Complementary cognitive roles for D2-MSNs and D1-MSNs during interval timing.

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds and involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway.

DNA Dendron Tagging as a Universal Way to Deliver Proteins to Cells.

The use of proteins as intracellular probes and therapeutic tools is often limited by poor intracellular delivery. One approach to enabling intracellular protein delivery is to transform proteins into spherical nucleic acid (proSNA) nanoconstructs, with surfaces chemically modified with a dense shell of radially oriented DNA that can engage with cell-surface receptors that facilitate endocytosis. However, proteins often have a limited number of available reactive surface residues for DNA conjugation such that the extent of DNA loading and cellular uptake is restricted.

Quantitative Proteomics Identifies Profilin-1 as a Pseudouridine-Binding Protein.

Pseudouridine (Ψ) is the most abundant RNA modification in nature; however, not much is known about the biological functions of this modified nucleoside. Employing an unbiased quantitative proteomics method, we identified multiple candidate reader proteins of Ψ in RNA, including a cytoskeletal protein profilin-1 (PFN1). We demonstrated that PFN1 binds directly and selectively to Ψ-containing RNA.

Synthesis of Chiral Saturated Heterocycles Bearing Quaternary Centers via Enantioselective β-C(sp)-H Activation of Lactams.

The development of catalytic methods for the synthesis of enantiopure saturated heterocycles has been a long-standing challenge in asymmetric catalysis. We describe the first highly enantioselective palladium-catalyzed βC(sp)-H arylation and olefination of lactams for the preparation of various chiral N-heterocycles bearing quaternary carbon centers. The presence of strongly electron-withdrawing groups on the chiral bifunctional MPAThio ligand is crucial to the reactivity of weakly coordinating lactams.

RNA Translocation through Protein Nanopores: Interlude of the Molten RNA Globule.

Direct translocation of RNA with secondary structures using single-molecule electrophoresis through protein nanopores shows significant fluctuations in the measured ionic current, in contrast to unstructured single-stranded RNA or DNA. We developed a multiscale model combining the oxRNA model for RNA with the 3-dimensional Poisson-Nernst-Planck formalism for electric fields within protein pores, aiming to map RNA conformations to ionic currents as RNA translocates through three protein nanopores: α-hemolysin, CsgG, and MspA. Our findings reveal three distinct stages of translocation (pseudoknot, melting, and molten globule) based on contact maps and current values.

DNA methylation patterns are influenced by Pax3::Foxo1 expression and developmental lineage in rhabdomyosarcoma tumours forming in genetically engineered mouse models.

Rhabdomyosarcoma (RMS) is a family of phenotypically myogenic paediatric cancers consisting of two major subtypes: fusion-positive (FP) RMS, most commonly involving the PAX3::FOXO1 fusion gene, formed by the fusion of paired box 3 (PAX3) and forkhead box O1 (FOXO1) genes, and fusion-negative (FN) RMS, lacking these gene fusions. In humans, DNA methylation patterns distinguish these two subtypes as well as mutation-associated subsets within these subtypes. To investigate the biological factors responsible for these methylation differences, we profiled DNA methylation in RMS tumours derived from genetically engineered mouse models (GEMMs) in which various driver mutations were introduced into different myogenic lineages.

Metabolic Characterization of Sarin, Cyclosarin, and Novichoks (A-230, A-232) in Human Liver Microsomes.

We have assessed the human liver microsomal (HLM) metabolism of the chemical warfare nerve agents' sarin (GB), cyclosarin (GF), and the Novichok agents A-230 and A-232. In HLM, GB showed drastically decreased stability ( = 1.4 h).

Does Parathyroid Autotransplantation Prevent Hypoparathyroidism after Thyroid Surgery?

Objective: To assess the impact of parathyroid gland autotransplantation on the restoration of parathyroid function in patients who are hypoparathyroid after thyroidectomy.

Background Data: Hypoparathyroidism post-thyroidectomy arises when all parathyroid glands are devascularized or injured. Autotransplantation of compromised parathyroids aims to preserve their function and prevent permanent hypoparathyroidism.

An Unexpected Activity of a Minor Cannabinoid: Cannabicyclol (CBL) Is a Potent Positive Allosteric Modulator of Serotonin 5-HT Receptor.

Cannabicyclol ((±)-CBL), a minor phytocannabinoid, is largely unexplored, with its biological activity previously undocumented. We studied its conversion from cannabichromene (CBC) using various acidic catalysts. Montmorillonite (K30) in chloroform at room temperature had the highest yield (60%) with minimal byproducts.

Polarization Upends Convention: Halogen Bonding Propensities of Main Group Halides.

The propensities for sigma hole bonding by halogen atoms bonded to central atoms below period 2 in the periodic table remain to be systematically examined. Using iodine as our reference halogen atom, a comprehensive analysis of the tendencies for halogen and other forms of significant sigma hole bonding by simple compounds of main group atoms from H to At is accomplished. An examination of the structure and bonding of complexes formed by those iodine-substituted main group compounds and sigma donating bases (ammonia and trimethylamine) is performed to probe the viability of halogen bonding by heavy main group RM-I compounds in particular, given the historic focus on period 2.

Trends in Osteoporosis Drug Therapy Receipt Among Commercial and Medicare Advantage Enrollees in the United States, 2011-2022.

Context: A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis.

Objective: The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis.

Methods: This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022.

Impact of Financial Toxicity on the Health-Related Quality of Life and Financial Well-Being of Cancer Patients and Survivors: A Comparative Study of the United Kingdom and United States.

Background: This study investigated and compared the impact of financial toxicity (FT) on the health-related quality of life (HRQoL) and financial well-being of cancer patients and survivors in the United Kingdom (UK) and United States (US).

Methods: UK & US participants (n = 600) completed an online questionnaire that consisted of a validated FT instrument (COmprehensive Score for financial Toxicity-COST), a standardised HRQoL instrument (EQ-5D-5L) and questions related to their financial well-being. Tobit regression models and descriptive statistics plus χ tests were used to analyse the association between FT and (i) HRQoL whilst controlling for sociodemographic characteristics; and (ii) financial well-being.

Concise Synthesis of (-)-Veratramine and (-)-20--Veratramine via Aromative Diels-Alder Reaction.

A concise and convergent synthesis of the isosteroidal alkaloids veratramine and 20--veratramine has been accomplished. A Horner-Wadsworth-Emmons olefination joins two chiral building blocks of approximately equal complexity and a transition-metal catalyzed intramolecular Diels-Alder cycloaddition-aromatization cascade constructs the tetrasubstituted arene. Other key steps include a highly diastereoselective crotylation of an -sulfonyl iminium ion and an Eschenmoser fragmentation.

Striving for Unity in a Culturally Fragmented World: Nested Multiple Cultural Identifications Associated With Well-Being Through Self-Concept Clarity.

In contemporary globalised societies, global awareness and identification, as well as local and regional identifications (other than national identity), may all become increasingly important for guiding people's sense of belonging and purpose and in turn their self-concept. As the world has become increasingly interconnected, people increasingly identify with various cultures and worldviews within both local and global contexts. Attempts to reconcile these multiple cultural identities can lead to a sense of cultural dissonance as people struggle to integrate these identities into a coherent sense of self.

Unilateral Versus Bilateral Endoscopic Resection of Olfactory Neuroblastoma: Pooled Analysis From Prospective and Retrospective Multicenter Data.

Background: Olfactory neuroblastoma (ONB) is a rare sinonasal malignancy primarily treated with surgery. For tumors arising from the olfactory area, traditional treatment involves transcribriform resection of the anterior cranial fossa. Surgery can be performed with unilateral or bilateral resection depending on extent of involvement; however, there are currently no studies comparing outcomes between the two.

Assessment of clinical characteristics and mortality in patients hospitalized with SARS-CoV-2 from January 2022 to November 2022, when Omicron variants were predominant in the United States.

Objective: To describe the demographic/clinical characteristics, treatment patterns, and mortality among patients hospitalized with COVID-19 during Omicron predominance by immunocompromised and high-risk status.

Methods: Retrospective observational study of patients hospitalized with COVID-19 between January 1, 2022 and November 30, 2022, using data from the Optum de-identified Clinformatics® Data Mart Database. Patient demographic/clinical characteristics, treatments, mortality and costs, were assessed, during the emergence of BA.

Exploring the perceptions and cultural differences surrounding mindfulness among early childhood education informal caregivers: A qualitative study.

Background: Early childhood education (ECE) caregivers experience high levels of stress and increased physical and emotional work demands. Promoting mindfulness practices may be an acceptable and feasible strategy to bolster mental health and well-being. The present study's goals were to explore the 1) perceptions and 2) cultural differences surrounding mindfulness practices and mental health among Spanish-speaking Hispanic (SSH), English-speaking Hispanic (ESH), and English-speaking non-Hispanic (ESNH) informal ECE caregivers.

Adenoid basal cell carcinoma: An underrecognized cervical malignancy.

Introduction: Adenoid basal cell carcinoma is a rare cervical malignancy which is indolent in nature but resembles more commonly occurring aggressive malignancies.

Cases: Here we describe three cases of cervical adenoid basal cell carcinoma. All patients had a history of cervical dysplasia with high-risk HPV.

Factors associated with willingness to perform expedited excisional treatment for patients at high risk for cervical precancer.

Background: The 2019 ASCCP Risk-Based Management Consensus Guidelines prefer expedited treatment, defined as proceeding to excisional treatment without first performing colposcopic biopsy, for patients with screening results indicating a high risk of cervical precancer. In this mixed methods study, we explored clinician attitudes toward expedited treatment.

Methods: In 2021, a national sample of 671 clinicians who performed colposcopy completed surveys; a subset (n = 41) of clinicians who performed colposcopy and/or directed patient treatment completed qualitative interviews.

Payment models and the sustainability of community pharmacy practice: a qualitative interview study with community pharmacists.

Background: The sustainability of community pharmacies in the United States depends, in large part, on policies enacted by the Centers for Medicare and Medicaid Services (CMS). In 2003, CMS policy allowed retrospective direct and indirect remuneration (DIR) fees to manage costs. From 2024, only prospective DIR fees are permitted.

Phylogenomics, reticulation, and biogeographical history of Elaeagnaceae.

The angiosperm family Elaeagnaceae comprises three genera and . 100 species distributed mainly in Eurasia and North America. Little family-wide phylogenetic and biogeographic research on Elaeagnaceae has been conducted, limiting the application and preservation of natural genetic resources.

Effectiveness of interventions to prevent drowning among children under age 20 years: a global scoping review.

Background: Drowning is a leading cause of death among young children. The United Nations Resolution on global drowning prevention (2021) and World Health Assembly Resolution in 2023 have drawn attention to the issue. This scoping review synthesizes the current evidence on the effectiveness of child drowning prevention interventions since the 2008 World Report on Child Injury Prevention and implications for their implementation.