tbuckley/cabot-search huggingface dataset:
Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α
Authors: Lu Xu, Zhe Huang, Tak-ho Lo, Jimmy Tsz Hang Lee, Ranyao Yang, Xingqun Yan, Dewei Ye, Aimin Xu, Chi-Ming Wong
Journal: Theranostics (2022)

Rationale: Over-nutrition will lead to overexpression of PRMT1 but protein hypomethylation is observed in the liver of obese subjects. The dynamic alteration of the expression and methyltransferase activity of PRMT1 in the progression of fatty liver diseases remains elusive. Methods: We used recombinant adeno-associated virus-mediated gene delivery system to manipulate the hepatic PRMT1 expression level in diet-induced obese mice to investigate the role of PRMT1 in hepatic steatosis. We further utilized a cohort of obese humans with biopsy-proven nonalcoholic fatty liver disease to support our observations in mouse model. Results: We demonstrated that knockdown of PRMT1 promoted steatosis development in liver of high-fat diet (HFD) fed mice. Over-expression of wild-type PRMT1, but not methyltransferase-defective mutant PRMT1G80R, could alleviate diet-induced hepatic steatosis. The observation is conserved in the specimens of obese humans with biopsy-proven nonalcoholic fatty liver disease. Mechanistically, methyltransferase activity of PRMT1 was required to induce PGC-1α mRNA expression via recruitment of HNF-4α to the promoter of PGC-1α, and hence attenuated HFD-induced hepatic steatosis by enhancing PGC-1α-mediated fatty acid oxidation. Conclusions: Our results identify that activation of the PRMT1/HNF-4α/PGC-1α signaling is a potential therapeutic strategy for combating non-alcoholic fatty liver disease of obese subjects.
Abstract EP62: Impact Of Smoking On In-hospital Mortality Following Type 2 Myocardial Infarction- A Nationwide Population-based Analysis
Authors: Akhil Jain, Ankit Vyas, Avilash Mondal, Frailyn Nunez, Siva Naga Yarrarapu, Hasnan Ijaz, Sonali Sachdeva, Rupak Desai
Journal: Circulation (2022)

Background: Smoking has been linked to coronary artery vasoconstriction and increased myocardial oxygen demand. However, its impact on the outcomes of type 2 myocardial infarction (T2MI) remains unknown. Methods: We analyzed odds and predictors of in-hospital mortality in smokers vs. non-smokers from National Inpatient Sample (2018) T2MI hospitalizations after excluding secondary diagnoses of Type 1 MI. Results: Of 33155 T2MI admissions, 55.4% (n=14780) were smokers and 44.6% non-smokers (n=18375). Smokers were often younger (median 68 vs 74 yrs) and males (57.7% vs. 44.9%) than non-smokers. Unadjusted (OR 0.67, 95CI 0.50-0.91 (p=0.01) and demographically adjusted (OR 0.71, 95CI 0.52-0.98 (p=0.034) regression analyses revealed “smokers’ paradox” for in-hospital mortality. However, when additionally adjusted for comorbidities, the lower risk of all-cause mortality in smokers vs non-smokers failed to reach a statistical significance (OR 0.81, 95CI 0.56-1.16, p=0.253) [Table 1a] . Smokers had a higher rate of substance abuse, depression, and prior MI/PCI/CABG/stroke (p&lt;0.05). Higher risk of all-cause mortality was found in patients with advanced age (OR 1.05), males (vs female OR 1.92) whereas whites (vs blacks OR 0.61, Hispanics OR 0.70), patients from higher-income quartile (76-100th vs. 0-25th OR 0.37) had a lower risk of mortality. CHF (OR 27.20), sepsis (OR 8.83), fluid-electrolyte disorders (OR 4.72), metastatic cancers (OR 3.29), coagulopathy (OR 2.16), prior VTE (OR 2.66) and CKD (OR 1.41) raised the odds of mortality in smokers whereas hypertension, hyperlipidemia, past cancer, prior PCI and prior TIA/Stroke showed lower odds of mortality (all p&lt;0.05) [Table 1b] . Conclusion: In-hospital mortality associated with T2MI in unadjusted and sociodemographically adjusted models showed "Smoker's Paradox" but when controlled for comorbidities the lower odds failed to reach a statistical significance. The predictors of T2MI related mortality in smokers may help clinicians to identify high-risk patients.
147P Chemo-immunotherapy with or without consolidative radiotherapy in extensive-stage small cell lung cancer: An initial report of clinical outcome and safety
Authors: A. Bruni, F. Bertolini, E. D'Angelo, F. Barbieri, J. Imbrescia, L. Trudu, A. Cappelli, F. Lohr, M. Dominici, G. Guaitoli
Journal: Annals of Oncology (2022)
Abstract P171: Effects Of Covid-19 On Cardiometabolic Outcomes (diabetes, Hypertension, And Obesity)
Authors: David Adzrago, Emmanuel Odame, Oluwabunmi M Dada, Cynthia Meyer, Valentine Nriagu, Trishita Paul, Florence M Weierbach, David W Stewart, Timir K Paul, Hadii M Mamudu
Journal: Circulation (2022)

Background: Prior studies have examined cardiometabolic outcomes, but literature on the effects of the COVID-19 pandemic on cardiometabolic outcomes (diabetes, hypertension, and obesity) among the general U.S. population is sparse. Objective: To examine differences in the prevalence of cardiometabolic outcomes by sexual identity, cigarette smoking, e-cigarette use, and anxiety/depression before and during the COVID-19 pandemic. Hypothesis: We assessed the hypothesis that there will be statistically significant differences in cardiometabolic outcomes between sexual minority and heterosexual individuals before and during the COVID-19 pandemic. Methods: Data were drawn from the 2019 (N= 5,359) and 2020 (N= 3,830) Health Information National Trends Surveys on adults. We conducted weighted descriptive and multivariable logistic regression analyses to assess the study objective. Results: During the pandemic, compared to before the pandemic, the prevalence of diabetes (18.10% vs. 17.28%) and obesity (34.68% vs. 34.18%) has increased, while the prevalence has decreased for hypertension (36.38% vs. 36.36%). In general, the prevalence of cardiometabolic outcomes was higher during the pandemic (56.09%) than before the pandemic (54.96%). The prevalence has also increased for sexual minority (53.50% vs. 51.12%) and heterosexual (56.45% vs. 54.96%) individuals, former (67.91% vs. 63.86%) and current (59.39% vs. 55.43%) cigarette smokers, current e-cigarette users (37.24% vs. 28.66%), and individuals with mild (59.62% vs. 55.43%) or moderate (61.98% vs. 57.83%) anxiety/depression symptoms. Contrary to our hypothesis, there were no statistically significant differences in the odds of cardiometabolic outcomes between sexual minority and heterosexual individuals before and during the pandemic. Former smokers, compared to never smokers, had higher odds of cardiometabolic outcomes (AOR= 1.38, 95% CI= 1.01, 1.87 vs. AOR= 1.57, 95% CI= 1.10, 2.25) before and during the pandemic, respectively. The odds were lower for current e-cigarette users (AOR= 0.44, 95% CI= 0.23, 0.85) compared to never e-cigarette users before the pandemic, but no significant differences were found in e-cigarette use groups during the pandemic. People with mild anxiety/depression symptoms (before: AOR= 1.52, 95% CI= 1.06, 2.19 vs. during: AOR= 1.55, 95% CI= 1.01, 2.38) relative to those with no anxiety/depression symptoms had higher odds of cardiometabolic outcomes, whereas the odds were higher for those with severe anxiety/depression symptoms (AOR= 2.44, 95% CI= 1.27, 4.69) before the pandemic but not during the pandemic. Conclusion: Positive associations were noted between tobacco use and mental health and the risks of cardiometabolic outcomes during the COVID-19 pandemic.
Cytogenetics in Chronic Lymphocytic Leukemia: ERIC Perspectives and Recommendations
Authors: Panagiotis Baliakas, Blanca Espinet, Clemens Mellink, Marie Jarosova, Anastasia Athanasiadou, Paolo Ghia, Arnon P. Kater, David Oscier, Claudia Haferlach, Kostas Stamatopoulos
Journal: HemaSphere (2022)

Mounting evidence underscores the clinical value of cytogenetic analysis in chronic lymphocytic leukemia (CLL), particularly as it allows the identification of complex karyotype, that has recently emerged as a prognostic and potentially predictive biomarker. That said, explicit recommendations regarding the methodology and clinical interpretation of either chromosome banding analysis (CBA) or chromosome microarray analysis (CMA) are still lacking. We herein present the consensus of the Cytogenetic Steering Scientific Committee of ERIC, the European Research Initiative on CLL, regarding methodological issues as well as clinical interpretation of CBA/CMA and discuss their relevance in CLL. ERIC considers CBA standardized and feasible for CLL on the condition that standards are met, extending from the use of novel mitogens to the accurate interpretation of the findings. On the other hand, CMA, is also standardized, however, robust data on its clinical utility are still scarce. In conclusion, cytogenetic analysis is not yet mature enough to guide treatment choices in CLL. That notwithstanding, ERIC encourages the wide application of CBA, and potentially also CMA, in clinical trials in order to obtain robust evidence regarding the predictive value of specific cytogenetic profiles towards refining risk stratification and improving the management of patients with CLL.
Effects of Wood Smoke Constituents on Mucin Gene Expression in Mice and Human Airway Epithelial Cells and on Nasal Epithelia of Subjects with a Susceptibility Gene Variant in <i>Tp53</i>
Authors: Dereje Tassew, Susan Fort, Yohannes Mebratu, Jacob McDonald, Hong Wei Chu, Hans Petersen, Yohannes Tesfaigzi
Journal: Environmental Health Perspectives (2022)

Exposure to wood smoke (WS) increases the risk for chronic bronchitis more than exposure to cigarette smoke (CS), but the underlying mechanisms are unclear.
Letter Regarding Repeated-Measures ANOVA
Authors: Jie Wei, Dalang Fang
Journal: Journal of Clinical Oncology (2021)

Lin et al 1 performed a clinical trial to assess the efficacy of pertuzumab plus high-dose trastuzumab in patients with progressive brain metastases and human epidermal growth factor receptor 2-positive metastatic breast cancer.They concluded that although the CNS objective response rate was modest, 68% of patients experienced clinical benefit, and two patients had ongoing stable intracranial and extracranial disease for 2 years.High-dose trastuzumab for human epidermal growth factor receptor 2-positive CNS metastases may warrant further study.After carefully reading, we wish to put forth the following suggestions.As the authors said in their Methods section, "LVEF was assessed at screening, at 6 weeks, at 12 weeks, and then every 3 months during the treatment period and every 6 months during survival follow-up (12 months after the treatment discontinuation visit)," and we can speculate that it is a study with repeated measurement data.Under these circumstances, repeated-measures analysis of variance (ANOVA) should be conducted for data analysis in this article.In general, repeatedmeasures ANOVA is a commonly used statistical approach to repeated-measures designs.With such designs, the repeated-measures factor is the withinsubjects factor, whereas the dependent quantitative variable on which each participant is measured is the dependent variable.However, repeated-measures ANOVA was not performed in this article.Therefore, if repeated-measures ANOVA were put into effect in this study, the result of this study would be more reliable.
98P Clinical characteristic of women under 55 years old who qualified for surgical treatment of lung cancer: Analysis of 1574 cases
Authors: A. Trojnar, M. Zbytniewski, G. Gryszko, M. Cackowski, K. Woźnica, T. Orłowski, J. Domagała-Kulawik, D. Dziedzic
Journal: Annals of Oncology (2022)
HPV and DNA Methylation Testing in Urine for Cervical Intraepithelial Neoplasia and Cervical Cancer Detection
Authors: Rianne van den Helder, Renske D.M. Steenbergen, Annina P. van Splunter, Constantijne H. Mom, Ming Y. Tjiong, Ivonne Martin, Fleur M.F. Rosier-van Dunné, Irene A.M. van der Avoort, Maaike C.G. Bleeker, Nienke E. van Trommel
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Biomarker detection in urine offers a potential solution to increase effectiveness of cervical cancer screening programs by attracting nonresponders. In this prospective study, the presence of high-risk human papillomavirus (hrHPV) DNA and the performance of DNA methylation analysis was determined for the detection of cervical cancer and high-grade cervical intraepithelial neoplasia (CIN2/3) in urine, and compared with paired cervicovaginal self-samples and clinician-taken cervical scrapes. Experimental Design: A total of 587 samples were included from 113 women with cervical cancer, 92 women with CIN2/3, and 64 controls. Samples were tested for hrHPV DNA and five methylation markers. Univariate and multivariate logistic regression and leave-one-out cross-validation were used to determine the methylation marker performance for CIN3 and cervical cancer (CIN3+) detection in urine. Agreement between samples was determined using Cohen kappa statistics and the Spearman correlation coefficients. Results: HrHPV presence was high in all sample types, 79% to 92%. Methylation levels of all markers in urine significantly increased with increasing severity of disease. The optimal marker panel (ASCL1/LHX8) resulted in an AUC of 0.84 for CIN3+ detection in urine, corresponding to an 86% sensitivity at a 70% predefined specificity. At this threshold 96% (109/113) of cervical cancers, 68% (46/64) of CIN3, and 58% (14/24) of CIN2 were detected. Between paired samples, a strong agreement for HPV16/18 genotyping and a fair to strong correlation for methylation was found. Conclusions: HrHPV DNA and DNA methylation testing in urine offers a promising solution to detect cervical cancer and CIN2/3 lesions, especially for women currently unreached by conventional screening methods.
Surgery No More? Managing the Primary Tumor in Stage IV Breast Cancer
Authors: David N. Anderson, Elisa R. Port
Journal: Journal of Clinical Oncology (2022)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
Pineal Gland Metastasis From Gastric Carcinoid—A Rare Manifestation
Authors: Gabriel C. Fine, Grace G. Zhu, Kathryn A. Morton, Nikolas Damme, Bhasker R. Koppula
Journal: Clinical Nuclear Medicine (2021)

Abstract Pineal region metastases are very rare, occurring in 0.4% to 3.8% of patients with solid tumors and most frequently arise from a lung cancer primary tumor. We present a case of a 67-year-old man with a gastric well-differentiated neuroendocrine tumor (NET) metastatic to the pineal gland identified on 68 Ga-DOTATATE PET/CT imaging followed by MRI confirmation. To our knowledge, this is the third NET case to be reported in the literature with such presentation and first case to be described on 68 Ga-DOTATATE PET/CT. A case of metastatic bronchial NET as well as a case of metastatic esophageal NET to the pineal gland were reported previously.
68Ga-FAPI PET/CT Imaging of Multiple Muscle Metastases of Pancreatic Cancer
Authors: Weidong Gong, Xiao Yang, Junhao Wu, Lei Ou, Chunyin Zhang
Journal: Clinical Nuclear Medicine (2021)

A 67-year-old man presented with generalized muscle pain for 2 months. A potential malignancy was suspected. The patient was subsequently enrolled in the clinical trial of 68Ga-FAPI. Increased activity of FAPI and FDG was observed in muscle lesions. Moreover, 68Ga-FAPI PET/CT showed intense FAPI uptake in the pancreas. Finally, pancreas and left iliopsoas muscle biopsies confirmed the diagnosis of pancreatic cancer with multiple muscle metastases.
DNA methylome-wide association study of genetic risk for depression implicates antigen processing and immune responses
Authors: Xueyi Shen, Doretta Caramaschi, Mark J. Adams, Rosie M. Walker, Josine L. Min, Alex Kwong, Gibran Hemani, Miruna C. Barbu, Heather C. Whalley, Sarah E. Harris, Ian J. Deary, Stewart W. Morris, Simon R. Cox, Caroline L. Relton, Riccardo E. Marioni, Kathryn L. Evans, Andrew M. McIntosh
Journal: Genome Medicine (2022)

Depression is a disabling and highly prevalent condition where genetic and epigenetic, such as DNA methylation (DNAm), differences contribute to disease risk. DNA methylation is influenced by genetic variation but the association between polygenic risk of depression and DNA methylation is unknown. We investigated the association between polygenic risk scores (PRS) for depression and DNAm by conducting a methylome-wide association study (MWAS) in Generation Scotland (N = 8898, mean age = 49.8 years) with replication in the Lothian Birth Cohorts of 1921 and 1936 and adults in the Avon Longitudinal Study of Parents and Children (ALSPAC) (Ncombined = 2049, mean age = 79.1, 69.6 and 47.2 years, respectively). We also conducted a replication MWAS in the ALSPAC children (N = 423, mean age = 17.1 years). Gene ontology analysis was conducted for the cytosine-guanine dinucleotide (CpG) probes significantly associated with depression PRS, followed by Mendelian randomisation (MR) analysis to infer the causal relationship between depression and DNAm. Widespread associations (NCpG = 71, pBonferroni < 0.05, p < 6.3 × 10-8) were found between PRS constructed using genetic risk variants for depression and DNAm in CpG probes that localised to genes involved in immune responses and neural development. The effect sizes for the significant associations were highly correlated between the discovery and replication samples in adults (r = 0.79) and in adolescents (r = 0.82). Gene Ontology analysis showed that significant CpG probes are enriched in immunological processes in the human leukocyte antigen system. Additional MWAS was conducted for each lead genetic risk variant. Over 47.9% of the independent genetic risk variants included in the PRS showed associations with DNAm in CpG probes located in both the same (cis) and distal (trans) locations to the genetic loci (pBonferroni < 0.045). Subsequent MR analysis showed that there are a greater number of causal effects found from DNAm to depression than vice versa (DNAm to depression: pFDR ranged from 0.024 to 7.45 × 10-30; depression to DNAm: pFDR ranged from 0.028 to 0.003). PRS for depression, especially those constructed from genome-wide significant genetic risk variants, showed methylome-wide differences associated with immune responses. Findings from MR analysis provided evidence for causal effect of DNAm to depression.
Highlights From the <i>Circulation</i> Family of Journals
Authors: Fahd Yunus, Alexander Perino, Dajuanicia Holmes, Roland Matsouaka, Anne Curtis, Kenneth Ellenbogen, David Frankel, Bradley Knight, Andrea Russo, William Lewis, Jonathan Piccini, Mintu Turakhia, Anastasia Vamvakidou, Mohamed-Salah Annabi, Phillipe Pibarot, ; Plonska-Gosciniak, Ana Almeida, Ezequiel Guzzetti, Abdellaziz Dahou, Ian Burwash, Matthias Koschutnik, Philipp Bartko, Jutta Bergler-Klein, Julia Mascherbauer, Stefan Orwat, Helmut Baumgartner, Joao Cavalcante, Fausto Pinto, Tomasz Kukulski, Jaroslaw Kasprzak, Marie-Annick Clavel, Frank Flachskampf, Roxy Senior, Juliane Jurga, ; Karolina, Elizabeth Szummer, Christian Lewinter, Linda Mellbin, Matthias Götberg, Sammy Zwackman, Johan Nilsson, Sebastian Völz, David Erlinge, Jonas Persson, Tomas Jernberg, Dimitrios Venetsanos, Rutao Wang, Hideyuki Kawashima, Hironori Hara, Chao Gao, Masafumi Ono, Kuniaki Takahashi, Shengxian Tu, Osama Soliman, Scot Garg, ; Robert, Jan Van Geuns, Ling Tao, William Wijns, Yoshinobu Onuma, Patrick Serruys, Emmanuel Akintoye, Paulino Alvarez, Doosup Shin, Alexander Egbe, Anthony Panos, Frank Sellke, Alexandros Briasoulis
Journal: Circulation (2021)

This month's highlights from the subspecialty journals cover a range of topics in cardiology.Sex differences in atrial fibrillation ablation are analyzed in Circulation: Arrhythmia and Electrophysiology.The usefulness of evaluating transaortic flow rate on dobutamine stress tests for low-flow, low-gradient aortic stenosis is presented in Circulation: Cardiovascular Imaging.Pretreatment with P2Y12 inhibitors before percutaneous coronary intervention for stable chronic coronary syndrome is evaluated in Circulation: Cardiovascular Interventions.Methods of adjudication for revascularization events are compared in Circulation: Cardiovascular Quality and Outcomes.Temporal trends in heart transplant waitlist characteristics and posttransplant outcomes over a nearly 30-year period are reported in Circulation: Heart Failure.
Efficacy of Air Filtration and Education Interventions on Indoor Fine Particulate Matter and Child Lower Respiratory Tract Infections among Rural U.S. Homes Heated with Wood Stoves: Results from the KidsAIR Randomized Trial
Authors: Ethan S. Walker, Erin O. Semmens, Annie Belcourt, Bert B. Boyer, Esther Erdei, Jon Graham, Scarlett E. Hopkins, Johnnye L. Lewis, Paul G. Smith, Desirae Ware, Emily Weiler, Tony J. Ward, Curtis W. Noonan
Journal: Environmental Health Perspectives (2022)

Background: Millions of rural U.S. households are heated with wood stoves. Wood stove use can lead to high indoor concentrations of fine particulate matter [airborne particles ≤2.5μm in aerodynamic diameter (PM2.5)] and is associated with lower respiratory tract infection (LRTI) in children. Objectives: We assessed the impact of low-cost educational and air filtration interventions on childhood LRTI and indoor PM2.5 in rural U.S. homes with wood stoves. Methods: The Kids Air Quality Interventions for Reducing Respiratory Infections (KidsAIR) study was a parallel three-arm (education, portable air filtration unit, control), post-only randomized trial in households from Alaska, Montana, and Navajo Nation (Arizona and New Mexico) with a wood stove and one or more children &lt;5 years of age. We tracked LRTI cases for two consecutive winter seasons and measured indoor PM2.5 over a 6-d period during the first winter. We assessed results using two analytical frameworks: a) intervention efficacy on LRTI and PM2.5 (intent-to-treat), and b) association between PM2.5 and LRTI (exposure–response). Results: There were 61 LRTI cases from 14,636 child-weeks of follow-up among 461 children. In the intent-to-treat analysis, children in the education arm [odds ratio (OR)=0.98; 95% confidence interval (CI): 0.35, 2.72] and the filtration arm (OR=1.23; 95% CI: 0.46, 3.32) had similar odds of LRTI vs. control. Geometric mean PM2.5 concentrations were similar to control in the education arm (11.77% higher; 95% CI: −16.57, 49.72) and air filtration arm (6.96% lower; 95% CI: −30.50, 24.55). In the exposure–response analysis, odds of LRTI were 1.45 times higher (95% CI: 1.02, 2.05) per interquartile range (25 μg/m3) increase in mean indoor PM2.5. Discussion: We did not observe meaningful differences in LRTI or indoor PM2.5 in the air filtration or education arms compared with the control arm. Results from the exposure–response analysis provide further evidence that biomass air pollution adversely impacts childhood LRTI. Our results highlight the need for novel, effective intervention strategies in households heated with wood stoves. https://doi.org/10.1289/EHP9932
Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial
Authors: Sylke Haal, Maimoena S S Guman, Thomas C C Boerlage, Yair I Z Acherman, L Maurits de Brauw, Sjoerd Bruin, Steve M M de Castro, Jeanin E van Hooft, Arnold W J M van de Laar, Daan E Moes, Manon Schouten, Ruben Schouten, Ellert J van Soest, Ruben N van Veen, Claire E E de Vries, Paul Fockens, Marcel G W Dijkgraaf, Victor E A Gerdes, Rogier P Voermans
Journal: The Lancet. Gastroenterology & hepatology (2021)