Effectiveness of Adaptive Support Ventilation in Facilitating Weaning from Mechanical Ventilation in Postoperative Patients.

OBJECTIVE: This meta-analysis aims to evaluate the effectiveness of adaptive support ventilation (ASV) in facilitating postoperative weaning from mechanical ventilation in cardiac surgery patients. DESIGN: A systematic review and meta-analysis to assess ASV in weaning postoperative cardiac surgery patients. Outcomes included early extubation, reintubation rates, time to extubation, and lengths of intensive care units and hospital stays. SETTING: We searched electronic databases from inception to March 2023 and included randomized controlled trials that compared ASV with conventional ventilation methods in this population. PARTICIPANTS: Postoperative cardiac surgery patients. MEASUREMENTS AND MAIN RESULTS: A random effects model was used for meta-analysis, and trial sequential analysis (TSA) was conducted to assess result robustness. The meta-analysis included 11 randomized controlled trials with a total of 1027 randomized patients. ASV was associated with a shorter time to extubation compared to conventional ventilation (random effects, mean difference -68.30 hours; 95% confidence interval, -115.50 to -21.09) with TSA providing a conclusive finding. While ASV indicated improved early extubation rates, no significant differences were found in reintubation rates or lengths of intensive care unit and hospital stays, with these TSA results being inclusive. CONCLUSIONS: ASV appears to facilitate a shorter time to extubation in postoperative cardiac surgery patients compared to conventional ventilation, suggesting benefits in accelerating the weaning process and reducing mechanical ventilation duration.

Transcriptome landscape reveals the chronic inflammatory response in kidneys affected by the combinatory effect of leptospirosis and nephrotoxic injury.

Leptospirosis can cause chronic kidney damage, putting patients at risk of additional kidney injury due to other factors that can lead to renal failure. To understand the combined effect, the transcriptome profiles of kidneys of mice with adenine-induced and chronically Leptospira-infected kidneys were analysed. Chronic inflammation and T-helper 17 immune responses were activated and a high-level expression of Indoleamine 2,3-dioxygenase 1 protein was found. The results indicate that the combination may predispose patients to chronic inflammation, kidney function disruption, and symptoms seen in progressive chronic kidney disease (CKD). Furthermore, immunometabolic regulation may contribute to renal injury caused by chronic leptospirosis with secondary nephrotoxic injury. This study identified several significantly disrupted genes that could serve as potential targets for the diagnosis or treatment of CKD. Our work provides insight into the combined effect of leptospirosis and secondary kidney damage and the molecular basis for rapid progression of CKD.

MetaSquare: an integrated metadatabase of 16S rRNA gene amplicon for microbiome taxonomic classification.

MOTIVATION: Taxonomic classification of 16S ribosomal RNA gene amplicon is an efficient and economic approach in microbiome analysis. 16S rRNA sequence databases like SILVA, RDP, EzBioCloud and HOMD used in downstream bioinformatic pipelines have limitations on either the sequence redundancy or the delay on new sequence recruitment. To improve the 16S rRNA gene-based taxonomic classification, we merged these widely used databases and a collection of novel sequences systemically into an integrated resource. RESULTS: MetaSquare version 1.0 is an integrated 16S rRNA sequence database. It is composed of more than 6 million sequences and improves taxonomic classification resolution on both long-read and short-read methods. AVAILABILITY AND IMPLEMENTATION: Accessible at https://hub.docker.com/r/lsbnb/metasquare_db and https://github.com/lsbnb/MetaSquare. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Renin-Angiotensin-Aldosterone System Inhibitors and Development of Gynecologic Cancers: A 23 Million Individual Population-Based Study.

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan's Health and Welfare Data Science Center (2000-2016) and linked with Taiwan Cancer Registry (1979-2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85-0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20-39 years (aOR: 0.70, 95% CI: 0.58-0.85), 40-64 years (aOR: 0.77, 95% CI: 0.74-0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.91), and overall (aOR: 0.81, 95% CI: 0.79-0.84). Ovarian cancer risk was significantly lower in the groups aged 40-64 years (aOR: 0.76, 95% CI: 0.69-0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75-092), and overall (aOR: 0.79, 95% CI: 0.74-0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20-39 years (aOR: 2.54, 95% CI: 1.79-3.61), 40-64 years (aOR: 1.08, 95% CI: 1.02-1.14), and overall (aOR: 1.06, 95% CI: 1.01-1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40-64 years (aOR: 0.88, 95% CI: 0.84-0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.90), and overall (aOR: 0.88, 95% CI: 0.85-0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86-0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality.

Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase.

4-Hydroxylphenylpyruvate dioxygenase (HPPD) catalyzes the conversion of 4-hydroxylphenylpyruvate (HPP) to homogentisate, the important step for tyrosine catabolism. Comparison of the structure of human HPPD with the substrate-bound structure of A. thaliana HPPD revealed notably different orientations of the C-terminal helix. This helix performed as a closed conformation in human enzyme. Simulation revealed a different substrate-binding mode in which the carboxyl group of HPP interacted by a H-bond network formed by Gln334, Glu349 (the metal-binding ligand), and Asn363 (in the C-terminal helix). The 4-hydroxyl group of HPP interacted with Gln251 and Gln265. The relative activity and substrate-binding affinity were preserved for the Q334A mutant, implying the alternative role of Asn363 for HPP binding and catalysis. The reduction in kcat/Km of the Asn363 mutants confirmed the critical role in catalysis. Compared to the N363A mutant, the dramatic reduction in the Kd and thermal stability of the N363D mutant implies the side-chain effect in the hinge region rotation of the C-terminal helix. The activity and binding affinity were not recovered by double mutation; however, the 4-hydroxyphenylacetate intermediate formation by the uncoupled reaction of Q334N/N363Q and Q334A/N363D mutants indicated the importance of the H-bond network in the electrophilic reaction. These results highlight the functional role of the H-bond network in a closed conformation of the C-terminal helix to stabilize the bound substrate. The extremely low activity and reduction in Q251E's Kd suggest that interaction coupled with the H-bond network is crucial to locate the substrate for nucleophilic reaction.

How Can Research on Artificial Empathy Be Enhanced by Applying Deepfakes?

We propose the idea of using an open data set of doctor-patient interactions to develop artificial empathy based on facial emotion recognition. Facial emotion recognition allows a doctor to analyze patients' emotions, so that they can reach out to their patients through empathic care. However, face recognition data sets are often difficult to acquire; many researchers struggle with small samples of face recognition data sets. Further, sharing medical images or videos has not been possible, as this approach may violate patient privacy. The use of deepfake technology is a promising approach to deidentifying video recordings of patients' clinical encounters. Such technology can revolutionize the implementation of facial emotion recognition by replacing a patient's face in an image or video with an unrecognizable face-one with a facial expression that is similar to that of the original. This technology will further enhance the potential use of artificial empathy in helping doctors provide empathic care to achieve good doctor-patient therapeutic relationships, and this may result in better patient satisfaction and adherence to treatment.

mHealth Research for Weight Loss, Physical Activity, and Sedentary Behavior: Bibliometric Analysis.

BACKGROUND: Research into mobile health (mHealth) technologies on weight loss, physical activity, and sedentary behavior has increased substantially over the last decade; however, no research has been published showing the research trend in this field. OBJECTIVE: The purpose of this study was to provide a dynamic and longitudinal bibliometric analysis of recent trends of mHealth research for weight loss, physical activity, and sedentary behavior. METHODS: A comprehensive search was conducted through Web of Science to retrieve all existing relevant documents published in English between January 1, 2010, and November 1, 2021. We developed appropriate research questions; based on the proven bibliometric approaches, a search strategy was formulated to screen the title for eligibility. Finally, we conducted bibliometric analyses to explore the growth rate of publications; publication patterns; and the most productive authors, institutions, and countries, and visualized the trends in the field using a keyword co-occurrence network. RESULTS: The initial search identified 8739 articles, of which 1035 were included in the analyses. Our findings show an exponential growth trend in the number of annual publications of mHealth technology research in these fields. JMIR mHealth and uHealth (n=214, 20.67%), Journal of Medical Internet Research (n=71, 6.86%), and BMC Public Health (n=36, 3.47%) were the top 3 journals, publishing higher numbers of articles. The United States remained the leading contributor in these areas (n=405, 39.13%), followed by Australia (n=154, 14.87%) and England (n=125, 12.07%). Among the universities, the University of Sydney (n=36, 3.47%) contributed the most mHealth technology research in these areas; however, Deakin University (n=25, 2.41%) and the National University of Singapore (n=23, 2.22%) were in the second and third positions, respectively. CONCLUSIONS: Although the number of papers published on mobile technologies for weight loss, physical activity, and sedentary behavior was initially low, there has been an overall increase in these areas in recent years. The findings of the study indicate that mobile apps and technologies have substantial potential to reduce weight, increase physical activity, and change sedentary behavior. Indeed, this study provides a useful overview of the publication trends and valuable guidance on future research directions and perspectives in this rapidly developing field.

Oil Cyst Formation after Lower Blepharoplasty with Fat Grafts.

BACKGROUND: Fat grafting is increasingly used as an adjuvant surgery to blepharoplasty to refill the volume loss of an aged face and promote cellular regeneration. Complications, such as hematoma, infection, seroma, and palpable mass, may occur. We collected the patients that underwent lower blepharoplasty combined with fat graft to evaluate the incidence of oil cyst formation in the lower eyelid and to identify risk factors. MATERIAL AND METHODS: A retrospective review was performed of all patients who underwent lower or total blepharoplasty combined with fat graft at the authors' institution between January 2018 and June 2020. Complication rates were observed, and associations between preoperative variables and outcomes were assessed. RESULTS: A total of 119 patients were included in the series (all bilateral, 238 eyelids). The average patient age was 54.88 ± 11.94 years, and the average grafted fat was 1.88 ± 1.0 mL. On a per-eyelid basis for all patients, the complication rate of oil cyst formation was 6.72% (16 of 238 eyelids). The occurrence of oil cyst formation was associated with hypertension (P = 0.012; adjusted odds ratio, 9.27; 95% confidence interval, 1.62-52.99) and diabetes mellitus (P = 0.005; adjusted odds ratio, 14.02; 95% confidence interval, 2.22-88.45), but not associated with anticoagulants use (P = 0.931), age (P = 0.784), sex (P = 0.317), or fat volume (P = 0.215). The mean interval between the fat graft procedure and oil cyst noted was 236.5 ± 118.9 days. CONCLUSIONS: Oil cyst in lower eyelid can be defined as a palpable, firm, and persistent subcutaneous cystic lesion found postoperatively in any size during physical examination. The complication rate of oil cyst formation occurring after lower blepharoplasty with autologous fat grafting is 6.72%. Hypertension and diabetes mellitus maybe are risk factors of oil cyst formation. Steroid injection, needle capsulotomy, liposuction, and excision are safe and effective treatments. Reduce surgical trauma by diminishing anterior lamina trauma and capsulopalpebral fascia repair might decrease the complication rate of oil cyst formation.Transconjunctival lower blepharoplasty with fat graft or 2-stage surgery may be a choice to prevent oil cyst formation.

Amelioration of Maternal Immune Activation-Induced Autism Relevant Behaviors by Gut Commensal Parabacteroides goldsteinii.

Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease development. Transcriptomic analyses of MIA offspring indicated that in the intestine, P. goldsteinii MTS01 enhanced neuropeptide-related signaling and suppressed aberrant cell proliferation and inflammatory responses. In the hippocampus, P. goldsteinii MTS01 increased ribosomal/mitochondrial and antioxidant activities and decreased glutamate receptor signaling. Together, significant ameliorative effects of P. goldsteinii MTS01 on ASD relevant behaviors in MIA offspring were identified. Therefore, P. goldsteinii MTS01 could be developed as a next-generation probiotic for ameliorating ASD.

Niche partitioning among three snail-eating snakes revealed by dentition asymmetry and prey specialisation.

The level of dentition asymmetry in snail-eating snakes may reflect their prey choice and feeding efficiency on asymmetric land snails. The three species of Pareas snakes (Squamata: Pareidae) in Taiwan, which form partially sympatric distribution on the island, provide a potential case to test the hypothesis of niche partitioning and character displacement with regard to dentition asymmetry and specialisation in feeding behaviour. In this study, behavioural experiments confirmed that P. formosensis feeds exclusively on slugs, whereas P. atayal and P. komaii consumed both. However, P. atayal more efficiently preys on land snails than P. komaii, exhibiting a shorter handling time and fewer mandibular retractions. Micro-CT and ancestral character reconstruction demonstrated the lowest asymmetry in P. formosensis (the slug specialist), the highest dentition asymmetry in P. atayal (the land snail specialist) and flexibility in P. komaii (the niche switcher): increased dentition asymmetry when sympatrically distributed with the slug eater (character displacement), and decreased asymmetry when living alone (ecological niche release). Ecological niche modelling showed that the distribution of P. formosensis is associated with the presence of slugs, while that of P. atayal could be explained by the land snails. Combining the results from morphology, phylogeny, behavioural experiments and ecological niche modelling, we showed that competition in the sympatric region might have facilitated character displacement among congeners, while the absence of competition in allopatric region has led to ecological niche release.

Localization of goose haemorrhagic polyomavirus in naturally infected geese using in situ hybridization.

Goose haemorrhagic polyomavirus (GHPV) is the aetiological agent of haemorrhagic nephritis enteritis of geese (HNEG), a fatal disease that impacts geese and has been recorded only in Europe. The present study describes the first clinical cases of HNEG in Taiwan and the phylogenesis of Taiwanese GHPV, and it elucidates the pathogenesis of GHPV infection using in situ hybridization (ISH). The genomes of Taiwanese GHPV were highly similar to the previously reported strains. The diseased geese showed various degrees of vascular damage, especially in the digestive tract. The affected geese in the early stage showed transmural haemorrhagic enteritis in the intestine. In the middle to late stages, the most obvious lesion was hypoxic necrosis of renal tubules around intralobular central veins. Mineralization deposited in the kidney and systemic gout were also found. ISH revealed GHPV DNA in the vascular endothelial cells throughout the body, but not in the parenchymal cells of organs. Accordingly, the pathogenesis of GHPV infection was consistent with viral tropism in the endothelial cells. Specific attack of vascular endothelium by GHPV resulted in endothelial cell necrosis and subsequent increases of blood vessel permeability, as well as secondary circulation disorders, such as oedema, haemorrhage, and ischaemic necrosis in the adjacent parenchyma. RESEARCH HIGHLIGHTS Cell tropism of GHPV is determined by in situ hybridization. The tropism results in vascular dysfunction and subsequent pathobiology. Haemorrhagic nephritis and enteritis of geese described outside Europe for the first time.

Differential miRNA Expression Profiling Reveals Correlation of miR125b-5p with Persistent Infection of Japanese Encephalitis Virus.

MicroRNAs (miRNAs) play versatile roles in multiple biological processes. However, little is known about miRNA's involvement in flavivirus persistent infection. Here, we used an miRNA array analysis of Japanese encephalitis virus (JEV)-infected cells to search for persistent infection-associated miRNAs in comparison to acute infection. Among all differentially expressed miRNAs, the miR-125b-5p is the most significantly increased one. The high level of miR-125b-5p in persistently JEV-infected cells was confirmed by Northern analysis and real-time quantitative polymerase chain reaction. As soon as the cells established a persistent infection, a significantly high expression of miR-125b-5p was readily observed. Transfecting excess quantities of a miR-125b-5p mimic into acutely infected cells reduced genome replication and virus titers. Host targets of miR125b-5p were analyzed by target prediction algorithms, and six candidates were confirmed by a dual-luciferase reporter assay. These genes were upregulated in the acutely infected cells and sharply declined in the persistently infected cells. The transfection of the miR125b-5p mimic reduced the expression levels of Stat3, Map2k7, and Triap1. Our studies indicated that miR-125b-5p targets both viral and host sequences, suggesting its role in coordinating viral replication and host antiviral responses. This is the first report to characterize the potential roles of miR-125b-5p in persistent JEV infections.

Statins use and its impact in EGFR-TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan.

Statins have been shown to be a beneficial treatment as chemotherapy and target therapy for lung cancer. This study aimed to investigate the effectiveness of statins in combination with epidermal growth factor receptor-tyrosine kinase inhibitor therapy for the resistance and mortality of lung cancer patients. A population-based cohort study was conducted using the Taiwan Cancer Registry database. From January 1, 2007, to December 31, 2012, in total 792 non-statins and 41 statins users who had undergone EGFR-TKIs treatment were included in this study. All patients were monitored until the event of death or when changed to another therapy. Kaplan-Meier estimators and Cox proportional hazards regression models were used to calculate overall survival. We found that the mortality was significantly lower in patients in the statins group compared with patients in the non-statins group (4-y cumulative mortality, 77.3%; 95% confidence interval (CI), 36.6%-81.4% vs. 85.5%; 95% CI, 78.5%-98%; P = .004). Statin use was associated with a reduced risk of death in patients the group who had tumor sizes <3 cm (hazard ratio [HR], 0.51, 95% CI, 0.29-0.89) and for patients in the group who had CCI scores <3 (HR, 0.6; 95% CI, 0.41-0.88; P = .009). In our study, statins were found to be associated with prolonged survival time in patients with lung cancer who were treated with EGFR-TKIs and played a synergistic anticancer role.

Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia.

PURPOSE: Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. DATA SOURCES: A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. STUDY SELECTION: We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. DATA EXTRACTION: Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. RESULTS OF DATA SYNTHESIS: Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30-2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22-2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3-6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22-3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83-3.66). CONCLUSION: We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

Polysubstituted Hexa-cata-hexabenzocoronenes: Syntheses, Characterization, and Their Potential as Semiconducting Materials in Transistor Applications.

A series of tetra- and octa-substituted hexa-cata-hexabenzocoronenes (cata-HBCs) were synthesized from tetraryl olefins via iodine- and iron chloride-catalyzed oxidative cyclodehydrogenation reactions. The substitutions on the periphery of the parent HBC serve to modify the photophysical properties, highest occupied molecular orbital-lowest unoccupied molecular orbital gaps, and thermal stabilities of the respective derivatives. The crystal structures were determined to display multiple twists in the framework, resulting in different packing motifs depending on the position, type, and number of functional groups on the hexabenzocoronene framework. Nearly perfect co-facial packing to marginally or extensively shifted co-facial stacks were obtained due to substitution. The single crystals of parent HBC were used to fabricate single-crystal field-effect transistors, from which the highest p-channel mobility of 0.51 cm2 V-1 s-1 was measured. Thin-film transistors of selected HBCs were also prepared, and 0.61 cm2 V-1 s-1 was obtained for MeHBC-2. These results attest the potential of these materials as semiconducting materials.

Opportunities and challenges in Taiwan for implementing the learning health system.

Due to the low ratio of medical decisions made upon solid scientific evidence (4%) and the low efficiency of deploying knowledge in practice (17 years), the concept of a learning health system (LHS) was initiated to speed up knowledge generation and adoption and systematically approach continuous improvement in clinical practice. This concept can be illustrated by a so-called learning health cycle. This cycle, the first version as well as its variants, provides a framework for discussion on a common basis and has been well-accepted by the medical communities. Though the idea attracted major attention widely, very little has been done in way of actual adoption in real practices in the past 10 years. Nevertheless, as one of the pioneers in Taiwan, we have been involved in the effort to implement the LHS locally since 2016. In this article, we systematically summarize the evolution of the learning health cycle, review cases of its applications and briefly introduce the work we have done for promoting LHSs in Taiwan. Based on the experience we have gained, we try to identify the challenges and opportunities in Taiwan. While full-scale electronic medical records powered by the National Health Insurance system give Taiwan a special advantage in achieving a nationwide LHS, the medical community is not yet ready for a dramatic change. The lack of infrastructure for this use and motivation to take action right away makes the implementation of a LHS in Taiwan challenging.

Differential genetic responses to the stress revealed the mutation-order adaptive divergence between two sympatric ginger species.

BACKGROUND: Divergent genetic responses to the same environmental pressures may lead sympatric ecological speciation possible. Such speciation process possibly explains rapid sympatric speciation of island species. Two island endemic ginger species Zingiber kawagoii and Z. shuanglongensis was suggested to be independently originated from inland ancestors, but their island endemism and similar morphologies and habitats lead another hypothesis of in situ ecological speciation. For understanding when and how these two species diverged, intraspecific variation was estimated from three chloroplast DNA fragments (cpDNA) and interspecific genome-wide SNPs and expression differences after saline treatment were examined by transcriptomic analyses. RESULTS: Extremely low intraspecific genetic variation was estimated by cpDNA sequences in both species: nucleotide diversity π = 0.00002 in Z. kawagoii and no nucleotide substitution but only indels found in Z. shuanglongensis. Nonsignificant inter-population genetic differentiation suggests homogenized genetic variation within species. Based on 53,683 SNPs from 13,842 polymorphic transcripts, in which 10,693 SNPs are fixed between species, Z. kawagoii and Z. shuanglongensis were estimated to be diverged since 218~ 238 thousand generations ago (complete divergence since 41.5~ 43.5 thousand generations ago). This time is more recent than the time of Taiwan Island formation. In addition, high proportion of differential expression genes (DEGs) is non-polymorphic or non-positively selected, suggesting key roles of plastic genetic divergence in broaden the selectability in incipient speciation. While some positive selected DEGs were mainly the biotic and abiotic stress-resistance genes, emphasizing the importance of adaptive divergence of stress-related genes in sympatric ecological speciation. Furthermore, the higher proportional expression of functional classes in Z. kawagoii than in Z. shuanglongensis explains the more widespread distribution of Z. kawagoii in Taiwan. CONCLUSIONS: Our results contradict the previous hypothesis of independent origination of these two island endemic ginger species from SE China and SW China. Adaptive divergent responses to the stress explain how these gingers maintain genetic differentiation in sympatry. However, the recent speciation and rapid expansion make extremely low intraspecific genetic variation in these two species. This study arise a more probable speciation hypothesis of sympatric speciation within an island via the mutation-order mechanism underlying the same environmental pressure.

Exploring the Association between Statin Use and the Risk of Parkinson's Disease: A Meta-Analysis of Observational Studies.

BACKGROUND: Parkinson's disease (PD) is a progressive disorder of the central nervous system. The prevalence of PD varies considerably by age group; it has a higher prevalence in patients aged 60 years and more. Several studies have shown that statin, a cholesterol-lowering medication, reduces the risk of developing PD, but evidence for this is so far inconclusive. The objective of this study is to evaluate the association between statin use and the risk of developing PD. METHODS: PubMed, EMBASE, and the bibliographies of articles were searched for studies published between January 1, 1990, and January 1, 2017, which reported on the association between statin use and PD. Articles were included if they (1) were published in English, (2) reported patients treated with statin, and the outcome of interest was PD, (3) provided OR/HR with 95% CI or sufficient information to calculate the 95% CI. All abstracts, full-text articles, and sources were reviewed, with duplicate data excluded. Summary relative risk (RRs) with 95% CI was pooled using a random-effects model. Subgroup and sensitivity analyses were also conducted. RESULTS: We selected 16 out of 529 unique abstracts for full-text review using our selection criteria, and 13 out of these 16 studies, comprising 4,877,059 persons, met all of our inclusion criteria. The overall pooled RR of PD was 0.70 (95% CI 0.58-0.84) with significant heterogeneity between estimates (I2 = 93.41%, p = 0.000) for the random-effects model. In subgroup analysis, the greater decreased risk was found in studies from Asia (RR 0.62 95% CI 0.51-0.76), whereas a moderate reduction was observed in studies from North America (RR 0.69 95% CI 0.47-1.00), but less reduction was observed in studies from Europe (RR 0.86 95% CI 0.80-0.92). Also, long-term statin use, simvastatin, and atorvastatin showed a higher rate of reduction with significance heterogeneity. CONCLUSION: Our results showed that statin use is significantly associated with a lower risk of developing PD. Physicians should consider statin drug therapy, monitor its outcomes, and empower their patients to improve their knowledge, therapeutic outcomes, and quality of life. However, preventive measures and their associated mechanisms must be further assessed and explored.

Benzodiazepines use and breast cancer risk: A population-based study and gene expression profiling evidence.

The aim of this study was to investigate whether long-term use of Benzodiazepines (BZDs) is associated with breast cancer risk through the combination of population-based observational and gene expression profiling evidence. We conducted a population-based case-control study by using 1998 to 2009year Taiwan National Health Insurance Research Database and investigated the association between BZDs use and breast cancer risk. We selected subjects age of >20years old and six eligible controls matched for age, sex and the index date (i.e., free of any cancer at the case diagnosis date) by using propensity scores. A bioinformatics analysis approach was also performed for the identification of oncogenesis effects of BZDs on breast cancer. We used breast cancer gene expression data from the Cancer Genome Atlas and perturbagen signatures of BZDs from the Library of Integrated Cellular Signatures database in order to identify the oncogenesis effects of BZDs on breast cancer. We found evidence of increased breast cancer risk for diazepam (OR, 1.16; 95%CI, 0.95-1.42; connectivity score [CS], 0.3016), zolpidem (OR, 1.11; 95%CI, 0.95-1.30; CS, 0.2738), but not for lorazepam (OR, 1.04; 95%CI, 0.89-1.23; CS, -0.2952) consistently in both methods. The finding for alparazolam was contradictory from the two methods. Diazepam and zolpidem trends showed association, although not statistically significant, with breast cancer risk in both epidemiological and bioinformatics analyses outcomes. The methodological value of our study is in introducing the way of combining epidemiological and bioinformatics approaches in order to answer a common scientific question. Combining the two approaches would be a substantial step towards uncovering, validation and further application of previously unknown scientific knowledge to the emerging field of precision medicine informatics.

The different catalytic roles of the metal-binding ligands in human 4-hydroxyphenylpyruvate dioxygenase.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a non-haem iron(II)-dependent oxygenase that catalyses the conversion of 4-hydroxyphenylpyruvate (HPP) to homogentisate (HG). In the active site, a strictly conserved 2-His-1-Glu facial triad co-ordinates the iron ready for catalysis. Substitution of these residues resulted in about a 10-fold decrease in the metal binding affinity, as measured by isothermal titration calorimetry, and a large reduction in enzyme catalytic efficiencies. The present study revealed the vital role of the ligand Glu(349) in enzyme function. Replacing this residue with alanine resulted in loss of activity. The E349G variant retained 5% activity for the coupled reaction, suggesting that co-ordinating water may be able to support activation of the trans-bound dioxygen upon substrate binding. The reaction catalysed by the H183A variant was fully uncoupled. H183A variant catalytic activity resulted in protein cleavage between Ile(267) and Ala(268) and the production of an N-terminal fragment. The H266A variant was able to produce 4-hydroxyphenylacetate (HPA), demonstrating that decarboxylation had occurred but that there was no subsequent product formation. Structural modelling of the variant enzyme with bound dioxygen revealed the rearrangement of the co-ordination environment and the dynamic behaviour of bound dioxygen in the H266A and H183A variants respectively. These models suggest that the residues regulate the geometry of the reactive oxygen intermediate during the oxidation reaction. The mutagenesis and structural simulation studies demonstrate the critical and unique role of each ligand in the function of HPPD, and which correlates with their respective co-ordination position.