Yulius

ABSTRACTMetabolic dysfunction‐Associated Steatotic Liver Disease (MASLD) is a growing clinical challenge, necessitating effective diagnostic strategies to identify advanced liver fibrosis while minimising unnecessary referrals of mild cases. Current clinical guidelines recommend care pathways utilising non‐invasive tests (NITs) to stratify patients, but the optimal diagnostic algorithm across care settings remains unclear. This state‐of‐the‐art review systematically examines studies describing clinical care pathways for detecting advanced fibrotic MASLD and stratifying patients at risk. A comprehensive literature search of MEDLINE, Embase, Cochrane Library, and Scopus, finalised in January 2026, identified nine relevant studies that met predefined criteria including structured care plans and applicability beyond diagnosis alone. Pathway populations included patients at risk for MASLD (type 2 diabetes (n = 4) or broad range cardiometabolic risk factors (n = 1)) or confirmed MASLD (n = 4). The most frequently employed NITs were FIB‐4 and vibration‐controlled transient elastography (VCTE). Numbers needed to screen (NNS) for hepatology referral and advanced fibrosis detection varied considerably across pathways and populations, reflecting heterogeneity in design and fibrosis assessment methods. All studies reported improved patient risk stratification; attendance rates declined at each pathway step. Findings suggest that NIT‐based clinical care pathways can effectively align patient management and optimise transmural care for MASLD. Nonetheless, heterogeneity in pathway design and fibrosis determination highlights the need for standardised protocols and validation in larger, at‐risk cohorts to strengthen evidence supporting widespread adoption. This review contributes to advancing MASLD management within evolving clinical frameworks.

PurposeApplying standardized Brighton Collaboration (BC) case definitions retrospectively to heterogeneous real-world data (RWD) is challenging due to inconsistent clinical detail and data structures across settings. To address this, the Vaccine Monitoring Collaboration for Europe (VAC4EU) developed a structured validation pipeline that operationalizes BC case definitions for vaccine safety outcomes in RWD in a harmonized, scalable, and reusable manner.MethodsVAC4EU developed a systematic, stepwise approach to validate vaccine safety outcomes. BC case definitions were utilized when available, adapted for RWD as needed, and newly developed for outcomes without an existing BC definition. The approach involves: 1) Critical review and adaptation of BC definition by clinical and RWD experts; 2) Creation of dummy cases based on published reports; 3) Creation of REDCap electronic data collection forms (eDCF) incorporating decision logic to assigned levels of certainty (LOC); 4) Iterative testing of decision logic; and 5) comprehensive training of abstractors with real-time feedback. A dedicated task force assigned reference LOCs for dummy cases. Inter-rater reliability was measured using Fleiss’ kappa (κ) by comparing abstractor LOCs to the reference standard.ResultsThe pipeline was applied to 16 COVID-19 vaccine safety outcomes, of which 13 had existing BC definition. In total, 78 dummy case descriptions were developed across the outcomes for training of abstractors, and 15 REDCap eDCFs were created. Myocarditis and pericarditis shared an eDCF. Across 33 abstractors, 747 dummy case abstractions were completed. Agreement analysis showed 93 discrepancies (12.4%) and moderate overall concordance (κ = 0.55, across all outcomes), with the lowest for thrombosis with thrombocytopenia syndrome (κ = –0.05).ConclusionThe VAC4EU validation pipeline provides a standardized framework for training and validating vaccine safety outcome in RWD. By adapting BC case definitions and dedicated training of abstractors, we will reduce variability in outcome validation in post-authorization safety studies.

Este artigo analisa as estratégias discursivas do bolsonarismo no Brasil em comparação com o trumpismo nos Estados Unidos, investigando como narrativas de medo, ressentimento e moralidade são mobilizadas para consolidar hegemonias políticas. O estudo recorre à perspectiva de Ernesto Laclau e Chantal Mouffe, destacando conceitos como hegemonia, antagonismo e articulação discursiva na análise da construção de significados políticos em contextos de polarização e exclusão social. A pesquisa adota metodologia de revisão bibliográfica e análise documental, combinando fontes acadêmicas, jornalísticas e institucionais. Foram utilizados conceitos de racismo estrutural, câmaras de eco digitais, desinformação e agência política da população negra, a partir de autores como Abdias do Nascimento, Lélia Gonzalez, Silvio de Almeida, Nego Bispo, além de estudos sobre populismo digital (Kalil, 2018; Cunha, 2021; Cesarino, 2020; Recuero & Gruzd, 2019). Os resultados indicam que o bolsonarismo e o trumpismo compartilham estratégias discursivas convergentes, centradas na criação de antagonismos morais, raciais e culturais, amplificados em plataformas digitais segmentadas.

Identifying young service users whose depressive symptoms persist into adulthood is crucial to avert potential difficulties they may face when transitioning from Child and Adolescent Mental Healthcare Services (CAMHS) to Adult Mental Healthcare Services (AMHS). As depressive symptoms are diverse in severity and stability, it is important to objectively identify those who require continued support. A clinical cohort of 763 young people from eight European countries, reaching the upper age limit of their CAMHS, was studied to identify trajectories of self-reported depressive problems (ASEBA Youth Self-Report and Adult Self-Report) over a 24-month follow-up period, as well as associated risk factors for persistent depression and service use, using growth mixture modeling. Self-reported, parent-reported, and clinician-reported interviews and questionnaires were used to collect information on risk factors for persistent depression and service use. We identified a low, a decreasing, an increasing and a high trajectory of depressive symptoms. The high trajectory could be predicted with almost all risk factors for persistent depression (i.g. higher clinician-rated psychopathology, more suicidality, comorbidity and being a victim of bullying) and these young people were likely to transition to AMHS or require specialist mental health care at a later date. More importantly, young people whose depressive symptoms increase to similar levels as the group with persistent high-levels of depressive symptoms (the increasing trajectory) could not be properly distinguished from other young people based on risk factors, while their needed continuation of treatment (either in AMHS or CAMHS) was equally likely as the end of care.

Abstract In the final essay, the author gives priority to the voices of those working on historically black colleges and universities (HBCU) campuses with an explicit charge to maintain a religious orientation and provide spiritual counsel—e.g., Deans of the Chapel and chaplains. Using a social science informed methodology, the author argues religion is at the core of HBCUs’ self-understanding as reflected in their mottos and guiding principles, and as advanced by leaders responsible for the religious and spiritual well-being of those higher education communities. By highlighting the voices of figures doing the work, the author aims to describe the manner in which issues of identity are worked out through engagement with a religiously motivated vocabulary and grammar of life.

Human cytomegalovirus (HCMV) is a master of immune evasion and a potent modulator of the human immune system. The best-characterized mechanism employed by HCMV to suppress host immunity is the production of a viral interleukin-10 homolog (CMVIL-10). While CMVIL-10 is known to suppress immune responses and promote viral persistence, its capacity to promote increased susceptibility to co-infecting pathogens like Aspergillus fumigatus remains unknown. Therefore, we studied the impact of wild-type (WT) HCMV (strain TB40 BAC4), a CMVIL-10-deficient HCMV mutant (ΔUL111A), and recombinant CMVIL-10 on the immune activity of monocyte-derived dendritic cells (moDCs) during co-infection with A. fumigatus. Using a combination of transcriptomic and phenotypic readouts, our data revealed a strong and time-dependent immuno-paralytic effect of HCMV by suppressing pathogen recognition pathways, cytokine production, DC maturation, and expression of genes that are essential for host defense and tissue repair. Although infection with ΔUL111A lacking CMVIL-10 led to stronger expression of type I interferons, IFN-γ-inducible chemokines, and proinflammatory cytokines than WT infection, interference with antifungal immune defense and fungal clearance during co-infection was largely similar between both strains. The limited effect of CMVIL-10 on antifungal immune defense persisted even after prolonged pre-exposure of DCs to the recombinant virokine. In summary, although CMVIL-10 contributes to shaping an anti-inflammatory environment, HCMV's suppression of antifungal immunity appears to be multifactorial, with CMVIL-10 alone playing a rather subtle role in altering DC responses to A. fumigatus during viral-fungal co-infection.

ObjectiveImpaired fetal and infant growth may cause alterations in developmental programming of the hypothalamic–pituitary–gonadal axis and subsequently pubertal development. We aimed to assess associations between fetal and infant growth and pubertal development.DesignPopulation-based prospective birth cohort.SettingRotterdam, the Netherlands.Patients5830 singleton born children.InterventionsWe estimated fetal weight in second and third trimester by ultrasound. Infant growth measures were gestational age and weight at birth and infant weight at 6, 12 and 24 months.Main outcome measuresPubertal timing outcomes included difference between chronological and skeletal age assessed using dual-energy X-ray absorptiometry, testicular or ovarian volumes assessed using MRI at 10 years, age at menarche and Tanner staging at 13 years.ResultsAmong girls, 1-SD scores birth weight increase was associated with larger ovarian volume at 10 years (0.07 SD (95% CI 0.02 to 0.12) and later age at menarche (0.06 (0.02 to 0.11)). Among girls, increased infant growth was associated with an older skeletal age at 10 years (difference 2.67 (95% CI 2.26 to 3.08) months), earlier menarche (difference 0.10 (95% CI −0.14 to –0.06) years) and more advance breast and pubic hair development at 13 years (difference in Tanner stages 0.09 (0.05 to 0.13) and 0.07 (0.03 to 0.12)). In boys, increased infant growth was associated with an older skeletal age (3.13 (95% CI 2.58 to 3.69) months) and a larger testicular volume (0.07 (95% 0.02 to 0.12) SD) at 10 years, and with more advance pubic hair development (0.09 (95% CI 0.05 to 0.14) at 13 years).ConclusionBirth anthropometrics and early-life growth patterns are associated with altered pubertal development in a sex-specific manner.

Dupuytren's contracture is afibroproliferative systemic disease that cannot be stopped by medication. The overall prevalence is 7-8%. Men are affected 3-4times more frequently. The cause of the disease is not known. Agenetic disposition and thus familial clustering are being discussed. Risk factors for the development of aDupuytren's contracture are work-related stress (microtrauma), nicotine and alcohol consumption, epilepsy and diabetes mellitus as well as advanced age. The prognosis is poor in cases with apositive family history, bilateral involvement, age < 50years and male gender. Several treatment options are available. Conservative therapy has no lasting benefit. Minimally invasive procedures include partial needle aponeurectomy or the injection of collagenase. Surgical procedures range from partial aponeurectomy to dermatoaponeurectomy. The recurrence risk of the gold standard treatment of surgery (partial aponeurectomy) is 20.9%.

BackgroundTetralogy of Fallot (TOF) is typically treated in infancy but often done late in many resource-limited countries, jeopardizing surgical outcomes. This study examined the early results of children undergoing primary complete TOF repair at the Jakaya Kikwete Cardiac Institute (JKCI) in Tanzania, an emerging cardiac center in Eastern Africa.MethodsA retrospective cohort study of children ≤ 18 years undergoing primary TOF complete repair between 2019 and 2021 was conducted. Patients with complex TOF and those with obvious genetic syndrome were excluded. Data on socio-demography, pre-and postoperative cardiac complications, Intensive Care Unit (ICU) and hospital stay, and in-hospital and 30-day mortality were analyzed. Logistic regressions were employed to find the factors for mortality, ICU, and hospital stays.ResultsThe I02 children underwent primary TOF complete repair were majority male (65.7%; n = 67), with a median age of 3.0 years (IQR: 2–6), ranging from 3 months to 17 years.Only 20 patients (19.6%) were below one year of age. Almost all (90%; n = 92) were underweight, with a mean BMI of 14.6 + 3.1 kg/m2 Haematocrits were high, with a median of 48.7 (IQR: 37.4–59.0). The median oxygen saturation was 81% (IQR:72–93). Over a third of patients (38.2%; n = 39) needed Trans annular patch (TAP) during surgery. The median ICU stay was 72 h (IQR:48–120), with ICU duration exceeding three days for most patients. The median hospital stay was 8.5 days (IQR:7–11), with 70 patients (68.2%)experiencing an extended hospital stay of > 7 days. Bacterial sepsis was more common than surgical site infection (5.6%; n = 6 vs. 0.9%;n = 1). No patient needed re-operation for the period of follow up. The in-hospital mortality rate was 5.9%, with no deaths occurring in children less than one year of age nor after discharge during the 30-day follow-up period. No statistically significant differences were observed in outcomes in relation to age, sex, levels of hematocrit and saturations, presence of medical illnesses, and placement of TAP.ConclusionTOF repairs in this African setting at a national cardiac referral hospital face challenges associated with patients’ older age and compromised nutritional status during the surgery. Perioperative mortality rates and morbidity for patients operated at an older age remain elevated. It’s important to address these issues to improve outcomes in these settings.

Considering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection. A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD] = 5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests. Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate, and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women. Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches.