tbuckley/cabot-search huggingface dataset:
On the pathogenesis of obesity: causal models and missing pieces of the puzzle
Authors: Faidon Magkos, Thorkild I. A. Sørensen, David Raubenheimer, Nikhil V. Dhurandhar, Ruth J. F. Loos, Anja Bosy-Westphal, Christoffer Clemmensen, Mads F. Hjorth, David B. Allison, Gary Taubes, Eric Ravussin, Mark I. Friedman, Kevin D. Hall, David S. Ludwig, John R. Speakman, Arne Astrup
Journal: Nature Metabolism (2024)

Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century. Here, we summarize outcomes of a recent workshop in Copenhagen that brought together obesity experts from around the world to discuss causal models of obesity pathogenesis. These discussions helped to operationally define commonly used terms; delineate the structure of each model, particularly focussing on areas of overlap and divergence; challenge ideas about the importance of purported causal factors for weight gain; and brainstorm on the key scientific questions that need to be answered. We hope that more experimental research in nutrition and other related fields, and more testing of the models and their predictions will pave the way and provide more answers about the pathogenesis of obesity than those currently available.
Clinical Ethics Fellowship Programs in the U.S. and Canada: A Descriptive Study of Program Characteristics and Practices
Authors: Ellen Fox, Jason Adam Wasserman
Journal: The American Journal of Bioethics (2024)

To address the current lack of knowledge about clinical ethics fellowship programs (CEFPs), we surveyed all 36 programs in the U.S. and Canada. The number of CEFPs has grown exponentially over the last 40 years and far exceeds previous estimates. Commonalities among CEFPs include: 88.8% require an advanced degree or rarely accept applicants without one; 91.7% of programs do not restrict applicants to a specific background such as medicine or philosophy; and 88.9% of programs compensate fellows. CEFPs vary widely on numbers of fellows trained in the last 3 years (1-111), numbers of consultations performed by each fellow (0-450), and salaries paid ($0-$95,000). Less than half of programs meet CEFP standards established by ABPD. Nonpaying programs and larger programs tend to have lower admission standards and lower expectations for fellows. We hope these data will help inform CEFP standards that promote quality and consistency without stifling desirable diversity and innovation.
Canonical effects of cytokines on glomerulonephritis: A new outlook in nephrology
Authors: Sepideh Zununi Vahed, Seyed Mahdi Hosseiniyan Khatibi, Mohammadreza Ardalan
Journal: Medicinal Research Reviews (2024)

Glomerulonephritis (GN) is an important cause of renal inflammation resulting from kidney-targeted adaptive and innate immune responses and consequent glomerular damage. Given the lack of autoantibodies, immune complexes, or the infiltrating immune cells in some forms of GN, for example, focal segmental glomerulosclerosis and minimal change disease, along with paraneoplastic syndrome and a special form of renal involvement in some viral infections, the likeliest causative scenario would be secreted factors, mainly cytokine(s). Since cytokines can modulate the inflammatory mechanisms, severity, and clinical outcomes of GN, it is rational to consider the umbrella term of cytokine GN as a new outlook to reclassify a group of previously known GN. We focus here, particularly, on cytokines that have the central "canonical effect" in the development of GN.
Chronic binge drinking-induced susceptibility to colonic inflammation is microbiome-dependent
Authors: Diogo Fonseca-Pereira, Sena Bae, Monia Michaud, Jonathan N. Glickman, Wendy S. Garrett
Journal: Gut Microbes (2024)

Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation.
Incidence of Medication-Related Osteonecrosis of the Jaw in Patients With Breast Cancer During a 20-Year Follow-Up: A Population-Based Multicenter Retrospective Study
Authors: Christine Brunner, Marjan Arvandi, Christian Marth, Daniel Egle, Florentina Baumgart, Miriam Emmelheinz, Benjamin Walch, Johanna Lercher, Claudia Iannetti, Ewald Wöll, Agnes Pechlaner, August Zabernigg, Birgit Volgger, Maria Castellan, Oliver Tibor Andraschofsky, Alice Markl, Michael Hubalek, Michael Schnallinger, Sibylle Puntscher, Uwe Siebert, Sebastian Schönherr, Lukas Forer, Emanuel Bruckmoser, Johannes Laimer
Journal: Journal of Clinical Oncology (2024)

Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of antiresorptive therapy, which is standard practice for patients with breast cancer and bone metastases. However, the population-based incidence of MRONJ is not well established. We therefore performed a retrospective multicenter study to assess the incidence for a whole Austrian federal state (Tyrol).
Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial
Authors: Bram De Laere, Alessio Crippa, Andrea Discacciati, Berit Larsson, Maria Persson, Susanne Johansson, Sanne D’hondt, Rebecka Bergström, Venkatesh Chellappa, Markus Mayrhofer, Mahsan Banijamali, Anastasijia Kotsalaynen, Céline Schelstraete, Jan Pieter Vanwelkenhuyzen, Marie Hjälm-Eriksson, Linn Pettersson, Anders Ullén, Nicolaas Lumen, Gunilla Enblad, Camilla Thellenberg Karlsson, Elin Jänes, Johan Sandzén, Peter Schatteman, Maria Nyre Vigmostad, Martha Olsson, Christophe Ghysel, Brieuc Sautois, Wendy De Roock, Siska Van Bruwaene, Mats Anden, Ingrida Verbiene, Daan De Maeseneer, Els Everaert, Jochen Darras, Bjørg Y. Aksnessether, Daisy Luyten, Michiel Strijbos, Ashkan Mortezavi, Jan Oldenburg, Piet Ost, Martin Eklund, Henrik Grönberg, Johan Lindberg
Journal: Nature Medicine (2024)

Abstract ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician’s choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician’s choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or ‘all’ patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician’s choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2–ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53 -altered patients. In summary, ARPIs outperform taxanes and physician’s choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835 .
Reviewing the benefits and clinical outcomes of oral fibroblasts over mesenchymal stem cells for repairing periodontal defects during or after orthodontic tooth movement
Authors: Ludovica Parisi, Eleni Mavrogonatou, Anton Sculean, Dimitris Kletsas, Martin Degen
Journal: Periodontology 2000 (2024)

Orthodontic therapy applies forces to teeth, causing an inflammatory reaction in the periodontal ligament. This is repaired by remodeling of the periodontium, allowing tooth displacement. Although orthodontic therapy is mostly initiated during childhood and adolescence, the number of adults seeking this treatment is increasing as our society's esthetic awareness rises. However, adults may already have periodontal tissue abnormalities, rendering orthodontic treatment inefficient because a healthy periodontium is essential for success. Numerous risk factors have been linked to periodontal lesions, with orthodontic tooth movement possibly playing a minimal influence. Although such tissue damages are mostly of esthetic rather than functional concern for patients, restoration frequently requires invasive procedures. Autologous cells for the treatment of periodontal complications have grown in popularity as a less intrusive alternative. The present review analyzed the literature on the use of mesenchymal stem cells and oral tissue-derived fibroblasts for the healing of periodontal defects that may be related to orthodontic tooth movement. Furthermore, the advantages and challenges of the two cell types have been examined. Although the number of clinical studies is currently limited, our study demonstrates that oral fibroblasts have the potential to be the next emergent frontrunners for tissue engineering in the periodontium.
Effects of Sedentary Behavior Reduction on Blood Pressure in Desk Workers: Results From the RESET-BP Randomized Clinical Trial
Authors: Bethany Barone Gibbs, Subashan Perera, Kimberly A. Huber, Joshua L. Paley, Molly B. Conroy, John M. Jakicic, Matthew F. Muldoon
Journal: Circulation (2024)

Sedentary behavior (SB) is observationally associated with cardiovascular disease risk. However, randomized clinical trials testing causation are limited. We hypothesized that reducing SB would decrease blood pressure (BP) and pulse wave velocity (PWV) in sedentary adults.
Do Reasons Matter? Navigating Parents’ Reasons in Healthcare Decisions for Children
Authors: Bryanna Moore, Amy Caruso Brown
Journal: The American Journal of Bioethics (2024)

Bioethics has dedicated itself to exploring and defending both reasons for and against certain aspects of clinical care, biomedical research and health policy, including what decisions must be made, who should make them, and how they should be made. In pediatrics, it's widely acknowledged that parents' reasons may matter pragmatically; attending to parents' reasons is important if we want to work with families. Yet the conventional view in pediatric ethics is that parents' reasons are irrelevant to whether a decision is permissible or impermissible according to accepted ethical standards. In this paper, we explore whether parents' reasons matter ethically and, if so, in what way and for whom. First, we clarify what we mean by 'reasons.' Second, we provide an overview of how reasons are typically treated in medical decision-making and pediatric ethics. Third, we analyze a hypothetical pediatric case to illustrate how changing reasons can transform ethical analyses, including by contributing to where and how clinicians and ethicists draw the boundaries intrinsic to common pediatric ethical frameworks. We push back against the conventional view and argue that parents' reasons matter ethically in several ways. We call for further research on the role of parents' reasons in clinical ethics deliberation.
Management of Prolonged Aerobic Exercise in People With Type 1 Diabetes on Automated Insulin Delivery Systems: A Randomized Controlled Study
Authors: Alessandra Corrado, Giuseppe Scidà, Jumana Abuqwider, Carmen Rainone, Roberta Lupoli, Maria Masulli, Lutgarda Bozzetto, Giovanni Annuzzi
Journal: Diabetes Care (2024)
Implications of PD-L1 expression on the immune microenvironment in HER2-positive gastric cancer
Authors: Yang Chen, Keren Jia, Xiaoyi Chong, Yi Xie, Lei Jiang, Haoxin Peng, Dan Liu, Jiajia Yuan, Yanyan Li, Xujiao Feng, Yu Sun, Jian Li, Xiaotian Zhang, Lin Shen
Journal: Molecular Cancer (2024)

In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS < 1 patients lacked notable benefits. We studied this in a real-world cohort of 106 HER2-positive, CPS < 1 patients and found no survival differences between those treated with anti-HER2 therapy alone or with added immunotherapy. Thus, we investigate the tumor microenvironment variations in 160 HER2-positive patients, CPS ≥ 1 cases exhibited elevated spatial effective scores of immune cells, including CD4, CD8 subtypes, and NK cells, compared to CPS < 1. Furthermore, through single-cell sequencing in eight HER2-positive individuals, gene expressions revealed regulation of T-cell co-stimulation in CPS ≥ 1 and IL-1 binding in CPS < 1 cases. Notably, we discovered a CPS < 1 subtype marked by CXCR4
Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial
Authors: Laure Gossec, Laura C Coates, Dafna D Gladman, Jacob A Aelion, Jitendra Vasandani, Andreas Pinter, Joseph F Merola, Arthur Kavanaugh, Jyotsna Reddy, Rebecca Wang, Michele Brunori, Yuri Klyachkin, Cynthia Deignan, Philip J Mease
Journal: Annals of the Rheumatic Diseases (2024)

Oligoarticular psoriatic arthritis (PsA) is frequent but rarely studied. The objective was to assess the efficacy of apremilast in early oligoarticular PsA.
Influenza vaccination stimulates maturation of the human T follicular helper cell response
Authors: Stefan A Schattgen, Jackson S Turner, Mohamed A Ghonim, Jeremy Chase Crawford, Aaron J Schmitz, Hyunjin Kim, Julian Q Zhou, Walid Awad, Robert C Mettelman, Wooseob Kim, Katherine M McIntire, Alem Haile, Michael K Klebert, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Ali H Ellebedy, Paul G Thomas
Journal: Nature Immunology (2024)

The differentiation and specificity of human CD4+ T follicular helper cells (TFH cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4+ TFH cell response. The first vaccination induced an increase in the frequency of circulating TFH (cTFH) and LN TFH cells at week 1 postvaccination. This increase was transient for cTFH cells, whereas the LN TFH cells further expanded during week 2 and remained elevated in frequency for at least 3 months. We observed several distinct subsets of TFH cells in the LN, including pre-TFH cells, memory TFH cells, germinal center (GC) TFH cells and interleukin-10+ TFH cell subsets beginning at baseline and at all time points postvaccination. The shift toward a GC TFH cell phenotype occurred with faster kinetics after the second vaccine compared to the first vaccine. We identified several influenza-specific TFH cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each TFH cell state was attainable within a clonal lineage. Thus, human TFH cells form a durable and dynamic multitissue network. Schattgen et al. profiled the subsets and clonality of CD4+ TFH cells in the blood and lymph nodes of human volunteers who received two influenza vaccines 1 year apart to characterize their dynamics and clonal evolution over 2 years.
Targeting mitochondrial quality control: new therapeutic strategies for major diseases
Authors: Wei-Long Hong, He Huang, Xue Zeng, Chen-Yang Duan
Journal: Military Medical Research (2024)

Abstract Mitochondria play a crucial role in maintaining the normal physiological state of cells. Hence, ensuring mitochondrial quality control is imperative for the prevention and treatment of numerous diseases. Previous reviews on this topic have however been inconsistencies and lack of systematic organization. Therefore, this review aims to provide a comprehensive and systematic overview of mitochondrial quality control and explore the possibility of targeting the same for the treatment of major diseases. This review systematically summarizes three fundamental characteristics of mitochondrial quality control, including mitochondrial morphology and dynamics, function and metabolism, and protein expression and regulation. It also extensively examines how imbalances in mitochondrial quality are linked to major diseases, such as ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, and tumors. Additionally, the review explores innovative approaches to target mitochondrial quality control, including using small molecule drugs that regulate critical steps in maintaining mitochondrial quality, nanomolecular materials designed for precise targeting of mitochondria, and novel cellular therapies, such as vesicle therapy and mitochondrial transplantation. This review offers a novel perspective on comprehending the shared mechanisms underlying the occurrence and progression of major diseases and provides theoretical support and practical guidance for the clinical implementation of innovative therapeutic strategies that target mitochondrial quality control for treating major diseases.
Application of the IOC Relative Energy Deficiency in Sport (REDs) Clinical Assessment Tool version 2 (CAT2) across 200+ elite athletes
Authors: Ida A Heikura, Walter T P McCluskey, Ming-Chang Tsai, Liz Johnson, Holly Murray, Margo Mountjoy, Kathryn E Ackerman, Matthew Fliss, Trent Stellingwerff
Journal: British Journal of Sports Medicine (2024)

Objective This cross-sectional retrospective and prospective study implemented the 2023 International Olympic Committee Relative Energy Deficiency in Sport (REDs) Clinical Assessment Tool version 2 (CAT2) to determine the current severity of REDs (primary outcome) and future risk of bone stress injuries (BSI, exploratory outcome) in elite athletes. Methods Female (n=143; 23.3±4.3 years) and male (n=70; 23.1±3.7 years) athletes (performance tier 3 (52%), tier 4 (36%), tier 5 (12%)) participated in a baseline CAT2 (with minor modifications) assessment, including a self-report questionnaire (menstrual function (females), BSI, Eating Disorder Examination Questionnaire (EDE-Q)), bone mineral density (BMD via DXA) and fasted blood analysis (triiodothyronine (T3), testosterone, cholesterol). Athletes were assigned a green, yellow, orange or red light via CAT2. The prospective risk of new self-report of physician-diagnosed BSI was assessed over a subsequent 6–24 months. Results REDs prevalence was 55% green, 36% yellow, 5% orange and 4% red light. The CAT2 identified a greater prevalence of amenorrhoea and BSI and lower T3, testosterone and BMD (p&lt;0.01) in red, orange and yellow (those with REDs) versus green light. ORs for a prospective self-reported BSI (majority physician diagnosed) were greater in orange vs green (OR 7.71, 95% CI (1.26 to 39.83)), in females with severe amenorrhoea (OR 4.6 (95% CI 0.98 to 17.85)), in males with low sex drive (OR 16.0 (95% CI 4.79 to 1038.87)), and athletes with elevated EDE-Q global scores (OR 1.45 (95% CI 0.97 to 1.97)). Conclusion The CAT2 has high validity in demonstrating current severity of REDs, with increased future risk of self-reported BSI in athletes with a more severe REDs traffic light category.
A prediction model for moderate to severe acute kidney injury in people with heart failure
Authors: Yu-Qi Yang, Jing-Jing Da, Sheng Nie, Jing Yuan, Bi-Cheng Liu, Hua-Feng Liu, Qiong-Qiong Yang, Hua Li, Gang Xu, Jian-Ping Weng, Yao-Zhong Kong, Qi-Jun Wan, Gui-Sen Li, Chun-Bo Chen, Hong Xu, Ying Hu, Yong-Jun Shi, Yi-Lun Zhou, Guo-Bin Su, Ying Tang, Fan-Fan Hou, Yan Zha
Journal: Military Medical Research (2024)
National Vaccination Coverage Among Adolescents Aged 13–17 Years — National Immunization Survey-Teen, United States, 2023
Authors: Cassandra Pingali, David Yankey, Michael Chen, Laurie D. Elam-Evans, Lauri E. Markowitz, Carla L. DeSisto, Sarah F. Schillie, Michelle Hughes, Madeleine R. Valier, Shannon Stokley, James A. Singleton
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Based on safety and efficacy data, vaccinations are the best defense to protect persons and communities from serious vaccine-preventable diseases. The Advisory Committee on Immunization Practices recommends routine vaccination of adolescents aged 11-12 years with three vaccines including tetanus, diphtheria, and acellular pertussis vaccine; quadrivalent meningococcal conjugate vaccine; and human papillomavirus vaccine. CDC analyzed data from the 2023 National Immunization Survey-Teen for 16,658 adolescents aged 13-17 years (born during January 2005-December 2010) to assess vaccination coverage in 2023, recent trends in coverage by birth year, and trends in coverage by eligibility for the Vaccines for Children (VFC) program and birth year. In 2023, coverage with all routine vaccines recommended for adolescents was similar to coverage in 2022. Vaccination coverage among VFC-eligible adolescents was generally stable during the COVID-19 pandemic, except for a decrease in the percentage of VFC-eligible adolescents who were up to date with HPV vaccination by age 13 years among those born in 2010 compared with those born in 2007. Whereas coverage differences were found between VFC-eligible and non-VFC-eligible adolescents before the COVID-19 pandemic, coverage was similar among the most recent birth years in the survey. Providers should make strong recommendations for all routine vaccines and review adolescent vaccination records to verify if adolescents are up to date with all recommended vaccines.