The Complete Inpatient Record Using Comprehensive Electronic Data (CIRCE) project: A team-based approach to clinically validated, research-ready electronic health record data.

Introduction: The rapid adoption of electronic health record (EHR) systems has resulted in extensive archives of data relevant to clinical research, hospital operations, and the development of learning health systems. However, EHR data are not frequently available, cleaned, standardized, validated, and ready for use by stakeholders. We describe an in-progress effort to overcome these challenges with cooperative, systematic data extraction and validation.

Development and External Validation of a Machine Learning Model to Predict Restriction from Spirometry.

Background: Though European Respiratory Society and American Thoracic Society (ERS/ATS) guidelines for pulmonary function test (PFT) interpretation recommend the use of the forced vital capacity (FVC) lower limit of normal (LLN) to exclude restriction, recent data suggest that the negative predictive value (NPV) of the FVC LLN is lower than has been accepted, particularly among non-Hispanic Black patients. We sought to develop and externally validate a machine learning (ML) model to predict restriction from spirometry and determine whether its use may improve the accuracy and equity of PFT interpretation.

Methods: We included PFTs with both static and dynamic lung volume measurements for patients between 18 and 80 years of age who were tested at pulmonary diagnostic labs within two health systems.

Making beads and bead making: an introduction.

Beads are a prominent category of material culture in the African past. Crosscutting their study across temporal periods and geographical areas are some general methodological and theoretical convergences: the categorisation of beads in terms of materials and methods of manufacture, an emphasis on provenance and distribution, and the analysis of beads as 'social signals' in relation to identity, networks and status. This paper outlines the conceptual framework of 'making' and discusses how such a framework can expand on existing analyses and provide new avenues for studying beads in the African past.

A Normal Forced Vital Capacity Does Not Reliably or Equitably Exclude Restriction.

Background: European Respiratory Society and American Thoracic Society (ERS/ATS) guidelines for pulmonary function test (PFT) interpretation recommend the use of a normal forced vital capacity (FVC) to exclude restriction. However, this recommendation is based upon a single study from 1999, which was limited to White patients, and used race-specific reference equations that are no longer recommended by ERS/ATS. We sought to reassess the support for this recommendation by calculating the negative predictive value (NPV) of a normal FVC in a diverse, multicenter cohort using race-neutral reference equations.

The Effect of a Post-Bronchodilator FEV/FVC < 0.7 on COPD Diagnosis and Treatment: A Regression Discontinuity Design.

Background: Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend the diagnosis of chronic obstructive pulmonary disease (COPD) only in patients with a post-bronchodilator forced expiratory volume in 1 second to forced vital capacity ratio (FEV/FVC) less than 0.7. However the impact of this recommendation on clinical practice is unknown.

Gender Differences in the Diagnosis of Chronic Obstructive Pulmonary Disease after Spirometry.

Background: Women are more likely than men to report delays in the diagnosis of chronic obstructive pulmonary disease (COPD), though the etiology of these delays is unknown. We sought to test whether delays in COPD diagnosis persist after the performance of spirometry.

Methods: We used the Optum Labs Data Warehouse to identify patients 18 years of age and older without a prior diagnosis of COPD, with a post-bronchodilator forced expiratory volume in 1 second (FEV) to forced vital capacity (FVC) ratio of less than 0.

Implementation challenges in preeclampsia care: perspectives from health care professionals in urban Uganda.

Background: Sub-Saharan Africa bears the burden of 70% of maternal deaths worldwide, of which ∼10% are attributable to hypertensive disorders of pregnancy, primarily complications of preeclampsia. In other global settings, outcomes of pregnancies affected by preeclampsia are improved with timely and effective medical care.

Objective: This study aimed to explore the perspectives of local health care professionals on how preeclampsia care is currently delivered in the study setting and what challenges they experience in providing prompt and safe care.

Trophoblast organoid systems to study human placentation.

Human trophoblast organoids provide a valuable in vitro system to investigate human placental development and function. In this issue of Developmental Cell, Shannon et al. benchmark two organoid models against primary trophoblast at single-cell resolution, identifying their strengths and limitations.

Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy.

In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is regulated by uterine natural killer (uNK) cells, but how they influence reproductive outcomes is unclear. Here, we used our trophoblast organoids and primary tissue samples to determine how uNK cells affect placentation.

Good practice recommendations on add-ons in reproductive medicine†.

Study Question: Which add-ons are safe and effective to be used in ART treatment?

Summary Answer: Forty-two recommendations were formulated on the use of add-ons in the diagnosis of fertility problems, the IVF laboratory and clinical management of IVF treatment.

What Is Known Already: The innovative nature of ART combined with the extremely high motivation of the patients has opened the door to the wide application of what has become known as 'add-ons' in reproductive medicine. These supplementary options are available to patients in addition to standard fertility procedures, typically incurring an additional cost.

Modeling the Role of Immune Cell Conversion in the Tumor-Immune Microenvironment.

Tumors develop in a complex physical, biochemical, and cellular milieu, referred to as the tumor microenvironment. Of special interest is the set of immune cells that reciprocally interact with the tumor, the tumor-immune microenvironment (TIME). The diversity of cell types and cell-cell interactions in the TIME has led researchers to apply concepts from ecology to describe the dynamics.

Barriers and facilitators to maternal death surveillance and response at a busy urban National Referral Hospital in Uganda.

Preventable maternal and newborn deaths remain a global concern, particularly in low- and- middle-income countries (LMICs) Timely maternal death surveillance and response (MDSR) is a recommended strategy to account for such deaths through identifying contextual factors that contributed to the deaths to inform recommendations to implement in order to reduce future deaths. Implementation of MDSR is still suboptimal due to barriers such as inadequate skills and leadership to support MDSR. With the leadership of WHO and UNFPA, there is momentum to roll out MDSR, however, the barriers and enablers for implementation have received limited attention.

Global, Race-Neutral Reference Equations and Pulmonary Function Test Interpretation.

Importance: Race and ethnicity are routinely used to inform pulmonary function test (PFT) interpretation. However, there is no biological justification for such use, and it may reinforce health disparities.

Objective: To compare the PFT interpretations produced with race-neutral and race-specific equations.

Primitive haematopoiesis in the human placenta gives rise to macrophages with epigenetically silenced HLA-DR.

The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. Although this process is thought to be spatially restricted to the yolk sac in the mouse, in humans, it remains poorly understood. Human foetal placental macrophages, or Hofbauer cells (HBC), arise during the primitive haematopoietic wave ~18 days post conception and lack expression of human leukocyte antigen (HLA) class II.

Spatial multiomics map of trophoblast development in early pregnancy.

The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia.

Natural Killer Cells in the Human Uterine Mucosa.

The presence of granulated lymphocytes in the human uterine mucosa, known as decidua during pregnancy, or endometrium otherwise, was first noted in the nineteenth century, but it was not until 1990 that these cells were identified as a type of natural killer (NK) cell. From the outset, uterine NK (uNK) cells were found to be less cytotoxic than their circulating counterparts, peripheral NK (pNK) cells. Recently, unbiased approaches have defined three subpopulations of uNK cells, all of which cluster separately from pNK cells.

Permissive and nonpermissive channel closings in CFTR revealed by a factor graph inference algorithm.

The closing of the gated ion channel in the cystic fibrosis transmembrane conductance regulator can be categorized as nonpermissive to reopening, which involves the unbinding of ADP or ATP, or permissive, which does not. Identifying the type of closing is of interest as interactions with nucleotides can be affected in mutants or by introducing agonists. However, all closings are electrically silent and difficult to differentiate.

Why mothers die at a busy tertiary urban hospital in Kampala, Uganda: a comprehensive review of maternal deaths 2016-2018 and implications for quality improvement to reduce deaths.

Background: Reviewing maternal deaths and drawing out lessons for clinical practice is part of an effective cohesive intervention strategy to reduce future deaths.

Objective: To review maternal deaths at the National Referral hospital in Kampala over a 3-year period (2016-2018) to determine causes of death, extent of preventability, proportion of deaths notified and audited as per national guidelines.

Methods: Trained-multidisciplinary panels (obstetricians and senior midwives) conducted retrospective reviews of maternal deaths that occurred.

Learning from maternal deaths due to uterine rupture: review of cases from peri-urban Uganda.

Background: Maternal deaths from uterine rupture continue to occur globally, with particularly high rates in sub-Saharan Africa. Maternal death reviews have been shown to be an effective part of cohesive strategies to prevent future deaths.

Objective: This study aimed to conduct maternal death reviews for all deaths following uterine rupture in the study center, to assess preventability, and to synthesize key learning points that may help to prevent future maternal deaths following uterine rupture.

Local immune recognition of trophoblast in early human pregnancy: controversies and questions.

The role of the maternal immune system in reproductive success in humans remains controversial. Here we focus on the events that occur in the maternal decidua during the first few weeks of human pregnancy, because this is the site at which maternal leukocytes initially interact with and can recognize fetal trophoblast cells, potentially involving allorecognition by both T cells and natural killer (NK) cells. NK cells are the dominant leukocyte population in first-trimester decidua, and genetic studies point to a role of allorecognition by uterine NK cells in establishing a boundary between the mother and the fetus.