tbuckley/cabot-search huggingface dataset:
Attitudes and Beliefs Associated With COVID-19 Vaccination During Pregnancy
Authors: Yiwen Cui, Kole Binger, Anna Palatnik
Journal: JAMA Network Open (2022)

interventions to address vaccine hesitancy in pregnant people.For example, local and national health campaigns can provide real-time access of pregnant people and their health care clinicians to the growing scientific evidence demonstrating transplacental and breastmilk antibody transfer following COVID-19 vaccination. [4]5][6] It is also important to continue research maintaining vaccination in pregnancy registries and publish data on long-term health outcomes of vaccinated pregnant people and their infants.The limitations of this study include low representation of racial groups other than Black and White, and the results may not be representative of other US regions, and a cross-sectional survey design with assessment of attitudes toward COVID-19 vaccination only once during pregnancy.
Fuzzy Logic: How the Practicalities of State Involvement Shape the Most Ethically Supportable Way Forward
Authors: Jessica M. Turnbull, Daniel J. Benedetti
Journal: The American Journal of Bioethics (2022)

"Fuzzy Logic: How the Practicalities of State Involvement Shape the Most Ethically Supportable Way Forward." The American Journal of Bioethics, 22(4), pp. 83–84This article refers to:Enrolling Adolescents with Rare Disease for Early Phase Clinical Trials While Under the Care of Child Protection Services: Balancing Protection and Access Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Triggering receptor expressed on myeloid cells-1 (TREM-1) inhibition in atherosclerosis
Authors: Anastasios Panagopoulos, Saurabhi Samant, Jules Joel Bakhos, Martin Liu, Behram Khan, Janaki Makadia, Fayaz Muhammad, Forrest M. Kievit, Devendra K. Agrawal, Yiannis S. Chatzizisis
Journal: Pharmacology & Therapeutics (2022)
Suboptimal antibody response against SARS-CoV-2 Omicron variant after third dose of mRNA vaccine in kidney transplant recipients
Authors: Ayman Al Jurdi, Rodrigo B. Gassen, Thiago J. Borges, Isadora T. Lape, Leela Morena, Orhan Efe, Zhabiz Solhjou, Rania El Fekih, Christa Deban, Brigid Bohan, Vikram Pattanayak, Camille N. Kotton, Jamil R. Azzi, Leonardo V. Riella
Journal: Kidney International (2022)
Benefits and Harms of ‘Smart Drugs’ (Nootropics) in Healthy Individuals
Authors: Fabrizio Schifano, Valeria Catalani, Safia Sharif, Flavia Napoletano, John Martin Corkery, Davide Arillotta, Suzanne Fergus, Alessandro Vento, Amira Guirguis
Journal: Drugs (2022)
Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study
Authors: William V Tamborlane, Lori M Laffel, Naim Shehadeh, Elvira Isganaitis, Michelle Van Name, Jayantha Ratnayake, Cecilia Karlsson, Ensio Norjavaara
Journal: The Lancet Diabetes & Endocrinology (2022)
Gene therapy access: Global challenges, opportunities, and views from Brazil, South Africa, and India
Authors: Kenneth Cornetta, Martín Bonamino, Johnny Mahlangu, Federico Mingozzi, Savita Rangarajan, Jayandharan Rao
Journal: Molecular Therapy (2022)

Gene and cell therapies for a variety of life-limiting illnesses are under investigation, and a small number of commercial products have successfully obtained regulatory approval. The cost of treatment is high, and clinical studies evaluating safety and efficacy are performed predominately in high-income countries. We reviewed the current status of gene and cell therapies in low- and middle-income countries and highlighted the need and current barriers to access. The state of product development in Brazil, South Africa, and India is discussed, including lessons learned from American Society of Gene and Cell Therapy (ASGCT)-sponsored virtual symposia in each of these countries. Gene and cell therapies for a variety of life-limiting illnesses are under investigation, and a small number of commercial products have successfully obtained regulatory approval. The cost of treatment is high, and clinical studies evaluating safety and efficacy are performed predominately in high-income countries. We reviewed the current status of gene and cell therapies in low- and middle-income countries and highlighted the need and current barriers to access. The state of product development in Brazil, South Africa, and India is discussed, including lessons learned from American Society of Gene and Cell Therapy (ASGCT)-sponsored virtual symposia in each of these countries.
Differential regulation of transcription factor T-bet induction during NK cell development and T helper-1 cell differentiation
Authors: Difeng Fang, Kairong Cui, Yaqiang Cao, Mingzhu Zheng, Takeshi Kawabe, Gangqing Hu, Jaspal S Khillan, Dan Li, Chao Zhong, Dragana Jankovic, Alan Sher, Keji Zhao, Jinfang Zhu
Journal: Immunity (2022)
Translocation of an Anteater (<i>Tamandua tetradactyla</i>) Infected with Rabies from Virginia to Tennessee Resulting in Multiple Human Exposures, 2021
Authors: Heather N. Grome, Jane Yackley, Dilani Goonewardene, Andrew Cushing, Marcy Souza, Ariel Carlson, Linden Craig, Bryan Cranmore, Ryan Wallace, Lillian Orciari, Michael Niezgoda, Satheshkumar Panayampalli, Crystal Gigante, Mary-Margaret Fill, Timothy Jones, William Schaffner, John Dunn
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

On August 16, 2021, the Tennessee Department of Health (TDH) was notified of a positive rabies test result from a South American collared anteater (Tamandua tetradactyla) in Washington County, Tennessee. Tamanduas, or lesser anteaters, are a species of anteater in which rabies has not previously been reported. The animal was living at a Tennessee zoo and had been recently translocated from a zoo in Virginia. TDH conducted an investigation to confirm the rabies result, characterize the rabies variant, and ascertain an exposure risk assessment among persons who came into contact with the tamandua. Risk assessments for 22 persons were completed to determine the need for rabies postexposure prophylaxis (rPEP); rPEP was recommended for 13 persons, all of whom agreed to receive it. Using phylogenetic results of the virus isolated from the tamandua and knowledge of rabies epidemiology, public health officials determined that the animal was likely exposed to wild raccoons present at the Virginia zoo. This report describes expansion of the wide mammalian species diversity susceptible to rabies virus infection and summarizes the investigation, highlighting coordination among veterinary and human public health partners and the importance of preexposure rabies vaccination for animal handlers and exotic zoo animals.
Three-Month FVC Change: A Trial Endpoint for Idiopathic Pulmonary Fibrosis Based on Individual Participant Data Meta-analysis
Authors: Fasihul A. Khan, Iain Stewart, Samuel Moss, Laura Fabbri, Karen A. Robinson, Simon R. Johnson, R. Gisli Jenkins
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Novel therapies for idiopathic pulmonary fibrosis (IPF) are in development, but there remains uncertainty about the optimal trial endpoint. An earlier endpoint would enable assessment of a greater number of therapies in adaptive trial designs. Objectives: To determine whether short-term changes in FVC, DlCO, and six-minute-walk distance could act as surrogate endpoints to accelerate early-phase trials in IPF. Methods: Individual participant data (IPD) from IPF clinical trials were included in a two-step random-effects meta-analysis to determine whether baseline or 3-month changes in FVC, DlCO, and 6-minute-walk distance were associated with mortality or disease progression in placebo arms. Three-month and 12-month FVC decline endpoints were compared with treatment arm data from antifibrotic studies by meta-regression. Measurements and Main Results: IPD were available from 12 placebo cohorts totaling 1,819 participants, with baseline and 3-month changes in all physiological variables independently associated with poorer outcomes. Treatment data were available from six cohorts with 1,684 participants. For each 2.5% relative decline in FVC over 3 months, there was an associated 15% (adjusted hazard ratio, 1.15; 95% confidence interval [CI], 1.06-1.24; I2 = 59.4%) and 20% (adjusted hazard ratio, 1.20; 95% CI, 1.12-1.28; I2 = 18.0%) increased risk for mortality in untreated and treated individuals, respectively. An FVC change treatment effect was observed between treatment and placebo arms at 3 months (difference in FVC change of 42.9 ml; 95% CI, 24.0-61.8 ml; P < 0.001). Conclusions: IPD meta-analysis demonstrated that 3-month changes in physiological variables, particularly FVC, were associated with mortality among individuals with IPF. FVC change over 3 months may hold potential as a surrogate endpoint in IPF adaptive trials.
Acute Achilles’ Tendon Rupture — Surgery or No Surgery
Authors: Kristoffer W. Barfod, Per Hölmich
Journal: New England Journal of Medicine (2022)

Acute rupture of the Achilles' tendon can be a life-changing event, since it leaves many patients with permanent deficits. One year after injury, 4 in 10 patients with Achilles' tendon rupture have returned to their preinjury sport activities, and 1 in 2 patients considers their level of symptoms to be acceptable.1 Achilles' tendon rupture can be treated nonoperatively with the use of an ankle orthosis or surgically with open repair or minimally invasive surgery followed by the use of an ankle orthosis. The orthosis is worn for 6 to 9 weeks; it can be static, with the ankle joint immobilized, . . .
The Clinical Science of Euthymia: A Conceptual Map
Authors: Jenny Guidi, Giovanni A. Fava
Journal: Psychotherapy and Psychosomatics (2022)

Euthymia is a trans-diagnostic construct characterized by lack of mood disturbances; presence of positive affect; balance of psychological well-being dimensions, flexibility, consistency, and resistance to stress. The aim of this critical review is to draw a conceptual map of euthymia. Relationships with other constructs, continuum between euthymia and dysthymia with discomfort as an intermediate area, associations with lifestyle, clinimetric assessment, role of psychotherapeutic interventions, establishment of therapeutic targets, and neurobiological mechanisms are discussed. The model is based on the bipolar nature of well-being dimensions. Euthymia means using allostasis optimally and maintaining a healthy balance that promotes positive aspects of brain and body health through health-promoting behaviors. It may provide a framework for a renewed definition of recovery, for measuring treatment outcome and for targeting interventions, including the sequential administration of therapeutic components. Clinical assessment requires a clinimetric approach encompassing a broad range of aspects, such as allostatic load and lifestyle behaviors, all interacting with each other and contributing to the euthymia/dysthymia balance. Clinimetric indices for assessing euthymia (the Clinical Interview for Euthymia and the Euthymia Scale) and related constructs (the Clinical Interview for Dysthymia and the Semi-Structured Interview for the Diagnostic Criteria for Psychosomatic Research) are presented here. Well-Being Therapy, a psychotherapeutic strategy specifically aimed at pursuing euthymia, relies on self-observation of well-being episodes using a structured diary as a distinct therapeutic ingredient. The clinical science of euthymia may unravel innovative approaches to assessment and treatment of psychiatric and medical disorders, according to a unitary conceptual framework.
Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers
Authors: Melissa Dsouza, Rajita Menon, Emily Crossette, Shakti K. Bhattarai, Jessica Schneider, Yun-Gi Kim, Shilpa Reddy, Silvia Caballero, Cintia Felix, Louis Cornacchione, Jared Hendrickson, Andrea R. Watson, Samuel S. Minot, Nick Greenfield, Lisa Schopf, Rose Szabady, Juan Patarroyo, William Smith, Pratibha Harrison, Ed J. Kuijper, Ciaran P. Kelly, Bernat Olle, Dmitri Bobilev, Jeffrey L. Silber, Vanni Bucci, Bruce Roberts, Jeremiah Faith, Jason M. Norman
Journal: Cell Host & Microbe (2022)
Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: a position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation
Authors: Dimitris Tousoulis, Tomasz Guzik, Teresa Padro, Dirk J Duncker, Giuseppe De Luca, Etto Eringa, Marija Vavlukis, Alexios S Antonopoulos, Themistoklis Katsimichas, Edina Cenko, Ana Djordjevic-Dikic, Ingrid Fleming, Olivia Manfrini, Danijela Trifunovic, Charalambos Antoniades, Filippo Crea
Journal: Cardiovascular Research (2022)

Abstract The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in the function of the gastrointestinal tract and the physiology of its host, protecting from pathogen colonization, and participating in vitamin synthesis, the functions of the immune system, as well as glucose homeostasis and lipid metabolism, among others. Mounting evidence from animal and human studies indicates that the composition and metabolic profiles of the gut microbiota are linked to the pathogenesis of cardiovascular disease, particularly arterial hypertension, atherosclerosis, and heart failure. In this review article, we provide an overview of the function of the human gut microbiota, summarize, and critically address the evidence linking compositional and functional alterations of the gut microbiota with atherosclerosis and coronary artery disease and discuss the potential of strategies for therapeutically targeting the gut microbiota through various interventions.
Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence
Authors: Arjun Muralidharan, Susana G. Sotocinal, Noosha Yousefpour, Nur Akkurt, Lucas V. Lima, Shannon Tansley, Marc Parisien, Chengyang Wang, Jean-Sebastien Austin, Boram Ham, Gabrielle M.G.S. Dutra, Philippe Rousseau, Sioui Maldonado-Bouchard, Teleri Clark, Sarah F. Rosen, Mariam R. Majeed, Olivia Silva, Rachel Nejade, Xinyu Li, Stephania Donayre Pimentel, Christopher S. Nielsen, G. Gregory Neely, Chantal Autexier, Luda Diatchenko, Alfredo Ribeiro-da-Silva, Jeffrey S. Mogil
Journal: Journal of Clinical Investigation (2022)

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.
Mitapivat versus Placebo for Pyruvate Kinase Deficiency
Authors: Hanny Al-Samkari, Frédéric Galactéros, Andreas Glenthøj, Jennifer A. Rothman, Oliver Andres, Rachael F. Grace, Marta Morado-Arias, D. Mark Layton, Koichi Onodera, Madeleine Verhovsek, Wilma Barcellini, Satheesh Chonat, Malia P. Judge, Erin Zagadailov, Rengyi Xu, Peter Hawkins, Vanessa Beynon, Sarah Gheuens, Eduard J. van Beers
Journal: New England Journal of Medicine (2022)

Pyruvate kinase deficiency is a rare, hereditary, chronic condition that is associated with hemolytic anemia. In a phase 2 study, mitapivat, an oral, first-in-class activator of erythrocyte pyruvate kinase, increased the hemoglobin level in patients with pyruvate kinase deficiency.In this global, phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency who were not receiving regular red-cell transfusions. The patients were assigned to receive either mitapivat (5 mg twice daily, with potential escalation to 20 or 50 mg twice daily) or placebo for 24 weeks. The primary end point was a hemoglobin response (an increase from baseline of ≥1.5 g per deciliter in the hemoglobin level) that was sustained at two or more scheduled assessments at weeks 16, 20, and 24. Secondary efficacy end points were the average change from baseline in the hemoglobin level, markers of hemolysis and hematopoiesis, and the change from baseline at week 24 in two pyruvate kinase deficiency-specific patient-reported outcome measures.Sixteen of the 40 patients (40%) in the mitapivat group had a hemoglobin response, as compared with none of the 40 patients in the placebo group (adjusted difference, 39.3 percentage points; 95% confidence interval, 24.1 to 54.6; two-sided P<0.001). Patients who received mitapivat had a greater response than those who received placebo with respect to each secondary end point, including the average change from baseline in the hemoglobin level. The most common adverse events were nausea (in 7 patients [18%] in the mitapivat group and 9 patients [23%] in the placebo group) and headache (in 6 patients [15%] and 13 patients [33%], respectively). Adverse events of grade 3 or higher occurred in 10 patients (25%) who received mitapivat and 5 patients (13%) who received placebo.In patients with pyruvate kinase deficiency, mitapivat significantly increased the hemoglobin level, decreased hemolysis, and improved patient-reported outcomes. No new safety signals were identified in the patients who received mitapivat. (Funded by Agios Pharmaceuticals; ACTIVATE ClinicalTrials.gov number, NCT03548220.).
Enrolling Adolescents with Rare Disease for Early Phase Clinical Trials While Under the Care of Child Protection Services: Balancing Protection and Access
Authors: Benjamin S. Wilfond, Devan M. Duenas, Liza-Marie Johnson
Journal: The American Journal of Bioethics (2022)

"Enrolling Adolescents with Rare Disease for Early Phase Clinical Trials While Under the Care of Child Protection Services: Balancing Protection and Access." The American Journal of Bioethics, 22(4), pp. 81–82
Evaluation of magnetic resonance imaging-based radiomics characteristics for differentiation of benign and malignant peripheral nerve sheath tumors in neurofibromatosis type 1
Authors: Inka Ristow, Frederic Madesta, Lennart Well, Farzad Shenas, Felicia Wright, Isabel Molwitz, Said Farschtschi, Peter Bannas, Gerhard Adam, Victor F Mautner, René Werner, Johannes Salamon
Journal: Neuro-Oncology (2022)

Abstract Background Patients with neurofibromatosis type 1 (NF1) develop benign (BPNST), premalignant atypical (ANF), and malignant (MPNST) peripheral nerve sheath tumors. Radiological differentiation of these entities is challenging. Therefore, we aimed to evaluate the value of a magnetic resonance imaging (MRI)-based radiomics machine-learning (ML) classifier for differentiation of these three entities of internal peripheral nerve sheath tumors in NF1 patients. Methods MRI was performed at 3T in 36 NF1 patients (20 male; age: 31 ± 11 years). Segmentation of 117 BPNSTs, 17 MPNSTs, and 8 ANFs was manually performed using T2w spectral attenuated inversion recovery sequences. One hundred seven features per lesion were extracted using PyRadiomics and applied for BPNST versus MPNST differentiation. A 5-feature radiomics signature was defined based on the most important features and tested for signature-based BPNST versus MPNST classification (random forest [RF] classification, leave-one-patient-out evaluation). In a second step, signature feature expressions for BPNSTs, ANFs, and MPNSTs were evaluated for radiomics-based classification for these three entities. Results The mean area under the receiver operator characteristic curve (AUC) for the radiomics-based BPNST versus MPNST differentiation was 0.94, corresponding to correct classification of on average 16/17 MPNSTs and 114/117 BPNSTs (sensitivity: 94%, specificity: 97%). Exploratory analysis with the eight ANFs revealed intermediate radiomic feature characteristics in-between BPNST and MPNST tumor feature expression. Conclusion In this proof-of-principle study, ML using MRI-based radiomics characteristics allows sensitive and specific differentiation of BPNSTs and MPNSTs in NF1 patients. Feature expression of premalignant atypical tumors was distributed in-between benign and malignant tumor feature expressions, which illustrates biological plausibility of the considered radiomics characteristics.
High‐Throughput, Living Single‐Cell, Multiple Secreted Biomarker Profiling Using Microfluidic Chip and Machine Learning for Tumor Cell Classification
Authors: Chao Wang, Chunhua Wang, Yu Wu, Jianwei Gao, Yingkuan Han, Yujin Chu, Le Qiang, Jiaoyan Qiu, Yakun Gao, Yanhao Wang, Fangteng Song, Yihe Wang, Xiaowei Shao, Yu Zhang, Lin Han
Journal: Advanced Healthcare Materials (2022)

Abstract Secreted proteins provide abundant functional information on living cells and can be used as important tumor diagnostic markers, of which profiling at the single‐cell level is helpful for accurate tumor cell classification. Currently, achieving living single‐cell multi‐index, high‐sensitivity, and quantitative secretion biomarker profiling remains a great challenge. Here, a high‐throughput living single‐cell multi‐index secreted biomarker profiling platform is proposed, combined with machine learning, to achieve accurate tumor cell classification. A single‐cell culture microfluidic chip with self‐assembled graphene oxide quantum dots (GOQDs) enables high‐activity single‐cell culture, ensuring normal secretion of biomarkers and high‐throughput single‐cell separation, providing sufficient statistical data for machine learning. At the same time, the antibody barcode chip with self‐assembled GOQDs performs multi‐index, highly sensitive, and quantitative detection of secreted biomarkers, in which each cell culture chamber covers a whole barcode array. Importantly, by combining the K‐means strategy with machine learning, thousands of single tumor cell secretion data are analyzed, enabling tumor cell classification with a recognition accuracy of 95.0%. In addition, further profiling of the grouping results reveals the unique secretion characteristics of subgroups. This work provides an intelligent platform for high‐throughput living single‐cell multiple secretion biomarker profiling, which has broad implications for cancer investigation and biomedical research.