Physiological Modeling of the Vascularized Human Lung Organoid.

Human lung organoids (hLOs) derived from induced pluripotent stem cells (iPSCs) are of great interest, as they inform lung development, such as differentiation of lung epithelial subtypes in the distal alveolar unit. An unaddressed question is whether introducing endothelial cells (ECs) and vascularization provides a better representation of hLOs. Here we describe a method in which vessels become integrated with hLOs.

A Protein Complex of Liver Origin Activates a Pro-inflammatory Program That Drives Hepatic and Intestinal Injury in Alcohol-Associated Liver Disease.

Background & Aims: There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1 (HMGB1) undergoes oxidation in hepatocytes and demonstrated elevated serum levels of oxidized HMGB1 ([O] HMGB1) in alcoholic patients. Since interleukin-1 beta (IL-1B) increases in AALD, we hypothesized hepatocyte-derived [O] HMGB1 could interact with IL-1B to activate a pro-inflammatory program that, besides being detrimental to the liver, drives intestinal barrier dysfunction.

Socioeconomic inequality and urban-rural disparity of antenatal care visits in Bangladesh: A trend and decomposition analysis.

Background: Socioeconomic inequality in antenatal care visits is a great concern in developing countries including Bangladesh; however, there is a scarcity of investigation to assess the factors of inequality and these changes over time. In this study, we investigated the trend of socioeconomic inequalities (2004-2017) in 1+ANC and 4+ANC visits, and extracted determinants contributions to the observed inequalities and urban-rural disparities in Bangladesh over the period from 2011 to 2017.

Methods: The data from the Bangladesh Demographic and Health Surveys (BDHS) conducted in 2004, 2007, 2011 and 2017 were analyzed in this study.

Ablation of secreted phosphoprotein-1 in hepatocytes increases fatty acid oxidation and ameliorates alcohol-associated liver disease.

Background: Previously, we demonstrated that Spp1 mice exhibit a greater susceptibility to alcohol-induced liver injury than wild-type (WT) mice. Notably, alcohol triggers the expression of osteopontin (encoded by SPP1) in hepatocytes. However, the specific role of hepatocyte-derived SPP1 in either mitigating or exacerbating alcohol-associated liver disease (AALD) has yet to be elucidated.

Dynamics of dissociative electron attachment to aliphatic thiols.

Dissociative electron attachment (DEA) shows functional group-dependent site selectivity in H ion channels. In this context, thiol functional groups have yet to be studied in great detail, although they carry importance in radiation damage studies where low-energy secondary electrons are known to induce damage through the DEA process. In this context, we report detailed measurements of absolute cross-sections and momentum images of various anion fragments formed in the DEA process in simple aliphatic thiols.

Overexpression of HMGB1 in hepatocytes accelerates PTEN inactivation-induced liver cancer.

Background: Liver cancer is increasing due to the rise in metabolic dysfunction-associated steatohepatitis (MASH). High-mobility group box-1 (HMGB1) is involved in the pathogenesis of chronic liver disease, but its role in MASH-associated liver cancer is unknown. We hypothesized that an increase in hepatocyte-derived HMGB1 in a mouse model of inactivation of PTEN that causes MASH could promote MASH-induced tumorigenesis.

Redox-sensitive high-mobility group box-1 isoforms contribute to liver fibrosis progression and resolution in mice.

Background & Aims: High-mobility group box-1 (HMGB1) significantly increases and undergoes post-translational modifications (PTMs) in response to liver injury. Since oxidative stress plays a major role in liver fibrosis and induces PTMs in proteins, we hypothesized that redox-sensitive HMGB1 isoforms contribute to liver fibrosis progression and resolution.

Methods: We used ESI-LC-MS (electrospray ionization-liquid chromatography-mass spectrometry) to study PTMs of HMGB1 during fibrosis progression and resolution.

Matrisome gene-based subclassification of patients with liver fibrosis identifies clinical and molecular heterogeneities.

Background Aims: Excessive deposition and crosslinking of extracellular matrix increases liver density and stiffness, promotes fibrogenesis, and increases resistance to fibrinolysis. An emerging therapeutic opportunity in liver fibrosis is to target the composition of the extracellular matrix or block pathogenic communication with surrounding cells. However, the type and extent of extracellular changes triggering liver fibrosis depend on the underlying etiology.

Macrophage-derived Osteopontin (SPP1) Protects From Nonalcoholic Steatohepatitis.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning degeneration, and fibrosis, all of which increase the risk of progression to end-stage liver disease. Osteopontin (OPN, SPP1) plays an important role in macrophage (MF) biology, but whether MF-derived OPN affects NASH progression is unknown.

Methods: We analyzed publicly available transcriptomic datasets from patients with NASH, and used mice with conditional overexpression or ablation of Spp1 in myeloid cells and liver MFs, and fed them a high-fat, fructose, and cholesterol diet mimicking the Western diet, to induce NASH.

Abundance of transcript is elevated during septic conditions: Perspectives obtained from a hands-on reductionist investigation.

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon exposure of neutrophils from healthy subjects with the serum of septic patients (GSE49755), and 2) absence or minimal overlap between ACVR1B, sepsis, inflammation, or neutrophil in published literature.

Deficiency of neutrophil high-mobility group box-1 in liver transplant recipients exacerbates early allograft injury in mice.

Background And Aims: Early allograft dysfunction (EAD) is a severe event leading to graft failure after liver transplant (LT). Extracellular high-mobility group box-1 (HMGB1) is a damage-associated molecular pattern that contributes to hepatic ischemia-reperfusion injury (IRI). However, the contribution of intracellular HMGB1 to LT graft injury remains elusive.

Hepatocellular carcinomas, exhibiting intratumor fibrosis, express cancer-specific extracellular matrix remodeling and WNT/TGFB signatures, associated with poor outcome.

Background And Aims: HCC, the third leading cause of cancer-related death, arises in the context of liver fibrosis. Although HCC is generally poorly fibrogenic, some tumors harbor focal intratumor extracellular matrix (ECM) deposits called "fibrous nests." To date, the molecular composition and clinical relevance of these ECM deposits have not been fully defined.

Anxiety and Stress Related to COVID-19 Among the Community Dwelling Older Adults Residing in the Largest Refugee Camp of the World.

The current cross-sectional study was conducted among 864 older adults aged ≥ 60 years residing in Rohingya refugee camp through face-to-face interviews during November-December 2021. COVID-19-related anxiety was measured using the five-point Coronavirus Anxiety Scale (CAS) and perceived stress using the 10-point Perceived Stress Scale (PSS). The linear regression model identified the factors associated with COVID-19-related anxiety and perceived stress.

COVID-19 related anxiety and its associated factors: a cross-sectional study on older adults in Bangladesh.

Background: The COVID-19 pandemic has resulted in serious mental health conditions, particularly among older adults. This research explored the prevalence of COVID-19-related anxiety and its associated factors among older adults residing in Bangladesh.

Methods: This cross-sectional study was conducted among 1,045 older Bangladeshi adults aged ≥ 60 years through telephone interviews in September 2021.

Virtual voltage vector based predictive current control of speed sensorless induction motor drives.

Nowadays, predictive current control (PCC) strategy has been recognized as a promising option for the control of electric drives for their control flexibility, fast dynamic response and weighting factorless structure of objective function. However, such kinds of conventional control strategies make drives to suffer from the ingress of significant harmonics in stator current, increasing further the steady state flux ripple followed by a noticeable torque ripple. To ameliorate these aforementioned shortcomings of conventional scheme, the present work employs the concept of virtual voltage vector (V) in PCC strategy.

Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function.

Background & Aims: The gut-liver axis plays a key role in the pathogenesis of alcohol-associated liver disease (ALD). We demonstrated that Opn develop worse ALD than wild-type (WT) mice; however, the role of intestinal osteopontin (OPN) in ALD remains unknown. We hypothesized that overexpression of OPN in intestinal epithelial cells (IECs) could ameliorate ALD by preserving the gut microbiome and the intestinal barrier function.

Association of overweight and obesity with hypertension, diabetes and comorbidity among adults in Bangladesh: evidence from nationwide Demographic and Health Survey 2017-2018 data.

Objectives: The study aimed to determine the association of overweight and obesity with hypertension, diabetes and comorbidity among the adults of Bangladesh.

Study Design: This study used cross-sectional data from the nationally representative Bangladesh Demographic and Health Survey conducted in 2017-2018. The main outcome variables were hypertension, diabetes and comorbidity.

Ablation of high-mobility group box-1 in the liver reduces hepatocellular carcinoma but causes hyperbilirubinemia in Hippo signaling-deficient mice.

Silencing the Hippo kinases mammalian sterile 20-like 1 and 2 (MST1/2) activates the transcriptional coactivator yes-associated protein (YAP) in human hepatocellular carcinoma (HCC). Hepatocyte-derived high-mobility group box-1 (HMGB1) regulates YAP expression; however, its contribution to HCC in the context of deregulated Hippo signaling is unknown. Here, we hypothesized that HMGB1 is required for hepatocarcinogenesis by activating YAP in Hippo signaling-deficient (Mst1/2 ) mice.

Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016-2017.

Background: Resistance to anti-malarials is a serious threat to the efforts to control and eliminate malaria. Surveillance based on simple field protocols with centralized testing to detect molecular markers associated with anti-malarial drug resistance can be used to identify locations where further investigations are needed.

Methods: Dried blood spots were collected from 398 patients (age range 5-59 years, 99% male) with Plasmodium falciparum infections detected using rapid diagnostic tests over two rounds of sample collection conducted in 2016 and 2017 in Komé, South-West Chad.

Role of Hepatocyte-Derived Osteopontin in Liver Carcinogenesis.

Osteopontin (OPN) expression correlates with tumor progression in many cancers, including hepatocellular carcinoma (HCC); however, its role in the onset of HCC remains unclear. We hypothesized that increased hepatocyte-derived OPN is a driver of hepatocarcinogenesis. Analysis of a tissue microarray of 366 human samples revealed a continuous increase in OPN expression during hepatocarcinogenesis.

The Integrated "Multiomics" Landscape at Peak Injury and Resolution From Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (ALD) is a significant clinical problem for which the most effective therapy is alcohol abstinence. The two aims of this study were, first, to identify the liver transcriptome, fecal microbiome, and portal serum metabolome at peak injury and during early and late resolution from ALD; and second, to integrate their interactions and understand better the pathogenesis of ALD. To provoke alcohol-induced liver injury, female and male wild-type mice were fed the control or ethanol Lieber-DeCarli diets for 6 weeks.

The Matrisome Genes From Hepatitis B-Related Hepatocellular Carcinoma Unveiled.

Chronic hepatitis B virus (HBV) infection changes the composition of the extracellular matrix (ECM) and enables the onset and progression of hepatocellular carcinoma (HCC). The ensemble of ECM proteins and associated factors is a major component of the tumor microenvironment. Our aim was to unveil the matrisome genes from HBV-related HCC.

Sexual dimorphism of body proportions and composition among 16-19-year-olds from South Asia (India) and Central Europe (Poland).

The purpose of this study was to assess the sexual dimorphism of body proportions and body composition among 16-19-year-olds from South Asia (India) and Central Europe (Poland). The study group consisted of the results of anthropometric measurements of 2008 youths (16-19-year-olds). 1098 of them came from Kolkata (India) and 910 from Kraków (Poland).

The pace of secular changes of body measurements of children and adolescents from Kolkata (India) in the context of socioeconomic inequalities between the sexes.

Objectives: To examine the pace of secular changes of selected body measurements and proportions of children and adolescents from Kolkata (India), between 1952-1966 and 1999-2011 in the context of differences between the sexes.

Methods: The study group consisted of 7753 children, adolescents and young adults (7-21 years of age) included in two series of studies (1952-1966 and 2005-2011). The measurements included: body height, sitting height, biacromial and biiliocristal diameters, as well as body mass.