tbuckley/cabot-search huggingface dataset:
A caution against customized AI in healthcare
Authors: Kristin M. Kostick-Quenet
Journal: npj Digital Medicine (2025)

This article critiques the shift towards personalized AI in healthcare and other high-stakes domains, cautioning that without careful deliberation, customized AI systems can compromise the diversity and reach of human knowledge by restricting exposure to critical information that may conflict with users' preferences and biases. Customized AI should be applied with caution and intention where access to a wide and diverse range of perspectives is essential for impartial, informed decision making.
Combination Therapy with SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney Disease
Authors: Mengyao Tang, Mario Luca Morieri, Sahir Kalim, Alessandro Doria
Journal: Journal of the American Society of Nephrology (2025)

1Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 2Department of Medicine, Harvard Medical School, Boston, MA 3Department of Medicine, University of Padua, Italy 4Research Division, Joslin Diabetes Center, Boston, MA aAddress for correspondence: Dr. Alessandro Doria, Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, TEL (617) 309-2406, FAX (617) 309-2667, [email protected]
Comprehensive 4D-Flow Cardiac Magnetic Resonance Evaluation of the Descending Thoracic Aorta in Aortic Regurgitation
Authors: J Urmeneta Ulloa, A Álvarez Vázquez, V Martínez de Vega, L Martínez de Vega, C Andreu-Vázquez, I J Thuissard-Vasallo, M Recio Rodríguez, J A Cabrera
Journal:  (2025)

Abstract Aims To assess the reproducibility of 4D-Flow cardiac magnetic resonance (CMR) parameters in the descending thoracic aorta—DTAo—(regurgitant fraction [RF], end-diastolic reverse flow [EDRF], and holodiastolic flow reversal [HDR]), and the relationship with RF in the sinotubular junction (STJ), and the left ventricular end-diastolic volume index (LVEDVI) in patients with chronic aortic regurgitation (AR). Methods and results A descriptive study of these variables was conducted. A receiver operating characteristic curve was used to determine the optimal cut-off point. Thirty patients had severe AR (RF ≥ 30%, STJ) and 60 mild-to-moderate (RF &amp;lt; 30%). The mean age was 59 ± 17 years. Left ventricular ejection fraction (LVEF) was 56% (53–61%) and LVEDVI was 94 (76–128) mL/m2. Flow in the DTAo at the left inferior pulmonary vein (LIPV) was easily identifiable and measurements were highly reproducible. The intraclass correlation coefficient was 0.969 (95% CI: 0.954–0.980) for RF and 0.929 (95% CI: 0.893–0.952) for EDRF. Flow parameters measured at the LIPV were all significantly greater in the severe AR group: RF (21% vs. 6%, P &amp;lt; 0.001), EDRF (20 vs. 4 mL/s; P &amp;lt; 0.001), and HDR (20% vs. 8%; P &amp;lt; 0.001). Three parameters—presence of HDR, RF ≥ 17%, and EDRF ≥ 7 mL/s at the LIPV—were associated with RF ≥ 30% in the STJ and elevated LVEDVI. Conclusion 4D-flow CMR can reproducibly assess flow in the DTAo in patients with chronic AR. An RF ≥ 17%, EDRF ≥ 7 mL/s, and/or the presence of HDR in the DTAo (LIPV) were associated with an RF ≥ 30% in STJ and elevated LVEDVI.
Genotype–Phenotype Correlations with TRPC6-Associated Podocytopathy
Authors: Jing Miao, Ladan Zand
Journal: Journal of the American Society of Nephrology (2025)

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota Correspondence: Dr. Ladan Zand, email: [email protected] See related article, "Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy," on pages 274–289.
TGM2-mediated histone serotonylation promotes HCC progression via MYC signalling pathway
Authors: Renshun Dong, Tianci Wang, Wei Dong, Haoquan Zhang, Yani Li, Ran Tao, Qiumeng Liu, Huifang Liang, Xiaoping Chen, Bixiang Zhang, Xuewu Zhang
Journal: Journal of Hepatology (2025)
ASH2L-Mediated H3K4 Methylation and Nephrogenesis
Authors: Ziyi Zhao, Xuantong Dai, Gengru Jiang, Fujun Lin
Journal: Journal of the American Society of Nephrology (2025)

Background Many congenital anomalies of the kidney and urinary tract involve deficits in the number of nephrons, which are associated with a higher risk of hypertension and chronic kidney disease later in life. Prior work has implicated histone modifications in regulating kidney lineage-specific gene transcription and nephron endowment. Our earlier study suggested that ASH2L, a core subunit of the H3K4 methyltransferase complex, plays a role in ureteric bud morphogenesis during mammalian kidney development. However, the potential involvement of ASH2L in nephron formation remains an open question. Methods To investigate the role of ASH2L in nephron development, we inactivated Ash2l specifically in nephron progenitor cells by crossing Six2 -e(Kozak-GFPCre-Wpre-polyA)1 mice with Ash2l fl/fl mice. We utilized RNA sequencing combined with Cleavage Under Targets and Tagmentation sequencing to screen for gene and epigenomic changes, which were further verified by rescue experiments conducted on ex vivo culture explants. Results Inactivating ASH2L in nephron progenitor cells disrupted H3K4 trimethylation establishment at promoters of genes controlling nephron progenitor cell stemness, differentiation and cell cycle, inhibiting their progression through the cell cycle and differentiation into epithelial cell types needed to form nephrons. Inhibition of the TGF-β/SMAD signaling pathway partially rescued the dysplastic phenotype of the mutants. Conclusions ASH2L-mediated H3K4 methylation was identified as a novel epigenetic regulator of kidney development. Downregulation of ASH2L expression or H3K4 trimethylation may be linked to congenital anomalies of the kidney and urinary tract.
Innovations in Targeting the V2 Receptor
Authors: Francesco Trepiccione, Anna Iervolino
Journal: Journal of the American Society of Nephrology (2025)

Department of Medical Translational Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy; and Biology and Molecular Genetics Institute, Biogem, Ariano Irpino, Italy Correspondence: Dr. Francesco Trepiccione, email: [email protected] See related article, "A Snake Toxin Derivative for Treatment of Hyponatremia and Polycystic Kidney Diseases," on pages 181–192.
Advancing Understanding of Cardiovascular Risk in CKD
Authors: Vikas S. Sridhar, Ayodele Odutayo
Journal: Journal of the American Society of Nephrology (2025)

1Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada 2Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada 3Department of Medicine, University of Toronto, Toronto, Ontario, Canada 4Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada Correspondence: Dr. Ayodele Odutayo, email: [email protected] See related article, "Proteomic Assessment of the Risk of Secondary Cardiovascular Events among Individuals with CKD," on pages 231–241.
CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection
Authors: Jian Zheng, Hima Dhakal, Enya Qing, Rejeena Shrestha, Anne E. Geller, Samantha M. Morrissey, Divyasha Saxena, Xiaoling Hu, Hong Li, Haiyan Li, Kevin Wilhelmsen, Linder H. Wendt, Klaus Klumpp, Patrick S. Hume, William J. Janssen, Rachel Brody, Kenneth E. Palmer, Silvia M. Uriarte, Patrick P. Ten Eyck, David K. Meyerholz, Michael L. Merchant, Kenneth McLeish, Tom Gallagher, Jiapeng Huang, Jun Yan, Stanley Perlman
Journal: Journal of Clinical Investigation (2025)

Neutrophils, particularly low-density neutrophils (LDNs), are believed to contribute to acute COVID-19 severity. Here, we showed that neutrophilia can be detected acutely and even months after SARS-CoV-2 infection in patients and mice, while neutrophil depletion reduced disease severity in mice. A key factor in neutrophilia and severe disease in infected mice was traced to the chemokine CXCL12 secreted by bone marrow cells and unexpectedly, endothelial cells. CXCL12 levels were negatively correlated with LDN numbers in longitudinal analyses of patient blood samples. CXCL12 blockade in SARS-CoV-2-infected mice increased blood/lung neutrophil numbers thereby accelerating disease progression without changing lung virus titers. The exaggerated mortality caused by CXCL12 blockade can be reversed by neutrophil depletion. In addition, blocking interactions between SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) reduced CXCL12 levels, suggesting a signal transduction from virus-mediated ACE2 ligation to increased CXCL12 secretion. Collectively, these results demonstrate a previously unappreciated role of CXCL12 in diminishing neutrophilia, including low density neutrophilia, and its deleterious effects in SARS-CoV-2 infections. The results also support the involvement of SARS-CoV-2-endothelial cell interactions in viral pathogenesis.
Grover disease shows Type 2 immune activation and improves with dupilumab
Authors: Michael J Murphy, Muhammad H Junejo, Okeroghene Rufin, Jeffrey M Cohen, Caroline A Nelson, William Damsky
Journal: British Journal of Dermatology (2025)

Molecular profiling on biopsies from 31 patients with Grover disease (GD) shows increased expression of interleukin 13 (a T helper 2 cell cytokine) to be a hallmark of GD. In a supportive retrospective series of nine patients with treatment-refractory GD, all improved with dupilumab. This work helps establish GD as a type 2 immune disorder.
When a NeF Is Not Enough
Authors: Pietro Canetta
Journal: Journal of the American Society of Nephrology (2025)

Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York Correspondence: Dr. Pietro Canetta, email: [email protected] See related article, "Functional Characterization of Anti-C3bBb Autoantibodies and C3 Glomerulopathy Phenotype," on pages 264–273.
Spliced exon9 ADRM1 promotes liver oncogenicity via selective degradation of tumor suppressor FBXW7
Authors: Yanmei Sun, Mingjing Xu, Ho Lee Wan, Xiaofan Ding, Alissa M Wong, Dandan Pu, Kelvin K Ng, Nathalie Wong
Journal: Journal of Hepatology (2025)

The ubiquitin receptor ADRM1/Rpn13 governs the specificity of eukaryotic protein degradation. By SMRT sequencing, we first discovered a novel spliced variant of ADRM1 with a skipped exon 9, termed ADRM1-ΔEx9, in human hepatocellular carcinoma (HCC). This study aimed to elucidate this novel ubiquitin receptor's underlying biology and clinical implications in HCC. The role of ADRM1-ΔEx9 in early liver carcinogenesis was studied using human liver-derived non-tumoral organoids and a murine model with hydrodynamic in vivo transfection. ADRM1-ΔEx9 biology in HCC and its potential as a biomarker for predicting Olaparib response were investigated using patient-derived tumor organoids and xenograft models. The underlying mechanism was delineated using the Proteome Profiler Human Ubiquitin Array. ADRM1-ΔEx9, not its full-length counterpart, conferred human liver organoids with pro-survival advantages and a more profound tumor formation in a hydrodynamic transfected murine model. Functional knockdown resulted in spontaneous apoptosis in cell lines and patient-derived organoids, highlighting a pivotal role for ADRM1-ΔEx9 in HCC oncogenicity. Mechanistically, the shortened C-terminus of ADRM1-ΔEx9 signified a specific deubiquitinase partner BAP1 and navigated proteasome specificity. The new exon 8-10 fusion in ADRM1-ΔEx9 created a de novo binding to tumor suppressor protein FBXW7, resulting in its selective proteasome-mediated degradation. The loss of FBXW7 protein in ADRM1-ΔEx9 expressing tumors underscores their sensitivity to PARP inhibitor Olaparib. Notably, findings on ADRM1-ΔEx9 in primary HCC tumors denote its overexpression in a subgroup of patients with inferior survival and a window of therapeutic opportunity through its synthetic lethality association with Olaparib. ADRM1-ΔEx9 redirects ubiquitin proteasome specificity to degrade the tumor suppressor protein FBXW7 selectively. This promotes HCC tumor formation and provides a synthetic lethal link for PARPi therapy. Reduced tumor suppressor protein FBXW7 expression is pivotal in HCC pathogenesis and other liver diseases. However, the regulatory mechanism governing FBXW7 protein expression remains elusive. Herein, we unveil a non-canonical spliced isoform of the ubiquitin receptor ADRM1 that selectively degrades FBXW7 protein, thereby promoting the premalignant transformation of hepatic cells and conferring growth advantages to HCC tumors. Furthermore, our results demonstrate that ADRM1-ΔEx9-expressing HCC tumors exhibited sensitivity to Olaparib in a dose-dependent manner, implicating the potential use of Olaparib in targeting ADRM1-ΔEx9-driven HCC growth.
Organoid models of drug resistant gastric adenosquamous carcinoma: Recapitulating tumor features and refining precision treatment
Authors: Kuan Li, Wenchao Li, Shuying Fu, Chen Wang, Kexin Wang, Huan Yang, Yumei Xian, Tengfei Hao, Shiwei Zhang, Tianshun Gao, Jie Zhou, Jia Li, Changhua Zhang, Wei Chen, Leli Zeng, Yulong He
Journal: Drug Resistance Updates (2025)
Challenges associated with the development of “trial ready cohorts” for dementia prevention trials
Authors: Richard Milne, Edo Richard, Carol Brayne
Journal: BMJ (2025)

The UK government is looking to accelerate clinical trials in dementia research by building a new trial ready cohort. <b>Richard Milne and colleagues</b> argue that the potential of this cohort to deliver better, more equitable trials and treatments will be limited unless the complex ethical challenges are tackled
Matt Morgan: A living funeral with my friends
Authors: Matt Morgan
Journal: BMJ (2025)

It was a familiar scene in the lead-up to Christmas: husbands looking lost in highly perfumed, dazzlingly lit shops.An expensive lipstick or cashmere scarf, seldom actually wanted, was bought as a surrogate object to represent "I love you."Parents strained to understand the latest craze in overpriced plastic toys that promised more quality time with their children, away from digital distractions, but which often led to less.I too stood in those shops and bought those scarves and toys for my wife and children.But I'd already bought the perfect present for my friends-a gift that no one wants.For Christmas last year I bought my friends a funeral.
Predatory journals: what can we do to protect their prey?
Authors: Christine Laine, Dianne Babski, Vivienne C Bachelet, Till W Bärnighausen, Christopher Baethge, Kirsten Bibbins-Domingo, Frank Frizelle, Laragh Gollogy, Sabine Kleinert, Elizabeth Loder, João Monteiro, Eric J Rubin, Peush Sahni, Christina C Wee, Jin-Hong Yoo, Lilia Zakhama
Journal: BMJ (2025)
Physical Activity and Dexamethasone for Cancer-Related Fatigue: A Preliminary Placebo-Controlled, Randomized, Double-Blind Trial
Authors: Sriram Yennurajalingam, Vicente Valero, Brandon G. Smalgo, Michael J. Overman, Aravind Dasari, Robert A. Wolff, Kanwal Pratap Singh Raghav, Carlos H. Barcenas, Naifa L. Busaidy, Bryan Fellman, Karen Basen-Engquist, Kenneth R. Hess, Debasish Tripathy, Eduardo Bruera
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Physical activity (PA) and dexamethasone (Dex) when used independently have modest benefits for cancer-related fatigue (CRF) in patients with advanced cancer. In this study we aimed to determine the feasibility (adherence, safety, and satisfaction) of combining PA with Dex versus PA with placebo (PBO) for CRF, and to explore the effects of PA+Dex and PA+PBO on CRF. Patients and Methods: In this phase II, randomized, double-blind controlled trial, eligible patients had advanced cancer and a CRF score of ≥4 on the Edmonton Symptom Assessment Scale (ESAS) for fatigue (0–10 scale). Patients were randomized to standardized PA for 4 weeks with either 4 mg of Dex (PA+Dex arm) or PBO (PA+PBO arm) twice daily for the first 7 days. Changes in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scores from baseline to days 8 and 29 were assessed. Other outcomes included change in quality-of-life scores. Results: A total of 64 (89%) patients were evaluable. Adherence rates for study medication, resistance exercise, and aerobic exercise were 91% and 92% ( P =.15), 83% and 70.6% ( P =.35), and 82.9% and 78.3% ( P =.73), respectively, in the PA+Dex and PA+PBO arms. The satisfaction rates for the PA+Dex and PA+PBO arms were 98% and 79%, respectively. Median (IQR) changes in FACIT-F scores at days 8 and 29 from baseline were 9 (2 to 16; P &lt;.001) and 5.75 (0 to 12.5; P =.015) for the PA+Dex arm, respectively, and 3.5 (−2.1 to 10; P =.054) and 6.5 (2.5 to 15.5; P =.006) for the PA+PBO arm, respectively. We found a significant treatment effect in the PA+Dex arm using exploratory linear mixed model analysis, with treatment showing an improvement of 5.63 units for FACIT-F scores (95% CI, 1.74–9.52; P =.005). We found significant improvement in Functional Assessment of Cancer Therapy-General (FACT-G), Patient-Reported Outcomes Measurement Information System-Fatigue Short Form 7a (PROMIS-Fatigue SF-7a), and Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) totals on days 8 and 29 in the PA+Dex arm. There was no significant difference in grade ≥3 adverse events between the arms ( P =.36). Conclusions: Our study found that the use of combination PA+Dex and PA+PBO for CRF was feasible and associated with high rates of satisfaction, adherence to medication and PA intervention, and tolerability. CRF improvement with PA+Dex was clinically significant at days 8 and 29. Further larger studies are justified. ClinicalTrials.gov identifier: NCT03583255
National Telehealth Contingency Staffing Program and Primary Care Quality in the VHA
Authors: Terrence Liu, Chelle L. Wheat, Jorge Rojas, Amy M. J. O’Shea, Karin M. Nelson, Ashok Reddy
Journal: JAMA Network Open (2025)

Importance The Veterans Health Administration (VHA) launched the Clinical Resource Hub (CRH), a national telehealth contingency staffing program, to address primary care staffing shortages and improve veteran access to primary care. How this large-scale telehealth intervention affects quality of care is unknown. Objective To assess the quality of care for chronic disease management among US veterans receiving high vs low levels of CRH-delivered primary care services and whether racial and ethnic minority veterans experience outcomes similar to those of White veterans when receiving CRH-delivered care. Design, Setting, and Participants This retrospective quality improvement study was conducted using VHA administrative data. Veterans receiving primary care services from CRH clinicians between October 1, 2022, to September 30, 2023, were included. Exposures Low, medium, and high tertiles of CRH intensity, defined as the proportion of a veteran’s CRH primary care visits to their total primary care visits within the study period. Main Outcomes and Measures The main outcomes were chronic disease quality measures for 2 common conditions in ambulatory care: diabetes and hypertension. Logistic regression models were used to estimate the association between individual-level receipt of care from a CRH clinician and the study outcomes. Results This study included 71 508 veterans (mean [SD] age, 66 [15] years; 91.4% were male). Veterans who received a higher proportion of care from CRH clinicians were more likely to have improved blood pressure control compared with those who received a lower proportion of care. Higher vs lower CRH intensity was associated with improved blood pressure control among veterans with diabetes (79.5% [95% CI, 78.5%-80.4%] vs 76.6% [95% CI, 75.7%-77.5%]) and veterans with hypertension (76.8% [95% CI, 76.0%-77.5%] vs 73.9% [95% CI, 73.2%-74.7%]). Among racial and ethnic minority veterans, no association between CRH intensity and clinical quality was observed. Conclusions and Relevance In this large retrospective cohort study among veterans receiving primary care services through a national telehealth contingency staffing program, veterans with a higher proportion of care from CRH clinicians had improvement in blood pressure outcomes. These findings suggest that the CRH program may be helpful in addressing veteran primary care needs without introducing or worsening disparities in ambulatory quality measures among racial and ethnic minority veterans. As health systems face staffing shortages in primary care, these findings can inform strategies for equitable implementation of large-scale telehealth initiatives to fill these gaps and maintain timely access to primary care.
Surgeon Recommendation and Outcomes of Decompression With vs Without Fusion in Patients With Degenerative Spondylolisthesis
Authors: Andreas Seip, Christian Hellum, Morten Wang Fagerland, Tore Solberg, Jens Ivar Brox, Kjersti Storheim, Erland Hermansen, Clemens Weber, Helena Brisby, Hasan Banitalebi, Håvard Furunes, Kari Indrekvam, Inger Ljøstad, Ivar Magne Austevoll
Journal: JAMA Network Open (2025)

Importance The ability of surgeons to choose the right patient for fusion in addition to decompression when operating for degenerative spondylolisthesis with symptomatic spinal stenosis is debated. The addition of fusion increases risk, morbidity, and costs but has been claimed to give better results for selected patients. Objective To investigate whether following surgeons’ opinions regarding fusion was associated with clinical outcomes. Design, Setting, and Participants This cohort study was conducted alongside the Norwegian Degenerative Spondylolisthesis and Spinal Stenosis randomized clinical trial, which showed noninferiority for decompression alone compared with decompression with fusion. From February 12, 2014, to December 18, 2017, trial surgeons from 16 Norwegian departments denoted their preferred treatment for 222 of 267 patients with symptomatic spinal stenosis and degenerative spondylolisthesis. For this analysis, the clinical outcomes of the patients who were and were not randomized to the recommended treatment were compared. Main Outcome and Measures The primary outcome was a reduction of at least 30% from baseline to 2 years after surgery on the Oswestry Disability Index, ranging from 0 (no impairment) to 100 (maximum impairment). Secondary outcomes included the Zürich Claudication Questionnaire, leg and back pain scores, and the EuroQol 5-Dimension score. Results Among 222 patients (155 [70%] female; mean [SD] age, 66.2 [7.7] years), decompression alone was recommended for 112 patients, of whom 59 received only decompression, and additional fusion for 110 patients, of whom 57 received fusion. At 2-year follow-up, 87 of 116 patients (75%) who received surgery in agreement with the surgeons’ recommendations and 77 of 106 (73%) who received surgery in disagreement with the surgeons’ recommendations reached the primary outcome (difference, 2.4 percentage points; 95% CI, −9.1 to 13.9 percentage points). All secondary outcomes were in the same direction as the primary outcome. Conclusions and Relevance In this cohort study of 222 patients with degenerative spondylolisthesis who participated in a randomized clinical trial, surgeons’ recommendations were not associated with better outcomes than a random allocation when deciding between decompression alone and decompression with instrumented fusion. The results suggest that surgeons performing degenerative spondylolisthesis surgery could rely safely on evidence of operating with decompression alone, despite the conflict of expert opinion.