Publications by Year: 2026

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BACKGROUND: Chronic hepatitis B (HBV) and hepatitis C (HCV) pose significant public health challenges in Viet Nam and the Philippines. Both countries have initiated national strategies aimed at decentralizing hepatitis care to primary healthcare facilities, but the availability and readiness of these facilities to manage hepatitis remains unclear. This study aimed to evaluate the availability and readiness of primary care facilities in Viet Nam and the Philippines to provide comprehensive hepatitis services and to identify key gaps in care delivery.

METHODS: A mixed-methods approach was used, combining health facility surveys and focus group discussions (FGDs) with healthcare workers to assess service availability and identify barriers and enablers of hepatitis care. Data were collected from 18 health facilities and 36 healthcare workers through 6 FGDs across both countries.

RESULTS: The study identified critical gaps in hepatitis service availability, healthcare worker training, diagnostic capacities, and community engagement at the primary care level. While provincial level facilities were well-equipped, most primary care facilities lacked essential resources such as viral load testing, medications, and adequately trained healthcare workers. A key barrier was the lack of social health insurance coverage or reimbursement for hepatitis services at the primary care level in both countries.

CONCLUSION: Gaps identified may require coordinated action from both national and subnational stakeholders. Expanding social health insurance coverage to include hepatitis services at the primary care level, improving healthcare worker training and support, and ensuring the availability of diagnostics and antivirals at the primary care level are essential steps to meet the 2030 hepatitis elimination targets in Viet Nam and the Philippines.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-026-14088-y.

The management of diabetes in women with gestational diabetes and in children and adolescents with type 1 diabetes presents challenges that require therapeutic options that address the unique needs of these patients. Technosphere® insulin (TI), the main component of the Afrezza® Inhalation System, has the potential to address these challenges by improving glycemic management, reducing hypoglycemia, and promoting treatment adherence. TI is characterized by a rapid onset of action and a short duration of effect, distinguishing it from traditional injectable rapid-acting insulin analogs. This article discusses greater flexibility in insulin delivery, along with potential applications, benefits, and challenges of treatment with Technosphere inhaled insulin in these two patient populations.

Aging impacts immune function, but the mechanisms driving age-related changes in immune cell subsets remain unclear. To explore age-dependent changes in immune cell populations, we analyzed human peripheral blood mononuclear cells (PBMCs) from a cohort of healthy donors aged 20-82 years using a 36-color spectral flow cytometry panel focused on T cells. We identified a unique population of memory CD8 T cells, which lack CXCR3 and produce a Th2-like cytokine response, and accumulate with age. We discovered an age-dependent bias in naïve CD8 T cells toward Th2 cytokine production, accompanied by transcriptional and epigenetic changes supporting this phenotype. Moreover, health outcome association analysis linked the accumulation of these unique CXCR3- central memory CD8 T cells to asthma, chronic liver conditions, and type 2 diabetes. Together, our results support the model that an age-dependent drift in epigenetic regulation toward a Th2-like phenotype drives a pathogenic Th2-like immune population.

Pharmaceutical companies place significant importance on the liver due to its crucial role in numerous biochemical processes, specifically in drug metabolism. This focus has led to significant progress in liver-on-a-chip (LoC) technology, which has proven useful not only in drug development but also in more advanced applications. As a result, elaboration and incorporation of advanced LoC models into preclinical workflows have great potential to decrease R&D expenses and reduce or even replace animal testing, while improving the safety and efficacy of new therapies. To explore this potential, the present review provides an overview of recent academic and commercial LoC models, examines their different designs and cellular compositions, and evaluates the advantages and disadvantages of their complexity. A systematic comparison of these models is then performed, along with a discussion of their current challenges and future perspectives. Ultimately, we hope this review will assist scientists and industry professionals in selecting optimal models and in contributing to future advancements in LoC technology.

Over the last 2 to 3 decades, we have seen incremental movement from the "Rule of 10s" for pheochromocytomas, particularly those regarding tumor bilaterality, malignancy, and patterns of inheritance. The biology and prevalence of these tumors have not changed, but there has been a great deal of progress in terms of our understanding of tumor genetics, variable modes of acquiring of both pheochromocytomas and paragangliomas (PPGL), and our approach to clinical management of these unpredictable neoplasias. Although these non-epithelial neuroendocrine tumors are rare, they are clinically significant due to their hormonal activity, association with hereditary syndromes, and biological potential. Their detection has increased in recent decades with improved biochemical testing and advanced imaging modalities, yet predicting clinical behavior continues to be a major challenge. Histologically, PPGL typically shows classic neuroendocrine architecture but may display morphologic diversity, occasionally mimicking other adrenal or paraganglionic tumors. Immunohistochemistry remains essential for diagnostic confirmation and as a surrogate for genetic alterations, offering valuable genotype-phenotype correlations. With increasing knowledge of tumor genetics, additional emphasis has been placed on histology-based risk-stratification for these lesions, particularly those prone to metastasis or multifocality, and the 2022 WHO endorses no individual risk-stratification system, as none seems to be of definitive merit over another. Instead, it promotes a comprehensive approach integrating morphologic, molecular, and clinical factors. Approximately 40% of PPGL harbor germline mutations, whereas somatic alterations account for additional subsets. Mutations in SDH x, VHL , RET , NF1 , and other susceptibility genes define molecular clusters with distinct signaling pathways and clinical behavior, underscoring the importance of multidisciplinary, lifelong management.

OBJECTIVE: Comprehensive prenatal screening (CPS) (carrier screening and cfDNA for aneuploidy, 22q11.2 deletion syndrome, CNVs > 7Mb, and single gene disorders) can non-invasively identify genetic conditions in fetuses with congenital heart defects (CHD). We calculated the theoretical performance of CPS for CHDs with underlying genetic diagnoses. Secondarily, we compared theoretical performances across CHD subtypes and by the presence of extracardiac anomalies.

METHODS: We retrospectively examined cases of fetal cardiac anomalies with known causative genetic diagnoses from January 2020 to October 2024. We calculated theoretical CPS performance by determining which genetic diagnoses were identifiable by CPS modalities.

RESULTS: We extracted 153 fetuses with CHD and a known causative genetic diagnosis. Diagnoses included aneuploidies (37%), single gene disorders (22%), CNVs (18%), 22q11.2 deletion syndrome (17%), multiple diagnoses (6%), and uniparental disomy (1%). Of the 153 cases, 117 were identifiable by CPS, corresponding to a theoretical performance of 76%. Theoretical performances did not differ significantly across CHD categories or by the presence of extracardiac anomalies.

CONCLUSIONS: Antenatal diagnostic testing remains the standard of care for fetal anomalies. Among individuals who decline diagnostic testing, our findings suggest that, in cases where a CHD has an underlying genetic cause, an optimal combination of currently available screening tests could theoretically identify up to 76% of genetic causes. However, actual performance will be lower in clinical practice.

OBJECTIVE: Avoidant/restrictive food intake disorder (ARFID) involves restrictive eating driven by sensory sensitivity, low interest in food, or fear of negative consequences of eating. ARFID affects males and females equally and presents across the weight spectrum. Leptin, an anorexigenic hormone linked to adiposity, may contribute to low hunger and early satiety in ARFID. Prior findings indicate low leptin levels in low-weight females with ARFID; however, the role of leptin in ARFID across weight status and sex remains unknown. We hypothesized that youth with full/subthreshold ARFID, including a subgroup of low-weight males, would exhibit lower fasting leptin levels than healthy controls (HCs). We explored cross-sectional and longitudinal associations between leptin and clinical characteristics.

METHOD: Participants were youth aged 10-23 years (BMI percentile M [SD] = 41.4 (33.6)) with full/subthreshold ARFID (n = 95; 49.5% female) and HCs (n = 28; 50.0% female). At baseline, participants completed questionnaires, a fasted blood draw, and a diagnostic interview for ARFID, readministered at 1- and 2year follow-ups.

RESULTS: Leptin levels did not differ between ARFID and HC groups. Low-weight ARFID males had significantly lower leptin than HC males (η2 = 0.258); however, this difference was nonsignificant after adjusting for BMI percentile. Leptin showed medium-to-large positive associations with age, BMI, and anxiety but not appetite or ARFID severity. Baseline leptin did not predict symptom or weight changes longitudinally.

DISCUSSION: Hypoleptinemia was only evident in low-weight ARIFD and strongly correlated with BMI percentile. However, relationships with anxiety may suggest additional roles of leptin in underlying ARFID psychopathology. Findings should be replicated in larger, more representative samples.