Search Results (44,027)

Background: Multisite digital psychiatry trials increasingly rely on complex onboarding and implementation processes at local research sites. While outcome-focused evaluations are common, less attention has been paid to the site-level labor required to operationalize such studies in real-world settings, particularly at smaller or resource-constrained sites. This study addresses this gap by examining hidden implementation labor from a single-site reflexive perspective. Methods: This study adopts a reflexive qualitative case study approach to examine onboarding and implementation processes at a single research site participating in a multisite digital psychiatry trial (ClinicalTrials.gov: NCT04953208). The analysis draws on longitudinal experiential data, supported by site-specific documentation, onboarding timelines, troubleshooting records, device-management materials, data quality assurance activities, and internal communications generated during site coordination and implementation activities. Results: Five interrelated themes were identified: hidden labor and role overload; resource scarcity at small research sites; fragmented remote communication and technical coordination; multi-role professional contexts and competing demands; and the impact of external systemic disruptions. Findings show how administrative, technical, logistical, and coordination tasks were absorbed into individual roles, often exceeding initial role expectations. Despite limited resources, the site achieved high performance through intensified individual effort, masking the true implementation burden. This pattern is conceptualized as a high-performance paradox, in which apparent site efficiency may conceal substantial hidden labor and role compression. Conclusions: This site-level reflexive account highlights the central role of hidden labor in sustaining implementation in multisite digital psychiatry trials. Recognizing and explicitly resourcing implementation work, particularly at small research sites, may improve feasibility, sustainability, and equity across study settings. The study contributes a practice-based methodological perspective on how implementation burden can be identified through reflexive analysis of site-level trial processes. Full article

Introduction: The role of immune checkpoint inhibitors (ICIs) in locally advanced head and neck squamous cell carcinoma (LA HNSCC) remains uncertain, with randomized trials showing inconsistent results in heterogeneous populations. We conducted a systematic review of randomized trials evaluating ICI-based strategies in LA HNSCC, with outcomes stratified by PD-L1 expression, HPV/p16 status, and cisplatin eligibility to identify patient subgroups most likely to benefit from ICIs. Methods: MEDLINE, Cochrane, and EMBASE databases were systematically searched up to 10 January 2026. Randomized controlled trials (RCTs) evaluating ICIs in patients with LA HNSCC were included. The primary outcome was pooled time-to-event efficacy, including event-free survival (EFS), progression-free survival (PFS), and disease-free survival (DFS) as reported across trials. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for PFS with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q test. Random effects model was applied. Results: A total of 3605 patients from seven phase II/III RCTs were included. In the overall population, no significant difference in EFS/PFS/DFS was observed between ICI and standard therapy (HR 0.90; 95% CI: 0.77–1.06; p = 0.20). However, in subgroup analyses stratified by PD-L1 expression, patients with PD-L1-positive tumors demonstrated improved PFS with ICIs compared with control (HR 0.78; 95% CI: 0.67–0.91; p < 0.0001). In contrast, PD-L1-negative tumors demonstrated inferior PFS in the ICIs arm (HR 1.31; 95% CI: 1.02–1.68; p = 0.03). No significant differences in PFS were observed based on HPV or p16 status. A subset analysis of cisplatin-eligible LA HNSCC trials evaluating the addition of ICIs to standard therapy showed a similar pattern. ICI use in PD-L1-positive patients demonstrated significantly improved PFS (HR 0.76; 95% CI: 0.63–0.92; p < 0.0001), while ICI use in PD-L1-negative patients demonstrated decreased PFS (HR 1.28; 95% CI: 0.99–1.66; p = 0.06). In cisplatin-ineligible populations, ICI regimens did not improve PFS compared with cetuximab plus RT. Conclusions: This study showed that although in the overall population there was no significant difference in EFS/PFS/DFS, in the PD-L1-positive subgroup, patients experienced significantly improved PFS with ICIs compared with control, while in the PD-L1-negative subgroup, patients demonstrated inferior PFS in the ICIs arm; these results were mirrored in the cisplatin-eligible subgroup. Full article

Background: Recurrent pregnancy loss (RPL) remains etiologically unexplained in 40–50% of cases following standard diagnostic workup. Non-criteria antiphospholipid antibodies (non-criteria aPL) are increasingly considered potential markers of seronegative obstetric antiphospholipid syndrome (APS); however, their diagnostic value in this clinical setting requires further investigation. Objective: To assess the diagnostic value of non-criteria aPL in women with RPL and to construct an exploratory immunological scoring model for diagnostic stratification. Methods: Antiphospholipid antibody detection was performed using a single-measurement semi-quantitative line immunoblot assay (Anti-Phospholipid 10 Dot, Generic Assays, Germany). Statistical analysis included χ², Fisher’s exact test, Mann–Whitney U test, binary logistic regression, and ROC analysis. Results: Statistically significant associations with RPL were observed for anti-prothrombin antibodies (OR = 11.1; 95% CI 1.8–68.0; p = 0.022 [Haldane–Anscombe correction]), anti-annexin V (OR = 4.28; 95% CI 1.18–15.6; p = 0.023), and anti-β₂GP I (OR = 3.31; 95% CI 1.18–9.28; p = 0.019). The exploratory composite immunological score demonstrated moderate discriminatory performance (AUC = 0.701; 95% CI 0.588–0.814; p = 0.005). The overall logistic regression model was statistically significant (χ² = 8.564; p = 0.036), although none of the individual predictors retained independent significance, indicating a contribution of cumulative immunological burden rather than any single marker. Conclusions: In this single-center cross-sectional study, non-criteria aPL were frequently detected in women with RPL and were statistically associated with the condition. The findings should be interpreted as hypothesis-generating only, given the cross-sectional design, single-measurement immunoblot, small control group, and absence of external validation. Confirmation in larger prospective multicenter cohorts using ELISA-based assays with the internationally recommended 12-week repeat measurement is required before any clinical implementation. Full article

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells, with particularly high prevalence in Sardinia, where it is strongly associated with favism. Public awareness remains incomplete and misconceptions persist—particularly regarding symptom onset from fava bean pollen or odors. This cross-sectional survey assessed G6PD self-reported deficiency, population knowledge, and persistence of false beliefs in Sardinia. Methods: A 16-item structured questionnaire was disseminated online (May–June 2025) to adults across diverse age groups and educational backgrounds. Results: Among 536 respondents (74.25% female; 97.39% Sardinia residents), 43.47% of respondents self-reported as G6PD-deficient, a figure substantially above the expected population estimate of 8–15% and consistent with affected-network recruitment. Moreover, 49.07% self-reported as non-deficient, and 7.46% were unaware of their status. While 99.07% correctly identified fava bean ingestion as a trigger and 74.25% identified certain medications, 62.50% incorrectly attributed hazard to pollen inhalation and 25.93% to pea consumption. Only 3.92% reported a hemolytic crisis, whereas 25.93% reported feeling unwell after smelling beans or inhaling pollen. Family and friends (49.81%) and healthcare providers (42.16%) were the primary information sources; schools (25.75%) and online resources (14.55%) were underrepresented. Overall, 90.45% perceived public information as insufficient—uniformly across G6PD strata (χ² = 0.09, p = 0.955). Exploratory analyses suggested lower perceived information adequacy among younger respondents (Cochran–Armitage Z = 2.92, p = 0.002) and, less robustly, among female respondents (χ² = 3.90, p = 0.048; borderline significance, unadjusted). Conclusions: Although recognition of fava bean ingestion as the principal dietary trigger is nearly universal, substantial gaps persist regarding non-ingestive exposures, less-recognized dietary triggers, and pharmacological risks. Perceived information insufficiency was independent of G6PD status but associated with younger age and female sex. Integrating targeted nutritional education into school curricula, primary care, and digital platforms is warranted for these priority groups and for G6PD-endemic populations worldwide. Full article

Caloric restriction (CR) is known to activate a broad spectrum of cytoprotective signaling pathways and enhance tissue tolerance to various stressors, including those associated with the cytotoxic effects of pharmaceutical agents. Nephrotoxic drugs, such as aminoglycoside antibiotics, remain a major clinical concern due to their frequent use and potential to cause acute kidney injury (AKI), for which effective preventive strategies are still limited. In this study, we investigated whether CR applied for 5 weeks (4-week pretreatment + 1-week concurrent with AKI induction) can alleviate AKI triggered by the antibiotic gentamicin, with a focus on evaluating changes in antioxidant-related parameters and autophagy-associated signaling during CR-mediated nephroprotection. CR’s nephroprotective effects were evaluated using diagnostic assays, Western blotting, and histological analysis. Additionally, oxidative stress markers and mitochondrial integrity were assessed to analyze the impact of CR on antioxidant-related pathways. CR significantly improved renal function and structure, with reduced kidney injury markers (KIM-1, NGAL) and alleviated histological damage. Critically, CR mitigated oxidative stress, evidenced by decreased thiobarbituric acid reactive substances (TBARS) and protein carbonylation, as well as increased levels of the reduced form of glutathione and activity of glutathione peroxidase (GPx). A lowered Bcl-X_L/X_S ratio was consistent with reduced apoptotic signaling, while reduced leukocyte infiltration reflected attenuated renal inflammation. Additionally, a reduction in mitochondrial DNA (mtDNA) lesions suggested that CR was associated with modulation of mitochondrial and metabolism-related pathways, with concurrent improvements in mitochondrial stability. Our findings demonstrate that CR attenuated gentamicin-induced AKI and was associated with changes in antioxidant-related parameters, reduced mtDNA damage, a decrease in inflammatory cell infiltration, and modulation of autophagy-related signaling. Full article

Background: Mild traumatic brain injuries (mTBIs) are a significant public health concern in the US. Understanding incidence and demographic patterns is essential for developing targeted prevention and intervention strategies. The most recent study using national healthcare records to examine incidence utilized data from 2016, highlighting the need for updated estimates that reflect current trends. Methods: The MarketScan^® Database was used for this study which includes person-specific clinical utilization, expenditures, and enrollment across different services. A query for mTBIs (S06.0x.xx) or post-concussion syndrome (F07.89) from January–December 2023 was performed for patients aged 0–64. Patients with the same diagnosis codes for the prior 12 months (i.e., chronic diagnosis), moderate to severe TBIs (S06.2–9), skull fractures (S02.xx), and/or brain hemorrhages (S06.3x) were excluded. Results: Out of 11,737,855 insured members with data in 2023, 43,213 new mTBIs were recorded (incidence rate = 0.37%), with the highest rate in adolescents (incidence rate = 1.27%). From the ages of 0–14 years, males had a higher incidence of concussion, but from 15 to 65 years, females had a higher incidence. Minimal differences were seen between urban and rural zip codes. Conclusions: Concussion incidence in adolescents is higher than other age groups, which may reflect increased participation in sports or heightened vulnerability during development. Males had a higher incidence than females during childhood, but females did later in life. These differences may reflect true disparities in injury risk, variations in reporting patterns, or a combination of both. Further research is warranted to understand the underlying mechanisms and to inform age- and sex-specific prevention efforts. Full article

The explosive growth of the Internet of Things (IoT) has brought an array of resource-constrained devices to domains such as smart homes, industrial automation, and healthcare, raising substantial cybersecurity challenges. Lightweight wireless protocols, such as Thread, Zigbee, and Z-Wave, are integral to IoT connectivity, but the degree to which their embedded cryptographic mechanisms satisfy formal cybersecurity certification schemes remains underexplored. This work draws primarily on recent peer-reviewed publications and major conference proceedings to rigorously evaluate Thread, Zigbee, and Z-Wave against the Common Criteria (CC) Functional Requirements for Cryptography (FCS) as specified in CC:2022 and the EU cybersecurity certification scheme on Common Criteria (EUCC). The assessment focuses on essential CC cryptographic components, including key generation (FCS_CKM.1), secure key distribution (FCS_CKM.2), agreement protocols (FCS_CKM_EXT.7), cryptographic operations (FCS_COP.1), and random bit generators (FCS_RBG.1). The analysis reveals that Thread demonstrates the strongest alignment with CC requirements by leveraging Advanced Encryption Standard—Counter with CBC-MAC mode (AES-CCM) authenticated encryption and Elliptic Curve Diffie-Hellman (ECDH)-based key exchange within a decentralized trust framework. Zigbee matches this cryptographic strength at the primitive level, but its dependency on a centralized Trust Center for key management complicates full compliance with key lifecycle and distribution controls. Z-Wave, especially through its S2 Security framework, improves by incorporating authenticated ECDH exchanges, though proprietary constraints and limited protocol transparency remain obstacles to independent assurance. This comparative study concludes that while all three protocols provide a baseline of robust cryptographic security, only Thread currently aligns with CC and EUCC certification schemes. Zigbee and Z-Wave will require additional protocol hardening and enhancement of cryptographic key lifecycle management to achieve comparable assurance levels. Ensuring conformance with formal cybersecurity standards is imperative for building trust and resilience across critical IoT infrastructures. Full article

Per- and polyfluoroalkyl substances (PFASs) are persistent micropollutants whose carbon–fluorine bonds resist conventional advanced oxidation. Nonthermal plasmas have emerged as a promising option for PFAS degradation, but the relative contributions of reactive oxygen species (ROS) and electrons are still being investigated. Herein, we compared sinusoidal alternating-current (AC) and nanosecond-pulsed discharges―in an identical plasma reactor with the same input power (30 W)―through diagnostics including voltage–current characterization, optical emission spectroscopy with vibrational and rotational temperatures and Hα Stark broadening for electron density, and aqueous H₂O₂ quantification. AC discharges produced more aqueous H₂O₂, stronger ·OH emission, and higher vibrational and rotational temperatures, yet showed lower perfluorooctanoic acid (PFOA) removal (85% ± 2%) and lower defluorination (61% ± 1%) than the pulsed discharge (96% ± 2% and 80% ± 2%, respectively). Among the diagnostics examined, electron density tracked the removal trend, being higher under pulsed operation (1.2 × 10¹⁶ vs. 8.3 × 10¹⁵ under AC operation). A pseudo-first-order kinetic model based on electron density qualitatively reproduced the observed PFOA decay rate, suggesting that the waveform may serve as a design variable for tuning electron and ROS-mediated pathways in plasma–water reactors. Full article

Background: A lean crystal engineering study was performed on the early pre-clinical POLθ inhibitor MSC178 to enable sufficient exposure for high-dose PK studies. Methods: COSMOquick-derived excess enthalpies in combination with a toxicological assessment of co-formers were used for the selection of four co-formers. Experimental crystallization trials were performed in a staged approach from a 15 mg scale, over a 50 mg upscale, to a final g-scale upscale of the most promising co-crystal form with 2,4-DHBA. Results: The 2,4-DHBA co-crystal form revealed more enhanced and sustained supersaturation plateaus in FaSSIF compared to the amorphous free base form, the 3,4-DHBA co-crystal form, and the 1,2-EDSA salt form. Moreover, the 2,4-DHBA co-crystal form was shown to be physically stable in the suspension vehicle for the PK study. The high physical stability toward physical-form conversion in the suspension vehicle as well as the more sustained supersaturation plateau in the non-sink dissolution profile could be attributed to the intrinsic features of the crystal structure as well as the assessed surface hydrophilicity of the co-crystal particles, both suggesting that rather hydrophobic surfaces are present that help preferentially attract stabilizing surfactants from the dissolution medium (taurocholate) and from the suspension vehicle (polysorbate, methocel), respectively. Successful upscale of the 2,4-DHBA co-crystal form was achieved in the small g-scale, revealing mainly isotropic crystal growth in primary particles as well as a pronounced tendency toward isotropically shaped dendrite-like secondary particles, both favored by a multi-dimensional hydrogen bonding network being present. Excellent agreement was shown for the extent of in vitro supersaturation behavior and in vivo exposure gain in the high-dose PK study for the 2,4-DHBA co-crystal form versus the amorphous free form. Conclusions: The co-crystal strategy can be successfully developed in early pre-clinical industrial research with lean methodologies to optimize sub-optimal phys.-chem. properties of a free base compound to achieve improved and less variable in vivo exposure between animals in high-dose PK studies. Full article

Emergency medical response is complex. The need to make time-based decisions that can impact people’s health requires careful examination. Network analysis, among other methods, can support that time-based decision making. This study explores network analysis through a multi-modal transportation network model to represent both fixed-wing air and ground Emergency Medical Services (EMS) resources. Methods: The study utilized open and EMS industry data to build a geospatial multi-modal network to model potential patient transfer across Alberta (Canada). Results: Within the study’s service area, ground transportation alone is more effective within 101 Km, at which threshold the addition of aerial transport begins to be more time effective, saving 9.7 min over ground transportation only. Between this distance and 417 Km, results show a mixed-use area where a combination of ground only and aerial travel is recommended based on the event pickup location, aircraft availability, and ambulance station location relative to high-speed roads. Beyond 417 Km, aerial transportation is consistently more efficient. There is a high correlation (R² = 0.82) between trip length and time difference between using ground only mode and combined air and ground. Lastly, the data showed air travel is 6.6 times more expensive than ground travel, with no modeled transfers identifying air as more time-effective than ground travel. Conclusions: Fixed-wing aircraft travel can have a positive impact on patient transfers; however, fluctuations in flight routes and times may require response agencies to implement time buffers to account for these variabilities. No cost savings were seen using fixed-wing aircraft, and the benefit of their use would be realized with efficient patient transfer times, as well as leaving ground ambulances in localized areas. Full article

Sexual violence against women frequently originates during adolescence, when structural inequalities and gendered power dynamics heighten vulnerability, making early identification of risk factors essential to prevent trajectories leading to sexual exploitation. This study presents the psychometric validation of the EDR-ESIA, a screening instrument designed to detect vulnerability to Child Sexual Exploitation (CSE) in healthcare, education, and social care settings, with particular relevance for prevention strategies targeting adolescent girls. The sample comprised 199 adolescents aged 11–17 years (M = 15.23; SD = 1.59) residing in Spain (58.8% female, 40.2% male, 1.0% unspecified), assessed by trained professionals using case records and reports. The 88-item instrument underwent expert review and pilot testing prior to validation, and its internal structure was examined using Partial Least Squares Structural Equation Modeling (PLS-SEM). The results indicated that all subdimensions and higher-order constructs showed an adequate fit to the theoretical model, supporting the instrument’s validity. Female adolescents scored significantly higher than males on CSE target indicators, reflecting a medium-to-large gender difference in vulnerability levels. Overall, the EDR-ESIA constitutes an evidence-based instrument for the timely recognition of CSE vulnerability, supporting prevention, education, and intervention efforts aimed at reducing sexual violence against women from early developmental stages. Full article

Background/Objectives: Wearable devices are increasingly used to support physical activity (PA), yet national patterns of use and their relationship with PA among cancer survivors remain unclear. Integration of wearable data into clinical care is also poorly understood. This study examined wearable use, its association with meeting PA guidelines, and health data-sharing with providers among U.S. adults with and without cancer. Methods: A cross-sectional analysis of the Health Information National Trends Survey (HINTS-7), a nationally representative survey of U.S. adults, was conducted. Survey weights and jackknife replication methods generated population-level estimates. Wearable use (yes/no), meeting PA guidelines (≥150 min/week moderate activity), and data-sharing behaviors were assessed. Weighted logistic regression evaluated associations between wearable use and meeting PA guidelines, including interaction by cancer history. Analyses also examined willingness to share and actual data-sharing. Results: The sample included 6084 U.S. adults. Wearable use was lower among cancer survivors (34.0%) than those without cancer (41.4%). Individuals using wearable devices were more likely to meet PA guidelines (ORs: 1.79–1.97), with the association being stronger among cancer survivors. Among cancer-surviving wearable users, willingness to share data with providers was high (77.5%), but actual sharing was substantially lower (35.4%). Few predictors of willingness were identified. Conclusions: Wearable use is associated with meeting PA guidelines at the population level, with potential relevance for cancer survivors. However, despite high willingness to share data, clinical integration remains limited, highlighting a gap between digital engagement and healthcare use. Strategies to improve integration of patient-generated data into care are needed. Full article

Background/Objectives: Heart failure (HF) remains a major cause of global mortality and morbidity; it is, therefore, of paramount importance that diagnosis and prognostication are made timely in order to better improve outcomes and reduce healthcare expenditure. This research presents a novel predictive model of heart failure that combines clinical criteria with demographic factors in order to maximize predictive performance and act as a reliable tool for individualized healthcare intervention. Methods: Complex machine learning techniques, including decision trees, random forest, and deep learning, are applied in analyzing a large dataset of subjects with heart failure. We collected a diverse dataset comprising clinical indicators such as echocardiographic data, biomarkers, electrocardiogram (ECG) features, and demographic information. Data preprocessing techniques, such as feature normalization and handling of missing values, were applied to ensure the integrity and reliability of the dataset. Results: The results indicate that integrating both clinical indicators and demographic characteristics significantly improves the predictive power of the model, compared to models based on clinical indicators alone. Specifically, the hybrid model demonstrated a superior ability to predict short- and long-term outcomes in heart failure patients, offering enhanced accuracy in risk stratification and prognosis prediction. Conclusions: This research highlights the potential of artificial intelligence (AI) and machine learning in revolutionizing heart failure care by providing healthcare professionals with more accurate, data-driven decision support tools. The proposed model not only holds promise for clinical applications but also offers insights for future research into personalized medicine. Full article

Counterfeit and unsafe medicines pose significant risks to patient safety and undermine trust in healthcare systems. This paper presents ACTMeds, a blockchain-supported pharmaceutical traceability and recall platform that considers pharmaceutical supply chain requirements and public health operational needs relevant to the Australian Capital Territory (ACT). The system integrates Ethereum smart contracts, developed using Ganache, with a React-based web application providing regulator, operator, pharmacy, and auditor interfaces, alongside a public verification portal leveraging QR and GS1 barcodes. In addition, role-based access control is enforced across the medicine lifecycle, including manufacture, custody transfer, dispensing, and recall, with immutable on-chain events generated to support auditability and accountability. To balance transparency with confidentiality, the platform prototypes a zero-knowledge (ZK) recall mechanism in which regulators can cryptographically prove that recall conditions meet predefined policy requirements without disclosing sensitive incident details. Threat modeling was conducted using the STRIDE framework, and security evaluation combined static application security testing (Solhint and ESLint) and dynamic testing. The paper further discusses deployment options, cost considerations, ZK recall performance analysis, ethical implications, and future enhancements. Security testing validated the platform’s resilience, with no high-severity vulnerabilities identified and medium-severity issues related to HTTP security headers addressed. The results indicate that a regulator-led, privacy-preserving, tamper-evident ledger can improve medicine authenticity verification and recall responsiveness while maintaining compliance and data protection obligations. Full article

Background: Diagnostic errors affect approximately 5–15% of clinical encounters globally, contributing to significant patient harm. Artificial intelligence-based clinical decision support systems (AI-CDSS) are increasingly deployed to augment clinician diagnostic performance, yet rigorous evidence from randomized controlled trials (RCTs) remains limited. This systematic review and meta-analysis aims to quantify the effect of AI-CDSS on diagnostic accuracy among healthcare professionals. Methods: We systematically searched PubMed/MEDLINE, CINAHL, Embase, Cochrane CENTRAL, and Google Scholar from 2000 to 2026. Eligible studies were peer-reviewed RCTs comparing AI-CDSS with standard care. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects meta-analysis was performed using standardized mean differences (SMD). Certainty of evidence was evaluated using GRADE. Results: Five RCTs (N = 12,657 participants) were included. The pooled SMD was 0.182 (95% CI: 0.003–0.362; p = 0.047; I² = 68.6%), with the lower confidence bound approaching zero, indicating preliminary evidence of a modest, statistically marginal improvement with AI-CDSS. Subgroup analyses suggested greater effects for deep learning systems and chest radiology applications, though single-study subgroups preclude definitive comparative conclusions. No significant publication bias was detected (Egger’s p = 0.18). GRADE certainty was rated MODERATE. Conclusions: This meta-analysis provides preliminary evidence that AI-CDSS may modestly improve diagnostic accuracy under specific conditions; however, the marginal statistical significance and near-zero lower confidence bound necessitate cautious interpretation. Implementation should prioritize contexts with demonstrated effectiveness and include ongoing outcome monitoring. Full article