Exploring the interplay between enhancer-promoter interactions and transcription.

Enhancers in metazoan genomes are known to activate their target genes across both short and long genomic distances. Recent advances in chromosome conformation capture assays and single-cell imaging have shed light on the underlying chromatin contacts and dynamics. Yet the relationship between 3D physical enhancer-promoter (E-P) interactions and transcriptional activation remains unresolved.

Simulations of the Potential for Diffraction Enhanced Imaging at 8 keV using Polycapillary Optics.

Conventional x-ray radiography relies on attenuation differences in the object, which often results in poor contrast in soft tissues. X-ray phase imaging has the potential to produce higher contrast but can be difficult to utilize. Instead of grating-based techniques, analyzer-based imaging, also known as diffraction enhanced imaging (DEI), uses a monochromator crystal with an analyzer crystal after the object.

Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multi-center prospective cohort study.

Background Aims: Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-comers" (AC)) have been limited by small sample size and short follow-up time, prompting this analysis.

Approach Results: 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed.

Continuing Education Certificate in Trauma Skills Among Emergency Nurses: A National Sample Survey Analysis.

Background: Trauma population health indicators are worsening in the United States. Nurses working in trauma care settings require specialized training for patient care. Little is known about national enumeration of nurses who hold skill-based trauma certificates.

Soft Coagulation Versus Argon Plasma Coagulation After Large Non-pedunculated Colorectal Polyp Resection: A Meta-analysis.

Introduction: Thermal ablative methods (such as argon plasma coagulation (APC) and soft tip snare coagulation (STSC) are commonly used to treat polyp margins. We aim to appraise the current literature and compare clinical outcomes between patients with treated (with APC vs. STSC) and non-treated endoscopic mucosal resection (EMR) margins.

Proteins and pathways involved in inflammation are longitudinally associated with total body bone mineral density among primarily hispanic overweight/obese adolescents and young adults.

Bone mineral density (BMD), an important marker of bone health, is regulated by a complex interaction of proteins. Plasma proteomic analyses can contribute to identification of proteins associated with changes in BMD. This may be especially informative in stages of bone accrual and peak BMD achievement (i.

Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to the benzimidazole (BZ) drug class is nearly ubiquitous in many species and is associated with mutations in beta-tubulin genes. However, mutations in beta-tubulin alone do not fully explain all BZ resistance.

Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only).

Vertebral Column Subluxation in Neurofibromatosis Type 1-Associated Dystrophic Scoliosis: A Report of Two Cases and Narrative Review.

Background And Objective: Neurofibromatosis-1 (NF1) dystrophic scoliosis is a challenging disease to manage surgically, with multiplanar curves progressing rapidly and unpredictably. Conservative management with bracing is often unsuccessful, and many patients necessitate instrumented fusion to halt progression of their curves. In rare cases, patients can present with spontaneous vertebral subluxation, significantly complicating the surgical management of this already complex disease process.

mTORC1 regulates the pyrimidine salvage pathway by controlling UCK2 turnover via the CTLH-WDR26 E3 ligase.

One critical aspect of cell proliferation is increased nucleotide synthesis, including pyrimidines. Pyrimidines are synthesized through de novo and salvage pathways. Prior studies established that the mammalian target of rapamycin complex 1 (mTORC1) promotes pyrimidine synthesis by activating the de novo pathway for cell proliferation.

Neurodevelopmental Outcomes after Multiple General Anesthetic Exposures before 5 Years of Age: A Cohort Study.

Background: The general anaesthesia or awake-regional anaesthesia in infancy (GAS) trial demonstrated evidence that most neurodevelopmental outcomes at 2 and 5 yr of age in infants who received a single general anesthetic for elective inguinal herniorrhaphy were clinically equivalent when compared to infants who did not receive general anesthesia. More than 20% of the children in the trial had at least one subsequent anesthetic exposure after their initial surgery. Using the GAS database, this study aimed to address whether multiple (two or more) general anesthetic exposures compared to one or no general anesthetic exposure in early childhood were associated with worse neurodevelopmental outcomes at 5 yr.

LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models.

Colorectal cancer (CRC) remains a leading cause of cancer death due to metastatic spread. LIN28B is overexpressed in 30% of CRCs and promotes metastasis, yet its mechanisms remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, resulting in enhanced PI3K/AKT pathway activation and liver metastasis in mice.

Analogue-Sensitive Inhibition of Histone Demethylases Uncovers Member-Specific Function in Ribosomal Protein Synthesis.

Lysine demethylases (KDMs) catalyze the oxidative removal of the methyl group from histones using earth-abundant iron and the metabolite 2-oxoglutarate (2OG). KDMs have emerged as master regulators of eukaryotic gene expression and are novel drug targets; small-molecule inhibitors of KDMs are in the clinical pipeline for the treatment of human cancer. Yet, mechanistic insights into the functional heterogeneity of human KDMs are limited, necessitating the development of chemical probes for precision targeting.

Use of the Ostial Flash balloon in aorto-ostial chronic total occlusion percutaneous coronary intervention.

Background: The use of the Ostial Flash balloon (Ostial Corporation) has received limited study in aorto-ostial chronic total occlusion (CTO) percutaneous coronary artery intervention (PCI).

Methods: The authors evaluated the outcomes of Ostial Flash balloon use in a large CTO-PCI registry (PROGRESS-CTO, NCT02061436).

Results: The Ostial Flash balloon was used in 54 of 907 aorto-ostial CTO PCIs in 905 patients (6.

Use and Costs of Supplemental Benefits in Medicare Advantage, 2017-2021.

Importance: Nearly all Medicare Advantage (MA) plans offer dental, vision, and hearing benefits not covered by traditional Medicare (TM). However, little is known about MA enrollees' use of those benefits or how much they cost MA insurers or enrollees.

Objective: To estimate use, out-of-pocket (OOP) spending, and insurer payments for dental, hearing, and vision services among Medicare beneficiaries.

Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement.

Importance: Osteoporotic fractures are associated with psychological distress, subsequent fractures, loss of independence, reduced ability to perform activities of daily living, and death.

Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening for osteoporosis to prevent fractures in adults 40 years or older with no known diagnosis of osteoporosis or history of fragility fracture.

Population: Adults 40 years or older without known osteoporosis or history of fragility fractures.

"The Environment Fostered True Growth": Harnessing Coaching on an Innovative Medicine Sub-internship.

Background: Medicine sub-internships aim to prepare students for residency. However, the traditional sub-internship structure, with multiple learners at varied levels, poses obstacles to providing the clinical exposure, learning environment, and direct observation and feedback necessary to develop essential skills.

Aim: Investigate the educational experience of learners on a coaching-centered sub-internship (CCSI) on a resident uncovered ward service.

A Phase 3, 28-week, multicentre, randomised, double-blind, placebo-controlled trial (OA-10) to evaluate the efficacy and safety of a single injection of lorecivivint in the target knee joint of moderately to severely symptomatic osteoarthritis patients.

Objectives: To assess the efficacy and safety of an intra-articular (IA) CLK/DYRK inhibitor, lorecivivint (LOR), for the treatment of moderate to severe symptomatic knee osteoarthritis (OA).

Methods: This was a Phase 3, 28-week, multicentre, double-blind, placebo-controlled study evaluating the efficacy and safety of a single IA injection of LOR. Patients with ACR-defined knee OA, Kellgren-Lawrence (KL) grades 2-3, and pain Numeric Rating Scale (NRS) ≥4 and ≤8 in the target knee were randomised (1:1) to receive LOR 0.

Phase 3, 56-week, randomised, double-blind, placebo-controlled study utilising patient-reported and radiographic outcomes evaluating the efficacy and safety of a lorecivivint injection in patients with moderate to severe knee osteoarthritis: OA-11 Study.

Objectives: To determine the efficacy, safety, and tolerability of intraarticular (IA) lorecivivint (LOR) in the treatment of knee osteoarthritis (OA).

Methods: Patients with American College of Rheumatology criteria-defined knee OA, Kellgren-Lawrence (KL) grades 2-3, and medial Joint Space Width (JSW) by radiograph between 1.5 and 4 mm in the target knee were enrolled in this phase 3, 56-week, multicentre, double-blind, placebo-controlled study.