tbuckley/cabot-search huggingface dataset:
Safety and efficacy of neoadjuvant durvalumab plus gemcitabine/cisplatin or carboplatin in patients with operable high-risk upper tract urothelial carcinoma: the iNDUCT trial.
Authors: Nadine Houédé, Thierry Chevallier, François Audenet, Constance Thibault, Yann Neuzillet, Christine Abraham, Alexandra Masson-Lecomte, Hélène Gauthier, Gwenaëlle Gravis, Géraldine Pignot, Sophie Tartas, Alain Ruffion, Damien Pouessel, Mathieu Roumiguié, Brigitte Laguerre, Karim Bensalah, Evanguelos Xylinas, Loïc Jaffrelot, Stéphane Droupy, Guillaume Luquiens, Morgan Rouprêt
Journal: Journal of Clinical Oncology (2025)

PURPOSE After radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), prognosis is poor for high-risk patients. This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients. PATIENTS AND METHODS This phase II trial (ClinicalTrials.gov identifier: NCT04617756 ) included patients with nonmetastatic, high-grade UTUC, on the basis of the ureteroscopic biopsy or urine cytology, and/or infiltrative aspect of the renal pelvis/ureteral wall by computed tomography imaging. Before RNU, patients received durvalumab plus gemcitabine/cisplatin (cohort 1) or durvalumab plus gemcitabine/carboplatin (cohort 2) once every 3 weeks for a total of four cycles (cohort choice on the basis of the glomerular filtration rate). The primary objective was the pathologic complete response (ypT0) rate in each cohort. RESULTS Fifty patients were enrolled between 2021 and 2024 (31 in cohort 1; 19 in cohort 2). Median age was 68 years (range, 38-79), and 59% were men. Forty-five patients received four cycles of treatment, three patients three cycles, and one patient two cycles. Five patients switched to carboplatin during treatment. At surgery (N = 45 patients), rates of pT0 were 13% (4/29) in cohort 1 and 5% (1/19) in cohort 2. Fifty percent (15/29) of patients were pTa/pT1 in cohort 1, and 42% (8/19) in cohort 2. No severe immunotherapy-mediated toxicity was observed. Four patients had chemotherapy-related grade 3 neutropenia, one grade 4; one patient had grade 3 thrombopenia, one grade 4; and four patients had grade 3 anemia. CONCLUSION Although our negative study did not meet its primary end point in either cohort, the combination of durvalumab and platin-based chemotherapy, especially cisplatin, showed promising results in terms of downstaging. The safety profile was good and the surgical risk was not increased.
Islet Transplantation Versus Standard of Care for Type 1 Diabetes Complicated by Severe Hypoglycemia From the Collaborative Islet Transplant Registry and the T1D Exchange Registry
Authors: Michael R. Rickels, Cassandra M. Ballou, Nicole C. Foster, Rodolfo Alejandro, David A. Baidal, Melena D. Bellin, Thomas L. Eggerman, Bernhard J. Hering, Fouad Kandeel, Adam Brand, Kellee M. Miller, Franca B. Barton, Elizabeth H. Payne
Journal: Diabetes Care (2025)

OBJECTIVE Islet transplantation was recently US Food and Drug Administration approved for adults with type 1 diabetes complicated by recurrent severe hypoglycemia events (SHEs). We sought to understand the long-term benefit for glycemic control and risk of immunosuppression to kidney function associated with islet transplantation compared with ongoing standard of care. RESEARCH DESIGN AND METHODS We performed a case-control analysis of prospectively collected data from patients in the Collaborative Islet Transplant Registry (CITR) with at least one SHE in the year (2000–2014) before transplantation (cases) and compared them with data from patients in the T1D Exchange (T1DX) Registry with at least one SHE in the year (2010–2012) before enrollment (controls), with both cohorts observed over 5 years. SHEs were restricted to those resulting in seizure or loss of consciousness. RESULTS Cases from CITR (n = 71) compared with controls from T1DX (n = 213) more often achieved the primary outcome of HbA1c &amp;lt;7.0% and absence of an SHE (71–80 vs. 21–33% over 5 years; P &amp;lt; 0.001) and the outcome of HbA1c ≤6.5% and absence of an SHE (60–75% vs. 10–20%; P &amp;lt; 0.001) while requiring significantly less insulin (majority in CITR were insulin independent). Kidney function, measured by estimated glomerular filtration rate, declined from baseline to a greater extent in CITR than in T1DX (−8.8 to −20 vs. −1.3 to −6.5 mL ⋅ min−1 ⋅ 1.73 m−2 over 5 years; P &amp;lt; 0.001). CONCLUSIONS Islet transplantation for adults with type 1 diabetes complicated by SHEs results in near-normal glycemic control in the absence of SHEs more often than observed with standard of care, but at the cost of greater reduction in kidney function.
Prevalence of Mismatch Repair Deficiency in Primary Prostate Cancer in a Large Prospective Cohort
Authors: Ciara S. McNevin, Anna Keogh, Mutaz Mohammed Nur, Brianán McGovern, Julie McFadden, Anne-Marie Baird, Karen Cadoo, Sarah Mc Carron, Cathal O’Brien, Martin P. Barr, Steven G. Gray, Orla Sheils, Lesley A. Sutton, Sinéad Flanagan, Lorelei A. Mucci, Konrad H. Stopsack, Stephen P. Finn
Journal: Clinical Cancer Research (2025)

Abstract Background: Mismatch repair (MMR) deficiency and microsatellite instability are predictive biomarkers for immunotherapy response. The best approach to identify patients with such tumors is unclear in prostate cancer. Methods: This study included 1,016 men diagnosed with primary prostate cancer during prospective follow-up of the Health Professionals Follow-up Study and Physicians’ Health Study. Highest-grade/index lesions from radical prostatectomy (95%) or transurethral resections of the prostate were mounted on tissue microarrays. Scoring of immunohistochemistry for the MMR proteins MLH1, MSH2, MSH6, and PMS2 required a non-tumor internal positive control for designating deficiency. Validation was done on full sections and with PCR-based quantification of microsatellite repeats. Results: Tumor stage was predominantly pathologically localized with a full distribution of Gleason scores. MMR tumor scoring could be performed with available internal positive control tissue in 75%–90% of cases, depending on the MMR protein. Of the 903 tumors evaluable for MSH2 protein loss, 4 tumors had loss of MSH2 (prevalence 0.4%, 95% confidence interval [CI] 0.2–1.1%), and 3 of 708 evaluable tumors had concomitant loss of MSH6 (prevalence 0.4%, 95% CI 0.1–1.2%). No tumor had loss of MLH1 or PMS2. The 4 MMR-deficient cases had higher Gleason scores, and 3 had non-zero microsatellite repeats. Conclusions: In this nationwide prospective study, MMR deficiency was rare in primary, surgically treated prostate cancer. The low prevalence and the need for an internal positive control for this assay are feasibility concerns for unselected routine immunohistochemistry-based screening for MMR deficiency on limited tissue specimens, such as prostate biopsies.
Optimizing Quality Care within a Bundled Framework
Authors: Matthew B. Rivara, Mallika Mendu
Journal: Journal of the American Society of Nephrology (2025)

1Division of Nephrology, Department of Medicine, University of Washington School of Medicine, and Northwest Kidney Centers, Seattle, WA 2Division of Nephrology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA aCorresponding author: Dr. Mallika Mendu, [email protected]
Letter to the Editor: Dynamics in liver stiffness to assess response in MASLD patients treated with resmetirom – one piece of the puzzle?
Authors: Georg Semmler, Maja Thiele, Thomas Reiberger, Mattias Mandorfer
Journal: Hepatology (2025)

1Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria 2Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria 3Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark 4Department of Clinical Research, University of Southern Denmark, Odense, Denmark Correspondence Mattias Mandorfer, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. Email: [email protected]
Better Dialysis Care in the United States Requires New Payment Policy
Authors: Suzanne Watnick, Elizabeth McNamara, Daniel E. Weiner
Journal: Journal of the American Society of Nephrology (2025)

1Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA 2Section of Nephrology, Seattle VA Medical Center, Seattle, WA, USA 3American Society of Nephrology, Washington, D.C., USA 4Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA aCorrespondence: Dr. Suzanne Watnick, University of Washington, 1959 NE Pacific Street, Box 356521, Health Sciences Building, BB-1271, Seattle, WA 98195, [email protected], (tel) 503-329-9820
Reply: AASLD Resmetirom Guidance
Authors: Vincent L. Chen, Timothy R. Morgan, Yaron Rotman, Heather M. Patton, Kenneth Cusi, Fasiha Kanwal, W Ray Kim
Journal: Hepatology (2025)

Chen, Vincent L.; Morgan, Timothy R.; Rotman, Yaron; Patton, Heather M.; Cusi, Kenneth; Kanwal, Fasiha; Kim, W Ray Author Information
Bundle Fix?
Authors: Graham Abra, Ankur D. Shah
Journal: Journal of the American Society of Nephrology (2025)

1Department of Medicine, Division of Nephrology, Stanford University School of Medicine, Palo Alto CA, USA 2Division of Kidney Diseases and Hypertension, Warren Alpert Medical School of Brown University, Providence RI, USA aCorresponding author: Dr. Graham Abra, [email protected], Nephrology Division, 3180 Porter Dr. Palo Alto, CA 94304
Autoimmunity in Long-COVID
Authors: Shubha Talwar, James A Harker, Peter J M Openshaw, Ryan S Thwaites
Journal: Journal of Allergy and Clinical Immunology (2025)

Long-COVID (also termed Post-Acute Sequelae of SARS-CoV-2 or PASC) affects up to 10% of people recovering from SARS-CoV-2 infection. Diagnosis is hampered by diffuse symptomatology, lack of biomarkers, an incomplete understanding of pathogenesis, and the lack of validated treatments. In terms of pathogenesis, hypothesised causes include viral persistence, the legacy of endotheliitis and thrombosis, low-grade tissue-based inflammation and/or scarring, perturbation of the host virome/microbiome, or triggering of autoimmunity. Several studies show pre-existing and/or de novo production of autoantibodies after infection with SARS-CoV-2, but the persistence of these antibodies and their role in causing long-COVID is debated. Here, we review the mechanisms through which autoimmune responses can arise during and after viral infection, focusing on the evidence for B-cell dysregulation and autoantibody production in acute and long-COVID.
Investigation of the applicability of adult definitions of disease severity for psoriasis in a pediatric cohort: a prospective registry study
Authors: M Al-Gawahiri, A S Paller, L Skov, P C M van de Kerkhof, E M G J de Jong, J M P A van den Reek, M M B Seyger
Journal: Journal of the American Academy of Dermatology (2025)
Universal opt-out syphilis screening in a UK emergency department
Authors: David Chadwick, Hannah Williams, Catriona Lane, Jane Knowles, Jim Woods, Sarah Bircham, Leanne Waters, Sandra Gittins, Buddhika Perera, Priyantha Batagalla, Kirsty Foster
Journal: Journal of Infection (2025)

The incidence of syphilis in several areas of England has risen substantially. National programmes for blood-borne viruses (BBV) screening in emergency departments (ED) have been ongoing for several years however have not included syphilis. We hypothesised that screening for syphilis in an ED in a region of high prevalence might identify significant numbers of cases. Universal opt-out syphilis screening was included with BBVs in a Northeast England ED, where a regional outbreak is ongoing. Those with reactive tests were invited to sexual health service (SHS) for further evaluation. Of 3,312 ED attenders having blood drawn, 38 (1.2%) were confirmed T. pallidum EIA positive (45% RPR-positive). Compared to ED attenders testing negative, those with positive tests were younger and lived in more deprived areas, however had similar gender and ethnicity. 71% of those identified as needing assessment were seen in the SHS and 59% treated. Universal screening for syphilis appears effective in identifying people with syphilis who traditionally don't access SHS. This population has different demographics to people with syphilis attending SHS in England, being predominantly heterosexual and equal proportions of women. Routine ED screening for syphilis along with BBVs may be warranted in areas of high transmission.
Nail plate crumbling is the most significant risk factor for severe psoriatic arthritis: A Chinese single-center retrospective study
Authors: Yijie Liu, Minjia Tan, Kun Hu, Jiashuai Li, Lu Jian, Yizhang Liu, Yongfang Duan, Ruizhen Liu, Haoqun Zhang, Junchen Chen, Mi Zhang, Yehong Kuang
Journal: Journal of the American Academy of Dermatology (2025)
Tezepelumab for the Treatment of Chronic Spontaneous Urticaria: Results of the Phase 2b INCEPTION Study
Authors: Julie McLaren, Yun Chon, Kevin S Gorski, Jonathan A Bernstein, Jonathan Corren, Koremasa Hayama, Vipul Jain, Hermenio Lima, Howard Sofen, Sandhia Ponnarambil, Nestor A Molfino, Marcus Maurer
Journal: Journal of Allergy and Clinical Immunology (2025)

Tezepelumab, a monoclonal antibody inhibiting thymic stromal lymphopoietin (TSLP), is an upstream-targeted therapy with potential to inhibit multiple pathways in chronic spontaneous urticaria (CSU). To evaluate tezepelumab efficacy and safety in CSU patients despite sgAH treatment. This phase 2b study randomized 183 patients (125 anti-IgE therapy-naïve; 58 anti-IgE therapy-experienced) to placebo Q2W, tezepelumab 210 mg Q4W, tezepelumab 420 mg Q2W, or omalizumab 300 mg Q4W (anti-IgE-naïve only) for 16-week treatment. The primary endpoint was change from baseline in UAS7 at week 16. Safety and exploratory endpoints were evaluated through week 32. The 16-week primary endpoint was not met: In the overall population, tezepelumab 210 mg and 420 mg did not significantly improve UAS7 versus placebo (LSM [SE]: -13.5 [1.6] and -14.7 [1.5], respectively, vs -13.6 [1.6], p = 0.99, nominal and p = 0.60, nominal, respectively). Greater improvement in UAS7 versus placebo was observed in the anti-IgE-naïve tezepelumab-treated populations (nominal significance); a trend toward significance was observed with omalizumab. In the anti-IgE-naïve population there was delayed, sustained, 32-week off-treatment improvement in UAS7 versus placebo with tezepelumab 210 mg (nominally significant) and 420 mg (trend), but not with omalizumab. This effect was larger in patients with lower baseline IgE levels and longer CSU duration and accompanied sustained IL-5 and IL-13 reductions. Tezepelumab and placebo safety findings were balanced. Although the 16-week primary endpoint was not met, tezepelumab showed post-treatment reductions in CSU activity through week 32, suggesting a delayed, sustained, TSLP blockade treatment effect.
Adulthood outcomes of thymic transplantation in a case of congenital athymia due to FOXN1 mutation
Authors: Margarida Paulo-Pedro, Beatriz Moleirinho, Diana F Santos, André M C Gomes, Margarida Rei, Afonso R M Almeida, José G Marques, Susana L Silva, Ana E Sousa
Journal: Journal of Allergy and Clinical Immunology (2025)
Improving medical machine learning models with generative balancing for equity and excellence
Authors: Brandon Theodorou, Benjamin Danek, Venkat Tummala, Shivam Pankaj Kumar, Bradley Malin, Jimeng Sun
Journal: npj Digital Medicine (2025)

Abstract Applying machine learning to clinical outcome prediction is challenging due to imbalanced datasets and sensitive tasks that contain rare yet critical outcomes and where equitable treatment across diverse patient groups is essential. Despite attempts, biases in predictions persist, driven by disparities in representation and exacerbated by the scarcity of positive labels, perpetuating health inequities. This paper introduces , a synthetic data generation approach leveraging large language models, to address these issues. enhances algorithmic performance and reduces bias by creating realistic, anonymous synthetic patient data that improves representation and augments dataset patterns while preserving privacy. Through experiments on multiple datasets, we demonstrate that boosts mortality prediction performance across diverse subgroups, achieving up to a 21% improvement in F1 Score without requiring additional data or altering downstream training pipelines. Furthermore, consistently reduces subgroup performance gaps, as shown by universal improvements in performance and fairness metrics across four experimental setups.
IFT80 and TRPA1 cooperatively regulate bone formation by calcium signaling in response to mechanical stimuli
Authors: Ting Wang, Yue Chen, Xinyi Zhu, Lihe Zheng, Yingyi Li, Xiaolei Ruan, Ziwei Yan, Zhaolan Guan, Wen Sun, Hua Wang
Journal: Metabolism (2025)

Intraflagellar transport 80 (IFT80) is vital for primary cilia which can sense and transduce mechanical signals. Mechanical stimuli expedite osteoblastic differentiation and bone formation in mesenchymal stem cells (MSCs). However, how IFT80 regulates mechanical transduction in MSCs remains unclear. To investigate the role of IFT80 in bone development and mechanical transduction, MSC-specific knock-out IFT80 (Prx1Cre; IFT80f/f) mice were generated. These mice exhibited significant skeletal abnormalities. The study further examined the effects of IFT80 deficiency on mechanical stimulation-induced osteoblastic differentiation and bone formation, as well as the underlying molecular mechanisms involving TRPA1 and calcium signaling pathways. In our study, Prx1Cre; IFT80f/f mice results in pronounced skeletal abnormalities including dwarfism, bone formation defect, malformations in the skull, limbs, and sternum, and abnormal joint structures. Furthermore, IFT80 deficiency in MSCs inhibits mechanical stimulation induced osteoblastic differentiation. Exercise training could not improve the bone formation in Prx1Cre; IFT80f/f mice. Mechanistically, IFT80 deficiency in MSCs downregulated the expression of transient receptor potential ankyrin 1 (TRPA1) and TRPA1-mediated Ca2+ influx, which further inhibited osteoblastic differentiation under mechanical stimulation by AKT and ERK signaling pathways. Finally, TRPA1 overexpression reversed impaired bone formation in Prx1Cre; IFT80f/f mice under exercise training. IFT80 and TRPA1 cooperatively regulate osteoblastic differentiation and bone formation in response to mechanical stimulation. These findings suggest that IFT80 and TRPA1 are critical for skeletal homeostasis and may serve as potential therapeutic targets for skeletal disorders.
Multifocal FDG Uptake of the Breasts Caused by Autologous Fat Injection for Breast Augmentation
Authors: Jiani He, Aisheng Dong
Journal: Clinical Nuclear Medicine (2025)

Abstract Autologous fat grafting for cosmetic breast augmentation is becoming increasingly popular. Late complications after intramammary fat injection include fat necrosis, liponecrotic cyst, calcification, and lymphadenopathy. We describe FDG PET/CT findings in a patient with multiple-injection-site fat necrosis after intramammary fat injection. FDG PET/CT showed multifocal activity in the subcutaneous and subglandular regions corresponding to the fat injection sites of the bilateral breasts and multiple FDG-avid lymph nodes of the axillae, mimicking malignancy. Careful correlation with clinical history and familiarity with the imaging findings of the complications after intramammary fat injection are helpful for avoiding misdiagnosis.
Getting to know ADA2 deficiency inside and out
Authors: Lisa Ehlers, Isabelle Meyts
Journal: Journal of Allergy and Clinical Immunology (2025)

Ten years after the description of the first cohorts of patients with ADA2 deficiency (DADA2), the pathomechanisms underlying the disease on a cellular level remain poorly understood. With the establishment of the lysosomal localization of the ADA2 protein and its involvement in nucleic acid sensing, the pathophysiological focus has shifted to the inside of the cell. At the same time, extracellular (serum) ADA2 enzyme activity continues to be the diagnostic gold standard in patients with suspected DADA2. The diverse clinical phenotype and weak genotype-phenotype correlations further complicate the identification of shared cellular mechanisms that cause inflammation, immunodeficiency as well as bone marrow failure in the absence of functional ADA2. This review inspects the characteristics of the ADA2 protein and its proposed function. The latter is discussed in the context of possible mechanisms driving the clinical phenotype in patients lacking functional ADA2. We discuss established processes and introduce unexplored pathways in the pathogenesis of DADA2.
Erratum: Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors
Authors: Leo Mascarenhas, Steven G. DuBois, Catherine M. Albert, Stefan Bielack, Daniel Orbach, Noah Federman, Birgit Geoerger, Ramamoorthy Nagasubramanian, Yizhou Zhang, Julia Chisholm, Soledad Gallego Melcon, Hiroaki Goto, Daniel A. Morgenstern, Cormac Owens, Alberto S. Pappo, Sébastien Perreault, Johannes H. Schulte, Neerav Shukla, Christian Michel Zwaan, Natascha Neu, Vadim Bernard-Gauthier, Esther De La Cuesta, Cornelis M. van Tilburg, Theodore W. Laetsch
Journal: Journal of Clinical Oncology (2025)
Focal Intense FDG Uptake of the Tongue Muscle Due to Repeated Tooth-Licking Mimicking Malignancy
Authors: Yajing Huo, Aisheng Dong, Yan Han
Journal: Clinical Nuclear Medicine (2025)

Abstract A 55-year-old woman underwent FDG PET/CT to detect possible multiple myeloma due to IgM κ paraproteinemia. FDG PET/CT showed a focal intense activity with SUV max of 21.3 in her anterior tongue, suspicious for malignancy. MRI and physical examination of the tongue were normal. On further inquiry, the patient reported she had a habit of licking her anterior mandibular teeth and licked her teeth repeatedly before and after injection of FDG. Consequently, the tongue activity was interpreted as physiological tongue muscle activity due to repeated tooth-licking.
Leveraging large language models for academic conference organization
Authors: Yuan Luo, Yikuan Li, Omolola Ogunyemi, Eileen Koski, Blanca E. Himes
Journal: npj Digital Medicine (2025)

We piloted using Large Language Models (LLMs) for organizing AMIA 2024 Informatics Summit. LLMs were prompt engineered to develop algorithms for reviewer assignments, group presentations into sessions, suggest session titles, and provide one-sentence summaries for presentations. These tools substantially reduced planning time while enhancing the coherence and efficiency of conference organization. Our experience shows the potential of generative AI and LLMs to complement human expertise in academic conference planning.