Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

High-throughput method characterizes hundreds of previously unknown antibiotic resistance mutations.

A fundamental obstacle to tackling the antimicrobial resistance crisis is identifying mutations that lead to resistance in a given genomic background and environment. We present a high-throughput technique - Quantitative Mutational Scan sequencing (QMS-seq) - that enables quantitative comparison of which genes are under antibiotic selection and captures how genetic background influences resistance evolution. We compare four E.

Approximate Hamiltonians from a Linear Vibronic Coupling Model for Solution-Phase Spin Dynamics.

The linear vibronic coupling (LVC) model is an approach for approximating how a molecular Hamiltonian changes in response to small changes in molecular geometry. The LVC framework thus has the ability to approximate molecular Hamiltonians at low computational expense but with quality approaching multiconfigurational calculations, when the change in geometry compared to the reference calculation used to parametrize it is small. Here, we show how the LVC approach can be used to project approximate spin Hamiltonians of a solvated lanthanide complex along a room-temperature molecular dynamics trajectory.

Guidance on the assessment of the functionality of biomaterials for periodontal tissue regeneration: Methodologies and testing procedures.

Innovative biomaterials and tissue engineering strategies show great promise in regenerating periodontal tissues. This guidance provides an overview and detailed recommendations for evaluating the biological functionality of these new biomaterials in vitro, focusing on mineralization, immunomodulatory effects, cellular differentiation, and angiogenesis. Additionally, it discusses the use of in vivo experimental models that mimic periodontitis and scrutinizes methods such as osteogenic differentiation, immunomodulation, and anti-inflammatory responses to assess the effectiveness of these biomaterials in promoting periodontal tissue reconstruction.

Evaluation of the diagnostic accuracy of Xpert® Mpox and STANDARD™ M10 MPX/OPX for the detection of monkeypox virus.

Objectives: Evaluation of diagnostic accuracy of two point-of-care (POC) molecular diagnostic tests for the detection of monkeypox virus (MPXV): Xpert® Mpox (Cepheid, Inc., USA) and STANDARD™ M10 MPX/OPX (SD Biosensor, Inc., Korea).

The impact of specialist cardiology inpatient care on the long-term outcomes of non-ST-segment elevation myocardial infarction (NSTEMI): A nationwide cohort study.

Background: Specialist cardiac care has been shown to reduce inpatient mortality following non-ST segment myocardial infarction (NSTEMI), but whether this benefit extends beyond index admission is unclear.

Methods: Using the linked Myocardial Ischaemia National Audit Project (MINAP) registry, and Office for National Statistics mortality recording, we included 425,205 NSTEMI patients admitted to UK hospitals, between January 2005 and March 2019 that survived to discharge. 217,964 (52 %) were admitted to a specialty cardiac ward.

Protecting monoclonal antibodies via competitive interfacial adsorption of nonionic surfactants.

Hypothesis: Bioengineered monoclonal antibodies (mAbs) have gained significant recognition as medical therapies. However, during processing, storage and use, mAbs are susceptible to interfacial adsorption and desorption, leading to structural deformation and aggregation, and undermining their bioactivity. To suppress antibody surface adsorption, nonionic surfactants are commonly used in formulation.

Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement.

Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.

First-line osimertinib compared to earlier generation TKIs in advanced EGFR-mutant NSCLC: A real-world survival analysis.

Objectives: This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies.

A highly magnetized long-period radio transient exhibiting unusual emission features.

Long-period radio transients are a new class of astrophysical objects that exhibit periodic radio emission on timescales of tens of minutes. Their true nature remains unknown; possibilities include magnetic white dwarfs, binary systems, or long-period magnetars; the latter class is predicted to produce fast radio bursts (FRBs). Using the MeerKAT radio telescope, we conducted follow-up observations of the long-period radio transient GPM J1839-10.

Lack of context modulation in human single neuron responses in the medial temporal lobe.

In subjects implanted with intracranial electrodes, we use two different stories involving the same person (or place) to evaluate whether and to what extent context modulates human single-neuron responses. Nearly all neurons (97% during encoding and 100% during recall) initially responding to a person/place do not modulate their response with context. Likewise, nearly none (<1%) of the initially non-responsive neurons show conjunctive coding, responding to particular persons/places in a particular context during the tasks.

"Three Sides to Every Story": Living the Patient, Carer and Staff Experience of COVID.

In 2020, the UK's National Health Service (NHS) braced itself for the challenge of the COVID pandemic. Older, frail adults were among those at highest risk for morbidity and mortality. This study aimed to capture the lived experiences of patients, families/carers and staff on a COVID ward.

Preservation of organic carbon in marine sediments sustained by sorption and transformation processes.

Controls on organic carbon preservation in marine sediments remain controversial but crucial for understanding past and future climate dynamics. Here we develop a conceptual-mathematical model to determine the key processes for the preservation of organic carbon. The model considers the major processes involved in the breakdown of organic carbon, including dissolved organic carbon hydrolysis, mixing, remineralization, mineral sorption and molecular transformation.

Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders.

Purpose: We sought to evaluate outcomes for clinical management after a genetic diagnosis from the Deciphering Developmental Disorders study.

Methods: Individuals in the Deciphering Developmental Disorders study who had a pathogenic/likely pathogenic genotype in the DECIPHER database were selected for inclusion ( = 5010). Clinical notes from regional clinical genetics services notes were reviewed to assess predefined clinical outcomes relating to interventions, prenatal choices, and information provision.

Silica hydrogels as a carbon-free solid media for the culture of diverse organisms.

Bacteriological agar plates are commonly used to carry out experiments for the selective growth of microorganisms and the isolation of single-strain colonies. However, the presence of agar itself may be a confounding factor since it may serve as a source of carbon and energy. Moreover, there have been ongoing constraints on the production and sourcing of agar.

Synthesis and Characterization of a 1,2,4-Diazarsolide Anion.

Cyclopentadienyl anions ([Cp]) are pervasive ligands in coordination chemistry. In contrast, heavy-element derivatives of these ligands, particularly those that feature arsenic, are not as well developed. In this work, a new arsenic-based heterocycle with a structure analogous to [Cp] is presented.

Understanding glucose metabolism and insulin action at the blood-brain barrier: Implications for brain health and neurodegenerative diseases.

The blood-brain barrier (BBB) is a highly selective, semipermeable barrier critical for maintaining brain homeostasis. The BBB regulates the transport of essential nutrients, hormones, and signaling molecules between the bloodstream and the central nervous system (CNS), while simultaneously protecting the brain from potentially harmful substances and pathogens. This selective permeability ensures that the brain is nourished and shielded from toxins.

Unifying biology of neurodegeneration in lysosomal storage diseases.

There are currently at least 70 characterised lysosomal storage diseases (LSD) resultant from inherited single-gene defects. Of these, at least 30 present with central nervous system (CNS) neurodegeneration and overlapping aetiology. Substrate accumulation and dysfunctional neuronal lysosomes are common denominator, but how variants in 30 different genes converge on this central cellular phenotype is unclear.

Utility of 3D facial reconstruction for forensic identification: a focus on facial soft tissue thickness and customized techniques.

Facial reconstruction, a crucial method in forensic identification, finds particular significance in cases where conventional means of identification are unavailable. This study addresses a significant gap in the field of forensic facial reconstruction focusing on facial soft tissue thickness (FSTT) and facial reconstruction techniques specifically tailored to the Thai population. By developing and implementing the 3D (three-dimensional) facial reconstruction program and compiling an extensive dataset of FSTT, this research makes substantial progress in advancing forensic facial reconstruction methodologies employing the combination Manchester Method, 3D skull images obtained through cone beam computed tomography (CBCT) scans were reconstructed using Autodesk Maya software.

The Renaissance of Reproductive Science: Leonardo da Vinci's Anatomical Contributions.

Leonardo de Vinci is considered one of the greatest artists that has ever lived. His work includes the Mona Lisa and The Last Supper are celebrated worldwide. His talents expand beyond his art and his contributions to disciplines such as engineering, astronomy, geometry, botany, geology have revealed is him as a polymath.

CAR T access and outcomes in large B-cell lymphoma according to ethnicity and socioeconomic deprivation in the UK.

Data on the impact of ethnic and socioeconomic factors on Chimeric antigen receptor (CAR) T-cell therapy (access and outcomes are limited, but key to understand whether results from the registration trials are generalizable to real-world patient populations. Here, we analysed ethnicity, socioeconomic deprivation and referral patterns in a cohort of 314 large B-cell lymphoma patients approved for third-line CD19 CAR-T across three large UK CAR-T centres. Patients from deprived areas had a lower infusion rate compared to low deprivation areas (73% vs.

Approach to Endocrine Hypertension: A Case-Based Discussion.

Purpose Of Review: Hypertension remains a major chronic disease morbidity across the world, even in the twenty-first century, affecting ≈40% of the global population, adversely impacting the healthcare budgets in managing the high incidence of cardiovascular disease (CVD) complications and mortality because of elevated blood pressure (BP). However, evaluation and management of endocrine hypertension are not optimal in clinical practice. With three unique clinical case scenarios, we update the evidence base for diagnostic evaluation and management of endocrine hypertension in this review to inform appropriate day-to-day clinical practice decisions.