PRC1 and CTCF-Mediated Transition from Poised to Active Chromatin Loops Drives Bivalent Gene Activation.

Polycomb Repressive Complex 1 (PRC1) and CCCTC-binding factor (CTCF) are critical regulators of 3D chromatin architecture that influence cellular transcriptional programs. Spatial chromatin structures comprise conserved compartments, topologically associating domains (TADs), and dynamic, cell-type-specific chromatin loops. Although the role of CTCF in chromatin organization is well-known, the involvement of PRC1 is less understood.

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.

Revisiting the scope and expectations of Implementation Science and Implementation Science Communications.

This editorial updates the scope and submission expectations of Implementation Science and Implementation Science Communications. We refine our protocol publishing policies and set out new expectations for reporting studies describing determinants and their relationship with implementation outcomes. Our central focus remains on the implementation of evidence-based interventions into healthcare practice and policy.

Methodological Approaches for Measuring the Association Between Heat Exposure and Health Outcomes: A Comprehensive Global Scoping Review.

Objective: To synthesize the methodologies of studies that evaluate the impacts of heat exposure on morbidity and mortality.

Methods: Embase, MEDLINE, Web of Science, and Scopus were searched from date of inception until 1 March 2023 for English language literature on heat exposure and health outcomes. Records were collated, deduplicated and screened, and full texts were reviewed for inclusion and data abstraction.

Utility of dynamic contrast enhancement for clinically significant prostate cancer detection.

Objective: This study aimed to evaluate the association of dynamic contrast enhancement (DCE) with clinically significant prostate cancer (csPCa, Gleason Grade Group ≥2) and compare biparametric magnetic resonance imaging (bpMRI) and multiparametric MRI (mpMRI) nomograms.

Subjects/patients And Methods: We identified a retrospective cohort of biopsy naïve patients who underwent pre-biopsy MRI separated by individual MRI series from 2018 to 2022. csPCa detection rates were calculated for patients with peripheral zone (PZ) lesions scored 3-5 on diffusion weighted imaging (DWI) with available DCE (annotated as - or +).

A SONAR report on Nirmatrelvir/ritonavir-associated rebound COVID-19: Using new databases for evaluating new diseases.

Introduction: In May 2022, the Centers for Disease Control and Prevention disseminated an alert advising that "a few" persons with Nirmatrelvir/ritonavir (NM/R)-associated rebound of COVID-19 infection had been identified. Three case reports appearing as pre-print postings described the first cases. Analyses in March 2023 by NM/R's manufacturer and the Food and Drug Administration (FDA) reported no association between NM/R and COVID-19 rebound in a large phase 3 randomized clinical trial.

Social Vulnerability and Receipt of Guideline-Concordant Care among Patients with Colorectal Cancer.

Background: Cancer outcome disparities have been reported in highly vulnerable communities. The objective of this study was to evaluate the association of social vulnerability with receipt of guideline-concordant care (GCC) and mortality risk for patients with colorectal cancer.

Study Design: This retrospective observational study identified patients with stage I-III colon or stage II-III rectal cancer between 2018 and 2020 from the National Program of Cancer Registries Database.

Multiorgan transplant for therapy-associated lung and liver failure in a patient with stage III lung cancer.

Immunotherapy can significantly improve efficacy of cancer treatments. For locally advanced stage III lung cancers, chemoimmunotherapy in the neoadjuvant setting can achieve complete pathological response in about 40% of cases. However, optimal cancer response in patients receiving immunotherapy is sometimes associated with potentially fatal bystander injury to lung and liver.

A Novel Variant Detected with Multiple Testing Modalities.

Chronic myeloid leukemia (CML) is associated with several breakpoint regions that result in different fusion transcripts. These include the major breakpoint region (M-BCR), minor breakpoint region (m-BCR), and mu breakpoint region (u-BCR) corresponding to p210, p190, and p230 fusion transcripts, respectively. This patient is a 38-year-old female with a new diagnosis of CML in chronic phase.

Learners' Spontaneous Gesture Before a Math Lesson Predicts the Efficacy of Seeing Versus Doing Gesture During the Lesson.

Gestures-hand movements that accompany speech and express ideas-can help children learn how to solve problems, flexibly generalize learning to novel problem-solving contexts, and retain what they have learned. But does it matter who is doing the gesturing? We know that producing gesture leads to better comprehension of a message than watching someone else produce gesture. But we do not know how producing versus observing gesture impacts deeper learning outcomes such as generalization and retention across time.

Reduction of Filamin C Results in Altered Proteostasis, Cardiomyopathy, and Arrhythmias.

Background: Many cardiomyopathy-associated pathogenic variants are heterozygous truncations, and pathogenic variants are associated with arrhythmias. Arrhythmia triggers in filaminopathy are incompletely understood.

Methods And Results: We describe an individual with biallelic pathogenic variants, p.

How can a behavioral economics lens contribute to implementation science?

Background: Implementation science in health is an interdisciplinary field with an emphasis on supporting behavior change required when clinicians and other actors implement evidence-based practices within organizational constraints. Behavioral economics has emerged in parallel and works towards developing realistic models of how humans behave and categorizes a wide range of features of choices that can influence behavior. We argue that implementation science can be enhanced by the incorporation of approaches from behavioral economics.

Hijacked enhancer-promoter and silencer-promoter loops in cancer.

Recent work has shown that besides inducing fusion genes, structural variations (SVs) can also contribute to oncogenesis by disrupting the three-dimensional genome organization and dysregulating gene expression. At the chromatin-loop level, SVs can relocate enhancers or silencers from their original genomic loci to activate oncogenes or repress tumor suppressor genes. On a larger scale, different types of alterations in topologically associating domains (TADs) have been reported in cancer, such as TAD expansion, shuffling, and SV-induced neo-TADs.

Kuragel: A biomimetic hydrogel scaffold designed to promote corneal regeneration.

Cornea-related injuries are the most common cause of blindness worldwide. Transplantation remains the primary approach for addressing corneal blindness, though the demand for donor corneas outmatches the supply by millions. Tissue adhesives employed to seal corneal wounds have shown inefficient healing and incomplete vision restoration.

In Vivo Mapping of Myocardial Injury Outside the Infarct Zone: Tissue at an Intermediate Pathological State.

Background: The goal was to determine the feasibility of mapping the injured-but-not-infarcted myocardium using Tc-duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted.

Methods And Results: Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30-minute ligation. In vivo single-photon emission computed tomography was acquired after 3 hours (n=6) using Tc-duramycin, a phosphatidylethanolamine-specific radiopharmaceutical.

A Comparison of 5 Measures of Accelerated Biological Aging and Their Association With Incident Cardiovascular Disease: The CARDIA Study.

Background: Accelerated biological aging is an increasingly popular way to track the acceleration of biology over time that may not be captured by calendar time. Biological aging has been linked to external and internal chronic stressors and has the potential to be used clinically to understand a person's personalized functioning and predict future disease. We compared the association of different measures of biological aging and incident cardiovascular disease (CVD) overall and by race.

The Current and Future Role of Insulin Therapy in the Management of Type 2 Diabetes: A Narrative Review.

Early initiation of intensive insulin therapy has been demonstrated to be effective in controlling glycemia and possibly preserving beta-cell function. Innovations in insulin formulations and delivery systems continue. However, we have seen an acceleration in the development of new classes of diabetes medications for individuals with type 2 diabetes and obesity, such as, for example, glucagon-like peptide-1 receptor agonists (GLP-1 RAs).

Cervicothoracic ventral-dorsal rhizotomy for bilateral upper-extremity hypertonia in cerebral palsy: illustrative case.

Background: Management of medically refractory limb-specific hypertonia is challenging. Neurosurgical options include deep brain stimulation, intrathecal baclofen, thalamotomy, pallidotomy, or rhizotomy. Cervical dorsal rhizotomy has been successful in the treatment of upper-extremity spasticity.