Identification of Factors Influencing Donor-Derived Cell-Free DNA Levels up to One Year After Kidney Transplant.

Donor-derived cell-free DNA (dd-cfDNA) in the peripheral blood of allograft recipients has shown to early identify allograft injury. In this study, we assessed the factors that influence the amount of circulating dd-cfDNA during the first month postkidney transplant as well as its longitudinal trend. A consecutive series of 98 adult kidney transplant recipients at a single center between July 2018 and January 2020 were included in this study.

Structure-Activity Relationship Studies in a Series of 2-Aryloxy--(pyrimidin-5-yl)acetamide Inhibitors of SLACK Potassium Channels.

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare, serious, and pharmacoresistant epileptic disorder often linked to gain-of-function mutations in the gene. encodes the sodium-activated potassium channel known as SLACK, making small molecule inhibitors of SLACK channels a compelling approach to the treatment of EIMFS and other epilepsies associated with mutations. In this manuscript, we describe a hit optimization effort executed within a series of 2-aryloxy--(pyrimidin-5-yl)acetamides that were identified via a high-throughput screen.

Differential bone calcium retention with the use of oral versus vaginal hormonal contraception: A randomized trial using calcium-41 radiotracer.

Objectives: This study aimed to assess if hormonal contraception administered orally (combined oral contraceptive pill, COC) or vaginally (contraceptive vaginal ring) differentially affected bone calcium retention in young females.

Study Design: Reproductive aged females (18-35 years) not using hormonal contraception were dosed with 50 nCi Ca as CaCl in 10 mL of sterile saline (0.9%).

WelQrate: Defining the Gold Standard in Small Molecule Drug Discovery Benchmarking.

While deep learning has revolutionized computer-aided drug discovery, the AI community has predominantly focused on model innovation and placed less emphasis on establishing best benchmarking practices. We posit that without a sound model evaluation framework, the AI community's efforts cannot reach their full potential, thereby slowing the progress and transfer of innovation into real-world drug discovery. Thus, in this paper, we seek to establish a new gold standard for small molecule drug discovery benchmarking, .

"Music Played a Role in Saving My Life and Getting Me Through All of This": A Descriptive Qualitative Study of Hope in Adolescents and Young Adults Living With Advanced Cancer.

Adolescents and young adults (AYAs) living with advanced cancer may experience a heightened risk for existential distress. Addressing AYAs' hopes can stimulate a dialogue about their concerns, values, and goals, provide a path to holistically support their existential needs, and potentially alleviate their distress. This study aimed to evaluate hope's role in a sample of AYAs living with advanced cancer.

Environmental public health research at the U.S. Environmental Protection Agency: A blueprint for exposure science in a connected world.

Exposure science plays an essential role in the U.S. Environmental Protection Agency's (U.

Biclustering Multivariate Longitudinal Data with Application to Recovery Trajectories of White Matter After Sport-Related Concussion.

Biclustering is the task of simultaneously clustering the samples and features of a data set. In doing so, subsets of samples that exhibit similar behaviors across subsets of features can be identified. Motivated by a longitudinal diffusion tensor imaging study of sport-related concussion (SRC), we present the problem of biclustering multivariate longitudinal data in which subjects and features are grouped simultaneously based on longitudinal patterns rather than magnitude.

Vitamin D-Do Diet Recommendations for Health Remain Strong?

How will the scientific community and authoritative bodies define future nutritional requirements for vitamin D? At the International Symposium on Nutritional Aspects of Musculoskeletal Health, the authors debated the strength of current evidence for setting vitamin D intake recommendations from diet: the positive side of the strength of the evidence (PRO) suggests there is a physiological requirement for vitamin D and the opposing view (CON) that in light of negative results from large, recent trials, particularly those with fractures and bone health outcomes, we are left rudderless. Should we provide recommendations based on empiric treatment of vitamin D for most groups and conditions? It is becoming increasingly evident that vitamin D plays a role in many physiological functions and processes associated with long-term human health; however, to what extent are these benefits apparent beyond what is needed for adequate nutritional status, measured as serum 25-hydroxyvitamin D levels, for active calcium absorption? The meeting attendees voted for the PRO vs. CON position at the end of the session.

Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children. Liver biopsy is considered the gold standard for diagnosis. Magnetic resonance elastography (MRE) and transient elastography (TE) are imaging modalities that can monitor fibrosis and steatosis noninvasively.

An integrated approach to neuroscience care: An innovative model to support the new integrated care system.

Integrated care systems join up health and care services, so that people have the support they need, in the right place, at the right time. The aims include improving outcomes in healthcare, tackling inequalities in access and enhancing productivity and value for money. This is needed for neuroscience care as the traditional delivery of neuroscience care is inefficient, outdated and expensive, and can involve complex referral pathways and long waiting times.

Toward a science-based classification of processed foods to support meaningful research and effective health policies.

Processed foods have been part of the American diet for decades, with key roles in providing a safe, available, affordable, and nutritious food supply. The USDA Food Guides beginning in 1916 and the US Dietary Guidelines for Americans (DGA) since 1980 have included various types of commonly consumed processed foods (e.g.

Myelin dystrophy impairs signal transmission and working memory in a multiscale model of the aging prefrontal cortex.

Normal aging leads to myelin alterations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC), which are positively correlated with degree of cognitive impairment. It is hypothesized that remyelination with shorter and thinner myelin sheaths partially compensates for myelin degradation, but computational modeling has not yet explored these two phenomena together systematically. Here, we used a two-pronged modeling approach to determine how age-related myelin changes affect a core cognitive function: spatial working memory.

Automated transient grating spectroscopy mapping and signal control for large samples.

We present developments for the mapping of large areas using transient grating spectroscopy (TGS) that allow for smoother, larger, autonomous measurements of material samples. The addition of a precise linear stage in the direction parallel to laser sampling coupled with signal optimizing control allows for hands free, self-correcting measurements. In addition, the simplification of the sample holding design to a form that is small enough to mount directly to the linear stage exhibits a straightforward, low-cost solution for automated TGS applications.

Proteomic features of gray matter layers and superficial white matter of the rhesus monkey neocortex: comparison of prefrontal area 46 and occipital area 17.

In this novel large-scale multiplexed immunofluorescence study we comprehensively characterized and compared layer-specific proteomic features within regions of interest of the widely divergent dorsolateral prefrontal cortex (A46) and primary visual cortex (A17) of adult rhesus monkeys. Twenty-eight markers were imaged in rounds of sequential staining, and their spatial distribution precisely quantified within gray matter layers and superficial white matter. Cells were classified as neurons, astrocytes, oligodendrocytes, microglia, or endothelial cells.

Structure-Activity Relationship Studies in a Series of Xanthine Inhibitors of SLACK Potassium Channels.

Gain-of-function mutations in the gene, which encodes the sodium-activated potassium channel known as SLACK, are associated with the rare but devastating developmental and epileptic encephalopathy known as epilepsy of infancy with migrating focal seizures (EIMFS). The design of small molecule inhibitors of SLACK channels represents a potential therapeutic approach to the treatment of EIMFS, other childhood epilepsies, and developmental disorders. Herein, we describe a hit optimization effort centered on a xanthine SLACK inhibitor () discovered via a high-throughput screen.

Interruption of the intratumor CD8 T cell:Treg crosstalk improves the efficacy of PD-1 immunotherapy.

PD-1 blockade unleashes potent antitumor activity in CD8 T cells but can also promote immunosuppressive T regulatory (Treg) cells, which may worsen the response to immunotherapy. Tumor-Treg inhibition is a promising strategy to improve the efficacy of checkpoint blockade immunotherapy; however, our understanding of the mechanisms supporting tumor-Tregs during PD-1 immunotherapy is incomplete. Here, we show that PD-1 blockade increases tumor-Tregs in mouse models of melanoma and metastatic melanoma patients.