Characterization of the binding features between SARS-CoV-2 5'-proximal transcripts of genomic RNA and nucleocapsid proteins.

Packaging signals (PSs) of coronaviruses (CoVs) are specific RNA elements recognized by nucleocapsid (N) proteins that direct the selective packaging of genomic RNAs (gRNAs). These signals have been identified in the coding regions of the nonstructural protein 15 (Nsp 15) in CoVs classified under , a subgenus of betacoronaviruses (beta-CoVs). The PSs in other alpha- and beta-CoVs have been proposed to reside in the 5'-proximal regions of gRNAs, supported by comprehensive phylogenetic evidence.

Evaluating Covid-19 publications for sex and gender-specific health content: A bibliometric analysis.

Background: Sex and gender are key variables which inform human health and disease. It remained unclear how sex and gender were considered, evaluated, reported, or analyzed within Covid-19 research. This article evaluates the proportion of Covid-19-related articles which highlighted sex- or gender-specific health content and examines associations with author gender.

Remote clinical trial to test mechanisms of 'practice quitting' treatment: Trial design and methodological report.

Background: Tobacco use disorder is a chronic, relapsing health condition that necessitates a chronic care approach. However, there are limited treatment strategies relevant to individuals who smoke across a continuum of motivation to quit. Further, there is no clear understanding of the mechanisms underlying treatment strategies to engage individuals who are not yet ready to quit smoking.

Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing.

Diabetic wounds are characterized by chronic inflammation, reduced angiogenesis, and insufficient collagen deposition, leading to impaired healing. Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSC) offer a promising cell-free therapeutic strategy, yet their efficacy and immunomodulation can be enhanced through bioactivation. In this study, we developed calcium silicate (CS)-stimulated ADSC-derived EVs (CSEV) incorporated into collagen hydrogels to create a sustained-release system for promoting diabetic wound healing.

Development of a novel calculator to predict gonadotropin dose and oocyte yield in oocyte cryopreservation cycles.

Purpose: To develop a predictive model for estimating the total dose of gonadotropins and the number mature oocytes in planned oocyte cryopreservation cycles.

Methods: In this retrospective study, oocyte cryopreservation cycles recorded in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System Database from 2013 to 2018 were analyzed. Bivariate copula additive models for location, scale, and shape were performed to create a predictive model for estimating total dose of gonadotropins and number of mature oocytes.

Structural insights into signaling promiscuity of the CBASS anti-phage defense system from a radiation-resistant bacterium.

Radiation-resistant bacteria are of great application potential in various fields, including bioindustry and bioremediation of radioactive waste. However, how radiation-resistant bacteria combat against invading phages is seldom addressed. Here, we present a series of crystal structures of a sensor and an effector of the cyclic oligonucleotide-based anti-phage signaling system (CBASS) from a radioresistant bacterium Deinococcus wulumuqiensis.

Factors associated with male recruitment in a multi-site randomized behavioral clinical trial targeting the metabolic syndrome: analysis of screening and recruitment data from the ELM trial.

Background: Males are underrepresented in behavioral clinical trials of lifestyle. The aim of this exploratory study was to investigate factors associated with trial interest in males at different stages of recruitment and overall, into a multi-site behavioral trial targeting lifestyle change and remission of the metabolic syndrome. Similar analyses were performed for female participation to investigate the uniqueness or consistency with the findings for males.

Assessing the inhibitory effects of some secondary amines, thioureas and 1,3-dimethyluracil conjugates of (-)-cytisine and thermopsine on the RNA-dependent RNA polymerase of SARS-CoV-1 and SARS-CoV-2.

SARS-CoV-2 causes COVID-19, with symptoms ranging from mild to severe, including pneumonia and death. This beta coronavirus has a 30-kilobase RNA genome and shares about 80 % of its nucleotide sequence with SARS-CoV-1. The replication/transcription complex, essential for viral RNA synthesis, includes RNA-dependent RNA polymerase (RdRp, nsp12) enhanced by nsp7 and nsp8.

Targeting Dual Immune Checkpoints PD-L1 and HLA-G by Trispecific T Cell Engager for Treating Heterogeneous Lung Cancer.

Immunotherapy targeting immune checkpoints (ICPs), such as programmed death-ligand-1 (PD-L1), is used as a treatment option for advanced or metastatic non-small cell lung cancer (NSCLC). However, overall response rate to anti-PD-L1 treatment is limited due to antigen heterogeneity and the immune-suppressive tumor microenvironment. Human leukocyte antigen-G (HLA-G), an ICP as well as a neoexpressed tumor-associated antigen, is previously demonstrated to be a beneficial target in combination with anti-PD-L1.

The use of an embryo transfer simulator to compare transfer techniques and pregnancy outcomes among physicians.

Objective: To evaluate the association between embryo transfer techniques and pregnancy outcomes.

Design: This is a prospective observational study with a retrospective cohort.

Setting: University Clinic.

Structural and functional characterization of cyclic pyrimidine-regulated anti-phage system.

3',5'-cyclic uridine monophosphate (cUMP) and 3',5'-cyclic cytidine monophosphate (cCMP) have been established as bacterial second messengers in the phage defense system, named pyrimidine cyclase system for anti-phage resistance (Pycsar). This system consists of a pyrimidine cyclase and a cyclic pyrimidine receptor protein. However, the molecular mechanism underlying cyclic pyrimidine synthesis and recognition remains unclear.

Glycyrrhizic acid conjugates with amino acid methyl esters target the main protease, exhibiting antiviral activity against wild-type and nirmatrelvir-resistant SARS-CoV-2 variants.

COVID-19 pandemic is predominantly caused by SARS-CoV-2, with its main protease, Mpro, playing a pivotal role in viral replication and serving as a potential target for inhibiting different variants. In this study, potent Mpro inhibitors were identified from glycyrrhizic acid (GL) derivatives with amino acid methyl/ethyl esters. Out of the 17 derivatives semisynthesized, Compounds 2, 6, 9, and 15, with methionine methyl esters, D-tyrosine methyl esters, glutamic acid methyl esters, and methionines in the carbohydrate moiety, respectively, significantly inhibited wild-type SARS-CoV-2 Mpro-mediated proteolysis, with IC50 values ranging from 0.

Neighborhood physical environments and change in cardiometabolic risk factors over 14 years in the study of Women's health across the nation.

Background: Neighborhood physical environments may influence cardiometabolic health, but prior studies have been inconsistent, and few included long follow-up periods.

Methods: Changes in cardiometabolic risk factors were measured for up to 14 years in 2830 midlife women in the Study of Women's Health Across the Nation, a multi-ethnic/racial cohort of women from seven U.S.

S100A8/A9 predicts response to PIM kinase and PD-1/PD-L1 inhibition in triple-negative breast cancer mouse models.

Background: Understanding why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well remains a challenge. This study aims to understand the potential underlying mechanisms distinguishing early-stage TNBC tumors that respond to clinical intervention from non-responders, as well as to identify clinically viable therapeutic strategies, specifically for TNBC patients who may not benefit from existing therapies.

Methods: We conducted retrospective bioinformatics analysis of historical gene expression datasets to identify a group of genes whose expression levels in early-stage tumors predict poor clinical outcomes in TNBC.

Natural Cycle Frozen Embryo Transfer: Evaluating Optimal Protocols for Preparation and Timing.

Background: While natural cycle frozen embryo transfer (NC-FET) is becoming increasingly common, significant practice variation exists in the use of ovulation induction medications, administration of ovulation trigger, and timing of embryo transfer without consensus as to the optimal protocol.

Aims: The objective of this study is to evaluate the association of key aspects of the NC-FET protocol with implantation, pregnancy and live birth.

Settings And Design: This was a retrospective cohort study of blastocyst stage NC-FET cycles from October 2019 to July 2021 at a single academic fertility centre.

Mapping the Postpartum Experience Through Obstetric Patient Navigation for Low-Income Individuals.

Although the postpartum period is an opportunity to address long-term health, fragmented care systems, inadequate attention to social needs, and a lack of structured transition to primary care threaten patient wellbeing, particularly for low-income individuals. Postpartum patient navigation is an emerging innovation to address these disparities. This mixed-methods analysis uses data from the first year of an ongoing randomized controlled trial to understand the needs of low-income postpartum individuals through 1 year of patient navigation.

Structural insights into the regulation, ligand recognition, and oligomerization of bacterial STING.

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) signaling pathway plays a critical protective role against viral infections. Metazoan STING undergoes multilayers of regulation to ensure specific signal transduction. However, the mechanisms underlying the regulation of bacterial STING remain unclear.

Association of Antenatal Housing Instability with Perinatal Care Utilization and Outcomes.

Social determinants of health are important contributors to maternal and child health outcomes. Limited existing research examines the relationship between housing instability during pregnancy and perinatal care utilization. Our objective was to evaluate whether antenatal housing instability is associated with differences in perinatal care utilization and outcomes.

S100A8/A9 predicts triple-negative breast cancer response to PIM kinase and PD-1/PD-L1 inhibition.

It remains elusive why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well. Our retrospective analysis of historical gene expression datasets reveals that increased expression of immunosuppressive cytokine S100A8/A9 in early-stage tumors is robustly associated with subsequent disease progression in TNBC. Although it has recently gained recognition as a potential anticancer target, S100A8/A9 has not been integrated into clinical study designs evaluating molecularly targeted therapies.

The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2.

The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further.

Crystal structure and functional implications of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases.

Purine-containing nucleotide second messengers regulate diverse cellular activities. Cyclic di-pyrimidines mediate anti-phage functions in bacteria; however, the synthesis mechanism remains elusive. Here, we determine the high-resolution structures of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases (CD-NTases) in clade E (CdnE) in its apo, substrate-, and intermediate-bound states.

Umbelliferone and eriodictyol suppress the cellular entry of SARS-CoV-2.

Background: Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A.

Enabling Real-World Data to Accelerate the Development of Innovative Cancer Biomarkers.

The molecular diagnostics industry has historically relied on sanitized clinical trials and commoditized data sources to inform its biomarker discovery and validation process-an under-substantiated approach that was ultra-expensive, resource-consuming and did not reflect how representative a new biomarker would be in broader patient populations. In an effort to gain more accurate insight into the patient experience and bring innovative biomarkers to market more efficiently and accurately, the industry is now expanding into extended real-world data. To access the needed breadth and depth of patient-centric data, diagnostic companies must collaborate with a healthcare data analytics partner that has three key assets: (i) a broad and deep megadata with metadata, (ii) a data-rich provider network, and (iii) an outcomes-improvement engine to support the next generation of molecular diagnostics (Dx) and therapeutics (Rx) development.

SweetMama: Usability Assessment of a Novel Mobile Application Among Low-Income Pregnant People to Assist With Diabetes Management and Support.

Background: Mobile health tools may be effective strategies to improve engagement, education, and diabetes-related health during pregnancy. We developed SweetMama, a patient-centered, interactive mobile application (app) designed to support and educate low-income pregnant people with diabetes. Our objective was to evaluate the SweetMama user experience and acceptability.