Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of pulse pressure index with left ventricular filling pressure and diastolic dysfunction in patients with chronic kidney disease.

BACKGROUND Patients with chronic kidney disease (CKD) often have poor vascular compliance and poor left ventricular diastolic dysfunction (LVDD). The pulse pressure index (PPI) defined as ((systolic blood pressure - diastolic blood pressure)/systolic blood pressure) reflects vascular compliance. Vascular compliance is reportedly associated with left ventricular diastolic function. This study of CKD patients investigated whether PPI correlates with the ratio of transmitral E wave velocity (E) to early diastole mitral annulus velocity (Ea) or with LVDD. METHODS This study enrolled 511 CKD patients who had been referred for echocardiographic examination. Blood pressure was automatically measured with an ABI-form device. The LVDD was defined as E-to-transmitral A wave velocity ratio of ≥0.9, Ea <8 cm/s, or E/Ea ≥15. RESULTS Compared with those with E/Ea <15, patients with E/Ea ≥15 had significantly higher systolic blood pressure, pulse pressure, and PPI (all P < 0.001). Multivariable analysis showed that PPI was independently associated with E/Ea (unstandardized coefficient β = 1.348; P < 0.001) and with LVDD (odds ratio = 1.441 per 0.064 increase; P < 0.001). CONCLUSIONS This study showed that increased PPI significantly correlates with elevated E/Ea and LVDD in CKD patients. Because PPI can be rapidly acquired during blood pressure measurement, it may be helpful for identifying CKD patients with a high left ventricular filling pressure and LVDD.
High-fat diet-induced renal cell apoptosis and oxidative stress in spontaneously hypertensive rat are ameliorated by fenofibrate through the PPARα-FoxO3a-PGC-1α pathway.

BACKGROUND The peroxisome proliferator-activated receptor-α (PPARα) is a lipid-sensing transcriptional factor that has a role in gluco-oxidative stress and lipotoxicity. Forkhead box O (FoxO)s and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α are also known to regulate cell metabolism, cell cycle arrest, apoptosis and oxidative stress during stressful conditions. We evaluated whether PPARα-FoxOs-PGC-1α signaling in overfed spontaneously hypertensive rats (SHR) has a protective role in the kidney. METHODS Male SHR and Wistar-Kyoto rats (WKY) fed a high-fat diet (HFD) received treatment with fenofibrate, PPARα agonist or tempol, antioxidants for 12 weeks and were evaluated about the PPARα-FoxOs-PGC-1α pathway. RESULTS The SHRs with an HFD had an elevated systolic pressure, plasma insulin, free fatty acid (FFA) and triglyceride (TGs) levels, and they had induced glucose intolerance as well as albuminuria, glomerular expansion and renal inflammation. An HFD caused the accumulation of intra-renal FFA and TGs and this was related to a decrease in the PPARα expression, the activation of phosphatidylinositol 3-kinase (PI3K)-Akt, phosphorylation of FoxO3a and decreases in the PGC-1α and estrogen-related receptor (ERR)-1α expressions, which suppressed the superoxide dismutase (SOD2) and Bcl-2 expressions and led to increases in oxidative stress and the number of apoptotic renal cells. Interestingly, administering fenofibrate or tempol to the HFD-induced SHRs reversed all of the renal phenotypes by increasing the PPARα expression with concomitant inactivation of the PI3K-Akt pathway, dephosphorylation of FoxO3a and activation of PGC-1α-ERR-1α signaling, and this all resulted in ameliorating the oxidative stress and apoptotic cell death. CONCLUSION Our results demonstrated that PPARα agonists or antioxidants are associated with improvement of the circulating FFA and TGs levels and this prevents HFD-induced renal lipotoxicity and hypertension by the activation of PPARα and its downstream signals of both FoxO3a and PGC-1α.
Lessons Learned from Secondary Schools using Technology for School Improvement: It's Just not that Simple!

The purpose of this article is to describe lessons learned from studying the leadership in eight award-winning secondary schools and districts that were recognized for successfully leveraging technology as part of their efforts for school improvement. Data were collected through observations, interviews, and document analysis in schools and districts with ethnically, linguistically, and socioeconomically diverse students in communities facing the types of challenges that many schools face today. Based on the cross-case analysis of eight intrinsic case studies, this article offers numerous examples and lessons learned about the role that leadership and vision, technology planning and support, professional development, curriculum and instructional practices, school culture, funding, and partnerships play in leveraging technology for school improvement.
Recent Advances in Retromer Biology

The endosomal network is an organized array of intracellular, membranous compartments that function as sorting sites for endosomal and biosynthetic cargo. The fate of endocytic cargo is reliant upon interactions with a number of molecularly distinct sorting complexes, which tightly control the relationship between sorting of their respective cargo and the physical process of membrane re‐scuplturing required for the formation of transport carries. One such complex, retromer, mediates retrograde transport from endosomes to the trans‐Golgi network (TGN). Disregulation of retromer has been implicated in a host of disease states including late‐onset Alzheimer's. Rather than give a broad overview of retromer biology, here we aim to outline the recent advances in understanding this complex, focussing on the involvement of both clathrin and the cytoskeleton in retromer function.
Resilience and vulnerability among preschool children: family functioning, temperament, and behavior problems.

OBJECTIVE To examine the effects of child temperament and stressful family functioning on child behavior problems among preschool children. METHOD One hundred forty-five preschool children, aged 2 to 5 years, were evaluated by teachers, mothers, and independent observers. Teachers reported on child temperament; from these ratings, two dimensions of temperament were derived: difficult/easy and approachability. Mothers reported on two dimensions of family functioning: conflict and expressiveness. Both teachers and independent observers rated child behavior problems. RESULTS Children with more difficult temperaments who were in high-conflict families had the most internalizing and externalizing behavior problems, while children with easy temperaments had fewer such problems, regardless of levels of family conflict. Difficult children whose families were highly expressive engaged in the most observed aggression. CONCLUSIONS Results suggest that temperament is involved in both protective and vulnerability processes. A difficult temperament operates as a vulnerability factor for internalizing and externalizing behavior problems and observed aggression, while an easy temperament functions as a protective mechanism for these outcomes.
Cost‐utility analysis of daily versus intermittent inhaled corticosteroids in mild‐persistent asthma

Despite the many benefits that have been demonstrated by the continuous administration of inhaled corticosteroids (ICS) in persistent asthma, a new strategy for mild‐asthma is emerging, consisting of using intermittent or as‐needed ICS treatment in conjunction with short‐acting beta2 agonists in response to symptoms. However, no previous studies have reported an economic evaluation comparing these two therapeutic strategies.
Automatic Goal Generation for Reinforcement Learning Agents

Reinforcement learning is a powerful technique to train an agent to perform a task. However, an agent that is trained using reinforcement learning is only capable of achieving the single task that is specified via its reward function. Such an approach does not scale well to settings in which an agent needs to perform a diverse set of tasks, such as navigating to varying positions in a room or moving objects to varying locations. Instead, we propose a method that allows an agent to automatically discover the range of tasks that it is capable of performing. We use a generator network to propose tasks for the agent to try to achieve, specified as goal states. The generator network is optimized using adversarial training to produce tasks that are always at the appropriate level of difficulty for the agent. Our method thus automatically produces a curriculum of tasks for the agent to learn. We show that, by using this framework, an agent can efficiently and automatically learn to perform a wide set of tasks without requiring any prior knowledge of its environment. Our method can also learn to achieve tasks with sparse rewards, which traditionally pose significant challenges.
Population screening for coeliac disease in a low prevalence area in Italy

Objective. A screening program was proposed for the village of Carcare (population 5700), located in a region of Italy with an apparently low prevalence of coeliac disease (CD): only 1 patient diagnosed out of 2557 inhabitants. The study group comprised 1002 individuals (568 F, 434 M, age range 13–90 years) recruited from blood donors, secondary school pupils and people referred to the local outpatient facilities for routine blood chemistry. Material and methods. Total IgA, IgA anti-tissue transglutaminase (tTG) (ELISA, recombinant human antigen) and IgA antiendomysium (EMA) (IFI, umbilical cord substrate) antibodies were measured in the serum of all participants. All patients with IgA deficiency were investigated for IgG tTG antibodies, and in the case of disagreement between tTG and EMA, they were typed for HLA DQ2-DQ8 haplotypes. Results. Thirteen subjects were positive and 988 negative for autoantibodies (3/988 had IgA deficiency). One serum sample was positive for tTG antibodies but negative for EMA. Ten out of 13 positive subjects consented to undergo duodenal biopsy, which invariably produced evidence of CD despite the absence of clinical signs/symptoms. A post-diagnostic clinical investigation provided evidence showing mild iron deficiency (4 subjects) and osteoporosis (2 subjects). After counselling, all subjects accepted a gluten-free diet. Conclusions. The prevalence of CD in the study group was 1:100 (1.0%; 95% CI: 0.5–1.8%): this indicates that CD is largely underdiagnosed in Carcare. Our results suggest that the low prevalence of CD observed in some regions is likely to be due to underdiagnosis.
Beneficial effects of an Andrographis paniculata extract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats

Abstract Context Andrographolide containing Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts is often used for treatments of diabetes and other inflammatory disorders commonly accompanying cognitive and other psychiatric disorders. Objective To compare the efficacies of a standardised A. paniculata extract (AP) and pure andrographolide on cognitive functions, oxidative stress and cholinergic function in diabetic rats. Materials and methods Streptozotocin-induced diabetic Charles Foster albino rats treated orally with a hydro-methanolic A. paniculata leaf extract (50, 100 and 200 mg/kg/day), or with pure andrographolide (15, 30 and 60 mg/kg/day) for 10 consecutive days, were subjected to Morris water maze test. After the test, acetylcholinesterase, superoxide dismutase (SOD), and catalase (CAT) activities and lipid peroxidation (LPO) in brain tissues were assessed. Results Acetylcholinesterase activity in pre-frontal cortex and hippocampus of diabetic rats was 2.1 and 2.6 times higher compared to nondiabetic rats. LPO was 1.6 times higher and decreased SOD (56.3%) and CAT (44.9%) activities in pre-frontal cortex of diabetic rats compared to nondiabetic rats. AP or andrographolide treatments dose dependently attenuated cognitive deficits, reduced acetylcholinesterase activity, oxidative stress, improved diabetic hyperglycemia and insulin deficiency. All observed effects of AP were quantitatively almost equal to those expected from its analytically quantified andrographolide content. Discussion and conclusion Reported observations are the very first ones suggesting beneficial effects of andrographolide against diabetes associated cognitive deficits, increased acetylcholinesterase activity and deteriorated antioxidative status. Efforts to exploit A. paniculata extracts enriched in andrographolide as preventive measures against such disorders can be warranted.
The Mitochondrial Protein hFis1 Regulates Mitochondrial Fission in Mammalian Cells through an Interaction with the Dynamin-Like Protein DLP1

ABSTRACT The yeast protein Fis1p has been shown to participate in mitochondrial fission mediated by the dynamin-related protein Dnm1p. In mammalian cells, the dynamin-like protein DLP1/Drp1 functions as a mitochondrial fission protein, but the mechanisms by which DLP1/Drp1 and the mitochondrial membrane interact during the fission process are undefined. In this study, we have tested the role of a mammalian homologue of Fis1p, hFis1, and provided new and mechanistic information about the control of mitochondrial fission in mammalian cells. Through differential tagging and deletion experiments, we demonstrate that the intact C-terminal structure of hFis1 is essential for mitochondrial localization, whereas the N-terminal region of hFis1 is necessary for mitochondrial fission. Remarkably, an increased level of cellular hFis1 strongly promotes mitochondrial fission, resulting in an accumulation of fragmented mitochondria. Conversely, cell microinjection of hFis1 antibodies or treatment with hFis1 antisense oligonucleotides induces an elongated and collapsed mitochondrial morphology. Further, fluorescence resonance energy transfer and coimmunoprecipitation studies demonstrate that hFis1 interacts with DLP1. These results suggest that hFis1 participates in mitochondrial fission through an interaction that recruits DLP1 from the cytosol. We propose that hFis1 is a limiting factor in mitochondrial fission and that the number of hFis1 molecules on the mitochondrial surface determines fission frequency.
Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies

Objective: To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European). Methods: After a 2-week placebo wash-out 1453 elderly hypertensive patients (65–89 years; sitting office DBP 90–109 mmHg and/or sitting office SBP 140–179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks. Results: In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [−2.8 (−4.9, −0.8) mmHg], whereas ramipril did not [+1.5 (–0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]. Conclusions: Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intake.
Networks of Loss: Relationships Among Symptoms of Prolonged Grief Following Spousal and Parental Loss

The death of a loved one can trigger a range of emotional, behavioral, motivational and cognitive reactions collectively labeled as “grief. ” There has been a recent resurgence of empirical interest in grief reactions, and there is now a general consensus that 7%-10% of bereaved individuals experience intense and chronic reactions termed Prolonged Grief (PG). However, there is ongoing debate about how best to conceptualize the construct. Recent studies have advanced this debate by applying a network, or causal systems approach. Whereas traditional views of psychopathology posit symptoms of disorders reflect the independent actions of latent entities, the network approach argues that the symptoms themselves interact to give rise to the disorder. A network conceptualization offers novel approaches to studying the mechanisms that contribute to PG. To date, however, research has focused only on spousal loss and only used a single archival data set. Therefore, in this paper we apply network analysis to examine relationships among PG symptoms in samples of individuals bereaved by loss of a spouse (Study 1, N = 193) and a parent (Study 2, N = 180). Participants completed the PG-13 and a measure of depression. A comparison test suggested the networks produced from each sample were not reliably different. The strongest link in both networks was between yearning and emotional pain. Meaninglessness was relatively central, whereas avoidance was peripheral in both networks. Findings are discussed with reference to theoretical models and the potential benefits a network approach may hold for understanding relationships between symptoms of PG.
High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: A prospective interventional study

Abstract Weight loss is an independent prognostic factor in amyotrophic lateral sclerosis (ALS). We investigated whether the body weight of ALS patients who previously lost weight can be stabilized by a high-caloric diet. For this purpose we compared two different high-caloric food supplements: one with high fat content and one with high carbohydrate content. Twenty-six patients were randomly allocated to one of the therapeutic groups. Body weight, ALS functional rating scale-revised (ALSFRS-R), static vital capacity (SVC), bioelectrical impedance analysis (BIA), metabolic serum parameters, and adverse events were investigated. Results showed that body weight of ALS patients could be stabilized in both therapeutic groups after 12 weeks of therapy (p = 0.008). The effect was greater in the group with high fat supplement though not statistically significant (p = 0.37). In conclusion, high-caloric food supplements with high fat as well as high carbohydrate content are both suitable to stabilize the body weight of ALS patients. The effect of a high fat diet might be more pronounced. Since body weight is an independent prognostic factor in ALS it is possible that a high-caloric food supplement improves survival in ALS. However, this hypothesis can only be tested by conducting a placebo-controlled double-blinded trial of sufficient power.
Qualification issues and pitfalls for advanced semiconductor devices in space

Increasing satellite performance within size, weight and power constraints demands access to advanced semiconductors, yet environmental, reliability and schedule requirements remain. Successful technology insertion requires knowledge of failure mechanisms, design limitations and screening flow. We review Boeing's approach, critical issues and potential pitfalls, illustrated by experience with IBM ASICs.
Reducing eating disorder onset in a very high risk sample with significant comorbid depression: A randomized controlled trial.

OBJECTIVE Eating disorders (EDs) are serious problems among college-age women and may be preventable. An indicated online eating disorder (ED) intervention, designed to reduce ED and comorbid pathology, was evaluated. METHOD 206 women (M age = 20 ± 1.8 years; 51% White/Caucasian, 11% African American, 10% Hispanic, 21% Asian/Asian American, 7% other) at very high risk for ED onset (i.e., with high weight/shape concerns plus a history of being teased, current or lifetime depression, and/or nonclinical levels of compensatory behaviors) were randomized to a 10-week, Internet-based, cognitive-behavioral intervention or waitlist control. Assessments included the Eating Disorder Examination (EDE, to assess ED onset), EDE-Questionnaire, Structured Clinical Interview for DSM Disorders, and Beck Depression Inventory-II. RESULTS ED attitudes and behaviors improved more in the intervention than control group (p = .02, d = 0.31); although ED onset rate was 27% lower, this difference was not significant (p = .28, NNT = 15). In the subgroup with highest shape concerns, ED onset rate was significantly lower in the intervention than control group (20% vs. 42%, p = .025, NNT = 5). For the 27 individuals with depression at baseline, depressive symptomatology improved more in the intervention than control group (p = .016, d = 0.96); although ED onset rate was lower in the intervention than control group, this difference was not significant (25% vs. 57%, NNT = 4). CONCLUSIONS An inexpensive, easily disseminated intervention might reduce ED onset among those at highest risk. Low adoption rates need to be addressed in future research.
Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening

Characteristics of inhibitors identified by prospective screening may differ from those detected clinically. In a prospective study at 17 hemophilia centers with central inhibitor measurement by Nijmegen‐Bethesda assay, 23 (2.8%) of 824 hemophilia A patients had new inhibitors detected: nine high‐titer inhibitors (HTI: 7 ≥ 5.0 NBU plus 2 of 2.6 and 3.4 NBU at immune tolerance induction initiation) and 14 low‐titer inhibitors (LTI: 0.5–1.9 NBU). HTI occurred at an earlier age (median 2 years, range 1–18, vs. median 11 years, range 2–61, P = 0.016). Both HTI (22%) and LTI (43%) occurred in non‐severe patients. All HTI, but only 64% of LTI, were found to be FVIII‐specific by chromogenic Bethesda assay or fluorescence immunoassay (FLI), indicating a high rate of false‐positive LTI. Repeat specimens confirmed all HTI, 7/9 LTI, and 7/7 FVIII‐specific LTI. FLI results were similar between HTI and FVIII‐specific LTI; all included IgG1 and IgG4 subclasses. A comparable prospective study conducted from 1975 to 1979 at 13 U.S. centers found 31 (2.4%) new inhibitors among 1,306 patients. In both studies, one‐third of inhibitors occurred in non‐severe patients and one‐quarter after 150 exposure days (ED). Significant differences were seen in the age at which inhibitors occurred (median 16 years in the older study vs. 5 years currently, P = 0.024) and in ED before inhibitor development, 10% in the older study and 43% currently study occurring within 20 ED, suggesting a temporal change in inhibitor development. Prospective screening detects inhibitors in patients of all severities, ages, and ED. Some LTI, however, are false positives. Am. J. Hematol. 90:871–876, 2015. © 2015 Wiley Periodicals, Inc.