SEARCH · Search PubMed

Results for “Proof of Concept Study”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

2,993 records · Page 16Linked to original sources

PubMed2026

Glucocorticoids and placental 11βHSD2 - A systematic review of human studies and animal models.

CONTEXT: Elevated prenatal glucocorticoid (GC) exposure is linked to adverse offspring outcomes. The placental enzyme 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2) protects the fetus by converting maternal derived cortisol to inactive cortisone. Although in vitro studies suggest GC mediated upregulation of 11βHSD2, in vivo evidence remains inconclusive. METHODS: PubMed, Embase, and PsycInfo were searched in October 2024 for human and mammalian animal studies on endogenous or exogenous GCs during pregnancy and associations with placental 11βHSD2 (mRNA, protein, activity, gene methylation). Narrative synthesis was conducted due to heterogeneity precluding meta-analysis. RESULTS: Eighteen studies (eight human, ten animal populations) met inclusion criteria. Exogenous GC exposure was associated with modifications in placental 11βHSD2 expression in animal models, with effects varying by substance, timing, and species. Dexamethasone trended towards increased expression in rodents, whereas betamethasone increased expression in non-human primates but not rodents. Human studies on endogenous GCs showed inconsistent associations with 11βHSD2 changes. In asthmatic pregnancies, moderate inhaled GC-use maintained enzyme activity compared to untreated patients. No convincing sex-specific trend emerged. CONCLUSIONS: GC exposure alters placental 11βHSD2 in a substance- and species-specific way; translational relevance remains limited based on current literature. Future studies should employ technological advances and include GC-sensitive biomarkers to clarify mechanisms of maternal-fetal stress transmission.

Female↗

PubMed2026

Comparative evaluation of molecular technologies for the identification of prevalent non-tuberculous mycobacteria in pulmonary infections: a systematic review and meta-analysis.

BACKGROUND: The increasing prevalence of non-tuberculous mycobacteria pulmonary disease (NTM PD) is a burden to public health. Successful management of NTM PD critically depends on accurate species identification and reliable drug susceptibility testing to guide appropriate antibiotic therapy. Emerging molecular technologies offer rapid diagnostic solutions compared to conventional methods, but their performance varies. This study aims to provide a comprehensive evaluation of current molecular techniques for NTM identification and to present a global antibiotic resistance profile. METHODS: A systematic literature search was conducted in PubMed and Web of Science for studies published between 2005 and 2024. Studies applying molecular methods for NTM identification and resistance detection in humans were included. Data on study characteristics, diagnostic methods, sample types, sample sizes, identification sensitivity, and drug susceptibility results were extracted. Meta-analysis was performed using R with the meta4diag package. The quality of included studies was assessed using the QUADAS-2 tool. RESULTS: The analysis included 49 studies on NTM identification and 33 studies on antibiotic resistance. For species identification, all evaluated molecular technologies (MALDI-TOF MS, PCR-based methods, Sequencing, DNA chip, and DNA strip) demonstrated high pooled sensitivities (>0.92). Subgroup analysis revealed that sample type significantly affected performance for MALDI-TOF MS. Preliminary analysis of antibiotic resistance rates revealed varying patterns. For slowly growing mycobacteria, a significantly high Ethambutol resistance rate was observed in M. avium (69.20%). Among rapidly growing mycobacteria, resistance to Imipenem was notable (54.22%), and Clarithromycin resistance varied significantly within the Mycobacterium abscessus complex. CONCLUSION: Emerging molecular technologies have revolutionized the methodology for NTM identification with excellent performance. However, their performance can be influenced by sample type, particularly for MALDI-TOF MS. The alarming and heterogeneous antibiotic resistance patterns also highlight the critical need for rapid and accurate species identification and drug susceptibility testing to inform effective therapeutic strategies. Key messagesMolecular technologies demonstrate high accuracy for NTM identification.Antibiotic resistance is a serious concern with variations among NTM species and subspecies.Rapid and accurate species identification and drug susceptibility testing are crucial for guiding effective clinical management of NTM PD.

Humans↗

PubMed2026

Feasibility and effectiveness of the Bergen 4-Day Treatment for obsessive-compulsive disorder in Australia: A pilot comparison with 3-week inpatient obsessive-compulsive disorder treatment.

OBJECTIVES: Obsessive-compulsive disorder is a debilitating and chronic condition that, when untreated or unresponsive to treatment, imposes a significant health and economic burden on individuals and families. This prospective non-randomised inpatient study compared the acceptability and clinical outcomes of the Bergen 4-Day Treatment programme with those of a standard 3-week specialised treatment programme for obsessive-compulsive disorder in Australia. METHOD: Twenty-five participants diagnosed with obsessive-compulsive disorder were non-randomly assigned to Bergen 4-Day Treatment (n = 12) or a 3-week standard (n = 13) inpatient programme. Independent assessments were completed at pre-treatment, 10 days post treatment and at 3-month follow-up. The Yale-Brown Obsessive-Compulsive Scale was rated to assess obsessive-compulsive disorder severity, while secondary measures of depression, anxiety, obsessive beliefs and wellbeing were self-rated by participants. RESULTS: Baseline characteristics of both groups were comparable, with obsessive-compulsive disorder symptom severity within the moderate to severe range. After treatment, obsessive-compulsive disorder symptoms as well as secondary depression and anxiety symptoms were reduced in both treatment groups. Participants receiving Bergen 4-Day Treatment had significantly lower Yale-Brown Obsessive-Compulsive Scale scores at 10 days (M = 13.46) and 3 months (M = 11.84), compared to standard treatment (M = 19.04 and M = 19.15, respectively). Response (91.9%) and remission (45.8%) rates for the Bergen 4-Day Treatment group were significantly higher at both post-treatment timepoints, compared to the standard treatment group. No dropouts occurred in the Bergen 4-Day Treatment group, and participant satisfaction was high. CONCLUSION: The findings of this pilot open-label study suggest that Bergen 4-Day Treatment shows promise as an acceptable, efficient and effective treatment for obsessive-compulsive disorder, warranting further investigation as a scalable alternative for improving access to specialised obsessive-compulsive disorder treatment in Australia.

Humans↗

PubMed2026

Donor Human Milk Utilization in a Level 1 Newborn Unit of a High-Volume Delivery Hospital: A Cautionary Tale.

INTRODUCTION: Donor human milk (DHM) is an alternative to formula for supplementation of breastfed newborns and has been associated with higher in-hospital exclusive breast milk feeding rates. Its use has increased substantially, most recently among term newborns, yet there is scarce data to describe patient characteristics and volumes administered. We aimed to characterize DHM utilization in our level 1 nursery. METHODS: We conducted a retrospective cross-sectional study of newborns discharged in 2022 from the level 1 nursery. Variables included sex, gestational age, birth weight, delivery type, hypoglycemia diagnosis, DHM volume, and length of stay. DHM use was compared across preferred language, race, ethnicity, and payer type using chi-square testing. RESULTS: A total of 10,432 discharges were reviewed-those transferred to Neonatal Intensive Care Unit (NICU) or another unit were excluded. Of 9,074 newborns receiving level 1 care, 1,094 (12.1%) received DHM. Newborns born between 35 and 37 weeks gestation, delivered by cesarean section, or diagnosed with hypoglycemia or small for gestational age were more likely to receive DHM (p < 0.05). DHM was also more common among newborns whose birth parent preferred the English language, identified as White or non-Hispanic, or had non-Medicaid insurance (p < 0.05). 6,552.6 ounces were consumed, with a total median of 3.9 ounces per newborn (dose range 2-50 mL). CONCLUSIONS: DHM use in the level 1 nursery varied by clinical and sociodemographic factors, revealing inequities. In addition, some doses exceeded recommended supplemental volumes. Future efforts should focus on ensuring equitable access to DHM, standardized dosing and discontinuation guidelines, and evaluation of impacts on exclusive breastfeeding rates.

Humans↗

PubMed2026

Design of an innovative framework based hybrid catalyst for simultaneous and sensitive monitoring of food additive and preservative of vanillin and nitrite in direct samples.

As vanillin (VAN) and nitrite (NIT) contamination in the food chain poses substantial threats to environmental and public health, rapid and portable detection is essential. The present study presents the first electrochemical sensor report based on a hybrid composite of Ni-TPA-MOF and MoS2/Co3O4. The oxidation of VAN and NIT exhibited sharp peaks and less over-potential on Ni-TPA-MOF/MoS2/Co3O4/GCE than on control electrode surfaces. On modified composite electrode surfaces, pH and scan rate were investigated for VAN and NIT. Further, the oxidation current exhibited high linearity at VAN and NIT concentrations of 5 nM-1000 μM and 3 nM-1250 μM, with detection limits of 0.102 nM and 0.073 nM (S/N = 3). We also applied anti-interfering ability (five/ten-fold excess of co-interfering compounds) and practical tests to various food-based real samples, with high recoveries of 98.85-102.41%. This study highlights the catalytic properties of Ni-TPA-MOF/MoS2/Co3O4 and demonstrates the sensor as a promising tool for food safety.

Benzaldehydes↗

PubMed2026

Which radiographic plane should be used to quantify the distal tibia angle on weightbearing CT images?

BACKGROUND: Precise quantification of distal tibial alignment is essential for planning corrective osteotomies and ankle joint replacement surgery. The lateral distal tibial angle (LDTA) is the principal radiographic parameter used for this purpose. While LDTA is increasingly measured on weightbearing cone-beam CT (WBCT) using two-dimensional coronal slices, the optimal measurement plane remains unclear. METHODS: In this retrospective comparative study, full-leg WBCT scans of patients scheduled for supramalleolar osteotomy (n = 20; mean age 47 ± 12.8 years) were analyzed. LDTA was measured on three coronal planes of the distal tibial plafond (anterior edge, mid-dome, posterior edge) and compared with semi-automated three-dimensional (3D) tibial alignment measurements as the reference standard. RESULTS: Mid-dome LDTA showed no significant difference from the 3D reference (p > 0.05) and demonstrated excellent agreement. Anterior measurements significantly overestimated LDTA, while posterior measurements underestimated it (both p < 0.05), with only fair agreement. CONCLUSION: LDTA should be measured at the mid-dome of the distal tibial plafond on WBCT to ensure accurate and reproducible alignment assessment. LEVEL OF EVIDENCE: Level III - Retrospective Comparative Study.

Humans↗

PubMed2026

Effects of an actuated ankle exoskeleton on walking stability in healthy adults: a controlled laboratory study.

BACKGROUND: Ankle exoskeletons are widely used to reduce the metabolic cost of walking, yet their effects on walking stability during unperturbed gait remain insufficiently understood. Walking stability can be characterized using complementary measures that capture stride-to-stride variability, global temporal organization, and local dynamic stability. Understanding how walking with an actuated ankle exoskeleton system influences these different aspects of gait stability is essential for the safe design and control of wearable robotic devices. METHODS: Eighteen healthy adults walked on a treadmill at a constant speed (1.1 m/s) with and without an actuated bilateral ankle exoskeleton in a randomized crossover design. Spatiotemporal variability was quantified using coefficients of variation (CoV) of stride length, step width, and stance ratio. Global gait stability was assessed using detrended fluctuation analysis of stride time. Local dynamic stability was evaluated using maximum Lyapunov exponent calculated for the trunk, hip, upper leg, lower leg, and foot. Paired-samples two-sided t-tests were used to compare conditions. RESULTS: Walking with the ankle exoskeleton resulted in increased stride-to-stride spatiotemporal variability, reflected by higher CoV values for stride length (p < 0.001) and stance ratio (p = 0.005), while mean stride length and step width remained unchanged. Mean stance ratio was reduced in the exoskeleton condition (p < 0.001). Global gait stability did not differ between conditions, indicating preserved long-range temporal gait organization. Local dynamic stability increased at the lower leg (p < 0.001) and foot (p = 0.019) when walking with the exoskeleton. CONCLUSIONS: Walking with the actuated ankle exoskeleton alters gait control across multiple levels during steady walking. While stride-to-stride variability in stride length and stance ratio increased, global gait stability remained unchanged. Local dynamic stability was increased at the lower leg and foot, suggesting segment-specific effects of ankle-level assistance close to the assisted joint. However, these findings should be interpreted as the combined effect of wearing the exoskeleton and receiving active assistance, rather than the isolated effect of plantarflexion assistance. These results provide insight for the design and control of ankle exoskeletons with respect to stability-related effects during walking.

Humans↗

PubMed2026

Vestibular schwannoma associated normal pressure hydrocephalus: clinical features and shunt responsiveness compared with idiopathic NPH.

BACKGROUND: Vestibular schwannoma (VS) is commonly associated with obstructive hydrocephalus due to mass effect; however, a rarer communicating form resembling normal pressure hydrocephalus (NPH) has also been described, possibly related to impaired CSF absorption from elevated CSF protein. We aimed to characterize the clinical and imaging features of VS-associated NPH (VS-NPH) and compare them with those of an idiopathic NPH (iNPH) cohort. METHODS: We retrospectively analyzed 18 patients with VS-NPH identified between 2008 and 2024. For comparison, 41 iNPH patients were drawn from a prospective longitudinal study at our center. Variables included demographics, tumor size, VS treatment modality, CSF parameters, Radscale imaging features, and shunt responsiveness. RESULTS: VS-NPH patients had markedly higher CSF protein levels than patients with iNPH (median 100 vs. 51 mg/dL, p < 0.001). Radiological features largely overlapped; however, parasagittal sulcal narrowing was more frequent in VS-NPH (61 % vs.13 %, p = 0.002). These differences remained significant in the sensitivity analysis excluding the two patients without gait impairment. VS-NPH patients were younger in the primary analysis (66.8 vs. 72.0 years, p = 0.03), while exploratory associations between larger tumor size and both earlier NPH symptom onset (r = -0.48, p = 0.049) and smaller callosal angle (r = -0.49, p = 0.048) attenuated to non-significant trends in the sensitivity analysis. Tumor size was < 30 mm in 89 % of patients. Ventriculoperitoneal shunt (VPS) resulted in clinical improvement in both groups, although response rates were numerically lower in VS-NPH than in iNPH (63 % vs.75 %). CTT was positive in 9 of 11 VS-NPH patients who underwent testing, although improvement after shunting also occurred in patients with negative CTT results or without prior CTT. CONCLUSIONS: VS-NPH may represent a secondary subtype of NPH with distinct biochemical and subtle imaging features. Elevated CSF protein may contribute to altered CSF dynamics. These findings are exploratory and require confirmation in larger prospective studies.

Humans↗

PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P < 0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-κB-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-κB-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗

PubMed2026

CoLchicine for Treatment of OsteoArthritis of the Knee (CLOAK): Clinical and biochemical outcomes from a three-month double-blind, placebo-controlled study.

OBJECTIVE: Knee osteoarthritis (KOA) causes pain and progressive disability, but pharmacologic treatments are limited. Colchicine inhibits inflammation that might modulate KOA, but efficacy trials have yielded mixed results. We tested whether colchicine, without concurrent NSAIDs, improved KOA pain, function, synovial effusion size, and OA-associated inflammatory serum biomarkers. METHODS: Participants with symptomatic KOA and radiographic Kellgren-Lawrence grades 2/3 were randomized to receive three months of daily colchicine or placebo in a double-blind manner, with no concurrent NSAID use. The primary outcome was between-group change in visual analog score (VAS) for index knee pain. Secondary outcomes included changes in Knee Osteoarthritis Outcome Scores (KOOS), size (depth in millimeters) of sonographically-identified effusions, acetaminophen use, and changes in OA-related serum biomarkers. RESULTS: From baseline to end of study of 120 enrolled participants, no significant differences were observed in improvement of VAS pain, KOOS scores or effusion size. Subsets of participants with more severe VAS pain, worse radiographic disease, or higher hsCRP or serum urate levels at baseline also showed no significant clinical benefit from colchicine compared to placebo. In contrast to the clinical outcomes, colchicine treatment was associated with significant or trending improvement in multiple OA-related serum biomarkers including hsCRP and β-NGF (p < 0.05) and PGE2, IL-1ra, IL-8, and VEGF (p < 0.16). CONCLUSION: This double-blind placebo-controlled trial of colchicine for KOA failed to demonstrate improvement in pain, function, or synovial effusion size in comparison to placebo at three months. Early improvement in OA-associated inflammatory biomarkers suggests a possible longer-term clinical benefit. Clinical Trials Registration No NCT03913442.

Humans↗

PubMed2026

A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.

PURPOSE: Survival for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains low with <20% immunotherapy response. Metformin increases tumor-infiltrating CD8+ T and natural killer (NK) cells, which harbor PD-1. In this phase II clinical trial (NCT04414540), we combined metformin and pembrolizumab to evaluate the overall response rate (ORR) in R/M HNSCC and assess NK-cell activity. PATIENTS AND METHODS: Eligible patients were randomized 1:1 into two arms: (i) metformin extended-release (ER) dose escalation to 2,000 mg over 14 days followed by combination with pembrolizumab 200 mg every 3 weeks or (ii) pembrolizumab 200 mg every 3 weeks followed by combination with metformin ER 2,000 mg daily. The primary endpoint was ORR per RECIST 1.1. Nineteen evaluable patients were planned to estimate the proportion of approximately 32% ORR. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0. The distribution, activation, and cytotoxic function of NK cells were analyzed via flow cytometry. RESULTS: Twenty-one patients were enrolled; 76% were male, 52% were smokers, and the median age was 64 years. Ten patients had oropharyngeal tumors, of which nine were p16+. Eighteen patients were evaluable for response, including four complete and five partial responses for an ORR of 50% [95% confidence interval (29-71)]. Combination therapy was well tolerated with no unexpected adverse events (AE). Five grade 3 AEs occurred: nausea, diarrhea, fatigue, and weight loss. Metformin led to increased peripheral NK-cell maturation and cytotoxic ability. CONCLUSIONS: The combination of metformin and pembrolizumab was well tolerated with mild gastrointestinal AEs and promising activity, warranting further investigation in a randomized trial.

Humans↗

PubMed2026

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

BACKGROUND: Ponesimod demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) in 24-week phase-2 core study, further confirmed by an interim combined analysis of the core and open-label long-term extension (LTE) studies (NCT01093326; up to 8 years). Current study evaluated safety and efficacy of ponesimod using combined core and LTE studies data for up to 13 years. METHODS: Of 393 participants completing the core study, 353 (90%) entered LTE, having 3 treatment periods (TP). In TP1 (∼1.85 years), participants continued core treatment (ponesimod: 10, 20, or 40 mg QD) whereas placebo-treated participants were re-randomized (1:1:1) to respective ponesimod doses. In TP2 (TP2 and TP3 combined duration: ∼10.4 years), participants on 40 mg were re-randomized (1:1) to 10/20 mg, while others continued same dose; in TP3 all participants received 20 mg. Study outcomes included safety and efficacy (ARR, time-to 24-week confirmed-disability-accumulation [24-week CDA], total T1-weighted Gadolinium-enhanced (T1 Gd+) lesions, new/enlarging T2 lesions and Combined Unique Active Lesions [CUALs]). RESULTS: For 20 mg dose, total 92.4% participants experienced ≥1 TEAEs (73.1% mild/moderate severity) and 19 (13%) participants discontinued study. Mean (95% CI) ARR=0.14 (0.10-0.20); Kaplan-Meier estimate (95% CI) of confirmed relapse and 24-week CDA=52.5% (42.3-63.5) and 31.3% (22.6-42.3). Mean [SD] T1 Gd+ lesions decreased from ponesimod baseline (2.62 [7.06]) to 12.4 years (0.26 [1.48]), mean (95% CI) CUALs per participant/year=3.97 (2.75-5.73). CONCLUSION: Ponesimod treatment for up to 13 years was not associated with new safety concerns. Participants continued to experience low levels of disease activity consistently across clinical and MRI outcomes.

Humans↗

PubMed2026

AI echo INSIGHT study: A prospective blinded randomized trial of artificial intelligence echocardiogram interpretation.

BACKGROUND: Transthoracic echocardiography (TTE) is the most commonly performed cardiac imaging modality with over 30 million studies annually. Demand for timely expert interpretation continues to outpace capacity, creating diagnostic delays and inter-observer variability that impact patient care. Recent research has suggested computer vision artificial intelligence (AI) models can generate accurate preliminary comprehensive TTE reports, however, prospective evaluation is needed to determine whether AI-assisted TTE interpretation can improve clinician efficiency while preserving diagnostic accuracy. METHODS: AI ECHO INSIGHT is a prospective randomized blinded clinical trial conducted at Kaiser Permanente Northern California that will evaluate 1200 historical TTE studies (1000 consecutive unselected studies plus 200 with moderate or greater valvular disease) interpreted using three workflows: (1) AI-generated preliminary report finalized by a blinded cardiologist (AI-assisted); (2) cardiologist-generated preliminary report finalized by a blinded cardiologist (cardiologist-assisted); and (3) sonographer-generated preliminary report finalized by a blinded cardiologist (sonographer-assisted). The primary outcome is the rate of substantial change between preliminary and final reports, comparing the AI-assisted workflow to the pooled cardiologist-assisted and sonographer-assisted workflows. Secondary outcomes include cardiologist interpretation time for report finalization, superiority testing for diagnostic accuracy, and reporting consistency. CONCLUSION: AI ECHO INSIGHT is a prospective randomized blinded clinical trial evaluating the clinical impact of AI-assisted TTE interpretation on diagnostic accuracy, cardiologist efficiency, and reporting consistency in real-world echocardiography workflows. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT07229300.

Humans↗

PubMed2026

Association between pulse pressure and markers of cognitive function: a systematic review and meta-analysis.

Our aim was to systematically review and meta-analyse evidence on the association between pulse pressure (PP) and cognitive function using PubMed, PsycInfo, Embase and Scopus (inception-July 2025) publication databases. Studies were included if they reported an association between PP and cognitive function and summarized narratively and by performing fixed-effects meta-analysis. The search identified 4171 publications with 43 studies meeting inclusion criteria. Domains assessed included global cognition, memory, language, attention, executive function, processing speed and visuospatial ability. Meta-analysis suggests a positive association between PP and global cognition, and a negative association with memory in both cross-sectional and longitudinal studies with inconsistent findings from narratively summarized studies. Processing speed, executive function and language negatively associated with PP in cross-sectional studies with limited evidence provided by longitudinal studies or narratively summarized studies. There was limited evidence of an association with attention and visuospatial ability.

Humans↗

PubMed2026

Storm and Stress 2.0? A Dual-Factor, Person-Centered Analysis of Adolescent Well-being Across Two Year 7 Cohorts and Gender.

PURPOSE: Concerns about the mental health and well-being of younger generations is a recurring theme across countries and time. Adolescence is debated as a period of volatility ("storm and stress") or growth. Recent trends have reignited worries about youth mental health and well-being, particularly for females, and revived a deficit-based view of adolescence. To advance understanding, this study adopts a dual-factor approach that incorporates both negative and positive well-being domains. Mental health trends were compared across two grade-matched Australian adolescent cohorts assessed 5 years apart. METHODS: Data were drawn from cross-sectional cohorts of year 7 students (12-13 years) in one Australian jurisdiction: 2,085 in 2018 and 2,378 in 2023. Positive affect, happiness, resilience, depression, and anxiety were assessed using latent profile analysis to identify mental health profiles, which were then compared between cohorts and gender. RESULTS: Four profiles were identified: complete mental health, symptomatic but positive, resilient but disaffected, and troubled. Approximately 80% of students were classified in profiles reflecting some positive mental health. Between 2018 and 2023, the proportion with complete mental health declined by 7.93%, while those categorized as troubled increased by 4.76%. Declines were most pronounced among female students. DISCUSSION: Findings highlight both resilience and vulnerability in adolescent mental health. While most students continue to show positive well-being, the decline among females signals an urgent need for gender-sensitive approaches. At the same time, the results add nuance to accounts of a youth mental health 'crisis' to some degree, by highlighting positive domains of well-being which are often overlooked.

Humans↗

PubMed2026

A qualitative study of cancer survivors' exercise behaviour 4 months after a telerehabilitation program.

PURPOSE: Although telerehabilitation can improve access to exercise programs for cancer survivors, it is not known if these programs lead to ongoing change in exercise habits. This study explored participant experiences of exercise 4 months after finishing specialized cancer exercise-based telerehabilitation. METHOD: A qualitative study embedded in a randomized controlled trial evaluated exercise-based cancer telerehabilitation delivered in groups. Data were collected via semistructured interviews that were audio-recorded and transcribed verbatim. Seventeen adult cancer survivors (age 21 to 80) were purposively sampled 4 months after completing exercise-based cancer telerehabilitation. Data were coded independently by two researchers and analyzed inductively within an interpretive description framework. RESULTS: The overarching theme was telerehabilitation was perceived to facilitate positive exercise intentions. Participants said they were empowered to exercise through knowledge, opportunity, and connection gained through telerehabilitation. They described acting on their positive intentions to exercise to varying degrees following telerehabilitation, depending on their context. A subtheme was that exercise was challenging in their new reality created by cancer. Comorbidities, ongoing side effects, previous exercise experience, and personal factors were considered by some to influence their ability to exercise. CONCLUSION: Telerehabilitation may facilitate positive intent to maintain exercise. Cancer survivors may need ongoing support after telerehabilitation to act on positive exercise intentions due to health-related difficulties. IMPLICATIONS FOR CANCER SURVIVORS: Participation in telerehabilitation may be a positive first step to initiate exercise, but ongoing support to maintain positive behavior changes is likely to be needed for people without previous exercise experience.

Humans↗

PubMed2026

Ultrasound-Guided Microwave Ablation Versus Open Surgery for Benign Breast Disease: Impact on Postoperative Lactation.

BACKGROUND: Benign breast disease (BBD) is common in adult women. While ultrasound-guided microwave ablation (MWA) is an established minimally invasive treatment, its comparative impact on postoperative lactation, particularly mastitis, remains understudied. This study aimed to evaluate mastitis outcomes following MWA versus open surgery for BBD. METHODS: In this retrospective study, 79 patients (105 nodules) treated between January 2018 and August 2023 were included 41 patients (62 nodules) underwent MWA and 38 patients (43 nodules) underwent open surgery. All patients lactated within 5 years post-procedure. The primary outcome was the incidence of lactational mastitis without systemic symptoms (MWoSS) and mastitis with systemic symptoms (MSS). Patient satisfaction was also assessed. RESULTS: The incidence of MWoSS was significantly lower in the MWA group (19.5%) than in the open surgery group (50.0%). Similarly, MSS occurred in 4.9% of the MWA group versus 34.2% of the open surgery group. Multivariate analysis identified open surgery as an independent risk factor, associated with a 4.13-fold increased risk of MWoSS (OR = 4.125, 95% CI: 1.517-11.218) and a 10.14-fold increased risk of MSS (OR = 10.140, 95% CI: 2.107-48.793). Patient satisfaction was significantly higher in the MWA group (9.29 ± 0.72 vs. 8.15 ± 1.13, p < 0.001). CONCLUSION: Compared to open surgery, ultrasound-guided MWA for BBD is associated with a significantly lower risk of postoperative mastitis and higher patient satisfaction, supporting its use for women of reproductive age, particularly when future breastfeeding is planned.

Humans↗

PubMed2026

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans↗