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Short-term safety of dual versus single antiplatelet therapy in flow diversion for distal intracranial aneurysms: results from the DART trial.

BACKGROUND AND PURPOSE: Flow diverters (FDs) have become one of the primary treatments for intracranial aneurysms (IAs). However, their use in distal IA has been associated with higher complication rates compared with other techniques. The development of coated FDs, in combination with novel antiplatelet regimens, offers promising strategies to improve the safety profile of FDs in this context. This trial aimed to compare mono antiplatelet therapy (MAPT) using prasugrel versus dual antiplatelet therapy (DAPT) with aspirin and prasugrel for the treatment of distal IA using the p48 MW HPC FD (WallabyPhenox). METHODS: This was a multicenter, prospective, parallel-group, single-blind, non-inferiority randomized trial. Between February 2021 and February 2025, 140 patients were enrolled. After excluding 11 patients, 129 were included in the final analysis. The primary endpoint was the absence of new neurological deficits, defined as no shift in the modified Rankin Scale (mRS) score. The secondary endpoint was the incidence of any stroke. RESULTS: At the 30-day follow-up, 66 patients (98.5%) in the MAPT group and 59 patients (95.2%) in the DAPT group showed no new neurological deficits. With a predefined non-inferiority margin of 5%, the difference of 3.35% confirmed the non-inferiority of MAPT compared with DAPT (p=0.002). The incidence of any stroke was 4/67 (5.9%) in the MAPT group and 6/62 (9.6%) in the DAPT group (p=0.431). CONCLUSION: Prasugrel monotherapy for the treatment of distal IAs using the p48 MW HPC was non-inferior to DAPT within the first 30 days following treatment. CLINICAL TRIAL REGISTRATION: https://ensaiosclinicos.gov.br/rg/RBR-3q9zb73. UTN code: U1111-1290-2489. Research Ethics Committee of the Hospital das Clínicas de Ribeirão Preto - Universidade de São Paulo. CAAE number: 29848720.0.1001.5440.

Humans

Impact of Commercial Artificial Intelligence on Radiologist Reading Time for Pulmonary Nodule Evaluation at Chest CT.

Background Chest CT is a primary method for identifying pulmonary nodules, yet interpreting scans remains time-intensive and demanding. Currently, artificial intelligence (AI) is expected to reduce reading times, but the effect of AI on reporting times in this setting is unknown. Purpose To evaluate the impact of a commercial AI software on radiologists' reading time for pulmonary nodule assessment on chest CT scans within a real-world clinical setting. Materials and Methods This retrospective study included patients who underwent chest CT examinations at a tertiary medical center between September 2021 and May 2024. The study period was divided into pre- and post-AI phases. The primary outcome was radiology reporting time. The association between AI implementation and reporting time was evaluated using a multivariable parametric Weibull shared frailty survival model adjusted for reader function, examination type, patient location, and requesting specialty, with clustering at the radiologist level. Interaction analyses assessed heterogeneity across prespecified subgroups. An exploratory extrapolation estimated projected workforce and financial impact. Results This study included 19&#x2009;433 patients (mean age, 62 years &#xb1; 14.2 [SD]; 21&#x2009;814 men; 39&#x2009;323 chest CT examinations, 19&#x2009;190 pre-AI, and 20&#x2009;133 post-AI). AI implementation was associated with faster report completion (adjusted hazard ratio, 1.17; 95% CI: 1.14, 1.21; P < .001). The adjusted median reporting time decreased from 21.3 minutes pre-AI to 18.2 minutes post-AI (14.6% reduction; P < .001). Heterogeneity was observed across reader function (P < .001), examination type (P = .048), and requesting specialty (P = .03). The largest relative reductions were observed for CT thorax electrocardiogram-gated examinations (-41.1%; P < .001) and thoracic radiologists (-25.0%; P < .001), whereas emergency department examinations showed increased median reporting time (7.1%; P < .001). At institutional scan volumes (approximately 20&#x2009;000-22&#x2009;000 chest CT examinations annually), exploratory modeling suggested an approximate reduction of 0.5 full-time equivalent radiologist workload. Conclusion Implementation of commercial AI-assisted pulmonary nodule assessment on chest CT scans reduced radiologist reporting time in a real-world clinical setting. &#xa9; The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Iwasawa in this issue.

Humans

Optimized AAV5-RPGR ORF15 Gene Therapy Rescues Photoreceptor Structure and Function in X-Linked Retinitis Pigmentosa Mouse Model.

PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa caused by RPGR mutations, addressing the challenges of cloning the unstable wild-type ORF15 sequence. DESIGN: This was a prospective experimental study. SUBJECTS: This was an animal study. METHODS: An optimized RPGR ORF15 sequence was designed to eliminate problematic secondary structures and cryptic splice sites. In vitro expression was validated in HEK 293T and photoreceptor-like 661 W cells. A complete Rpgr knockout mouse model (Rpgr-knockout [KO]) was generated and characterized phenotypically. Therapeutic efficacy was assessed in Rpgr-KO mice via subretinal injection of rAAV5-RPGR at low (1 &#xd7; 10&#x2079; vg/eye), medium (3 &#xd7; 10&#x2079; vg/eye), or high (1 &#xd7; 10&#xb9;&#x2070; vg/eye) doses. Structural and functional outcomes were evaluated at 12- and 14-month postinjection. Short-term safety was assessed in rabbits 1 month after subretinal injection. MAIN OUTCOME MEASURES: Level of RPGR protein expression and Protein isoform profile (elimination of truncated isoforms), Cellular localization of transgene expression and Dose-dependence of expression, outer nuclear layer thickness, and electroretinography parameters. RESULTS: (1) The optimized vector increased RPGR protein expression 3.3-fold in vitro compared to wild-type and eliminated truncated isoforms. (2) Subretinal delivery of rAAV5-RPGR in mice demonstrated dose-dependent transgene expression localized correctly to photoreceptor inner segments. (3) In Rpgr-KO mice, high-dose treatment significantly preserved outer nuclear layer thickness at the injection site (42% greater than controls at 14 months, P < .01) and central retina (P < .05), reduced aberrant rhodopsin mislocalization (P < .01), and partially restored retinal function. ERG showed significantly improved scotopic a-wave (&#x2265;100 vs <90 &#xb5;V in controls at 10 cd&#xb7;s/m&#xb2;) and photopic b-wave amplitudes (49-66 vs 31-46 &#xb5;V at 30 cd&#xb7;s/m&#xb2;) in treated mice. (4) No vector-related toxicity was observed in rabbits. CONCLUSIONS: rAAV5-RPGR mediated efficiently, targeted expression of optimized RPGR-ORF15, significantly preserved photoreceptor structure and function in a severe X-linked retinitis pigmentosa mouse model, and demonstrated a favorable safety profile. This study provides preclinical proof-of-concept for RPGR-targeted gene replacement therapy.

Animals

Cochlear Implantation in Sickle Cell Disease: A Systematic Review of Feasibility and Outcomes.

INTRODUCTION: Sickle cell disease (SCD) is associated with systemic complications, including sensorineural hearing loss (SNHL) from microvascular occlusion and chronic inflammation. Although reports link SCD to higher rates of SNHL, current evidence is limited by small sample size, varied audiologic methods, and lack of standardized screening. This systematic review summarizes available literature on SNHL and cochlear implantation (CI) in SCD. METHODS: A literature search of PubMed MEDLINE, Embase, Scopus, Web of Science, and CINAHL identified 79 citations. After removal of duplicates, 35 records were screened in Rayyan. Studies published between January 1, 2000, and June 30, 2025, were eligible if they reported patients with SCD who developed hearing loss and underwent CI. Nine full texts were reviewed, and 4 met the inclusion criteria. Screening and review were performed independently by 2 authors per PRISMA guidelines. RESULTS: Across 4 case reports, a total of 5 patients with SCD underwent CI, ranging in age from 2 to 42 years. Four presented with bilateral severe-to-profound SNHL and one with unilateral loss. Implantation was technically feasible in all cases, including patients with cochlear fibrosis or ossification requiring modified insertion techniques. Postoperative outcomes were favorable: all patients demonstrated reliable device function and low impedances. Only 60% showed meaningful auditory benefit, characterized by improved functional speech perception in 2 patients (40%) and access to the speech frequency range with hearing testing going from moderate/profound hearing loss to mild hearing loss in 3 patients (60%). Complications occurred in 2 patients (40%): one developed unilateral middle ear infection leading to meningitis, and another experienced a postoperative pulmonary embolism requiring anticoagulation. The remaining 3 patients (60%) had uncomplicated recoveries with reported improved hearing from moderate/profound hearing loss to mild hearing loss post implantation. CONCLUSION: While CI appears feasible in SCD, our findings suggest that additional data are needed to assess its effectiveness in this patient population. However, evidence is limited to case reports, and complications such as thromboembolism and rapid cochlear fibrosis highlight the need for close perioperative management. More comprehensive studies with larger sample size are required to define surgical risk, optimize management, and establish best practices for timely implantation in this population.

Humans

Application of Three-Dimensionally Printed Surgical Guides in Precise Sacral Tumor Excision and Defect Reconstruction.

OBJECTIVE: Precise resection of sacral tumors remains technically demanding due to their deep anatomical location and close proximity to critical neurovascular structures. Conventional freehand techniques often result in suboptimal resection margins, excessive blood loss, and compromised lumbopelvic stability. This study evaluated whether patient-specific three-dimensional (3D)-printed guiding templates improve surgical accuracy and perioperative outcomes in sacral tumor resection and reconstruction. METHODS: Nineteen patients undergoing en bloc sacral tumor resection (S1-S3 involvement) with spinopelvic reconstruction (2006-2020) were retrospectively analyzed. Patients were divided into a 3D-printing group (n&#x2009;=&#x2009;10) and a conventional freehand group (n&#x2009;=&#x2009;9). In the 3D-printing group, computer-aided design and 3D-printed templates were used for osteotomy, screw placement, and defect reconstruction. Perioperative metrics, surgical accuracy, and complications were compared between groups using Welch's t-test and the Hodges-Lehmann method; oncologic events during follow-up were recorded descriptively. RESULTS: The 3D-printing group demonstrated significantly shorter operative time (456.5&#x2009;&#xb1;&#x2009;62.36 vs. 574.44&#x2009;&#xb1;&#x2009;114.58&#x2009;min, p&#x2009;=&#x2009;0.012), reduced blood loss (4081.40&#x2009;&#xb1;&#x2009;838.99 vs. 5090.0&#x2009;&#xb1;&#x2009;1059.67&#x2009;mL, p&#x2009;=&#x2009;0.034), and fewer fluoroscopic exposures (4.2&#x2009;&#xb1;&#x2009;0.79 vs. 10.0&#x2009;&#xb1;&#x2009;1.58, p&#x2009;<&#x2009;0.001) compared with the conventional group. Osteotomy accuracy was also superior in the 3D-printing group, with significantly lower angular deviation (3.33&#xb0;&#x2009;&#xb1;&#x2009;0.45&#xb0; vs. 6.79&#xb0;&#x2009;&#xb1;&#x2009;2.16&#xb0;, p&#x2009;=&#x2009;0.0012). Postoperative complication rates were comparable (30% vs. 44.4%, p&#x2009;=&#x2009;0.649), but hospital stay was significantly shorter in the 3D-printing group (10.7&#x2009;&#xb1;&#x2009;2.71 vs. 18.11&#x2009;&#xb1;&#x2009;4.01&#x2009;days, p&#x2009;<&#x2009;0.001). CONCLUSION: Patient-specific 3D-printed guiding templates enhance precision in sacral tumor excision and reconstruction, improving surgical efficiency and perioperative safety. This computer-assisted, template-guided approach represents a valuable advancement for complex sacral oncologic surgery.

Humans

Critical insights on the application of the theory of planned behaviour to food handlers' food safety practices.

Foodborne diseases remain a significant public health concern, often linked to unsafe food-handling practices. The Theory of Planned Behaviour (TPB) is widely used to predict and explain food safety behaviours, yet its application in this field has not been systematically and in-depth evaluated. This review evaluated how the TPB has been applied to study food handlers' behaviour, focusing on methodological approaches, use of the TACT (Target, Action, Context, and Time) framework, validity, elicitation studies, and reliability. Seventeen studies were included following a systematic search of four databases (Scopus, Web of Science, Wiley Online Library, and Taylor & Francis Online). Data were extracted on behaviour definition, aim of study, main findings, use of indirect and direct TPB measures, use of elicitation studies, internal consistency, content validation, analytical methods used, and any extensions to the original TPB framework. Key elements related to adherence to core TPB principles and measurement practices were extracted using a Checklist. Most studies used direct measures of TPB constructs, and only a few reported procedures for content validation. Considerable variability was found in the reporting of key measurement and psychometric practices. Five studies fully applied the TACT framework, while nine incorporated additional factors such as knowledge and moral norms. Elicitation studies were conducted in five cases where indirect measures were employed. Analytical approaches were mainly based on multiple linear regression, with limited use of more advanced techniques such as structural equation modeling. Twelve studies reported internal consistency results. Overall, the review highlights opportunities to strengthen methodological practices in future TPB research on food safety. Greater attention to conducting and reporting content validation, full application of the TACT framework, reporting of internal consistency, and consistent inclusion of elicitation studies when using indirect measures may enhance transparency, reinforcing the credibility and trustworthiness of research findings. A major methodological limitation of this review was that screening and data extraction were conducted by a single reviewer and no formal quality or risk-of-bias assessment of the included studies was performed. Despite these limitations, the findings provide practical guidance for the development and validation of TPB-based questionnaires and may support more robust food safety research, interventions, and policy initiatives aimed at improving food handlers' practices.

Humans

Bivalirudin Versus Heparin in Low and Non-Low Bleeding Risk Patients Undergoing Primary PCI for STEMI: The BRIGHT-4 Trial.

BACKGROUND: In the BRIGHT-4 trial, among 6,016 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with a radial artery approach, procedural anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2 to 4 hours reduced the 30-day primary composite outcome of all-cause death or Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding, as well as death and bleeding individually, compared with heparin monotherapy. OBJECTIVES: We sought to determine whether the benefits of bivalirudin apply principally to patients who are at low bleeding risk (LBR) as well as non-LBR. METHODS: In a prespecified analysis from BRIGHT-4, outcomes were examined by baseline bleeding risk, with LBR defined as a CRUSADE score <30. RESULTS: At baseline, 4,581 patients (76.1%) were categorized as LBR. Non-LBR patients had higher rates of the 30-day primary endpoint (8.6% vs 2.2%; HR: 4.08 [95% CI: 3.14-5.31]; P < 0.0001), driven by both greater mortality and BARC types 3 to 5 bleeding. In non-LBR patients, the primary outcome occurred in 8.1% of patients randomized to bivalirudin vs 9.2% of those randomized to heparin (difference: -1.1% [95% CI: -4.0% to 1.8%]; HR: 0.88 [95% CI: 0.62-1.26]). In LBR patients, the primary outcome occurred in 1.4% of patients randomized to bivalirudin vs 2.9% of those randomized to heparin (difference: -1.5% [95% CI: -2.3% to -0.6%]; HR: 0.49 [95% CI: 0.32-0.75]) (Pabsolute interaction = 0.81; Prelative interaction = 0.04). The effects of bivalirudin compared with heparin in reducing all-cause death were as robust in LBR patients compared with non-LBR patients (Pabsolute interaction = 0.67; Prelative interaction = 0.06). CONCLUSIONS: Among patients with STEMI undergoing primary PCI with radial artery access, procedural anticoagulation with bivalirudin plus a high-dose post-PCI infusion for 2 to 4 hours reduced the 30-day risk of all-cause death and major bleeding in patients at low bleeding risk as well as in patients at higher-risk of bleeding. (Bivalirudin With Prolonged Full Dose Infusion Versus Heparin Alone During Emergency PCI [BRIGHT-4; NCT03822975]).

Humans

Low-Dose Perineural Dexamethasone Enhances Analgesia After Pediatric Hand Surgery Without Elevating Systemic Stress Markers: A Randomized Controlled Trial.

BACKGROUND: Supraclavicular brachial plexus block is a widely used technique for upper limb surgery in children. Although perineural dexamethasone has demonstrated efficacy in prolonging analgesia in adults, data on its optimal dosing and systemic safety in pediatric patients are limited. This study aimed to evaluate whether low-dose perineural dexamethasone can prolong postoperative analgesia without increasing systemic stress markers in young children undergoing hand or wrist surgery. METHODS: In this triple-blinded, randomized controlled trial (ClinicalTrials.gov Identifier: NCT06086392), 90 children aged 3 months to 6 years undergoing elective upper extremity surgery were assigned to receive supraclavicular brachial plexus block with 0.2% ropivacaine combined with either normal saline (control), dexamethasone 0.05&#xa0;mg/kg, or dexamethasone 0.1&#xa0;mg/kg. The primary outcome was time from arrival in the postanesthesia care unit to first administration of rescue opioid analgesia. Secondary outcomes included total opioid consumption, postoperative pain intensity using the FLACC scale, blood glucose levels, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and time to motor recovery. RESULTS: Both dexamethasone groups demonstrated significantly prolonged time to first opioid use compared with the control group (mean&#xb1;SD: 19.4&#xb1;2.2&#xa0;h in the 0.1&#xa0;mg/kg group, 16.0&#xb1;1.9&#xa0;h in the 0.05&#xa0;mg/kg group, and 8.5&#xb1;1.3&#xa0;h in controls; P <0.0001). Total opioid consumption was significantly reduced in the dexamethasone groups. Postoperative pain scores were lower in both intervention groups, especially during the first 12 hours. No significant differences were found among groups in blood glucose, inflammatory markers, or incidence of nerve deficits. Motor recovery was delayed in the dexamethasone groups but did not interfere with early mobilization. CONCLUSIONS: Low-dose perineural dexamethasone (0.05 to 0.1&#xa0;mg/kg) safely and effectively prolongs postoperative analgesia and reduces opioid needs in children undergoing upper limb surgery, without causing systemic metabolic or inflammatory disturbances. The 0.05&#xa0;mg/kg dose may offer a more favorable balance between analgesic efficacy and motor recovery time. LEVEL OF EVIDENCE: Level I-randomized controlled trial.

Humans

Early and late CTCAE and patient-reported outcomes following lung cancer radiotherapy: A sex-stratified descriptive analysis from the REQUITE cohort.

BACKGROUND: Long-term prospective data on lung cancer patients treated with radiotherapy are limited, restricting understanding of outcomes and sex-specific characteristics. The multicentre REQUITE study provides standardized follow-up data from an international cohort. METHODS: We analysed longitudinal data from 530 lung cancer patients treated with radical radiotherapy (sequential or concurrent chemoradiotherapy, or stereotactic body radiation therapy [SBRT]) between 2014 and 2017 at 16 centres in Europe and the USA. Healthcare professionals prospectively recorded 21 pulmonary, oesophageal, neurological, cardiac, and skin adverse events using CTCAE v4.0. Patient-reported outcomes assessed symptoms, quality-of-life, fatigue, and physical activity. Adverse event incidence was stratified by sex, radiotherapy technique, chemotherapy administration, smoking status, and other clinical factors. RESULTS: At 12&#xa0;months, 309 patients were evaluable, with 151 having follow-up beyond one year. Pulmonary adverse events were most frequent (40% grade&#xa0;&#x2265;&#xa0;2), mainly dyspnoea and cough. Women had higher rates of oesophagitis, and more frequently reported dysphagia, and chest wall pain, while men experienced a higher frequency of cardiac adverse events. Exploratory subgroup analyses identified significant sex-related differences in grade&#xa0;&#x2265;&#xa0;3 pulmonary adverse events following SBRT and in overall grade&#xa0;&#x2265;&#xa0;2 oesophageal adverse events among patients with clinical stage I-II and those aged >70&#xa0;years. Patient-reported outcomes showed persistent fatigue and reduced physical activity, particularly in females. Symptom prevalence and severity varied by sex, age, treatment modality, smoking status, and clinical stage. CONCLUSION: The REQUITE-Lung cohort provides prospectively collected real-world data on radiotherapy-related adverse events in lung cancer patients. This study describes patterns of adverse events and patient-reported outcomes according to sex, age, and treatment characteristics. These findings are hypothesis-generating and may support future validation in independent and pooled datasets.

Patient-reported outcomes

Open repairs with biceps rerouting does not impact retears in large to massive rotator cuff tears compared to conventional open repair: a randomized clinical trial.

BACKGROUND: The treatment of large to massive rotator cuff tears leads to a high failure rate and several techniques have been proposed to improve these results. Rerouting the long head of the biceps tendon (LHBT) appears to be a biological reinforcement to increase tendon healing. Therefore, this study aimed to compare the clinical and radiological outcomes of open repair for large and massive rotator cuff tears reinforced with the LHBT to conventional open repair. METHODS: A prospective randomized study was conducted with patients diagnosed with large to massive rotator posterosuperior rotator cuff tear and intact LHBT, randomized into 2 groups: biceps rerouting and conventional open repair. The functional outcomes were assessed by the American Shoulder and Elbow Surgeon score, University of California at Los Angeles score, and SF-12 questionnaire preoperatively and at 6, 12, and 24 months postoperatively. Pain level was also assessed by the visual analog scale including the first day and 2 weeks postoperatively. Structural outcomes were rotator cuff and LHBT healing with magnetic resonance imaging and acromiohumeral distance (AHD) through radiography. RESULTS: We evaluated 58 patients, 29 in each group. At the end of the follow-up there were no statistically significant differences between groups in American Shoulder and Elbow Surgeon (76.1 vs. 80.4, P = .761), University of California at Los Angeles (27.1 vs. 29.1, P = .634), or visual analog scale scores (1.3 vs. 1.1, P = .781). Additionally, rotator cuff healing rates (48.3% vs. 44.8%, P = .402) and LHBT healing rates (79.3% vs. 82.7%, P = .738) were similar. AHD increased in both groups, with no significant difference in delta AHD (P = .513). Both groups showed significant clinical improvement over time in all evaluated outcomes (P < 0,01). No postoperative complications were reported. CONCLUSIONS: We could not identify an advantage of open repair with LHBT rerouting as reinforcement over conventional open repair. Nonetheless, all clinical scores improved at the end of the 24 months of follow-up in both groups.

Humans

Longitudinal Repeated Protein Measurements in a Multiethnic Cohort Identify Novel Diabetes Biomarkers That Reveal Unique Disease Pathways.

There is up to a fourfold increase in diabetes biomarkers identified with longitudinal repeated versus single time point proteomic measurements. The increase in biomarkers identified with longitudinal repeated measurements is supported by a similar proportion being nominated as causal for type 2 diabetes with Mendelian randomization. Proteins unique to the longitudinal repeated analyses highlighted biological pathways (e.g., posttranslational protein modification and cellular structure and cycle regulation) that were distinct from pathways enriched among the shared proteins (e.g., small-molecule metabolic and catabolic processes). Longitudinal protein measurements identify additional novel disease biomarkers and disparate biological pathways compared with single measurement analyses.

Journal Article

Human endogenous retroviruses leading to autoimmune diseases.

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and were long regarded as inert remnants of ancestral retroviral infections. Increasing evidence indicates that HERVs are active genomic elements capable of influencing transcriptional programs, modulating immune responses, and contributing to disease pathogenesis. Under physiological conditions, HERV expression is tightly controlled by epigenetic mechanisms; however, infections, chronic inflammation, aging, and diverse environmental stimuli can promote HERV reactivation. HERV-derived RNAs and proteins engage innate immune sensors and trigger antiviral-like responses through mechanisms of viral mimicry, leading to activation of type I interferon and other inflammatory pathways. HERV dysregulation has been associated with disease-relevant immune pathways. This review summarizes recent advances linking HERVs to autoimmune disease pathogenesis and discusses their potential translational relevance as biomarkers and therapeutic targets.

Humans

Integrative genomic and transcriptomic analyses identify key regulators of skin pigmentation in Larimichthys crocea.

The yellow body coloration of large yellow croaker (Larimichthys crocea) constitutes a crucial economic trait, yet its underlying genetic regulatory mechanisms remain poorly understood. This study systematically elucidated the molecular basis of body color variation by integrating genome resequencing and skin transcriptome analyses, combined with the contextual analysis of key pigmentation-related genes and phenotypic histological validation. 200 phenotyped individuals (including yellow-selected lines, F1 progeny, and normal control groups, all derived from a well-characterized aquaculture stock) identified 39 significantly associated SNPs (-log&#x2081;&#x2080;(P)&#xa0;&#x2265;&#xa0;6), mapping to multiple candidate genes. These genes were significantly enriched in pathways related to pigment deposition (GO:0033059), melanosome organization (GO:0032438), melanogenesis, and tyrosine metabolism. Cross-developmental stage transcriptome analysis revealed 2395 differentially expressed genes (DEGs). Multi-omics integration identified eight overlapping candidate genes, including tyrp1, slc45a2, oca2, and dgat2, among which tyrp1 was prioritized for in-depth validation based on its core regulatory role in eumelanin synthesis, significant SNP association signal, and consistent downregulation in transcriptomic data. Experimental validation demonstrated that the g.895C&#xa0;>&#xa0;T mutation in exon 2 of tyrp1b was strongly significantly associated with the yellow phenotype: the frequency of mutant genotypes (TT/CT) reached 92.86%in the yellow-selected group, whereas the control group exclusively exhibited the wild-type genotype (CC). qPCR confirmed significantly downregulated tyrp1b expression in the skin of yellow individuals, consistent with the transcriptome trend. Histological and stereomicroscopic observations of skin tissues further validated the physiological basis of the yellow phenotype, revealing a significant reduction in melanophore number and abnormal melanosome morphology in yellow-phenotype individuals, accompanied by increased xanthophore density. These results suggest that tyrp1b mutation is strongly associated with the yellow phenotype. However, the presence of a wild-type CC individual in the yellow group indicates that this mutation is not strictly required for yellow coloration, suggesting that other genetic or environmental factors may also contribute to the phenotype, Additionally, downregulation of the carotenoid metabolism gene bco2 coupled with upregulation of xdh, together with the functional changes of slc45a2 and oca2, may synergistically promote xanthophore pigment deposition, contributing to the yellow phenotype. As melanin synthesis in large yellow croaker relies on the conserved tyrosinase pathway and transporter proteins, mutations in associated genes (tyrp1b, slc45a2, oca2) represent a primary underlying cause for the loss of melanin-based coloration and transition to a yellow phenotype in L. crocea. These findings provide key molecular targets and a theoretical foundation for molecular breeding of body color in this species, and also enrich the understanding of xanthism regulatory mechanisms in teleosts.

Animals

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n&#x2009;=&#x2009;101) and a "Low Symptom Burden-Relieving (LSBR)" type (n&#x2009;=&#x2009;88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P&#x2009;<&#x2009;0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.&#xa0; CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans

Emotional and Cognitive Processes Underlying Persuasion, Moderating Factors, and Physiological Reactions: A Systematic Review.

Persuasion is a type of social influence aiming to produce changes in others' attitudes or behaviors. This study explores the relationship between emotions and persuasion, principal moderating factors, and physiological reactions during persuasive attempts. Following PRISMA guidelines, 28 empirical articles were analyzed, addressing emotions, affective/cognitive orientations, framing effects, and psychophysiological reactions. Mixed findings emerged regarding emotions, with fear appeals being effective in health education, while more recent studies favor the use of positive persuasive messages to increase behavior intention. Principal moderating factors included personal relevance, need for cognition (NFC) and need for affect (NFA), thought confidence, vulnerability, and efficacy beliefs. Psychophysiological studies revealed distinct physiological arousal during persuasion processing compared to a rest state. In addition, a greater misalignment between current behavior and the persuasive attempt led to perceived freedom threat and psychological reactance. These insights enhance persuasive effectiveness and deepen understanding of persuasion processes, guiding future research directions.

Humans

Breastfeeding Outcomes After Radiofrequency Ablation and Surgical Excision of Fibroadenomas Compared to Natural History: A Retrospective Cohort Study.

BACKGROUND: Fibroadenomas, common benign breast tumors in women of reproductive age, are increasingly managed with minimally invasive radiofrequency ablation (RFA) or surgical excision. However, their impact on breastfeeding outcomes remains underexplored. We aimed to assess breastfeeding ability and breast tissue changes in women treated with RFA or surgery compared to those with untreated fibroadenomas. METHODS: In this retrospective cohort study, we evaluated 153 women with biopsy-confirmed fibroadenomas across five groups: RFA with prior breastfeeding (RFA-PreBF; n = 26), RFA with posttreatment breastfeeding (RFA-PostBF; n = 22), surgical excision with prior breastfeeding (Surgical-PreBF; n = 30), surgical excision with posttreatment breastfeeding (Surgical-PostBF; n = 20), and noninterventional with breastfeeding (Observation-BF; n = 55). Breastfeeding ability was assessed using a 5-point scale, and breast tissue changes were evaluated via ultrasound at 18 months, and all breastfeeding attempts occurred at a minimum of 12 months postprocedure. Fisher's exact test compared complete lactation failure rates, and a power analysis validated the study design (Fig. 1). FINDINGS: The combined RFA group (n = 48) had a higher complete lactation failure rate (14.6%) than the Observation-BF group (3.6%; Fisher's exact test, p = 0.045). Similarly, the combined surgical group (n = 50) had a higher complete lactation failure rate (16.0%) than the Observation-BF group (p = 0.034). When pooled, the combined intervention group (n = 98) showed a complete lactation failure rate of 15.3% versus 3.6% in the Observation-BF group. Residual tissue correlated with lactation impairment in the RFA group (Spearman's &#x3c1;, p < 0.05). Ultrasound showed no tumor recurrence, with cystic changes in some cases not linked to breastfeeding impairment. Power analysis confirmed 80% power to detect a medium effect size (f = 0.25, Fig. 1), supporting the study's robustness.7 RFA-PreBF (n = 26), RFA-PostBF (n = 22), Surgical-PreBF (n = 30), Surgical-PostBF (n = 20), and Observation-BF (n = 55). Breastfeeding ability was assessed using a 5-point scale, and breast tissue changes were evaluated via ultrasound at 18 months. Fisher's exact test compared complete lactation failure rates, and a power analysis validated the study design (Fig. 1).[Figure: see text]Interpretation:RFA and surgical excision are effective for fibroadenoma management but increase the risk of complete lactation failure compared to untreated fibroadenomas. Careful patient selection, precise procedural techniques, and vigilant posttreatment monitoring are essential to optimize breastfeeding outcomes, particularly for women planning future pregnancies.

Humans

The use of diode laser and scalpel blade in stage-two dental implant surgery: a comparative study.

OBJECTIVE: The use of lasers in dental implant procedures raises questions regarding the preservation of keratinized tissues and implant outcomes. This study aimed to compare the clinical effects (pain and impression time) and soft tissue healing (keratinization, peri-implant probing, bleeding, and healing) of diode lasers and scalpels used during stage-two dental implant surgery. METHOD AND MATERIALS: A prospective randomized clinical trial with a 1:1 allocation ratio was conducted. The study included 30 patients, each with a single, fully osseointegrated implant. Patients were categorized into two groups. The study group underwent stage-two implant surgery using a 970-nm diode laser. In the control group, implants were exposed using a conventional surgical blade. A comparison between the diode laser and conventional scalpel groups was made based on clinical outcomes (pain and impression time) and soft tissue healing (keratinization, peri-implant probing, bleeding, and healing). Data were analyzed using a paired t test. RESULTS: Pain intensity significantly decreased from immediate postoperative to 7 days in both scalpel (49.87 &#xb1; 6.78, t = 28.48, df = 14, P .001) and diode laser (7.67 &#xb1; 7.58, t = 3.91, df = 14, P = .002) groups. Immediately after surgery, pain scores were significantly higher in the scalpel group compared with the diode laser group (94.53 &#xb1; 4.45 vs 46.93 &#xb1; 5.85, t = 25.076, df = 26.151, P .001). Although pain decreased in both groups by day 7, the scalpel group continued to exhibit significantly greater pain (44.67 &#xb1; 5.96 vs 39.27 &#xb1; 3.73, t = 2.974, df = 23.513, P = .007). Impression time (P = .231) and gingival keratinized tissue (P = .736) did not differ significantly between the scalpel and diode laser approaches. At week 6, the scalpel group exhibited a significantly higher mean peri-implant bleeding index (2.60 &#xb1; 0.507) compared with the laser group (0.07 &#xb1; 0.258, P .001). However, after 12 weeks, no significant difference was observed (1.58 &#xb1; 0.19 vs 1.55 &#xb1; 0.21, P = .748). Laser surgery produced significantly better early wound healing at all intervals (P .001), while intraoperative bleeding was more common with the scalpel technique than with the diode laser (100.0% vs 66.7%, P = .042). CONCLUSION: Compared with the scalpel method, the diode laser method resulted in a significant reduction in pain intensity, improved wound healing, and less peri-implant bleeding during the stage-two dental implant surgery.

Humans

Comparative Evaluation of Virtual Reality versus Standard Nursing Care in Managing Pain and Fear during Lumbar Puncture Procedures: A Randomised Controlled Trial.

BACKGROUND: Meningitis is a serious infectious disease that can cause significant morbidity and long-term neurological problems. Although a lumbar puncture is a necessary diagnostic procedure, it is often accompanied by discomfort, anxiety, and fear, which can severely impact the patient's experience. Although there is few data on its application prior to lumbar puncture in adult patients with meningitis, immersive virtual reality (VR) has become a promising non-pharmacological technique for lowering procedural distress. Thus, among individuals undergoing lumbar punctures, this randomized controlled research assessed how well pre-procedural VR reduced pain, anxiety, and fear while enhancing patient satisfaction. OBJECTIVE: This study aims to evaluate the effectiveness of virtual reality (VR) in reducing pain and fear among adults undergoing lumbar puncture (LP) compared with standard care protocol. METHODS: A randomised clinical trial was conducted from May to October 2025, using a single-blind, true experimental design. A total of 85 patients were randomly assigned to either the VR intervention group ( n = 41) or the control group receiving standard care ( n = 44). Pain levels were assessed using a visual analogue scale. Fear was assessed using the Multidimensional Fear-of-Injection Scale. Data were analysed using SPSS version 26. RESULTS: According to the study, the findings revealed a significant reduction in pain levels among the study group following the VR intervention, with mean pain scores dropping from 7.54 &#xb1; 1.925 to 2.49 &#xb1; 0.675. In contrast, the control group showed increased pain intensity, with mean scores rising from 6.84 &#xb1; 1.842 to 8.36 &#xb1; 1.348. The VR group showed a significant reduction in fear scores across all domains, whereas no significant changes were observed in the control group. Direct fear decreased from 20.12 &#xb1; 1.71 to 9.44 &#xb1; 2.00, indirect fear from 17.24 &#xb1; 1.46 to 8.66 &#xb1; 2.24, physiological response improved from 0.34 &#xb1; 0.66 to 3.00 &#xb1; 1.00 and avoidance behaviour decreased from 16.71 &#xb1; 1.49 to 7.80 &#xb1; 1.85. CONCLUSIONS: The research shows that the use of VR prior to LP significantly reduces level of pain and fear compared to standard care. These results support VR as a non-pharmacological intervention for fear and pain to improve patient experience during invasive procedures. In contrast, the control group experienced no improvement.Trial Registration: The IRCT code for the trial was IRCT ID 20250803066743N1.

Humans