tbuckley/cabot-search huggingface dataset:
Melatonin ameliorates necrotizing enterocolitis by preventing Th17/Treg imbalance through activation of the AMPK/SIRT1 pathway
Authors: Fei Ma, Hu Hao, Xiaoyan Gao, Yao Cai, Jialiang Zhou, Puping Liang, Junjian Lv, Qiuming He, Congcong Shi, Dandan Hu, Bowei Chen, Lixin Zhu, Xin Xiao, Sitao Li
Journal: Theranostics (2020)

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting premature infants. Mounting evidence supports the therapeutic effect of melatonin on NEC, although the underlying mechanisms remain unclear. Methods: NEC was induced in 10-day-old C57BL/6 pups via hypoxia and gavage feeding of formula containing enteric bacteria, and then, mice received melatonin, melatonin + recombinant IL-17, melatonin + anti-CD25 monoclonal antibody, melatonin + Ex-527, or melatonin + Compound C treatment. Control mice were left with their dams to breastfeed and vehicle-treated NEC pups were used as controls for treatment. Ileal tissues were collected from mice and analyzed by histopathology, immunoblotting, and flow cytometry. FITC-labeled dextran was administered to all surviving pups to evaluate gut barrier function by fluorometry. We used molecular biology and cell culture approaches to study the related mechanisms in CD4+ T cells from umbilical cord blood. Results: We demonstrated that melatonin treatment ameliorates disease in an NEC mouse model in a manner dependent on improved intestinal Th17/Treg balance. We also showed that melatonin blocks the differentiation of pathogenic Th17 cells and augments the generation of protective Treg cells in vitro. We further demonstrated that the Th17/Treg balance is influenced by melatonin through activation of AMPK in the intestine, in turn promoting SIRT1 activation and stabilization. Conclusions: These results demonstrate that melatonin-induced activation of AMPK/SIRT1 signaling regulates the balance between Th17 and Treg cells and that therapeutic strategies targeting the Th17/Treg balance via the AMPK/SIRT1 pathway might be beneficial for the treatment of NEC.
Abstract 12355: Pro-Inflammatory Remodeling of High-Density Lipoprotein Precedes Development of Dyslipidemia and Hepatic Steatosis Upon Exposure to High Fat Diet for Four Weeks
Authors: Prabodh Sadana, Li Lin, Sergeui Ilchenko, Chandni Goel, Anuradha Kanaparthi, Werner J Geldenhuys, Takhar Kasumov
Journal: Circulation (2018)

Long-term high fat feeding leads to hepatic steatosis, dyslipidemia, and a pro-inflammatory state. In a previous study, we observed this dysregulated metabolic phenotype when C57BL/6 mice were fed ...
Long-term Outcomes of Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Not as Good as Previously Thought
Authors: Carlo A. Bravi, Nicola Fossati, Giorgio Gandaglia, Nazareno Suardi, Elio Mazzone, Daniele Robesti, Daniar Osmonov, Klaus-Peter Juenemann, Luca Boeri, R. Jeffrey Karnes, Alexander Kretschmer, Alexander Buchner, Christian Stief, Andreas Hiester, Alessandro Nini, Peter Albers, Gaëtan Devos, Steven Joniau, Hendrik Van Poppel, Shahrokh F. Shariat, Axel Heidenreich, David Pfister, Derya Tilki, Markus Graefen, Inderbir S. Gill, Alexander Mottrie, Pierre I. Karakiewicz, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2020)
Perspectives on Urinary Tract Infection and Race
Authors: Rachel H. Kowalsky, Ashley C. Rondini, Shari L. Platt
Journal: JAMA Pediatrics (2020)

In Reply We thank Cruz et al, Shaw et al, and Goza for their thoughtful response letters to our Viewpoint1 and this opportunity for important dialogue. We have great respect for the authors of these letters and their significant contributions to the field of pediatric emergency medicine.
Palmitoylated Proteins on AML-Derived Extracellular Vesicles Promote Myeloid-Derived Suppressor Cell Differentiation via TLR2/Akt/mTOR Signaling
Authors: Sehmus Tohumeken, Rebecca Baur, Martin Böttcher, Andrej Stoll, Romy Loschinski, Konstantinos Panagiotidis, Martina Braun, Domenica Saul, Simon Völkl, Andreas S. Baur, Heiko Bruns, Andreas Mackensen, Regina Jitschin, Dimitrios Mougiakakos
Journal: Cancer Research (2020)

Acute myeloid leukemia (AML) represents the most common acute leukemia among adults. Despite recent progress in diagnosis and treatment, long-term outcome remains unsatisfactory. The success of allogeneic stem cell transplantation underscores the immunoresponsive nature of AML, creating the basis for further exploiting immunotherapies. However, emerging evidence suggests that AML, similar to other malignant entities, employs a variety of mechanisms to evade immunosurveillance. In light of this, T-cell inhibitory myeloid-derived suppressor cells (MDSC) are gaining interest as key facilitators of immunoescape. Accumulation of CD14+HLA-DRlow monocytic MDSCs has been described in newly diagnosed AML patients, and deciphering the underlying mechanisms could help to improve anti-AML immunity. Here, we report that conventional monocytes readily take-up AML-derived extracellular vesicles (EV) and subsequently undergo MDSC differentiation. They acquired an CD14+HLA-DRlow phenotype, expressed the immunomodulatory indoleamine-2,3-dioxygenase, and upregulated expression of genes characteristic for MDSCs, such as S100A8/9 and cEBPβ. The Akt/mTOR pathway played a critical role in the AML-EV-induced phenotypical and functional transition of monocytes. Generated MDSCs displayed a glycolytic switch, which rendered them more susceptible toward glycolytic inhibitors. Furthermore, palmitoylated proteins on the AML-EV surface activated Toll-like receptor 2 as the initiating event of Akt/mTOR-dependent induction of MDSC. Therefore, targeting protein palmitoylation in AML blasts could block MDSC accumulation to improve immune responses. SIGNIFICANCE: These findings indicate that targeting protein palmitoylation in AML could interfere with the leukemogenic potential and block MDSC accumulation to improve immunity.
COVID-19 Network: the response of an Italian Reference Institute to research challenges about a new pandemia
Authors: A. Bandera, S. Aliberti, R. Gualtierotti, M. Baldini, F. Blasi, M. Cesari, G. Costantino, A.L. Fracanzani, A. Gori, N. Montano, V. Monzani, A. Nobili, F. Peyvandi, A. Pesenti, D. Prati, L. Valenti, G. Fusetti, L. Scudeller, S. Bosari, S. Bosari, L. Scudeller, G. Fusetti, L. Rusconi, S. Dell Orto, D. Prati, L. Valenti, G. Lamorte, M. Manunta, G. Baselli, L. Santoro, A. Gori, A. Bandera, A. Muscatello, D. Mangioni, L. Alagna, G. Bozzi, A. Lombardi, R. Ungaro, T. Itri, V. Ferroni, V. Pastore, R. Massafra, I. Rondolini, F. Peyvandi, R. Gualtierotti, B. Ferrari, R. Rossio, E. Corona, N. Rampi, C. Massimo, N. Montano, B. Vigone, C. Bellocchi, E. Fiorelli, V. Melli, E. Tobaldini, F. Blasi, S. Aliberti, M. Spotti, E. Simonetta, L. Terranova, F. Amati, C. Miele, S. Misuraca, A. D'Adda, S. Della Fiore, M. Di Pasquale, M.M.M. Contarini, M. Ori, L. Morlacchi, V. Rossetti, A. Gramegna, M. Pappalettera, M. Cavallini, A. Vigni, M. Vicenzi, I. Rota, G. Costantino, M. Solbiati, L. Furlan, M. Mancarella, G. Colombo, G. Colombo, A. Fanin, V. Monzani, A. Rovellini, L. Barbetta, F. Billi, C. Folli, M. Baldini, I. Motta, N. Scaramellini, A.L. Fracanzani, R. Lombardi, F. Iuculano, M. Cesari, M. Proietti, L. Calcaterra, A. Nobili, M. Tettamanti, I. Monti
Journal: Clinical Microbiology and Infection (2020)
Translation of Computational Psychiatry in the Context of Addiction
Authors: Shuyan Liu, Raymond J. Dolan, Andreas Heinz
Journal: JAMA Psychiatry (2020)

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 Psychiatry 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 Psychiatry journal
Development of a polygenic risk score to improve screening for fracture risk: A genetic risk prediction study
Authors: Vincenzo Forgetta, Julyan Keller-Baruch, Marie Forest, Audrey Durand, Sahir Bhatnagar, John P. Kemp, Maria Nethander, Daniel Evans, John A. Morris, Douglas P. Kiel, Fernando Rivadeneira, Helena Johansson, Nicholas C. Harvey, Dan Mellström, Magnus Karlsson, Cyrus Cooper, David M. Evans, Robert Clarke, John A. Kanis, Eric Orwoll, Eugene V. McCloskey, Claes Ohlsson, Joelle Pineau, William D. Leslie, Celia M. T. Greenwood, J. Brent Richards
Journal: PLoS Medicine (2020)

Since screening programs identify only a small proportion of the population as eligible for an intervention, genomic prediction of heritable risk factors could decrease the number needing to be screened by removing individuals at low genetic risk. We therefore tested whether a polygenic risk score for heel quantitative ultrasound speed of sound (SOS)-a heritable risk factor for osteoporotic fracture-can identify low-risk individuals who can safely be excluded from a fracture risk screening program.
Abstract 15227: Sleep, Blood Pressure Variability, and Cardiovascular Outcomes
Authors: Soojung Ahn, Younghoon Kwon, Jeongok Logan, Jennifer M Lobo, Hyojung Kang, Min-Woong Sohn
Journal: Circulation (2019)

Introduction: Impaired sleep and high blood pressure variability (BPV) are both known to be risk factors for cardiovascular disease (CVD). Sleep disorder such as sleep apnea has been linked to high...
Limited Evidence for the Health Effects and Safety of Intermittent Fasting Among Patients With Type 2 Diabetes
Authors: Benjamin D. Horne, Martin M. Grajower, Jeffrey L. Anderson
Journal: JAMA (2020)

This Viewpoint summarizes evidence about the effects of intermittent fasting on chronic disease markers and considers potential concerns about fasting as a strategy for weight management and glycemic control in people with type 2 diabetes.
Adipose Tissue-Derived Wnt5a as a Novel Link Between Obesity and Vascular Disease
Authors: I Akoumianakis, F Sanna, M Margaritis, N Akawi, L Herdman, P Coutinho, H Fagan, A S Antonopoulos, E K Oikonomou, S Thomas, C Christodoulides, F Karpe, M Petrou, G Krasopoulos, R Sayeed, L Lv, A Hale, E McNeill, G Douglas, S George, K M Channon, C Antoniades
Journal: Circulation (2018)
TRAF3 Modulation: Novel Mechanism for the Anti-inflammatory Effects of the Vitamin D Receptor Agonist Paricalcitol in Renal Disease
Authors: Sandra Rayego-Mateos, Jose Luis Morgado-Pascual, José Manuel Valdivielso, Ana Belén Sanz, Enrique Bosch-Panadero, Raúl R. Rodrigues-Díez, Jesús Egido, Alberto Ortiz, Emilio González-Parra, Marta Ruiz-Ortega
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement TNF receptor–associated factor 3 (TRAF3) downregulation is a key feature promoting inflammation in CKD, and noncanonical NF- κ B2 activation is a key driver of inflammation in this context. TRAF3 levels in PBMCs are decreased in patients on hemodialysis and could be a biomarker for the inflammatory state. Paricalcitol may reverse TRAF3 downregulation in a vitamin D receptor–independent manner, suggesting novel signaling pathways behind the anti-inflammatory effect of paricalcitol. Background CKD leads to vitamin D deficiency. Treatment with vitamin D receptor agonists (VDRAs) may have nephroprotective and anti-inflammatory actions, but their mechanisms of action are poorly understood. Methods Modulation of the noncanonical NF- κ B2 pathway and its component TNF receptor–associated factor 3 (TRAF3) by the VDRA paricalcitol was studied in PBMCs from patients with ESKD, cytokine-stimulated cells, and preclinical kidney injury models. Results In PBMCs isolated from patients with ESKD, TRAF3 protein levels were lower than in healthy controls. This finding was associated with evidence of noncanonical NF- κ B2 activation and a proinflammatory state. However, PBMCs from patients with ESKD treated with paricalcitol did not exhibit these features. Experiments in cultured cells confirmed the link between TRAF3 and NF- κ B2/inflammation. Decreased TRAF3 ubiquitination in K48-linked chains and cIAP1-TRAF3 interaction mediated the mechanisms of paricalcitol action.TRAF3 overexpression by CRISPR/Cas9 technology mimicked VDRA’s effects. In a preclinical model of kidney injury, paricalcitol inhibited renal NF- κ B2 activation and decreased renal inflammation. In VDR knockout mice with renal injury, paricalcitol prevented TRAF3 downregulation and NF- κ B2–dependent gene upregulation, suggesting a VDR-independent anti-inflammatory effect of paricalcitol. Conclusions These data suggest the anti-inflammatory actions of paricalcitol depend on TRAF3 modulation and subsequent inhibition of the noncanonical NF- κ B2 pathway, identifying a novel mechanism for VDRA’s effects. Circulating TRAF3 levels could be a biomarker of renal damage associated with the inflammatory state.
Pyrotinib in <i>HER2</i>-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study
Authors: Caicun Zhou, Xingya Li, Qiming Wang, Guanghui Gao, Yiping Zhang, Jianhua Chen, Yongqian Shu, Yanping Hu, Yun Fan, Jian Fang, Gongyan Chen, Jun Zhao, Jianxing He, Fengying Wu, Jianjun Zou, Xiaoyu Zhu, Xiang Lin
Journal: Journal of Clinical Oncology (2020)

Targeted therapies against non-small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study.Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC).Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported.Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.
Circulating transcripts in maternal blood reflect a molecular signature of early-onset preeclampsia
Authors: Sarah Munchel, Suzanne Rohrback, Carlo Randise-Hinchliff, Sarah Kinnings, Shweta Deshmukh, Nagesh Alla, Catherine Tan, Amirali Kia, Grainger Greene, Linda Leety, Matthew Rhoa, Scott Yeats, Matthew Saul, Julia Chou, Kimberley Bianco, Kevin O’Shea, Emmanuel Bujold, Errol Norwitz, Ronald Wapner, George Saade, Fiona Kaper
Journal: Science Translational Medicine (2020)

Circulating transcripts reflect biologically relevant changes in early-onset severe preeclampsia and can accurately classify patient status.
COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study
Authors: Reina S Sikkema, Suzan D Pas, David F Nieuwenhuijse, Áine O'Toole, Jaco Verweij, Anne van der Linden, Irina Chestakova, Claudia Schapendonk, Mark Pronk, Pascal Lexmond, Theo Bestebroer, Ronald J Overmars, Stefan van Nieuwkoop, Wouter van den Bijllaardt, Robbert G Bentvelsen, Miranda M L van Rijen, Anton G M Buiting, Anne J G van Oudheusden, Bram M Diederen, Anneke M C Bergmans, Annemiek van der Eijk, Richard Molenkamp, Andrew Rambaut, Aura Timen, Jan A J W Kluytmans, Bas B Oude Munnink, Marjolein F Q Kluytmans van den Bergh, Marion P G Koopmans
Journal: The Lancet Infectious Diseases (2020)

10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers.We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients.Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community.Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers.EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Chilblain‐like lesions during the COVID‐19 pandemic: a serological study on a case series
Authors: L. Rizzoli, L. Collini, M. Magnano, S. Termine, R. Barcelli, S.D. Infusino, P. Bauer, G. Rech, C.R. Girardelli, R. Balestri
Journal: British Journal of Dermatology (2020)

The outbreak of chilblain‐like lesions (CLL) coincidentally to the COVID‐19 pandemic is a topic of great concern. SARS‐CoV‐2 has been hypothesized as the etiologic agent of CLL, on the basis of the temporal correlation between the “burst” of skin manifestations and the viral pandemic. However, the relationship between CLL and COVID‐19 remains unclear, since authors failed to confirm the SARS‐CoV‐2 infection in these patients using a real‐time reverse transcription polymerase chain reaction (rt‐PCR) test from nasopharyngeal swabs, which seldom resulted positive. Indeed, the most recent articles on the prevalence of the SARS‐CoV‐2 infection in CLL reported a positive swab test in only about a fifth of these patients.
Reevaluation of excessive erythrocytosis in diagnosing chronic mountain sickness in men from the world’s highest city
Authors: Laura Oberholzer, Carsten Lundby, Emeric Stauffer, Mathilde Ulliel-Roche, Ivan Hancco, Aurélien Pichon, Anne-Kristine Meinild Lundby, Francisco C. Villafuerte, Samuel Verges, Paul Robach
Journal: Blood (2020)
Lessons from Leicester: a covid-19 testing system that’s not fit for purpose
Authors: Mike Gill, Devi Sridhar, Fiona Godlee
Journal: BMJ (2020)

With the flare-up of covid-19 and re-imposition of lockdown, the population of Leicester is suffering the fallout of a chaotic testing system that seems to have forgotten its prime purpose, namely to trigger prompt, targeted measures, informed by local knowledge and up-to-date surveillance.Without swift and decisive action by those at local and national levels who understand communicable disease control, England will see further lockdowns and more avoidable deaths.Leicester was a city at risk, with high levels of social deprivation and ethnic diversity.We now know that cases spiked in late May and that new cases were being detected throughout June at rates of over 100 per 100 000 population per week.But these data were made available to the local authority only days before lockdown was re-imposed on 30 June 1 and were not made public for several days after that.In Germany the rates required to trigger local lockdown are 35-50 cases per 100 000 per week, 2 supported by a well functioning, locally based track and trace system.