Medication Hazards and Outcome Patterns of Pediatric Drug-Associated Liver Injury in Taiwan: An Analysis of 1998-2017 Spontaneous Adverse Drug Reaction Reports.

Background And Objectives: Accumulating pediatric efficacy and safety data on drug use is inherently challenging yet essential. This study aimed to analyze the frequency and compute the odds of pediatric drug-associated liver injury across age groups (early childhood, middle childhood, and adolescence) and therapeutic categories using adverse drug reactions (ADRs) reporting data spanning nearly two decades.

Methods: We analyzed the reports of suspected ADRs occurring in children and adolescents in the Taiwan National Adverse Drug Reaction Reporting System during the period from May 1998 until July 2017.

Clinician Perspectives Highlight the Need for Early Dyadic Coping Skills for People Living With Amyotrophic Lateral Sclerosis.

Context: A diagnosis of ALS can be challenging, and many people find ways to adapt. At the same time, emotional distress can arise early after an ALS diagnosis even when high quality multidisciplinary care is provided. When emotional distress occurs, it can become chronic over time, and can affect both the person living with ALS and their care-partner (together called a dyad).

Nationwide, Couple-Based Genetic Carrier Screening.

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.

Targeting Dual Immune Checkpoints PD-L1 and HLA-G by Trispecific T Cell Engager for Treating Heterogeneous Lung Cancer.

Immunotherapy targeting immune checkpoints (ICPs), such as programmed death-ligand-1 (PD-L1), is used as a treatment option for advanced or metastatic non-small cell lung cancer (NSCLC). However, overall response rate to anti-PD-L1 treatment is limited due to antigen heterogeneity and the immune-suppressive tumor microenvironment. Human leukocyte antigen-G (HLA-G), an ICP as well as a neoexpressed tumor-associated antigen, is previously demonstrated to be a beneficial target in combination with anti-PD-L1.

Frontostriatal salience network expansion in individuals in depression.

Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset. Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals, but this approach has not been applied in depression.

BRCA1 secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance.

PARP inhibitor (PARPi) therapy has transformed outcomes for patients with homologous recombination DNA repair (HRR) deficient ovarian cancers, for example those with BRCA1 or BRCA2 gene defects. Unfortunately, PARPi resistance is common. Multiple resistance mechanisms have been described, including secondary mutations that restore the HR gene reading frame.

Optimizing Concussion Care Seeking: Using Machine Learning to Predict Delayed Concussion Reporting.

Background: Early medical attention after concussion may minimize symptom duration and burden; however, many concussions are undiagnosed or have a delay in diagnosis after injury. Many concussion symptoms (eg, headache, dizziness) are not visible, meaning that early identification is often contingent on individuals reporting their injury to medical staff. A fundamental understanding of the types and levels of factors that explain when concussions are reported can help identify promising directions for intervention.

CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and amplified ovarian cancer.

High-grade serous ovarian cancers (HGSOCs) with homologous recombination deficiency (HRD) are initially responsive to poly (ADP-ribose) polymerase inhibitors (PARPi), but resistance ultimately emerges. HGSOC with amplification ( ) are associated with resistance to PARPi and platinum treatments. High replication stress in HRD and HGSOC leads to increased reliance on checkpoint kinase 1 (CHK1), a key regulator of cell cycle progression and the replication stress response.

Tai Chi and Aerobic Exercise on Cancer-Related Dyspnea in Advanced Lung Cancer Patients: A Randomized Clinical Trial.

Context: Dyspnea, a prevalent and debilitating symptom in patients with advanced lung cancer, negatively affects symptom burden and prognosis. Physical activity has emerged as a promising non-pharmacological intervention for managing dyspnea.

Objectives: This study compared the effectiveness of two widely-recognized physical activity modalities, namely Tai Chi (TC) and aerobic exercise (AE) for treating dyspnea in patients with advanced lung cancer.

Polymeric Nanoparticles Enable mRNA Transfection and Its Translation in Intervertebral Disc and Human Joint Cells, Except for M1 Macrophages.

Chronic lower back pain caused by intervertebral disc degeneration and osteoarthritis (OA) are highly prevalent chronic diseases. Although pain management and surgery can alleviate symptoms, no disease-modifying treatments are available. mRNA delivery could halt inflammation and degeneration and induce regeneration by overexpressing anti-inflammatory cytokines or growth factors involved in cartilage regeneration.

Effectiveness of Dyadic Advance Care Planning: A Systematic Review and Meta-Analysis.

Context: Making decisions regarding end-of-life care is particularly challenging for patients and their family caregivers. Studies have advocated that family involvement in advance care planning is important to provide goal-concordant care and to increase family caregivers' preparation for surrogate decision-making. However, there is a lack of evidence to examine the effectiveness of advance care planning using the patient-caregiver dyadic approach.

Prognostic Nutritional Index as a Prognostic Factor for Very Early-Stage Hepatocellular Carcinoma.

Introduction: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC.

MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis.

Oncogene-induced replication stress generates endogenous DNA damage that activates cGAS-STING-mediated signalling and tumour suppression. However, the precise mechanism of cGAS activation by endogenous DNA damage remains enigmatic, particularly given that high-affinity histone acidic patch (AP) binding constitutively inhibits cGAS by sterically hindering its activation by double-stranded DNA (dsDNA). Here we report that the DNA double-strand break sensor MRE11 suppresses mammary tumorigenesis through a pivotal role in regulating cGAS activation.

Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability.

Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV.

Directional Endothelial Communication by Polarized Extracellular Vesicle Release.

Background: Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments.

Peri-operative extracorporeal membrane oxygenation in adult and pediatric living donor liver transplantation: a single-center experience.

Background: Extracorporeal membrane oxygenation (ECMO) is a potential rescue therapy for patients with acute cardiopulmonary dysfunction refractory to conventional treatment. In this study, we described the clinical profiles and outcomes of adult and pediatric living donor liver transplantation (LDLT) patients who received ECMO support during the peri-operative period.

Methods: From June 1994 to December 2020, eleven out of the 1,812 LDLTs performed at Kaohsiung Chang Gung Memorial Hospital required ECMO support: six for respiratory failure, three for cardiogenic shock, and two for refractory septic shock.

Pembrolizumab With R-CHOP in Previously Untreated DLBCL: Sustained, High Efficacy, and Safety With Long-Term Follow-Up.

Background: While generally ineffective in relapsed diffuse large B cell lymphoma (DLBCL), immune checkpoint inhibitors (ICIs) may hold greater promise in untreated, immunocompetent patients. We previously reported safety and early efficacy of pembrolizumab plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (PR-CHOP) in a phase I trial of untreated DLBCL, noting responses in 90% of patients (complete response 77%) and a 2-year progression-free survival (PFS) of 83%. We herein report long-term safety and efficacy at 5-year follow up.

A Resilience Program for Hospital Security Officers During the COVID-19 Pandemic Using a Community Engagement Model.

Security officers in health systems are subject to high levels of stress and current support interventions do not necessarily target their needs. To address this gap, a resilience center at a major urban tertiary care hospital utilized community engagement principles to adapt and implement resilience and mental health awareness workshops, which were informed by initial piloting. The program consisted of twelve short briefings in which officers were provided psychoeducation on psychological first aid and adaptive coping.

T790M detection rate after first-line combination therapy with bevacizumab and EGFR-TKIs in advanced NSCLC (TERRA Study).

Real-world data regarding the T790M mutation rate after acquiring resistance to first-line combination therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and bevacizumab in patients with advanced non-small-cell lung cancer (NSCLC) are limited. The present study was aimed at analyzing predictors of acquired T790M mutations in this patient group. A total of 107 patients who received first-line combination therapy with EGFR-TKIs and bevacizumab at 11 tertiary referral centers in Taiwan were enrolled in this multicenter retrospective study.