Marginalized measures: The harmonization of diversity in precision medicine research.

The production of large, shareable datasets is increasingly prioritized for a wide range of research purposes. In biomedicine, especially in the United States, calls to enhance representation of historically underrepresented populations in databases that integrate genomic, health history, demographic and lifestyle data have also increased in order to support the goals of precision medicine. Understanding the assumptions and values that shape the design of such datasets and the practices through which they are constructed are a pressing area of social inquiry.

Development and validation of a national clinical pharmacy competency framework for hospital pharmacists in Austria: a multi-method study.

Background: Despite the publication of a European wide competency framework for hospital pharmacy by the European Association of Hospital Pharmacist (EAHP) in 2017, not all countries have adopted and implemented such a framework.

Aim: This study aimed to develop and validate a bespoke national hospital pharmacy competency framework for Austria that supports the hospital pharmacy workforce development.

Method: A multi-method study was carried out in three phases.

ReLo is a simple and rapid colocalization assay to identify and characterize direct protein-protein interactions.

The characterization of protein-protein interactions (PPIs) is fundamental to the understanding of biochemical processes. Many methods have been established to identify and study direct PPIs; however, screening and investigating PPIs involving large or poorly soluble proteins remains challenging. Here, we introduce ReLo, a simple, rapid, and versatile cell culture-based method for detecting and investigating interactions in a cellular context.

Interrogating the Value of Return of Results for Diverse Populations: Perspectives from Precision Medicine Researchers.

Background: Over the last decade, the return of results (ROR) in precision medicine research (PMR) has become increasingly routine. Calls for individual rights to research results have extended the "duty to report" from clinically useful genetic information to traits and ancestry results. ROR has thus been reframed as inherently beneficial to research participants, without a needed focus on who benefits and how.

Structural basis for binding of Smaug to the GPCR Smoothened and to the germline inducer Oskar.

Smaug and its orthologs comprise a family of mRNA repressor proteins that exhibit various functions during animal development. Smaug proteins contain a characteristic RNA-binding sterile-α motif (SAM) domain and a conserved but uncharacterized N-terminal domain (NTD). Here, we resolved the crystal structure of the NTD of the human SAM domain-containing protein 4A (SAMD4A, a.

Rethinking Benefit and Responsibility in the Context of Diversity: Perspectives from the Front Lines of Precision Medicine Research.

Introduction: Federal agencies have instituted guidelines to prioritize the enrollment and retention of diverse participants in precision medicine research (PMR). Prior studies examining participation of minoritized communities have shown that potential benefits represent a key determinant. Human subject research guidance, however, conceptualizes potential benefits narrowly, emphasizing generalized advances in medical knowledge.

Community Engagement in Precision Medicine Research: Organizational Practices and Their Impacts for Equity.

Background: In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal.

Methods: Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for.

Results: We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant consequences for the time and resources devoted to engagement and the ultimate impacts it has on research.

Diagnosis and the practices of patienthood: How diagnostic journeys shape illness experiences.

Sociologists have a rich history of studying the process of diagnosis and how people experience illness. Yet, the sociology of diagnosis and illness experience literatures have seldom been fully integrated. Instead, these literatures highlight one element of the illness journey, wherein scholars either primarily study diagnostic processes and categories or people's illness experiences.

Targeting Representation: Interpreting Calls for Diversity in Precision Medicine Research.

Scientists have identified a "diversity gap" in genetic samples and health data, which have been drawn predominantly from individuals of European ancestry, as posing an existential threat to the promise of precision medicine. Inadequate inclusion as articulated by scientists, policymakers, and ethicists has prompted large-scale initiatives aimed at recruiting populations historically underrepresented in biomedical research. Despite explicit calls to increase diversity, the meaning of diversity - which dimensions matter for what outcomes and why - remain strikingly imprecise.

Strategies of inclusion: The tradeoffs of pursuing "baked in" diversity through place-based recruitment.

US funding agencies have begun to institutionalize expectations that biomedical studies achieve defined thresholds for diversity among research participants, including in precision medicine research (PMR). In this paper, we examine how practices of recruitment have unfolded in the wake of these diversity mandates. We find that a very common approach to seeking diverse participants leverages understandings of spatial, geographic, and site diversity as proxies and access points for participant diversity.

Beyond inclusion: Enacting team equity in precision medicine research.

Purpose: To identify meanings of and challenges to enacting equitable diversification of genomics research, and specifically precision medicine research (PMR), teams.

Methods: We conducted in-depth interviews with 102 individuals involved in three U.S.

Stability evaluation of morphine, hydromorphone, metamizole and esketamine containing analgesic mixtures applied for patient-controlled analgesia in hospice and palliative care.

In this study, different injection solutions containing opioid and nonopioid compounds used for patient-controlled analgesia in hospice and palliative care were evaluated in terms of analyte stability. Investigated injection solutions contained different combinations of morphine, hydromorphone, metamizole and esketamine. For the practical implementation, samples from infusion pumps were daily drawn over a period of 7 days at 22 and 37°C.

LOTUS-domain proteins - developmental effectors from a molecular perspective.

The LOTUS domain (also known as OST-HTH) is a highly conserved protein domain found in a variety of bacteria and eukaryotes. In animals, the LOTUS domain is present in the proteins Oskar, TDRD5/Tejas, TDRD7/TRAP/Tapas, and MARF1/Limkain B1, all of which play essential roles in animal development, in particular during oogenesis and/or spermatogenesis. This review summarizes the diverse biological as well as molecular functions of LOTUS-domain proteins and discusses their roles as helicase effectors, post-transcriptional regulators, and critical cofactors of piRNA-mediated transcript silencing.

Overcoming limitations in the availability of swabs systems used for SARS-CoV-2 laboratory diagnostics.

The diagnosis of COVID-19 relies on the direct detection of SARS-CoV-2 RNA in respiratory specimens by RT-PCR. The pandemic spread of the disease caused an imbalance between demand and supply of materials and reagents needed for diagnostic purposes including swab sets. In a comparative effectiveness study, we conducted serial follow-up swabs in hospitalized laboratory-confirmed COVID-19 patients.

Anidulafungin and Micafungin Concentrations in Cerebrospinal Fluid and in Cerebral Cortex.

Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01 to 0.

Using autoimmune strategically: Diagnostic lumping, splitting, and the experience of illness.

Experience of illness and sociology of diagnosis literatures offer valuable insights into how people live with chronic illness. In this article, we argue that investigating autoimmune illnesses contributes to the sociological understanding of illness experiences and diagnosis practices. Autoimmune is a broad category of illnesses in which a person's immune system identifies healthy cells as pathological.

Implementing Pediatric Asthma Pathways in Community Hospitals: A National Qualitative Study.

Background: Pathways can improve the quality of care and outcomes for children with asthma; however, we know little about how to successfully implement pathways across diverse hospital settings. Prior studies of pathways have focused on determining clinical effectiveness and the majority were conducted in children's hospitals. These approaches have left crucial gaps in our understanding of how to successfully implement pathways in community hospitals, where most of the children with asthma are treated nationally.

Use of technology for delivery of mental health and substance use services to youth living with HIV: a mixed-methods perspective.

Disparities in HIV treatment outcomes among youth living with HIV (YLWH) present a challenge for ending the HIV epidemic. Antiretroviral therapy (ART) adherence can be impacted by comorbidities such as mental health and substance use. Technology use has shown promise in increasing access to mental health and substance use services.

Discovery of Molidustat (BAY 85-3934): A Small-Molecule Oral HIF-Prolyl Hydroxylase (HIF-PH) Inhibitor for the Treatment of Renal Anemia.

Small-molecule inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clinical development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increased erythropoiesis. Herein we describe the discovery, synthesis, structure-activity relationship (SAR), and proposed binding mode of novel 2,4-diheteroaryl-1,2-dihydro-3H-pyrazol-3-ones as orally bioavailable HIF-PH inhibitors for the treatment of anemia.

The LOTUS domain is a conserved DEAD-box RNA helicase regulator essential for the recruitment of Vasa to the germ plasm and nuage.

DEAD-box RNA helicases play important roles in a wide range of metabolic processes. Regulatory proteins can stimulate or block the activity of DEAD-box helicases. Here, we show that LOTUS (Limkain, Oskar, and Tudor containing proteins 5 and 7) domains present in the germline proteins Oskar, TDRD5 (Tudor domain-containing 5), and TDRD7 bind and stimulate the germline-specific DEAD-box RNA helicase Vasa.

Correlation of Secretory Activity of Neutrophils With Genotype in Patients With Familial Mediterranean Fever.

Objective: Familial Mediterranean fever (FMF) is an autoinflammatory disorder caused by pyrin-encoding MEFV mutations. Patients present with recurrent but self-limiting episodes of acute inflammation and often have persistent subclinical inflammation. The pathophysiology is only partially understood, but neutrophil overactivation is a hallmark of the disease.