Klein

Clinical genetic laboratories must have access to clinically validated biomedical data for precision medicine. A lack of accessibility, normalized structure, and consistency in evaluation complicates interpretation of disease causality, resulting in confusion in assessing the clinical validity of genes and genetic variants for diagnosis. A key goal of the Clinical Genome Resource (ClinGen) is to fill the knowledge gap concerning the strength of evidence supporting the role of a gene in a monogenic disease, which is achieved through a process known as Gene-Disease Validity curation...

High injury rates and long injury-related downtimes demonstrate the need for effective and differentiated injury prevention strategies in football. Preventive measures should take place in various fields and should not be reduced to training programmes or medical approaches. The so-called "Big 6 of injury prevention" provide an overview of the key areas that should be addressed. In modern sports medicine, it should be a matter of course that the team doctor already participates in the primary prevention strategies and does not only get involved in the post-traumatic treatment...

10% of pancreatic neuroendocrine tumors (pNETs) are related to inherited syndromes (MEN1, MEN4, VHL, NF1, TSC). Growing evidence suggests that clinically sporadic pNETs can also harbor germline pathogenic variants. In this study, we report the prevalence of pathological/likely pathological germline variants (P/LP) in a high-risk cohort and an unselected cohort. We collected clinical data of patients with pNETs seen at MD Anderson Cancer Center (MDACC) and Johns Hopkins Hospital (JHH). High-risk cohort included (n=132) patients seen at MDACC who underwent germline testing for high-risk criteria (early onset, personal or family history of cancer and syndromic features) between 2013-2019...

Incorporating Curcumin into animal diets holds significant promise for enhancing both animal health and productivity, with demonstrated positive impacts on antioxidant activity, anti-microbial responses. Therefore, this study aimed to determine whether adding Curcumin to the diet of dairy calves would influence ruminal fermentation, hematologic, immunological, oxidative, and metabolism variables. Fourteen Jersey calves were divided into a control group (GCON) and a treatment group (GTRA). The animals in the GTRA received a diet containing 65...

Studies have demonstrated associations between cumulative concussion and repetitive head impact exposure (RHI) via contact sports with white matter (WM) alterations later in life. The course of WM changes associated with exposure earlier in the lifespan are unclear. This study investigated alterations in white matter (WM hyperintensity [WMH] volume and microstructural changes) associated with concussion and RHI exposure from adolescence to early midlife, as well as the interaction between exposure and age-cohort (i...

While pregnancy is a time of relative immunosuppression, infective endocarditis and bacterial meningitis remain rare. We present a case of a pregnant woman with Streptococcus oralis endocarditis and meningitis. This is the first reported case of Streptococcus oralis meningitis in a patient without predisposing risk factors. This case highlights the importance of collecting blood cultures in febrile illness during pregnancy and illustrates that effective management plans can be formulated without performing invasive diagnostic tests such as transesophageal echocardiography...

INTRODUCTION: Ultraviolet (UV) light is a known trigger of both cutaneous and systemic disease manifestations in lupus patients. Lupus skin has elevated expression of type I interferons (IFNs) that promote increased keratinocyte (KC) death after UV exposure. The mechanisms by which KC cell death is increased by type I IFNs are unknown. METHODS: Here, we examine the specific cell death pathways that are activated in KCs by type I IFN priming and UVB exposure using a variety of pharmacological and genetic approaches...

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Dissolvable microneedles (DMNs), fabricated from biocompatible materials that dissolve in both water and skin have gained popularity in dermatology. However, limited research exists on their application in compromised skin conditions. This study compares the hyaluronic acid-based DMNs penetration, formation of microchannels, dissolution, and diffusion kinetics in intact, barrier-disrupted (tape stripped), and dry (acetone-treated) porcine ear skin ex vivo. After DMNs application, comprehensive investigations including dermoscopy, stereomicroscope, skin hydration, transepidermal water loss (TEWL), optical coherence tomography (OCT), reflectance confocal laser scanning microscopy (RCLSM), confocal Raman micro-spectroscopy (CRM), two-photon tomography combined with fluorescence lifetime imaging (TPT-FLIM), histology, and scanning electron microscopy (SEM) were conducted...

Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure, but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein serving as the final downstream effector of pyroptosis/interleukin (IL)-1pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd-deficiency ameliorated immunothrombosis, acute tissue injury and failure...

IMPORTANCE: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown. OBJECTIVE: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings...

The evolution of cognition can be understood in terms of a few major transitions-changes in the computational architecture of nervous systems that changed what cognitive capacities could be evolved by downstream lineages. We demonstrate how the idea of a major cognitive transition can be modeled in terms of where a system's effective computational architecture falls on the well-studied hierarchy of formal automata (HFA). We then use recent work connecting artificial neural networks to the HFA, which provides a way to make the structure-architecture link in natural systems...

PURPOSE OF REVIEW: Oral contraceptive pills are among the most popular contraceptives worldwide, including among adolescents, and are available over the counter in over 100 countries. However, when a prescription is required, oral contraceptives may be difficult to obtain, particularly for adolescents. Recent approvals of over-the-counter progestin-only pills in the United Kingdom and United States have brought widespread attention to this topic. RECENT FINDINGS: Progestin-only pills, including the norgestrel pill recently approved for over-the-counter use in the United States, are highly effective and may be used safely without a prescription or medical monitoring, including by adolescents...

This paper is an exploration of gratitude as a fundamental concept in psychoanalysis. Melanie Klein's classic article "Envy and Gratitude" (1957) named gratitude at one pole on an axis of human suffering and flourishing, but with a few notable exceptions, the article stimulated research into envy. This paper explores the historical and philosophical traditions that have, to some extent unconsciously, influenced our contemporary understandings of gratitude. The paper also works to explore the social and ethical meanings of gratitude as well as gratitude's psychoanalytic significance...

This article explores the impact of the analyst's life-threatening illness on the analytic couple; it is informed through two theoretical lenses - Freud's ideas about the vicissitudes of mourning, which have been elaborated on by Melanie Klein and John Steiner, and Christopher Bollas's ideas about destiny and idiom. Clinical material will focus on my on-going work with a middle-aged man who has a history of early abandonment and loss and who struggles with being able to remain separate from his objects while being in relationship with them...

To facilitate a prospective estimation of the effective dose of an CT scan prior to the actual scanning in order to use sophisticated patient risk minimizing methods, a prospective spatial dose estimation and the known anatomical structures are required. To this end, a CT reconstruction method is required to reconstruct CT volumes from as few projections as possible, i.e. by using the topograms, with anatomical structures as correct as possible. In this work, an optimized CT reconstruction model based on a generative adversarial network (GAN) is proposed...

PURPOSE: Minimal-invasive liver surgery (MILS) reduces surgical trauma and is associated with fewer postoperative complications. To amplify these benefits, perioperative multimodal concepts like Enhanced Recovery after Surgery (ERAS), can play a crucial role. We aimed to evaluate the cost-effectiveness for MILS in an ERAS program, considering the necessary additional workforce and associated expenses. METHODS: A prospective observational study comparing surgical approach in patients within an ERAS program compared to standard care from 2018-2022 at the Charité - Universitätsmedizin Berlin...

Based on the UN Convention on the Rights of the Child, children and young people have the right to participate in all matters and decisions that affect them. This applies in particular when they are patients in a children's hospital. In the international context, established formats for the participation of young patients regarding health issues already exist, for example "Children's Councils" or "Young Person's Advisory Groups". In Germany, such approaches are still mostly lacking. It thus remains important to develop suitable formats that enable meaningful and effective participation of young patients in the health system...

INTRODUCTION: Studies of gonadotropin-releasing hormone analogues [intramuscular (IM) leuprolide acetate (LA) and triptorelin] for treatment monitoring of central precocious puberty (CPP) demonstrate this approach is effective for confirming pubertal hormone suppression. Herein, we provide new data using subcutaneous LA (SC LA) suggesting similar efficacy for treatment monitoring. METHODS: PubMed, Embase, and CINAHL were searched for studies of GnRHa use to monitor treatment of CPP...

Negative life events (NLE) have been associated with increased alcohol use (AU) during adolescence. However, whether this risk association may be modified by leisure activities such as sports participation (SP) remains poorly understood. This study examined whether accumulated family-specific NLE in particular were associated with greater AU, and if so, whether SP moderated this association to reduce AU among high-NLE adolescents. We examined five annual assessments from a nationwide cohort of 3,422 Norwegian adolescents (13-15 year-olds; 55...