Characteristics and treatment patterns in patients with multiple myeloma in Japan: A retrospective cohort analysis.

Background: Approval of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies (mAbs), such as daratumumab, has reshaped treatment patterns in patients with multiple myeloma (MM) in Japan. This retrospective study evaluated patient characteristics, treatment patterns, and trends in MM patients using Medical Data Vision, the largest electronic health records database in Japan with anonymous inpatient and outpatient health information.

Methods: Patients aged ≥18 years, with ≥2 records of an MM diagnostic and disease code and ≥1 record of MM treatment between 01 April 2008 and 30 June 2023 were included.

Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.

Malaria is a complex parasitic disease caused by species of Plasmodium parasites. Infection with the parasites can lead to a spectrum of symptoms and disease severity, influenced by various parasite, host, and environmental factors. There have been some successes in developing vaccines against the disease recently, but the vaccine efficacies require improvement.

Atypical memory B cells from natural malaria infection produced broadly neutralizing antibodies against Plasmodium vivax variants.

Expansion of atypical memory B cells (aMBCs) was demonstrated in malaria-exposed individuals. To date, the generation of P. vivax-specific aMBCs and their function in protective humoral immune responses is unknown.

Leptospirosis, melioidosis, and rickettsioses in the vicious circle of neglect.

The global priorities in the field of infectious diseases are constantly changing. While emerging viral infections have regularly dominated public health attention, which has only intensified after the COVID-19 pandemic, numerous bacterial diseases have previously caused, and continue to cause, significant morbidity and mortality-deserving equal attention. Three potentially life-threatening endemic bacterial diseases (leptospirosis, melioidosis, and rickettsioses) are a huge public health concern especially in low- and middle-income countries.

The impact of anions on electrooxidation of perfluoroalkyl acids by porous Magnéli phase titanium suboxide anodes.

Previous studies have indicated the great performance of electrooxidation (EO) to mineralize per- and polyfluoroalkyl substances (PFASs) in water, but different anions presented in wastewater may affect the implementation of EO treatment in field applications. This study invetigated EO treatment of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two representative perfluoroalkyl acids (PFAAs), using porous Magnéli phase titanium suboxide anodes in electrolyte solutions with different anions present, including NO3-, SO42-, CO32- and PO43-. The experiment results indicate that CO32- enhanced PFAS degradation, while NO3- suppressed the degradation reactions with its concentration higher than 10 mM.

Characteristics influencing COVID-19 testing and vaccination among Spanish-speaking Latine persons in North Carolina.

Background: Latine populations in the United States continue to be disproportionately affected by COVID-19 with high rates of infection and mortality. Our community-based participatory research partnership examined factors associated with COVID-19 testing and vaccination within a particularly hidden, underserved, and vulnerable population: Spanish-speaking Latines.

Methods: In 2023, native Spanish-speaking Latine interviewers conducted phone-based structured individual assessments with 180 Spanish-speaking, predominantly immigrant Latines across North Carolina.

MEGA-GO: Functions prediction of diverse protein sequence length using Multi-scalE Graph Adaptive neural network.

Motivation: The increasing accessibility of large-scale protein sequences through advanced sequencing technologies has necessitated the development of efficient and accurate methods for predicting protein function. Computational prediction models have emerged as a promising solution to expedite the annotation process. However, despite making significant progress in protein research, graph neural networks face challenges in capturing long-range structural correlations and identifying critical residues in protein graphs.

Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS).

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.

QM Investigation of Rare Earth Ion Interactions with First Hydration Shell Waters and Protein-Based Coordination Models.

Conventional methods for extracting rare earth metals (REMs) from mined mineral ores are inefficient, expensive, and environmentally damaging. Recent discovery of lanmodulin (LanM), a protein that coordinates REMs with high-affinity and selectivity over competing ions, provides inspiration for new REM refinement methods. Here, we used quantum mechanical (QM) methods to investigate trivalent lanthanide cation (Ln) interactions with coordination systems representing bulk solvent water and protein binding sites.

Enantiocontrolled Cyclization to Form Chiral 7- and 8-Membered Rings Unified by the Same Catalyst Operating with Different Mechanisms.

Chiral medium-sized rings, albeit displaying attractive properties for drug development, suffer from numerous synthetic challenges due to difficult cyclization steps that must take place to form these unusually strained, atropisomeric rings from sterically crowded precursors. In fact, catalytic enantioselective cyclization methods for the formation of chiral seven-membered rings are unknown, and the corresponding eight-membered variants are also sparse. In this work, we present a substrate preorganization-based, enantioselective, organocatalytic strategy to construct seven- and eight-membered rings featuring chirality that is intrinsic to the ring in the absence of singular stereogenic atoms or single bond axes of chirality.

Selectivity Effects of Hydrogen Acceptors and Catalyst Structures in Alcohol Oxidations Using (Cyclopentadienone)iron Tricarbonyl Compounds.

Oppenauer-type oxidations are catalyzed by air- and moisture-stable, sustainable, (cyclopentadienone)iron carbonyl compounds, but the substrate scope is limited due to the low reduction potential of acetone, which is the most commonly used hydrogen acceptor. We discovered that furfural, an aldehyde derived from cellulosic biomass, is an effective hydrogen acceptor with this class of catalysts. In general, reactions using furfural as the hydrogen acceptor led to higher isolated yields of ketones and aldehydes compared to those using acetone.

Neonatal but not Juvenile Gene Therapy Reduces Seizures and Prolongs Lifespan in SCN1B-Dravet Syndrome Mice.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy (DEE) that begins in the first year of life. While most cases of DS are caused by variants in SCN1A, variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are also linked to DS or to the more severe early infantile DEE. Both disorders fall under the OMIM term DEE52.

Polarimetric Compressed Sensing with Hollow, Self-Assembled Diffractive Films.

Sensing light's polarization and wavefront direction enables surface curvature assessment, material identification, shadow differentiation, and improved image quality in turbid environments. Traditional polarization cameras utilize multiple sensor measurements per pixel and polarization-filtering optics, which result in reduced image resolution. We propose a nanophotonic pipeline that enables compressive sensing and reduces the sampling requirements with a low-refractive-index, self-assembled optical encoder.

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.

Modeling Biases from Low-Pass Genome Sequencing to Enable Accurate Population Genetic Inferences.

Low-pass genome sequencing is cost-effective and enables analysis of large cohorts. However, it introduces biases by reducing heterozygous genotypes and low-frequency alleles, impacting subsequent analyses such as model-based demographic history inference. Several approaches exist for inferring an unbiased allele frequency spectrum (AFS) from low-pass data, but they can introduce spurious noise into the AFS.

Pharmacogenetics: Opportunities for the Research Program and Other Large Data Sets to Advance the Field.

Pharmacogenetic variation is common and an established driver of response for many drugs. There has been tremendous progress in pharmacogenetics knowledge over the last 30 years and in clinical implementation of that knowledge over the last 15 years. But there have also been many examples where translation has stalled because of the lack of available data sets for discovery or validation research.

Exploiting YES1-driven EGFR expression improves the efficacy of EGFR inhibitors.

Epidermal growth factor receptor (EGFR) is a highly expressed driver of many cancers, yet the utility of EGFR inhibitors is limited to cancers that harbor sensitizing mutations in the EGFR gene due to dose limiting toxicities. Rather than conventionally blocking the kinase activity of EGFR, we sought to reduce its transcription as an alternative approach to broaden the therapeutic window for EGFR inhibitors targeting wildtype or mutant EGFR. We found that YES1 is highly expressed in triple negative breast cancer (TNBC) and drives cell growth by elevating EGFR levels.

Influence of Source of Origin and Region of Finishing on Growth Performance and Carcass Characteristics of Finishing Heifers Fed in the United States.

The objective was to evaluate growth performance and carcass traits of finishing beef heifers sourced and finished in different regions in the U.S. Heifers [n = 190; initial body weight (BW) 483 ± 0.

Distribution of opioid analgesics by community racial/ethnic and socioeconomic profiles, 2011-2021.

Rapid declines in opioid analgesics dispensed in American communities since 2011 raise concerns about inadequate access to effective pain management among patients for whom opioid therapies are appropriate, especially for those living in racial/ethnic minority and socioeconomically deprived communities. Using 2011 to 2021 national data from the Automated Reports and Consolidated Ordering System and generalized linear models, this study examined quarterly per capita distribution of oxycodone, hydrocodone, and morphine (in oral morphine milligram equivalents [MMEs]) by communities' racial/ethnic and socioeconomic profiles. Communities (defined by 3-digit-zip codes areas) were classified as "majority White" (≥50% self-reported non-Hispanic White population) vs "majority non-White.

Permanent defects in renal medullary structure and function after reversal of urinary obstruction.

Urinary obstruction causes injury to the renal medulla, impairing the ability to concentrate urine, and increasing the risk of progressive kidney disease. However, the regenerative capacity of the renal medulla after reversal of obstruction is poorly understood. To investigate this, we developed a mouse model of reversible urinary obstruction.

Schizophrenia and retention in HIV care among adults insured through Medicaid in the United States: a population-based retrospective cohort study.

Background: People with schizophrenia spectrum disorders are at elevated risk of HIV, and people with both HIV and schizophrenia are at elevated risk of death compared to individuals with either diagnosis alone. Limited research has assessed the HIV care cascade, and in particular retention in care, among people with HIV (PWH) and schizophrenia in the U.S.

Updates to HIV transmission rate estimates along the HIV care continuum in the United States, 2019.

Background: In 2019, there were an estimated 1.2 million persons with HIV (PWH) and 35,100 new infections in the United States. The HIV care continuum has a large influence on transmission dynamics.

Tuberculosis in the US Kidney Failure Population.

Background: People with chronic kidney disease (CKD) have a higher risk for progression to tuberculosis disease following infection with Mycobacterium tuberculosis. We produced a nationwide incidence estimate and description of tuberculosis among people with kidney failure.

Methods: We completed a cross-sectional descriptive analysis of people with a reported case of tuberculosis in the United States between 2010 and 2021.

A Pilot Trial of Nicotinamide Riboside and Coenzyme Q10 on Inflammation and Oxidative Stress in Chronic Kidney Disease.

Background: Mitochondria-driven oxidative/redox stress and inflammation play a major role in chronic kidney disease (CKD) pathophysiology. Compounds targeting mitochondrial metabolism may improve mitochondrial function, inflammation, and redox stress; however, there is limited evidence of their efficacy in CKD.

Methods: We conducted a pilot randomized, double-blind, placebo-controlled crossover trial comparing the effects of 1200 mg/day of coenzyme Q10 (CoQ10) or 1000 mg/day of nicotinamide riboside (NR) supplementation to placebo in 25 people with moderate-to-severe CKD (estimated glomerular filtration rate [eGFR] <60mL/min/1.