tbuckley/cabot-search huggingface dataset:
Screening of Environmental Chemicals to Characterize Exposures in Participants With Systemic Lupus Erythematosus
Authors: Cristina M. Lanata, Kimberly E. Taylor, James Hurst‐Hopf, Joanne Nititham, Ashira Blazer, Laura Trupin, Patricia Katz, Maria Dall'Era, Jinoos Yazdany, Sharon A. Chung, Dimitri Abrahamsson, Roy Gerona, Lindsey A. Criswell
Journal: Arthritis & Rheumatology (2023)

Objective There is a need to characterize exposures associated with the pathogenesis of systemic lupus erythematosus (SLE). In this pilot study, we explore a hypothesis‐free approach that can measure thousands of exogenous chemicals in blood (“exposome”) in patients with SLE and unaffected controls. Methods This cross‐sectional study analyzed a cohort of patients with prevalent SLE (n = 285) and controls (n = 106). Plasma was analyzed by liquid chromatography–quadrupole time‐of‐flight mass spectrometry (LC‐QTOF/MS). Mass spectrometry features present in at least 25% of all samples were selected for association analysis (n = 2,737). Features were matched to potential chemicals using available databases. Association analysis of abundances of features with SLE status was performed, adjusting for age and sex. We also explored features associated with SLE phenotypes, sociodemographic factors, and current medication use. Results We found 30 features significantly associated with SLE status (Bonferroni P &lt; 0.05). Of these, seven matched chemical names based on databases. These seven features included phthalate metabolites, a formetanate metabolite, and eugenol. The abundance of acid pesticides differed between patients with SLE and controls (Bonferroni P &lt; 0.05). Two unmatched features were associated with a history of lupus nephritis, and one with anti–double‐stranded DNA antibody production (Bonferroni P &lt; 0.05). Seventeen features varied by self‐reported race and ethnicity, including a polyfluoroalkyl substance (analysis of variance P &lt; 1.69 × 10 −5 ). Eleven features correlated with antimalarials, 6 with mycophenolate mofetil, and 29 with prednisone use. Conclusion This proof‐of‐concept study demonstrates that LC‐QTOF/MS is a powerful tool that agnostically detects circulating exogenous compounds. These analyses can generate hypotheses of disease‐related exposures for future prospective, longitudinal studies. image
Advances in machine intelligence‐driven virtual screening approaches for big‐data
Authors: Neeraj Kumar, Vishal Acharya
Journal: Medicinal Research Reviews (2023)

Virtual screening (VS) is an integral and ever-evolving domain of drug discovery framework. The VS is traditionally classified into ligand-based (LB) and structure-based (SB) approaches. Machine intelligence or artificial intelligence has wide applications in the drug discovery domain to reduce time and resource consumption. In combination with machine intelligence algorithms, VS has emerged into revolutionarily progressive technology that learns within robust decision orders for data curation and hit molecule screening from large VS libraries in minutes or hours. The exponential growth of chemical and biological data has evolved as "big-data" in the public domain demands modern and advanced machine intelligence-driven VS approaches to screen hit molecules from ultra-large VS libraries. VS has evolved from an individual approach (LB and SB) to integrated LB and SB techniques to explore various ligand and target protein aspects for the enhanced rate of appropriate hit molecule prediction. Current trends demand advanced and intelligent solutions to handle enormous data in drug discovery domain for screening and optimizing hits or lead with fewer or no false positive hits. Following the big-data drift and tremendous growth in computational architecture, we presented this review. Here, the article categorized and emphasized individual VS techniques, detailed literature presented for machine learning implementation, modern machine intelligence approaches, and limitations and deliberated the future prospects.
Edge computing in wildlife behavior and ecology
Authors: Hui Yu, Guillermo J. Amador, Antoine Cribellier, Marcel Klaassen, Henrik J. de Knegt, Marc Naguib, Reindert Nijland, Lukasz Nowak, Herbert H.T. Prins, Lysanne Snijders, Chris Tyson, Florian T. Muijres
Journal: Trends in Ecology & Evolution (2023)

Modern sensor technologies increasingly enrich studies in wildlife behavior and ecology. However, constraints on weight, connectivity, energy and memory availability limit their implementation. With the advent of edge computing, there is increasing potential to mitigate these constraints, and drive major advancements in wildlife studies.
SGLT2 Inhibition and Tubular Sodium Handling
Authors: Biff F. Palmer, Deborah J. Clegg
Journal: Journal of the American Society of Nephrology (2023)

1Internal Medicine, Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas 2Internal Medicine, Vice President for Research, Texas Tech Health Sciences Center, El Paso, Texas Correspondence: Dr. Biff F. Palmer, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390. Email: [email protected] See related article, "Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects," on pages 189–201.
Unsupervised machine learning to investigate trajectory patterns of COVID-19 symptoms and physical activity measured via the MyHeart Counts App and smart devices
Authors: Varsha Gupta, Sokratis Kariotis, Mohammed D. Rajab, Niamh Errington, Elham Alhathli, Emmanuel Jammeh, Martin Brook, Naomi Meardon, Paul Collini, Joby Cole, Jim M. Wild, Steven Hershman, Ali Javed, A. A. Roger Thompson, Thushan de Silva, Euan A. Ashley, Dennis Wang, Allan Lawrie
Journal: npj Digital Medicine (2023)

Abstract Previous studies have associated COVID-19 symptoms severity with levels of physical activity. We therefore investigated longitudinal trajectories of COVID-19 symptoms in a cohort of healthcare workers (HCWs) with non-hospitalised COVID-19 and their real-world physical activity. 121 HCWs with a history of COVID-19 infection who had symptoms monitored through at least two research clinic visits, and via smartphone were examined. HCWs with a compatible smartphone were provided with an Apple Watch Series 4 and were asked to install the MyHeart Counts Study App to collect COVID-19 symptom data and multiple physical activity parameters. Unsupervised classification analysis of symptoms identified two trajectory patterns of long and short symptom duration. The prevalence for longitudinal persistence of any COVID-19 symptom was 36% with fatigue and loss of smell being the two most prevalent individual symptom trajectories (24.8% and 21.5%, respectively). 8 physical activity features obtained via the MyHeart Counts App identified two groups of trajectories for high and low activity. Of these 8 parameters only ‘distance moved walking or running’ was associated with COVID-19 symptom trajectories. We report a high prevalence of long-term symptoms of COVID-19 in a non-hospitalised cohort of HCWs, a method to identify physical activity trends, and investigate their association. These data highlight the importance of tracking symptoms from onset to recovery even in non-hospitalised COVID-19 individuals. The increasing ease in collecting real-world physical activity data non-invasively from wearable devices provides opportunity to investigate the association of physical activity to symptoms of COVID-19 and other cardio-respiratory diseases.
Real life evaluation of AlphaMissense predictions in hematological malignancies
Authors: Kaddour Chabane, Carole Charlot, Dan Gugenheim, Thomas Simonet, David Armisen, Pierre-Julien Viailly, Guillaume Codet de Boisse, Sarah Huet, Sandrine Hayette, Vincent Alcazer, Pierre Sujobert
Journal: Leukemia (2023)
Early life risk factors of Atopic March in a high‐risk, minority, urban, low‐income, prospective birth cohort
Authors: Gaofeng Wang, Junjun Chen, Joy Wan, Yuelong Ji, Chunhua Zhang, Evan Sweren, Sashank K. Reddy, Xiaobin Wang, Luis A. Garza, Xiumei Hong
Journal: Allergy (2023)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The role of multimorbidity in patients with heart failure across the left ventricular ejection fraction spectrum: Data from the Swedish Heart Failure Registry
Authors: Daniela Tomasoni, Cristiana Vitale, Federica Guidetti, Lina Benson, Frieder Braunschweig, Ulf Dahlström, Michael Melin, Giuseppe M.C. Rosano, Lars H. Lund, Marco Metra, Gianluigi Savarese
Journal: European Journal of Heart Failure (2023)

The aim of this analysis was to provide data on the overall comorbidity burden, both cardiovascular (CV) and non-CV, in a large real-world heart failure (HF) population across the ejection fraction (EF).
Effects of calibrated blue–yellow changes in light on the human circadian clock
Authors: Christine Blume, Christian Cajochen, Isabel Schöllhorn, Helen C. Slawik, Manuel Spitschan
Journal: Nature Human Behaviour (2023)

Evening exposure to short-wavelength light can affect the circadian clock, sleep and alertness. Intrinsically photosensitive retinal ganglion cells expressing melanopsin are thought to be the primary drivers of these effects. Whether colour-sensitive cones also contribute is unclear. Here, using calibrated silent-substitution changes in light colour along the blue-yellow axis, we investigated whether mechanisms of colour vision affect the human circadian system and sleep. In a 32.5-h repeated within-subjects protocol, 16 healthy participants were exposed to three different light scenarios for 1 h starting 30 min after habitual bedtime: baseline control condition (93.5 photopic lux), intermittently flickering (1 Hz, 30 s on-off) yellow-bright light (123.5 photopic lux) and intermittently flickering blue-dim light (67.0 photopic lux), all calibrated to have equal melanopsin excitation. We did not find conclusive evidence for differences between the three lighting conditions regarding circadian melatonin phase delays, melatonin suppression, subjective sleepiness, psychomotor vigilance or sleep.The Stage 1 protocol for this Registered Report was accepted in principle on 9 September 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13050215.v1 .
Diminished airway host innate response in people with cystic fibrosis who experience frequent pulmonary exacerbations
Authors: Claire J. Houston, Aya Alkhatib, Gísli G. Einarsson, Michael M. Tunney, Clifford C. Taggart, Damian G. Downey
Journal: European Respiratory Journal (2023)

Rationale Pulmonary exacerbations are clinically impactful events that accelerate cystic fibrosis (CF) lung disease progression. The pathophysiological mechanisms underlying an increased frequency of pulmonary exacerbations have not been explored. Objectives To compare host immune response during intravenous antibiotic treatment of pulmonary exacerbations in people with CF who have a history of frequent versus infrequent exacerbations. Methods Adults with CF were recruited at onset of antibiotic treatment of a pulmonary exacerbation and were categorised as infrequent or frequent exacerbators based on their pulmonary exacerbation frequency in the previous 12 months. Clinical parameters, sputum bacterial load and sputum inflammatory markers were measured on day 0, day 5 and at the end of treatment. Shotgun proteomic analysis was performed on sputum using liquid chromatography-mass spectrometry. Measurements and main results Many sputum proteins were differentially enriched between infrequent and frequent exacerbators (day 0 n=23 and day 5 n=31). The majority of these proteins had a higher abundance in infrequent exacerbators and were secreted innate host defence proteins with antimicrobial, antiprotease and immunomodulatory functions. Several differentially enriched proteins were validated using ELISA and Western blot including secretory leukocyte protease inhibitor (SLPI), lipocalin-1 and cystatin SA. Sputum from frequent exacerbators demonstrated potent ability to cleave exogenous recombinant SLPI in a neutrophil elastase dependent manner. Frequent exacerbators had increased sputum inflammatory markers (interleukin (IL)-1β and IL-8) and total bacterial load compared to infrequent exacerbators. Conclusions A diminished innate host protein defence may play a role in the pathophysiological mechanisms of frequent CF pulmonary exacerbations. Frequent exacerbators may benefit from therapies targeting this dysregulated host immune response.
Efficacy and safety of adjuvant immunoadsorption in pemphigus vulgaris and pemphigus foliaceus (IA-Pem Study): a multicentre randomised controlled trial
Authors: Nina van Beek, Rüdiger Eming, Alexander Reuss, Detlef Zillikens, Miklós Sárdy, Claudia Günther, Dimitra Kiritsi, Sandrine Benoit, Stefan Beissert, Regine Gläser, Harald Gollnick, Orsolya N Horváth, Christiane Pfeiffer, Martin Röcken, Franziska Schauer, Stephan Schreml, Kerstin Steinbrink, Alexander Zink, Carmen Schade-Brittinger, Michael Hertl, Enno Schmidt
Journal: British Journal of Dermatology (2023)

Abstract Background Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. Objectives To assess the clinical efficacy of IA in addition to best medical treatment (BMT). Methods We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42–72 years) comparing BMT (prednisolone 1.0 mg kg−1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan–Meier and Cox regression methods. Results The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68–2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference −1214, 95% CI −2225 to −70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). Conclusions In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.
Glucose‐mediated mitochondrial reprogramming by cholesterol export at TM4SF5‐enriched mitochondria‐lysosome contact sites
Authors: Ji Eon Kim, So‐Young Park, Chulhwan Kwak, Yoonji Lee, Dae‐Geun Song, Jae Woo Jung, Haesong Lee, Eun‐Ae Shin, Yangie Pinanga, Kyung‐hee Pyo, Eun Hae Lee, Wonsik Kim, Soyeon Kim, Chang‐Duck Jun, Jeanho Yun, Sun Choi, Hyun‐Woo Rhee, Kwang‐Hyeon Liu, Jung Weon Lee
Journal: Cancer Communications (2023)

Transmembrane 4 L six family member 5 (TM4SF5) translocates subcellularly and functions metabolically, although it is unclear how intracellular TM4SF5 translocation is linked to metabolic contexts. It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms.
Skin photoageing following sun exposure is associated with decreased epigenetic and biologic age, and correlates with basal cell carcinoma phenotype
Authors: Richie Jeremian, Alexandra Malinowski, Yuliya Lytvyn, Jorge R Georgakopoulos, Anastasiya Muntyanu, Asfandyar Mufti, Philippe Lefrançois, Jensen Yeung, Ivan V Litvinov
Journal: British Journal of Dermatology (2023)

This study investigated epigenetic changes, specifically epigenetic ageing, in an adult cohort of healthy individuals using five validated epigenetic clock algorithms and a DNA methylation-based estimator of telomere length. Our study demonstrated significant biologic/epigenetic age dysregulation in sun-exposed vs. sun-protected dermal and epidermal skin, with a strong correlation to the validated Helfrich skin photoageing scale, occurring in patterns that overlap with those seen in basal cell carcinoma. This work highlights the power of novel epigenetic analyses in studying photoageing and skin cancer predisposition.
Paving the way for greater open science in sports and exercise medicine: navigating the barriers to adopting open and accessible data practices
Authors: Garrett S Bullock, Patrick Ward, Stefan Kluzek, Tom Hughes, Ellen Shanley, Amelia Joanna Hanford Arundale, Craig Ranson, Sophia Nimphius, Richard D Riley, Gary S Collins, Franco M Impellizzeri
Journal: British Journal of Sports Medicine (2023)
Guselkumab demonstrates long-term efficacy and maintenance of treatment response postwithdrawal in systemic treatment-naïve patients and nonresponders to fumaric acid esters: results from parts II and III of a randomized active-comparator-controlled phase IIIb trial (POLARIS)
Authors: Diamant Thaçi, Andreas Pinter, Michael Sebastian, Christian Termeer, Michael Sticherling, Sascha Gerdes, Knut Schäkel, Sven Wegner, Stefanie Krampe, Holger Bartz, Christian Rausch, Friedemann Taut, Kilian Eyerich
Journal: British Journal of Dermatology (2023)

The anti-interleukin-23 antibody guselkumab (GUS) demonstrated favourable week 24 efficacy and safety over fumaric acid esters (FAE) in systemic treatment-naïve patients with moderate-to-severe plaque psoriasis (study part I).
Dexamethasone potentiates chimeric antigen receptor T cell persistence and function by enhancing IL-7Rα expression
Authors: Ashlie M Munoz, Ryan Urak, Ellie Taus, Hui-Ju Hsieh, Dennis Awuah, Vibhuti Vyas, Laura Lim, Katherine Jin, Shu-Hong Lin, Saul J Priceman, Mary C Clark, Lior Goldberg, Stephen J Forman, Xiuli Wang
Journal: Molecular Therapy (2023)

Dexamethasone (dex) is a glucocorticoid that is a mainstay for the treatment of inflammatory pathologies, including immunotherapy-associated toxicities, yet the specific impact of dex on the activity of CAR T cells is not fully understood. We assessed whether dex treatment given ex vivo or as an adjuvant in vivo with CAR T cells impacted the phenotype or function of CAR T cells. We demonstrated that CAR T cell expansion and function were not inhibited by dex. We confirmed this observation using multiple CAR constructs and tumor models, suggesting that this is a general phenomenon. Moreover, we determined that dex upregulated interleukin-7 receptor α on CAR T cells and increased the expression of genes involved in activation, migration, and persistence when supplemented ex vivo. Direct delivery of dex and IL-7 into tumor-bearing mice resulted in increased persistence of adoptively transferred CAR T cells and complete tumor regression. Overall, our studies provide insight into the use of dex to enhance CAR T cell therapy and represent potential novel strategies for augmenting CAR T cell function during production as well as following infusion into patients.
Catheter size and risk of short-term peripheral venous catheter-associated bloodstream infections: an observational study
Authors: Matteo Faltoni, Gaud Catho, Eva Pianca, Basilice Minka-Obama, Marie-Céline Zanella, Marie-Nöelle Chraiti, Loïc Fortchantre, Stephan Harbarth, Niccolὸ Buetti
Journal: Clinical Microbiology and Infection (2023)
Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas
Authors: Odessica Hughes, Amy R. Bentley, Charles E. Breeze, Francois Aguet, Xiaoguang Xu, Girish Nadkarni, Quan Sun, Bridget M. Lin, Thomas Gilliland, Mariah C. Meyer, Jiawen Du, Laura M. Raffield, Holly Kramer, Robert W. Morton, Mateus H. Gouveia, Elizabeth G. Atkinson, Adan Valladares-Salgado, Niels Wacher-Rodarte, Nicole D. Dueker, Xiuqing Guo, Yang Hai, Adebowale Adeyemo, Lyle G. Best, Jianwen Cai, Guanjie Chen, Michael Chong, Ayo Doumatey, James Eales, Mark O. Goodarzi, Eli Ipp, Marguerite Ryan Irvin, Minzhi Jiang, Alana C. Jones, Charles Kooperberg, Jose E. Krieger, Ethan M. Lange, Matthew B. Lanktree, James P. Lash, Paulo A. Lotufo, Ruth J.F. Loos, Vy Thi Ha My, Jesús Peralta-Romero, Lihong Qi, Leslie J. Raffel, Stephen S. Rich, Erik J. Rodriquez, Eduardo Tarazona-Santos, Kent D. Taylor, Jason G. Umans, Jia Wen, Bessie A. Young, Zhi Yu, Ying Zhang, Yii-Der Ida Chen, Tanja Rundek, Jerome I. Rotter, Miguel Cruz, Myriam Fornage, Maria Fernanda Lima-Costa, Alexandre C. Pereira, Guillaume Paré, Pradeep Natarajan, Shelley A. Cole, April P. Carson, Leslie A. Lange, Yun Li, Eliseo J. Perez-Stable, Ron Do, Fadi J. Charchar, Maciej Tomaszewski, Josyf C. Mychaleckyj, Charles Rotimi, Andrew P. Morris, Nora Franceschini
Journal: Cell Genomics (2023)

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.
Restoration of a paraventricular thalamo-accumbal behavioral suppression circuit prevents reinstatement of heroin seeking
Authors: Jacqueline E. Paniccia, Kelsey M. Vollmer, Lisa M. Green, Roger I. Grant, Kion T. Winston, Sophie Buchmaier, Annaka M. Westphal, Rachel E. Clarke, Elizabeth M. Doncheck, Bogdan Bordieanu, Logan M. Manusky, Michael R. Martino, Amy L. Ward, Jennifer A. Rinker, Jacqueline F. McGinty, Michael D. Scofield, James M. Otis
Journal: Neuron (2023)
Tissue factor binds to and inhibits interferon-α receptor 1 signaling
Authors: Jayakumar Manoharan, Rajiv Rana, Georg Kuenze, Dheerendra Gupta, Ahmed Elwakiel, Saira Ambreen, Hongjie Wang, Kuheli Banerjee, Silke Zimmermann, Kunal Singh, Anubhuti Gupta, Sameen Fatima, Stefanie Kretschmer, Liliana Schaefer, Jinyang Zeng-Brouwers, Constantin Schwab, Moh’d Mohanad Al-Dabet, Ihsan Gadi, Heidi Altmann, Thea Koch, David M. Poitz, Ronny Baber, Shrey Kohli, Khurrum Shahzad, Robert Geffers, Min Ae Lee-Kirsch, Ulrich Kalinke, Jens Meiler, Nigel Mackman, Berend Isermann
Journal: Immunity (2023)