Courtly Connections: Anthony Sherley’s \u3ci\u3eRelation of his travels\u3c/i\u3e (1613) in a Global Context

This article revisits Anthony Sherley’s Relation of his travels into Persia (1613), reading the text within the larger context of early modern Eurasia. It highlights the ways in which at least one European traveler sought and found not alterity, but commensurable structures, social roles, political ideologies, and personal motivations in the Islamic polities to the east and emphasized these connections to his European readers. Furthermore, in making the case that Sherley’s narrative is informed by local actors in Safavid Persia, it maintains that a certain level of Eastern knowledge is present within Western texts from this period and awaits scholarly excavation

Finite element error analysis of a mantle convection model

A mantle convection model consisting of the stationary Stokes equations and a time-dependent convection-diffusion equation for the temperature is studied. The Stokes problem is discretized with a conforming inf-sup stable pair of finite element spaces and the temperature equation is stabilized with the SUPG method. Finite element error estimates are derived which show the dependency of the error of the solution of one problem on the error of the solution of the other equation. The dependency of the error bounds on the coefficients of the problem is monitored

Strategi Pembelajaran Anak Usia Dini Berbasis Inovasi Kreatif di Masa Pembiasaan Baru

Strategi Pembelajaran Anak Usia Dini  Berbasis Inovasi Kreatif  Di Masa Pembiasaan Baru. Kreativitas penting diberikan pada lebih awal. Oleh karena itu diperlukan bimbingan untuk mengembangkan kreativitas seseorang. Pada masa pandemi COVID-19 ini para guru senantiasa harus kreatif dalam menciptakan desain pengajaran yang kreatif. Pembelajaran kreatif akan membuat siswa aktif dalam mengembangkan kreativitas mereka sendiri. Mengembangkan kreativitas dapat dilakukan dengan menggunakan berbagai cara untuk membangun iklim belajar yang memicu berkembangnya kemampuan berpikir dan bekerja. Strategi yang bisa ditempuh untuk mengembangkan kreativitas seseorang adalah dengan mengajukan beberapa pertanyaan yang menantang tingkat proses berpikir tertinggi sesuai dengan konsep pengembangan ide kreatif, juga kreatif dan inovatif. Pertanyaan yang diberikan dikategorikan berdasarkan peta profil kreativitas seseorang (yaitu) profil individu imajinatif, investasi, improver, dan gagasan inkubasi

Electronic vapor product use and suicidal behavior in adolescents

Objective: To determine whether an association exists between electronic vapor product use (EVP) and suicidal behavior in middle and high school students Methods: Multilevel logistic regression analysis for suicidal behaviors using data from the 2017 Vermont Youth Risk Behavior Survey. Results: Middle school EVP users were significantly more likely to report suicidal behavior than non-users. No statistically significant association was found in high school students. Discussion: While further study is necessary to clarify the relationship between EVP use and suicidal behavior, these findings highlight the need for suicide prevention and smoking cessation efforts

Effect of the 3q26-coding oncogene SEC62 as a potential prognostic marker in patients with ovarian neoplasia

With approximately 220,000 newly diagnosed cases per year, ovarian cancer is among the most frequently occurring cancers among women and the second leading cause of death from gynecological malignancies worldwide. About 70% of these cancers are diagnosed in advanced stages (FIGO IIB–IV), with a 5-year survival rate of 20–30%. Due to the poor prognosis of this disease, research has focused on its pathogenesis and the identification of prognostic factors. One possible approach for the identification of biological markers is the identification of tumor entity-specific genetic “driver mutations”. One such mutation is 3q26 amplification in the tumor driver SEC62, which has been identified as relevant to the pathogenesis of ovarian cancer. This study was conducted to investigate the role of SEC62 in ovarian malignancies. Patients with ovarian neoplasias (borderline tumors of the ovary and ovarian cancer) who were treated between January 2007 and April 2019 at the Department of Gynecology and Obstetrics, Saarland University Hospital, were included in this retrospective study. SEC62 expression in tumor tissue samples taken during clinical treatment was assessed immunohistochemically, with the calculation of immunoreactivity scores according to Remmele and Stegner, Pathologe, 1987, 8, 138–140. Correlations of SEC62 expression with the TNM stage, histological subtype, tumor entity, and oncological outcomes (progression-free and overall survival) were examined. The sample comprised 167 patients (123 with ovarian cancer and 44 with borderline tumors of the ovary) with a median age of 60 (range, 15–87) years. At the time of diagnosis, 77 (46%) cases were FIGO stage III. All tissue slides showed SEC62 overexpression in tumor cells and no SEC62 expression in other cells. Median immunoreactivity scores were 8 (range, 2–12) for ovarian cancer and 9 (range, 4–12) for borderline tumors of the ovary. Patients with borderline tumors of the ovary as well as patients with ovarian cancer and an immunoreactive score (IRS) ≤ 9 showed an improved overall survival compared to those presenting with an IRS score >9 (p = 0.03). SEC62 seems to be a prognostic biomarker for the overall survival of patients with ovarian malignancies

ASO Author Reflections: An Alternative to Sentinel-Node Biopsy? Preoperative Sonographic Prediction of Limited Axillary Disease in Breast Cancer Patients Meeting the Z0011 Criteria

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Preoperative Sonographic Prediction of Limited Axillary Disease in Patients with Primary Breast Cancer Meeting the Z0011 Criteria: an Alternative to Sentinel Node Biopsy?

Purpose To assess the accuracy of preoperative sonographic staging for prediction of limited axillary disease (LAD, one or two metastatic lymph nodes) and to identify factors associated with high prediction–pathology concordance in patients with early-stage breast cancer meeting the Z0011 criteria. Materials and Methods Patients treated between January 2015 and January 2020 were included in this retrospective, multicentric analysis of prospectively acquired service databases. The accuracy of LAD prediction was assessed separately for patients with one and two suspicious lymph nodes on preoperative sonography. Test validity outcomes for LAD prediction were calculated for both groups, and a multivariate model was used to identify factors associated with high accuracy of LAD prediction. Results Of 2059 enrolled patients, 1513 underwent sentinel node biopsy, 436 primary and 110 secondary axillary dissection. For LAD prediction in patients with one suspicious lymph node on preoperative ultrasound, sensitivity was 92% (95% CI 87–95%), negative predictive value (NPV) was 92% (95% CI 87–95%), and the false-negative rate (FNR) was 8% (95% CI 5–13%). For patients with two preoperatively suspicious nodes, the sensitivity, NPV, and FNR were 89% (95% CI 84–93%), 73% (62–83%), and 11% (95% CI 7–16%), respectively. On multivariate analysis, the number of suspicious lymph nodes was associated inversely with correct LAD prediction ([OR 0.01 (95% CI 0.01–0.93), p ≤ 0.01]. Conclusions Sonographic axillary staging in patients with one metastatic lymph node predicted by preoperative ultrasound showed high accuracy and a false-negative rate comparable to sentinel node biopsy for prediction of limited axillary disease

Inflammation modulates intercellular adhesion and mechanotransduction in human epidermis via ROCK2

Aberrant mechanotransduction and compromised epithelial barrier function are associated with numerous human pathologies including inflammatory skin disorders. However, the cytoskeletal mechanisms regulating inflammatory responses in the epidermis are not well understood. Here we addressed this question by inducing a psoriatic phenotype in human keratinocytes and reconstructed human epidermis using a cytokine stimulation model. We show that the inflammation upregulates the Rho-myosin II pathway and destabilizes adherens junctions (AJs) promoting YAP nuclear entry. The integrity of cell-cell adhesion but not the myosin II contractilityper seis the determinative factor for the YAP regulation in epidermal keratinocytes. The inflammation-induced disruption of AJs, increased paracellular permeability, and YAP nuclear translocation are regulated by ROCK2, independently from myosin II activation. Using a specific inhibitor KD025, we show that ROCK2 executes its effects via cytoskeletal and transcription-dependent mechanisms to shape the inflammatory response in the epidermis

Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension

Genome-wide association studies of blood pressure (BP) have identified >1,000 loci, but the effector genes and biological pathways at these loci are mostly unknown. Using published association summary statistics, we conducted annotation-informed fine-mapping incorporating tissue-specific chromatin segmentation and colocalization to identify causal variants and candidate effector genes for systolic BP, diastolic BP, and pulse pressure. We observed 532 distinct signals associated with ≥2 BP traits and 84 with all three. For >20% of signals, a single variant accounted for >75% posterior probability, 65 were missense variants in known (SLC39A8, ADRB2, and DBH) and previously unreported BP candidate genes (NRIP1 and MMP14). In disease-relevant tissues, we colocalized >80 and >400 distinct signals for each BP trait with cis-eQTLs and regulatory regions from promoter capture Hi-C, respectively. Integrating mouse, human disorder, gene expression and tissue abundance data, and literature review, we provide consolidated evidence for 436 BP candidate genes for future functional validation and discover several potential drug targets

Laparoscopic Fertility-Sparing Surgery for Early Ovarian Malignancies

The demand for fertility-sparing surgery (FSS) has increased in the last decade due to increased maternal age, increased incidence of ovarian malignancies in younger patients, and technical advances in surgery. Data on oncological safety and fertility outcomes of patients with ovarian cancer after laparoscopic FSS are sparse, but some retrospective studies have shown that open FSS may be offered to selected patients. We assessed the role of minimally invasive FSS in comparison with radical surgery (RS) in terms of oncological safety and reproductive outcomes after FSS in this multicenter study. Eighty patients with FIGO stage I/II ovarian cancer treated with laparoscopic FSS or RS between 01/2000 and 10/2018 at the participating centers (comprehensive gynecological cancer centers with minimally invasive surgical expertise) were included in this retrospective analysis of prospectively kept data. Case–control (n = 40 each) matching according to the FIGO stage was performed. Progression-free survival [150 (3–150) and 150 (5–150) months; p = 0.61] and overall survival [36 (3–150) and 50 (1–275) months; p = 0.65] did not differ between the FSS and RS groups. Eight (25.8%) women became pregnant after FSS, resulting in seven (22.5%) deliveries; three (37.5%) patients conceived after in vitro fertilization, and five (62.5%) conceived spontaneously. Laparoscopic FSS seems to be applicable and oncologically safe for patients with early-stage ovarian cancer, with adequate fertility outcomes