tbuckley/cabot-search huggingface dataset:
Caution Against Overinterpreting Time-Restricted Eating Results
Authors: Dipti Agarwal, Subhash Chandra
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine 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 Internal Medicine journal
Grounding together: Shared reality and cleansing practices
Authors: Maya Rossignac-Milon, E. Tory Higgins
Journal: Behavioral and Brain Sciences (2021)

Abstract We propose that cleansing behaviors and other acts of separation or connection have more powerful effects when they are grounded in shared practices – in a shared reality. We conceptualize sensorimotor and shared reality effects as synergistic. Most potent should be physical behaviors performed collectively as a shared practice (e.g., communal bathing), grounded both in sensorimotor experience and in shared reality.
Baclofen to Prevent Agitation Caused by Alcohol Withdrawal in the ICU
Authors: Michael C. Reade
Journal: JAMA (2021)

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
Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis
Authors: Ben Wang, Shiwei Zhu, Zuojing Liu, Hui Wei, Lu Zhang, Meibo He, Fei Pei, Jindong Zhang, Qinghua Sun, Liping Duan
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HCs) were recruited. Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.
The impact of time to tracheostomy on mechanical ventilation duration, length of stay, and mortality in intensive care unit patients.
Authors: Jamal Alhashemi
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Arabi YM, Alhashemi JA, Tamim HM, Esteban A, Haddad SH, Dawood A, Shirawi N, Alshimemeri AA.
Department of Intensive Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia. yaseenarabi@yahoo.com
INTRODUCTION: This study examined the potential effects of time to tracheostomy on mechanical ventilation duration, intensive care unit (ICU), and hospital length of stay (LOS), and ICU and hospital mortality. METHODS: Cohort observational study was conducted in a tertiary care medical-surgical ICU based on a prospectively collected ICU database. We included 531 consecutive patients who were admitted between March 1999 and February 2005, and underwent tracheostomy during their ICU stay. The effect of time to tracheostomy on the different outcomes assessed was estimated using multivariate regression analyses (linear or logistic, based on the type of variables). Other independent variables that were included in the analyses included selected admission characteristics. RESULTS: Mean +/- SD was 12.0 +/- 7.3 days for time to tracheostomy, and 23.1 +/- 18.9 days for ICU LOS. Time to tracheostomy was associated with an increased duration of mechanical ventilation (beta-coefficient = 1.31 for each day; 95% confidence interval [CI], 1.14-1.48), ICU LOS (beta-coefficient = 1.31 for each day; 95% CI, 1.13-1.48), and hospital LOS (beta-coefficient = 1.80 for each day; 95% CI, 0.65-2.94). On the other hand, time to tracheostomy was not associated with increased ICU or hospital mortality. CONCLUSIONS: Time to tracheostomy was independently associated with increased mechanical ventilation duration, ICU LOS, and hospital LOS, but was not associated with increased mortality. Performing tracheostomy earlier in the course of ICU stay may have an effect on ICU resources and could entail significant cost-savings without adversely affecting patient mortality.
PMID: 19327302 [PubMed - indexed for MEDLINE]
Frequent amplification of HDAC genes and efficacy of HDAC inhibitor chidamide and PD-1 blockade combination in soft tissue sarcoma
Authors: Yi Que, Xiao-Long Zhang, Ze-Xian Liu, Jing-Jing Zhao, Qiu-Zhong Pan, Xi-Zhi Wen, Wei Xiao, Bu-Shu Xu, Dong-Chun Hong, Tian-Hui Guo, Lu-Jun Shen, Wei-Jun Fan, Huo-Ying Chen, De-Sheng Weng, Hai-Rong Xu, Peng-Hui Zhou, Yi-Zhuo Zhang, Xiao-Hui Niu, Xing Zhang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival. Methods Whole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study. Results The HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8 + T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1. Conclusions The combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.
Abstract PS8-24: Clinical and pathologic characteristics of Turkish breast cancer (BC) patients screened with BRCA1, BRCA2 or 26 - gene inherited cancer panel testing: Single institution experience
Authors: Aysun Isiklar, Aykut Soyder, Kanay Yararbas, Cumhur Ekmekci, Hulya Yazici, Gul Basaran
Journal: Cancer Research (2021)

Abstract Background: BRCA1 and BRCA2 mutations are responsible for two thirds of hereditary BC. Germline genetic testing for BC susceptibility has evolved from a single-gene analysis to a multigene panel testing. Identification of a pathogenic mutation in BRCA and other panel represent a therapeutic opportunity today. Methods: We aimed to investigate clinical and pathologic characteristics of BC patients who were referred to our center between 2011-2019 and underwent BRCA1, BRCA2 or 26-gene inherited cancer panel testing based on NCCN criteria for hereditary breast/ovarian cancer testing. We analyzed the frequency of pathogenic mutations and its relationship with clinical and pathologic factors. Results: A total of 576 patients were identified. Among them 356 (63%) had their test in our university, 218 (38%) patients had their test at other centers. Sixty-six % (n:376) of patients had panel testing, 34% had only BRCA 1-2 mutation test. Median age was 42(22-87) and 5 patients were male. Ten % of patients had metastatic disease, 70% had early BC and 20% had locally advanced stage at the time of referral. The indication for genetic testing was family history in 169 (29%) patients, triple negative (TN) subtype in 100 (17%) patients and age &amp;lt;45 years in 260 (45%) patients. Seventy-nine % of patients were premenopausal. A total of 114 (19%) patients had pathogenic mutations. The most commonly mutated genes were BRCA1 (n:38, 6%), BRCA2 (n:35, 6%), ATM (n:6), p53 (n:5), PALB2 (n:5), CHEK2 (n:5). Six patients had more than one pathogenic mutation. Among patients with pathogenic mutations 58% had ER positive, 27% had TN and 15 % had Her-2 positive disease. Thirty-four % of patients with TN tumors have pathogenic mutations, 23% of patients with TN tumors had BRCA mutations. TP53, PALB2 and CHEK2 mutations were more frequent in HR positive disease. Age &amp;lt;35 (p:0.002), triple negative subtype (p: 0.005) and menopausal status (p:0.001) were significantly associated with having pathogenic mutations in multivariate analysis. Conclusion: Two thirds of BC patients &amp;lt;35 years-old and one third of patients with TN tumors have pathogenic germline mutations in BC predisposing genes when they were screened in line with NCCN criteria. Citation Format: Aysun Isiklar, Aykut Soyder, Kanay Yararbas, Cumhur Ekmekci, Hulya Yazici, Gul Basaran. Clinical and pathologic characteristics of Turkish breast cancer (BC) patients screened with BRCA1, BRCA2 or 26 - gene inherited cancer panel testing: Single institution experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-24.
A Step Ahead in Metastatic Renal Cell Carcinoma
Authors: Alain Ravaud
Journal: New England Journal of Medicine (2021)

Motzer et al. report in the Journal the efficacy and safety of pembrolizumab, an anti–programmed cell death 1 (PD-1) monoclonal antibody, used in combination with lenvatinib, an antiangiogenic drug (a vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor), as compared with the standard first-line treatment (sunitinib, also a VEGFR tyrosine kinase inhibitor) in patients with advanced renal cell carcinoma.1 This trial adds to the existing evidence of positive outcomes for overall survival and progression-free survival obtained with anti–PD-1–based therapy in combination with ipilimumab2 or axitinib.3 Nivolumab and ipilimumab are indicated for patients with intermediate or poor risk according to . . .
Priorities for the COVID-19 pandemic at the start of 2021: statement of the Lancet COVID-19 Commission
Authors: Jeffrey D Sachs, Salim Abdool Karim, Lara Aknin, Joseph Allen, Kirsten Brosbøl, Gabriela Cuevas Barron, Peter Daszak, María Fernanda Espinosa, Vitor Gaspar, Alejandro Gaviria, Andy Haines, Peter J Hotez, Phoebe Koundouri, Felipe Larraín B., Jong-Koo Lee, Muhammad Pate, Paul Polman, Gabriela Ramos, K Srinath Reddy, Ismail Serageldin, Rajiv Shah, John Thwaites, Vaira Vike-Freiberga, Chen Wang, Miriam Khamadi Were, Lan Xue, Min Zhu, Maria Elena Bottazzi, Francesca Colombo, George Laryea-Adjei, Yanis Ben Amor, Ozge Karadag Caman, Guillaume Lafortune, Emma Torres, Ismini Ethridge, Juliana Bartels
Journal: The Lancet (2021)

The Lancet COVID-19 Commission calls for three urgent actions in the COVID-19 response (our broader overview is available on our website). First, all regions with high rates of new COVID-19 cases, including the USA and the European Union (EU), should intensify measures to minimise community transmission alongside rapid deployment of COVID-19 vaccines. Second, governments should urgently and fully fund WHO and the Access to COVID-19 Tools (ACT) Accelerator,1 including COVAX. Third, the G20 countries should empower the International Monetary Fund (IMF) and multilateral development banks to increase the scale of financing and debt relief.
G-quadruplexes: a promising target for cancer therapy
Authors: Nils Kosiol, Stefan Juranek, Peter Brossart, Annkristin Heine, Katrin Paeschke
Journal: Molecular Cancer (2021)

DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). G4 structure formation can drive genome instability by creating mutations, deletions and stimulating recombination events. The importance of G4 structures in the characterization of malignant cells was currently demonstrated in breast cancer samples. In this analysis a correlation between G4 structure formation and an increased intratumor heterogeneity was identified. This suggests that G4 structures might allow breast cancer stratification and supports the identification of new personalized treatment options. Because of the stability of G4 structures and their presence within most human oncogenic promoters and at telomeres, G4 structures are currently tested as a therapeutic target to downregulate transcription or to block telomere elongation in cancer cells. To date, different chemical molecules (G4 ligands) have been developed that aim to target G4 structures. In this review we discuss and compare G4 function and relevance for therapeutic approaches and their impact on cancer development for three cancer entities, which differ significantly in their amount and type of mutations: pancreatic cancer, leukemia and malignant melanoma. G4 structures might present a promising new strategy to individually target tumor cells and could support personalized treatment approaches in the future.
Correction to: Exosomes derived from gemcitabine resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p
Authors: Feng Wei, Chengyuan Ma, Tong Zhou, Xuechao Dong, Qinghua Luo, Li Geng, Lijuan Ding, Yandong Zhang, Li Zhang, Nan Li, Yang Li, Yan Liu
Journal: Molecular Cancer (2021)

An amendment to this paper has been published and can be accessed via the original article.
Lactate-induced M2 polarization of tumor-associated macrophages promotes the invasion of pituitary adenoma by secreting CCL17
Authors: Anke Zhang, Yuanzhi Xu, Houshi Xu, Jie Ren, Tong Meng, Yunjia Ni, Qingwei Zhu, Wen-Bo Zhang, Yuan-Bo Pan, Jiali Jin, Yunke Bi, Zhe Bao Wu, Shaojian Lin, Meiqing Lou
Journal: Theranostics (2021)

Background: Lactate greatly contributes to the regulation of intracellular communication within the tumor microenvironment (TME). However, the role of lactate in pituitary adenoma (PA) invasion is unclear. In this study, we aimed to clarify the effects of lactate on the TME and the effects of TME on PA invasion. Methods: To explore the correlation between TME acidosis and tumor invasion, LDHA and LAMP2 expression levels were quantified in invasive (n = 32) and noninvasive (n = 32) PA samples. The correlation between immune cell infiltration and tumor invasion was evaluated in 64 PAs. Critical chemokine and key signaling pathway components were detected by qPCR, Western blotting, siRNA knockdown, and specific inhibitors. The functional consequences of CCR4 signaling inhibition were evaluated in vitro and in vivo. Results: Lactate was positively associated with PA invasion. Of the 64 PA tissues, invasive PAs were related to high infiltration of M2-like tumor-associated macrophages (TAMs) (P < 0.05). Moreover, lactate secreted from PA cells facilitated M2 polarization via the mTORC2 and ERK signaling pathways, while activated TAMs secreted CCL17 to promote PA invasion via the CCL17/CCR4/mTORC1 axis. According to univariate analysis of clinical data, high CCL17 expression was associated with larger tumor size (P = 0.0438), greater invasion (P = 0.0334), and higher susceptibility to postoperative recurrence (P = 0.0195) in human PAs. Conclusion: This study illustrates the dynamics between PA cells and immune TME in promoting PA invasion via M2 polarization. CCL17 levels in the TME are related to the PA invasiveness and clinical prognosis, and the CCL17/CCR4/mTOCR1 axis may serve as potential therapeutic targets for Pas.
Transitional B cell cytokines predict renal allograft outcomes
Authors: Aravind Cherukuri, Alan D. Salama, Rajil Mehta, Kanishka Mohib, Leting Zheng, Ciara Magee, Mark Harber, Hans Stauss, Richard J. Baker, Amit Tevar, Douglas Landsittel, Fadi G. Lakkis, Sundaram Hariharan, David M. Rothstein
Journal: Science Translational Medicine (2021)

Early immunological biomarkers that predict rejection and chronic allograft loss are needed to inform preemptive therapy and improve long-term outcomes. Here, we prospectively examined the ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNFα) produced by transitional-1 B cells (T1B) 3 months after transplantation as a predictive biomarker for clinical and subclinical renal allograft rejection and subsequent clinical course. In both Training (n = 162) and Internal Validation (n = 82) Sets, the T1B IL-10/TNFα ratio 3 months after transplantation predicted both clinical and subclinical rejection anytime in the first year. The biomarker also predicted subsequent late rejection with a lead time averaging 8 months. Among biomarker high-risk patients, 60% had early rejection, of which 48% recurred later in the first posttransplant year. Among high-risk patients without early rejection, 74% developed rejection later in the first year. In contrast, only 5% of low-risk patients had early and 5% late rejection. The biomarker also predicted rejection in an External Validation Set (n = 95) and in key patient subgroups, confirming generalizability. Biomarker high-risk patients exhibited progressively worse renal function and decreased 5-year graft survival compared to low-risk patients. Treatment of B cells with anti-TNFα in vitro augmented the IL-10/TNFα ratio, restored regulatory activity, and inhibited plasmablast differentiation. To conclude, the T1B IL-10/TNFα ratio was validated as a strong predictive biomarker of renal allograft outcomes and provides a rationale for preemptive therapeutic intervention with TNF blockade.
Wound Dressings for Obese Women After Cesarean Delivery
Authors: Uyen G. Vo, Toby Richards
Journal: JAMA (2021)

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