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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.

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.

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.

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.

Although pneumorrhachis is usually considered a benign radiological finding, in the epidural setting it may act as a compressive lesion and mimic surgically urgent pathology. This report describes a case of acute paraplegia following thoracic epidural analgesia caused by epidural air and highlights diagnostic and systems-related pitfalls. A 68-year-old man with chronic pelvic osteomyelitis developed sudden thoracic pain and rapidly progressive bilateral lower extremity paresis during a programmed bolus administration through a thoracic epidural catheter. Emergency MRI demonstrated a dorsal epidural collection at T11-12 with marked conus medullaris compression that was interpreted as a spinal epidural abscess. Urgent surgical decompression was undertaken. Surgical exploration revealed epidural air without purulence or inflammatory tissue. The patient's neurological function recovered rapidly after decompression. Root cause analysis identified residual air within the infusion cassette combined with deactivated air-in-line detection as the most plausible mechanism for inadvertent epidural air delivery. Epidural pneumorrhachis should be considered in patients with acute neurological deterioration after epidural analgesia. When MRI findings are equivocal, CT can rapidly confirm the presence of air. Strict air-priming protocols and active air detection safeguards are essential to prevent neuraxial air complications. https://thejns.org/doi/10.3171/CASE26351.

Accurate calculation of energy changes upon mutation is a key requirement for the effective use of computational methods in protein design. In this study, we applied free energy perturbation (FEP) calculations to predict the effects of mutations on the binding free energy between the immunoglobulin G (IgG) antibody fragment-crystallizable (Fc) region and the neonatal Fc receptor (FcRn), an interaction that is primarily responsible for antibody half-life. We assembled an extensive experimental dataset of Fc-FcRn binding affinities for wild-type (wt) and mutant complexes, including values from literature and from newly measured results. Starting from a crystal structure of the M252Y/S254T/T256E ("YTE") Fc variant bound to FcRn, we prepared all-atom models of human IgG1-subtype wt and YTE variant Fc-FcRn complexes, adding explicit hydrogens and assigning protonation states for key ionizable residues. Initial results using standard FEP protocols to compute relative binding free energies were promising but exhibited multiple outliers. By accounting for coupling effects for FEP mutations near key histidine residues, we improved the results for several outliers, suggesting such coupling as an important approach for pH-sensitive systems. Further, upon determining new crystal structures of wt Fc and three Fc variants at multiple pH values, we observed subtle conformational changes in unbound Fc; by accounting for these conformational changes in FEP calculations, we additionally improved agreement with experiment. The detailed structural and energetic analyses of the Fc-FcRn system we present here thus provide a practical energy-calculation framework to enable rational in silico design of novel Fc variants. SIGNIFICANCE: The ability to determine changes in binding affinity upon mutation is critical to structure-based protein design. In this study, we demonstrate a successful computational approach using free energy perturbation (FEP) calculations on the antibody Fc-FcRn complex, a medically relevant system with implications for both therapeutic and prophylactic antibody use. Our successful calculation of accurate binding energies across a wide range of cases speaks to the power of the FEP methodology in navigating the free energy landscapes of dynamic molecular complexes. Furthermore, we show that accurate Fc-FcRn affinity calculations required careful consideration of conformational flexibility between bound and unbound states, contributing to our functional understanding of a system that will be important for future rational antibody-design efforts.

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.

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.
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.
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.
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 = 0.034), anemia (P = 0.035), and high tick infestation (P = 0.017) were associated. No variable was associated with positivity for E. canis (P > 0.05). For Hepatozoon (including H. canis), the ingestion of untreated water (P = 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.

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/0.5µl 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.

Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique, emerging as a potential therapeutic option for musculoskeletal pain management. To comprehensively evaluate the efficacy and safety of tACS for alleviating pain and improving sleep quality in adults with musculoskeletal pain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Seven major databases and other sources were searched from inception until April 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias. A random-effects model was used to pool standardized mean differences (SMDs). The certainty of evidence was evaluated using the Grading of Recommendation Assessment, Development, and Evaluation framework. Six RCTs involving 232 participants were included. Meta-analysis showed that tACS could significantly reduce pain intensity compared to control (SMD = -0.355, 95% CI: -0.625 to -0.084, p = 0.010, I² = 28.7%). However, no significant improvement was found for sleep quality (SMD = 0.004, 95% CI: -0.310 to 0.317, p = 0.982, I² = 0.0%). Adverse effects were mild and transient, comparable to sham stimulation. The overall certainty of evidence was rated as low for both pain and sleep quality outcomes. Current evidence suggests that tACS may be beneficial for musculoskeletal pain; however, the available evidence remains limited and should be interpreted cautiously. The effect of tACS on sleep quality remains uncertain because of the limited number of available studies. Future well-designed RCTs with standardized outcome measures, condition-specific stimulation protocols, and longer follow-up are required to establish the efficacy and long-term safety of tACS.

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.

This scoping review maps the current development landscape of wearable hand exoskeletons for motor rehabilitation, covering publications from 2010 to October 2025 across four major databases. A total of 134 articles were included, identifying 116 unique devices validated with human subjects. The results show a clear predominance of soft structures over rigid or hybrid ones, with electric motors and tendon-driven mechanisms being the most frequent actuation and transmission choices. However, there is a lack of uniformity in the information on device metrics, such as total weight and system dimensions, or usability metrics, like donning and doffing times, which hinders the direct comparison of different technologies. This review synthesizes current trends and emphasizes the need for standardized validation protocols to advance toward effective clinical solutions.

To systematically compare the diagnostic accuracy of abbreviated breast MRI (AB-MRI) and full diagnostic protocol MRI (FDP-MRI) for breast cancer detection. Ovid-MEDLINE, Embase, Cochrane Library, and Web of Science were searched up to December 1, 2025. Risk of bias was assessed using the modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Forty studies (14,266 patients) were included. In screening settings, the first postcontrast subtracted (FAST) protocol achieved sensitivity comparable to FDP&#x2011;MRI but significantly lower specificity; adding T2&#x2011;weighted (T2W) imaging raised specificity to a level not statistically different from FDP&#x2011;MRI. In enriched&#x2011;screening settings, FAST with or without T2W performed comparably. In diagnostic settings, FAST combined with ultrafast (UF) and T2W demonstrated significantly higher specificity than FDP&#x2011;MRI (ratio 1.61, p&#xa0;<&#xa0;0.001), while FAST and rapid abridged multiphase (RAMP) with or without T2W or diffusion&#x2011;weighted imaging (DWI) were comparable to FDP&#x2011;MRI. T2W&#xa0;+&#xa0;DWI alone showed significantly reduced sensitivity in diagnostic settings. The diagnostic performance of AB&#x2011;MRI protocols relative to FDP&#x2011;MRI varies by protocol and clinical setting; findings apply only to the specific regimens evaluated. FAST maintains high sensitivity, with T2W offsetting specificity limitations in screening, while FAST&#xa0;+&#xa0;UF&#xa0;+&#xa0;T2W offers superior specificity in diagnostic settings. However, most subgroup analyses included only 3-4 studies, and others fewer than three; all results therefore require cautious interpretation and validation in larger, prospective studies before clinical adoption.

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.

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.

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.