Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis.

Molecular allergy diagnosis enabling personalized medicine.

Allergic patients are characterized by complex and patient-specific IgE sensitization profiles to various allergens, which are accompanied by different phenotypes of allergic disease. Molecular allergy (MA) diagnosis establishes the patient's IgE reactivity profile at a molecular allergen level and has moved allergology into the "Precision Medicine" era. Molecular allergology started in the late 1980s with the isolation of the first allergen-encoding DNA sequences.

CT perfusion and MRI: A combined approach for hepatocellular carcinoma diagnosis and follow-up after locoregional treatment.

Objective: CT liver perfusion (CTLP) has been well validated for hepatocellular carcinoma (HCC) detection, characterization, and treatment response evaluation. However, its role in HCC management algorithms remains unclear. This study aims to assess the diagnostic performance of CTLP alone or as an adjunct to MRI in patients considered for- or undergoing locoregional treatment for HCC.

One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Communicating scientific evidence: drugs for Alzheimer's disease as a case study.

This paper reviews the scientific evidence on new anti-amyloid monoclonal antibodies for treating Alzheimer's disease as a case study for improving scientific evidence communication. We introduce five guidelines condensed from the biomedical evidence literature but adapted to the short format of science communication in e.g.

ATM Expression and Activation in Ataxia Telangiectasia Patients with and without Class Switch Recombination Defects.

Background: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

Short-term outcomes from the 'Watch and Wait' (WoW) study: prospective cohort study.

Background: Despite absence of level 1 evidence on the long-term oncological safety of non-operative management for rectal cancer (watch and wait), increased implementation has occurred globally over the past decades. In Sweden, a pan-national prospective non-randomized study was initiated in 2017 to assess its implementation.

Method: Patients with biopsy-proven rectal cancer receiving neoadjuvant therapy according to national guidelines in whom a clinical complete response was detected at reassessment were eligible for inclusion following informed consent.

Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.

The scope of emergency nursing viewed through the lens of complex adaptive systems: A discussion paper.

Across the world, emergency department nurses care for patients around the clock all year long. They perform tasks ranging from direct nursing care to managing patient flow, working in an environment characterised by interdependencies among numerous actors. The complex context in which emergency nurses operate has not been thoroughly described or discussed, indicating a knowledge gap.

Colorectal carcinogenesis in the Lynch syndromes and familial adenomatous polyposis: trigger events and downstream consequences.

Carcinogenesis encompasses processes that lead to increased mutation rates, enhanced cellular division (tumour growth), and invasive growth. Colorectal cancer (CRC) carcinogenesis in carriers of pathogenic APC (path_APC) and pathogenic mismatch repair gene (path_MMR) variants is initiated by a second hit affecting the corresponding wild-type allele. In path_APC carriers, second hits result in the development of multiple adenomas, with CRC typically emerging after an additional 20 years.

Challenges and possibilities when doing research on active school travel interventions in a school setting - a non-randomized pilot study assessing feasibility of an evaluation design.

Background: A wide range of school interventions have been launched to increase childrens' physical activity. Evaluation of the effectiveness of interventions requires suitable study designs and feasible quantitative evaluations relating to the school setting. The purpose of this study was to assess the evaluation design and methods for data collection, in order to make decisions about approaching forthcoming studies of the effectiveness of active school travel (AST) interventions.

A STRONG call for intensive oral heart failure therapy in acute heart failure patients.

Heart failure (HF), a chronic and progressive disease, is increasing in prevalence worldwide and is associated with increased hospitalizations and death. Despite notable improvements in medical therapy for HF, patients are still at risk of future negative outcomes. Current guidelines recommend four classes of medication for treating patients with HF, deemed guideline-directed medical therapy (GDMT).

A de novo, mosaic and complex chromosome 21 rearrangement causes APP triplication and familial autosomal dominant early onset Alzheimer disease.

Copy number variation (CNV) of the amyloid-β precursor protein gene (APP) is a known cause of autosomal dominant Alzheimer disease (ADAD), but de novo genetic variants causing ADAD are rare. We report a mother and daughter with neuropathologically confirmed definite Alzheimer disease (AD) and extensive cerebral amyloid angiopathy (CAA). Copy number analysis identified an increased number of APP copies and genome sequencing (GS) revealed the underlying complex genomic rearrangement (CGR) including a triplication of APP with two unique breakpoint junctions (BPJs).

Comparative effectiveness of antipsychotic treatment strategies for relapse prevention in first-episode schizophrenia in Finland: a population-based cohort study.

Background: The best pharmacological treatment practices for relapse prevention in patients with first-episode schizophrenia are unclear. We aimed to assess different treatment strategies used before and after the first relapse, and their associations with subsequent relapse risk.

Methods: In this population-based cohort study, we enrolled individuals (aged ≤45 years) with first-episode schizophrenia who were hospitalised and subsequently relapsed between 1996 and 2014 from the nationwide Finnish Hospital Discharge Register.

First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies.

Background: ATOR-1017 (evunzekibart) is a human agonistic immunoglobulin G4 antibody targeting the costimulatory receptor 4-1BB (CD137). ATOR-1017 activates T cells and natural killer cells in the tumor environment, leading to immune-mediated tumor cell death.

Methods: In this first-in-human, multicenter, phase I study, ATOR-1017 was administered intravenously every 21 days as a monotherapy to patients with advanced, unresectable solid tumors having received multiple standard-of-care treatments.

A new Mediterranean Lifestyle Pyramid for children and youth: a critical lifestyle tool for preventing obesity and associated cardiometabolic diseases in a sustainable context.

Cardiovascular risk factors begin in childhood and track into adulthood, increasing the possibility of impaired cardiometabolic health. Adopting healthy dietary patterns can help curb childhood obesity, a worrisome epidemic problem at present. In the era of personalized nutrition, dietary recommendations should be adapted to different stages of life, including children (older than 3 years) and adolescents.

Structural elucidation of the O-antigen polysaccharide from shigatoxin-producing E. coli O179 using genetic information, NMR spectroscopy and the CASPER program.

The serological properties of the O-antigen polysaccharide region of the lipopolysaccharides are used to differentiate E. coli strains into serogroups. In this study, we report the structure elucidation of the O-specific chain of E.

Selenoprotein P predicting mortallity in acute ill patients with dyspnea.

Background And Aims: Good Selenium (Se) status predicts favorable prognoses for various diseases and a reduced overall mortality. The primary objective of the study was to determine whether Selenium status, i.e.

Circuit Modules for Flexible Locomotion.

Locomotion, like all behaviors, possesses an inherent flexibility that allows for the scaling of movement kinematic features, such as speed and vigor, in response to an ever-changing external world and internal drives. This flexibility is embedded in the organization of the spinal locomotor circuits, which encode and decode commands from the brainstem and proprioceptive feedback. This review highlights our current understanding of the modular organization of these locomotor circuits and how this modularity endows them with intrinsic mechanisms to adjust speed and vigor, thereby contributing to the flexibility of locomotor movements.

Short, extended and continuous infusion of β-lactams: predicted impact on target attainment and risk for toxicity in an ICU patient cohort.

Objectives: This study aimed to predict the impact of different infusion strategies on pharmacokinetic/pharmacodynamic (PK/PD) target attainment and the potential risk for toxicity in an ICU cohort treated with β-lactams.

Method: Using collected patient data from 137 adult ICU patients, and applying population PK models, individual PK parameters were estimated and used to predict concentrations and target attainment following cefotaxime 2 g q8h, piperacillin/tazobactam 4.5 g q6h and meropenem 1 g q8h, applying 15 min short infusions (SI), 3 h extended infusions (EI) and 24 h continuous infusion (CI).

TIGIT-expression on natural killer cell subsets is an early indicator of alleviating liver inflammation following bulevirtide treatment in chronic hepatitis D.

Background Aims: Bulevirtide (BLV) is a novel and the only approved treatment option for patients with chronic hepatitis D (CHD). BLV alleviates liver inflammation already early during treatment when only minor HDV RNA changes are observed. We hypothesized that BLV-treatment may influence immune cells in CHD patients and performed a high-resolution analysis of natural killer (NK) cells before and during BLV-therapy.