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PubMed2026

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

Humans↗

PubMed2026

Dual-tasking reveals severity-dependent reorganization of cortical beta energy landscapes in Parkinson's disease.

Dual-task impairment is a hallmark of Parkinson's disease (PD), yet the large-scale neural mechanisms underlying postural-motor interference remain poorly understood. In particular, it is unclear how cortical network dynamics reorganize across disease severity when postural control competes with concurrent task demands. This study investigated EEG-derived beta-band cortical energy landscapes in healthy older adults, early-stage PD, and mid-stage PD during single- and dual-task conditions. Dual-task behavioral cost increased with disease severity for concurrent manual performance (p < 0.001), whereas a quadratic pattern was observed for postural performance. Energy landscape analysis revealed severity-dependent reconfiguration of cortical beta dynamics. Dual-task-related landscape changes in effective network flexibility (ΔNeff), landscape geometry (ΔEvar and ΔGmag), and dominant low-energy attractor organization (ΔLow mass and ΔLow area) showed significant monotonic trends (p < 0.05), reflecting progressive constrained cortical network dynamics with advancing PD severity. In addition, dual-task-related landscape alterations were associated with clinical severity, as indexed by Hoehn and Yahr stage (|r| = 0.353-0.423, p = 0.016-0.048), and showed associations with motor impairment, as measured by MDS-UPDRS part III scores (|r| = 0.333-0.455, p = 0.009-0.063). These findings demonstrate that dual-task demands induce severity-dependent reconfiguration of cortical beta energy landscapes in PD. Energy landscape geometry may capture systems-level neural constraints associated with dual-task susceptibility in PD, providing a physiologically grounded framework to characterize disease-related functional vulnerability.

Humans↗

PubMed2026

Molecular characterization and biological characteristics of a highly pathogenic recombinant ALV-J strain (HUE2023) with cross-clade gp85 recombination.

Avian leukosis virus subgroup J (ALV-J) has undergone extensive diversification into phylogenetically distinct clades, yet whether recombination between these clades within the gp85 envelope glycoprotein generates variants with altered pathogenicity has received little direct investigation. A field strain (HUE2023) was recovered from breeding roosters displaying vascular tumors. The viral genome was sequenced and subjected to phylogenetic and recombination analyses. The three-dimensional structure of gp85 was predicted with AlphaFold3; electrostatic surface potentials and surface hydrophobicity were computed using the Adaptive Poisson-Boltzmann Solver and the Eisenberg hydrophobicity scale, respectively. Pathogenicity and immunosuppressive effects were assessed in Hy-Line Brown chickens. Recombination analysis revealed that HUE2023 is an inter-clade recombinant derived from Clade 1.1 (major parent: JS14NT01) and Clade 1.2 (minor parent: JS09GY3). A single-residue deletion at position 61 within receptor-binding domain 1 (RBD-1), unique to the recombinant, induced a localized conformational rearrangement that generated a concentrated electronegative surface patch and a contiguous hydrophobic pocket not observed in either parental gp85. Animal challenge showed that HUE2023 is highly pathogenic: female chickens in the high-dose group reached only 61% survival and displayed significant growth retardation (P < 0.05) together with marked immunosuppression. The recombination in the RBD-1 led to local conformational rearrangement, resulting in a concentrated and negatively charged surface area as well as a continuous hydrophobic pocket, which were never present in any of the parental gp85 sequences. These results indicate that gp85 recombination across clades can yield variants with fundamentally altered receptor-binding surfaces and argue for integrating structural surveillance into ALV-J monitoring programmes.

Animals↗

PubMed2026

Positive conversion of latent tuberculosis screening in patients with inflammatory bowel disease on antitumor necrosis factor alpha drugs: a systematic review and meta-analysis.

Inflammatory bowel disease (IBD) patients undergoing antitumor necrosis factor-alpha (anti-TNF) therapy are at increased risk of developing tuberculosis (TB), making screening before anti-TNF initiation mandatory. Repeated screening during treatment is not yet recommended because of a lack of studies to support this practice. We aimed to determine the proportion of patients who develop latent TB during anti-TNF therapy. We systematically searched studies from MEDLINE, Embase, and Lilacs, and performed a single-arm meta-analysis investigating the positive conversion rate in IBD patients under anti-TNF therapy with previous negative TB screening. We calculated the combined proportion with 95% confidence interval, using the random-effects model. A P value less than 0.05 was considered statistically significant for subgroup differences. We included 13 studies from nine countries with 1153 patients. The overall positive conversion rate was 9.20%. Portugal had 18.01% of positive conversion, Spain 4.51%, and the USA 1.11%. Tests for subgroup differences were statistically significant for subgroup analysis by country and consistency of test used (performig same test as baseline). Subgroup analyses by continent, study design, or specific test (tuberculin skin test or interferon-gamma release assay) showed no statistical difference. Meta-regression analysis showed a significant positive association between positive conversion and TB incidence. In conclusion, IBD patients on anti-TNF therapy can have a positive conversion rate of 9.20%. Higher conversion rates were seen in European and Asian studies compared with those in the Americas (particularly the USA). TB prevention strategies should, therefore, be individualized and based on geographic location and risk factors.

Humans↗

PubMed2026

A randomized study of antibiotic prophylaxis after hypospadias repair in children.

BACKGROUND AND OBJECTIVE: Antibiotic resistance is a challenge in contemporary world. Urethroplasty for hypospadias is one of the most common urological surgeries performed around the world, yet, there is still no consensus on the use of antibiotics pre- and post-operatively. Our objective was to analyze the effectiveness of antibiotic prophylaxis and therapy before, during, and after hypospadias repair in children. METHODS: A prospective randomized trial was carried out including patients with coronal hypospadias who underwent urethroplasty performed by one surgeon. Urethral catheters were used in all cases for 10 days. Study participants were randomly assigned in a 1:1:1 ratio to receive a single intraoperative administration of antibiotics (Group I); an intraoperative antibiotic prophylaxis and antibiotic therapy for 10 days until the removal of urethral catheter (Group II); no antibiotic administration (Group III). Randomization was performed using computer-generated permuted blocks with randomly varying block sizes, prepared by an independent statistician. The results were analyzed using the analysis of variance (ANOVA). The following criteria were compared: postoperative functional complications, such as: urethral fistula, stenosis, diverticulum; wound infection symptoms: hyperemia of surgical site, pain during palpation, and symptomatic urinary tract infection. RESULTS: A total of 300 patients were included in the study. Two patients (2%) in Group I, two patients (2%) in Group II, and four patients (4%) in Group III had urethral fistulas, requiring surgery 6 months after primary repair, yet without statistical difference between groups. We found no significant difference in frequency of symptomatic UTIs between three groups (p = 0.182). CONCLUSION: There is no effect of antibiotic prophylaxis and therapy on the frequency of postoperative surgical and infectious complications after urethroplasty for coronal hypospadias repair in children.

Humans↗

PubMed2026

Current Concepts and Emerging Technologies in Aesthetic Outcome Assessment of Breast Reconstruction.

Aesthetic outcomes are a crucial determinant of the overall success of breast reconstruction. Recently, aesthetic assessment has evolved from relying mainly on subjective impressions to incorporating more quantitative methods. This systematic review summarizes current concepts and emerging technologies in aesthetic outcome assessment after breast reconstruction. A comprehensive search of studies evaluating aesthetic outcomes following implant-based, autologous or hybrid breast reconstruction was performed between 2000 and 2025. Assessments were classified as subjective or objective. Extracted variables included assessment characteristics, aesthetic outcome domains, and patient-centered outcomes. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Levels of evidence were classified according to the Oxford Centre for Evidence-Based Medicine. A total of 51 studies involving 7711 participants from 16 countries were included. Subjective tools were most frequently employed, led by the BREAST-Q (35/51, 69%), followed by expert- or panel-based evaluations (17/51, 33%) and the visual analog scale (2/51, 4%). Objective methods were applied in 19 studies and included 3-dimensional surface imaging (8/51, 16%), BCCT.core (7/51, 14%), eye tracking (3/51, 6%), and artificial intelligence-based analyses (3/51, 6%). Although subjective tools captured satisfaction with breast appearance, objective tools quantified morphological parameters and positional landmarks. BREAST-Q remains the cornerstone of outcome evaluation after breast reconstruction, providing patient-centered perspectives, including, but not limited to, aesthetic perception. A progressive shift toward multimodal evaluation was noticed, as no single modality comprehensively addressed all aesthetic domains. Future research should focus on integrating subjective and objective assessment methods within a unified framework. Level of Evidence: 3 (Therapeutic) For image description, please refer to the figure legend and surrounding text.

Humans↗

PubMed2026

The Impact of Video Game Experience on Surgical Performance: A Systematic Review.

OBJECTIVE: To assess whether video gaming experience is associated with improved surgical performance in the surgeon population across laparoscopic, robotic, and other surgical modalities, and evaluate its implications on surgical training and education. METHODS: A structured literature search was conducted across five databases on 29th November 2024 in adherence to PRISMA guidelines. Comparative studies evaluating surgical performance outcome data between surgeons with differing video game experience were eligible for inclusion. Outcomes evaluated were time to complete task, error rate, accuracy, economy of motion, and overall score. Included studies were assessed for risk of bias using ROBINS-I and RoB 2. RESULTS: 15 studies involving 641 participants were included, comprising one randomized controlled trial and 14 nonrandomized studies. All nonrandomized studies were judged to be at moderate or serious risk of bias, and the single randomized controlled trial was judged to be at serious risk of bias. Differences in study design and outcome measures meant that quantitative synthesis could not be performed. Across laparoscopic studies, video gaming experience was associated with improved overall score and time to task completion predominantly in the period prior to structured training interventions, with accuracy findings consistently favoring gamers in the two studies reporting this outcome. Error rate and economy of motion findings were inconsistent or predominantly nonsignificant. No meaningful association was identified across nonlaparoscopic modalities. CONCLUSIONS: Video gaming may be associated with improved surgical performance in surgeons, though this appears restricted to laparoscopic tasks and the pretraining intervention period. As a low-cost and accessible activity, video gaming may represent a practical informal adjunct to formal surgical training to help ease the transition into structured technical training. Surgical program directors need not alter existing selection criteria or training modules based on the available literature.

Video Games↗

PubMed2026

Randomized study of the effects of testosterone administration on severity of asthma in horses.

BACKGROUND: Low testosterone concentrations are associated with poor lung function in human asthmatics, and androgen administration improves airway obstruction in women with asthma. HYPOTHESIS/OBJECTIVES: Testosterone improves clinical scores, lung function, airway neutrophilia, and airway remodeling in horses with severe asthma. ANIMALS: Ten horses affected by severe asthma from a research herd. METHODS: In a randomized, blinded, crossover study, horses received dexamethasone (0.06 mg/kg PO q24h for 10 days) or a single intramuscular injection of testosterone cypionate (0.35 mg/kg), with a 2-week washout period. Clinical respiratory scores were assessed at days 0, 2, 5, and 10; lung function was evaluated at days 0, 5, and 10; and bronchoalveolar lavage fluid cytology and central airway remodeling at days 0 and 10. Mixed linear models were used for analysis. RESULTS: The respiratory clinical scores improved with dexamethasone administration (median [95% CI], from 12 (9-13) to 5 (3-6), P < .001), and remained unchanged with testosterone administration (from 10 [8-12] to 9 [8-11], P = .6). Pulmonary elastance improved with both treatments, but the effect was more pronounced with dexamethasone administration (from 5.1 cm H2O/L [2.4-5.8] to 0.5 [0.4-0.8], P < .001) than with testosterone administration (from 4.5 cm H2O/L [1.6-8.5] to 3.0 [1.0-4.1], P = .04). Pleural pressure and pulmonary resistance decreased only with dexamethasone. Neither treatment altered airway neutrophilia or bronchial remodeling. CONCLUSIONS AND CLINICAL IMPORTANCE: Testosterone is less effective than dexamethasone and only mildly improves pulmonary elastance in horses with severe asthma.

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

Comparison of summative assessments between simulated electronic health records versus traditional paper-based patient cases: A non-inferiority randomized controlled trial.

INTRODUCTION: Electronic health records are fundamental to contemporary pharmacy practice, yet evidence supporting their use in pharmacy education is lacking. This single-center, non-inferiority randomized controlled trial with blinded outcome assessment evaluated whether delivering patient cases via a simulated academic EHR (aEHR) was non-inferior to a traditional paper-based format in student exam performance. METHODS: 53 third-year PharmD students at the University of British Columbia were randomized 1:1 to complete a mock summative examination using either the aEHR or paper-based case delivery, stratified by self-reported EHR comfort level. The primary outcome was mean written exam score (%). Non-inferiority was pre-specified at a margin of 14%. Adjusted linear regression was used for the primary analysis, with a multiple imputation sensitivity analysis. Student perceptions were explored through post-exam focus groups analyzed using inductive thematic analysis. RESULTS: 42 students (21 per group) completed the exam and were included in the primary analysis. Mean scores were 66% (SD 11) in the aEHR group and 68% (SD 10) in the paper group. The adjusted mean difference (paper minus aEHR) was -2.2% (95% CI -9.2% to +4.8%), satisfying non-inferiority but not superiority. Sensitivity analysis (n = 53) yielded consistent results (-2.3%; 95% CI -7.1% to +4.1%). Focus groups revealed initial student anxiety with the aEHR but recognized its alignment with clinical practice. DISCUSSION: These findings support the feasibility of integrating simulated EHRs into summative pharmacy assessments without compromising performance. CONCLUSION: Simulated EHRs are a non-inferior assessment medium compared with paper-based formats and represent a viable step toward technology-driven pharmacy practice environments.

Humans↗

PubMed2026

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p = 0.002; FDR q = 0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p = 0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

Humans↗

PubMed2026

Can ChatGPT Replace Human Clinical Coders? A Comparative Study in Otology Billing.

OBJECTIVE: Evaluate the utility of the large language model (LLM), ChatGPT, for the analysis of operative notes and the generation of Current Procedural Terminology (CPT) codes in comparison to human clinical coders. STUDY DESIGN: CPT billing codes assigned by ChatGPT were compared to existing billing data. Otology practice within a tertiary academic center. METHODS: About 191 operative notes from a single surgeon (9/2022-10/2023) were analyzed. ChatGPT-3.5 and 4 models were prompted for CPT codes based on operative notes. Assessment included determining exact and partial match rates, sensitivity and specificity for targeted procedures, and work Relative Value Units (wRVU) differences between ChatGPT-generated and human-assigned codes. RESULTS: ChatGPT-3.5 achieved exact matches in 22% of cases and partial matches in 32%, while ChatGPT-4 achieved 14% exact and 33% partial matches. When cochlear implantation (CI) was excluded, performance dropped significantly. For CI, ChatGPT-3.5 demonstrated a sensitivity of 94% and specificity of 90%, while ChatGPT-4 showed a sensitivity of 96% and specificity of 92%. In contrast, performance on cartilage grafting was poor, with sensitivities of 4.2% for ChatGPT-3.5 and 0% for ChatGPT-4. ChatGPT-3.5 and 4 showed moderate CPT code matching accuracy among themselves, with slight agreement to human coders. Both models tended to underbill for wRVUs compared to human coders, with significant differences in the values generated. CONCLUSION: This study assessed ChatGPT's effectiveness in automating CPT code assignment for otologic surgeries. While the models achieved high sensitivity values for assigning codes related to cochlear implantation, both models struggled with complex cases, failed to apply modifiers, and often assigned fewer wRVUs. The findings highlight ChatGPT's potential in medical billing but indicate a need for further refinement.

Humans↗

PubMed2026

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans↗

PubMed2026

Prioritizing Parkinson's disease risk-associated mitochondrial candidate genes via multi-omics integrative analysis.

BACKGROUND: Mitochondrial dysfunction has been implicated in Parkinson's disease (PD), but the genetically regulated mitochondrial genes associated with PD risk remain incompletely defined. METHODS: We conducted a summary-data-based genetic epidemiology study integrating summary-based Mendelian randomization (SMR), Heterogeneity in dependent instruments (HEIDI) filtering, and Bayesian colocalization to prioritize mitochondrial-related molecular features associated with PD risk. Mitochondrial-related genes were defined using MitoCarta3.0. Genetically predicted gene expression and plasma protein abundance were evaluated using expression quantitative trait loci (eQTL) data from eQTLGen and GTEx v8, and protein quantitative trait loci (pQTL) data was assessed using International Parkinson's Disease Genomics Consortium (IPDGC) as the discovery genome-wide association study (GWAS) and FinnGen as the replication dataset. Prespecified QTL analyses were interpreted using FDR correction, HEIDI filtering, and colocalization support. DNA methylation QTL analysis, mitochondrial phenotype MR, and single-nucleus RNA-seq analysis were performed as complementary analyses. RESULTS: In the primary eQTL analysis, higher genetically predicted TTC19 expression was associated with lower PD risk (OR = 0.80, 95% CI: 0.74-0.87, PPH4 = 0.80), whereas higher MALSU1 expression was associated with increased PD risk (OR = 2.21, 95% CI: 1.59-3.06, PPH4 = 0.96). Both associations survived FDR correction, passed HEIDI filtering, and showed colocalization support. GTEx whole-blood data supported the direction of the TTC19 association. No mitochondrial protein reached significance after FDR correction and colocalization filtering in the primary pQTL analysis. Complementary methylation analysis highlighted cg06270993 as an exploratory regulatory signal for MALSU1. CONCLUSIONS: This MR-colocalization study prioritizes TTC19 and MALSU1 as genetically supported mitochondrial-related candidate genes associated with PD risk. Further validation is required to define their functional roles in PD pathogenesis.

Humans↗

PubMed2026

Genome-wide identification of CXE gene family in soybean and functional characterization of GmCXE31 in lipid biosynthesis and salt tolerance.

GmCXE31 negatively regulates salt tolerance and lipid synthesis in soybean, and the cxe31-edited lines improve soybean yield and seed quality. Carboxylesterases (CXEs), as essential lipid hydrolases of the α/β-hydrolase fold superfamily, are critical for plant stress responses, hormone signaling and secondary metabolism. The key candidate gene GmCXE31 was previously identified in our laboratory through a genome‑wide association study (GWAS) of soybean lipid‑related traits. In the present study, we further identified 60 GmCXE family genes in soybean. Phylogenetic analysis clustered them into 11 conserved subfamilies. Cis-acting element analysis showed their promoters are enriched with elements related to abiotic stress, growth and hormone signaling, suggesting potential roles in soybean development and stress adaptation. GmCXE31 is highly expressed in seedling roots and responsive to strigolactones (SLs) and salt stress. Functional assays revealed that GmCXE31 negatively regulates soybean salt tolerance: its overexpression reduced salt tolerance in Arabidopsis and soybean under 150 mM NaCl stress, while its knockout enhanced this trait. Lipid profiling revealed GmCXE31-edited lines had higher seed oil content, elevated oleic/linoleic acid ratio and lower saturated fatty acid proportion, which was achieved by regulating lipid synthesis-related genes like GmNFYA. Agronomic trait analysis showed GmCXE31-edited lines had increased nodule number, plant height and single-plant yield at maturity, with opposite phenotypes in overexpression lines. In conclusion, this study elucidates the multifaceted roles of GmCXE31 in coordinating soybean salt tolerance, lipid metabolism and agronomic traits, providing theoretical and genetic resources for salt-tolerant and high-quality soybean molecular breeding.

Glycine max↗

PubMed2026

Molecular targeted therapy in combination with chemotherapy for the treatment of platinum-resistant/refractory ovarian cancer (PROC): a systematic review and network meta-analysis.

BACKGROUND: Although single-agent chemotherapy is the most common approach for treating platinum-resistant or refractory ovarian cancer (PROC), there is growing evidence that combining molecular targeted agents with chemotherapy is beneficial, especially for certain patient groups. However, the most effective combination regimen remains elusive. OBJECTIVES: This Bayesian network meta-analysis (NMA) aims to identify the best combination therapy for PROC. METHODS: Relevant studies were searched in PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials from their inception until October 2024. The primary outcomes were overall survival (OS), progression-free survival (PFS) and adverse events (AEs). Statistical analyses were performed using the GEMTC package (1.0-2) and R 4.2.0. This review was registered in PROSPERO (CRD42023428414). RESULTS: Our analysis of 22 randomized controlled trials (RCTs) (n = 3408) demonstrated that chemotherapy combinations with bevacizumab (hazard ratio (HR) = 0.52-0.65), sorafenib (HR = 0.65, 95% confidence interval (CI): 0.45-0.93) or adavosertib (HR = 0.56, 95%CI: 0.35-0.90) significantly improved OS and PFS versus chemotherapy alone. Notably, adavosertib + gemcitabine was associated with an increased risk of grade 3-4 AEs (relative risk (RR) = 1.8, 95%CI: 1.3-2.7), but these were generally manageable. CONCLUSIONS: Bevacizumab-based combinations demonstrate consistent benefits across multiple regimens for PROC. Paclitaxel + bevacizumab emerges as the optimal balance of efficacy and safety. Topotecan + sorafenib could be an alternative for patients who are ineligible for anti-angiogenic therapy.

Humans↗

PubMed2026

Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.

BACKGROUND: Research on the pharmacokinetic influence of cannabidiol (CBD) on delta-9-tetrahydrocannabinol (THC) has produced equivocal results. METHODS: We conducted a systematic search following PRISMA guidelines (last search: 24th November 2025, PROSPERO: CRD42023480695). Included studies were acute dosing trials that administered a) a single, fixed dose of THC and b) a matched dose of THC co-administered with CBD. Our objective was to investigate between-group differences in the Cmax, AUCt and AUCinf of circulating THC and its active metabolite, 11-hydroxy-THC (11-OH-THC). Hedges' g and ratio of means (RoM) were pooled from random-effects meta-analyses. The dose-effects of CBD and THC on Hedges' g were explored using meta-regression. Risk of bias was assessed using the Cochrane Collaboration tool RoB 2. RESULTS: 14 studies were included (12 crossover, two parallel group; seven oral administration, five inhalation, one IV, one mixed IV and oral; total participants: 341). In meta-analyses, average AUCt of THC was significantly higher in CBD co-administration study arms versus THC-only (Hedges' g= 0.526, 95%CI= 0.222-0.830), with very low certainty evidence. Both Cmax and AUCt of 11-OH-THC were significantly higher in CBD co-administration study arms (Cmax: g= 0.428, 0.115-0.741; AUCt: g= 0.692, 0.284-1.099), both with medium certainty evidence. In meta-regression analyses, CBD demonstrated dose effects on the Hedges' g of the Cmax and AUCt of 11-OH-THC (P < 0.05), but not THC levels. CONCLUSIONS: Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC.

Humans↗

PubMed2026

Evidence Gap in Managing Lateral Pelvic Lymph Nodes in Rectal Cancer: a Systematic Review of Radiation Boost Strategies.

PURPOSE: Lateral pelvic lymph node (LPLN) involvement is a significant predictor of local recurrence in patients with locally advanced rectal cancer (LARC). While lateral pelvic lymph node dissection (LPLND) is routinely used in some countries to manage suspicious nodes, it is associated with increased morbidity and is not widely adopted in Western practice. Radiation boost (dose escalation) to involved LPLNs during neoadjuvant chemoradiotherapy (nCRT) has emerged as a potential non-surgical alternative. Despite increasing adoption of radiation boost to clinically involved LPLNs, there remains limited evidence defining its safety, oncologic benefit, and role relative to LPLND. METHODS: A systematic search of MEDLINE, EMBASE, ClinicalTrials.gov, and Cochrane databases was conducted following PRISMA guidelines. Studies were included if they reported outcomes of radiation dose escalation specifically targeting radiologically suspicious LPLNs in the context of nCRT. RESULTS: Ten retrospective cohort studies encompassing 482 radiation boosted patients were included. Boost doses ranged from 35.0 to 60.2 Gy. Rates of Grade 2-3 toxicity ranged from 28.0% to 39.3% across individual studies, with only one study reporting a single Grade 4 adverse event. Across individual studies, reported nodal response rates ranged from 62.3% to 100%. Comparative studies suggest that radiation boost may improve local control and reduce LPLN recurrence. CONCLUSION: Current retrospective evidence suggests that radiation dose escalation to involved LPLNs is a promising treatment strategy; however, the available data are limited by retrospective study designs and substantial clinical heterogeneity. Given the absence of prospective evidence and lack of consensus in current guidelines, an important evidence gap remains. Well-designed prospective trials are warranted to define the role of LPLN boost relative to LPLND.

Humans↗