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Cognitive behavioural therapy-based interventions on stress outcomes in pregnant women: A systematic review and meta-analysis.

BACKGROUND: Stress symptoms were the most common psychological problem in pregnancy. Cognitive behavioural therapy-based interventions are effective for antenatal depression and anxiety symptoms; but there are fewer studies for stress symptoms. OBJECTIVE: The review aims to (1) examine the effectiveness of cognitive behavioural therapy-based interventions in reducing stress outcomes (pregnancy-specific stress symptoms, generic symptoms, and objective stress) in pregnant women, and (2) identify significant moderators affecting the effectiveness of the intervention. DESIGN: Systematic review, meta-analysis, and meta-regression analysis of randomised controlled trials. METHODS: We conducted a three-step search (12 databases, 4 clinical registries, and citation searches) in English and Chinese up to July 24, 2025, by two independent reviewers. Meta-analysis, subgroup, and meta-regression analyses were performed using the R software. Quality assessment and certainty of the evidence were assessed with the Cochrane risk-of-bias tool version 2 and Grading of Recommendations, Assessment, Development, and Evaluation criteria. Publication bias was assessed using funnel plots and Egger's test. RESULTS: We included 20 randomised controlled trials involving a total of 6966 pregnant women from nine countries. Random-effects meta-analyses found that interventions significantly alleviated pregnancy-specific stress symptoms (Hedges' g&#xa0;=&#xa0;-0.84, 95% Confidence Interval, CI -1.42, -0.26, p&#xa0;<&#xa0;.01, I2&#xa0;=&#xa0;92.3%), reduced generic stress symptoms (g&#xa0;=&#xa0;-0.64, 95% CI -1.09, -0.20, p&#xa0;<&#xa0;.01, I2&#xa0;=&#xa0;87.4%) with median and large effect sizes at post-intervention. No effect was found in lowering cortisol levels (g&#xa0;=&#xa0;-0.99, 95% CI -2.58, -0.60, p&#xa0;=&#xa0;.12, I2&#xa0;=&#xa0;84%) at post-intervention. Subgroup and meta-regression analyses indicated that region, age of participants, use of intention-to-treat, missing data management analyses, frequency, modalities, and approaches of interventions, use of different comparators, and attrition rate were significant factors affecting the effectiveness of interventions. Subgroup analyses suggested that the intensity of intervention should be more than once per week using a blended mode among Asian populations. Multivariate meta-regression analyses indicated that both younger age (&#x3b2;&#xa0;=&#xa0;0.13, p&#xa0;=&#xa0;.02) and a lower attrition rate (&#x3b2;&#xa0;=&#xa0;0.03, p&#xa0;=&#xa0;.03) significantly improved the effectiveness of interventions. The overall certainty of the evidence was rated as either very low or low. CONCLUSIONS: Cognitive behavioural therapy-based interventions can supplement antenatal care to alleviate pregnancy-specific stress symptoms and generic stress symptoms, particularly in young Asian women. However, the evidence has some uncertainties. These findings should be interpreted with caution due to substantial heterogeneity. Well-designed trials on a large-scale with long-term follow-ups were needed. REGISTRATION: PROSPERO registration ID: CRD420251115913.

Humans

Orbital involvement in sickle cell disease: A systematic review.

Orbital involvement in sickle cell disease (SCD) is rare but potentially vision-threatening and is often misdiagnosed due to overlap with infectious orbital disease. We conducted a systematic review of case reports and series describing orbital complications in patients with confirmed SCD, following PRISMA and MOOSE guidelines. Across 53 studies, 76 cases were identified. Patients were predominantly male (77.6%), with an average age of 13.2 years. Orbital disease was the initial SCD manifestation in 6.6%. Presentations included periorbital edema in all, proptosis in 64.1%, restricted ocular motility in 56.5%, reduced visual acuity in 28.1%, and bilateral involvement in 38.2%. Laboratory findings commonly included leukocytosis (73%) and raised inflammatory markers (86.7%). Radiologically, orbital subperiosteal hematoma were observed in 70%, combined orbital bone infarction and hematoma in 38.2%, and orbital bone infarction alone in 19.7%. Magnetic resonance imaging is critical for accurate diagnosis. Intracranial hemorrhage was present in 9.2%. Less frequent manifestations included orbital apex syndrome, lacrimal gland disease, and nonspecific soft tissue swelling. Management was primarily conservative (82.9%), and surgery was reserved for vision-threatening or intracranial complications. Complete recovery was achieved in 93.1% of cases. While severe vision-threatening complications are uncommon, early recognition remains critical to optimising outcomes in sickle cell orbitopathy.

Humans

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 (&#x394;CAPS) 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&#x202f;=&#x202f;0.049), particularly for those with higher non-planning impulsivity (p&#x202f;=&#x202f;0.012). In participants randomized to CPT improvement in PTSD symptom severity (&#x394;CAPS) was negatively related to baseline total impulsivity (p&#x202f;=&#x202f;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

Neuroimaging anxious children and adolescents before and after cognitive behavioral therapy: a systematic review.

OBJECTIVE: This systematic review investigates brain changes in youths with anxiety disorders following cognitive behavioral therapy (CBT) and neural markers that predict CBT responses. METHODS: We conducted a systematic search using the electronic databases PubMed, Web of Science, and ProQuest. The inclusion deadline was set to October 27, 2025. We included fifteen peer-reviewed neuroimaging studies that examined the effects of CBT in youths under 19 years old with a primary clinical diagnosis of an anxiety disorder based on DSM-5 criteria. RESULTS: Although the existing literature is marked by substantial diversity in methods and outcomes, task-related neural response in the anterior cingulate cortex (ACC, 2/8, 25.0%), insula (1/8, 12.5%) increased from pre to post CBT and these changes were further correlated with clinical symptom improvements. Moreover, CBT outcomes were predicted by pre-treatment activity or connectivity in the ACC and amygdala (3/13, 23.0%). A smaller proportion of studies (2/13, 15.3%) found that activity or connectivity in the insula, precuneus/cuneus, postcentral gyrus, and activity or structure in the nucleus accumbens (NAcc) predicted response to CBT. The low consistency of these findings was driven by methodological variability, low reliability of the neural markers, and relatively small sample sizes. CONCLUSIONS: This review highlights promises of neural predictors and outcomes to enhance anxiety disorder treatments in children and adolescents, facilitating future personalized and effective CBT. Beyond this initial promise, the field is hindered by methodological inconsistencies and limited replications. While longitudinal and personalized approaches are important next steps, the central challenge remains: identifying neural markers that are both reliable and robust.

Adolescent

Modulating sentence comprehension in people with aphasia through anodal tDCS: A double-blind randomized cross-over study.

This double-blind randomized cross-over study investigated the effects of perilesional anodal transcranial direct current stimulation (AtDCS) combined with speech-language therapy on sentence comprehension in eight individuals with chronic nonfluent agrammatic aphasia. The behavioral therapy consisted of an intensive comprehension treatment including drilling in sentence-to-picture matching and Mapping Therapy. Each participant underwent both the anodal tDCS and sham stimulation conditions (five received sham first followed by real stimulation, and the remaining three the reverse sequence), with each condition paired with the same behavioral treatment and separated by a four-month washout period. Stimulation was applied over the perilesional area (left BA6) for 20&#x202f;min during daily 40-min therapy sessions over four consecutive weeks. Sentence comprehension was assessed with the RiComprendo battery and functional communication with the Communicative Effectiveness Index (CETI). Data were analyzed using paired t-tests, Bayesian analyses, and linear mixed-effects models to control for baseline performance and individual variability. Both stimulation conditions produced significant pre-to-post improvements in sentence comprehension, particularly for syntactically complex structures such as passives and center-embedded object relatives. However, gains were overall greater following AtDCS, as reflected in larger effect sizes, stronger Bayes factors, and a significant treatment effect in the mixed-effects models. Only the AtDCS condition yielded significant improvements in self-perceived comprehension abilities on the CETI. These findings suggest that AtDCS over perilesional cortical areas may boost the effects of traditional language therapy on sentence comprehension, supporting its feasibility and potential as an adjuvant intervention in post-stroke aphasia rehabilitation.

Humans

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a &#x2265; 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans

Clinical outcomes of Epstein-Barr virus infection/reactivation following CAR-T cell therapy: A systematic review.

BACKGROUND: Epstein-Barr virus (EBV) infection or reactivation is an emerging but underrecognized complication following chimeric antigen receptor T-cell (CAR-T) therapy and is likely associated with treatment-induced immune dysregulation. Data regarding its clinical impact remain limited. OBJECTIVE: To evaluate the reported occurrence, clinical manifestations, and outcomes of EBV infection or reactivation in adults undergoing CAR-T therapy. METHODS: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, and Cochrane CENTRAL were searched from inception to March 2025 for studies reporting EBV infection or reactivation after CAR-T therapy in adults. Due to limited and heterogeneous data, results were synthesized descriptively. RESULTS: Five studies comprising 80 patients were included (median age, 55&#xa0;years; 52.6% male among patients with reported sex data [10/19]). Across the included studies, 11 EBV infection/reactivation events were identified among 80 described CAR-T recipients, representing 13.8% of the reported sample rather than a true incidence estimate. Among events with usable individualized timing data, the median interval from CAR-T infusion to EBV detection/reactivation was 9.8&#xa0;months (approximate range, 1-44&#xa0;months). Because EBV surveillance strategies and definitions were inconsistently reported across studies, this proportion should not be interpreted as a true incidence estimate. Four patients (36.4%) developed EBV-associated disease, including three cases of EBV-related lymphoproliferative disorder and one case of EBV-associated diffuse large B-cell lymphoma. Among seven patients with reported post-CAR-T treatment response, four achieved Complete Remission/ Continuous Complete Remission; treatment response should be interpreted separately from final survival status. Confirmed EBV-related mortality occurred in 2/11 patients with reported EBV infection/reactivation and in 2/4 patients with EBV-associated disease; all-cause mortality could not be reliably estimated because patient-level vital status could not be fully attributed to the EBV-reactivated subgroup. Reported toxicities predominantly consisted of low-grade cytokine-release syndrome; however, toxicity data were limited. CONCLUSION: Although infrequently reported, EBV infection or reactivation after CAR-T therapy may be associated with substantial morbidity and mortality among affected patients. However, the available evidence is limited by the small sample size, heterogeneous study designs, and inconsistent EBV surveillance practices.

Humans

Multicenter randomized effectiveness/implementation trial of a digital self-management support tool to improve the quality of life during adjuvant hormonal therapy for patients with early breast cancer: The HOPE trial.

BACKGROUND: For patients with hormone receptor (HR) positive early breast cancer (BC), adjuvant endocrine therapy (ET) represents the cornerstone of treatment. However, 75% of patients experience ET-related symptoms that negatively affect their quality of life (QOL). Despite their high prevalence, these symptoms are often underestimated and under-addressed during consultations. As a result, non-adherence to ET is common and remains a major barrier for optimal disease and survival outcomes. METHODS: National, prospective, randomized, open-label hybrid type 1 effectiveness/implementation trial conducted in France comparing a personalized digital health pathway plus standard of care (SoC) vs. SoC alone in patients with HR+ early BC reporting ET-related symptoms. 180 patients will be randomized 1:1 to receive either 12&#xa0;weeks of the digital health pathway or 12&#xa0;weeks of SoC. The intervention is anchored by the Resilience&#xa9; digital companion including remote symptom and needs assessment, an introductory nurse-navigator phone call, and access to personalized, symptom-specific online educational and self-management programs (physical activity, yoga, meditation or cognitive behavioral therapy). In both arms, patients will be invited to wear a wearable device to objectively monitor behavioral parameters. The primary endpoint is the ET symptoms scale of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR45 over 12-weeks. Secondary endpoints include other QOL domains, self-reported ET adherence, eHealth literacy, self-efficacy, and evaluation of the implementation process. DISCUSSION: This study should provide evidence on the effectiveness and real-world implementation of a personalized digital health pathway to improve QOL in patients experiencing ET-related symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT06781996; Protocol version 3.0.

Humans

Effectiveness and moderators of PE and CPT in adult PTSD treatment: a systematic review and meta-analysis.

Background: Posttraumatic Stress Disorder (PTSD) is a prevalent and debilitating condition that challenges mental health services worldwide. Effective psychological interventions are crucial for treatment, among which Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT) are prominent. Comparative analyses of these treatments, considering moderators such as patient demographics and treatment specifics, are necessary to tailor interventions effectively.Objective: This meta-analysis synthesised findings from 175 treatment arms across 163 studies to evaluate the comparative effectiveness of PE and CPT for PTSD. Effect sizes were calculated as Hedges' g for between-group (treatment vs. control) and within-group (pre-post) comparisons.Results: Using a random-effects model, the overall pooled effect size was large (Hedges' g&#x2009;=&#x2009;1.67, 95% CI [1.56, 1.79]), suggesting substantial treatment-related symptom improvement. Multivariate meta-regression revealed, across the full sample, none of the main effects or interactions was significant. A sensitivity analysis excluding 10 influential outliers reduced the overall effect size (g&#x2009;=&#x2009;1.55), indicating that PE was associated with larger effects than CPT among non-military samples, and larger effects were observed in studies with a higher proportion of female participants, military samples, and samples with lower proportions of sexual trauma. Treatment-by-sample-characteristic interactions were not significant in the trimmed model.Conclusions: Findings suggest that PE and CPT produce large effects in reducing PTSD symptoms, with some variation across treatment type and sample characteristics. Results underscore the importance of examining contextual moderators such as treatment setting and population type and highlight the need for transparent reporting of key sample features to improve future meta-analytic precision.

Humans

Frontline therapies for adult patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia: a systematic literature review.

OBJECTIVES: Philadelphia (Ph) chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL) is the most common ALL in adults. Overall survival (OS) with frontline chemotherapy remains poor. Blinatumomab is currently the only targeted agent approved for frontline treatment. METHODS: We systematically reviewed 96 studies (43 interventional, 53 observational) between 2012-2026 evaluating frontline pharmacologic therapy in adults with Ph- B-ALL. RESULTS: Across chemotherapy studies, nearly half of patients relapsed within 3 years, and only 49%-69% survived beyond 3 years. Blinatumomab demonstrated robust and consistent efficacy in first complete response (CR1), supported by 2 randomized controlled trials (RCT) and 16 single-arm trials (SAT). In one RCT, blinatumomab reduced the risk of death by 59% versus chemotherapy alone (HR 0.41) when added to frontline consolidation in minimal residual disease (MRD) negative patients. Median OS reached 41.2 months in a SAT where blinatumomab monotherapy was administered to patients in MRD-positive CR1. SATs showed consistent efficacy outcomes regardless of age, MRD status, or chemotherapy backbone. DISCUSSION: Additional targeted therapies still under investigation have shown mixed results. CONCLUSION: Frontline inotuzumab (&#xb1;blinatumomab) plus chemotherapy showed promise in older populations, while the efficacy benefit of rituximab was inconclusive. No new safety signals were identified in the frontline setting for targeted therapies.

Humans

Repeated low-level red-light therapy for improving asthenopic symptoms and accommodation in presbyopia.

BACKGROUND: To assess the short-term effectiveness of repeated low-level red light (RLRL) therapy in relieving asthenopia and enhancing accommodation in presbyopia. METHODS: This randomized, parallel-group, double-masked clinical trial enrolled adults with presbyopia and self-reported asthenopia. Participants were allocated using computer-generated randomization and randomly assigned at a 1:1 ratio to RLRL or sham groups. Blinding included participants, examiners, assessors, and statisticians. The primary outcome was the change from baseline in the Computer Vision Syndrome Questionnaire (CVS-Q) score at day 31. Secondary outcomes were the change in accommodative amplitude (AA), Near Activity Visual Questionnaire (NAVQ) score, habitual near visual acuity, near-addition power, accommodative facility, positive and negative relative accommodation, binocular cross-cylinder response, and accommodative convergence-to-accommodation ratio. Continuous outcomes were analyzed using linear mixed-effects models. RESULTS: Sixty-four of 66 randomized participants (aged 41-62&#x2009;years) completed the 1-month trial. At day 31, RLRL showed greater improvement than sham in CVS-Q score (adjusted mean difference, -1.75 points; 95% CI, -3.10 to -0.39), binocular AA (1.09 D; 95% CI, 0.37 to 1.82), and NAVQ score (-8.07 points; 95% CI, -14.17 to -1.97). The effect on AA was most pronounced in a subgroup of eyes with baseline amplitude >2.0&#x2009;D (adjusted mean difference 1.33&#x2009;D; 95% CI 0.32-2.34). Other measures did not differ between groups at each visit. No treatment-related adverse events were reported. Adherence was similar between groups (mean compliance: 98.2% vs 97.5%). CONCLUSIONS: Short-term treatment with RLRL significantly reduced asthenopic symptoms and improved accommodative amplitude in individuals with presbyopia.Trial registration: NCT06745661 (registered December 8, 2024).

Humans

Anabolic androgen therapy in critically ill adults: A systematic review and meta-analysis.

Critical illness is characterized by a catabolic, proinflammatory state. Anabolic agents, such as testosterone, have therefore been proposed as therapeutic targets. Our objectives were to assess the effects of testosterone in critically ill populations on patient-important outcomes and identify design limitations to inform future studies. We searched for randomized control trials (RCTs) through Medline, Embase, and EBM Reviews databases from inception through February 24, 2026, including English language articles enrolling adults (&#x2265;18&#xa0;years) admitted to ICU where anabolic androgen therapies (AAT) were compared with placebo or standard of care. Studies had to report at least one of: mortality, ICU and hospital lengths of stay, or duration of mechanical ventilation. We extracted data independently using a standardized data extraction tool, and feedback was received from all co-authors to ensure agreement. For each outcome, we performed meta-analyses using a random-effects model with inverse variance weighting in RevMan. We used the GRADE approach to assess certainty in pooled estimates of effect. Of 1325 screened articles, we found 4 that fit our inclusion criteria. Together, we judged risk of bias as 'some concerns' in 3 trials and 'high' in the final trial, and ultimately found that the effects of anabolic-androgen therapy on patient-important outcomes uncertain. With the uncertainty of current evidence for the effects of anabolic-androgen therapy in critically ill adults, there is insufficient support for its routine use. Future randomized evidence is needed to determine whether anabolic-androgen therapy improves clinically-important outcomes and better define its safety profile in critically ill adults.

Humans

Comparative genomics and full-length transcriptome profiling of wing morphs in Tetrix grossus (Orthoptera: Tetrigidae).

Wing polymorphism represents a paradigmatic dispersal-reproduction trade-off, yet its molecular basis remains uncharacterised in the phylogenetically distant pygmy grasshoppers (Tetrigidae). Here we integrate comparative genomics across ten orthopteran species with full-length transcriptomics of long-winged (FL) and short-winged (FS) Tetrix grossus. OrthoFinder recovered 118 orthogroups specific to T. grossus. Against a backdrop of pronounced gene-family contraction (36 expansions versus 222 contractions; net -186, mirrored at the ancestral Tetrix node, +37/-140), we identified an ancestral, Tetrix-specific expansion of hormone-regulation (12 genes; fold enrichment 7.93) and lipid/carbohydrate-metabolic families organised into syntenic clusters, alongside 513 positively selected genes enriched for integrin-mediated cell adhesion (6 genes), a process relevant to epithelial and appendage morphogenesis. Full-length transcriptomics of one long-winged (FL) and one short-winged (FS) adult female detected 7530 (FL) and 7515 (FS) expressed genes, with 794 FL- and 776 FS-restricted transcriptome-derived SNP-associated genes. The FL morph was enriched for an EGFR/Ras-Rho developmental-patterning axis and neuromuscular flight genes, whereas the FS morph was enriched for insulin/peptide-hormone response and growth-regulatory loci. Overall, we present genomic resources and testable hypotheses concerning the evolution and regulation of wing morphs in Tetrigidae rather than a validated genetic architecture of wing-morph determination.

Animals

Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies.

Fluoride is widely used for caries prevention due to its effects on mineralized tissues, yet its potential role as a modifier of systemic metal homeostasis remains insufficiently explored. This systematic review synthesizes preclinical evidence on the association between fluoride exposure and changes in metal and semi-metal concentrations across biological matrices. A comprehensive search strategy was conducted across major databases without language or date restrictions, following SyRF, CAMARADES and PRISMA 2020 guidelines. Thirty-one animal studies were included, encompassing multiple species, exposure conditions and analytical approaches. Despite substantial methodological heterogeneity, consistent patterns emerged. Fluoride exposure was associated with element-specific redistribution of the metallome rather than uniform change. Essential elements were predominantly depleted, most consistently zinc, copper and manganese, whereas the toxic metals lead and cadmium tended to be retained. This contrast between homeostatically regulated essential elements that are lost and non-regulated toxic metals that accumulate supports the hypothesis that fluoride differentially modifies the distribution and retention of co-existing elements. The novelty of this review lies in integrating metallomic outcomes across experimental models, highlighting fluoride as a potential systemic modulator rather than a tissue-specific agent. Although variability in study design and risk of bias limits causal inference, the consistent directionality of findings across models reinforces their biological plausibility and translational relevance.

Animals

Clinical efficacy and brain mechanism characteristics of guide chi and regulate spirit tuina therapy in the treatment of post-stroke walking dysfunction: A randomized controlled trial based on fNIRS.

BACKGROUND: This study aims to preliminarily evaluate the role of Guide Chi and Regulate Spirit(GCRS) Tuina in enhancing walking function in post-stroke patients with walking dysfunction; secondly, by using functional near-infrared spectroscopy (fNIRS), it investigates the effect of GCRS Tuina on the restoration of brain function in this patient population. METHODS: Participants in the control group received 4-week rehabilitation treatment, while those in the Combined Tuina Group (CTG) additionally received GCRS Tuina therapy for another 4 weeks on this basis. Functional Ambulation Category (FAC), Fugl - Meyer Assessment Scale for Lower Extremity Motor Function (FMA - LE), and Modified Barthel Index (MBI) were evaluated at the baseline and after 4 treatment weeks. A gait and motion analysis system was used to measure step length, stride, walking speed, and step frequency. FNIRS was used to measure the resting-state functional connectivity(FC) strength, as well as the &#x3b2; - value and HbO2 concentration mean during the walking task. RESULTS: A total of 60 participants completed the randomized, and 53 completed the trial and entered the statistical analysis. Compared with the Single Rehabilitation Group(SRG), the CTG group had higher FAC, FMA-LE, and MBI scores after 4 weeks. After the treatment course, the standardized step length, stride, walking speed, and step frequency of the CTG were higher than SRG. At the Region of Interest(ROI) level, the CTG exhibited 13 inter-ROI FC strengths that were higher than SRG, and the differences could survive the FDR correction (PFDR<0.05). Under the walking task, the CTG group had higher &#x3b2; values in 18 channels and higher Oxyhemoglobin(HbO2) concentrations in 19 channels than the SRG (PFDR <0.05). CONCLUSION: GCRS Tuina therapy can significantly improve patients' walking function, enhance lower limb motor ability and daily living ability. It can improve walking efficiency. Tuina can significantly increase the FC and enhance the activation levels and HbO2 concentrations. The stimulation of Tuina may help reconstruct the brain's motor control network, restore impaired motor function, promote the occurrence of neural plasticity, strengthen the neural circuits in the cognitive-motor-sensory cortex to improve walking function. TRIAL REGISTRATION: This study has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR2024000654).

Humans

Molecular mechanisms of neuroendocrine regulation of molting in the Chinese mitten crab (Eriocheir sinensis): A transcriptomic analysis based on eyestalk ablation model.

Molting disability severely restricts the sustainable aquaculture of the Chinese mitten crab, yet the neuroendocrine mechanisms coordinating physiological responses remain poorly understood. Using unilateral eyestalk ablation to remove the primary source of molt-inhibiting hormone (MIH), we performed time-resolved transcriptomic profiling of the thoracic ganglion at 24&#xa0;h (early premolt) and 48&#xa0;h (ecdysis) post-ablation. We identified 2825 differentially expressed genes and uncovered a biphasic molecular response. At 24&#xa0;h, the thoracic ganglion activates pathways associated with neuromuscular adaptation, oxidative stress, and cardiac muscle contraction. Notably, the arachidonic acid metabolism pathway is selectively rewired: cytochrome P450 &#x3c9;-hydroxylases (CYP2J2, CYP4V2) are upregulated, while competing branches (epoxide hydrolase, cyclooxygenase) are suppressed, promoting local synthesis of the potent vasoconstrictor 20-HETE within the thoracic ganglion. This enzymatic switch provides a mechanistic link between MIH withdrawal and the local generation of elevated hemolymph pressure required for molting. By 48&#xa0;h, the transcriptional program shifts toward chitin-based extracellular matrix remodeling, glycosphingolipid biosynthesis, and synaptic reorganization. Collectively, our findings redefine the thoracic ganglion as an active neuroendocrine integrator that translates reduced MIH signaling into phased physiological outputs, revealing a "neuro-endocrine-hemolymph pressure" regulatory axis. This study provides novel molecular targets (e.g., CYP2J2, CHS1, UGCG) for mitigating molting disability in E. sinensis aquaculture.

Animals

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

OBJECTIVES: To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures. MATERIALS AND METHODS: Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5&#x2009;&#xb1;&#x2009;7.7 years; 17 men); 30 completed the MRI extension at 1.5&#x2009;T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs). RESULTS: PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p&#x2009;<&#x2009;0.05). PWV decreased after multiple doses (-0.87&#x2009;m/s, 95% CI: -1.26 to -0.48&#x2009;m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (&#x3c1;&#x2009;=&#x2009;0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and &#xb9;&#xb2;&#x2079;Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. CONCLUSION: PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. KEY POINTS: Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized &#xb9;&#xb2;&#x2079;Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Humans

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1&#x2009;year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1&#x2009;year occurred in 44% of the MDT group vs 75% in the OBS group (P&#x2009;=&#x2009;0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4&#x2009;months) compared to the OBS arm (2.9&#x2009;months, P&#x2009;=&#x2009;0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans