Hepatic stellate cells control liver zonation, size and functions via R-spondin 3.

Hepatic stellate cells (HSCs) have a central pathogenetic role in the development of liver fibrosis. However, their fibrosis-independent and homeostatic functions remain poorly understood. Here we demonstrate that genetic depletion of HSCs changes WNT activity and zonation of hepatocytes, leading to marked alterations in liver regeneration, cytochrome P450 metabolism and injury.

Molecular Classification of Hepatocellular Carcinoma based on Zoned Metabolic Feature and Oncogenic Signaling Pathway.

Background/aims: Previously, we advocated the importance of classifying hepatocellular carcinoma (HCC) based on physiological functions. This study aims to classify HCC by focusing on liver-intrinsic metabolism and glycolytic pathway in cancer cells.

Methods: Comprehensive RNA/DNA sequencing, immunohistochemistry, and radiological evaluations were performed on HCC tissues from the training cohort (n=136) and validated in 916 public samples.

Involvement of lncRNA MIR205HG in idiopathic pulmonary fibrosis and IL-33 regulation via Alu elements.

Idiopathic pulmonary fibrosis (IPF) causes remodeling of the distal lung. Pulmonary remodeling is histologically characterized by fibrosis, as well as appearance of basal cells; however, the involvement of basal cells in IPF remains unclear. Here, we focus on the long noncoding RNA MIR205HG, which is highly expressed in basal cells, using RNA sequencing.

Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic.

Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly HCC and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease. Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients.

Directional intermodular coupling enriches functional complexity in biological neuronal networks.

Hierarchically modular organization is a canonical network topology that is evolutionarily conserved in the nervous systems of animals. Within the network, neurons form directional connections defined by the growth of their axonal terminals. However, this topology is dissimilar to the network formed by dissociated neurons in culture because they form randomly connected networks on homogeneous substrates.

Development of a new Bridgman-type high-pressure cell by using built-in gasket up to 9.4 GPa and evaluation of deformation.

We have developed a built-in gasket for the Bridgman-type opposed-anvil high-pressure cell, featuring a PTFE (Teflon) capsule of ϕ 2.0 (1.5) × 2.

Influence of the shortened warming protocol on human blastocyst viability: an in-vitro experimental study.

Research Question: Does the shortened warming protocol impact the cell viability and outgrowth competence of human vitrified blastocysts warmed with or without fatty acids?

Design: In this study, 326 discarded vitrified human blastocysts donated for research by consenting couples were used. The blastocysts were randomly allocated to five groups depending on the warming solutions, protocols and recovery culture media: the control-conventional, control-shortened, FA-conventional, FA-shortened, and FA-shortened/recovery culture with fatty acid (FA-shortened/RF) groups. The blastocysts were warmed with or without fatty acids following the manufacturer's instruction (conventional method) or using the shortened method, in which blastocysts were immersed in a thawing solution for 1 min and then cultured in the recovery medium for 2 h.

Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis.

Background & Aims: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.

Methods: Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events.

How to optimize and evaluate diversity in gynecologic cancer clinical trials: statements from the GCIG Barcelona Meeting.

Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups.

Enhancement of enteric neural stem cell neurogenesis by glial cell-derived neurotrophic factor in experimental Hirschsprung's disease.

Purpose: Stem cell therapy offers a promising solution for congenital diseases like Hirschsprung's disease (HSCR). Optimizing stem cell efficacy by modifying the cells and their environment is crucial, but in vitro culture conditions need to be further improved. Glial cell-derived neurotrophic factor (GDNF) plays an important role in neuronal survival, proliferation, migration and differentiation during enteric nervous system (ENS) development.

Prognostic Significance of Psoas Muscle Index in Unresectable Hepatocellular Carcinoma: Comparative Analysis of Lenvatinib and Atezolizumab Plus Bevacizumab.

Skeletal muscle loss has been identified as a prognostic factor in patients with unresectable hepatocellular carcinoma (uHCC) undergoing treatment with lenvatinib (LEN). While atezolizumab plus bevacizumab (ATZ-BEV) is recommended as first-line therapy for uHCC, the impact of skeletal muscle loss in these patients remains unclear. We enrolled 97 patients treated with either LEN or ATZ-BEV as their first-line therapy and divided them into two groups based on the presence or absence of a low psoas muscle index (low PMI) before treatment.

Flavonoids in breast milk and their absorption, metabolism, and bioactivity in infants.

Flavonoids are present in plant foods such as vegetables and fruits and exhibit various physiological effects, including antioxidant and anti-inflammatory properties. Ingested flavonoids are absorbed from the intestinal tract and circulated in the blood. Some studies have indicated the presence of flavonoids in breast milk.

Cost-effectiveness of a precision hepatocellular carcinoma surveillance strategy in patients with cirrhosis.

Background: Hepatocellular carcinoma (HCC) surveillance is currently performed using a one-size-fits-all strategy with ultrasound plus AFP (US + AFP). There is increasing interest in risk-stratified and precision surveillance strategies incorporating individual risk and variance in surveillance test performance; however, the cost-effectiveness of these approaches has not been evaluated.

Methods: We conducted a cost-effectiveness analysis to evaluate four surveillance strategies (no surveillance, universal US + AFP surveillance, risk-stratified surveillance, and precision surveillance) in a simulated cohort of 50-year-old patients with compensated cirrhosis.

Robot-assisted cervical esophagectomy with simultaneous transhiatal abdominal procedure for thoracic esophageal carcinoma.

Background: Minimally invasive robot-assisted cervical esophagectomy has been sporadically reported as a novel thoracic esophagectomy technique for patients with thoracic esophageal carcinoma. Most reports indicate that the abdominal component of robot-assisted cervical esophagectomy is performed sequentially after the cervical phase. However, if the cervical and abdominal phases are performed simultaneously using a nerve integrity monitoring system with no administration of muscle relaxants, there are two major advantages: a reduced risk of recurrent nerve palsy and a shorter operative time.

An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection.

Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice.

Assessing the outcomes of posterior thoracic para-aortic lymph node dissection after induction chemotherapy in patients with esophageal squamous cell carcinoma.

Posterior thoracic para-aortic lymph node (TPAN) metastasis is a distant metastasis of esophageal cancer. Several case reports have shown that radical esophagectomy and lymphadenectomy for posterior TPAN improve the prognosis of patients with cStage IVB esophageal cancer and solitary posterior TPAN metastasis; however, the true value of this procedure is unclear. The primary objective of this study was to evaluate the short- and long-term outcomes of lymphadenectomy for posterior TPAN after induction chemotherapy in esophageal cancer.

The Ile35 Residue of the ALS-Associated Mutant SOD1 Plays a Crucial Role in the Intracellular Aggregation of the Molecule.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an unknown pathogenesis. It has been reported that mutations in the gene for Cu/Zn superoxide dismutase (SOD1) cause familial ALS. Mutant SOD1 undergoes aggregation and forms amyloid more easily, and SOD1-immunopositive inclusions have been observed in the spinal cords of ALS patients.