Biology subjects

Chang, W.-S.

Publications and source records attributed to Chang, W.-S..

9 recordsLinked to original sources

bioRxiv2024

Renal outcomes of combination therapy with sodium-glucose cotransporter 2 inhibitors plus renin-angiotensin system blockers in patients with type 2 diabetes mellitus: A population-based cohort study

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) can benefit patients with type 2 diabetes mellitus by reducing hazardous renal outcomes. This study aimed to evaluate whether the combination of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and conventional renin-angiotensin system blockers (RASB) provides a synergistic effect on renal outcomes in patients with type 2 diabetes mellitus, compared to the combination of RASB and dipeptidyl peptidase 4 inhibitors (DPP4i). MethodsThis is a retrospective cohort study. The study utilized data from the Taiwan National Health Insurance Research Database (NHIRD), including patients with type 2 diabetes mellitus enrolled between January 1, 2016, and December 31, 2016. Participants were divided into two groups: the case group (n = 3,622) receiving RASB plus SGLT2i and the comparison group (n = 3,622) receiving RASB plus DPP4i. The groups were matched 1:1 based on gender, age, and Charlson comorbidity index. Additionally, TriNetX was used for external validation. ResultsPrior to matching, unadjusted hazard ratios (HRs) showed significant differences favoring the SGLT2i group for chronic kidney disease (CKD) (HR: 0.66; 95% CI, 0.58-0.74), advanced kidney failure (HR: 0.64; 95% CI, 0.44-0.93), and initiation of long-term dialysis (HR: 0.61; 95% CI, 0.38-0.97). These differences remained significant post-matching: CKD (HR: 0.74; 95% CI, 0.65-0.84), advanced kidney failure (HR: 0.62; 95% CI, 0.42-0.92), and commencement of long-term dialysis (HR: 0.53; 95% CI, 0.32-0.87). The renal benefits of the combination therapy were consistently observed in the TriNetX dataset. LimitationsNHIRD lacks key clinical factors (e.g., physical features, lab data), potential baseline disparities due to retrospective design, and limited generalizability beyond Taiwanese patients, despite TriNexT validation. ConclusionsIn patients with type 2 diabetes mellitus, combination therapy with SGLT2i and RASB yielded better renal outcomes.

pharmacology and toxicology↗

bioRxiv2022

Gammaretroviruses, novel viruses and pathogenic bacteria in Australian bats with neurological signs, pneumonia and skin lesions

More than 70 bat species are found in mainland Australia, including five species of megabat from a single genus (family Pteropodidae) and more than 65 species representing six families of microbats. The conservation status of these animals varies from least concern to endangered. Research directed at evaluating the impact of microorganisms on bat health has been generally restricted to surveillance for specific pathogens. While most of the current bat virome studies focus on sampling apparently healthy individuals, little is known about the infectome of diseased bats. We performed traditional diagnostic techniques and metatranscriptomic sequencing on tissue samples from 43 individual bats, comprising three flying fox and two microbat species experiencing a range of disease syndromes, including mass mortality, neurological signs, pneumonia and skin lesions. We identified reads from four pathogenic bacteria and two pathogenic fungi, including Pseudomonas aeruginosa in lung samples from flying foxes with peracute pneumonia, and with dermatitis. Of note, we identified the recently discovered Hervey pteropid gammaretrovirus, with evidence of replication consistent with an exogenous virus, in a bat with lymphoid leukemia. In addition, one novel picornavirus, at least three novel astroviruses and bat pegiviruses were identified. We suggest that the most likely cause of peracute lung disease was Pseudomonas aeruginosa, while we suspect Hervey pteropid gammaretrovirus was associated with lymphoid leukemia. It is possible that any of the novel astroviruses could have contributed to the presentation of skin lesions in individual microbats. This study highlights the importance of studying the role of microorganisms in bat health and conservation. IMPORTANCEBats have been implicated as reservoir hosts for zoonotic disease of concern, however, the burden of microorganism including viruses on bat health and disease is understudied. Here we incorporated veterinary diagnostics and RNA sequencing to identify the presence of microbes and viruses with possible pathogenic status in Australian bats with varying disease presentations. These techniques were able to effectively identify and describe several pathogenic species of bacteria and fungi in addition to known and novel viruses. This study emphasises the importance of screening pathogens in cases of bat mortality for the conservation of this diverse order.

microbiology↗

bioRxiv2022

Unusual Morphological Changes of Rugositalea oryzae, A Novel Wrinkled Bacterium Isolated from The Rice Rhizosphere, Under Nutrient Stress

Bacterial cell morphology might result from natural selection to gain a competitive advantage under environmentally stressful conditions such as nutrient limitation. A bacterial strain YC6860T isolated from the rhizosphere of rice (Oryza sativa L.) showed pleomorphic behavior with smooth cell morphology and wrinkled surface rods depending upon nutritional conditions. Based on scanning and transmission electron microscopy studies, we hypothesized that the surface-to-volume ratio of cells increases with decreasing nutrient concentrations. The transition from smooth to wrinkled cell surface morphology could be one of the adaptation strategies by which YC6860T maximizes its ability to access available nutrients. To characterize the properties of the wrinkled strain, we performed taxonomic and phylogenetic analyses. 16S rRNA gene sequencing results showed that the strain represented a novel, deep-rooting lineage within the order Rhizobiales with the highest similarity of 94.2% to Pseudorhodoplanes sinuspersici RIPI 110T. Whole genome sequencing was also performed to characterize its genetic features. The strain YC6860T might belong to a new genus, named Rugositalea, and a new species, named Rugositalea oryzae, In addition, taxonomic analysis showed that YC6860T is Gram-negative, aerobic, and rod-shaped with large regular wrinkles resembling a delicate twist of fusilli, measuring 0.5-0.6 {micro}m in width and 1.5-1.6 {micro}m in length under nutrient-limiting conditions. This unique cell structure with regular rugosity could be the first finding that has not been reported in the existing bacterial morphology.

microbiology↗

bioRxiv2022

The association between working memory precision and the nonlinear dynamics of frontal and parieto-occipital EEG activity.

Electrophysiological working memory (WM) research has shown that distinct brain areas communicate through macroscopic oscillatory activities across multiple frequency bands. Such cross-frequency interactions generate nonlinear amplitude modulations (AM) in the observed signal. Traditionally, the AM of a signal is expressed as coupling strength between the signal and a pre-specified modulator at a lower frequency. Therefore, the idea of AM and coupling cannot be separately studied. This EEG study shows that the AM of parieto-occipital alpha/beta power and the coupling between frontal theta phase and parieto-occipital alpha/beta AM provide different information on WM processing. Thirty-three participants completed a color recall task with simultaneous EEG recording. The results showed that individual differences in WM precision are associated with frontal theta power enhancement and parieto-occipital alpha/beta power suppression. Furthermore, the AM of parieto-occipital alpha/beta power predicted WM precision after presenting a target-defining probe array. The phase-amplitude coupling (PAC) between frontal theta phase and parieto-occipital alpha/beta AM increased with WM load during the processing of incoming stimuli, but they did not predict the subsequent recall performance. These results indicate that the frontoparietal PAC reflects the executive control for selecting relevant WM representations, but whether the memorized information can be retrieved depends on the subsequent amplitude variation of parieto-occipital alpha/beta power. In conclusion, individuals with higher working memory precision are associated with enhanced frontal theta power and parieto-occipital alpha/beta power suppression.

neuroscience↗

bioRxiv2020

Meta-transcriptomic discovery of a divergent circovirus and a chaphamaparvovirus in captive reptiles with proliferative respiratory syndrome

Viral pathogens are being increasingly described in association with mass morbidity and mortality events in reptiles. However, our knowledge of reptile viruses and their role in population health remains limited. Herein, we describe a meta-transcriptomic investigation of a mass morbidity and mortality event in a colony of central bearded dragons (Pogona vitticeps) in 2014. Severe, extensive proliferation of the respiratory epithelium was consistently found in affected dragons. Similar proliferative lung lesions were identified in bearded dragons from the same colony in 2020 in association with increased intermittent mortality. Total RNA sequencing of bearded dragon tissue identified two divergent DNA viruses: a reptile-infecting circovirus, denoted bearded dragon circovirus (BDCV), and the first exogeneous reptilian chaphamaparvovirus - bearded dragon chaphamaparvovirus (BDchPV). Phylogenetic analysis revealed that BDCV was most closely related to bat-associated circoviruses, exhibiting 70% amino acid sequence identity. In contrast, the newly discovered BDchPV showed approximately 35-40% identity in the non-structural (NS) protein to parvoviruses obtained from tilapia fish and crocodiles in China. Subsequent specific PCR assays detected BDCV exclusively and comprehensively within animals with proliferative pulmonary lesions and respiratory disease. This study expands our understanding of viral diversity in the context of diseased reptiles in captivity.

microbiology↗

bioRxiv2020

Metagenomic identification of diverse animal hepaciviruses and pegiviruses

The RNA virus family Flaviviridae harbours several important pathogens of humans and other animals, including Zika virus, dengue virus and hepatitis C virus. The Flaviviridae are currently divided into four genera - Hepacivirus, Pegivirus, Pestivirus and Flavivirus - each of which have a diverse host range. Members of the genus Hepacivirus are associated with a diverse array of animal species, including humans and non-human primates, other mammalian species, as well as birds and fish, while the closely related pegiviruses have been identified in a variety of mammalian taxa including humans. Using a combination of meta-transcriptomic and whole genome sequencing we identified four novel hepaciviruses and one novel variant of a known virus, in five species of native Australian wildlife, expanding our knowledge of the diversity in this important group of RNA viruses. The infected hosts comprised native Australian marsupials and birds, as well as a native gecko (Gehyra lauta). The addition of these novel viruses led to the identification of a distinct marsupial clade within the hepacivirus phylogeny that also included an engorged Ixodes holocyclus tick collected while feeding on Australian long-nosed bandicoots (Perameles nasuta). Gecko and avian associated hepacivirus lineages were also identified. In addition, by mining the short-read archive (SRA) database we identified another five novel members of Flaviviridae, comprising three new hepaciviruses from avian and primate hosts, as well as two primate-associated pegiviruses. The large-scale phylogenetic analysis of these novel hepacivirus and pegivirus genomes provides additional support for virus-host co-divergence over evolutionary time-scales.

microbiology↗

bioRxiv2020

Meta-transcriptomic analysis of virus diversity in urban wild birds with paretic disease

Wild birds are major natural reservoirs and potential dispersers of a variety of infectious diseases. As such, it is important to determine the diversity of viruses they carry and use this information to help understand the potential risks of spill-over to humans, domestic animals, and other wildlife. We investigated the potential viral causes of paresis in long-standing, but undiagnosed disease syndromes in wild Australian birds. RNA from diseased birds was extracted and pooled based on tissue type, host species and clinical manifestation for metagenomic sequencing. Using a bulk and unbiased meta-transcriptomic approach, combined with careful clinical investigation and histopathology, we identified a number of novel viruses from the families Astroviridae, Picornaviridae, Polyomaviridae, Paramyxoviridae, Parvoviridae, Flaviviridae, and Circoviridae in common urban wild birds including Australian magpies, magpie lark, pied currawongs, Australian ravens, and rainbow lorikeets. In each case the presence of the virus was confirmed by RT-PCR. These data revealed a number of candidate viral pathogens that may contribute to coronary, skeletal muscle, vascular and neuropathology in birds of the Corvidae and Artamidae families, and neuropathology in members of the Psittaculidae. The existence of such a diverse virome in urban avian species highlights the importance and challenges in elucidating the etiology and ecology of wildlife pathogens in urban environments. This information will be increasingly important for managing disease risks and conducting surveillance for potential viral threats to wildlife, livestock and human health. More broadly, our work shows how meta-transcriptomics brings a new utility to pathogen discovery in wildlife diseases. ImportanceWildlife naturally harbor a diverse array of infectious microorganisms and can be a source of novel diseases in domestic animals and human populations. Using unbiased RNA sequencing we identified highly diverse viruses in native birds in Australian urban environments presenting with paresis. This investigation included the clinical investigation and description of poorly understood recurring syndromes of unknown etiology: clenched claw syndrome, and black and white bird disease. As well as identifying a range of potentially disease-causing viral pathogens, this study describes methods that can effectively and efficiently characterize emergent disease syndromes in free ranging wildlife, and promotes further surveillance for specific potential pathogens of potential conservation and zoonotic concern.

microbiology↗

bioRxiv2019

Metagenomic discovery and co-infection of diverse wobbly possum disease viruses and novel hepaciviruses in Australian brushtail possums

BackgroundAustralian brushtail possums (Trichosurus vulpecula) are an introduced pest species in New Zealand, but native to Australia where they are protected for biodiversity conservation. Wobbly possum disease (WPD) is a fatal neurological disease of Australian brushtail possums described in New Zealand populations that has been associated with infection by the arterivirus (Arteriviridae) wobbly possum disease virus (WPDV-NZ). Clinically, WPD-infected possums present with chronic meningoencephalitis, choroiditis and multifocal neurological symptoms including ataxia, incoordination, and abnormal gait. MethodsWe conducted a retrospective investigation to characterise WPD in native Australian brushtail possums, and used a bulk meta-transcriptomic approach (i.e. total RNA-sequencing) to investigate its potential viral aetiology. PCR assays were developed for case diagnosis and full genome recovery in the face of extensive genetic variation. ResultsWe identified a distinct lineage of arteriviruses from archival tissues of WPD-infected possums in Australia, termed wobbly possum disease virus AU1 and AU2. Phylogenetically, WPDV-AU1 and WPDV-AU2 shared only [~]70% nucleotide similarity to each other and the WPDV-NZ strain, suggestive of a relatively ancient divergence. Notably, we identified a novel and divergent hepacivirus (Flaviviridae) - the first in a marsupial - in both WPD-infected and uninfected possums, indicative of virus co-infection. ConclusionsWe have identified a distinctive marsupial-specific lineage of arteriviruses in mainland Australia that is genetically distinct from that in New Zealand, in some cases co-infecting animals with a novel hepacivirus. Our study provides new insight into the hidden genetic diversity of arteriviruses, the capacity for virus co-infection, and highlights the utility of meta-transcriptomics for disease investigation and surveillance in a One Health context.

pathology↗

bioRxiv2019

Novel hepatitis D-like agents in vertebrates and invertebrates

Hepatitis delta virus (HDV) is the smallest known RNA virus and encodes a single protein. Until recently, HDV had only been identified in humans, where it is strongly associated with co-infection with hepatitis B virus (HBV). However, the recent discovery of HDV-like viruses in metagenomic samples from birds and snakes suggests that this virus has a far longer evolutionary history. Herein, using additional meta-transcriptomic data, we show that highly divergent HDV-like viruses are also present in fish, amphibians and invertebrates. Notably, the novel viruses identified here share HDV-like genomic features such as a small genome size of ~1.7kb in length, circular genomes, and self-complementary, unbranched rod-like structures. Coiled-coil domains, leucine zippers, conserved residues with essential biological functions and isoelectronic points similar to those in the human hepatitis delta virus antigens (HDAgs) were also identified in the putative non-human HDAgs. Notably, none of these novel HDV-like viruses were associated with hepadnavirus infection, supporting the idea that the HDV-HBV association may be specific to humans. Collectively, these data not only broaden our understanding of the diversity and host range of HDV in non-human species, but shed light on its origin and evolutionary history.

evolutionary biology↗