Screen Time, Nature, and Development: Baseline of the Randomized Controlled Study "Screen-free till 3".

In the first years of life, increased screen media use is presumably associated with health consequences and developmental impairments. "Screen-free till 3" is a prospective Germany-wide randomized intervention study, started in May 2022 with a duration of 3 years. In the intervention group, 2581 pediatric practices received stickers, which were systematically placed in the screening booklet of all children, along with advice to parents to keep children free from screens until the age of 3.

The hidden work of general practitioners: An ethnography.

High quality primary care is a foundational element of effective health services. Internationally, primary care physicians (general practitioners (GPs), family doctors) are experiencing significant workload pressures. How non-patient-facing work contributes to these pressures and what constitutes this work is poorly understood and often unrecognised and undervalued by patients, policy makers, and even clinicians engaged in it.

Enhancing High-Pressure Capillary Rheometer Viscosity Data Calculation with the Propagation of Uncertainties for Subsequent Cross-Williams, Landel, and Ferry (WLF) Parameter Fitting.

Measuring the shear viscosity of polymeric melts is an extensive effort frequently performed in high-pressure capillary rheometers, where the pressures required to push the melt through a capillary at various temperatures and volumetric flow rates are recorded. Then, the viscosity values are obtained through Bagley and Weissenberg-Rabinowitsch corrections involving parameter fitting. However, uncertainties in those conversions due to pressure variations and measurement inaccuracies (random errors) affect the accuracy of the consequently calculated viscosities.

Parameter Study on Force Curves of Assembled Electronic Components on Foils during Injection Overmolding Using Simulation.

The integration of assembled foils in injection-molded parts is a challenging step. Such assembled foils typically comprise a plastic foil on which a circuit board is printed and electronic components are mounted. Those components can detach during overmolding when high pressures and shear stresses prevail due to the injected viscous thermoplastic melt.

'That's as hard a decision as you will ever have to make': the experiences of people who discussed Do Not Attempt Cardiopulmonary Resuscitation on behalf of a relative during the COVID-19 pandemic.

Background: COVID-19 brought additional challenges to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decision-making, which was already a contentious issue. In the UK, reports of poor DNACPR decision-making and communication emerged in 2020, including from the regulator, the Care Quality Commission. This paper explores the experiences of people who discussed DNACPR with a healthcare professional on behalf of a relative during the coronavirus pandemic, with the aim of identifying areas of good practice and what needs to be improved.

Influence of Injection Molding Parameters on the Peel Strength between Plasma-Treated Fluoropolymer Films and Polycarbonate.

Light guiding is used to direct light from an emitting source to a different location. It is frequently realized through a clad-core structure with a difference in the refractive index of the materials. This paper explores the possibility of combining a fluoropolymer (THV) film of low refractive index, serving as a cladding layer, with a polycarbonate (PC) core, via injection molding.

Process Optimization of Injection Overmolding Structural Electronics with Regard to Film Distortion.

The integration of structural electronics in injection-molded parts is a challenging step. The films-comprising of laminated stacks with electronics-are exposed to shear stresses and elevated temperatures by the molten thermoplastic. Hence, molding settings have a significant impact on the successful, damage-free manufacturing of such parts.

SARS-CoV-2 Seroprevalence in Preschool and School-Age Children—Population Screening Findings From January 2020 to June 2022.

Background: The SARS-CoV-2 pandemic is ongoing in Germany. Children and adolescents are increasingly being infected, and many cases presumably remain undetected and unreported. Sero-epidemiological studies can help estimate the true number of infections.

A Study on Over-Molded Copper-Based Flexible Electronic Circuits.

Over-molding has been proposed in recent years as an integrated functional flexible circuit board in a plastic part. This method uses the conventional process for film insert technology. Over-molding has attracted significant attention across many industries due to its potential to deliver different electrical functions in a variety of different part geometries, especially in automotive interiors and home appliances.

A Real-Time Energy Monitoring System for an MRI Hybrid Ablation System.

The MRI hybrid ablation system is an approach to use the MR (magnetic resonance) scanner's radiofrequency amplifier itself as power source for ablation. Hereby, an electrode is connected to the MR internal radiofrequency amplifier. An average RF power is provided through a train of short RF pulses, which is sufficient to thermally destroy tissue.

Multilayered VBC score predicts sgRNAs that efficiently generate loss-of-function alleles.

CRISPR-Cas9 screens have emerged as a transformative approach to systematically probe gene functions. The quality and success of these screens depends on the frequencies of loss-of-function alleles, particularly in negative-selection screens widely applied for probing essential genes. Using optimized screening workflows, we performed essentialome screens in cancer cell lines and embryonic stem cells and achieved dropout efficiencies that could not be explained by common frameshift frequencies.

CRISPR-Switch regulates sgRNA activity by Cre recombination for sequential editing of two loci.

CRISPR-Cas9 is an efficient and versatile tool for genome engineering in many species. However, inducible CRISPR-Cas9 editing systems that regulate Cas9 activity or sgRNA expression often suffer from significant limitations, including reduced editing capacity, off-target effects, or leaky expression. Here, we develop a precisely controlled sgRNA expression cassette that can be combined with widely-used Cre systems, termed CRISPR-Switch (SgRNA With Induction/Termination by Cre Homologous recombination).

Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequential conditioning-a matched pair analysis.

In acute myeloid leukemia (AML), primary refractory or relapsed disease, secondary AML, and leukemia with unfavorable genetics are considered high-risk AML (hrAML), with allogeneic stem cell transplantation (SCT) representing the standard treatment. Sequential conditioning has been successfully used for SCT in hrAML in HLA-matched transplants, and found its way into HLA-haploidentical SCT (haplo-SCT) later on. Hence, sequential conditioning had become standard for all patients with hrAML in our two centers, regardless of donor type.

Sequential HLA-haploidentical transplantation utilizing post-transplantation cyclophosphamide for GvHD prophylaxis in high-risk and relapsed/refractory AML/MDS.

This study evaluates the role of sequential therapy in HLA-haploidentical transplantation (haplo-HSCT) of high-risk, relapsed/refractory AML/MDS. We analyzed the course of 33 adults with active disease at time of transplantation (AML n = 30; MDS n = 3; median age 58 years, range: 32-71). Sequential therapy consisted of cytoreductive chemotherapy (FLAMSA n = 21; clofarabine n = 12) applied shortly prior to reduced intensity conditioning for T-cell-replete haplo-HSCT using post-transplantation cyclophosphamide as GvHD prophylaxis.

Clonal heterogeneity of -ITD detected by high-throughput amplicon sequencing correlates with adverse prognosis in acute myeloid leukemia.

In acute myeloid leukemia (AML), internal tandem duplications (ITDs) of are frequent mutations associated with unfavorable prognosis. At diagnosis, the ITD status is routinely assessed by fragment analysis, providing information about the length but not the position and sequence of the ITD. To overcome this limitation, we performed cDNA-based high-throughput amplicon sequencing (HTAS) in 250 ITD positive AML patients, treated on German AML Cooperative Group (AMLCG) trials.

PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum.

Background: Primary microcephaly and profound global developmental delay have been considered the core clinical phenotype in patients with bi-allelic mutations.

Methods: Linkage analysis and whole-exome sequencing (WES) in a multiplex family and extraction of further cases from a WES repository containing 571 children with severe developmental disabilities and neurologic symptoms.

Results: We identified bi-allelic mutations in twelve children from six unrelated families.

Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia.

Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes.

Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia.

Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes.

CRISPR-UMI: single-cell lineage tracing of pooled CRISPR-Cas9 screens.

Pooled CRISPR screens are a powerful tool for assessments of gene function. However, conventional analysis is based exclusively on the relative abundance of integrated single guide RNAs (sgRNAs) between populations, which does not discern distinct phenotypes and editing outcomes generated by identical sgRNAs. Here we present CRISPR-UMI, a single-cell lineage-tracing methodology for pooled screening to account for cell heterogeneity.

A reversible haploid mouse embryonic stem cell biobank resource for functional genomics.

The ability to directly uncover the contributions of genes to a given phenotype is fundamental for biology research. However, ostensibly homogeneous cell populations exhibit large clonal variance that can confound analyses and undermine reproducibility. Here we used genome-saturated mutagenesis to create a biobank of over 100,000 individual haploid mouse embryonic stem (mES) cell lines targeting 16,970 genes with genetically barcoded, conditional and reversible mutations.

Modified sequential extraction for biochar and petroleum coke: Metal release potential and its environmental implications.

A modified Community Bureau of Reference (CBR) sequential extraction method was tested to assess the composition of untreated pyrogenic carbon (biochar) and oil sands petroleum coke. Wood biochar samples were found to contain lower concentrations of metals, but had higher fractions of easily mobilized alkaline earth and transition metals. Sewage sludge biochar was determined to be less recalcitrant and had higher total metal concentrations, with most of the metals found in the more resilient extraction fractions (oxidizable, residual).

Occurrence, risk factors and outcome of adenovirus infection in adult recipients of allogeneic hematopoietic stem cell transplantation.

Background: Adenovirus (ADV) infections can have a high mortality in immunocompromised patients and are difficult to treat.

Objectives And Study Design: We retrospectively analyzed occurrence and risk factors of ADV infection in 399 adults with hematological disorders undergoing hematopoietic stem cell transplantation (allo-HSCT), focusing on alternative donor transplantation (ADT) and disseminated disease.

Results: ADV infection occurred in 42 patients (10.

The histone chaperone CAF-1 safeguards somatic cell identity.

Cellular differentiation involves profound remodelling of chromatic landscapes, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNA interference (RNAi) screens targeting chromatin factors during transcription-factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPS cells). Subunits of the chromatin assembly factor-1 (CAF-1) complex, including Chaf1a and Chaf1b, emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance.