tbuckley/cabot-search huggingface dataset:
The future of patient-reported outcome measurement in hyperhidrosis lies in thoughtful, evidence-based implementation
Authors: Liam Jackman, Rakhshan Kamran
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript The future of patient-reported outcome measurement in hyperhidrosis lies in thoughtful, evidence-based implementation Get access Liam Jackman, Liam Jackman Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada https://orcid.org/0009-0009-4475-7893 Search for other works by this author on: Oxford Academic Google Scholar Rakhshan Kamran Rakhshan Kamran Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK Corresponding Author: Rakhshan Kamran, DPhil, MBA, BSc (Hons), Email:rakhshan.kamran@hertford.ox.ac.uk https://orcid.org/0000-0003-4298-4848 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae428, https://doi.org/10.1093/bjd/ljae428 Published: 01 November 2024 Article history Received: 28 October 2024 Accepted: 30 October 2024 Published: 01 November 2024
Implantation of MSC Spheroid-derived 3D Decellularized ECM Enriched with the MSC Secretome Ameliorates Traumatic Brain Injury and Promotes Brain Repair
Authors: Grace H Chen, Kee-Chin Sia, Shao-Wen Liu, Ying-Chi Kao, Pei-Ching Yang, Chia-Hsin Ho, Shih-Chen Huang, Peng-Ying Lee, Min-Zong Liang, Linyi Chen, Chieh-Cheng Huang
Journal: Biomaterials (2024)
The US overdose crisis: the next administration needs to move beyond criminalisation to a comprehensive public health approach
Authors: Magdalena Cerdá, Noa Krawczyk
Journal: BMJ (2024)

To tackle one of the most urgent public health challenges facing the US, the next administration needs to focus on prevention, treatment, and harm reduction, say <b>Magdalena Cerdá</b> and <b>Noa Krawczyk</b>
Vitamin D Supplementation, Long-Term PM<sub>2.5</sub> Exposure, and Severe Asthma Exacerbations in Children with Low Vitamin D: A Post Hoc Analysis of a Double-Blind, Randomized, Placebo-Controlled Trial (VDKA)
Authors: Franziska J. Rosser, Yueh-Ying Han, Erick Forno, Theresa W Guilbert, Leonard B Bacharier, Wanda Phipatanakul, Juan C. Celedón
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
New Approaches to the Treatment of Hypercortisolism
Authors: Riccardo Pofi, Dario De Alcubierre, Jiawen Dong, Jeremy W. Tomlinson
Journal: Annual Review of Medicine (2024)

This review explores the evolving landscape of treatments for hypercortisolism, highlighting both established and emerging therapies. Although surgery remains the cornerstone of management, medical therapies play a crucial and expanding role, especially in cases of persistent, recurrent, or severe hypercortisolism. We discuss the effectiveness and limitations of steroidogenesis inhibitors, pituitary-directed drugs, glucocorticoid receptor antagonists, and experimental drugs targeting novel molecular pathways that have been implicated in the pathogenesis of hypercortisolism. Despite advancements, significant unmet needs persist, underscoring the importance of personalized treatment approaches and the development of targeted therapies. Ongoing and future clinical trials are crucial for validating the safety and efficacy of these innovative treatments in Cushing disease management.
14-3-3 protein and its isoforms: A common diagnostic marker for Alzheimer’s disease, Parkinson’s disease and glaucomatous neurodegeneration
Authors: Siva Prasad Panda, Adarsh Kesharwani, Bhoopendra Singh, Arya Lakshmi Marisetti, Mvnl Chaitanya, Saurabh Dahiya, S Ponnusankar, Sanjesh Kumar, Mansi Singh, Praveen Kumar Shakya, P Dharani Prasad, Ajay Guru
Journal: Ageing Research Reviews (2024)
Pharmacological activation of STAT1-GSDME pyroptotic circuitry reinforces epigenetic immunotherapy for hepatocellular carcinoma
Authors: Yalin Tu, Haoran Wu, Chengpeng Zhong, Yan Liu, Zhewen Xiong, Siyun Chen, Jing Wang, Patrick Pak-Chun Wong, Weiqin Yang, Zhixian Liang, Jiahuan Lu, Shufen Chen, Lingyun Zhang, Yu Feng, Willis Wai-Yiu Si-Tou, Baoyi Yin, Yingnan Lin, Jianxin Liang, Liying Liang, Joaquim S L Vong, Weida Ren, Tsz Tung Kwong, Howard Leung, Ka Fai To, Stephanie Ma, Man Tong, Hanyong Sun, Qiang Xia, Jingying Zhou, David Kerr, Nick La Thangue, Joseph J Y Sung, Stephen Lam Chan, Alfred Sze-Lok Cheng
Journal: Gut (2024)

Genomic screening uncovered interferon-gamma (IFNγ) pathway defects in tumours refractory to immune checkpoint blockade (ICB). However, its non-mutational regulation and reversibility for therapeutic development remain less understood.
Uncovering specific genetic-respiratory disease endotypes for rheumatoid arthritis risk
Authors: Vanessa L. Kronzer, Katrina A. Williamson, Keigo Hayashi, Elizabeth J. Atkinson, Cynthia S. Crowson, Xiaosong Wang, Jing Cui, James R. Cerhan, Jennifer A. Sletten, Gregory C. McDermott, Elena K. Joerns, Robert Vassallo, John M. Davis, Jeffrey A. Sparks
Journal: Annals of the Rheumatic Diseases (2024)

We aimed to identify specific genetic-respiratory disease endotypes for rheumatoid arthritis (RA) risk. This case-control study used the Mass General Brigham (MGB) and Mayo Clinic (MC) Biobanks for discovery and replication, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex and health record history. Genetic exposures included the top 11 RA risk alleles, and a validated human leucocyte antigen (HLA) genetic risk score (GRS). We identified seven respiratory diseases by codes. Using logistic regression models adjusting for potential confounders, we estimated Rs with 95% CIs for the interactions between genetic and respiratory exposures for RA risk. We identified 653 RA cases and 2607 controls in MGB, and 428 incident RA cases and 1712 non-RA controls in MC (mean age 64, 69% female). Respiratory diseases were associated with an increased risk of RA (OR 1.34, 95% CI 1.05, 1.71). Six out of 11 non-HLA RA risk alleles interacted strongly with specific respiratory diseases for RA risk, including NFKBIE and sinusitis (OR 5.49, 95% CI 1.56, 19.4 MGB; 5.26, 95% CI 2.00, 13.86 MC) and FAM167A and acute sinusitis for seronegative RA (OR 6.00, 95% CI 2.09, 17.24 MGB; 4.90, 95% CI 1.71, 14.1 MC). The RA HLA GRS interacted synergistically with interstitial lung disease for RA risk (OR 5.41, 95% CI 2.71, 10.8 in MC), with DPB1*02:01, DRB1*16:01 and DRB1*04:04 best predicting RA (positive predictive value 61%). Several genetic-respiratory disease interactions strongly drive RA onset. If confirmed, these novel associations may reflect RA endotypes that can facilitate individualised prevention, diagnosis and treatment.
ITGA5<sup>+</sup>synovial fibroblasts orchestrate proinflammatory niche formation by remodelling the local immune microenvironment in rheumatoid arthritis
Authors: Linli Zheng, Minghui Gu, Xiang Li, Xuantao Hu, Chen Chen, Yunze Kang, Baiqi Pan, Weishen Chen, Guoyan Xian, Xiaoyu Wu, Chengxin Li, Chao Wang, Zhiwen Li, Mingqiang Guan, Guanming Zhou, Ali Mobasheri, Weidong Song, Sui Peng, Puyi Sheng, Ziji Zhang
Journal: Annals of the Rheumatic Diseases (2024)

To investigate the phenotypic heterogeneity of tissue-resident synovial fibroblasts and their role in inflammatory response in rheumatoid arthritis (RA). We used single-cell and spatial transcriptomics to profile synovial cells and spatial gene expressions of synovial tissues to identify phenotypic changes in patients with osteoarthritis, RA in sustained remission and active state. Immunohistology, multiplex immunofluorescence and flow cytometry were used to identify synovial fibroblasts subsets. Deconvolution methods further validated our findings in two cohorts (PEAC and R4RA) with treatment response. Cell coculture was used to access the potential cell-cell interactions. Adoptive transfer of synovial cells in collagen-induced arthritis (CIA) mice and bulk RNA sequencing of synovial joints further validate the cellular functions. We identified a novel tissue-remodelling CD45-CD31-PDPN+ITGA5+ synovial fibroblast population with unique transcriptome of POSTN, COL3A1, CCL5 and TGFB1, and enriched in immunoregulatory pathways. This subset was upregulated in active and lympho-myeloid type of RA, associated with an increased risk of multidrug resistance. Transforming growth factor (TGF)-β1 might participate in the differentiation of this subset. Moreover, ITGA5+ synovial fibroblasts might occur in early stage of inflammation and induce the differentiation of CXCL13hiPD-1hi peripheral helper T cells (TPHs) from naïve CD4+ T cells, by secreting TGF-β1. Intra-articular injection of ITGA5+ synovial fibroblasts exacerbates RA development and upregulates TPHs in CIA mice. We demonstrate that ITGA5+ synovial fibroblasts might regulate the RA progression by inducing the differentiation of CXCL13hiPD-1hi TPHs and remodelling the proinflammatory microenvironments. Therapeutic modulation of this subpopulation could therefore be a potential treatment strategy for RA.
Standardising health history and injury surveillance of participants in endurance events: a modified Delphi consensus statement from the AMSSM runner health consortium
Authors: Adam S Tenforde, Emily Kraus, Stephanie A Kliethermes, Mark A Fontana, Michelle T Barrack, Mary Dubon, Ida A Heikura, Karsten Hollander, Emily Kroshus, Mikel R Joachim, Alexandre Dias Lopes, Mitchell J Rauh, Ragen Chastain, Mark Harrast, Bryan Heiderscheit, Brian J Krabak, Emily M Miller, Christopher Napier, William O Roberts, Deborah Roche, Megan Roche, Allison N Schroeder, Dezmond Taylor-Douglas, Kate Tenforde, Evert Verhagen, Stuart J Warden, Richard W Willy, Brett G Toresdahl
Journal: British Journal of Sports Medicine (2024)

Endurance events are popular worldwide and have many health benefits. However, runners and Para athletes may sustain musculoskeletal injuries or experience other health consequences from endurance events. The American Medical Society for Sports Medicine (AMSSM) Runner Health Consortium aimed to generate consensus-based survey items for use in prospective research to identify risk factors for injuries in runners and Para athletes training and competing in endurance events. The study design employed a modified Delphi approach, with a panel comprising 28 experts, including healthcare professionals, coaches, and athletes. Potential survey items were generated by panel members who subsequently engaged in three rounds of voting using Research Electronic Data Capture. Items were graded by clarity, relevance, and importance. Items achieving 80% consensus on all three aspects were retained. The response rate was 100% in R round 1 and 96% in Rrounds 2 and 3. Of 124 initial survey items, consensus was reached on 53, 34 and 22 items during Rrounds 1, 2, and 3, respectively. Two accepted items were removed due to redundancy. Combined with 10 non-voting items, 117 items covered key domains, including training and injury history, dietary behaviours and associated factors (such as menstrual function), footwear, mental health, and specific considerations for Para athletes. The consensus-based survey items should be considered by researchers to better understand the health of runners and Para athletes who train and compete in endurance sports to identify risk factors for injury.
Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems
Authors: Ludger J E Goeminne, Anastasiya Vladimirova, Alec Eames, Alexander Tyshkovskiy, M Austin Argentieri, Kejun Ying, Mahdi Moqri, Vadim N Gladyshev
Journal: Cell Metabolism (2024)
Zero-shot counting with a dual-stream neural network model
Authors: Jessica A.F. Thompson, Hannah Sheahan, Tsvetomira Dumbalska, Julian D. Sandbrink, Manuela Piazza, Christopher Summerfield
Journal: Neuron (2024)

To understand a visual scene, observers need to both recognize objects and encode relational structure. For example, a scene comprising three apples requires the observer to encode concepts of "apple" and "three." In the primate brain, these functions rely on dual (ventral and dorsal) processing streams. Object recognition in primates has been successfully modeled with deep neural networks, but how scene structure (including numerosity) is encoded remains poorly understood. Here, we built a deep learning model, based on the dual-stream architecture of the primate brain, which is able to count items "zero-shot"-even if the objects themselves are unfamiliar. Our dual-stream network forms spatial response fields and lognormal number codes that resemble those observed in the macaque posterior parietal cortex. The dual-stream network also makes successful predictions about human counting behavior. Our results provide evidence for an enactive theory of the role of the posterior parietal cortex in visual scene understanding.
Concurrent SOS1 and MEK suppression inhibits signaling and growth of NF1-null melanoma
Authors: Michelangelo Marasco, Dinesh Kumar, Tessa Seale, Santiago Garcia Borrego, Esther Kaplun, Ilinca Aricescu, Soren Cole, Besnik Qeriqi, Juan Qiu, Xiaoping Chen, Amber Bahr, Deborah Fidele, Marco H. Hofmann, Daniel Gerlach, Fabio Savarese, Taha Merghoub, Jedd D. Wolchok, Zhan Yao, Elisa de Stanchina, David Solit, Sandra Misale, Neal Rosen
Journal: Cell Reports Medicine (2024)

Neurofibromin (NF1) is a negative regulator of RAS signaling, frequently mutated in cancer. NF1-mutant melanoma is a highly malignant tumor for which targeted therapies are lacking. Here, we use biochemical and pharmacological assays on patient-derived models and isogenic cell lines to identify potential pharmacologic targets, revealing that NF1-null melanomas are dependent on RAS activation and that MEK inhibition relieves ERK-dependent negative feedback, increasing RAS signaling. MEK inhibition with avutometinib abrogates the adaptive rebound in ERK signaling, but the antitumor effects are limited. However, concurrent inhibition of MEK and SOS1 abrogates ERK activation, induces cell death, and suppresses tumor growth. In contrast to the NF1-deficient setting, concurrent SOS1 and SOS2 depletion is required to completely inhibit RAS signaling in NF1 wild-type cells. In sum, our data provide a mechanistic rationale for enhancing the therapeutic efficacy of MEK inhibitors by exploiting the lower residual SOS activity in NF1-null tumor cells.
Navigating the changing landscape of BTK-targeted therapies for B cell lymphomas and chronic lymphocytic leukaemia
Authors: Michele D. Stanchina, Skye Montoya, Alexey V. Danilov, Jorge J. Castillo, Alvaro J. Alencar, Julio C. Chavez, Chan Y. Cheah, Carlos Chiattone, Yucai Wang, Meghan Thompson, Paolo Ghia, Justin Taylor, Juan Pablo Alderuccio
Journal: Nature Reviews Clinical Oncology (2024)
Characterization of a novel HIV-1 second-generation circulating recombinant form (CRF172_0755) among men who have sex with men in China
Authors: Huan Li, Yi Feng, Yang Xu, Tang Li, Qi Li, Wei Lin, Wanqi Ni, Jianwei Yang, Wansi Mao, Zheng Wang, Hui Xing
Journal: Journal of Infection (2024)
The influence of lifestyle and environmental factors on host resilience through a homeostatic skin microbiota: An <scp>EAACI</scp> Task Force Report
Authors: Inge Kortekaas Krohn, Chris Callewaert, Hafsa Belasri, Britta De Pessemier, Celia Diez Lopez, Charlotte G. Mortz, Liam O'Mahony, Marina Pérez‐Gordo, Milena Sokolowska, Zsofia Unger, Eva Untersmayr, Bernhard Homey, Cristina Gomez‐Casado
Journal: Allergy (2024)

Abstract Human skin is colonized with skin microbiota that includes commensal bacteria, fungi, arthropods, archaea and viruses. The composition of the microbiota varies at different anatomical locations according to changes in body temperature, pH, humidity/hydration or sebum content. A homeostatic skin microbiota is crucial to maintain epithelial barrier functions, to protect from invading pathogens and to interact with the immune system. Therefore, maintaining homeostasis holds promise to be an achievable goal for microbiome‐directed treatment strategies as well as a prophylactic strategy to prevent the development of skin diseases, as dysbiosis or disruption of homeostatic skin microbiota is associated with skin inflammation. A healthy skin microbiome is likely modulated by genetic as well as environmental and lifestyle factors. In this review, we aim to provide a complete overview of the lifestyle and environmental factors that can contribute to maintaining the skin microbiome healthy. Awareness of these factors could be the basis for a prophylactic strategy to prevent the development of skin diseases or to be used as a therapeutic approach.
Near Real-Time Severe Acute Respiratory Illness Surveillance Characterising Influenza and COVID-19 Epidemiology in Hospitalised Adults, 2021-22
Authors: Antonia Ho, Neil McInnes, Andrew Blunsum, Joanna Quinn, Daniel Lynagh, Michael E. Murphy, Rory Gunson, Alisdair MacConnachie, David J. Lowe
Journal: Journal of Infection (2024)

Highlights•Syndromic adult SARI surveillance provided near real-time data to PHS & clinicians•SARS-CoV-2 dominant pathogen in 2021/22 season, but influenza activity was low•60% required supplemental oxygen, but only ~1% required mechanical ventilation•45% had appropriate microbiological investigations but 75% received antibiotics•Male, multimorbidity, frailty, RR>30, low GCS & consolidation predicted mortalityAbstractObjectivesWe report the findings of a novel enhanced syndromic surveillance which characterised influenza- and SARS-CoV-2-associated severe acute respiratory illness (SARI) in the 2021/2022 winter season.MethodsProspective cohort study of adults admitted to the Queen Elizabeth University Hospital, Glasgow, with a severe acute respiratory illness. Patient demographics, clinical history, admission details, and outcome were recorded. Data were available to Public Health Scotland (PHS) and clinicians weekly.ResultsBetween November 2021 and May 2022, 1,063 hospitalised SARI episodes in 1,037 adult patients were identified. Median age was 72.0 years and 44.5% were male. Most (82.6%) SARI cases had >1 co-morbidity; chronic lung disease (50.0%) and malignancy (22.5%) were the most frequently reported.Overall, 229 (22%) and 33 (3%) SARI episodes were SARS-CoV-2 and influenza A PCR positive, respectively. 74.7%, 6.5% and 43.0% SARI episodes received antibiotics, antivirals, and steroids, respectively (54.5, 11.0 and 51.3% among COVID-19 patients). 1.1% required mechanical ventilation and 7.8% died. Male sex, multimorbidity, frailty, respiratory rate >30, low GCS and chest X-ray consolidation were predictive of in-hospital mortality.ConclusionNear real-time hospitalised SARI syndromic surveillance characterised the evolving clinical epidemiology of SARS-CoV-2 and influenza, high antimicrobial use, and predictors of inpatient mortality among hospitalised SARI patients.
Neuroplasticity and neuroimmune interactions in fatal asthma
Authors: Guilherme Dragunas, Carli S. Koster, Natalia de Souza Xavier Costa, Barbro N. Melgert, Carolina D. Munhoz, Reinoud Gosens, Thais Mauad
Journal: Allergy (2024)

Alteration of airway neuronal function and density and bidirectional interaction between immune cells and sensory peripheral nerves have been proposed to trigger and perpetuate inflammation that contribute to asthma severity. To date, few studies analysed neuroplasticity and neuroinflammation in tissue of asthmatic individuals. We hypothesized that the presence of these phenomena would be a pathological feature in fatal asthma. We have quantified the expression of the pan-neuronal marker PGP9.5 and the neuronal sensory-derived neuropeptide calcitonin gene-related peptide (CGRP) in the large airways of 12 individuals deceased due to an asthma attack and compared to 10 control lung samples. The proximity between nerve bundles to eosinophils, mast cells and CADM1+ cells was also quantified. We have additionally developed a hPSC-derived sensory neuron/mast cell co-culture model, from where mast cells were purified and differences in gene expression profile assessed. Fatal asthma patients presented a higher PGP9.5 and CGRP positive area in the airways, indicating sensory neuroplasticity. Eosinophils, mast cells and CADM1+ cells were observed in close contact or touching the airway nerve bundles, and this was found to be statistically higher in fatal asthma samples. In vitro co-culture model showed that human mast cells adhere to sensory neurons and develop a distinct gene expression profile characterized by upregulated expression of genes related to heterophilic adhesion, activation and differentiation markers, such as CADM4, PTGS2, C-KIT, GATA2, HDC, CPA3, ATXN1 and VCAM1. Our results support a significant role for neuroplasticity and neuroimmune interactions in fatal asthma, that could be implicated in the severity of the fatal attack. Accordingly, the presence of physical neuron and mast cell interaction leads to differential gene expression profile in the later cell type.
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Authors: Xue-Ping Wang, Stephanie M. Mutchler, Rolando Carrisoza-Gaytan, Andrew J. Nickerson, Catherine J. Baty, Mohammad Al-Bataineh, Amber Vandevender, Tetsuji Morimoto, Priyanka Srinivasan, Roderick J. Tan, Michael J. Jurczak, Lisa M. Satlin, Ossama B. Kashlan
Journal: Journal of the American Society of Nephrology (2024)
Why is alcohol so normalised in Europe?
Authors: None The Lancet Regional Health – Europe
Journal: The Lancet Regional Health - Europe (2024)

Eight of the ten countries with the highest global alcohol consumption per-capita are located in the WHO European Region. Considering this level of consumption, it is not surprising that the Region has the highest number of alcohol-attributable deaths per 100,000 persons accounting for nearly one in 11 of all deaths.