Genomic and cellular responses to aspirin in colonic organoids from African- and European-Americans.

Aspirin (ASA) is a proven chemoprotective agent for colorectal cancer (CRC), though inter-individual responses and cellular mechanisms are not well characterized. Human organoids are ideal to study treatment responses across individuals. Here, colonic organoids from African-Americans (AA) and European-Americans (EA)were used to profile genomic and cellular ASA responses.

Predicting Alzheimer's disease subtypes and understanding their molecular characteristics in living patients with transcriptomic trajectory profiling.

Introduction: Deciphering the diverse molecular mechanisms in living Alzheimer's disease (AD) patients is a big challenge but is pivotal for disease prognosis and precision medicine development.

Methods: Utilizing an optimal transport approach, we conducted graph-based mapping of transcriptomic profiles to transfer AD subtype labels from ROSMAP monocyte samples to ADNI and ANMerge peripheral blood mononuclear cells. Subsequently, differential expression followed by comparative pathway and diffusion pseudotime analysis were applied to each cohort to infer the progression trajectories.

Primary Effusion Lymphoma Prognostic Score (PEL-PS): A Validated International Prognostic Score in HIV-Associated Primary Effusion Lymphoma.

Primary effusion lymphoma (PEL) is an HIV-associated B-cell non-Hodgkin lymphoma (NHL) caused by Kaposi sarcoma herpesvirus (KSHV). There is no validated prognostic model in PEL, and prognosis is thought to be poor compared to other HIV-associated NHL. We derived the PEL-Prognostic score (PEL-PS) from an international real-world training set of 59 patients with HIV-associated PEL who received first-line anthracycline-containing chemotherapy from the HIV and AIDS Malignancy Branch at the National Cancer Institute (NCI) in the United States and the National Center for HIV Malignancy at the Chelsea and Westminster Hospital (CWH) in England from 2000 to 2022.

The low-lying electronic states of 4H-pyran-4-thione; a photoionization and vacuum ultraviolet absorption study, with interpretation by configuration interaction and density functional calculations for the ionic and singlet states.

Two synchrotron-based studies on 4H-pyran-4-thione, photoelectron spectroscopy and vacuum ultraviolet (VUV) absorption spectra were performed. A highly resolved structure was observed in the photoelectron spectrum (PES), in contrast to an earlier PES study, where little structure was observed. The sequence of ionic states was determined using configuration interaction and coupled cluster methods.

Health Care Resource Utilization With Dronedarone Versus Sotalol Following Catheter Ablation in Adults With Atrial Fibrillation.

Background: Clinical trials support dronedarone use for atrial fibrillation (AF) following catheter ablation (CA); however, comparative data on health care resource utilization (HCRU) with other antiarrhythmic drugs are lacking.

Methods: Retrospective analysis of Merative MarketScan databases (January 01, 2012-March 31, 2020) comparatively assessed HCRU in US adults with AF who received dronedarone or sotalol post-CA. Patients with ≥ 12-months' pre-CA data were followed from post-CA index treatment to disenrollment, death, or study end.

Language Predictors of Word-Problem Performance Among Third-Grade Students With Mathematics Difficulty.

We examined how generalized and mathematics-specific language skills predicted the word-problem performance of students with mathematics difficulty. Participants included 325 third-grade students in the southwestern United States who performed at or below the 25th percentile on a word-problem measure. We assessed generalized language skills in word reading, passage comprehension, and vocabulary knowledge.

Mortality and Function After Hip Fracture or Pneumonia in People With and Without Dementia.

Background: The extent to which disruptive surgical or medical events impact mortality and function is critical for anticipatory planning and informing goal-aligned care.

Methods: Using Health and Retirement Study data (2008-2018), we employed propensity score matching to compare the impact of hospitalization for hip fracture (a surgical event) or pneumonia (a medical event) among people with dementia to two groups: (1) people with dementia who did not experience these events; and (2) people without dementia who experienced an event. Dementia status was determined using validated cognitive assessments (Hurd method); hip fracture and pneumonia were identified from Medicare claims.

Respectful Maternity Care in the United States: A Scoping Review of the Research and Birthing People's Experiences.

Introduction: Birthing people around the world experience mistreatment during labor and birth, contributing to adverse maternal health outcomes. The adoption of respectful maternity care (RMC) has been recommended to address this mistreatment and improve care quality. Most RMC and mistreatment research has been conducted internationally.

Reduction of vancomycin-associated acute kidney injury with montelukast.

Background: Vancomycin ranks amongst the most utilized antimicrobial agents in the treatment of serious β-lactam-resistant Gram-positive infections, but its use has been associated with nephrotoxicity. Reduction of acute kidney injury (AKI) has been reported in pre-clinical models with adjuvant montelukast. The purpose of the study was to ascertain if montelukast was associated with a reduction in the prevalence of vancomycin-associated AKI.

Serendipitous high-resolution structure of Escherichia coli carbonic anhydrase 2.

X-ray crystallography remains the dominant method of determining the three-dimensional structure of proteins. Nevertheless, this resource-intensive process may be hindered by the unintended crystallization of contaminant proteins from the expression source. Here, the serendipitous discovery of two novel crystal forms and one new, high-resolution structure of carbonic anhydrase 2 (CA2) from Escherichia coli that arose during a crystallization campaign for an unrelated target is reported.

White Matter Tract Crossing and Bottleneck Regions in the Fetal Brain.

There is a growing interest in using diffusion MRI to study the white matter tracts and structural connectivity of the fetal brain. Recent progress in data acquisition and processing suggests that this imaging modality has a unique role in elucidating the normal and abnormal patterns of neurodevelopment in utero. However, there have been no efforts to quantify the prevalence of crossing tracts and bottleneck regions, important issues that have been investigated for adult brains.

Naturally Acquired Genotype-Specific HPV Seroreactivity and Subsequent HPV Detection Among Heterosexual Partners.

The protective effect of naturally acquired humoral immunity against human papillomavirus (HPV) infection remains unclear. To investigate the role of infection-induced antibodies on HPV detection in heterosexual partners, we used data from 392 unvaccinated couples (females aged 18-25 years attended up to six visits over 2 years; males aged 17-37 years attended up to two visits 4 months apart) enrolled (2005-2011) in Montreal. Genital and blood samples were HPV DNA genotyped and tested for L1 antibody titers of 14 HPV genotypes.

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.