HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia.

Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.

Characterization of cognitive decline in long-duration type 1 diabetes by cognitive, neuroimaging and pathological examinations.

Background: We aimed to characterize factors associated with the under-studied complication of cognitive decline in aging people with long-duration type 1 diabetes (T1D).

Methods: Joslin "Medalists" (n = 222; T1D ≥ 50 years) underwent cognitive testing. Medalists (n = 52) and age-matched non-diabetic controls (n = 20) underwent neuro- and retinal imaging.

Monocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension.

Hypoxia is a major cause of pulmonary hypertension (PH) worldwide, and it is likely that interstitial pulmonary macrophages contribute to this vascular pathology. We observed in hypoxia-exposed mice an increase in resident interstitial macrophages, which expanded through proliferation and expressed the monocyte recruitment ligand CCL2. We also observed an increase in CCR2+ macrophages through recruitment, which express the protein thrombospondin-1 that functionally activates TGF-beta to cause vascular disease.

Graph contrastive learning of subcellular-resolution spatial transcriptomics improves cell type annotation and reveals critical molecular pathways.

Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.

Using Large Language Models to Detect and Understand Drug Discontinuation Events in Web-Based Forums: Development and Validation Study.

Background: The implementation of large language models (LLMs), such as BART (Bidirectional and Auto-Regressive Transformers) and GPT-4, has revolutionized the extraction of insights from unstructured text. These advancements have expanded into health care, allowing analysis of social media for public health insights. However, the detection of drug discontinuation events (DDEs) remains underexplored.

Glia control experience-dependent plasticity in an olfactory critical period.

Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience.

Disentangling Driving Force Effects, Polar Effects, /H Imbalance, and Other Influences on H-Atom Transfer Reactions.

Hydrogen atom transfer (HAT) reactions and their kinetic barriers Δ are important in organic and inorganic chemistry. This study examines factors that influence Δ, reporting the kinetics and thermodynamics of HAT from various ruthenium bis(acetylacetonate) pyridine-imidazole complexes to nitroxyl radicals. Across these 36 reactions, the Δ and Δ can be independently varied, with different sets of Ru complexes primarily tuning either their ps or their °s.

Procedural Prescription Denials and Risk of Acute Care Utilization and Spending Among Medicaid Patients.

Importance: Rising prescription medication costs under Medicaid have led to increased procedural prescription denials by health plans. The effect of unresolved denials on chronic condition exacerbation and subsequent acute care utilization remains unclear.

Objective: To examine whether procedural prescription denials are associated with increased net spending through downstream acute care utilization among Medicaid patients not obtaining prescribed medication following a denial.

Transportation Insecurity, Social Support, and Adherence to Cancer Screening.

Importance: Transportation insecurity and lack of social support are 2 understudied social determinants of health that contribute to excess morbidity, mortality, and acute health care utilization. However, whether and how these social determinants of health are associated with cancer screening has not been determined and has implications for preventive care.

Objective: To determine whether transportation insecurity or social support are associated with screening adherence for colorectal, breast, and cervical cancer.

The nonbinary god: Disaggregating spirituality and Christian religiosity among nonbinary Black womxn (NBBW).

This study examined how 11 nonbinary Black womxn (NBBW) in the United States experience and distinguish between spirituality and religion using an endarkened Black feminist decolonial paradigm and an Afro-Indigenous eco-womxnist cosmological theoretic framework. Data were from Project NBBW, a community-based participatory action research project led by Black sexual and gender minority womxn community members and researchers. We conducted individual semistructured interviews and examined participant's qualitative responses to the following research inquiry: How do NBBW perceive their relationship to spirituality and religion? Participants were 11 NBBW, aged 21-30, living in the United States.

Exploring melatonin's signalling pathways in the protection against age-related skin deterioration.

Melatonin, renowned for regulating sleep-wake cycles, also exhibits notable anti-aging properties for the skin. Synthesized in the pineal gland and various tissues including the skin, melatonin's efficacy arises from its capacity to combat oxidative stress and shield the skin from ultraviolet (UV)-induced damage. Moreover, it curbs melanin production, thereby potentially ameliorating hyperpigmentation.

Knowledge, Attitudes, and Practices of Healthcare Providers and Healthcare Experiences of Women Regarding Female Genital Mutilation/Cutting (FGM/C): A Scoping Review of Evidence from Canada and the United States.

Healthcare providers (HCPs) play a critical role in the care of women with experience of FGM/C although there is limited research on knowledge about FGM/C among HCPs in Canada and USA. Research evidence suggests that many women with experience of FGM/C have negative care experiences. We sought to investigate the knowledge, attitudes, and practices of Canadian and USA HCPs regarding FGM/C, along with women's healthcare experiences with FGM/C in both countries.

Experiences of Disclosure, Resilience and Viral Suppression among People Living with HIV in Ghana.

Support for people living with HIV (PLHIV) as they disclose their HIV status can impact continuity of HIV treatment and adherence to antiretrovirals. In the presence of multi-level adversities, resilience among PLHIV can promote health-seeking behaviors and better health outcomes. However, few studies have examined how disclosure experience and resilience work together to impact HIV treatment outcomes among PLHIV.

Pre-exposure Prophylaxis (PrEP) Awareness and Engagement Among MSM at High Risk of HIV Infection in China: A Multi-City Cross-Sectional Survey.

This study aimed to explore the awareness, willingness, and engagement with pre-exposure prophylaxis (PrEP) among high-risk Chinese men who have sex with men (MSM) and to investigate the factors influencing its use. A cross-sectional survey of 1800 HIV-negative MSM was conducted in Chengdu, Suzhou, and Wuhan between June 2022 and February 2023 through in-person and online recruitment methods. Univariate and multivariate logistic regression analyses were used to identify predictors of PrEP use.

Brief Report: Preferences and Acceptability in Methods of Tenofovir Diphosphate in Dried Blood Spots Collection and Feedback in a Cohort of PLWH in Cape Town South Africa.

Antiretroviral therapy (ART) adherence is crucial for HIV viral suppression. Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) offer a potential tool for monitoring and supporting adherence. We assessed acceptability and preferences of fingerstick-based DBS collection and drug-level feedback among 224 people living with HIV (PLWH) in South Africa.

Growth hormone-releasing hormone signaling and manifestations within the cardiovascular system.

Growth hormone (GH)-releasing hormone (GHRH), a hypothalamic peptide initially characterized for its role in GH regulation, has gained increasing attention due to its GH-independent action on peripheral physiology, including that of the cardiovascular system. While its effects on the peripheral vasculature are still under investigation, GHRH and synthetic agonists have exhibited remarkable receptor-mediated cardioprotective properties in preclinical models. GHRH and its analogs enhance myocardial function by improving contractility, reducing oxidative stress, inflammation, and offsetting pathological remodeling.

The Impact of Racial and Low Socioeconomic Status on the Implementation of Spinal Cord Stimulation for Chronic Pain in the United States.

Objectives: This study aims to review the societal, economic, and racial factors that impact the usage of spinal cord stimulation for chronic pain. Our working hypothesis is that patients of ethnic minority groups or of lower socioeconomic status (SES) status may have lower implantation rates and usage of spinal cord stimulation (SCS).

Materials And Methods: Our study sourced publications from PubMed, Embase, and Cochrane Library on December 21st, 2023 for SCS for the purposes of pain management.

Genetic evidence for functions of Chloroplast CA in Pyropia yezoensis: decreased CCM but increased starch accumulation.

In response to the changing intertidal environment, intertidal macroalgae have evolved complicated Ci utilization mechanisms. However, our knowledge regarding the CO concentrating mechanism (CCM) of macroalgae is limited. Carbonic anhydrase (CA), a key component of CCM, plays essential roles in many physiological reactions in various organisms.

Shear wave elastography primer for the abdominal radiologist.

Purpose: Shear wave elastography (SWE) provides a means for adding information about the mechanical properties of tissues to a diagnostic ultrasound examination. It is important to understand the physics and methods by which the measurements are made to aid interpretation of the results as they relate to disease processes.

Methods: The components of how ultrasound is used to generate shear waves and make measurements of the induced motion are reviewed.

Medications That May be Contributing to Your Patient's Weight Gain.

Nearly 42% of adults in the United States are considered obese. Although there are a number of contributing factors to obesity, one sometimes overlooked contributor to weight gain is medications. Within many classes of medications that may affect weight, the degree of weight gain varies.

Undervaluation of Perioperative Work for ACL Reconstruction by Relative Value Scale Update Committee Methodology in a Single Surgeon's Practice.

Objectives: The purpose of this study was to determine the accuracy of the Relative Value Update Committee (RUC) and Centers for Medicare & Medicaid Services current times and work relative value units (wRVUs) for the perioperative work involved in anterior cruciate ligament (ACL) reconstruction by directly timing perioperative tasks as they occur in real time.

Methods: The RUC was contacted to obtain a list of perioperative tasks and the corresponding times allotted for the tasks involved in arthroscopically aided ACL reconstruction (Current Procedural Terminology code 29888). The tasks that occurred both inside and outside the operating room were timed by the attending physician as the event occurred.

Maternal and Infant Outcomes in a Subset of Patients with Sickle Cell Disease in South Carolina.

Objectives: Sickle cell disease (SCD), which disproportionately affects minorities, increases complications during pregnancy. Severe maternal mortality is increased in women with SCD, including morbidity related to the disease and other nondisease-related complications. It also can have devastating complications for fetuses, with increases in premature birth and low birth weight.

Distinct Aggregation Behavior of -Terminally Truncated Aβ Over Aβ in the Presence of Zn(II).

The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark of Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, -terminal truncation at Phe4, yielding Aβ, is highly prevalent in AD-affected brains and significantly alters Aβ's metal-binding and aggregation profiles. Despite the abundance of Zn(II) in senile plaques, its impact on the aggregation and toxicity of Aβ remains unexplored.

Lowering LDL cholesterol by PCSK9 inhibition: a new era of gene silencing, RNA, and alternative therapies.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has added a new paradigm to our understanding of cholesterol homeostasis and lipid metabolism. Since its discovery, PCSK9 inhibitors have become a widely investigated therapeutic class for lipid management in cardiovascular diseases and hypercholesterolemia. Scientists have explored different approaches for PCSK9 inhibition, such as monoclonal antibodies (mAbs), gene silencing and gene editing techniques, vaccines, mimetic peptides, and small molecules.

Understanding Anionic Hyperporphyrins: TDDFT Calculations on Peripherally Deprotonated -Tetrakis(4-hydroxyphenyl)porphyrin.

Presented herein is a DFT/TDDFT study of -tetrakis(4-hydroxyphenyl)porphyrin (H[THPP]) and its -deprotonated tetraanionic form; the latter was modeled as both a free tetraanion and with various counterions. Based on our calculations, the experimentally observed hyperporphyrin spectra are attributed to an admixture of phenol/phenoxide character into the a-type HOMO of tetraphenylporphyrin. The admixture results in an elevation of the orbital energy of the HOMO in relation to other frontier orbitals, which accounts for the observed spectral redshifts.