Determinants of Racial and Ethnic Differences in Maternal Cardiovascular Health in Early Pregnancy.

Background: Suboptimal cardiovascular health (CVH) in pregnancy is associated with adverse maternal and offspring outcomes. To guide public health efforts to reduce disparities in maternal CVH, we determined the contribution of individual- and neighborhood-level factors to racial and ethnic differences in early pregnancy CVH.

Methods: We included nulliparous individuals with singleton pregnancies who self-identified as Hispanic, non-Hispanic Black (NHB), or non-Hispanic White (NHW) and participated in the nuMoM2b cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be).

Effect of Occupational Noise on Employee Health: A Longitudinal Study.

Objective: This study investigated the long-term health risks associated with occupational noise exposure. By using 9 years of health examination data from a major manufacturing company in Taiwan, this study compared the health indices of employees in noise-intensive and non-noise-intensive work environments.

Methods: A retrospective analysis of 6278 health examination reports spanning 9 years was conducted to compare 20 health indices among 166 employees evenly distributed between noise-intensive and non-noise-intensive workgroups.

Comparative genetic analysis of blood and semen samples in sperm donors from Hunan, China.

Objectives: At present, most genetic tests or carrier screening are performed with blood samples, and the known carrier rate of disease-causing variants is also derived from blood. For semen donors, what is really passed on to offspring is the pathogenic variant in their sperm. This study aimed to determine whether pathogenic variants identified in the sperm of young semen donors are also present in their blood, and whether matching results for blood are consistent with results for sperm.

INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform.

Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume.

Structural and antigenic characterization of novel and diverse glycoproteins.

(HNVs), a genus within the family, includes the highly virulent Nipah and Hendra viruses that cause yearly reoccurring outbreaks of deadly disease. Recent discoveries of several new species, including the zoonotic Langya virus, have revealed much higher antigenic diversity than currently characterized. Here, to explore the limits of structural and antigenic variation in HNVs, we construct an expanded, antigenically diverse panel of HNV fusion (F) and attachment (G) glycoproteins from 56 unique HNV strains that better reflects global HNV diversity.

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes.

The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved.

Non-invasive lipid panel of MASLD fibrosis transition underscores the role of lipoprotein sulfatides in hepatic immunomodulation.

There exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n = 324) from non-fibrosis (F0, n = 195), with an area under receiver operating characteristic curve (AUROC) at 0.

Spatial organization of PI3K-PI(3,4,5)P-AKT signaling by focal adhesions.

The class I phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is a key regulator of cell survival, growth, and proliferation and is among the most frequently mutated pathways in cancer. However, where and how PI3K-AKT signaling is spatially activated and organized in mammalian cells remains poorly understood. Here, we identify focal adhesions (FAs) as subcellular signaling hubs organizing the activation of PI3K-PI(3,4,5)P-AKT signaling in human cancer cells containing p110α mutations under basal conditions.

Predicting Short-term and Long-term Efficacy of HIFU Treatment for Uterine Fibroids Based on Clinical Information and MRI: A Retrospective Study.

Rationale And Objectives: This study aimed to address the challenge of predicting treatment outcomes for patients with uterine fibroids undergoing high-intensity focused ultrasound (HIFU) ablation. We developed medical-assisted diagnostic models to accurately predict the ablation rates and volume reduction rates, thus assessing both short-term and long-term treatment effects of fibroids.

Materials And Methods: For the ablation rate prediction, our study included 348 fibroids, categorized into 181 fully ablated and 167 inadequately ablated fibroids.

Sequential Immune Acquisition of Monoclonal Antibodies Enhances Phagocytosis of by Recognizing ATP Synthase.

: The aim of this study was to prepare monoclonal antibodies (mAbs) that broadly target and protect against infection by multi-drug-resistant (MDR) from different sources. : mAb 8E6 and mAb 1B5 were prepared by sequentially immunizing mice with a sublethal inoculation of three heterogeneous serotypes of pan-drug-resistant (PDR) , ST-208, ST-195, and ST-229. : The cross-recognition of heterogeneous bacteria (n = 13) by two mAbs and potential targets was verified, and the in vitro antibacterial efficacy of mAbs was assessed.

Microvascular Inflammation of Kidney Allografts and Clinical Outcomes.

Background: The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear.

Methods: We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023.

Central nervous system tumors in adolescents and young adults: A Society for Neuro-Oncology Consensus Review on diagnosis, management, and future directions.

Adolescents and young adults (AYAs; ages 15-39 years) are a vulnerable population facing challenges in oncological care, including access to specialized care, transition of care, unique tumor biology, and poor representation in clinical trials. Brain tumors are the second most common tumor type in AYA, with malignant brain tumors being the most common cause of cancer-related death. The 2021 WHO Classification for central nervous system (CNS) Tumors highlights the importance of integrated molecular characterization with histologic diagnosis in several tumors relevant to the AYA population.

Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation.

Background: CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor).

Extensive Biotransformation Profiling of AZD8205, an Anti-B7-H4 Antibody-Drug Conjugate, Elucidates Pathways Underlying Its Stability .

What happens to macromolecules ? What drives the structure-activity relationship and stability for antibody-drug conjugates (ADCs)? These interrelated questions are increasingly relevant due to the re-emerging importance of ADCs as an impactful therapeutic modality and the gaps that exist in our understanding of ADC structural determinants that underlie ADC stability. Complex macromolecules, such as ADCs, may undergo changes due to their intricate structure as biotransformations may occur on the linker, the payload, and/or at the modified conjugation site. Furthermore, the dissection of ADC metabolism presents a substantial analytical challenge due to the difficulty in the identification or quantification of minor changes on a large macromolecule.

Intraoperative Guidance of Pancreatic Cancer Resection Using a Toll-like Receptor 2-Targeted Fluorescence Molecular Imaging Agent.

Unlabelled: To increase the achievement of negative R0 surgical margins and increase the low survival rates of pancreatic cancer, improvements in assessing tumor margins during surgical resections are needed. This can be accomplished by using pancreatic cancer-targeted fluorescence molecular imaging agents to intraoperatively detect tumor margins in real time. Because Toll-like receptor 2 (TLR2) is broadly expressed among many cancer types including pancreatic adenocarcinomas, a high-affinity TLR2-targeted fluorescence molecular imaging agent (TLR2L-800) was developed.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

Background: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear.

Methods: A total of 2395 participants (41.

Myocardial Infarction Quality of Care and Outcomes in Asian Ethnic Groups in the United States.

Background: National-level differences in myocardial infarction (MI) quality of care among Asian patients in the United States are unclear. We assessed the quality of MI care in the 6 largest US Asian ethnic groups.

Methods: Patients aged ≥18 years with ST-segment-elevation MI or non-ST-segment-elevation MI in the Get With The Guidelines-Coronary Artery Disease registry (711 US hospitals, 2015-2021) were assessed.

Defining Breast Cryoablation Treatment Success: A Guide for the Curative and Palliative Treatment of Breast Cancer.

Rationale And Objectives: Recent ICE3 trial of breast cryoablation for breast cancer demonstrated 98% success rate, similar to breast-conserving surgery. However, ICE3 and other published studies did not differentiate curative from palliative treatment nor define patient-specific treatment objectives. We sought to define treatment success of curative and palliative breast cryoablation for breast cancer in meeting procedure objectives and patient-specific treatment objectives.