Inferring complex evolutionary history of the closely related East Asian wild roses in Rosa sect. Synstylae (Rosaceae) based on genomic evidence from conserved orthologs.

BACKGROUND AND AIMS: The section Synstylae in genus Rosa (Rosaceae) comprises 25-36 species and includes several major progenitors of modern rose cultivars. East Asian Synstylae species have recently diverged and are closely related, and their phylogenetic relationships remain unclear. In the present study, we employed a conserved ortholog set (COS) markers and genome-wide nuclear orthologs to elucidate their phylogenetic relationships and unravel their complex evolutionary history. METHODS: Utilising on eight Rosaceae COS (RosCOS) markers, we analysed a total of 137 accessions representing 15 East Asian Synstylae taxa to establish a robust phylogenetic framework and reconstruct ancestral areas. Furthermore, we constructed the species tree for eight representative species and estimated their divergence times based on 1,683 genome-wide orthologs. The species tree-gene tree coalescence time comparison, Patterson's D, f4-ratio, and f-branch statistics were analysed to identify incomplete lineage sorting (ILS), genetic introgression, and reticulation events using conserved ortholog data. KEY RESULTS: RosCOS markers and genome-wide orthologs effectively resolved the robust phylogeny of East Asian Rosa sect. Synstylae. Species divergence times estimated with genome-wide orthologs indicated that East Asian Synstylae species have recently diverged, with an estimated crown age of approximately 2 Mya. The rampant gene tree discordance indicated the possibility of ILS and/or genetic introgression. In the section Synstylae, deeper coalescence in the gene trees compared to the species tree suggested ILS as a source of gene tree discordance. Further, Patterson's D and f-branch statistics indicated that several lineages in the section were involved in genetic introgression. CONCLUSIONS: We have unravelled the complex evolutionary history of East Asian Rosa sect. Synstylae, including recent species divergences, ILS, and genetic introgression. Coupled with the geographical and ecological complexity of East Asia, ILS and genetic introgression may have contributed to the rapid diversification of East Asian Synstylae species by permitting adaptation to diverse environments.

Lower Late Development Rate of Acute Respiratory Distress Syndrome in Patients with Lower Mechanical Power or Driving Pressure.

For patients on ventilation without acute respiratory distress syndrome (ARDS), there are, as yet, limited data on ventilation strategies. We hypothesized that driving pressure (DP) and mechanical power (MP) may play key roles for the late development of ARDS in patients without initial ARDS. A post hoc analysis of a database from our previous cohort was performed. The mean DP/MP was computed from the data before ARDS development or until ventilator support was discontinued within 28 days. The association between DP/MP and late development of ARDS within 28 days was determined. One hundred and twelve patients were enrolled, among whom seven developed ARDS. Univariate Cox regression showed that congestive heart failure (CHF) history and higher levels of mean MP and DP were associated with ARDS development. Multivariate models revealed that the mean MP and mean DP were still factors independently associated with ARDS development at hazard ratios of 1.177 and 1.226 after adjusting for the CHF effect. Areas under the receiver operating characteristic curves for mean DP/MP in predicting ARDS development were 0.813 and 0.759, respectively. In conclusion, high mean DP and MP values may be key factors associated with late ARDS development. The mean DP had a better predicted value for the development of ARDS than the mean MP.

Evaluating a Natural Language Processing-Driven, AI-Assisted International Classification of Diseases, 10th Revision, Clinical Modification, Coding System for Diagnosis Related Groups in a Real Hospital Environment: Algorithm Development and Validation Study.

BACKGROUND: International Classification of Diseases codes are widely used to describe diagnosis information, but manual coding relies heavily on human interpretation, which can be expensive, time consuming, and prone to errors. With the transition from the International Classification of Diseases, Ninth Revision, to the International Classification of Diseases, Tenth Revision (ICD-10), the coding process has become more complex, highlighting the need for automated approaches to enhance coding efficiency and accuracy. Inaccurate coding can result in substantial financial losses for hospitals, and a precise assessment of outcomes generated by a natural language processing (NLP)-driven autocoding system thus assumes a critical role in safeguarding the accuracy of the Taiwan diagnosis related groups (Tw-DRGs). OBJECTIVE: This study aims to evaluate the feasibility of applying an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), autocoding system that can automatically determine diagnoses and codes based on free-text discharge summaries to facilitate the assessment of Tw-DRGs, specifically principal diagnosis and major diagnostic categories (MDCs). METHODS: By using the patient discharge summaries from Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUCHH) from April 2019 to December 2020 as a reference data set we developed artificial intelligence (AI)-assisted ICD-10-CM coding systems based on deep learning models. We constructed a web-based user interface for the AI-assisted coding system and deployed the system to the workflow of the certified coding specialists (CCSs) of KMUCHH. The data used for the assessment of Tw-DRGs were manually curated by a CCS with the principal diagnosis and MDC was determined from discharge summaries collected at KMUCHH from February 2023 to April 2023. RESULTS: Both the reference data set and real hospital data were used to assess performance in determining ICD-10-CM coding, principal diagnosis, and MDC for Tw-DRGs. Among all methods, the GPT-2 (OpenAI)-based model achieved the highest F1-score, 0.667 (F1-score 0.851 for the top 50 codes), on the KMUCHH test set and a slightly lower F1-score, 0.621, in real hospital data. Cohen κ evaluation for the agreement of MDC between the models and the CCS revealed that the overall average κ value for GPT-2 (κ=0.714) was approximately 12.2 percentage points higher than that of the hierarchy attention network (κ=0.592). GPT-2 demonstrated superior agreement with the CCS across 6 categories of MDC, with an average κ value of approximately 0.869 (SD 0.033), underscoring the effectiveness of the developed AI-assisted coding system in supporting the work of CCSs. CONCLUSIONS: An NLP-driven AI-assisted coding system can assist CCSs in ICD-10-CM coding by offering coding references via a user interface, demonstrating the potential to reduce the manual workload and expedite Tw-DRG assessment. Consistency in performance affirmed the effectiveness of the system in supporting CCSs in ICD-10-CM coding and the judgment of Tw-DRGs.

Construction of Cu2Y2O5/g-C3N4 Novel Composite for the Sensitive and Selective Trace-Level Electrochemical Detection of Sulfamethazine in Food and Water Samples.

The most frequently used sulfonamide is sulfamethazine (SMZ) because it is often found in foods made from livestock, which is hazardous for individuals. Here, we have developed an easy, quick, selective, and sensitive analytical technique to efficiently detect SMZ. Recently, transition metal oxides have attracted many researchers for their excellent performance as a promising sensor for SMZ analysis because of their superior redox activity, electrocatalytic activity, electroactive sites, and electron transfer properties. Further, Cu-based oxides have a resilient electrical conductivity; however, to boost it to an extreme extent, a composite including two-dimensional (2D) graphitic carbon nitride (g-C3N4) nanosheets needs to be constructed and ready as a composite (denoted as g-C3N4/Cu2Y2O5). Moreover, several techniques, including X-ray diffraction analysis, scanning electron microscopy analysis, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy were employed to analyze the composites. The electrochemical measurements have revealed that the constructed g-C3N4/Cu2Y2O5 composites exhibit great electrochemical activity. Nevertheless, the sensor achieved outstanding repeatability and reproducibility alongside a low limit of detection (LOD) of 0.23 µM, a long linear range of 2 to 276 µM, and an electrode sensitivity of 8.86 µA µM-1 cm-2. Finally, the proposed GCE/g-C3N4/Cu2Y2O5 electrode proved highly effective for detection of SMZ in food samples, with acceptable recoveries. The GCE/g-C3N4/Cu2Y2O5 electrode has been successfully applied to SMZ detection in food and water samples.

Cryptococcosis in wait-listed liver transplant candidates: Prevalence, manifestations, and risk factors.

BACKGROUND: Liver cirrhosis compromises immunity against cryptococcosis, and liver transplant recipients tend to develop the disease earlier after transplantation, possibly due to unrecognized pretransplant infection. We assessed the prevalence and characteristics of cryptococcosis among liver transplant candidates and whether pre-transplant cryptococcal antigen (CrAg) can detect the disease before transplantation. METHODS: We retrospectively included liver transplant candidates in a tertiary hospital during 2017-2022. Serum CrAg and pulmonary computed tomography were incorporated in routine transplant evaluation. Other investigations were done if indicated. Cryptococcosis was diagnosed by positive culture or CrAg. Risk factors for cryptococcosis were also assessed. RESULTS: Of the 377 candidates with a median MELD-Na score of 18, 84.4% had hepatitis B virus (HBV) infection. Cryptococcosis was diagnosed in 10 (2.6%) candidates, by CrAg in 6, culture in 2, or both in 2. Only 3 had fever, and 3 were asymptomatic; 7 had pulmonary cryptococcosis. Of the 10 candidates with cryptococcosis, one underwent transplantation after 143-day antifungals. Of the 87 candidates undergoing liver transplantation, one (1.2%) recipient developed cryptococcosis 14 days post-transplant with negative CrAg three weeks before transplantation. HBsAg-positive chronic HBV infection with HBV DNA loads <2000 IU/mL was significantly associated with cryptococcosis (odds ratio 4.4, 95% confidence interval 1.2-16.5, p = 0.03) after the adjustment of MELD-Na score. CONCLUSIONS: The prevalence of cryptococcosis was 2.6% among our liver transplant candidates and CrAg detected 80% of the cases. Disease presentation was mild and pulmonary disease predominated. HBsAg-positive chronic HBV infection with HBV DNA loads <2000 IU/mL was significantly associated with cryptococcosis.

Inability to Sit-to-Stand in Medical ICUs Survivors: When and Why We Should Care.

OBJECTIVES: To investigate the prevalence and association with mortality of inability to perform sit-to-stand independently in critically ill survivors 3 months following medical ICU (MICU) discharge. DESIGN: Prospective cohort study. SETTING: Six MICUs at a tertiary care hospital. PATIENTS: MICU survivors who could sit-to-stand independently before the index hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Inability to sit-to-stand (yes/no) was measured at four points following MICU discharge: upon ICU discharge, 1, 2, and 3 months afterward. Mortality was evaluated at 6- and 12-month post-MICU discharge. Among 194 participants, 128 (66%) had inability to sit-to-stand upon MICU discharge. Recovery occurred, with rates decreasing to 50% at 1 month, 38% at 2 months, and 36% at 3 months post-MICU discharge, plateauing at 2 months. Inability to sit-to-stand at 3 months was significantly associated with 21% mortality at 12 months and a 4.2-fold increased risk of mortality (adjusted hazard ratio, 4.2; 95% CI, 1.61-10.99), independent of age, Sequential Organ Failure Assessment score, and ICU-acquired weakness. Notably, improvement in sit-to-stand ability, even from "totally unable" to "able with assistance," correlates with reduced mortality risk. CONCLUSIONS: Inability to sit-to-stand affects about 36% of MICU survivors even at 3 months post-ICU discharge, highlighting rehabilitation challenges. Revisiting sit-to-stand ability post-ICU discharge is warranted. Additionally, using sit-to-stand as a screening tool for interventions to improve return of its function and mortality is suggested.

Ameliorative effect of α-tocopherol and tocotrienol-rich palm oil extract on menopause-associated mood disorder in ovariectomized mice.

Menopause-associated mood disorder is characterized by emotional depression, anxiety, and stress, which accompany hypogonadism in women in the menopausal phase. The current treatment for menopause-associated mood disorder provides only symptomatic relief and is associated with many side effects. Supplementation with vitamin E has been shown to be effective in ameliorating anxiety and depression. However, the effects of vitamin E and its underlying mechanism in ameliorating menopause-associated mood disorders remain uncertain. This work evaluated the effects of α-tocopherol and tocotrienol-rich palm oil extract on depressive and anxiety-related phenotypes induced by estrogen deficiency through ovariectomy in mice. Our study revealed that ovariectomized mice exhibited alterations in behavior indicative of depressive- and anxiety-like behaviors. The serum corticosterone level, a glucocorticoid hormone associated with stress, was found to be elevated in ovariectomized mice as compared to the sham group. Oral administration of α-tocopherol (50 and 100 mg/kg) and tocotrienol-rich palm oil extract (100 and 200 mg/kg) for 14 days alleviated these behavioral changes, as observed in open field, social interaction, and tail suspension tests. However, treatment with tocotrienol-rich palm oil extract, but not α-tocopherol, modulated the depressive- and anxiety-like responses in ovariectomized mice subjected to chronic restraint stress. Both treatments suppressed the elevated serum corticosterone level. Our findings suggested that α-tocopherol and tocotrienol-rich palm oil extract alleviated menopause-associated mood disorder, at least in part, by modulating the hypothalamic-pituitary-adrenal (HPA) axis. The findings of this study can provide a new foundation for the treatment of menopause-associated depressive- and anxiety-like phenotypes, for the betterment of psychological wellbeing.

Genome-Wide Association Study of Susceptibility to Pseudomonas aeruginosa Infection in Cystic Fibrosis.

QUESTION: Pseudomonas aeruginosa (Pa) is a common pathogen that contributes to progressive lung disease in Cystic Fibrosis (CF). Genetic factors other than CF-causing CFTR variations contribute approximately 85% of the variation in chronic Pa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to Pa infection. MATERIALS AND METHODS: We conducted a genome-wide association study (GWAS) of chronic Pa infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic Pa infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bi-directional Mendelian Randomization analysis. RESULTS: Two novel genome-wide significant loci with lead SNPs rs62369766 (chr5p12; p-value= 1.98 ×10-8) and rs927553 (chr13q12.12; p-value= 1.91 × 10-8) were associated with chronic Pa infection age. The rs62369766 locus was validated using an independent French cohort (N=501). Furthermore, PRS constructed from CF lung function-associated SNPs was significantly associated with chronic Pa infection age (p-value=0.002). Finally, our analysis presented evidence for a causal effect of lung function on the chronic Pa infection age (Beta=0.782 years, p-value= 4.24 × 10-4). In the reverse direction, we observed a moderate effect (Beta=0.002, p-value=0.012). CONCLUSIONS: We identified two novel loci that are associated with chronic Pa infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between Pa infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections which accounts for significant remaining morbidity in CF.

Intelligent Clinic Nurse Scheduling Considering Nurses Paired with Doctors and Preference of Nurses.

The nurse scheduling problem (NSP) has been a crucial and challenging research issue for hospitals, especially considering the serious deterioration in nursing shortages in recent years owing to long working hours, considerable work pressure, and irregular lifestyle, which are important in the service industry. This study investigates the NSP that aims to maximize nurse satisfaction with the generated schedule subject to government laws, internal regulations of hospitals, doctor-nurse pairing rules, shift and day off preferences of nurses, etc. The computational experiment results show that our proposed hybrid metaheuristic outperforms other metaheuristics and manual scheduling in terms of both computation time and solution quality. The presented solution procedure is implemented in a real-world clinic, which is used as a case study. The developed scheduling technique reduced the time spent on scheduling by 93% and increased the satisfaction of the schedule by 21%, which further enhanced the operating efficiency and service quality.

Emerging Norovirus GII.12 infection in 2010 in Northern Taiwan.

Norovirus (NoV) has been an emerging pathogen of enteric infections in the post-rotavirus vaccine era. GII.4 have played a major role in NoV infections while other genotypes were reported in sporadic outbreaks. In this study, we reported novel variant NoV GII.12 outbreaks in 2010, Taiwan with their genomic analysis and clinical manifestations compared to GII.4 infections. There were 30.5% (29 out of 95 cases) with NoV infection. The most common genotype was GII.4 (22, 75.9%) followed by GII.12 (5, 17.2%) and GII.3 (2, 6.9%). Phylogenetic analysis showed that our GII.12 sequences were closely aligned with reference genomes identified in the United Kingdom and the United States of America. When compared to patients infected by GII.4 NoV, those with GII.12 infection experienced a lower frequency and shorter duration of diarrhea. Continued research is essential to unravel the intricate relationship between NoV genotypes and clinical outcomes, guiding public health interventions and therapeutic strategies.

A Computational Study of Reactions with Boric Acid Aimed to Promote the Utilization of Lignin.

For exploring the reaction between the hydroxyl groups of lignin and boric acid under the alkaline condition, we study three proposed mechanisms for the formation of the anionic borate diester (ABDE) using the salicyl alcohol anion as the model compound by the density functional theory. ABDE has high flame retardancy and is a potentially practical application of lignin. The catalysis of sodium cation is found to enhance the deprotonation of the water cluster. The deprotonated product, hydroxide anion, is essential to the critical step, which is the cleavage of B-O bonds of the boric acid molecule, in reaction mechanisms. The energy profiles of the mechanisms show that the reaction between lignin and boric acid may start from the hydroxymethyl moieties of lignin since it requires less energy for the aforementioned critical step than from the phenol moieties of lignin. Moreover, the hydroxide anions compete with the hydroxymethyl groups in lignin for the formation of B-O bonds by forming tetrahydroxyborate anion (TBA) which requires very high activation energies to further react to the desired product ABDE. The optimal condition is to enhance the catalytic effect of sodium cations and meanwhile to control the formation of TBA.

Macrocyclic porphyrin photocatalysts without metal chelation: A novel pathway for complete degradation of tough halophenols with longwave visible LED light source.

Halophenols are toxic and persistent pollutants in water environments which poses harm to various organisms. Due to their high stability and long residence time, ultraviolet radiation, heavy metals and oxidizing agents have been largely adopted on treating these compounds. However, these treatment methods could pose toxicity or hazardous risks to the marine environment and plant operators. In this study, a water-soluble porphyrin photocatalyst was synthesized and introduced for halophenol treatment using UV-free LED white light. The porphyrin catalyst is a macrocyclic ring consisting of pyrroles linked with methine bridges, the highly conjugated ring provided the superior functionality of visible light absorption. Surprisingly, over 99 % degradation of halophenols and over 90 % dehalogenation have been achieved without metal chelation, even higher than those of transition metal porphyrins with inclusion of Fe3+, Zn2+, Cu2+, Co2+, Ni2+, and Mn2+. Ring-opening reactions were confirmed with the formation of carboxylic acids; dicarboxylic acids like acrylic acid, and malonic acid; while fumaric acid was the main product. Total organic carbon results indicated no CO2 produced during the reaction. Triplet absorbance and scavenger studies also indicated that singlet oxygen and conduction band electrons are the main radical species for halophenol degradation. The 100-fold singlet emission quenching over triplet absorption quenching indicated that the excited electrons tend to be transferred via singlet state. This concept brings along new approaches detoxifying halophenol-related wastewater without UV, metals and other additives, which is more environmentally-friendly and sheds light to the conversion of toxic materials into useful chemical precursors.

A holistic lifestyle mobile health intervention for the prevention of type 2 diabetes and common mental disorders in Asian women with a history of gestational diabetes: a randomised control trial with 3-year follow-up protocol.

BACKGROUND: Women with a history of gestational diabetes mellitus (GDM) are 12-fold more likely to develop type 2 diabetes (T2D) 4-6 years after delivery than women without GDM. Similarly, GDM is associated with the development of common mental disorders (CMDs) (e.g. anxiety and depression). Evidence shows that holistic lifestyle interventions focusing on physical activity (PA), dietary intake, sleep, and mental well-being strategies can prevent T2D and CMDs. This study aims to assess the effectiveness of a holistic lifestyle mobile health intervention (mHealth) with post-GDM women in preventing T2D and CMDs in a community setting in Singapore. METHODS: The study consists of a 1-year randomised controlled trial (RCT) with a 3-year follow-up period. Post-GDM women with no current diabetes diagnosis and not planning to become pregnant will be eligible for the study. In addition, participants will complete mental well-being questionnaires (e.g. depression, anxiety, sleep) and their child's socio-emotional and cognitive development. The participants will be randomised to either Group 1 (Intervention) or Group 2 (comparison). The intervention group will receive the "LVL UP App", a smartphone-based, conversational agent-delivered holistic lifestyle intervention focused on three pillars: Move More (PA), Eat Well (Diet), and Stress Less (mental wellbeing). The intervention consists of health literacy and psychoeducational coaching sessions, daily "Life Hacks" (healthy activity suggestions), slow-paced breathing exercises, a step tracker (including brisk steps), a low-burden food diary, and a journaling tool. Women from both groups will be provided with an Oura ring for tracking physical activity, sleep, and heart rate variability (a proxy for stress), and the "HAPPY App", a mHealth app which provides health promotion information about PA, diet, sleep, and mental wellbeing, as well as display body mass index, blood pressure, and results from the oral glucose tolerance tests. Short-term aggregate effects will be assessed at 26/27 weeks (midpoint) and a 1-year visit, followed by a 2, 3, and 4-year follow-up period. DISCUSSION: High rates of progression of T2D and CMDs in women with post-GDM suggest an urgent need to promote a healthy lifestyle, including diet, PA, sleep, and mental well-being. Preventive interventions through a holistic, healthy lifestyle may be the solution, considering the inextricable relationship between physical and psychological health. We expect that holistic lifestyle mHealth may effectively support behavioural changes among women with a history of GDM to prevent T2D and CMDs. TRIAL STATUS: The protocol study was approved by the National Healthcare Group in Singapore, Domain Specific Review Board (DSRB) [2023/00178]; June 2023. Recruitment began on October 18, 2023. TRIAL REGISTRATION: ClinicalTrials.gov NCT05949957. The first submission date is June 08, 2023.

Single-cell atlas of ABCA7 loss-of-function reveals impaired neuronal respiration via choline-dependent lipid imbalances.

Loss-of-function (LoF) variants in the lipid transporter ABCA7 significantly increase the risk of Alzheimer's disease (odds ratio ∼2), yet the pathogenic mechanisms and the neural cell types affected by these variants remain largely unknown. Here, we performed single-nuclear RNA sequencing of 36 human post-mortem samples from the prefrontal cortex of 12 ABCA7 LoF carriers and 24 matched non-carrier control individuals. ABCA7 LoF was associated with gene expression changes in all major cell types. Excitatory neurons, which expressed the highest levels of ABCA7, showed transcriptional changes related to lipid metabolism, mitochondrial function, cell cycle-related pathways, and synaptic signaling. ABCA7 LoF-associated transcriptional changes in neurons were similarly perturbed in carriers of the common AD missense variant ABCA7 p.Ala1527Gly (n = 240 controls, 135 carriers), indicating that findings from our study may extend to large portions of the at-risk population. Consistent with ABCA7's function as a lipid exporter, lipidomic analysis of isogenic iPSC-derived neurons (iNs) revealed profound intracellular triglyceride accumulation in ABCA7 LoF, which was accompanied by a relative decrease in phosphatidylcholine abundance. Metabolomic and biochemical analyses of iNs further indicated that ABCA7 LoF was associated with disrupted mitochondrial bioenergetics that suggested impaired lipid breakdown by uncoupled respiration. Treatment of ABCA7 LoF iNs with CDP-choline (a rate-limiting precursor of phosphatidylcholine synthesis) reduced triglyceride accumulation and restored mitochondrial function, indicating that ABCA7 LoF-induced phosphatidylcholine dyshomeostasis may directly disrupt mitochondrial metabolism of lipids. Treatment with CDP-choline also rescued intracellular amyloid ß -42 levels in ABCA7 LoF iNs, further suggesting a link between ABCA7 LoF metabolic disruptions in neurons and AD pathology. This study provides a detailed transcriptomic atlas of ABCA7 LoF in the human brain and mechanistically links ABCA7 LoF-induced lipid perturbations to neuronal energy dyshomeostasis. In line with a growing body of evidence, our study highlights the central role of lipid metabolism in the etiology of Alzheimer's disease.

Streptococcus taoyuanensis sp. nov., a Novel Species Isolated from a Patient with Bacteremia.

Streptococcus spp. are important opportunistic pathogen of bacteremia in both immunocompetent and immunosuppressed patients. A streptococcal strain, designated ST2T, was isolated from the blood specimen of a bacteremic patient. Comparative analyses of 16S rRNA, rpoB and groEL gene sequences demonstrated that the novel strain ST2T is a member of the genus Streptococcus. Based on of 16S rRNA gene sequence similarities, the type strains of Streptococcus (S.) parasanguinis (99.2%), S. ilei (98.8%), S. oralis subsp. oralis (97.6%), S. australis (97.5%) and S. sanguinis (97.5%) were the closest neighbours to strain ST2T. The housekeeping gene sequences (rpoB and groEL) similarities of strain ST2T to these closely related type strains were 80.4-97.4%, respectively. The complete draft genome of strain ST2T consisted of 2,155,906 bp with a G + C content of 42.0%. Strain ST2T has an average nucleotide identity (ANI) value of 94.1 and 81.3% with S. parasanguinis ATCC 15912T and S. ilei I-G2T, respectively. The highest in silico DNA-DNA hybridization value with respect to the closest species S. parasanguinis was 55.6%, below the species cut-off of 70% hybridization. The primary cellular fatty acids of strain ST2T were C16:0, C18:1 ω9c, C18:0 and C14:0. Based on biochemical criteria and molecular genetic evidence, it is proposed that strain ST2T be assigned to a new species of the genus Streptococcus as Streptococcus taoyuanensis sp. nov. The type strain of Streptococcus taoyuanensis is ST2T (=NBRC 115928T = BCRC 81374T) as the type strain.

Suppression of Ventilation-Induced Diaphragm Fibrosis through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K-γ pathway. Five days after receiving a single bolus of 0.075 units of bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg of MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-ß1, oxidative loads, Masson's trichrome staining, extracellular collagen levels, positive staining of α-smooth muscle actin, PI3K-γ expression, and myonuclear apoptosis (p < 0.05). Decreased diaphragm contractility and peroxisome proliferator-activated receptor-γ coactivator-1α levels were also observed (p < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K-γ activity (p < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated by PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Implication of genotypes for prognosis of Candida glabrata bloodstream infections.

BACKGROUND: Genotyping isolates of a specific pathogen may demonstrate unique patterns of antimicrobial resistance, virulence or outcomes. However, evidence for genotype-outcome association in Candida glabrata is scarce. We aimed to characterize the mycological and clinical relevance of genotypes on C. glabrata bloodstream infections (BSIs). METHODS: Non-duplicated C. glabrata blood isolates from hospitalized adults were genotyped by MLST, and further clustered by the unweighted pair group method with arithmetic averages (UPGMA). A clonal complex (CC) was defined by UPGMA similarities of >90%. Antifungal susceptibility testing was performed by a colorimetric microdilution method and interpreted following CLSI criteria. RESULTS: Of 48 blood isolates evaluated, 13 STs were identified. CC7 was the leading CC (n = 14; 29.2%), including 13 ST7. The overall fluconazole and echinocandin resistance rates were 6.6% and 0%, respectively. No specific resistance patterns were associated with CC7 or other CCs. Charlson comorbidity index (adjusted OR, 1.49; 95% CI, 1.05-3.11) was the only predictor for CC7. By multivariable Cox regression analyses, CC7 was independently associated with 28 day mortality [adjusted HR (aHR), 3.28; 95% CI, 1.31-8.23], even after considering potential interaction with neutropenia (aHR, 3.41; 95% CI, 1.23-9.42; P for interaction, 0.24) or limited to 34 patients with monomicrobial BSIs (aHR, 2.85; 95% CI, 1.15-7.08). Also, the Kaplan-Meier estimate showed greater mortality with CC7 (P = 0.003). Fluconazole resistance or echinocandin therapy had no significant impact on mortality. CONCLUSIONS: Our data suggested comorbid patients were at risk of developing CC7 BSIs. Further, CC7 was independently associated with worse outcomes.

RSU-1 regulates the integrity of dense bodies in muscle cells of aging Caenorhabditis elegans.

Muscle contraction is vital for animal survival, and the sarcomere is the fundamental unit for this process. However, the functions of many conserved sarcomere proteins remain unknown, as their mutants do not exhibit obvious defects. To address this, Caenorhabditis elegans was utilized as a model organism to investigate RSU-1 function in the body wall muscle. RSU-1 is found to colocalize with UNC-97 at the dense body and M-line, and it is particularly crucial for regulating locomotion in aging worms, rather than in young worms. This suggests that RSU-1 has a specific function in maintaining muscle function during aging. Furthermore, the interaction between RSU-1 and UNC-97/PINCH is essential for RSU-1 to modulate locomotion, preserve filament structure, and sustain the M-line and dense body throughout aging. Overall, these findings highlight the significant contribution of RSU-1, through its interaction with UNC-97, in maintaining proper muscle cell function in aging worms.

Validation of Downloadable Mobile Snore Applications by Polysomnography (PSG).

Purpose: Obstructive sleep apnea (OSA) is a common breathing disorder during sleep that is associated with symptoms such as snoring, excessive daytime sleepiness, and breathing interruptions. Polysomnography (PSG) is the most reliable diagnostic test for OSA; however, its high cost and lengthy testing duration make it difficult to access for many patients. With the availability of free snore applications for home-monitoring, this study aimed to validate the top three ranked snore applications, namely SnoreLab (SL), Anti Snore Solution (ASS), and Sleep Cycle Alarm (SCA), using PSG. Patients and Methods: Sixty participants underwent an overnight PSG while simultaneously using three identical smartphones with the tested apps to gather sleep and snoring data. Results: The study discovered that all three applications were significantly correlated with the total recording time and snore counts of PSG, with ASS showing good agreement with snore counts. Furthermore, the Snore Score, Time Snoring of SL, and Sleep Quality of SCA had a significant correlation with the natural logarithm of apnea hypopnea index (lnAHI) of PSG. The Snore Score of SL and the Sleep Quality of SCA were shown to be useful for evaluating snore severity and for pre-diagnosing or predicting OSA above moderate levels. Conclusion: These findings suggest that some parameters of free snore applications can be employed to monitor OSA progress, and future research could involve adjusted algorithms and larger-scale studies to further authenticate these downloadable snore and sleep applications.