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PubMed2026

Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584 mM (OXD) and 0.1498 mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10 ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines↗

PubMed2026

Engineered MXene-based nanozyme platform: NIR-II photothermal and dual enzyme-mimetic potentiated chemodynamic synergy for precision tumor eradication.

The antioxidant defense barrier in the tumor microenvironment, particularly glutathione (GSH), considerably restricts the therapeutic efficacy of chemodynamic therapy (CDT). Moreover, CDT generally exhibits relatively mild therapeutic efficacy owing to its intrinsic reaction kinetics, making it difficult to achieve complete tumor eradication within a short time. To address these issues, we construct a functionalized nanotherapeutic platform, Nb2CTx@Ru-PEG2000-FA (NCRPF), for tumor photothermal ablation and enhanced CDT resulting from GSH depletion. NCRPF possesses three key advantages: 1. Efficient near-infrared II photothermal conversion (η = 42.08%), raising the tumor temperature above 45 °C within 90 s for rapid ablation; 2. Dual peroxidase-like and glutathione peroxidase-like activities, simultaneously depleting GSH and generating a burst of ·OH to eliminate residual tumors; 3. Targeted tumor accumulation with 2.9-fold higher efficiency than passive diffusion. Both in vitro and in vivo results confirm that this combined strategy achieves complete tumor eradication with favorable biosafety. Collectively, the NCRPF nanotherapeutic system provides a powerful new paradigm with high translational potential for the complete eradication of breast cancer.

Animals↗

PubMed2026

Future promise, current clinical ambiguity: a systematic review of machine learning algorithm outputs predicting risk of cardiovascular disease.

OBJECTIVE: To examine whether the outputs of machine learning algorithms designed to predict risk of cardiovascular disease (CVD) address known deficiencies of the Framingham Risk Score (FRS) and improve risk estimates. METHODS: For this critical review, Medline, Embase and IEEE were searched from inception to 1 January 2025. Included were studies describing machine learning algorithms designed to specifically compare output of cardiovascular risk assessment with the FRS. Commentaries, letters, unpublished work or non-peer-reviewed papers were excluded.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two reviewers screened titles and abstracts independently, then populated a purpose-built data extraction form. A subsequent qualitative thematic analysis focused on algorithms' strengths, added value, potential harms, unintended consequences and equity implications.The main outcome assessed was whether, among healthy adults, the algorithm improved CVD risk prediction relative to the FRS. RESULTS: Of 707 studies retrieved, 29 met inclusion criteria. 23 reported improved predictive ability relative to the FRS. Most datasets and/or medical records used included sociodemographic predictors of CVD not included among FRS inputs. Some added costly diagnostic tests like CT angiography to FRS screening indicators. When they were defined, inputs and outcomes such as hypertension or myocardial infarction did not always adhere to FRS values. Statistical significance was generally taken as a proxy for clinical significance. Some algorithms overestimated the number at risk compared with the FRS without discussing whether that larger proportion might be at risk of overdiagnosis rather than CVD, while a few decreased the proportion found to be at risk. CONCLUSIONS: Use of artificial intelligence to improve accuracy of risk assessment for CVD demonstrates the technological capacity to merge known sociodemographic predictors with biologic variables and examine non-linear interactions among these. Still needed to achieve patient benefit is clinical insight, adherence to screening principles and cost-benefit assessment of inputs selected.

Humans↗

PubMed2026

The glucagon and GLP-1 receptor dual agonist DD01 for metabolic dysfunction-associated steatotic liver disease and steatohepatitis (DD01-DN-02): 12-week results from a randomised, double-blind, multicentre, placebo-controlled, phase 2 trial.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a major public health problem arising in the context of metabolic syndrome and obesity. DD01 is a liver-targeted GLP-1 receptor and glucagon dual agonist being investigated for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASH. The DD01-DN-02 trial aimed to evaluate the efficacy and safety of DD01 in adults with MASLD or MASH; this initial analysis reports prespecified 12-week outcomes to assess early hepatic effects. METHODS: DD01-DN-02 is an ongoing, randomised, double-blind, multicentre, placebo-controlled, phase 2 trial conducted at 12 outpatient clinical sites in the USA. Adults aged 18-70 years with obesity or who were overweight (BMI ≥25 kg/m2) were included in the study. Patients with MASLD or MASH underwent liver biopsy and MRI-proton density fat fraction (PDFF) and were eligible if liver fat content was 10% or higher with metabolic risk factors, or if the biopsy confirmed MASH with a non-alcoholic fatty liver disease activity score of at least 4. Participants were randomly assigned (1:1) to receive once-weekly subcutaneous DD01 40 mg or matched placebo over 48 weeks, dose-escalated over 2 weeks, using a centrally administered interactive response technology system. The randomisation sequence was computer-generated by an independent statistician. Participants, investigators, study staff, outcome assessors, and the sponsor were masked to treatment assignment. The primary endpoint was the proportion of participants having at least a 30% relative reduction in liver fat by MRI-PDFF at week 12, which was analysed in all randomly assigned participants receiving at least one dose of study drug or placebo. Safety analyses included all participants who received at least one dose of study drug. Missing primary endpoint data were handled using multiple imputation under a missing-at-random assumption. This trial is registered with ClinicalTrials.gov (NCT06410924) and is ongoing but closed to new participants. FINDINGS: Between June 13, 2024, and Jan 30, 2025, 67 eligible participants were enrolled, of whom 33 were randomly assigned to DD01 and 34 to placebo. The mean age of participants was 48·4 years (SD 10·6), 42 (63%) were female, 25 (37%) were male, 57 (85%) were White, and 52 (78%) participants had biopsy-confirmed MASH. At week 12, 25 (76%) of 33 participants receiving DD01 had a 30% or higher reduction in liver fat versus four (12%) of 34 participants receiving placebo (adjusted common odds ratio 28·8 [95% CI 7·2-115·2]; adjusted relative risk 6·3 [95% CI 2·5-15·9]; p<0·0001). Treatment-emergent adverse events occurred in 28 (85%) of 33 participants receiving DD01 and 23 (68%) of 34 participants receiving placebo. The most common adverse events were nausea (18 [55%] of 33 participants assigned DD01; six [18%] of 34 participants assigned placebo), diarrhoea (nine [27%] of 33; six [18%] of 34), and vomiting (ten [30%] of 33; four [12%] of 34). Treatment-emergent adverse events led to treatment discontinuation in four (12%) of 33 participants in the DD01 group and one (3%) of 34 participants in the placebo group. Two (6%) treatment-emergent serious adverse events occurred in the DD01 group (abdominal pain and acute cholecystitis) and zero in the placebo group. No deaths occurred. INTERPRETATION: In this prespecified 12-week primary analysis, DD01 produced rapid reductions in liver fat compared with placebo, supporting further evaluation in long-term studies. FUNDING: D&D Pharmatech, Neuraly.

Humans↗

PubMed2026

Adverse Experiences in Brief Meditation Practices: Randomized Controlled Trial.

BACKGROUND: Meditation has become increasingly popular in recent decades. However, relatively little remains known about the prevalence of and risk factors for adverse experiences related to a single meditation practice. OBJECTIVE: The objective of our study was to examine adverse experiences associated with 3 brief, digitally delivered meditation practices (mindfulness, self-compassion, and gratitude) relative to using the internet as usual, as well as to investigate whether preintervention characteristics could predict such outcomes. METHODS: In a secondary analysis of a randomized controlled trial using samples that were representative of the US and UK adult populations with regard to ethnicity, sex, and age, we examined adverse experiences associated with 3 brief (ie, 5 or 10 minutes) meditation practices (ie, mindfulness, self-compassion, and gratitude) relative to using the internet as usual. We also investigated the potential of using preintervention characteristics to predict such outcomes. RESULTS: A total of 5049 participants completed all preintervention measures and were randomly assigned to meditation or control conditions. Across the sample, 4.1% (204/4925) of participants reported having a distressing experience during the intervention, and 7.1% (348/4908) of participants experienced an increase in negative affect from before to after the intervention. The results showed that participants who were randomized to a brief meditation intervention were no more likely to report a distressing experience than those who were randomized to use the internet as usual (odds ratio [OR] 1.05, 95% CI 0.76-1.47; P=.76). The results also showed that participants who were randomized to a brief meditation intervention were less likely to report clinically relevant increases in negative affect relative to using the internet as usual (OR 0.63, 95% CI 0.50-0.80; P<.001). Notably, participants in the 10-minute condition had a significantly higher likelihood of reporting a distressing experience than those in the 5-minute condition (OR 1.42, 95% CI 1.07-1.89; P=.02). Preintervention characteristics showed acceptable discrimination ability to predict a distressing experience (area under the curve=0.73) and slightly lower ability to predict increased negative affect (area under the curve=0.67). CONCLUSIONS: Taken together, we found that the brief, digitally delivered meditation practices tested in this study carry risks of adverse experiences that are comparable to or lower than those of typical activities on the internet; 10-minute condition was more likely to result in distressing experiences than 5-minute condition; and adverse responses to a brief meditation practice can, at least to a certain degree, be predicted using preintervention characteristics. TRIAL REGISTRATION: Open Science Framework 94HKS; https://osf.io/94hks/overview.

Humans↗

PubMed2026

Clinical characteristics and outcomes of post-stroke seizures following reperfusion therapy: a retrospective single-center study.

BACKGROUND: Post-stroke seizures (PSS) are a recognized complication of ischemic stroke and may adversely affect functional outcomes and survival; however, their characteristics in patients receiving contemporary reperfusion therapy remain incompletely defined. We aimed to describe the clinical characteristics, treatment patterns, and outcomes of patients who developed PSS following reperfusion therapy and to compare early- and late-onset seizure subgroups. METHODS: This single-center retrospective study included adult patients with acute ischemic stroke treated with intravenous thrombolysis (IV-tPA), mechanical thrombectomy (MT), or combined therapy between January 2020 and September 2025. Early seizures were defined as occurring within 7 days of stroke onset. Clinical, radiological, and treatment-related variables were analyzed, and functional outcome was assessed using the modified Rankin Scale at 3 months. RESULTS: Of 1242 patients who received reperfusion therapy, 53 (4.27 %; 95 % CI 3.28-5.54) developed PSS. Observed seizure rates were 3.39 % in the MT group, 4.06 % in the IV-tPA group, and 7.02 % in the combined therapy group; these observed rates did not differ significantly across treatment modalities. Early seizures occurred in 23 patients and late seizures in 30. No significant differences were found between early- and late-onset seizure subgroups in demographic characteristics, vascular risk factors, stroke severity, reperfusion success, or clinical outcomes, with the exception of an isolated, exploratory difference in stroke laterality. Three-month mortality among patients with PSS was 45.28 % (95 % CI 32.66-58.55), and in-hospital mortality was 20.75 %. CONCLUSIONS: In this single-center cohort, the incidence of PSS after reperfusion therapy was comparable to previously reported rates, with no marked differences across treatment modalities. The high mortality among patients with PSS likely reflects underlying stroke severity rather than a treatment-specific risk.

Humans↗

PubMed2026

Genomic and Phenotypic Characterization of Two Novel Enterobacter Phages With EDTA-Enhanced Antibiofilm Activity.

Multidrug-resistant members of the Enterobacter cloacae complex (ECC) are increasingly linked to difficult-to-treat infections and biofilm-mediated antimicrobial tolerance. Here, two lytic phages, vB_EhoIP_HHH and vB_EluM_RZH, displaying podovirus-like and myovirus-like morphology, respectively, were isolated from the River Chelt. HHH has a 39,582 bp genome (51.2% GC, 63 ORFs), while RZH has a 174,197 bp genome (39.4% GC, 314 ORFs), with neither genome carrying antimicrobial resistance, virulence or lysogeny-associated genes. VIRIDIC and VICTOR analyses placed HHH within Kayfunavirus and RZH within Karamvirus, supporting their classification as distinct species. Both phages demonstrated rapid adsorption, short latent periods and stability across physiological pH and temperature ranges. A phage cocktail targeting MDR ECC strain was evaluated with EDTA against established biofilms. Crystal violet assays showed the greatest biomass reduction at MOI 10 with 0.5-0.75 mM EDTA. Bliss independence analysis revealed localized synergy within this window but significant overall antagonism at higher EDTA concentrations. CFU enumeration confirmed greater activity against 24 h than 48 h biofilms. The optimized combination also reduced recoverable bacteria in a fibroblast infection model while maintaining low LDH release. These findings identify two novel lytic Enterobacter phages and support a narrow EDTA concentration window for enhanced phage-mediated antibiofilm activity.

Biofilms↗

PubMed2026

Domestication-associated reduction of methyl salicylate in tomato root and its significance for resistance to root-knot nematode.

Methyl salicylate (MeSA) plays diverse roles in the aerial parts of plants. By contrast, its biosynthesis and function in roots remain poorly understood. Here, we investigated root MeSA biosynthesis and function in tomato. Genome-wide association studies (GWAS) were performed using root MeSA levels as the phenotype in a diversity panel of 167 accessions to identify associated loci. Candidate genes were biochemically characterized, and the role of MeSA in defense against root-knot nematode (RKN, Meloidogyne incognita) was evaluated using transgenic plants. MeSA was identified as a major root volatile in tomato and showed a domestication-associated reduction. GWAS revealed multiple loci associated with natural variation in root MeSA, including a major locus on Chromosome 9 encoding the salicylic acid methyltransferase (SlSAMT). SlSAMT-overexpressing plants showed reduced resistance to RKNs, whereas SlSAMT-knockdown plants exhibited enhanced resistance. Our results suggest complex roles of MeSA and the salicylic acid (SA) signaling pathway in belowground plant defense. The SA signaling pathway likely plays critical roles in protecting roots against diverse natural enemies, including RKNs. Nevertheless, RKNs appear to have co-opted MeSA as a host-location signal, and the domestication-associated reduction of root MeSA in tomato has likely contributed to enhanced resistance against RKNs.

Solanum lycopersicum↗

PubMed2026

Mitochondrial dysfunction in muscle cells induced by snoring vibrations.

Snoring-related vibrations have been proposed as a pathogenic factor contributing to upper airway muscle dysfunction in patients with obstructive sleep apnea (OSA). To investigate whether exposure to snoring vibration is linked to muscle weakness, we used an in vitro vibration model to examine its effects on mitochondrial homeostasis in L6 muscle cells at 8, 12, 24, and 48 h. The findings were then compared with mitochondrial alterations in the upper airway muscles from snorers and patients with OSA. Proteomic analysis of L6 myoblasts revealed extensive remodeling of the mitochondrial proteome at 8 h, affecting pathways involved in oxidative phosphorylation, protein import, ribosome biogenesis, and RNA processing. Respiratory chain remodeling was subunit-specific, with increased abundance of selected components of Complexes I, IV, and V, including NDUFS4, COX5A, and ATP5PD. However, reductions in spliceosome-associated factors, such as SRSF2 and DDX46, along with alterations in mitochondrial ribosomal proteins, indicated impaired RNA processing and protein synthesis. Furthermore, both proteomic and transcriptomic analyses revealed activation of a mechanosensing-mechanotransduction axis, with early upregulation of integrin subunits and mechanosensitive ion channels, followed by transient activation of focal adhesion signaling. Despite transcriptional upregulation of selected Complex IV subunits Cox5a and Cox6a2, this response was accompanied by accumulation of unspliced pre-mRNA, indicating impaired RNA processing efficiency and a decoupling between transcript and protein levels. Real-time Seahorse assay revealed a collapse of mitochondrial respiration and glycolytic reserve at 8 h. Although mitochondrial oxygen consumption recovered after 48 h, the ability to dynamically upregulate glycolysis remained impaired. In patients, muscle capillarization was impaired, COX activity was reduced, and mitochondrial organization was disrupted. Moreover, transcription of Complex IV subunits COX5A and COX6A2 was, as in vibrated L6 cells, upregulated, suggesting a mismatch between transcript levels and protein expression. We conclude that snoring-induced vibrations are an unrecognized stressor that disrupts mitochondrial homeostasis in muscle by impairing RNA processing, protein synthesis, and mechanotransduction-driven mitochondrial remodeling, leading to transcript-protein uncoupling and likely muscle dysfunction.

Humans↗

PubMed2026

Characteristics of children with ureteroceles presenting for urological evaluation in the modern medical era.

INTRODUCTION: Historically, children with ureteroceles presented symptomatically and were managed surgically. It is unclear if this changed in the modern medical era of prenatal imaging and shared decision making. We aimed to describe the presentation and management of ureteroceles during initial urological evaluation of children in the era of widespread prenatal ultrasonography. PATIENTS AND METHODS: We retrospectively reviewed records of children (<18 years old [yo]) initially evaluated at our center with a ureterocele (2011-2020). We analyzed demographics, renal anatomy, initial presentation for evaluation, and initial management with non-parametric statistics. Febrile urinary tract infections (fUTIs, ≥ 38 °C) were classified as 1) urosepsis (positive urine culture admitted to pediatric intensive care), 2) documented (positive urine culture) or 3) family-reported. RESULTS: We identified 188 children (65% female). Median age at presentation was 1.2 months old (mo) (IQR 18 days-4.4 mo). Antenatally-detected congenital anomalies of the kidney and urinary tract (aCAKUT) were noted in 143 (76%) children with a confirmed postnatal diagnosis of ureterocele. Overall, 129/188 (69%) children presented without symptoms and 59 (31%) presented with symptoms. fUTI was the most common symptomatic presentation (46/188, 24%): urosepsis (6 children), documented (30), and family-reported (10). Children with aCAKUT presented earlier than those without aCAKUT (27 days vs. 1.6 yo, p < 0.0001). They were also less likely to present with symptoms (11% vs. 96%, p < 0.0001), including fUTIs (7% vs. 78%, p < 0.0001). In total, 108 children (57%) were initially managed with transurethral incision, 73 (39%) were observed, and 7 (4%) had reconstructive surgery. Asymptomatic children with aCAKUT (42%) and symptomatic children without aCAKUT (37%) were more likely to be observed than symptomatic children with aCAKUT (7%, p = 0.02). Among 143 children with aCAKUT, those on antibiotic prophylaxis were less likely to present with a history of a fUTI compared to those not on prophylaxis (4/106 vs. 6/37, 4% vs. 16%, p = 0.02). COMMENT: We present a large observational study describing clinical and anatomical characteristics of children presenting with ureteroceles in a medical era of ubiquitous prenatal ultrasonography. Our retrospective study was limited by incomplete documentation of all antenatal ultrasonography and adherence with antibiotic prophylaxis. Long-term clinical outcomes will be the focus of future work. CONCLUSION: In contrast to historical cohorts, most children presented to urologists with asymptomatic ureteroceles diagnosed with aCAKUT. Most children without aCAKUT presented with a fUTI. Overall, 39% of children were initially observed, indicating an increased use of observation in the modern medical era.

Humans↗

PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗

PubMed2026

Distinct cell morphotypes of Aureobasidium melanogenum ZN exhibit differential functional profiles in promoting maize growth.

Black yeast-like fungi of the genus Aureobasidium exhibit morphological plasticity, but whether distinct cellular states within the same genetic background are associated with different plant growth-promoting functions remains unclear. Here, yeast-like cells (YL), swollen cells (SC), and chlamydospores (CH) of Aureobasidium melanogenum ZN were characterized. YL was associated mainly with siderophore production and laccase activity, SC with extracellular polysaccharide accumulation, and CH with phosphate mobilization and higher ammonia and IAA production. Whole-genome and comparative genomic analyses revealed a shared repertoire related to nutrient acquisition, auxin-associated metabolism, extracellular oxidation, and carbohydrate remodeling, with expansions in nutrient- and cell-surface-related gene families. Transcriptomic and metabolomic analyses showed distinct deployment of these capacities, with CH exhibiting broad reprogramming of tryptophan-associated, nitrogen, phosphate, central-carbon, and amino-acid metabolism. In maize, CH at the optimal inoculation concentration of 105 CFU·mL-1 produced the strongest growth promotion, increasing plant height, dry biomass, root length, root surface area, and root volume by 58.6%, 365.1%, 191.0%, 194.3%, and 222.4%, respectively. Consistent with this pronounced growth phenotype, maize root transcriptomics showed coordinated CH-induced responses involving root development, nutrient transport, redox regulation, and root-interface remodeling. Root-zone tracking showed greater short-term stability and persistence of CH. These findings identify cellular state as an important functional dimension of Aureobasidium-plant interactions and provide a basis for developing fungal inoculants with defined beneficial cellular states.

Zea mays↗

PubMed2026

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (ΔCAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p = 0.049), particularly for those with higher non-planning impulsivity (p = 0.012). In participants randomized to CPT improvement in PTSD symptom severity (ΔCAPS) was negatively related to baseline total impulsivity (p = 0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans↗

PubMed2026

Extragenital testing for gonorrhea and chlamydia in health department clinics in Virginia, 2018-2023.

BACKGROUND: Extragenital testing for chlamydia and gonorrhea infections is now routine in many settings. We assessed temporal and demographic trends in extragenital testing and positivity in public health department clinics in Virginia. METHODS: We analyzed urogenital and extragenital chlamydia/gonorrhea laboratory results for clients aged 15 years or older who attended 116 health department clinics from 2018 to 2023. Test volume and positivity was stratified by anatomic site, year, sex, and age. RESULTS: There were 181,471 client visits with valid test results. The proportion of visits with any extragenital testing increased from 19% to 46% during this time. Male clients were twice as likely as females to receive pharyngeal testing (46% vs. 22%) and five times as likely to be tested rectally (15% vs. 3%). Rectal specimen positivity surpassed urogenital positivity for chlamydia (females and males) and gonorrhea (males only). Overall, one-quarter of clients diagnosed with gonorrhea infections were identified exclusively through extragenital testing, as were 9% of clients with positive chlamydia tests. These proportions increased over time and were greater for younger clients and for males relative to females. Two-thirds of extragenital infections would have been missed by urogenital testing alone, including 40% and 49% of females and 86% and 73% of males with extragenital chlamydia and gonorrhea infections respectively. CONCLUSIONS: The proportion of clients who received extragenital chlamydia/gonorrhea testing increased over time, extragenital test positivity was high, and it identified infections that would have been missed otherwise. The impact on sexually transmitted infection sequelae and transmission remains unclear.

NAAT↗

PubMed2026

Effects of Transcranial Direct Current Stimulation and Individualized Physical Therapy on Pain and Function in Individuals With Chronic Knee Pain: A Pilot Study.

BACKGROUND AND PURPOSE: Noninvasive brain stimulation is a promising neuromodulatory intervention for chronic pain. This study aimed to determine the impact that transcranial direct current stimulation (tDCS) in combination with individualized physical therapy (PT) has on pain and function in individuals with chronic knee pain. METHODS: This study was a preliminary pragmatic, triple-blinded, randomized, and sham-controlled clinical trial performed in an outpatient orthopedic physical therapy clinic. Participants participated in 5 sessions of active or sham tDCS followed by individualized PT intervention. Pain outcomes included the Numeric Pain Rating Scale, Movement-Evoked Pain, pressure pain thresholds (PPT), and the Central Sensitization Inventory. Functional outcomes included the 2-minute walk test, 5-time sit-to-stand test, quadriceps strength, knee range of motion, Patient Specific Functional Scale, and the Lower Extremity Functional Scale. RESULTS: Thirty participants with chronic knee pain completed the study. There were no significant differences observed for primary patient-centered pain and functional outcomes. For secondary outcomes, the active tDCS group had a significant effect (p < 0.05) on percent change in lateral joint line PPT and a significant multivariate effect of group on PPT change scores for 3-site and 5-site clusters (p < 0.05). Exploratory responder analyses demonstrated that the active tDCS group was 12.8 times more likely to achieve the minimum detectable change in quadriceps strength improvement compared with the sham tDCS group (p < 0.05). DISCUSSION: There were no significant between-group differences for primary pain and functional outcomes. However, the active tDCS group showed improvements in pain sensitivity, as measured by PPT, and quadriceps strength, which were superior to those seen in the sham tDCS group. These preliminary findings provide insight into possible mechanisms of tDCS in addressing pain as opposed to efficacy. Given that there were no clear between-group differences in patient-centered outcomes, there is insufficient evidence for routine tDCS use for chronic knee pain. TRIAL REGISTRATION: NCT06132412.

Humans↗

PubMed2026

Astigmatic vector outcomes after FS-LASIK versus SMILE for high myopic astigmatism: a single-center retrospective comparative cohort study without cyclotorsion compensation.

PURPOSE: To compare astigmatic correction vector outcomes between femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small-incision lenticule extraction (SMILE, also termed Keratorefractive Lenticule Extraction, KLEx) without intraoperative cyclotorsion compensation in patients with high myopic astigmatism (- 2.00 to - 3.75 D), and to clarify procedure-specific correction tendencies under this non-standardized alignment protocol. METHODS: This single-center retrospective comparative cohort study enrolled 155 eyes (one eye randomly selected per patient) that underwent FS-LASIK (80 eyes) or SMILE/KLEx (75 eyes) for high myopic astigmatism correction from January 2023 to July 2024 in Beijing Fenglian Jiayue Lige Clinic. Intraoperative cyclotorsion compensation was intentionally disabled to isolate inherent procedural astigmatism correction characteristics. Standardized Alpins vectorial analysis was performed at 3 months and 12 months postoperatively. PRIMARY ENDPOINT: 12-month Alpins correction index (CI). Multivariable propensity score adjustment was applied to mitigate confounding by clinical treatment selection bias. Statistical multiplicity control was implemented for secondary vector and visual outcomes. RESULTS: Baseline demographic, refractive, corneal and ocular biometric parameters were balanced between groups after propensity matching. No statistically significant intergroup differences were detected in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), residual cylinder, safety index or efficacy index at 3 and 12 months (all P > 0.05). Under the non-cyclotorsion-compensated protocol, significant intergroup differences were identified in the magnitude of surgically induced astigmatism (SIA), correction index (CI), and magnitude error (ME) at both follow-up timepoints (all P < 0.0001). Target induced astigmatism (TIA), difference vector (DV), index of success (IOS), and angle error (AE) magnitudes were comparable between groups (all P > 0.05). The vector mean axis of DV differed significantly between groups at 3 and 12 months (Watson-Williams circular test, all P < 0.0001). No reoperations were documented in clinic medical records for either cohort. No standardized dry eye questionnaires, tear film testing or corneal nerve density metrics were collected to quantify dry eye adverse events; only unstructured clinical notes were reviewed for complication screening. CONCLUSIONS: Under surgical alignment without cyclotorsion compensation, FS-LASIK and SMILE/KLEx both yielded acceptable visual and refractive safety/efficacy for high myopic astigmatism (- 2.00 to - 3.75 D) at 1-year follow-up, but demonstrated divergent astigmatism correction tendencies: FS-LASIK exhibited relative astigmatism overcorrection (vector mean DV: - 0.35 ± 0.43 D × 91°, CI > 1), while SMILE/KLEx showed relative undercorrection (vector mean DV: - 0.21 ± 0.53 D × 12°, CI < 1). These correction biases are specific to the study's manual limbal alignment protocol without cyclotorsion tracking and cannot be generalized to modern optimized surgical platforms equipped with automated cyclotorsion compensation. Residual refractive errors across both groups are likely multifactorial, including differential corneal stromal healing responses, divergent femtosecond/excimer laser tissue modification mechanisms, and uncorrected intraoperative ocular cyclotorsion.

Humans↗

PubMed2026

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-β1-dependent senescence and normalizing mitochondrial indices.

OBJECTIVES: Serum from patients with hypertension (HT) causes endothelial cell (EC) damage, leading to senescence and dysfunctional phenotype. This study investigated whether serum from patients treated with the antihypertensive drugs could normalize EC activity. METHODS: This study involved 71 patients with newly diagnosed HT, who were randomly assigned to one of three groups based on the antihypertensive treatment: amlodipine, nebivolol, or perindopril. Serum samples collected before and 6 weeks after treatment were applied to ECs in vitro to assess their angiogenic activity, cellular senescence, mitochondrial metabolism, and oxidative stress. RESULTS: Results showed that exposure of ECs to serum from patients treated for 6 weeks significantly altered EC function, with varying effects among the drugs. Serum from nebivolol-treated patients produced the most consistent benefits, reducing EC proliferation and HIF-1α expression, likely due to lower levels of angiogenic factors such as angiopoietin-1, basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Additionally, this serum contained reduced levels of pro-inflammatory cytokines (E-selectin, P-selectin, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNFα)) and lower TGF-β1, which are linked to HT-related EC senescence. Nebivolol treatment decreased senescence biomarkers such as SA-β-Gal, 53BP1, and p16, with SA-β-Gal reduction comparable to that of TGF-β1 neutralizing antibodies. Oxidative stress was reduced, indicated by lower oxidized DNA product levels. CONCLUSIONS: Nebivolol was the most effective at reducing the factors, associated with HT induced cellular senescence of endothelium, through reducing TGF-β1.

Humans↗

PubMed2026

Timeliness of publication of randomized controlled trials in rheumatology: A systematic review.

OBJECTIVE: To systematically review the (1) timeliness of publication of randomized controlled trials (RCTs) in rheumatology, (2) impact of the COVID-19 pandemic on time to publication, and (3) factors associated with publication delays. METHODS: We searched Medline, Embase, EBM Reviews, Cochrane Central Register of Controlled Trials, and Scopus from January 1, 2018, to June 30, 2023 for Phase 3, superiority, parallel-design RCTs that evaluated any treatment for a rheumatologic illness or a rheumatologic treatment for COVID-19 and reported clinical primary efficacy outcome. Outcomes of interest were time to publication after trial completion and publication delay of >2 years after trial completion. RESULTS: 448 RCTs were included in this systematic review. Median time from completion to publication was 549 days and 65.9 % RCTs were published within 2 years of completion. Compared with RCTs on rheumatologic diseases, RCTs on COVID-19 were published sooner (253 vs. 549 days; p < 0.001) and were more likely to be published within 2 years (adjusted OR 9.49, 95 % CI 2.07 to 43.61). Compared with RCTs completed before March 1, 2020, RCTs completed after March 1, 2020, were published sooner (327 vs. 724 days; p < 0.001) and were more likely to be published within 2 years (adjusted OR 9.40, 95 % CI 5.14 to 17.21). Time from RCT completion to submission accounted for most (67 %) of the time to publication. CONCLUSIONS: Publication delay continues to be an important concern in dissemination of clinical research. Most of the delays in publication were attributable to delays in submission to journals after trial completion.

Humans↗