tbuckley/cabot-search huggingface dataset:
Proenkephalin produced by neonatal T-bet+ Treg cells promotes periportal hepatocyte maturation
Authors: Yujia Wang, Lijun Yang, Mingyang Li, Jie Hao, Xiuyuan Sun, Zhongjun Dong, Lin Lin, Baidong Hou, Yu Zhang, Yong Zhao, Cheng-Ran Xu, Xuyu Zhou, Rong Jin, Qing Ge
Journal: Hepatology (2025)

The mechanisms that govern postnatal hepatocyte differentiation and maturation in the periportal region, where Notch signaling is high, remain incompletely understood. Here we demonstrate that 2-week-old mice deficient in lymphocytes, CD4 + T cells or T-bet + regulatory T (Treg) cells exhibit comparable increases in ductal plate cell/cholangiocyte differentiation and impaired periportal hepatocyte maturation. We found that the transient enrichment of periportal region-localized T-bet + Treg cells and their expression of proenkephalin (PENK) are crucial for coordinating hepatocyte and cholangiocyte differentiation in this region. T-bet deletion in Treg cells impacts their acquirement of a tissue residence signature and their PENK expression. Depletion of Penk in Tregs or the administration of naltrexone, an antagonist of the opioid growth factor receptor (OGFr), results in similar liver defects. The supplementation of PENK-derived methionine enkephalin (Met-ENK) reduces ductal plate cholangiocytes and enhances hepatocyte maturation in mice lacking T-bet + Tregs and in 3-dimensional hepatocyte culture. Molecularly, the Met-ENK/OGFr axis counteracts periportal Notch signaling by downregulating Adam10 expression and promotes adult splicing program by upregulating Esrp2 expression. Our findings uncover a previously unrecognized mechanism through which periportal T-bet + Treg cells foster liver maturation independently of their immune regulatory functions. It also underscores the critical role of Treg-associated immune zonation in facilitating periportal hepatocyte maturation in neonatal mice.
Mouse models of Anti-Aβ immunotherapies
Authors: Philip Pikus, R Scott Turner, G William Rebeck
Journal: Molecular Neurodegeneration (2025)

Abstract Background The development of anti-amyloid-beta (Aβ) immunotherapies as the first disease modifying therapy for Alzheimer’s Disease (AD) is a breakthrough of basic research and translational science. Main text Genetically modified mouse models developed to study AD neuropathology and physiology were used for the discovery of Aβ immunotherapies and helped ultimately propel therapies to FDA approval. Nonetheless, the combination of modest efficacy and significant rates of an adverse side effect (amyloid related imaging abnormalities, ARIA), has prompted reverse translational research in these same mouse models to better understand the mechanism of the therapies. Conclusion This review considers the use of these mouse models in understanding the mechanisms of Aβ clearance, cerebral amyloid angiopathy (CAA), blood brain barrier breakdown, neuroinflammation, and neuronal dysfunction in response to Aβ immunotherapy.
False-positive Uptake in Splenic Hamartoma on 68Ga-DOTATATE PET/CT
Authors: Chenxi Wu, Julia W. Foster, Shahein Tajmir, Hardik Shah, Mihir M. Shah, Saima Muzahir
Journal: Clinical Nuclear Medicine (2025)

68 Ga-DOTATATE is not completely specific for neuroendocrine tumors, and a wide range of benign and malignant tumors may reveal high uptake of 68 Ga-DOTATATE on PET scan. Spleen hamartoma is a rare benign solid lesion of the spleen, composed of a mixture of normal splenic structures. Here we present a case of a 49-year-old woman who underwent a 68Ga-DOTATATE PET/CT scan for complete staging of a duodenal neuroendocrine tumor, and it incidentally demonstrated intense radiotracer uptake in a splenic lesion, with surgical pathology demonstrating a splenic hamartoma.
Multimodal generative AI for interpreting 3D medical images and videos
Authors: Jung-Oh Lee, Hong-Yu Zhou, Tyler M Berzin, Daniel K Sodickson, Pranav Rajpurkar
Journal: npj Digital Medicine (2025)

Abstract This perspective proposes adapting video-text generative AI to 3D medical imaging (CT/MRI) and medical videos (endoscopy/laparoscopy) by treating 3D images as videos. The approach leverages modern video models to analyze multiple sequences simultaneously and provide real-time AI assistance during procedures. The paper examines medical imaging’s unique characteristics (synergistic information, metadata, and world model), outlines applications in automated reporting, case retrieval, and education, and addresses challenges of limited datasets, benchmarks, and specialized training.
Head-to-head comparison of MASH resolution index versus FAST for non-invasive prediction of resolution of MASH on biopsy
Authors: Rohit Loomba, Peter Chen-Yang Nikhil Daniel, Maral Amangurbanova, Ricki Bettencourt, Egbert Madamba, Harris Siddiqi, Lisa Richards, Mildred D. Gottwald, Shibao Feng, Maya Margalit, Daniel Q. Huang
Journal: Hepatology (2025)

Background: The MASH Resolution Index and FibroScan-aspartate aminotransferase (FAST) score have been reported to non-invasively predict the resolution of metabolic dysfunction-associated steatohepatitis (MASH) on histology. This study aimed to examine head-to-head the diagnostic accuracy of the MASH Resolution Index (MASHResInd) versus FAST score in detecting MASH resolution. Methods: This prospective study included 160 participants (64% female) with biopsy-proven MASH and stage 2 or stage 3 fibrosis from a randomized, multicenter trial of pegozafermin. Participants received either pegozafermin or placebo and underwent contemporaneous liver biopsies, magnetic resonance imaging-proton density fat fraction, and vibration-controlled transient elastography at 2-time points spaced 24 weeks apart. The primary objective was the detection of MASH resolution with no worsening of fibrosis. Diagnostic models were assessed by the area under the receiver operating curves (AUC) and compared with the Delong test. Results: The median (IQR) age and body mass index of participants were 56.0 (49.0–62.0) years and 36.5 (32.2–40.4) kg/m 2 , respectively. The MASHResInd outperformed FAST for identifying MASH resolution without worsening fibrosis (AUC 0.83, 95% CI 0.75–0.91 vs. 0.65, 95% CI 0.55–0.75, p =0.001). The positive predictive values for MASH resolution were 29% and 26% for the MASHResInd and FAST using rule-in criteria, respectively. The negative predictive values were 100% and 94% for the MASHResInd and FAST using rule-out criteria, respectively. Conclusion: The MASH Resolution Index is better than the FAST score in the non-invasive prediction of MASH resolution. These data may have implications for clinical practice and trials.
Safety and Efficacy of Vadadustat for the Treatment of CKD-Related Anemia within and outside the United States
Authors: Glenn M. Chertow, Kai-Uwe Eckardt, Mark J. Sarnak, Wolfgang C. Winkelmayer, Rajiv Agarwal, Todd Minga, Wenli Luo, Steven K. Burke
Journal: Journal of the American Society of Nephrology (2025)

Background: Vadadustat’s global clinical program was comprised of four noninferiority trials comparing vadadustat and darbepoetin alfa for CKD-related anemia: two in dialysis-dependent (DD)-CKD and two in non–dialysis-dependent (NDD)-CKD. While vadadustat met prespecified noninferiority criteria for hematological efficacy globally, it did not meet noninferiority criteria for cardiovascular safety in the NDD-CKD trials. The trials considered regional differences in treatment practices, including hemoglobin targets within (10-11 g/dL) and outside the US (10-12 g/dL). Methods: To examine region-specific outcomes, we performed prespecified analyses for US and non-US patient subgroups from the vadadustat global program. The primary safety end point was first occurrence of MACE (death from any cause, or nonfatal myocardial infarction or stroke). The primary efficacy end point was change in hemoglobin from baseline to average values during weeks 24-36. Results: 4084/7399 (55%) randomized patients were enrolled in the US. In pooled analyses of all US patients, MACE risk was similar among vadadustat-treated and darbepoetin alfa–treated patients (hazard ratio [HR] 1.03; 95% CI 0.90–1.17). HRs were similar for US patients with DD-CKD (HR 1.00; 95% CI 0.84–1.18) and NDD-CKD (HR 1.06; 95% CI 0.87–1.29). In pooled analyses of non-US patients, MACE risk was numerically higher among vadadustat-treated patients (HR 1.12; 95% CI 0.94–1.33); the higher risk was primarily attributed to the NDD-CKD subgroup (HR 1.29; 95% CI 1.03–1.60). In the non-US DD-CKD subgroup, MACE risk was similar among vadadustat-treated and darbepoetin alfa-treated patients (HR 0.88; 95% CI 0.67–1.17). Changes in hemoglobin were similar among treatment groups in all regions, as were rates of treatment-emergent and serious adverse events. Conclusions: In patients with DD-CKD, safety (vis-à-vis MACE) and efficacy (vis-à-vis change in hemoglobin) of vadadustat and darbepoetin alfa were similar when stratified by region (US versus non-US). In US patients with NDD-CKD, safety and efficacy of vadadustat and darbepoetin alfa were similar.
Dampening of Microglial Activation With Nasal Foralumab Administration in Moderate Alzheimer’s Disease Dementia
Authors: Tarun Singhal, Steven Cicero, Seth A. Gale, Nicolas Horan, Shipra Dubey, Gad A. Marshall, Howard L. Weiner
Journal: Clinical Nuclear Medicine (2025)

A 78-year-old man with moderate Alzheimer disease (AD) dementia was treated with nasal-foralumab, a fully human anti-CD3 monoclonal antibody, as part of a Food and Drug Administration expanded-access-program, based on previously demonstrated efficacy of anti-CD3 antibody in animal models. 18 F-PBR06-PET, utilizing a second-generation 18-kDa-translocator-protein ligand targeting microglia, showed diffuse reduction of radiotracer uptake throughout the brain, following 3 months of nasal-foralumab compared with baseline. In particular, precuneus, posterior cingulate and anterior cingulate gyri, regions that had high levels of amyloid deposition on a baseline 18 F-Florbetapir-PET scan, showed reduction in microglial activation after nasal-foralumab treatment for 3 months.
Artificial Intelligence in Sincalide-Stimulated Cholescintigraphy: A Pilot Study
Authors: Nghi C. Nguyen, Jun Luo, Dooman Arefan, Anil K. Vasireddi, Shandong Wu
Journal: Clinical Nuclear Medicine (2025)

Purpose: Sincalide-stimulated cholescintigraphy (SSC) calculates the gallbladder ejection fraction (GBEF) to diagnose functional gallbladder disorder. Currently, artificial intelligence (AI)-driven workflows that integrate real-time image processing and organ function calculation remain unexplored in nuclear medicine practice. This pilot study explored an AI-based application for gallbladder radioactivity tracking. Methods: We retrospectively analyzed 20 SSC exams, categorized into 10 easy and 10 challenging cases. Two human operators (H1 and H2) independently annotated the gallbladder regions of interest manually over the course of the 60-minute SSC. A U-Net–based deep learning model was developed to automatically segment gallbladder masks, and a 10-fold cross-validation was performed for both easy and challenging cases. The AI-generated masks were compared with human-annotated ones, with Dice similarity coefficients (DICE) used to assess agreement. Results: AI achieved an average DICE of 0.746 against H1 and 0.676 against H2, performing better in easy cases (0.781) than in challenging ones (0.641). Visual inspection showed AI was prone to errors with patient motion or low-count activity. Conclusions: This study highlights AI’s potential in real-time gallbladder tracking and GBEF calculation during SSC. AI-enabled real-time evaluation of nuclear imaging data holds promise for advancing clinical workflows by providing instantaneous organ function assessments and feedback to technologists. This AI-enabled workflow could enhance diagnostic efficiency, reduce scan duration, and improve patient comfort by alleviating symptoms associated with SSC, such as abdominal discomfort due to sincalide administration.
Hepatic Eosinophilic Granuloma Mimicking Liver Metastases of Unknown Primary Focus on 18F-FDG and 68Ga-FAPI PET/CT
Authors: Meng Dai, Kai Yang, Xiujuan Zhao, Jingmian Zhang, Xinming Zhao
Journal: Clinical Nuclear Medicine (2025)

A 53-year-old man presented with right upper abdominal pain for more than 3 weeks without an apparent cause. Multiple sequences of MR imaging detected multiple liver nodules with irregular peripheral enhancement. 18 F-FDG and 68 Ga-FAPI PET showed multiple elevated tracer uptake, which mimicked multiple liver metastases of unknown primary focus. Finally, the pathology of ultrasound-guided biopsy confirmed the diagnosis of hepatic eosinophilic granuloma (HEG).
A Case of 99mTc-Pyrophosphate Myocardial Scintigraphy Positivity in Fabry Disease
Authors: Yang-Yun Chen, Yong-Rong Zhou, Zhen-Peng Jiang, Shu-Xia Wang, Dan Shao
Journal: Clinical Nuclear Medicine (2025)

A 62-year-old man with echocardiographic findings suggestive of cardiac amyloidosis and positive 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy was ultimately diagnosed with Fabry disease confirmed by genetic testing. This case highlights myocardial 99m Tc-PYP uptake in Fabry cardiomyopathy, expanding the differential diagnosis of non-amyloid cardiomyopathies associated with myocardial radiotracer retention.
Low FDG Uptake of a Mass Initially Suspected of Being a Nasopharyngeal Carcinoma
Authors: Léo Morin, Héléna Pencroffi, Lucas Jallet, Clément Drouet
Journal: Clinical Nuclear Medicine (2025)

This case illustrates an atypical clinical presentation of a nasopharyngeal invasive process in a 56-year-old woman, which corresponded to a chordoma, a rare malignant primary bone tumor with unfavorable prognosis, derived from remnants of the notochord.
Primary Extranodal Natural Killer/T-cell Lymphoma of the Bladder on 18F-FDG PET/CT
Authors: Lulu Zhang, Jiahao Tian, He Huang
Journal: Clinical Nuclear Medicine (2025)

Extranodal NK/T cell lymphoma (ENKTCL) is an aggressive lymphoma associated with Epstein-Barr virus (EBV) infection, with bladder involvement being extremely rare and only a few cases reported. We present a case of a 75-year-old man with hematuria, where 18 F-FDG PET/CT revealed focal bladder hypermetabolism (SUVmax: 9.7) and mural thickening. Then, histopathology confirmed ENKTCL. After chemotherapy, 18 F-FDG PET/CT showed complete metabolic resolution, demonstrating the diagnostic and therapeutic monitoring value of it.
Activation of intestinal endogenous retroviruses by alcohol exacerbates liver disease
Authors: Noemí Cabré, Marcos F Fondevila, Wenchao Wei, Tomoo Yamazaki, Fernanda Raya Tonetti, Alvaro Eguileor, Ricard Garcia-Carbonell, Abraham S Meijnikman, Yukiko Miyamoto, Susan Mayo, Yanhan Wang, Xinlian Zhang, Thorsten Trimbuch, Seija Lehnardt, Lars Eckmann, Derrick E Fouts, Cristina Llorente, Hidekazu Tsukamoto, Peter Stärkel, Bernd Schnabl
Journal: Journal of Clinical Investigation (2025)

Alcohol-associated liver disease represents a significant global health challenge, with gut microbial dysbiosis and bacterial translocation playing a critical role in its pathogenesis. Patients with alcohol-associated hepatitis had increased fecal abundance of mammalian viruses including retroviruses. This study investigated the role of endogenous retroviruses (ERVs) in the development of alcohol-associated liver disease. Transcriptomic analysis of duodenal and liver biopsies revealed increased expression of several human ERVs, including HERV-K and HERV-H, in patients with alcohol-associated liver disease compared with controls. Chronic-binge ethanol feeding markedly induced ERV abundance in intestinal epithelial cells, but not the liver of mice. Ethanol increased ERV expression and activated the Z-DNA binding protein 1 (Zbp1)-mixed lineage kinase domain-like pseudokinase (Mlkl) signaling pathways to induce necroptosis in intestinal epithelial cells. Antiretroviral treatment reduced ethanol-induced intestinal ERV expression, stabilized the gut barrier, and decreased liver disease in microbiota-humanized mice. Furthermore, mice with an intestine-specific deletion of Zbp1 were protected against bacterial translocation and ethanol-induced steatohepatitis. These findings indicate that ethanol exploits this pathway by inducing ERVs and promoting innate immune responses, which results in the death of intestinal epithelial cells, gut barrier dysfunction and liver disease. Targeting the ERV-Zbp1 pathway may offer new therapies for patients with alcohol-associated liver disease.
Efficacy, safety, and B-cell depletion capacity of three rituximab dosing regimens in the treatment of moderate-to-severe pemphigus vulgaris and pemphigus foliaceus: a 52-week clinical trial
Authors: Shan Cao, Baoqi Yang, Zhenzhen Wang, Tingting Liu, Yonghu Sun, Zhaoxia Zhang, Futang Pan, Qing Yang, Hanqing Geng, Qing Zhao, Hong Liu, Furen Zhang
Journal: Journal of the American Academy of Dermatology (2025)

Rituximab (RTX) is effective for pemphigus, but optimal dosing remains uncertain. Compare efficacy, safety, and B-cell depletion of three RTX regimens over 52 weeks. In an open-label trial (May 2023-October 2024), 52 pemphigus vulgaris and pemphigus foliaceus patients received ultralow-(ULRTX; 100mg), low-(LRTX; 500mg), and standard-dose RTX (SDRTX; 1000 mg) at weeks 0 and 2, with supplemental doses guided by CD20+B-cell reconstitution. All received concomitant glucocorticoids. time to disease control, complete remission (CR), CR off therapy (CROT), CR on minimal therapy (CRMT). pemphigus disease area index (PDAI) changes, glucocorticoid use, relapse rates, and autoantibody seroconversion. All achieved disease control (median days: ULRTX=15.5, LRTX=14.0, SDRTX=13.0; P=0.02). CD20+B-cell depletion occurred universally by week 2, with faster reconstitution in ULRTX by 26 weeks. CR rates: 92.3% (ULRTX) vs 100% (LRTX/SDRTX); CROT/CRMT showed no intergroup differences. Median PDAI reduction, cumulative glucocorticoid doses, relapse rates and autoantibody seroconversion were comparable. No significant difference was found in adverse events (AEs). ULRTX demonstrated cost advantages. Single-center, non-randomized design, small sample. All regimens demonstrated comparable efficacy and B-cell depletion. ULRTX, despite a marginally longer time to disease, had the lowest AEs and cost, supporting its utility in pemphigus management.
The gut microbiome controls reactive astrocytosis during Aβ amyloidosis via propionate-mediated regulation of IL-17
Authors: Sidhanth Chandra, Jelena Popovic, Naveen K Singhal, Elyse A Watkins, Hemraj B Dodiya, Ian Q Weigle, Miranda A Salvo, Abhirami Ramakrishnan, Zhangying Chen, James T Watson, Aashutosh Shetti, Natalie Piehl, Xiaoqiong Zhang, Leah K Cuddy, Katherine R Sadleir, Steven J Schwulst, Murali Prakriya, David Gate, Sangram S Sisodia, Robert Vassar
Journal: Journal of Clinical Investigation (2025)

Accumulating evidence implicates the gut microbiome (GMB) in the pathogenesis and progression of Alzheimer's disease (AD). We recently showed that the GMB regulates reactive astrocytosis and Aβ plaque accumulation in male APPPS1-21 AD model mice. Yet, the mechanism(s) by which GMB perturbation alters reactive astrocytosis in a manner that reduces Aβ deposition remain unknown. Here, we performed metabolomics on plasma from mice treated with antibiotics (abx) and identified a significant increase in plasma propionate, a gut-derived short chain fatty acid, only in male mice. Administration of sodium propionate reduced reactive astrocytosis and Aβ plaques in APPPS1-21 mice, phenocopying the abx-induced phenotype. Astrocyte-specific RNA sequencing on abx and propionate treated mice showed reduced expression of pro-inflammatory and increased expression of neurotrophic genes. Next, we performed flow cytometry experiments where we found abx and propionate decreased peripheral RAR-related orphan receptor-γ (Rorγt)+ CD4+ (Th17) cells and IL-17 secretion, which positively correlated with reactive astrocytosis. Lastly, using an IL-17 monoclonal antibody to deplete IL-17, we found that propionate reduces reactive astrocytosis and Aβ plaques in an IL-17-dependent manner. Together, these results suggest that gut-derived propionate regulates reactive astrocytosis and Aβ amyloidosis by decreasing peripheral Th17 cells and IL-17 release. Thus, propionate treatment or strategies boosting propionate production may represent novel therapeutic strategies for AD.
LAG3 regulates antibody responses in a murine model of kidney transplantation
Authors: Michael Nicosia, Ran Fan, Juyeun Lee, Gabriella L All, Victoria Gorbacheva, José Ignacio Valenzuela, Yosuke Yamamoto, Ashley Beavers, Nina Dvorina, William M Baldwin Iii, Eduardo Chuluyan, Motoo Araki, Brian T Gaudette, Robert L Fairchild, Booki Min, Anna Valujskikh
Journal: Journal of Clinical Investigation (2025)

Lymphocyte activation gene-3 (LAG3) is a coinhibitory receptor expressed by various immune cells. While immunomodulatory potential of LAG3 is being explored in cancer and autoimmunity, there is no information on its role following organ transplantation. Our study investigated the functions of LAG3 in a mouse model of renal allograft rejection. LAG3-/- recipients rapidly reject MHC-mismatched renal allografts that are spontaneously accepted by WT recipients, with graft histology characteristic of antibody mediated rejection (ABMR). Depletion of recipient B cells but not CD8+ T cells significantly extended kidney allograft survival in LAG3-/- recipients. Treatment of WT recipients with an antagonistic LAG3 antibody enhanced anti-donor immune responses and induced kidney damage associated with chronic rejection. The studies of conditional LAG3-/- recipients and mixed bone marrow chimeras demonstrated that LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity but not to induce acute allograft rejection. The numbers and proinflammatory functions of graft-infiltrating NK cells were markedly increased in LAG3-/- recipients suggesting that LAG3 also regulates the effector stage of ABMR. These results are the first to identify LAG3 as a regulator of immune responses to kidney allografts and a potential therapeutic target for ABMR prevention and treatment.
Electronic Patient Message Burdens: An Analysis of Factors Associated with Electronic Patient Message Quantity and Turnaround Time in Dermatology
Authors: Matthew D Viveiros, Jordyn Puccio, Layna Mager, Zaynah Awethe, Sydney Gilkey, Pragi Patel, Catherine A Ulman, Brittany Dulmage, Jessica Kaffenberger, Kelly Tyler, Benjamin Kaffenberger
Journal: Journal of the American Academy of Dermatology (2025)