Search Results (52,918)

Background: Reducing critically ill patients’ exposure to antibiotics is mandatory. In randomized controlled trials, procalcitonin (PCT)-guided algorithms (i.e., antibiotic therapy [ABT] should be stopped whenever PCT is less than 0.5 µg/L or is below 80% of the peak value) reduced the duration of (ABT) more than compliance with the current guidelines. However, the interest of such stopping rules in daily practice remains debated. Thus, we carried out a real-life study addressing this issue. Results: During the study period, 112 patients with sepsis upon intensive care unit admittance were included. The median age was 66 years (56–79). Half of the patients presented with acute respiratory failure. Pneumonia was diagnosed in 78% of them, and 41% met septic shock criteria. The initial ABT was empirical in most cases, and appropriateness rate to the isolated bacteria reached 71%. A median number of four PCT measurements was achieved in both groups. The compliance rate with the PCT algorithm was 54%. The median duration of ABT was 5 (4–7) days if the PCT algorithm was followed, as compared to 7 (5–10) days otherwise (p < 0.001). This ABT stopping rule allowed a 2-day reduction in the treatment duration as compared with those recommended by the guidelines (p < 0.001). The only independent factor associated with shorter treatment duration was compliance with the PCT algorithm (OR = 0.74, 95% CI [0.62; 0.88]; p < 0.001). Regarding safety, no difference in outcome was found between the two groups. Conclusions: Complying with one PCT-based stopping rule is associated with a significant reduction in the duration of ABT in septic critically ill patients, without apparent impact on patient outcomes. Full article

Background/Objectives: Limited access to mental health services contributes to poorer outcomes among individuals with mental health conditions, including major depressive disorder (MDD). Nurse-led interventions serve as a strategic model of care to improve mental health service delivery and enhance patient outcomes. This project aims to co-design a nurse-led telehealth family psychoeducation (FPE) for MDD and primarily assess its feasibility by evaluating the recruitment and retention rates. Methods: A multi-methods study encompassing a co-design phase (Study Phase 1) and a feasibility study (Study Phase 2). Study Phase 1 will involve semi-structured interviews with individuals with MDD and their families or significant others, as well as surveys and focus groups with mental health professionals to develop telehealth FPE for MDD. Study Phase 2 will evaluate the feasibility and acceptability of the intervention, which comprises three biweekly FPE sessions and a six-week follow-up with patient–family dyads using a single-group pre-post design. The primary outcomes comprise the feasibility and acceptability of intervention. Exploratory secondary outcomes include personal recovery, medication necessity beliefs and concerns, antidepressant adherence, and depression severity, measured at baseline, immediately post-intervention, and at 6-week follow-up using validated measures. Data analysis will primarily involve descriptive statistics and thematic analysis. The TIDieR checklist will be followed in reporting the intervention development. Conclusions: Findings from the proposed study will inform the design and protocol for a future randomised trial of telehealth FPE for improving clinical and non-clinical outcomes in MDD. The feasibility study was prospectively registered with the ClinicalTrial.gov on 8 June 2025 (NCT07014241). Full article

Accurate recognition of basic facial emotions is well documented, yet the mechanisms of misclassification and their relation to gaze allocation remain under-reported. The present study utilized a within-subjects eye-tracking design to examine both accurate and inaccurate recognition of five basic emotions (anger, disgust, fear, happiness, and sadness) in healthy young adults. Fifty participants (twenty-four women) completed a forced-choice categorization task with 10 stimuli (female/male poser × emotion). A remote eye tracker (60 Hz) recorded fixations mapped to eyes, nose, and mouth areas of interest (AOIs). The analyses combined accuracy and decision-time statistics with heatmap comparisons of misclassified versus accurate trials within the same image. Overall accuracy was 87.8% (439/500). Misclassification patterns depended on the target emotion, but not on participant gender. Fear male was most often misclassified (typically as disgust), and sadness female was frequently labeled as fear or disgust; disgust was the most incorrectly attributed response. For accurate trials, decision time showed main effects of emotion (p < 0.001) and participant gender (p = 0.033): happiness was categorized fastest and anger slowest, and women responded faster overall, with particularly fast response times for sadness. The AOI results revealed strong main effects and an AOI × emotion interaction (p < 0.001): eyes received the most fixations, but fear drew relatively more mouth sampling and sadness more nose sampling. Crucially, heatmaps showed an upper-face bias (eye AOI) in inaccurate trials, whereas accurate trials retained eye sampling and added nose and mouth AOI coverage, which aligned with diagnostic cues. These findings indicate that the scanpath strategy, in addition to information availability, underpins success and failure in basic-emotion recognition, with implications for theory, targeted training, and affective technologies. Full article

Purpose: Decentralized hearing care models facilitated by community health workers (CHWs) can improve access to care in low-income settings. Preset hearing aids, which offer user-selectable pre-developed amplification programs, may support such models, but little is known about their real-world use and alignment with clinical recommendations. Method: This longitudinal study formed part of a feasibility project implementing the World Health Organization’s (WHO’s) hearing aid service delivery approach in three low-income South African communities. Adults (≥18 years) with confirmed moderate-to-severe bilateral hearing loss were fitted with preset hearing aids by trained CHWs. Devices offered four preset amplification programs. Participant-driven selections were recorded at four distinct time points: fitting and follow-ups at 2 weeks, 2 months, and 6 months post-fitting. Results: In total, 36 participants (mean age = 76 years, SD = 8.9, range 50–96) were fitted with devices. Although over half (right: 52.8%, left: 58.3%) presented with high-frequency loss, only 34% initially selected the corresponding program. Most participants (80.6%, n = 29) changed their selections at least once over the six months. Significant associations between hearing loss configuration and selection occurred at some time points only in the left ear, but agreement with clinically recommended programs declined from 42% at baseline to 28% at six months. Conclusions: CHW-facilitated hearing aid delivery supports user autonomy in low-resource settings. However, frequent changes and divergence from clinically recommended programs suggest reliance on user-driven trial-and-error adjustments rather than audiometric fit, which may limit long-term benefit. Ongoing, person-centred guidance is needed for the effective use of preset hearing aids. Full article

Hypertension is a leading global cause of cardiovascular disease and mortality, with resistant hypertension (RH) posing treatment challenges. Aldosterone synthase inhibitors (ASIs) are a novel drug class that reduce blood pressure by lowering aldosterone levels. Baxdrostat is a selective ASI that inhibits the CYP11B2 enzyme, responsible for aldosterone synthesis, without affecting cortisol production. This selectivity minimizes hormonal side effects. Clinical trials have shown that baxdrostat reduces plasma aldosterone in a dose-dependent manner while preserving cortisol levels. In the Phase 2 BrigHTN trial, baxdrostat significantly lowered systolic and diastolic blood pressure in patients with RH, with the 2 mg dose showing the most consistent efficacy. However, in the HALO trial, similar blood pressure reductions were observed in the placebo group, possibly due to improved adherence to background antihypertensive therapy. Baxdrostat has demonstrated a favorable safety profile, with mostly mild adverse effects and no significant impact on kidney function. It is considered safe for use with other medications, including metformin. Ongoing trials are investigating its potential in patients with chronic kidney disease (CKD) and primary hyperaldosteronism (PA). Baxdrostat represents a promising therapeutic option for aldosterone-driven hypertension, especially in patients unresponsive to standard treatments. Full article

Background/Objectives: To assess the effectiveness of the most commonly used swallowing manoeuvres, exercises, and postural strategies as standalone interventions in the behavioural management of oropharyngeal dysphagia in adults. Methods: Systematic searches of two electronic databases, Embase and PubMed, were conducted in accordance with PRISMA guidelines to identify studies with comparison groups, including (pseudo) randomised controlled trials, comparative studies with concurrent controls, and within-subject or crossover study designs. The methodological quality of the included studies was assessed using the standard quality assessment tool (QualSyst). Results: Seventeen studies met the eligibility criteria, evaluating the effects of chin tuck, effortful swallow, the Mendelsohn manoeuvre, the modified jaw opening exercise, the volitional laryngeal vestibule closure manoeuvre, and the Shaker exercise. Most studies reported positive treatment outcomes, supporting the benefits of both compensatory and rehabilitative interventions across diverse populations, mainly derived from mixed groups and individuals post stroke. However, due to the limited number and significant heterogeneity of studies, a meta-analysis was only performed for the chin tuck, which showed a moderate positive effect. Overall, the evidence is preliminary and should be interpreted with caution. Conclusions: While current findings support the benefits of standalone behavioural interventions in oropharyngeal dysphagia, future research should focus on high-quality study designs with larger populations. Such studies need to consider variability in patient characteristics, intervention protocols, and outcome measures, with the use of advanced statistical methods enabling more definitive conclusions about the effectiveness of these interventions. Full article

Objectives: To evaluate the role of breech progression angle (BPA), a novel transperineal ultrasound parameter, as a predictor of external cephalic version (ECV) success, and to compare BPA between breech and transverse lie presentations. Methods: This prospective exploratory study was nested within a randomized clinical trial (NCT06449430) at Virgen de la Arrixaca University Hospital, Murcia, Spain. Eligible participants were pregnant women ≥18 years with a singleton fetus in non-cephalic presentation at term, without contraindications to vaginal birth. BPA was measured transperineally following standardized methodology prior to ECV, performed under either spinal analgesia or propofol sedation. Logistic regression models adjusted for maternal and obstetric variables assessed the association between BPA and ECV success. Receiver operating characteristic (ROC) curves were generated to evaluate predictive accuracy. Results: A total of 117 women were included: 100 with breech and 17 with transverse lie presentations. Median BPA was significantly higher in breech compared with transverse lie (87.2° vs. 70.2°, p < 0.001). In the overall cohort, BPA was not significantly associated with ECV success (OR 0.97, 95% CI 0.94–1.00; p = 0.068). However, in breech presentations, BPA was independently associated with ECV success (adjusted OR 0.95, 95% CI 0.91–0.99; p = 0.015). The area under the ROC curve for BPA predicting ECV success in breech cases was 0.64 (95% CI 0.53–0.73). Predictive accuracy was poor for transverse lie (AUC 0.27, 95% CI 0.08–0.56). Conclusions: BPA measured by transperineal ultrasound does not provide clinically useful information for predicting the success of external cephalic version, either in breech or transverse lie. Full article

Background: Anthracycline-based chemotherapy is associated with a risk of cancer therapy-related cardiac dysfunction (CTRCD), particularly in patients with moderate to high cardiovascular risk. Left ventricular global longitudinal strain (GLS) is a sensitive marker for early myocardial dysfunction, but the prognostic value of baseline GLS in this population remains unclear. Objective: We aimed to evaluate whether baseline GLS can predict CTRCD in moderate- to high-risk cancer patients undergoing anthracycline chemotherapy. Methods: In this prospective, single-center observational study, 80 anthracycline-naive cancer patients classified as moderate or high risk were enrolled. Baseline GLS was assessed via speckle-tracking echocardiography, with a threshold of ≥−18% considered decreased. Patients were followed for 12 months, and the primary endpoint was the development of CTRCD per ESC 2022 Cardio-oncology guidelines. Results: Of the 77 patients completing follow-up, 27.3% had decreased baseline GLS. CTRCD occurred in 62.4% of patients, with higher incidence among those with decreased GLS (76.7%) compared to those with normal GLS. In multivariable analysis, GLS ≥−18% was the only significant independent predictor of CTRCD (RR 12.0, 95% CI 2.0–71.9; p = 0.0065). All-cause mortality was also significantly higher in patients with decreased baseline GLS (19.1% vs. 1.8%, p = 0.018). Conclusions: Decreased baseline global longitudinal strain is an independent predictor of cancer therapy-related cardiac dysfunction and all-cause mortality in moderate- to high-risk patients receiving anthracycline therapy. These findings support the inclusion of baseline GLS in pre-treatment cardiovascular risk assessment, particularly in patients with an LVEF above 54%, to more effectively identify those who may benefit from early cardioprotective interventions. Full article

Background: Hyaluronic acid (HA) fillers are commonly used for midface augmentation because of their biocompatibility and reversibility. Nonetheless, discussions continue about their effectiveness and safety relative to other options. This systematic review and meta-analysis assess the effectiveness, duration, and side effects of HA fillers in midface volume restoration. Methods: Following PRISMA guidelines, a thorough search was performed on PubMed, CENTRAL, Web of Science, Scopus, and EMBASE up to March 2025. The review included randomized controlled trials (RCTs) that compared HA fillers with controls, such as placebo or alternative treatments, for midface augmentation. Results: A total of fourteen studies were included in the review, and five studies in the statistical analysis. Analysis of five RCTs involving 748 participants showed a higher and significant difference in GAIS responder rates between HA and control groups (RR = 3.27, 95% CI: 2.26–4.75, p = 0.79; I² = 95%). GAIS scores at 4, 8, and 24 weeks demonstrated no notable improvements (all p > 0.05). Adverse events were rarely reported, and there was no significant rise in moderate-to-severe adverse events associated with HA fillers (RR = 1.70, 95% CI: 0.08–34.55, p = 0.73). Conclusions: HA fillers used for midface augmentation are generally safe, they have very high midface augmentation and patient satisfaction value, but they might not provide a notable subjective aesthetic benefit over the other fillers. Clinicians need to take into account patient expectations and refine their techniques, all while recognizing the limitations of existing evidence. Future research should include objective volumetric measurements and extend follow-up durations. Full article

The quality and durability of adhesive joints in wood flooring are determined by both the type of adhesive and the parameters of the bonding process. This study examines the effects of pressing time and seasoning time on the bending strength of adhesive joints in the middle layer of floorboards manufactured using innovative block-bonding technology. Experimental trials were conducted with two adhesive systems—polyvinyl acetate (PVAC) and polyurethane (PUR)—using a full factorial design and statistical evaluation of joint strength in terms of pressing time and seasoning time. For PVAC, an overall tendency toward increased strength with extended pressing time was observed; however, the strongest effects were associated with interactions between pressing and seasoning times, with the most favorable results obtained for short pressing (5 min) combined with extended seasoning (5 h). In the case of PUR, the relationships were non-linear, and the only statistically significant factor was the interaction between pressing and seasoning times, confirming the necessity of joint optimization. The findings demonstrate that simple one-factor analyses are insufficient to explain adhesive performance, as non-linear and interaction effects are critical in defining joint strength. The results provide new insights for optimizing bonding processes in floorboard production, supporting improvements in material efficiency and mechanical reliability of wood flooring. Full article

As a staple cereal worldwide, winter wheat plays a pivotal role in food security. Leaf chlorophyll serves as a direct indicator of photosynthetic performance and nitrogen nutrition, making it critical for precision management and yield gains. Consequently, rapid, nondestructive, and high-accuracy remote-sensing retrievals are urgently needed to underpin field operations and precision fertilization. In this study, canopy hyperspectral reflectance together with destructive chlorophyll assays were systematically acquired from Yangling field trials conducted during 2018–2020. Three families of spectral indices were devised: classical empirical indices; two-dimensional optimal spectral indices (2D OSI) selected by correlation-matrix screening; and novel three-dimensional optimal spectral indices (3D OSI). The main contribution lies in devising novel 3D OSIs that combine three spectral bands and demonstrating how their fusion with classic two-band indices can improve chlorophyll quantification. Correlation analysis showed that most empirical vegetation indices were significantly associated with chlorophyll (p < 0.05), with the new double difference index (NDDI) giving the strongest relationship (R = 0.637). Within the optimal-index sets, the difference three-dimensional spectral index (DTSI; 680, 807, and 1822 nm) achieved a correlation coefficient of 0.703 (p < 0.05). Among all multi-input fusion schemes, fusing empirical indices with 3D OSI and training with RF delivered the best validation performance (R² = 0.816, RMSE = 0.307 mg g⁻¹, MRE = 11.472%), and external data further corroborated its feasibility. Altogether, integrating 3D spectral indices with classical vegetation indices and deploying RF enabled accurate, nondestructive estimation of winter wheat chlorophyll, offering a new hyperspectral pathway for monitoring crop physiological status and advancing precision agricultural management and fertilization, can guide in-season fertilization to optimize nitrogen use, thereby advancing precision agriculture. Full article

Underwater exploration relies heavily on autonomous underwater vehicles and sensor platforms for sustained monitoring of marine environments, yet their operational duration is limited by energy constraints. To enhance energy efficiency, various control strategies have been proposed, including robust, optimal, and disturbance-aware approaches. Recent work introduced a variable structure controller (VSC) with a constant-amplitude control action for depth control of a platform equipped with a variable buoyancy module, achieving an average 22% reduction in energy use in comparison with conventional PID-based controllers. In a separate paper, the conditions for its closed-loop stability were proven. This study extends these works by proposing a controller with a variable-amplitude control action designed to minimize energy consumption. A formal proof of stability is provided to guarantee safe operation even under conservative assumptions. The controller is applied to a previously developed depth-regulated sensor platform using a validated physical model. Additionally, this study analyzes how the controller parameters and mission requirements affect stability regions, offering practical guidelines for parameter tuning. A method to estimate oscillation amplitude during hovering tasks is also introduced. Simulation trials validate the proposed approach, showing energy savings of up to 16% when compared to the controller using a constant-amplitude control action. Full article

Background: Small cell lung cancer (SCLC) is a malignant carcinoma characterized by high proliferative rate and early metastatization with limited treatment options and poor prognosis. The approval of ICIs has established a new standard of care for extensive-stage (ES)-SCLC (5). Atezolizumab, an anti PD-L1 monoclonal antibody, has been the first immune checkpoint inhibitor (ICI) to be approved for SCLC patients. This study aims to retrospectively evaluate the real-world effectiveness and safety of atezolizumab in a cohort of patients with ES-SCLC. Methods: We conducted a monocentric retrospective analysis of SCLC patients who received atezolizumab in addition to chemotherapy, between January 2020 and December 2023. Study design endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Results: A total of 134 patients were included in this study. Out of 134 patients who began the CEA protocol, 100 continued maintenance. Currently, 25 are alive, 17 still on atezolizumab, 5 on second-line therapy, and 3 receiving best supportive care. The median age was 65 years. Patients received a median of four cycles of CEA (range 1–6 cycles), while the median number of atezolizumab maintenance cycles was eight (range 0–75). The overall median survival was 15 months, with patients who received more than 30 cycles of atezolizumab showing OS of 46.7% at 48 months. Common adverse events included skin disorders, pneumonitis, colitis, alanine, and aspartate deaminase increment, dysthyroidism, and blood disorders with only 3% of patients experiencing grade 3 or higher toxicities. Conclusions: In this real-world cohort, atezolizumab demonstrated comparable effectiveness to clinical trial results, with a manageable safety profile. These findings support the use of atezolizumab as a viable treatment option for ES-SCLC in routine clinical practice. Full article

Ferroptosis, an iron-dependent form of regulated cell death marked by lipid peroxidation, has emerged as a promising therapeutic target in breast cancer, particularly in aggressive subtypes such as triple-negative breast cancer (TNBC). This systematic review explores the molecular mechanisms underlying ferroptosis sensitivity and resistance, focusing on the interplay between iron metabolism, antioxidant defenses, and tumor microenvironmental factors. Literature retrieved from PubMed and Scopus up to May was analyzed in accordance with PRISMA guidelines, including mechanistic studies, preclinical experiments, and ongoing clinical trials. Findings reveal that breast cancer cells evade ferroptosis through enhanced glutathione synthesis, upregulation of GPX4 and system Xc- and adaptive metabolic reprogramming; yet these same mechanisms create exploitable vulnerabilities, including dependence on cystine, polyunsaturated lipids, and dysregulated iron handling. Therapeutic strategies that target key ferroptosis regulators, such as GPX4, ACSL4, and SLC7A11, or that harness agents like statins, sulfasalazine, and nanoparticle-based iron complexes demonstrate strong potential to overcome chemoresistance and selectively eliminate therapy-resistant cancer cell populations. Taken together, the evidence highlights ferroptosis as a critical Achilles’ heel of breast cancer biology and supports further clinical translation of ferroptosis-inducing therapies to improve outcomes in otherwise refractory breast cancer subtypes. Full article

Background: Remote ischemic conditioning (RIC) has shown promise as a neuroprotective strategy, but its application in children with cerebral palsy (CP) remains unexplored. We conducted a randomized controlled trial to evaluate the feasibility, safety, and tolerability of repeated, 6–7 sessions of RIC in children with unilateral CP. Methods: Fifty-one children aged 6–16 years with unilateral CP were randomized (1:1) to receive RIC or sham conditioning on the more affected arm. Primary feasibility outcomes included recruitment metrics, intervention adherence, retention, and protocol fidelity. Safety endpoints included continuous monitoring of oxygen saturation, blood pressure, heart rate, and adverse event incidence. Tolerability was assessed via child-reported pain ratings, conditioning pressure tolerance, skin integrity evaluations, and session adherence. Results: Of 148 children screened, 51 were randomized to RIC (n = 25), sham (n = 26) groups; 48 (94.1%) completed the intervention as allocated. Recruitment yielded 2.04 participants/month. Intervention adherence was 100% in both groups. RIC was well tolerated, with mean pain scores 2.8 ± 3.1 during inflation in RIC and 0.3 ± 0.8 in Sham group. No serious adverse events occurred. Physiological parameters remained stable across 314 conditioning sessions; no clinically significant hypoxemia, blood pressure derangements, or arrhythmias were detected. Minor adverse events (transient erythema, mild discomfort) were rare (2.22%) and self-limiting. Skin integrity was preserved, and no participants required session termination. Conclusions: Repeated RIC is feasible, safe, and tolerable in children with unilateral CP. These findings support the design of future trials using RIC as a priming agent to enhance pediatric neurorehabilitation outcomes. Full article