Outcomes of Importance to Patients Living With Cutaneous Chronic Graft-vs-Host Disease.

Importance: Cutaneous chronic graft-vs-host disease (GVHD) is independently associated with morbidity and mortality after allogeneic hematopoietic cell transplant. However, the health-related quality-of-life (HRQOL) domains that are most important to patients are poorly understood.

Objective: To perform a concept elicitation study to define HRQOL in cutaneous chronic GVHD from the patient perspective and to compare experiences of patients with epidermal vs sclerotic disease.

Integrating Payor-Segregated Outpatient Obstetrics and Gynecology Care Models: The Patient Perspective.

Objective:  Significant racial and ethnic disparities in maternal morbidity and mortality as well as gynecologic outcomes persist in the United States. The role of ambulatory care in obstetrics and gynecology (OBGYN), particularly in facilities that separate resident and attending care along payor (and de facto racial) lines, remains unclear. This study examines patient perspectives on payor-segregated health care delivery in an academic medical center (AMC) and opinions on possible integration.

Probe my Pathway (PmP): a portal to explore the chemical coverage of the human Reactome.

Deciphering pathway-phenotype associations is critical for a system-wide understanding of cells and the chemistry of life. An approach to reach this goal is to systematically modulate pathways pharmacologically. The targeted and controlled regulation of an increasing number of proteins is becoming possible, thanks to the growing list of chemical probes and chemogenomic compounds available to cell biologists, but no resource is available that directly maps these chemical tools on cellular pathways.

Skeptical reactions to breast cancer screening benefits and harms: Antecedents, consequences, and implications for screening communication.

Objective: When people receive information about the benefits and harms of mammography screening, they do not always accept it at face value and instead express skepticism. The purpose of this research was to identify the psychological drivers of this skepticism. Two theory-driven hypotheses were considered: One hypothesis proposes that skeptical reactions reflect a psychological defense against information that is emotionally aversive.

CACHE Challenge #1: Targeting the WDR Domain of LRRK2, A Parkinson's Disease Associated Protein.

The CACHE challenges are a series of prospective benchmarking exercises to evaluate progress in the field of computational hit-finding. Here we report the results of the inaugural CACHE challenge in which 23 computational teams each selected up to 100 commercially available compounds that they predicted would bind to the WDR domain of the Parkinson's disease target LRRK2, a domain with no known ligand and only an apo structure in the PDB. The lack of known binding data and presumably low druggability of the target is a challenge to computational hit finding methods.

A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins.

Target class-focused drug discovery has a strong track record in pharmaceutical research, yet public domain data indicate that many members of protein families remain unliganded. Here we present a systematic approach to scale up the discovery and characterization of small molecule ligands for the WD40 repeat (WDR) protein family. We developed a comprehensive suite of protocols for protein production, crystallography, and biophysical, biochemical, and cellular assays.

Strategies to Limit Benzodiazepine Use in Anesthesia for Older Adults: A Randomized Clinical Trial.

Importance: Despite guidelines recommending avoidance of benzodiazepine administration to older patients, many of them now receive benzodiazepines as a part of anesthesia care. The effectiveness of clinician- and patient-facing interventions to discourage such use remains insufficiently characterized.

Objective: To evaluate the effect of clinician peer comparison, patient informational mail, or a combination of these interventions compared with usual care on the rate of perioperative benzodiazepine administration to older patients.

Telemedicine and Access to Elective Cholecystectomy for Socially Vulnerable Adults: A Pilot Randomized Clinical Trial.

Importance: Socially vulnerable patients with symptomatic cholelithiasis are more likely to face barriers to accessing surgical care. This barrier to access can lead to delays in treatment, the need for emergent cholecystectomy, and worse outcomes.

Objectives: To determine the effectiveness of telemedicine vs in-person surgical consultation on access to elective cholecystectomy in socially vulnerable populations and to evaluate the association of scheduling navigation with access to elective cholecystectomy in these populations.

Benchmarking Methods for PROTAC Ternary Complex Structure Prediction.

Proteolysis targeting chimeras (PROTACs) are bifunctional compounds that recruit an E3 ligase to a target protein to induce ubiquitination and degradation of the target. Rational optimization of PROTAC requires a structural model of the ternary complex. In the absence of an experimental structure, computational tools have emerged that attempt to predict PROTAC ternary complexes.

Mammography Screening Preferences Among Screening-Eligible Women in Their 40s : A National U.S. Survey.

Background: The U.S. Preventive Services Task Force (USPSTF) recently changed its recommendation for mammography screening from informed decision making to biennial screening for women aged 40 to 49 years.

A data science roadmap for open science organizations engaged in early-stage drug discovery.

The Structural Genomics Consortium is an international open science research organization with a focus on accelerating early-stage drug discovery, namely hit discovery and optimization. We, as many others, believe that artificial intelligence (AI) is poised to be a main accelerator in the field. The question is then how to best benefit from recent advances in AI and how to generate, format and disseminate data to enable future breakthroughs in AI-guided drug discovery.

University of Pennsylvania Telehealth Research Center of Excellence.

Drawing from insights from communication science and behavioral economics, the University of Pennsylvania Telehealth Research Center of Excellence (Penn TRACE) is designing and testing telehealth strategies with the potential to transform access to care, care quality, outcomes, health equity, and health-care efficiency across the cancer care continuum, with an emphasis on understanding mechanisms of action. Penn TRACE uses lung cancer care as an exemplar model for telehealth across the care continuum, from screening to treatment to survivorship. We bring together a diverse and interdisciplinary team of international experts and incorporate rapid-cycle approaches and mixed methods evaluation in all center projects.

Subpocket Similarity-Based Hit Identification for Challenging Targets: Application to the WDR Domain of LRRK2.

We herewith applied a generic hit identification method (POEM) for difficult targets of known three-dimensional structure, relying on the simple knowledge of physicochemical and topological properties of a user-selected cavity. Searching for local similarity to a set of fragment-bound protein microenvironments of known structure, a point cloud registration algorithm is first applied to align known subpockets to the target cavity. The resulting alignment then permits us to directly pose the corresponding seed fragments in a target cavity space not typically amenable to classical docking approaches.

Patient Preferences for Immediate Compared With Delayed Postpartum Intrauterine Device Placement.

Objective: To use choice-based conjoint survey methodology to evaluate patient values and decision making regarding immediate compared with delayed placement of postpartum intrauterine devices (IUDs).

Methods: We conducted a cross-sectional study in which we surveyed 200 nonpregnant, parous patients. Participants chose between hypothetical postpartum IUDs varying in multiple attributes (hormonal or nonhormonal IUD type, placement timing, 1-year efficacy, expulsion risk, risk of lost strings, and malposition risk).

The Pan-Canadian Chemical Library: A Mechanism to Open Academic Chemistry to High-Throughput Virtual Screening.

Computationally screening chemical libraries to discover molecules with desired properties is a common technique used in early-stage drug discovery. Recent progress in the field now enables the efficient exploration of billions of molecules within days or hours, but this exploration remains confined within the boundaries of the accessible chemistry space. While the number of commercially available compounds grows rapidly, it remains a limited subset of all druglike small molecules that could be synthesized.

Development of Peptide Displacement Assays to Screen for Antagonists of DDB1 Interactions.

The DNA damage binding protein 1 (DDB1) is an essential component of protein complexes involved in DNA damage repair and the ubiquitin-proteasome system (UPS) for protein degradation. As an adaptor protein specific to Cullin-RING E3 ligases, DDB1 binds different receptors that poise protein substrates for ubiquitination and subsequent degradation by the 26S proteasome. Examples of DDB1-binding protein receptors are Cereblon (CRBN) and the WD-repeat containing DB1- and UL4-ssociated actors (DCAFs).

Emerging structure-based computational methods to screen the exploding accessible chemical space.

Structure-based virtual screening can be a valuable approach to computationally select hit candidates based on their predicted interaction with a protein of interest. The recent explosion in the size of chemical libraries increases the chances of hitting high-quality compounds during virtual screening exercises but also poses new challenges as the number of chemically accessible molecules grows faster than the computing power necessary to screen them. We review here two novel approaches rapidly gaining in popularity to address this problem: machine learning-accelerated and synthon-based library screening.

Five Dimensions of Needs for Help: The Efficacy of a Technology-Based Intervention Among Asian American Breast Cancer Survivors.

Cancer survivors including Asian American breast cancer survivors have reported their high needs for help during their survivorship process. With the COVID-19 pandemic, the necessity of technology-based programs to address their needs for help without face-to-face interactions has been highlighted. The purpose of this randomized intervention study was to determine the efficacy of a technology-based program in reducing various types of needs for help among this specific population.

Measuring Quality-weighted Hospital-Free Days in Acute Respiratory Failure: A Modified Delphi Study.

Hospital-free days (HFDs), a measure of the number of days alive spent outside the hospital, is increasingly used as an endpoint in studies of patients with acute respiratory failure (ARF) or other critical and serious illnesses. Current approaches to measuring HFDs do not account for decrements in functional status or quality of life that ARF survivors and family members value. To develop an acceptable approach to measure quality-weighted HFDs using patient-reported outcomes.

Microscopic colitis related to food supplement containing turmeric: a review of 3 cases.

Microscopic colitis is a chronic inflammatory disorder of the colon characterized by microscopic changes in the intestinal lining. Turmeric, a commonly used spice, is generally regarded as beneficial for digestive and articular health thanks to its anti-inflammatory properties. No cases of microscopic colitis under a food supplement containing turmeric has been previously described in the literature.

Small Molecule Screen Identifies Non-catalytic USP3 Chemical Handle.

Zinc-finger ubiquitin-binding domains (ZnF-UBDs) are noncatalytic domains mostly found in deubiquitylases (DUBs) such as USP3. They represent an underexplored opportunity for the development of deubiquitylase-targeting chimeras (DUBTACs) to pharmacologically induce the deubiquitylation of target proteins. We previously showed that ZnF-UBDs are ligandable domains.