tbuckley/cabot-search huggingface dataset:
TNF-α+ CD4+ T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies
Authors: Kattria van der Ploeg, Adam S. Kirosingh, Diego A.M. Mori, Saborni Chakraborty, Zicheng Hu, Benjamin L. Sievers, Karen B. Jacobson, Hector Bonilla, Julie Parsonnet, Jason R. Andrews, Kathleen D. Press, Maureen C. Ty, Daniel R. Ruiz-Betancourt, Lauren de la Parte, Gene S. Tan, Catherine A. Blish, Saki Takahashi, Isabel Rodriguez-Barraquer, Bryan Greenhouse, Upinder Singh, Taia T. Wang, Prasanna Jagannathan
Journal: Cell Reports Medicine (2022)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4+ longitudinal dynamics following infection and of specific features that correlate with the maintenance of neutralizing antibodies remains limited. Here, we characterize SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4+ response shifts from cells producing interferon gamma (IFNγ) to tumor necrosis factor alpha (TNF-α) from 5 days to 4 months post-enrollment, with IFNγ-IL-21-TNF-α+ CD4+ T cells the predominant population detected at later time points. Greater percentages of IFNγ-IL-21-TNF-α+ CD4+ T cells on day 28 correlate with SARS-CoV-2-neutralizing antibodies measured 7 months post-infection (⍴ = 0.4, p = 0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ- and TNF-α-producing, spike-protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.
Keep moving: overcoming physical, mental and pandemic challenges to stay active
Authors: Dina Christina (Christa) Janse van Rensburg, Sharief Hendricks
Journal: British Journal of Sports Medicine (2022)

There is a little argument against the benefits of physical activity for any cohort: healthy individuals, patients with non-communicable disease, auto-immune conditions and cancer patients.However, the physical activity requirements and the challenges to fulfil those requirements may vary for different populations.Athletes overcome many challenges to reach their goals.Recently, a major hurdle to fulfilling physical activity requirements was COVID-19.To represent this conquering spirit we have Michaela Whitebooi on the cover of this edition.Michaela is a multiple African Senior Judo Champion (under 48kg category) who has overcome injuries and personal factors to reach not only her sporting goals as a 2020 Tokyo Olympian, but also her academic goals through obtaining an Honours degree in Internal Auditing and a Post Graduate Diploma in Entrepreneurship.
Expansion of Gastric Intestinal Metaplasia with Copy Number Aberrations Contributes to Field Cancerization
Authors: Ken Kumagai, Takahiro Shimizu, Atsushi Takai, Nobuyuki Kakiuchi, Yasuhide Takeuchi, Tomonori Hirano, Haruhiko Takeda, Aya Mizuguchi, Mari Teramura, Takahiko Ito, Eriko Iguchi, Mitsuhiro Nikaido, Yuji Eso, Ken Takahashi, Yoshihide Ueda, Shin'ichi Miyamoto, Kazutaka Obama, Seishi Ogawa, Hiroyuki Marusawa, Hiroshi Seno
Journal: Cancer Research (2022)

Abstract Intestinal metaplasia (IM) is a risk factor for gastric cancer following infection with Helicobacter pylori. To explore the susceptibility of pure gastric IM to cancer development, we investigated genetic alterations in single IM gastric glands. We isolated 50 single IM or non-IM glands from the inflamed gastric mucosa of 11 patients with intramucosal gastric carcinoma (IGC) and 4 patients without IGC; 19 single glands in the noninflamed gastric mucosa of 11 individuals from our cohort and previous dataset were also included as controls. Whole-exome sequencing of single glands revealed significantly higher accumulation of somatic mutations in various genes within IM glands compared with non-IM glands. Clonal ordering analysis showed that IM glands expanded to form clusters with shared mutations. In addition, targeted-capture deep sequencing and copy number (CN) analyses were performed in 96 clustered IM or non-IM gastric glands from 26 patients with IGC. CN analyses were also performed on 41 IGC samples and The Cancer Genome Atlas-Stomach Adenocarcinoma datasets. These analyses revealed that polyclonally expanded IM commonly acquired CN aberrations (CNA), including amplification of chromosomes 8, 20, and 2. A large portion of clustered IM glands typically consisted of common CNAs rather than other cancer-related mutations. Moreover, the CNA patterns of clustered IM glands were similar to those of IGC, indicative of precancerous conditions. Taken together, these findings suggest that, in the gastric mucosa inflamed with H. pylori infection, IM glands expand via acquisition of CNAs comparable with those of IGC, contributing to field cancerization. Significance: This study contributes to our understanding of gastric intestinal metaplasia as a risk factor for gastric adenocarcinoma via their multifocal expansion and acquisition of CNAs and somatic mutations.
NOGOB receptor deficiency increases cerebrovascular permeability and hemorrhage via impairing histone acetylation–mediated CCM1/2 expression
Authors: Zhi Fang, Xiaoran Sun, Xiang Wang, Ji Ma, Thomas Palaia, Ujala Rana, Benjamin Miao, Louis Ragolia, Wenquan Hu, Qing Robert Miao
Journal: Journal of Clinical Investigation (2022)

The loss function of cerebral cavernous malformation (CCM) genes leads to most CCM lesions characterized by enlarged leaking vascular lesions in the brain. Although we previously showed that NOGOB receptor (NGBR) knockout in endothelial cells (ECs) results in cerebrovascular lesions in the mouse embryo, the molecular mechanism by which NGBR regulates CCM1/2 expression has not been elucidated. Here, we show that genetic depletion of Ngbr in ECs at both postnatal and adult stages results in CCM1/2 expression deficiency and cerebrovascular lesions such as enlarged vessels, blood-brain-barrier hyperpermeability, and cerebral hemorrhage. To reveal the molecular mechanism, we used RNA-sequencing analysis to examine changes in the transcriptome. Surprisingly, we found that the acetyltransferase HBO1 and histone acetylation were downregulated in NGBR-deficient ECs. The mechanistic studies elucidated that NGBR is required for maintaining the expression of CCM1/2 in ECs via HBO1-mediated histone acetylation. ChIP-qPCR data further demonstrated that loss of NGBR impairs the binding of HBO1 and acetylated histone H4K5 and H4K12 on the promotor of the CCM1 and CCM2 genes. Our findings on epigenetic regulation of CCM1 and CCM2 that is modulated by NGBR and HBO1-mediated histone H4 acetylation provide a perspective on the pathogenesis of sporadic CCMs.
Efficient targeting of NY-ESO-1 tumor antigen to human cDC1s by lymphotactin results in cross-presentation and antigen-specific T cell expansion
Authors: Camille Le Gall, Anna Cammarata, Lukas de Haas, Iván Ramos-Tomillero, Jorge Cuenca-Escalona, Kayleigh Schouren, Zacharias Wijfjes, Anouk M D Becker, Johanna Bödder, Yusuf Dölen, I Jolanda M de Vries, Carl G Figdor, Georgina Flórez-Grau, Martijn Verdoes
Journal: Journal for ImmunoTherapy of Cancer (2022)

Type 1 conventional dendritic cells (cDC1s) are characterized by their ability to induce potent CD8+ T cell responses. In efforts to generate novel vaccination strategies, notably against cancer, human cDC1s emerge as an ideal target to deliver antigens. cDC1s uniquely express XCR1, a seven transmembrane G protein-coupled receptor. Due to its restricted expression and endocytic nature, XCR1 represents an attractive receptor to mediate antigen-delivery to human cDC1s. To explore tumor antigen delivery to human cDC1s, we used an engineered version of XCR1-binding lymphotactin (XCL1), XCL1(CC3). Site-specific sortase-mediated transpeptidation was performed to conjugate XCL1(CC3) to an analog of the HLA-A*02:01 epitope of the cancer testis antigen New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1). While poor epitope solubility prevented isolation of stable XCL1-antigen conjugates, incorporation of a single polyethylene glycol (PEG) chain upstream of the epitope-containing peptide enabled generation of soluble XCL1(CC3)-antigen fusion constructs. Binding and chemotactic characteristics of the XCL1-antigen conjugate, as well as its ability to induce antigen-specific CD8+ T cell activation by cDC1s, was assessed. PEGylated XCL1(CC3)-antigen conjugates retained binding to XCR1, and induced cDC1 chemoattraction in vitro. The model epitope was efficiently cross-presented by human cDC1s to activate NY-ESO-1-specific CD8+ T cells. Importantly, vaccine activity was increased by targeting XCR1 at the surface of cDC1s. Our results present a novel strategy for the generation of targeted vaccines fused to insoluble antigens. Moreover, our data emphasize the potential of targeting XCR1 at the surface of primary human cDC1s to induce potent CD8+ T cell responses.
Findings from a survey about hidradenitis suppurativa in the Netherlands
Journal: British Journal of Dermatology (2022)

Prens et al. Br J Dermatol 2022; 186:814-822. Hidradenitis suppurativa (HS) is a long-term, recurrent and painful disease where there is inflammation (redness, tenderness and swelling) in the armpits, breasts and groin. Within HS there is a blockage of the hair follicles. This causes a mixture of boil-like lumps, areas leaking pus and scarring. This has an impact on people's quality of life. The authors set out to find out how common HS is in the Northern Netherlands and also to learn more about what other health problems occur in people with HS. A self-report questionnaire was sent to over 167,000 people and about 56,000 replied. They had expected to find that about 1% of the population had HS but the figure was higher at 2%. Many of them were not yet diagnosed with HS, and were not receiving treatment. We already knew that obesity, type 2 diabetes, chronic obstructive pulmonary disease, depression and Crohn disease are more often found in people with HS. This study also found some other conditions that are more common in people with HS such as fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome and migraine. Like other studies this study also found that people with HS are more likely to smoke. This study shows that many people are not currently being diagnosed with HS or receiving treatment for it.
Representing sex chromosomes in genome assemblies
Authors: Sarah B. Carey, John T. Lovell, Jerry Jenkins, Jim Leebens-Mack, Jeremy Schmutz, Melissa A. Wilson, Alex Harkess
Journal: Cell Genomics (2022)

Sex chromosomes have evolved hundreds of independent times across eukaryotes. As genome sequencing, assembly, and scaffolding techniques rapidly improve, it is now feasible to build fully phased sex chromosome assemblies. Despite technological advances enabling phased assembly of whole chromosomes, there are currently no standards for representing sex chromosomes when publicly releasing a genome. Furthermore, most computational analysis tools are unable to efficiently investigate their unique biology relative to autosomes. We discuss a diversity of sex chromosome systems and consider the challenges of representing sex chromosome pairs in genome assemblies. By addressing these issues now as technologies for full phasing of chromosomal assemblies are maturing, we can collectively ensure that future genome analysis toolkits can be broadly applied to all eukaryotes with diverse types of sex chromosome systems. Here we provide best practice guidelines for presenting a genome assembly that contains sex chromosomes. These guidelines can also be applied to other non-recombining genomic regions, such as S-loci in plants and mating-type loci in fungi and algae.
问卷调查青少年斑秃患者的体验以及对其毛发脱落情况的评分
Journal: British Journal of Dermatology (2022)

British Journal of DermatologyVolume 186, Issue 5 p. e211-e211 Plain Language Summary 问卷调查青少年斑秃患者的体验以及对其毛发脱落情况的评分 First published: 02 May 2022 https://doi.org/10.1111/bjd.21264AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Macey et al. Br J Dermatol 2022; 186:849–860. 斑秃(AA)是一种患病率约为 2%的疾病。AA会导致毛发脱落和指甲损伤。毛发脱落，特别是面部和头部，会使患者感到苦恼和困窘。眉毛和/或睫毛脱落会导致灰尘对眼睛产生刺激。 目前正在开发治疗AA的新方法，我们需要用问卷来了解治疗对患者有何等影响。我们已经知道，问卷以及衡量头发脱落、眉毛脱落、睫毛脱落、指甲损伤和眼睛刺激的照片指南对于AA成年患者是可以接受且适当的。但还需要通过研究来了解，调查问卷对于AA青少年患者是否可以接受且适当。 这项研究的研究者来自美国和英国。在研究中，对 11 位美国的AA青少年患者(年龄为 12-17 岁)进行了访谈，了解他们的AA体验以及是否能够使用问卷。 对于青少年患者，头发脱落最为困扰，其次是眉毛脱落和睫毛脱落。他们描述了烦恼、自我意识、社会评判、难过、隐藏脱发所花费的时间、避免活动、在学校遇到困难和眼睛刺激的情况。 青少年患者理解并能够准确使用问卷和照片指南来给自己的毛发脱落情况评分。与成年患者一样，青少年患者也认为，如果能够达到至少80%发量(发量损失少于20%)，AA治疗即为成功。 这些结果表明，此问卷适合青少年AA患者使用，在临床试验中评估新治疗方法的效果。 Volume186, Issue5May 2022Pages e211-e211 RelatedInformation
mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant
Authors: Henning Gruell, Kanika Vanshylla, Pinkus Tober-Lau, David Hillus, Philipp Schommers, Clara Lehmann, Florian Kurth, Leif E. Sander, Florian Klein
Journal: Nature Medicine (2022)

The Omicron variant of SARS-CoV-2 is causing a rapid increase in infections across the globe. This new variant of concern carries an unusually high number of mutations in key epitopes of neutralizing antibodies on the viral spike glycoprotein, suggesting potential immune evasion. Here we assessed serum neutralizing capacity in longitudinal cohorts of vaccinated and convalescent individuals, as well as monoclonal antibody activity against Omicron using pseudovirus neutralization assays. We report a near-complete lack of neutralizing activity against Omicron in polyclonal sera from individuals vaccinated with two doses of the BNT162b2 COVID-19 vaccine and from convalescent individuals, as well as resistance to different monoclonal antibodies in clinical use. However, mRNA booster immunizations in vaccinated and convalescent individuals resulted in a significant increase of serum neutralizing activity against Omicron. This study demonstrates that booster immunizations can critically improve the humoral immune response against the Omicron variant.
Affirmative Action Bans and Enrollment of Students From Underrepresented Racial and Ethnic Groups in U.S. Public Medical Schools
Authors: Dan P. Ly, Utibe R. Essien, Andrew R. Olenski, Anupam B. Jena
Journal: Annals of Internal Medicine (2022)

The percentage of U.S. physicians who identify as being from an underrepresented racial or ethnic group remains low relative to their proportion in the U.S. population. How this percentage may have been affected by state bans on affirmative action in public postsecondary institutions has received relatively little attention.To examine the association between state affirmative action bans and percentage of enrollment in U.S. public medical schools from underrepresented racial and ethnic groups.Event study comparing public medical schools in states that implemented affirmative action bans with those in states without bans.U.S. public medical schools.21 public medical schools in 8 states with affirmative action bans matched to 32 public medical schools in 24 states without bans from 1985 to 2019.Percentage of total enrollment from racial and ethnic groups underrepresented in medicine (Black, Hispanic, American Indian or Alaska Native, and Native Hawaiian or other Pacific Islander).The percentage of enrollment from underrepresented racial and ethnic groups was 14.8% in U.S. public medical schools in the year before ban implementation in states with bans. The adjusted percentage of underrepresented students in ban schools decreased by 4.8 percentage points (95% CI, -6.3 to -3.2 percentage points) 5 years after ban implementation relative to the year before implementation, whereas the adjusted percentage in control schools increased by 0.7 percentage point (CI, -0.1 to 1.6 percentage points), for a relative difference, or difference-in-differences estimate, of -5.5 percentage points (CI, -7.1 to -3.9 percentage points).Inability to account for the effect of these bans on undergraduate enrollment.State affirmative action bans were associated with significant reductions in the percentage of students in U.S. public medical schools from underrepresented racial and ethnic groups.None.
Normothermic Machine Perfusion Increases Donor Liver Use
Authors: James F. Markmann, Parsia A. Vagefi, Malcolm P. MacConmara
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
The Incidence of Adult-Onset Type 1 Diabetes: A Systematic Review From 32 Countries and Regions
Authors: Jessica L. Harding, Pandora L. Wander, Xinge Zhang, Xia Li, Suvi Karuranga, Hongzhi Chen, Hong Sun, Yuting Xie, Richard A. Oram, Dianna J. Magliano, Zhiguang Zhou, Alicia J. Jenkins, Ronald C.W. Ma
Journal: Diabetes Care (2022)

The epidemiology of adult-onset type 1 diabetes (T1D) incidence is not well-characterized due to the historic focus on T1D as a childhood-onset disease.We assess the incidence of adult-onset (≥20 years) T1D, by country, from available data.A systematic review of MEDLINE, Embase, and the gray literature, through 11 May 2021, was undertaken.We included all population-based studies reporting on adult-onset T1D incidence and published from 1990 onward in English.With the search we identified 1,374 references of which 46 were included for data extraction. Estimates of annual T1D incidence were allocated into broad age categories (20-39, 40-59, ≥60, or ≥20 years) as appropriate.Overall, we observed the following patterns: 1) there is a paucity of data, particularly in low- and middle-income countries; 2) the incidence of adult-onset T1D is lowest in Asian and highest in Nordic countries; 3) adult-onset T1D is higher in men versus women; 4) it is unclear whether adult-onset T1D incidence declines with increasing age; and 5) it is unclear whether incidence of adult-onset T1D has changed over time.Results are generalizable to high-income countries, and misclassification of diabetes type cannot be ruled out.From available data, this systematic review suggests that the incidence of T1D in adulthood is substantial and highlights the pressing need to better distinguish T1D from T2D in adults so that we may better assess and respond to the true burden of T1D in adults.
Benzodiazepines Remain Important Therapeutic Options in Psychiatric Practice
Authors: Steven L. Dubovsky, Dori Marshall
Journal: Psychotherapy and Psychosomatics (2022)

Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory bodies as having limited benefit and significant risks. Data presented in this article support the use of these medications as treatments of choice for acute situational anxiety, chronic anxiety disorders, insomnia, alcohol withdrawal syndromes, and catatonia. They may also be useful adjuncts in the treatment of anxious depression and mania, and for medically ill patients. Tolerance develops to sedation and possibly psychomotor impairment, but not to the anxiolytic effect of benzodiazepines. Sedation can impair cognitive function in some patients, but assertions that benzodiazepines increase the risk of dementia are not supported by recent data. Contrary to popular opinion, benzodiazepines are not frequently misused or conduits to misuse of other substances in patients without substance use disorders who are prescribed these medications for appropriate indications; most benzodiazepine misuse involves medications that are obtained from other people. Benzodiazepines are usually not lethal in overdose except when ingested with other substances, especially alcohol and opioids. Benzodiazepines comprise one of the few classes of psychotropic medication the mechanisms of action of which are clearly delineated, allowing for greater precision in their clinical use. These medications, therefore, belong in the therapeutic armamentarium of the knowledgeable clinician.
Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial
Authors: Walter Heindel, Stefanie Weigel, Joachim Gerß, Hans-Werner Hense, Alexander Sommer, Miriam Krischke, Laura Kerschke
Journal: The Lancet Oncology (2022)
Corrigendum to “Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury in advanced rheumatoid arthritis via regulating inflammatory environment” [Bioact. Mater. 18C (2022) 1–14]
Authors: Lei Zhang, Zhiguo Qin, Han Sun, Xiang Chen, Jian Dong, Siyu Shen, Liming Zheng, Ning Gu, Qing Jiang
Journal: Bioactive Materials (2022)

[This corrects the article DOI: 10.1016/j.bioactmat.2022.02.017.].
Injectable Acylhydrazone‐Linked RAFT Polymer Hydrogels for Sustained Protein Release and Cell Encapsulation (Adv. Healthcare Mater. 7/2022)
Authors: Fang‐Yi Lin, Nathan H. Dimmitt, Mariana Moraes de Lima Perini, Jiliang Li, Chien‐Chi Lin
Journal: Advanced Healthcare Materials (2022)

Injectable Hydrogels In article number 2101284 by Chien-Chi Lin and co-workers, a biocompatible and pH/thermo dual responsive injectable hydrogel is synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization and acylhdrazone click chemistry. Upon injection, sol-gel transition occurs rapidly at body temperature and the porous hydrogels degrade slowly under mild acidic condition due to pH-sensitive cleavages of acylhydrazone bonds. The slow hydrogel degradation may be leveraged for long-term sustained protein delivery.