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PubMed2026

Wildlife forensic DNA evidence links a suspected vehicle to a fatal lowland tapir (Tapirus terrestris) collision in Misiones, Argentina.

Vehicle collisions are recognized as a major driver of biodiversity loss, particularly in road-dense landscapes, exceeding the impact of invasive species and wildlife trafficking. For large-bodied, slow-reproducing, and low-abundance species, such as the lowland tapir (Tapirus terrestris), this threat can have major impacts. Here, we present a wildlife forensic investigation in Misiones, Argentina, involving a tapir, a species afforded the highest level of legal protection as a Provincial Natural Monument. The fatal hit-by-vehicle (HBV) incident occurred in northern Misiones on 31 March 2019 along Provincial Route 19, in a portion that bisects Parque Provincial Urugua-í, with the driver involved in the collision leaving the scene. The suspect was later located and claimed that the damage to the vehicle resulted from a collision with a horse (Equus caballus) rather than a tapir. To legally resolve the incident, DNA (hair and blood) recovered from the suspected vehicle's bumper (evidence) was compared with tissue samples from the tapir carcass (reference). Genetic confirmation of species identity used a 110-bp region of the mitochondrial cytochrome b gene, and individual identity was assessed using 12 species-specific microsatellite loci. These analyses confirmed that all evidence matched the tapir carcass at both species and individual levels, strongly supporting the association between the suspected vehicle and the HBV tapir, and refuting the alternative explanation proposed by the driver. This case demonstrates the value of using wildlife forensic genetics to reconstruct wildlife-vehicle collisions, supporting environmental law enforcement, and strengthening conservation efforts in the Atlantic Forest of Misiones, Argentina.

Animals↗

PubMed2026

Evolutionary conservation of heat shock proteins in Blattodea and their roles in wing morphogenesis and ovarian development of Blattella germanica.

Heat shock proteins (Hsps) are essential molecular chaperones for protein homeostasis and stress responses. However, the Hsp repertoires and functions in Blattodea remain underexplored. Our genome-scale survey of nine Blattodea species revealed 37-46 conserved Hsp90, Hsp70, and DNAJ (Hsp40) genes, with DNAJ the most abundant and Hsp90 the least. Phylogenetic analysis confirmed the evolutionary conservation of three Hsp90, seven Hsp70, and 29 DNAJ subclades in Blattodea. Selection pressure analysis revealed predominant purifying selection (dN/dS ≪ 1) across lineages, strongest in DNAJ and highest in Hsp90 conservation. In Blattella germanica, expression of six representative BgHsp genes progressively increased during development, peaking in fifth-instar nymphs. Tissue expression profiling revealed that BgHspA1-2/3/4 were predominantly expressed in legs, BgDNAJB5 and BgHsp90AB1-2 were enriched in the fat body, and BgHsp90AB1 was highly expressed in the head. dsRNA injection targeting conserved Hsp gene regions achieved 61.9-94.1% knockdown of all six target genes. RNAi knockdown of six BgHsp genes disrupted wing morphogenesis, causing distinct phenotypes: wing whitening (56.7%, dsBgHspA1-4), unequal length (66.7%, dsBgHspA1-3; 76.7%, dsBgDNAJB5), and wing wrinkling (70%, dsBgHspA1-2; 63.3%, dsBgHsp90AB1; 76.7%, dsBgHsp90AB1-2). During ovarian formation, the developmental delay was most severe in the dsBgHsp90AB1 group, moderate in the dsBgHsp90AB1-2 and dsBgHspA1-2/3/4 groups, and weakest in the dsBgDNAJB5 group. Besides, knockdown significantly downregulated key developmental genes (apterous-a, nubbin, scalloped, ultrabithorax, wingless, and vitellogenin). These findings provide a reference for understanding the evolutionary patterns of Hsps in Blattodea, and offer mechanistic insights into the developmental regulation mediated by Hsps in this important public-health pest.

Animals↗

PubMed2026

Herd-level heterogeneity of antimicrobial resistance in commensal Escherichia coli: A nationwide high-throughput survey of Australian pig herds.

Antimicrobial resistance in commensal Escherichia coli provides a useful indicator for overall antimicrobial resistance burden. We applied this approach to assess antimicrobial resistance within and between commercial pig herds across Australia. A high-throughput robotic workflow was used to isolate 2730 E. coli colonies from rectal contents collected in 2022 from healthy slaughter pigs (n = 300) representing 30 herds (∼70% of national production). Up to 94 isolates per herd underwent antimicrobial susceptibility testing using the Robotic Antimicrobial Susceptibility Platform. Isolate- and herd-level antimicrobial resistance indices were calculated, weighting antimicrobials by their human health importance. Resistance to first-line agents was widespread: ampicillin 77% and tetracycline 79%. By contrast, resistance to critically important antimicrobials was rare (ciprofloxacin 0.11%; extended-spectrum cephalosporins 0.04%), and no clinical resistance to carbapenems or colistin was detected. Overall, 56.9% of isolates were multi-class resistant. Herd-level antimicrobial resistance within indices ranged from 1.51 to 5.76, revealing substantial between-herd heterogeneity. Three herds carried critically important antimicrobials-resistant isolates that would likely have been missed using conventional, lower-density sampling approaches. Whole-genome sequencing identified fluoroquinolone-resistant isolates belonging to ST10 and ST69 (both qnrS1), and ST744 (Quinolone Resistance Determining Region mutations plus blaCTX-M-27). By testing approximately tenfold more isolates than conventional surveys, we uncovered considerable antimicrobial resistance with heterogeneity within and between animals and herds, including farm-specific variability. This expanded sampling also enabled detection of critically important antimicrobial resistance at very low prevalence. In conclusion, high-throughput, high-density testing offers a practical early-warning system and herd-level benchmark to inform surveillance and targeted interventions.

Animals↗

PubMed2026

Postoperative chemoradiotherapy in Wilms tumor with concurrent lung and lymph node metastasis.

BACKGROUND: An effective treatment strategy is essential for metastatic Wilms tumor (WT) management. To improve prognostic accuracy, this study examined metastatic patterns and key prognostic factors. METHODS: Children diagnosed with WT from 2010 to 2021 were identified from the SEER database. All patients underwent chemotherapy and surgical resection. Metastatic patterns, metastasis-related predictors, and prognostic factors were evaluated. RESULTS: Of the 1040 patients analyzed, 226 (21.7%) experienced lung metastasis, 31 (3.0%) liver metastasis, 6 (0.6%) bone metastasis, and 220 (21.2%) regional lymph node metastasis. Distant metastasis was associated with a higher incidence of lymph node metastasis (OR = 1.506, 95% CI 1.346-1.685, p < 0.001). Age 3-17 years (OR = 1.933, 95% CI 1.406-2.680, p < 0.001), left-sided (OR = 1.383, 95% CI 1.016-1.890, p = 0.040), bilateral (OR = 2.303, 95% CI 1.215-4.243, p = 0.009), and tumor size ≥135 mm (OR = 2.020, 95% CI 1.481-2.749, p < 0.001) were identified as predictors of metastasis. Both lymph node (p < 0.001) and lung metastasis (p < 0.001) were high-risk factors for WT. Radiotherapy provided long-term survival benefits for the metastatic population (p = 0.027), while postoperative chemotherapy showed better outcomes than preoperative or other strategies (p < 0.001). Further analysis demonstrated that the concurrent lung and lymph node metastasis group benefited more from postoperative chemoradiotherapy, with HRs of 0.226 (p = 0.028) for overall survival and 0.255 (p = 0.048) for cancer-specific survival. CONCLUSION: WT with concurrent lung and lymph node metastasis represents a distinct and aggressive metastatic phenotype associated with a significantly poor prognosis. Postoperative chemoradiotherapy may provide superior survival benefits for this high-risk population.

Humans↗

PubMed2025

Preoperative Patient Education on Opioid Use and Pain After Surgery: A Randomized Trial.

OBJECTIVE: To evaluate the impact of preoperative analgesic education on postoperative opioid consumption, pain scores, and patient satisfaction with analgesia. BACKGROUND: Effective postoperative pain management is crucial for patient recovery and satisfaction, yet opioid use poses risks of tolerance and addiction. Preoperative patient education offers a potential avenue to mitigate opioid reliance and improve pain management outcomes. METHODS: This single-center randomized trial was conducted at the Cleveland Clinic Main Campus between October 2021 and October 2023. Adult patients scheduled for hip arthroplasty or laparoscopic-assisted abdominal surgery with an ASA physical status of 1 to 4 were eligible. Patients with a history of prolonged opioid use, planned regional block or epidural analgesia, or limited English fluency were excluded. Participants were randomized 1:1 to receive either an analgesic educational video or a generic video about surgery and hospitalization. The primary outcome was opioid consumption during the initial 72 postoperative hours. Secondary outcomes included time-weighted average pain scores and patient satisfaction with analgesia. RESULTS: Among 957 analyzed patients, preoperative analgesic education did not significantly reduce opioid consumption (adjusted ratio of geometric means, 1.01; 95% CI, 0.86-1.18; P =0.890) or improve pain scores (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P =0.617). Patient satisfaction scores also did not differ significantly between groups (adjusted mean difference, -0.1; 95% CI, -0.3 to 0.2; P = 0.611). CONCLUSIONS: Preoperative analgesic education did not result in clinically meaningful reductions in opioid consumption or improvements in pain management outcomes. Further research may explore more intensive educational interventions to optimize postoperative pain management strategies.

Humans↗

PubMed2026

Whole genome sequencing of unusual Hepatitis C virus subtypes and drug resistance analysis during direct-acting antiviral therapy in India.

INTRODUCTION AND OBJECTIVES: Pangenotypic direct-acting antivirals (DAA) are effective against highly prevalent Hepatitis C virus (HCV) subtypes, but have been clinically validated almost exclusively in high-income countries. Unusual HCV subtypes may carry natural polymorphisms, potentially impacting DAA susceptibility. We conducted full-genome characterization and resistance analysis of unusual HCV subtypes in patients receiving DAA treatment. PATIENTS AND METHODS: In this prospective hospital-based study, eligible patients were screened for anti-HCV antibodies and active infection was confirmed by diagnostic 5'NCR-based HCV RNA detection. Genotyping was performed by core region sequencing, and viral load quantified by real-time PCR. For whole genome sequencing, multiplex primers were designed using alignments of global reference sequences. Sequencing was carried out using the Oxford Nanopore Technology platform. Phylogenetic analysis used multiple sequence alignment and the HCV-GLUE resource for resistance-associated substitution (RAS) analysis. RESULTS: Predominant genotype was genotype 3 in 64.3% (n = 45); genotype 6 in 21.4% (n = 15); and genotype 1 in 14.2% (n = 10). Unusual HCV subtype 6xa was detected in two patients and showed no NS5A resistance mutations. One genotype 3b patient relapsed at 24 weeks post-DAA treatment completion and carried NS5A resistance-associated substitutions 30 K and 31 M both at baseline and at relapse, conferring high-level resistance to NS5A inhibitors. CONCLUSION: This is the first report from India of whole genome sequencing of HCV subtype 6xa. The identification of NS5A resistance mutations in the 3b relapse case underscores challenges for global HCV elimination strategies.

Humans↗

PubMed2026

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals↗

PubMed2026

Global prevalence and associated factors of turnover intention among intensive care nurses: A systematic review and meta-analysis.

OBJECTIVES: To estimate the global prevalence of two distinct turnover intentions among intensive care unit (ICU) nurses-intention to leave the ICU and intention to leave the nursing profession-identify significant sources of heterogeneity, and synthesise associated psychosocial factors. METHODS: Ten databases were systematically searched from inception to September 28, 2025. Two reviewers independently conducted study selection, data extraction, and quality appraisal using Joanna Briggs Institute checklists. Random-effects meta-analyses were performed to estimate pooled prevalence and associated factors. Subgroup and meta-regression analyses explored potential sources of heterogeneity. Associated factors were pooled as odds ratios (ORs) and interpreted within an integrated Job Demands-Resources and Theory of Planned Behavior framework. RESULTS: Forty-six studies published between 2007 and 2025, involving 39,246 ICU nurses, were included. The pooled prevalence was 30.7% for intention to leave the ICU and 27.5% for intention to leave the nursing profession. Significant sources of heterogeneity included ICU type, geographic region, publication year, study design, measurement tool, and sampling method. Depression, burnout, high workload, and unsafe patient-to-nurse ratios were associated with increased turnover intention, whereas positive work environments, perceived organisational support, and nursing competence were protective factors. No significant publication bias was detected. CONCLUSIONS: Turnover intention affects approximately one-third of ICU nurses globally and varies across clinical and geographical contexts. Excessive workload, inadequate organisational support, and unfavourable work environments appear to be important contributors to turnover intention among ICU nurses. IMPLICATIONS FOR CLINICAL PRACTICE: Strategies to reduce turnover intention among ICU nurses should focus on reducing excessive workload, improving staffing conditions, strengthening organisational support, and fostering positive work environments. Promoting supportive and sustainable ICU work environments may help improve nurse retention and maintain the quality of critical care services.

Humans↗

PubMed2026

Continuous theta-burst stimulation over the right DLPFC modulates central executive network connectivity in depression: exploratory analysis of a randomized clinical trial.

Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects and is associated with alterations in functional connectivity (FC), but the neural correlates remain unclear. This exploratory sham-controlled trial investigated the effect of continuous theta-burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on FC in major depressive disorder (MDD). Seventy MDD patients were randomized to receive two-week treatment of personalized cTBS or sham stimulation. Resting-state fMRI was performed at baseline and post-treatment. Ultimately, 31 patients in the active cTBS group and 28 patients in the sham group passed imaging quality control and were included in the final analysis. To identify the FC that may have been influenced by cTBS treatment, two complementary FC analyses were conducted: (1) voxel-wise degree centrality (DC) followed by seed-based FC, and (2) an individual FC analysis based on the stimulation targets. Furthermore, correlations between FC changes and clinical symptoms improvement were examined. Both groups exhibited reductions of depression scores, with greater improvement in the active group. Compared to the sham group, active cTBS showed increased DC in the precuneus and elevated FC between the precuneus (within the para-cingulate network) and the right inferior parietal lobule (IPL) and DLPFC. Further stimulation target-based analysis revealed increased FC between stimulation targets and both the precuneus and visual regions following treatment. Our findings reveal neural changes associated with cTBS over the right DLPFC in MDD, notably involving the precuneus and its connectivity with the right IPL/DLPFC, suggesting alterations within the central executive network. TRIAL REGISTRATION: chictr.org.cn; ChiCTR2300068273.

Humans↗

PubMed2026

Maternal obesity in rats results in male-specific increases in genome-wide DNA methylation in postnatal offspring liver.

Male-specific peripubertal DNA demethylation in the liver has been reported in mice. Here, we investigated whether it also occurs in rats, the influence of maternal obesity and whether DNA demethylation changes contribute to observed sex-specific effects of maternal obesity in offspring. Female rats were fed a high-fat, high-sugar 'cafeteria' (Caf) diet before mating with standard chow-fed males. The offspring liver methylome and transcriptome were examined. Body weight was higher in Caf-fed dams prior to mating, during gestation and at parturition. Male and female offspring from Caf-fed dams had lower birth weights but higher adult weights and adiposity than offspring from chow-fed dams. A comparison of DNA methylation in 3-week-old weaner males versus female siblings from chow-fed dams did not reveal the male-specific DNA demethylation that was previously reported in mice. However, strong maternal diet effects in male weaner offspring methylation were observed. A comparison of female weaners from chow- versus Caf-fed dams showed a range of differences, with 39% of differentially methylated regions (DMRs) having higher methylation in Caf offspring and 61% of DMRs having higher methylation in chow offspring. In stark contrast, 99% of maternal-diet-induced DMRs in male weaner offspring had higher methylation in offspring from Caf-fed dams. This suggests that maternal obesity induces widespread hypermethylation in the male offspring liver at weaning. However, a comparison with RNA sequencing data revealed limited transcriptional changes at this developmental stage or in adult offspring. While these data highlight how environmentally sensitive DNA methylation is in the male rodent perinatal period, these methylation changes may not be a major contributor to sex differences in developmentally programmed liver disease.

Animals↗

PubMed2026

Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.

BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.

Humans↗

PubMed2026

Acupuncture improves depressive symptoms and prefrontal cortical function in mild to moderate depressive disorder: A randomized sham-controlled trial and fNIRS study.

BACKGROUND: Depressive disorder is a common mental illness associated with substantial functional impairment. Although pharmacotherapy is widely used, its effectiveness is often limited by adverse effects and poor adherence. Acupuncture has been increasingly applied as a complementary treatment for depression, and its neurobiological characteristics remain unclear. OBJECTIVE: This randomized, sham-controlled trial aimed to evaluate the clinical efficacy of acupuncture for mild to moderate depressive disorder and to investigate its effects on prefrontal cortical function using functional near-infrared spectroscopy (fNIRS). METHODS: Patients with mild to moderate depressive disorder were randomly assigned to a real acupuncture (RA) group or a sham acupuncture (SA) group and received standardized treatment for 8 weeks. Clinical outcomes were assessed using the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Short Form-36 Health Survey (SF-36), and a traditional Chinese medicine syndrome score. A subset of participants underwent fNIRS assessment during resting-state and task-based conditions to evaluate prefrontal cortical activation and functional connectivity. RESULTS: Compared with baseline, the RA group showed significant reductions in SDS and SAS scores and significant improvements in SF-36 emotional domains, with effects emerging at Week 4 and persisting up to 12 weeks after treatment. Improvements were greater and more stable in the RA group than in the SA group. fNIRS analyses revealed enhanced activation in dorsolateral and medial prefrontal regions and strengthened prefrontal functional connectivity following acupuncture, whereas neural changes in the SA group were limited. CONCLUSION: Acupuncture is effective for improving depressive and anxiety symptoms and quality of life in patients with mild to moderate depressive disorder. Modulation of prefrontal cortical activation and connectivity may underlie its antidepressant effects.

Humans↗

PubMed2026

On-filter fractionation by empFASP improves identification of membrane peptides in proteomic experiments.

Membrane proteins remain among the most analytically challenging targets in bottom-up proteomics due to their limited solubility and low abundance of protease-accessible sites within transmembrane domains. In addition, hydrophobic peptides are frequently lost during detergent removal and the on-filter processing steps. Here, we present empFASP, a straightforward on-filter-fractionation-based modification of the enhanced filter-aided sample preparation (eFASP) workflow that enhances recovery of membrane-embedded peptides otherwise lost during digestion and cleanup. The method combines controlled on-filter inversion with sequential ethyl acetate extraction at defined pH values, enabling recovery of peptide material retained on the filter and redistributed into detergent micelles. Compared with SP3 and SP4 in HEK293T lysates, empFASP increased unique hydrophobic peptide identifications by up to 48% and increased the proportion of detected transmembrane peptides. Application to mouse mitochondrial membranes and phosphatidylethanolamine-deficient and PE-containing Escherichia coli membranes showed that the additional fractions of empFASP contribute complementary recovery of hydrophobic and membrane-associated peptides, with the strongest gains observed at the peptide level. Because empFASP requires no specialized reagents or instrumentation, it can be readily implemented in standard proteomics workflows to improve coverage of membrane-embedded regions. SIGNIFICANCE: The empFASP (enhanced membrane peptide) workflow offers a practical solution to one of the persistent limitations in membrane proteomics-the underrepresentation of hydrophobic and transmembrane peptides in standard digests. By integrating simple pH-controlled extractions into an on-filter format, empFASP recovers peptides otherwise lost through adsorption or detergent micelle retention, substantially improving coverage of the membrane proteome. This method expands the analytical reach of bottom-up proteomics without requiring specialized instrumentation, making it immediately applicable for studies of membrane topology, protein-lipid interactions, and the structural consequences of altered membrane composition.

Proteomics↗

PubMed2026

Chemoradiotherapy versus short-course radiotherapy for response-adapted organ preservation in early-stage and intermediate-stage rectal cancer (STAR-TREC): 12-month results of an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial.

BACKGROUND: Total mesorectal excision (TME) is the standard treatment for most early-stage and intermediate-stage rectal cancer but can cause substantial perioperative morbidity, functional impairment, and reduced quality of life. We assessed whether long-course chemoradiotherapy (LCCRT) or short-course radiotherapy (SCRT) could increase organ preservation and reduce surgery, toxicity, and quality-of-life harms without compromising oncological outcomes. METHODS: STAR-TREC is an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial in five European countries. Eligible patients were aged 16 years or older in the UK or aged 18 years or older elsewhere, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and rectal adenocarcinoma (≤40 mm staged as mrT1-T3bN0). In phase 2, participants were randomly assigned (1:1:1) to LCCRT-based organ preservation (LCCRT-OP; 50 Gy in 25 fractions plus oral capecitabine 825 mg/m2 twice daily), SCRT-based organ preservation (SCRT-OP; 25 Gy in five fractions), or primary TME. Phase 2 assessed feasibility, with recruitment at months 12 and 24 as the primary endpoint and feasibility thresholds of four or more and six or more randomisations per month, respectively. Phase 3 adopted a partially randomised patient-preference design, allowing participants to choose either organ preservation or TME. Participants that chose organ preservation were randomly assigned (1:1) to receive LCCRT-OP or SCRT-OP using centralised, computer-generated assignment, with stratification by country and MRI T category (≤T3a vs T3b) using minimisation. The phase 3 primary endpoint was organ-preservation 30 months after treatment initiation, defined as absence of TME, stoma, or local recurrence, which was assessed in the modified intention-to-treat population, which included participants in phase 2 and phase 3. After a planned interim analysis of unmasked phase 2 data, the trial steering committee and independent data monitoring committee recommended reporting a 12-month, modified intention-to-treat analysis of implementation outcomes for participants recruited before Aug 8, 2023. This study is registered with ISRCTN (14240288) and is closed. FINDINGS: Between June 14, 2017, and April 8, 2024, 503 participants were enrolled at 37 sites. Phase 2 enrolled 120 participants, with recruitment rates of three and six participants per month at months 12 and 24, respectively. Overall, 12-month TME-free survival was 60% (47 of 78 participants). After phase 3 recruitment ended, interim analysis of unmasked phase 2 data showed an early TME-free survival benefit with LCCRT versus SCRT (12-month median TME-free survival not reached [95% CI not reached-not reached] vs 7·6 months [95% CI 6·4-not reached]; hazard ratio [HR] 3·7 [95% CI 1·7-8·0]; posterior probability of superiority >99·5%). The trial steering committee and independent data monitoring committee therefore recommended expanded analysis of 426 participants recruited before Aug 8, 2023: 120 from phase 2 and 306 from phase 3. 17 participants withdrew before treatment, leaving 409 in the modified intention-to-treat population: 163 allocated to LCCRT, 168 to SCRT, and 78 to primary TME. 116 (28%) participants were female and 293 (72%) were male. Among participants who opted for organ preservation, 12-month TME-free survival was 78·5% (95% CI 72·4-85·1) with LCCRT and 60·6% (53·6-68·4) with SCRT (HR 1·90 [95% CI 1·29-2·81]). The most common grade 3-4 serious adverse events were gastrointestinal disorders (four [2%] with LCCRT vs six [4%] with SCRT vs six [8%] with TME) and procedural complications (three [2%] with LCCRT vs five [3%] with SCRT vs five [6%] with TME). One participant allocated to primary TME died after an anastomotic leak. INTERPRETATION: These early results support a response-adapted organ-preservation approach, with LCCRT appearing more effective than SCRT at 12 months. Organ-preservation might also reduce treatment-related toxicity compared with primary TME. Longer follow-up is needed for the prespecified 30-month endpoint and definitive functional and oncological outcomes. FUNDING: Cancer Research UK, Stand Up to Cancer, Dutch Cancer Society, Danish Cancer Society, Kom Op Tegen Kanker, Cancerfonden, ALF Region Stockholm, RCC Region Stockholm.

Humans↗

PubMed2026

Treatment of Established Groin Lymphatic Complications After Arterial Surgery: A Systematic Review.

BACKGROUND: To systematically review the effectiveness and safety of interventions for established groin lymphatic complications after arterial vascular surgery. METHODS: PubMed, Embase, and Cochrane CENTRAL were searched from inception to May 28, 2025. This review was registered in PROSPERO (CRD420251061708) and conducted according to PRISMA, PRISMA-S, and Synthesis Without Meta-analysis (SWiM) guidance. Eligible studies included adults with established groin lymphorrhea/lymphocutaneous fistula or seroma/lymphocele after arterial exposure in the common femoral or iliofemoral region. Prophylactic studies were excluded. Two reviewers independently screened studies and assessed full texts. Prespecified outcomes were resolution, time to resolution, length of stay, surgical site infection, wound complications, reintervention, and recurrence. Owing to substantial heterogeneity, meta-analysis was not performed. RESULTS: Eighteen retrospective single-center studies were included; no randomized trials were identified. Reported strategy-family totals were operative control (n = 240, including 55 dye-assisted cases), intranodal lymphangiography with glue embolization (n = 39), intracavitary or chemical instillation (n = 52), negative-pressure wound therapy (n = 20), radiotherapy (n = 206), and drainage or aspiration alone (n = 7). One additional cohort compared nonsurgical with surgical management. Definitions, follow-up windows, and statistical reporting were inconsistent, and arm-level denominators were frequently incomplete. Risk of bias was serious to critical across the evidence base, mainly because of retrospective design, confounding by indication, treatment-selection bias, inconsistent outcome definitions, and incomplete reporting. Using GRADE principles, certainty of evidence was very low across strategies and phenotypes. Across study arms, conduit-directed approaches for external leak and cavity-directed approaches for encapsulated collections often achieved control, but valid comparative inference was not possible. CONCLUSION: Evidence is limited to small retrospective series with heterogeneous definitions, serious to critical risk of bias, and very low certainty. Reliable comparisons between interventions cannot currently be made. Standardized phenotype-specific definitions and outcome reporting are needed to support prospective studies and future trials.

Humans↗

PubMed2026

Complexity in disguise: a systematic review of fractal analysis in psychiatric neuroimaging.

OBJECTIVES: Psychiatric diagnosis and fractal studies are complex processes that extend beyond clinical evaluation and require careful methodological considerations in neuroimaging. Over the years, fractals have helped reduce these complexities in research, but they still cannot grant clinical diagnoses. Thus, the main objective was a systematic review exploring the potential applications of fractal analysis in characterizing psychiatric conditions through neuroimaging techniques-including both functional and structural MRI. MATERIALS AND METHODS: A systematic literature review was conducted on PubMed, identifying thirty-nine original studies that met the inclusion criteria. Areas showing statistical significance (p < 0.05) were reported. These studies were categorized according to DSM-V classification and examined for the description of psychiatric conditions through the fractal analysis. RESULTS: The review primarily focuses on young adults with psychiatric conditions compared to control groups. Schizophrenia and Autism Spectrum Disorder are major areas of investigation, and fractal dimension (FD) is the primary analysis method used to reflect brain patterns. Studies that calculated whole-brain FD may have underestimated local abnormalities due to the inclusion of a high percentage of tissue, potentially resulting in overlooked findings. Notably, abnormalities in the frontal cortex represent a common neurobiological feature across several psychiatric conditions. CONCLUSIONS: The findings from this systematic review shed light on the use of fractal analysis to quantify complex brain patterns in both psychiatric patients and healthy individuals. However, it is essential to recognize the need for further research to elucidate a fractal analysis protocol that allows for optimal extraction of psychiatric insights. KEY POINTS: Question Fractal analysis applied to structural and functional MRI help characterize brain alterations across psychiatric conditions. Findings This review shows consistent fractal patterns across multiple psychiatric disorders, especially in frontal regions. Despite heterogeneous methodologies, results highlight shared structural and functional abnormalities. Clinical relevance Fractal analysis may offer complementary characterization of subtle brain organization across psychiatric disorders. Its potential clinical utility-such as improving diagnostic characterization, earlier detection, among others-remains limited by the current absence of a standardized protocol.

Humans↗

PubMed2026

Analgesia for Awake Internal Jugular Vein Cannulation in Trauma Emergency Bay: A Randomized Comparison of Ultrasound-Guided Superficial Cervical Plexus Block With Local Infiltration.

BACKGROUND: Internal jugular vein (IJV) cannulation is a critical component of trauma resuscitation but is often associated with significant pain during vessel dilation and suturing when performed under local anesthetic (LA) infiltration. OBJECTIVES: We hypothesized that an ultrasound (USG)-guided superficial cervical plexus block (SCPB) would provide superior analgesia and improve procedural efficiency in awake trauma patients compared to standard LA infiltration. METHODS: This was a prospective, randomized study of conscious, adult trauma patients requiring IJV cannulation. Participants were randomized to receive either 10 mL of 1% lignocaine via ultrasound-guided SCPB (Group S) or LA infiltration (Group L). The primary outcome was procedural pain measured by Numeric Rating Scale (NRS 0-10) during skin puncture, vessel dilation, catheter insertion, and suturing. Secondary outcomes included total procedure time, Verbal Numeric Rating Discomfort Scale (0-10), and complications. RESULTS: We enrolled 60 patients, with 30 patients assigned to each study group. Median NRS pain scores were significantly lower in Group S compared to Group L at all procedural time points (p < 0.01). The total procedure time was reduced by approximately 50% in Group S (7.5 min [interquartile range (IQR) 6.0-9.3]) compared to Group L (15.5 min [IQR 9.5-16.5]; p < 0.01). Patient discomfort scores were also significantly lower in Group S (p < 0.01). No periprocedural complications were reported in either group. CONCLUSION: Ultrasound-guided SCPB may be a useful alternative to local infiltration for IJV cannulation in selected awake trauma patients, when performed by clinicians experienced in ultrasound-guided regional anesthesia. By providing comprehensive sensory coverage, the technique significantly reduces procedural time and enhances patient cooperation without need for systemic sedation.

Humans↗

PubMed2026

Contemporary surgical decision-making for hallux valgus and hallux rigidus in Switzerland: A national cross-sectional survey using standardized clinical scenarios.

BACKGROUND: Surgical management of hallux valgus and hallux rigidus is influenced by deformity severity, surgeon training, and evolving techniques. Previous surveys in Australia (2012), Switzerland (2015), and Israel (2023) using identical hypothetical cases demonstrated marked regional differences and a recent rise in minimally invasive Chevron-Akin (MICA). Whether these advances have altered contemporary Swiss practice remains unclear. METHODS: An electronic survey replicating the original questionnaire was distributed to members of the Swiss Foot and Ankle Society. Three standardized clinical cases were presented: mild hallux valgus, severe hallux valgus, and hallux valgus et rigidus. Respondents selected nonoperative versus operative management and specified procedures and fixation methods. Demographics, subspecialty training, and surgical volume were recorded. Current results were compared with prior Swiss data to assess temporal change. RESULTS: Eighty surgeons completed the survey (94% foot and ankle specialists). For mild hallux valgus, 87.7% recommended surgery; Scarf osteotomy remained most common (49.4%), followed by Chevron (21.0%) and Minimally Invasive Hallux Valgus correction (14.8%). Minimally Invasive adopters were predominantly mid-career (83% aged 41-50), high-volume surgeons. For severe hallux valgus, 95.1% favoured surgery; MTPJ arthrodesis was preferred (50.6% isolated; 11.1% with Lapidus), while Minimally Invasive Hallux Valgus correction was rarely chosen (2.5%). In hallux valgus et rigidus, 96% selected MTPJ fusion, most commonly plate-and-screw fixation (45.1%). Compared with 2015, fixation strategies evolved, yet procedure selection remained largely unchanged. CONCLUSION: Despite global expansion of minimally invasive bunion surgery, Swiss surgeons continue to favour established open techniques, particularly Scarf osteotomy and fusion-based strategies. Adoption of MIS remains limited and concentrated among high-volume, mid-career specialists, indicating a cautious national diffusion pattern. LEVEL OF EVIDENCE: IV, survey study.

Hallux Valgus↗