tbuckley/cabot-search huggingface dataset:
Optimizing Ethical Care, Quality, and Safety in Long-Term Services and Supports: A Position Paper From the American College of Physicians
Authors: Mark Aaron Unruh, Jan K. Carney, Alejandro Moreno, Lois Snyder Sulmasy, Jan K. Carney, Alejandro Moreno, Alicia Arbaje, Omar T. Atiq, Eileen D. Barrett, Eduardo Bruera, Angelique N. Collamer, Noel N. Deep, Charlene M. Dewey, Kari L. Esbensen, Ashley W. Fellers McKenzie, William E. Fox, Amy K. Holbrook, Diana Jung, Kyle E. Karches, Laurel J. Lyckholm, Isaac O. Opole, Kenneth Prager, Ikaasa Suri, Erik A. Wallace
Journal: Annals of Internal Medicine (2025)

Long-term services and supports (LTSS) in the United States have faced substantial and enduring challenges. They encompass services for persons who can no longer independently care for themselves because of cognitive decline, functional limitations, chronic illness, or the sequelae of such conditions. These services are delivered in institutional and noninstitutional settings, such as nursing homes, assisted living facilities, and home- and community-based programs. This position paper by the American College of Physicians examines the ethical implications of current LTSS business models and practices and their effect on vulnerable persons receiving care in these settings. These models and practices include approaches to staffing, resource allocation, health equity, and attention to patient preferences and patient-centered care, as well as business strategies that focus on profit rather than patient care and ownership structures that can lack transparency and hinder accountability. Addressing these challenges necessitates a collaborative approach among policymakers, health care systems, researchers, physicians and other health care professionals, LTSS facility and agency owners, patients, and caregivers. By embracing shared goals through a collaborative approach, an LTSS system can be cultivated that optimizes ethical care, quality, and safety, ensuring respect for all individuals across their lifespan.
In patients with subclinical AF, apixaban vs. aspirin reduced stroke or systemic embolism at 3.5 y in those with previous stroke or TIA
Authors: Mark J. Alberts
Journal: Annals of Internal Medicine (2025)

GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Neurology: [Formula: see text] Hematology: [Formula: see text].
Diet and Risk for Incident Diverticulitis in Women
Authors: Trevor Barlowe, Chelsea Anderson, Hazel B. Nichols, Anna C. Salvador, Robert S. Sandler, Dale P. Sandler, Anne F. Peery
Journal: Annals of Internal Medicine (2025)

Patients with diverticulitis often attempt to control their diet with a particular focus on avoiding nuts and seeds. However, whether dietary patterns or dietary intake of nuts and seeds are associated with diverticulitis risk is poorly studied, particularly in women. To determine whether select diets affect incident diverticulitis risk in women. Prospective cohort study. Cohort study in the United States and Puerto Rico. Women aged 35 to 74 years at enrollment who responded to food frequency and diverticulitis questionnaires and had no history of inflammatory bowel disease, cancer, or diverticulitis (n = 29 916). Food frequency questionnaires were used to calculate dietary index scores and to assess intake of nuts, seeds, and corn. Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and 95% CIs for the associations between each dietary component or dietary index and diverticulitis risk. 1531 cases of incident diverticulitis for 415 103 person-years of follow-up were identified. Intake of peanuts, nuts, and seeds (aHR,1.07 [95% CI, 0.91 to 1.25]) and fresh fruits with edible seeds (aHR,1.06 [CI, 0.90 to 1.24]) was not associated with incident diverticulitis. There was a reduced risk for incident diverticulitis in women in the highest quartile of healthy diets compared with the lowest quartile: the Dietary Approaches to Stop Hypertension diet (aHR, 0.77 [CI, 0.65 to 0.90]), the Healthy Eating Index (aHR, 0.78 [CI, 0.66 to 0.91]), the Alternative Healthy Eating Index (aHR, 0.81 [CI, 0.69 to 0.95]), and the Alternative Mediterranean diet (aHR, 0.91 [CI, 0.78 to 1.06]). Confounding, selection bias, and measurement bias are possible. Healthy diets were associated with a reduced risk for incident diverticulitis in women. Consumption of nuts and seeds was not associated with diverticulitis risk. National Institutes of Health.
Quality Indicators for Diabetes in Adults: A Review of Performance Measures by the American College of Physicians
Authors: Amir Qaseem, Peter Basch, Karen Campos, Scott T. MacDonald, Cristin A. Mount, Samantha Tierney, Rebecca A. Andrews, Rebecca A. Andrews, Nick Fitterman, Peter Basch, Elisa I. Choi, Roger S. Khetan, Scott T. MacDonald, Nancy L. Miller, Cristin A. Mount, Nicole J. Van Groningen, Brook Watts, Karen Campos, Amir Qaseem, Samantha Tierney, Rebecca A. Andrews, Nick Fitterman, Peter Basch, Elisa I. Choi, Roger S. Khetan, Scott T. MacDonald, Nancy L. Miller, Cristin A. Mount, Nicole J. Van Groningen, Brook Watts, Karen Campos, Amir Qaseem, Samantha Tierney
Journal: Annals of Internal Medicine (2025)

Type 1 and type 2 diabetes are prevalent chronic illnesses, are leading causes of mortality and morbidity, and result in substantial public health burden. Timely identification and appropriate management of diabetes can help reduce adverse consequences of diabetes. The American College of Physicians (ACP) embraces performance measurement as a means to improve quality of care but believes that a performance measure must be methodologically sound and evidence-based in order to be considered for inclusion in payment, accountability, or reporting programs. These principles are critical given the potential impact on physician administrative work, reputation, and reimbursement and to prevent unintended consequences for patient care. To help improve performance measurement and reduce burden, the ACP Performance Measurement Committee (PMC) reviews performance measures using a rigorous process to recognize high-quality measures and address gaps and areas for improvement. In this article, the PMC presents its review of 14 current performance measures for diabetes that are relevant to internal medicine. The PMC supports kidney health evaluation at the individual and group practice levels, hemoglobin A1c control at the health plan level, eye examination at the health plan level, and angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy at the individual physician level.
Thyroid Function Reference Intervals by Age, Sex, and Race
Authors: Qihang Li, Yida Tang, Xuefeng Yu, Guijun Qin, Limin Tian, Lianjiang Cheng, Yi Lu, Zhigang Zhao, Libin Liu, Kai Zhang, Changjun Wang, Shuqing Zhang, Yong Xu, Guangyao Song, Fang Zhong, Xiude Fan, Zhixiang Wang, Yafei Wu, Yongfeng Song, Jiajun Zhao
Journal: Annals of Internal Medicine (2025)

Current clinical practice uses a one-size-fits-all approach to define reference intervals for the results of diagnostic tests about thyroid function. This approach does not recognize subgroup differences according to age, sex, or race. To identify age-, sex-, and race-specific reference intervals for the common diagnostic tests that measure thyroid function and to examine how these new reference intervals reclassify persons into disease categories when compared with current reference intervals. Cross-sectional analysis. Data from the U.S. NHANES (National Health and Nutrition Examination Survey) supplemented with data from a multicenter Chinese study. A nationally representative sample from NHANES aged 20 years or older (n = 8308) supplemented with a Chinese database of routine health checkups from 49 hospitals in 10 provinces aged 18 years or older (n = 314 302). The thyroid function reference interval was defined as the interval of diagnostic indicator levels from the 2.5th (lower limit) to the 97.5th (upper limit) percentile by age, sex, and race subgroups. In 8308 NHANES participants, the 97.5th percentile levels of thyroid-stimulating hormone (TSH) increased with age, whereas total triiodothyronine (TT3) levels declined with age and total thyroxine (TT4) levels were stable across different ages. Women had higher TT4 levels, and White participants had higher TSH levels. Using current reference intervals, the prevalence of subclinical hypothyroidism increased from 2.4% for ages 20 to 29 years to 5.9% for ages 70 years and older. In contrast, using age-, sex-, and race-specific reference intervals reclassified 48.5% of persons with subclinical hypothyroidism as normal, especially women and White participants, and reclassified 31.2% of persons with subclinical hyperthyroidism as normal, especially women, Black participants, and Hispanic participants. When compared with the findings from U.S. participants, many of the findings from 314 302 Chinese participants were similar. Cross-sectional data; sample size limitations for subgroup. These findings should help establish more accurate reference intervals for thyroid diseases and facilitate development of a consensus about how to define and manage those diseases. National Key Research and Development Program of China and National Natural Science Foundation.
Confirmatory Testing for Primary Aldosteronism
Authors: Alexander A. Leung, Raj S. Padwal, Gregory L. Hundemer, Erik Venos, David J.T. Campbell, Daniel T. Holmes, Dennis J. Orton, C. Benny So, Stefan J. Przybojewski, Cori E. Caughlin, Janice L. Pasieka, Doreen M. Rabi, Gregory A. Kline
Journal: Annals of Internal Medicine (2025)

Confirmatory testing to verify the diagnosis of primary aldosteronism (PA) in patients who have an abnormal screening result is of uncertain benefit. To perform a blinded assessment of the seated saline suppression test (SSST). Diagnostic test accuracy study. (ClinicalTrials.gov: NCT04422756). The regional Endocrine Hypertension Clinic in Calgary, Alberta, Canada. 156 adults with a positive screening result for PA. The SSST was done by administering 2 L of 0.9% sodium chloride intravenously over 4 hours with the patient seated. Treatment response was considered the reference standard for determining disease status and was based on blood pressure lowering, reduction of antihypertensive drug dose, and normalization of biochemistry. Measures of diagnostic test accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value, were estimated. Post-SSST aldosterone concentrations measured using immunoassay overlapped between treatment responders (median, 329 pmol/L [IQR, 227 to 525 pmol/L]) and nonresponders (median, 255 pmol/L [IQR, 162 to 346 pmol/L]). The SSST could not discriminate between response statuses (area under the curve, 62.1% [95% CI, 45.1% to 79.1%]). The positive and negative likelihood ratios were equivocal for aldosterone cutoffs ranging from 140 to 300 pmol/L. These findings remained consistent after differences in treatment, occurrence of hypokalemia, and laboratory assay used were accounted for. The study population had many patients with high-risk features of PA and few nonresponders. The SSST is associated with a high false-negative rate, and reliance on it may lead to missed opportunities for intervention. The Canadian Institutes of Health Research, Hypertension Canada, and the Heart and Stroke Foundation of Canada.
Characteristics of Patients and Prognostic Factors Across Treatment Lines in Metastatic Colorectal Cancer: An Analysis From the Aide et Recherche en Cancérologie Digestive Database
Authors: Jean-Baptiste Bachet, Aimery de Gramont, Morteza Raeisi, Manel Rakez, Richard M. Goldberg, Niall C. Tebbutt, Eric Van Cutsem, Daniel G. Haller, J. Randolph Hecht, Robert J. Mayer, Stuart M. Lichtman, Al B. Benson, Alberto F. Sobrero, Josep Tabernero, Richard Adams, John R. Zalcberg, Axel Grothey, Takayuki Yoshino, Thierry André, Qian Shi, Benoist Chibaudel
Journal: Journal of Clinical Oncology (2025)

PURPOSE Several lines of treatment can be used sequentially in patients with metastatic colorectal cancer. We investigated the evolution of patient/tumor characteristics and their prognostic impact across treatment lines to develop an overall prognostic score (OPS). PATIENTS AND METHODS Individual patient data from 48 randomized trials were analyzed. The end point was overall survival (from random assignment to death). Missing data were imputed. The complete data set was then separated into construction (80%) and validation sets (20%). The Cox's model was used to define risk groups for survival using the OPS. The discrimination capability was assessed in each treatment-line via bootstrapping to obtain optimism-corrected calibration and discrimination C-indices. Internal validation was done in the validation set. RESULTS A total of 37,560 patients (26,974 in first-line [1L], 7,693 in second-line [2L], and 2,893 in third-line [3L]) were analyzed. Some clinical, biological, and molecular characteristics of patients/tumors included in therapeutic trials evolve over the lines. Seven independent prognostic variables were retained in the final multivariate model common to all lines: Eastern Cooperative Oncology Group performance status, hemoglobin, platelet count, WBC/absolute neutrophil count ratio, lactate dehydrogenase, alkaline phosphatase, and the number of metastatic sites. The OPS was used to define four patient subgroups with significantly different prognoses in 1L, 2L, and 3L, separately, with adequate C-indices: 0.65, 0.66, and 0.69 in the construction set and 0.65, 0.66, and 0.68 in the validation set, respectively. The OPS was not predictive, with 3L drugs ( v placebo) or subsequent line (2L/1L or 3L/2L) extending survival in all prognostic groups. CONCLUSION The same prognostic model using practical variables can be used before all treatment lines. The OPS could better stratify patients in future clinical trials and help to therapeutic decision in routine practice.
Air Pollution and Autism Spectrum Disorder: Unveiling Multipollutant Risks and Sociodemographic Influences in California
Authors: Karl O'Sharkey, Sanjali Mitra, Ting Chow, Laura Thompson, Jason Su, Myles Cockburn, Beate Ritz
Journal: Environmental Health Perspectives (2025)

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition of increasing prevalence worldwide. Air pollution may be a major contributor to the rise in ASD cases. This study investigated how the risk of ASD from prenatal and early postnatal exposure to specific air pollutants is being modified by key sociodemographic factors exploring vulnerable exposure periods. We conducted a California (CA) population-based cohort study of 44,173 ASD cases among 2,371,379 children born between 2013-2018 (CA birth registry) linked to CA Department of Developmental Services (DDS) records to extract ASD diagnoses prior to the end of 2022. Prenatal and 1-year postnatal air pollution exposures (fine particulate matter - PM2.5, nitrogen dioxide - NO2, and Ozone - O3) were estimated using an advanced land-use regression (LUR) spatiotemporal model with machine learning. Logistic regression was used to estimate odds ratios and 95% confidence intervals for four models: single-pollutant at a single-period (prenatal or postnatal), multi-pollutant at a single-period, single-pollutant with dual-periods (prenatal and postnatal), and multi-pollutant with dual-time period co-adjustment, adjusting for relevant individual and regional covariates. Prenatal and postnatal PM2.5 exposure increased ASD odds in all models. NO2 was associated with ASD pre- and postnatally in single and multi-pollutant but postnatally only in dual time period models. In contrast, O3 showed the opposite pattern of NO2 with slightly negative associations in single and multi-pollutant models that turned positive for the prenatal period in dual time period models. The postnatal NO2 effect was strongest among Black and Hispanic children, suggesting higher contributions from traffic-related exposures. Exposure to specific air pollutants during pregnancy and in the postnatal periods are associated with an increased risk of ASD, with sociodemographic differences potentially highlighting exposure hot spots and sources as well as subpopulation vulnerabilities. https://doi.org/10.1289/EHP15573.
Development and Validation of a Novel Prediction Model for Hearing Loss From Cisplatin Chemotherapy
Authors: Joshua Millstein, Shahrad R. Rassekh, Austin L. Brown, Qi Nie, Adam J. Esbenshade, Kristin R. Knight, Michael E. Scheurer, Lillian Sung, Beth Brooks, Diana J. Moke, Colin J.D. Ross, Michael Wright, Victoria Mena, Teresa Rushing, Bruce C. Carleton, Etan Orgel
Journal: Journal of Clinical Oncology (2025)

PURPOSE Cisplatin treats many common tumors but causes permanent and debilitating hearing loss (HL). The objective of this study was to develop and externally validate a predictive model of HL in cisplatin-treated children and adolescent cancer survivors. METHODS The Pediatric Holistic Evaluation of Auditory Risk (PedsHEAR) model architecture used several machine learning approaches followed by an ensemble predictor. The primary end point was post-treatment communication–affecting HL (International Society of Pediatric Oncology Ototoxicity Scale [SIOP] Grade ≥2). PedsHEAR was developed from a multicenter data set of cisplatin-exposed patients up to 21 years old (1984-2017) and externally validated using data from the Children's Oncology Group ACCL05C1 study (2007-2012) and two combined institutional cohorts (1988-2022). The model predicts post-treatment HL in each patient (probability [%], 95% CI) and classifies patients as low, intermediate, or high risk for HL (probability HL &lt;0.33, 0.33-0.60, &gt;0.60, respectively). RESULTS In the training data set (n = 1,115, median age 6.3 years, SIOP Grade ≥2 HL 44%), PedsHEAR demonstrated excellent discrimination (AUC, 0.93 [95% CI, 0.92 to 0.95]) and then successfully validated within the internal (testing; AUC, 0.79 [95% CI, 0.74 to 0.85]) and two external validation cohorts (AUC, 0.74 and AUC, 0.67). In an aggregate validation cohort (n = 631), the model predicted the probability of HL (AUC, 0.76 [95% CI, 0.72 to 0.79]) and classified 22% (141/631), 71% (447/631), and 7% (43/631) of patients as low, intermediate, or high risk for HL. CONCLUSION PedsHEAR predicted SIOP Grade ≥2 HL in pediatric cisplatin-treated patients. This is the first validated model to successfully predict cisplatin-induced HL in a broadly representative population treated with diverse regimens across a range of treatment settings.
Metabolic reprograming of immune cells in MASH
Authors: ChuHan Ma, Shuyue Wang, Bingning Dong, Yu Tian
Journal: Hepatology (2025)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), affects approximately 30% of adults worldwide. Approximately 1/6 of MASLD patients progress to metabolic dysfunction-associated steatohepatitis (MASH) and potentially evolve towards cirrhosis and hepatocellular carcinoma (HCC). This condition imposes a significant burden on the global health. Although MASH is primarily a metabolic disorder, immune cells play a crucial role in its development. The activation of immune cells involves alterations in transcription and protein synthesis, which require metabolic adaptation of cellular substrate metabolism, including glucose and lipid metabolism. Moreover, the lipid-rich environment of the liver can affect the metabolism of immune cells. In this review, we delineate the metabolic profiles of immune cells in MASH, focusing on macrophages and T cells, and discuss the impact of targeting cellular metabolism on these cells along with clinical trial outcomes. Macrophages in MASH are characterized by increased glycolysis, compromised oxidative phosphorylation, and augmented lipid uptake, synthesis, and fatty acid oxidation, all of which contribute to their inflammatory phenotype. Lymphocytes, such as T cells and NK cells, exhibit impaired metabolic functions that hamper their immune surveillance capabilities and facilitate the development of HCC. However, research on the metabolic characteristics of other types of immune cells remains limited. With the development of single-cell genomics and animal models of MASH, we anticipate that further studies in this compelling field may shed light on the pathogenesis of MASH and pave the way for novel therapeutic strategies.
Cryo-EM structure of coagulation factor Va bound to activated protein C
Authors: Bassem M. Mohammed, Katherine Basore, Enrico Di Cera
Journal: Blood (2025)

Coagulation factor Va (fVa) is the cofactor component of the prothrombinase complex required for rapid generation of thrombin from prothrombin in the penultimate step of the coagulation cascade. In addition, fVa is a target for proteolytic inactivation by activated protein C (APC). Like other protein-protein interactions in the coagulation cascade, the fVa-APC interaction has long posed a challenge to structural biology and its molecular underpinnings remain unknown. A recent cryogenic electron microscopy (cryo-EM) structure of fVa has revealed the arrangement of its A1-A2-A3-C1-C2 domains and the environment of the sites of APC cleavage at R306 and R506. Here we report the cryo-EM structure of the fVa-APC complex at 3.15 Å resolution where the protease domain of APC engages R506 in the A2 domain of fVa mainly through electrostatic interactions between positively charged residues in the 30- and 70- loops of APC and an electronegative surface of fVa. The auxiliary Gla and EGF domains of APC are highly dynamic and point to solvent, without making contacts with fVa. Binding of APC displaces a large portion of the A2 domain of fVa and projects the 654VKCIPDDDEDSYEIFEP670 segment as a "latch", or exosite ligand, over the 70-loop of the enzyme. The latch induces a large conformational change of the autolysis loop of APC which in turn promotes docking of R506 into the primary specificity pocket. The cryo-EM structure of the fVa-APC complex validates the bulk of existing biochemical data and offers molecular context for a key regulatory interaction of the coagulation cascade.
A Novel Mouse Model of Hemoglobin SC Disease Reveals Mechanisms Underlying Beneficial Effects of Hydroxyurea
Authors: Tahereh Setayesh, Mengna Chi, Zachery Oestreicher, Masahide Sakabe, Katie Giger Seu, Zhenqi Zhu, Harsimran Kaur, Anifat Tijani, Mei Xin, Amy Shova, Kenneth D Greis, Tim M. Townes, Jozsef Balla, Katherine VandenHeuvel, Yueh-Chiang Hu, Punam Malik
Journal: Blood (2025)
Evidence Generation and Implementation of Transcatheter Interventions for Atrioventricular Valvular Heart Disease in Heart Failure: Current Status and Future Directions
Authors: Marco Metra, Daniela Tomasoni, Marianna Adamo, Stefan D. Anker, Antoni Bayes-Genis, Ralph Stephan von Bardeleben, Michael Böhm, Erwan Donal, Gerasimos S. Filippatos, Francesco Maisano, Piotr Ponikowski, Gianluigi Savarese, Fabien Praz, Javed Butler
Journal: Circulation (2025)

Mitral regurgitation and tricuspid regurgitation are the most common valvular heart diseases in patients with heart failure and have independent prognostic value. Transcatheter interventions are now available for the treatment of valvular heart disease, and their efficacy and safety have been tested in randomized controlled trials. However, evidence is still limited and sometimes inconclusive because several aspects of these trials limit their interpretation or consistency. These include heterogeneity in the pathogenesis and clinical characteristics of patients, the dynamic nature of secondary atrioventricular valve disease severity, the role of heart failure medications and devices, dependency on procedural results and operators’ skills, smaller number of patients enrolled and the power to detect differences in trials, and limitations to use patients’ reported outcomes with unblinded study protocols. These specific aspects of trials in patients with atrioventricular valve disease are reviewed in this article with a focus on possible solutions to generate further evidence for the efficacy and safety for transcatheter treatments of atrioventricular valve disease in patients with heart failure.