The tyrosine kinase Yes1 is a druggable host factor of HEV.

Background: HEV is a positive-sense, single-stranded RNA virus of the Hepeviridae family. Although HEV accounts for more than 3 million symptomatic cases of viral hepatitis per year, specific anti-HEV therapy and knowledge about HEV pathogenesis are scarce.

Methods: To gain a deeper understanding of the HEV infectious cycle and guide the development of novel antiviral strategies, we here used an RNAi mini screen targeting a selection of kinases, including mitogen-activated protein kinases, receptor tyrosine kinases, and Src-family kinases.

Family communication and courageous coping in Korean adolescents and young adults: a cross-sectional study.

Objective: Adolescents and young adults (AYAs) with cancer are a vulnerable population during a critical developmental transition that can benefit from the adoption of courageous coping. Parental support is crucial in enhancing adjustment and coping skills. The linkage between parent-adolescent communication (PAC) and the use of courageous coping (UCC), however, remains unclear.

Targeting cellular cathepsins inhibits hepatitis E virus entry.

Background And Aims: HEV is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise and has proven effective for other viruses. However, the precise mechanisms and host factors required during HEV entry remain unclear.

Positive effects of tree species diversity on productivity switch to negative after severe drought mortality in a temperate forest experiment.

The synthesis of a large body of evidence from field experiments suggests more diverse plant communities are more productive as well as more resistant to the effects of climatic extremes like drought. However, this view is strongly based on data from grasslands due to the limited empirical evidence from tree diversity experiments. Here we report on the relationship between tree diversity and productivity over 10 years in a field experiment established in 2005 that was then affected by the 2018 mega-drought in central Europe.

Serotonin Signaling through Lipid Membranes.

Serotonin (5-HT) is a vital modulatory neurotransmitter responsible for regulating most behaviors in the brain. An inefficient 5-HT synaptic function is often linked to various mental disorders. Primarily, membrane proteins controlling the expression and activity of 5-HT synthesis, storage, release, receptor activation, and inactivation are critical to 5-HT signaling in synaptic and extra-synaptic sites.

Effects of plant diversity on productivity strengthen over time due to trait-dependent shifts in species overyielding.

Plant diversity effects on community productivity often increase over time. Whether the strengthening of diversity effects is caused by temporal shifts in species-level overyielding (i.e.

Quantitative Zn, Al and H MAS NMR spectroscopy for the characterization of Zn species in ZSM-5 catalysts.

Zn MAS NMR spectroscopy was used to characterize the state of Zn in Zn-modified zeolites ZSM-5. Two Zn enriched zeolite samples were prepared: by solid-state exchange with metal Zn (Zn/ZSM-5 sample) and by ion exchange with zinc formate solution (ZnO/H-ZSM-5 sample), both containing 3.8 wt% Zn.

The Concept of Double Protection in the Childhood Cancer Context.

Background: The concept of double protection is used to describe communication avoidance used by parents and their child or adolescents with cancer in attempts to protect the other against disease-related stress and emotions, resulting from communication about the cancer, its treatment, and thoughts. This concept has received limited attention in the research literature.

Objectives: The aims of this concept analysis are to (1) explore its defining characteristics, applicability, and utility, (2) spotlight the concept and increase awareness and interest among healthcare providers and researchers, and (3) provide a direction for future interventions to improve parent-child communication in the childhood cancer context.

Telomerase Upregulation Induces Progression of Mouse BrafV600E-Driven Thyroid Cancers and Triggers Nontelomeric Effects.

Unlabelled: Mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the paradigm of a cross-cancer alteration in a noncoding region. TERT promoter mutations (TPM) are biomarkers of poor prognosis in cancer, including thyroid tumors. TPMs enhance TERT transcription, which is otherwise silenced in adult tissues, thus reactivating a bona fide oncoprotein.

Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes.

Purpose: RAS mutations occur across the spectrum of thyroid neoplasms, and more tools are needed for better prognostication. The objective of this study was to evaluate how additional genetic events affecting key genes modify prognosis in patients with RAS-mutant thyroid cancers, and specifically differentiated thyroid cancers (DTC).

Experimental Design: We performed a clinical-genomic analysis of consecutive patients with DTC, poorly differentiated (PDTC), or anaplastic thyroid cancer (ATC) between January 2014 and December 2021, in whom a custom-targeted next-generation sequencing assay was performed.

Papillary Thyroid Carcinomas with Tall Cell Features: An Intermediate Entity Between Classic and Tall Cell Subtypes.

While the diagnosis of papillary thyroid carcinomas (PTCs) with tall cell features (PTCtcf) is often made for carcinomas with histological features intermediate between classic and tall cell subtypes of PTC (tcPTC), its comparative signature to that of either tcPTC or classic PTC is less clear. The objective of this study was to perform an integrative clinicopathologic and genomic analysis elucidating the spectrum of tcPTC, PTCtcf, and classic PTC. We analyzed all consecutive patients with tcPTC and PTCtcf evaluated at a tertiary academic referral center between 2005 and 2020, as well as a comparative cohort of classic PTC, in a retrospective observational cohort analysis.

Telomerase reactivation induces progression of mouse Braf -driven thyroid cancers without telomere lengthening.

Mutations in the promoter of the telomerase reverse transcriptase ( ) gene are the paradigm of a cross-cancer alteration in a non-coding region. promoter mutations (TPMs) are biomarkers of poor prognosis in several tumors, including thyroid cancers. TPMs enhance transcription, which is otherwise silenced in adult tissues, thus reactivating a oncoprotein.

Understanding Processes, Outcomes, and Contexts in Medication Adherence: The Medication Adherence Context and Outcomes (MACO) Framework.

Poor medication adherence is a significant problem, yet interventions to improve it have been largely ineffective. Existing ecological models indicate that adherence is multi-dimensional; however, they do not reflect understanding of context-specific processes and how they lead to adherence outcomes. A framework that reflects context-specific processes is important because it could be used to inform context-specific intervention delivery and measure associated adherence outcomes.

How pressure enhances the critical temperature of superconductivity in YBaCuO.

High-temperature superconducting cuprates respond to doping with a dome-like dependence of their critical temperature (). But the family-specific maximum can be surpassed by application of pressure, a compelling observation known for decades. We investigate the phenomenon with high-pressure anvil cell NMR and measure the charge content at planar Cu and O, and with it the doping of the ubiquitous CuO plane with atomic-scale resolution.

The Effects of Dietary Interventions on Brain Aging and Neurological Diseases.

Dietary interventions can ameliorate age-related neurological decline. Decades of research of in vitro studies, animal models, and clinical trials support their ability and efficacy to improve behavioral outcomes by inducing biochemical and physiological changes that lead to a more resilient brain. Dietary interventions including calorie restriction, alternate day fasting, time restricted feeding, and fasting mimicking diets not only improve normal brain aging but also slow down, or even reverse, the progression of neurological diseases.

Tuning the Mechanism of H/D Exchange for Isobutane on H-BEA by Loading Zn Species in Zeolite.

Kinetics of H/D hydrogen exchange between deuterated isobutane-d and Brønsted acid sites (BAS) of three zeolite samples (H-BEA, ZnO/H-BEA, Zn /H-BEA) were monitored with H MAS NMR in situ at 343-468 K. The regioselective H/D exchange in the methyl groups detected on H-BEA can be rationalized in terms of the mechanism of indirect exchange, which involves protonation of the intermediate olefin and further hydride abstraction from the other alkane molecule by the formed carbenium ion. Loading of Zn species in the zeolite results in a decrease of the rate and an increase of the activation energy of the exchange.

Quantitating Diffusion Enhancement in Pore Hierarchies.

A microporous continuum traversed by a set of mutually perpendicular channels is considered to be a model for a hierarchically porous system of the mesoporous zeolite type. Transient profiles of molecular uptake as determined by kinetic Monte Carlo (kMC) simulation are found to be in excellent agreement with the result attained by the application of the two-region model (the Kärger model) of molecular diffusion. In particular, it is found that, in the two limiting cases referred to as fast exchange and slow exchange, there exist two simple analytical expressions for the rate of molecular uptake and hence for the quantification of transport enhancement in comparison with the purely microporous adsorbent.

The TFIIH complex is required to establish and maintain mitotic chromosome structure.

Condensins compact chromosomes to promote their equal segregation during mitosis, but the mechanism of condensin engagement with and action on chromatin is incompletely understood. Here, we show that the general transcription factor TFIIH complex is continuously required to establish and maintain a compacted chromosome structure in transcriptionally silent egg extracts. Inhibiting the DNA-dependent ATPase activity of the TFIIH complex subunit XPB rapidly and reversibly induces a complete loss of chromosome structure and prevents the enrichment of condensins I and II, but not topoisomerase II, on chromatin.

Interprofessional spiritual care education in pediatric hematology-oncology: A pilot study.

Background: Evidence and clinical guidelines call care team members to address the spiritual well-being of pediatric patients, especially adolescents and young adults (AYA), with cancer and blood disorders. However, the lack of relevant training in generalist spiritual care has been a key barrier. Therefore, we aimed to improve clinicians' capabilities by utilizing the Interprofessional Spiritual Care Education Curriculum (ISPEC) to close this gap in pediatric hematology-oncology.

MiRNA Deregulation Distinguishes Anaplastic Thyroid Carcinoma (ATC) and Supports Upregulation of Oncogene Expression.

Anaplastic thyroid carcinoma (ATC) is the most fatal and rapidly evolving endocrine malignancy invading the head and neck region and accounts for up to 50% of thyroid cancer-associated deaths. Deregulation of the microRNA (miRNA) expression promotes thyroid carcinoma progression by modulating the reorganization of the ATC transcriptome. Here, we applied comparative miRNA-mRNA sequencing on a cohort of 28 thyroid carcinomas to unravel the association of deregulated miRNA and mRNA expression.

Moissanite anvil cell single crystal NMR at pressures of up to 4.4 GPa.

High-pressure anvil cell nuclear magnetic resonance (NMR) studies of single crystals are challenging, but they can offer much insight into material properties. A microcoil inside the high-pressure region that encloses the crystal offers a good signal-to-noise ratio, but special care has to be taken to warrant hydrostatic conditions or to avoid rupture of the crystal or coil. By introducing precise monitoring of the height and diameter of the pressurized sample chamber, this can be ensured, and the data reveal the behavior of the sample chamber under pressure.

Randomized Clinical Trial of a Self-care and Communication Intervention for Parents of Adolescent/Young Adults Undergoing High-Risk Cancer Treatment: A Report From the Children's Oncology Group.

Background: Parents of adolescents and young adults (AYAs) with cancer offer primary support to their children and often experience their own high levels of distress, affecting parent-AYA communication and quality of life.

Objective: To reduce parent distress and improve communication during high-risk cancer treatment, we examined efficacy of a self-care and communication intervention for parents and indirect benefit for AYAs receiving a therapeutic music video (TMV) intervention.

Methods: In this study, we conducted a multisite, randomized controlled trial with AYAs and parents enrolled as dyads (n = 110).

SU(2) hadrons on a quantum computer via a variational approach.

Quantum computers have the potential to create important new opportunities for ongoing essential research on gauge theories. They can provide simulations that are unattainable on classical computers such as sign-problem afflicted models or time evolutions. In this work, we variationally prepare the low-lying eigenstates of a non-Abelian gauge theory with dynamically coupled matter on a quantum computer.

Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects.

Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation.