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PubMed2026

A qualitative study of cancer survivors' exercise behaviour 4 months after a telerehabilitation program.

PURPOSE: Although telerehabilitation can improve access to exercise programs for cancer survivors, it is not known if these programs lead to ongoing change in exercise habits. This study explored participant experiences of exercise 4 months after finishing specialized cancer exercise-based telerehabilitation. METHOD: A qualitative study embedded in a randomized controlled trial evaluated exercise-based cancer telerehabilitation delivered in groups. Data were collected via semistructured interviews that were audio-recorded and transcribed verbatim. Seventeen adult cancer survivors (age 21 to 80) were purposively sampled 4 months after completing exercise-based cancer telerehabilitation. Data were coded independently by two researchers and analyzed inductively within an interpretive description framework. RESULTS: The overarching theme was telerehabilitation was perceived to facilitate positive exercise intentions. Participants said they were empowered to exercise through knowledge, opportunity, and connection gained through telerehabilitation. They described acting on their positive intentions to exercise to varying degrees following telerehabilitation, depending on their context. A subtheme was that exercise was challenging in their new reality created by cancer. Comorbidities, ongoing side effects, previous exercise experience, and personal factors were considered by some to influence their ability to exercise. CONCLUSION: Telerehabilitation may facilitate positive intent to maintain exercise. Cancer survivors may need ongoing support after telerehabilitation to act on positive exercise intentions due to health-related difficulties. IMPLICATIONS FOR CANCER SURVIVORS: Participation in telerehabilitation may be a positive first step to initiate exercise, but ongoing support to maintain positive behavior changes is likely to be needed for people without previous exercise experience.

Humans↗
PubMed2026

Faster N1 latency in response to homeostatic-like plasticity of PREPs is impaired during pain: A randomized-placebo capsaicin-pain study.

INTRODUCTION: Homeostatic-like plasticity (HP-like) stabilizes cortical excitability through long-term potentiation and depression-like mechanisms. The efficacy of homeostatic regulation in the corticomotor system is impaired during pain, which may have functional relevance for chronic pain. This study investigated whether a cortical HP-like response could be assessed by nociceptive stimulation, and if such response was impaired by experimental tonic pain. METHODS: Twenty-eight healthy participants completed placebo and capsaicin sessions, with 11 sham controls for time and design. HP-like plasticity was induced with two blocks of anodal tDCS over the primary motor cortex. The N1 (TP7) and N2P2 (Cz) components of electrically induced pain-related evoked potentials (PREPs) were assessed from the volar forearm before and after patch application, and again immediately and 20 min after HP-like induction. An HP-like response was defined by PREP decrease after induction, and further normalization to baseline. RESULTS: Anodal tDCS did not induce an HP-like regulation of PREP amplitudes. Interestingly, an HP-like response was observed as a fastening of N1 latency after HP-like induction, which returned to baseline values after 20 min. The latter effect was impaired during capsaicin-induced pain, where N1 was slower. The N2P2 component showed habituation over time in all sessions. CONCLUSION: This is the first study that investigates the HP-like regulation of nociceptive-evoked responses. An HP-like response was observed as a shortening of N1 latency, suggesting that early nociceptive processing may be susceptible to homeostatic regulation. In contrast, the later component, N2P2, showed habituation over time, which prevented evaluation of HP-like effects.

Humans↗
PubMed2026

Integrated exome and mitochondrial genome sequencing reveals the genetic landscape of primary mitochondrial diseases: findings from a large Tunisian cohort.

Primary mitochondrial diseases are a heterogeneous group of neurometabolic disorders recognized as the most common metabolic genetic diseases. They manifest at any age, affecting any tissue or organ, especially those with high energy demands, and are caused by pathogenic variants in both mitochondrial and nuclear genomes. Here, we aimed to describe the genetic spectrum of a Tunisian pediatric cohort with suspected mitochondrial diseases. We recruited 47 unrelated families who underwent exome sequencing as a first-tier test followed by whole mitochondrial genome sequencing for unsolved cases. Dedicated bioinformatic pipelines and prediction tools were used to determine the potential disease-causing variants. Sanger sequencing confirmed the presence and segregation within parents. For the newly identified variants, structural modeling was conducted to study the impact of these variants on protein structure and motions. Dual genome sequencing yielded a molecular diagnosis in 33/47 families (70%) and 18/47 (38%) showed disease-causing variants in genes encoding mitochondrial proteins. Among them, four families disclosed novel variants in FASTKD2, SERAC1 and GATB, which were supported by in-depth in silico and structural analyses demonstrating their deleterious effect. The remaining families (32%, 15/47) disclosed other metabolic and neurological disorders. An exome-first strategy delivers a high diagnostic yield in Tunisia, where consanguinity remains high and simultaneously captures mitochondrial and non-mitochondrial etiologies. Mitochondrial sequencing remains indispensable in the case of an inconclusive exome. Thus, our data expand the clinical and genetic spectrum of primary mitochondrial diseases in Tunisia, an underrepresented and admixed population.

Humans↗
PubMed2026

Emerging Principles in Spatial Functional Genomics.

Spatial transcriptomic and proteomic atlases have enabled mapping of gene programs within intact tissues, but these measurements remain largely descriptive and do not define the mechanisms controlling tissue biology. Pooled CRISPR screening provides scalable causal interrogation of gene function but remains largely confined to dissociated systems that lack spatial context. In vivo spatial functional genomics (SFG) bridges these approaches by integrating genetic perturbations with in situ transcriptomic and proteomic readouts to measure gene function within intact tissue ecosystems. By preserving spatial organization, SFG enables interpretation of perturbations through effects on cell-cell interactions, diffusible signals, multicellular niches, and tissue architecture. Here, we outline key design axes of SFG: perturbation strategy, barcoding strategy, and phenotypic readout. We discuss computational challenges, including spatial autocorrelation, neighborhood dependence, and context-aware null modeling, and highlight how SFG reveals non-cell-autonomous, architecture-dependent mechanisms of gene function, advancing toward predictive models of tissue organization and gene function.

Genomics↗
PubMed2026

Sex-stratified analyses of femoral intercondylar notch morphology and ACL injury risk: a systematic review and meta-analysis.

BACKGROUND: Anterior cruciate ligament (ACL) injury is more common in females. Although ACL injury risk is multifactorial, involving neuromuscular, hormonal, and biomechanical factors, femoral intercondylar notch morphology is a proposed non-modifiable anatomical contributor that may help explain this disparity. This review synthesizes evidence on its association with ACL injury risk, analyses stratified by male and female sex. METHODS: A literature search of PubMed, Web of Science, and Scopus was conducted through January 2026. After duplicate removal, 527 unique records were screened and 134 full texts assessed for eligibility. Twenty-four studies met inclusion criteria, with 22 providing quantitative data. Data were extracted on ACL-injured (ACLi) and control (ACLc) knees, stratified by sex. RESULTS: ACLi knees had narrower notch widths than ACLc knees in both females (MD -1.74 mm, 95% CI -2.54 to -0.95) and males (MD -1.31 mm, 95% CI -1.94 to -0.68), with substantial heterogeneity (I2 81-95%). NWI differences were significant in males (MD -0.01, 95% CI -0.02 to 0.00) but not females. Limited notch shape data suggested higher ACL injury odds with A-shaped notches in females (OR 2.85, 95% CI 0.07-110.66) and males (OR 1.67, 95% CI 0.00-3.98 × 105). CONCLUSION: Narrower femoral intercondylar notch width was consistently associated with ACL injury in both sexes, whereas findings for NWI and notch shape were limited by heterogeneity and sparse data. These results provide a structured synthesis of sex-specific anatomical risk factors and support femoral notch narrowing as a shared contributor, while highlighting the need for prospective, standardized studies in the future.

Humans↗
PubMed2026

Genome-wide Identification and Expression Profiling Reveal the Galectin Gene Family Diversity and their Possible Role in Antibacterial Mucosal Immunity in Japanese Flounder (Paralichthys olivaceus).

Galectins are a family of proteins that bind specifically to β-galactosides. Their importance in innate immunity of mammals has been well-documented. However, the systematic identification and characterization of galectin gene family remain limited in teleost. In this study, we identified 13 galectin genes (lgals2, lgals2a, lgals2b, lgals3, lgals3a, lgals3b, lgals4, lgals8, lgals8a, lgals9, grp, grp-b, grp-c) from Paralichthys olivaceus genome and analyzed their tissue expressions and expressions in response to Gram-negative and Gram-positive bacterial infections in mucosal tissues (gills, intestine and skin). The P. olivaceus galections were classified into three distinct types based on carbohydrate recognition domains (CRDs). Phylogenetic and syntenic analyses revealed that these galectins are closely related to their counterparts in turbot and zebrafish. Moreover, the transcripts of the 13 galectins were widespread across all tested tissues of healthy fish and regulated following challenge with Vibrio anguillarum or Streptococcus iniae in mucosal tissues, indicating their involvement in P. olivaceus immune response to bacterial infections. The lgals2a was significantly upregulated in the three mucosal tissues by either bacterial infection, whereas lgals9 and grp were basically downregulated in these tissues by either infection. On the other hand, the lgals3b and lgals4 exhibited a bacteria-specific responsive expression as they were upregulated by V. anguillarum whereas remained stable upon S. iniae infection in the gills. We also observed a positive correlation between expression level and bacterial load for the upregulated galectin genes and a negative correlation for the downregulated galectin genes. These results suggest a functional divergence among galectin members in mucosal immunity against bacterial infection in P. olivaceus.

Animals↗
PubMed2026

Evaluating the need for late angiography for complete obliteration of AVMs after endovascular treatment: collaborative AVM center experience and a systematic review.

Brain arteriovenous malformations (bAVMs) can be treated curatively by endovascular embolization. However, limited data exist on late recanalization rates. We investigated the rate of late bAVM recanalization following complete endovascular obliteration, confirmed by primary control angiography.We performed a single-center retrospective cohort study on late recurrences in adult patients with bAVMs after complete endovascular obliteration at a Radboud - Isala - MUMC+ (RIM) collaborative AVM center in the Netherlands between 2014 and 2022.Additionally, we conducted a systematic review to evaluate the rate of late recanalization following complete endovascular obliteration, confirmed on primary control angiography, in adults with bAVMs. The protocol for this review was registered in PROSPERO (CRD42024546875).Our retrospective study revealed 42 adult patients treated by endovascular means only; 90.5% (38 patients with mean age of 48.1 years) had confirmed complete obliteration. Both primary (6 months post-treatment) and secondary (more than 1 year post-treatment) angiographic control confirmed complete obliteration in 21 of 23 patients with complete follow-up. Mean follow-up was 47.8 months. Two late recurrences (9.5%) were detected at 5- and 6-years' follow-up imaging.Our systematic review included two studies encompassing a total of 19 patients with mean angiographical follow-up of 20.8 months. There were no late recurrences.Late bAVM recurrence after endovascular treatment with proven complete obliteration may be underestimated owing to limited long-term follow-up. Our findings suggest that after a 6-month angiographic confirmed obliteration, a 5-year angiographic imaging control is justified.

Humans↗
PubMed2026

Integrative machine learning and transcriptomic analysis reveals molecular mechanisms underlying low survival rate in larval Chinese Bahaba (Bahaba taipingensis).

Chinese Bahaba (Bahaba taipingensis) is a Class I protected marine fish endemic to China. Low larvae survival during artificial breeding severely hinder population recovery. To investigate the molecular mechanism of high mortality in larval fish, this study performed RNA-seq on liver from naturally deceased (ND) and mass-dead (MD) individuals, combined with least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms to screen for core signature genes. A total of 873 differentially expressed genes (DEGs) were identified, including 112 upregulated and 761 downregulated genes. GO and KEGG enrichment analyses revealed significant enrichment in amino acid metabolism disorders, one‑carbon folate pool impairment, PPAR signaling abnormalities, ECM-receptor interaction, focal adhesion pathway, indicating widespread metabolic suppression accompanied by extracellular matrix remodeling and signaling disturbances in the livers of MD fish. MAD pre-filtering combined with dual machine learning algorithms yielded 18 robust core signature genes, among which SLC38A4, MMP1, FADD, FKBP5, and APOB were consistently identified as high-frequency core genes by both algorithms. SLC38A4 exhibited the highest importance score in the RF model and was significantly downregulated, making it the primary molecule distinguishing ND from MD phenotypes. ROC curve analysis showed that both models achieved an AUC of 1.000 (95% CI lower bound: 0.610), confirming the precise discriminatory ability of the core genes. GSEA further demonstrated significant enrichment of this core gene set in ND samples. This study provides the first systematic elucidation of the molecular mechanisms underlying liver dysfunction in low survival rate B. taipingensis, characterized by amino acid transport impairment, metabolic reprogramming, and structural remodeling, offering theoretical foundations for health assessment, early mortality risk warning, and artificial breeding conservation of this species.

Animals↗
PubMed2026

Insights into the fate and dynamics of antibiotic resistance in multidrug-resistant Bacillus cereus during in vitro simulated gastrointestinal digestion.

Bacillus cereus, an important pathogen responsible for causing foodborne diseases worldwide, releases pore-forming enterotoxins, which target host epithelial cells, leading to osmotic lysis and ultimately manifesting as diarrheal syndrome. Moreover, some B. cereus strains carry antimicrobial resistance genes that confer multidrug resistance against a spectrum of antibiotics. Characterizing the survival traits of multidrug-resistant (MDR) B. cereus strains in the intestinal microenvironment is essential for developing targeted strategies to effectively manage diarrheal foodborne diseases caused by this pathogen. This study used whole-genome sequencing (WGS) to evaluate the pre- and post-digestion toxigenic potential, antimicrobial resistance profiles, and genetic diversity of MDR B. cereus strains isolated from food samples in Guangdong Province, China. The four B. cereus isolates investigated in this study exhibited a genetic diversity, as determined by multilocus sequence typing analysis of WGS data. All four isolates produced the diarrheal toxins Hbl, Nhe, and CytK to varying levels, indicative of their potential to cause outbreaks of foodborne diseases. Each of the four isolates exhibited resistance to more than three classes of antibiotics, fulfilling the criterion for multidrug resistance. At an initial concentration of 9 log colony-forming units (CFU)/mL, the intestinal concentration of these four isolates crossed the threshold required to induce widespread diarrhea in the general population. Under rice slurry protection, all tested isolates maintained intestinal concentration beyond the threshold when the initial concentration was increased to ≥8 log CFU/mL. Moreover, the upregulations of genes associated with acid tolerance, bile tolerance and stress response were observed in the surviving MDR B. cereus isolates. Digestion markedly altered the antibiotic resistance profiles of the MDR B. cereus isolates. In the absence of a food matrix, the MDR isolates lost their resistance to imipenem, meropenem, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole post-digestion and was influenced by the initial concentration of the strains. In the presence of food matrix rice slurry, the effects of digestion on the antibiotic resistance of MDR B. cereus isolates can be mitigated, enabling them to maintain their antibiotic resistance to the greatest extent. Most remarkably, after digestion, the isolates Bce055 and Bce166 exhibited newly emergent resistance to cefotetan and trimethoprim-sulfamethoxazole, respectively. Our findings clarify the fate of MDR B. cereus isolates in the gastrointestinal tract and inform the development of prevention and control strategies for foodborne diseases caused by this pathogen.

Drug Resistance, Multiple, Bacterial↗
PubMed2026

Introgression shapes the genomic conflict landscape of Malus, providing evidence for a reticulate backbone in a woody crop lineage.

Phylogenomic discordance is widespread across plants, but its evolutionary significance is often obscured when conflict is treated primarily as analytical noise rather than as evidence of underlying processes. In woody lineages in particular, incomplete lineage sorting, introgression, and genome duplication can interact over long timescales to produce complex genomic histories that are not adequately summarized by a strictly bifurcating tree. Here, we use Malus as a model woody genus to investigate how these processes structure conflict across a genus-scale, accession-based phylogenomic framework. Using broad taxon sampling, hundreds of nuclear loci, plastid genomes, and genome-wide SNP summaries, we reconstruct a robust nuclear backbone for sampled Malus lineages and evaluate where discordance is concentrated and which processes best explain it. Nuclear analyses resolve eight major clades, whereas conflict is non-random and localized to recurrent hotspots rather than evenly distributed across the tree. Cytonuclear discordance is similarly concentrated, especially around Clade H, represented by sampled accessions of M. tschonoskii, where localized plastid-nuclear disagreement is consistent with candidate plastid capture or organellar introgression. Multiple complementary analyses further indicate that the strongest conflict is not explained by ILS alone, but instead reflects lineage-structured introgression, while polyploid complexes represent additional localized sources of evolutionary complexity. Together, these results provide evidence for a reticulate genomic backbone in Malus and show how integrating nuclear, plastid, and genome-wide conflict analyses can help distinguish background discordance from process-specific signals in woody plant radiations. Several lineage-level reticulation hypotheses identified here should now be tested with broader population-level sampling and curated reference accessions.

Malus↗
PubMed2026

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 × 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans↗
PubMed2026

Temporal Trends and Spatial Variation in Preterm Prelabour Rupture of Membranes: A Population-Based Study.

OBJECTIVE: To describe the temporal trends in Preterm prelabour rupture of membranes (PPROM) in metropolitan France and the geographical distribution at the administrative division level. DESIGN: Exploratory population-based study using administrative data of the French National Health Data System. SETTING: Metropolitan France, 2015 to 2023. POPULATION: Pregnancy with a diagnosis of PROM before 37 SA. METHODS: Annual crude incidence of PPROM was calculated by dividing the number of pregnancies with PPROM diagnosis by the number of live births recorded during the same period. Annual trend was estimated by a binomial negative mixed model. Smoothed standardised incidence ratios were estimated based on a BYM2 model, which accounts for spatial variability between departments. MAIN OUTCOME: PPROM cases, defined as pregnancies with first hospitalizations with a diagnosis of PROM before 37 weeks. RESULTS: Over the study period, we included 150 615 PPROM cases representing 16 735 (±596) per year. Incidence of PPROM cases showed an ascending trend over time (incidence rate ratio 1.023 per year; 95% CI: 1.017-1.030) with an annual crude incidence ranging from 2.2% in 2015 to 2.7% in 2023. A decrease in the incidence was observed in 2020 relative to other years (incidence rate ratio 0.903, 95% CI: 0.887-0.920). A map of smoothed SIRs of PPROM cases at the French administrative division level revealed geographical inequalities. CONCLUSIONS: This first population-based study describing PPROM cases in metropolitan France paves the way for further studies to explore environmental hypotheses. Identifying temporal and geographical disparities in PPROM incidence is relevant to public health policy and practice as such disparities argue for the development of targeted prevention strategies in high-risk areas.

French national health data system↗
PubMed2026

Frequent mutations in the BIRC3 gene promote metastatic potential of nasopharyngeal carcinoma cells through the TRAF2-NF-κB pathway.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer characterized by highly locoregionally invasive behavior attributable to the latent infection with Epstein-Barr virus (EBV) and genomic instability. It is well established that EBV-encoded oncogenic molecules actively contribute to the malignant behavior of NPC cells. However, the mechanism by which aberrant genomic alterations enable NPC cells to become aggressive remains largely unknown. In the present study, whole-exome sequencing (WES) revealed that the gene encoding the baculoviral IAP repeat-containing 3 (BIRC3) protein was frequently mutated in circulating tumor cells (CTCs) but not in paired primary tumor cells from patients with metastatic NPC. A minigene assay indicated that the c.637 A > G mutation disrupted normal mRNA splicing, resulting in the partial deletion of Exons 2 and 3 and altered stability of BIRC3 mRNA. In vitro experiments demonstrated that ectopic expression of the BIRC3c.637A>G mutant enhanced NPC cell invasive properties, including proliferation, resistance to apoptosis, migration, and invasion. Furthermore, overexpression of wild-type BIRC3 promoted invasive characteristics in NPC cells through the TRAF2-NF-κB signaling axis. In summary, BIRC3 acts as a regulator of the malignant features of NPC cells. Frequent BIRC3 mutations in CTCs, such as the c.637 A > G mutation, further enhance the metastatic potential of disseminated NPC cells by inducing aberrant alternative splicing. These findings suggest the therapeutic feasibility of targeting the BIRC3/TRAF2/NF-κB axis in the treatment of NPC.

Humans↗
PubMed2026

Ossicle occurrence characteristics and related molecular mechanisms in the sea cucumber Apostichopus japonicus.

To investigate the morphogenetic pattern and molecular mechanism of ossicle formation in the sea cucumber Apostichopus japonicus, this study systematically examined the morphological development and temporal sequence of spicules using the NaClO maceration method, in-situ squash preparation and microscopic observation. Comparative transcriptome sequencing was performed between doliolaria and pentactula larvae to screen differentially expressed genes (DEGs) related to ossicles formation, followed by pathway enrichment analysis. The function of the candidate key gene papilin-like was verified using siRNA-mediated gene silencing. The results were as follows: 1) Ossicles of A. japonicus first appeared at the late auricularia stage, initiating as X-shaped ossicles at the base of the oral tentacles. The number of X-shaped ossicles increased dramatically during the doliolaria stage. X-shaped ossicles were gradually replaced by table-shaped and rosette-shaped ossicles at the pentactula stage, suggesting that X-shaped ossicles may differentiate into these two ossicle types. The morphology of table-shaped ossicles showed a "simple-complex-simple" pattern with development. 2) Key genes related to ossicles formation, including CA1, COL1A2, and papilin-like, were identified by transcriptome analysis. After papilin-like knockdown, abnormal morphologies were observed in table-shaped ossicles of 1-year-old A. japonicus, such as spine-like protrusions on the outer margin of the disc and loss of table legs, confirming its crucial roles in maintaining ossicle morphology. This study clarified the morphological development pattern of ossicles in A. japonicus and identified a key regulatory gene (papilin-like) involved in ossicle morphogenesis, providing preliminary insights into the underlying molecular regulatory mechanism. These findings enrich our understanding on ossicles formation in echinoderms, and provide important morphological and molecular biological information for further studies on the developmental mechanism of ossicles in A. japonicus.

Animals↗
PubMed2026

Migration intentions among nigerian neurosurgeons: a national survey of workforce retention.

Physician emigration from low- and middle-income countries creates critical workforce shortages. This study explored factors influencing migration intentions among Nigerian neurosurgeons and trainees. We conducted an anonymized survey of consultant neurosurgeons, fellows, and residents practicing in Nigeria. Invitations were sent by email and professional messaging platforms, and snowball sampling was used to increase participation. The survey included quantitative and open-ended questions on demographics, income, migration plans, and retention factors. Seventy-nine respondents participated (61.5 % consultants; 93.7 % male; median age: 44 years). Nearly all practiced general neurosurgery (97.3 %), and many also performed trauma (65.3 %) and spine (61.3 %) neurosurgery. Most (85.7 %) reported that their earnings were insufficient to support their families. Nearly 40 % were considering emigration, most often citing financial pressures (88.5 %) and poor working conditions (63.5 %) as push factors. By contrast, personal or family ties (63.0 %) and relocation costs (45.2 %) were cited as reasons to stay. Respondents identified higher salaries (58.1 %) and greater investment in the health sector (51.4 %) as key measures to improve retention. In univariable analyses, younger age, income insufficiency, income dissatisfaction, and feeling undervalued at work were associated with migration intention. Financial insecurity emerged as the dominant driver of migration intentions among Nigerian neurosurgeons. In addition to salary increases, sustained investment in healthcare infrastructure and workforce support is essential to improve retention. International partnerships may complement these efforts by building neurosurgical capacity and mitigating brain drain.

Humans↗
PubMed2026

A prospective pharmacokinetic interaction study between rifampicin and fusidic acid for the treatment of staphylococcal infections.

OBJECTIVE: Fusidic acid with rifampicin is used for the treatment of severe staphylococcal infection, particularly prosthetic joint infections. Previous studies using twice daily fusidic acid showed rifampicin increases fusidic acid clearance, potentially causing sub-therapeutic concentrations. It is uncertain whether this occurs with three-times daily dosing. This study sought to re-evaluate this potential drug-drug interaction. METHODS: In this prospective, open-label drug-drug interaction population pharmacokinetic (PK) study, participants were randomized to receive fusidic acid or rifampicin for 24 hours, followed by combination therapy for the duration of treatment. Drug concentration assays used liquid-chromatography mass spectroscopy on dried blood spots. Population PK models were built for fusidic acid, rifampicin and 25-desacetyl rifampicin. RESULTS: Ten participants were recruited. Inter-individual variability for both absorption (98.1%) and clearance (77.8%) were high for fusidic acid. A population pharmacokinetic model for fusidic acid revealed that early autoinhibition dominated over later rifampicin-mediated induction, resulting in a net decrease in fusidic acid clearance. The mean fusidic acid area under the curve during each dosing interval (AUCτ) at steady state was 1.76-fold [0.049, 34.918] higher relative to Day 1, despite high uncertainty.Large inter-individual (110%) variability in absorption was observed for rifampicin. There was no apparent effect on rifampicin metabolism by fusidic acid co-administration, however, fusidic acid decreased clearance of 25-desacetyl rifampicin. CONCLUSION: In patients treated with fusidic acid three times daily in combination with rifampicin, autoinhibition potentially counteracted rifampicin induction such that fusidic acid concentrations were not reduced. Rifampicin clearance was not affected by fusidic acid, but 25-desacetyl rifampicin clearance was decreased. There was large inter-individual variability in the observed concentrations and final parameter estimates.

Fusidic Acid↗
PubMed2026

Hierarchical modeling of tumor subtypes in cell lines using large-scale genomic datasets.

Cancer cell lines (CLs) are widely used to study tumor biology and drug response, yet their translational relevance is often limited by inaccurate subtype annotations. Existing CL-tumor matching approaches are frequently constrained by flat classification schemes, weak subtype definitions, and the exclusion of normal tissue references, leading to potential confounding of tumor-specific and tissue-of-origin signals. To address these limitations, a hierarchical classification (HC) framework is presented in which CLs are aligned with patient tumors across biological resolutions, from organ to molecular subtype. Gene expression profiles from 802 CLs, 5,612 tumors from The Cancer Genome Atlas (TCGA) , and 8,939 non-cancerous tissues were integrated to separate oncogenic signals from tissue-specific signals. Node-specific features were selected using maximum relevance minimum redundancy, and balanced accuracies of 89% in cross-validation and 75%, and 80% on external datasets were achieved. Through the framework, 43 CLs were reassigned, and clinically relevant underrepresented subtypes were identified.

cancer cell lines↗
PubMed2026

Storm and Stress 2.0? A Dual-Factor, Person-Centered Analysis of Adolescent Well-being Across Two Year 7 Cohorts and Gender.

PURPOSE: Concerns about the mental health and well-being of younger generations is a recurring theme across countries and time. Adolescence is debated as a period of volatility ("storm and stress") or growth. Recent trends have reignited worries about youth mental health and well-being, particularly for females, and revived a deficit-based view of adolescence. To advance understanding, this study adopts a dual-factor approach that incorporates both negative and positive well-being domains. Mental health trends were compared across two grade-matched Australian adolescent cohorts assessed 5 years apart. METHODS: Data were drawn from cross-sectional cohorts of year 7 students (12-13 years) in one Australian jurisdiction: 2,085 in 2018 and 2,378 in 2023. Positive affect, happiness, resilience, depression, and anxiety were assessed using latent profile analysis to identify mental health profiles, which were then compared between cohorts and gender. RESULTS: Four profiles were identified: complete mental health, symptomatic but positive, resilient but disaffected, and troubled. Approximately 80% of students were classified in profiles reflecting some positive mental health. Between 2018 and 2023, the proportion with complete mental health declined by 7.93%, while those categorized as troubled increased by 4.76%. Declines were most pronounced among female students. DISCUSSION: Findings highlight both resilience and vulnerability in adolescent mental health. While most students continue to show positive well-being, the decline among females signals an urgent need for gender-sensitive approaches. At the same time, the results add nuance to accounts of a youth mental health 'crisis' to some degree, by highlighting positive domains of well-being which are often overlooked.

Humans↗