Brain metastases (BrM) are a major cause of morbidity among patients with breast cancer (BC), particularly those with HER2+ or triple-negative disease. The relationship between neoadjuvant chemotherapy (NAC) and subsequent risk of BrM in patients with early-stage BC remains poorly defined. We conducted a single-centre retrospective cohort study of 457 consecutive patients who were treated with NAC for early-stage BC at Sunnybrook Odette Cancer Centre between 2008 to 2019, among whom 25 developed BrM (cohort 1). To evaluate factors associated with shorter time to BrM development, an additional 129 patients with BC who received NAC and were subsequently diagnosed with BrM were identified (cohort 2). Descriptive statistics were used to summarize patient and treatment characteristics. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and identify factors associated with the development of BrM. Univariable analyses (UVA) were performed for all covariates. Bayesian Information Criteria determined best models from subsets of covariates when performing multivariable analyses (MVA). Among 586 patients, the median age at BC diagnosis was 49.0 (IQR: 42-58) years. The most common BC subtype was HER2+ (n = 225, 38.4%), followed by hormone receptor (HR)+/HER2- (n = 213, 36.3%) and triple negative BC (n = 132, 22.5%). Following NAC, 134 patients (22.9%) had a pathologic complete response (pCR) and 409 (69.8%) had residual disease. In the overall cohort, the median time from BC diagnosis to BrM development was 38.0 (IQR 19.1-70.9) months. In cohort 1, 25 patients (5.5%) developed BrM with a median follow-up of 43.1 months. Median time to BrM was shortest for patients with triple-negative BC (18.0 months), followed by those with HER2+ (32.0 months), and HR+/HER2- disease (49.1 months). In the pooled cohort (n=586), multivariable analysis identified residual nodal involvement (HR 4.46 [95% CI 2.67-7.45], p<0.0001), inflammatory BC (HR 3.11 [95% CI 1.95-4.96], p<0.0001), and HER2+ or triple-negative subtype (HR 2.87 [95% CI 1.80-4.58], p<0.0001) as independently associated with shorter time to BrM development. Among patients treated with NAC for early-stage BC, residual nodal disease, inflammatory BC, and HER2+ or triple-negative subtype are associated with a higher risk of BrM development. Whether BrM screening is warranted among patients with these high-risk features warrants evaluation. Not applicable.
Accurate prognostication after aneurysmal subarachnoid hemorrhage (aSAH) remains challenging. Conventional clinical and radiological grading systems, including the World Federation of Neurosurgical Societies (WFNS), Hunt-Hess, and Fisher scales, are widely used but have limited discriminative capacity. This study aimed to systematically compare machine learning (ML)-based prognostic models with conventional grading systems for predicting functional outcomes and mortality after aSAH, and to evaluate factors influencing ML performance. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched for studies published between 2010 and 2025. Eligible studies evaluated ML-based models for outcome prediction in adult aSAH patients and reported performance of conventional grading systems. Prognostic discrimination was pooled using random-effects meta-analysis of the area under the receiver operating characteristic curve (AUC), with predefined subgroup analyses. Fourteen studies including 6,247 patients were analyzed. ML models demonstrated good to excellent discrimination, with AUCs ranging from 0.81 to 0.97. The pooled ML AUC for predicting unfavourable neurological outcome was 0.86 (95% CI 0.83-0.89; p < 0.0001), with substantial heterogeneity (I² = 96.1%). ML models outperformed conventional grading systems in most studies and showed comparable performance in the remainder. Subgroup analyses confirmed statistically significant prognostic accuracy across clinical-only, imaging-based, and multimodal ML models. Machine learning-based prognostic models demonstrate statistically significant and clinically meaningful performance for outcome prediction after aSAH, exceeding conventional grading systems and supporting their role as complementary risk stratification tools.
Concussions are increasingly common in older adults, with falls as the leading mechanism of injury. Older adults often experience prolonged recovery, and lingering post-concussive symptoms, perpetuating the cycle of elevated fall risk with significant public health implications. This highlights the need for age-specific concussion care incorporating multidomain assessment and individualized treatment. This retrospective case series explores the effect of a structured, stepwise evaluation and treatment framework on post-concussive symptoms in older adults. Five females over 60 years old with post-concussive symptoms completed the targeted concussion protocol as part of a larger prospective study. The protocol included modules addressing key rehabilitation domains: aerobic exercise to support autonomic regulation, brain-body integration exercises to improve motor control, and progressive visual-vestibular rehabilitation incorporating oculomotor training, postural stability challenges, and dual-tasking. Objective measures included the Post-Concussion Symptom Scale, Brain Injury Vision Symptom Survey (BIVSS), Dizziness Handicap Inventory, King Devick, a binocular vision screening tool, and an enhanced version of the Vestibulo-Oculomotor Screen (VOMS). All patients demonstrated reduced symptom burden and functional improvements. Vestibular-oculomotor and motor control gains included a 53.9% average improvement in BIVSS scores, a mean 10-s reduction in King Devick time, and a 19.05-cm improvement in binocular vision measured via Brock String. Three patients normalized ocular alignment and near point convergence, while all showed improved Super Saccades performance. Participation in a multimodal protocol shows potential in reducing post-concussive impairments and symptoms in older adults. Larger studies are needed to establish effectiveness and feasibility in this population.
Piperacillin/tazobactam (TZP) is widely used in hospitalised adults. Real‑world data suggest a higher risk of hypokalaemia than previously recognised. To investigate incidence, severity and risk factors of TZP‑induced hypokalaemia, and to develop and externally validate a nomogram for individualised risk prediction. This retrospective study included hospitalised adults receiving TZP (2021-2025). TZP‑induced hypokalaemia was defined as serum potassium < 3.5 mmol/L ≥ 48 h after TZP initiation. Logistic regression identified predictors. A nomogram was constructed. Model performance was assessed by discrimination (area under the ROC curve, AUC), calibration (Hosmer‑Lemeshow test, calibration intercept/slope), Brier score and decision‑curve analysis (DCA), with internal and external validation. Among 643 patients, 122 (19.0%) developed TZP‑induced hypokalaemia (mild: 78.7%; moderate: 16.4%; severe: 4.9%). Median time to onset was 5.0 days. Independent predictors were age ≥ 65 years (OR = 2.118, 95% CI 1.003-4.472, p = 0.049), body mass index (OR = 0.671, 95% CI 0.591-0.762, p < 0.001), intensive care unit admission (OR = 2.915, 95% CI 1.504-5.651, p = 0.002), daily dose (OR = 1.280, 95% CI 1.110-1.476, p < 0.001), and baseline serum potassium (OR = 0.123, 95% CI 0.056-0.271, p < 0.001). The nomogram showed good discrimination (training AUC 0.881, internal 0.876, external 0.813), calibration (Hosmer‑Lemeshow p > 0.05), Brier scores < 0.25 and positive net benefit on DCA. TZP‑induced hypokalaemia is common in hospitalised adults. A nomogram based on five readily available clinical variables may facilitate early identification of high‑risk patients, although prospective validation in diverse settings is required before clinical implementation.
Survival rates for pediatric acute lymphoblastic leukemia (ALL) have markedly improved; however, survivors remain at risk of long-term hepatic complications, including progressive fibrosis related to chemotherapy and prior viral infections. The objective of this study is to evaluate hepatic fibrosis in pediatric ALL survivors using a sequential non-invasive algorithm combining transient elastography (TE) and enhanced liver fibrosis (ELF) score. This comparative cross-sectional study included 159 pediatric ALL survivors who had completed therapy at least 2 years earlier and 99 age- and sex-matched healthy controls from two Egyptian oncology centers. Liver fibrosis was assessed using TE and serum biomarkers for calculation of the ELF score. The mean age at diagnosis was 6.9 ± 2.7 years, and at assessment, 11.1 ± 2.7 years. Hepatitis C virus (HCV) prevalence declined significantly from 75% during treatment to 5% at enrollment following antiviral therapy (p < 0.001). Fibrosis was detected in 75% of survivors by TE, predominantly moderate (F2) fibrosis. Combined TE/ELF assessment identified advanced fibrosis (≥ F3) in 6% of patients, while most survivors had mild-to-moderate fibrosis. Mean ELF score was significantly higher in survivors than controls (9.3 ± 1.2 vs. 4.5 ± 1.03, p < 0.0001). Agreement between TE and ELF was fair (Cohen's κ = 0.34-0.39). HCV-positive survivors had significantly higher ELF scores than HCV-negative peers.Conclusion: Persistent hepatic fibrosis in pediatric ALL survivors was observed predominantly among patients with current or previous HCV exposure. A combined TE/ELF approach represents an effective non-invasive strategy for early detection and monitoring.
The comparative effects of non-insulin glucose-lowering therapies on coronary plaque progression in type 2 diabetes (T2DM) remain unclear. This study aimed to evaluate the impact of five major classes of non-insulin therapies on the progression of coronary atherosclerosis using serial coronary computed tomography angiography (CCTA). This was a retrospective, registry-based cohort study analyzing 880 serial CCTA scans from patients with T2DM enrolled in the TOCCATA (Tomography of Coronary Artery Plaque and Treatment) registry. Patients were stratified based on their prescribed therapy: metformin (n = 357), dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 97), glucagon-like peptide-1 receptor agonists (GLP-1 RAs, n = 88), sodium-glucose cotransporter-2 inhibitors (SGLT2i, n = 258), and thiazolidinediones (TZDs, n = 80). The primary endpoints were vessel-level stenosis progression and changes in patient-level plaque scores, including the Maximum coronary stenosis score (MAXS), segment involvement score (SIS), and segment stenosis score (SSS). Multivariable Cox regression models, adjusted for relevant covariates, were used for the analysis. GLP-1 RAs were associated with the most significant reduction in vessel-level stenosis progression (adjusted Hazard Ratio [HR] 0.68, 95% Confidence Interval [CI]: 0.49-0.95, p = 0.024). This therapy class also consistently inhibited patient-level plaque progression across all scores (MAXS: HR 0.34, p = 0.002; SIS: HR 0.34, p < 0.001; SSS: HR 0.41, p < 0.001).In contrast, SGLT2i showed no significant effect on stenosis progression (HR 0.99, 95% CI: 0.82-1.19, p = 0.90) or SSS progression (HR 1.23, 95% CI: 1.00-1.52, p = 0.055). DPP-4 inhibitors showed a trend toward increased stenosis progression (HR 1.31, 95% CI: 1.01-1.69, p = 0.039). Metformin and TZDs had neutral effects on plaque progression. In this real-world cohort of patients with type 2 diabetes, GLP-1 receptor agonists were associated with significantly slower coronary plaque progression compared to other glucose-lowering therapies. Other therapies, including SGLT2i, demonstrated no similar protective effects. These findings suggest that GLP-1 receptor agonists may offer particular benefits for patients with advanced atherosclerosis and underscore the potential value of CCTA in informing personalized therapeutic decisions in type 2 diabetes management.
This study investigated 11 psychoactive contaminants in wastewater influents at a municipal wastewater treatment plant in Slovakia between 2015 and 2018, based on 44 samples collected under regular conditions and an additional five samples collected during two music festivals in 2018. In addition, 17 progestagens were analyzed only in 2018 during festival days and their corresponding background days. Seasonal variation in normalized mass loads was generally minor, whereas interannual differences were more pronounced, particularly for psychoactive pharmaceuticals, which showed an overall decrease in 2018. Short-term but substantial increases in contaminant loads were observed during the festivals. During the multi-genre music festival, the normalized mass load of 3,4-methylenedioxymethamphetamine increased by more than 110-fold on the second festival day compared to the pre-festival average, while benzoylecgonine increased approximately 17-fold and dienogest by 1.3-fold. During the country/folk music festival, tramadol loads increased approximately twofold. Principal component analysis explained 70.75% of the total variance using the first two components and revealed a clear separation between festival and background samples. Overall, the results demonstrate that music festivals represent episodic pollution events capable of markedly altering wastewater influent composition over short time periods.
Ethnic inequalities in cancer care have long been a concern in the UK, with minoritised populations facing inequalities in access, diagnosis, treatment, and outcomes. The COVID-19 pandemic exacerbated these inequities, worsening barriers to care. This narrative literature review, which incorporates a systematic search, examines the impact of the pandemic on ethnic inequalities in cancer care in the UK. Findings indicate that due to the pandemic, ethnic minority patients experienced lower screening uptake, greater delays in diagnosis, and reduced access to timely treatment. GP referral thresholds were higher for ethnic minority groups, leading to later-stage diagnoses, while emergency presentations and treatment delays were more frequent. Systemic healthcare pressures and communication gaps further contributed to inequalities. Addressing these inequities requires urgent policy interventions, including improved access to screening, equitable referral processes, and culturally sensitive care pathways. Further research is needed to assess post-treatment outcomes and evaluate targeted interventions. As the NHS recovers from the COVID-19 pandemic's disruptions, ensuring equitable access to high-quality cancer care for all ethnic groups must remain a priority.
BARD1 germline pathogenic variants (gPV) have been primarily associated with moderate breast cancer risk but their rarity limits accurate risk assessment and tailored follow-up guidelines. Our study evaluates the association between BARD1 gPV and breast cancer while exploring the role of BARD1 in mammary oncogenesis. In this case-control study, 7,309 women with breast cancer and no gPV identified in the French hereditary breast and ovarian cancer (HBOC) gene panel at the Institut Curie were compared to 57,681 female controls from the gnomAD European non-cancer database. Tumors were analyzed for biallelic BARD1 inactivation and homologous recombination deficiency (HRD). A significant association was observed between BARD1 gPV and breast cancer (OR = 5.2, 95% CI [3-8.9], p = 5.9 × 10- 9). Molecular data were obtained and interpretable for seven tumors. Among these, two triple-negative (TN) primary tumors exhibited both biallelic BARD1 inactivation via loss of heterozygosity (LOH) and an HRD phenotype; one metastasis displayed LOH without HRD. All non-TN primary tumors lacked both biallelic inactivation and HRD. We found a strong enrichment of BARD1 gPV among women selected for personal and family history of breast cancer, reinforcing their relevance for genetic testing for suspected hereditary predisposition. Tumor analysis suggests a potential association between biallelic inactivation of BARD1 and the HRD phenotype in TN primary breast tumors, providing new treatment perspectives.
Aquaculture intensification is increasingly recognized as a strategic pathway to fight food insecurity. It is also harnessed to meet the rising global demand for high-quality animal protein. This has led to a growing need for fish seed and a heightened concerned for broodstock nutrition, reproductive efficiency, and quality of seeds. In the present study, reproductive responses of African catfish Heterobranchus bidorsalis broodstock were evaluated at graded levels of ethanolic Moringa oleifera leaf extract (EMOLE) as a phytogenic feed additive. A total of 84 broodstock (800.00 ± 150.00 g) were randomly assigned to 4 isonitrogenous (40% crude protein) diets containing 0.0% (control), 1.0%, 2.0% and 3.0% EMOLE in a completely randomized design with three replications. Fish were fed at 5% body weight, twice daily for 16 weeks. Reproductive indices assessed included milt motility, sperm morphology, milt volume and concentration, gonadosomatic index, egg diameter, fecundity, fertilization rate, hatching rate, and hatchling survival. Data were analyzed using descriptive statistics, one-way analysis of variance at α 0.05, using SPSS 20 software. Results showed that dietary EMOLE significantly improved reproductive performance. Fish fed 3.0% EMOLE exhibited the highest sperm motility (92.00 ± 2.31%), sperm concentration (225.33 ± 0.02 × 10⁶ ml⁻1), fecundity (6118.00 ± 200.70), fertilization rate (78.63 ± 0.51%), hatchability (78.20 ± 0.67%), and larval survival (78.07 ± 1.27%). Sperm abnormalities were significantly reduced in supplemented groups. These findings indicate that 3.0% EMOLE can serve as a natural phytogenic feed additive for improving gonadal development and reproductive performance in Heterobranchus bidorsalis broodstock. This further places Moringa as a natural, cost-effective phytogenic additive for enhancing broodstock performance and sustainable seed production.
 Lymph node metastasis (LNM) is a crucial prognostic indicator in perihilar cholangiocarcinoma (pCCA); however, preoperative tools for assessing LNM risk and determining the optimal extent of lymph node (LN) dissection remain limited. This study aimed to identify preoperative LNM predictors to guide regional LN dissections. This multi-institutional retrospective study included 364 patients who underwent curative-intent pCCA resection (2020-2024). Multivariate logistic regression was used to identify independent predictors of preoperative LNM. Eventually, 148 (40.7%) patients were pathologically LNM-positive. The independent preoperative predictors were age < 65 years (odds ratio [OR]: 1.634, P = 0.041), carbohydrate antigen 19-9 (CA19-9) ≥ 200 U/mL (OR: 1.868, P = 0.006), and imaging suspicion of LNM (OR: 2.863, P = 0.001). The high-risk group (imaging suspicion of LNM + CA19-9 ≥ 200 U/mL or age < 65 years) had a 66.0% pathological LNM rate, and ≥ 6 LN dissections significantly improved recurrence-free survival (RFS) compared to < 6 LN dissections (P = 0.002). The low-risk group (no risk factors) had a 23.5% pathological LNM rate, and no RFS difference was observed between the groups (P = 0.360). Preoperative imaging suspicion of LNM, elevated CA19-9 levels, and younger age can effectively identify the high-risk group with LNM in pCCA. Adequate LN dissection may be associated with improved recurrence-free survival in the high-risk group, suggesting a risk-stratified approach to the extent of LN dissection.
Injection site reactions (ISRs) are a key consideration when selecting long-acting injectables (LAIs), and are central to healthcare provider (HCP) and patient shared decision-making. We evaluated the acceptability of ISR profiles alongside participant and HCP-reported preferences for long-acting cabotegravir (CAB LA) and lenacapavir (LEN LA). CLARITY (NCT06970223) is an open-label, randomized, crossover study. Adults without HIV received single-dose CAB LA (intramuscular) and LEN LA (subcutaneous) on Days 1 and 15 (randomized so either CAB LA or LEN LA was the first injection). The primary endpoint was the proportion of participants reporting "very acceptable or totally acceptable" local reactions and pain 7 days post-injection using the Perception of Injection (PIN) questionnaire. Secondary endpoints included characterization of the ISR profile. Exploratory endpoints included participant and HCP preferences and participant perspectives using questionnaires and interviews. Overall, 61 participants received CAB LA and 62 received LEN LA. A higher proportion of participants reported local reactions and pain as "totally or very acceptable" with CAB LA injections versus LEN LA [69% (42/61) vs. 48% (29/60); odds ratio, 3.4 (95% CI, 1.25 to 9.22); P < 0.019 post hoc]. CAB LA consistently showed more favorable PIN domain and individual items of assessment scores versus LEN LA. CAB LA demonstrated a favorable ISR profile versus LEN LA, including fewer visible ISR events (36 vs. 221). Ninety percent (54/60) of participants preferred CAB LA, whereas 10% (6/60) preferred LEN LA; 86% (6/7) of HCPs preferred CAB LA and 14% (1/7) preferred LEN LA. Participants reported less pain during CAB LA versus LEN LA injections. CAB LA was more acceptable than LEN LA, had a more favorable ISR profile, and was preferred by a majority of participants and HCPs. These findings highlight differences in the injection experience that can inform shared decision-making when choosing LAIs.
Integrating high-throughput sequencing with phylogenetic analysis now spans everything from single genes to long-read pangenomes and metagenomes, yet practitioners still face fragmented, tool-centric guidance. This review revisits algorithms, tools, and workflows for sequence and phylogenetic analysis in the NGS-based omics era, with a focus on comparative performance and scenario-driven decision-making. We first organise classical approaches to tree reconstruction - distance methods, maximum parsimony, maximum likelihood, and Bayesian inference - around core criteria of consistency, efficiency, robustness, and computational cost. We then examine multiple sequence alignment strategies, contrasting progressive, consistency-based, and structure-aware algorithms (such as MAFFT variants and T-Coffee family tools) with segment-based and incremental approaches (for example DIALIGN, anchored domains, and local updates) and alignment-free representations based on k-mers, absent words, and related statistics. For inference, we compare heuristic engines optimised for ultra-large alignments (FastTree, VeryFastTree, online tree optimisation) with full ML frameworks (IQ-TREE, RAxML-NG) and Bayesian platforms for time-scaled phylogenies and phylodynamics (MrBayes, BEAST family). We explicitly discuss trade-offs in accuracy, memory, scalability, and uncertainty support, and show how GPU-enabled implementations change the feasible design space. Beyond these core components, we address current trends that strongly influence method choice: long-read assemblies and pangenomes; data quality issues, contamination, recombination, and horizontal gene transfer; phylogenetic placement and alignment-free screening in metagenomics; and real-time pathogen surveillance using Nextstrain-style workflows. A dedicated section covers workflow management and containerisation (Snakemake, Nextflow, Docker/Singularity) together with benchmarking datasets and FAIR reporting, positioning reproducible pipelines as a first-class requirement rather than an afterthought. To make the review directly actionable, we provide a methodological checklist, a decision framework figure mapping input data to recommended strategies, and a large comparative table summarising algorithmic principles, best use cases, strengths, limitations, scalability, uncertainty support, and reproducibility notes for widely used tools. Applications in infectious disease genomics, oncology, and microbiome research illustrate how these choices translate into biological and clinical insight in practice.
Rocbrutinib is a fourth-generation Bruton's tyrosine kinase (BTK) inhibitor that binds covalently to the wild type BTK and non-covalently to the cysteine 481 mutant variant. This phase I study evaluated the pharmacokinetics (PK), safety, and efficacy of rocbrutinib in Chinese patients with relapsed or refractory (R/R) non-germinal center B cell-like (non-GCB) diffuse large B cell lymphoma (DLBCL). Eligible participants were adults with non-GCB DLBCL and had received ≥ 2 prior lines of systemic therapy, including an anti-CD20 antibody-based regimen. Patients received rocbrutinib at 100, 150, 200 or 300 mg once daily (QD) as single agent till disease progression or unacceptable toxicity. Response was evaluated using computerized tomography (CT) and positron emission tomography (PET)-CT at the protocol-defined timepoints by the investigators. PK samples and adverse events were collected per protocol. A total of 45 patients were enrolled, of whom 44.4% had received ≥ 3 lines of therapy. The overall response rate (ORR) was 57.8% [95% confidence interval (CI): 42.2, 72.3], and the complete response (CR) rate was 33.3% (95% CI 20.0, 49.0). In the ≥ 200 mg QD cohort (n = 18), the ORR was 72.2% (95% CI 46.5, 90.3) and the CR rate was 44.4% (95% CI 21.5, 69.2). Treatment-emergent adverse events (TEAEs) were reported in 97.8% patients, ≥ grade 3 TEAEs in 51.1% patients. Due to TEAEs, 2 patients (4.4%) with dose reduction and 1 (2.2%) discontinued study treatment, respectively. No atrial fibrillation/flutter was reported. In the ≥ 200 mg QD cohort, the safety profile was consistent with the overall population. Rocbrutinib demonstrated promising efficacy and favorable tolerability profile in heavily pre-treated R/R non-GCB DLBCL. A 200 mg QD dose was selected as recommended phase 2 dose for monotherapy. A randomized phase II clinical trial in this population is currently enrolling. ClinicalTrials.gov identifier, NCT04993690.
Epicardial cryoablation is increasingly utilized in open surgical procedures for treatment of ventricular arrhythmias in patients with structural heart disease when percutaneous epicardial access cannot be obtained. There are limited data regarding the effects of cryoablation within ventricular scar tissue, particularly in comparison to the performance of radiofrequency (RF) catheter ablation. This study aimed to investigate the comparative performance of ablation delivered epicardially in an open chest animal model with a linear cryoprobe versus a radiofrequency catheter. An infarct model was created in five Yorkshire swine using microsphere injection into the left anterior descending artery. After 6-8 weeks, animals underwent median sternotomy with targeted epicardial RF ablation lesions, and linear cryoablation lesions were delivered to myocardial infarct scar regions. Specimens were pressure perfused with 10% formalin, and histological analysis was performed. Out of 25 epicardial RF lesions, 13 were visible and able to be analyzed. All 15 epicardial cryoablation lesions were visible. All 15 cryoablation lesions had transmural effect within scar where tissue thickness was ≤6 mm, whereas only 62% of evaluable RF lesions were transmural in scar (p = 0.01). Average cryoablation lesion depth was 4.2 ± 1.1 mm in scar and 5.6 ± 1.4 mm in border zone. Linear epicardial cryoablation is a useful tool in open surgical procedures to treat ventricular arrhythmias in structural heart disease. Cryoablation can achieve transmurality in tissue with ≤ 6 mm thickness with more technically reliable effect compared to catheter RF in the open chest.
Forward trauma care remains a critical gap in emergency responses to armed conflict, particularly where conventional medical evacuation is disrupted. Trauma Stabilization Points (TSPs) were introduced in previous conflicts to bring life-saving care closer to the point of injury. To improve standards and adaptability, the World Health Organization convened a Technical Working Group to develop operational guidance for TSPs, drawing on diverse field experiences, including the ongoing Gaza deployments. Between February and July 2024, three TSPs were established in Gaza, managing over 4,000 consultations. Initially focused on trauma stabilization and referral, these sites quickly adapted to minor injuries and non-traumatic conditions, reflecting population needs and access challenges. Referral rates varied across sites due to hospital proximity, ambulance availability, and shifting frontlines. Security threats limited forward deployment and safe patient access, requiring high mobility and rapid relocation. Experience from Gaza highlighted key operational principles: locating TSPs near the point of injury; integrating within a functioning trauma referral pathway supported by evacuation capacity and hospital readiness; maintaining clear clinical functions and staffing standards; and using standardized documentation for quality assurance and continuity. Lessons from Gaza aligned with those from other conflict zones, emphasizing challenges such as insecurity, fragmented oversight, and disrupted referral systems. The guidance recognizes the need for adaptable models that balance mobility with advanced interventions, including damage control resuscitation in austere settings. The Gaza experience, together with lessons from other conflict settings, is shaping the development of flexible, context-sensitive operational guidance for TSPs. This guidance aims to support emergency care actors and national authorities in determining when and how to deploy TSPs in complex emergencies, balancing core trauma functions with the realities of modern warfare.
Cereals are emerging as attractive platforms for the sustainable production of high-value lipids through metabolic engineering. Although plant lipids play essential biological roles and have considerable economic value, their conventional production from natural sources is often limited by sustainability, scalability and cost. Recent advances in synthetic biology enable the reprogramming of seed lipid metabolism for the tailored synthesis of valuable lipid compounds. In this review, we first summarize the core pathways of fatty acid biosynthesis and triacylglycerol assembly in seeds, together with the genetic transformation and genome editing toolkits available for major cereals. We then highlight recent progress in the heterologous production of specialized lipids, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), wax esters, and insect sex pheromones, in engineered plant systems. Finally, we discuss the potential of cereals as scalable and sustainable platforms for the production of high-value lipids. Together, these advances position engineered cereals as promising plant-based factories for applications in agriculture, nutrition, and the emerging bio-based economy.
This study examined differences in social anxiety, social avoidance, loneliness, and self-esteem among autistic adolescents attending special education versus general classes, and whether class type moderated associations among these variables. Participants included 137 autistic adolescents without intellectual disability from multiple mainstream schools in central Israel. They completed validated self-report questionnaires: Liebowitz Social Anxiety Scale, UCLA Loneliness Scale, and Rosenberg Self-Esteem Scale. Autistic adolescents in special education classes reported higher social anxiety, social avoidance, and loneliness than peers in general classes, while self-esteem did not differ. Class type moderated associations between social anxiety and loneliness, and between social avoidance and loneliness, with stronger associations in general classes. Self-esteem consistently served as a protective factor across both class types. Educational context relates to autistic adolescents' social-emotional experiences, with stronger associations between social anxiety, avoidance, and loneliness in general versus special education classes. These findings provide a descriptive comparison of educational contexts, suggesting that observed differences may reflect variations in social exposure or pre-existing needs that influenced placement, rather than the effects of the placement itself. While self-esteem remains a consistent protective factor, these results highlight the need for supportive strategies that promote inclusion and wellbeing for autistic adolescents across all settings.
Pelvic mesh implants are commonly used in female urology for the treatment of stress urinary incontinence and pelvic organ prolapse. However complications can be substantial and a number of the patients in this cohort proceed to mesh explantation. We evaluated urinary morbidity after pelvic mesh removal within New Zealand's National Mesh Service. Retrospective review of women undergoing pelvic mesh removal between March 2009 and December 2024 by the National Mesh Service. Primary outcomes were patient-reported urinary symptoms using validated instruments: Pelvic Floor Distress Inventory [PFDI] and International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF]. Secondary outcomes included clinician-reported symptoms at last follow-up, reintervention for incontinence, and complications (Clavien-Dindo). Of 345 patients (median age 58 years; median 105.3 months from insertion to removal), pain was the commonest indication for explantation, followed by bladder outlet obstruction/lower urinary tract symptoms. Among 184 with urodynamics, 32% met criteria for likely/definite outlet obstruction. Robotic assistance was used in 97 cases. Eight patients (2.3%) developed Grade III complications. Mean follow-up was 27.2 months. Post-removal, clinician-reported persistence of SUI, pain, and overactive bladder was seen in 30-40%, dyspareunia in 20%, recurrent urinary tract infection in 9%, and obstructive voiding in 12%. Overall, 25% needed concurrent procedure during pelvic mesh removal and 48% required ≥ 1 subsequent incontinence procedure. 6 patients ultimately underwent cystectomy. In 83 patients with paired PFDI, mean total scores improved from 168.4 to 149.6 (p < 0.05) with concordant subscale improvements. ICIQ-SF severity categories showed minimal overall shift. Urinary morbidity after pelvic mesh removal is common and frequently persists despite explantation, with high reintervention rates indicating chronicity. Findings support robust pre-operative counselling, multidisciplinary care, and prospective studies to define predictors and optimise surgical pathways.