CUSP06, a Novel CDH6-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Multiple CDH6-Expressing Human Cancer Models.

Cadherin-6 (CDH6), also known as K-cadherin, is a type II classic cadherin molecule that plays an important role in the embryonic development of the kidney but has very limited expression in adult tissues. It is overexpressed in several human malignancies, primarily in ovarian cancer, renal cell carcinoma, as well as, less frequently, cholangiocarcinoma, uterine serous carcinoma, glioma, lung, pancreatic and thyroid cancers. The characteristic of limited expression in normal tissues, high expression in tumor tissues, and rapid internalization upon antibody binding makes CDH6 a well-suited antibody-drug conjugate (ADC) target.

Validating 8 Area-Based Measures of Social Risk for Predicting Health and Mortality.

Importance: Area-based measures of social risk are increasingly being used in policy applications in the US. While several have been demonstrated to be predictive of health and mortality in the general population, there is a need to identify area-based measures that are most reliable for policy applications, including measures that are associated with health and mortality consistently across subpopulations.

Objective: To compare the relative strength with which area and individual social risk measures are correlated with health outcomes and mortality, and the extent to which these associations are consistent across race, ethnicity, rurality, age, and gender.

Natural Language Processing Improves Reliable Identification of COVID-19 Compared to Diagnostic Codes Alone.

Observational COVID-19 studies often rely on diagnostic codes, but their accuracy and potential for differential misclassification across patient subgroups are unclear. In this proof of concept study, we examined age, race, and ethnicity as predictors of differential misclassification by comparing the classification accuracy of diagnostic codes to classifiers based on natural language processing (NLP) of clinical notes. We assessed differential misclassification in two primary care-based samples from the American Family Cohort: first, a cohort of 5000 patients with COVID-19 status assessed by physicians based on notes; and second, 21,659 patients (out of 1,560,564) who received COVID-specific antivirals.

Data Transformation to Advance AI/ML Research and Implementation in Primary Care.

Artificial intelligence and machine learning (AI/ML) in health care is accelerating at a breathtaking pace. As the largest health care delivery platform, primary care is where the power, opportunity, and future of AI/ML are most likely to be realized in the broadest and most ambitious scale. However, there is a relative lack of organized, open, large-scale primary care datasets to attract industry and academia in primary care-focused research and development.

An Intersectional Analysis of Social Deprivation and Patient Characteristics on Nirmatrelvir-Ritonavir for Treatment of COVID-19 in U.S. Primary Care Practices, 2021 to 2023.

Objective: Calculate rates of nirmatrelvir-ritonavir prescription and assess area-level social deprivation as an effect modifier of patient characteristics on nirmatrelvir-ritonavir for the treatment of COVID-19.

Methods: Retrospective cohort study December 22, 2021 to June 30, 2023 using electronic health record (EHR) data of primary care patients from the American Family Cohort (AFC). Eligible patients had documented COVID-19 between December 15, 2021 and February 28, 2023; ≥1 healthcare encounter between January 1, 2020 and December 14, 2021; and ≥1 healthcare encounter between December 15, 2021 and June 30, 2023.

Factors Associated with Documenting Social Determinants of Health in Electronic Health Records.

Introduction: Social determinants of health (SDOH) significantly impact health outcomes, yet their integration into clinical decision making is inconsistent. We examined how family physicians document SDOH in electronic health records (EHRs) and identified factors influencing this practice.

Methods: We performed a cross-sectional analysis of 2,089 family physicians completing the 2022 American Board of Family Medicine Continuous Certification Questionnaire.

Primary care screening for sexually transmitted infections in the United States from 2019 to 2021.

Background: Early identification and treatment of sexually transmitted infections (STIs) is critical to improve patient outcomes. Barriers to healthcare seeking are potentially exacerbated by COVID-19. This study examined trends in STI testing and positivity from 2019 to 2021 in primary care in the United States.

Impact of Community Health Center Losses on County-Level Mortality: A Natural Experiment in the United States, 2011-2019.

Objective: To estimate the effect of Community Health Center (CHC) site losses on county-level mortality rates.

Study Setting And Design: We conducted a natural experiment study using difference-in-differences analysis of propensity score-matched US counties from 2011 through 2019.

Data Sources And Analytic Sample: The study included 3142 US counties, with 177 counties experiencing CHC site losses in 2014, per data from the health resources and services administration.

α-Hydrazino Acids Inhibit Pyridoxal Phosphate-Dependent Decarboxylases via "Catalytically Correct" Ketoenamine Tautomers: A Special Motif for Chemical Biology and Drug Discovery?

We present evidence that supports a 'correct hydrazone tautomer/Dunathan alignment model' for how α-hydrazino analogues of α-amino acids inhibit PLP enzymes. Described is the asymmetric synthesis of l- and d-α-hydrazino acid l-lysine analogues and their inhibition of lysine decarboxylase (LdcI) via kinetic analysis, stopped-flow spectrophotometry, and cryo-EM. We describe a similar investigation of the important anti-Parkinsonism drug, carbidopa, with its human DOPA decarboxylase (hDdc) target.

Heterogeneity of diagnosis and documentation of post-COVID conditions in primary care: A machine learning analysis.

Background: Post-COVID conditions (PCC) have proven difficult to diagnose. In this retrospective observational study, we aimed to characterize the level of variation in PCC diagnoses observed across clinicians from a number of methodological angles and to determine whether natural language classifiers trained on clinical notes can reconcile differences in diagnostic definitions.

Methods: We used data from 519 primary care clinics around the United States who were in the American Family Cohort registry between October 1, 2021 (when the ICD-10 code for PCC was activated) and November 1, 2023.

Nitration of Deactivated Aromatic Compounds Using Lithium Nitrate.

Nitroarenes are critically important in medicinal chemistry, material science, and the chemical industry. In this paper, we introduce a new strategy for the electrophilic nitration of deactivated aromatic compounds, utilizing lithium nitrate (LiNO) in the presence of sulfuric acid in trifluoroacetic acid. This method has demonstrated moderate to excellent yield.

Serum Amino Acid Profiles in Dogs with a Congenital Portosystemic Shunt.

: A functional liver is vital for normal protein metabolism. Alterations of circulating amino acid (AA) concentrations have previously been reported in dogs with hepatocellular carcinoma, chronic hepatitis, and hepatocutaneous syndrome. The purpose of this study was to compare serum AA profiles between dogs with a congenital portosystemic shunt (CPSS) and healthy control dogs.

Structure and dynamics of Proteus vulgaris tryptophan indole-lyase complexes with l-ethionine and l-alanine.

Tryptophan indole-lyase (TIL; [E.C. 4.

Treatment of Chlamydia and Gonorrhea in Primary Care and Its Patient-Level Variation: An American Family Cohort Study.

Purpose: Chlamydia and gonorrhea are the 2 most common bacterial sexually transmitted infections in the United States. Nonadherence to the Centers for Disease Control and Prevention treatment guidelines remains a concern. We examined how well chlamydia and gonorrhea treatment in primary care settings adhered to guidelines.

Use of food restrictions to prevent infections in paediatric patients with cancer and haematopoietic cell transplantation recipients: a systematic review and clinical practice guideline.

Background: Food restrictions during periods of neutropenia have been widely used in oncology settings to prevent infections. As there is a lack of clearly demonstrated effectiveness, this strategy is being increasingly questioned.

Methods: A multi-national panel of 23 individuals was convened to develop a clinical practice guideline (CPG) on the use of food restrictions to prevent infections in paediatric patients with cancer and haematopoietic cell transplantation (HCT) recipients.

A Proof-of-Concept Solution for Co-locating 2D Histology Images in 3D for Histology-to-CT and MR Image Registration: Closing the Loop for Bone Sarcoma Treatment Planning.

This work presents a proof-of-concept solution designed to facilitate more accurate radiographic feature characterisation in pre-surgical CT/MR volumes. The solution involves 3D co-location of 2D digital histology slides within ex-vivo, tumour tissue CT volumes. Initially, laboratory dissection measurements seed the placement of histology slices in corresponding CT volumes, followed by in-plane point-based registration of bone in histology images to the bone in CT.

Transcriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species.

The lateral septum (LS) is a midline, subcortical structure that is a critical regulator of social behaviors. Mouse studies have identified molecularly distinct neuronal populations within the LS, which control specific facets of social behavior. Despite its known molecular heterogeneity in the mouse and critical role in regulating social behavior, comprehensive molecular profiling of the human LS has not been performed.

Every Day I Write the Book: Transforming EHR Data from Daily Practice into New Knowledge.

Despite producing mountains of data in the daily course of care, the documentation labors of frontline clinicians currently return very little value to them or to the health system. The potential of these painstakingly collected data are enormous and clinical registries can extract the extraordinary capacity of these data and transform them into research-ready datasets while protecting the confidentiality of the patients and clinicians. Clinical registries represent transformative tools for primary care research, bringing together the dimensions of clinical practice, research, quality improvement, and policy impact from a large, nationally reflective, diverse sample of practices and patients.

Accurate sample deconvolution of pooled snRNA-seq using sex-dependent gene expression patterns.

Single-nucleus RNA sequencing (snRNA-seq) technology offers unprecedented resolution for studying cell type-specific gene expression patterns. However, snRNA-seq poses high costs and technical limitations, often requiring the pooling of independent biological samples and the loss of individual sample-level data. Deconvolution of sample identity using inherent features would enable the incorporation of pooled barcoding and sequencing protocols, thereby increasing data throughput and analytical sample size without requiring increases in experimental sample size and sequencing costs.

The Essential Role of Primary Health Care for Health Security.

In July 2023, primary health care experts from more than 20 countries, the World Health Organization (WHO), and most agencies within the US Department of Health and Human Services (HHS) met at the National Academy of Sciences in Washington, DC, to catalyze action toward revitalizing primary care in the United States align efforts to advance primary health care worldwide, and improve health and security for all. This meeting was informed by the NASEM's critical primary care report, which highlighted the need for federal leadership to strengthen primary care services in the United States, especially for underserved populations, and to inform primary care systems around the world. To that end, this meeting was designed to explore the challenges and opportunities of investing in primary health care as a common good and critical for health security and resilience across the globe.

Linking national primary care electronic health records to individual records from the U.S. Census Bureau's American Community Survey: evaluating the likelihood of linkage based on patient health.

Objectives: To evaluate the likelihood of linking electronic health records (EHRs) to restricted individual-level American Community Survey (ACS) data based on patient health condition.

Materials And Methods: Electronic health records (2019-2021) are derived from a primary care registry collected by the American Board of Family Medicine. These data were assigned anonymized person-level identifiers (Protected Identification Keys [PIKs]) at the U.

Team and Electronic Health Record Features and Burnout Among Family Physicians.

Importance: In the context of a growing volume of electronic health record (EHR)-based work and post-COVID-19 pandemic staffing pressures, health system leaders need an up-to-date understanding of changes in family physicians' experiences of burnout, determinants of burnout, and how to enhance the family physicians' experience.

Objective: To evaluate the association of family physicians' perceptions of team structure and EHR experiences with burnout and identify modifiable practice structure factors associated with team and EHR experiences.

Design, Setting, And Participants: A serial cross-sectional survey study was conducted from December 1, 2016, to October 24, 2023.

Only One Quarter of Family Physicians Are Very Satisfied with Their Electronic Health Records Platform.

Two decades into the era of Electronic Health Records (EHRs), the promise of streamlining clinical care, reducing burden, and improving patient outcomes has yet to be realized. A cross-sectional family physician census conducted by the American Board of Family Medicine in 2022 and 2023 included self-reported physician EHR satisfaction. Of the nearly 10,000 responding family physicians, only one-in-four (26.