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  • Saunders Yates posted an update 5 days, 3 hours ago

    Tumor microenvironment and chemokines play a significant role in cancer chemoresistance. This study was designed to reveal the important role of CXCL2 in platinum resistance in epithelial ovarian cancer (EOC). Differently expressed (DE) genes were screen out based on analysis of GSE114206 dataset in GEO database. The expression of DE chemokines was further validated in platinum- resistant and sensitive EOC. Cell viability assay and cell apoptosis assay were performed to explore the roles of CXCL2 in EOC. Cell stemness characteristics and the signaling pathway regulated by CXCL2 were also investigated in this study. As the results showed, CXCL2 was identified up-regulated in platinum-resistant EOC. The functional assays showed overexpressing CXCL2 or co-culturing with recombinant human CXCL2 promoted cell resistance to cisplatin. Conversely, knocking down CXCL2 or co-culturing with neutralizing antibody to CXCL2 increased cell response to cisplatin. CXCL2 overexpressing maintained cell stemness and activated ATR/CHK1 signaling pathway in EOC. Moreover, we further demonstrated that CXCL2-mediated resistance to cisplatin could be saved by SB225002, the inhibitor of CXCL2 receptor, as well as be rescued by SAR-020106, the inhibitor of ATR/CHK1 signaling pathway. This study identified a CXCL2-mediated mechanism in EOC platinum resistance. Our findings provided a novel target for chemoresistance prevention in EOC.

    Ajzen’s theory of planned behavior (TPB) postulates that individuals’ behavioral intention is influenced by their attitudes, subjective norms, and perceived behavioral control. Therefore, it can be used to broaden the understanding of particular behaviors, including healthcare workers’ professional activities.

    In this study, we used TPB as a theoretical framework to evaluate semi-structured interviews with pharmacists and physicians to build an understanding of the interprofessional collaboration between them. Sixteen semi-structured interviews were conducted with pharmacists and eleven with physicians. The sample of participants comprised a diverse group with varying work experience and workplaces. Data were analyzed independently by two researchers following the thematic analysis method using ATLAS.ti software. Data saturation was set in the absence of new issues arising during the interviews.

    The content analysis allowed for the determination of six main themes the relationship between previous experimpede the process.

    Combination drug therapy for lower urinary tract symptoms (LUTS) is beneficial to selected patients and recommended by guidelines. Patterns of real-world LUTS drug use, especially combination drug therapy, have not been studied extensively. Moreover, further understanding of the recent landscape is required following the introduction of the beta-3-adrenoceptor agonist mirabegron in the UK in 2013 for overactive bladder (OAB). The objective was to describe mono- and combination drug therapy use for LUTS in patients in UK clinical practice.

    This was a retrospective, descriptive, observational database study using UK Clinical Practice Research Datalink GOLD and linked databases. Men and women ≥ 18years with a first prescription for any LUTS drug from 2014 to 2016 with ≥ 12months continuous enrollment pre- and post-index date were included. Apoptosis inhibitor Primary endpoints were mono- or combination drug therapy use for LUTS in male and female cohorts. Secondary endpoints were description of treatment prescribed, treatment puse in UK clinical practice. It highlights potential undertreatment of storage symptoms in men with LUTS and the low use of combination OAB treatments.

    This study provides a better understanding of the recent landscape of LUTS drug use in UK clinical practice. It highlights potential undertreatment of storage symptoms in men with LUTS and the low use of combination OAB treatments.

    Definitions of postoperative hypoparathyroidism (hypoPT) have never reached consent until the American Thyroid Association (ATA) statement was released, with new characteristics and challenges.

    Patients with papillary thyroid carcinoma who underwent primary total thyroidectomy between January 2013 and June 2018 were retrospectively enrolled. Symptoms of hypocalcemia and their frequency were stringently followed. Patients were divided into groups according to the ATA statement. Incidence of postoperative hypoPT and serum parathyroid hormone levels accompanied by calcium levels, from 1-day to at least 24-month follow-up.

    A total of 1749 patients were included 458 (26.2%) had transient and 63 (3.6%) had permanent hypoPT. Transient hypoPT was found in 363 (20.7%) patients with biochemical hypoPT, 72 (4.1%) with clinical hypoPT, and 23 (1.3%) with relative hypoPT; permanent hypoPT was detected in 8 (0.5%) patients with biochemical hypoPT, 55 (3.1%) with clinical hypoPT, and none with relative hypoPT. Female ence.

    Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival.

    PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC).

    Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by “MD Anderson Cancer Center Residual Cancer Burden Index” (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFlly advanced disease.

    Academic medical centers invest considerably in faculty development efforts to support the career success and promotion of their faculty, and to minimize faculty attrition. This study evaluated the impact of a faculty development program called the Leadership in Academic Medicine Program (LAMP) on participants’ (1) self-ratings of efficacy, (2) promotion in academic rank, and (3) institutional retention.

    Participants from the 2013-2020 LAMP cohorts were surveyed pre and post program to assess their level of agreement with statements that spanned domains of self-awareness, self-efficacy, satisfaction with work and work environment. Pre and post responses were compared using McNemar’s tests. Changes in scores across gender were compared using Wilcoxon Rank Sum/Mann-Whitney tests. LAMP participants were matched to nonparticipant controls by gender, rank, department, and time of hire to compare promotions in academic rank and departures from the organization. Kaplan Meier curves and Cox proportional hazards mods. LAMP faculty were 77% less likely to leave compared to controls (HR 0.23, 95% CI 0.16-0.34, p < 0.0001).

    LAMP is an effective faculty development program as measured subjectively by participant self-ratings and objectively through comparative improvements in academic promotions and institutional retention.

    LAMP is an effective faculty development program as measured subjectively by participant self-ratings and objectively through comparative improvements in academic promotions and institutional retention.

    It is a challenging problem to differentiate obstructive hydronephrosis from noninvasive evaluation of renal pelvis and ureteral motility in patients. The purpose of this study was to explore the value of 640-slice dynamic volume CT (DVCT) in the quantitative measurement of upper urinary tract (UUT) pump function after acute unilateral lower ureteral obstruction in pigs.

    In this study, a perfusion pig model was constructed by constant pressure perfusion testing of the renal pelvis and left nephrostomy. The perfusion and pressure measuring devices were connected to create a state of no obstruction and acute obstruction of the lower part of the left ureter. After successful modelling, continuous dynamic volume scanning of the bilateral renal excretion phase was performed with 640-slice DVCT, and pump functions of the renal pelvis and part of the upper ureter were calculated and analysed. No obstruction or acute obstruction of the lower part of the left ureter was observed. Pump functions of the renal pelvis and part of the upper ureter were determined.

    The results showed that after LUUT fistulostomy, the time difference between the average UUT volume and positive volume value increased gradually, and the calculated flow velocity decreased, which was significantly different from that of the RUUT. The volume difference of the LUUT increased significantly in mild obstruction. In the bilateral control, the volume change rate of the LUUT increased with mild obstruction and decreased with severe obstruction, and there was a significant difference between the left and right sides.

    The continuous dynamic volume scan and measurement of 640-slice DVCT can obtain five pump function datasets of UUT in pigs with acute lower ureteral obstruction.

    The continuous dynamic volume scan and measurement of 640-slice DVCT can obtain five pump function datasets of UUT in pigs with acute lower ureteral obstruction.

    Current methods for cervical cancer screening result in an increased number of referrals and unnecessary diagnostic procedures. This study aimed to develop and evaluate a more accurate model for cervical cancer screening.

    Multiple predictors including age, cytology, high-risk human papillomavirus (hrHPV) DNA/mRNA, E6 oncoprotein, HPV genotyping, and p16/Ki-67 were used for model construction in a cross-sectional population including women with normal cervix (N = 1085), cervical intraepithelial neoplasia (CIN, N = 279), and cervical cancer (N = 551) to predict CIN2+ or CIN3+. A base model using age, cytology, and hrHPV was calculated, and extended versions with additional biomarkers were considered. External validations in two screening cohorts with 3-year follow-up were further conducted (N

    = 3179, N

    = 3082).

    The base model increased the area under the curve (AUC, 0.91, 95% confidence interval [CI] = 0.88-0.93) and reduced colposcopy referral rates (42.76%, 95% CI = 38.67-46.92) compared to hrHPV and cytology co-testing in the cross-sectional population (AUC 0.80, 95% CI = 0.79-0.82, referrals rates 61.62, 95% CI = 59.4-63.8) to predict CIN2+. The AUC further improved when HPV genotyping and/or E6 oncoprotein were included in the base model. External validation in two screening cohorts further demonstrated that our models had better clinical performances than routine screening methods, yielded AUCs of 0.92 (95% CI = 0.91-0.93) and 0.94 (95% CI = 0.91-0.97) to predict CIN2+ and referrals rates of 17.55% (95% CI = 16.24-18.92) and 7.40% (95% CI = 6.50-8.38) in screening cohort I and II, respectively. Similar results were observed for CIN3+ prediction.

    Compared to routine screening methods, our model using current cervical screening indicators can improve the clinical performance and reduce referral rates.

    Compared to routine screening methods, our model using current cervical screening indicators can improve the clinical performance and reduce referral rates.