedural Terminology code accounts for. However, empirical studies of the use and efficacy of modifier 22 are lacking. Objective To assess the use of modifier 22 in common surgical procedures and the association of use with compensation. Design, Setting, and Participants This was a cross-sectional analysis of the 2021 Physician/Supplier Procedure Summary Limited Data Set including all Part B carrier and durable medical equipment fee-for-service claims. Claims for 10 common surgical procedures were evaluated, including mastectomy, total hip arthroplasty, total knee arthroplasty, coronary artery bypass grafting, laparoscopic right colectomy, laparoscopic appendectomy, laparoscopic cholecystectomy, kidney transplant, laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy, and lumbar laminectomy. Data were analyzed from August to November 2023. Main Outcomes and Measures Rate of modifier 22 use, rate of claim denial, mean charges, mean payment for accepted claims, and mean payment for all claims. Results The sample included 625 316 surgical procedures performed in calendar year 2021. The proportion of modifier 22 coding for a procedure ranged from 5725 of 251 521 (2.3%) in total knee arthroplasty to 1566 of 18 459 (8.5%) in laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy. Submitted charges were 11.1% (95% CI, 9.1-13.2) to 22.8% (95% CI, 21.3-24.3) higher for claims with modifier 22, depending on the procedure. Among accepted claims, those with modifier 22 had increased payments ranging from 0.8% (95% CI, 0.7-1.0) to 4.8% (95% CI, 4.5-5.1). However, claims with modifier 22 were more likely to be denied (7.4% vs 4.0%; P &amp;amp;lt; .001). As a result, overall mean payments were mixed, with 4 procedures having lower payments when modifier 22 was appended, 4 procedures having higher payments with modifier 22, and 2 procedures with no difference. The largest increase in mean payment for modifier 22 claims was for kidney transplant with an increased payment of $71.46 (95% CI, 55.32-87.60), which translates to a relative increase of 3.4% (95% CI, 2.9-4.6). Conclusions and Relevance The findings in this study suggest that modifier 22 had little to no financial benefit when appended to claims for a diverse panel of surgical procedures. In the current system, surgeons have little reason to request modifier 22, and no mechanisms currently exist for surgeons to recoup payment for difficult operations.
Phase I Trial of Viral Vector-Based Personalized Vaccination Elicits Robust Neoantigen-Specific Antitumor T-Cell Responses
Authors: Anna Morena D'Alise, Guido Leoni, Gabriella Cotugno, Loredana Siani, Rosa Vitale, Valentino Ruzza, Irene Garzia, Laura Antonucci, Elisa Micarelli, Veronica Venafra, Sven Gogov, Alessia Capone, Sarah Runswick, Juan Martin-Liberal, Emiliano Calvo, Victor Moreno, Stefan N. Symeonides, Elisa Scarselli, Oliver Bechter
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T-cell response to overcome tumor heterogeneity. NOUS-PEV is a vector-based personalized vaccine, expressing 60 nAgs and consists of priming with a nonhuman Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara. Here, we report data of a phase Ib trial of NOUS-PEV in combination with pembrolizumab in treatment-naïve patients with metastatic melanoma (NCT04990479). Patients and Methods: The feasibility of this approach was demonstrated by producing, releasing, and administering to 6 patients 11 of 12 vaccines within 8 weeks from biopsy collection to GAd20 administration. Results: The regimen was safe, with no treatment-related serious adverse events observed and mild vaccine-related reactions. Vaccine immunogenicity was demonstrated in all evaluable patients receiving the prime/boost regimen, with detection of robust neoantigen-specific immune responses to multiple neoantigens comprising both CD4 and CD8 T cells. Expansion and diversification of vaccine-induced T-cell receptor (TCR) clonotypes was observed in the posttreatment biopsies of patients with clinical response, providing evidence of tumor infiltration by vaccine-induced neoantigen-specific T cells. Conclusions: These findings indicate the ability of NOUS-PEV to amplify and broaden the repertoire of tumor-reactive T cells to empower a diverse, potent, and durable antitumor immune response. Finally, a gene signature indicative of the reduced presence of activated T cells together with very poor expression of the antigen-processing machinery genes has been identified in pretreatment biopsies as a potential biomarker of resistance to the treatment.
Mechanical and Oral Antibiotic Bowel Preparation in Elective Rectal Resection
Authors: Antonio M. Lacy, F. Borja de Lacy
Journal: JAMA Surgery (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Cell Context Is the Third Axis of Synergy for the Combination of ATR Inhibition and Cisplatin in Ewing Sarcoma
Authors: Jennifer Jess, Katie M. Sorensen, Elissa A. Boguslawski, Matthew C. Stout, Zachary B. Madaj, Benjamin P. Caiello, Monica Pomaville, Elizabeth R. Wilson, Seneca S. Kinn-Gurzo, Curtis C. Parker, Sridhar M. Veluvolu, Taylor V. Brysgel, Rebecca Kaufman, Susan M. Kitchen-Goosen, Jenna M. Gedminas, Patrick J. Grohar
Journal: Clinical Cancer Research (2024)

The importance of cellular context to the synergy of DNA damage response (DDR)-targeted agents is important for tumors with mutations in DDR pathways, but less well-established for tumors driven by oncogenic transcription factors. In this study, we exploit the widespread transcriptional dysregulation of the EWS-FLI1 transcription factor to identify an effective DDR-targeted combination therapy for Ewing sarcoma.
Tumour fibrosis in dopamine agonist-exposed prolactinomas is a diminishing concern
Authors: Sunita M. C. De Sousa, Alistair K. Jukes, Nicholas G. Candy, Ian M. Chapman, David J. Torpy, Brindha Shivalingam, Peter-John Wormald, Stephen Santoreneos
Journal: Nature Reviews Endocrinology (2024)
Heart-brain axis: low blood pressure during off-pump CABG surgery is associated with postoperative heart failure
Authors: Xiu-Yun Liu, Jing-Jing Mu, Jian-Ge Han, Mei-Jun Pang, Kuo Zhang, Wen-Qian Zhai, Nan Su, Guang-Jian Ni, Zhi-Gang Guo, Dong Ming
Journal: Military Medical Research (2024)
scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases
Authors: Samuel Schäfer, Martin Smelik, Oleg Sysoev, Yelin Zhao, Desiré Eklund, Sandra Lilja, Mika Gustafsson, Holger Heyn, Antonio Julia, István A. Kovács, Joseph Loscalzo, Sara Marsal, Huan Zhang, Xinxiu Li, Danuta Gawel, Hui Wang, Mikael Benson
Journal: Genome Medicine (2024)

Abstract Background Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs. Methods Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs. Results scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn’s disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn’s disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment. Conclusions We propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio’s potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package ( https://github.com/SDTC-CPMed/scDrugPrio ).
Chimeric antigen receptor‐T cell therapy shows similar efficacy and toxicity in patients with diffuse large B‐cell lymphoma aged 70 and older compared to younger patients: A multicenter cohort study
Authors: Philipp Berning, Evgenii Shumilov, Markus Maulhardt, Hristo Boyadzhiev, Andrea Kerkhoff, Simon Call, Christian Reicherts, Anna O. Saidy, Enver Aydilek, Michèle Hoffmann, Urban Novak, Michael Daskalakis, Norbert Schmitz, Matthias Stelljes, Gerald Wulf, Ulrike Bacher, Georg Lenz, Thomas Pabst
Journal: HemaSphere (2024)

Abstract CD19‐directed chimeric antigen receptor (CAR)‐T cell therapy has become a standard treatment for relapsed/refractory diffuse large B‐cell lymphoma (r/r DLBCL). While the benefits of CAR‐T cell treatment are clear in the general patient population, there remains a relative scarcity of real‐world evidence regarding its efficacy and toxicity in patients (pts) aged ≥70 years with DLBCL. We conducted a multicenter retrospective analysis including 172 r/r DLBCL pts with CAR‐T cell treatment, axicabtagene ciloleucel or tisagenlecleucel, between 2019 and 2023 at three tertiary centers. Pts were grouped by age at CAR‐T infusion (&lt;70 vs. ≥70 years). Subsequently, descriptive and survival analyses, including propensity score matching, were performed to compare outcomes between both age groups. We identified 109 pts aged &lt;70 and 63 pts aged ≥70 years. Overall response rates for both age groups were comparable (77.7% vs. 78.3%; p = 0.63). With a median follow‐up of 8.3 months, median progression‐free survival was 10.2 months (95% confidence interval [CI]: 6.5–21.8) and 11.1 months (95% CI: 4.9–NR) ( p = 0.93) for both cohorts. Median overall survival reached 21.8 months (95% CI: 11.8–NR) and 34.4 months (95% CI: 10.1–NR) ( p = 0.97), respectively. No significant differences in the incidence of cytokine release syndrome ( p = 0.53) or grade ≥3 neurotoxicity ( p = 0.56) were observed. Relapse and nonrelapse mortality were not significantly different between both groups. Our findings provide additional support that CAR‐T cell therapy is feasible and effective in patients with r/r DLBCL aged 70 years or older, demonstrating outcomes comparable to those observed in younger patients. CAR‐T cell therapy should be not withheld for elderly patients with r/r DLBCL.
Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation
Authors: Mohammad Arifuzzaman, Tae Hyung Won, Hiroshi Yano, Jazib Uddin, Elizabeth R. Emanuel, Elin Hu, Wen Zhang, Ting-Ting Li, Wen-Bing Jin, Alex Grier, Sanchita Kashyap, David Artis, Randy Longman, Gregory F. Sonnenberg, Ellen Scherl, Robbyn Sockolow, Dana Lukin, Vinita Jacob, Laura Sahyoun, Michael Mintz, Lasha Gogokhia, Thomas Ciecierega, Aliza Solomon, Arielle Bergman, Kimberley Chein, Elliott Gordon, Michelle Ramos, Kenny Joselin Castro Ochoa, Victoria Ribeiro de Godoy, Adriana Brcic-Susak, Seun Oguntunmibi, Dario Garone, Caitlin Mason, Chun-Jun Guo, Frank C. Schroeder, David Artis
Journal: The Journal of Experimental Medicine (2024)

Innate lymphoid cells (ILCs) can promote host defense, chronic inflammation, or tissue protection and are regulated by cytokines and neuropeptides. However, their regulation by diet and microbiota-derived signals remains unclear. We show that an inulin fiber diet promotes Tph1-expressing inflammatory ILC2s (ILC2INFLAM) in the colon, which produce IL-5 but not tissue-protective amphiregulin (AREG), resulting in the accumulation of eosinophils. This exacerbates inflammation in a murine model of intestinal damage and inflammation in an ILC2- and eosinophil-dependent manner. Mechanistically, the inulin fiber diet elevated microbiota-derived bile acids, including cholic acid (CA) that induced expression of ILC2-activating IL-33. In IBD patients, bile acids, their receptor farnesoid X receptor (FXR), IL-33, and eosinophils were all upregulated compared with controls, implicating this diet–microbiota–ILC2 axis in human IBD pathogenesis. Together, these data reveal that dietary fiber–induced changes in microbial metabolites operate as a rheostat that governs protective versus pathologic ILC2 responses with relevance to precision nutrition for inflammatory diseases.
An <i>Ex Vivo</i> Study Examining Migration of Microplastics from an Infused Neonatal Parenteral Nutrition Circuit
Authors: Maaike Vercauteren, Lucas Panneel, Philippe G. Jorens, Adrian Covaci, Paulien Cleys, Antonius Mulder, Colin R. Janssen, Jana Asselman
Journal: Environmental Health Perspectives (2024)

Figure 1.Overview of microplastic concentration (A), polymer composition (B), and size distribution (C) in the crystalloid solution collected in a simulated parenteral nutrition circuit and administered over a course of maximum 72 h with samples at time 0 (T0), T12, T24, T48, T72.The T0 measurements represent information on microplastics in the original fluid, without transition through the circuits.The number of samples per time point is indicated in panel A with "N=."Two particles (size 976 and 1,274:9 lm) are not included in the figure of the size distribution (Figure 1C).Plastic polymer types (Figure 1B), are polyacrylamide (PAM), polyester (PES), polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), and polystyrene (PS).Corresponding numeric data of the figure can be found in Supplementary data at https://zenodo.org/records/10102884("Supporting data -Numeric data.docx").