tbuckley/cabot-search huggingface dataset:
Combination of oligo-fractionated irradiation with nivolumab can induce immune modulation in gastric cancer
Authors: Kosaku Mimura, Takashi Ogata, Phuong H D Nguyen, Souvick Roy, Hassen Kared, Yate-Ching Yuan, Michael Fehlings, Yuya Yoshimoto, Daisaku Yoshida, Shotaro Nakajima, Hisashi Sato, Nozomu Machida, Takanobu Yamada, Yohei Watanabe, Tomoaki Tamaki, Hirohito Fujikawa, Yasuhiro Inokuchi, Suguru Hayase, Hiroyuki Hanayama, Zenichiro Saze, Hiroyuki Katoh, Fumiaki Takahashi, Takashi Oshima, Ajay Goel, Alessandra Nardin, Yoshiyuki Suzuki, Koji Kono
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown. Methods Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164 ). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor β-chain (TCRβ), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB). Results Although most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRβ clonality (inverted Pielou’s evenness) increased and TCRβ diversity (Pielou’s evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023). Conclusion Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.
Identification of MGMT promoter methylation as a specific lipid metabolism biomarker, reveals the feasibility of atorvastatin application in glioblastoma
Authors: Zhaonian Hao, Jiejun Wang, Yifan Lv, Weiqi Wu, Shaodong Zhang, Shuyu Hao, Junsheng Chu, Hong Wan, Jie Feng, Nan Ji
Journal: Metabolism (2024)
Self-Rated Health and Semen Quality in Men Undergoing Assisted Reproductive Technology
Authors: Xiao-Ying Liu, Yan-Ling Deng, Pan-Pan Chen, Chong Liu, Yu Miao, Min Zhang, Fei-Peng Cui, Jia-Yue Zeng, Yang Wu, Cheng-Ru Li, Chang-Jiang Liu, Qiang Zeng
Journal: JAMA Network Open (2024)

Numerous studies have documented the association of self-rated health (SRH) with chronic diseases. However, few studies have investigated its association with semen quality.
Health and the 2024 Elections Globally—A Call for Papers
Authors: Kirsten Bibbins-Domingo, Gregory Curfman, Hannah Park, Annette Flanagin
Journal: JAMA (2024)

Alison Galbraith, MD, MPH; Annette Flanagin, RN, MA; Aaron E. Carroll, MD, MS; John Z. Ayanian, MD, MPP; Robert O. Bonow, MD, MS; Neil Bressler, MD; Dimitri Christakis, MD, MPH; Mary L. (Nora) Disis, MD; Sharon K. Inouye, MD, MPH; Andrew Josephson, MD; Dost Öngür, MD, PhD; Jay F. Piccirillo, MD; Kanade Shinkai, MD, PhD; Kirsten Bibbins-Domingo, PhD, MD, MAS
Preoperative Concerns of Older US Adults and Decisions About Elective Surgery
Authors: Nicholas L. Berlin, Matthias Kirch, Dianne C. Singer, Erica Solway, Preeti N. Malani, Jeffrey T. Kullgren
Journal: JAMA Network Open (2024)

This cross-sectional study examines the preoperative concerns among US adults aged 50 to 80 years who considered elective surgery.
Transportability Analysis—A Tool for Extending Trial Results to a Representative Target Population
Authors: Kosuke Inoue, William Hsu
Journal: JAMA Network Open (2024)

Sarah E. Robertson, PhD; Nina R. Joyce, PhD; Jon A. Steingrimsson, PhD; Elizabeth A. Stuart, PhD; Denise R. Aberle, MD; Constantine A. Gatsonis, PhD; Issa J. Dahabreh, MD, ScD
Building the Evidence for Advance Care Planning for Patients Receiving Dialysis
Authors: Manjula Kurella Tamura, Laura M. Holdsworth
Journal: JAMA Network Open (2024)

Mi-Kyung Song, PhD, RN; Amita Manatunga, PhD; Laura Plantinga, PhD; Maureen Metzger, PhD, RN; Abhijit V. Kshirsagar, MD, MPH; Janice Lea, MD, MSc; Emaad M. Abdel-Rahman, MD; Manisha Jhamb, MD, MPH; Emily Wu, BS; Jacob Englert, MS; Sandra E. Ward, PhD, RN
Comparison of Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass
Authors: Suzanne Hedberg, Anders Thorell, Johanna Österberg, Markku Peltonen, Ellen Andersson, Erik Näslund, Jens Kristoffer Hertel, Marius Svanevik, Erik Stenberg, Martin Neovius, Ingmar Näslund, Mikael Wirén, Johan Ottosson, Torsten Olbers, Anna Laurenius, Jarl Torgersson
Journal: JAMA Network Open (2024)

Laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) are widely used bariatric procedures for which comparative efficacy and safety remain unclear.
Mobile Critical Care Recovery Program for Survivors of Acute Respiratory Failure
Authors: Babar A. Khan, Anthony J. Perkins, Sikandar Hayat Khan, Frederick W. Unverzagt, Sue Lasiter, Sujuan Gao, Sophia Wang, Ben L. Zarzaur, Omar Rahman, Ahmed Eltarras, Hadi Qureshi, Malaz A. Boustani
Journal: JAMA Network Open (2024)

Importance Over 50% of Acute Respiratory Failure (ARF) survivors experience cognitive, physical, and psychological impairments that negatively impact their quality of life (QOL). Objective To evaluate the efficacy of a post–intensive care unit (ICU) program, the Mobile Critical Care Recovery Program (m-CCRP) consisting of a nurse care coordinator supported by an interdisciplinary team, in improving the QOL of ARF survivors. Design, Setting, and Participants This randomized clinical trial with concealed outcome assessments among ARF survivors was conducted from March 1, 2017, to April 30, 2022, with a 12-month follow-up. Patients were admitted to the ICU services of 4 Indiana hospitals (1 community, 1 county, 2 academic), affiliated with the Indiana University School of Medicine. Intervention A 12-month nurse-led collaborative care intervention (m-CCRP) supported by an interdisciplinary group of clinicians (2 intensivists, 1 geriatrician, 1 ICU nurse, and 1 neuropsychologist) was compared with a telephone-based control. The intervention comprised longitudinal symptom monitoring coupled with nurse-delivered care protocols targeting cognition, physical function, personal care, mobility, sleep disturbances, pain, depression, anxiety, agitation or aggression, delusions or hallucinations, stress and physical health, legal and financial needs, and medication adherence. Main Outcomes and Measures The primary outcome was QOL as measured by the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), with scores on each component ranging from 0-100, and higher scores indicating better health status. Results In an intention-to-treat analysis among 466 ARF survivors (mean [SD] age, 56.1 [14.4] years; 250 [53.6%] female; 233 assigned to each group), the m-CCRP intervention for 12 months did not significantly improve the QOL compared with the control group (estimated difference in change from baseline between m-CCRP and control group: 1.61 [95% CI, −1.06 to 4.29] for SF-36 PCS; −2.50 [95% CI, −5.29 to 0.30] for SF-36 MCS. Compared with the control group, the rates of hospitalization were higher in the m-CCRP group (117 [50.2%] vs 95 [40.8%]; P = .04), whereas the 12-month mortality rates were not statistically significantly lower (24 [10.3%] vs 38 [16.3%]; P = .05). Conclusions and Relevance Findings from this randomized clinical trial indicated that a nurse-led 12-month comprehensive interdisciplinary care intervention did not significantly improve the QOL of ARF survivors after ICU hospitalization. These results suggest that further research is needed to identify specific patient groups who could benefit from tailored post-ICU interventions. Trial Registration ClinicalTrials.gov Identifier: NCT03053245
Delivering on the Promise of Human Milk for Extremely Preterm Infants in the NICU
Authors: Mandy Brown Belfort, Maryanne Perrin
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
A gut aging clock using microbiome multi-view profiles is associated with health and frail risk
Authors: Hongchao Wang, Yutao Chen, Ling Feng, Shourong Lu, Jinlin Zhu, Jianxin Zhao, Hao Zhang, Wei Chen, Wenwei Lu
Journal: Gut Microbes (2024)

Age-related changes in the microbiome have been reported in previous studies; however, direct evidence for their association with frailty is lacking. Here, we introduce biological age based on gut microbiota (gAge), an integrated prediction model that integrates gut microbiota data from different perspectives with potential background factors for aging assessment. Simulation results show that, compared with a single model, the ensemble model can not only significantly improve the prediction accuracy, but also make full use of the data in unpaired samples. From this, we identified markers associated with age development and grouped markers into accelerated aging and mitigated aging according to their effect on the prediction. Importantly, the application of gAge to an elderly cohort with different frailty levels confirmed that gAge and its predictive residuals are closely related to the individual's health status and frailty stage, and age-related markers overlap significantly with disease and frailty characteristics. Furthermore, we applied the gAge prediction model to another independent cohort of the elderly population for aging assessment and found that gAge could effectively represent the aging population. Overall, our study explains the association between the gut microbiota and frailty, providing potential targets for the development of gut microbiota-based targeted intervention strategies for aging.
Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2
Authors: Chen Yu, Eleonora M. Lad, Rose Mathew, Nobuhiko Shiraki, Sejiro Littleton, Yun Chen, Jinchao Hou, Kai Schlepckow, Simone Degan, Lindsey Chew, Joshua Amason, Joan Kalnitsky, Catherine Bowes Rickman, Alan D. Proia, Marco Colonna, Christian Haass, Daniel R. Saban
Journal: The Journal of Experimental Medicine (2024)

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection but in a galectin-3–dependent manner. In elderly human subjects, we identified this highly conserved microglial population that expressed galectin-3 and Trem2. This population was significantly enriched in the macular RPE-choroid of AMD subjects. Collectively, our findings reveal a neuroprotective population of microglia and a potential therapeutic target for mitigating retinal degeneration.
A Rare Severe Adverse Reaction to Adenosine During a Myocardial Perfusion Scan
Authors: Billur Caliskan
Journal: Clinical Nuclear Medicine (2024)

Department of Nuclear Medicine, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey. [email protected]. Conflicts of interest and sources of funding: none declared. The English in this document has been checked by at least 2 professional editors, both native speakers of English. For a certificate, please see http://www.textcheck.com/certificate/ISb3Cp.
Opportunities for CMS to improve healthcare access and equity through advancing technology-enabled startups and digital health innovations
Authors: Shobha Dasari, Raihana Mehreen, Kristin Baker Spohn, Andrey Ostrovsky
Journal: npj Digital Medicine (2024)

Historically, the Centers for Medicare and Medicaid Services (CMS) has formed partnerships with select private sector entities, including large traditional hospital and health system networks, nursing homes, and payer groups. However, innovations from technology-enabled services companies and digital technology companies are uniquely poised to aid CMS in addressing key barriers toward advancing its mission of improving healthcare access and equity. There are four pivotal opportunity areas where partnerships with technology businesses and tools would enhance the work of CMS: (1) improving consumer awareness about CMS programs, (2) mitigating access gaps through virtual care programs, (3) streamlining the complexity of different payer plan models, and (4) using technology-enabled services to address social risk factors without imposing additional burdens on providers. We offer examples of digital and technology-enabled solutions that improve patient access to care and close equity gaps, as well as propose specific recommendations for CMS to advance and expand the reach and impact of these solutions. Namely, these recommendations include partnerships with private sector companies that can educate and support consumers about their benefits, the extension of telehealth reimbursement parity for virtual care solutions, allowing for cross-state licensure across plans and reimbursement for care coordination services that alleviate provider burden to screen and address patients' social determinants of health needs. We argue that CMS has an imperative role in leveraging the innovations of technology-enabled services and digital health technologies to lower healthcare access barriers, mitigate provider burden, stimulate innovation, and close equity gaps at the patient, provider, and innovator levels.
Targeting CD20-expressing malignant melanoma cells augments BRAF inhibitor killing
Authors: Abdullahi B Mukhtar, Huw J Morgan, Alex Gibbs, Gemma E Davies, Charlotte Lovatt, Girish K Patel
Journal: British Journal of Dermatology (2024)

Mutant BRAF targeted therapies remain a standard of care for the treatment of metastatic malignant melanoma (MM); however, high initial response rates are tempered by the persistence of residual MM cells that eventually lead to disease recurrence and mortality. As MM recurrence during targeted therapy can present with the simultaneous occurrence of multiple tumour nodules at the original body sites, we hypothesized the presence of an intrinsically resistant MM cell subpopulation.
Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance
Authors: Hao Zheng, Jinming Liu, Qi Cheng, Qianping Zhang, Yaoyao Zhang, Lingyu Jiang, Yan Huang, Wenlei Li, Yanping Zhao, Guo Chen, Fan Yu, Lei Liu, Yanjun Li, Xudong Liao, Lai Xu, Yi Xiao, Zhibo Zheng, Ming Li, Hongyi Wang, Gang Hu, Lei Du, Quan Chen
Journal: Nature Cancer (2024)
Cell-type-specific CAG repeat expansions and toxicity of mutant Huntingtin in human striatum and cerebellum
Authors: Kert Mätlik, Matthew Baffuto, Laura Kus, Amit Laxmikant Deshmukh, David A. Davis, Matthew R. Paul, Thomas S. Carroll, Marie-Christine Caron, Jean-Yves Masson, Christopher E. Pearson, Nathaniel Heintz
Journal: Nature Genetics (2024)

Abstract Brain region-specific degeneration and somatic expansions of the mutant Huntingtin ( mHTT ) CAG tract are key features of Huntington’s disease (HD). However, the relationships among CAG expansions, death of specific cell types and molecular events associated with these processes are not established. Here, we used fluorescence-activated nuclear sorting (FANS) and deep molecular profiling to gain insight into the properties of cell types of the human striatum and cerebellum in HD and control donors. CAG expansions arise at mHTT in striatal medium spiny neurons (MSNs), cholinergic interneurons and cerebellar Purkinje neurons, and at mutant ATXN3 in MSNs from SCA3 donors. CAG expansions in MSNs are associated with higher levels of MSH2 and MSH3 (forming MutSβ), which can inhibit nucleolytic excision of CAG slip-outs by FAN1. Our data support a model in which CAG expansions are necessary but may not be sufficient for cell death and identify transcriptional changes associated with somatic CAG expansions and striatal toxicity.
How to diversify the dwindling physician–scientist workforce after the US affirmative action ban
Authors: Jessica L. Ding, Briana Christophers, Deborah D. Rupert, Cynthia Y. Tang, Randal A. Serafini, Caroline S. Jansen, Micaila D. E. Curtis, Anthony G. Chesebro, Alex D. Waldman
Journal: Nature Medicine (2024)
In vitro reconstitution of chromatin domains shows a role for nucleosome positioning in 3D genome organization
Authors: Elisa Oberbeckmann, Kimberly Quililan, Patrick Cramer, A. Marieke Oudelaar
Journal: Nature Genetics (2024)

Abstract Eukaryotic genomes are organized into chromatin domains. The molecular mechanisms driving the formation of these domains are difficult to dissect in vivo and remain poorly understood. Here we reconstitute Saccharomyces cerevisiae chromatin in vitro and determine its 3D organization at subnucleosome resolution by micrococcal nuclease-based chromosome conformation capture and molecular dynamics simulations. We show that regularly spaced and phased nucleosome arrays form chromatin domains in vitro that resemble domains in vivo. This demonstrates that neither loop extrusion nor transcription is required for basic domain formation in yeast. In addition, we find that the boundaries of reconstituted domains correspond to nucleosome-free regions and that insulation strength scales with their width. Finally, we show that domain compaction depends on nucleosome linker length, with longer linkers forming more compact structures. Together, our results demonstrate that regular nucleosome positioning is important for the formation of chromatin domains and provide a proof-of-principle for bottom-up 3D genome studies.
Effects of the WHO Labour Care Guide on cesarean section in India: a pragmatic, stepped-wedge, cluster-randomized pilot trial
Authors: Joshua P. Vogel, Yeshita Pujar, Sunil S. Vernekar, Elizabeth Armari, Veronica Pingray, Fernando Althabe, Luz Gibbons, Mabel Berrueta, Manjunath Somannavar, Alvaro Ciganda, Rocio Rodriguez, Savitri Bendigeri, Jayashree Ashok Kumar, Shruti Bhavi Patil, Aravind Karinagannanavar, Raveendra R. Anteen, Pavithra Mallappa Ramachandrappa, Shukla Shetty, Latha Bommanal, Megha Haralahalli Mallesh, Suman S. Gaddi, Shaila Chikkagowdra, Bellara Raghavendra, Caroline S. E. Homer, Tina Lavender, Pralhad Kushtagi, G. Justus Hofmeyr, Richard Derman, Shivaprasad Goudar
Journal: Nature Medicine (2024)

Abstract Cesarean section rates worldwide are rising, driven by medically unnecessary cesarean use. The new World Health Organization Labour Care Guide (LCG) aims to improve the quality of care for women during labor and childbirth. Using the LCG might reduce overuse of cesarean; however, its effects have not been evaluated in randomized trials. We conducted a stepped-wedge, cluster-randomized pilot trial in four hospitals in India to evaluate the implementation of an LCG strategy intervention, compared with routine care. We performed this trial to pilot the intervention and obtain preliminary effectiveness data, informing future research. Eligible clusters were four hospitals with &gt;4,000 births annually and cesarean rates ≥30%. Eligible women were those giving birth at ≥20 weeks’ gestation. One hospital transitioned to intervention every 2 months, according to a random sequence. The primary outcome was the cesarean rate among women in Robson Group 1 (that is, those who were nulliparous and gave birth to a singleton, term pregnancy in cephalic presentation and in spontaneous labor). A total of 26,331 participants gave birth. A 5.5% crude absolute reduction in the primary outcome was observed (45.2% versus 39.7%; relative risk 0.85, 95% confidence interval 0.54–1.33). Maternal process-of-care outcomes were not significantly different, though labor augmentation with oxytocin was 18.0% lower with the LCG strategy. No differences were observed for other health outcomes or women’s birth experiences. These findings can guide future definitive effectiveness trials, particularly in settings where urgent reversal of rising cesarean section rates is needed. Clinical Trials Registry India number: CTRI/2021/01/030695 .