Stard1 promotes cholestatic liver injury and disease progression by sensitizing to bile acid hepatotoxicity.

Background And Aims: Cholestatic liver diseases (CLD) are often accompanied by hepatocellular injury, fibrosis, and cirrhosis due to the intracellular accumulation of solutes that cannot be excreted into bile, including bile acids (BAs). These are synthesized in hepatocytes from cholesterol mainly via the classic pathway and in a lower proportion through the mitochondrial acidic pathway. The latter requires STARD1-dependent cholesterol transport to the mitochondrial inner membrane for metabolism, whose contribution to BA-induced hepatotoxicity and CLD is unknown.

People with type 1 diabetes exhibit lower exercise capacity compared to a control population with similar physical activity levels.

Aims: We aimed to assess physical activity (PA) levels, adherence to PA guidelines, and fitness capacity in individuals with type 1 diabetes (T1D) and control population.

Methods: This cross-sectional study included 232 T1D and 248 controls. PA levels (IPAQ-SF questionnaire), adherence to guidelines (>150 min/week of moderate-to-vigorous PA), fitness capacity (VOmax, maximal incremental test on a cycle ergometer and 1RM test) were assessed, along with other clinical variables.

Vitamin C deficiency in critically ill COVID-19 patients admitted to intensive care unit.

Objectives: To determine vitamin C plasma kinetics, through the measurement of vitamin C plasma concentrations, in critically ill Coronavirus infectious disease 2019 (COVID-19) patients, identifying eventually the onset of vitamin C deficiency.

Design: Prospective, observational, single-center study.

Setting: Intensive Care Unit (ICU), Vall d'Hebron University Hospital, Barcelona.

AI-Based Glioma Grading for a Trustworthy Diagnosis: An Analytical Pipeline for Improved Reliability.

Glioma is the most common type of tumor in humans originating in the brain. According to the World Health Organization, gliomas can be graded on a four-stage scale, ranging from the most benign to the most malignant. The grading of these tumors from image information is a far from trivial task for radiologists and one in which they could be assisted by machine-learning-based decision support.

Prediction of Lung Nodule Progression with an Uncertainty-Aware Hierarchical Probabilistic Network.

Predicting whether a lung nodule will grow, remain stable or regress over time, especially early in its follow-up, would help doctors prescribe personalized treatments and better surgical planning. However, the multifactorial nature of lung tumour progression hampers the identification of growth patterns. In this work, we propose a deep hierarchical generative and probabilistic network that, given an initial image of the nodule, predicts whether it will grow, quantifies its future size and provides its expected semantic appearance at a future time.

Precision medicine in sepsis and septic shock: From omics to clinical tools.

Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support.

Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders.

Obesity and type 2 diabetes are associated with cognitive dysfunction. Because the hypothalamus is implicated in energy balance control and memory disorders, we hypothesized that specific neurons in this brain region are at the interface of metabolism and cognition. Acute obesogenic diet administration in mice impaired recognition memory due to defective production of the neurosteroid precursor pregnenolone in the hypothalamus.

Dietary and Genetic Cholesterol Loading Rather Than Steatosis Promotes Liver Tumorigenesis and NASH-Driven HCC.

The association of nonalcoholic steatohepatitis (NASH) with obesity and type 2 diabetes is a major determinant factor for the continued rise of NASH-driven HCC. Unfortunately, the mechanisms underlying the progression from NASH to HCC are not well-understood. Steatosis is characterized by the accumulation of different lipid species, and cholesterol has emerged as an important player in NASH development, which has been shown to promote NASH-driven HCC.

STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway.

Background & Aims: Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored.

Re-Identification and growth detection of pulmonary nodules without image registration using 3D siamese neural networks.

Lung cancer follow-up is a complex, error prone, and time consuming task for clinical radiologists. Several lung CT scan images taken at different time points of a given patient need to be individually inspected, looking for possible cancerogenous nodules. Radiologists mainly focus their attention in nodule size, density, and growth to assess the existence of malignancy.

ERα in the Control of Mitochondrial Function and Metabolic Health.

Decrements in metabolic health elevate disease risk, including type 2 diabetes, heart disease, and certain cancers. Thus, treatment strategies to combat metabolic dysfunction are needed. Reduced ESR1 (estrogen receptor, ERα) expression is observed in muscle from women, men, and animals presenting clinical features of the metabolic syndrome.

MITOCHONDRIAL CHOLESTEROL AND CANCER.

Cholesterol is a crucial component of membrane bilayers that determines their physical and functional properties. Cells largely satisfy their need for cholesterol through the novo synthesis from acetyl-CoA and this demand is particularly critical for cancer cells to sustain dysregulated cell proliferation. However, the association between serum or tissue cholesterol levels and cancer development is not well established as epidemiologic data do not consistently support this link.

Estrogen receptor α controls metabolism in white and brown adipocytes by regulating and mitochondrial remodeling.

Obesity is heightened during aging, and although the estrogen receptor α (ERα) has been implicated in the prevention of obesity, its molecular actions in adipocytes remain inadequately understood. Here, we show that adipose tissue expression inversely associated with adiposity and positively associated with genes involved in mitochondrial metabolism and markers of metabolic health in 700 Finnish men and 100 strains of inbred mice from the UCLA Hybrid Mouse Diversity Panel. To determine the anti-obesity actions of ERα in fat, we selectively deleted from white and brown adipocytes in mice.

Type D personality and global positioning system tracked social behavior in patients with cardiovascular disease.

Objective: Social behavior (e.g., loneliness, isolation) has been indicated as an important risk factor for cardiovascular disease.

The Impact of Skeletal Muscle ERα on Mitochondrial Function and Metabolic Health.

The incidence of chronic disease is elevated in women after menopause. Increased expression of ESR1 (the gene that encodes the estrogen receptor alpha, ERα) in muscle is highly associated with metabolic health and insulin sensitivity. Moreover, reduced muscle expression levels of ESR1 are observed in women, men, and animals presenting clinical features of the metabolic syndrome (MetSyn).

Class Imbalance Impact on the Prediction of Complications during Home Hospitalization: A Comparative Study.

Home hospitalization (HH) is presented as a healthcare alternative capable of providing high standards of care when patients no longer need hospital facilities. Although HH seems to lower healthcare costs by shortening hospital stays and improving patient's quality of life, the lack of continuous observation at home may lead to complications in some patients. Since blood tests have been proven to provide relevant prognosis information in many diseases, this paper analyzes the impact of different sampling methods on the prediction of HH outcomes.

Usefulness of a Lifestyle Intervention in Patients With Cardiovascular Disease.

The importance of modifying lifestyle factors in order to improve prognosis in cardiac patients is well-known. Current study aims to evaluate the effects of a lifestyle intervention on changes in lifestyle- and health data derived from wearable devices. Cardiac patients from Spain (n = 34) and The Netherlands (n = 36) were included in the current analysis.

Integration of convolutional neural networks for pulmonary nodule malignancy assessment in a lung cancer classification pipeline.

The early identification of malignant pulmonary nodules is critical for a better lung cancer prognosis and less invasive chemo or radio therapies. Nodule malignancy assessment done by radiologists is extremely useful for planning a preventive intervention but is, unfortunately, a complex, time-consuming and error-prone task. This explains the lack of large datasets containing radiologists malignancy characterization of nodules; METHODS: In this article, we propose to assess nodule malignancy through 3D convolutional neural networks and to integrate it in an automated end-to-end existing pipeline of lung cancer detection.

Endoplasmic Reticulum Stress-Induced Upregulation of STARD1 Promotes Acetaminophen-Induced Acute Liver Failure.

Background & Aims: Acetaminophen (APAP) overdose is a major cause of acute liver failure (ALF). Mitochondrial SH3BP5 (also called SAB) and phosphorylation of c-Jun N-terminal kinase (JNK) mediate the hepatotoxic effects of APAP. We investigated the involvement of steroidogenic acute regulatory protein (STARD1), a mitochondrial cholesterol transporter, in this process and sensitization by valproic acid (VPA), which depletes glutathione and stimulates steroidogenesis.

Consumption of decaffeinated coffee protects against the development of early non-alcoholic steatohepatitis: Role of intestinal barrier function.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide lacking universally accepted therapies. Studies suggest that coffee consumption is associated with a reduced risk of NAFLD; however, molecular mechanisms and ingredients involved remain to be fully understood. Here, we determined the effects of regular intake of decaffeinated coffee on the development of NAFLD in mice, and molecular mechanisms involved.

Machine learning in critical care: state-of-the-art and a sepsis case study.

Background: Like other scientific fields, such as cosmology, high-energy physics, or even the life sciences, medicine and healthcare face the challenge of an extremely quick transformation into data-driven sciences. This challenge entails the daunting task of extracting usable knowledge from these data using algorithmic methods. In the medical context this may for instance realized through the design of medical decision support systems for diagnosis, prognosis and patient management.

The impact of ERα action on muscle metabolism and insulin sensitivity - Strong enough for a man, made for a woman.

Background: The incidence of chronic disease is elevated in women after menopause. Natural variation in muscle expression of the estrogen receptor (ER)α is inversely associated with plasma insulin and adiposity. Moreover, reduced muscle ERα expression levels are observed in women and animals presenting clinical features of the metabolic syndrome (MetSyn).

Estrogen receptor α protects pancreatic β-cells from apoptosis by preserving mitochondrial function and suppressing endoplasmic reticulum stress.

Estrogen receptor α (ERα) action plays an important role in pancreatic β-cell function and survival; thus, it is considered a potential therapeutic target for the treatment of type 2 diabetes in women. However, the mechanisms underlying the protective effects of ERα remain unclear. Because ERα regulates mitochondrial metabolism in other cell types, we hypothesized that ERα may act to preserve insulin secretion and promote β-cell survival by regulating mitochondrial-endoplasmic reticulum (EndoRetic) function.