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We reported a female presented with an initial diagnosis of metastatic axillary lymph‐node carcinoma that comprehensive assessments revealed a definitive diagnosis of high‐grade serous ovarian carcinoma as the primary tumor.  相似文献   
994.
RAS mutations prevalent in high-risk leukemia have been linked to relapse and chemotherapy resistance. Efforts to directly target RAS proteins have been largely unsuccessful. However, since RAS-mediated transformation is dependent on signaling through the RAS-related C3 botulinum toxin substrate (RAC) small GTPase, we hypothesized that targeting RAC may be an effective therapeutic approach in RAS mutated tumors. Here we describe multiple small molecules capable of inhibiting RAC activation in acute lymphoblastic leukemia cell lines. One of these, DW0254, also demonstrates promising anti-leukemic activity in RAS-mutated cells. Using chemical proteomics and biophysical methods, we identified the hydrophobic pocket of phosphodiester 6 subunit delta (PDE6D), a known RAS chaperone, as a target for this compound. Inhibition of RAS localization to the plasma membrane upon DW0254 treatment is associated with RAC inhibition through a phosphatidylinositol-3-kinase/AKT-dependent mechanism. Our findings provide new insights into the importance of PDE6D-mediated transport for RAS-dependent RAC activation and leukemic cell survival.Subject terms: Acute lymphocytic leukaemia, Acute myeloid leukaemia, Drug development, Targeted therapies  相似文献   
995.
INTRODUCTION AND OBJECTIVE: Treatment of acute myocardial infarction by percutaneous coronary intervention with stenting leads to excellent immediate clinical results and a good prognosis. The aim of this study was to compare in this selected population the safety and effectiveness of radial artery access versus femoral artery access. PATIENTS AND METHOD: Between May 2001 and June 2003, 162 consecutive patients with acute myocardial infarction < 12 hours treated by percutaneous stenting were included in an observational study. The radial artery approach was used in 103 patients, and the femoral artery approach in the remaining 59 patients. The success of the procedure, incidence of major adverse cardiac events and local puncture complications were compared in patients treated with the radial artery versus the femoral artery approach. RESULTS: Fluoroscopy time (22.4 [15.4] min vs 24.5 [19.5] min), immediate success of the procedure (96.1% vs 94.9%), and the incidence of major adverse cardiac events (6.8% vs 8.5%) did not differ between the two groups. Bleeding complications due to local puncture were present only in the femoral artery access group (0 vs 5 patients; P= .007). CONCLUSIONS: In selected patients with acute myocardial infarction treated with primary stent implantation, the success rate and clinical safety of the radial artery approach are similar to those of the femoral artery approach, but the incidence of local complications, especially bleeding, is significantly lower in the former. Thus the radial artery approach should become the approach of choice in patients at high risk for bleeding complications.  相似文献   
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BACKGROUND: Preterm premature rupture of membranes (pPROM) complicates up to one-third of preterm deliveries. We studied the Amniotic Fluid Index (AFI) in order to ascertain its validity as a predictive variable of maternal-fetal outcome in pregnancies complicated by pPROM. STUDY DESIGN: One hundred and fourteen pregnant women with gestational age between 24 and 34 weeks' gestation at the time of pPROM. Patients were categorized into two groups on the basis of AFI value (AFI <5 cm=63 or AFI >or=5 cm=51) performed at the time of admission. RESULTS: AFI numeric values were significantly related to the following maternal-neonatal variables: high maternal body temperature (P7 at 5 min (P相似文献   
997.
OBJECTIVE: To assess whether supracervical hysterectomy (SCH) is a reasonable alternative to total abdominal hysterectomy in patients with advanced ovarian cancer. METHODS: We reviewed the records of patients with advanced ovarian cancer who underwent a SCH at one institution between 1993 and 2004 and a similar cohort who underwent total abdominal hysterectomy (TAH) at the same institution during the same period. Patients without complete surgical staging done at the institution were excluded. Independent-sample t tests, Fisher exact test, and log rank tests were used for statistical analysis. RESULTS: The study included 47 patients who underwent SCH (mean age, 59.6 years) and 190 who underwent TAH. There were no significant differences between the two groups in age (P=.51), preoperative CA 125 level (P=.55), or receipt of taxane-based and platinum-based chemotherapy (P=.84). Although limited by sample size, there were no significant differences between the two groups in rates of intraoperative complications (4 of 47 in the SCH group, or 8.5%, compared with 7 of 190 in the TAH group, or 3.7%; P=.24), vaginal or cervical recurrence (5 of 47 in the SCH group, or 10.6%, compared with 22 of 190 in the TAH group, or 11.6%; P=1.00), or in progression-free survival (SCH of 1.01 years compared with TAH of 1.19 years; P=.64) or overall survival (SCH of 3.28 years compared with TAH of 3.36 years; P=.12). CONCLUSION: Supracervical hysterectomy may be a reasonable alternative to TAH in patients with advanced ovarian cancer. LEVEL OF EVIDENCE: II.  相似文献   
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Background: The Pediatrics Milestones Assessment Pilot employed a new multisource feedback (MSF) instrument to assess nine Pediatrics Milestones among interns and subinterns in the inpatient context.

Objective: To report validity evidence for the MSF tool for informing milestone classification decisions.

Methods: We obtained MSF instruments by different raters per learner per rotation. We present evidence for validity based on the unified validity framework.

Results: One hundred and ninety two interns and 41 subinterns at 18 Pediatrics residency programs received a total of 1084 MSF forms from faculty (40%), senior residents (34%), nurses (22%), and other staff (4%). Variance in ratings was associated primarily with rater (32%) and learner (22%). The milestone factor structure fit data better than simpler structures. In domains except professionalism, ratings by nurses were significantly lower than those by faculty and ratings by other staff were significantly higher. Ratings were higher when the rater observed the learner for longer periods and had a positive global opinion of the learner. Ratings of interns and subinterns did not differ, except for ratings by senior residents. MSF-based scales correlated with summative milestone scores.

Conclusion: We obtain moderately reliable MSF ratings of interns and subinterns in the inpatient context to inform some milestone assignments.  相似文献   
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