Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Small-Animal PET Outcome Measures to Detect Disease Modification Induced by BACE Inhibition in a Transgenic Mouse Model of Alzheimer Disease

In this study, we investigated the effects of chronic administration of an inhibitor of the β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) on Alzheimer-related pathology by multitracer PET imaging in transgenic APPPS1-21 (TG) mice. Methods: Wild-type (WT) and TG mice received vehicle or BACE inhibitor (60 mg/kg) starting at 7 wk of age. Outcome measures of brain metabolism, neuroinflammation, and amyloid-β pathology were obtained through small-animal PET imaging with 18F-FDG, 18F-peripheral benzodiazepine receptor (18F-PBR), and 18F-florbetapir (18F-AV45), respectively. Baseline scans were acquired at 6–7 wk of age and follow-up scans at 4, 7, and 12 mo. 18F-AV45 uptake was measured at 8 and 13 mo of age. After the final scans, histologic measures of amyloid-β (4G8), microglia (ionized calcium binding adaptor molecule 1), astrocytes (glial fibrillary acidic protein), and neuronal nuclei were performed. Results: TG mice demonstrated significant age-associated increases in 18F-AV45 uptake. An effect of treatment was observed in the cortex (P = 0.0014), hippocampus (P = 0.0005), and thalamus (P < 0.0001). Histology confirmed reduction of amyloid-β pathology in TG-BACE mice. Regardless of treatment, TG mice demonstrated significantly lower 18F-FDG uptake than WT mice in the thalamus (P = 0.0004) and hippocampus (P = 0.0332). Neuronal nucleus staining was lower in both TG groups in the thalamus and cortex. 18F-PBR111 detected a significant age-related increase in TG mice (P < 0.0001) but did not detect the treatment-induced reduction in activated microglia as demonstrated by histology. Conclusion: Although 18F-FDG, 18F-PBR111, and 18F-AV45 all detected pathologic alterations between TG and WT mice, only 18F-AV45 could detect an effect of BACE inhibitor treatment. However, changes in WT binding of 18F-AV45 undermine the specificity of this effect.
Identification of an aggressive prostate cancer predisposing variant at 11q13

Prostate cancer is the most frequently diagnosed cancer in men; however, the genetic basis of susceptibility remains elusive. The EMSY gene is located in the prostate cancer linked chromosome region at 11q13.5. The aim of this study was to screen EMSY for sequence variants and to evaluate its association with the risk of prostate cancer. We performed a Finnish population‐based case–control study with 923 controls, 184 familial prostate cancer cases and 2,301 unselected prostate cancer cases. Variants were screened using sequencing and validated using the TaqMan assay and High Resolution Melting analysis. A total of 27 sequence variants were found, and 17 of them were novel. A rare intronic variant, IVS6‐43A>G (minor allele frequency of 0.004), increased the prostate cancer risk in familial cases (odds ratio [OR] = 7.5; 95% confidence interval [CI] = 1.3–45.5; p = 0.02). Further analysis with clinicopathological data revealed that the variant is associated with aggressive unselected cases (prostate specific antigen ≥ 20 μg/L or Gleason grade ≥ 7), based on both case–control (OR = 6.0; 95% CI = 1.3–26.4; p = 0.03) and case–case analyses (OR = 6.5; 95% CI = 1.5–28.4; p = 0.002). In addition, all variant‐positive familial cases had aggressive cancer. Our results indicate that the intronic variant IVS6‐43A>G increases the familial and unselected prostate cancer risk in a Finnish population and contributes to the aggressive progression of the disease in a high‐penetrance manner. The potential role of the variant as a predictive genetic marker for aggressive prostate cancer should be further evaluated.
Animation Shows Promise in Initiating Timely Cardiopulmonary Resuscitation: Results of a Pilot Study

Delayed responses during cardiac arrest are common. Timely interventions during cardiac arrest have a direct impact on patient survival. Integration of technology in nursing education is crucial to enhance teaching effectiveness. The goal of this study was to investigate the effect of animation on nursing students’ response time to cardiac arrest, including initiation of timely chest compression. Nursing students were randomized into experimental and control groups prior to practicing in a high-fidelity simulation laboratory. The experimental group was educated, by discussion and animation, about the importance of starting cardiopulmonary resuscitation upon recognizing an unresponsive patient. Afterward, a discussion session allowed students in the experimental group to gain more in-depth knowledge about the most recent changes in the cardiac resuscitation guidelines from the American Heart Association. A linear mixed model was run to investigate differences in time of response between the experimental and control groups while controlling for differences in those with additional degrees, prior code experience, and basic life support certification. The experimental group had a faster response time compared with the control group and initiated timely cardiopulmonary resuscitation upon recognition of deteriorating conditions (P < .0001). The results demonstrated the efficacy of combined teaching modalities for timely cardiopulmonary resuscitation. Providing opportunities for repetitious practice when a patient’s condition is deteriorating is crucial for teaching safe practice.
Are metabolic syndrome and its components in obese children influenced by the overweight status or the insulin resistance?

INTRODUCTION The aim of this study was to determine which factors increase the risk of metabolic syndrome (MS) and its components in obese children and adolescents. MATERIAL AND METHODS In 78 obese children (42 girls, 36 boys), mean age 14.6 ± 3.5 years, blood pressure, total cholesterol, triglycerides, HDL-cholesterol (HDL), insulin and glucose at fasting state as well as in OGTT were measured. Body mass index (BMI) Z-score, LDLcholesterol, and insulin resistance indices (FIGR, R-HOMA) were calculated. RESULTS Metabolic syndrome was diagnosed in ten (12.8%) children. Hyperinsulinaemia was present in 42 (53.8%) subjects, increased FIGR in eight (10.3%) and increased R-HOMA in 49 (62.3%). Significant correlations between BMI Z-score ≥ 2.5 and MS occurrence and its components (hypertriglyceridaemia, isolated systolic and diastolic hypertension) were found. Hypertriglyceridaemia, low HDL and hypertension, as well as MS occurrence, correlated significantly with stimulated hyperinsulinaemia and increased FIGR. Risk of hypertension was increased 5.6 times by fasting hyperinsulinaemia. Stimulated hyperinsulinaemia increased the risk of hypertriglyceridaemia 3.7 times, risk of low HDL 14.4 times and risk of MS 10.3 times. These risks did not change significantly when adjusted for BMI Z-score. CONCLUSIONS Our study results show that both BMI Z-score and OGTT stimulated hyperinsulinaemia are good predictors of MS occurrence in obese children and adolescents. The risk of dyslipidaemia and hypertension increase significantly with hyperinsulinaemia and insulin resistance, with low HDL cholesterol being the most affected.
Transmission electron microscopy of yeast

The challenges of sample preparation can limit a researcher's selection of transmission electron microcopy (TEM) for analysis of yeast. However, with the exception of thin sectioning, preparation of well‐fixed and infiltrated samples of yeast cells is achievable by any reasonably equipped laboratory. This review presents a general overview of TEM sample preparation methods and detailed protocols for chemical fixation of yeast for ultrastructural analysis and immunolabeling. For ultrastructural analysis, the most commonly used chemical fixation involves treatment with glutaraldehyde followed by either potassium permanganate or osmium. Prior to osmium postfixation, the cell wall must be enzymatically digested to allow optimal fixation and embedding. Freeze substitution methods continue to provide the highest quality of fixation, but equipment needed for these protocols is not generally available to many labs. The low viscosity of Spurr's resin makes it the resin of choice for ultrastructure studies. Immunoelectron microscopy has enjoyed great success in analysis of yeast molecular organization. For immunoelectron microscopy, glutaraldehyde/formaldehyde‐fixed cells are embedded in LR White resin. The thin sections are then treated in much the same way as an immunoblot: following blocking, they are incubated in primary antiserum, washed, and then incubated in gold‐labeled secondary antiserum. Microsc. Res. Tech. 51:496–510, 2000. © 2000 Wiley‐Liss, Inc.
Sunitinib Treatment for Patients with Advanced Clear-Cell Renal-Cell Carcinoma after Progression on Sorafenib

Background: Sorafenib and sunitinib are tyrosine kinase inhibitors with largely overlapping specificities, approved for the treatment of metastatic renal-cell carcinoma (RCC). It was unclear whether the similarities of the two drugs would lead to complete cross-resistance, or whether sequential application would be efficacious. Methods: Patients with metastatic RCC and progression on sorafenib treatment were treated with repeated cycles of sunitinib, 50 mg for 4 weeks, followed by a 2-week break. Response (Response Evaluation Criteria in Solid Tumors, RECIST) was assessed every second cycle. Results: A total of 22 patients with progression on sorafenib were accrued. Initially, sorafenib treatment was efficacious in all patients, with 7 showing partial response (PR) and 15 stable disease (SD), and subsequent disease progression. With 4 PRs (18%) and 12 SD (55%) a disease control rate of 73% was achieved. The median progression-free survival (PFS) on sunitinib was 21.5 weeks; median overall survival (OS) was not reached. Estimated 1-year PFS and OS were 31 and 60%, respectively. There was no apparent relationship between response to sorafenib and outcome on sunitinib. Conclusion: In our cohort of patients with RCC and progression after initial efficacy of sorafenib, the efficacy data of second-line sunitinib were close to published results of first-line treatment, suggesting limited clinically relevant cross-resistance.
AVOIDANCE MODERATES THE ASSOCIATION BETWEEN MOTHERS’ AND CHILDREN'S FEARS: FINDINGS FROM A NOVEL MOTION‐TRACKING BEHAVIORAL ASSESSMENT

Fear and anxiety in children are associated with similar symptoms in parents. Parental modeling of fearful or avoidant behavior is believed to contribute to this association. We employed a novel motion‐tracking experimentation platform to test the hypothesis that mothers’ behavioral avoidance of spiders moderates the association between fear of spiders in mothers and children.
High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome

There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.
Combinational Build-Up Index (CBI) for Effective Impervious Surface Mapping in Urban Areas

The distribution of urban impervious surface is a significant indicator of the degree of urbanization, as well as a major indicator of environmental quality. Hence, taking advantage of remotely sensed imagery to map impervious surface has become an important topic. Spectral indices have been developed due to its convenience to apply, among which feature extraction approach has shown superiority in reliability and applicability. However, impervious surface is often confused with bare soil when the current existing indices are used as well as their sensor-specific limitations. In this study, a new index, combinational build-up index (CBI), is proposed to extract impervious surface. The new index combines the first component of a principal component analysis (PC1), normalized difference water index (NDWI), and soil-adjusted vegetation index (SAVI), representing high albedo, low albedo, and vegetation, respectively, to reduce the original bands into three thematic-oriented features. The new index was tested using various remote sensing images at different spectral and spatial resolutions. Qualitative and quantitative assessments of the accuracy and separability of CBI, together with the comparison with other existing indices, were performed. The result of this study indicates that the proposed method is able to serve as an effective impervious index and can be applied widely.
Delft University of Technology Design and comparison of a 10-kW interleaved boost converter for PV application using Si and SiC devices

Grid connected PV inverters have a DC/DC converter connected to the PV for executing the maximum power point tracking (MPPT). The design of an interleaved boost converter (IBC) with three switching legs for 10kW PV inverter is presented in this paper. The paper shows how the use of SiC switches and powdered iron core inductors enables the operation of the converter at a higher switching frequency and increasing the converter power density. The IBC is designed using 1.2kV SiC MOSFET and Schottky diodes and KoolMμ powdered iron inductors. The design is compared with an IBC built with Si IGBT, fast recovery Si diodes and ferrite cores. The use of SiC devices reduces the switching loses drastically and there is no reverse recovery losses, resulting in improved efficiency. The higher frequency and higher saturation flux density of the powdered iron core enables the reduction in core size by three times. A 10kW prototype is built and tested for both the Si and SiC design and compared with theoretical estimations.
Endovascular Repair Is Associated With Superior Clinical Outcomes in Patients Transferred for Treatment of Ruptured Abdominal Aortic Aneurysms

Purpose To compare in a population-based analysis the inhospital mortality and complications following endovascular aneurysm repair (EVAR) vs. open repair in patients transferred for the management of ruptured abdominal aortic aneurysm (RAAA). Methods Interrogation of the 2003–2007 Nationwide Inpatient Sample database identified 271 patients (205 men; mean age 71.7 years) who were transferred for RAAA treatment. Demographic, patient, and hospital characteristics were analyzed. Hierarchical multivariate logistic regression analyses were employed to identify predictors of inhospital mortality and complications; results are presented as the odds ratio (OR) and 95% confidence interval (CI). Results In comparison to open repair (n=207), endovascular repair (n = 64) was associated with lower in-hospital mortality (36% vs. <18%, p<0.01) and a lower complication rate (78% vs. 66%, p<0.05). Transferred RAAA patients undergoing EVAR had lower in-hospital mortality (OR 0.21, 95% CI 0.09 to 0.49, p<0.01) and fewer complications (OR 0.49, 95% CI 0.26 to 0.95, p<0.05) than transferred patients having open repair. Conclusion Compared to open repair, EVAR led to superior short-term clinical outcomes in transferred RAAA patients. In this clinical situation, transfer of stable RAAA patients to institutions capable of performing EVAR is recommended.
[Study on hepatitis C virus genotyping in some parts of China].

OBJECTIVE To study the genotypes of hepatitis C virus in some parts of China. METHODS Twenty-seven sera of plasma donors from Guan county of Hebei province, Zhoukou district of Henan province, and 36 patients with chronic hepatitis C from Beijing and Qingdao cities were tested for HCV RNA by Amplicor PCR kit. Thirty-six of 38 HCV RNA positive sera were further genotyped, using INNO-LiP A HCV II kit. RESULTS The HCV RNA positive rates of plasma donors and patients with chronic hepatitis C were 48.15% (13/27) and 69.44% (25/36) respectively. Genotyping data from 13 plasma donors and 23 patients with chronic hepatitis C showed that 29 (80.55%) were 1b, 5 (13.89%) were genotype 2, and 2 (5.56%) remained untyped. CONCLUSION 1b seemed to be the prevalent HCV genotype in some parts of China.
Sensor (Group Feature) Selection with Controlled Redundancy in a Connectionist Framework

For many applications, to reduce the processing time and the cost of decision making, we need to reduce the number of sensors, where each sensor produces a set of features. This sensor selection problem is a generalized feature selection problem. Here, we first present a sensor (group-feature) selection scheme based on Multi-Layered Perceptron Networks. This scheme sometimes selects redundant groups of features. So, we propose a selection scheme which can control the level of redundancy between the selected groups. The idea is general and can be used with any learning scheme. We have demonstrated the effectiveness of our scheme on several data sets. In this context, we define different measures of sensor dependency (dependency between groups of features). We have also presented an alternative learning scheme which is more effective than our old scheme. The proposed scheme is also adapted to radial basis function (RBS) network. The advantages of our scheme are threefold. It looks at all the groups together and hence can exploit nonlinear interaction between groups, if any. Our scheme can simultaneously select useful groups as well as learn the underlying system. The level of redundancy among groups can also be controlled.
Intracellular Infection by the Human Granulocytic Ehrlichiosis Agent Inhibits Human Neutrophil Apoptosis

ABSTRACT In patients with human granulocytic ehrlichiosis (HGE), the HGE agent has been seen only in the peripheral blood granulocytes, which have a life span too short for ehrlichial proliferation. To determine if the HGE agent delays the apoptosis of human peripheral blood neutrophils for its advantage, peripheral blood granulocytes consisting mostly of neutrophils were incubated with freshly freed host cell-free HGE agent in vitro. The HGE agent induced a significant delay in morphological apoptosis and the cytoplasmic appearance of histone-associated DNA fragments in the granulocytes. This antiapoptotic effect was dose dependent. Although much weaker than the HGE agent freshly freed from the host cells, noninfectious purified HGE agent stored frozen and thawed also had antiapoptotic effect, which was lost with proteinase K treatment but not with periodate treatment. Treatment of neutrophils with a transglutaminase inhibitor, monodansylcadaverine, blocked the antiapoptotic effect of the HGE agent. Addition of oxytetracycline, however, did not prevent or reverse the antiapoptotic effect of the HGE agent. These results suggest that binding of a protein component(s) of the HGE agent to neutrophils and subsequent cross-linking and/or internalization of the receptor and ehrlichiae are required for antiapoptotic signaling, but ehrlichial protein synthesis and/or proliferation is not required. MG-132, a proteasome inhibitor, and cycloheximide accelerated the apoptosis of neutrophils and overrode the antiapoptotic effect of the HGE agent. Studies with specific inhibitors suggest that protein kinase A, NF-κB, and interleukin 1β are not involved in the antiapoptotic mechanism of the HGE agent.
Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: analysis of transplantation timing and modality.

PURPOSE To examine the outcomes of patients with chemotherapy-sensitive mantle-cell lymphoma (MCL) following a first hematopoietic stem-cell transplantation (HCT), comparing outcomes with autologous (auto) versus reduced-intensity conditioning allogeneic (RIC allo) HCT and with transplantation applied at different times in the disease course. PATIENTS AND METHODS In all, 519 patients who received transplantations between 1996 and 2007 and were reported to the Center for International Blood and Marrow Transplant Research were analyzed. The early transplantation cohort was defined as those patients in first partial or complete remission with no more than two lines of chemotherapy. The late transplantation cohort was defined as all the remaining patients. RESULTS Auto-HCT and RIC allo-HCT resulted in similar overall survival from transplantation for both the early (at 5 years: 61% auto-HCT v 62% RIC allo-HCT; P = .951) and late cohorts (at 5 years: 44% auto-HCT v 31% RIC allo-HCT; P = .202). In both early and late transplantation cohorts, progression/relapse was lower and nonrelapse mortality was higher in the allo-HCT group. Overall survival and progression-free survival were highest in patients who underwent auto-HCT in first complete response. Multivariate analysis of survival from diagnosis identified a survival benefit favoring early HCT for both auto-HCT and RIC allo-HCT. CONCLUSION For patients with chemotherapy-sensitive MCL, the optimal timing for HCT is early in the disease course. Outcomes are particularly favorable for patients undergoing auto-HCT in first complete remission. For those unable to achieve complete remission after two lines of chemotherapy or those with relapsed disease, either auto-HCT or RIC allo-HCT may be effective, although the chance for long-term remission and survival is lower.
S-Ketamine Rapidly Reverses Synaptic and Vascular Deficits of Hippocampus in Genetic Animal Model of Depression

Abstract Background: The neurovascular plasticity of hippocampus is an important theory underlying major depression. Ketamine as a novel glutamatergic antidepressant drug can induce a rapid antidepressant effect within hours. In a mechanistic proof of this concept, we examined whether ketamine leads to an increase in synaptogenesis and vascularization within 24 hours after a single injection in a genetic rat model of depression. Methods: Flinders Sensitive Line and Flinders Resistant Line rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline. One day later, their behavior was evaluated by a modified forced swim test. Microvessel length was evaluated with global spatial sampling and optical microscopy, whereas the number of asymmetric synapses was quantified through serial section electron microscopy by using physical disector method in the CA1.stratum radiatum area of hippocampus. Results: The immobility time in the forced swim test among Flinders Sensitive Line rats with ketamine treatment was significantly lower compared with Flinders Sensitive Line rats without treatment. The number of nonperforated and perforated synapses was significantly higher in the Flinders Sensitive Line-ketamine vs the Flinders Sensitive Line-vehicle group; however, ketamine did not induce a significant increase in the number of shaft synapses. Additionally, total length of microvessels was significantly increased 1 day after ketamine treatment in Flinders Sensitive Line rats in the hippocampal subregions, including the CA1.stratum radiatum. Conclusion: Our findings indicate that hippocampal vascularization and synaptogenesis is co-regulated rapidly after ketamine, and microvascular elongation may be a supportive factor for synaptic plasticity and neuronal activity. These findings go hand-in-hand with the behavioral observations, where ketamine acts as a potent antidepressant.