tbuckley/cabot-search huggingface dataset:
TET3-overexpressing macrophages promote endometriosis
Authors: Haining Lv, Beibei Liu, Yangyang Dai, Feng Li, Stefania Bellone, Yuping Zhou, Ramanaiah Mamillapalli, Dejian Zhao, Muthukumaran Venkatachalapathy, Yali Hu, Gordon G. Carmichael, Da Li, Hugh S. Taylor, Yingqun Huang
Journal: Journal of Clinical Investigation (2024)

Endometriosis is a debilitating, chronic inflammatory disease affecting approximately 10% of reproductive-age women worldwide with no cure. While macrophages have been intrinsically linked to the pathophysiology of endometriosis, targeting them therapeutically has been extremely challenging due to their high heterogeneity and because these disease-associated macrophages (DAMs) can be either pathogenic or protective. Here, we report identification of pathogenic macrophages characterized by TET3 overexpression in human endometriosis lesions. We show that factors from the disease microenvironment upregulated TET3 expression, transforming macrophages into pathogenic DAMs. TET3 overexpression stimulated proinflammatory cytokine production via a feedback mechanism involving inhibition of let-7 miRNA expression. Remarkably, these cells relied on TET3 overexpression for survival and hence were vulnerable to TET3 knockdown. We demonstrated that Bobcat339, a synthetic cytosine derivative, triggered TET3 degradation in both human and mouse macrophages. This degradation was dependent on a von Hippel-Lindau (VHL) E3 ubiquitin ligase whose expression was also upregulated in TET3-overexpressing macrophages. Furthermore, depleting TET3-overexpressing macrophages either through myeloid-specific Tet3 ablation or using Bobcat339 strongly inhibited endometriosis progression in mice. Our results defined TET3-overexpressing macrophages as key pathogenic contributors to and attractive therapeutic targets for endometriosis. Our findings may also be applicable to other chronic inflammatory diseases where DAMs have important roles.
Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the 2<sup>nd</sup> International Post-Tuberculosis Symposium
Authors: Sara C. Auld, Amy K. Barczak, William Bishai, Anna K. Coussens, Intan M. W. Dewi, Steven C. Mitini-Nkhoma, Caleb Muefong, Threnesan Naidoo, Anil Pooran, Cari Stek, Adrie J. C. Steyn, Liku Tezera, Naomi F. Walker
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Post-tuberculosis (post-TB) lung disease is increasingly recognized as a major contributor to the global burden of chronic lung disease, with recent estimates indicating that over half of TB survivors have impaired lung function after successful completion of TB treatment. However, the pathologic mechanisms that contribute to post-TB lung disease are not well understood, thus limiting the development of therapeutic interventions to improve long-term outcomes after TB. This report summarizes the work of the Pathogenesis and Risk Factors Committee for the Second International Post-Tuberculosis Symposium, which took place in Stellenbosch, South Africa, in April 2023. The committee first identified six areas with high translational potential: 1) tissue matrix destruction, including the role of matrix metalloproteinase dysregulation and neutrophil activity; 2) fibroblasts and profibrotic activity; 3) granuloma fate and cell death pathways; 4) mycobacterial factors, including pathogen burden; 5) animal models; and 6) the impact of key clinical risk factors, including HIV, diabetes, smoking, malnutrition, and alcohol. We share the key findings from a literature review of those areas, highlighting knowledge gaps and areas where further research is needed.
Unveiling Commonalities: Exploring Shared Characteristics in Clear Cell Carcinomas of the Gynecologic Tract
Authors: Felix Blanc-Durand, Natalie Y.L. Ngoi, Diana G.S. Lim, David S.P. Tan
Journal: Clinical Cancer Research (2024)

Clear-cell carcinomas (CCC) arising from the gynecologic tract (including from the ovary, endometrium, cervix, vulva, or vagina) represent rare but clinically significant entities with intriguing overlapping characteristics. Epidemiologically, CCCs exhibit a predilection for women of Asian ethnicity and are often associated with a previous or synchronous diagnosis of endometriosis. Pathologically, despite originating from different primary organs, CCCs of the gynecologic tract show similar morphologic and immunophenotypic features on traditional histopathology, such as the expression of napsin A and hepatocyte nuclear factor 1β on IHC, without the expression of Wilms tumor 1. Well-described molecular characteristics of these cancers include recurrent mutations in genes such as ARID1A, PIK3CA, and/or PTEN, although significant variations exist across the different anatomic sites. Therapeutically, optimal management remains challenging due to the relative rarity of CCCs and limited subtype-specific clinical trials. Surgery remains the cornerstone of treatment, often complemented by systemic chemotherapy. However, promising drugs targeting angiogenesis or the immune microenvironment have emerged in recent years, leading to clinical successes, and are likely to reshape the therapeutic landscape of gynecologic CCC. This review summarizes the commonalities and disparities in terms of epidemiology, pathology, molecular features, and therapeutic approach, among CCCs of different anatomic origin, offering a foundation for further research and dedicated therapeutic interventions for these malignancies.
Maternal antibiotic prophylaxis during cesarean section has a limited impact on the infant gut microbiome
Authors: Trishla Sinha, Jelmer R Prins, Asier Fernández-Pato, Marloes Kruk, Thomas Dierikx, Tim de Meij, Marjon de Boer, Jan Freark de Boer, Sicco Scherjon, Alexander Kurilshikov, Alexandra Zhernakova
Journal: Cell Host & Microbe (2024)

Pregnant women undergoing a cesarean section (CS) typically receive antibiotics prior to skin incision to prevent infections. To investigate if the timing of antibiotics influences the infant gut microbiome, we conducted a randomized controlled trial (NCT06030713) in women delivering via a scheduled CS who received antibiotics either before skin incision or after umbilical cord clamping. We performed a longitudinal analysis on 172 samples from 28 infants at 8 post-birth time points and a cross-sectional analysis at 1 month in 79 infants from 3 cohorts. Although no significant associations with bacterial composition, metabolic pathways, short-chain fatty acids, and bile acids were found, we observed subtle differences between the groups at the bacterial strain level and in the load of antibiotic resistance genes. Rather, feeding mode was a predominant and defining factor impacting infant microbial composition. In conclusion, antibiotic administration during CS has only limited effects on the early-life gut microbiome.
Mental Health Diagnoses in People Experiencing Homelessness—Reply
Authors: Rebecca Barry, Dallas Seitz
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Umbilical Cord pH Levels and Neonatal Morbidity and Mortality
Authors: Charlotte Brix Andersson, Claus Klingenberg, Line Thellesen, Søren Paaske Johnsen, Ulrik Schiøler Kesmodel, Jesper Padkaer Petersen
Journal: JAMA Network Open (2024)

Importance Umbilical cord pH (UC-pH) level is an important objective indicator of intrapartum fetal hypoxia and is used to predict neonatal morbidity and mortality. A UC-pH value of less than 7.00 is often defined as a threshold for severe acidosis, but existing evidence is divergent and largely based on UC-pH measurements from selected populations; consequently, the results are challenging to interpret. Objective To investigate the association between UC-pH levels and the risk of adverse neonatal outcomes in a national setting with universal UC-pH measurement. Design, Setting, and Participants This national, population-based cohort study included all liveborn, singleton, full-term infants without malformations born in Denmark from January 1, 2012, to December 31, 2018. Data were analyzed from January 1, 2023, to March 1, 2024. Exposure Umbilical cord pH level categorized as less than 7.00, 7.00 to 7.09, 7.10 to 7.19 and 7.20 to 7.50 (reference group). Main Outcomes and Measures The primary outcome was a composite of severe adverse neonatal outcomes: neonatal death, therapeutic hypothermia, mechanical ventilation, treatment with inhaled nitric oxide, or seizures. Secondary outcomes were individual components of the primary outcome, Apgar score, respiratory outcomes, and hypoglycemia. Data are presented as adjusted risk ratios (ARRs) with 95% CIs. Results Among the 340 431 infants included, mean (SD) gestational age was 39.9 (1.6) weeks; mean (SD) birth weight was 3561 (480) g; and 51.3% were male. Umbilical cord pH of less than 7.20 was observed more often among infants with a gestational age of 40 or 41 weeks (31.6%-33.6% compared with 18.2%-20.2% at a gestational age of 39 weeks) and among male infants (53.9%-55.4% vs 44.6%-46.1% among female infants). Compared with the pH reference group (576 of 253 540 [0.2%]), the risk for the primary outcome was increased for the groups with UC-pH levels of less than 7.00 (171 of 1743 [9.8%]), 7.00 to 7.09 (101 of 11 904 [0.8%]), and 7.10 to 7.19 (259 of 73 244 [0.4%]). Comparable patterns were observed for the individual outcomes, except for neonatal death, which was only increased in the group with UC-pH levels of less than 7.10. The risk of treatment with continuous positive airway pressure was increased when UC-pH levels were less than 7.20, and the risk of hypoglycemia was 21.5% if UC-pH levels were less than 7.10. Conclusions and Relevance In this cohort study of 340 431 newborn infants, results support and extend previous studies indicating a higher risk of adverse outcomes even at UC-pH levels above 7.00. The threshold for more intensive observation and treatment may be reconsidered.
The Intersection of Endometriosis and Ovarian Cancer Prevention
Authors: Kari L. Ring
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
Exploring the Germline Genetics of In Situ and Invasive Cutaneous Melanoma
Authors: Nathan Ingold, Mathias Seviiri, Jue Sheng Ong, Rachel E. Neale, Nirmala Pandeya, David C. Whiteman, Catherine M. Olsen, Nicholas G. Martin, David L. Duffy, Kiarash Khosrotehrani, Nicholas Hayward, Grant W. Montgomery, Stuart MacGregor, Matthew H. Law
Journal: JAMA Dermatology (2024)

Importance It is unknown whether germline genetic factors influence in situ melanoma risk differently than invasive melanoma risk. Objective To determine whether differences in risk of in situ melanoma and invasive melanoma are heritable. Design, Setting, and Participants Three genome-wide association study meta-analyses were conducted of in situ melanoma vs controls, invasive melanoma vs controls, and in situ vs invasive melanoma (case-case) using 4 population-based genetic cohorts: the UK Biobank, the FinnGen cohort, the QSkin Sun and Health Study, and the Queensland Study of Melanoma: Environmental and Genetic Associations (Q-MEGA). Melanoma status was determined using International Statistical Classification of Diseases and Related Health Problems codes from cancer registry data. Data were collected from 1987 to 2022, and data were analyzed from September 2022 to June 2023. Exposure In situ and invasive cutaneous melanoma. Main Outcomes and Measures To test whether in situ and invasive melanoma have independent heritable components, genetic effect estimates were calculated for single-nucleotide variants (SNV; formerly single-nucleotide polymorphisms) throughout the genome for each melanoma. Then, SNV-based heritability was estimated, the genetic correlation between melanoma subtypes was assessed, and polygenic risk scores (PRS) were generated for in situ vs invasive status in Q-MEGA participants. Results A total of 6 genome-wide significant loci associated with in situ melanoma and 18 loci with invasive melanoma were identified. A strong genetic correlation (genetic r = 0.96; 95% CI, 0.76-1.15) was observed between the 2 classifications. Notably, loci near IRF4 , KLF4 , and HULC had significantly larger effects for in situ melanoma compared with invasive melanoma, while MC1R had a significantly larger effect on invasive melanoma compared with in situ melanoma. Heritability estimates were consistent for both, with in situ melanoma heritability of 6.7% (95% CI, 4.1-9.3) and invasive melanoma heritability of 4.9% (95% CI, 2.8-7.2). Finally, a PRS, derived from comparing invasive melanoma with in situ melanoma genetic risk, was on average significantly higher in participants with invasive melanoma (odds ratio per 1-SD increase in PRS, 1.43; 95% CI, 1.16-1.77). Conclusions and Relevance There is much shared genetic architecture between in situ melanoma and invasive melanoma. Despite indistinguishable heritability estimates between the melanoma classifications, PRS suggest germline genetics may influence whether a person gets in situ melanoma or invasive melanoma. PRS could potentially help stratify populations based on invasive melanoma risk, informing future screening programs without exacerbating the current burden of melanoma overdiagnosis.
Leading Health-Related Concerns of Older Adults Before the 2024 Election
Authors: John Z. Ayanian, Matthias Kirch, Dianne C. Singer, Erica Solway, J. Scott Roberts, Nicholas Box, Jeffrey T. Kullgren
Journal: JAMA (2024)

This national cohort survey of older adults assesses which health-related concerns they consider to be most salient in the 2024 election.
Long-Term Survival in Patients With Advanced Melanoma
Authors: Olivier J. van Not, Alfons J. M. van den Eertwegh, Hilde Jalving, Manja Bloem, John B. Haanen, Rozemarijn S. van Rijn, Maureen J. B. Aarts, Franchette W. P. J. van den Berkmortel, Christian U. Blank, Marye J. Boers-Sonderen, Jan Willem de Groot J. W. B., Geke A. P. Hospers, Ellen Kapiteijn, Brenda Leeneman, Piersma D., Marion Stevense-den Boer, Astrid A. M. van der Veldt, Gerard Vreugdenhil G., Michel W. J. M. Wouters, Willeke A. M. Blokx, Karijn P. M. Suijkerbuijk
Journal: JAMA Network Open (2024)

IMPORTANCE Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival. OBJECTIVE To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials. DESIGN, SETTING, AND PARTICIPANTS Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019. Data were analyzed from January to September 2023. EXPOSURES Patients were treated with first-line ipilimumab-nivolumab, antibodies that target programmed cell death (anti–PD-1), or ipilimumab. MAIN OUTCOMES AND MEASURES Progression-free survival (PFS) and melanoma-specific survival were analyzed, and a Cox proportional hazards model was used to investigate factors associated with PFS after reaching partial response (PR) or complete response (CR). RESULTS A total of 2490 patients treated with first-line ICIs were included (median [IQR] age, 65.0 [55.3-73.0] years; 1561 male patients [62.7%]). Most patients had an Eastern Cooperative Oncology Group Performance Status of 1 or lower (2202 patients [88.5%]) and normal lactate dehydrogenase levels (1715 patients [68.9%]). PFS for all patients was 23.4% (95% CI, 21.7%-25.2%) after 3 years and 19.7% (95% CI, 18.0%-21.4%) after 5 years. Overall survival for all patients was 44.0% (95% CI, 42.1%-46.1%) after 3 years and 35.9% (95% CI, 33.9%-38.0%) after 5 years. Patients with metastases in 3 or more organ sites had a significantly higher hazard of progression after reaching PR or CR (adjusted hazard ratio, 1.37; 95% CI, 1.11-1.69). CONCLUSIONS AND RELEVANCE This cohort study of patients with advanced melanoma treated with ICIs in clinical practice showed that their survival reached a plateau, comparable with patients participating in clinical trials. These findings can be used in daily clinical practice to guide long-term surveillance strategies and inform both physicians and patients regarding long-term treatment outcomes.
Doctor
Authors: Audrey Shafer
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Providing a Safe Pregnancy Experience for Surgeons
Authors: Tiffany A. Glazer, Kirsten A. Gunderson, Elise Deroo, Ellen C. Shaffrey, Hayley Mann, Maya N. Matabele, Rebecca M. Minter, J. Igor Iruretagoyena, John E. Rectenwald
Journal: JAMA Surgery (2024)

Childbearing has been a particular barrier to successful recruitment and retention of women in surgery. Pregnant surgeons are more likely to have major pregnancy complications, such as preterm delivery, intrauterine growth restriction, infertility, and miscarriage, compared with nonsurgeons. The average obstetric complication rate for surgeons ranges between 25% and 82% in the literature and is considerably higher than that in the general US population at 5% to 15%.
Minimal Access vs Conventional Nipple-Sparing Mastectomy
Authors: Joo Heung Kim, Jai Min Ryu, Soong June Bae, Beom Seok Ko, Jung Eun Choi, Ku Sang Kim, Chihwan Cha, Young Jin Choi, Hye Yoon Lee, Sang Eun Nam, Zisun Kim, Young-Joon Kang, Moo Hyun Lee, Jong Eun Lee, Eunhwa Park, Hyuk Jai Shin, Min Kyoon Kim, Hee Jun Choi, Seong Uk Kwon, Nak-Hoon Son, Hyung Seok Park, Jeeyeon Lee, Jeea Lee, Sae Byul Lee, Young Woo Chang, Jee Ye Kim
Journal: JAMA Surgery (2024)

While nipple-sparing mastectomy (NSM) for breast cancer was only performed using the open method in the past, its frequency using endoscopic and robotic surgical instruments has been increasing rapidly. However, there are limited studies regarding postoperative complications and the benefits and drawbacks of minimal access NSM (M-NSM) compared with conventional NSM (C-NSM).
Clinical Implications of New Drinking Water Regulation for “Forever Chemicals”
Authors: Rachel Criswell, Abby F. Fleisch, Alan Ducatman
Journal: JAMA (2024)

This Viewpoint describes new maximum contaminant levels set by the Environmental Protection Agency for specific perfluoroalkyl and polyfluoroalkyl substances (PFASs) and discusses the role clinicians can play in addressing their patients’ PFAS health concerns.
Does the Germline Genome Encode for the Invasiveness of a Cutaneous Melanoma?
Authors: Hildur Helgadottir
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Epicardial and Pericardial Fat—Separated But Under the Same Roof
Authors: Gianluca Iacobellis
Journal: JAMA Cardiology (2024)

To the Editor I read the article by Ramo et al1 titled "Cardiovascular Significance and Genetics of Epicardial and Pericardial Adiposity" that was recently published in JAMA Cardiology with great interest.
Site-of-Care Shifts and Payments—A Viable Strategy to Control Health Care Costs?
Authors: Lee A. Fleisher, Sheila P. Burke
Journal: JAMA Network Open (2024)

Nikhil R. Sahni, MBA, MPA/ID; Crosbie Marine, BSc; David M. Cutler, PhD; Laura N. Medford-Davis, MD; Melvin Mezue, MD, PhD; Omar Kattan, MD; Ed Levine, MD; Karen E. Joynt Maddox, MD, MPH