tbuckley/cabot-search huggingface dataset:
Association between birth weight, preterm birth, and nonalcoholic fatty liver disease in a community‐based cohort
Authors: Coralie Amadou, Oumarou Nabi, Lawrence Serfaty, Karine Lacombe, Jérôme Boursier, Philippe Mathurin, Céline Ribet, Victor de Ledinghen, Marie Zins, Marie‐Aline Charles
Journal: Hepatology (2022)

Abstract Background and Aims The association between birth weight (BW) and metabolic outcomes has been described since the 1980s but NAFLD has been rarely studied. This study aimed to investigate the association between BW and NAFLD occurrence in adult subjects. Approach and Results The study population consisted of participants from the French nationwide Constances cohort from 2012 to 2019. Participants with a history of chronic viral hepatitis or excessive alcohol consumption were excluded. Noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The relationship between BW and NAFLD was analyzed with a sex‐stratified logistic regression model adjusted for sociodemographic parameters, lifestyle, and birth term, whereas liver fibrosis was analyzed with a sex‐stratified linear regression model. In total, 55,034 individuals with reliable BW were included (43% men, mean age: 38 years). NAFLD (FLI ≥ 60) was present in 5530 individuals (10%). Multivariate logistic regression showed a significant U‐shaped relationship between BW and NAFLD, with no significant interaction with sex. A significant and slightly decreasing association was found between BW and Forns Index ( β = −0.05; p = 0.04). Premature birth (OR, 1.23; 95% CI, 1.03–1.48 for birth between 33 and 37 weeks versus ≥ 37 weeks) was associated with NAFLD, with a significant direct effect of premature birth, and without an indirect effect of low BW in mediation analysis. Forns Index was not significantly higher in participants with preterm birth compared to full‐term birth. Conclusions This large prospective adult‐based cohort confirms the relationship between BW and NAFLD occurrence.
Epicardial adipose tissue related to left atrial and ventricular function in heart failure with preserved versus reduced and mildly reduced ejection fraction
Authors: Xuanyi Jin, Chung‐Lieh Hung, Wan Ting Tay, Dinna Soon, David Sim, Kuo‐Tzu Sung, Seet Yoong Loh, Sheldonn Lee, Fazlur Jaufeerally, Lieng Hsi Ling, A Mark Richards, Joost P. van Melle, Adriaan A. Voors, Carolyn S.P. Lam
Journal: European Journal of Heart Failure (2022)
IFN-γ+ cytotoxic CD4+ T lymphocytes are involved in the pathogenesis of colitis induced by IL-23 and the food colorant Red 40
Authors: Lili Chen, Zhengxiang He, Bernardo S. Reis, Jesse D. Gelles, Jerry Edward Chipuk, Adrian T. Ting, Julie A. Spicer, Joseph A. Trapani, Glaucia C. Furtado, Sergio A. Lira
Journal: Cellular and Molecular Immunology (2022)

Abstract The food colorant Red 40 is an environmental risk factor for colitis development in mice with increased expression of interleukin (IL)-23. This immune response is mediated by CD4 + T cells, but mechanistic insights into how these CD4 + T cells trigger and perpetuate colitis have remained elusive. Here, using single-cell transcriptomic analysis, we found that several CD4 + T-cell subsets are present in the intestines of colitic mice, including an interferon (IFN)-γ-producing subset. In vivo challenge of primed mice with Red 40 promoted rapid activation of CD4 + T cells and caused marked intestinal epithelial cell (IEC) apoptosis that was attenuated by depletion of CD4 + cells and blockade of IFN-γ. Ex vivo experiments showed that intestinal CD4 + T cells from colitic mice directly promoted apoptosis of IECs and intestinal enteroids. CD4 + T cell-mediated cytotoxicity was contact-dependent and required FasL, which promoted caspase-dependent cell death in target IECs. Genetic ablation of IFN-γ constrained IL-23- and Red 40-induced colitis development, and blockade of IFN-γ inhibited epithelial cell death in vivo. These results advance the understanding of the mechanisms regulating colitis development caused by IL-23 and food colorants and identify IFN-γ + cytotoxic CD4 + T cells as a new potential therapeutic target for colitis.
Metabolic engineering of yeasts for green and sustainable production of bioactive ginsenosides F2 and 3β,20S-Di-O-Glc-DM
Authors: Fenglin Jiang, Chen Zhou, Yan Li, Haidong Deng, Ting Gong, Jingjing Chen, Tianjiao Chen, Jinling Yang, Ping Zhu
Journal: Acta Pharmaceutica Sinica B (2022)

Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3β,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.
Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis
Authors: Dan Zhao, Dexuan Xiao, Mengting Liu, Jiajie Li, Shuanglin Peng, Qing He, Yue Sun, Jingang Xiao, Yunfeng Lin
Journal: International Journal of Oral Science (2022)

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients' life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.
Long noncoding RNA TLNC1 promotes the growth and metastasis of liver cancer via inhibition of p53 signaling
Authors: Kefei Yuan, Jiang Lan, Lin Xu, Xuping Feng, Haotian Liao, Kunlin Xie, Hong Wu, Yong Zeng
Journal: Molecular Cancer (2022)

Long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in cancer development and progression. However, their biological roles and function mechanisms in liver cancer remain largely unknown.RNA-seq was performed with clinical hepatoma tissues and paired adjacent normal liver tissues to identify differentially expressed lncRNAs. qPCR was utilized to examine the expression levels of lncRNAs. We studied the function of TLNC1 in cell growth and metastasis of hepatoma with both cell and mouse models. RNA-seq, RNA pull-down coupled with mass spectrometry, RNA immunoprecipitation, dual luciferase reporter assay, and surface plasmon resonance analysis were used to analyze the functional mechanism of TLNC1.Based on the intersection of our own RNA-seq, TCGA RNA-seq, and TCGA survival analysis data, TLNC1 was identified as a potential tumorigenic lncRNA of liver cancer. TLNC1 significantly enhanced the growth and metastasis of hepatoma cells both in vitro and in vivo. TLNC1 exerted its tumorigenic function through interaction with TPR and inducing the TPR-mediated transportation of p53 from nucleus to cytoplasm, thus repressing the transcription of p53 target genes and finally contributing to the progression of liver cancer.TLNC1 is a promising prognostic factor of liver cancer, and the TLNC1-TPR-p53 axis can serve as a potential therapeutic target for hepatoma treatment.
Oncohistone Mutations Occur at Functional Sites of Regulatory ADP-Ribosylation
Authors: Dan Huang, Cristel V. Camacho, Sara Martire, Anusha Nagari, Rohit Setlem, Xuan Gong, Andrea D. Edwards, Shu-Ping Chiu, Laura A. Banaszynski, W. Lee Kraus
Journal: Cancer Research (2022)

Abstract Recent studies have identified cancer-associated mutations in histone genes that lead to the expression of mutant versions of core histones called oncohistones. Many oncohistone mutations occur at Asp and Glu residues, two amino acids known to be ADP-ribosylated (ADPRylated) by PARP1. We screened 25 Glu or Asp oncohistone mutants for their effects on cell growth in breast and ovarian cancer cells. Ectopic expression of six mutants of three different core histones (H2B, H3, and H4) altered cell growth in at least two different cell lines. Two of these sites, H2B-D51 and H4-D68, were indeed sites of ADPRylation in wild-type (unmutated) histones, and mutation of these sites inhibited ADPRylation. Mutation of H2B-D51 dramatically altered chromatin accessibility at enhancers and promoters, as well as gene expression outcomes, whereas mutation of H4-D68 did not. Additional biochemical, cellular, proteomic, and genomic analyses demonstrated that ADPRylation of H2B-D51 inhibits p300-mediated acetylation of H2B at many Lys residues. In breast cancer cell xenografts in mice, H2B-D51A promoted tumor growth, but did not confer resistance to the cytotoxic effects of PARP inhibition. Collectively, these results demonstrate that functional Asp and Glu ADPRylation sites on histones are mutated in cancers, allowing cancer cells to escape the growth-regulating effects of post-translational modifications via distinct mechanisms. Significance: This study identifies cancer-driving mutations in histones as sites of PARP1–mediated ADP-ribosylation in breast and ovarian cancers, providing a molecular pathway by which cancers may subvert the growth-regulating effects of PARP1.
Reply to Martinez-Garcia <i>et al</i>. and to Abreu and Punjabi
Authors: Bastien Lechat, Peter Catcheside, Amy Reynolds, Robert J. Adams, R. Doug McEvoy, Danny J. Eckert
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

OSA from the contactless sensor are available.Given that the previous validation study (3) and the supplementary data comparing the contactless sensor and polysomnography showed no difference in AHI between the two tests, reporting the prevalence of different OSA categories using AHI thresholds would be of value.Second, the authors have opted to use the mean AHI of all available nights to calculate the reference AHI against which the reliability of a subset of the nights is compared.It could be easily argued that the median AHI may be a better estimator of central tendency than the mean AHI, particularly if a person has extreme AHI values that may result from factors such as being in the supine position only or consumption of alcohol on any particular night.A possible alternative to the median could be the mode of the AHI distribution from each person.Although we are not proponents, an argument could also be made that the "diagnosis of OSA" should be based on the highest AHI value.Did the authors examine whether the prevalence and misclassification of OSA would be different if the median or mode were used for the reference AHI instead of the mean?Third, the data on operating characteristics of multinight testing suggest that the increase in positive predictive and the drop in negative predictive values when comparing 7 with 14 nights is relatively small.Thus, what is the minimum number of nights of monitoring necessary to reliably estimate AHI in clinical practice within a 65% margin of error?Having such information would help change the paradigm of clinical testing in which 1 night is always used despite the capability for multinight testing.It is time that multinight testing became mainstream practice, because the body of empirical evidence on AHI variability is unquestionable (4).One night is just not enough
Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC)
Authors: Inna M. Chen, Julia S. Johansen, Susann Theile, Jessica X. Hjaltelin, Sif I. Novitski, Søren Brunak, Jane P. Hasselby, Gro L. Willemoe, Torben Lorentzen, Kasper Madsen, Benny V. Jensen, Eva E. Wilken, Poul Geertsen, Claus Behrens, Christian Nolsoe, Kirstine L. Hermann, Inge Marie Svane, Dorte Nielsen
Journal: Journal of Clinical Oncology (2022)

To evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with refractory metastatic pancreatic cancer (mPC).Between November 2016 and December 2019, patients with refractory mPC were randomly assigned 1:1 to SBRT of 15 Gy with nivolumab or nivolumab/ipilimumab stratified by performance status (ClinicalTrials.gov identifier: NCT02866383). The primary end point was the clinical benefit rate (CBR), defined as the percentage of patients with complete or partial response (PR) or stable disease, according to RECIST 1.1. Simon's 2-stage phase II optimal design was used independently for both arms, with CBR determining expansion to the second stage. Secondary end points included safety, response rate, duration of response, progression-free survival, and overall survival. Exploratory analyses included biomarkers related to the benefits.Eighty-four patients (41 SBRT/nivolumab and 43 SBRT/nivolumab/ipilimumab) received at least one dose of study treatment. CBR was 17.1% (8.0 to 30.6) for patients receiving SBRT/nivolumab and 37.2% (24.0 to 52.1) for SBRT/nivolumab/ipilimumab. PR was observed in one patient receiving SBRT/nivolumab and lasted for 4.6 months. Six patients receiving SBRT/nivolumab/ipilimumab achieved a PR with a median duration of response of 5.4 months (4.2 to not reached). Grade 3 or higher treatment-related adverse events occurred in 10 (24.4%) and 13 (30.2%) patients in the SBRT/nivolumab and SBRT/nivolumab/ipilimumab groups, respectively. Programmed cell death ligand-1 expression by tumor proportion score or combined positivity score of ≥ 1% was not associated with clinical benefits. On-treatment decreased serum interleukin-6, interleukin-8, and C-reactive protein levels were associated with better overall survival.Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with SBRT/nivolumab/ipilimumab in patients with refractory mPC. However, the contribution from SBRT is unknown. Further studies are warranted.
Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study
Authors: Tommy Nyberg, Neil M Ferguson, Sophie G Nash, Harriet H Webster, Seth Flaxman, Nick Andrews, Wes Hinsley, Jamie Lopez Bernal, Meaghan Kall, Samir Bhatt, Paula Blomquist, Asad Zaidi, Erik Volz, Nurin Abdul Aziz, Katie Harman, Sebastian Funk, Sam Abbott, Russell Hope, Andre Charlett, Meera Chand, Azra C Ghani, Shaun R Seaman, Gavin Dabrera, Daniela De Angelis, Anne M Presanis, Simon Thelwall, Tommy Nyberg, Neil M Ferguson, Sophie G Nash, Harriet H Webster, Seth Flaxman, Nick Andrews, Wes Hinsley, Jamie Lopez Bernal, Meaghan Kall, Samir Bhatt, Paula Blomquist, Asad Zaidi, Erik Volz, Nurin Abdul Aziz, Katie Harman, Sebastian Funk, Sam Abbott, Russell Hope, Andre Charlett, Meera Chand, Azra C Ghani, Shaun R Seaman, Gavin Dabrera, Daniela De Angelis, Anne M Presanis, Simon Thelwall
Journal: The Lancet (2022)

The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.
Reply to Chen <i>et al.</i>: Mild Intermittent Hypoxia: A New Treatment Approach for Patients with Obstructive Sleep Apnea and Hypertension
Authors: Gino S. Panza, Shipra Puri, Ho-Sheng Lin, M. Safwan Badr, Jason H. Mateika
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
Ultrasound-guided versus laparoscopic-guided subcostal transversus abdominis plane (TAP) block versus No TAP block in laparoscopic cholecystectomy; a randomized double-blind controlled trial
Authors: Sameh Hany Emile, Hossam Elfeki, Khaled Elbahrawy, Ahmad Sakr, Mostafa Shalaby
Journal: International Journal of Surgery (2022)
Molecular reactivity profiling upon immunotherapy with a 300 IR sublingual house dust mite tablet reveals marked humoral changes towards major allergens
Authors: Ekaterina Potapova, Véronique Bordas‐Le Floch, Thomas Schlederer, Susanne Vrtala, Huey‐Jy Huang, Giorgio W. Canonica, Rudolf Valenta, Paolo M. Matricardi, Laurent Mascarell
Journal: Allergy (2022)

Molecular antibody reactivity profiles have not yet been studied in depth in patients treated by sublingual house dust mite (HDM) tablet immunotherapy. Humoral immune responses to a large panel of HDM mite allergens were studied using allergen microarray technology in a subset of clinically defined high and low responder patients from a double-blind placebo-controlled allergen-specific immunotherapy (AIT) trial using sublingual 300 IR HDM tablets.Serum levels of IgE, IgG and IgG4 to 13 Dermatophagoides pteronyssinus molecules were measured at baseline and after 1-year AIT, using allergen microarrays in 100 subjects exhibiting high or low clinical benefit.Der p 1, Der p 2 and Der p 23 were the most frequently recognized allergens in the study population. Patients with HDM-related asthma had significantly higher allergen-specific IgE levels to Der p 1 and Der p 23. No significant difference in the distribution of allergen sensitization pattern was observed between high and low responders. An increase in serum allergen-specific IgG and IgG4 occurred upon AIT, in particular to allergens Der p 1, Der p 2 and Der p 23 (p < 0.0001).We confirm for our study population that Der p 1- and Der p 23-specific IgE levels are associated with asthma. IgE reactivity profiles were not predicitive of sublingual AIT outcomes, with 300 IR tablets as efficacious in pauci- and multi-sensitized subjects. Our study is the first to demonstrate the induction of IgG and IgG4 specific for the HDM allergens Der p 1, Der p 2 and Der p 23 by sublingual AIT.
Supervised Consumption Sites—A Tool for Reducing Risk of Overdose Deaths and Infectious Diseases in People Who Use Illicit Drugs
Authors: Rita Rubin, Melissa Suran
Journal: JAMA (2022)

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Harbor Seal
Authors: Zeynep Berrak Uzumcu
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal