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This study aimed to evaluate the performance of LUS aeration score in predicting extubation failure among mechanically ventilated neonates. This review was conducted in accordance with PRISMA-DTA 2018. Electronic searches were performed in PubMed, ScienceDirect, Wiley, Nature, and Springer. Methodological quality was assessed using QUADAS-3. Diagnostic meta-analysis was performed in Stata 17.0 using MIDAS, while univariable bivariate meta-regression was conducted in R using the mada package. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), log diagnostic odds ratio (logDOR), and area under the curve (AUC) were calculated. Clinical applicability was assessed using Fagan nomograms, while sensitivity analysis, subgroup analysis, and Deeks' funnel plot asymmetry test were conducted to evaluate robustness, heterogeneity, and publication bias. Ten studies involving 859 neonates were included. LUS aeration score showed high diagnostic accuracy, with a pooled sensitivity of 0.87, specificity of 0.86, PLR of 6.13, NLR of 0.15, logDOR of 3.71, and AUC of 0.93. Heterogeneity was moderate for sensitivity and substantial for specificity. Anatomical scanning coverage was the only significant moderator in meta-regression (p = 0.049), with posterior-inclusive protocols associated with a lower false-positive rate. Deeks' test showed no significant publication bias. LUS aeration score demonstrates good diagnostic performance for predicting neonatal extubation failure and may support clinical decision-making as an adjunct to conventional extubation readiness assessment. Standardized, validated scoring protocols and age-specific external validation are required before a universal cutoff can be recommended. What is Known: • Extubation failure remains a clinically important complication in mechanically ventilated neonates and is associated with increased morbidity. • Lung ultrasound (LUS) is a bedside, radiation-free imaging method, whereas the LUS aeration score is a quantitative measure of regional aeration loss; reported accuracy for predicting extubation failure varies across studies. What is New: • This updated diagnostic meta-analysis of 10 studies involving 859 neonates found strong pooled diagnostic performance of the LUS aeration score for predicting extubation failure, with a sensitivity of 0.87, specificity of 0.86, and AUC of 0.93. • Exploratory univariable bivariate meta-regression identified anatomical scanning coverage as the only significant overall moderator, with posterior-inclusive protocols associated with a lower false-positive rate.

Clinicians use various voice therapy protocols to rehabilitate patients with voice disorders; voice hygienic advice (VHA) is a standard component in most protocols. The list of patient instructions included in VHA targets eliminating the ill effects of dehydration, vocal abuse, and misuse of the vocal mechanism. An objective prognostic evaluation of a vocal intervention's efficiency is performed by comparing pre- and post-intervention changes in acoustic parameters. The effect of retesting via collecting a second sample may have a physiological impact on the acoustic parameters. This study is an exploratory investigation of the interaction between VHA and retesting on acoustic voice parameters in vocally healthy university lecturers. We collected a standardized maximum phonation time (MPT) acoustic signal from 15 university lecturers and delivered VHA. Fourteen days later, we collected a second MPT acoustic signal and a self-rated VHA compliance score. We used the Multidimensional Voice Program (MDVP) for analysis and calculated the Dysphonia Severity Index (DSI) before and after delivering VHA. The parameter is an inverted scale index where higher scores represent better vocal function and vice versa. There was a significant deterioration in DSI across the study. Multiple regression models suggest that lecturers with higher VHA compliance tend to have higher DSI scores. Lower DSI scores in our data are not associated with the number of students per class or the number of teaching hours per week. The results indicate a need to understand the impact of retesting on acoustic analysis findings and highlight methodological caution regarding short-term variability in DSI interpretation. The secondary regression analysis in this work is hypothesis-generating rather than providing direct evidence of the physiological mechanism driving variability in DSI.

To evaluate the feasibility, reproducibility, and operational impact of a structured, dose-aware 5-star CT image quality (IQ) rating system across multiple institutions and clinical indications. This retrospective, multinational, IAEA study included 2737 adult (1247 chest, 1490 abdomen) CT examinations across six hospitals in five countries of Europe. Three radiologists per hospital scored CT images using a standardized 5-star system designed to evaluate diagnostic IQ with consideration of radiation dose. Data collected included CT scanner type, clinical indication, patient characteristics, CTDIvol, and DLP. Inter-reader agreement, concordance of star ratings, and dose metrics were evaluated per hospital and clinical indication. The rating framework demonstrated robust reproducibility, with three-reader concordance reaching up to 93% in highly standardized centers and complete discordance remaining exceptionally rare (1.6% cases overall). A compelling inverse correlation between CTDIvol and star ratings was observed, especially for larger patients. Analysis by clinical indication revealed that some intrinsically noise-tolerant exams (for pulmonary nodules and kidney stones) showed high radiation exposure, highlighting an opportunity for optimization. Certain centers used higher-dose protocols, heavily skewing toward 2-star ratings. The 5-star CT IQ rating system is reproducible and supports dose-aware CT optimization. Noise-tolerant examinations should maintain diagnostic quality at lower radiation dose, supporting wider use of low-dose protocols. The method highlights opportunities for multinational and manufacturer-level protocol harmonization and may guide optimization strategies, including the number of series and reconstruction approaches.

Sleep disturbances are common in older adults with MCI, associated with cognitive decline and reduced quality of life. Pharmacological treatment remains common despite safety concerns. Meditation-based interventions may improve sleep and psychological well-being, yet evidence among individuals with MCI remains limited. This systematic review evaluated the effects of MBIs on sleep quality among adults aged ≥55 years with MCI, following PRISMA 2020 guidelines. Five databases were searched through June 2025, identifying RCTs, pilot RCTs, and quasi-experimental studies using validated sleep measures. Seven studies (n = 434) met inclusion criteria, with interventions lasting 4-12 weeks and encompassing mindfulness, mantra, sound meditation, and hybrid programs. Five studies showed significant improvements in subjective sleep quality; one actigraphy-based study reported reduced daytime napping. A random-effects meta-analysis of six studies reporting PSQI outcomes demonstrated a significant overall improvement in sleep quality (Hedges' g = -0.75, 95% CI -1.23 to -0.28), although substantial heterogeneity was observed (I² = 77.9%). Secondary outcomes included reduced anxiety, stress, and depression, and improved attention and memory. Evidence indicated moderate certainty that MBIs improve sleep quality in MCI. These findings suggest MBIs are promising non-pharmacological strategies to enhance subjective sleep quality and psychological well-being in older adults with MCI. Integrating meditation-based strategies could be explored as a potential, supportive approach within gerontological nursing and community programs, but caution is warranted given the limited and heterogeneous evidence base. Larger, multi-site RCTs with standardized protocols, including both objective and subjective sleep assessments, are needed to strengthen generalizability and guide evidence-based practice.

To measure the association between treatment options and clinical outcomes in adolescent patients with acute uterine bleeding. A cohort study was conducted using data collected on chart review of all patients under 19 years-old treated for acute uterine bleeding from 2012 until 2022 in our tertiary-care hospital center. The association between the treatment options (high-dose estrogens versus progestins) and two primary outcomes (delta of hemoglobin level from baseline to discharge and time to bleeding cessation) were measured using linear regressions with adjustment for potential confounding variables. As secondary outcomes, delta of hemoglobin from baseline to 1 and 4 months, side effects and adverse events were analyzed. We included 150 patients in our study, 116 exposed to high-dose estrogens and 34 to high-dose progestins. The median time to bleeding cessation was 36 hours overall (Q25,75: 17.5, 85.5) without statistically significant difference between treatment groups. The delta of hemoglobin at discharge and at 4 months, after adjustment, showed a tendency towards a better increase in hemoglobin levels for the progestin group, without statistical significance. The progestin group experienced less side effects compared to estrogen group (adjusted OR = 0.31 (95%CI: 0.10, 0.89 for a composite nausea outcome). Treatment failure occurred in 23.1% of cases, without significant difference across groups and no thromboembolic event were reported. This study suggests no statistically significant difference in the effectiveness between the two treatment protocols, but a better side effect profile for high-dose progestins.

In the U.S., nearly 8 million people are incarcerated in jail each year, a majority of whom are structurally vulnerable and at elevated risk for poor health, including HIV. Jails have been identified as strategic settings for health interventions, offering opportunities to deliver "status neutral" HIV services (testing, prevention, and linkage to care) to people who may otherwise have intermittent access to care. To understand barriers and facilitators to integrating HIV care into routine jail health services, we conducted semi-structured, in-person interviews with 15 incarcerated individuals and 13 jail staff at two county jails. While interview guides focused on HIV care, participants largely reflected on the provision of healthcare in jail more generally. Both groups converged on their understanding of institutional constraints (e.g., resource and capacity limitations; an absence of protocols), with staff additionally highlighting organizational silos and threats to their clinical autonomy as obstacles to adopting status-neutral HIV care. However, staff and incarcerated individuals diverged on care experiences. Staff described respect for patient autonomy, whereas incarcerated individuals described feeling unheard, invalidated, or subject to care delays. Participants' reactions to these limitations varied and are interpreted using concepts of street-level bureaucracy and relational autonomy, which highlight how frontline decision-making and interpersonal dynamics interact in carceral settings to restrict clinical staff autonomy, and in turn, medical autonomy of incarcerated individuals. Our findings show that the provision of routine healthcare and integration of status-neutral HIV care requires addressing institutional constraints and relational dynamics that shape perceived autonomy and trust in carceral settings.

The global demand for surgical care continues to rise, yet access and affordability remain disproportionately limited in low- and middle-income countries (LMICs). Postoperative complications significantly drive surgical costs, with even minor complications doubling expenditures. While Enhanced Recovery After Surgery (ERAS) protocols have reduced costs and improved outcomes in high-income countries, their economic impact in LMICs remains underexplored. This study evaluates the cost implications of implementing selected postoperative ERAS components in Ethiopia. We conducted cost-effectiveness analyses alongside a cluster-randomized trial evaluating postoperative ERAS protocol implementation across 10 hospitals in Ethiopia among patients undergoing major abdominal surgery, including cesarean delivery and emergency laparotomy. Cost data were extracted from hospital financial records, procurement logs, and the National Perioperative Quality Improvement Network (NaPQIN) clinical registry. Capital and recurrent costs were estimated, and complication-related expenses were stratified using the Clavien-Dindo classification. Inpatient costs were calculated by multiplying the mean length of stay by the unit bed cost. Implementation of the ERAS intervention was associated with reduced complication-related costs and shorter postoperative hospital stay. Training costs totaled $5651.60 across five hospitals (intervention arm). Additional per-patient implementation costs during routine ERAS delivery were minimal, averaging $3.21 per patient for ERAS-related consumables, while educational materials required a one-time institutional printing cost, equivalent to $2.80 per patient when amortized across participants. ERAS reduced the cost of managing severe complications by $325.60 per patient (P = .04) and shortened postoperative stay from 8.10 to 5.64 days. The intervention improved clinical outcomes while reducing costs compared with routine care. The incremental cost-effectiveness analysis indicated savings of $3516 per complication prevented and $35.50 per hospital day avoided. These findings suggest that simplified ERAS interventions can deliver meaningful cost savings and improved outcomes in Ethiopian surgical facilities and may be feasible in comparable low-resource settings. The results support integration of ERAS into national surgical strategies, emphasizing its feasibility, affordability, and potential to enhance surgical care efficiency without major capital investment.

Real-world glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapies face substantial attrition rates in commercial digital weight loss services (DWLSs). Conversational artificial intelligence (AI) has been proposed to enhance patient support at production scale, but robust evidence of its effectiveness in improving medication retention is scarce. To evaluate the effect of integrating an asynchronous AI patient support agent (Junebot) into a commercial DWLS on 6-month medication adherence and to assess the independent relationship of digital engagement on retention. This retrospective analysis evaluated 16&#x2009;556 adults prescribed semaglutide within an Australian DWLS between May 2024 and October 2025. The primary endpoint was 6-month medication adherence (&#x2265;&#x2009;6 orders fulfilled within 183&#x2009;days). Analytical protocols featured a multivariate binary logistic regression on the full intention-to-treat cohort and three distinct 1:1 propensity score matching (PSM) sensitivity analyses to isolate era-based and tier-specific engagement effects. Six-month adherence was higher post-Junebot than in the pre-Junebot control (53.2% vs. 47.3%; p&#x2009;<&#x2009;0.001). However, the full cohort model (R2&#x2009;=&#x2009;0.2236) revealed that the post-Junebot operational era was independently associated with an increase in the odds of attrition (OR: 1.178; 95% CI [1.052-1.318]; p&#x2009;=&#x2009;0.004), a trend corroborated by the era-matched PSM model (OR of attrition: 1.309; p&#x2009;=&#x2009;0.038). Non-automation factors dominated retention trajectories: high-intensity tracking during month 1 (>&#x2009;25 tracks) dramatically predicted attrition (OR: 15.753; p&#x2009;<&#x2009;0.001), alongside program pauses (OR: 2.508; p&#x2009;<&#x2009;0.001) and higher program cost (OR: 2.458; p&#x2009;<&#x2009;0.001). Within-cohort analysis demonstrated a profound, linear curve for active interaction; structured digital engagement spanning 50%-74.99% of weeks significantly optimised adherence odds across both medication-only (OR: 32.016) and medication plus health coaching cohorts (OR: 13.311). Integrating an AI digital assistant did not independently improve medication adherence; programmatic costs, program pauses and initial tracking anxiety were stronger predictors of long-term retention. After matching post-Junebot cohorts, moderate, active digital engagement appeared to correlate with 6-month retention. Digital providers should prioritise proactive behavioural risk screening and financial accessibility over baseline AI integration.

The purpose of this study was to determine if the ventilatory responses during mechanically sensitive afferent stimulation were augmented in hypertension (HTN). Participants with HTN (n=11; 52&#xb1;12yrs; 27&#xb1;3kg/m2) and controls (CTL, n=11; 56&#xb1;12yrs; 27&#xb1;4kg/m2) were recruited. Following a resting period, the muscle mechanically sensitive afferents were stimulated with passive leg movement for 30-seconds. Ventilatory variables were measured (breath-by-breath) at rest and during passive leg movement protocols. All data was analyzed with a two-way repeated measures ANOVA. Significance was set at p&#x2264;0.05. For ventilation and breathing frequency, there were significant main effects of time (both, p<0.01), but no significant main effects of group or interaction (all, p>0.67). There were no significant main effects of time, group, or interaction for tidal volume (all, p>0.13). These data support that mechanically sensitive afferent stimulation does not elicit an augmented ventilatory response in adults with HTN.

Cancer is an enormous worldwide health burden; traditional treatments are often limited by systemic toxicities, drug resistance and/or patient-to-patient differences, stressing the importance of holistic personalized treatment approaches. Ayurveda and Siddha are the indigenous systems of medicine in India; both provide an analytical and holistic approach with patient-oriented management for treating various diseases including cancer. Ayurveda, dating back over 5000 years, is based on the principle of restoring the body's natural healing systems, immunity and good health through tailored protocols, regulate diet intake and use of botanical remedies. The review aims to evaluate the emerging evidence of Traditional Indian Medicine approaches in cancer care with respect to established mechanisms of action of Indian botanicals, Withania somnifera (Ashwagandha) and Curcuma longa (Curcumin), examine Bhasma effects that represent herbo-mineral nanomedicines, and discuss the potential use of Ayurveda and Rasayana therapy to decrease treatment toxicity and improve overall survival. The review integrates available evidence related to the pharmacological mechanisms, therapeutic formulations, and clinical implications of traditional Indian medical systems in cancer management. Traditional Indian medicinal approaches possess strong anti-proliferative, pro-apoptotic, and chemoprotective potential. However, there remain considerable hiccups with respect to the lack of larger controlled trials in humans, the standardisation of their complex formulations, and rigorous scientific validation necessary to integrate ancient wisdom with modern integrative oncology. This review provides an integrated perspective on the pharmacological mechanisms, therapeutic formulations, and clinical implications of traditional Indian medical systems, highlighting their potential role in integrative oncology.

IgE-mediated food allergy and eosinophilic esophagitis (EoE) represent distinct yet interconnected manifestations of food-induced immune dysregulation. Rather than separate entities, emerging evidence supports a model that is on a continuum, in which clinical phenotypes are determined by antigen exposure patterns, dose, chronicity, and individual immune responses. This relationship has critical implications for food allergy immunotherapy, particularly oral immunotherapy. Among children with IgE-mediated food allergy, EoE prevalence is nearly 100-fold higher than the general population at 4.7%. During oral immunotherapy, gastrointestinal symptoms are common, with confirmed EoE developing in 1% to 10% of participants. Mechanistically, antigen avoidance favors IgE-mediated responses through T follicular helper cells, whereas sustained exposure promotes TH2-driven esophageal inflammation via pathogenic effector TH2 cells. Regulatory T-cell dysfunction appears central to this phenotypic switching. Clinical management requires risk stratification, systematic monitoring strategies, and individualized protocols that balance desensitization benefits against esophageal inflammation risks. Future directions include noninvasive diagnostic biomarkers, biologic therapies, and evidence-based prevention strategies. Understanding the food allergy-EoE continuum is essential for optimizing safety and efficacy of food allergen immunotherapy while minimizing complications.

This study systematically investigates the robustness of radiomics-based machine learning models to distribution shifts caused by variations in MRI acquisition protocols and image segmentation strategies, and evaluates strategies for maintaining predictive performance and uncertainty calibration under such shifts.&#xD;Approach. Using a controlled phantom comprising 16 fruits of four types, we acquired images across five MRI sequences (T2-HASTE, T2-TSE, T2-MAP, T1-TSE, T2-FLAIR) with multiple scans, observers, and segmentation variants (full, partial, rotated). XGBoost classifiers were trained using three feature selection strategies: eight protocol-invariant features, sequence-specific robust features, and all 107 available features. Model performance and calibration were evaluated under in-domain, cross-protocol, segmentation-induced, and compound distribution shift scenarios using a nested, group-wise (leave-one-row-out) cross-validation scheme that prevents instance-level data leakage. Because all data derive from a controlled phantom comprising only 16 independent physical objects, reported variability reflects repeated technical evaluation conditions (scans, observers, segmentation variants) rather than uncertainty across independent biological samples.&#xD;Main results. Under in-domain conditions, all three feature strategies achieved comparable performance. Under distribution shifts, protocol-invariant features retained substantially more predictive power than sequence-specific or all-feature models, and multi-protocol training further improved generalization, though residual degradation persisted. Calibration proved far more vulnerable than accuracy, with ECE reaching 0.4 under compound shifts. Training-time feature-space augmentation yielded more consistent improvements in calibration than post-hoc temperature scaling, though its effect on predictive performance was mixed.&#xD;Significance. These findings establish protocol-invariant feature selection, multi-protocol training, and feature-space augmentation as complementary strategies for improving radiomics model resilience, and identify calibration as a vulnerable dimension of model reliability under distribution shift. The controlled phantom framework isolates specific failure modes and enables quantitative benchmarking of robustness strategies prior to clinical validation. As this study is based on a controlled phantom, these findings are hypothesis-generating and require independent validation in clinical cohorts before clinical translation.

Tick-borne diseases represent important illnesses in dogs, but information about their occurrence in some regions of northeastern Brazil is still limited. Considering the possible differences in the distribution of these agents among the various regions of the country, this study aimed to investigate the prevalence of Babesia vogeli, Ehrlichia canis, Hepatozoon spp., and Borrelia spp., as well as factors associated with these infections in urban dogs from the Brejo Paraibano microregion. To this end, canine blood samples were analyzed using TaqMan real-time PCR protocols or conventional PCR. Overall, of the 398 dogs sampled 109 (27.3%) tested positive for at least one of the four pathogens investigated. Deeming each pathogen, B. vogeli was detected in 25 animals, E. canis in 32, and Hepatozoon spp. in 71, the latter confirmed as H. canis by DNA sequencing in at least 10 dogs. Borrelia spp. was not detected in any dog. After multivariate analysis, for B. vogeli, the presence of apathy (P&#xa0;=&#xa0;0.034), anemia (P&#xa0;=&#xa0;0.035), and high tick infestation (P&#xa0;=&#xa0;0.017) were associated. No variable was associated with positivity for E. canis (P&#xa0;>&#xa0;0.05). For Hepatozoon (including H. canis), the ingestion of untreated water (P&#xa0;=&#xa0;0.002) was associated. The results confirm the circulation of pathogens of veterinary importance in the state, and report, for the first time, the molecular detection of Hepatozoon canis in the state. Furthermore, they provide information on associated factors that contribute to the planning of surveillance and control measures in the region.

Genomic characteristics play a critical role in the diagnosis, prognosis, and treatment of hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Germline profiling of MDS/AML patients who are candidates for allogeneic hematopoietic stem cell transplant (allo-HSCT) can identify inherited monogenic risk mutations, which can guide therapy selection and donor compatibility. Guidelines exist to suggest which allo-HSCT candidates should undergo germline testing. However, the rate of execution of this testing by transplant centers, as well as the perceived practicality of its implementation, has not been evaluated. This study aims to describe the current state of programmatic germline testing for individuals treating MDS/AML patients who are allo-HSCT candidates. Through a cross-sectional survey, we analyzed provider perspectives on genetic counseling services, institutional and current practice guidelines, and insights to germline testing for this patient population. A total of 21 participants completed the survey, most of whom were bone marrow transplant (BMT) coordinators (52.4%) from academic centers (66.7%). While 85.7% of participants reported offering germline evaluation/testing, practices varied widely across centers, with no standardized protocols for patient selection or sample collection. Provider comfort in discussing germline testing implications was variable and often limited, particularly among non-genetics providers, highlighting potential gaps in genetics training. Key barriers included inconsistent guidelines, insurance challenges, and limited provider awareness. Facilitators included collaboration with genetics services-especially genetic counselors-and involvement of BMT physicians and advanced practice providers to support appropriate and timely testing. Standardizing germline testing in HSCT for hematologic malignancies is essential, with sample type and timing as key barriers. We propose integrating routine skin punch biopsy with bone marrow biopsy for patients meeting NCCN criteria for germline testing to streamline cell culturing and sequencing alongside allo-HSCT planning. Involving the BMT team in early referrals and integrating a genetic counselor could improve coordination, address insurance and turnaround challenges, and ensure patients receive timely, actionable genetic insights to their personalized care.

Vaccines are among the most cost-effective public health interventions and remain central to global strategies for preventing and controlling infectious diseases. Evidence generated from clinical trials informs policy decisions regarding vaccine development, regulatory approval and large-scale implementation. The low-income and middle-income countries (LMICs) bear a disproportionately higher burden of vaccine-preventable diseases and are frequently the primary targets of global immunisation programmes. In spite of this, there have been long-standing concerns regarding inequities in the geographical distribution of vaccine clinical trials. Such inequities may limit the external validity and generalisability of trial findings for LMIC settings.This systematic review and meta-epidemiological analysis aims to assess the representation of LMICs in global vaccine clinical trials and to examine patterns associated with trial characteristics, sponsorship, funding source and time. This systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 statement. Eligible studies will be identified through comprehensive searches of bibliographic databases, including MEDLINE (via PubMed), Embase, Web of Science Core Collection, Scopus and the Cochrane Central Register of Controlled Trials, as well as clinical trial registries, including the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, the EU Clinical Trials Register, the Pan African Clinical Trials Registry and ISRCTN. Published and unpublished phase I-IV interventional vaccine clinical trials conducted on human participants will be eligible without restrictions on disease area, vaccine platform, language or publication status.Title, abstract and full-text screening will be conducted independently by two reviewers. Trial-level data on geographical location, trial phase, vaccine type, study design, sponsor type, funding source, participant distribution and publication status will be extracted using a standardised form. The primary unit of analysis will be the individual clinical trial. Descriptive and meta-epidemiological analyses will be undertaken to assess patterns of LMIC representation. Multivariable logistic regression analyses will be conducted, where appropriate, to identify trial-level factors associated with LMIC participation.The primary outcome will be the proportion of vaccine clinical trials including at least one LMIC study site. Secondary outcomes will include geographical distribution by income group and region, representation by trial phase, vaccine category and platform, sponsor and funding source, temporal trends in LMIC participation, and reporting transparency assessed through concordance between trial registry records and published reports. Ethical approval is not required because this review will use publicly available data and will not involve human participants. Findings will be disseminated through peer-reviewed publications and presentations at scientific and policy forums. CRD420261295568.

Brain-derived neurotrophic factor (BDNF), a critical modulator of neuroplasticity, has been strongly implicated in the pathophysiology of major depressive disorder (MDD). Non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), shows therapeutic promise for MDD. However, their impact on peripheral BDNF levels remains inconclusive. This meta-analysis aimed to quantify the effects of NIBS on peripheral BDNF levels in MDD patients and to evaluate BDNF as a potential biomarker of treatment response. Following PRISMA guidelines, randomized controlled trials (RCTs) comparing NIBS with sham stimulation in MDD were identified through a systematic search of five databases. Sixteen RCTs (n&#x202f;=&#x202f;1271) were included. Random-effects models were used to estimate pooled standardized mean differences (SMDs) for peripheral BDNF levels and depressive symptom severity. Subgroup and moderator analyses examined the effects of BDNF elevation, stimulation modality, and treatment duration. NIBS significantly increased peripheral BDNF levels (SMD&#x202f;=&#x202f;1.05, 95% CI: 0.57 to 1.52, p&#x202f;<&#x202f;0.001) and reduced depressive symptoms (SMD&#x202f;=&#x202f;-0.90, 95% CI: -1.13 to -0.67, p&#x202f;<&#x202f;0.001). Moderator analyses demonstrated that BDNF elevation was associated with greater antidepressant effects. Subgroup analyses revealed that rTMS significantly increased BDNF levels, whereas tDCS did not. Extended rTMS protocols (&#x2265;4 weeks) were associated with greater BDNF increases than shorter durations. NIBS is associated with increased peripheral BDNF levels and improved depressive symptoms in MDD patients, suggesting the potential utility of BDNF as a biomarker for neuromodulation efficacy. CRD42025630845.

Internal mammary node (IMN) irradiation has the potential to improve the overall survival in nodal positive breast cancer patients. Nevertheless, to achieve these benefits while keeping treatment related morbidity low is technically complex and requires careful patient selection and treatment planning. For this, detection of IMN involvement is of particular importance. This study aims to investigate response of visible IMN to neoadjuvant chemotherapy as potential surrogate for initial IMN involvement. We analyzed 298 non-metastatic breast cancer patients who underwent high-resolution pre-treatment MRI and follow-up MRI after neoadjuvant chemotherapy. If visible IMN were present, diameters were measured in axial and coronal planes on both pre- and post- neoadjuvant chemotherapy (NACT) MRIs. Differences in size were assessed and response systematically classified and correlated with clinical and histopathological response, axillary lymph node metastases (AXN) and tumor characteristics. 175 (58.7%) of 298 breast cancer patients had visible IMN on pretreatment MRI and 158 patients had a histopathological response of the primary tumor. Among these, 62 patients (39.3%) had a response of visible IMN. In patients with AXN the rate of IMN response was particular high with 48.6 %. In patients without AXN 21.8 % of patients with visible IMN showed a response to NACT. Response of visible IMN correlated significantly with medial tumor location and predominant tumor contact with internal mammary perforator vessels (IMPVc). The large majority (76.3 %) of IMN with response to NACT were initially rated as non-suspicious during initial staging and in the interdisciplinary tumor board consensus. Clinical IMN response to NACT may serve as an indicator of previously undetected IMN involvement in a relevant proportion of early breast cancer patients. The observation that approximately 20% of patients without AXN metastases demonstrated a radiologic IMN response warrants further investigation, as this subgroup is not routinely considered for IMN irradiation. These findings highlight the need for prospective validation in larger, well-characterized cohorts using standardized imaging protocols to better define the clinical significance of IMN response to systemic therapy.

Engineered in vitro cardiac tissues are being developed and increasingly used for disease modeling and drug evaluation, but reproducing cardiac cell composition and three-dimensional architecture alone does not ensure physiologically meaningful function. Native myocardial performance arises from coordinated electrical activation, active force generation, and passive mechanical resistance governed by stiffness, anisotropy, nonlinear elasticity, and viscoelastic relaxation. Failure to reproduce these coupled properties can alter force transmission, tissue deformation, mechanosensitive cellular responses, and the interpretation of disease phenotypes or drug effects. Yet myocardial mechanics, computational modeling, biomaterial design, and biofabrication are commonly developed as separate domains. This review integrates these areas through a biomechanics-guided property-parameter-function framework. We first examine the multiscale structural determinants of myocardial mechanics and critically compare cellular, continuum, phenomenological, microstructure-informed, viscoelastic, and pathology-informed models with respect to predictive scope, computational demand, parameter identifiability, experimental validation, and engineering relevance. We then show how model-derived descriptors-including active stress, baseline and nonlinear stiffness, anisotropy, relaxation behavior, and remodeling-related parameters-can be translated into controllable biomaterial properties, scaffold architecture, fabrication and conditioning protocols, and mechanical boundary conditions. Emerging approaches involving artificial intelligence, inverse design, uncertainty quantification, and digital twins are discussed as routes toward adaptive and patient-relevant tissue models. By positioning computational biomechanics as a design and validation tool, this review provides a systematic basis for engineering cardiac tissues with more predictable mechanical function and more reproducible disease- and drug-response readouts.

The neuropeptide orexin/hypocretin regulates adaptive behaviors needed for survival, including food intake, sleep-wake regulation, mating, and maternal behavior. However, the orexinergic system plays a critical role in addictive behavior and promotes seeking and rewarding substances of abuse and palatable food. Plenty of orexin receptors exist in the medial prefrontal cortex (mPFC). The PFC input to the NAc mediates goal-directed behaviors such as seeking behavior and planning actions to obtain rewarding substances. This study investigated the role of mPFC orexin-2 receptors (Orx2Rs) in natural-and drug-reward-seeking behaviors. One hundred sixteen adult male Wistar rats received TCS OX2 29 (3, 10, and 30 nmol/0.5&#xb5;l DMSO 12%) as an Orx2R antagonist in the mPFC during the acquisition and expression phases of two different CPP paradigms, morphine- and food-induced CPP protocols. Findings demonstrated that intra-mPFC administration of Orx2R antagonist reduced the acquisition and expression of morphine- and food-induced CPP in the rats. However, blockades of Orx2Rs in the mPFC have more inhibitory effects in food-induced CPP than in morphine-induced CPP. In conclusion, this study proposes a differential involvement of mPFC Orx2Rs in the acquisition and expression phases of CPP, suggesting distinguishable behavioral effects between food and morphine reward models. However, further mechanistic studies are required to clarify the underlying neural substrates.