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Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Abstract Key message A Soil Monitoring Law to improve soil health across all land uses has been proposed by the European Commission. As forests soils have different chemical and physical properties as well as biogeochemical dynamics compared to agricultural land, they also face different challenges in maintaining and restoring soil health. Examples are soil acidification, eutrophication by atmospheric deposition, responses to climate change, and loss of biodiversity. Therefore, we propose forest soil specific health descriptors and thresholds based on experience and knowledge from existing long-term monitoring programs.

Background: Despite the many guidelines for reprocessing of medical instruments, challenges persist such as microbial resistance to biocides, corrosive effects on materials, and time-consuming reprocessing procedures. Ultraviolet (UV) C light-emitting diode (LED) chambers might provide a solution but the integration in healthcare is still in its infancy. Here, we evaluated the efficacy of a novel ZAPARAY™ UVC LED chamber as a time and energy-efficient alternative for reprocessing of medical instruments for which current disinfection protocols exhibit limitations. Methods: We verified the disinfection efficacy of the UVC LED chamber on a Petri dish and contaminated several medical devices with Staphylococcus aureus ATCC 25923. The bacterial reduction was assessed after 5 min of UVC LED exposure. Additionally, we investigated the impact of rinsing before UVC exposure. Results: We demonstrated a bacterial reduction of 9 log10 on a Petri dish. Non-rinsed dental tools exhibited varied reduction levels ranging from a 3.23 log10 to a 6.25 log10 reduction. Rinsing alone yielded an average reduction of 2.7 log10 and additional UVC exposure further reduced the bacterial load by an average of 3.65 log10. We showed an average 4.90 log10 reduction on thermistors, 2 log10 or less on orthodontic pliers, and no reduction on handpieces. Conclusions: This study demonstrates that UVC LED chambers may be used as a standardized substitute for specific (manual) disinfection procedures of certain medical devices, offering a time-efficient and more sustainable alternative. However, its use should be preceded by efficacy testing for each specific type of instrument.

A library of knowledge that contains a fabric database, 3D human body models database, and 3D garment database has been developed in the framework of the Erasmus+ project DigitalFashion – “Collaborative Online International Learning in Digital Fashion”, which is a collaboration of 6 European partners who would like to strengthen their working together through collaboration in online international teaching. The fabric database contains 49 physical textile fabrics, both woven and knitted fabrics. Each partner provided at least eight fabrics. The library contains also 3D human body models of different sizes (male, and female), and 48 pattern designs for women’s and men’s garments. The fabric’s physical and visual parameters have been determined using known textile standards, including their draping images taken using a Cusick Drape Tester. These fabric parameters have been used to predict the equivalent digital twin fabric based on Lectra digital fabrics, thereby completing the fabric database with their matching digital twin fabric. The digital twin fabrics have been used to simulate the 3D garments for the 3D garment database, based on the selected patterns and styles. To test the robustness of the fabric digitization process, a woman A-line skirt (real) was made by each partner using their fabric. These skirts were then compared with their simulated (virtual) skirts. The investigation has shown that the digital twin fabrics represent the real fabrics well. The virtual training library will support the specially developed training platform for virtual fashion design.

Introduction Modern intraocular lens (IOL) designs for cataract treatment can be broadly classified into three focal range categories; monofocal, extended depth-of-focus (EDOF) and multifocal IOLs.Monofocal IOLs allow spectacle independence for one focus, typically distance. In contrast, EDOF IOLs provide a greater range of vision, extending spectacle independence to intermediate distance, while multifocal IOLs enable spectacle independence at all distances with the drawback of positive dysphotopsias and reduced contrast perception.EDOF lenses are an attractive compromise with fewer dysphotopic side effects than multifocals. The purpose of this study is to assess whether implanting an EDOF IOL in the second eye of a patient who received a monofocal IOL in the first eye can improve spectacle independence while maintaining the same optical quality as bilateral monofocal IOL implantation.Methods and analysis This study compares combined monofocal and EDOF IOL implantation versus bilateral monofocal IOL implantation in terms of clinical and patient-reported outcomes in a monocentric, randomised, patient-masked and assessor-masked, parallel group trial in 88 bilateral cataract patients. The primary outcome measure is binocular photopic distance corrected intermediate visual acuity. The secondary outcome measures include (un)corrected distance and near visual acuity, reading speed at intermediate distance, quality of visual function assessments, patient-reported spectacle independence, contrast sensitivity, aberrometry, stereopsis and straylight measurement at the 3-month follow-up.Ethics and dissemination The protocol was approved by the ethical committee of the University Hospital of Brussels (BUN 23219_EDOF).Trial registration number NCT06002399

Abstract Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication system. Besides the use of EVs in biomarker studies and diagnostics, the potential of EV‐therapeutics has been seen by many. They provide unique properties for disease therapy, including strong immune‐modulatory actions, the possibility of engineering, low immunogenicity, and the capability of crossing biological barriers. Proof‐of‐concept of EV‐therapeutics for various pathologies has been achieved in preclinical studies. However, clinical trials with EVs have only been emerging slowly. Here, we aim to provide a comprehensive overview of the current state‐of‐the‐art concerning clinical studies using EVs in human therapy. By approaching the current knowledge in a systematic manner, we were able to include 21 reports for meta‐analysis of safety and evaluation of efficacy outcomes. Overall, we have shown that EV‐based therapy is safe with a low incidence of serious adverse events (SAE; 0.7% (95%‐CI: 0.1–5.2%), and adverse events (AE; 4.4% (95%‐CI: 0.7–22.2%). Subgroup analysis showed no significant difference in SAE when comparing autologous versus allogeneic administration, as well as engineered versus non‐engineered EV products. A significantly higher number of AE was seen in autologous versus allogeneic administration. However, the clinical relevance remains questionable. Evaluation of the clinical outcomes of immunostimulatory, immunosuppressive or regenerative EV‐therapies indicated improvement in the majority of treated patients. Despite these promising results, data need to be approached with caution due to a high heterogeneity in the EVs manufacturing methods, study design, and reporting of (S)AE. Overall, we conclude that EV‐based therapy is safe and presents a promising opportunity in therapy. More efforts are needed in the standardization and harmonization of reporting of EV isolation and characterization data as well as in the reporting of (S)AE to allow inter‐study comparison.

Abstract Background Direct oral anticoagulants for the treatment of venous thromboembolism are supported by robust clinical trial evidence. Despite published guidance, general practitioners are faced with increasingly complex decisions and implementation remains sub-optimal in certain real-world scenarios. Methods A two stage formal consensus exercise was performed to formulate consensus statements and a summary guide, facilitating optimal management of direct oral anticoagulants in venous thromboembolism patients by generalist physicians across Europe. An online questionnaire distributed to a broad panel (Phase 1), followed by a virtual panel discussion by an expert group (Phase 2) were conducted. Phase 1 statements covered nine management domains, and were developed via a literature review and expert steering committee. Participants rated statements by their level of agreement. Phase 1 responses were collated and analysed prior to discussion and iterative refinement in Phase 2. Results In total 56 participants from across Europe responded to Phase 1. The majority had experience working as general practitioners. Consensus indicated that direct oral anticoagulants are the treatment of choice for managing patients with venous thromboembolism, at initiation and for extended treatment, with a review at three to six months to re-assess treatment effect and risk profile. Direct oral anticoagulant choice should be based on individual patient factors and include shared treatment choice between clinicians and patients; the only sub-group of patients requiring specific guidance are those with cancer. Conclusion Results demonstrate an appreciation of best practices, but highlight challenges in clinical practice. The patient pathway and consensus recommendations provided, aim to highlight key considerations for general practice decision making, and aid optimal venous thromboembolism treatment.

Abstract Background Rotator cuff (RC) tendinopathy is the most reported shoulder disorder in the general population with highest prevalence in overhead athletes and adult working-age population. A growing body of evidence support exercise therapy as an effective intervention, but to date there are no prospective randomized controlled trials addressing pain as an intervention variable. Methods A single-site, prospective, pragmatic, assessor-blinded randomized controlled superiority trial. Eighty-four patients aged 18–55 years with chronic (symptom duration over 3 months) RC tendinopathy are randomized 1:1 to receive shoulder exercise during which pain is either allowed or avoided. The intervention period lasts 26 weeks. During that period, participants in both groups are offered 8 individual on-site sessions with an assigned sports physiotherapist. Participants perform home exercises and are provided with a pain and exercise logbook and asked to report completed home-based exercise sessions and reasons for not completing sessions (pain or other reasons). Patients are also asked to report load and the number of sets and repetitions per sets for each exercise session. The logbooks are collected continuously throughout the intervention period. The primary and secondary outcomes are obtained at baseline, 6 weeks, 26 weeks, and 1 year after baseline. The primary outcome is patient-reported pain and disability using the Shoulder PAin and Disability Index (SPADI). Secondary outcomes are patient-reported pain and disability using Disability Arm Shoulder and Hand short-form (Quick DASH), and shoulder pain using Numeric Pain Rating Scale. Objective outcomes are shoulder range of motion, isometric shoulder muscle strength, pain sensitivity, working ability, and structural changes in the supraspinatus tendon and muscle using ultrasound. Discussion The results of this study will contribute knowledge about the treatment strategies for patients with RC tendinopathy and help physiotherapists in clinical decision-making. This is the first randomized controlled trial comparing the effects of allowing pain versus avoiding pain during shoulder exercises in patients with chronic RC tendinopathy. If tolerating pain during and after exercise proves to be effective, it will potentially expand our understanding of “exercising into pain” for this patient group, as there is currently no consensus. Trial registration ClinicalTrials.gov NCT05124769. Registered on August 11, 2021.

Background: Septic arthritis (SA) of the native adult hip is a rare orthopaedic emergency requiring prompt diagnosis and treatment. As clinical presentation and laboratory findings are frequently atypical, advanced imaging is often requested. This retrospective study aimed to investigate the prevalence and pattern of extra-articular infectious manifestations and their implications for pre-operative advanced imaging in patients with proven SA of the native hip joint. Methods: Out of 41 patients treated surgically for SA of the native hip during a 16-year period at our tertiary referral hospital, 25 received advanced imaging (computed tomography (CT), magnetic resonance imaging (MRI), or fluorodeoxyglucose positron emission tomography (FDG PET-CT)) prior to initial intervention. For each investigation, a specific set of variables was systematically interpreted, and the most suitable surgical approach was determined. The prognostic value was evaluated by comparing specific outcome measures and the extent of extra-articular involvement. Results: It was found that 32 % of patients had an abscess in one anatomical region, 32 % of patients had abscesses in multiple anatomical regions, and only 36 % of patients had no substantial abscess. Gluteal abscesses were especially common in patients with SA due to contiguous spread. Abscesses in the iliopsoas region were more common in patients with SA due to hematogenous seeding. A combination of several different surgical approaches was deemed necessary to adequately deal with the various presentations. No significant prognostic factors could be identified. Conclusion: We recommend performing advanced imaging in patients with suspected or proven septic arthritis of the native hip joint, as extra-articular abscesses are present in 64 % and might require varying anatomical approaches.

Abstract Actions are biased by the outcomes they can produce: Humans are more likely to show action under reward prospect, but hold back under punishment prospect. Such motivational biases derive not only from biased response selection, but also from biased learning: humans tend to attribute rewards to their own actions, but are reluctant to attribute punishments to having held back. The neural origin of these biases is unclear. Specifically, it remains open whether motivational biases arise primarily from the architecture of subcortical regions or also reflect cortical influences, the latter being typically associated with increased behavioral flexibility and control beyond stereotyped behaviors. Simultaneous EEG-fMRI allowed us to track which regions encoded biased prediction errors in which order. Biased prediction errors occurred in cortical regions (dorsal anterior and posterior cingulate cortices) before subcortical regions (striatum). These results highlight that biased learning is not a mere feature of the basal ganglia, but arises through prefrontal cortical contributions, revealing motivational biases to be a potentially flexible, sophisticated mechanism.

Background: Conventional treatment options for end-stage heart failure (ESHF) in children include heart transplantation (HT) and ventricular assist devices (VADs), both with significant drawbacks in the pediatric population. Pulmonary artery banding (PAB) has been effectively used as bridge to transplant or recovery in pediatric ESHF. We herein describe the early and mid-term clinical outcomes from a multicenter international experience. Methods: This is a multicenter retrospective study including children admitted for ESHF caused by dilated cardiomyopathy and treated with PAB. The primary outcome was the freedom from death/VAD/HT. Results: Thirty-one patients (median age 210 days [131-357]) with ESHF underwent PAB in 5 centers. Pediatric Interagency Registry for Mechanically Assisted Circulatory Support (PEDIMACS) score was I to III in 90%; 15 patients were intubated preoperatively. Preoperative left ventricular (LV) ejection fraction was

Abstract Background Bacterial vaginosis increases risk of preterm birth and low birthweight, adverse pregnancy outcomes that disproportionately affect low‐ and middle‐income countries (LMICs). Objectives We aimed to estimate the prevalence of bacterial vaginosis among pregnant women attending antenatal care in LMICs between 2000 and 2020. Search Strategy We conducted a systematic review of PubMed, Embase and five regional databases. Selection Criteria We included studies conducted in LMICs and published between 2000 and 2020 in which bacterial vaginosis prevalence was reported among pregnant women attending antenatal care. Data Collection and Analysis We corrected point estimates and applied random‐effects models to generate pool prevalence estimates. We carried out subgroup analyses by study year, country‐income level, HIV prevalence, sample size, diagnostic method, trimester of pregnancy, presence of symptoms at diagnosis and risk of bias. Main Results Of 1132 publications, 74 studies met inclusion criteria, contributing 80 data points from 46 661 pregnant women. Overall pooled mean prevalence across LMICs was 15.7%. Regional prevalence ranged from 25.1% in sub‐Saharan Africa to 7.4% in Central and Southern Asia. Prevalence was 33.4% in studies where HIV prevalence was ≥10%, and 6.6% in which HIV prevalence was

Introduction There is a lack of distinct and measurable outcomes in psychiatric and/or mental health nursing which negatively impacts guiding clinical practice, assessing evidence-based nursing interventions, ensuring future-proof nursing education and establishing visibility as a profession and discipline. Psychiatric and/or mental health nursing struggle to demonstrate patient-reported outcomes to assess the effectiveness of their practice. A systematic review that summarising patient-reported outcomes, associated factors, measured nursing care/interventions and used measurement scales of psychiatric and/or mental health nursing in the adult population in acute, intensive and forensic psychiatric wards in hospitals will capture important information on how care can be improved by better understanding what matters and what is important to patients themselves. This review can contribute to the design, planning, delivery and assessment of the quality of current and future nursing careMethods and analysis This protocol follows the Cochrane methodological guidance on systematic reviews of interventions and The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol. The search strategy will be identified by consultations with clinical and methodological experts and by exploring the literature. The databases Ovid MEDLINE, CINAHL, EMBASE, APA PsychARTICLES, Web of Science and Scopus will be searched for all published studies. Studies will be screened and selected with criteria described in the population, intervention, control and outcomes format after a pilot test by two researchers. Studies will be screened in two stages: (1) title and abstract screening and (2) full-text screening. Data extraction and the quality assessment based on the Johanna Briggs Institute guidelines will be conducted by two researchers. Data will be presented in a narrative synthesis.Ethics and dissemination No ethical approval is needed since all data are already publicly accessible. The results of this work will be published in a peer-reviewed scientific journal.PROSPERO registration number CRD42023363806.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of leukemia caused by accumulation of multiple genetic alterations in T-cell progenitors. However, for many genes it remains unknown how their mutations contribute to disease development. Therefore, we performed two single-cell CRISPR screens in primary pro-T cells ex vivo to study the transcriptional impact of loss-of-function alterations in T-ALL and correlate this with effects on cell fitness. The various perturbations were clustered based on their effects on E2F/MYC or STAT/NOTCH signatures, which play a defining role in driving T-cell proliferation. Many of the perturbations resulted in positive effects on the STAT and NOTCH signatures and were predicted to behave as haploinsufficient tumor suppressors in T-ALL. Additionally, Spi1 was identified as an essential gene for pro-T cell survival, associated with deregulation of the MYC signature and epigenetic consequences. In contrast, Bcl11b was identified a strong tumor suppressor gene in immature T lymphocytes, associated with deregulation of NF-kB and JAK/STAT signaling. We found a correlation between BCL11B expression level and JAK/STAT pathway mutations in T-ALL patients and demonstrated oncogenic cooperation between Bcl11b inactivation and JAK3 hyperactivation in pro-T cells. Altogether, these single-cell CRISPR screens in pro-T cells provide fundamental insights in the mechanisms of transcriptional deregulation caused by genetic alterations in T-ALL.

IntroductionVaginal Candida colonization (CC) can lead to vulvovaginal candidiasis, the second most prevalent vaginal condition worldwide, and has been associated with adverse birth outcomes. However, no data on CC in the Democratic Republic of the Congo are available. We investigated the prevalence, Candida species, clinical correlates, risk factors and pregnancy outcomes in women with CC in the second trimester of pregnancy.Material and methodsIn Bukavu, the Democratic Republic of the Congo, pregnant women were recruited during antenatal care between 16 and 20 weeks of gestation from January 2017 to October 2017 and followed until delivery. Sociodemographics, sexual behavioral, hygienic and clinical characteristics, microbiological data and pregnancy outcomes were collected. Candida detection and speciation was performed with microscopy (Gram-stained smears and wet-mount) and/or quantitative PCR. Multivariate regression models were used to estimate the different associations with CC.ResultsThe prevalence of CC by wet mount, microscopy of Gram-stain smears and qPCR was 27.9%, 28.1% and 38.2%, respectively. C. albicans was the most prevalent Candida species (91.0%). Previous genital infections, an intermediate vaginal microbiota, bacterial vaginosis, and the use of pit toilets were risk factors for CC. Clinically, CC was associated with itching only. Women with CC had twice the odds for preterm birth, if Candida concentration was high, the odds were four times higher.ConclusionsIn Bukavu, the Democratic Republic of the Congo, the prevalence of CC was high and associated with microbiological and modifiable risk factors. Screening and treatment for CC during antenatal care should be investigated as a possible strategy to reduce preterm birth.

We describe vaginal microbiota, including Gardnerella species and sexually transmitted infections (STIs), during pregnancy and their associations with recurrent spontaneous preterm birth (sPTB). We performed a prospective cohort study in a tertiary referral centre in the Netherlands, among pregnant women with previous sPTB

IntroductionImplementing a self-refereeing system presents a unique challenge in sports education, particularly in academic and training settings where officiated sports prevail. However, Ultimate Frisbee stands out by entrusting players with both athlete and referee roles, introducing distinctive ethical complexities. This manuscript is intended to evaluate ethical behavior and self-control within the Spirit of the Game (SOTG) scoring system in Elite Ultimate. To address these, Ultimate employs the (SOTG) scoring system, integral since the sport's inception in the late 1980s. SOTG aims to enhance and evaluate athletes’ ethical conduct. This study evaluates SOTG's effectiveness in elite-level Ultimate, analyzing variations across divisions and age groups in three high-level tournaments.MethodsUsing a cross-sectional design, data were collected from five international Ultimate tournaments in 2022. Teams spanned diverse age groups (under 17 to over 50) and divisions (women's, mixed, open). Post-match, teams assessed opponents’ SOTG in five domains: Rules knowledge, fouls, fairness, attitude/self-control, and communication. Ratings used a 5-point Likert scale (“poor” to “excellent”). An overall SOTG score was calculated by aggregating domain scores.ResultsOur study consistently revealed high SOTG scores, reflecting strong sportsmanship. “Positive attitude and self-control” consistently ranked highest, while “Knowledge and use of the rules” scored lowest. Divisional differences in SOTG were statistically insignificant. Notably, WMUCC2022 (participants aged 30+) had significantly higher SOTG scores, possibly indicating age-related self-control improvement or evolving sport culture. Lower rules knowledge scores may stem from linguistic translation challenges.ConclusionSelf-refereeing promotes ethical behavior across divisions and age groups. SOTG underscores sportsmanship's importance and aligns with International Olympic Committee (IOC) and with Sustainable Development Goals (SDGs), particularly SDG 3, 4, 5 and 16 fostering a fairer, healthier, and more peaceful world.