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Accurate prediction of the water quality index (WQI) in karst water systems remains challenging due to pronounced seasonal hydrological heterogeneity, dual-porosity flow regimes, and complex multi-factor pollution mechanisms. This study developed a season-stratified, explainable machine-learning framework for the Guilin karst water system (Guangxi, China), based on 208 samples from 104 stations covering the wet (June to August) and dry (December to February) seasons. A sample-adaptive feature engineering step, followed by a three-stage selection pipeline (Pearson correlation filtering, variance inflation factor (VIF) screening, and Random Forest importance ranking), reduced 16 candidate features to ten predictors per season. Ten base learners (Ridge, Lasso, ElasticNet, support vector regression (SVR), random forest (RF), gradient boosting (GBM), eXtreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), categorical boosting (CatBoost) and adaptive boosting (AdaBoost)) were trained separately for each season, and the top three per season were stacked through a regularised Ridge meta-learner. XGBoost performed best in the wet season (R2 = 0.9655, RMSE = 3.0938, MAE = 2.6754); the Stacking ensemble performed best in the dry season (R2 = 0.9785, RMSE = 2.9142, MAE = 2.4278), beating every individual learner. regression receiver operating characteristic (RROC) analysis confirmed these rankings via the Area Over the Curve (|AOC|) and exposed a cross-seasonal inversion: ensemble models improved from wet to dry season (|AOC| ratio 0.45-0.54), while linear baselines worsened by a factor of 4.1 to 4.3, supporting season-specific model selection. SHAP analysis showed a clear seasonal shift in the dominant drivers. NH3-N controlled wet-season WQI (53.47% importance); in the dry season, control was shared by NH3-N (26.00%), TN (25.09%), DO (21.29%) and the pollution-load index (20.19%), and total phosphorus dropped from 7.73 to 0.06%, reflecting carbonate-mediated sequestration specific to karst. The framework offers a transferable, interpretable template for season-aware WQI modelling in monsoonal subtropical karst settings and provides a practical basis for season-differentiated pollution control.

Affective and psychotic disorders often emerge during adolescence and early adulthood. Early detection and timely treatment of individuals with mental disorders (particularly affective and psychotic disorders) can play a decisive role in improving the course of disease and treatment outcomes. To bridge the gap between early detection and evidence-based, integrated, and cross-setting treatment, there is a need for conceptual advancement and closer coordination of outpatient, day clinic, and inpatient care services, particularly during the transition between child and adolescent psychiatry and adult psychiatry. The aim of this paper is to present the services offered by the "Young People" track at the Carl Gustav Carus University Hospital in Dresden as a potential best-practice example. It addresses established workflows, team structure, and the nature and frequency of interventions. In addition, descriptive data on all individuals seeking help at the Early Detection and Intervention Center between May 2018 and October 2025 as well as those treated in the day clinic between December 2019 and December 2024 are analyzed. Care is provided through a stepped pathway-starting with an initial general, low-threshold point of contact, moving on to specialized early detection of affective and psychotic disorders, and culminating in targeted referrals to established outpatient, day-care, and inpatient treatment programs for young people. From May 2018 to October 2025, 859 young people made their first visit to the Early Detection and Intervention Center (52.5% female; average age: 24 years). 31.4% did not meet the criteria for a mental disorder, 35.4% fulfilled the criteria of one, 20.6% of two, and 12.6% of at least three diagnoses. N = 63 met the risk criteria for developing bipolar disorder, n = 77 for developing psychosis. More than 100 young people were treated in the outpatient setting. The day clinic treated N = 283 patients (average duration: 7 weeks) with high treatment acceptance and significant improvements in symptom burden, self-management, and quality of life. Initial steps towards establishing a specialized inpatient treatment programme are currently underway with the allocation of six beds for young people, enabling continuous care even in times of increased treatment needs. The services offered by the "Young People" track at Dresden University Hospital bridge potential gaps in care during the transition from adolescent to adult psychiatry. Through low-threshold early detection and risk-adapted, continuous, and cross-setting care, young people-with or without previous treatment experience-receive targeted support. Treatment tailored to their developmental needs facilitates inter alia processes of maturation, career orientation, and the gradual achievement of independence. The accompanying research ensures the continuous, evidence-based development of the integrative and patient-centered care concept, which, as a potential best-practice example in Germany, can represent a decisive step towards an effective and person-centered care system for young people with affective and psychotic disorders.

Appendiceal goblet cell adenocarcinoma (GCA) is an uncommon malignancy that has been described under various names and grading schemes. The 5th Edition of the World Health Organization (WHO) Classification of Digestive System Tumours provides a three-tiered system for grading these neoplasms, but the reproducibility of this classification scheme has not been studied. We scanned 58 H&E-stained slides from 20 GCA and circulated the whole-slide images among seven pathologists with interest in appendiceal pathology. They evaluated each slide for the presence of 15 histological patterns defined by the WHO as criteria for low-grade (n = 5) and high-grade (n = 10) GCA. Cases were also evaluated for the presence of extracellular mucin. Participants also reported the percentage of high-grade features in each whole slide image and each case. Interobserver variability was assessed statistically. All seven observers agreed on the WHO grade for four of the 20 cases (20%; one grade 1, three grade 3). Using Fleiss's kappa statistic, overall agreement for cases was fair at 0.29 (95% confidence interval [CI]: 0.14-0.44), and pairwise agreement between observers ranged from 0.00 to 0.82 (median = 0.13). Gwet's agreement coefficient ranged from 0.10 to 0.87 (median = 0.28), while overall agreement was 0.36 (95% CI: 0.17-0.54). There was significant variability with respect to assessing the presence of individual features. The best agreement was seen for extracellular mucin (neutral feature, κ = 0.43) and tumour sheets (high-grade feature, κ = 0.41), whereas the worst agreement was seen for mild architectural disarray/tubular fusion (low-grade feature, κ = 0.05) and necrosis (high-grade feature, κ = 0.07). We conclude that interobserver agreement for grading GCA using the three-tiered WHO 5th Edition classification system is fair at best. A validated two-tiered system (i.e. low- versus high-grade) may be more reproducible.

Inherited retinal diseases (IRDs) typically follow a single inheritance pattern, but some genes cause disease through both autosomal recessive (AR) and autosomal dominant (AD) patterns, challenging genetic counselling. This study aims to identify dual inheritance genes in a Portuguese cohort and characterise the prevalence of each inheritance mode and associated phenotypes. Cross-sectional study at Portugal's largest IRD referral centre. Genes reported with dual inheritance were identified through literature search and screened in IRD-PT registry. For each gene, AR versus AD proportion was determined and clinical features were analysed to establish genotype-phenotype correlations. Among 40 genes reported with dual inheritance, 22 were present in the IRD-PT registry and nine displayed both patterns (102 families, 141 patients). PRPH2 (95.0% AD) was associated with retinitis pigmentosa (RP) and macular dystrophies. ABCC6 (91.3% AR) was linked to pseudoxanthoma elasticum (PXE). BEST1 (91.7% AD) mainly caused Best disease, while PROM1 (76.9% AR) was linked to RP, macular dystrophy and cone-rod dystrophy. PRPF31 (88.9% AD) was exclusively associated with RP. IMPG2 (75.0% AR) and IMPG1 (87.5% AD) caused RP and adult-onset vitelliform macular dystrophy. NR2E3 (85.7% AR) was linked to enhanced S-cone syndrome and RP, and RP1 was detected in two families (one AR, one AD), presenting with RP. Dual inheritance genes accounted for 12% of our genetic diagnoses. This spectrum, modulated by variant location and allele dosage, determines phenotypes and contributes to IRD heterogeneity. Deep phenotyping and comprehensive molecular diagnosis are essential for accurate genetic counselling and patient management.

HPV infection is a major contributor to cervical and other anogenital cancers, with people living with HIV (PLWH) at particularly high risk due to persistent infection. Although prophylactic HPV vaccines are widely used and generally safe, their efficacy and safety in PLWH remain uncertain. To evaluate the efficacy and safety of HPV vaccination in PLWH through an overview and network meta-analysis (NMA). An electronic search was conducted in several databases up to August 12, 2025, without date or language restrictions, using keywords related to HPV vaccines, efficacy, and safety. We included systematic reviews of randomized controlled trials (RCTs) involving PLWH with HIV who received bivalent (bHPV), quadrivalent (qHPV), or nonavalent (9vHPV) HPV vaccines. Study selection (Rayyan software) and data extraction were conducted by two independent researchers, and discrepancies were resolved by a third author. Quantitative synthesis was performed using R software. Risk of bias was assessed using AMSTAR 2. The certainty of the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA). NMA identified that the qHPV vaccine showed significant immunological efficacy, with a significant increase in seroconversion for anti-HPV 6 (odds ratio [OR]: 17.72; 95% confidence interval [CI]: 2.55, 123.19) and anti-HPV 18 (OR: 22.81; 95% CI: 2.31, 225.32) antibodies, compared to the control group. No significant differences were observed for types 11 and 16. Regarding safety, qHPV demonstrated the best profile regarding pain outcomes at all doses analyzed, with a P score greater than 0.98. The qHPV vaccine presented the best safety profile regarding pain, including at all doses. Regarding immunological efficacy, significant differences were only found between patients vaccinated with qHPV for anti-HPV 6 and 18. No trials directly evaluated the 9vHPV in PLWH, limiting the applicability of these findings to current vaccination programs.

Adapting programs to fit the needs of different contexts allows for greater reach. Live Long Walk Strong is a physical therapy program designed to improve mobility among older adults. To describe adaptation of Live Long Walk Strong, an age-friendly physical therapy program, across four different clinical settings. Process evaluation. Urban outpatient, rural outpatient, skilled nursing facility, and virtual (telehealth) settings within the Veterans Health Administration. Physical therapists and physical therapist assistants delivering Live Long Walk Strong (n = 11). Not applicable. Barriers encountered and adaptations made to the program as it was implemented across settings. We used the Consolidated Framework for Implementation Research (CFIR) to organize and analyze collected data. We identified barriers across the Innovation, Outer Setting, Inner Setting, and Individuals domains of the CFIR. Several barriers were encountered across all contexts. These barriers related to CFIR constructs Design, Partnerships & Connections, and Access to Knowledge & Information. The shared barriers led to central adaptations beneficial to all current and future sites. We also identified barriers unique to specific contexts, which resulted in adaptations to improve fit and allow the program to best meet the needs of patient populations in those settings. Facilitators were similar across settings and did not result in further adaptation of the program; however, they likely contributed to the program's successful spread across different contexts. Facilitators fell under the Design and Relative Advantage constructs of the Innovation domain, as well as under the Relational Connections and Mission Alignment constructs of the Inner Setting domain. We present practice-based evidence on adaptations to an age-friendly physical therapy program implemented across diverse settings. Our findings provide practical information that may improve the efficiency of implementation of future programs, as potential barriers can be addressed during the planning phase.

Genome-wide association studies (GWAS) have identified numerous disease-associated single nucleotide polymorphisms (SNPs), yet many potential disease-SNP associations remain undiscovered due to the high dimensionality and sparsity of genomic data. Computational approaches that integrate biological network information can complement existing GWAS resources by prioritizing candidate disease-associated SNPs for downstream investigation. In this study, we propose DeepDisSNP, a deep learning framework for disease-SNP association prediction that integrates disease similarity networks and chromosome-specific SNP linkage disequilibrium (LD) networks through graph attention network (GAT)-based representation learning. Disease similarity networks were constructed from MeSH-based disease relationships, while SNP LD networks were generated from Phase 1 and Phase 3 datasets of the 1000 Genomes Project under multiple LD thresholds. DeepDisSNP independently learns disease and SNP embeddings using weighted GAT encoders and subsequently predicts disease-SNP associations using a multilayer perceptron classifier. Extensive experiments across all 22 autosomal chromosomes demonstrated that DeepDisSNP consistently outperformed the state-of-the-art DisSNPNet framework under multiple experimental settings. Under the best-performing configuration, DeepDisSNP achieved AUROC and AUPRC values of approximately 0.96 and 0.95, respectively. Additional analyses demonstrated robustness across LD thresholds, 1000 Genomes Project phases, and increasingly imbalanced negative sampling settings. External GWAS resources, including NHGRI-EBI GWAS Catalog, PhenoScanner, and OpenGWAS, provided supportive biological evidence for many highly ranked predicted associations. Functional enrichment analyses further suggested biological relevance of the predicted SNP-associated genes. Overall, DeepDisSNP provides an effective network-based framework for large-scale disease-SNP association prioritization and may facilitate downstream genomic and translational research.

Repeated high-pressure water rubber removal can damage the surface texture of airport cement concrete pavements and reduce skid resistance. To address this problem, three composite coating systems, namely styrene-acrylic copolymer emulsion (H), water-based epoxy (S), and pure water (N), were developed and evaluated by laboratory tests. Within the tested thickness range, the pull-off force reached its maximum at a coating thickness of 3 mm, and the S coating showed the highest adhesion to concrete. Compared with the uncoated surface, the mean profile depth increased by 84.3, 60.0, and 32.8% for the H, S, and N coatings, respectively, while the slope spectral density peak wavelength shifted from 1.78 to 0.5-0.6 mm. The British Pendulum Number increased by 39.5, 31.8, and 21.5% for the H, S, and N coatings, respectively, and showed a strong positive correlation with mean profile depth (R2 = 0.959). After 100 freeze-thaw cycles, the S-series coatings showed the best durability, with coating retention rates up to 98% and a relative dynamic modulus of elasticity of about 89%. Overall, H was more effective for surface texture reconstruction and skid-resistance improvement, whereas S provided better bonding performance and freeze-thaw durability. These results demonstrate the potential of the proposed coating systems for rapid surface repair of cement concrete pavements.

The goal of this study was to investigate the impact of absolute pitch (AP) on statistical learning and on cross-modal associative learning. Previous studies have demonstrated that compared to non-musicians, musicians have an advantage in statistical learning and that musical expertise leads to a reorganization in the network supporting statistical learning. As the brains of AP possessors show stronger connectivity in this network, we hypothesized that they show a further advantage in statistical learning. We used a paradigm with fixed tone-color pairs presented to participants in a stream of adjacent three-element sequences. We assessed statistical learning by asking participants subsequently to give frequency judgements for presented and not presented sequences. We assessed cross-modal associative learning of tone-color pairs by probing memory for the colors that were presented with each tone. We compared musicians with AP (N = 24), musicians without AP (N = 22), and a non-musician control group without AP (N = 20). The results showed an advantage in statistical learning for both groups of musicians. AP musicians had a long-lasting advantage in the incidental learning of tone-color associations (indicated by follow-up assessments after one week and one month). One third of the musicians with AP also had sound-color synesthesia (N = 7), and additional analyses revealed that they had a unique statistical learning advantage. The results indicate that musical expertise, AP, and synesthesia provide specific learning advantages. We suggest that the results can be best explained in a framework that considers for each group of participants the different experiential consequences of the task requirements.

Hypoxia is associated with poor outcomes in soft tissue sarcoma (STS) and is linked to increased expression of hypoxia-inducible factor 1-alpha (HIF-1α), carbonic anhydrase IX (CAIX), and lysyl hydroxylase 2 (PLOD2). These factors are potential therapeutic targets. This exploratory study aimed to investigate the correlation between 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET) imaging, a marker of hypoxia, and the expression of these biomarkers in STS. This imaging phase II clinical trial (NCT #03730077) recruited 5 patients with suspected soft tissue sarcoma (STS) and imaged these patients with 18F-Fluorodeoxyglucose (18F-FDG) and 18F-FMISO within 2 weeks of each other. STS tissue was analyzed for HIF-1α, CAIX, and PLOD2 expression using immunohistochemistry and western blotting. Collagen formation was assessed by Masson's trichrome. In this small sample, a correlation was found between STS size and PLOD2 expression (r = 0.996, P = 0.004). STS grade correlated positively with 18F-FMISO T/M (tumor/muscle) SUVmax (r = 0.894, P = 0.041). 18F-FDG correlated positively with 18F-FMISO SUVmax (r = 0.994, P = 0.006). Positive but non-significant associations were noted between 18F-FMISO T/M SUVmax and CAIX (r = 0.95, P > 0.05) and PLOD2 (r = 0.93, P > 0.05). These preliminary observations in a small sample are hypothesis-generating at best and must be interpreted with substantial caution due to the extremely limited number of patients, which precludes robust statistical inference and generalizability. No definitive conclusions can be drawn regarding the relationship between 18F-FMISO uptake and hypoxia biomarker expression. Larger, adequately powered prospective studies are essential to validate these findings, clarify potential correlations, and determine the clinical utility of 18F-FMISO PET/CT as a noninvasive hypoxia biomarker in STS.

Hormone and sugar signalling pathways have evolved from intermediates of central metabolic flow into conserved core interacting regulatory modules that balance resource acquisition and growth. Hormones play extensive yet often specialised functions, whereas sugar signalling through trehalose 6-phosphate (T6P) is active throughout plant development to integrate sucrose availability into all aspects of growth and physiology. Interaction between T6P and hormones is an emerging area and the focus of this review. The best mechanistically understood interactions are between T6P and auxin, strigolactones and abscisic acid (ABA), with reciprocal interaction for auxin-T6P and ABA-T6P. These interactions regulate root and shoot branching, seed development and stomatal function and converge on SnRK1 and TOR as a major integrating hub. Analysis of cis-acting regulatory elements in the promoters of Arabidopsis trehalose phosphate synthase (TPS) and trehalose phosphate phosphatase (TPP) genes confirms auxin and ABA as major regulators of TPSs and TPPs with an indication also of strong regulation by methyl jasmonate. Intervention in crop improvement will come from understanding how to disrupt the productivity-survival trade off regulated by T6P-hormones that has evolved in the natural environment.

The MD Anderson Radiation Quality Assurance Lab (including its IROC activities) monitors more than 2500 radiotherapy facilities worldwide to ensure accurate radiotherapy delivery. This study reviews the 30-year history of the RQALab's anthropomorphic phantom program for advanced photon therapy. The RQALab offers anthropomorphic phantoms as end-to-end tests of the accuracy of advanced radiotherapy. Phantoms are mailed to the institution where they are treated like a patient, including planning and delivery, and are returned to the RQALab for analysis. Several types of phantoms exist that test IMRT, motion management, SBRT, SRS, multi-target delivery, and more. Institutions may perform this audit as an internal quality assurance test or as a credentialing requirement to participate in clinical trials. Passing criteria typically require the dose to be within 5-7% and 3-4 mm. A total of 9,879 photon phantoms have been irradiated since 1996, most frequently the IMRT H&N phantom (3,429), moving lung phantom (2,788), and SRS phantom (1,898). Overall, the average pass rate is 86.4%, with the highest pass rate seen for the IMRT H&N phantom (89%) and the lowest pass rate seen for the moving multi-target liver phantom (73%). Overall, pass rates have significantly increased with time, which is particularly noteworthy because treatments have gotten more complex over this time period. Independent audits of radiotherapy practice continue to highlight challenges in implementing advanced radiotherapy. As such, they serve an important role in the community, helping guide individual clinics and the community at large, to achieve best practice.

Injection opioid use is associated with fatal and non-fatal harms including accidental overdose and infectious diseases. Syringe service programs offer sterile injection equipment and safer injection training to reduce the incidence of injection-related harms. Nevertheless, factors that might reduce adherence to safer injection practices are understudied. This report explores pain as one such factor. People who inject opioids (n&#x2009;=&#x2009;130) were recruited from a syringe service program for a cross-sectional survey assessing the relationship between fluctuations in pain severity and adherence to safer injection practices over the past 7&#xa0;days. A within-subjects Sign Test analysis revealed participants' adherence to safer injection practices fluctuated with changes in pain severity. When their pain was at its worst, participants reported they less often engaged in hand washing (Z -5.63, P&#x2009;<&#x2009;.001), cleaning the injection site (Z -5.29, P &#x2009;<&#x2009;.001), and waiting until in a clean safe place to inject (Z -3.94, P&#x2009;<&#x2009;.001). Additionally, they more often reused their own injection equipment (Z -2.55, P&#x2009;=&#x2009;.011), and injected faster, or at a higher dose (Z -2.71, P&#x2009;=&#x2009;.007) when in worse pain. This study provides initial evidence that pain is associated with reduced adherence to safer injection practices among people who inject opioids. Although all study participants received training in safer injection practices and cost-free sterile injection equipment, within-subject adherence to safer use practices varied significantly under conditions of best and worst pain.

Early-career operating room nurses work in highly technical, high-demand environments and are at elevated risk of stress, stalled development and turnover. Yet little is known about how their career growth patterns differ, or which resource configurations are associated with more favorable profiles. Guided by Conservation of Resources (COR) theory, this study aimed to (1) identify latent profiles of career growth among early-career operating room nurses and (2) examine how COR-based foundational resource indicators and selected work-related psychological and organisational variables are associated with these profiles. We conducted a multicenter cross-sectional online survey between March and August 2025 among early-career operating room nurses working in tertiary hospitals in Zhejiang Province, China. Using multicentre convenience sampling, 516 nurses from 102 hospitals provided valid responses. Career growth was assessed using the Career Growth of Nurses Scale. Guided by COR theory, resource-related indicators and selected work-related psychological and organisational variables were examined in relation to profile membership. Latent profile analysis was used to identify distinct career growth profiles. Multinomial logistic regression examined associations between resource variables and profile membership, with statistical significance set at &#x3b1;&#x2009;=&#x2009;0.05. A three-profile solution provided the best fit to the data. We identified three latent classes based on cross-sectional response patterns: a lower-level uneven group (C1, n&#x2009;=&#x2009;66, 12.8%), a moderate-level balanced group (C2, n&#x2009;=&#x2009;238, 46.1%), and a higher-level comprehensive group (C3, n&#x2009;=&#x2009;212, 41.1%). Compared with C1, formal employment contracts, employment in higher-tier hospitals, higher monthly income, better self-rated health, and stronger interest in the nursing profession were cross-sectionally associated with higher odds of membership in C2 and C3. Higher thriving at work, organisational commitment, and perceived organisational career management were also cross-sectionally associated with membership in the more favorable profiles. The examined object resource (homeownership status) was not associated with profile membership in the univariate analysis and was therefore not retained in the adjusted model. Early-career operating room nurses showed heterogeneous patterns of career growth, which could be classified into three profiles: a lower-level uneven profile, a moderate-level balanced profile, and a higher-level comprehensive profile. Multiple resource-related indicators were associated with more adaptive profile membership among early-career operating room nurses. These findings suggest that career growth is linked to the combined influence of employment, organisational, health, motivational, and work-related psychological factors rather than any single dominant factor. Nurse managers can use these findings to design resource-focused strategies and targeted development programs to support sustainable career growth and retention among early-career operating room nurses.

This study compared the relative effectiveness of different inspiratory muscle training (IMT) modalities within intensive care unit-acquired weakness (ICU-AW) prevention and rehabilitation strategies using network meta-analysis (NMA) and component network meta-analysis (CNMA). A systematic search of electronic databases in both Chinese and English was conducted to identify randomized controlled trials (RCTs) enrolling adult patients (&#x2265;&#x2009;18 years) admitted to the intensive care unit (ICU). Eligible studies evaluated strategies for the prevention and rehabilitation of ICU-AW, including inspiratory muscle training IMT-related interventions, systemic physical rehabilitation, and their combinations. The Cochrane Risk of Bias 2 (RoB2) tool was used to assess the risk of bias in the included RCTs, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to evaluate the quality of the evidence. Heterogeneity was initially assessed using conventional pooled analyses and was not used as the sole criterion for model selection in the subsequent NMA. Outcomes with substantial heterogeneity were further analyzed using random-effects NMA, for which 95% prediction intervals (PIs) were additionally reported. For outcomes with low apparent heterogeneity, fixed-effect NMA was applied, with heterogeneity interpreted in light of clinical and methodological diversity across studies. Component network meta-analysis (CNMA) was additionally conducted to quantify the independent treatment effect of each intervention component. For continuous outcome measures (Medical Research Council [MRC] score, maximal inspiratory pressure [MIP], and duration of mechanical ventilation [MV]), results were presented as mean differences (MDs) and their 95% confidence intervals (CIs). For binary outcome measures (incidence of ICU-AW and weaning success rate), treatment effects were expressed as odds ratios (ORs) with 95% CIs. A total of 23 eligible randomized controlled trials (RCTs) were included in this analysis, which evaluated 11 distinct intervention strategies. These strategies were categorized into 5 multicomponent interventions and 6 single-component interventions. The 6 single-component interventions included 4 IMT modalities, a systemic physical rehabilitation intervention, and routine care, which was designated as the reference control group. Compared with the routine care reference group, mechanical threshold showed a non-statistically significant trend toward lower ICU-AW incidence (OR&#x2009;=&#x2009;0.19, 95% CI [0.04, 1.01]); hence, the best-ranked results based on SUCRA should be interpreted as exploratory findings only. The combination of systemic physical rehabilitation and routine inspiratory muscle training was associated with improved MRC scores and higher weaning success rates. For MIP, the combination of systemic physical rehabilitation and mechanical threshold achieved the highest ranking. CNMA further indicated that the addition of systemic physical rehabilitation to mechanical threshold was associated with incremental therapeutic benefit. For duration of MV, combined strategies incorporating systemic physical rehabilitation and IMT also ranked favorably; however, this outcome was associated with a higher degree of uncertainty and should be interpreted with caution. According to the GRADE approach, the certainty of evidence was rated as low for the incidence of ICU-AW, moderate for the MRC score, weaning success rate, and MIP, and very low for the duration of mechanical ventilation. While combined interventions incorporating systemic physical rehabilitation and IMT ranked highest across multiple outcomes, evidence supporting the superiority of any specific IMT regimen over another remains limited. For MIP, CNMA further demonstrated that the addition of systemic physical rehabilitation to mechanical threshold was associated with a statistically significant incremental therapeutic benefit compared with mechanical threshold alone, although definitive isolation of the independent effects of most individual components was not possible. Overall, these findings provide a more differentiated assessment of IMT-related strategies within ICU-AW prevention and rehabilitation. However, the overall certainty of evidence ranged from moderate to very low across all outcomes according to the GRADE framework, highlighting the need for further high-quality randomized controlled trials to validate these findings. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251208302.

To analyse and compare cost consequences of two evidence-based non-surgical periodontal treatment protocols performed by dental hygienists (DHs) in general practice. Six-hundred and fifteen patients were included. Treatment approaches compared were (i) conventional non-surgical therapy (CNST), often performed at multiple sessions, and (ii) a 'full-mouth' concept called guided periodontal infection control (GPIC), with initial focus on patient education followed by one session of ultrasonic instrumentation. A cost consequence analysis was conducted regarding the two approaches, including treatment costs, travelling costs and productivity costs, as well as non-monetary consequences (closed pockets and bleeding on probing). In data analysis, the 95% confidence intervals were obtained using the percentile method based on 5000 bootstrap replications. Treatment costs were higher for CNST compared to GPIC by &#x20ac;60 (&#x20ac;359.5 [95% CI: 345.5-374.2] vs. &#x20ac;299.4 [95% CI: 289.3-309.1]). Productivity costs related to treatment were also greater in CNST by +&#x20ac;15. Travel costs showed minor differences (+&#x20ac;1 for CNST). Non-monetary outcomes showed no significant differences between groups. CNST was more costly than GPIC while maintaining comparable clinical outcomes at 6&#x2009;months. When designing policy and practice for non-surgical treatment approaches, both evidence-based practice and how shared resources are best used should be acknowledged.

Ion channels are central to regulating neuronal communication, cardiac rhythm, and muscle contraction. Their modulation can induce therapeutic benefits but may also lead to adverse or toxic effects. This study presents IonNTxPred, a protein language model (PLM)-based method for predicting protein ion channel modulators, including channel-specific (such as sodium, potassium, calcium, and others) and moonlighting proteins capable of modulating multiple ion channels. We train, test, and evaluate our models on the largest dataset of non-redundant ion channel modulating proteins, where no two proteins have more than 40% sequence identity. Composition analysis revealed that residues Cys, Gly, and Trp are highly prevalent, whereas Ala, Glu, Leu, Gln, and Val are scarce in ion channel modulating proteins, with Cys identified as a key discriminative residue. We explored both alignment-based (BLAST, MERCI) and alignment-free (machine learning, deep learning, and PLM-based) approaches. Among these, our evolutionary information-based PLM (ESM2-t33) achieved the best performance, with an AUROC of 0.97 across ion channels, which further improved to 0.98 when integrated with BLAST output. The proposed method outperformed existing approaches on independent datasets. We used IonNTxPred to screen FDA-approved and organismal proteins to identify candidates with ion channel modulating potential, supporting drug repurposing, discovery of new therapeutic proteins, and safety assessment of existing biologics. We implemented these models in a user-friendly web server, IonNTxPred, which facilitates the design and discovery of ion channel modulating protein-based drugs and supports the biosafety evaluation of therapeutic proteins through neurotoxin screening (https://webs.iiitd.edu.in/raghava/ionntxpred/).

Accurate restoration of femoral offset (FO) and head center in total hip arthroplasty (THA) is critical for joint function, yet the intraoperative range of achievable stem positions remains unquantified. This study developed and validated a fully automated CT-based virtual implantation algorithm that maps patient- and implant-specific "feasibility spaces" of achievable postoperative femoral head center locations to identify best-fit stem-head configurations. Eight cadaveric specimens (16 hips) underwent bilateral THA with a cementless femoral stem. Preoperative CT and postoperative optical scans were used to quantify native anatomy and stem positions. The algorithm segmented the boundaries of femoral canal and probabilistically simulated valid 3D stem alignments across multiple component sizes to generate feasibility spaces. Validation was performed by comparing experimental stem positions to the closest predicted virtual alignments. Experimentally, head centers deviated 12.7&#xa0;&#xb1;&#xa0;4.8&#xa0;mm from native targets. The algorithm predicted these placements within 1.9&#xa0;&#xb1;&#xa0;0.5&#xa0;mm. The feasibility spaces exhibited a conical distribution with an inferior apex, and all implanted head centers clustered on the medial boundary. For each specimen, at least one stem-head option produced a feasibility space within 5&#xa0;mm of the native head center. The anterior-posterior controllable ranges (11.2-35.7&#xa0;mm within 10&#xa0;mm superior seating) significantly exceeded medial-lateral ranges (4.2-14.4&#xa0;mm), with both expanding with superior stem seating. This framework shifted single static templating to dynamic templated volumes of surgical control. By quantifying the "forgivingness" of patient-specific anatomy, this tool enables systematic risk stratification and objective implant design comparison, providing a foundation to minimize biomechanical errors and enhance surgical consistency across diverse populations.