Machine learning-based prediction models in medical decision-making in kidney disease: patient, caregiver, and clinician perspectives on trust and appropriate use.

Objectives: This study aims to improve the ethical use of machine learning (ML)-based clinical prediction models (CPMs) in shared decision-making for patients with kidney failure on dialysis. We explore factors that inform acceptability, interpretability, and implementation of ML-based CPMs among multiple constituent groups.

Materials And Methods: We collected and analyzed qualitative data from focus groups with varied end users, including: dialysis support providers (clinical providers and additional dialysis support providers such as dialysis clinic staff and social workers); patients; patients' caregivers (n = 52).

Supporting students from underrepresented minority backgrounds in graduate school: A mixed-methods formative study to inform post-baccalaureate design.

The US biomedical research workforce suffers from systemic barriers causing insufficient diversity and perpetuating inequity. To inform programming enhancing graduate program access, we implemented a formative mixed-method study to identify needed supports for program applications and graduate program success. Overall, results indicate value in added supports for understanding application needs, network development, critical thinking, time management, and reading academic/scientific literature.

Preclinical Evaluation of Sigma 1 Receptor Antagonists as a Novel Treatment for Painful Diabetic Neuropathy.

The global prevalence of diabetes is steadily rising, with an estimated 537 million adults affected by diabetes in 2021, projected to reach 783 million by 2045. A severe consequence of diabetes is the development of painful diabetic neuropathy (PDN), afflicting approximately one in every three diabetic patients and significantly compromising their quality of life. Current pharmacotherapies for PDN provide inadequate pain relief for many patients, underscoring the need for novel treatments that are both safe and effective.

Homophily and social mixing in a small community: Implications for infectious disease transmission.

Community mixing patterns by sociodemographic traits can inform the risk of epidemic spread among groups, and the balance of in- and out-group mixing affects epidemic potential. Understanding mixing patterns can provide insight about potential transmission pathways throughout a community. We used a snowball sampling design to enroll people recently diagnosed with SARS-CoV-2 in an ethnically and racially diverse county and asked them to describe their close contacts and recruit some contacts to enroll in the study.

Machine learning models to predict ligand binding affinity for the orexin 1 receptor.

The orexin 1 receptor (OX1R) is a G-protein coupled receptor that regulates a variety of physiological processes through interactions with the neuropeptides orexin A and B. Selective OX1R antagonists exhibit therapeutic effects in preclinical models of several behavioral disorders, including drug seeking and overeating. However, currently there are no selective OX1R antagonists approved for clinical use, fueling demand for novel compounds that act at this target.

Racial Differences in Shared Decision-Making About Critical Illness.

Importance: Shared decision-making is the preferred method for evaluating complex tradeoffs in the care of patients with critical illness. However, it remains unknown whether critical care clinicians engage diverse patients and caregivers equitably in shared decision-making.

Objective: To compare critical care clinicians' approaches to shared decision-making in recorded conversations with Black and White caregivers of patients with critical illness.

Clinical Care of Patients with Neurocognitive Disorders: A Qualitative Study of the Psychiatric Residency Training Experience.

Objective: Few data describe how general psychiatry residencies prepare trainees to care for individuals with neurocognitive disorders (NCDs), despite increasing recognition of the need for psychiatrists to provide care for the growing numbers of patients with NCD. This study aims to identify training needs and approaches, as the resident experience is one important perspective that can be added to others, such as milestones developed by expert educators.

Methods: The authors conducted three focus groups of third- and fourth-year general adult psychiatry residency trainees from three different training programs in May and June of 2021.

Recent advances in drug discovery efforts targeting the sigma 1 receptor system: Implications for novel medications designed to reduce excessive drug and food seeking.

Psychiatric disorders characterized by uncontrolled reward seeking, such as substance use disorders (SUDs), alcohol use disorder (AUD) and some eating disorders, impose a significant burden on individuals and society. Despite their high prevalence and substantial morbidity and mortality rates, treatment options for these disorders remain limited. Over the past two decades, there has been a gradual accumulation of evidence pointing to the sigma-1 receptor (S1R) system as a promising target for therapeutic interventions designed to treat these disorders.

Scalable Strategies to Increase Efficiency and Augment Public Health Activities During Epidemic Peaks.

Objective: Scalable strategies to reduce the time burden and increase contact tracing efficiency are crucial during early waves and peaks of infectious transmission.

Design: We enrolled a cohort of SARS-CoV-2-positive seed cases into a peer recruitment study testing social network methodology and a novel electronic platform to increase contact tracing efficiency.

Setting: Index cases were recruited from an academic medical center and requested to recruit their local social contacts for enrollment and SARS-CoV-2 testing.

Implementation Strategy Fidelity and Organizational Outcomes in a Randomized Trial: Implications for Reentry from Corrections to Community Treatment.

This study examined fidelity of implementation strategies used in an organizational process improvement intervention (OPII) designed to improve evidence-based practices related to assessments for drug-involved clients exiting incarceration. Leadership was studied as a moderating factor between fidelity and outcomes. A mixed-method cluster randomized design was used to randomize 21 sites to early- or delayed-start within 9 research centers.

Using structured implementation interventions to improve referral to substance use treatment among justice-involved youth: Findings from a multisite cluster randomized trial.

Introduction: Youth involved in the justice system have high rates of alcohol and other drug use, but limited treatment engagement. JJ-TRIALS tested implementation activities with community supervision (CS) and behavioral health (BH) agencies to improve screening, identification of substance use service need, referral, and treatment initiation and engagement, guided by the BH Services Cascade and EPIS frameworks. This paper summarizes intervention impacts on referrals to treatment among youth on CS.

QSAR-Based Computational Approaches to Accelerate the Discovery of Sigma-2 Receptor (S2R) Ligands as Therapeutic Drugs.

S2R overexpression is associated with various forms of cancer as well as both neuropsychiatric disorders (e.g., schizophrenia) and neurodegenerative diseases (Alzheimer's disease: AD).

Novel Sigma 1 Receptor Antagonists as Potential Therapeutics for Pain Management.

The sigma 1 receptor (S1R) is a molecular chaperone protein located in the endoplasmic reticulum and plasma membranes and has been shown to play important roles in various pathological disorders including pain and, as recently discovered, COVID-19. Employing structure- and QSAR-based drug design strategies, we rationally designed, synthesized, and biologically evaluated a series of novel triazole-based S1R antagonists. Compound exhibited potent binding affinity for S1R, high selectivity over S2R and 87 other human targets, acceptable metabolic stability, slow clearance in liver microsomes, and excellent blood-brain barrier permeability in rats.

Identification of an irreversible PPARγ antagonist with potent anticancer activity.

Melanoma is responsible for most skin cancer deaths, and its incidence continues to rise year after year. Different treatment options have been developed for melanoma depending on the stage of the disease. Despite recent advances in immuno- and targeted therapies, advanced melanoma remains incurable and thus an urgent need persists for safe and more effective melanoma therapeutics.

Critical Factors Influencing Interorganizational Relationships Between Juvenile Probation and Behavioral Health Agencies.

Although interorganizational relationships (IORs) are essential to the effective delivery of human services, very little research has examined relationships between juvenile justice agencies and behavioral health providers, and few studies have identified the most critical organizational and individual-level characteristics influencing IORs. Across 36 sites, juvenile probation officials (n = 458) and community behavioral health providers (n = 91) were surveyed about characteristics of their agencies, themselves, and IORs with each other. Generalized Linear Mixed Models were used to analyze the data.

Comprehensive 3D-QSAR Model Predicts Binding Affinity of Structurally Diverse Sigma 1 Receptor Ligands.

The Sigma 1 Receptor (S1R) has attracted intense interest as a pharmaceutical target for various therapeutic indications, including the treatment of neuropathic pain and the potentiation of opioid analgesia. Efforts by drug developers to rationally design S1R antagonists have been spurred recently by the 2016 publication of the high-resolution X-ray crystal structure of the ligand-bound human S1R. Until now, however, the absence in the published literature of a single, large-scale, and comprehensive quantitative structure-activity relationship (QSAR) model that encompasses a structurally diverse collection of S1R ligands has impaired rapid progress.

Virtual Screening and Experimental Testing of B1 Metallo-β-lactamase Inhibitors.

The global rise of metallo-β-lactamases (MBLs) is problematic due to their ability to inactivate most β-lactam antibiotics. MBL inhibitors that could be coadministered with and restore the efficacy of β-lactams are highly sought after. In this study, we employ virtual screening of candidate MBL inhibitors without thiols or carboxylates to avoid off-target effects using the Avalanche software package, followed by experimental validation of the selected compounds.

A model for rigorously applying the Exploration, Preparation, Implementation, Sustainment (EPIS) framework in the design and measurement of a large scale collaborative multi-site study.

Background: This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners.

Methods: The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols.

PLANETARY CANDIDATES OBSERVED BY . VIII. A FULLY AUTOMATED CATALOG WITH MEASURED COMPLETENESS AND RELIABILITY BASED ON DATA RELEASE 25.

We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching four years of time series photometry (Data Release 25, Q1-Q17). The catalog contains 8054 KOIs of which 4034 are planet candidates with periods between 0.25 and 632 days.

Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity.

TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6.

Niclosamide is a Negative Allosteric Modulator of Group I Metabotropic Glutamate Receptors: Implications for Neuropathic Pain.

Purpose: Novel therapeutics are greatly needed that target specific pathological receptors and pathways involved in Neuropathic Pain (NP). Extending our previous work published in this Journal on Group I metabotropic glutamate receptor (mGluR) modulators, we now investigate the therapeutic potential of niclosamide in modulating aberrant glutamate transmission in NP.

Method: Calcium mobilization assays and cross-receptor selectivity experiments are conducted to characterize the pharmacological activity of niclosamide.

CORRELATES OF INTERORGANIZATIONAL SERVICE COORDINATION IN COMMUNITY CORRECTIONS.

Because weak interagency coordination between community correctional agencies (e.g., probation and parole) and community-based treatment providers has been identified as a major barrier to the use of evidence-based practices (EBPs) for treating druginvolved offenders, this study sought to examine how key organizational (e.

Influence of Organizational Characteristics on Success in Implementing Process Improvement Goals in Correctional Treatment Settings.

Although research indicates that organizational characteristics substantially influence the adoption and use of evidence-based practices (EBPs), there has been little empirical research on organizational factors most likely to influence successful implementation of EBPs, particularly in criminal justice settings. This study examined organizational characteristics related to the success of change teams in achieving improvements in assessment and case-planning procedures for persons leaving correctional settings and receiving community services. In this evaluation of the Organizational Process Improvement Intervention (OPII), part of the National Institute on Drug Abuse's (NIDA's) Criminal Justice Drug Abuse Treatment Studies (CJDATS) cooperative, 21 sites were randomized to an early-start or a delayed-start condition.

Examining Treatment Climate Across Prison-Based Substance Abuse Treatment Groups.

Background: With notable exceptions, few studies have looked critically at the role and effects of factors other than individual or programmatic differences that contribute to the climate within substance abuse treatment programs. De Leon's work on the therapeutic community, however, indicates that factors beyond the individual and program can contribute to the overall functioning of similarly situated communities.

Objectives: In this study, we introduce and examine the concept of the "treatment group," the level of aggregation between the individual who participates in treatment and the organization that provides it.

Stepping into the omics era: Opportunities and challenges for biomaterials science and engineering.

Unlabelled: The research paradigm in biomaterials science and engineering is evolving from using low-throughput and iterative experimental designs towards high-throughput experimental designs for materials optimization and the evaluation of materials properties. Computational science plays an important role in this transition. With the emergence of the omics approach in the biomaterials field, referred to as materiomics, high-throughput approaches hold the promise of tackling the complexity of materials and understanding correlations between material properties and their effects on complex biological systems.