The insidious onset of osteoporosis and the high cost of DXA examination make it urgent to develop suitable prediction or screening tools. The NHANES cohort contains standardized DXA-BMD results and comprehensive nutrition-related information. Therefore, this study aimed to develop and validate a nomogram clinical prediction model dedicated to predicting the exact probability of osteoporosis occurrence in the elderly population. Data of elderly participants were extracted from the NHANES database and categorized into the training (n = 3181) and validation (n = 1622) groups. Clinical characteristics and BMD results were obtained and analyzed. Univariate and multivariate logistic regression analyses were performed. General and dynamic nomogram clinical prediction models were constructed. The models were validated using ROC curves, calibration curves, DCA curves, and clinical impact curves. Based on 11 variables, including age, gender, race, poverty income ratio (PIR), waist circumference, DBP, physical exercise, protein intake, carbohydrate intake, caffeine intake, and fracture history, a nomogram clinical prediction model was constructed. This model exhibited moderate predictive value (AUC = 0.795), alongside good calibration, clinical benefit, and clinical impact. The constructed online dynamic nomogram (https://jialinwang.shinyapps.io/OP-Prediction-Model/) is interactive, accessible, and user-friendly. This nomogram prediction model and the web-based dynamic nomogram exhibit good practical application value within the U.S. elderly population. However, external validation in non-U.S. cohorts is necessary before widespread global promotion. Ultimately, this tool could facilitate the early prediction, diagnosis, and treatment of osteoporosis, thus contributing to the bone health of the elderly population and promoting the development of public health.
Assembling high-quality genomes from underexplored environments can be helpful for understanding microbial diversity and identifying novel species. The Cyanobacterium type strain Capilliphycus salinus ALCB114379 is a representative of Oscillatoriales order isolated from a supralittoral zone of the south Atlantic Ocean in Brazil, an ecotone characterized by significant environmental fluctuations due to its transitional nature between the tidal and terrestrial environments. Here, we present its genome assembled into a single contig and circularized, with a total size of 7.7 Mb and 99.67% completeness. The genome has 6204 protein-coding genes, including several involved in the biosynthesis of secondary metabolites. Despite being a homocytous genus, C. salinus ALCB114379 possesses a gene cluster for the biosynthesis of molybdenum-type nitrogenase, indicating a potential for N2 fixation. Additionally, the genome contains other gene clusters related to the biosynthesis of biotechnologically relevant compounds, such as microcyclamide (mca), a cytotoxic cyanopeptide, and mycosporine-like amino acids (MAAs), with photoprotective and antioxidant functions. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis showed the detectable production of three MAAs, with shinorine being the most abundantly produced compared with porphyra-334 and palythine. This work provides insights into the Cyanobacteria phylogenomics and metabolism, highlighting the potential of C. salinus ALCB114379 as a source of specific metabolites for biotechnological applications.
Interstrand DNA crosslinks (ICLs) are a highly toxic form of DNA damage. ICL repair in both eukaryotes and bacteria involves unhooking of the two strands by specialized DNA glycosylases. We recently established that the human pathogen Acinetobacter baumannii contains an ICL glycosylase (AlkX) that facilitates pathogenesis and protects the bacteria from DNA damage and acid stress. However, the physical basis for glycosylase-catalyzed ICL unhooking is unknown. Here, we describe a crystal structure of AlkX bound to DNA representing a product of the ICL unhooking reaction. Mutational analysis of ICL unhooking in vitro and A. baumannii sensitivity to the crosslinking agent mechlorethamine enable the identification of several AlkX motifs critical for ICL repair. We also find that a genetic variant from an antibiotic-resistant strain of the human pathogen Salmonella enterica reduces AlkX activity in vitro and increases A. baumannii sensitivity to DNA crosslinking. This work provides a structural basis for how bacterial ICL glycosylases recognize and repair DNA adducts and contributes additional evidence that ICL repair is important for fitness of human pathogens.
25-Hydroxyvitamin D3 (25(OH)D3) has been reported to improve production performance and egg quality in ducks during late laying period, but its effects during the peak laying period remain rarely studied. The aim of this study was to investigate the effects of dietary 25(OH)D3 supplementation on the production performance, egg quality, tibia quality and mineral metabolism of ducks during peak laying period in a cage rearing system. A total of 360 Liancheng white laying ducks at 30 weeks (wks) of age were randomly assigned to 5 groups, each consisting of 6 replicates with 12 ducks per replicate. Ducks were fed a basal diet with 25(OH)D3 supplementation at 0, 1000, 2000, 3000, and 4000 IU/kg throughout the trial for 8 wks. One-way ANOVA was employed to assess the influence of supplementation level, and linear and quadratic regression analyses were performed for statistical evaluation of dose-dependent effects. 25(OH)D3 supplementation linearly and quadratically increased the laying rate, average egg weight and egg mass and quadratically decreased the feed conversion ratio (FCR). The mean of eggshell strength and thickness at 4 and 8 wks increased linearly and quadratically with increasing 25(OH)D3 levels, and the 4000 IU/kg 25(OH)D3 increasing the eggshell thickness by 5.7% (at 4 wks) and 2.9% (mean of those at 4 and 8 wks) relative to those of the non-supplemented group. At the end of wks 4 and 8 of the trial, serum 25(OH)D3, bone glutamyl protein (BGP) and carbonic anhydrase (CA) increased linearly (P < 0.05), and serum parathyroid hormone (PTH) decreased linearly (P < 0.05); the 4000 IU/kg group had the highest serum 25(OH)D3 (4.24 ng/mL) and BGP (3.11 ng/mL) concentrations at 8 wks. Additionally, the tibial breaking strength, trabecular bone number, BGP content, and alkaline phosphatase (ALP) activity and mRNA levels increased linearly with 25(OH)D3 supplementation (P < 0.05). The optimal dietary 25(OH)D3 supplementation levels were approximately 2355, 2347 and 3269 IU/kg on the basis of the quadratic model of the laying rate, FCR and eggshell strength, respectively. In summary, 25(OH)D3 supplementation improved the production performance and eggshell quality of ducks during peak laying period by maintaining calcium and phosphorus homeostasis and enhancing tibia quality. A diet that contains 2347-3269 IU/kg of 25(OH)D3 displayed beneficial effects on maintaining calcium and phosphorus homeostasis, and improving the tibial quality, which was recommended for ducks during peak laying period in the cage rearing system (30-38 wks of age). 25-Hydroxyvitamin D3 (25(OH)D3) has been demonstrated to improve production performance and egg quality in ducks during late laying period. However, its effects on ducks during peak laying period in the cage rearing system within a cage rearing system remain inadequately explored. The purpose of the present study was to investigate the effects of dietary supplemental levels of 25(OH)D3 on the production performance, egg quality, tibia quality and mineral metabolism of ducks during 30-38 wks of age in a cage rearing system. Ducks were fed a basal diet without 25(OH)D3 supplementation or with 25(OH)D3 supplementation at 1000, 2000, 3000, and 4000 IU/kg throughout the trial for 8 wks. The results indicated that dietary 25(OH)D3 supplementation improved the production performance, eggshell and tibia quality and mineral metabolism of ducks during peak laying period. Supplementing the basal diet with 2347-3269 IU/kg 25(OH)D3 is recommended for laying ducks during peak laying period of production (30-38 wks of age).
Children and adolescents are disadvantaged when it comes to drug therapy, as drugs are frequently used off-label for this age group. Despite regulatory measures such as the EU Paediatric Regulation, off-label use in paediatrics remains widespread. Since 2021, the online platform "Kinderformularium.DE" has been providing evidence-based dosing recommendations for on- and off-label drug use in Germany, establishing itself as reliable source of information in paediatric practice. This study aims to analyse the scope of age-appropriate (off-label) dosage recommendations provided and to evaluate usage patterns and user satisfaction. Drug monographs were examined to determine the availability and licensing status of age-specific dosing recommendations, taking into account different indications and routes of administration. A user survey was conducted between November 2024 and February 2025 and analysed using a mixed-methods approach. Kinderformularium.DE contains 637 monographs with 5536 individual age-specific dosage recommendations. Both the number of dosage recommendations and the licensing status vary by age: there is less dosage information available for preterm and newborn infants, and this information is more frequently classified as off-label. The survey confirms the platform's high level of acceptance-it is used frequently, particularly by doctors-and highlights its importance in the care of paediatric patients. With its age-specific (off-label) dosage recommendations, Kinderformularium.DE is an important tool for ensuring medication safety in paediatric clinical practice in Germany. The platform must continue to be updated and expanded on an ongoing basis. EINLEITUNG: Kinder und Jugendliche sind bei der Arzneimitteltherapie benachteiligt, da Medikamente in dieser Altersgruppe häufig außerhalb der Zulassung (off-label) angewendet werden. Trotz der Zunahme an Kinderzulassungen durch die EU-Kinderarzneimittelverordnung werden Off-Label-Anwendungen weiterhin Teil der pädiatrischen Therapien bleiben. Die Online-Plattform „Kinderformularium.DE“ stellt seit 2021 evidenzbasierte Dosierungsempfehlungen für den On- und Off-Label-Bereich in Deutschland bereit und hat sich als feste Informationsquelle in der pädiatrischen Praxis etabliert. Ziel dieser Arbeit ist es, den Umfang und den Zulassungsstatus der enthaltenen altersspezifischen (Off-Label‑)Dosierungsempfehlungen zu analysieren und die Nutzung und Akzeptanz zu evaluieren. In den Wirkstoffmonographien wurden die Verfügbarkeit und der Zulassungsstatus altersspezifischer Dosierungsempfehlungen unter Berücksichtigung unterschiedlicher Indikationen und Applikationswege untersucht. Eine Nutzerumfrage (von 11/2024 bis 02/2025) wurde mittels Mixed-Methods-Analyse ausgewertet. Kinderformularium.DE enthält 637 Monographien mit 5536 spezifischen Dosierungsempfehlungen. Diese sind altersabhängig verteilt: Für Früh- und Neugeborene gibt es weniger Dosierungsinformationen, die zudem häufiger als off-label eingestuft sind. Die hohe Akzeptanz der Plattform, die vor allem von Ärztinnen und Ärzten häufig genutzt wird, bestätigt ihren Stellenwert in der pädiatrischen Versorgung. Mit seinen altersspezifischen (Off-Label‑)Dosierungsempfehlungen ist Kinderformularium.DE ein wichtiges Instrument zur Förderung der Arzneimitteltherapiesicherheit in der pädiatrischen Versorgung in Deutschland. Die Plattform muss weiterhin kontinuierlich aktualisiert und ergänzt werden.
H9N2 avian influenza virus (AIV) has been circulating in poultry in China for decades and are undergoing adaptation to mammals, posing potential pandemic risks. To investigate the prevalence of H9N2 AIVs in swine, we conducted surveillance in Shandong Province from 2021 to 2023. Two H9N2 influenza virus strains, A/swine/Shandong/417/2021(Sw/SD/417/21) and A/swine/Shandong/662/2022 (Sw/SD/662/22), were successfully isolated from swine and genetically characterized. Phylogenetic analyses showed that both isolates were reassortants containing gene segments from multiple H9N2 AIV lineages and closely related to currently circulating H9N2 AIV. Key molecular marker analysis revealed that both isolates carried mammalian-adaptive residues in the HA receptor-binding sites (183 N, 190 V, 226 L), a novel HA cleavage site variant (PSKSSRGL), PB2 mutations (A588V, E627V), and the M2 S31N substitution, suggesting potential adaptation to mammalian hosts and resistance to adamantane antivirals. Mice infection experiments demonstrated efficient viral replication in the respiratory tract, particularly in the lungs, but only mild histopathological changes were observed, with no significant weight loss or mortality, indicating low pathogenicity in mice. Serological surveillance of 3,172 swine serum samples showed a low prevalence of H9N2 influenza virus infection (0.44%), with positive samples sporadically distributed across regions and years. In summary, although H9N2 AIV infection in swine is rare and generally mild, the presence of mammalian-adaptive markers and reassortant genomes highlights the potential risk of cross-species transmission and subclinical adaptation. Continuous avian-swine-human influenza surveillance is therefore essential to mitigate the potential threat posed by H9N2 AIV.
Polymeric nanoparticles represent one of the most promising classes of non-lipid-based drug delivery vehicles. However, their clinical translation remains limited by poor drug loading capacity and suboptimal delivery efficiency. We here develop one type of polymeric nanoparticles, referred to as PCCMs (Polymeric Coacervate Core Micelles), which are assembled from a sulfoxide-containing block polymer. Hydrophobic drugs can be efficiently encapsulated into PCCMs via a fast, low-energy "Mix-and-Go" approach, reducing reliance on organic solvents and simplifying the drug-loading process. Moreover, PCCMs show high drug loading capacities and improved stability towards versatile hydrophobic drugs. Upon evaluating 40 different drugs, 45% of the tested compounds achieve drug loading contents exceeding 40%, 80% exceed 30%, and 100% surpass 20%. Both quantitative structure-property relationship (QSPR) calculations and experimental methods identify that hydration water within PCCMs' self-coacervated cores acts as the molecular barrier, substantially inhibiting long-range-ordered drug molecule packing and stabilizing drug aggregates at the nanoscale via bridging hydrogen bonds among the polymer-water-drug. Finally, we demonstrate that PCCMs exhibit significantly higher systemic delivery efficacy compared to commercial polymeric micelle formulations in female BALB/c mice. The high loading capacity, versatility, and efficacy of PCCMs pave the way for the clinical translation of polymeric nanoparticles.
Corneal confocal microscopy enables in vivo visualisation of the sub-basal nerve plexus; however, most available datasets provide only centreline annotations, and open pixel-level annotations are comparatively scarce, limiting broader pixel-level segmentation research. Existing resources vary in quality, annotation strategy, and clinical coverage, complicating objective algorithm comparisons and reducing their utility in developing robust models. To address these gaps, we introduce a new dataset of 410 high-quality images from 88 participants, each paired with an expert-reviewed pixel-level nerve mask. These images span two independently collected subsets with distinct acquisition conditions and participant groups. Demographic information is available for each participant, and one subset contained detailed clinical and laboratory data. The dataset offers detailed, manually curated delineations of nerve fibres, consistent formatting, and clear provenance. It is intended to support the training and validation of segmentation models, assess generalisability across imaging conditions, and explore the associations between image-derived metrics and clinical characteristics.
Mental health problems among university students predated COVID-19, but pandemic-period conditions coincided with changes in how academic, relational, behavioral, and internalizing difficulties co-occurred. Prior studies often modeled single outcomes or symptom clusters separately. This secondary analysis used a construct-level network to describe conditional associations among contextual stressors, adaptive-functioning indicators, and multidimensional mental health indicators in one archived student dataset. We analyzed cross-sectional survey data from 10,745 students collected January 13-March 26, 2021. Fourteen nodes were included: media time, online adaptation, learning efficiency, family conflict, friendship change, epidemic attitude, epidemic attention, exercise, perceived stress, anxiety, depression, sleep problems, loneliness, and resilience. After correcting exercise-frequency coding and anxiety-score derivation errors, we estimated an EBICglasso-regularized partial-correlation network using Spearman correlations. Expected influence, bridge expected influence, and nodewise R2 were interpreted as descriptive, model-dependent indices. We examined edge accuracy, centrality stability, bridge stability, edge-weight differences, data-quality exclusions, alternative estimators, community definitions, and counterintuitive partial edges. The fitted network retained 53 of 91 possible edges (density = 0.582). In this specification, depression, perceived stress, and anxiety had the highest expected-influence values (1.428, 1.064, and 0.782). The strongest absolute partial-correlation edges linked sleep problems with depression (0.736), depression with anxiety (0.668), anxiety with perceived stress (0.459), and sleep problems with anxiety (-0.423). Under the prespecified two-community partition, bridge expected influence was largest for perceived stress (0.461), loneliness (0.343), family conflict (0.233), epidemic attitude (0.184), and learning efficiency (0.126). Expected influence and bridge expected influence showed high case-dropping stability within this analytic specification (CS = 0.75). Data-quality exclusions and an ordinal/mixed-correlation EBICglasso model yielded estimates very similar to the primary network, whereas an unsigned-weight mixed graphical model yielded different centrality rankings. The findings describe a construct-level snapshot of conditional associations among students from one institutional context during a specific COVID-19 period. Perceived stress showed the highest and most stable bridge expected-influence value across the tested community specifications, while other bridge rankings and centrality values were specification-dependent. The results are hypothesis-generating, not evidence of causal pathways, intervention targets, or population-representative student mental health structure.
To estimate the short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval (QTc) by emulating a published randomized controlled trial (RCT) using electronic health record (EHR) data, and to assess whether target trial emulation (TTE) can replicate RCT findings for a pharmacological safety outcome at substantially greater scale. Retrospective cohort study emulating a target trial, reported according to the Transparent Reporting of Observational Studies Emulating a Target Trial (TARGET) guideline. Single tertiary A teaching hospital in China, March 2012 to September 2024. Of 619,216 cardiology hospitalizations, 165,460 new statin users with suspected coronary artery disease met all eligibility criteria. After 1:1 propensity score matching, 98,860 patients (49,430 per group) constituted the analytic cohort. All standardized mean differences were below 0.013 after matching. The primary outcome was the change in Fridericia-corrected QT interval (ΔQTcF) from baseline to first follow-up electrocardiogram (24-72 h). Secondary outcomes included newly emerged QTc prolongation, any QTc increase, clinically significant increase (> 30 ms), severe QTc prolongation, and a composite cardiac safety endpoint. Both intention-to-treat and per-protocol effects were estimated. The mean ΔQTcF in the rosuvastatin group was + 7.71 ms (SD 20.41) versus + 0.31 ms (SD 22.30) in the atorvastatin group, yielding a between-group difference of 7.40 ms (95% CI 7.13 to 7.67; P < 0.001). Newly emerged QTc prolongation occurred in 14.7% versus 10.5% (risk ratio 1.40, 95% CI 1.35 to 1.45). The composite cardiac safety endpoint did not differ (0.4% versus 0.5%; P = 0.24). Results were consistent across eight subgroups and six sensitivity analyses. The TTE estimate was concordant with the published RCT finding of 7.40 ms (heterogeneity P = 1.00), with a 14-fold narrower confidence interval. The negative control outcome analysis showed no residual bias. Rosuvastatin was associated with a 7.40 ms greater short-term QTcF prolongation than atorvastatin in a cohort 212 times larger than the emulated RCT, without excess clinical cardiac events over a mean follow-up of 48 h. Target trial emulation successfully replicated the RCT finding for a short-term drug safety outcome, demonstrating the framework's value for pharmacovigilance research using routine clinical data.
This study investigates the relationships among job satisfaction, school climate, and career sustainability among native language teachers working in rural regions of Türkiye, with a particular focus on the mediating role of school climate. Designed within a correlational research framework, the study aims to address a gap in the literature regarding factors influencing teachers' long-term professional continuity in rural educational settings. Data were collected from 313 teachers using the Career Sustainability Scale, the Job Satisfaction Short Index, and the School Climate Scale, and analyzed through structural equation modeling. The validity and reliability of the measurement instruments were confirmed via confirmatory factor analysis. Findings indicate a strong and significant positive association between job satisfaction and career sustainability, underscoring the central role of job satisfaction in supporting teachers' long-term engagement in rural contexts. Job satisfaction was also positively related to perceptions of school climate. However, no significant relationship emerged between school climate and career sustainability. Mediation analysis further revealed that school climate does not significantly mediate the link between job satisfaction and career sustainability. Overall, the results suggest that teachers' career sustainability in rural settings is shaped predominantly by job satisfaction, individual efficacy perceptions, and structural conditions rather than by school climate.
Lactobacillaceae have shown promise with their potential to outcompete pathogens and restore a healthy microbial balance in otitis externa (OE). This study aimed to evaluate the presence of viable Lactobacillaceae over time and in vitro ability to inhibit growth of common OE pathogens. Fifteen healthy dogs were enrolled and randomised into five groups (n = 3 per group) to receive six probiotic ear drops containing live Lactiplantibacillus plantarum YUN-V2.0 and Lacticaseibacillus rhamnosus YUN-S1.0. Ear swabs were taken 24, 48, 72, 96 h and 7 days post single application for culturing. For pathogen inhibition, clinical isolates of Pseudomonas aeruginosa, Staphylococcus pseudintermedius and Malassezia pachydermatis were tested against the probiotic ear drop and antimicrobial disks of florfenicol 30 μg, gentamicin 30 μg, marbofloxacin 5 μg, miconazole 10 μg, neomycin 120 μg and terbinafine 1.5 μg. A relatively basal low abundance of commensal and Lactobacillaceae micro-organisms was detected (1.34 × 103 colony-forming units [cfu]/mL). At 24 h post-application, Lactobacillaceae increased significantly (2.3 × 106 cfu/mL; p < 0.001), and remained above 105 cfu/mL at 1 week post-application (1.6 × 105 cfu/mL). Lactobacilli demonstrated better growth inhibition of P. aeruginosa than gentamicin and marbofloxacin, and of S. pseudintermedius than gentamicin, neomycin and marbofloxacin. For M. pachydermatis similar growth inhibition versus miconazole and terbinafine was observed. These results suggest that probiotic strains exhibit excellent retention and can inhibit the growth of S. pseudintermedius, P. aeruginosa, and M. pachydermatis.
Taiwan Hard Clam (Meretrix taiwanica) is an economically important aquaculture species in Taiwan, yet genomic resources for this species have remained fragmented. We present a telomere-to-telomere (T2T), haplotype-resolved, chromosome-level genome assembly for M. taiwanica, generated using PacBio HiFi long reads and Hi-C sequencing. The two haploid assemblies (hap1 and hap2) span 1,006.48 Mb and 1,007.28 Mb, comprising 126 and 66 sequences, respectively, and each containing 19 chromosomes. Hap1 and hap2 exhibit sequence N50 values of 53.87 Mb and 51.57 Mb, with average scaffold lengths of 7.99 Mb and 15.26 Mb, and contain 0.0176% and 0.1313% ambiguous bases. Comparative analyses revealed 81.59% and 83.78% syntenic regions between haplotypes and identified 10,175 structural variations. Repetitive elements constitute 47.06% and 47.02% of the hap1 and hap2 genomes. We annotated 23,320 and 23,598 protein-coding gene models, with median gene lengths of 7,721 bp and 7,657.5 bp, respectively. The mitochondrial genome was assembled at 21,164 bp and encodes 13 protein-coding genes, 22 tRNAs, and 2 rRNAs. Functional annotation covered 16.23% and 16.33% of the nuclear and mitochondrial gene sets. BUSCO analysis indicated genome completeness of 92.4% and 92.5%, and proteome completeness of 95.4% and 94.5% for hap1 and hap2. By providing the first T2T-level reference, this dataset enables precise identification of trait-associated markers for marker-assisted selection (MAS), thereby facilitating genetic improvement of growth and stress-resistance traits. Furthermore, it serves as a robust genomic framework for conservation genomics to assess the genetic diversity of both wild and hatchery populations of this economically vital species.
To determine whether physalin A (PA) safeguards the outer blood-retinal barrier under diabetic stress by engaging nuclear factor erythroid 2-related factor 2 (Nrf2) to restore redox balance and restrain ferroptosis in human retinal pigment epithelial (hRPE) cells and C57BLKS/J Iar -+Leprdb/+Leprdb mice. In high-glucose challenged hRPE cells, PA dose-dependently preserved viability, maintained claudin-1/occludin/zonula occludens-1 abundance and membrane localization, and reversed ferroptosis hallmarks (restored solute carrier family 7 member 11 [SLC7A11], SLC3A2, and glutathione peroxidase 4; reduced ferrous iron [Fe2+] overload and lipid peroxidation). PA restored glutathione levels, reduced malondialdehyde (MDA), and enhanced the antioxidant defense pathway mediated by Nrf2, including upregulation of heme oxygenase 1, NAD(P)H quinone dehydrogenase 1, and superoxide dismutase 2. Silencing Nrf2 abolished the effects of PA on barrier integrity and ferroptosis suppression, with rebounds in reactive oxygen species, MDA, Fe2+, and tight junction loss. In db/db mice treated systemically for 20 weeks, PA reduced Evans Blue leakage, increased retinal thickness, restored RPE tight junction proteins, and normalized mitochondrial architecture by transmission electron microscopy. PA rebalanced mitochondrial dynamics (dynamin 1-like, optic atrophy 1, fission 1, mitofusin 1, FUN14 domain containing 1), increased retinal mitochondrial DNA copy number, and partially stabilized glycemia and weight. PA restores redox tone, restrains ferroptosis, and preserves junctional integrity to protect the diabetic retina, with Nrf2 being indispensable for these benefits. These findings position PA as a promising adjunctive candidate for early diabetic retinopathy and support Nrf2-centered strategies to reinforce the outer blood-retinal barrier. Antioxid. Redox Signal. 00, 000-000.
Palliative care requires timely and accurate assessment to support patient-centred outcomes. However, existing tools vary widely in purpose, design, and implementation. Understanding the current landscape of available tools is essential to guide future innovation. This review aimed to systematically identify and map published literature on palliative care assessment tools, focusing on their purpose and domains assessed, with consideration of reported validation, usability, and implementation characteristics. Scoping review conducted using the Joanna Briggs Institute (JBI) methodology and reported according to the PRISMA-ScR checklist. Ovid MEDLINE, CINAHL, and the Cochrane Library were searched for peer-reviewed studies published in English from 2005 to 2024. Studies were included if they assessed tools used in palliative care populations for symptom assessment, quality of life, early identification, psychosocial evaluation, or caregiver support. Study screening, data extraction, and synthesis were completed in Covidence. A total of 299 studies from over 40 countries were included, representing 813,819 participants. The Edmonton Symptom Assessment System (52.1%) was the most frequently used tool. Most tools focused on symptom assessment (27%) and quality of life (22%), with limited attention to caregiver burden (4%), spiritual wellbeing (4%), or social support (4%). Ninety-four studies (31%) reported positive perceptions of tool utility, and one reported a negative outcome. Key gaps included cultural adaptation, digital integration, multi-user access, and holistic scope. Although many tools support clinical assessment, few address the complexity of holistic, person-centred care. There is an urgent need for co-designed, culturally sensitive, and digitally enabled tools to support equitable palliative care delivery.
Tuberculosis (TB) is one of the deadliest bacterial infectious diseases worldwide, with rising cases of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Bedaquiline (BDQ)-containing regimens have become important for the treatment of MDR/XDR-TB, and resistance to BDQ is increasing. Understanding genetic mutations is crucial for early detection of BDQ-resistant strains and thus maintaining the effectiveness of these drugs. This study aimed to review mutations associated with BDQ-resistant TB globally. This study systematically searched the keywords TB, XDR, MDR, BDQ, and genes in the PubMed, Scopus, Web of Science, and Embase databases for studies reporting BDQ-resistant TB and their associated genes globally from 2014 to 2025. This systematic review included 40 studies and 25,234 patient samples with MDR and XDR-TB from around the world. Results showed significant variation in BDQ resistance across the World Health Organization (WHO) regions, with the highest in the Eastern Mediterranean and the lowest in the Western Pacific. Furthermore, the data collected showed that, among the continents studied, resistance was highest in Africa and lowest in the Americas. The country distribution showed that resistance rates were higher in Iran (n = 24), Moldova (n = 26), and Armenia (n = 35), and lower in Italy (n = 1001) and the Philippines (n = 724) than in other countries in the analysis. Genetically, the most resistance-associated mutations were observed in the Rv0678, atpE, and pepQ genes, respectively. Given the increasing BDQ resistance and regional variability, it is essential to develop early detection systems, genomic surveillance, robust drug policy enforcement, and rapid diagnostics to maintain treatment effectiveness and curb the spread of resistance. Future research should focus on elucidating resistance mechanisms and developing novel therapeutic strategies.
Selenoproteins represent a structurally and functionally distinct class of proteins that contribute to cellular antioxidant defense and a wide range of other essential biological processes in specific organisms. They contain the 21st amino acid selenocysteine (Sec) in their active sites, which is encoded by an in-frame UGA stop codon through a translational reprogramming mechanism. Due to the dual functionality of the UGA codon, selenoprotein genes are frequently misidentified and misannotated in genomic databases, especially in bacteria where selenoproteins exhibit greater complexity and diversity compared to their eukaryotic counterparts. Thus, a comprehensive resource is urgently required to enable accurate identification of selenoprotein genes across diverse bacterial genomes. We have developed BSepDB, a specialized database dedicated to systematic curation of bacterial selenoprotein genes and proteins, providing an exhaustive resource for the research community. The current version (BSepDB v. 1.0) encompasses over 57,000 selenoprotein entries derived from 16,621 bacterial species, representing the largest and most taxonomically diverse repository of bacterial selenoproteins to date. To facilitate intuitive data exploration, BSepDB offers multiple user-friendly interfaces, such as interactive browsing and search tools, an integrated BLAST search function, and options for bulk data download. Additionally, the curated entries in BSepDB are cross-referenced with established genomic databases (e.g., GenBank and RefSeq) to improve the accuracy of selenoprotein annotations in large-scale genomic projects. BSepDB serves as a valuable resource for researchers investigating selenium utilization and the functional diversity of selenoproteins in bacteria. The database is freely available at https://bsepdb.metalbioinfolab.net.
The taxonomic status of strain KL5T, a novel actinobacterium isolated from the rhizosphere soil of Dryopteris championii, was described using a polyphasic approach. Strain KL5T contained rich meso and ll-diaminopimelic acids in the cell-wall peptidoglycan. Whole-cell hydrolysates of strain KL5T were galactose and ribose. The major fatty acids were iso-C15:0, anteiso-C15:0, iso-C16:0, C16:0 and anteiso-C17:0. The polar lipids mainly consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides. 16S rRNA gene sequence analysis indicated that this strain shared the highest sequence similarity to Kitasatospora arboriphila HKI 0189 T (99.29%). Phylogenetic analysis based on 16S rRNA gene sequences revealed strain KL5T was most related to K. arboriphila HKI 0189 T, as was also confirmed by phylogenomic analysis. But strain KL5T exhibited low average nucleotide identity and digital DNA-DNA hybridization values with K. arboriphila JCM 13002 T (90.40% and 37.2%, respectively), suggesting that strain KL5T was a new Kitasatospora species. The results of phenotypic and chemotaxonomic analyses further verified the above conclusion. Consequently, strain KL5T represents a novel species of the genus Kitasatospora, for which the name Kitasatospora dryopteridis sp. nov. is proposed. The type strain is KL5T ( = MCCC 1K10066T = KCTC 59627 T). In addition, the comparative genomic analysis suggested that Kitasatospora cinereorecta and Kitasatospora paracochleata should belong to the same species. Based on the principle of priority, it is proposed Kitasatospora paracochleata corrig. (Nakagaito et al. 1993) Zhang et al. [1] is a later heterotypic synonym of Kitasatospora cinereorecta (Terekhova and Preobrazhenskaya 1986) Labeda et al. [2].
Eupentacta fraudatrix is the only species of sea cucumbers for which transdifferentiation has been described. This type of cell type switching occurs during gut regeneration after evisceration, which makes this species a scientifically valuable model for studying regeneration mechanisms. Moreover, chromosome-level genomes for the family Sclerodactylidae have not been available until now. In this study, we employed the MGI short-read, Oxford Nanopore, and Hi-C technologies to assemble and annotate two chromosome-level, high-quality haplotypes of E. fraudatrix. The estimated heterozygosity was 5.1%, which is much higher than the known values for sea cucumber genomes. Both haplotypes are nearly equivalent, containing 23 chromosomes with a total length of approximately 1.6 gigabase pairs, and 99% of assembled bases anchored to chromosome-level scaffolds. The annotation predicted 26,352 protein-coding genes for one haplotype and 25,238 genes for the other, with BUSCO assessment revealing 98.1 and 97.9% complete metazoa_odb12 core genes. The chromosome-level assembly and annotation of E. fraudatrix genome will provide a genomic basis for further phylogenetic, comparative, and molecular biological studies of echinoderm regeneration.
Buruli ulcer (BU), a neglected tropical disease caused by Mycobacterium ulcerans (Mul), is treated with an 8-week regimen of rifampicin (RIF) and clarithromycin (CLA). Clinical trials are currently evaluating amoxicillin/clavulanate (AMX/CLV) co-administration to reduce treatment duration. However, conventional methods for assessing in vitro drug efficacy against Mul, like colony-forming units (CFUs), are slow and cumbersome. The ribosomal RNA synthesis ratio (RS-ratio) measures ribosome biogenesis and serves as a proxy of metabolic activity. While it is a promising predictive biomarker for treatment shortening in tuberculosis, its application in Mul remains unexplored. Here, we evaluated the RS-ratio for Mul drug activity assessment through RNA extractions from time-kill assays using RIF, CLA, and AMX/CLV, alone or in combinations. RIF + AMX/CLV-containing combinations produced a potent, rapid RS-ratio reduction, decreasing from a baseline of ≈2000 to ≈200 as early as day 3, and reaching their maximal inhibition (≈50-60) between days 7 and 10. Notably, this metabolic decline preceded the CFUs and luminescence drops observed in prior studies. Interestingly, the RS-ratio detected a metabolic recovery between days 14 and 28 (≈400), suggesting remaining bacterial viability, a phenomenon not observed by CFUs or luminescence. In summary, this is the first report using the RS-ratio to evaluate antibiotic activity against Mul. Our findings validate the RS-ratio as a molecular tool for assessing the sterilizing potential of new regimens to inform future research and clinical trial designs for the treatment of BU. Our results support the RIF + CLA + AMX/CLV regimen selection for BU treatment shortening in the BLMs4BU clinical trials (NCT05169554, PACTR202209521256638).