tbuckley/cabot-search huggingface dataset:
PCDH15 Dual-AAV Gene Therapy for Deafness and Blindness in Usher Syndrome Type 1F Models
Authors: Maryna V. Ivanchenko, Daniel M. Hathaway, Eric M. Mulhall, Kevin TA Booth, Mantian Wang, Cole W. Peters, Alex J. Klein, Xinlan Chen, Yaqiao Li, Bence György, David P. Corey
Journal: Journal of Clinical Investigation (2024)

Usher syndrome type 1F (USH1F), resulting from mutations in the protocadherin-15 (PCDH15) gene, is characterized by congenital lack of hearing and balance, and progressive blindness in the form of retinitis pigmentosa. In this study, we explore an approach for USH1F gene therapy, exceeding the single AAV packaging limit by employing a dual adeno-associated virus (AAV) strategy to deliver the full-length PCDH15 coding sequence. We demonstrate the efficacy of this strategy in mouse USH1F models, effectively restoring hearing and balance in these mice. Importantly, our approach also proves successful in expressing PCDH15 protein in clinically relevant retinal models, including human retinal organoids and non-human primate retina, showing efficient targeting of photoreceptors and proper protein expression in the calyceal processes. This research represents a major step toward advancing gene therapy for USH1F and the multiple challenges of hearing, balance, and vision impairment.
Biomimetic Non-Collagenous Proteins-Calcium Phosphate Complex with Superior Osteogenesis via Regulating Macrophage IL-27 Secretion
Authors: Shenglong Tan, Xinghong Luo, Yifan Wang, Shangsi Chen, Tao Jiang, Xiaoshan Yang, Xinyi Peng, Xinyao Zhang, Sheng Zhang, Chengfei Zhang, Zhenzhen Liu, Dandan Ma
Journal: Biomaterials (2024)
m7G-modified mt-tRF3b-LeuTAA regulates mitophagy and metabolic reprogramming via SUMOylation of SIRT3 in chondrocytes
Authors: Dianbo Long, Zengfa Deng, Xiaoyi Zhao, Yiyang Xu, Wei Li, Xiaolin Mo, Yanlin Zhong, Ming Li, Aishan He, Ziji Zhang, Yan Kang, Guping Mao
Journal: Biomaterials (2024)
Exposure, infection and disease with the tick-borne pathogen Borrelia miyamotoi in the Netherlands and Sweden, 2007-2019.
Authors: Dieuwertje Hoornstra, Olga A Stukolova, Jacqueline A van Eck, Marina I Sokolova, Alexander E Platonov, Agnetha Hofhuis, Erik R A Vos, Johan H Reimerink, Oda E van den Berg, Cees C van den Wijngaard, Malin Lager, Peter Wilhelmsson, Per-Eric Lindgren, Pia Forsberg, Anna J Henningsson, Joppe W Hovius
Journal: Journal of Infection (2024)
Transmembrane Serine Protease 2 and Proteolytic Activation of the Epithelial Sodium Channel in Mouse Kidney
Authors: Florian Sure, Sara Afonso, Daniel Essigke, Paul Schmidt, M. Zaher Kalo, Viatcheslav Nesterov, Alicia Kißler, Marko Bertog, Ralf Rinke, Sabine Wittmann, Katharina A.E. Broeker, Thomas Gramberg, Ferruh Artunc, Christoph Korbmacher, Alexandr V. Ilyaskin
Journal: Journal of the American Society of Nephrology (2024)

Key Points Proteolytic activation of the epithelial sodium channel (ENaC) was compromised by transmembrane serine protease 2 deficiency in murine cortical collecting duct cells and native mouse kidney. To compensate for impaired ENaC activation, rise in plasma aldosterone in response to low-salt diet was enhanced in Tmprss2 −/− mice. Transmembrane serine protease 2 may be a potential drug target to limit proteolytic ENaC activation in disorders with increased renal ENaC activity. Background The renal epithelial sodium channel (ENaC) is essential for sodium balance and BP control. ENaC undergoes complex proteolytic activation by not yet clearly identified tubular proteases. Here, we examined a potential role of transmembrane serine protease 2 (TMPRSS2). Methods Murine ENaC and TMPRSS2 were (co)expressed in Xenopus laevis oocytes. ENaC cleavage and function were studied in TMPRSS2-deficient murine cortical collecting duct (mCCD cl1 ) cells and TMPRSS2-knockout ( Tmprss2 −/− ) mice. Short-circuit currents ( I SC ) were measured to assess ENaC-mediated transepithelial sodium transport of mCCD cl1 cells. The mCCD cl1 cell transcriptome was studied using RNA sequencing. The effect of low-sodium diet with or without high potassium were compared in Tmprss2 −/− and wild-type mice using metabolic cages. ENaC-mediated whole-cell currents were recorded from microdissected tubules of Tmprss2 −/− and wild-type mice. Results In oocytes, coexpression of murine TMPRSS2 and ENaC resulted in fully cleaved γ -ENaC and approximately two-fold stimulation of ENaC currents. High baseline expression of TMPRSS2 was detected in mCCD cl1 cells without a stimulatory effect of aldosterone on its function or transcription. TMPRSS2 knockout in mCCD cl1 cells compromised γ -ENaC cleavage and reduced baseline and aldosterone-stimulated I SC , which could be rescued by chymotrypsin. A compensatory transcriptional upregulation of other proteases was not observed. Tmprss2 −/− mice kept on standard diet exhibited no apparent phenotype, but renal γ -ENaC cleavage was altered. In response to a low-salt diet, particularly with high potassium intake, Tmprss2 −/− mice increased plasma aldosterone significantly more than wild-type mice to achieve a similar reduction of renal sodium excretion. Importantly, the stimulatory effect of trypsin on renal tubular ENaC currents was much more pronounced in Tmprss2 −/− mice than that in wild-type mice. This indicated the presence of incompletely cleaved and less active channels at the cell surface of TMPRSS2-deficient tubular epithelial cells. Conclusions TMPRSS2 contributes to proteolytic ENaC activation in mouse kidney in vivo .
Detection of Borrelia burgdorferi sensu lato by proteomics: a complementary diagnosis tool on erythema migrans biopsies.
Authors: Paola Cantero, Laurence Ehret-Sabatier, Cédric Lenormand, Yves Hansmann, Erik Sauleau, Laurence Zilliox, Benoit Westermann, Benoit Jaulhac, Didier Mutter, Cathy Barthel, Pauline Perdu-Alloy, Martin Martinot, Dan Lipsker, Nathalie Boulanger
Journal: Clinical Microbiology and Infection (2024)
Efficacy of a Standalone Smartphone Application to Treat Postnatal Depression: A Randomized Controlled Trial
Authors: Pedro F Zuccolo, André R Brunoni, Tatiane Borja, Alicia Matijasevich, Guilherme V Polanczyk, Daniel Fatori
Journal: Psychotherapy and Psychosomatics (2024)

Introduction: Smartphone app interventions based on cognitive-behavioral therapy (CBT) are promising scalable alternatives for treating mental disorders, but the evidence of their efficacy for postpartum depression is limited. We assessed the efficacy of Motherly, a standalone CBT-based smartphone app, in reducing symptoms of postpartum depression. Methods: Women aged 18–40 with symptoms of postpartum depression were randomized either to intervention (Motherly app) or active control (COMVC app). The primary outcome was symptoms of depression measured by the Edinburgh Postnatal Depression Scale (EPDS) at post-treatment. Secondary outcomes were anxiety symptoms, parental stress, quality of sleep, behavioral activation, availability of response-contingent positive reinforcement, and clinical improvement at post-treatment and 1-month follow-up. Exploratory analyses were performed to investigate if app engagement was associated with treatment response. Results: From November 2021 to August 2022, 1,751 women volunteered, of which 264 were randomized, and 215 provided primary outcome data. No statistically significant differences were found between groups at post-treatment: intervention: mean (SD): 12.75 (5.52); active control: 13.28 (5.32); p = 0.604. There was a statistically significant effect of the intervention on some of the secondary outcomes. Exploratory analyses suggest a dose-response relationship between Motherly app engagement and outcomes. Conclusion: Our standalone app intervention did not significantly reduce postnatal depression symptoms when compared to active control. Exploratory findings suggest that negative findings might be associated with insufficient app engagement. Consistent with current literature, our findings suggest that standalone app interventions for postpartum depression are not ready to be implemented in clinical practice.
Pregabalin for Neuropathic Pain and Itch in Recessive Dystrophic Epidermolysis Bullosa
Authors: Margarita Calvo, Macarena Tejos-Bravo, Alvaro Passi-Solar, Fernanda Espinoza, Ignacia Fuentes, Irene Lara-Corrales, Elena Pope
Journal: JAMA Dermatology (2024)

Importance Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB. Objectives To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB. Design, Setting, and Participants A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the Douleur Neuropathique 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023. Intervention Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg/day) in a randomized sequence so that comparisons could be made within participants and between groups. Main Outcomes and Measures Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention. Results In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated. Conclusions and Relevance The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial. Trial Registration ClinicalTrials.gov Identifier: NCT03928093
Maternal Downward Neighborhood Income Mobility and Newborn Discharge to Child Protective Services
Authors: Jennifer A. Jairam, Eyal Cohen, Christina Diong, Howard Berger, Jun Guan, Emily Ana Butler, Joel G. Ray
Journal: JAMA Network Open (2024)

This cohort study examines whether there is an association between a mother moving into a neighborhood with lower income between births and newborn custody by child protective services at birth.
The Diagnosis
Authors: Edward John Gaudet
Journal: JAMA (2024)

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Impaired unsaturated fatty acid elongation alters mitochondrial function and accelerates metabolic dysfunction-associated steatohepatitis progression
Authors: Adrien Vouilloz, Thibaut Bourgeois, Marc Diedisheim, Thomas Pilot, Antoine Jalil, Naig Le Guern, Victoria Bergas, Noéline Rohmer, Florence Castelli, Damien Leleu, Alexis Varin, Jean-Paul Pais de Barros, Pascal Degrace, Mickael Rialland, Camille Blériot, Nicolas Venteclef, Charles Thomas, David Masson
Journal: Metabolism (2024)
Long-Term Outcomes of Prostate-Specific Membrane Antigen–PET Imaging of Recurrent Prostate Cancer
Authors: Natalia Kunst, Jessica B. Long, Sarah Westvold, Preston C. Sprenkle, Isaac Y. Kim, Lawrence Saperstein, Maximilian Rabil, Umar Ghaffar, R. Jeffrey Karnes, Xiaomei Ma, Cary P. Gross, Shi-Yi Wang, Michael S. Leapman
Journal: JAMA Network Open (2024)

Importance Although prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown. Objective To estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer. Design, Setting, and Participants This decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy. Inputs used were from the literature and a retrospective cohort study conducted at 2 institutions. The base case analysis assumed modest benefits of earlier detection and treatment, and scenario analyses considered prostate-specific antigen (PSA) level at imaging and different outcomes of earlier vs delayed treatment. The analysis was performed between April 1, 2023, and May 1, 2024. Exposures (1) Immediate PSMA-PET imaging, (2) conventional imaging (computed tomography and bone scan [CTBS]) followed by PSMA-PET if CTBS findings were negative or equivocal, and (3) CTBS alone. Main Outcomes and Measures The main outcomes were detection of metastases, deaths from prostate cancer, and life-years and quality-adjusted life-years (QALYs) gained. Results The model estimated that per 1000 simulated patients with BCR (assumed median age, 66 years), PSMA-PET is expected to diagnose 611 (95% uncertainty interval [UI], 565-656) patients with metastasis compared with 630 (95% UI, 586-675) patients diagnosed using CTBS followed by PSMA-PET and 297 (95% UI, 202-410) patients diagnosed using CTBS alone. Moreover, the estimated number of prostate cancer deaths was 512 (95% UI, 472-552 deaths) with PSMA-PET, 520 (95% UI, 480-559 deaths) with CTBS followed by PSMA-PET, and 587 (95% UI, 538-632 deaths) with CTBS alone. Imaging with PSMA-PET yielded the highest number of QALYs, which were 824 (95% UI, 698-885) higher than CTBS. These results differed by PSA level at the time of testing, with the highest incremental life-years and QALYs and lowest number of deaths from prostate cancer among patients with PSA levels of at least 5.0 ng/mL. Finally, the estimates were sensitive to the expected benefit of initiating therapy for recurrent prostate cancer earlier in the disease course. Conclusions and Relevance The results of this decision-analytic model suggest that upfront PSMA-PET imaging for the evaluation of BCR is expected to be associated with reduced cancer mortality and gains in life-years and QALYs compared with the conventional imaging strategy, assuming modest benefits of earlier detection and treatment.
State Minimum Wage and Mental Health Among Children and Adolescents
Authors: Nolan M. Kavanagh, Margaret McConnell, Natalie Slopen
Journal: JAMA Network Open (2024)

Importance Mental health disorders are increasing for children and adolescents in the US, with those in poverty having especially high rates. More evidence is needed about the association between economic policies, such as the minimum wage, and children’s mental health. Objective To test the association between minimum wages and the mental health of children and adolescents. Design, Setting, and Participants This repeated cross-sectional, population-based US study used data from 2001 to 2022. Participants included state-representative, stratified random samples of children from the National Survey of Children’s Health and adolescents from the Youth Risk Behavior Surveillance System. Data analysis was performed from January 2023 to August 2024. Exposure State minimum wage policies. Main Outcomes and Measures A total of 15 outcomes reported by caregivers or adolescents from survey data were evaluated: depression, anxiety, attention deficit disorder and/or attention-deficit/hyperactivity disorder, behavior disorders, mood symptoms, gastrointestinal symptoms, considered and attempted suicide, any unmet health care and mental health care, alcohol and marijuana use, physical fights, school absenteeism, and paid employment. The associations between minimum wage policies and mental health were tested using 2-way fixed-effects models, lifetime minimum wage models, and difference-in-differences models with event studies, all with state, year, and birth cohort fixed effects. Additional controls included individual-level demographics and state-level health insurance and welfare policies. Results Analyses included 239 534 children (aged 3-17 years; 117 111 girls [48.9%]) from the 2016 to 2022 National Survey of Children’s Health, and 1 453 043 adolescents (aged 12-18 years; 711 380 girls [49.0%]) from the 2001 to 2021 Youth Risk Behavior Surveillance System. Across diverse modeling approaches, increases in minimum wages were not associated with clear, consistent improvements in mental health. For example, in 2-way fixed-effects models, a $1 increase in the minimum wage was not associated with changes in rates of depression (0.06 percentage points [pp]; 95% CI, –0.11 to 0.23 pp; P = .48), unmet mental health care (0.13 pp; 95% CI, –0.04 to 0.30 pp; P = .14), or attempted suicide (–0.17 pp; 95% CI, –0.47 to 0.13 pp; P = .26). There also were no clear improvements when stratifying by household income, parental education, race and ethnicity, nativity, or urbanicity. Conclusions and Relevance In this repeated cross-sectional study, changes in minimum wage policies over the past 2 decades were not accompanied by clear improvements in children’s and adolescents’ mental health. More evidence is needed on policy approaches to improve the mental well-being of children, particularly those from economically disadvantaged families.
Evaluation of A Non-Nucleoside Inhibitor of the RSV RNA-Dependent RNA Polymerase in Translatable Animals Models
Authors: Michael P Citron, Xiaowei Zang, Andrew Leithead, Shi Meng, William A Rose Ii, Edward Murray, Jane Fontenot, John Bilello, Douglas C Beshore, John A Howe
Journal: Journal of Infection (2024)
Monilethrix
Authors: Vincenzo Piccolo, Giuseppe Argenziano
Journal: JAMA Dermatology (2024)

This case report describes sparse, unruly, fragile, and easily breakable hair, with patchy alopecia with diffuse follicular papules throughout the scalp as well as short hair with an alternation of darker elliptical nodes, with paler nonmedullated paler internodes giving a necklace appearance.
Performance of Multimodal Artificial Intelligence Chatbots Evaluated on Clinical Oncology Cases
Authors: David Chen, Ryan S. Huang, Jane Jomy, Philip Wong, Michael Yan, Jennifer Croke, Daniel Tong, Andrew Hope, Lawson Eng, Srinivas Raman
Journal: JAMA Network Open (2024)

Importance Multimodal artificial intelligence (AI) chatbots can process complex medical image and text-based information that may improve their accuracy as a clinical diagnostic and management tool compared with unimodal, text-only AI chatbots. However, the difference in medical accuracy of multimodal and text-only chatbots in addressing questions about clinical oncology cases remains to be tested. Objective To evaluate the utility of prompt engineering (zero-shot chain-of-thought) and compare the competency of multimodal and unimodal AI chatbots to generate medically accurate responses to questions about clinical oncology cases. Design, Setting, and Participants This cross-sectional study benchmarked the medical accuracy of multiple-choice and free-text responses generated by AI chatbots in response to 79 questions about clinical oncology cases with images. Exposures A unique set of 79 clinical oncology cases from JAMA Network Learning accessed on April 2, 2024, was posed to 10 AI chatbots. Main Outcomes and Measures The primary outcome was medical accuracy evaluated by the number of correct responses by each AI chatbot. Multiple-choice responses were marked as correct based on the ground-truth, correct answer. Free-text responses were rated by a team of oncology specialists in duplicate and marked as correct based on consensus or resolved by a review of a third oncology specialist. Results This study evaluated 10 chatbots, including 3 multimodal and 7 unimodal chatbots. On the multiple-choice evaluation, the top-performing chatbot was chatbot 10 (57 of 79 [72.15%]), followed by the multimodal chatbot 2 (56 of 79 [70.89%]) and chatbot 5 (54 of 79 [68.35%]). On the free-text evaluation, the top-performing chatbots were chatbot 5, chatbot 7, and the multimodal chatbot 2 (30 of 79 [37.97%]), followed by chatbot 10 (29 of 79 [36.71%]) and chatbot 8 and the multimodal chatbot 3 (25 of 79 [31.65%]). The accuracy of multimodal chatbots decreased when tested on cases with multiple images compared with questions with single images. Nine out of 10 chatbots, including all 3 multimodal chatbots, demonstrated decreased accuracy of their free-text responses compared with multiple-choice responses to questions about cancer cases. Conclusions and Relevance In this cross-sectional study of chatbot accuracy tested on clinical oncology cases, multimodal chatbots were not consistently more accurate than unimodal chatbots. These results suggest that further research is required to optimize multimodal chatbots to make more use of information from images to improve oncology-specific medical accuracy and reliability.
Limitations in Gauging the Effects of Allocation Policy Changes on Liver Transplant
Authors: Ri-Hui Xiong, Zhao-Ping Wu, Deng-Chao Wang
Journal: JAMA Surgery (2024)

To the Editor We read with great interest the article by Ahmed and colleagues.1 This study provided a detailed analysis of the changes in costs and activities associated with liver transplant after the 2020 United Network for Organ Sharing policy changes.