tbuckley/cabot-search huggingface dataset:
Subclinical versus advanced forms of alcohol-related liver disease: Need for early detection
Authors: Concepción Gómez-Medina, Luma Melo, David Martí-Aguado, Ramón Bataller
Journal: Clinical and Molecular Hepatology (2022)

Alcohol-related liver disease (ALD) consists of a wide spectrum of clinical manifestations and pathological features, ranging from asymptomatic patients to decompensated cirrhosis and hepatocellular carcinoma. Patients with heavy alcohol intake and advanced fibrosis often develop a subacute form of liver failure called alcohol-induced hepatitis (AH). Globally, most patients with ALD are identified at late stages of the disease, limiting therapeutic interventions. Thus, there is a need for early detection of ALD patients, which is lacking in most countries. The identification of alcohol misuse is hampered by the existence of alcohol underreporting by many patients. There are useful biomarkers that can detect recent alcohol use. Moreover, there are several non-invasive techniques to assess the presence of advanced fibrosis among patients with alcohol misuse, which could identify patients at high risk of liver related events or early death. In this review, we discuss differences between early stages of ALD and AH as the cornerstone of advanced forms. A global overview of epidemiological, anthropometric, clinical, analytical, histological, and molecular differences is summarized in this article. We propose that campaigns aimed at identifying patients with subclinical forms can prevent the development of life-threatening forms.
Association of Standardized Radiology Reporting and Management of Abdominal CT and MRI With Diagnosis of Pancreatic Cancer
Authors: Eleanor L Ormsby, Kourosh Kojouri, Patrick C Chang, Teresa Y Lin, Brooke Vuong, Rene M Ramirez, Kristin M Schueler, Clifford F Sweet, Lisa J Herrinton
Journal: Clinical Gastroenterology and Hepatology (2022)
Idiopathic mast cell activation syndrome is more often suspected than diagnosed—A prospective real‐life study
Authors: Thomas Buttgereit, Sophie Gu, Leonor Carneiro‐Leão, Annika Gutsche, Marcus Maurer, Frank Siebenhaar
Journal: Allergy (2022)

Idiopathic mast cell activation syndrome (MCAS) is characterized by three diagnostic criteria: (1) episodic mast cell (MC)-driven signs/symptoms of at least two organ systems in the absence of clonal MC expansion and definite triggers, (2) episodic increase in tryptase, and (3) response to MC-targeted treatment. Many patients believe they have MCAS, but how often this is the case remains unknown.We prospectively investigated patients with suspected MCAS (n = 100) for the diagnostic criteria including baseline tryptase, KIT D816V mutation, and patient-reported outcome measures (PROMs) over the course of 12 weeks. Comorbid depression and anxiety were explored with the Hospital Anxiety and Depression Scale (HADS).In 53% of our patients (80% females), suspicion of MCAS was based on self-evaluation. In total, patients reported 87 different symptoms, mostly fatigue (n = 57), musculoskeletal pain/weakness (n = 49), and abdominal pain (n = 43), with overall high disease activity and impact. Two of 79 patients had increased tryptase (by >20% +2 ng/ml) following an episode. Only 5%, with any of the PROMs used, showed complete response to MC-targeted treatment. Depression and anxiety disorders were frequent comorbidities (n = 23 each), and 65 patients had pathological HADS values, which were linked to high disease impact and poor symptom control.Mast cell activation syndrome was confirmed in only 2% of patients, which implies that it is not MC activation that drives signs and symptoms in most patients with suspected MCAS. There is a high need for comprehensive research efforts aimed at the identification of the true underlying pathomechanism(s) in patients with suspected MCAS.
Explainable multiview framework for dissecting spatial relationships from highly multiplexed data
Authors: Jovan Tanevski, Ricardo Omar Ramirez Flores, Attila Gabor, Denis Schapiro, Julio Saez-Rodriguez
Journal: Genome biology (2022)

Abstract The advancement of highly multiplexed spatial technologies requires scalable methods that can leverage spatial information. We present MISTy, a flexible, scalable, and explainable machine learning framework for extracting relationships from any spatial omics data, from dozens to thousands of measured markers. MISTy builds multiple views focusing on different spatial or functional contexts to dissect different effects. We evaluated MISTy on in silico and breast cancer datasets measured by imaging mass cytometry and spatial transcriptomics. We estimated structural and functional interactions coming from different spatial contexts in breast cancer and demonstrated how to relate MISTy’s results to clinical features.
Caring for children with cancer evacuated from Ukraine
Authors: Maura Massimino, Giovanna Casiraghi, Mariangela Armiraglio, Daniele Cabibbe, Roberto Luksch, Monica Terenziani, Michela Casanova, Filippo Spreafico, Cristina Meazza, Marta Podda, Veronica Biassoni, Elisabetta Schiavello, Stefano Chiaravalli, Nadia Puma, Luca Bergamaschi, Giovanna Gattuso, Giovanna Sironi, Olga Nigro, Virginia Livellara, Shushan Hovsepyan, Andrea Ferrari, Carlo Alfredo Clerici
Journal: The Lancet Child & Adolescent Health (2022)
Geography-Dependent Horizontal Gene Transfer from Vertebrate Predators to Their Prey
Authors: Chiaki Kambayashi, Ryosuke Kakehashi, Yusuke Sato, Hideaki Mizuno, Hideyuki Tanabe, Andolalao Rakotoarison, Sven Künzel, Nobuaki Furuno, Kazuhiko Ohshima, Yoshinori Kumazawa, Zoltán T. Nagy, Akira Mori, Allen Allison, Stephen C. Donnellan, Hidetoshi Ota, Masaki Hoso, Tetsuya Yanagida, Hiroshi Sato, Miguel Vences, Atsushi Kurabayashi
Journal: Molecular Biology and Evolution (2022)

Horizontal transfer (HT) of genes between multicellular animals, once thought to be extremely rare, is being more commonly detected, but its global geographic trend and transfer mechanism have not been investigated. We discovered a unique HT pattern of Bovine-B (BovB) LINE retrotransposons in vertebrates, with a bizarre transfer direction from predators (snakes) to their prey (frogs). At least 54 instances of BovB HT were detected, which we estimate to have occurred across time between 85 and 1.3 Ma. Using comprehensive transcontinental sampling, our study demonstrates that BovB HT is highly prevalent in one geographical region, Madagascar, suggesting important regional differences in the occurrence of HTs. We discovered parasite vectors that may plausibly transmit BovB and found that the proportion of BovB-positive parasites is also high in Madagascar where BovB thus might be physically transported by parasites to diverse vertebrates, potentially including humans. Remarkably, in two frog lineages, BovB HT occurred after migration from a non-HT area (Africa) to the HT hotspot (Madagascar). These results provide a novel perspective on how the prevalence of parasites influences the occurrence of HT in a region, similar to pathogens and their vectors in some endemic diseases.
EP3 enhances adhesion and cytotoxicity of NK cells toward hepatic stellate cells in a murine liver fibrosis model
Authors: Xixi Tao, Rui Zhang, Ronglu Du, Tingting Yu, Hui Yang, Jiwen Li, Yuhong Wang, Qian Liu, Shengkai Zuo, Xi Wang, Michael Lazarus, Lu Zhou, Bangmao Wang, Ying Yu, Yujun Shen
Journal: The Journal of Experimental Medicine (2022)

Natural killer (NK) cells exhibit antifibrotic properties in liver fibrosis (LF) by suppressing activated hepatic stellate cell (HSC) populations. Prostaglandin E2 (PGE2) plays a dual role in innate and adaptive immunity. Here, we found that E-prostanoid 3 receptor (EP3) was markedly downregulated in NK cells from liver fibrosis mice and patients with liver cirrhosis. NK cell–specific deletion of EP3 aggravated hepatic fibrogenesis in mouse models of LF. Loss of EP3 selectively reduced the cytotoxicity of the CD27+CD11b+ double positive (DP) NK subset against activated HSCs. Mechanistically, deletion of EP3 impaired the adhesion and cytotoxicity of DP NK cells toward HSCs through modulation of Itga4-VCAM1 binding. EP3 upregulated Itga4 expression in NK cells through promoting Spic nuclear translocation via PKC-mediated phosphorylation of Spic at T191. Activation of EP3 by sulprostone alleviated CCL4-induced liver fibrosis in mice. Thus, EP3 is required for adhesion and cytotoxicity of NK cells toward HSCs and may serve as a therapeutic target for the management of LF.
Author correction to “A nanocleaner specifically penetrates the blood‒brain barrier at lesions to clean toxic proteins and regulate inflammation in Alzheimer’s disease” [Acta Pharmaceutica Sinica B 12, (2021) 4032–4044]
Authors: Ting Lei, Zhihang Yang, Xue Xia, Yuxiu Chen, Xiaotong Yang, Rou Xie, Fan Tong, Xiaolin Wang, Huile Gao
Journal: Acta Pharmaceutica Sinica B (2022)

[This corrects the article DOI: 10.1016/j.apsb.2021.04.022.].
Airway Aging and Methylation Disruptions in HIV-associated Chronic Obstructive Pulmonary Disease
Authors: Ana I. Hernández Cordero, Chen Xi Yang, Julia Yang, Steve Horvath, Tawimas Shaipanich, Julia MacIsaac, David T. S. Lin, Michael S. Kobor, Silvia Guillemi, Marianne Harris, Wan Lam, Stephen Lam, Julio Montaner, S. F. Paul Man, Don D. Sin, Janice M. Leung
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Age-related diseases like chronic obstructive pulmonary disease (COPD) occur at higher rates in people living with human immunodeficiency virus (PLWH) than in uninfected populations. Objectives: To identify whether accelerated aging can be observed in the airways of PLWH with COPD, manifest by a unique DNA methylation signature. Methods: Bronchial epithelial brushings from PLWH with and without COPD and HIV-uninfected adults with and without COPD (N = 76) were profiled for DNA methylation and gene expression. We evaluated global Alu and LINE-1 methylation and calculated the epigenetic age using the Horvath clock and the methylation telomere length estimator. To identify genome-wide differential DNA methylation and gene expression associated with HIV and COPD, robust linear models were used followed by an expression quantitative trait methylation (eQTM) analysis. Measurements and Main Results: Epigenetic age acceleration and shorter methylation estimates of telomere length were found in PLWH with COPD compared with PLWH without COPD and uninfected patients with and without COPD. Global hypomethylation was identified in PLWH. We identified 7,970 cytosine bases located next to a guanine base (CpG sites), 293 genes, and 9 expression quantitative trait methylation-gene pairs associated with the interaction between HIV and COPD. Actin binding LIM protein family member 3 (ABLIM3) was one of the novel candidate genes for HIV-associated COPD highlighted by our analysis. Conclusions: Methylation age acceleration is observed in the airway epithelium of PLWH with COPD, a process that may be responsible for the heightened risk of COPD in this population. Their distinct methylation profile, differing from that observed in patients with COPD alone, suggests a unique pathogenesis to HIV-associated COPD. The associations warrant further investigation to establish causality.
Genetic perturbations go spatial
Authors: Katie Teng, Hartland Warren Jackson
Journal: Cell Genomics (2022)

Tissue-tumor interactivity is the culmination of cell intrinsic features and their extrinsic interactions with the environment. Recently in Cell, Dhainaut and Rose et al. established a strategy to track pooled CRISPR-modified cells in vivo using protein barcodes (Pro-Codes) and measure their impact on the tumor microenvironment through multiplexed imaging and spatial transcriptomics of intact tissues.1.
The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass
Authors: Jean Debédat, Tiphaine Le Roy, Lise Voland, Eugeni Belda, Rohia Alili, Solia Adriouch, Pierre Bel Lassen, Kazuyuki Kasahara, Evan Hutchison, Laurent Genser, Licia Torres, Camille Gamblin, Christine Rouault, Jean-Daniel Zucker, Nathalie Kapel, Christine Poitou, Geneviève Marcelin, Federico E. Rey, Judith Aron-Wisnewsky, Karine Clément
Journal: Gut Microbes (2022)

Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.
Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects
Authors: Sara Canovas Nunes, Serena De Vita, Andrew Anighoro, François Autelitano, Edward Beaumont, Pamela Klingbeil, Meaghan McGuinness, Beatrice Duvert, Chad Harris, Lu Yang, Sheela Pangeni Pokharel, Chun-Wei Chen, Monika Ermann, David A. Williams, Haiming Xu
Journal: Blood Cancer Journal (2022)

RAS mutations prevalent in high-risk leukemia have been linked to relapse and chemotherapy resistance. Efforts to directly target RAS proteins have been largely unsuccessful. However, since RAS-mediated transformation is dependent on signaling through the RAS-related C3 botulinum toxin substrate (RAC) small GTPase, we hypothesized that targeting RAC may be an effective therapeutic approach in RAS mutated tumors. Here we describe multiple small molecules capable of inhibiting RAC activation in acute lymphoblastic leukemia cell lines. One of these, DW0254, also demonstrates promising anti-leukemic activity in RAS-mutated cells. Using chemical proteomics and biophysical methods, we identified the hydrophobic pocket of phosphodiester 6 subunit delta (PDE6D), a known RAS chaperone, as a target for this compound. Inhibition of RAS localization to the plasma membrane upon DW0254 treatment is associated with RAC inhibition through a phosphatidylinositol-3-kinase/AKT-dependent mechanism. Our findings provide new insights into the importance of PDE6D-mediated transport for RAS-dependent RAC activation and leukemic cell survival.
A late sharp increase in influenza detections and low interim vaccine effectiveness against the circulating A(H3N2) strain, Denmark, 2021/22 influenza season up to 25 March 2022
Authors: Hanne-Dorthe Emborg, Lasse S Vestergaard, Amanda Bolt Botnen, Jens Nielsen, Tyra G Krause, Ramona Trebbien
Journal: Eurosurveillance (2022)

We estimated interim influenza A vaccine effectiveness (VE) following a late sharp rise in cases during an influenza A(H3N2)-dominated 2021/22 season, after lifting COVID-19 restrictions. In children aged 2-6 years offered a live attenuated influenza vaccine, adjusted VE was 62.7% (95% CI: 10.9-84.4) in hospitalised and 64.2% (95% CI: 50.5-74.1) in non-hospitalised children. In non-hospitalised patients aged 7-44 years, VE was 24.8% (95% CI: 12.8-35.2); VE was non-significant in remaining age groups and hospital/non-hospital settings.
Healthy lifestyle and life expectancy with and without Alzheimer’s dementia: population based cohort study
Authors: Klodian Dhana, Oscar H Franco, Ethan M Ritz, Christopher N Ford, Pankaja Desai, Kristin R Krueger, Thomas M Holland, Anisa Dhana, Xiaoran Liu, Neelum T Aggarwal, Denis A Evans, Kumar B Rajan
Journal: BMJ (2022)

Abstract Objective To determine the impact of lifestyle factors on life expectancy lived with and without Alzheimer’s dementia. Design Prospective cohort study. Setting The Chicago Health and Aging Project, a population based cohort study in the United States. Participants 2449 men and women aged 65 years and older. Main exposure A healthy lifestyle score was developed based on five modifiable lifestyle factors: a diet for brain health (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay—MIND diet score in upper 40% of cohort distribution), late life cognitive activities (composite score in upper 40%), moderate or vigorous physical activity (≥150 min/week), no smoking, and light to moderate alcohol consumption (women 1-15 g/day; men 1-30 g/day). Main outcome Life expectancy with and without Alzheimer’s dementia in women and men. Results Women aged 65 with four or five healthy factors had a life expectancy of 24.2 years (95% confidence interval 22.8 to 25.5) and lived 3.1 years longer than women aged 65 with zero or one healthy factor (life expectancy 21.1 years, 19.5 to 22.4). Of the total life expectancy at age 65, women with four or five healthy factors spent 10.8% (2.6 years, 2.0 to 3.3) of their remaining years with Alzheimer’s dementia, whereas women with zero or one healthy factor spent 19.3% (4.1 years, 3.2 to 5.1) with the disease. Life expectancy for women aged 65 without Alzheimer’s dementia and four or five healthy factors was 21.5 years (20.0 to 22.7), and for those with zero or one healthy factor it was 17.0 years (15.5 to 18.3). Men aged 65 with four or five healthy factors had a total life expectancy of 23.1 years (21.4 to 25.6), which is 5.7 years longer than men aged 65 with zero or one healthy factor (life expectancy 17.4 years, 15.8 to 20.1). Of the total life expectancy at age 65, men with four or five healthy factors spent 6.1% (1.4 years, 0.3 to 2.0) of their remaining years with Alzheimer’s dementia, and those with zero or one healthy factor spent 12.0% (2.1 years, 0.2 to 3.0) with the disease. Life expectancy for men aged 65 without Alzheimer’s dementia and four or five healthy factors was 21.7 years (19.7 to 24.9), and for those with zero or one healthy factor life expectancy was 15.3 years (13.4 to 19.1). Conclusion A healthy lifestyle was associated with a longer life expectancy among men and women, and they lived a larger proportion of their remaining years without Alzheimer’s dementia. The life expectancy estimates might help health professionals, policy makers, and stakeholders to plan future healthcare services, costs, and needs.
Sex as a Biological Variable in Nutrition Research: From Human Studies to Animal Models
Authors: Yilin Chen, Minhoo Kim, Sanjana Paye, Bérénice A. Benayoun
Journal: Annual Review of Nutrition (2022)

Biological sex is a fundamental source of phenotypic variability across species. Males and females have different nutritional needs and exhibit differences in nutrient digestion and utilization, leading to different health outcomes throughout life. With personalized nutrition gaining popularity in scientific research and clinical practice, it is important to understand the fundamentals of sex differences in nutrition research. Here, we review key studies that investigate sex dimorphism in nutrition research: sex differences in nutrient intake and metabolism, sex-dimorphic response in nutrient-restricted conditions, and sex differences in diet and gut microbiome interactions. Within each area above, factors from sex chromosomes, sex hormones, and sex-specific loci are highlighted.
The IFNγ-PDL1 Pathway Enhances CD8T-DCT Interaction to Promote Hypertension
Authors: Lance N. Benson, Yunmeng Liu, Xiangting Wang, Yunzhao Xiong, Sung W. Rhee, Yunping Guo, Katherine S. Deck, Christoph J. Mora, Lin-Xi Li, Lu Huang, J. Tucker Andrews, Zhiqiang Qin, Robert S. Hoover, Benjamin Ko, Ryan M. Williams, Daniel A. Heller, Edgar A. Jaimes, Shengyu Mu
Journal: Circulation Research (2022)

Renal T cells contribute importantly to hypertension, but the underlying mechanism is incompletely understood. We reported that CD8Ts directly stimulate distal convoluted tubule cells (DCTs) to increase NCC (sodium chloride co-transporter) expression and salt reabsorption. However, the mechanistic basis of this pathogenic pathway that promotes hypertension remains to be elucidated.
Prediction of drug capturing by lipid emulsions in vivo for the treatment of a drug overdose
Authors: Zhi Li, Meng Li, Hao Sun, Zhiyuan Yang, Qingqing Huo, Yuancheng Bai, Yong Mei, Yuanai Li, Peng Quan, Jinsong Zhang, Dongfei Liu
Journal: Journal of Controlled Release (2022)
Advanced Healthcare Materials
Authors: Ashutosh Tiwari
Journal: Advanced Healthcare Materials (2018)

Graphical Abstract This review highlights the strategies to enhance the reactive oxygen species generation through optimizing photoinduced electron transfer and energy transfer processes of photosensitizers (PSs). The approaches that combine photodynamic therapy with other therapeutics (e.g., chemotherapy, photothermal therapy, and radiotherapy) and the targeted delivery in cancer cells or tumor tissue are introduced. The main challenges for the clinical application of PSs are also discussed.
Cancer risk in individuals with autism spectrum disorder
Authors: Q. Liu, W. Yin, J.J. Meijsen, A. Reichenberg, J.R. Gådin, A.J. Schork, H.-O. Adami, A. Kolevzon, S. Sandin, F. Fang
Journal: Annals of Oncology (2022)

Whether individuals with autism spectrum disorders (ASDs) have a higher-than-expected risk of cancer remains unknown.We carried out a population-based cohort study including 2.3 million individuals live-born to mothers from Nordic countries during 1987-2013 in Sweden with follow-up through 2016 (up to age 30 years). Individuals with ASD were ascertained through the Swedish National Patient Register. We estimated the relative risk of cancer in relation to ASD by odds ratios (ORs) and associated 95% confidence intervals (CIs) derived from logistic regression, after detailed adjustment for potential confounders. We also carried out a sibling comparison to address familial confounding and a genetic correlation analysis using the genome-wide association study summary statistics to address confounding due to potential polygenetic pleiotropy between ASD and cancer.We observed an overall increased risk of any cancer among individuals with ASD (OR 1.3, 95% CI 1.2-1.5), compared with individuals without ASD. The association for any cancer was primarily noted for narrowly defined autistic disorder (OR 1.7, 95% CI 1.3-2.1) and ASD with comorbid birth defects (OR 2.1, 95% CI 1.5-2.9) or both birth defects and intellectual disability (ID; OR 4.8, 95% CI 3.4-6.6). An association was also suggested for ASD with comorbid ID (OR 1.4; 95% CI 0.9-2.1), but was not statistically significant. ASD alone (i.e. without comorbid ID or birth defects) was not associated with an increased risk of any cancer (OR 1.0, 95% CI 0.8-1.2). Sibling comparison and genetic correlation analysis showed little evidence for familial confounding or confounding due to polygenetic pleiotropy between ASD and cancer.ASD per se is not associated with an increased risk for cancer in early life. The increased cancer risk among individuals with ASD is likely mainly attributable to co-occurring ID and/or birth defects in ASD.