tbuckley/cabot-search huggingface dataset:
Reticulon 3 regulates sphingosine‐1‐phosphate synthesis in endothelial cells to control blood pressure
Authors: Jie‐Yuan Jin, Si‐Hua Chang, Ya‐Qin Chen, Meng‐Wei Liu, Yi Dong, Ji‐Shi Liu, Qin Wang, Hao Huang, Liang‐Liang Fan, Rong Xiang
Journal: MedComm (2024)

Abstract The discovery of the endothelium as a major regulator of vascular tone triggered intense research among basic and clinical investigators to unravel the physiologic and pathophysiologic significance of this phenomenon. Sphingosine‐l‐phosphate (S1P), derived from the vascular endothelium, is a significant regulator of blood pressure. However, the mechanisms underlying the regulation of S1P biosynthetic pathways in arteries remain to be further clarified. Here, we reported that Reticulon 3 (RTN3) regulated endothelial sphingolipid biosynthesis and blood pressure. We employed public datasets, patients, and mouse models to explore the pathophysiological roles of RTN3 in blood pressure control. The underlying mechanisms were studied in human umbilical vein endothelial cells (HUVECs). We reported that increased RTN3 was found in patients and that RTN3‐null mice presented hypotension. In HUVECs, RTN3 can regulate migration and tube formation via the S1P signaling pathway. Mechanistically, RTN3 can interact with CERS2 to promote the selective autophagy of CERS2 and further influence S1P signals to control blood pressure. We also identified an RTN3 variant (c.116C&gt;T, p.T39M) in a family with hypertension. Our data provided the first evidence of the association between RTN3 level changes and blood pressure anomalies and preliminarily elucidated the importance of RTN3 in S1P metabolism and blood pressure regulation.
Metformin-grafted polycaprolactone nanoscaffold targeting sensory nerve controlled fibroblasts reprograming to alleviate epidural fibrosis
Authors: Zeng Xu, Bo Hu, Genjiang Zheng, Wei Yu, Chen Yang, Hui Wang, Keyi Chen, Shatong He, Lei Liang, Chen Xu, Xiaodong Wu, Fazhi Zang, Wei-En Yuan, Huajiang Chen
Journal: Journal of Controlled Release (2024)
Nano-chemical priming strategy to enhance TGF-β resistance and anti-tumor activity of natural killer cells
Authors: Seung Hee Choi, Hui Bang Cho, Jin-Ho Choi, Hye Jin Kim, Hye Jung Jang, Seohyun Cho, Eunchong Maeng, Hail Park, Ki Seo Ryu, Keun-Hong Park, Kyung-Soon Park
Journal: Journal of Controlled Release (2024)
In vivo activation of FAP-cleavable small molecule-drug conjugates for the targeted delivery of camptothecins and tubulin poisons to the tumor microenvironment
Authors: Matilde Bocci, Aureliano Zana, Lucrezia Principi, Laura Lucaroni, Luca Prati, Ettore Gilardoni, Dario Neri, Samuele Cazzamalli, Andrea Galbiati
Journal: Journal of Controlled Release (2024)
Digital mental health: small steps for big gains
Authors: None The Lancet Psychiatry
Journal: The Lancet Psychiatry (2024)

Like all areas of psychiatry, demand on child mental health services far exceeds capacity. Digital technologies are eagerly promoted as ways to redress the gap but the evidence base for sustained clinical impact in real-world mental health settings is often poor. In The Lancet Psychiatry, Cathy Creswell and colleagues present findings from a pragmatic trial based in child mental health services across England and Northern Ireland that investigated whether digital augmentation of parent-led cognitive behavioural therapy (CBT) could improve efficiency without negatively affecting clinical efficacy.
Pharmacological treatments for psychotic depression: a systematic review and network meta-analysis
Authors: Vincenzo Oliva, Chiara Possidente, Michele De Prisco, Giovanna Fico, Gerard Anmella, Diego Hidalgo-Mazzei, Andrea Murru, Giuseppe Fanelli, Chiara Fabbri, Michele Fornaro, Andrea de Bartolomeis, Marco Solmi, Joaquim Radua, Eduard Vieta, Alessandro Serretti
Journal: The Lancet Psychiatry (2024)
Uncommon Detection of Leiomyoma in the Penile Corpus Spongiosum Using FDG PET/CT
Authors: Nir Hod, Daniel Levin, Gal Ben-Arie, Ilia Pinsk, Lidia Osyntsov, Matan Mekayten
Journal: Clinical Nuclear Medicine (2024)

Abstract Primary tumors of the penile corpus spongiosum are rare. Hereby we describe the scintigraphic findings of a case of penile leiomyoma within the corpus spongiosum tissue, which was incidentally detected on FDG PET/CT. The benign neoplasm was growing in close proximity to the urethra showing increased focal FDG uptake on sequential PET/CT studies. Subsequently, the patient experienced obstructive urinary symptoms, and the tumor was resected. We concluded that the possibility of neoplasm should be kept in mind while evaluating a patient with persistent focal penile FDG uptake, which may be the first and only manifestation of the disease.
Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study
Authors: Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Journal: BMJ (2024)

Abstract Objective To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM). Design Nationwide population based study. Setting Longitudinal cohort study in Korea. Participants 7 796 763 participants in the National Health Screening Programme in 2009 were divided into three groups based on NAFLD status: no NAFLD (fatty liver index&lt;30); grade 1 NAFLD (30≤fatty liver index&lt;60); and grade 2 NAFLD (fatty liver index≥60). Median follow-up was 8.13 years. Main outcome measures The primary outcome was incident cardiovascular disease (myocardial infarction, ischaemic stroke) or all cause death. Results Of 7 796 763 participants, 6.49% (n=505 763) had T2DM. More patients with T2DM had grade 1 NAFLD (34.06%) and grade 2 NAFLD (26.73%) than those without T2DM (grade 1 NAFLD: 21.20%; grade 2 NAFLD: 10.02%). The incidence rate (per 1000 person years) of cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD, and the incidence rates in patients with T2DM were higher than those in patients without T2DM. The five year absolute risk for cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD in patients without and with T2DM (no NAFLD, without T2DM: 1.03, 95% confidence interval 1.02 to 1.04, and 1.25, 1.24 to 1.26, respectively; grade 1 NAFLD, without T2DM: 1.23, 1.22 to 1.25, and 1.50, 1.48 to 1.51, respectively; grade 2 NAFLD, without T2DM: 1.42, 1.40 to 1.45, and 2.09, 2.06 to 2.12, respectively; no NAFLD, with T2DM: 3.34, 3.27 to 3.41, and 3.68, 3.61 to 3.74, respectively; grade 1 NAFLD, with T2DM: 3.94, 3.87 to 4.02, and 4.25, 4.18 to 4.33, respectively; grade 2 NAFLD, with T2DM: 4.66, 4.54 to 4.78, and 5.91, 5.78 to 6.05, respectively). Patients with T2DM and without NAFLD had a higher five year absolute risk for cardiovascular disease and all cause death than those without T2DM and with grade 2 NAFLD. Risk differences for cardiovascular disease and all cause death between no NAFLD and grade 1 or grade 2 NAFLD were higher in patients with T2DM than in those without T2DM. Conclusions NAFLD in patients with T2DM seems to be associated with a higher risk of cardiovascular disease and all cause death, even in patients with mild NAFLD. Risk differences for cardiovascular disease and all cause death between the no NAFLD group and the grade 1 or grade 2 NAFLD groups were higher in patients with T2DM than in those without T2DM.
Anterior cingulate cortex projections to the dorsal medial striatum underlie insomnia associated with chronic pain
Authors: Ya-Dong Li, Yan-Jia Luo, Wei-Kun Su, Jing Ge, Andrew Crowther, Ze-Ka Chen, Lu Wang, Michael Lazarus, Zi-Long Liu, Wei-Min Qu, Zhi-Li Huang
Journal: Neuron (2024)

Chronic pain often leads to the development of sleep disturbances. However, the precise neural circuit mechanisms responsible for sleep disorders in chronic pain have remained largely unknown. Here, we present compelling evidence that hyperactivity of pyramidal neurons (PNs) in the anterior cingulate cortex (ACC) drives insomnia in a mouse model of nerve-injury-induced chronic pain. After nerve injury, ACC PNs displayed spontaneous hyperactivity selectively in periods of insomnia. We then show that ACC PNs were both necessary for developing chronic-pain-induced insomnia and sufficient to mimic sleep loss in naive mice. Importantly, combining optogenetics and electrophysiological recordings, we found that the ACC projection to the dorsal medial striatum (DMS) underlies chronic-pain-induced insomnia through enhanced activity and plasticity of ACC-DMS dopamine D1R neuron synapses. Our findings shed light on the pivotal role of ACC PNs in developing chronic-pain-induced sleep disorders.
CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration
Authors: Sára Mravinacová, Vilma Alanko, Sofia Bergström, Claire Bridel, Yolande Pijnenburg, Göran Hagman, Miia Kivipelto, Charlotte Teunissen, Peter Nilsson, Anna Matton, Anna Månberg
Journal: Molecular Neurodegeneration (2024)

Abstract Background Amyloid and tau aggregates are considered to cause neurodegeneration and consequently cognitive decline in individuals with Alzheimer’s disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins to reflect AD pathology and cognitive decline, aiming to identify potential biomarkers for monitoring outcomes of disease-modifying therapies targeting these aggregates. Method We used a multiplex antibody-based suspension bead array to measure the levels of 49 proteins in CSF from the Swedish GEDOC memory clinic cohort at the Karolinska University Hospital. The cohort comprised 148 amyloid- and tau-negative individuals (A-T-) and 65 amyloid- and tau-positive individuals (A+T+). An independent sample set of 26 A-T- and 26 A+T+ individuals from the Amsterdam Dementia Cohort was used for validation. The measured proteins were clustered based on their correlation to CSF amyloid beta peptides, tau and NfL levels. Further, we used support vector machine modelling to identify protein pairs, matched based on their cluster origin, that reflect AD pathology and cognitive decline with improved performance compared to single proteins. Results The protein-clustering revealed 11 proteins strongly correlated to t-tau and p-tau (tau-associated group), including mainly synaptic proteins previously found elevated in AD such as NRGN, GAP43 and SNCB. Another 16 proteins showed predominant correlation with Aβ42 (amyloid-associated group), including PTPRN2, NCAN and CHL1. Support vector machine modelling revealed that proteins from the two groups combined in pairs discriminated A-T- from A+T+ individuals with higher accuracy compared to single proteins, as well as compared to protein pairs composed of proteins originating from the same group. Moreover, combining the proteins from different groups in ratios (tau-associated protein/amyloid-associated protein) significantly increased their correlation to cognitive decline measured with cognitive scores. The results were validated in an independent cohort. Conclusions Combining brain-derived proteins in pairs largely enhanced their capacity to discriminate between AD pathology-affected and unaffected individuals and increased their correlation to cognitive decline, potentially due to adjustment of inter-individual variability. With these results, we highlight the potential of protein pairs to monitor neurodegeneration and thereby possibly the efficacy of AD disease-modifying therapies.
Targeting lysine demethylase 5 (KDM5) in mantle cell lymphoma
Authors: Danmei Xu, Findlay Bewicke-Copley, Karina Close, Jessica Okosun, Robert Peter Gale, Jane Apperley, David M. Weinstock, Hans-Guido Wendel, Jude Fitzgibbon
Journal: Blood Cancer Journal (2024)
Duration of SARS-CoV-2 Culturable Virus Shedding in Children by Vaccination Status
Authors: Alberto Donzelli, Franco Berrino
Journal: JAMA Pediatrics (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Electronic Cigarettes for Smoking Cessation — Have We Reached a Tipping Point?
Authors: Nancy A Rigotti
Journal: New England Journal of Medicine (2024)

After more than a decade on the market as consumer products in the United States, electronic nicotine-delivery systems — or e-cigarettes — remain highly controversial in medical and public health communities.1 These battery-operated devices allow users to inhale ("vape") a nicotine aerosol, which sustains the nicotine dependence that keeps people smoking but avoids exposing the smoker to the many toxic chemicals that are generated when a cigarette burns tobacco.2,3 The products of tobacco combustion account for the bulk of tobacco-related diseases that make cigarette smoking the leading preventable cause of death worldwide. Nicotine exposure alone has far fewer risks, making . . .
Case 5-2024: A 36-Year-Old Man with Fevers
Authors: Eric A. Meyerowitz, Shambo Guha Roy, Anne M. Neilan, Douglas S. Ross, Grace K. Mahowald
Journal: New England Journal of Medicine (2024)

A 36-year-old man was evaluated in the infectious diseases clinic of the hospital because of fevers and throat discomfort that had begun 18 days earlier. An extensive workup was unrevealing. A diagnosis was made.
HIV-1 Remission after Allogeneic Hematopoietic-Cell Transplantation
Authors: Jana K. Dickter, Ahmed Aribi, Angelo A. Cardoso, Sara Gianella, Ketevan Gendzekhadze, Shirley Li, Ye Feng, Antoine Chaillon, Gregory M. Laird, Diana L. Browning, Justine A. Ross, Deepa D. Nanayakkara, Alfredo Puing, Rodica Stan, Lily L. Lai, Sue Chang, Trilokesh D. Kidambi, Sandra Thomas, Monzr M. Al Malki, Ryo Nakamura, Joseph Alvarnas, Randy A. Taplitz, Sanjeet S. Dadwal, Stephen J. Forman, John A. Zaia
Journal: New England Journal of Medicine (2024)
A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder
Authors: Justin O Szot, Hartmut Cuny, Ella Mma Martin, Delicia Z Sheng, Kavitha Iyer, Stephanie Portelli, Vivien Nguyen, Jessica M Gereis, Dimuthu Alankarage, David Chitayat, Karen Chong, Ingrid M Wentzensen, Catherine Vincent-Delormé, Alban Lermine, Emma Burkitt-Wright, Weizhen Ji, Lauren Jeffries, Lynn S Pais, Tiong Y Tan, James Pitt, Cheryl A Wise, Helen Wright, Israel D Andrews, Brianna Pruniski, Theresa A Grebe, Nicole Corsten-Janssen, Katelijne Bouman, Cathryn Poulton, Supraja Prakash, Boris Keren, Natasha J Brown, Matthew F Hunter, Oliver Heath, Saquib A Lakhani, John H McDermott, David B Ascher, Gavin Chapman, Kayleigh Bozon, Sally L Dunwoodie
Journal: Journal of Clinical Investigation (2024)

Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 - have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation. Enzymatic assessment of variant deleteriousness in vitro revealed protein domain-specific perturbation, complemented by protein structure modeling in silico. We reproduced NADSYN1-dependent CNDD in mice and assessed various maternal NAD precursor supplementation strategies to prevent adverse pregnancy outcomes. While for Nadsyn1+/- mothers, any B3 vitamer was suitable to raise NAD, preventing embryo loss and malformation, Nadsyn1-/- mothers required supplementation with amidated NAD precursors (nicotinamide or nicotinamide mononucleotide) bypassing their metabolic block. The circulatory NAD metabolome in mice and humans before and after NAD precursor supplementation revealed a consistent metabolic signature with utility for patient identification. Our data collectively improve clinical diagnostics of NADSYN1-dependent CNDD, provide guidance for the therapeutic prevention of CNDD, and suggest an ongoing need to maintain NAD levels via amidated NAD precursor supplementation after birth.
Hierarchical Computed Tomography Scoring Systems Cannot Discriminate Between Reversible Bronchiectasis and Mucus Plugs
Authors: Gaël Dournes, Ilyes Benlala
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Hierarchical CT Scoring Systems Cannot Discriminate Between Reversible Bronchiectasis and Mucus Plugs." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Reply to Dournes and Benlala: Hierarchical Computed Tomography Scoring Systems Cannot Discriminate Between Reversible Bronchiectasis and Mucus Plugs
Authors: Paul McNally, Jane Davies, Pierluigi Ciet, Harm Tiddens
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Reply to: Hierarchical CT Scoring Systems Cannot Discriminate Between Reversible Bronchiectasis and Mucus Plugs." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Enhancing the Repair of Substantial Volumetric Muscle Loss by Creating Different Levels of Blood Vessel Networks Using Pre‐Vascularized Nerve Hydrogel Implants
Authors: Shih‐Yen Wei, Po‐Yu Chen, Min‐Chun Tsai, Ting‐Lun Hsu, Chia‐Chang Hsieh, Hsiu‐Wei Fan, Tzu‐Hsuan Chen, Ren‐Hao Xie, Guan‐Yu Chen, Ying‐Chieh Chen
Journal: Advanced Healthcare Materials (2024)

Abstract Volumetric muscle loss (VML), a severe muscle tissue loss from trauma or surgery, results in scarring, limited regeneration, and significant fibrosis, leading to lasting reductions in muscle mass and function. A promising approach for VML recovery involves restoring vascular and neural networks at the injury site, a process not extensively studied yet. Collagen hydrogels have been investigated as scaffolds for blood vessel formation due to their biocompatibility, but reconstructing blood vessels and guiding innervation at the injury site is still difficult. In this study, collagen hydrogels with varied densities of vessel‐forming cells are implanted subcutaneously in mice, generating pre‐vascularized hydrogels with diverse vessel densities (0–145 numbers/mm 2 ) within a week. These hydrogels, after being transplanted into muscle injury sites, are assessed for muscle repair capabilities. Results showed that hydrogels with high microvessel densities, filling the wound area, effectively reconnected with host vasculature and neural networks, promoting neovascularization and muscle integration, and addressing about 63% of the VML.
Physical fitness in male adolescents and atherosclerosis in middle age: a population-based cohort study
Authors: Ángel Herraiz-Adillo, Viktor H Ahlqvist, Sara Higueras-Fresnillo, Kristofer Hedman, Emil Hagström, Melony Fortuin-de Smidt, Bledar Daka, Cecilia Lenander, Daniel Berglind, Carl Johan Östgren, Karin Rådholm, Francisco B Ortega, Pontus Henriksson
Journal: British Journal of Sports Medicine (2024)

Objectives To examine the associations between physical fitness in male adolescents and coronary and carotid atherosclerosis in middle age. Methods This population-based cohort study linked physical fitness data from the Swedish Military Conscription Register during adolescence to atherosclerosis data from the Swedish CArdioPulmonary bioImage Study in middle age. Cardiorespiratory fitness was assessed using a maximal cycle-ergometer test, and knee extension muscular strength was evaluated through an isometric dynamometer. Coronary atherosclerosis was evaluated via Coronary Computed Tomography Angiography (CCTA) stenosis and Coronary Artery Calcium (CAC) scores, while carotid plaques were evaluated by ultrasound. The associations were analysed using multinomial logistic regression, adjusted (marginal) prevalences and restricted cubic splines. Results The analysis included 8986 male adolescents (mean age 18.3 years) with a mean follow-up of 38.2 years. Physical fitness showed a reversed J-shaped association with CCTA stenosis and CAC, but no consistent association was observed for carotid plaques. After adjustments, compared with adolescents in the lowest tertile of cardiorespiratory fitness and muscular strength, those in the highest tertile had 22% (OR 0.78; 95% CI 0.61 to 0.99) and 26% (OR 0.74; 95% CI 0.58 to 0.93) lower ORs for severe (≥50%) coronary stenosis, respectively. The highest physical fitness group (high cardiorespiratory fitness and muscular strength) had 33% (OR 0.67; 95% CI 0.52 to 0.87) lower OR for severe coronary stenosis compared with those with the lowest physical fitness. Conclusion This study supports that a combination of high cardiorespiratory fitness and high muscular strength in adolescence is associated with lower coronary atherosclerosis, particularly severe coronary stenosis, almost 40 years later.
Quantifying the impact of telemedicine and patient medical advice request messages on physicians' work-outside-work
Authors: Soumik Mandal, Batia M. Wiesenfeld, Devin M. Mann, Adam C. Szerencsy, Eduardo Iturrate, Oded Nov
Journal: npj Digital Medicine (2024)

Abstract The COVID-19 pandemic has boosted digital health utilization, raising concerns about increased physicians’ after-hours clinical work ("work-outside-work”). The surge in patients’ digital messages and additional time spent on work-outside-work by telemedicine providers underscores the need to evaluate the connection between digital health utilization and physicians’ after-hours commitments. We examined the impact on physicians’ workload from two types of digital demands - patients’ messages requesting medical advice ( PMAR s) sent to physicians’ inbox (inbasket), and telemedicine. Our study included 1716 ambulatory-care physicians in New York City regularly practicing between November 2022 and March 2023. Regression analyses assessed primary and interaction effects of ( PMAR s) and telemedicine on work-outside-work. The study revealed a significant effect of PMAR s on physicians’ work-outside-work and that this relationship is moderated by physicians’ specialties. Non-primary care physicians or specialists experienced a more pronounced effect than their primary care peers. Analysis of their telemedicine load revealed that primary care physicians received fewer PMAR s and spent less time in work-outside-work with more telemedicine. Specialists faced increased PMAR s and did more work-outside-work as telemedicine visits increased which could be due to the difference in patient panels. Reducing PMAR volumes and efficient inbasket management strategies needed to reduce physicians’ work-outside-work. Policymakers need to be cognizant of potential disruptions in physicians carefully balanced workload caused by the digital health services.