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Mindfulness and Sex Education for Sexual Dysfunction in Breast Cancer Survivors: Mediators and Moderators of Treatment Outcome.

Mindfulness-based cognitive therapy (MBCT) and supportive-expressive sex education therapy (STEP) are effective group treatments for sexual dysfunction after breast cancer (BrCa). We explored mediators and moderators of outcomes following the 8-week groups. BrCa survivors (n = 116, mean age = 49.9 ± 9.5) were randomized to group and completed measures before, immediately after, and 6 months after treatment. Mediators assessed were changes in depression, chronic pain acceptance, pain catastrophizing, and trait mindfulness. Potential moderators included age, treatment expectations, baseline mental health, cancer treatment duration, use of chemotherapy, and adjuvant endocrine therapy. Longitudinal mediation and moderation were assessed using linear mixed models. Increases in pain acceptance mediated improvements in sexual desire and reductions in both sexual distress and vaginal pain. Decreases in pain catastrophizing mediated improvements in sexual distress. Higher expectations for treatment led to greater reductions in sexual distress. Those with low baseline anxiety showed greater improvements in desire and distress. Low baseline depression predicted greater improvements in desire, but only in the STEP arm. Older STEP participants improved significantly more than younger STEP participants. Cancer-related treatment variables, and the impact of adjuvant endocrine therapy, had differential effects on outcomes based on the treatment arm of the study. In conclusion, treatments aimed at improving pain acceptance and pain catastrophizing are likely to promote improvements in sexual health among BrCa survivors, and factoring in patients' expectations about treatment improvements, depression and anxiety, age, duration of cancer treatment, chemotherapy, and adjuvant hormonal therapy may help to guide treatment recommendations for sexual dysfunction.

Humans

The Impact of Oncological Treatments on Return to Work, Work Ability, and Sickness Absence in Breast Cancer Survivors: A Systematic Review.

PURPOSE: Returning to work and maintaining an adequate ability to work serve as key indicators of quality of life, psychological well-being and psychosocial adjustment. Therefore, this study aims to analyze the impact of breast cancer treatments on return to work (RTW), work ability (WA), and sick leave (SL) among breast cancer survivors. METHODS: A systematic review was conducted according to the PRISMA guidelines. The sample consisted of 26 studies published between 2016 and 2025, including prospective multicenter cohorts and national registries from fifteen countries across four continents, with more than 25,000 participants. A methodological quality assessment and a narrative synthesis were performed to synthesize the results. RESULTS: Chemotherapy is the most consistent predictor of prolonged SL, delayed RTW, and significantly reduced WA. Radical surgery and axillary lymph node dissection (ALND) are associated with a significantly delayed RTW due to physical sequelae. While outcomes showed strong relationship with clinical factors, certain psychosocial variables such as depression, anxiety, and low self-efficacy seemed to act as important secondary factors that can further complicate the process. CONCLUSION: The findings suggest that more invasive or aggressive treatments (chemotherapy, ALND, and radical surgery) were associated with poorer outcomes on RTW, WA, and SL. Furthermore, the clinical recovery associated with treatment completion did not necessarily equate to a functional recovery in WA that facilitated a successful RTW. Thus, it is necessary to explore in depth the impact of cancer treatments on WA, alongside psychosocial variables, to design multidisciplinary interventions that enable sustainable occupational reintegration. REGISTRATION: PROSPERO 2026 (CRD420261322638).

Breast cancer survivors

Fourteen-Day Amoxicillin- or Tetracycline-Containing Bismuth Quadruple Therapy versus 14-Day Metronidazole-Based Triple Therapy as the Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial.

BACKGROUND/AIMS: Combination therapy comprising a proton pump inhibitor (PPI), amoxicillin, and metronidazole (PAM) is used to treat clarithromycin-resistant Helicobacter pylori in the Republic of Korea, but eradication rates are decreasing due to an increasing incidence of clarithromycin resistance. We compared PAM, bismuth compounds plus PAM (PAM-B), and the combination of PPI, bismuth compounds, metronidazole, and tetracycline (PBMT) to determine whether PAM-B can achieve an eradication rate higher than that of PAM and comparable to that of PBMT. METHODS: This prospective multicenter study enrolled patients with clarithromycin-resistant H. pylori infections in the Busan and Gyeongsangnam-do of the Republic of Korea between December 2022 and February 2024. RESULTS: In the intention-to-treat (ITT) analysis, the eradication rate was significantly lower in the PAM group (68.2%) than in the PAM-B group (84.8%, p=0.024), whereas the difference from the PBMT group (81.8%) was not significant (p=0.070). The rate remained lowest in the PAM group (75.4%) in the per-protocol (PP) analysis (PAM-B, 96.5%, p=0.001; PBMT, 94.6%, p=0.004). Eradication rates were comparable between the PAM-B and PBMT groups in both the ITT (p=0.640) and PP analyses (p=0.633). Nausea and vomiting were significantly less frequent in the PAM-B group than in the PBMT group (6.8% vs 25.0%; p=0.007). Severe adverse events were rare, and all symptoms resolved after treatment discontinuation. CONCLUSIONS: PAM-B yielded eradication rates higher than those of PAM and comparable to those of PBMT, with no significant increase in the incidence of adverse events, suggesting the potential of PAM-B as a first-line treatment for clarithromycin-resistant H. pylori infection. Further large-scale studies are needed to validate these results. Registered retrospectively with the Clinical Research Information Service (CRIS; KCT0012265).

Humans

Evaluation of pilocarpine effects on sweat proteome.

BACKGROUND: Sweat is increasingly recognized as a valuable, non-invasive biofluid for biomarker discovery, yet its composition depends on the stimulation method. This study aimed to determine how pharmacological induction with pilocarpine compares to physiologically induced sweat through exercise in shaping the sweat proteome. RESULTS: We analyzed thermoregulatory sweat from exercise, pilocarpine-induced sweat, and combined pilocarpine plus exercise sweat. Total protein concentrations were similar across conditions, but pilocarpine markedly increased proteomic diversity, with combined pilocarpine plus exercise sweat showing the highest number of identifications. The core sweat proteome remained stable, while pilocarpine selectively enriched low-abundance proteins involved in vesicular trafficking, cytoskeletal remodelling, and metabolism. Proteins linked to the canonical M3-Gq-PLC-Ca2+ pathway, including AQP5, CALML5, and CLIC1, were consistently enriched, confirming cholinergic activation. Pilocarpine-induced sweat also contained plasma-derived and immune-related proteins, reflecting enhanced secretion and reduced ductal reabsorption. CONCLUSIONS: Exercise yields a physiologically relevant but less complex proteome, pilocarpine-induced sweat produces a pharmacologically enriched yet biased profile, and combined pilocarpine plus exercise sweat maximizes protein detection at the expense of interpretability. These findings highlight the critical impact of stimulation paradigm on sweat proteomics and provide a reference framework for biomarker research. SIGNIFICANCE: This study employed LC-MS/MS to systematically characterize eccrine sweat and delineate how stimulation paradigms-exercise, pilocarpine, and their combination-shape its proteomic landscape. By demonstrating that pharmacological induction profoundly alters protein diversity and composition compared to physiologically induced sweat, these findings establish a critical benchmark for sweat-based biomarker research and highlight the need for paradigm-aware sampling strategies in clinical and translational contexts. Nonetheless, several methodological constraints warrant consideration: the limited sample size (five individuals per group), the exclusive inclusion of women under combined oral contraceptive treatment (21 active pills followed by 7 pill-free days), which restricts extrapolation to naturally cycling women, and the focus on healthy young adults (18-25 years), limiting generalizability to older or clinically heterogeneous populations. Despite these limitations, this work provides a foundational framework for optimizing sweat collection protocols and advancing precision approaches in non-invasive diagnostics.

Pilocarpine

Infra-low-frequency neurofeedback alters EEG network efficiency: exploratory evidence from healthy volunteers.

Infra-Low-Frequency Neurofeedback (ILF-NFB) combines classic frequency-band (FB) and infra-low-frequency (ILF) EEG components in implicit training protocols and is increasingly applied in clinical contexts. Yet, the neurophysiological mechanisms underlying ILF-NFB remain to be further elucidated. In this randomized, sham-controlled and double-blind study, we explored the online impact of a one-session ILF-NFB application on EEG correlates in healthy participants (39 analyzed datasets). Continuous 31-channel EEG was recorded during verum and sham feedback in a double-blind, randomized crossover design. In this exploratory analysis approach, functional connectivity was estimated using the debiased weighted phase-lag index (dwPLI) and analyzed with graph-theoretical measures. The results revealed higher global efficiency during verum compared to sham in the Beta1 band (12-15 Hz), reaching significance in the primary comparison but not surviving Bonferroni correction across the five tested bands; block-wise follow-ups showed a significant verum-sham difference in the first half of the neurofeedback session and a directionally consistent pattern in the second half. The Condition × Block interaction was not significant. No consistent differences were observed in other frequency bands, nor for betweenness centrality. While preliminary, these exploratory results point to possible network-level effects during ILF-NFB and motivate further confirmatory work in extended training protocols and clinical populations.

Humans

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

BACKGROUND: An effective treatment strategy is essential for metastatic Wilms tumor (WT) management. To improve prognostic accuracy, this study examined metastatic patterns and key prognostic factors. METHODS: Children diagnosed with WT from 2010 to 2021 were identified from the SEER database. All patients underwent chemotherapy and surgical resection. Metastatic patterns, metastasis-related predictors, and prognostic factors were evaluated. RESULTS: Of the 1040 patients analyzed, 226 (21.7%) experienced lung metastasis, 31 (3.0%) liver metastasis, 6 (0.6%) bone metastasis, and 220 (21.2%) regional lymph node metastasis. Distant metastasis was associated with a higher incidence of lymph node metastasis (OR = 1.506, 95% CI 1.346-1.685, p < 0.001). Age 3-17 years (OR = 1.933, 95% CI 1.406-2.680, p < 0.001), left-sided (OR = 1.383, 95% CI 1.016-1.890, p = 0.040), bilateral (OR = 2.303, 95% CI 1.215-4.243, p = 0.009), and tumor size &#x2265;135 mm (OR = 2.020, 95% CI 1.481-2.749, p < 0.001) were identified as predictors of metastasis. Both lymph node (p < 0.001) and lung metastasis (p < 0.001) were high-risk factors for WT. Radiotherapy provided long-term survival benefits for the metastatic population (p = 0.027), while postoperative chemotherapy showed better outcomes than preoperative or other strategies (p < 0.001). Further analysis demonstrated that the concurrent lung and lymph node metastasis group benefited more from postoperative chemoradiotherapy, with HRs of 0.226 (p = 0.028) for overall survival and 0.255 (p = 0.048) for cancer-specific survival. CONCLUSION: WT with concurrent lung and lymph node metastasis represents a distinct and aggressive metastatic phenotype associated with a significantly poor prognosis. Postoperative chemoradiotherapy may provide superior survival benefits for this high-risk population.

Humans

Transverse Tibial Transport for Limb Salvage in Ischemic Lower Extremity Disease: Technique, Mechanisms, and Clinical Outcomes-A Systematic Review.

Transverse tibial transport (TTT) is a surgical technique derived from Ilizarov's distraction osteogenesis principles that stimulates angiogenesis and microcirculatory regeneration in the ischemic lower limb without directly manipulating macrovascular anatomy. By creating a proximal tibial cortical bone window and distracting it transversely using an external fixator, TTT triggers converging cascades of growth factor release, endothelial progenitor cell mobilization, and immunomodulation that translate into improved distal limb perfusion and wound healing. Combined TTT plus endovascular therapy improves amputation-free survival versus endovascular therapy alone. Prospective randomized trials and standardized international protocols are needed to consolidate TTT's role in multidisciplinary limb salvage pathways.

Humans

Comparison of Keverprazan-based versus esomeprazole-based dual therapy for initial treatment of Helicobacter pylori infection: a prospective, multicenter, randomized controlled trial.

BACKGROUND: Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS: This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20&#x2009;mg b.i.d plus amoxicillin 1&#x2009;g t.i.d) or 14-day of EA therapy (Esomeprazole 40&#x2009;mg b.i.d plus amoxicillin 1&#x2009;g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS: A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p&#x2009;=&#x2009;0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p&#x2009;=&#x2009;0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p&#x2009;=&#x2009;0.155). Non-inferiority was confirmed between the two groups (all p&#x2009;<&#x2009;0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION: For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.

Humans

Aflibercept With Versus Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: Optical Coherence Tomography Angiographic Changes From a Randomized Clinical Trial.

OBJECTIVES: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT. DESIGN: Image analysis of a double-masked, sham-controlled, randomized clinical trial. SUBJECTS: 55 eyes of 55 treatment-na&#xef;ve participants with symptomatic macular PCV completing 52 weeks of follow-up. METHODS: Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52. MAIN OUTCOME MEASURES: Longitudinal OCTA changes and predictors of PL closure at week 52. RESULTS: We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72 &#xb1; 3.01mm2 at baseline, 2.86 &#xb1; 2.50mm2 at week 12, 3.59 &#xb1; 3.26mm2 at week 52; monotherapy: 3.77 &#xb1; 2.23mm2 at baseline, 3.27 &#xb1; 2.36mm2 at week 12, and 3.47 &#xb1; 2.58mm2 at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29 &#xb1; 2.08 mm2 at baseline, 1.46 &#xb1; 1.36mm2 at week 12, and 1.53 &#xb1; 1.32mm2 at week 52; monotherapy: 2.39 &#xb1; 1.85mm2 at baseline, 1.87 &#xb1; 1.68mm2 at week 12, and 1.82 &#xb1; 1.38mm2 at week 52). BNN VD reduction was greater in the combination arm at week 12 (-10 &#xb1; 15% vs - 3 &#xb1; 12%, P = .02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52). In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (&#x3b2;=-0.96 [-1.21 to -0.72], P < .01), and baseline CST predicted CST change (&#x3b2;=0.93 [0.75 to 1.10], P < .01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], P = .03). CONCLUSIONS: Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as noninvasive biomarkers for predicting treatment response in PCV.

Humans

Predicting training outcomes for developmental dyslexia from EEG data.

Developmental dyslexia (DD) is characterised by lower-than-average reading abilities and is diagnosed in approximately 10% of individuals. The societal barriers may limit professional fulfilment and psychological wellbeing of individuals with DD, calling for the development of effective interventions to counteract them. As DD is associated with challenges in both phonological and visuo-attentional domains, different longitudinal training approaches were developed to strengthen them. However, they require a considerable amount of personal, social and economic resources and the outcomes may vary depending on individual differences in behavioural and neurophysiological functionality. Hence, predicting training outcomes might help in developing personalised treatment protocols and optimising the use of resources. In the present work we applied machine learning to resting-state EEG to predict longitudinal training outcomes in adults with DD enrolled in a randomized clinical trial. In particular, one group received a visuo-attentional training combined with transcranial alternating current stimulation (tACS), another group received visuo-attentional training with sham/placebo stimulation, and the third group received a phonological training with sham/placebo stimulation. The improvement in text reading speed was associated with spectral power in low-beta and individual frequencies in the alpha (IAF) and beta (IBF) bands, while the improvement in pseudoword reading was associated with IBF. The findings highlight the potential of capturing neural markers of treatment responsiveness in DD. Future studies should focus on the generalisability of predictive models to real-world settings, while investigating whether specific EEG markers predict responsiveness to distinct remediation protocols, thus supporting the development of personalised interventions.

Humans

Outcomes and Associated Prognostic Factors for Orthograde Canal Obturation Using Ortho MTA III: A Randomised Prospective Clinical Trial.

AIM: To prospectively compare treatment outcomes for orthograde canal obturation using Ortho MTA III (OMTA) with the continuous wave of compaction (CWC) using gutta-percha (GP) and AH Plus sealer, and to identify associated predictive factors. METHODOLOGY: Informed consent was obtained (110 patients), and single- or two-rooted permanent teeth (n&#x2009;=&#x2009;120) diagnosed with pulp necrosis (or previously treated) and asymptomatic apical periodontitis or chronic apical abscess (periapical index, PAI&#x2009;&#x2265;&#x2009;3) were randomly assigned to two groups (n&#x2009;=&#x2009;60/group). The canals were prepared to a minimal apical size #40 (ISO) based on their initial file size, disinfected and obturated by either CWC or OMTA using an enhanced disinfection protocol (GP disinfected, new gloves after each intraoperative radiograph and before starting obturation). Clinical and periapical radiographic examinations were conducted by two calibrated, independent endodontists during follow-up periods of at least 12&#x2009;months. Success rates and associated predictive factors (tooth-, operator- and patient-related) were analysed statistically using binary and multiple logistic regression (p&#x2009;<&#x2009;0.05). RESULTS: The median recall period was 30&#x2009;months (14-48&#x2009;months), and 104 teeth were finally analysed (recall rate: 86.67%). No significant differences in success rate were observed between the groups (p&#x2009;>&#x2009;0.05) under both loose (OMTA: 88.24%, CWC: 83.02%) and strict criteria (OMTA: 64.71%, CWC: 58.49%). Multivariate analysis revealed that age (OR&#x2009;=&#x2009;5.735, 95% CI: 1.286-25.577, p&#x2009;=&#x2009;0.022), periapical lesion size (OR&#x2009;=&#x2009;6.596, 95% CI: 1.397-31.138, p&#x2009;=&#x2009;0.017) and PAI score (OR&#x2009;=&#x2009;2.081, 95% CI: 1.047-4.136, p&#x2009;=&#x2009;0.036) were significant predictors of treatment failure. CONCLUSIONS: Orthograde obturation of infected canals with Ortho MTA III demonstrated comparable success and treatment outcomes to those filled with GP and sealer by CWC, supporting its potential as a clinically viable alternative for the obturation of infected root canals. TRIAL REGISTRATION: cris.nih.go.kr registration number: KCT00099939.

Humans

The Case for Master Protocols for Rare Neurological Diseases.

Master protocol trials allow for simultaneous multiple hypothesis testing within a common framework and might be applicable for rare diseases. In May 2025, the Network for Excellence in Neuroscience Clinical Trials convened a multistakeholder conference to discuss master protocol trials in rare neurological disorders. In this paper, we explore how master protocol trial designs may apply to rare neurological disorders, using the neuronal ceroid lipofuscinoses as an example. Through shared protocol elements and trial infrastructure, master protocols may decrease cost and improve efficiency in testing potential therapeutics in rare disease, accelerating the delivery of urgently needed therapies to patients. ANN NEUROL 2026;100:477-486.

Humans

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n&#x2009;=&#x2009;60) and a control group (n&#x2009;=&#x2009;60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P&#x2009;<&#x2009;0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P&#x2009;<&#x2009;0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans

Imaging&#x2011;based models for predicting cerebrovascular complications of carotid stenosis.

This is a protocol for a Cochrane review (prognosis). The objectives are as follows: Primary objective To systematically review and critically appraise multivariable prognostic models developed for adults (&#x2265;&#x202f;18&#x202f;years) with carotid stenosis in which imaging biomarkers (e.g. plaque characteristics derived from magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) constitute the core predictors. The primary focus is to evaluate the predictive performance of these models for cerebrovascular complications - specifically ipsilateral ischaemic stroke and transient ischaemic attack (TIA) - which are the clinical outcomes to be predicted. Where feasible, we will summarise and compare the models' discrimination (C&#x2011;statistic/area under the curve (AUC)) and calibration (calibration&#x2011;in&#x2011;the&#x2011;large, calibration slope, observed&#x2011;to&#x2011;expected ratio) across studies, and assess their potential for clinical application and external validation. For the purpose of defining symptomatic carotid stenosis as an eligibility criterion and subgroup variable, we will include studies that also considered retinal ischaemia (e.g. retinal embolism, amaurosis fugax) as a qualifying event. Secondary objectives To describe the combinations of imaging markers, modelling techniques, sample sizes, and variable&#x2011;selection strategies used in the development of the included models To evaluate the performance of these models for additional secondary clinical outcomes: plaque progression or regression, incident high&#x2011;risk imaging features, and the transition from asymptomatic to symptomatic disease To explore whether predictive performance differs according to imaging modality (MRI versus CT versus contrast&#x2011;enhanced ultrasound (CEUS)) or technical protocol (e.g. 3&#x202f;T versus 1.5&#x202f;T, spectral CT versus conventional CT) For studies that report both cerebrovascular and broader cardiovascular outcomes (major adverse cardiovascular events, myocardial infarction, etc.), we will only extract the performance metrics relating to cerebrovascular events for the primary analysis. Performance metrics for cardiovascular outcomes will be considered exploratory and will not form part of the main synthesis.

Humans

The efficacy of non-invasive brain stimulation interventions in obsessive-compulsive disorder management: A network meta-analysis of randomized controlled trials.

Non-invasive brain stimulation (NIBS) has been widely used as an alternative treatment for obsessive compulsive disorder (OCD). However, the most effective NIBS parameters are unclear. To compare the efficacy of NIBS in OCD. We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of NIBS.Systematic searches were conducted in Cochrane CENTRAL, EMBASE, PubMed, and Web of Science from inception to June 20, 2025. Forty-two randomized sham-controlled trials (n = 1456) were included. All statistical analyses were conducted with R statistical software. Bayesian NMAs mainly using the BUGSnet package and gemtc package. Five NIBS protocols produced statistically significant reductions in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores compared with sham stimulation: high-frequency rTMS over the FzFCz (Hf-rTMS-FzFCz; MD -11.77, 95% CrI -20.62 to -3.09), low-frequency rTMS over F3F4 (Lf-rTMS-F3F4; MD -9.93, 95% CrI -18.07 to -1.65), low-frequency rTMS over FCz (Lf-rTMS-FCz; MD -3.25, 95% CrI -6.06 to -0.40), high-frequency deep TMS over FzFC (Hf-dTMS-FzFC; MD -6.48, 95% CrI -12.32 to -0.50), and 2 mA anodal tDCS over F3 with cathodal over Fp2 (MD -9.34, 95% CrI -16.01 to -3.03).For secondary outcomes, high-frequency deep rTMS over FzFCz produced the largest reduction both in depressive symptoms (SMD -1.24, 95% CrI -1.92 to -0.55) and anxiety scores (SMD -1.88, 95% CrI -2.62 to -1.11), but had no effect on Clinical Global Impression-Severity (CGI-S) scores.Specific NIBS protocols are safe and effective adjunctive treatments for OCD, with promising yet inconclusive improvements in comorbid depressive symptoms. Further high-quality, head-to-head trials are needed.

Humans

A Standardized Nursing-Led Protocol Integrated Pain, Sleep, Medication Adherence, and Symptom Management in Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition after herpes zoster that frequently coexists with sleep disturbance, medication-related problems, and fluctuating symptoms. This study evaluated whether a standardized nursing-led protocol could improve multidimensional short-term outcomes beyond usual care. In this prospective, parallel-group randomized controlled trial, 128 adults with PHN were allocated 1:1 to usual care or usual care plus an eight-week protocol integrating structured pain assessment, sleep monitoring, medication-adherence support, and rule-based digital symptom monitoring. The primary outcome was the between-group difference in change in Numeric Rating Scale (NRS) pain score from baseline to Week 8. Secondary outcomes included Pittsburgh Sleep Quality Index (PSQI), MMAS-8 medication adherence, symptom burden, pain-related nocturnal awakenings, breakthrough pain, rescue analgesic use, adverse events, rule-based alerts, and nursing satisfaction. Week-8 data were available for 116 participants (57 usual care; 59 protocol). Mean NRS scores decreased from 7.19 &#xb1; 1.08 to 4.82 &#xb1; 1.53 in the usual-care group and from 7.28 &#xb1; 1.05 to 3.24 &#xb1; 1.28 in the protocol group. An NRS reduction of at least 2 points occurred in 49.1% and 76.3% of participants, respectively. The protocol group also showed larger improvements in PSQI, MMAS-8, symptom burden, and nocturnal awakenings, with fewer breakthrough-pain episodes and less rescue-analgesic use. These findings support further evaluation of the standardized nursing-led protocol in preregistered multicenter trials with intention-to-treat analyses and longer follow-up.

Humans

A User-Friendly Protocol for Microinjection into Teleost Embryos to Study Gene Function.

Zebrafish (Danio rerio) and medaka (Oryzias latipes) are popular teleost models used in developmental biology and functional genomics. To achieve high-quality and reproducible microinjections, it is essential to have robust protocols for breeding, egg collection, and the precise delivery of genetic material. In this protocol, we present a comprehensive and optimized methodology for setting up breeding tanks under controlled photoperiod conditions to maximize egg yield while minimizing contamination. We provide detailed procedures for sex identification, pair selection, the use of grated breeding inserts, and methods to increase egg collection efficiency. We outline procedures for making injection gel beds, pulling needles, and calibration using one-microliter microcapillaries to achieve consistent nanoliter-scale injections. Our protocol outlines settings for the pico-liter injector that are optimized to deliver a precise amount per pulse with minimal variability. Finally, we demonstrate the application of these methods for gene knockdown using morpholino antisense oligonucleotides, gene knockout using CRISPR-Cas9, and gain-of-function mRNA overexpression experiments. Phenotypic assessments conducted at various developmental stages to evaluate gene-specific effects reveal consistent phenotypic outcomes between the morpholino and CRISPR-Cas9 approaches. This easy and comprehensive protocol enables efficient, precise, and scalable genetic manipulation of zebrafish and medaka embryos, thereby supporting advanced functional studies in developmental biology and disease modeling. To our knowledge, this is the first unified protocol for both zebrafish and medaka microinjection systems achieving 97.7% phenotype penetrance in CRISPR-Cas9 knockouts with precision together with a triple validation approach that confirms gene function across multiple techniques.

Animals

A stent-plus-irrigation protocol after adolescent hypospadias repair: a multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether a stent-plus-irrigation protocol reduces complication rates following hypospadias repair in adolescents compared with catheter drainage alone. PATIENTS AND METHODS: In this multicentre randomised controlled trial, adolescents (Tanner Stage II-V) undergoing hypospadias repair were randomly assigned to either a stent-plus-irrigation group or a catheter-drainage group. The catheter-drainage group received standard urethral catheter drainage alone, whereas the stent-plus-irrigation group received an additional small-calibre urethral stent positioned within the reconstructed urethra and twice-daily saline irrigation. The primary outcome was the overall postoperative complication rate; secondary outcomes included urinary function and cosmetic outcomes. RESULTS: A total of 172 adolescents were assessed for eligibility, with 150 participants (75 in the stent-plus-irrigation group and 75 in the catheter-drainage group) included in the final analysis. Compared with the catheter-drainage group, the stent-plus-irrigation group demonstrated a significantly lower overall complication rate (risk ratio [RR] 0.33, 95% confidence interval [CI] 0.20-0.56; P&#x2009;<&#x2009;0.001), urethral fistula rate (RR 0.27, 95% CI 0.14-0.51; P&#x2009;<&#x2009;0.001), and surgical site infection (SSI) rate (RR 0.43, 95% CI 0.21-0.87; P&#x2009;=&#x2009;0.020). CONCLUSIONS: A postoperative stent-plus-irrigation protocol was associated with lower rates of postoperative complications, particularly urethral fistula and SSI, compared with catheter drainage alone after adolescent hypospadias repair. Because the intervention included both an additional urethral stent and saline irrigation, the independent contribution of irrigation cannot be determined in this two-arm trial.

Humans