tbuckley/cabot-search huggingface dataset:
Disrupting Circadian Rhythm via the PER1–HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer
Authors: Jiao Wang, Qiong Huang, Xingbin Hu, Shuyi Zhang, Yu Jiang, Guangyu Yao, Kongzhen Hu, Xin Xu, Bishan Liang, Qijing Wu, Zhenfeng Ma, Yawen Wang, Chunlin Wang, Zhenzhen Wu, Xiaoxiang Rong, Wangjun Liao, Min Shi
Journal: Cancer Research (2022)

Trastuzumab is the only approved targeted drug for first-line treatment of HER2-positive advanced gastric cancer, but the high rate of primary resistance and rapid emergence of secondary resistance limit its clinical benefits. We found that trastuzumab-resistant (TR) gastric cancer cells exhibited high glycolytic activity, which was controlled by hexokinase 2 (HK2)-dependent glycolysis with a circadian pattern [higher at zeitgeber time (ZT) 6, lower at ZT18]. Mechanistically, HK2 circadian oscillation was regulated by a transcriptional complex composed of PPARγ and the core clock gene PER1. In vivo and in vitro experiments demonstrated that silencing PER1 disrupted the circadian rhythm of PER1-HK2 and reversed trastuzumab resistance. Moreover, metformin, which inhibits glycolysis and PER1, combined with trastuzumab at ZT6, significantly improved trastuzumab efficacy in gastric cancer. Collectively, these data introduce the circadian clock into trastuzumab therapy and propose a potentially effective chronotherapy strategy to reverse trastuzumab resistance in gastric cancer.In trastuzumab-resistant HER2-positive gastric cancer, glycolysis fluctuates with a circadian oscillation regulated by the BMAL1-CLOCK-PER1-HK2 axis, which can be disrupted with a metformin-based chronotherapy to overcome trastuzumab resistance.
Indicators of carbohydrate and fat metabolism in patients with various degrees of fatty liver dystrophy
Authors: V.B. Yagmur, R.M. Kislova, I.A. Klenina, O.M. Tatarchuk, S.L. Melanich
Journal: GASTROENTEROLOGY (2022)

Background. Non-alcoholic fatty liver disease (NAFLD) ranks first among chronic liver diseases and covers almost a quarter of the population. Enough data have been accumulated on the mutual influence of metabolic changes and steatosis of the liver of varying degrees on the existence and progression of each other. The coexistence of non-alcoholic steatohepatitis (NASH) with various comorbidal conditions has already been recorded in many studies, a direct relationship has been determined between the presence of fatty degeneration and various components of the metabolic syndrome— arterial hypertension, type 2 diabetes, obesity and dyslipidemia. The purpose was to determine the relationship between carbohydrate and fat metabolism in patients with NAFLD depending on the degree of fat accumulation in the liver. Materials and methods. Data were obtained from 72 patients with NAFLD, who were divided into two groups according to the degree of steatosis. The I group included 46 patients with moderate steatosis (the proportion of hepatocytes containing fatty is 33–66%). The indicator of the controlled parameter of ultrasonic attenuation (CAP) ranged from 232 to 256dB/m. The II group consisted of 26 patients with severe steatosis (the proportion of hepatocytes containing fatty inclusions more than 66%), with CAP more than 256dB/m. The trophological status, the parameters of carbohydrate and fat metabolism were determined. A statistical analysis of the data was carried out— the mean values in the groups were compared and the contribution of variables to the value of CAP was estimated using the method of multiple regression analysis. Results. The level of insulin and HOMA-IR in patients with severe fatty degeneration of the liver was (22.7±9.7) and (5.4±2.7) μU/ml, respectively. These indicators were higher than the corresponding indicators of group I (p&lt;0.05), (17.1±10.3) and (4.01±2.9) μU/ml for insulin and HOMA-IR, respectively. Glucose, lipid spectrum did not differ significantly between the groups, except for the fraction of very-low density lipoproteins (VLDL), which were significantly higher in patients with a higher degree of fatty degeneration and amounted to 3.4 (2.3–4.1) and 3.0 (2.4–3.8) mmol/L in groupsII and I, respectively. Multiple regression analysis was performed to determine the contribution of fat and carbohydrate metabolism to CAP values. As a result of step-by-step analysis, two indicators remained in the model, namely the HOMA index (regression coefficient β 5.285, p=0.04) and BMI (regression coefficient β 4.666, p=0.001). Itwas determined that changes in BMI and HOMA are responsible for 31% of changes in the value of CAP. Conclusions. Insulin values, HOMA index, BMI and VLDL are higher in patients with severe steatosis. According to the results of multiple regression analysis, a significant contribution of HOMA and BMI values to the CAP was revealed.
Allostasis, Action, and Affect in Depression: Insights from the Theory of Constructed Emotion
Authors: Clare Shaffer, Christiana Westlin, Karen S. Quigley, Susan Whitfield-Gabrieli, Lisa Feldman Barrett
Journal: Annual Review of Clinical Psychology (2022)

The theory of constructed emotion is a systems neuroscience approach to understanding the nature of emotion. It is also a general theoretical framework to guide hypothesis generation for how actions and experiences are constructed as the brain continually anticipates metabolic needs and attempts to meet those needs before they arise (termed allostasis). In this review, we introduce this framework and hypothesize that allostatic dysregulation is a trans-disorder vulnerability for mental and physical illness. We then review published findings consistent with the hypothesis that several symptoms in major depressive disorder (MDD), such as fatigue, distress, context insensitivity, reward insensitivity, and motor retardation, are associated with persistent problems in energy regulation. Our approach transforms the current understanding of MDD as resulting from enhanced emotional reactivity combined with reduced cognitive control and, in doing so, offers novel hypotheses regarding the development, progression, treatment, and prevention of MDD.
Diabetes Screening by Race and Ethnicity in the United States: Equivalent Body Mass Index and Age Thresholds
Authors: Rahul Aggarwal, Kirsten Bibbins-Domingo, Robert W. Yeh, Yang Song, Nicholas Chiu, Rishi K. Wadhera, Changyu Shen, Dhruv S. Kazi
Journal: Annals of Internal Medicine (2022)

Racial/ethnic minority populations in the United States have increased rates of diabetes compared with White populations. The 2021 guidelines from the U.S. Preventive Services Task Force recommend diabetes screening for adults aged 35 to 70 years with a body mass index (BMI) of 25 kg/m2 or greater.To determine the BMI threshold for diabetes screening in major racial/ethnic minority populations with benefits and harms equivalent to those of the current diabetes screening threshold in White adults.Cross-sectional study.NHANES (National Health and Nutrition Examination Survey), 2011 to 2018.Nonpregnant U.S. adults aged 18 to 70 years (n = 19 335).A logistic regression model was used to estimate diabetes prevalence at various BMIs for White, Asian, Black, and Hispanic Americans. For each racial/ethnic minority group, the equivalent BMI threshold was defined as the BMI at which the prevalence of diabetes in 35-year-old persons in that group is equal to that in 35-year-old White adults at a BMI of 25 kg/m2. Ranges were estimated to account for the uncertainty in prevalence estimates for White and racial/ethnic minority populations.Among adults aged 35 years with a BMI of 25 kg/m2, the prevalence of diabetes in Asian Americans (3.8% [95% CI, 2.8% to 5.1%]), Black Americans (3.5% [CI, 2.7% to 4.7%]), and Hispanic Americans (3.0% [CI, 2.1% to 4.2%]) was significantly higher than that in White Americans (1.4% [CI, 1.0% to 2.0%]). Compared with a BMI threshold of 25 kg/m2 in White Americans, the equivalent BMI thresholds for diabetes prevalence were 20 kg/m2 (range, <18.5 to 23 kg/m2) for Asian Americans, less than 18.5 kg/m2 (range, <18.5 to 23 kg/m2) for Black Americans, and 18.5 kg/m2 (range, <18.5 to 24 kg/m2) for Hispanic Americans.Sample size limitations precluded assessment of heterogeneity within racial/ethnic groups.Among U.S. adults aged 35 years or older, offering diabetes screening to Black Americans and Hispanic Americans with a BMI of 18.5 kg/m2 or greater and Asian Americans with a BMI of 20 kg/m2 or greater would be equivalent to screening White adults with a BMI of 25 kg/m2 or greater. Using screening thresholds specific to race/ethnicity has the potential to reduce disparities in diabetes diagnosis.Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology.
Examination of Young US Adults’ Reasons for Not Seeking Mental Health Care for Depression, 2011-2019
Authors: Wenhua Lu, Melissa Bessaha, Miguel Muñoz-Laboy
Journal: JAMA Network Open (2022)

Although this study is limited by potential social desirability bias based on self-reports, cost was consistently the most prominent barrier to seeking depression treatment among young adults from 2011 to 2019.In addition, young adults increasingly reported inadequate insurance coverage for mental health treatment.Since its implementation in 2014, the Medicaid expansion has reduced the rate of uninsured individuals and improved access to care for adults with depression. 6Immediate policy actions are needed, therefore, to close the Medicaid coverage gap, especially for Native American individuals.More outreach campaigns are also warranted to increase young adults' awareness of local mental health services, particularly among Hispanic and Asian communities.Last, destigmatizing mental health treatment should be prioritized among young adults, with genderspecific engagement interventions for men.
Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome
Authors: Michael S. Rafii, Olivier Sol, William C. Mobley, Saskia Delpretti, Brian G. Skotko, Anna D. Burke, Marwan N. Sabbagh, Shauna H. Yuan, Robert A. Rissman, Margaret Pulsifer, Casey Evans, A. Carol Evans, Gregory Beth, Nicolas Fournier, Julian A. Gray, Antonio Melo dos Santos, Valerie Hliva, Marija Vukicevic, Marie Kosco-Vilbois, Johannes Streffer, Andrea Pfeifer, Howard H. Feldman
Journal: JAMA Neurology (2022)

Individuals with Down syndrome (DS) are at high risk of developing Alzheimer disease due to an increased dose of the amyloid precursor protein gene, APP, which leads to increased levels of full-length APP and its products, including amyloid-β (Aβ). The liposome-based antiamyloid ACI-24 vaccine is intended to treat neurological disorders caused by misfolded Aβ pathological protein. However, the safety, tolerability, and immunogenicity of the ACI-24 vaccine among adults with DS have not been fully examined.
The disordered N-terminal domain of DNMT3A recognizes H2AK119ub and is required for postnatal development
Authors: Tianpeng Gu, Dapeng Hao, Junsung Woo, Teng-Wei Huang, Lei Guo, Xueqiu Lin, Anna G. Guzman, Ayala Tovy, Carina Rosas, Mira Jeong, Yubin Zhou, Benjamin Deneen, Yun Huang, Wei Li, Margaret A. Goodell
Journal: Nature Genetics (2022)
Germline Pathogenic Variants in <i>BRCA1</i> and <i>BRCA2</i>: Malignancies Beyond Female Breast and Ovarian Cancers
Authors: Sari Lieberman, Hadar Goldvaser, Ephrat Levy-Lahad
Journal: Journal of Clinical Oncology (2022)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants. January 25, 2022 ARTICLE CITATION DOI: 10.1200/JCO.22.00003 Journal of Clinical Oncology - published online before print March 14, 2022 PMID: 35286153 Germline Pathogenic Variants in BRCA1 and BRCA2: Malignancies Beyond Female Breast and Ovarian Cancers Sari Lieberman , PhD1xSari LiebermanSearch for articles by this author; Hadar Goldvaser, MD2,3xHadar GoldvaserSearch for articles by this author; and Ephrat Levy-Lahad , MD1,3xEphrat Levy-LahadSearch for articles by this author Show More 1Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel2Institute of Oncology, Shaare Zedek Medical Center, Jerusalem, Israel3Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel https://doi.org/10.1200/JCO.22.00003 First Page Full Text PDF Figures and Tables © 2022 by American Society of Clinical OncologySUPPORTSupported by the Breast Cancer Research Foundation (NY, to E.L.L.).AUTHOR CONTRIBUTIONSFinancial support: Ephrat Levy-LahadCollection and assembly of data: All authorsData analysis and interpretation: All authorsManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTGermline Pathogenic Variants in BRCA1 and BRCA2: Malignancies Beyond Female Breast and Ovarian CancersThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Sari LiebermanHonoraria: AstraZenea/IsraelHadar GoldvaserHonoraria: Roche, Novartis, Genomic Health, PfizerConsulting or Advisory Role: Novartis, Lilly, Gilead Sciences, PfizerEphrat Levy-LahadHonoraria: NovartisConsulting or Advisory Role: AstraZenecaNo other potential conflicts of interest were reported. Companion Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
The Increasing Role of Rhythm Control in Patients With Atrial Fibrillation
Authors: A. John Camm, Gerald V. Naccarelli, Suneet Mittal, Harry J.G.M. Crijns, Stefan H. Hohnloser, Chang-Sheng Ma, Andrea Natale, Mintu P. Turakhia, Paulus Kirchhof
Journal: Journal of the American College of Cardiology (2022)

The considerable mortality and morbidity associated with atrial fibrillation (AF) pose a substantial burden on patients and health care services. Although the management of AF historically focused on decreasing AF recurrence, it evolved over time in favor of rate control. Recently, more emphasis has been placed on reducing adverse cardiovascular outcomes using rhythm control, generally by using safe and effective rhythm-control therapies (typically antiarrhythmic drugs and/or AF ablation). Evidence increasingly supports early rhythm control in patients with AF that has not become long-standing, but current clinical practice and guidelines do not yet fully reflect this change. Early rhythm control may effectively reduce irreversible atrial remodeling and prevent AF-related deaths, heart failure, and strokes in high-risk patients. It has the potential to halt progression and potentially save patients from years of symptomatic AF; therefore, it should be offered more widely.
Testing, Surveillance, and Mitigation Strategies for COVID-19
Authors: Judy Chen, Zaid A. M. Al-Azzawi, Tarek Taifour
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 Journals 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 2024 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
Algorithmic fairness in pandemic forecasting: lessons from COVID-19
Authors: Thomas C. Tsai, Sercan Arik, Benjamin H. Jacobson, Jinsung Yoon, Nate Yoder, Dario Sava, Margaret Mitchell, Garth Graham, Tomas Pfister
Journal: npj Digital Medicine (2022)

Racial and ethnic minorities have borne a particularly acute burden of the COVID-19 pandemic in the United States. There is a growing awareness from both researchers and public health leaders of the critical need to ensure fairness in forecast results. Without careful and deliberate bias mitigation, inequities embedded in data can be transferred to model predictions, perpetuating disparities, and exacerbating the disproportionate harms of the COVID-19 pandemic. These biases in data and forecasts can be viewed through both statistical and sociological lenses, and the challenges of both building hierarchical models with limited data availability and drawing on data that reflects structural inequities must be confronted. We present an outline of key modeling domains in which unfairness may be introduced and draw on our experience building and testing the Google-Harvard COVID-19 Public Forecasting model to illustrate these challenges and offer strategies to address them. While targeted toward pandemic forecasting, these domains of potentially biased modeling and concurrent approaches to pursuing fairness present important considerations for equitable machine-learning innovation.
Targeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression
Authors: Xinbo Zhang, Noemi Rotllan, Alberto Canfrán-Duque, Jonathan Sun, Jakub Toczek, Anna Moshnikova, Shipra Malik, Nathan L. Price, Elisa Araldi, Wen Zhong, Mehran M. Sadeghi, Oleg A. Andreev, Raman Bahal, Yana K. Reshetnyak, Yajaira Suárez, Carlos Fernández-Hernando
Journal: Circulation Research (2022)

miRNA therapeutics have gained attention during the past decade. These oligonucleotide treatments can modulate the expression of miRNAs in vivo and could be used to correct the imbalance of gene expression found in human diseases such as obesity, metabolic syndrome, and atherosclerosis. The in vivo efficacy of current anti-miRNA technologies hindered by physiological and cellular barriers to delivery into targeted cells and the nature of miRNAs that allows one to target an entire pathway that may lead to deleterious off-target effects. For these reasons, novel targeted delivery systems to inhibit miRNAs in specific tissues will be important for developing effective therapeutic strategies for numerous diseases including atherosclerosis.
The Genetic, Environmental, and Cultural Forces Influencing Youth Antisocial Behavior Are Tightly Intertwined
Authors: S. Alexandra Burt
Journal: Annual Review of Clinical Psychology (2022)

The aggressive and rule-breaking behaviors that constitute youth antisocial behavior (ASB) are shaped by intertwined genetic, developmental, familial, spatial, temporal, cultural, interpersonal, and contextual influences operating across multiple levels of analysis. Genetic influences on ASB, for example, manifest in different ways during different developmental periods, and do so in part as a function of exposure to harsh parenting, delinquent peers, and disadvantaged neighborhoods. There is also clear evidence documenting societal effects, time-period effects, sex-assigned-at-birth effects, and cohort effects, all of which point to prominent (and possibly interconnected) cultural influences on ASB. In short, ASB is shaped by individuals’ current and prior environmental experiences, genetic risks, and the time and place in which they live. This review seeks to illuminate already documented instances of interplay among the multilevel etiologic forces impinging on youth ASB, with the goal of facilitating additional research.
We Are Drowning
Authors: Diana Halloran
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 Journals 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
The role of the intestinal permeability in the progression of nonalcoholic fatty liver disease in obese children
Authors: Yu.M. Stepanov, N.Yu. Zavhorodnia, N.O. Zhyhyr
Journal: GASTROENTEROLOGY (2022)

Many studies in recent years have revealed increased intestinal permeability in the non-alcoholic fatty liver disease (NAFLD) development and progression to nonalcoholic steatohepatitis (NASH) and liver fibrosis. The prevalence, course, and diagnostic criteria of pediatric NAFLD were considered in the article. The role of increased intestinal permeability in the pathogenesis of NAFLD has been demonstrated. Attention was paid to the structure of the intestinal barrier and possible methods for its permeability examination. Current studies of intestinal permeability in NAFLD in adults and children, which confirm its key role in the progression of NAFLD, were reviewed. A literature search was conducted in electronic databases Scopus, MedLine, EMBASE, Pubmed, Google Scholar, etc.