PIAS1 S510G variant acts as a genetic modifier of spinocerebellar ataxia type 3 by selectively impairing mutant ataxin-3 proteostasis.

Dysregulated protein homeostasis, characterized by abnormal protein accumulation and aggregation, is a key contributor to the progression of neurodegenerative disorders such as Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Previous studies have identified PIAS1 gene variants in patients with late-onset SCA3 and Huntington's disease. This study aims to elucidate the role of PIAS1 and its S510G variant in modulating the pathogenic mechanisms of SCA3.

Sarcopenia-related gut microbial changes are associated with the risk of complications in people with cirrhosis.

Background & Aims: Sarcopenia and gut dysbiosis are common in individuals with cirrhosis. However, the association between sarcopenia and microbial alterations, and the subsequent impact on cirrhotic outcomes are poorly understood. This study aimed to identify muscle-dependent microbial changes and related risks of cirrhotic complications.

High BRCA1 gene expression increases the risk of early distant metastasis in ER breast cancers.

Although the function of the BRCA1 gene has been extensively studied, the relationship between BRCA1 gene expression and tumor aggressiveness remains controversial in sporadic breast cancers. Because the BRCA1 protein is known to regulate estrogen signaling, we selected microarray data of ER breast cancers from the GEO public repository to resolve previous conflicting findings. The BRCA1 gene expression level in highly proliferative luminal B tumors was shown to be higher than that in luminal A tumors.

A PIAS1 Protective Variant S510G Delays polyQ Disease Onset by Modifying Protein Homeostasis.

Background: Polyglutamine (polyQ) diseases are dominant neurodegenerative diseases caused by an expansion of the polyQ-encoding CAG repeats in the disease-causing gene. The length of the CAG repeats is the major determiner of the age at onset (AO) of polyQ diseases, including Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3).

Objective: We set out to identify common genetic variant(s) that may affect the AO of polyQ diseases.

Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection.

Background/purpose: Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan.

Deletion of intestinal SIRT1 exacerbated muscle wasting in cirrhotic mice by decreasing the intestinal concentration of short-chain fatty acids and inflammation.

Systemic sirtuin 1 (SIRT1) activation alleviates muscle wasting and improves muscle function by downregulation of myotropic and proteolytic markers. In this study, we evaluated the effects of the intestinal Sirt1 deletion on the dysregulated gutmuscle axis in cirrhotic mice. Cirrhosis-related muscle wasting was induced by common bile duct ligated (BDL) in either wild-type (WT) or intestine-specific Sirt1-deleted (Sirt1) mice, including WT-BDL, WT-sham, Sirt1-BDL and Sirt1-sham mice.

Fecal microbiota profile in patients with inflammatory bowel disease in Taiwan.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with complicated interaction between immune, gut microbiota, and environmental factors in a genetically vulnerable host. Dysbiosis is often seen in patients with IBD. We aimed to investigate the fecal microbiota in patients with IBD and compared them with a control group in Taiwan.

Differences in intestinal microbiota profiling after upper and lower gastrointestinal surgery.

Background: We aimed to investigate the long-term effects of metabolic profiles and microbiota status in patients after upper gastrointestinal (GI) surgery and lower GI surgery and compared them with a control group.

Methods: In this cross-sectional study, we analyzed the occurrence of metabolic syndrome (MS) in 10 patients who underwent curative total gastrectomy with Roux-en-Y esophagojejunostomy (RYEJ) anastomosis, 11 patients who underwent curative partial colectomy with right hemicolectomy (RH), and 33 age- and sex-matched controls. Fecal samples were also analyzed by a next-generation sequencing method.

Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice.

In advanced cirrhosis, the TNFα-mediated intestinal inflammation and bacteria dysbiosis are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and acute kidney injury models, activation of SIRT1 attenuates the TNFα-mediated intestinal and renal abnormalities. This study explores the impacts of intestinal SIRT1 deficiency and TNFα-mediated intestinal abnormalities on the development of cirrhosis-related renal dysfunction.

Active Vitamin D Treatment Attenuated Bacterial Translocation via Improving Intestinal Barriers in Cirrhotic Rats.

Scope: Pathological bacterial translocation from the disrupted intestinal barrier leads to substantial complications and mortality in liver cirrhosis. Vitamin D is reported as beneficial to gut barriers in some animal models. However, its effect on cirrhotic bacterial translocation is unknown.

Integrative LHS for precision medicine research: A shared NIH and Taiwan CIMS experience.

Introduction: Precision medicine is an important milestone toward the attainment of personalized medicine. A learning health system (LHS) may facilitate the evidence collection and knowledge generation process for disease-based research and for the diagnosis, classification, or treatment of each disease subtype to improve patient care.

Methods: The LHS design and implementation used by Taichung Veterans General Hospital (TCVGH) in Taiwan for their newly funded precision medicine research, a dementia registry study, was modeled from an LHS developed at the National Institutes of Health in the United States.

The long term microbiota and metabolic status in patients with colorectal cancer after curative colon surgery.

Whether there are subsequent changes of metabolic profiles and microbiota status after partial colectomy remains unknown. We evaluated and compared long-term effects of microbiota status and metabolic profiles in early colorectal cancer (CRC) patients after curative colectomy to the controls. In this cross-sectional study, we analyzed metabolic syndrome occurrence in 165 patients after curative partial colectomy with right hemicolectomy (RH) or low anterior resection (LAR) and 333 age-sex matched controls.

A standard-driven approach for electronic submission to pharmaceutical regulatory authorities.

Objective: Using standards is not only useful for data interchange during the process of a clinical trial, but also useful for analyzing data in a review process. Any step, which speeds up approval of new drugs, may benefit patients. As a result, adopting standards for regulatory submission becomes mandatory in some countries.

Involvement of cecropin B in the formation of the Aedes aegypti mosquito cuticle.

In this study, we found a mosquito antimicrobial peptide (AMP), Aedes aegypti cecropin B (Aacec B), was expressed constitutively in pupae. Knockdown in the pupae of Aacec B using double-stranded RNA (dsRNA) resulted in high mortality, the emergence of deformed adults and an impairment of pharate adult cuticle formation with fewer lamellae being deposited and the helicoidal pattern of the chitin microfibrils being disorganized. Simultaneous injection of Aacec B dsRNA and Aacec B peptide into pupae significantly reduced this mortality and no deformed adults then emerged.

A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy.

Distal hereditary motor neuropathy is a heterogeneous group of inherited neuropathies characterized by distal limb muscle weakness and atrophy. Although at least 15 genes have been implicated in distal hereditary motor neuropathy, the genetic causes remain elusive in many families. To identify an additional causal gene for distal hereditary motor neuropathy, we performed exome sequencing for two affected individuals and two unaffected members in a Taiwanese family with an autosomal dominant distal hereditary motor neuropathy in which mutations in common distal hereditary motor neuropathy-implicated genes had been excluded.

A new strategy for emergency department crowding: High-turnover utility bed intervention.

Background: This study applied a new strategy, termed high-turnover utility bed intervention, to offer early admission chances for emergency department (ED) patients and alleviate ED crowding.

Methods: This before-and-after observational cohort study was conducted at the ED of an urban tertiary hospital. On January 1, 2012, 14 utility beds were prepared exclusively for ED patient use.

Haplotypes of the D-Amino Acid Oxidase Gene Are Significantly Associated with Schizophrenia and Its Neurocognitive Deficits.

D-amino acid oxidase (DAO) has been reported to be associated with schizophrenia. This study aimed to search for genetic variants associated with this gene. The genomic regions of all exons, highly conserved regions of introns, and promoters of this gene were sequenced.

Fine-tuning of microRNA-mediated repression of mRNA by splicing-regulated and highly repressive microRNA recognition element.

Background: MicroRNAs are very small non-coding RNAs that interact with microRNA recognition elements (MREs) on their target messenger RNAs. Varying the concentration of a given microRNA may influence the expression of many target proteins. Yet, the expression of a specific target protein can be fine-tuned by alternative cleavage and polyadenylation to the corresponding mRNA.

Generation and analysis of the expressed sequence tags from the mycelium of Ganoderma lucidum.

Ganoderma lucidum (G. lucidum) is a medicinal mushroom renowned in East Asia for its potential biological effects. To enable a systematic exploration of the genes associated with the various phenotypes of the fungus, the genome consortium of G.

The DAO gene is associated with schizophrenia and interacts with other genes in the Taiwan Han Chinese population.

Background: Schizophrenia is a highly heritable disease with a polygenic mode of inheritance. Many studies have contributed to our understanding of the genetic underpinnings of schizophrenia, but little is known about how interactions among genes affect the risk of schizophrenia. This study aimed to assess the associations and interactions among genes that confer vulnerability to schizophrenia and to examine the moderating effect of neuropsychological impairment.

Discovering pathway cross-talks based on functional relations between pathways.

Background: In biological systems, pathways coordinate or interact with one another to achieve a complex biological process. Studying how they influence each other is essential for understanding the intricacies of a biological system. However, current methods rely on statistical tests to determine pathway relations, and may lose numerous biologically significant relations.