tbuckley/cabot-search huggingface dataset:
<i>JAMA</i>’s incoming chief editor promises to get political to improve health for all
Authors: Adele Waters
Journal: BMJ (2022)

promises to get political to improve health for allThe racism row that engulfed the American Medicine Association's flagship journal last year will usher in a fresh approach to tackling inequalities, hears Adele Waters Adele WatersIt's 7.30 am, but there is no whiff of morning weariness from Kirsten Bibbins-Domingo as she begins her morning conference calls. Race rowIn her case, these include biochemist, physician, scholar, and leader.Her stepping into the top job at JAMA will be a symbol of change, but especially so given that the
Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity
Authors: Zhongyi Jiang, Haitao Zhu, Pusen Wang, Weitao Que, Lin Zhong, Xiao‐Kang Li, Futian Du
Journal: MedComm (2022)

Abstract CD4 + CD25 + regulatory T cells (Tregs), a subpopulation of naturally CD4 + T cells that characteristically express transcription factor Forkhead box P3 (FOXP3), play a pivotal role in the maintenance of immune homeostasis and the prevention of autoimmunity. With the development of biological technology, the understanding of plasticity and stability of Tregs has been further developed. Recent studies have suggested that human Tregs are functionally and phenotypically diverse. The functions and mechanisms of different phenotypes of Tregs in different disease settings, such as tumor microenvironment, autoimmune diseases, and transplantation, have gradually become hot spots of immunology research that arouse extensive attention. Among the complex functions, CD4 + CD25 + FOXP3 + Tregs possess a potent immunosuppressive capacity and can produce various cytokines, such as IL‐2, IL‐10, and TGF‐β, to regulate immune homeostasis. They can alleviate the progression of diseases by resisting inflammatory immune responses, whereas promoting the poor prognosis of diseases by helping cells evade immune surveillance or suppressing effector T cells activity. Therefore, methods for targeting Tregs to regulate their functions in the immune microenvironment, such as depleting them to strengthen tumor immunity or expanding them to treat immunological diseases, need to be developed. Here, we discuss that different subpopulations of Tregs are essential for the development of immunotherapeutic strategies involving Tregs in human diseases.
GelNB molecular coating as a biophysical barrier to isolate intestinal irritating metabolites and regulate intestinal microbial homeostasis in the treatment of inflammatory bowel disease
Authors: Qijiang Mao, Haoqi Pan, Yiyin Zhang, Yi Zhang, Qiuwen Zhu, Yi Hong, Zhengze Huang, Yang Li, Xu Feng, Yifeng Fang, WenChao Chen, Pengfei Chen, Bo Shen, Hongwei Ouyang, Yuelong Liang
Journal: Bioactive Materials (2022)

Inflammatory bowel disease (IBD) is a chronic, immune-mediated inflammatory disease characterized by the destruction of the structure and function of the intestinal epithelial barrier. Due to the poor remission effect and severe adverse events associated with current clinical medications, IBD remains an incurable disease. Here, we demonstrated a novel treatment strategy with high safety and effective inflammation remission via tissue-adhesive molecular coating. The molecular coating is composed of o-nitrobenzaldehyde (NB)-modified Gelatin (GelNB), which can strongly bond with -NH2 on the intestinal surface of tissue to form a thin biophysical barrier. We found that this molecular coating was able to stay on the surface of the intestine for long periods of time, effectively protecting the damaged intestinal epithelium from irritations of external intestinal metabolites and harmful flora. In addition, our results showed that this coating not only provided a beneficial environment for cell migration and proliferation to promote intestinal repair and regeneration, but also achieved a better outcome of IBD by reducing intestinal inflammation. Moreover, the in vivo experiments showed that the GelNB was better than the classic clinical medication-mesalazine. Therefore, our molecular coating showed potential as a promising strategy for the prevention and treatment of IBD.
Yes-Associated Protein Targets the Transforming Growth Factor β Pathway to Mediate High-Fat/High-Sucrose Diet-induced Arterial Stiffness.
Authors: Yanan Liu, Mengke Li, Xue Lv, Kaiwen Bao, Xiao Yu Tian, Lei He, Lei Shi, Yi Zhu, Ding Ai
Journal: Circulation Research (2022)

Metabolic syndrome is related to cardiovascular diseases, which is attributed in part, to arterial stiffness; however, the mechanisms remain unclear. The present study aimed to investigate the molecular mechanisms of metabolic syndrome-induced arterial stiffness and to identify new therapeutic targets.Arterial stiffness was induced by high-fat/high-sucrose diet in mice, which was quantified by Doppler ultrasound. Four-dimensional label-free quantitative proteomic analysis, affinity purification and mass spectrometry, and immunoprecipitation and GST (glutathione S-transferase) pull-down experiments were performed to explore the mechanism of YAP (Yes-associated protein)-mediated TGF (transforming growth factor) β pathway activation.YAP protein was upregulated in the aortic tunica media of mice fed a high-fat/high-sucrose diet for 2 weeks and precedes arterial stiffness. Smooth muscle cell-specific YAP knockdown attenuated high-fat/high-sucrose diet-induced arterial stiffness and activation of TGFβ-Smad2/3 signaling pathway in arteries. By contrast, Myh11CreERT2-YapTg mice exhibited exacerbated high-fat/high-sucrose diet-induced arterial stiffness and enhanced TGFβ-activated Smad2/3 phosphorylation in arteries. PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) was identified as a YAP-bound phosphatase that translocates into the nucleus to dephosphorylate Smads (mothers against decapentaplegic homologs) in response to TGFβ. This process was inhibited by YAP through removal of the K63-linked ubiquitin chain of PPM1B at K326.This study provides a new mechanism by which smooth muscle cell YAP regulates the TGFβ pathway and a potential therapeutic target in metabolic syndrome-associated arterial stiffness.
Inflammatory Cytokine Profiles Do Not Differ Between Patients With Idiopathic Cytopenias of Undetermined Significance and Myelodysplastic Syndromes
Authors: Amalie Bach Nielsen, Jakob Werner Hansen, Andreas Due Ørskov, Konstantinos Dimopoulos, Mohammad Salem, Mariam Grigorian, Helle Bruunsgaard, Kirsten Grønbæk
Journal: HemaSphere (2022)

Immune dysregulation has been highlighted as a key player in the pathogenesis of myelodysplastic syndromes (MDS), but little is known about cytokine profiles in patients with unexplained cytopenia with or without mutations in MDS-associated genes (clonal cytopenias of undetermined significance [CCUS] and idiopathic cytopenias of undetermined significance [ICUS], respectively), which often precede MDS. Here, we study the cytokine profiles in 111 patients with ICUS (N = 41), CCUS (N = 30), lower-risk MDS (LR-MDS; N = 22) and higher-risk MDS (HR-MDS; N = 18), and in healthy elderly controls (N = 21). Twenty cytokines were examined in blood plasma at time of diagnosis using Luminex assays and enzyme linked immunosorbent assays. The cytokine levels were compared between patient groups, and in patients versus controls. Associations between cytokines and MDS-associated mutations were evaluated. An aberrant cytokine profile was observed in all patient groups relative to healthy elderly controls. Patients had significantly higher levels of IL-6 (P< 0 .001), tumor necrosis factor α (P < 0.001), IL-10 (P < 0.001), and C-X-C motif chemokine 10 (P < 0.001) and lower levels of transforming growth factor beta 1 (P < 0.001), CCL5/regulated on activation normal T-cell expressed and secreted (P < 0.001), and S100A4 (P < 0.001) compared with healthy controls. Survival was significantly shorter in CCUS and MDS patients with a high systemic inflammatory cytokine load (median overall survival [OS] 21 months) compared with those with low-moderate systemic inflammatory cytokine load (median OS 64 months; P < 0.0001). These data suggest that patients with ICUS and CCUS have cytokine levels as abnormal as in LR-MDS. Indeed, high cytokine levels are present before MDS is diagnosed and cytokine levels are elevated irrespective of the presence or size of the myeloid clones. Cytokines may have a prognostic impact at a very early premalignant stage of myeloid disorders.
The performance of wearable sensors in the detection of SARS-CoV-2 infection: a systematic review
Authors: Marianna Mitratza, Brianna Mae Goodale, Aizhan Shagadatova, Vladimir Kovacevic, Janneke van de Wijgert, Timo B Brakenhoff, Richard Dobson, Billy Franks, Duco Veen, Amos A Folarin, Pieter Stolk, Diederick E Grobbee, Maureen Cronin, George S Downward
Journal: The Lancet Digital Health (2022)
Bacteremia Detection in Second or Subsequent Blood Cultures Among Hospitalized Patients in a Tertiary Care Hospital
Authors: Marie-Céline Zanella, Mikaël de Lorenzi-Tognon, Adrien Fischer, Nathalie Vernaz, Jacques Schrenzel
Journal: JAMA Network Open (2022)

This cohort study assesses the likelihood of detecting microbiological positivity or bacteremia in second or subsequent blood cultures among hospitalized patients while the first culture is still incubating after 24 hours.
Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial
Authors: Eric Armstrong, Anke Hemmerling, Steve Miller, Kerianne E Burke, Sara J Newmann, Sheldon R Morris, Hilary Reno, Sanja Huibner, Maria Kulikova, Nico Nagelkerke, Bryan Coburn, Craig R Cohen, Rupert Kaul
Journal: The Lancet Microbe (2022)
War in Ukraine: an immense threat to the fight against tuberculosis
Authors: Victor Dahl, Giovanni Battista Migliori, Christoph Lange, Christian Wejse
Journal: European Respiratory Journal (2022)

<b>The eastern areas of Europe, including Ukraine and Russia, account for the largest burden of drug-resistant TB in the world. With the ongoing war, a risk of increase in TB burden appears high and not necessarily confined to the war-stricken countries.</b>https://bit.ly/3NuNA0b
3D printing of bio-instructive materials: Toward directing the cell
Authors: Piotr Stanisław Zieliński, Pavan Kumar Reddy Gudeti, Timo Rikmanspoel, Małgorzata Katarzyna Włodarczyk-Biegun
Journal: Bioactive Materials (2022)

Fabrication of functional scaffolds for tissue engineering and regenerative medicine applications requires material systems with precise control over cellular performance. 3D printing is a powerful technique to create highly complex and multicomponent structures with well-defined architecture and composition. In this review paper, we explore extrusion-based 3D printing methods (EBP, i.e., Near Field Electrospinning (NFES), Melt Electrowriting (MEW), Fused Deposition Modeling (FDM), and extrusion bioprinting) in terms of their ability to produce scaffolds with bio-instructive properties. These material systems provide spatio-temporal guidance for cells, allowing controlled tissue regeneration and maturation. Multiple physical and biochemical cues introduced to the EBP scaffolds are evaluated in their ability to direct cell alignment, proliferation, differentiation, specific ECM production, and tissue maturation. We indicate that the cues have different impacts depending on the material system, cell type used, or coexistence of multiple cues. Therefore, they must be carefully chosen based on the targeted application. We propose future directions in bio-instructive materials development, including such concepts as metamaterials, hybrid living materials, and 4D printing. The review gathers the knowledge essential for designing new materials with a controlled cellular response, fabrication of advanced engineered tissue, and developing a better understanding of cell biology, especially in response to the biomaterial.
Correction: Flat-based over-the-scope clip-assisted endoscopic full-thickness resection of a duodenal neuroendocrine tumour: a safe alternative to endoscopic submucosal dissection
Authors: Nikhil Sonthalia, Bhavik Bharat Shah, Mahesh Kumar Goenka
Journal: Endoscopy (2022)

Correction to: Flat-based over-the-scope clip-assisted endoscopic full-thickness resection of a duodenal neuroendocrine tumour: a safe alternative to endoscopic submucosal dissectionEndoscopy 2022; 54(07): E391-E393DOI: 10.1055/a-1546-9958
Immunogenicity of BNT162b2 vaccine booster against SARS-CoV-2 Delta and Omicron variants in nursing home residents: A prospective observational study in older adults aged from 68 to 98 years
Authors: Enagnon Kazali Alidjinou, Julie Demaret, Bénédicte Corroyer-Simovic, Julien Labreuche, Anne Goffard, Jacques Trauet, Daniela Lupau, Sophie Miczek, Fanny Vuotto, Arnaud Dendooven, Dominique Huvent-Grelle, Juliette Podvin, Daniel Dreuil, Karine Faure, Dominique Deplanque, Laurence Bocket, Alain Duhamel, Annie Sobaszek, Didier Hober, Michael Hisbergues, Francois Puisieux, Brigitte Autran, Yazdan Yazdanpanah, Myriam Labalette, Guillaume Lefèvre
Journal: The Lancet Regional Health - Europe (2022)

The present study aimed to evaluate the persistent immunogenicity offered by a third dose of BNT162b2 against Delta and Omicron variants, in nursing home (NH) residents.In this monocenter prospective observational study, anti-spike IgG levels, S1 domain reactive T cell counts, serum neutralizing antibody titers against Delta and Omicron variants were compared before and up to three months after the BNT162b2 booster dose, in NH residents without COVID-19 (COVID-19 naive) or with COVID-19 prior to initial vaccination (COVID-19 recovered).106 NH residents (median [interquartile range] age: 86·5 [81;91] years) were included. The booster dose induced a high increase of anti-spike antibody levels in all subjects (p < 0.0001) and a mild transient increase of specific T cells. Before the booster dose, Delta neutralization was detected in 19% (n = 8/43) and 88% (n = 37/42) of COVID-19 naive and COVID-19 recovered subjects, respectively. Three months after the booster dose, all NH residents developed and maintained a higher Delta neutralization (p < 0·0001). Before the booster dose, Omicron neutralization was detected in 5% (n = 2/43) and 55% (n = 23/42) of COVID-19 naive and COVID-19 recovered subjects, respectively, and three months after, in 84% and 95%, respectively. Neutralizing titers to Omicron were lower than to Delta in both groups with a 35-fold reduction compared to Delta.The booster dose restores high neutralization titers against Delta in all NH residents, and at a lower level against Omicron in a large majority of participants. Future studies are warranted to assess if repeated BNT162b2 booster doses or new specific vaccines might be considered for protecting such fragile patients against Omicron and/or future SARS-CoV-2 variants.French government through the Programme Investissement d'Avenir (I-SITE ULNE/ANR-16-IDEX-0004 ULNE) and the Label of COVID-19 National Research Priority (National Steering Committee on Therapeutic Trials and Other COVID-19 Research, CAPNET).
Protection with a Third Dose of mRNA Vaccine against SARS-CoV-2 Variants in Frontline Workers
Authors: Sarang K Yoon, Kurt T Hegmann, Matthew S Thiese, Jefferey L Burgess, Katherine Ellingson, Karen Lutrick, Lauren E W Olsho, Laura J Edwards, Brian Sokol, Alberto J Caban-Martinez, Natasha Schaefer-Solle, John M Jones, Harmony Tyner, Angela Hunt, Karley Respet, Manjusha Gaglani, Kayan Dunnigan, Spencer Rose, Allison Naleway, Holly Groom, Jennifer Kuntz, Ashley L Fowlkes, Mark G Thompson, Young M Yoo
Journal: New England Journal of Medicine (2022)

Protection with a Third Dose of mRNA Vaccine against SARS-CoV-2 Variants in Frontline Workers To the Editor: Data are needed regarding the effectiveness of a third dose of a messenger RNA (mRNA) vaccine against the B.1.1.529(omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are based on scientifically rigorous, population-level surveillance.Health care personnel, first responders, and other essential and frontline workers who are being evaluated in the HEROES-RECOVER cohorts at eight sites in six states across the United States underwent weekly reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing regardless of the presence or absence of coronavirus disease 2019 (Covid-19) symptoms. 1-3Here, we report the vaccine effectiveness of two or three doses of an mRNA vaccine against infection caused by the omicron and B.1.617.2 (delta) variants.][3] Vaccination was documented by the workers through vaccine cards and medical records or state immunization information systems.Cohort participants could have received three doses of the BNT162b2 vaccine (Pfizer-BioNTech) (administered in 74%), the mRNA-1273 vaccine (Moderna) (in 24%), or a combination of the two vaccines (in 2%); recipients of the Ad26.COV2.S vaccine (Johnson & Johnson-Janssen) were excluded from the analysis.The study period began on August 26, 2021, shortly after the Food and Drug Administration recommended that recipients of the initial twodose mRNA vaccination series receive a third (booster) dose.Hazard ratios were estimated with the use of the Andersen-Gill extension of the Cox proportional-hazards model that accounts for time-varying vaccination status.We adjusted the estimates of vaccine effectiveness using inverse-propensity weighting.We performed SARS-CoV-2 whole-genome sequencing using published protocols.The study was reviewed and approved by the institutional review board at each participating study site or under reliance agreements.From the initiation of the study until January 22, 2022, we detected 202 infections with the delta variant and 419 with the omicron variant in samples obtained from 3241 participants.Among unvaccinated adults, the percentage of asymptomatic infection (no reported symptoms) this week's letters 1855 Protection with a Third Dose of mRNA Vaccine against SARS-CoV-2 Variants in Frontline Workers
A bio-responsive, cargo-catchable gel for postsurgical tumor treatment via ICD-based immunotherapy
Authors: Qian Chen, Shuai Zhou, Yuan Ding, Dali Chen, Naseer Sintali Dahiru, Hailei Tang, Hui Xu, Meng Ji, Xueyi Wang, Zixuan Li, Qinying Chen, Yanan Li, Jiasheng Tu, Chunmeng Sun
Journal: Journal of Controlled Release (2022)
Adverse Events Associated With Coprescription of Phosphodiesterase Type 5 Inhibitors and Oral Organic Nitrates in Male Patients With Ischemic Heart Disease
Authors: Anders Holt, Paul Blanche, Aksel Karl Georg Jensen, Nina Nouhravesh, Deepthi Rajan, Mads Hashiba Jensen, Mohammed El-Sheikh, Anne-Marie Schjerning, Morten Schou, Gunnar Gislason, Christian Torp-Pedersen, Patricia McGettigan, Morten Lamberts
Journal: Annals of Internal Medicine (2022)

Background: Concomitant use of oral organic nitrates (nitrates) and phosphodiesterase type 5 (PDE5) inhibitors is contraindicated. Objective: To measure temporal trends in the coprescription of nitrates and PDE5 inhibitors and to measure the association between cardiovascular outcomes and the coprescription of nitrates with PDE5 inhibitors. Design: Case-crossover design. Setting: Nationwide study of Danish patients from 2000 to 2018. Patients: Male patients with International Classification of Diseases, 10th Revision (ICD-10) codes for ischemic heart disease (IHD), including those who had a continuing prescription for nitrates and a new, filled prescription for PDE5 inhibitors. Measurements: Two composite outcomes were measured: 1) cardiac arrest, shock, myocardial infarction, ischemic stroke, or acute coronary arteriography and 2) syncope, angina pectoris, or drug-related adverse event. Results: From 2000 to 2018, 249 541 male patients with IHD were identified. Of these, 42 073 patients had continuing prescriptions for nitrates. During this period, the prescription rate for PDE5 inhibitors in patients with IHD who were taking nitrates increased from an average of 0.9 prescriptions (95% CI, 0.5 to 1.2 prescriptions) per 100 persons per year in 2000 to 19.5 prescriptions (CI, 18.0 to 21.1 prescriptions) in 2018. No statistically significant association was found between the coprescription of nitrates with PDE5 inhibitors and the risk for either composite outcome (odds ratio [OR], 0.58 [CI, 0.28 to 1.13] for the first outcome and OR, 0.73 [CI, 0.40 to 1.32] for the second outcome). Limitation: An assumption was made that concurrently filled prescriptions for nitrates and PDE5 inhibitors equaled concomitant use. Conclusion: From 2000 to 2018, the use of PDE5 inhibitors increased 20-fold among Danish patients with IHD who were taking nitrates. A statistically significant association between concomitant use of these medications and cardiovascular adverse events could not be identified. Primary Funding Source: Ib Mogens Kristiansens Almene Fond and Helsefonden.
Life-threatening viral disease in a novel form of autosomal recessive <i>IFNAR2</i> deficiency in the Arctic
Authors: Christopher J.A. Duncan, Morten K. Skouboe, Sophie Howarth, Anne K. Hollensen, Rui Chen, Malene L. Børresen, Benjamin J. Thompson, Jarmila Stremenova Spegarova, Catherine F. Hatton, Frederik F. Stæger, Mette K. Andersen, John Whittaker, Søren R. Paludan, Sofie E. Jørgensen, Martin K. Thomsen, Jacob G. Mikkelsen, Carsten Heilmann, Daniela Buhas, Nina F. Øbro, Jakob T. Bay, Hanne V. Marquart, M. Teresa de la Morena, Joseph A. Klejka, Matthew Hirschfeld, Line Borgwardt, Isabel Forss, Tania Masmas, Anja Poulsen, Francisco Noya, Guy Rouleau, Torben Hansen, Sirui Zhou, Anders Albrechtsen, Reza Alizadehfar, Eric J. Allenspach, Sophie Hambleton, Trine H. Mogensen
Journal: The Journal of Experimental Medicine (2022)

Type I interferons (IFN-I) play a critical role in human antiviral immunity, as demonstrated by the exceptionally rare deleterious variants of IFNAR1 or IFNAR2. We investigated five children from Greenland, Canada, and Alaska presenting with viral diseases, including life-threatening COVID-19 or influenza, in addition to meningoencephalitis and/or hemophagocytic lymphohistiocytosis following live-attenuated viral vaccination. The affected individuals bore the same homozygous IFNAR2 c.157T&amp;gt;C, p.Ser53Pro missense variant. Although absent from reference databases, p.Ser53Pro occurred with a minor allele frequency of 0.034 in their Inuit ancestry. The serine to proline substitution prevented cell surface expression of IFNAR2 protein, small amounts of which persisted intracellularly in an aberrantly glycosylated state. Cells exclusively expressing the p.Ser53Pro variant lacked responses to recombinant IFN-I and displayed heightened vulnerability to multiple viruses in vitro—a phenotype rescued by wild-type IFNAR2 complementation. This novel form of autosomal recessive IFNAR2 deficiency reinforces the essential role of IFN-I in viral immunity. Further studies are warranted to assess the need for population screening.