Association between infertility and incident onset of systemic autoimmune rheumatic disease after childbirth: a population-based cohort study.

Study Question: What is the association between infertility with or without fertility treatment and incident onset of systemic autoimmune rheumatic disease (SARD) among women who give birth?

Summary Answer: Women who experienced infertility but did not use fertility treatment had a higher incidence of SARD up to 9 years after delivery than those who did not experience infertility, even after accounting for their higher rates of preeclampsia, spontaneous preterm birth, and stillbirth.

What Is Known Already: Infertility is increasingly common and is an under-appreciated risk marker for chronic diseases in women. Despite several studies documenting abnormal immune activity in women with infertility, little is known about the association between infertility and incidence of autoimmune diseases such as SARD which disproportionately develops in reproductive-aged women.

Predicting Recurrence after Sublobar Resection in Patients with Lung Adenocarcinoma Using Preoperative Chest CT Scans.

Background Sublobar resection for lung cancer is usually guided by cutoff values for consolidation size (maximal diameter of the solid tumor component) and consolidation-to-tumor ratio (CTR). The effects of these factors as continuous variables and the reason for established cutoffs are, to the knowledge of the authors, unexplored. Purpose To quantitatively assess the predictive value of CTR and consolidation size for cancer recurrence risk after sublobar resection in clinical stage IA lung adenocarcinoma.

Artificial intelligence-based real-time histopathology of gastric cancer using confocal laser endomicroscopy.

There has been a persistent demand for an innovative modality in real-time histologic imaging, distinct from the conventional frozen section technique. We developed an artificial intelligence-driven real-time evaluation model for gastric cancer tissue using confocal laser endomicroscopic system. The remarkable performance of the model suggests its potential utilization as a standalone modality for instantaneous histologic assessment and as a complementary tool for pathologists' interpretation.

Safety of Gadoxetate Disodium for Hepatobiliary MRI in Children and Adolescents.

Background Despite a proven role in the characterization of liver lesions, use of the gadolinium-based contrast agent (GBCA) gadoxetate disodium at MRI is limited in children due to a lack of comparative safety data. Purpose To evaluate the safety of the GBCA gadoxetate disodium (a linear ionic hepatobiliary contrast agent [HBA]) in children and adolescents, compared with extracellular contrast agents (ECA). Materials and Methods A retrospective analysis was conducted in children and adolescents aged 18 years or younger who underwent HBA-enhanced MRI at one of three tertiary hospitals from January 2010 to December 2022.

A + AVD for Treatment of Hodgkin Lymphoma Variant of Richter's Transformation.

Hodgkin lymphoma variant of Richter's transformation (HvRT) is a rare complication for patients with chronic lymphocytic leukemia (CLL), with an overall poor prognosis. We present the first known case series of patients with HvRT treated with the combination of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A + AVD). In our series of 4 patients, two patients treated with A + AVD for HvRT had durable remissions of 40 and 42 months, while two patients had disease progression and ultimately died.

No drug-drug interactions between selective prolyl-tRNA synthetase inhibitor, bersiporocin, and pirfenidone or nintedanib in healthy participants.

Bersiporocin, a potent and selective prolyl-tRNA synthetase inhibitor, is expected to show a synergistic effect with pirfenidone or nintedanib in patients with idiopathic pulmonary fibrosis. To validate the combination therapy of bersiporocin with pirfenidone or nintedanib, a randomized, open-label, two-part, one-sequence, three-period, three-treatment study was designed to evaluate the effect of drug-drug interactions (DDI) regarding their pharmacokinetics, safety, and tolerability in healthy participants. In addition, the pharmacokinetic profiles of the newly formulated, enteric-coated bersiporocin tablet were evaluated after single and multiple administrations.

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities.

Effects of Saffron Extract (Affron) with 100 mg/kg and 200 mg/kg on Hypothalamic-Pituitary-Adrenal Axis and Stress Resilience in Chronic Mild Stress-Induced Depression in Wistar Rats.

Stress-related symptoms are a global concern, impacting millions of individuals, yet effective and safe treatments remain scarce. Although multiple studies have highlighted the stress- alleviating properties of saffron extract, the underlying mechanisms remain unclear. This study employs the unpredictable chronic mild stress (CMS) animal model to investigate the impact of a standardized saffron extract, Affron (AFN), on hypothalamic-pituitary-adrenal (HPA) axis regulation and neuroplasticity in Wistar rats following repeated oral administration.

Update on autoantibodies and related biomarkers in autoimmune inflammatory myopathies.

Purpose Of Review: This manuscript reviews recently published advances in the identification of autoimmune inflammatory myopathies (AIM)-specific and AIM-related autoantibodies considered of value in the workup of patients suspected of having AIM. Newer autoantibodies, developments, and advances in the methodology of testing, the gaps and pitfalls in using these assays as diagnostic biomarkers, and the importance of considering overlap diseases and unique clinical AIM phenotypes are discussed.

Recent Findings: a).

Location-Specific Hematoma Volume Cutoff and Clinical Outcomes in Intracerebral Hemorrhage.

Background: Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes.

Screening Outcomes of Supplemental Automated Breast US in Asian Women with Dense and Nondense Breasts.

Background Automated breast (AB) US effectively depicts mammographically occult breast cancers in Western women. However, few studies have focused on the outcome of supplemental AB US in Asian women who have denser breasts than Western women. Purpose To evaluate the performance of supplemental AB US on mammography-based breast cancer screening in Asian women with dense breasts and those with nondense breasts.

Nonhuman Primates Are Protected against Marburg Virus Disease by Vaccination with a Vesicular Stomatitis Virus Vector-Based Vaccine Prepared under Conditions to Allow Advancement to Human Clinical Trials.

Vaccines are needed to disrupt or prevent continued outbreaks of filoviruses in humans across Western and Central Africa, including outbreaks of Marburg virus (MARV). As part of a filovirus vaccine product development plan, it is important to investigate dose response early in preclinical development to identify the dose range that may be optimal for safety, immunogenicity, and efficacy, and perhaps demonstrate that using lower doses is feasible, which will improve product access. To determine the efficacious dose range for a manufacturing-ready live recombinant vesicular stomatitis virus vaccine vector (rVSV∆G-MARV-GP) encoding the MARV glycoprotein (GP), a dose-range study was conducted in cynomolgus macaques.

Preclinical immunogenicity and efficacy of a candidate COVID-19 vaccine based on a vesicular stomatitis virus-SARS-CoV-2 chimera.

Background: To investigate a vaccine technology with potential to protect against coronavirus disease 2019 (COVID-19) and reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a single vaccine dose, we developed a SARS-CoV-2 candidate vaccine using the live vesicular stomatitis virus (VSV) chimeric virus approach previously used to develop a licensed Ebola virus vaccine.

Methods: We generated a replication-competent chimeric VSV-SARS-CoV-2 vaccine candidate by replacing the VSV glycoprotein (G) gene with coding sequence for the SARS-CoV-2 Spike glycoprotein (S). Immunogenicity of the lead vaccine candidate (VSV∆G-SARS-CoV-2) was evaluated in cotton rats and golden Syrian hamsters, and protection from SARS-CoV-2 infection also was assessed in hamsters.

Diagnostic Performance of Five Adult-based US Risk Stratification Systems in Pediatric Thyroid Nodules.

Background The validation of adult-based US risk stratification systems (RSSs) in the discrimination of malignant thyroid nodules in a pediatric population remains lacking. Purpose To estimate and compare the diagnostic performance of pediatric US RSSs based on five adult-based RSSs in the discrimination of malignant thyroid nodules in a pediatric sample. Materials and methods Pediatric patients (age ≤18 years) with histopathologically confirmed US-detected thyroid nodules at a tertiary referral hospital between January 2000 and April 2020 were analyzed retrospectively.

Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with Zr Radioisotope in Mice and Rats.

For the successful clinical advancement of exosome therapeutics, the biodistribution and pharmacokinetic profile of exogenous exosomes in various animal models must be determined. Compared with fluorescence or bioluminescence imaging, radionuclide imaging confers multiple advantages for the in vivo tracking of biomolecular therapeutics because of its excellent sensitivity for deep tissue imaging and potential for quantitative measurement. Herein, we assessed the quantitative biodistribution and pharmacokinetics of good manufacturing practice-grade therapeutic exosomes labeled with zirconium-89 (Zr) after systemic intravenous administration in mice and rats.

Effects of Blood Pressure According to Age on End-Stage Renal Disease Development in Patients With Diabetes: A Nationwide Population-Based Cohort Study.

Background: Recent hypertension guidelines have recommended lower blood pressure (BP) targets in high-risk patients. However, there are no specific guidelines based on age or systolic and diastolic blood pressure (SBP and DBP, respectively). We aimed to assess the effects of age-related BP on development of end-stage renal disease (ESRD) in patients with diabetes.

Cardiovascular Implications of Immune Disorders in Women.

Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including HIV and hepatitis C virus. Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female predominant), HIV (male-female equivalent), and hepatitis C virus (male predominant).

A prognostic and predictive computational pathology image signature for added benefit of adjuvant chemotherapy in early stage non-small-cell lung cancer.

Background: We developed and validated a prognostic and predictive computational pathology risk score (CoRiS) using H&E stained tissue images from patients with early-stage non-small cell lung cancer (ES-NSCLC).

Methods: 1330 patients with ES-NSCLC were acquired from 3 independent sources and divided into four cohorts D. D comprised 100 surgery treated patients and was used to identify prognostic features via an elastic-net Cox model to predict overall and disease-free survival.