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PubMed2026

Characteristics and functions of a cell adhesion molecule PvCadN in Penaeus vannamei during WSSV infection.

Cell adhesion not only maintains the integrity of the organism, but also plays an important role in the immune system, which is involved in modulation in the interaction between host and virus. In this study, a novel cell adhesion molecule from Penaeus vannamei, designated as PvCadN, was investigated. It had the typical molecular characteristics of cadherin family, with multiple extracellular cadherin repeat domains, a transmembrane region, and a conserved β-catenin-binding motif. Pvcadn is expressed ubiquitously across all detected tissues, with the highest transcriptional level in gills. RNA interference-mediated silencing of pvcadn significantly impaired the adhesion ability of shrimp hemocytes. Upon WSSV infection, pvcadn showed a tissue-specific expression pattern, with upregulation in gills and downregulation in hemocytes. Knockdown of pvcadn markedly suppressed the transcription of WSSV immediate-early gene ie1 and replication of the viral genome in vivo, suggesting that PvCadN acted as a potential virus-associated molecule. Furthermore, it was found that PvCadN was regulated by Lvβ-catenin, a core molecule in the Wnt signaling pathway that functions in innate immunity, at the transcriptional and protein levels. Silencing of lvβ-catenin significantly downregulated pvcadn transcription, and Lvβ-catenin bound directly to the Cadherin C domain of PvCadN. In summary, the study revealed that PvCadN was a key cell adhesion molecule involved in WSSV infection, which was regulated by Lvβ-catenin. Our findings will provide fundamental data for further investigation into cadherin-mediated immune regulation in shrimp, and offer new insights for the prevention and control of WSSV.

Animals↗

PubMed2026

Mechanisms of high-humidity hot air impingement blanching (HHAIB) on microbial counts, functional properties, phenolic profile transformation, and volatile compounds in celery stalks (Apium graveolens L.).

In this study, celery stalks were pretreated with different durations (0-150 s) of high-humidity hot air impingement blanching (HHAIB), followed by far-infrared radiation assisted pulsed vacuum freeze-drying (FIR-PVFD) at 60, 65, and 70 °C. The effects of HHAIB on the physicochemical properties, composition and transformation of phenolic compounds, volatile components, and antioxidant capacity of FIR-PVFD-dried celery stalks were systematically investigated. The results showed that HHAIB not only effectively reduced the counts of total mesophilic aerobic bacteria (TMAB) and total yeast and mold (TYM), but also decreased the relative activities of polyphenol oxidase (PPO) and lipoxygenase (LOX) by more than 91% after 90 s of treatment. HHAIB altered the cellular structure of celery stalks, shortened the drying time by 29.33-41.43%, and improved their hydration properties. HHAIB pretreatment promoted the conversion of bound phenolics to free phenolics in celery stalks, with significant increases in the contents of p-coumaric acid, apigenin, graveobioside A, and other components. The total free phenolic content increased by 56.99%, thus HHAIB enhanced the antioxidant activity. An electronic nose and sensory evaluation revealed that HHAIB-pretreated celery stalks better retained the characteristic herbal and pungent notes. GC-MS results indicated that HHAIB treatment optimized the aroma profile by regulating the contents and composition of terpenes, aldehydes, ketones, alcohols, and aromatic compounds.

Apium↗

PubMed2026

A novel urease-producing strain effectively induces cadmium biomineralization under low-temperature stress.

Microbially induced carbonate precipitation (MICP) has been widely used to immobilize Cadmium (Cd) in contaminated soils in mining-affected regions. However, its remediation efficacy under low-temperature stress, as well as the nucleation process that regulates Cd biomineralization via carbonate precipitation by psychrophilic bacteria, has yet to be investigated. Here, we isolated Pseudomonas sp. J-6, a novel urease-producing strain from tailings in high-altitude cold regions, exhibiting unparalleled cold adaptability at 5 °C and achieving 95.85 % Cd removal efficiency by MICP at 10 °C. Furthermore, the coprecipitation process of Ca1-xCdxCO3 was clarified through the continuous observation of the precipitates after the low-temperature MICP reaction. The crystal morphology transitioned from loose vaterite in the early stage to a dense square-block morphology in the middle stage. Cd2+ progressively shifted from a surface-bound state to lattice incorporation, ultimately resulting in the formation of stable Cd-substituted calcite crystals. In this process, low temperatures led to the formation of larger, highly ordered Cd-substituted calcite crystals, thereby strengthening Cd sequestration and its long-term stability. In addition, under low-temperature stress, Pseudomonas sp. J-6 induced MICP reaction decreased the bioavailable Cd in alpine slag soil by 44.85 % and enhanced physical properties. In the freeze-thaw cycles, the remediation efficiency remained stable. This study clarified the biomineralization potential in high-altitude cryogenic environments and the nucleation process of Cd biomineralization by psychrophilic bacteria-induced carbonate precipitation, filling a critical research gap in its application under extreme conditions and highlighting its promise for sustainable remediation of heavy metal pollution under low-temperature stress.

Cadmium↗

PubMed2026

Pollution characteristics and health risks of PAHs and OPAHs in PM2.5 of an inland basin city in China under the influence of the clean air action plan.

Since the implementation of China's Clean Air Action, remarkable progress has been made in air pollution control, with continuous air quality improvement in Xi'an, a typical inland basin city in the Fenwei Plain. To clarify winter organic aerosol pollution variations and pinpoint targeted control needs under policy regulation, this study investigated PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) and oxygenated derivatives (OPAHs) in winter Xi'an, focusing on pollution levels, chemical compositions, source contributions, meteorological impacts, regional transport and health risks. Historical comparison showed generally lower wintertime PAH concentrations in Xi'an during the period of China's clean-air actions. PMF results indicated mixed source influences on PAHs and OPAHs, with biomass-burning-related mixed combustion showing the largest contribution. During haze episodes, absolute concentrations of both PAHs and OPAHs increased; the increase was statistically significant for OPAHs but not for parent PAHs, while 4-5 ring PAHs and BcdPQ dominated the PAH and OPAH profiles, respectively. Meteorological variability, particularly synoptic pressure patterns, was strongly associated with pollutant concentrations, and regional pollution was dominated by in-basin accumulation combined with short-range transport from northern Shaanxi industrial zones. Haze periods exhibited higher toxic-equivalent concentrations, with OPAHs, particularly BcdPQ, dominating the toxicity-equivalent burden. Screening-level ILCR estimates generally remained below 10⁻4 but increased during haze episodes, especially for adult and elderly groups. In conclusion, China's clean air actions have coincided with lower wintertime PAH pollution, but stronger control of residential biomass and other solid-fuel combustion, traffic emissions, and OPAH formation remains necessary in the Fenwei Plain.

China↗

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

Malnutrition and adverse outcomes after spine surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Malnutrition is linked to adverse surgical outcomes, but its impact in spine surgery remains unclear due to inconsistent findings and heterogeneous definitions, including use of serum albumin, prealbumin, lymphocyte count, the Geriatric Nutritional Risk Index, and the Prognostic Nutritional Index. We conducted a systematic review and meta-analysis to evaluate the relationship between malnutrition and postoperative outcomes in spine surgery. PURPOSE: To systematically evaluate the association between preoperative malnutrition and postoperative outcomes in patients undergoing spine surgery. STUDY DESIGN: Systematic review and meta-analysis. PATIENT SAMPLE: Patients undergoing elective or urgent spine surgery across included observational studies comparing malnourished vs well-nourished cohorts. OUTCOME MEASURES: Primary outcomes included postoperative mortality and overall surgical complications. Secondary outcomes included infectious complications (sepsis, urinary tract infection, wound complications), delirium, reoperation, 30-day and 90-day readmission, and prolonged length of hospital stay. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed on April 7, 2025, following PRISMA guidelines. Studies directly comparing postoperative outcomes in malnourished vs well-nourished spine surgery patients were included. A random-effects model generated pooled odds ratios for complications. Outcomes assessed included mortality, surgical complications, infectious outcomes, readmission, reoperation, delirium, prolonged length of stay, and wound complications. RESULTS: Of 2,851 screened articles, 37 met the inclusion criteria, encompassing 16,987 malnourished patients. Malnutrition was associated with significantly increased odds of mortality (OR: 4.05, 95% CI [2.97-5.54]), delirium (OR: 3.95, 95% CI [2.49-6.27]), sepsis (OR: 2.77, 95% CI [2.31-3.33]), surgical complications (OR: 1.79, 95% CI [1.57-2.04]), urinary tract infection (OR: 1.81, 95% CI [1.59-2.06), wound complications (OR: 2.10, 95% CI [1.80-2.45]), reoperation (OR: 1.70, 95% CI [1.46-1.97]), prolonged length of hospital stay (OR: 3.46, 95% CI [2.57-4.65]), 30-day readmission (OR: 1.59, 95% CI [1.36-1.86]), and 90-day readmission (OR: 2.13, 95% CI [1.67-2.71]). CONCLUSIONS: Malnutrition was consistently associated with adverse outcomes after spine surgery. Routine nutritional assessment and targeted preoperative optimization should be considered a standard component of perioperative spine care to help reduce postoperative complications and improve recovery.

Humans↗

PubMed2026

The Association Between NT-Pro BNP, Nephropathy and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) is an established biomarker of heart failure and has been recommended for cardiovascular risk stratification in type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy and endothelial dysfunction across varying stages of kidney impairment remains unclear. This study examined the associations of NT-Pro BNP, renal impairment, albuminuria and endothelial dysfunction in patients with T2DM without overt heart failure. METHODS: A comparative cross-sectional study was conducted among 192 adults with T2DM. Participants were stratified by KDIGO eGFR groups (≥ 90, 60-89, 30-59 mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of ≥ 125 pg/mL. Albuminuria was categorized using the urinary albumin-to-creatinine ratio (uACR). Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Logistic regression analysis was performed to identify independent factors of elevated NT-Pro BNP, with p-values < 0.05 considered statistically significant. RESULTS: NT-Pro BNP levels were significantly higher in the lower eGFR groups compared with normal eGFR (204.3 vs. 96.8 vs. 62.2 pg/mL, p < 0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r = 0.31, p < 0.001). However, no significant association was found between NT-Pro BNP and FMD (p = 0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p < 0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p = 0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p = 0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p < 0.001) were independently associated with elevated NT-Pro BNP. CONCLUSION: In patients with T2DM without overt heart failure, elevated NT-Pro BNP showed a statistically significant association with lower eGFR and higher albuminuria. Moderate to severe albuminuria becomes an independent factor for elevated NT-Pro BNP after adjustment excluding eGFR. The lack of association with endothelial dysfunction suggests that NT-Pro BNP may reflect different pathophysiological pathways. NT-Pro BNP may serve as a useful biomarker for early cardiovascular risk stratification and identification of individuals at risk of pre-heart failure in diabetic kidney disease.

NT‐Pro BNP↗

PubMed2026

Phosphorus modulates starch granule development and metabolic partitioning in wheat grain: Insights from SGAP proteomics and nutrition and processing quality.

This study investigates how phosphorus (P) levels are associated with carbon-nitrogen metabolism in wheat grains. Optimal P application (105 kg P₂O₅ ha⁻¹) was associated with enhanced pericarp-endosperm coordination, increased carbon allocation to the endosperm, and early B‑type starch granule formation. Starch granule‑associated protein (SGAP) proteomics showed that optimal P upregulated cytoskeletal and starch‑synthesis proteins bound to starch granules in the endosperm, while reducing storage protein degradation‑related SGAPs in the pericarp. These metabolic adjustments were correlated with increased grain‑filling intensity and duration, and were associated with the highest theoretical grain weight (50.70 mg). Furthermore, optimal P was associated with enrichment of amino acid biosynthesis pathways and with higher levels of essential amino acids (e.g., lysine and threonine by 17.0--26.8%) and an improved essential amino acid profile without altering total protein content. In contrast, excessive P (210 kg P₂O₅ ha⁻¹) was associated with disrupted inter‑tissue coordination but did not simply impair grain filling; instead, HP corresponded to a unique developmental program: it was linked to an early burst of C‑type starch granules (0∼5 µm) at 7 DPA, yet by maturity achieved the highest proportion of large A‑type granules (56.8%) and the highest total starch content (63.5%), together with elevated endosperm phosphorus at 14 DPA and enrichment of spliceosome‑related pathways. HP also showed higher levels of several functional amino acids (glutamate, cysteine, histidine, proline) compared to P0. However, HP was associated with a higher gliadin/globulin ratio and did not improve grain yield. These findings suggest that phosphorus supply is associated with grain quality through tissue‑specific metabolic reprogramming, and that precision management-rather than maximized application-warrants consideration for optimizing both yield and processing quality.

Triticum↗

PubMed2026

Physicochemical effects of bicarbonate-buffered solution versus compound sodium lactate during major abdominal surgery: A randomized, open-label, non-inferiority trial.

INTRODUCTION: Bicarbonate-buffered crystalloids avoid exogenous lactate and have physicochemical properties distinct from compound sodium lactate (CSL), but direct comparative evidence during major abdominal surgery remains limited. METHODS: This single-center, open-label, randomized non-inferiority trial enrolled high-risk adults undergoing elective major abdominal surgery. Participants received bicarbonate-buffered solution or CSL as the allocated intraoperative crystalloid. The primary estimand was the arithmetic mean difference in standard base excess (SBE) at skin closure (bicarbonate-buffered solution minus CSL). The non-inferiority margin was -1.5 mEq/L. The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619001228178). RESULTS: Fifty participants were randomized (25 per group) and received their allocated intervention. End-of-surgery arterial blood gas data were missing for two CSL participants. In the intention-to-treat analysis using multiple imputation, the estimated mean difference in end-of-surgery SBE was -0.42 mEq/L (95% confidence interval [CI], -1.92 to 1.09 mEq/L). The complete-case per-protocol estimate was -0.48 mEq/L (95% CI, -2.02 to 1.06 mEq/L). In both analyses, the lower CI bound was below the prespecified non-inferiority margin; non-inferiority was not established. Secondary outcomes were exploratory; observed end-of-surgery lactate was lower with bicarbonate-buffered solution (median 0.9 vs 1.2 mmol/L; unadjusted P = 0.031), without a corresponding difference in SBE or pH. CONCLUSIONS: In this small trial of hemodynamically stable adults undergoing elective major abdominal surgery, the primary non-inferiority result was inconclusive. The data did not establish interchangeability, equivalence, superiority, or inferiority of the two fluids. As the trial was powered for a physiologic endpoint, no comparative inference can be made about organ dysfunction, postoperative complications, recovery, or mortality. Larger trials with standardized co-interventions and patient-important outcomes are required before routine substitution for CSL can be recommended.

Humans↗

PubMed2026

Integrative quantum and systems biology of cancer: From molecular fluctuations to ecological outcomes.

This review treats cancer as a multiscale adaptive system, asks what the framework must predict to be worth adopting, and separates at each scale what the evidence establishes from what is proposed. It is an expert narrative synthesis, not a systematic review, and states the limits of that design. Proton transfer and tautomeric shifts contribute to spontaneous mispairing but do not license claims of directed or non-random mutation: replication timing, three-dimensional chromatin organization, sequence context and known mutagenic processes explain most mutational heterogeneity, leaving any quantum contribution as a residual against that baseline. The Waddington quasi-potential is bounded: outside detailed balance the dynamics are not gradient-derivable and require a probability-flux term. Hysteresis, rate-limited bimodality and return to state after perturbation distinguish an attractor from a transcriptomic cluster. Single-cell karyotype and live-imaging evidence supports whole-genome doubling as an unstable intermediate of heterogeneous origin and context-dependent consequence, not a uniform adaptive strategy. Systems and synthetic biology, virtual cells and digital twins are assessed against benchmarks, not promise. Tissue-scale ecology is reported with the spatial measurements now quantifying it, including evidence that stromal niche construction is not uniformly tumor-supporting. RNA modification is a layer in its own right, showing that the interpretation of a regulatory signal, not its magnitude, is biologically decisive. A dedicated section states the framework's commitments, the observable and evidence at each scale, and what would falsify them, asking what this adds to somatic mutation theory with clonal evolution and plasticity.

Neoplasms↗

PubMed2026

MIS-TLIF Versus Open TLIF in Combined Lumbar Stenosis and Low-Grade Spondylolisthesis : Of Discharge Timing and Treatment Pricing.

STUDY DESIGN: An open-label, randomized, noninferiority clinical trial. OBJECTIVE: To determine the effectiveness of the MIS-TLIF over the O-TLIF in patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis by comparing the clinical efficacy and safety. SUMMARY OF BACKGROUND DATA: In patients with combined lumbar spinal stenosis and spondylolisthesis, it remains uncertain whether minimally invasive fusion surgery is noninferior to the open approach. MATERIALS AND METHODS: We conducted an open-label, noninferiority trial involving patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis. Patients were randomly assigned in a 1:1 ratio to undergo either MIS-TLIF or open TLIF surgery. The primary endpoint was the reduction in the Oswestry disability index (ODI) score from baseline to three months postsurgery, with a noninferiority margin of 12 points. Secondary outcomes included three-month changes from baseline in back and leg pain, neuropathic pain, satisfaction with treatment, intraoperative data, and cost-effectiveness. RESULTS: In the modified intention-to-treat population, the mean difference was 0.4, with the corresponding 90% CI of -5.7 to 6.5, having a lower bound below the noninferiority margin of 12. Similar results were obtained by analysis of the per-protocol population. 82.8% of patients achieved the MCID for the ODI. Results for secondary outcomes (clinical scales, complications) showed no significant differences between the treatment groups (all P >0.05). Although the open TLIF group had a hospital stay that was 1.5 days longer ( P =0.005) and required additional analgesia more frequently ( P =0.026), direct costs were 10.5% higher in the MIS-TLIF group ( P <0.001). CONCLUSIONS: This is the first high-quality study comparing open TLIF and MIS-TLIF with a validated primary endpoint. Among patients with combined lumbar degenerative stenosis and degenerative spondylolisthesis, MIS-TLIF resulted in clinical outcomes at three months that were noninferior to those with open TLIF.

Humans↗

PubMed2026

A single session of high-definition transcranial direct current stimulation does not modulate effects of knee two-point discrimination training or sensorimotor function in healthy adults: Double-blind randomised controlled trial.

BACKGROUND: Benefits of sensory-training interventions on sensorimotor outcomes are inconsistent, and it is unclear whether transcranial direct current stimulation (tDCS) can enhance proprioception, which is fundamental to neuromuscular control. Existing evidence is dominated by upper-limb studies, so transferability to the knee is unclear. This study investigated whether a single session of anodal high-definition (HD)-tDCS, alone or combined with brief two-point discrimination (TPD) training, enhances knee sensorimotor function and performance in healthy adults. METHODS: In a double-blind randomised-controlled trial, 57 healthy participants received (1) 20-min, 1 mA anodal HD-tDCS over the knee primary somatosensory (S1) map or sham stimulation, and (2) 15-min knee TPD training or no training. Knee somatosensory, sensorimotor, and functional performance measures were assessed pre- and immediately post-intervention. Three-way mixed-design ANOVAs, equivalence testing (smallest effect size of interest η2 = 0.02), Bayes factors, and linear mixed-effects models quantified effects. RESULTS: HD-tDCS, TPD training, and their sequential combination had no effect on any outcome measure (p ≥ 0.05; η2 ≤ 0.015). Confidence intervals spanned equivalence bounds, and equivalence testing results were non-significant (p ≥ 0.05). Bayes factors (<0.33) showed moderate evidence for the null (no effect). Mixed-effects modelling attributed ≤8% of total variance to intervention fixed effects, with the remainder captured by participant-level random effects. CONCLUSION: A single 20-minute session of 1 mA HD-tDCS, with or without brief TPD training, does not acutely modify knee somatosensory, sensorimotor, or functional performance in healthy adults. Existing evidence at the hand may not translate to the lower limb. Future work should investigate higher-dose, multi-session, task-concurrent, or network-targeted strategies in clinical populations.

Humans↗

PubMed2026

Multidisciplinary mHealth Rehabilitation for Patients With Abdominal Cancer Who Are Receiving Chemoradiotherapy: Randomized Phase II Trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. OBJECTIVE: This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. METHODS: In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. RESULTS: Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. CONCLUSIONS: In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Humans↗

PubMed2026

Pedagogical Efficacy of LLM-Generated Synthetic Data Versus Real-World Clinical Records: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND: Expert-reviewed clinical cases generated by large language models (LLMs) may supplement case resources in medical education, but their short-term educational performance relative to real-case-derived teaching materials remains uncertain. We compared immediate post-training test performance after teaching with the two types of case materials and assessed non-inferiority against a prespecified margin. METHODS: We conducted a prospective, parallel-group, randomized non-inferiority trial. Through the Wenjuanxing online platform, participants were randomized 1:1 to learn with either real-case-derived teaching cases compiled by clinicians and reviewed by experts or AI-generated clinical cases produced by Gemini 3.0 Pro from fully de-identified matched real cases and reviewed by three senior general surgery specialists with full-professor rank. The primary outcome was the total score on an independent 10-item immediate post-training test (0-10 points), with a prespecified non-inferiority margin of -0.5 points. Secondary outcomes included the training-phase performance score, learning efficiency index, single-item mental effort rating, case realism, and case-source judgment. RESULTS: A total of 403 participants were randomized, of whom 386 were included in the modified intention-to-treat analysis: 192 in the real-case group and 194 in the AI-generated case group. The mean post-training test score was 4.95 (SD, 3.35) in the real-case group and 4.61 (SD, 3.35) in the AI-generated case group. The mean difference (AI-generated minus real-case group) was -0.335 points (95% CI, -1.006 to 0.337). Because the lower bound of the confidence interval was below the prespecified non-inferiority margin of -0.5 points, non-inferiority was not demonstrated (one-sided P = 0.314). No significant between-group differences were observed in the training-phase performance score, learning efficiency index, or single-item mental effort rating. AI-generated cases received lower realism ratings for Level 3 cases. The proportion of participants with at least one high-confidence completely incorrect response was 1.6% in the real-case group and 2.1% in the AI-generated case group. CONCLUSIONS: In this short-term, text-based online case-learning setting, no statistically significant between-group difference was observed in immediate post-training test performance; however, non-inferiority of AI-generated clinical cases relative to real-case-derived teaching materials was not demonstrated.

Humans↗

PubMed2026

A multi-center, open-labelled, randomized controlled extended phase III non-inferiority clinical trial to evaluate the immunogenicity and tolerability of poliomyelitis vaccine (Vero cells), inactivated, Sabin strains administered with or without routine infant vaccines.

BACKGROUND: Oral poliovirus vaccine (OPV) has been reported to cause vaccine-derived poliovirus and vaccine-associated paralytic poliomyelitis, and the limited global supply of conventional IPV has led many countries to rely on fractional-dose IPV regimens alongside OPV. The current study aims to assess the sIPV safety and immunogenicity when given concurrently with or in a staggered manner with routine immunization. METHODS: A multi-country, multi-center, open-label, randomized controlled, extended phase III non-inferiority clinical trial was conducted with 1442 healthy infants aged 6-8 weeks from Bangladesh and Pakistan enrolled and randomized into four groups, i.e., co-administration group 1 (group C1), co-administration group 2 (group C2), staggered administration group 1 (group S1) and staggered administration group 2 (group S2). Antibody levels were determined using the collected sera for immunogenicity evaluation. The difference in seroconversion rates between the coadministration group and the staggered administration group is compared using the Cochran-Mantel-Haenszel χ2 (CMH-χ2) test, stratified by study site. Non-inferiority is concluded if the lower bound of the 95% confidence interval (CI) for the rate difference (coadministration group minus staggered administration group) is greater than -10%. The trial was registered prior to patient enrollment at clinicaltrials.gov (NCT05850364), and the protocol and statistical analysis plan are available at https://clinicaltrials.gov/study/NCT05850364. The trial is closed to new participants. FINDINGS: The post-vaccination seroconversion rates for PV I were 90.3% (306/339) in group C1 and 87.0% (261/300) in group S1, for PV II, 91.7% (311/339) in group C1 and 91.3% (274/300) in group S1 and for PV III, 86.4% (293/339) in group C1 and 92.3% (277/300) in group S1. Among adverse reactions (ARs) reported within 7 days of vaccination, the incidence was similarly high in both the co-administration and staggered vaccination groups (92.8% vs. 95.5%). INTERPRETATION: Our results demonstrated favorable safety and immunogenicity of co-administration of sIPV with other routine infant vaccines according to a 3-dose primary immunization schedule.

Humans↗

PubMed2026

Comparative Effectiveness of Exercise Interventions for Hamstring Injury Prevention in Football Players: A Systematic Review and Network Meta-analysis.

BACKGROUND: Hamstring strain injury is a leading time-loss injury in football, yet trials have evaluated diverse exercise-based prevention programs with limited direct head-to-head evidence. This systematic review and network meta-analysis aimed to compare the effectiveness of exercise-based interventions for preventing hamstring injuries in football players using exposure-adjusted incidence rate ratios. METHODS: We conducted a PRISMA-aligned systematic review and random-effects network meta-analysis of randomized controlled trials in football players comparing exercise-based interventions to prevent hamstring injuries. Searches covered PubMed, Cochrane Library, Embase and Web of Science from inception to January 5, 2026. Interventions were modeled as separate nodes (Nordic hamstring exercise [NHE], FIFA 11, FIFA 11 + , FIFA 11 + Kids, bounding exercise program [BEP], usual training). The primary effect measure was incidence rate ratio (IRR) versus usual training, with ranking by P-scores; exploratory subgroup analyses were conducted by sex-restricted male-only evidence and age group. RESULTS: Eleven randomized controlled trials involving 9,282 participants were included. The network was connected but largely star-shaped, with most evidence comparing active interventions against usual training and no direct active-active comparisons. FIFA 11 + showed the most consistent exposure-adjusted association with reduced hamstring injury incidence versus usual training (IRR = 0.55, 95% CI 0.31-0.98; P-score = 0.84). FIFA 11 + Kids showed a favorable but imprecise estimate, whereas NHE showed a modest non-significant reduction and FIFA 11 and BEP showed no clear benefit. Male-only findings were broadly consistent with the primary analysis. Age-stratified analyses suggested that the apparent hierarchy was not fully identical across age strata, but subgroup networks were sparse and exploratory. RoB 2 judged three studies as high risk and eight as having some concerns; no trial was judged as overall low risk. Between-study heterogeneity was substantial, and treatment rankings were, therefore, interpreted cautiously. CONCLUSIONS: In this IRR-based network meta-analysis, FIFA 11 + showed the most consistent exposure-adjusted association with reduced hamstring injury incidence compared with usual training. However, certainty across the primary comparisons ranged from low to very low because of clinical and methodological heterogeneity, sparse direct evidence for several nodes, reliance on indirect active-active comparisons, substantial between-study heterogeneity, and moderate-to-high risk of bias across the included studies. The treatment hierarchy should, therefore, be interpreted as a low-to-very-low-certainty, population-level summary rather than as a basis for firm recommendations. Further well-reported, age- and population-specific head-to-head trials with consistent exposure, injury-definition, adherence, and intervention-dose reporting are needed. Registration Systematic review registration PROSPERO (CRD420251243576).

FIFA 11 + ↗

PubMed2026

Soft Tissue Volume Augmentation at Single Implant Sites Applying Collagen Matrices or Connective Tissue Grafts: 10-Year Follow-Up of a Randomized Controlled Trial.

AIM: To compare up to 10 years clinical, profilometric and patient-reported outcomes of implant sites previously augmented using a volume-stable collagen matrix (VCMX) or connective tissue graft (SCTG) in the aesthetic zone. METHODS: The original non-inferiority randomized controlled trial (RCT) enrolled 20 patients who received soft tissue volume augmentation with VCMX or SCTG at single implant sites. Clinical assessments and standardized measurements were performed at baseline after crown insertion and at 6 months, 1, 3, 5, 7.5, and 10 years. The primary outcome was mucosal thickness. Secondary outcomes included marginal bone levels (MBL), probing depth (PD), bleeding on probing (BOP), plaque control record, Pink Aesthetic Score (PES), OHIP-14 and buccal profilometric changes. Group comparisons were performed using mixed-effects and generalized estimating equation (GEE) models, which account for within-patient correlations due to repeated measurements and allow inclusion of all available data without requiring imputation for missing observations. RESULTS: Of the 20 originally enrolled patients, 10 (5 in the SCTG group and 5 in the VCMX group) were available for re-examination at 10 years. The adjusted between-group difference in mucosal thickness was -0.02 mm (95% CI -0.99 to 0.96). As the lower bound of the confidence interval remained above the prespecified non-inferiority margin of -1 mm, non-inferiority of VCMX was shown. Buccal contour changes were comparable during the early follow-up, while a trend toward a greater long-term contour decrease was observed in group VCMX (-0.31 mm [95% CI, -0.65 to 0.03]; p = 0.07). Mean PES values were 10.6 in the SCTG group and 9.6 in the VCMX group, with no significant between-group differences (p = 0.45). Both groups revealed high levels of oral health-related quality of life, with low median OHIP-14 scores (SCTG, 0.0; VCMX, 1.0; p = 0.26). CONCLUSION: These preliminary long-term findings showed no clinically relevant differences between SCTG and VCMX in terms of clinical, profilometric and patient-reported outcomes. While SCTG remains the reference standard, VCMX represents a less invasive alternative but with a slight tendency toward greater long-term contour reduction. CLINICAL SIGNIFICANCE: Volume-stable collagen matrices serve as a viable alternative to autogenous connective tissue grafts for peri-implant soft tissue volume augmentation, particularly in patients seeking a reduced morbidity, without compromising long-term clinical or aesthetic outcomes. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017484.

Humans↗