Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploration of the in vitro Antiviral Activity of a Series of New Pyrimidine Analogues on the Replication of HIV and HCV

Background: In continuation of our search for new anti-HIV and anti-HCV agents, the suggestion, synthesis and structure elucidation of a new series of 2,6-diamino-4-alkylthio- or (2-benzylhydrazinyl)-5-p-chlorophenylazopyrimidines), 2,6-diamino-4-(2-benzylhydrazinyl)-5-(aryl-[1,1′-biphenyl]-4-yl)pyrimidines, 2,6-diamino-4-(aryl)-5-(aryl[1,1′-biphenyl]-4-yl) pyrimidines), 6-(aryl)-1,3-dimethyl-5-nitro pyrimidine-2,4-dione and 6-amino-4-methoxy-N,N-dimethyl-6-arylpyrimidines were described. Methods: The anti-HIV-1 (strain IIIB) and HIV-2 (strain ROD) activity of the newly synthesized pyrimidine analogues was evaluated in vitro in human MT-4 cells using the MT-4/MTT assay. Similarly, the same compounds were evaluated in vitro for their selective antiviral activity against HCV in the Huh 5–2 replicon system (type 1b, Con1 strain). Results: None of the tested compounds exhibited inhibition of HIV-1 and HIV-2 replication in cell culture. Even though many compounds yielded a 50% effective concentration in the HCV replicon system with selectivity indexes up to 6.9, none of the compounds matched the selection criteria of a selective inhibitor of virus replication in this assay (that is, >70% inhibition at concentrations that do not elicit an anti-metabolic effect on the host cells). Conclusions: Structural modification of these compounds might optimize their anti-HCV activity by introducing diverse and potent functional groups at the pyrimidine backbone, like nitrile residue. Because of the nature of the molecules, these new derivatives will also be evaluated for their potential anti-HIV activity.
Diastolic and Systolic Heart Failure Are Distinct Phenotypes Within the Heart Failure Spectrum

Heart failure (HF) is a major worldwide public health problem. One in 5 people aged 40 years in the United States will develop HF during his or her lifetime,1 and HF remains the leading cause for hospitalization among the elderly.2 Although age- and sex-specific HF incidence is not increasing,3 overall HF survival has improved, and the number of people aged >65 years is increasing rapidly. Thus, the absolute number of patients with HF will continue to increase. Half of the patients with HF have a preserved ejection fraction (HFpEF), and the remainder display reduced ejection fraction (HFrEF). 4,–,6 The proportion of patients with normal ejection fraction (EF) is increasing steadily because of increased incidence and/or increasing physician recognition of the syndrome.4 Resource utilization associated with HF is high in both the inpatient and outpatient settings, regardless of EF. Response by De Keulenaer and Brutsaert on p 2014 Heart failure is a syndrome that can be defined clinically by a collection of symptoms (dyspnea, fatigue, exertional intolerance) and signs (edema, gallop, rales) that are attributable to a cardiac disorder.2 Heart failure may also be defined hemodynamically by an inability to provide adequate cardiac output to the body at rest or with exertion, or to do so only in the setting of elevated cardiac filling pressures. The cardiovascular system responds to a wide variety of insults (eg, myocardial disease, ischemia, valvular or pericardial disease) in a finite number of ways, both hemodynamically (elevated filling pressures, depressed output) and symptomatically (dyspnea, fatigue, angina). However, these similarities in clinical expression do not indicate that the underlying mechanisms of disease are the same or that treatment will be similar. For example, a headache may be noted with a migraine or brain tumor; dyspnea may be reported …
Linear Quadratic Nash Games on Positive Linear Systems

In this paper two-player Nash differential games, on an infinite time horizon, with two different information structures have been considered: the open loop and the deterministic feedback information structure. The performance indices were assumed to be of quadratic type and the constraint to be a linear positive differential system. As the main result, a convergent Newtonian algorithm to solve the associated algebraic matrix Riccati equation and generalized algebraic matrix Riccati equation in order to obtain stabilizing solutions which are directly related to the existence of a Nash equilibrium, is presented for each information structure. Finally, we discuss a numerical example to illustrate both algorithms presented.
AAV Vectors Expressing LDLR Gain-of-Function Variants Demonstrate Increased Efficacy in Mouse Models of Familial Hypercholesterolemia

Rationale: Familial hypercholesterolemia is a genetic disorder that arises because of loss-of-function mutations in the low-density lipoprotein receptor (LDLR) and homozygous familial hypercholesterolemia is a candidate for gene therapy using adeno-associated viral vectors. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL) negatively regulate LDLR protein and could dampen adeno-associated viral vector encoded LDLR expression. Objective: We sought to create vectors expressing gain-of-function human LDLR variants that are resistant to degradation by human PCSK9 (hPCSK9) and IDOL and thereby enhance hepatic LDLR protein abundance and plasma LDL cholesterol reduction. Methods and Results: Amino acid substitutions were introduced into the coding sequence of human LDLR cDNA to reduce interaction with hPCSK9 and human IDOL. A panel of mutant human LDLRs was initially screened in vitro for escape from PCSK9. The variant human LDLR-L318D was further evaluated using a mouse model of homozygous familial hypercholesterolemia lacking endogenous LDLR and apolipoprotein B mRNA editing enzyme catalytic, APOBEC-1 (double knockout). Administration of wild-type human LDLR to double knockout mice, expressing hPCSK9, led to diminished LDLR activity. However, LDLR-L318D was resistant to hPCSK9-mediated degradation and effectively reduced cholesterol levels. Similarly, the LDLR-K809R\C818A construct avoided human IDOL regulation and achieved stable reductions in serum cholesterol. An adeno-associated viral vector serotype 8.LDLR-L318D\K809R\C818A vector that carried all 3 amino acid substitutions conferred partial resistance to both hPCSK9- and human IDOL–mediated degradation. Conclusions: Amino acid substitutions in the human LDLR confer partial resistance to PCSK9 and IDOL regulatory pathways with improved reduction in cholesterol levels and improve on a potential gene therapeutic approach to treat homozygous familial hypercholesterolemia subjects.
Predictors of Depression among Older Adults in Long-term Care Facilities

Purpose: Although it is known that depression is highly prevalent in institutionalized older adults, little is known about its predictors in long-term care facility in Korea. The aim of this study was to identify the predictors of depression among institutionalized older adults. Methods: This study was a secondary analysis of a large data set which was used in a cross-sectional research method conducted in seven geriatric long-term care facilities located in Seoul, Kyunggi-do, and Kangwon-do, Korea. The participants were 305 older adults over 65 years old. Data were collected during November and December, 2011, using structured questionnaires which included general characteristics, cognitive function, and depression. Data analysis included descriptive statistics, t-test, one-way ANOVA, and logistic regression. Results: Mean age of the participants was 80.38±7.14 and 38.7% of the participants presented symptoms of depression; 24.3% showed minor depression and 14.4% showed probable major depression. Depressive symptoms were related to insomnia, delirium/confusion, bad eyesight, bad communication, and limb impairment. Insomnia (OR=5.94; 95% CI=3.31~10.64) and delirium/confusion (OR=4.77; 95% CI=2.24~10.20) were the significant predictors of depression among institutionalized older adults. Conclusion: Nursing interventions should be developed considering the factors of insomnia and delirium/confusion to decrease depression in this population.
Pulmonary Physiology and Pathophysiology in Obesity Obesity , adipokines , and lung disease

Sood A. Obesity, adipokines, and lung disease. J Appl Physiol 108: 744–753, 2010. First published November 19, 2009; doi:10.1152/japplphysiol.00838. 2009. — This review summarizes the state of the current literature relating to the associations of lung disease on obesity and adipokines (proteins produced by adipose tissue) in humans. Obesity is an independent risk factor for asthma. Recent studies suggest that obesity is also an independent risk factor for chronic airflow obstruction, as is seen with chronic obstructive pulmonary disease (COPD). The mechanistic basis for these associations in humans is not established, although a possible role for adipokines has been invoked. Leptin, a proinflammatory adipokine, and adiponectin, an anti-inflammatory adipokine, are causally associated with asthma in mice. Although human studies are currently inconclusive, high-serum leptin and low-serum adiponectin concentrations predict asthma, independent of obesity, in select population groups, such as premenopausal women in the United States. In contradistinction, low-serum leptin and high-serum adiponectin concentrations are associated with stable COPD, although these associations are likely confounded by fat mass. Interestingly, leptin may promote systemic and airway inflammation in stable COPD patients. On the other hand, COPD may upregulate systemic and lung adiponectin expression. The precise mechanism and significance of the associations between these adipokines and lung disease at the current stage is confusing and frankly paradoxical in places. This area of research needs additional study that may open up novel therapeutic strategies for these lung diseases.
The dispersal process of asexual propagules and the contribution to population persistence in Marchantia (Marchantiaceae).

PREMISE OF THE STUDY The dispersal process involves emigration from a focal source, dispersal through the landscape, and immigration into a new population or habitat. Despite the fact that dispersal is vital for the long-term persistence of a species, key stages of the process are unknown or understudied for many species, including the importance and contribution of asexual reproduction. Focusing only on a single stage in the dispersal process may give an incomplete and potentially flawed picture of the effects of asexual reproduction on metapopulation dynamics in plant species. METHODS Using a multifaceted approach that combines laboratory experiments, field studies, and mathematical models, we quantify the production, dispersal, and survival of immigrants of water-dispersed asexual offspring (gemmae) of the clonal liverwort Marchantia inflexa. KEY RESULTS Compared to female plants, male plants of Marchantia inflexa produce gemmae more quickly and in higher numbers, but due to desiccation have lower gemmae survival rates. Gemmae move up to 20 cm per minute in light rain, suggesting they can leave the source population. Long distance dispersal of gemmae is supported by the mathematical analysis of unisexual metapopulations. Upon reaching the new habitat, gemmae survival is high if they stay moist. CONCLUSIONS By integrating multiple experiments to quantify the effects of gemmae on metapopulation dynamics, we found that different stages of dispersal can lead to different conclusions on which sex has an advantage. Gemmae are critical for the maintenance of both sexes, the persistence of single-sex metapopulations and species, and the invasibility of clonal organisms.
Identification of bacterial agents and antimicrobial susceptibility of neonatal sepsis: A 54-month study in a tertiary hospital

The spectrum of bacteria which cause neonatal sepsis varies in different parts of the world. Antibiotic resistance is an increasing problem of these bacteria. The aim of this study was to detect the most common bacterial causes of neonatal sepsis and determination of their sensitivity to antibiotics. In a descriptive cross-sectional study, records of the neonates suspicious to neonatal sepsis who were admitted to Neonatal Intensive Care Unit (NICU) were assessed. Neonates with positive blood culture along with clinical signs of sepsis were entered in the study. Evaluated data included: age, sex, birth weight, type of infection, type of isolated pathogen, antibiotic sensitivity and disease outcome. Of 3700 screened blood cultures, 153 (4.1%) reported as positive, 76.5% of the evaluated neonates were preterm, 142 (92.8%) had gram negative sepsis and 11 (7.2%) had gram positive sepsis. The most common isolated gram negative bacteria were Klebsiella pneumoniae (46.4%), enterobacter spp. (17.6%) and Escherishia coli (14.4%). Coagulase negative staphylococci (CONS) were the most prevalent gram positive bacteria (5.9%) in this study. All of the klebsiella and enterobacter strains were resistant to ampicillin and gentamicin. The sensitivity of K. pneumoniae and enterobacter to imipenem was: 90 and 92.5%, respectively. Prevalence of early and late-onset sepsis was 64.7 and 35.3% respectively. Mortality rate of sepsis in this study was reported as 53.5%. In conclusion, the most common cause of bacterial sepsis in this study was K. pneumoniae which was completely resistant to ampicillin and gentamicin. So empirical treatment of sepsis with ampicillin and gentamicin in Imam Khomeini NICU must be reconsidered.
Influence of dietary protein intake and glycemic index on the association between TCF7L2 HapA and weight gain.

BACKGROUND Genetic polymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BMI. OBJECTIVE The objective was to investigate whether TCF7L2 HapA is associated with weight development and whether such an association is modulated by protein intake or by the glycemic index (GI). DESIGN The investigation was based on prospective data from 5 cohort studies nested within the European Prospective Investigation into Cancer and Nutrition. Weight change was followed up for a mean (±SD) of 6.8 ± 2.5 y. TCF7L2 rs7903146 and rs10885406 were successfully genotyped in 11,069 individuals and used to derive HapA. Multiple logistic and linear regression analysis was applied to test for the main effect of HapA and its interaction with dietary protein or GI. Analyses from the cohorts were combined by random-effects meta-analysis. RESULTS HapA was associated neither with baseline BMI (0.03 ± 0.07 BMI units per allele; P = 0.6) nor with annual weight change (8.8 ± 11.7 g/y per allele; P = 0.5). However, a previously shown positive association between intake of protein, particularly of animal origin, and subsequent weight change in this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01). We showed that weight gain becomes independent of protein intake with an increasing number of HapA alleles. Substitution of protein with either fat or carbohydrates showed the same effects. No interaction with GI was observed. CONCLUSION TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet.
FEEDING BELIEFS AND PRACTICES OF MOTHERS/ CAREGIVERS FOR THEIR INFANTS

th November to 16 th December, 2001. METHODS: One hundred infants admitted in paediatrics ward were selected for the study. Study was based on a questionnaire, developed to collect information by interviewing mothers to ascertain their infant feeding practices and various beliefs/taboos affecting these practices. RESULTS: One hundred mothers belonging to urban and rural areas were interviewed. At birth, 71% of mothers discarded colostrum. The frequency of breast-feeding was high initially but due to variety of socio-cultural reasons, it declined rapidly with early supplementation of bottlefeeding. Pre-lacteal feeding was a major reason for breast feeding delay. Exclusive breastfeeding was of short duration. Inadequate weaning in terms of quality and quantity was observed common. Cultural beliefs and taboos were affecting the weaning in majority of the cases. CONCLUSION: Lack of maternal education about feeding the infant is significant in our set up. There is, therefore, a need to educate the mothers about correct feeding practices so that healthy growth of the infants can be maintained.
Psychosocial experiences of foreign and native patients with/without pain

The psychosocial experiences of foreign/native primary care patients with/without pain were examined. The study comprised 328 foreign patients and 794 native patients who completed various scales (e.g. burnout). The design was cross-sectional and data were collected over 15 consecutive days at 20 randomly selected primary care centres. Pain patients were faring worse than pain-free patients concerning demographics/finances, depression, burnout and job demands/control/strain. Foreign pain patients had the worst situation of all patients. Foreign background was a risk factor for depression and burnout. Foreign pain patients also had a more severe clinical situation (e.g. disability) than native pain patients and being a foreign pain patient was associated with a higher risk of disability/the diagnosis of multiple pain. However, foreign background was not a pain risk factor. Female gender was a risk factor for pain and for complex/constant pain/disability. Variables such as sick leave were also important. The authors confirmed previous research and may have provided new insights into the experiences of foreign/native primary care patients with/without pain. However, further research appears necessary, not the least concerning the role of burnout as an antecedent to pain and the role of ethnicity.
The role of -1984A> G adrenomedullin gene polymorphism in tubal ectopic pregnancy

Objective: Tubal ectopic pregnancy is a health issue that can cause maternal death in first trimester and our knowledge about its pathogenesis is limited. Adrenomedullin (ADM) is responsible from regulation of ciliary motility in fallopian tubes. Its expression is known to be reduced in tubal tissue in ectopic pregnancy. In this study, it was aimed to investigate the relationship between -1984A>G functional polymorphism affecting the expression level of the ADM gene and tubal ectopic pregnancies. Material and Methods: This prospective case-control study consisted of 64 women. Peripheral blood samples were obtained from 31 women diagnosed with tubal pregnancy (the study group) and 33 fertile women without a history of ectopic pregnancy (the control group). Genomic DNA was extracted from peripheral blood. The frequency of genotypes and alleles of â"1984A>G ADM (rs3814700) gene polymorphism was examined by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP) method. Results: For -1984A>G polymorphism the study group had an A allele frequency of 90% and a G allele frequency of 10%; the control group had an A allele frequency of 91.7% and a G allele frequency of 7.3% (p=0.75). AA genotype frequency was 80% and AG allele frequency was 20% in the study group while they were 83.3% and 16.7%, respectively, in the control group (p=0.73). There were no significant differences between the study and control groups with respect to allele and genotype frequencies. Conclusion: This study found no significant relationship between tubal ectopic pregnancy and -1984A>G ADM gene polymorphism. Further studies are needed to explore other factors that affect ADM expression.
Impression Management 2.0

Investigated the relationship between self-reported (offline) personality traits and (online) self-presentation in social networking profiles on the Internet. Social networking sites like MySpace, Facebook, and StudiVZ are popular means of communicating personality. Recent theoretical and empirical considerations of homepages and Web 2.0 platforms show that impression management is a major motive for actively participating in social networking sites. 58 users (mean age 22.98 years) of the German Web 2.0 site, StudiVZ.net, completed online questionnaires assessing extraversion (NEO Personality Inventory, NEO-FFI), self-esteem (Rosenberg Self-Esteem Scale, RSES), and efficacy of self-presentation, and their profiles were subject to a content analysis. Findings reveal a slight influence of extraversion on self-presentation, whereas there was no significant effect for self-esteem. Moveover, analyses of respondents' profiles showed that self-efficacy with regard to impression management is strongly related to the number of virtual friends, the level of profile detail, and the style of the personal photo.
Risk of Adverse Health Outcomes with Increasing Duration and Regularity of Opioid Therapy

Purpose: The purpose of this study was to examine trends in frequency and daily dosage of opioid use and related adverse health outcomes in a commercially insured population. Methods: We examined medical claims from the Truven Health MarketScan commercial claims database for 789,457 continuously enrolled patients ages 18 to 64 years to whom opioids were dispensed during the first half of 2008. We tracked them every 6 months until either opioid use was discontinued or the end of 2010. We compared outcomes among all opioid users with those for patients who used opioids with only limited interruptions during the index period, referred to as “daily users. ” We contrasted the experience of daily users, other users, and nonusers for various outcomes. Results: Of all claimants, 10.7% had at least one opioid prescription during the first 6 months of 2008. Of these, 39.9% continued through a second 6-month period, and 18.0% continued through the end of 2010. Only 9.0% of all users qualified as daily users, but 87.1% of them continued some use of opioids through the end of 2010. Only 43.8% of all users who continued use through 2010 initially qualified as daily users. Among all users who continued use through 2010, days of use and daily dosage increased with duration of use. Among daily users, only dosage increased, rising from 101 to 114 morphine milligram equivalents/day over the 3 years. The prevalence of benzodiazepine use was greater for daily than all users, exceeding 40% among daily users who continued opioid use for 3 years. Drug abuse and overdose rates increased with longer use. Daily users accounted for 25.0%, other users for 43.6%, and nonusers for 31.4% of opioid analgesic overdoses. Conclusions: Adverse health outcomes can increase with accumulating opioid use and increasing dosage. Existing guidelines developed by specialty societies for managing patients using opioids daily or nearly daily do not address the larger number of patients who use opioids intermittently over periods of years. Practitioners should consider applying such guidelines to patients who use opioids less frequently.