tbuckley/cabot-search huggingface dataset:
The level of melatonin and serotonin neurohormones in blood serum in patients with non-alcoholic fatty liver disease and kidney lesions infected with COVID-19 virus
Authors: Ye.S. Szircsak, K.V. Sabovchyk, V.V. Stryzhak, O.Yu. Reho
Journal: GASTROENTEROLOGY (2022)

Background. Research aimed at determining the possible mechanisms of progression in the damage to various organs and systems against the background of COVID-19 infection is an urgent, not thoroughly studied issue in contemporary clinical medicine. The purpose was to determine the peculiarities of changes in serum melatonin (МТ) and serotonin (ST) neurohormone levels in patients with non-alcoholic fatty liver disease (NAFLD) and kidney damage infected with the COVID-19 virus. Materials and methods. 84 patients with NAFLD (steatohepatitis) combined with increased body mass index were examined. NAFLD patients were divided into two groups depending on the presence or absence of type 2 diabetes mellitus (DM), and namely: Group 1 included 34 NAFLD and insulin resistance (IR) patients; Group 2 comprised 38 patients with NAFLD and type 2 DM. All examined patients were tested for MT and ST levels in blood serum. Results. There was a significant decrease in serum MT level in both examined groups— by 2.2 and 3.2 times respectively in group 1 and 2 patients at the time of admission to the hospital. The same trend was identified in the indicators of serum MT level in both groups of patients on day 1 of inpatient treatment (IT)— and namely, its decrease by 1.5 and 2.3 times. Revealed a correlation between the progression of liver damage and the decrease of MT and ST levels in blood serum, which is probably a consequence of its toxic damage against the background of the conducted treatment of patients infected with COVID-19. The decreased serum neurohormone levels also correlate with the insulin level and IR index. There is also a strong correlation between renal damage occurring at the IT stage in NAFLD patients and impaired carbohydrate metabolism during COVID-19 infection and decreased levels of MT and ST in the blood, according to glomerular filtration rate MDRD MDRD (r=0,88; р&lt;0,01 and r=0,94; р&lt;0,01 accordance). Conclusions. COVID-19 infection and its treatment in NAFLD patients with impaired carbohydrate metabolism lead to impaired renal functional status. In patients with NAFLD and carbohydrate metabolism disorders, a decrease in serum levels of the neurohormones MT and ST was found, which progressively decreased against the background of COVID-19 infection and kidney damage in these patients.
Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription
Authors: Isabel Paiva, Lucrezia Cellai, Céline Meriaux, Lauranne Poncelet, Ouada Nebie, Jean-Michel Saliou, Anne-Sophie Lacoste, Anthony Papegaey, Hervé Drobecq, Stéphanie Le Gras, Marion Schneider, Enas M. Malik, Christa E. Müller, Emilie Faivre, Kevin Carvalho, Victoria Gomez-Murcia, Didier Vieau, Bryan Thiroux, Sabiha Eddarkaoui, Thibaud Lebouvier, Estelle Schueller, Laura Tzeplaeff, Iris Grgurina, Jonathan Seguin, Jonathan Stauber, Luisa V. Lopes, Luc Buée, Valérie Buée-Scherrer, Rodrigo A. Cunha, Rima Ait-Belkacem, Nicolas Sergeant, Jean-Sébastien Annicotte, Anne-Laurence Boutillier, David Blum
Journal: Journal of Clinical Investigation (2022)

Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus at the epigenomic, proteomic, and metabolomic levels. Caffeine lowered metabolism-related processes (e.g., at the level of metabolomics and gene expression) in bulk tissue, while it induced neuron-specific epigenetic changes at synaptic transmission/plasticity-related genes and increased experience-driven transcriptional activity. Altogether, these findings suggest that regular caffeine intake improves the signal-to-noise ratio during information encoding, in part through fine-tuning of metabolic genes, while boosting the salience of information processing during learning in neuronal circuits.
Diversity in the Expressed Genomic Host Response to Myocardial Infarction
Authors: Augustin Toma, Claudia dos Santos, Beata Burzyńska, Monika Góra, Marek Kiliszek, Natalie Stickle, Holger Kirsten, Leah B. Kosyakovsky, Bo Wang, Sean van Diepen, Slava Epelman, Yishay Szekely, John C. Marshall, Filio Billia, Patrick R. Lawler
Journal: Circulation Research (2022)
Possibilities of ultrasound diagnostics in inflammatory bowel diseases
Authors: M. Stoikevych, N. Fedorova, N. Nedzvetska, I. Konenko
Journal: GASTROENTEROLOGY (2022)

The article deals with nosologies that are complex for diagnostic search and management of the patient— ulcerative colitis and Crohn’s disease. To date, the main diagnostic procedure for these diseases is endoscopy with biopsy and histology. However, there are limitations in their conduct and in the assessment of complications and proximal spread of CD. European guidelines for the diagnosis of UC and CD recommend additional imaging methods to diagnose and determine the location, degree and complications, namely ultrasound of the gastrointestinal tract. The article presents clinical cases of UC and CD, in patients who underwent ultrasound of the intestine and shows its high diagnostic value.
Call to Action for Cardiovascular Disease in Women: Epidemiology, Awareness, Access, and Delivery of Equitable Health Care: A Presidential Advisory From the American Heart Association
Authors: Nanette K. Wenger, Donald M. Lloyd-Jones, Mitchell S.V. Elkind, Gregg C. Fonarow, John J. Warner, Heather M. Alger, Susan Cheng, Claire Kinzy, Jennifer L. Hall, Véronique L. Roger
Journal: Circulation (2022)

Addressing the pervasive gaps in knowledge and care delivery to reduce sex-based disparities and achieve equity is fundamental to the American Heart Association’s commitment to advancing cardiovascular health for all by 2024. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders around the globe to identify and remove barriers to health care access and quality for women. A concise and current summary of existing data across the areas of risk and prevention, access and delivery of equitable care, and awareness and education provides a framework to consider knowledge gaps and research needs critical toward achieving significant progress for the health and well-being of all women.
Antibodies induced by an ancestral SARS-CoV-2 strain that cross-neutralize variants from Alpha to Omicron BA.1
Authors: Ian W. Windsor, Pei Tong, Olivia Lavidor, Ali Sanjari Moghaddam, Lindsay G.A. McKay, Avneesh Gautam, Yuezhou Chen, Elizabeth A. MacDonald, Duck Kyun Yoo, Anthony Griffths, Duane R. Wesemann, Stephen C. Harrison
Journal: Science Immunology (2022)

Neutralizing antibodies that recognize the SARS-CoV-2 spike glycoprotein are the principal host defense against viral invasion. Variants of SARS-CoV-2 bear mutations that allow escape from neutralization by many human antibodies, especially those in widely distributed (“public”) classes. Identifying antibodies that neutralize these variants of concern and determining their prevalence are important goals for understanding immune protection. To determine the Delta and Omicron BA.1 variant specificity of B cell repertoires established by an initial Wuhan strain infection, we measured neutralization potencies of 73 antibodies from an unbiased survey of the early memory B cell response. Antibodies recognizing each of three previously defined epitopic regions on the spike receptor binding domain (RBD) varied in neutralization potency and variant-escape resistance. The ACE2 binding surface (“RBD-2”) harbored the binding sites of neutralizing antibodies with the highest potency but with the greatest sensitivity to viral escape; two other epitopic regions on the RBD (“RBD-1” and “RBD-3”) bound antibodies of more modest potency but greater breadth. The structures of several Fab:spike complexes that neutralized all five variants of concern tested, including one Fab each from the RBD-1, -2, and -3 clusters, illustrated the determinants of broad neutralization and showed that B cell repertoires can have specificities that avoid immune escape driven by public antibodies. The structure of the RBD-2 binding, broad neutralizer shows why it retains neutralizing activity for Omicron BA.1, unlike most others in the same public class. Our results correlate with real-world data on vaccine efficacy, which indicate mitigation of disease caused by Omicron BA.1.
Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth
Authors: Chunming Cheng, Feng Geng, Zoe Li, Yaogang Zhong, Huabao Wang, Xiang Cheng, Yue Zhao, Xiaokui Mo, Craig Horbinski, Wenrui Duan, Arnab Chakravarti, Xiaolin Cheng, Deliang Guo
Journal: Nature Metabolism (2022)
Distribution of Coronary Artery Calcium by Age, Sex, and Race Among Patients 30-45 Years Old
Authors: Aamir Javaid, Zeina A. Dardari, Joshua D. Mitchell, Seamus P. Whelton, Omar Dzaye, Joao A.C. Lima, Donald M. Lloyd-Jones, Matthew Budoff, Khurram Nasir, Daniel S. Berman, John Rumberger, Michael D. Miedema, Todd C. Villines, Michael J. Blaha
Journal: Journal of the American College of Cardiology (2022)
Association Between a Policy to Subsidize Supermarkets in Underserved Areas and Childhood Obesity Risk
Authors: Pasquale Rummo, Jeremy Sze, Brian Elbel
Journal: JAMA Pediatrics (2022)

The establishment and renovation of supermarkets may promote healthy diet practices among youth by increasing retail infrastructure for fresh foods.To estimate the association between the Food Retail Expansion to Support Health (FRESH) program and the weight status of children and adolescents.Using a difference-in-differences (DiD) design and including 12 months before and after a FRESH supermarket opened, data were analyzed for residentially stable public school students in kindergarten through 12th grade with objectively measured height and weight data from the academic years 2009 through 2016. Of the 8 FRESH-subsidized supermarkets in residential neighborhoods in New York City, New York, 5 were new and 3 were renovation projects between December 2011 and June 2014. Data were analyzed from June 2021 to January 2022.The treatment group included students who resided within 0.50 miles of a FRESH-subsidized supermarket and had at least 1 body mass index (BMI) measurement within 12 months before and 3 to 12 months after the month a FRESH supermarket opened (n = 22 712 student-year observations). A 2-stage matching-weighting approach was used to construct a control group of students who resided more than 0.50 miles from a FRESH supermarket in a FRESH-eligible area (n = 86 744 student-year observations).BMI z score was calculated using objectively measured height and weight data from FITNESSGRAM, an annual, school-based, standardized fitness assessment of every New York City public school student. Obesity was defined as 95th percentile or greater of the BMI z score using Centers for Disease Control and Prevention growth charts.The treatment group in the analytic sample had 11 356 students (22 712 student-year observations), and the control group had 43 372 students (86 744 student-year observations). The students were predominately Black (18.8%) and Hispanic and Latino (68.5%) and eligible for free or reduced-priced lunch (84.6%). There was a significant decrease in BMI z score among students who resided within 0.50 miles of a FRESH supermarket (vs control group students) in the 3- to 12-month follow-up period (DiD, -0.04; 95% CI, -0.06 to -0.02). This was true for those exposed to supermarkets that were either new (DiD, -0.07; 95% CI, -0.11 to -0.03) or renovated (DiD, -0.03; 95% CI, -0.06 to -0.01). A statistically significant decrease was also observed in the likelihood of obesity (DiD, -0.01; 95% CI, -0.02 to -0.002).Government-subsidized supermarkets may contribute to a small decrease in obesity risk among children residing near those supermarkets, if part of a comprehensive policy approach.
The Physician and the Hospital
Journal: JAMA (2022)

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CDK4/6 Inhibition Suppresses p73 Phosphorylation and Activates DR5 to Potentiate Chemotherapy and Immune Checkpoint Blockade
Authors: Jingshan Tong, Xiao Tan, Xiangping Song, Man Gao, Denise Risnik, Suisui Hao, Kaylee Ermine, Peng Wang, Hua Li, Yi Huang, Jian Yu, Lin Zhang
Journal: Cancer Research (2022)

Abstract Targeting cyclin-dependent kinases 4 and 6 (CDK4/6) is a successful therapeutic approach against breast and other solid tumors. Inhibition of CDK4/6 halts cell cycle progression and promotes antitumor immunity. However, the mechanisms underlying the antitumor activity of CDK4/6 inhibitors are not fully understood. We found that CDK4/6 bind and phosphorylate the p53 family member p73 at threonine 86, which sequesters p73 in the cytoplasm. Inhibition of CDK4/6 led to dephosphorylation and nuclear translocation of p73, which transcriptionally activated death receptor 5 (DR5), a cytokine receptor and key component of the extrinsic apoptotic pathway. p73-mediated induction of DR5 by CDK4/6 inhibitors promoted immunogenic cell death of cancer cells. Deletion of DR5 in cancer cells in vitro and in vivo abrogated the potentiating effects of CDK4/6 inhibitors on immune cytokine TRAIL, 5-fluorouracil chemotherapy, and anti–PD-1 immunotherapy. Together, these results reveal a previously unrecognized consequence of CDK4/6 inhibition, which may be critical for potentiating the killing and immunogenic effects on cancer cells. Significance: This work demonstrates how inhibition of CDK4/6 sensitizes cancer cells to chemotherapy and immune checkpoint blockade and may provide a new molecular marker for improving CDK4/6-targeted cancer therapies. See related commentary by Frank, p. 1170
Prefusion F Protein–Based Respiratory Syncytial Virus Immunization in Pregnancy
Authors: Eric A.F. Simões, Kimberly J. Center, Alan T.N. Tita, Kena A. Swanson, David Radley, John Houghton, Stephanie B. McGrory, Emily Gomme, Marquita Anderson, John P. Roberts, Daniel A. Scott, Kathrin U. Jansen, William C. Gruber, Philip R. Dormitzer, Alejandra C. Gurtman
Journal: New England Journal of Medicine (2022)

Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein–based (RSVpreF) vaccine in pregnant women and their infants are uncertain.
Annals Graphic Medicine - More Than Skin Deep
Authors: Justin H. Lee
Journal: Annals of Internal Medicine (2022)

Web ExclusivesMay 2022Annals Graphic Medicine - More Than Skin DeepFREEJustin H. LeeJustin H. LeeFort Lee, New Jersey (J.H.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G21-0059 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Justin H. LeeAffiliations: Fort Lee, New Jersey (J.H.L.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G21-0059.Author/Illustrator Information: Justin H. Lee is a rising junior at Brown University concentrating in biology (e-mail, [email protected]com).This article was published at Annals.org on 10 May 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics May 2022Volume 175, Issue 5Page: W62-W63 ePublished: 10 May 2022 Issue Published: May 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A retrospective analysis of the impact of the COVID-19 pandemic on staging at presentation of patients with invasive melanoma
Authors: Saba S. Shaikh, Xi Yang, Dylan D. Fortman, Hong Wang, Diwakar Davar, Jason J. Luke, Hassane Zarour, John M. Kirkwood, Yana G. Najjar
Journal: Journal of the American Academy of Dermatology (2022)
Deep learning-based brain age prediction in normal aging and dementia
Authors: Jeyeon Lee, Brian J. Burkett, Hoon-Ki Min, Matthew L. Senjem, Emily S. Lundt, Hugo Botha, Jonathan Graff-Radford, Leland R. Barnard, Jeffrey L. Gunter, Christopher G. Schwarz, Kejal Kantarci, David S. Knopman, Bradley F. Boeve, Val J. Lowe, Ronald C. Petersen, Clifford R. Jack, David T. Jones
Journal: Nature Aging (2022)
A personified approach to the treatment of vegetative disorders in patients with prevential stomach conditions using Pure Purr complex
Authors: L.M. Mosyichuk, E.V. Zyhalo, O.M. Shevtsova, O.M. Serdiychenko, O.P. Petishko
Journal: GASTROENTEROLOGY (2022)

Background. Indicators of heart rate variability are reliable and objective indicators of the tone of the autonomic nervous system (ANS), which reflects changes in the psycho-emotional state of man against the background of stress. Stress management programs include a variety of relaxation techniques and cognitive behavioral therapy. Therefore, the purpose of the study was to optimize the treatment of patients with chronic atrophic gastritis with autonomic disorders using software and hardware for parasympathetic activation of the ANS. Materials and methods. Indicators of heart rate variability were studied in 80 patients with chronic atrophic gastritis based on the results of PRECISE diagnostics, which allowed to identify patients with hypersympathicotonia and treat them with 10 sessions on Pure Purr software and hardware complex to assess the dynamics of heart rate variability. Results. 72.7% of patients with chronic atrophic gastritis, who showed a decrease in heart rate variability due to activation of the sympathetic tonic ANS and insufficient activity of its parasympathetic tonic, breakdown of adaptation, lack of stress and functional reserves of the body were treated with neurostimulation. After treatment, positive dynamics was determined in the form of a significant increase in heart rate variability by increasing its components due to the parasympathetic nervous system, which prevents increased sympathetic influences and improves disease and prognosis by normalizing adaptation, functional reserves and stress resistance. Conclusions. Treatment of patients with chronic atrophic gastritis with autonomic disorders should be comprehensive with the inclusion of hardware with neurostimulation software aimed at reducing hypersympathicotonia with increasing adaptive capacity of the body.
TGF-β1-supplemented decellularized annulus fibrosus matrix hydrogels promote annulus fibrosus repair
Authors: Qiang Wei, Dachuan Liu, Genglei Chu, Qifan Yu, Zhao Liu, Jiaying Li, Qingchen Meng, Weishan Wang, Fengxuan Han, Bin Li
Journal: Bioactive Materials (2022)

Annulus fibrosus (AF) repair remains a challenge because of its limited self-healing ability. Endogenous repair strategies combining scaffolds and growth factors show great promise in AF repair. Although the unique and beneficial characteristics of decellularized extracellular matrix (ECM) in tissue repair have been demonstrated, the poor mechanical property of ECM hydrogels largely hinders their applications in tissue regeneration. In the present study, we combined polyethylene glycol diacrylate (PEGDA) and decellularized annulus fibrosus matrix (DAFM) to develop an injectable, photocurable hydrogel for AF repair. We found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous structure. Transforming growth factor-β1 (TGF-β1) was further incorporated into PEGDA/DAFM hydrogels, and it could be continuously released from the hydrogel. The
A novel inhibitor of ARfl and ARv7 induces protein degradation to overcome enzalutamide resistance in advanced prostate cancer
Authors: Yan Li, Ya Chu, Guangjiang Shi, Xiaobin Wang, Wanli Ye, Chun Shan, Dajia Wang, Di Zhang, Wei He, Jingwei Jiang, Shuqian Ma, Yuhong Han, Zhili Zhao, Shijia Du, Zhen Chen, Zhiyu Li, Yong Yang, Chen Wang, Xi Xu, Hongxi Wu
Journal: Acta Pharmaceutica Sinica B (2022)

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.
An integrated wearable microneedle array for the continuous monitoring of multiple biomarkers in interstitial fluid
Authors: Farshad Tehrani, Hazhir Teymourian, Brian Wuerstle, Jonathan Kavner, Ravi Patel, Allison Furmidge, Reza Aghavali, Hamed Hosseini-Toudeshki, Christopher Brown, Fangyu Zhang, Kuldeep Mahato, Zhengxing Li, Abbas Barfidokht, Lu Yin, Paul Warren, Nickey Huang, Zina Patel, Patrick P. Mercier, Joseph Wang
Journal: Nature Biomedical Engineering (2022)