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The effects of haptonomy and virtual reality, anxiety, prenatal attachment and acceptance of pregnancy in unplanned pregnancy.

AIM: Unplanned pregnancies are an important public health problem that negatively affects the health of women and babies. This study aimed to determine the effects of haptonomy and virtual reality on anxiety, prenatal attachment and acceptance of pregnancy in unplanned pregnancies. Haptonomy, a touch-based bonding technique, and virtual reality, an immersive fetal visualisation tool, were used as interventions. METHODS: The sample of this randomised controlled study consisted of 217 pregnant women (haptonomy: 73, virtual reality: 72 and control: 72) who applied to the Obstetrics and Gynaecology outpatient clinics of a public hospital in eastern Turkey between July 2020 and April 2021. For both experimental groups, four interviews were conducted with the pregnant women between the 24thand32nd gestational weeks at intervals of 7-10&#x2009;days. Data were collected on pregnancy-related anxiety, prenatal attachment and pregnancy acceptance. Group differences were analysed using appropriate statistical comparisons. RESULTS: Pregnancy-related anxiety was lower, and acceptance of pregnancy was higher in the experimental groups compared to the control group (p&#x2009;<&#x2009;.001). Prenatal attachment level was higher in the haptonomy and virtual reality groups compared to the control group (p&#x2009;<&#x2009;.001). Notably, prenatal attachment scores were significantly higher in the haptonomy group compared to the virtual reality group (p&#x2009;<&#x2009;.001). CONCLUSION: In unplanned pregnancies, imagining the baby through haptonomy and imagining the baby through virtual reality are techniques that reduce the level of anxiety related to pregnancy and increase the level of prenatal attachment and acceptance of pregnancy. Especially haptonomy showed a higher effect on prenatal attachment.

Humans

Joint association of sedentary behaviour and physical activity with cardiovascular disease: a systematic review and meta-analysis.

This systematic review and meta-analysis of cohort studies aimed to synthesize existing evidence on the joint association of physical activity (PA) and sedentary behaviour (SB) with cardiovascular disease (CVD) risk among adults. We searched PubMed, EMBASE, and Cochrane for English studies published between January 2010 and February 2025 that examined the joint association of PA and SB (fatal and non-fatal) CVD among adults and pooled their results through meta-analyses using study-level data. Using findings from 17 studies, the pooled effect size for the lowest PA + highest SB group was 1.78 (95% CI: 1.59-2.00), suggesting increased risk for CVD compared with the reference group (i.e. highest PA + lowest SB). Compared with the same reference group, we found an increased risk for CVD in the lowest PA + lowest SB (HR = 1.25, 95% CI: 1.12-1.40) and the highest PA + highest SB (HR = 1.16, 95% CI: 1.06-1.27) groups. Subgroup analyses according to domains or types of PA and SB exposure, outcome measures, and exposure measurement method revealed a similar pattern. In conclusion, individuals with the lowest PA combined with the highest SB may experience an increased risk for CVD events compared with those with the highest PA and lowest SB. There was also an increased risk for individuals with a combination of either low PA + low SB and high PA + high SB, albeit to a lesser extent. Although substantial study-level heterogeneity exists, the results highlight the potential value of considering both behaviours jointly in relation to CVD risk.

Humans

Serum Copeptin Rises After Tolvaptan for Hyponatraemia, but Does Not Predict Risk of Rapid Sodium Rise: Pre-Specified Secondary Analysis of the TVFR Trial.

OBJECTIVE: Hyponatraemia is a common electrolyte disorder often driven by excess arginine vasopressin (AVP). Copeptin is a stable surrogate marker co-secreted with AVP. It is unclear whether treatment of hyponatraemia with tolvaptan, an AVP-V2 receptor antagonist, impacts copeptin. We aimed to assess the effects of tolvaptan on serum copeptin, compared to fluid restriction. DESIGN: Pre-specified secondary analysis of an open-label randomised trial comparing tolvaptan or fluid restriction for 3 days. PATIENTS: Hospitalised patients with plasma sodium (pNa) 115-130&#x2009;mmol/L at a single-centre tertiary hospital in Melbourne, Australia. MEASUREMENTS: Copeptin measured at baseline and completion (Day 4, or discharge if sooner). RESULTS: Copeptin results were available in 45/54 participants, randomised to tolvaptan (n&#x2009;=&#x2009;25) or FR (n&#x2009;=&#x2009;20). Mean baseline copeptin was 10.4&#x2009;pmol/L. pNa increased in both groups, significantly more with tolvaptan as previously reported. Copeptin remained stable after FR, but significantly increased after tolvaptan (mean adjusted difference between groups over 3 days 8.4&#x2009;pmol/L, 95% CI 2.1-14.6, p&#x2009;=&#x2009;0.01). Baseline copeptin did not predict rapid sodium rise. The rise in copeptin after tolvaptan may represent an exaggerated response to osmolality rise in these patients ('reset osmostat'), or feedback mechanisms from AVP blockade. CONCLUSION: Tolvaptan increased serum copeptin compared to fluid restriction. Further research is required to determine if there is clinical utility for measuring copeptin in hyponatraemia before it is adopted into practice. TRIAL REGISTRATION: ACTRN12619001683123.

Humans

Multiplexed CRISPR/Cas9 mediated knockdown of BCH gene in potato enhances beta-carotene to combat vitamin A deficiency.

The inadequate amounts of provitamin A carotenoids in crops contribute to the widespread vitamin A deficiency, leading to malnutrition and blindness in humans. Suppression of the &#x3b2;-carotene hydroxylase (BCH) increases &#x3b2;-carotene levels. In the current study, we utilized the multiplexed CRISPR/Cas9 approach by designing three targets against the BCH gene in a local potato cultivar. Transformation efficiency was recorded as 15%, the successful integration of the CRISPR/Cas9-BCH multiplex construct in potatoes was confirmed through PCR. When analysed using TIDE software, Sanger sequencing revealed the highest indel efficacy of 92.1% in plant 7 and 26.6% in plant 1. qRT-PCR (quantitative real-time PCR) analysis indicated a significant 89-fold reduction in BCH transcript levels in genome-edited potato lines compared to control plants. Spectrophotometry demonstrated a notable increase in beta-carotene levels in genome-edited potato plants, ranging from 0.831&#x202f;&#xb5;g/mL FW to 4.236&#x202f;&#xb5;g/mL FW, compared to the control plant with the lowest beta-carotene concentration (0.344&#x202f;&#xb5;g/mL FW). HPLC analysis further confirmed increased beta-carotene levels in genome-edited potato plants, ranging from 0.11&#x202f;mg/mL FW to 0.36&#x202f;mg/mL FW, compared to the unmodified control plant with a minimum beta-carotene value of 0.09&#x202f;mg/mL. Our results revealed that the multiplexed CRISPR-Cas9 approach targeting the BCH gene results in enhanced beta-carotene contents in potato tubers.

Solanum tuberosum

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult

Photon-counting detector computed tomography (PCD-CT) in multiple myeloma: a systematic review and trial sequential meta-analysis on image quality and radiation dose.

OBJECTIVES: To systematically review and perform a meta-analysis comparing the effects of PCD-CT versus EID-CT on image quality (sharpness) and radiation dose (CTDIvol) in patients with bone lesions due to multiple myeloma&#xa0;(MM). METHODS: A comprehensive search of PubMed, Embase, Scopus, and Cochrane Central was conducted from inception to October 2025. Studies comparing PCD-CT and EID-CT in MM patients were included. Methodological quality was assessed using ROBINS-I, and the certainty of evidence was assessed using GRADE. RESULTS: A total of 41 studies were identified that matched our search criteria. After duplicate removal and screening, five studies (n = 170 patients) were included in the systematic review, with four contributing to the meta-analysis. PCD-CT showed a significant pooled mean difference in image sharpness (mean difference, + 0.99 points; 95% CI, 0.62-1.37; p < 0.001). PCD-CT also demonstrated a reduction in radiation dose (mean difference, -4.95 milligrays; 95% CI, -8.39 to -1.50; p = 0.005). Trial sequential analysis (TSA) confirmed stability of pooled estimates, with conclusive evidence for image sharpness improvement, and suggestive yet incomplete evidence for radiation dose reduction. CONCLUSION: Compared to EID-CT in MM, PCD-CT significantly improves subjective image sharpness as supported by trial sequential analysis. Conventional meta-analysis suggested a reduction in radiation dose with PCD-CT; however, trial sequential analysis indicated that the cumulative evidence remains inconclusive. Further large-scale studies are suggested to confirm the magnitude of the radiation dose reduction benefit.

Humans

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p&#x2009;<&#x2009;0.001), PVAS (p&#x2009;<&#x2009;0.001), TEWL (p&#x2009;=&#x2009;0.014), IgE (p&#x2009;<&#x2009;0.001) and QoL scores (p&#x2009;<&#x2009;0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p&#x2009;<&#x2009;0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals

Ciliochoroidal Effusion and Regional Scleral Thickening in Peripapillary Pachychoroid Syndrome.

PURPOSE: To assess anterior scleral thickness and the presence of ciliochoroidal effusion (CE) in eyes with peripapillary pachychoroid syndrome (PPS), and to compare the results with a cohort of healthy age-matched controls. DESIGN: Retrospective cross-sectional study METHODS: A total of 20 eyes from 12 patients diagnosed with PPS and 30 eyes from 15 healthy control subjects. All participants underwent a comprehensive ophthalmic examination, including spectral-domain optical coherence tomography with enhanced depth imaging (EDI-OCT) and anterior segment OCT (AS-OCT). Choroidal thickness was measured at predefined macular and peripapillary locations, while anterior scleral thickness was assessed 6 mm posterior to the scleral spur in 4 quadrants. Ciliochoroidal effusion was evaluated qualitatively using AS-OCT. Comparisons between groups were performed using linear mixed models with Bonferroni correction (scleral thickness corrected P < .010) RESULTS: The mean age of PPS patients was 75.6 &#xb1; 9.8 years, and 16% were females. Anterior scleral thickness was significantly greater in the temporal quadrant in PPS eyes compared to controls (396.85 &#xb1; 74.97 &#xb5;m vs 331.13 &#xb1; 62.65 &#xb5;m: P = .007). Ciliochoroidal effusion was detected in 60% of PPS eyes, predominantly in the superior and temporal sectors, whereas no effusion was observed in healthy controls (P < .001). Eyes with CE exhibited a thicker mean scleral thickness and a thicker subfoveal choroidal thickness compared to eyes without effusion (P < .05). CONCLUSION: Eyes with PPS demonstrated increased temporal scleral thickness and a high prevalence of CE. These findings suggest that scleral characteristics may represent a predisposing anatomical factor in PPS, although the precise pathophysiological mechanisms remain to be elucidated.

Humans

Non-smoked cannabis consumption formats and Cannabis Use Disorder severity in an illicit setting: Evidence from Chile, 2020-2024.

BACKGROUND: Cannabis Use Disorder (CUD) has become an increasing public health burden, particularly in Chile. Non-smoked cannabis formats and products have been independently associated with CUD but remain understudied in the region. This study compares CUD severity among individuals aged 12 to 65 in Chile who consume cannabis via edibles, vaporization or both versus those who exclusively smoke it. METHODS: We obtained secondary data from three waves of the Chilean National Survey on Drugs in the General Population (ENPG), a three-stage stratified probabilistic sampling design study conducted in 2020, 2022, and 2024. Our pooled cross-sectional sample included individuals (n = 3543) who reported cannabis use in vaped, edible, both vaped and edible or exclusively smoked format in the past 12 months. We used a partial proportional odds model to estimate the association between CUD severity and consumption formats. RESULTS: Cannabis vaping group showed higher odds of presenting at least mild CUD (OR = 6.21 [95% CI: 3.75-10.3]), as did the edible group (OR = 1.73 [95% CI: 1.08-2.78]) and both group (OR = 5.92 [95% CI: 2.72-12.87]), compared to exclusive smokers. However, only the vaped group demonstrated higher odds for all severity levels. CONCLUSION: Compared with exclusive smokers, users of vaporizers and/or edibles showed a stronger association with CUD. This association may be explained by consumption patterns and total THC exposure. Further research is needed to characterize the average THC exposure by consumption format, acknowledging contextual confounders such as the legal framework.

Humans

Diagnostic accuracy of nuclear STAT6 immunohistochemistry for solitary fibrous tumour: a systematic review and meta-analysis.

Nuclear STAT6 immunohistochemistry is the diagnostic surrogate for the NAB2::STAT6 fusion of solitary fibrous tumour (SFT); its sensitivity is established, but specificity varies for unexamined reasons. This review quantified pooled accuracy and tested whether antibody clone and nuclear threshold govern specificity. PubMed, Scopus and Web of Science were searched to 29 June 2026 for studies reporting nuclear STAT6 immunohistochemistry against a reference standard (NAB2::STAT6 confirmation and/or expert consensus) in SFT and comparators, with extractable two-by-two data. Two reviewers screened, extracted data and applied QUADAS-2. A bivariate generalised linear mixed model gave summary sensitivity and specificity, and exploratory subgroup analysis and meta-regression tested antibody clone, anatomical site and reference-standard type. Twenty-three studies (1216 SFT and 4715 comparators) were included. Summary sensitivity was 98.7% (95% confidence interval 96.7-99.5) and specificity 99.1% (97.8-99.6); the diagnostic odds ratio was approximately 8656. The monoclonal YE361 subgroup (8 studies) reached specificity 99.9% (99.3-100), with one false positive among 861 comparators, versus 98.1% (96.0-99.1) for polyclonal and other antibodies. False positives concentrated in dedifferentiated liposarcoma and prostatic stromal tumours. Estimates were stable after removing studies at higher risk of bias (98.9%/99.1%) and on leave-one-out analysis; the Deeks test was non-significant (p&#xa0;=&#xa0;0.08). Nuclear STAT6 immunohistochemistry is therefore highly sensitive and specific for SFT, and the residual specificity loss is structured and largely avoidable: the monoclonal YE361 read at a strict nuclear threshold is preferred, with MDM2 and CDK4 applied to exclude dedifferentiated liposarcoma when nuclear STAT6 is unexpectedly positive.

Humans

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p&#x2009;<&#x2009;0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p&#x2009;<&#x2009;0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans

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

Assessment of atypical glandular cell interpretation in Pap tests using the Hologic Genius Digital Diagnostics System.

Atypical glandular cells (AGC) are a diagnostic challenge. The aim of this study was to evaluate the efficacy and diagnostic performance of AGC detection on the Hologic Genius Digital Diagnostics System (HGDDS). A retrospective analysis of 451 ThinPrep Pap cases was conducted, including 207 cases of AGC, 27 cases of high-grade squamous intraepithelial lesion (HSIL), 25 cases of low-grade squamous intraepithelial lesion (LSIL), and 192 benign cases. All AGC cases had follow-up histologic diagnoses, with 66 cases subsequently diagnosed as adenocarcinoma. The slides were randomized, scanned, and analyzed by the HGDDS. Patient age and HPV test results were provided to reviewers, an experienced cytologist, who screened the cases, followed by two cytopathologists who independently examined the cases on the HGDDS. Diagnostic concordance between the two cytopathologists indicated strong agreement (&#x3ba; = 0.829). Sensitivity of AGC on Papanicolaou (Pap) tests for adenocarcinoma detection on HGDDS was 98.5% and 95.5%, respectively, comparable to the original ThinPrep interpretation (OTPI). Specificity for adenocarcinoma detection was significantly higher (84.6% and 85.6%) with the HGDDS than 27.7% with OTPI. Overall, the diagnostic performance for AGC/HSIL interpretation to detect CIN2/3/adenocarcinoma appeared to have improved with HGDDS compared with OTPI, particularly for specificity and positive predictive value (PPV). This is the first study evaluating AGC diagnosis using the HGDDS. The findings demonstrate that the sensitivity of adenocarcinoma detection as AGC on HGDDS is comparable to the ThinPrep Imaging System, but the specificity and PPV are improved. This suggests the potential of artificial intelligence to augment the performance of cervical cancer screening.

Humans

Efficacy of smartphone- and bibliotherapy-delivered multicomponent lifestyle medicine interventions for probable depression: A three-arm randomized controlled trial.

BACKGROUND: This study examined the efficacy of smartphone- (AG) and bibliotherapy-delivered (BG) lifestyle medicine (LM) interventions compared with a waitlist control group (WLG) in reducing depressive symptoms. METHODS: A total of 122 adults with probable depression were randomized to AG (n&#xa0;=&#xa0;41), BG (n&#xa0;=&#xa0;40), or WLG (n&#xa0;=&#xa0;41). AG and BG received the same core 8-week multicomponent LM intervention via a smartphone application or booklets, respectively. The core content included lifestyle psychoeducation, physical activity, diet and nutrition, stress and sleep management, goal-setting, and motivational techniques. Outcomes were assessed at baseline and immediate post-intervention (Week 9) in all groups, with 1-month (Week 13) and 3-month (Week 21) follow-ups conducted in the intervention groups only. RESULTS: At Week 9, AG (d&#xa0;=&#xa0;0.89) and BG (d&#xa0;=&#xa0;0.64) showed significantly greater reductions in depressive symptoms than WLG, with within-group improvements maintained at 1- and 3-month follow-ups (ps&#xa0;<.001, d&#xa0;=&#xa0;0.77-0.96). Clinically significant improvement was achieved by 78% of AG and 55% of BG participants, both significantly higher than WLG (19.5%; ps&#xa0;<.001). Compared with WLG, both interventions yielded greater improvements in overall lifestyle and physical activity (d&#xa0;=&#xa0;0.59-0.91) at Week 9. The AG showed additional benefits for perceived stress, health responsibility, nutrition, spiritual growth, and stress management (d&#xa0;=&#xa0;0.58-0.73), whereas BG uniquely improved insomnia symptoms (d&#xa0;=&#xa0;0.83). CONCLUSION: Smartphone- and bibliotherapy-delivered LM interventions are efficacious for managing probable depression. Further RCTs comparing them with established treatments are warranted.

Humans

Radiographic assessment and orthodontic intervention effects on orthodontically induced root resorption: a systematic review and meta-analysis of clinical trials.

The relative contribution of radiographic methods and characteristics of the orthodontic intervention to orthodontically induced root resorption (OIRR) remains unknown. The aims of this systematic review and meta-analysis were to (1) estimate the pooled OIRR effect across orthodontic intervention versus comparator contrasts, (2) compare pooled estimates by radiographic method (2D [two-dimensional] vs. 3D/CBCT [three-dimensional/cone-beam computed tomography]), and (3) explore whether force mechanics (intrusive versus nonintrusive) modified OIRR magnitude. Seven randomized controlled trials and one prospective study (January 2010-October 2025) were included. Only OIRR was the outcome, reported as correlation coefficients (r). The primary analysis combined within-study intervention-versus-comparator estimates. Subgroup analysis of 2D versus 3D/CBCT imaging was prespecified, whereas post-hoc analysis of intrusive versus nonintrusive mechanics was performed. The pooled analysis for the primary outcome showed a small, nonsignificant OIRR effect (r = 0.07; 95% confidence interval [CI]: -0.12 to 0.27; p = 0.372) with high heterogeneity (I2 = 84.0%). Radiographic method did not change the pooled estimates significantly (p = 0.331). Force-mechanics analysis showed that intrusive mechanics was related to significantly higher root resorption than nonintrusive mechanics (r = 0.40; 95% CI = 0.15 to 0.65 versus r = -0.03; 95% CI = -0.16 to 0.10; p < 0.001). This accounted for 87.1% of the between-study variance. The average orthodontic intervention effect on OIRR was small and not significant; however, the OIRR magnitude was strongly affected by force mechanics, particularly by intrusive forces. There was no significant difference in pooled estimates by radiographic method; however, 3D/CBCT provides superior volumetric quantification and should be used judiciously according ALARA (as low as reasonably achievable) principles.

Root Resorption

Auditory brainstem response in the identification of cochlear synaptopathy in aged rodents: a systematic review with meta-analysis.

PURPOSE: This systematic review and meta-analysis evaluated the diagnostic performance of auditory brainstem response (ABR) for identifying age-related cochlear synaptopathies in rodents. METHOD: Following PRISMA guidelines, searches were conducted in PubMed/MEDLINE, Cochrane Library, Scopus, Embase, Web of Science, SciELO, LILACS, and gray literature. Studies evaluating CS in naturally aged rodents using short-latency auditory evoked potentials (AEPs) were included. Study selection, data extraction, risk-of-bias (JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies), and certainty of the evidence (GRADE&#xae; system) assessment were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model, with standardized mean differences and 95% confidence intervals. ABR wave I amplitudes were analyzed for click (80 and 90&#xa0;dB SPL) and tone-burst stimuli stratified by frequency. RESULTS: Among 3,008 identified records, 12 studies were included in the review and five in the meta-analysis. All included studies used ABR measures to investigate CS, with wave I amplitude being the most frequently evaluated biomarker. Meta-analysis demonstrated a significant reduction in ABR wave I amplitude in aged rodents compared with young controls for both click- and tone-burst-evoked responses. Tone-burst ABR showed no significant differences among the evaluated frequencies. These findings should be interpreted with caution due to the limited number of studies and the methodological heterogeneity, which may have reduced statistical power and comparability. CONCLUSIONS: The evidence supports ABR wave I amplitude as a sensitive electrophysiological marker of age-related CS in rodents. Nevertheless, further studies with standardized protocols are needed to strengthen its diagnostic utility and improve comparability across studies.

Animals

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