Midpregnancy Placental Growth Factor Screening and Early Preterm Birth.

Importance: Early preterm birth (ie, at less than 34 weeks' gestation) confers a high risk for adverse health outcomes, yet no universal screening strategy exists, preventing targeted delivery of effective interventions.

Objective: To evaluate the ability of midpregnancy placental growth factor (PlGF) screening to identify pregnancies at highest risk for early preterm birth.

Design, Setting, And Participants: This prospective cohort study was conducted at an urban, tertiary care center from 2020 to 2023.

Limited Use of Supervised Physical Rehabilitation Beyond 3 Months After Arthroscopic Anterior Cruciate Ligament Reconstruction With Greater Use in Female and Younger Patients.

Purpose: To characterize the initiation and use of supervised physical rehabilitation after arthroscopic anterior cruciate ligament reconstruction (ACLR), including overall duration of rehabilitation and number of rehabilitation visits, and to describe demographic and clinical predictors of rehabilitation initiation and use characteristics.

Methods: Patients aged 14 to 64 years in the United States who underwent ACLR from 2017 to 2020 were identified using the Merative MarketScan Database. For patients initiating rehabilitation within 45 days postoperatively, the overall duration and number of visits within 1 year after surgery were determined.

Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19.

Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19.

Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer's disease model.

Despite strong evidence supporting the important roles of both apolipoprotein E4 (APOE4) and microglia in Alzheimer's disease (AD) pathogenesis, the effects of microglia on neuronal APOE4-related AD pathogenesis remain elusive. To examine such effects, we utilized microglial depletion in a chimeric model with induced pluripotent stem cell (iPSC)-derived human neurons in mouse hippocampus. Specifically, we transplanted homozygous APOE4, isogenic APOE3, and APOE-knockout (APOE-KO) iPSC-derived human neurons into the hippocampus of human APOE3 or APOE4 knockin mice and then depleted microglia in half of the chimeric mice.

Young people's lived sexual and reproductive health citizenship: participation and power of youth in Malawi.

This qualitative, focused critical ethnographic study explores how young people's 'lived SRH citizenship' and their active roles realising their sexual and reproductive health (SRH) and rights, shape their agency and participation in decision-making in Malawi. Informed by postcolonial feminist and difference-centred citizenship theories, our findings reveal that age-based power differentials, systems of gerontocracy and a culture of adultism impede bona fide youth involvement in SRH policymaking, making young citizens' participation more of an illusion than reality. Although democratisation and decentralisation aim to promote youth engagement, SRH policy spaces/processes lack institutionalised processes for integrating youth and remain dominated by donors and government.

Intercalated Amygdala Dysfunction Drives Avoidance Extinction Deficits in the Sapap3 Mouse Model of Obsessive-Compulsive Disorder.

Background: The avoidance of aversive stimuli through negative reinforcement learning, which demands dynamic responding to both positive and negative stimuli that often conflict with each other, is critical for survival in real-world environments. Individuals with obsessive-compulsive disorder commonly exhibit impaired negative reinforcement and extinction, perhaps involving deficits in amygdala functioning. The intercalated nuclei of the amygdala (ITC) is an amygdala subregion of particular interest that has been linked to negative reinforcement and extinction, with distinct clusters mediating separate aspects of behavior.

Optogenetic patterning generates multi-strain biofilms with spatially distributed antibiotic resistance.

Spatial organization of microbes in biofilms enables crucial community function such as division of labor. However, quantitative understanding of such emergent community properties remains limited due to a scarcity of tools for patterning heterogeneous biofilms. Here we develop a synthetic optogenetic toolkit 'Multipattern Biofilm Lithography' for rational engineering and orthogonal patterning of multi-strain biofilms, inspired by successive adhesion and phenotypic differentiation in natural biofilms.

An integrated view of the structure and function of the human 4D nucleome.

The dynamic three-dimensional (3D) organization of the human genome (the "4D Nucleome") is closely linked to genome function. Here, we integrate a wide variety of genomic data generated by the 4D Nucleome Project to provide a detailed view of human 3D genome organization in widely used embryonic stem cells (H1-hESCs) and immortalized fibroblasts (HFFc6). We provide extensive benchmarking of 3D genome mapping assays and integrate these diverse datasets to annotate spatial genomic features across scales.

Diagnosis of Incident Cancer After Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Trial.

Objectives: The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke.

Methods: We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event.

A Novel Mouse Model for Cerebral Inflammatory Demyelination in X-Linked Adrenoleukodystrophy: Insights into Pathogenesis and Potential Therapeutic Targets.

Objective: X-linked adrenoleukodystrophy (ALD) is caused by mutations in ABCD1, a peroxisomal gene. More than half of males with an ABCD1 mutation develop inflammatory cerebral demyelination (cALD), but underlying mechanisms remain unknown and therapies are limited. We sought to develop and characterize a mouse model of cALD to facilitate study of disease mechanisms and therapy development.

Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing.

Effective genome editing requires a sufficient dose of CRISPR-Cas9 ribonucleoproteins (RNPs) to enter the target cell while minimizing immune responses, off-target editing and cytotoxicity. Clinical use of Cas9 RNPs currently entails electroporation into cells , but no systematic comparison of this method to packaged RNP delivery has been made. Here we compared two delivery strategies, electroporation and enveloped delivery vehicles (EDVs), to investigate the Cas9 dosage requirements for genome editing.

Oxygen Consumption In Vivo by Ultra-High Dose Rate Electron Irradiation Depends Upon Baseline Tissue Oxygenation.

Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship.

Methods And Materials: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator.

Chromatin remodelling drives immune cell-fibroblast communication in heart failure.

Chronic inflammation and tissue fibrosis are common responses that worsen organ function, yet the molecular mechanisms governing their cross-talk are poorly understood. In diseased organs, stress-induced gene expression changes fuel maladaptive cell state transitions and pathological interaction between cellular compartments. Although chronic fibroblast activation worsens dysfunction in the lungs, liver, kidneys and heart, and exacerbates many cancers, the stress-sensing mechanisms initiating transcriptional activation of fibroblasts are poorly understood.

Association of preoperative to postoperative change in cerebrospinal fluid fibrinogen with postoperative delirium.

Background: We aimed to assess perioperative changes in fibrinogen in the cerebrospinal fluid (CSF), their association with markers of blood-brain barrier breakdown and neuroinflammation, and their association with postoperative delirium severity.

Methods: We conducted a secondary analysis of the Interventions for Postoperative Delirium-Biomarker 2 (IPOD-B2, NCT02926417) study, a prospective observational cohort study. We included 24 patients aged >21 yr undergoing aortic aneurysm repair.

Pioneering discovery and therapeutics at the brain-vascular-immune interface.

The brain-vascular-immune interface has emerged as a dynamic player in brain physiology and disease. We propose integrating vascular risk factors with genetic susceptibility as the nexus for the discovery of mechanisms and therapies for neuroinflammation, neurodegeneration, and neurorepair across polygenic neurologic diseases.

Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency.

Tissue-resident memory T (T) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common T cell fate remains poorly understood. Here, we show that whereas skin T cells strictly require transforming growth factor β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β to drive T cells in the small intestine.