Impact of genetic test interpretation on a missense variant in Cohen syndrome.

Introduction: Cohen syndrome (CS) is an early-onset pediatric neurodevelopmental disorder characterized by postnatal microcephaly and intellectual disability. An accurate diagnosis for individuals with CS is crucial, particularly for their caretakers and future prospects. CS is predominantly caused by rare homozygous or compound heterozygous pathogenic variants in the vacuolar protein sorting-associated 13B () gene, which disrupt protein translation and lead to a loss of function (LoF) of the encoded VPS13B protein.

Real-Time Neurophysiological and Subjective Indices of Cognitive Engagement in High-Speed Flight.

Introduction: Managing cognitive demand is critical for aviation safety. Yet, accurately assessing pilot workload during complex flight maneuvers remains challenging. This study evaluated an integrated methodology combining real-time cognitive engagement indicators to provide a comprehensive assessment and assess the reliability of physiological and subjective measures for monitoring operator state.

Permanent cilia loss during cerebellar granule cell neurogenesis involves withdrawal of cilia maintenance and centriole capping.

Brain neurons utilize the primary cilium as a privileged compartment to detect and respond to extracellular ligands such as Sonic hedgehog (SHH). However, cilia in cerebellar granule cell (GC) neurons disassemble during differentiation through ultrastructurally unique intermediates, a process we refer to as cilia deconstruction. In addition, mature neurons do not reciliate despite having docked centrioles.

Radiographic and Patient-Reported Outcomes for First Tarsometatarsal Arthrodesis Using an Intramedullary Nail for Hallux Valgus Deformity A Consecutive Case Series.

Background: First tarsometatarsal (TMT) arthrodesis is one of the most common procedures performed each year for the correction of hallux valgus deformity, and nonunion rates for first TMT arthrodesis are commonly reported to be between 4% and 15%. The purpose of this study was to evaluate the effectiveness of an intramedullary nail system in patients requiring first TMT arthrodesis.

Methods: An ambispective, multisurgeon, consecutive case series was conducted, in which retrospective and prospective collection of patient-reported outcome measure (PROM) and radiologic data were conducted.

Role of AMPK and Sirtuins in Aging Heart: Basic and Translational Aspects.

Aging is a key risk factor for numerous diseases, including cardiac diseases. High energy demands of the heart require precise cellular energy sensing to prevent metabolic stress. AMPK and sirtuins are key intracellular metabolic sensors regulating numerous cell functions, like mitochondrial function and biogenesis, autophagy, and redox balance.

A qualitative exploration of the client-provider relationship and its role in discussing sexual health and HIV among African American women in the US South.

Objective: Sexually transmitted infections (STIs), including HIV, are a key contributor to psychological and physical morbidity across the United States (US). African American (AA) women are disproportionately impacted by STIs, particularly in the Deep South of the US. Strong patient-provider communication can help to increase client understanding of STI prevention and treatment options.

Differential Plin5 response to high-fat diet in cardiomyocytes isolated from young and aged mice.

This study investigates the differences in the heart response to an 8-week high-fat diet between young and aged mice. Isolated cardiomyocytes reveal a significant lower level in the lipid droplet-associated protein Plin5 in aged mice. High-fat diet, however, leads to an induction of Plin5 in aged mice and a low-response of lipid metabolism, whereas in cardiomyocytes from young animals the Plin5 level was largely unaffected by high-fat diet whereas several lipid metabolizing enzymes were induced.

DNAJB1-PRKACA fusion drives fibrolamellar liver cancer through impaired SIK signaling and CRTC2/p300-mediated transcriptional reprogramming.

Fibrolamellar carcinoma (FLC) is a liver cancer of adolescents and young adults characterized by fusions of the genes encoding the protein kinase A catalytic subunit, PRKACA, and heat shock protein, DNAJB1. The chimeric DNAJB1-PRKACA protein has increased kinase activity and is essential for FLC xenograft growth. Here, we explore the critical oncogenic pathways controlled by DNAJB1-PRKACA using patient-derived FLC models, engineered systems, and patient samples.

A 9-Fr Endovascular Therapy Transducer with an Acoustic Metamaterial Lens for Rapid Stroke Thrombectomy.

Large vessel occlusion (LVO) stroke, in which major cerebral arteries such as the internal carotid and middle cerebral arteries supplying the brain are occluded, is the most debilitating form of acute ischemic stroke (AIS). The current gold standard treatment for LVO stroke is mechanical thrombectomy, however, initial attempts to recanalize these large, proximal arteries supplying the brain fail in up to 75% of cases, leading to repeated passes that decrease the likelihood of success and affect patient outcomes. We report the design, fabrication, and testing of a 3 mm × 3 mm forward-treating US transducer with an acoustic metamaterial lens to dissolve blood clots recalcitrant to first pass mechanical thrombectomy in LVO stroke.

Faith-based Community Engagement in HIV-Testing and Awareness of HIV Status in Southern, Rural, African American Communities.

The Deep South is the epicenter of the HIV-epidemic in the United States, with rural AAs bearing the greatest burden. Traditional efforts to improve testing efforts have been largely unsuccessful due to their failure to recognize and leverage the sociopolitical and cultural factors that affect the uptake of HIV-screening interventions at the community level. The purpose of this study was to gain a deeper understanding of the socio-cultural contexts impacting HIV-testing in the rural South, and to assess strategies to increase testing in rural, Southern communities.

An experimental study of the sensorized strain wave gear RT1-T and its capabilities for torque control in robotic joints.

The idea of sensorizing a strain wave gear to measure the transmitted torque has been reported since the 1980s. The strain in the elastic flex spline is typically measured by strain gages attached to it. The resulting voltages relate to the transmitted torque in the gear.

Clinical Presentation of Enterovirus D68 in a Swiss Pediatric University Center.

Background: Enterovirus D68 (EV-D68) is responsible for millions of infections. In the last decade, there has been an increase in the number of children requiring hospital or critical care admission due to severe respiratory illness. Nevertheless, the epidemiological and clinical importance of EV-D68 infections remains unclear.

Microbiology of human spaceflight: microbial responses to mechanical forces that impact health and habitat sustainability.

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches.

Permanent deconstruction of intracellular primary cilia in differentiating granule cell neurons.

Primary cilia on granule cell neuron progenitors in the developing cerebellum detect sonic hedgehog to facilitate proliferation. Following differentiation, cerebellar granule cells become the most abundant neuronal cell type in the brain. While granule cell cilia are essential during early developmental stages, they become infrequent upon maturation.

Skeletal muscle p53-depletion uncovers a mechanism of fuel usage suppression that enables efficient energy conservation.

Background: The ability of skeletal muscle to respond adequately to changes in nutrient availability, known as metabolic flexibility, is essential for the maintenance of metabolic health and loss of flexibility contributes to the development of diabetes and obesity. The tumour suppressor protein, p53, has been linked to the control of energy metabolism. We assessed its role in the acute control of nutrient allocation in skeletal muscle in the context of limited nutrient availability.

Strategies for assessing the limit of detection in voltammetric methods: comparison and evaluation of approaches.

The realm of analytical chemistry continues to struggle with defining and evaluating the limit of detection in analytical methods in the sense that a multitude of definitions, criteria, caveats, and methods have been proposed, developed, and adopted across disciplines. The last decade has seen a surge in the growth of electrochemical methods and studies in the field of forensic science and forensic chemistry. While many disciplines within forensic science have established method validation guidelines, the historical and current lack of electrochemical methods within forensic laboratories throughout the United States has left a major gap in knowledge, inhibiting the adoption and utilization of electrochemistry, which may serve as a powerful tool in many subdisciplines of forensics.

Subzero project: comparing trace element profiles of enriched mitochondria fractions from frozen and fresh liver tissue.

From organs to subcellular organelles, trace element (TE) homeostasis is fundamental for many physiological processes. While often overlooked in early stages, manifested TE disbalance can have severe health consequences, particularly in the context of aging or pathological conditions. Monitoring TE concentrations at the mitochondrial level could identify organelle-specific imbalances, contributing to targeted diagnostics and a healthier aging process.

Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network.

Unlabelled: Cyclin-dependent kinase 9 (CDK9) coordinates signaling events that regulate RNA polymerase II (Pol II) pause-release states. It is an important co-factor for transcription factors, such as MYC, that drive aberrant cell proliferation when their expression is deregulated. CDK9 modulation offers an approach for attenuating dysregulation in such transcriptional programs.

A diagnostic challenge of KIT p.V559D and BRAF p.G469A mutations in a paragastric mass.

A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss therapeutic implications.

Incremental increases in physiological fluid shear progressively alter pathogenic phenotypes and gene expression in multidrug resistant .

The ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant .