Miracle-dz/UniFAR-FTUs huggingface dataset:
HDAC inhibition attenuates cardiac hypertrophy by acetylation and deacetylation of target genes

Pharmacological histone deacetylase (HDAC) inhibitors attenuate pathological cardiac remodeling and hypertrophic gene expression; yet, the direct histone targets remain poorly characterized. Since the inhibition of HDAC activity is associated with suppressing hypertrophy, we hypothesized histone acetylation would target genes implicated in cardiac remodeling. Trichostatin A (TSA) regulates cardiac gene expression and attenuates transverse aortic constriction (TAC) induced hypertrophy. We used chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq) to map, for the first time, genome-wide histone acetylation changes in a preclinical model of pathological cardiac hypertrophy and attenuation of pathogenesis with TSA. Pressure overload-induced cardiac hypertrophy was associated with histone acetylation of genes implicated in cardiac contraction, collagen deposition, inflammation, and extracellular matrix identified by ChIP-seq. Gene set enrichment analysis identified NF-kappa B (NF-κB) transcription factor activation with load induced hypertrophy. Increased histone acetylation was observed on the promoters of NFκB target genes (Icam1, Vcam1, Il21r, Il6ra, Ticam2, Cxcl10) consistent with gene activation in the hypertrophied heart. Surprisingly, TSA attenuated pressure overload-induced cardiac hypertrophy and the suppression of NFκB target genes by broad histone deacetylation. Our results suggest a mechanism for cardioprotection subject to histone deacetylation as a previously unknown target, implicating the importance of inflammation by pharmacological HDAC inhibition. The results of this study provides a framework for HDAC inhibitor function in the heart and argues the long held views of acetylation is subject to more flexibility than previously thought.
Irrational exuberance: the national bestseller that will help tou survive in todays stock market

Robert Shiller’s Irrational Exuberance predicted that the stock market bubble of the s would burst. Yale economist Shiller argued that the stock market was overpriced, and his prediction came true just as Irrational Exuberance was published in March . The book became an instant New York Times bestseller and has since been translated into more than a dozen languages. Shiller, now one of the most widely consulted authorities on the behavior of capital markets, advises leaders, writes, and lectures around the globe. Irrational Exuberance not only predicted the stunning loss of value in the financial markets in ; it also provided an accurate analysis of the psychology of overzealous investing, including the aggressive salesmanship of financial professionals and the spin created by a news media that fed what turned out to be the greatest run-up of share prices in memory. The book immediately became a standard work of modern economic criticism. Irrational Exuberance also paved the way for Shiller’s  Princeton book, The New Financial Order. In this farsighted followup, Shiller presented his ideas for designing financial markets and new forms of insurance to protect people’s livelihoods and home values against the depredations of economic misfortune, and to propel forward the economies of developing nations.
Serum Nucleic Acids in an Experimental Bovine Transmissible Spongiform Encephalopathy Model

Repetitive genomic nucleic acid sequences (RGNASs) have been detected in serum samples from both PrPres confirmed cows and cohorts and unexposed cattle. These RGNASs have polymorphisms that can be candidates for detecting subclinical disease processes. To confirm the presence of serum RGNAS polymorphisms in bovine spongiform encephalopathy (BSE), samples were obtained from an experimental study whereby cows were inoculated orally with BSE‐infectious or control brain material. Fleckvieh/Brown Swiss cattle were fed 100 g of either PrPres‐positive brain stem macerate or normal brain material (controls). Serum samples were taken 40 months post‐inoculation (15 infected, 6 control non‐infected and 5 randomly selected normal animals). Approximately, 6e5 sequences were analysed and the results showed that serum RGNAS polymorphisms could be detected in all of the infected animals but not in the control animals. In addition, polymorphisms in serum non‐RGNASs were detected in BSE‐infected animals that differed significantly from the controls (P < 0.01). These data reveal the complexity of serum nucleic acid sequences that can be detected in 200 μl of serum and further add to the guidelines for using serum nucleic acids in diagnostics. In conclusion, RGNAS polymorphism detection may have general applications for the study of other emerging zoonoses.
Functional results after orthotopic bladder substitution: A prospective multicentre study comparing four types of neobladder

Abstract Objective. The aim of this study was to evaluate enterocystometry, voiding pattern and urine leakage of four types of orthotopic bladder substitute. Material and methods. At eight urological departments, 78 consecutive men were studied: 66 with an ileal neobladder [30 Studer pouches (S), 24 Hautmann pouches (H) and 12 T-pouches (T)] and 12 with a right colonic [Goldwasser type (G)] neobladder. Enterocystometry, determination of residual urine, micturition protocol and 24 h pad weight test were performed 6 and 12 months postoperatively. Results. Colonic neobladders had higher pouch pressure at first desire, normal desire and strong desire than ileal neobladders (except at first and normal desire at 12 months) (p < 0.02) and contraction was present more often at both 6 and 12 months (p < 0.01 and p < 0.01). Compliance was good in all types of pouch. Intermittent self-catheterization was more common in H patients at 6 months (p = 0.033). All patients with colonic neobladders used pads during the day and night. In patients with ileal pouches 32% used pads during the day and 70% during the night at 12 months. Urine leakage was higher in patients with colonic bladders at 6 and 12 months during the day (mean/median of 98/31 ml and 82/16 ml versus 10/0 ml and 4/0 ml, p < 0.001). T-pouches had excellent day-time continence, but nocturnal leakage was high. Conclusions. The Hautmann pouch and the Studer pouch behaved similarly at enterocystometry and clinically, and continence was good in the majority of patients. The low number of patients with the other two types of pouch precludes definitive statements.
Identification of Inhibitors for a Virally Encoded Protein Kinase by 2 Different Screening Systems: In Vitro Kinase Assay and In-Cell Activity Assay

The human cytomegalovirus (HCMV) protein kinase pUL97 represents an important determinant for viral replication and thus is a promising target for the treatment of HCMV. The authors screened a compound library of nearly 5000 entities based on known kinase inhibitors in 2 distinct ways. A radioactive in vitro kinase assay was performed with recombinant pUL97, purified from baculovirus-infected insect cells, on myelin basic protein-coated FlashPlates. About 20% of all compounds tested inhibited pUL97 kinase activity by more than 50% at a concentration of 10 μM. These hits belonged to various structural classes. To elucidate their potential to inhibit pUL97 in a cellular context, all compounds of the library were also tested in a cell-based activity assay. For this reason, a HEK293 cell line was established that ectopically expressed pUL97. When these cells were incubated with ganciclovir (GCV), pUL97 phosphorylated GCV to its monophosphate, which subsequently became phosphorylated to cytotoxic metabolites by cellular enzymes. Thereby, pUL97 converted cells into a GCV-sensitive phenotype. Inhibition of the pUL97 kinase activity resulted in protection of the cells against the cytotoxic effects of GCV. In total, 199 compounds of the library were cellular active at nontoxic concentrations, and 93 of them inhibited pUL97 in the in vitro kinase assay. Among these, promising inhibitors of HCMV replication were identified. The 2-fold screening system described here should facilitate the development of pUL97 inhibitors into potent drug candidates. (Journal of Biomolecular Screening 2005:36-45)
The Role of CEO experience and CEO multiple directorships in Palestinian firm performance: the moderating effect of political connection

There is little doubt that political environment issues have tremendously affected application of corporate governance. Palestine experienced instability in the political situation due to Israeli occupation and for the pluralism of its party structure (Fatah is the ruling party and Hamas the opposition party). Hence, political connection serves as unique kind of external resources which can enhance the firm's performance, through political mechanisms, companies attempt to create for itself an environment that is better for its interest. The CEO characteristics play major role in the Palestinian firms and have been seen among the most important factors to enhance the firm’s performance. Many companies excelled as a result of their CEOs attributes. However, previous studies document mix and inconclusive results on CEO characteristics and firm performance. This paper provides conceptual arguments that allow for better understanding of the role of political connection on the relationship between CEO experience and firm performance. For companies, this study proposes that they should put more efforts on enhancing the role and the quality of the CEOs. Besides providing suggestions for future research, this study provides several recommendations to the Palestinian Capital Market Authority and PSE to improve its rule and regulation with respect to CG mechanisms.
Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial

OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of standard diabetes care. RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes (T2D) were treated with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique. RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment. Intrahepatic lipid content also remained unaffected by resveratrol; however, the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels (R = −0.68, P = 0.03). Intramyocellular lipid content increased in type 2 muscle fibers (P = 0.03), and systolic blood pressure tended to decrease (P = 0.09) upon resveratrol treatment. In addition, resveratrol significantly improved ex vivo mitochondrial function (state 3 and state U respiration upon malate with octanoyl-carnitine, P < 0.005). Intriguingly, a correlation was found between plasma levels of a metabolite of resveratrol (dihydroresveratrol) and the metformin dose used by the patients (R = 0.66, P = 0.005), suggesting an interaction between metformin and resveratrol. It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction. CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity. Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes.
Comparison of acute myeloid leukemia occurring de novo or preceded by a myelodysplastic stage: Differences in cellular DNA content

The DNA content of bone marrow cells in patients with acute leukemia preceded by a myelodysplastic stage (MDS‐AML) was compared to that in patients with de novo AML. We studied granulocytes, lymphocytes, monocytes, and blasts/promyelocytes from Feul‐gen‐stained bone marrow smears of 11 patients with de novo AML, ten patients with MDS‐AML, and 13 apparently healthy controls. The mean amount of DNA per cell (DNA index; Dl) in each cell population was determined using a digital video‐based imageanalyzing system (CAS‐100). Analysis of variance (F test) showed a significant difference in the DNA content between de novo AML on one hand and MDS‐AML and controls on the other as regards to blasts/promyelocytes (P < 0.01), lymphocytes (P < 0.05), and monocytes (P < 0.01), respectively. In three of 11 (27%) patients with de novo AML, a lower than normal limit Dl was found both in immature and mature bone marrow cells. Patients with MDS‐AML had those of Dl values similar to normal controls. In consequence, a significantly reduced mean Dl was found in patients with de novo AML in blasts/promyelocytes (P < 0.01), and monocytes (P < 0.05) compared to both normal controls and MDS‐AML. Together with data published separately, suggesting differences in granulocyte morphology, clonality, and HLA‐DR expression, these data suggest biological differences between the two diseases. © 1993 Wiley‐Liss, Inc.
Evaluation of ethical reflections in community healthcare

Background: Ethical reflections over care practices are important. In order to be able to perform such reflections, healthcare professionals must learn to think critically about their care practice. Aim: The aim of this study was to evaluate whether an introduction to and practice in ethical reflections in community healthcare have consequences for the healthcare personnel’s practice. Research design: A mixed-methods design was adopted with five focus group interviews and an electronic questionnaire based on results from the interviews. Participants and research context: A total of 29 community healthcare personnel with experience in ethical reflections participated in the interviews. The electronic questionnaire was sent via email to 2382 employees in community healthcare services in 13 municipalities in southern part of Norway. Ethical considerations: The study was guided by the intentions of the Declaration of Helsinki and ethical standard principles and approved by the Norwegian Social Science Data Services. Results: An introduction to and practice in performing ethical reflections brought about an ethical awareness with understanding and respect for both colleagues and patients. The leader had a key role. Lack of time was a hindrance for ethical reflections. Three factors could predict meaningful ethical reflections: higher age of personnel, higher percentage of employment and longer experience with ethical reflections. Discussion: According to other studies, ethical reflections may enhance moral development of colleagues and their actions as advocates for the patients. A deepened ethical awareness, professional competency and sufficient time resources will guarantee proper caregiving. Conclusion: A supportive environment that prioritizes participation in reflection meetings is decisive. To practice ethical reflections will provide better care for patients. A challenge for the community healthcare system is to offer adequate positions that provide the personnel an opportunity to be involved as caregivers and to participate in ethical reflections.
Neuropsychiatric Issues in Parkinson Disease

ABSTRACTPurpose of Review: This article reviews the recognition and management of neuropsychiatric issues in Parkinson disease (PD), including mood disorders, cognitive impairment, and behavioral disturbances.Recent Findings: Patients with PD frequently develop neuropsychiatric issues, and these issues can greatly affect their quality of life. In recent years, mood, cognitive, and behavioral issues in PD have received greater recognition, with increasing attention directed toward improved screening and therapeutic interventions for symptomatic treatment. Taken together as a group, neuropsychiatric issues can be found throughout the whole course of PD, from early in the disease, potentially even in a premotor stage, to the time of diagnosis and later in the course with more advanced disease.Summary: In the comprehensive care of patients with PD, recognition of neuropsychiatric issues is critical. Advances in therapeutics for the different neuropsychiatric symptoms are still needed, although several pharmacologic and nonpharmacologic options are available. Patient management frequently requires a multidisciplinary approach, with collaboration of neurologists with neuropsychologists, psychologists, psychiatrists, and other health professionals.
Local communities’ perceptions and use of urban green infrastructure in two Ethiopian cities: Bahir Dar and Hawassa

The main objective of this study is to examine local communities’ perceptions and use of green infrastructure (GI) in two case study cities: Bahir Dar and Hawassa in Ethiopia. The study employed a binary logistic regression model to identify factors that affect perceptions of GI. The result shows that people have distinct patterns of usage and positive perceptions towards GI in their respective cities. The regression results show that gender, age, accessibility, safety, education level, type of green infrastructure, level of awareness, location and opportunities for social activities are statistically significant predictors of perception. It is evident that urban GI development that addresses local communities’ perceptions needs to be sensitive to these variables.
Artificial Neural Network Model Is Superior to Logistic Regression Model in Predicting Treatment Outcomes of Interferon-Based Combination Therapy in Patients with Chronic Hepatitis C

Background/Aims: Patients with chronic hepatitis C (CHC) can achieve a sustained virologic response if they received pegylated interferon plus ribavirin therapy; however, some of them do not respond or relapse after treatment. The aim of this study was to compare the ability of two statistical models to predict treatment outcomes. Methods: Clinical data, biochemical values, and liver histological features of 107 patients with CHC were collected and assessed using a logistic regression (LR) model and an artificial neural network (ANN) model. Both the LR and ANN models were compared by receiver-operating characteristics curves. Results: Aspartate aminotransferase (p = 0.017), prothrombin time (p = 0.002), body mass index (BMI; p = 0.003), and fibrosis score of liver histology (p = 0.002) were found to be significant predictive factors by univariate analysis. The independent significant predicting factor was BMI by multivariate LR analysis (p = 0.0095). The area under receiver-operating characteristics of the ANN model was larger than that of the LR model (85 vs. 58.4%). Conclusions: It was found that BMI is an independent factor for identifying patients with favorable treatment response. A useful ANN model in predicting outcomes of standard treatment for CHC infection was developed and showed greater accuracy than the LR model.
Housing activism in urban China: the quest for autonomy in neighbourhood governance

Abstract The creation of a neoliberal housing regime triggered extensive housing activism during the last decade by middle class homeowners who were protecting their rights to their neighbourhood. Yet such actions also signify the quest for autonomy from the ubiquitous control of the local state as the vanguard of political power hegemony at the grassroots level. Yet there is evidence of an escalation in “non-peaceful” actions in the richest cities in China despite the tight control of the authoritarian state. With data taken from official documents and interviews as well as from news reports about neighbourhood disputes in Beijing, Shanghai, Guangzhou and Shenzhen, this article gives an analytic account of the disputes and actions of homeowners in residential neighbourhoods while making their claims as well as on the strategies used by the local state in controlling the homeowners' associations. The article is able to enrich our understanding of housing activism in a non-democratic regime.
Clinical Validation of PD Adeouest Software: Modeling Error Assessment

Objective PD ADEQUEST software (Baxter Healthcare, Deerfield, IL, U.S.A.) is used in peritoneal dialysis for calculating the indices of dialysis efficiency and for the mathematical simulation of the results of various dialysis regimens. The aim of our study was to quantify the modeling errors and find the methods which give best results. Design Nonrandomized, repeated measurement, clinical validation study. Patients The study included 78 patients on continuous ambulatory peritoneal dialysis (PD), daytime ambulatory PD, and automated PD. Measurements We used 207 collections of dialysate and urine associated with peritoneal equilibration tests (PETs) performed with different glucose concentrations (1.36%,2.27%,3.86%). The measured urea Kt/V, creatinine clearance (CRCL) and ultrafiltration (UF) were compared with the same data simulated mathematically using the PD ADEQUEST software version 1.4. Results The Kt/V, CRCL, and UF measured values were significantly correlated and in agreement with modeled data [concordance correlation (rc) was 0.849,0.839,0.625 respectively]. The errors (modeled -measured) were: Kt/V = -0.04± 0.27 (p = ns), CRCL = 2.1 ± 7.7 L (p < 0.001), UF = -121 ± 711 mL (p = 0.016). Applying ANOVA to both the peritoneal transport data calculated by PD ADEQUEST (mass transfer area coefficient of the solutes, fluid reabsorption, and hydraulic permeability) and the modeling errors, significant differences were found in relation to the PET glucose concentrations. Conclusion PD ADEQUEST proves to be a useful instrument in peritoneal dialysis, although there is undoubtedly still room for improvement in its prediction efficacy, which is influenced by the glucose concentration used in the PET.
A Phase 2, Single Arm Study of Iniparib in Patients With BRCA1 or BRCA2 Associated Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Objective The aim of the study was to evaluate the activity and tolerability of iniparib monotherapy in women with BRCA1 or BRCA2-associated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. Methods and Materials Eligible patients had advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, germline BRCA1 or BRCA2 mutation, measurable disease, and at least 1 previous treatment regimen of platinum/taxane chemotherapy. Patients received iniparib 8 mg/kg intravenously on days 1 and 4 weekly, with imaging every 8 weeks. Treatment continued until disease progression or adverse events (AEs) prohibited further therapy. Common Terminology Criteria for AEs v3.0 was used to grade AEs. The primary endpoint was tumor response. The study was conducted with a Simon 2-stage design with 12 and 23 patients planned in the first and second stage, respectively. The study was designed to distinguish between 10% and 30% responding with types 1 and 2 error of 0.10. Results Twelve patients were treated on study, with median exposure to iniparib of 7.5 weeks. The median number of previous chemotherapeutic regimens was 7. Treatment-related AEs (≥10%) included asthenia (83.3%), constipation (25%), diarrhea (25%), nausea (25%), abdominal pain (16.7%), and decreased hemoglobin (16.7%). All treatment-related AEs were grades 1 or 2 with the following 2 exceptions: 1 grade 3 diarrhea and 1 grade 3 hypertension. One patient had stable disease lasting 2 cycles; the remaining 11 patients had progressive disease. The study did not proceed to second stage enrollment. Conclusions Iniparib did not show significant activity in this heavily pretreated ovarian cancer population, all of whom had BRCA1 or BRCA2 mutations.