tbuckley/cabot-search huggingface dataset:
Abstract P223: The Relationship Between Positive Psychological Well-being And Dietary Intakes During The Covid-19 Pandemic: A Cross-sectional Analysis
Authors: Giada Benasi, Marie-Pierre St-Onge
Journal: Circulation (2022)

Introduction: The Covid-19 pandemic had a negative impact on mental health and lifestyle behaviors, including dietary habits. Negative psychological factors are known to adversely impact lifestyle behaviors, but the influence of positive psychological well-being on dietary intakes is relatively unknown. Hypothesis: We assessed the hypothesis that psychological factors related to both negative emotional states and positive psychological well-being would have an impact on dietary intakes among adults reporting poor sleep quality and at least moderate perceived stress during the Covid-19 pandemic. Methods: Thirty-one individuals (age 40.2±13.0 y, 81% women, 55% White, BMI 23.2±2.6 kg/m 2 ) were enrolled in a pilot study testing the efficacy of a well-being and sleep hygiene intervention to improve sleep, diet, and mental health. Questionnaires were administered at baseline to assess diet (single-day food recall), psychological well-being (Psychological Well-Being scales of autonomy, environmental mastery, personal growth, purpose in life, positive relations with others, and self-acceptance) and negative emotional states (Symptom Questionnaire scales of anxiety, depression, hostility, and somatization). Separate linear regression models were estimated for each psychological variable that was significantly correlated with diet at baseline, controlling for age, sex, and BMI. Results: Linear regression models showed that, at baseline, higher depression and hostility were associated with higher energy ( B = 77.6±20.3 ( SE ), p &lt; 0.001 and B = 65.2±25.7, p = 0.01, respectively) and fat ( B = 4.6±1.5, p = 0.004 and B = 4.9±1.7, p = 0.008, respectively) intakes. Higher depression was also associated with higher intakes of protein ( B = 3.0±1.0, p = 0.006), carbohydrate ( B = 6.5±2.5, p = 0.01), sugar ( B = 3.9±1.1, p = 0.001), and sodium ( B = 130.7±36.6, p = 0.001). Higher positive relations was associated with lower carbohydrate ( B = -5.1±2.4, p = 0.04) and sugar ( B = -3.6±1.0, p = 0.001) intakes, and higher purpose in life was associated with lower sugar ( B = -3.3±1.2, p = 0.008), cholesterol ( B = -14.7±5.9, p = 0.01), and saturated fat ( B = -1.2±0.4, p = 0.008) intakes. When controlling for baseline levels of depression, hostility and purpose in life were no longer associated with dietary intakes, while positive relations remained associated with sugar intakes ( B = -2.3±1.2, p = 0.04). Conclusions: Under stressful circumstances, both negative emotional states and positive psychological well-being are associated with dietary intakes. Despite depression having the strongest overall impact on dietary intakes, positive relations with others independently affected sugar intakes. Personalized approaches focused on positive psychological well-being, along with distress reduction, should be considered in interventions aimed at promoting healthy dietary behaviors.
25P Tepotinib in Asian patients with advanced NSCLC with MET exon 14 (METex14) skipping
Authors: J.C-H. Yang, M-J. Ahn, H. Sakai, M. Morise, T. Kato, Y-M. Chen, J-Y. Han, J-J. Yang, J. Zhao, J. Huang, K. Berghoff, R. Bruns, G. Otto, X. Le, P. Paik
Journal: Annals of Oncology (2022)
Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial
Authors: Rajiv Agarwal, Amer Joseph, Stefan D. Anker, Gerasimos Filippatos, Peter Rossing, Luis M. Ruilope, Bertram Pitt, Peter Kolkhof, Charlie Scott, Robert Lawatscheck, Daniel J. Wilson, George L. Bakris
Journal: Journal of the American Society of Nephrology (2021)

Finerenone reduced risk of cardiorenal outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD trial. We report incidences and risk factors for hyperkalemia with finerenone and placebo in FIDELIO-DKD.This post hoc safety analysis defined hyperkalemia as ≥mild or ≥moderate based on serum potassium concentrations of >5.5 or >6.0 mmol/L, respectively, assessed at all regular visits. Cumulative incidences of hyperkalemia were based on the Aalen-Johansen estimator using death as competing risk. A multivariate Cox proportional hazards model identified significant independent predictors of hyperkalemia. Restricted cubic splines assessed relationships between short-term post-baseline changes in serum potassium or eGFR and subsequent hyperkalemia risk. During the study, serum potassium levels guided drug dosing. Patients in either group who experienced ≥mild hyperkalemia had the study drug withheld until serum potassium was ≤5.0 mmol/L; then the drug was restarted at the 10 mg daily dose. Placebo-treated patients underwent sham treatment interruption and downtitration.Over 2.6 years' median follow-up, 597 of 2785 (21.4%) and 256 of 2775 (9.2%) patients treated with finerenone and placebo, respectively, experienced treatment-emergent ≥mild hyperkalemia; 126 of 2802 (4.5%) and 38 of 2796 (1.4%) patients, respectively, experienced moderate hyperkalemia. Independent risk factors for ≥mild hyperkalemia were higher serum potassium, lower eGFR, increased urine albumin-creatinine ratio, younger age, female sex, β-blocker use, and finerenone assignment. Diuretic or sodium-glucose cotransporter-2 inhibitor use reduced risk. In both groups, short-term increases in serum potassium and decreases in eGFR were associated with subsequent hyperkalemia. At month 4, the magnitude of increased hyperkalemia risk for any change from baseline was smaller with finerenone than with placebo.Finerenone was independently associated with hyperkalemia. However, routine potassium monitoring and hyperkalemia management strategies employed in FIDELIO-DKD minimized the impact of hyperkalemia, providing a basis for clinical use of finerenone.
Immune Infiltrate and Tumor Microenvironment Transcriptional Programs Stratify Pediatric Osteosarcoma into Prognostic Groups at Diagnosis
Authors: Antonin Marchais, Maria Eugenia Marques da Costa, Bastien Job, Rachid Abbas, Damien Drubay, Sophie Piperno-Neumann, Olivia Fromigué, Anne Gomez-Brouchet, Françoise Redini, Robin Droit, Cyril Lervat, Natacha Entz-Werle, Hélène Pacquement, Catherine Devoldere, Didier Cupissol, Damien Bodet, Virginie Gandemer, Marc Berger, Perrine Marec-Berard, Marta Jimenez, Gilles Vassal, Birgit Geoerger, Laurence Brugières, Nathalie Gaspar
Journal: Cancer Research (2022)

Abstract The outcomes of adolescents/young adults with osteosarcoma have not improved in decades. The chaotic karyotype of this rare tumor has precluded the identification of prognostic biomarkers and patient stratification. We reasoned that transcriptomic studies should overcome this genetic complexity. RNA sequencing (RNA-seq) of 79 osteosarcoma diagnostic biopsies identified stable independent components that recapitulate the tumor and microenvironment cell composition. Unsupervised classification of the independent components stratified this cohort into favorable (G1) and unfavorable (G2) prognostic tumors in terms of overall survival. Multivariate survival analysis ranked this stratification as the most influential variable. Functional characterization associated G1 tumors with innate immunity and G2 tumors with angiogenic, osteoclastic, and adipogenic activities as well as PPARγ pathway upregulation. A focused gene signature that predicted G1/G2 tumors from RNA-seq data was developed and validated within an independent cohort of 82 osteosarcomas. This signature was further validated with a custom NanoString panel in 96 additional osteosarcomas. This study thus proposes new biomarkers to detect high-risk patients and new therapeutic options for osteosarcoma. Significance: These findings indicate that the osteosarcoma microenvironment composition is a major feature to identify hard-to-treat patient tumors at diagnosis and define the biological pathways and potential actionable targets associated with these tumors.
Health-care provision and policy for non-alcoholic fatty liver disease in sub-Saharan Africa
Authors: C Wendy Spearman, Abdelmounem Abdo, Aggrey Ambali, Yaw A Awuku, Chris Kassianides, Olufunmilayo A Lesi, Margareth Ndomondo-Sigonda, Charles A Onyekwere, John Rwegasha, Abate B Shewaye, Mark W Sonderup
Journal: The Lancet. Gastroenterology & hepatology (2021)
AGK regulates the progression to NASH by affecting mitochondria complex I function
Authors: Nan Ding, Kang Wang, Haojie Jiang, Mina Yang, Lin Zhang, Xuemei Fan, Qiang Zou, Jianxiu Yu, Hui Dong, Shuqun Cheng, Yanyan Xu, Junling Liu
Journal: Theranostics (2022)

Background: Impaired mitochondrial function contributes to non-alcoholic steatohepatitis (NASH).Acylglycerol kinase (AGK) is a subunit of the translocase of the mitochondrial inner membrane 22 (TIM22) protein import complex.AGK mutation is the leading cause of Sengers syndrome, characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, lactic acidosis, and liver dysfunction.The potential roles and mechanisms of AGK in NASH are not yet elucidated.Methods: Hepatic-specific AGK-deficient mice and AGK G126E mutation (AGK kinase activity arrest) mice were on a choline-deficient and high-fat diet (CDAHFD) and a methionine choline-deficient diet (MCD).The mitochondrial function and the molecular mechanisms underlying AGK were investigated in the pathogenesis of NASH.Results: The levels of AGK were significantly downregulated in human NASH liver samples.AGK deficiency led to severe liver damage and lipid accumulation in mice.Aged mice lacking hepatocyte AGK spontaneously developed NASH.AGK G126E mutation did not affect the structure and function of hepatocytes.AGK deficiency, but not AGK G126E mice, aggravated CDAHFD-and MCD-induced NASH symptoms.AGK deficiency-induced liver damage could be attributed to hepatic mitochondrial dysfunction.The mechanism revealed that AGK interacts with mitochondrial respiratory chain complex I subunits, NDUFS2 and NDUFA10, and regulates mitochondrial fatty acid metabolism.Moreover, the AGK DGK domain might directly interact with NDUFS2 and NDUFA10 to maintain the hepatic mitochondrial respiratory chain complex I function. Conclusions:The current study revealed the critical roles of AGK in NASH.AGK interacts with mitochondrial respiratory chain complex I to maintain mitochondrial integrity via the kinase-independent pathway.
Efficacy and tolerability of a third dose of an mRNA anti-SARS-CoV-2 vaccine in patients with rheumatoid arthritis with absent or minimal serological response to two previous doses
Authors: Kristin Schmiedeberg, Nicolas Vuilleumier, Sabrina Pagano, Werner C Albrich, Burkhard Ludewig, Johannes von Kempis, Andrea Rubbert-Roth
Journal: The Lancet Rheumatology (2021)
Efficacy and safety of itacitinib versus placebo in combination with corticosteroids for initial treatment of acute graft-versus-host disease (GRAVITAS-301): a randomised, multicentre, double-blind, phase 3 trial
Authors: Robert Zeiser, Gérard Socié, Mark A Schroeder, Sunil Abhyankar, Carlos Pinho Vaz, Mi Kwon, Johannes Clausen, Leonid Volodin, Sebastian Giebel, Manuel Jurado Chacon, Gabrielle Meyers, Monalisa Ghosh, Dries Deeren, Jaime Sanz, Rodica Morariu-Zamfir, Michael Arbushites, Mani Lakshminarayanan, April M Barbour, Yi-Bin Chen
Journal: The Lancet Haematology (2021)
Abstract P215: A Qualitative Exploration Of Barriers And Facilitators To A Cardiac Rehabilitation-based Weight Loss Program For Patients With Atrial Fibrillation And Obesity.
Authors: Tamara M Williamson, Stephen Wilton, Ross Arena, Sandeep Aggarwal, Tavis Campbell, Codie Rouleau
Journal: Circulation (2022)

Background: Cardiac rehabilitation (CR) programs are ideal treatment settings for atrial fibrillation (AF) risk factor management, yet few CR curricula include a behavioral weight loss treatment (BWLT) component for patients with comorbid obesity (BMI ≥ 30 kg/m 2 ). Aim: To identify perceived barriers, facilitators, and preferences regarding CR with added BWLT among patients with AF and obesity using a qualitative descriptive approach. Methods: Patients (18+) with paroxysmal or persistent AF and obesity were recruited from a Canadian AF clinic. Patients completed questionnaires assessing socio-demographic variables and participated in semi-structured interviews to elicit their potential barriers, facilitators, and preferences regarding a proposed 12-week CR+BWLT program (i.e., twice-weekly supervised exercise, risk factor management, and weekly group-based cognitive-behavioral weight management support). Interviews were recorded and transcribed. Conventional content analysis was used to derive themes from qualitative data. Results: Twenty patients (9 women; 63±12 years; BMI=35.50±6.00 kg/m 2 ) participated. Data were categorized to describe patients' barriers, facilitators, and preferences/perspectives (Figure 1). Four overarching themes emerged from the categories: 1) frustration with weight management; 2) AF symptoms are manageable; 3) AF information needs; and 4) desire for program flexibility. Conclusion &amp; Future Directions: The proposal to offer BWLT alongside CR was acceptable to patients with AF and obesity, with most reporting few barriers to participating. The results will inform AF-specific adaptations to an established BWLT (e.g., modules on AF pathophysiology and exercise recommendations). The AF-adapted BWLT will be piloted in the target population prior to testing the full intervention package in a randomized controlled trial. The novel combination of CR+BWLT, tailored to an AF population, has potential to improve AF management and outcomes for patients with comorbid obesity.
Legumain Is an Endogenous Modulator of Integrin αvβ3 Triggering Vascular Degeneration, Dissection, and Rupture
Authors: Lihong Pan, Peiyuan Bai, Xinyu Weng, Jin Liu, Yingjie Chen, Siqin Chen, Xiurui Ma, Kai Hu, Aijun Sun, Junbo Ge
Journal: Circulation (2022)

The development of thoracic aortic dissection (TAD) is closely related to extracellular matrix degradation and vascular smooth muscle cell (VSMC) transformation from contractile to synthetic type. LGMN (legumain) degrades extracellular matrix components directly or by activating downstream signals. The role of LGMN in VSMC differentiation and the occurrence of TAD remains elusive. Microarray datasets concerning vascular dissection or aneurysm were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes. Four-week-old male Lgmn knockout mice (Lgmn-/-), macrophage-specific Lgmn knockout mice (LgmnF/F;LysMCre), and RR-11a-treated C57BL/6 mice were given BAPN (β-aminopropionitrile monofumarate; 1 g/kg/d) in drinking water for 4 weeks for TAD modeling. RNA sequencing analysis was performed to recapitulate transcriptome profile changes. Cell interaction was examined in macrophage and VSMC coculture system. The reciprocity of macrophage-derived LGMN with integrin αvβ3 in VSMCs was tested by coimmunoprecipitation assay and colocalization analyses. Microarray datasets from the Gene Expression Omnibus database indicated upregulated LGMN in aorta from patients with TAD and mice with angiotensin II-induced AAA. Elevated LGMN was evidenced in aorta and sera from patients with TAD and mice with BAPN-induced TAD. BAPN-induced TAD progression was significantly ameliorated in Lgmn-deficient or inhibited mice. Macrophage-specific deletion of Lgmn alleviated BAPN-induced extracellular matrix degradation. Unbiased profiler polymerase chain reaction array and Gene Ontology analysis displayed that LGMN regulated VSMC phenotype transformation. Macrophage-specific deletion of Lgmn ameliorated VSMC phenotypic switch in BAPN-treated mice. Macrophage-derived LGMN inhibited VSMC differentiation in vitro as assessed by macrophages and the VSMC coculture system. Macrophage-derived LGMN bound to integrin αvβ3 in VSMCs and blocked integrin αvβ3, thereby attenuating Rho GTPase activation, downregulating VSMC differentiation markers and eventually exacerbating TAD development. ROCK (Rho kinase) inhibitor Y-27632 reversed the protective role of LGMN depletion in vascular dissection. LGMN signaling may be a novel target for the prevention and treatment of TAD.
Differential bioactivity of four BMP-family members as function of biomaterial stiffness
Authors: Adrià Sales, Valia Khodr, Paul Machillot, Line Chaar, Laure Fourel, Amaris Guevara-Garcia, Elisa Migliorini, Corinne Albigès-Rizo, Catherine Picart
Journal: Biomaterials (2022)
Human Papillomavirus Infection Determines Prognosis in Cervical Cancer
Authors: Jiayao Lei, Laila Sara Arroyo-Mühr, Camilla Lagheden, Carina Eklund, Sara Nordqvist Kleppe, Miriam Elfström, Bengt Andrae, Pär Sparén, Joakim Dillner, Karin Sundström
Journal: Journal of Clinical Oncology (2022)

PURPOSE Detection of human papillomavirus (HPV) by polymerase chain reaction in invasive cervical cancer is strongly associated with prognosis but previous studies have not considered sequencing efforts. We aimed to assess the association when also including comprehensive analysis of HPV infection by deep sequencing and a longer follow-up period. MATERIALS AND METHODS We subjected all 392 of 2,845 invasive cervical cancer cases that were polymerase chain reaction–negative for HPV to RNA sequencing on the NovaSeq 6000 platform (Illumina) and identified an additional 169 cases as HPV-positive. We followed all women from date of diagnosis to December 31, 2016, emigration, or death, whichever occurred first. The main outcome was all-cause mortality by December 31, 2016. We calculated 5-year cumulative relative survival ratios compared with the female general population and used Poisson regression to estimate excess hazard ratios of all-cause mortality by infection with any of the 13 most oncogenic (high-risk [hr]) HPV types in the tumor. All models were adjusted for age, time since diagnosis, stage, histology, and education level. RESULTS The 5-year cumulative relative survival ratio was 0.45 (95% CI, 0.39 to 0.51) in the hrHPV-negative group, and 0.74 (95% CI, 0.72 to 0.75) in the hrHPV-positive group. This translated to a statistically significantly 43% lower excess mortality in the hrHPV-positive group compared with the hrHPV-negative (corresponding to an excess hazard ratio 0.57; 95% CI, 0.48 to 0.69). There was no association between HPV risk group, clade, or number of HPV infections and prognosis. CONCLUSION hrHPV status is a strong determinant of cervical cancer prognosis over 15 years after diagnosis, above and beyond other established factors.
Glioblastoma: The Current State of Biology and Therapeutic Strategies
Authors: Zev A. Binder, Donald M. O'Rourke
Journal: Cancer Research (2022)

Abstract Over the past two decades, there have been advances in surgical technologies and chemoradiation strategies for glioblastoma, yet durable remissions are rarely seen. As the biological challenges and genetic basis of glioblastoma have become more understood, new therapeutic strategies may lead to more durable clinical responses and long-term remissions. We believe specialized academic centers that form meaningful corporate partnerships to complement basic science infrastructure and use adaptive clinical trial designs will achieve more rapid translation of innovative approaches to glioblastoma. Here we outline the core biological challenges to be overcome in the management of glioblastoma.
Salt-Induced Hepatic Inflammatory Memory Contributes to Cardiovascular Damage Through Epigenetic Modulation of SIRT3
Authors: Peng Gao, Mei You, Li Li, Qin Zhang, Xia Fang, Xiao Wei, Qing Zhou, Hexuan Zhang, Miao Wang, Zongshi Lu, Lijuan Wang, Fang Sun, Daoyan Liu, Hongting Zheng, Zhencheng Yan, Gangyi Yang, Zhiming Zhu
Journal: Circulation (2022)

High salt intake is the leading dietary risk factor for cardiovascular diseases. Although clinical evidence suggests that high salt intake is associated with nonalcoholic fatty liver disease, which is an independent risk factor for cardiovascular diseases, it remains elusive whether salt-induced hepatic damage leads to the development of cardiovascular diseases.Mice were fed with normal or high-salt diet for 8 weeks to determine the effect of salt loading on liver histological changes and blood pressure, and salt withdrawal and metformin treatment were also conducted on some high-salt diet-fed mice. Adeno-associated virus 8, global knockout, or tissue-specific knockout mice were used to manipulate the expression of some target genes in vivo, including SIRT3 (sirtuin 3), NRF2 (NF-E2-related factor 2), and AMPK (AMP-activated protein kinase).Mice fed with a high-salt diet displayed obvious hepatic steatosis and inflammation, accompanied with hypertension and cardiac dysfunction. All these pathological changes persisted after salt withdrawal, displaying a memory phenomenon. Gene expression analysis and phenotypes of SIRT3 knockout mice revealed that reduced expression of SIRT3 was a chief culprit responsible for the persistent inflammation in the liver, and recovering SIRT3 expression in the liver effectively inhibits the sustained hepatic inflammation and cardiovascular damage. Mechanistical studies reveal that high salt increases acetylated histone 3 lysine 27 (H3K27ac) on SIRT3 promoter in hepatocytes, thus inhibiting the binding of NRF2, and results in the sustained inhibition of SIRT3 expression. Treatment with metformin activated AMPK, which inhibited salt-induced hepatic inflammatory memory and cardiovascular damage by lowering the H3K27ac level on SIRT3 promoter, and increased NRF2 binding ability to activate SIRT3 expression.This study demonstrates that SIRT3 inhibition caused by histone modification is the key factor for the persistent hepatic steatosis and inflammation that contributes to cardiovascular damage under high salt loading. Avoidance of excessive salt intake and active intervention of epigenetic modification may help to stave off the persistent inflammatory status that underlies high-salt-induced cardiovascular damage in clinical practice.