tbuckley/cabot-search huggingface dataset:
Testosterone Replacement Therapy and Diabetes in Men With Hypogonadism
Authors: Lona Mody, Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2024)

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Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism
Authors: Shalender Bhasin, A. Michael Lincoff, Steven E. Nissen, Kathleen Wannemuehler, Marie E. McDonnell, Anne L. Peters, Nader Khan, Michael C. Snabes, Xue Li, Geng Li, Kevin Buhr, Karol M. Pencina, Thomas G. Travison
Journal: JAMA Internal Medicine (2024)

The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission in those with diabetes is unknown.
Perspectives on Admissions and Care for Residents With Opioid Use Disorder in Skilled Nursing Facilities
Authors: Patience Moyo, Shivani Nishar, Charlotte Merrick, Nicholas Streltzov, Emmanuella Asiedu, Corinne Roma, Rahul Vanjani, Jon Soske
Journal: JAMA Network Open (2024)

Importance Skilled nursing facilities (SNFs) are being referred more individuals with opioid use disorder (OUD), even when their medical needs are not directly associated with OUD. Objective To characterize factors that influence SNF admission for individuals with OUD and identify strategies for providing medications for OUD (MOUD) in SNFs. Design, Setting, and Participants In this semistructured qualitative study, interviews were conducted with SNF administrators from 27 SNFs in Rhode Island from November 5, 2021, to April 27, 2022. Data analysis occurred from August 22, 2022, to May 31, 2023. Main Outcomes and Measures Themes and subthemes on administrator perspectives on admissions and care for people with OUD in SNFs. Audio interviews were transcribed, coded, and analyzed using codebook thematic analysis and guided by community-engaged and participatory research principles. Results The study included 29 participants representing 27 SNFs in Rhode Island. Participant roles were administrators (17 participants [59%]), directors of nursing (6 participants [21%]), directors of admissions (5 participants [17%]), and unit managers (1 participant [3%]). Participants described active substance use, Medicaid insurance, housing instability, and younger age as potential barriers to SNF admission for individuals with OUD. The lack of formal guidelines for OUD management, staff shortages, facility liability, state regulations, and skills and training deficits among staff were cited among challenges of effectively meeting the needs of residents with OUD. Many participants reported inadequate institutional capacity as a source of negative outcomes for people with OUD yet expressed their concerns by characterizing individuals with OUD as potentially violent, nonadherent, or likely to bring undesirable elements into facilities. Participants also shared strategies they used to better serve residents with OUD, including providing transportation to support group meetings in the community, delivery in advance of resident arrival of predosed methadone, and telemedicine through the state’s hotline to prescribe buprenorphine. Conclusions and Relevance In this qualitative study of administrator perspectives about admissions and care for individuals with OUD in SNFs, gaps in institutional capacity overlapped with stigmatizing beliefs about OUD; such beliefs perpetuate discrimination of individuals with OUD. Adequate SNF funding and staffing combined with OUD-specific interventions (eg, antistigma training, community partnerships for MOUD and recovery support) could incentivize SNFs to serve individuals with OUD and facilitate OUD care consistent with practice guidelines.
Error in Nonauthor Collaborator Supplement
Journal: JAMA Internal Medicine (2024)

Theodore J. Iwashyna, MD, PhD; Sarah Seelye, PhD; Theodore S. Berkowitz, MS; John Pura, PhD; Amy S. B. Bohnert, PhD; C. Barrett Bowling, MD, MSPH; Edward J. Boyko, MD, MPH; Denise M. Hynes, MPH, PhD, RN; George N. Ioannou, BMBCh, MS; Matthew L. Maciejewski, PhD; Ann M. O’Hare, MA, MD; Elizabeth M. Viglianti, MD; James Womer, MD; Hallie C. Prescott, MD, MSc; Valerie A. Smith, DrPH; VA HSR&D COVID-19 Observational Research Collaboratory; Andrew Admon; Kathleen Akgun; Stacy Anderson; Mihaela Aslan; David Au; Lisa Backus; Kristina Bajema; Aaron Baraff; Lisa Batten; Theodore Berkowitz; Taylor Bernstein; Kristin Berry Wyatt; Joseph Bogdan; Hayden Bosworth; Nathan Boucher; Nicholas Burwick; Aissa Cabrales; Jennifer Cano; Wen Chai; Jason Chen; Kei-Hoi Cheung; Kristina Crothers; Jeffrey Curtis; Marie Davis; Emily Del Monico; Aram Dobalian; Jacob Doll; Jason Dominitz; McKenna Eastment; Vincent Fan; Jacqueline Ferguson; Breanna Floyd; Alexandra Fox; Matthew Goetz; Diana Govier; Pamela Green; Susan Nicole Hastings; Katie Hauschildt; Eric Hawkins; Paul Hebert; Mark Helfand; Alex Hickok; Dana Horowitz; Catherine Hough; Elaine Hu; Kevin Ikuta; Barbara Jones; Makoto Jones; Lee Kamphuis; Brystana Kaufman; Sara Knight; Anna Korpak; Peggy Korpela; Kyle Kumbier; Kenneth Langa; Ryan Laundry; Stacy Lavin; Yuli Li; Jennifer Linquist; Holly McCready; Martha Michel; Amy Miles; Jessie Milne; Max Monahan; Daniel Morelli; Pradeep Mutalik; Jennifer Naylor; Meike Neiderhausen; Summer Newell; Shannon Nugent; Michael Ong; Thomas Osborne; Matthew Peterson; Alexander Peterson; Nallakkandi Rajeevan; Ashok Reddy; Marylena Rouse; Mazhgan Rowneki; Som Saha; Sameer Saini; Javeed Shah; Troy Shahoumian; Aasma Shaukat; Megan Shepherd-Banigan; Whitney Showalter; Christopher Slatore; Nicholas Smith; Battista Smith; Pradeep Suri; Jeremy Sussman; Yumie Takata; Alan Teo; Eva Thomas; Laura Thomas; Anais Tuepker; Zachary Veigulis; Elizabeth Vig; Kelly Vranas; Xiao Qing Wang; Katrina Wicks; Kara Winchell; Edwin Wong; Chris Woods; Katherine Wysham; Lei Yan; Donna Zulman
Erratum. 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: <i>Standards of Care in Diabetes—2024</i>. Diabetes Care 2024;47(Suppl. 1):S77–S110
Authors: Nuha A. ElSayed, Grazia Aleppo, Raveendhara R. Bannuru, Elizabeth A. Beverly, Dennis Bruemmer, Billy S. Collins, Audrey Darville, Laya Ekhlaspour, Mohamed Hassanein, Marisa E. Hilliard, Eric L. Johnson, Kamlesh Khunti, Ildiko Lingvay, Glenn Matfin, Rozalina G. McCoy, Mary Lou Perry, Scott J. Pilla, Sarit Polsky, Priya Prahalad, Richard E. Pratley, Alissa R. Segal, Jane Jeffrie Seley, Robert C. Stanton, Robert A. Gabbay
Journal: Diabetes Care (2024)

In the article cited above, the content regarding the times to evaluate the need for diabetes self-management education (DSMES) has been reworded for better clarity. The original Recommendation 5.2 appeared as follows: “There are five critical times to evaluate the need for DSMES to promote skills acquisition to aid treatment plan implementation, medical nutrition therapy, and well-being: at diagnosis, when not meeting treatment goals, annually, when complicating factors develop (medical, physical, and psychosocial), and when transitions in life and care occur. E” The revised Recommendation 5.2 now reads: “In addition to annually, there are critical times to evaluate the need for DSMES to promote skills acquisition to aid treatment plan implementation, medical nutrition therapy, and well-being: at diagnosis, when not meeting treatment goals, when complicating factors develop (medical, physical, and psychosocial), and when transitions in life and care occur. E” The original supporting text appeared as follows: “There are five critical time points when the need for DSMES should be evaluated by the health care professional and/or interprofessional team, with referrals made as needed (2): At diagnosis Annually When not meeting treatment goals When complicating factors (e.g., health conditions, physical limitations, emotional factors, or basic living needs) that influence self-management develop When transitions in life and care occur” The revised supporting text now reads: “In addition to annually, there are critical time points when the need for DSMES should be evaluated by the health care professional and/or interprofessional team, with referrals made as needed (2):At diagnosisWhen not meeting treatment goalsWhen complicating factors (e.g., health conditions, physical limitations, emotional factors, or basic living needs) that influence self-management developWhen transitions in life and care occur” The online version of Section 5 (https://doi.org/10.2337/dc24-S005) has been updated with the revised text. The online version of the Summary of Revisions (https://doi.org/10.2337/dc24-SREV) has also been updated to reflect these changes.
Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment
Authors: Xiaoling Fu, Yutong Song, Xianquan Feng, Zhihong Liu, Wenhao Gao, Hongtao Song, Qian Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

In this study, a multifunctional liposomal polydopamine nanoparticle (MPM@Lipo) was designed to combine chemotherapy, photothermal therapy (PTT) and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis (RA) treatment. MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia, thus contributing to the repolarization of M1 macrophages into M2 phenotype. Furthermore, MPM@Lipo could accumulate at inflammatory joints, inhibit the production of inflammatory factors, and protect cartilage in vivo, effectively alleviating RA progression in a rat adjuvant-induced arthritis model. Moreover, upon laser irradiation, MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen, resulting in excellent RA treatment effects. Overall, the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.
Nivolumab monotherapy or combination with ipilimumab with or without cobimetinib in previously treated patients with pancreatic adenocarcinoma (CheckMate 032)
Authors: Margaret Callahan, Asim Amin, Frederic J Kaye, Michael A Morse, Matthew H Taylor, Katriina J Peltola, Padmanee Sharma, Eileen M O'Reilly, Stephanie Meadows Shropshire, Shaun O'Brien, Marina Tschaika, Dung T Le
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Pancreatic cancer is one of the deadliest cancer types and represents a major unmet medical need. CheckMate 032 investigated safety and efficacy of nivolumab monotherapy and nivolumab plus ipilimumab with/without cobimetinib in advanced/metastatic solid tumors, including pancreatic cancer. Methods In the original pancreatic cancer cohort, previously treated patients (≥1 prior regimen) with advanced/metastatic pancreatic adenocarcinoma were assigned to nivolumab 3 mg/kg every 2 weeks (monotherapy arm) or nivolumab 1 mg/kg and ipilimumab 1 mg/kg or 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks (combination arm). A subsequent modified pancreatic cohort (one or two prior regimens) received nivolumab 3 mg/kg every 2 weeks, ipilimumab 1 mg/kg every 6 weeks, and cobimetinib 60 mg orally once daily for 21 days on and 7 days off (triplet arm). The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints were investigator-assessed progression-free survival (PFS), PFS rate, overall survival (OS), OS rate, safety, and tolerability. Additionally, ORR, PFS, and duration of response were assessed by blinded independent central review (BICR) in the triplet arm. Results 18 patients received nivolumab monotherapy, 21 received nivolumab plus ipilimumab, and 30 received nivolumab plus ipilimumab plus cobimetinib. In the triplet arm, partial responses were observed in two patients per investigator (ORR 6.7% (95% CI 0.8% to 22.1%)) and in three patients per BICR (ORR 10% (95% CI 2.1% to 26.5%)); no responses were observed in the other arms. Median (95% CI) PFS per investigator was 1.4 (1.3 to 2.0), 1.4 (1.2 to 2.7), and 3.0 (1.5 to 4.1) months for the monotherapy, nivolumab plus ipilimumab, and triplet arms, respectively. Median (95% CI) OS was 5.1 (2.0 to 9.0) months, 4.0 (1.9 to 5.6) months, and 6.2 (3.9 to 11.4) months, respectively. Most treatment-related adverse events were grade 2 or less. Conclusions Nivolumab with or without ipilimumab did not elicit objective responses in previously treated patients with advanced pancreatic adenocarcinoma, although three confirmed partial responses and manageable safety were observed with cobimetinib-containing triplet therapy. The small sample size and differences in baseline disease-specific characteristics between arms limit interpretation of these results.
Heterotopic mineralization (ossification or calcification) in aged musculoskeletal soft tissues: A new candidate marker for aging
Authors: Guang-Chun Dai, Hao Wang, Zhang Ming, Pan-Pan Lu, Ying-Juan Li, Yu-Cheng Gao, Liu Shi, Zhang Cheng, Xiao-Yu Liu, Yun-Feng Rui
Journal: Ageing Research Reviews (2024)
Publisher Correction: Advancing T cell–based cancer therapy with single-cell technologies
Authors: Samantha L. Bucktrout, Nicholas E. Banovich, Lisa H. Butterfield, Cansu Cimen-Bozkus, Josephine R. Giles, Zinaida Good, Daniel Goodman, Vanessa D. Jonsson, Caleb Lareau, Alexander Marson, Deena M. Maurer, Paul V. Munson, Mike Stubbington, Sarah Taylor, Abbey Cutchin
Journal: Nature Medicine (2024)
Development of biomedical hydrogels for rheumatoid arthritis treatment
Authors: Mirza Muhammad Faran Ashraf Baig, Lee Ki Wong, Abdul Wasy Zia, Hongkai Wu
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Rheumatoid Arthritis (RA) is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces quality of human life. Every year millions of people are diagnosed with RA worldwide which particularly includes elderly and women groups. Therefore, this global cause warrants the development of new biomaterials, medicines, and therapeutic methods for RA treatment. This will improve Healthcare Access and Quality Index and will also relieve administrative and financial burdens of healthcare service providers at a global scale. Hydrogels are soft and cross-linked polymeric materials that can store a certain number of fluids, drugs and biomolecules for hydration and therapeutic applications. Hydrogels are biocompatible and exhibit excellent mechanical properties like providing elastic cushions to articulating joints by mimicking the natural synovial fluid. Hence, hydrogels create a natural biological environment within the synovial cavity to decrease autoimmune reactions and friction. Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage, thus conceiting high potential to treat RA. This work reviews the progress in injectable and implantable hydrogels, synthesis methods, types of drugs, advantages and challenges, and also discusses the role of targeted drug delivery, mechanistic behaviour, and tribological performance for RA treatment.
Unlocking the Mitochondria for Nanomedicine-based Treatments: Overcoming Biological Barriers, Improving Designs, and Selecting Verification Techniques
Authors: Camilla Pegoraro, Inés Domingo-Ortí, Inmaculada Conejos-Sánchez, María J. Vicent
Journal: Advanced Drug Delivery Reviews (2024)

Enhanced targeting approaches will support the treatment of diseases associated with dysfunctional mitochondria, which play critical roles in energy generation and cell survival. Obstacles to mitochondria-specific targeting include the presence of distinct biological barriers and the need to pass through (or avoid) various cell internalization mechanisms. A range of studies have reported the design of mitochondrially-targeted nanomedicines that navigate the complex routes required to influence mitochondrial function; nonetheless, a significant journey lies ahead before mitochondrially-targeted nanomedicines become suitable for clinical use. Moving swiftly forward will require safety studies, in vivo assays confirming effectiveness, and methodologies to validate mitochondria-targeted nanomedicines' subcellular location/activity. From a nanomedicine standpoint, we describe the biological routes involved (from administration to arrival within the mitochondria), the features influencing rational design, and the techniques used to identify/validate successful targeting. Overall, rationally-designed mitochondria-targeted-based nanomedicines hold great promise for precise subcellular therapeutic delivery.
Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury
Authors: Yunhan Zhang, Zhulin Zou, Shuang Liu, Fangfang Chen, Minglu Li, Haoyang Zou, Haiyan Liu, Jianxun Ding
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 μM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.
All-cause mortality risks among participants in mass-participation sporting events
Authors: Esmée A Bakker, Vincent L. Aengevaeren, Duck-Chul Lee, Paul D Thompson, Thijs M.H. Eijsvogels
Journal: British Journal of Sports Medicine (2024)

Objectives Exercise transiently increases the risk for sudden death, whereas long-term exercise promotes longevity. This study assessed acute and intermediate-term mortality risks of participants in mass-participation sporting events. Methods Data of participants in Dutch running, cycling and walking events were collected between 1995 and 2017. Survival status was obtained from the Dutch Population Register. A time-stratified, case-crossover design examined if deceased participants more frequently participated in mass-participation sporting events 0–7 days before death compared with the reference period (14–21 days before death). Mortality risks during follow-up were compared between participants and non-participants from the general population using Cox regression. Results 546 876 participants (median (IQR) age 41 (31–50) years, 56% male, 72% runners) and 211 592 non-participants (41 (31–50) years, 67% male) were included. In total, 4625 participants died of which more participants had partaken in a sporting event 0–7 days before death (n=23) compared with the reference period (n=12), and the mortality risk associated with acute exercise was greater but did not reach statistical significance (OR 1.92; 95% CI 0.95 to 3.85). During 3.3 (1.1–7.4) years of follow-up, participants had a 30% lower risk of death (HR 0.70; 95% CI 0.67 to 0.74) compared with non-participants after adjustment for age and sex. Runners (HR 0.65; 95% CI 0.62 to 0.69) and cyclists (HR 0.70; 95% CI 0.64 to 0.77) had the best survival during follow-up followed by walkers (HR 0.88; 95% CI 0.80 to 0.94). Conclusion Participating in mass-participation sporting events was associated with a non-significant increased odds (1.92) of mortality and a low absolute event rate (4.2/100 000 participants) within 7 days post-event, whereas a 30% lower risk of death was observed compared with non-participants during 3.3 years of follow-up. These results suggest that the health benefits of mass sporting event participation outweigh potential risks.
Burden of Vernal Keratoconjunctivitis in the United States: A Retrospective Claims Database Analysis
Authors: Euna B. Koo, Tiffany M. Yu, Andrew J. Layton, Steven Babineaux, Simon Fung
Journal: Ophthalmology (2024)

In this claims analysis, vernal keratoconjunctivitis (VKC) patients (≤18 years) treated with immunomodulators or corticosteroids had more corneal complications and higher ophthalmic care costs versus matched non-VKC controls, indicating a need for more effective treatments.
Immune cell-derived signals governing epithelial phenotypes in homeostasis and inflammation
Authors: Annika Hausmann, Casper Steenholdt, Ole H. Nielsen, Kim B. Jensen
Journal: Trends in Molecular Medicine (2024)

The intestinal epithelium fulfills important physiological functions and forms a physical barrier to the intestinal lumen. Barrier function is regulated by several pathways, and its impairment contributes to the pathogenesis of inflammatory bowel disease (IBD), a chronic inflammatory condition affecting more than seven million people worldwide. Current treatment options specifically target inflammatory mediators and have led to improvement of clinical outcomes; however, a significant proportion of patients experience treatment failure. Pro-repair effects of inflammatory mediators on the epithelium are emerging. In this review we summarize current knowledge on involved epithelial pathways, identify open questions, and put recent findings into clinical perspective, and pro-repair effects. A detailed understanding of epithelial pathways integrating mucosal stimuli in homeostasis and inflammation is crucial for the development of novel, more targeted therapies.
Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer
Authors: Lujia Chen, Ying Wang, Chunhui Cai, Ying Ding, Rim S. Kim, Corey Lipchik, Patrick G. Gavin, Greg Yothers, Carmen J. Allegra, Nicholas J. Petrelli, Jennifer Marie Suga, Judith O. Hopkins, Naoyuki G. Saito, Terry Evans, Srinivas Jujjavarapu, Norman Wolmark, Peter C. Lucas, Soonmyung Paik, Min Sun, Katherine L. Pogue-Geile, Xinghua Lu
Journal: Journal of Clinical Oncology (2024)

A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects.