tbuckley/cabot-search huggingface dataset:
A Person-Centered Approach to Supplemental Oxygen Therapy in the Outpatient Setting
Authors: Angela O. Suen, Susan S. Jacobs, Mary R. Kitlowski, Richard D. Branson, Anand S. Iyer
Journal: JAMA Internal Medicine (2025)

Importance Approximately 1.5 million adults in the US use supplemental oxygen annually in the outpatient setting. However, many do not receive delivery systems that adequately meet their needs, and few receive education about devices or how to maintain independence. This Review summarizes guidelines and evidence on outpatient supplemental oxygen across several cardiopulmonary conditions, highlights evidence gaps where benefits are unclear, and discusses outcomes that inform a person-centered framework for supplemental oxygen therapy. Observations Most studies of supplemental oxygen have been conducted in chronic obstructive pulmonary disease, with limited high-quality data in other cardiopulmonary conditions. Data strongly support supplemental oxygen therapy in people with severe resting desaturation (oxygen saturation [SpO 2 ] of 88% or less), with demonstrated improvement in mortality. Whether supplemental oxygen improves symptoms or function in patients with isolated severe exertional desaturation remains inconclusive, prompting an individualized approach and exertional oxygen testing if a patient is mobile and reporting exertional symptoms. Apart from cor pulmonale, evidence does not support supplemental oxygen therapy in patients with moderate resting or exertional desaturation (SpO 2 of 89% to 93%). Supplemental oxygen’s broad impact on patient-centered outcomes; the supplemental oxygen landscape of devices, testing, prescription, and delivery; and how to weigh the potential harms vs benefits with patients are summarized. These data inform a person-centered supplemental oxygen framework to help patients minimize loss of independence and improve quality of life across the following domains: (1) health care values and preferences; (2) functional status, mobility, and frailty; (3) cognition and supplemental oxygen education; (4) physical symptoms; (5) psychological and social impact; and (6) caregiver support. Guidance on deimplementation and future directions are also summarized. Conclusions and Relevance Supplemental oxygen therapy should follow a person-centered approach that empowers patients and caregivers; helps patients improve independence and quality of life by optimizing function, mobility, and social well-being; weighs benefits and burdens; and engages in shared decision-making when the evidence is unclear.
Correction to: Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration–Tobacco Working Group
Authors: Zhiqi Yao, Erfan Tasdighi, Zeina A. Dardari, Kunal K. Jha, Ngozi Osuji, Tanuja Rajan, Ellen Boakye, Carlos J. Rodriguez, Kunihiro Matsushita, Eleanor M. Simonsick, Joao A.C. Lima, Rachel Widome, Debbie L. Cohen, Lawrence J. Appel, Amit Khera, Michael E. Hall, Suzanne Judd, Shelley A. Cole, Ramachandran S. Vasan, Emelia J. Benjamin, Aruni Bhatnagar, Andrew P. DeFilippis, Michael J. Blaha
Journal: Circulation (2025)
Correction to: 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Authors: Heather L. Gornik, Herbert D. Aronow, Philip P. Goodney, Shipra Arya, Luke Packard Brewster, Lori Byrd, Venita Chandra, Douglas E. Drachman, Jennifer M. Eaves, Jonathan K. Ehrman, John N. Evans, Thomas S.D. Getchius, J. Antonio Gutiérrez, Beau M. Hawkins, Connie N. Hess, Karen J. Ho, W. Schuyler Jones, Esther S.H. Kim, Scott Kinlay, Lee Kirksey, Debra Kohlman-Trigoboff, Chandler A. Long, Amy West Pollak, Saher S. Sabri, Lawrence B. Sadwin, Eric A. Secemsky, Maya Serhal, Mehdi H. Shishehbor, Diane Treat-Jacobson, Luke R. Wilkins
Journal: Circulation (2025)
A Real-World International Staging System (RW-ISS) for patients with newly diagnosed multiple myeloma
Authors: Christian Brieghel, Tobias Schmidt Slørdahl, Morten Nørgaard Andersen, Agoston Gyula Szabo, Carsten Utoft Niemann, Sigrún Thorsteinsdóttir
Journal: Blood Cancer Journal (2025)

The revised international staging system (R-ISS) in multiple myeloma (MM) was recently updated as the second R-ISS (R2-ISS) and refined prognostication in clinical trial populations. By including 2929 Danish patients with MM and complete data on R2-ISS registered from 2005 through 2019, we validated the R2-ISS for overall survival (OS) in a population-based cohort; however, only partly among younger patients. We thus developed a real-world international staging system (RW-ISS) from a 75% training cohort. Feature selection and weighted scores of high-risk variables from a Cox regression model of OS included age >70 years (2 points), performance status (PS) > 1 (2 points), PS 1 (1 point), t(14;16) (1 point), ISS III (1 point), ISS II (0.5 points), high lactate dehydrogenase (0.5 points), and del(17p) (0.5 points). In the test set, patients with RW-ISS I (0-2.0 points, 38.2%), II (2.5-3.0 points, 19.8%), III (3.5-4.5 points, 27.1%), and IV (5.0-7.0 points, 15.0%) demonstrated a median OS of 9.5, 5.5, 3.4, and 1.1 years, respectively (P < 0.0001) and the C-index was superior for RW-ISS as compared to both R2-ISS and R-ISS (0.708 vs 0.604 vs 0.595, respectively). RW-ISS was in part externally validated. We thus recommend using RW-ISS in routine clinical care of NDMM.
Photothermal treatment of prostate tumor with micellar indocyanine green and Napabucasin to co-ablate cancer cells and cancer stem cells
Authors: Yanyi Qu, Beibei Guo, Songsong Zhao, Juan Sun, Jun Cao, Mingyu Xia, Zhiyuan Zhong, Fenghua Meng
Journal: Journal of Controlled Release (2025)
Investigation into biased signaling, glycosylation, and drug vulnerability of acute myeloid leukemia
Authors: Tomasz Pienkowski, Aleksandra Golonko, Lukasz Bolkun, Katarzyna Wawrzak-Pienkowska, Lukasz Szczerbinski, Adam Kretowski, Michal Ciborowski, Wlodzimierz Lewandowski, Waldemar Priebe, Renata Swislocka
Journal: Pharmacology & Therapeutics (2025)
Umbrella Review of Nonpharmacological Interventions for Intrinsic Capacity in Older Adults
Authors: Yu-Tai Lo, Hui-Chen Su, Chanisara Chuenchomnoy, Ting-Wei Liao, Yi-Lin Wu, Sin-Hang Tam, Chieh-Hsiu Liu, Chih-Wen Chou, Yi-Ching Yang, Yen-Hsu Chen, Yen-Chin Chen
Journal: Ageing Research Reviews (2025)
Insurer-Level Estimates of Revenue From Differential Coding in Medicare Advantage
Authors: Richard Kronick, F. Michael Chua, Ramona Krauss, Logan Johnson, Daniel Waldo
Journal: Annals of Internal Medicine (2025)

Medicare Advantage (MA) plans report diagnoses more intensely than providers in the traditional Medicare (TM) program, and there is wide variation in coding intensity across MA plans. To estimate the extent to which coding differs among MA insurers and how much extra revenue each insurer receives as a result. Analysis of differential patterns of coding between MA and TM and the effects of differential coding on revenue received by each MA insurer. The U.S. Medicare program. 697 MA contracts offered by 193 insurers. Estimates of the effects of differential coding on contract-level risk scores used in payment and on revenue. In 2021, the average MA risk score was 1.26; the average for a comparable group in TM was 1.07. The average MA risk score was 0.19 (95% CI, 0.17 to 0.21) higher than it would have been if MA coding patterns had been identical to coding in TM. The average risk score at UnitedHealth Group was 0.28 (CI, 0.26 to 0.31) higher than it would have been if its plans had coded identically to TM. In contrast, Kaiser Permanente coded only slightly more intensely than TM. As a result of differential coding, MA plans received an estimated $33 billion (CI, $28 billion to $38.5 billion) in additional payment in 2021, $13.9 billion (CI, $12.4 billion to $15.5 billion) (42%) of which went to UnitedHealth. The estimates may have been affected by differences in the demographic characteristics or health status of beneficiaries between MA and TM. Any MA payment policy reform that effectively targets differential coding will have a widely disparate effect across insurers. Arnold Ventures.
How Would You Manage This Patient With Decreased Bone Density? Grand Rounds Discussion From Beth Israel Deaconess Medical Center
Authors: Howard Libman, Elaine W. Yu, Alan O. Malabanan, Gerald W. Smetana
Journal: Annals of Internal Medicine (2025)

Osteoporosis is a skeletal condition characterized by low bone mass and fragility resulting in an increased risk for fracture. It affects all bones, but fractures most often occur in the hip and spine. Osteoporosis is common in postmenopausal women, with estrogen deficiency thought to be a major contributing factor. Screening for osteoporosis with bone densitometry is recommended in all women 65 years of age or older and in postmenopausal women younger than 65 who are at increased risk. In 2023, the American College of Physicians published updated guidance on the pharmacologic treatment of osteoporosis. Among the recommendations was for clinicians to take an individualized approach regarding whether to start treatment with a bisphosphonate in women older than 65 years with osteopenia (a lesser degree of bone loss) to reduce the risk for fractures. Here, 2 bone endocrinologists debate how to manage a patient with both osteopenia and osteoporosis on bone densitometry. They discuss how to interpret and address these findings.
Epilepsy
Authors: Kaarkuzhali B. Krishnamurthy
Journal: Annals of Internal Medicine (2025)

Epilepsy is a common neurologic condition characterized by at least 1 unprovoked seizure and a high risk for recurrent seizures. Distinguishing epilepsy from conditions that can mimic seizures is important for accurate diagnosis and effective treatment. This article reviews the evaluation of patients suspected of having epilepsy and discusses behavioral strategies and pharmacologic and surgical therapies that can help reduce morbidity associated with recurrent seizures.
Standardization and Prediction to Control Confounding: Estimating Risk Differences and Ratios for Clinical Interpretations and Decision Making
Authors: A. Russell Localio, James A. Henegan, Stephanie Chang, Anne R. Meibohm, Eric A. Ross, Steven N. Goodman, David Couper, Eliseo Guallar, Michael E. Griswold
Journal: Annals of Internal Medicine (2025)

What is the added risk for death from smoking? Logistic regression has become the most common statistical method to answer such questions in the biomedical literature. However, the typical analyses estimate odds ratios, a metric too often misunderstood and misinterpreted. Although estimates of risks, and their differences and ratios, offer transparent clinical interpretations, commonly used statistical models have known methodological shortcomings. "Standardization" through modeling, weighting, or matching offers a solution. The goals of this article are to review classical concepts of standardization and to link them to regression modeling for causal inference. The authors also describe approaches based on weighting and matching compared with regression-based standardization. Using an example of smoking from the ARIC (Atherosclerosis Risk in Communities) study, they explain the value of standardization, long used in medicine and public health, to estimate risks and their differences and ratios for binary outcomes. The authors demonstrate how standard statistical software using models that best fit the data and respect underlying biological or clinical processes can reexpress results in clinically meaningful metrics. The Supplement offers examples with common software packages.
Erratum: Mitogen-activated protein kinase kinase kinase 4 deficiency in intrahepatic cholangiocarcinoma leads to invasive growth and epithelial-mesenchymal transition
Authors: Liu-Xiao Yang, Qiang Gao, Jie-Yi Shi, Zhi-Chao Wang, Yong Zhang, Ping-Ting Gao, Xiao-Ying Wang, Ying-Hong Shi, Ai-Wu Ke, Guo-Ming Shi, Jia-Bin Cai, Wei-Ren Liu, Meng Duan, Ying-Jun Zhao, Yuan Ji, Dong-Mei Gao, Kai Zhu, Jian Zhou, Shuang-Jian Qiu, Ya Cao, Qi-Qun Tang, Jia Fan
Journal: Hepatology (2025)
Portal sinusoidal vascular diseases: Assessment and therapy
Authors: Maria Mironova, Harish Gopalakrishna, Christopher Koh, David E. Kleiner, Theo Heller
Journal: Hepatology (2025)

The term porto-sinusoidal vascular disease (PSVD) was introduced in 2019 to describe a group of liver conditions that can lead to portal hypertension (PH) in the absence of cirrhosis or portal vein thrombosis, with or without specific findings on liver histology. The new nomenclature has facilitated the consolidation of knowledge on diseases previously referred to by various terms, including Banti’s disease, non-cirrhotic portal hypertension, non-cirrhotic portal fibrosis, and idiopathic portal hypertension, while excluding certain etiologies like sarcoidosis, congenital hepatic fibrosis, and Budd-Chiari syndrome. The prevalence and recognition of the disorder has been increasing. Advances in diagnostics and treatment have improved life expectancy for patients with associated conditions, such as immunodeficiencies and autoimmune diseases. Similar to cirrhosis, patients with PSVD may experience complications of PH, including variceal bleeding and ascites. However, less is known about its natural history, screening strategies, prognosis, and treatment options. This review discusses methods for assessing PSVD, including clinical and histological features, imaging techniques, and currently available treatments. It also addresses the challenges posed by the new nomenclature and the remaining questions in disease assessment.
Simulating the impact of survival benefit-based liver transplant organ allocation
Authors: David Goldberg, Catherine Blandon, Cindy Delgado, Binu John, Ezekiel Emanuel, David Kaplan, Peter Reese
Journal: Hepatology (2025)

Background &amp; Aims: In the US, and much of the world, prioritization for a deceased donor liver transplant focuses on sickest-first based on allocating organs using the MELD score. There have been calls to instead allocate organs based on transplant survival benefit, but the impact of such a system on the broader waitlist population is unknown. Approach &amp; Results: We performed a simulation study using the Liver Simulated Allocation Model (LSAM) to compare the current US system of liver allocation to one, using different time horizons, focused on: pre-transplant survival only, post-transplant survival only, and survival benefit (difference of post-transplant survival and pre-transplant survival). Changing liver allocation to a survival benefit-based system was simulated to lead to a small improvement in average patient-level post-transplant survival (mean survival over 5-year time horizon of 4.24 y vs. 4.19 y in current system). However, this small improvement was associated with a simulated decrease in transplants and an increase in waitlist mortality of 400 deaths per year. The resulting net benefit overall (pre-transplant deaths and post-transplant survival) was negligible under a survival benefit-based allocation approach. Conclusions: Our simulations predicted that survival benefit-based allocation would only increase post-transplant survival by an average of 18 days per recipient, at the expense of a simulated increase in waitlist mortality of 400 deaths per year. The current practice of liver transplantation, with sickest-first allocation operating in a system where transplant physicians ration organs to maximize outcomes, survival benefit overall is maintained and not compromised.
Glycolysis Induces Abnormal Transcription Through Histone Lactylation in T-lineage Acute Lymphoblastic Leukemia
Authors: Wenyan Wu, Jingyi Zhang, Huiying Sun, Xiaoyu Wu, Han Wang, Bowen Cui, Shuang Zhao, Kefei Wu, Yanjun Pan, Rongrong Fan, Ying Zhong, Xiang Wang, Ying Wang, Xiaoxiao Chen, Jianan Rao, Ronghua Wang, Kai Luo, Xinrong Liu, Liang Zheng, Shuhong Shen, Meng Yin, Yangyang Xie, Yu Liu
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract The Warburg effect, which excessively produce lactate, and transcriptional dysregulation are two hallmarks of tumors. However, the precise influence of lactate on epigenetic modifications at a genome-wide level and its impact on gene transcription in tumor cells remain unclear. We conducted an analysis of genome-wide histone H3 lysine 18 lactylation (H3K18la) modifications in T-cell acute lymphoblastic leukemia (T-ALL). We found an increased level of lactate and H3K18la in T-ALL tumor cells compared to normal T cells and the H3K18la modification is associated with cell proliferation. Accordingly, we observed a significant shift in genome-wide H3K18la modification from T cell immunity in normal T cells to leukemogenesis in T-ALL, which correlated with altered gene transcription profiles. We showed that H3K18la is primarily involved in actively regulating gene transcription and observed clusters of H3K18la modifications exhibiting patterns reminiscent of super-enhancers. Disrupting H3K18la modification revealed both synergistic and divergent changes between H3K18la and histone H3 lysine 27 acetylation (H3K27ac) modifications. Finally, we found that the high transcription of H3K18la target genes, IGFBP2 and IARS, is associated with inferior prognosis of T-ALL. These findings enhance our understanding of how metabolic disruptions contribute to transcription dysregulation through epigenetic changes in T-ALL, underscoring the interplay of histone modifications in maintaining oncogenic epigenetic stability.
Lower extremity lymphatic flow is associated with diuretic response in acute heart failure
Authors: Barbara Ponikowska, Robert Zymliński, Marat Fudim, Beata Ponikowska, Gracjan Iwanek, Mateusz Guzik, Jan Biegus
Journal: European Journal of Heart Failure (2025)

Abstract Aims The dysfunctional lymphatic system appears to play an important role in the development and progression of congestion in heart failure. We hypothesized that in acute heart failure (AHF), diuretic efficacy is associated with peripheral lymph flow. Methods and results We prospectively studied AHF patients who received protocolized diuretics followed by assessment of lower limb flow using indocyanine green lymphangiography (a validated method for visualization of lymphatic drainage). The lymph flow was defined as ‘present’ when it reached the ankle and ‘significant’ when it reached &gt;10 cm within 10 min of dye injection, respectively. Based on diuretic efficacy (defined as cumulative diuresis and weight loss), patients were classified as diuretic responders vs. non‐responders. Overall, 65 patients (mean age: 67 ± 15 years, median [Q1–Q3] N‐terminal pro‐B‐type natriuretic peptide: 6901 [4478–12 723] pg/ml) were examined. There were 43 (66%) diuretic responders and 22 (34%) non‐responders who did not differ in baseline clinical/laboratory characteristics. Among the responders, there were more patients with lymph flow either ‘present’ or ‘significant’ (95% vs. 73% and 88% vs. 45% vs non‐responders, respectively, p &lt; 0.01). Responders had significantly longer median distance lymph reached within 10 min (50 [24–75] vs. 10 [3–38] cm; p &lt; 0.0005). There was a significant association between lymph flow and 6‐h diuresis with β (standard error) of 0.45 (0.13) ( p &lt; 0.005). In the multivariable analyses, lymph flow distance (odds ratio 1.48, 95% confidence interval 1.08–2.03) independently predicted diuretic efficacy ( p &lt; 0.05). Conclusion For the first time, faster lower limb lymph flow was linked with better diuretic efficacy in AHF. Studies are needed to determine whether the lymphatic system can become a therapeutic target for decongestion.
The comprehensive clinical benefits of digital phenotyping: from broad adoption to full impact
Authors: Yingbo Zhang, Jiao Wang, Hui Zong, Rajeev K Singla, Amin Ullah, Xingyun Liu, Rongrong Wu, Shumin Ren, Bairong Shen
Journal: npj Digital Medicine (2025)

Digital phenotyping collects health data digitally, supporting early disease diagnosis and health management. This paper systematically reviews the diversity of research methods in digital phenotyping and its clinical benefits, while also focusing on its importance within the P4 medicine paradigm and its core role in advancing its application in biobanks. Furthermore, the paper envisions the continued clinical benefits of digital phenotyping, driven by technological innovation, global collaboration, and policy support.
Alterations in DNA Methylation, Proteomic, and Metabolomic Profiles in African Ancestry Populations with APOL1 Risk Alleles
Authors: Xinruo Zhang, Ashley W. Scadden, Amarnath Marthi, Victoria L. Buchanan, Yishu Qu, Kendra R. Ferrier, Brian D. Chen, Mariaelisa Graff, Julian Avila, Eric Boerwinkle, Steve Buyske, Clary B. Clish, Dan Cruz, Myriam Fornage, Robert E. Gerzsten, Christopher R. Gignoux, LaShaunta Glover, Lifang Hou, Anne E. Justice, Charles Kooperberg, Holly Kramer, Leslie Lange, Ruth J.F. Loos, Tara Matise, Josyf C. Mychaleckyj, Opeyemi A. Olabisi, Ulrike Peters, Laura M. Raffield, Alex P. Reiner, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Bing Yu, Yinan Zheng, Kari E. North, Amy K. Mottl, Heather M. Highland, Maggie A. Stanislawski
Journal: Journal of the American Society of Nephrology (2025)

Background: The APOL1 high-risk haplotype has been associated with chronic kidney disease (CKD) and the deterioration of kidney function, particularly in populations with West African ancestry. However, the mechanisms by which APOL1 risk variants increase the risk for kidney disease and its progression have not been fully elucidated. Methods: We compared methylation (N = 3,191; 715 [22%] carriers), proteomic (N = 1,240; 169 [14%] carriers), and metabolomic (N = 6,309; 674 [11%] carriers) profiles in African and Hispanic/Latino carriers of two APOL1 high-risk alleles (G1/G1, G2/G2, G1/G2) and non-carriers (G0/G0), excluding heterozygotes (G0/G1, G0/G2), from the PAGE Consortium and UK BioBank. In each study, the associations between the APOL1 high-risk haplotype and up to 722,719 CpG sites, 2,923 proteins, or 836 metabolites were estimated using covariate-adjusted linear regression models, followed by fixed-effects sample size weighted meta-analyses. Results: Significant associations were observed between APOL1 high-risk haplotype and methylation at 52 CpG sites, with 48 located on chromosome 22 and 18 in the vicinity of APOL1 – 4 and MYH9 . All significant CpG sites near APOL2 were hypomethylated, whereas those near APOL3 and APOL4 were hypermethylated. APOL1 -associated CpG sites were also identified in genes involved in ion transport and mitochondrial stress pathways. Sensitivity analyses indicated consistent yet attenuated effects among heterozygotes, supporting an additive effect of APOL1 risk alleles. Further analyses of the 52 CpG sites identified two near APOL4 exhibiting G1-specific effects, eight associated with CKD but none with eGFR, and three showing heterogeneity by CKD status. Additionally, carrying two APOL1 risk alleles was associated with higher plasma APOL1 protein (β = 1.12, P FDR = 2.26e-70) and lower C18:1 cholesteryl ester metabolite (Z = -4.50, P FDR = 4.83e-3). Conclusions: Our results demonstrate differential methylation, proteomic, and metabolomic profiles associated with APOL1 high-risk haplotypes.