Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

"DNA Doesn't Lie:" Genetic Essentialism and Determinism in Law & Order: Special Victims Unit.

Law and Order: Special Victims Unit (SVU) (1999-present) is a popular primetime drama that spotlights the use of genetic information to solve crimes. Despite the show's heavy reliance on the forensic use of DNA evidence, the role of genetics in defining family and identity arises in complex ways. Many episodes wrestle with social, ethical, and legal questions that reflect assumptions about genetic essentialism and genetic determinism, but counterarguments about the importance of non-biological relationships, social factors, and legal entitlements are given equal or greater weight.

Developing a core outcome set for interventions in people with mild cognitive impairment: study protocol.

Introduction: There is no standardised national guidance on clinical management for people living with mild cognitive impairment (MCI), and therapeutic interventions are limited. Understanding what outcomes are important and meaningful to people living with MCI and developing a core outcome set (COS) for research and clinical practice will improve the impact of clinical research and contribute towards developing effective care pathways for MCI. This study aims to develop a COS for adults living with MCI intended for use in interventional and clinical settings.

Using community engagement with : Framework for reporting adaptations and modifications to evidence-based interventions.

Community engagement is increasingly considered a key component of intervention development, as it can leverage community members' knowledge, experiences, and insights to create a nuanced intervention which meets the needs, preferences, and realities of the population of interest. Community engagement exists along a spectrum from outreach to the community to partnership with community members and organizations, and all levels of community engagement can benefit from systematic documentation of community feedback and decision-making processes. This paper demonstrates how we utilized the "Framework for Reporting Adaptations and Modifications to Evidence-based Interventions" (FRAME; Wiltsey Stirman et al.

Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial.

Importance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.

Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.

Design, Setting, And Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.

On symmetries of higher-order elastic constants.

In elastic crystals, a hyperelastic description is conventionally assumed, and the strain energy potential is idealized as a Taylor-series expansion in strain about an unstrained reference state. Coefficients of quadratic terms are second-order or linear elastic constants. Coefficients of higher-order terms are elastic constants of third order, fourth order, and so on.

Exploiting fourth-generation synchrotron radiation for enzyme and photoreceptor characterization.

The upgrade of the European Synchrotron Radiation Facility (ESRF) in Grenoble, France to an Extremely Brilliant Source (EBS) is expected to enable time-resolved synchrotron serial crystallography (SSX) experiments with sub-millisecond time resolution. ID29 is a new beamline dedicated to SSX experiments at ESRF-EBS. Here, we report experiments emerging from the initial phase of user operation at ID29.

Universal phase-field mixture representation of thermodynamics and shock-wave mechanics in porous soft biologic continua.

A continuum mixture theory is formulated for large deformations, thermal effects, phase interactions, and degradation of soft biologic tissues suitable at high pressures and low to very high strain rates. Tissues consist of one or more solid and fluid phases and can demonstrate nonlinear anisotropic elastic, viscoelastic, thermoelastic, and poroelastic physics. Under extreme deformations or shock loading, tissues may fracture, tear, or rupture.

Health professionals' and caregivers' perspectives on improving paramedics' provision of palliative care in Australian communities: a qualitative study.

Objectives: Paramedics have the potential to make a substantial contribution to community-based palliative care provision. However, they are hindered by a lack of policy and institutional support, as well as targeted education and training. This study aimed to elicit paramedics', palliative care doctors' and nurses', general practitioners', residential aged care nurses' and bereaved families and carers' attitudes and perspectives on how palliative paramedicine can be improved to better suit the needs of community-based patients, their families and carers, and the clinicians involved in delivering the care.

Factors Associated with Advance Care Planning Engagement Among Community-Dwelling Older Adults: A Cross-Sectional Study.

Aim: To explore the associations between depression, anxiety, decisional conflict and advance care planning engagement and the potential mediating role of decisional conflict in the associations between depression, anxiety and advance care planning among community-dwelling older adults.

Design: A cross-sectional study was conducted with 262 community-dwelling older Australians across metropolitan, regional and rural communities between August and October 2022.

Methods: Validated self-reported questions were used to collect data on anxiety, depression (Hospital Anxiety and Depression Scale), decisional conflict (Decisional Conflict Scale), advance care planning engagement (Advance Care Planning Engagement Survey) and covariates (demographic characteristics, health literacy [Health Literacy Screening Questions]), overall health status (Short form 36).

The HEALthy Brain and Child Development Study (HBCD): NIH collaboration to understand the impacts of prenatal and early life experiences on brain development.

The human brain undergoes rapid development during the first years of life. Beginning in utero, a wide array of biological, social, and environmental factors can have lasting impacts on brain structure and function. To understand how prenatal and early life experiences alter neurodevelopmental trajectories and shape health outcomes, several NIH Institutes, Centers, and Offices collaborated to support and launch the HEALthy Brain and Child Development (HBCD) Study.

Generation of iPSC lines from three Laing distal myopathy patients with a recurrent MYH7 p.Lys1617del variant.

Variants in MYH7 cause cardiomyopathies as well as myosin storage myopathy and Laing early-onset distal myopathy (MPD1). MPD1 is characterized by muscle weakness and atrophy usually beginning in the lower legs. Here, we generated iPSC lines from lymphoblastoid cells of three unrelated individuals heterozygous for the most common MPD1-causing variant; p.

Inclusion of Sex and Gender to Improve the State of the Science in Women's Health.

The influence of sex and gender-related factors on health and disease at all levels of scale, across all health conditions, and throughout the entire life course is increasingly clear. A series of policies instituted by the National Institutes of Health (NIH) that require researchers to include appropriate populations and to analyze the data accordingly have strengthened the evidence base around the health of women. Translating these advances to the entire research ecosystem can catalyze rigorous biomedical discovery that can improve health.

Molecular Epidemiology of Colonization in Families With Infants.

Background: Community-associated infection is a major public health hazard to adults and older children. Infants frequently excrete toxigenic asymptomatically in their stool, but their importance as a community reservoir of is uncertain.

Methods: Families of healthy infants were recruited at the baby's 4-month well child visit and were followed longitudinally until the baby was approximately 9 months old.

Workshop summary: National Institutes of Health (NIH) 2022 scientific workshop on gender and health.

In this manuscript, we summarize the goals, content, and impact of the Gender and Health: Impacts of Structural Sexism, Gender Norms, Relational Power Dynamics, and Gender Inequities workshop held by the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) in collaboration with 10 NIH Institutes, Centers, and Offices. Specifically, we outline the key points emerging from the workshop presentations, which are the focus of the collection of articles in this supplement. The overarching goals of the workshop were to convene NIH staff, the external scientific community, and the public to discuss methods, measurement, modifiable factors, interventions, and best practices in health research on gender as a social and cultural variable and to identify opportunities to advance research and foster collaborations on these key topics.

Ensuring accountability for consideration of sex as a biological variable in research.

The National Institute of Health (NIH) policy, Consideration of Sex as a Biological Variable (SABV) in NIH-funded Research (2015), focuses on the expectation that researchers account for the influence of SABV in vertebrate animal and human studies and provide a strong justification for single-sex investigations. When SABV is considered in the research design, data analyses, and reporting, the rigor and reproducibility of the research are elevated and inform best practices and precision health for all people. Additional recommendations include the appropriate use of terminology, integration into curricula, intersection with social determinants of health, and application of sex and gender equity guidelines when disseminating research.

Putting science to work for women's health.

The Office of Research on Women's Health (ORWH)'s whole health paradigm expands the scope of women's health research, incorporating a life-course perspective that recognizes the profound influences of sex and gender on health. From childhood through adulthood, external and societal factors along with internal factors and biology shape women's health and influence access to quality healthcare. This comprehensive approach integrates data-driven sex- and gender-aware strategies to prevent, diagnose, and treat disease, focusing on the unique needs of women.

Machine Learning Models to Interrogate Proteome-Wide Covalent Ligandabilities Directed at Cysteines.

Machine learning (ML) identification of covalently ligandable sites may accelerate targeted covalent inhibitor design and help expand the druggable proteome space. Here, we report the rigorous development and validation of the tree-based models and convolutional neural networks (CNNs) trained on a newly curated database (LigCys3D) of over 1000 liganded cysteines in nearly 800 proteins represented by over 10,000 three-dimensional structures in the protein data bank. The unseen tests yielded 94 and 93% area under the receiver operating characteristic curves for the tree models and CNNs, respectively.