Miracle-dz/UniFAR-FTUs huggingface dataset:
Masking the 5′ terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex

Hepatitis C virus subverts liver-specific microRNA, miR-122, to upregulate viral RNA abundance in both infected cultured cells and in the liver of infected chimpanzees. These findings have identified miR-122 as an attractive antiviral target. Thus, it is imperative to know whether a distinct functional complex exists between miR-122 and the viral RNA versus its normal cellular target mRNAs. Toward this goal, effects on viral RNA abundance of mutated miR-122 duplex molecules, bound at each of the two target sites in the viral genome, were compared to effects on microRNA- or siRNA-mediated regulation of reporter target mRNAs. It was found that miR-122 formed an unusual microRNA complex with the viral RNA that is distinct from miR-122 complexes with reporter mRNAs. Notably, miR-122 forms an oligomeric complex in which one miR-122 molecule binds to the 5′ terminus of the hepatitis C virus (HCV) RNA with 3′ overhanging nucleotides, masking the 5′ terminal sequences of the HCV genome. Furthermore, specific internal nucleotides as well as the 3′ terminal nucleotides in miR-122 were absolutely required for maintaining HCV RNA abundance but not for microRNA function. Both miR-122 molecules utilize similar internal nucleotides to interact with the viral genome, creating a bulge and tail in the miR-122 molecules, revealing tandemly oriented oligomeric RNA complexes. These findings suggest that miR-122 protects the 5′ terminal viral sequences from nucleolytic degradation or from inducing innate immune responses to the RNA terminus. Finally, this remarkable microRNA-mRNA complex could be targeted with compounds that inactivate miR-122 or interfere with this unique RNA structure.
Gender Differences in Predictors of Quality of Life at the Initiation of Radiation Therapy.

PURPOSE/OBJECTIVES To evaluate gender differences in quality of life (QOL), demographic, clinical, and symptom characteristics. DESIGN Prospective, observational. SETTING Two radiation oncology departments in northern California. SAMPLE 185 patients before initiation of radiation therapy (RT). METHODS At their RT simulation visit, patients completed a demographic questionnaire, a measure of QOL, and symptom-specific scales. Backward elimination regression analyses were conducted to determine the significant predictors of QOL . MAIN RESEARCH VARIABLES QOL, gender, and 20 potential predictors . FINDINGS In women, depressive symptoms, functional status, age, and having children at home explained 64% of the variance in QOL. In men, depressive symptoms, state anxiety, number of comorbidities, being a member of a racial or ethnic minority, and age explained 70% of the variance in QOL . CONCLUSIONS Predictors of QOL differed by gender. Depressive symptom score was the greatest contributor to QOL in both genders. IMPLICATIONS FOR NURSING Nurses need to assess for QOL and depression at the initiation of RT. Knowledge of the different predictors of QOL may be useful in the design of gender-specific interventions to improve QOL.
Parents Seeking Health-Related Information on the Internet: Cross-Sectional Study

Background The Internet represents an increasingly common source of health-related information, and it has facilitated a wide range of interactions between people and the health care delivery system. Objective To establish the extent of Internet access and use to gather information about health topics and the potential implications to health care among the adult population in Calabria region, Italy. Methods This cross-sectional study was conducted from April to June 2012. The sample consisted of 1544 adults aged ≥18 years selected among parents of public school students in the geographic area of Catanzaro in southern Italy. A 2-stage sample design was planned. A letter summarizing the purpose of the study, an informed consent form, and a questionnaire were given to selected student to deliver to their parents. The final survey was formulated in 5 sections: (1) sociodemographic characteristics, (2) information about chronic diseases and main sources of health care information, (3) information about Internet use, (4) data about the effects of using the Internet to search for health information, and (5) knowledge and use of social networks. Results A total of 1039 parents completed the questionnaire, with a response rate equivalent to 67.29%. Regarding health-related information types, 84.7% of respondents used the Internet to search for their own medical conditions or those of family members or relatives, 40.7% of parents reported looking for diet, body weight, or physical activity information, 29.6% searched for vaccines, 28.5% for screening programs, and 16.5% for smoking cessation tools and products. The results of the multiple logistic regression analysis showed that parents who looked for health-related information on the Internet were more likely to be female (OR 1.53, 95% CI 1.05-2.25), with a high school diploma (OR 1.69, 95% CI 1.02-2.81) or college degree (OR 2.14, 95% CI 1.21-3.78), younger aged (OR 0.96, 95% CI 0.94-0.99), with chronic conditions (OR 1.94, 95% CI 1.17-3.19), not satisfied with their general practitioner’s health-related information (OR 0.6, 95% CI 0.38-0.97), but satisfied with information from scientific journals (OR 1.99, 95% CI 1.33-2.98). Conclusions Our analyses provide important insights into Internet use and health information–seeking behaviors of the Italian population and contribute to the evidence base for health communication planning. Health and public health professionals should educate the public about acquiring health information online and how to critically appraise it, and provide tools to navigate to the highest-quality information. The challenge to public health practice is to facilitate the health-promoting use of the Web among consumers in conjunction with their health care providers.
A Single Long‐Term Acute Care Hospital Experience with a Pressure Ulcer Prevention Program

Purpose: The occurrence of pressure ulcers (PrUs) challenges care facilities. Few studies report PrU reduction efforts in long‐term acute care (LTAC). This study described the PrU reduction efforts of a single, LTAC facility using the Medline Pressure Ulcer Prevention Program (mPUPP). Design: This study was a quasi‐experimental, quality improvement project, with pre‐ and postmeasurement design. Methods: Outcomes were tracked for 24 months. The mPUPP was implemented in month 11. Education for caregivers was provided through an interactive web‐based suite. In addition, all Patient Care Technicians attended a 4‐week 1‐hour inservice. New skin care products were implemented. The facility also implemented an algorithm for treatment of wounds. Findings: There was a significant reduction in the mean monthly hospital‐acquired PrU (nPrU) rate when preprogram is compared to postprogram. Conclusions: Sustainable nPrU reduction can be achieved with mPUPP. Clinical Relevance: LTAC hospitals could expect to reduce nPrU with education and incentive of caregivers.
SR 141716A differentially attenuates the behavioral effects of Δ9-THC in rhesus monkeys

The prototypic cannabinoid CB1 antagonist SR 141716A is one important pharmacologic tool for examining CB1 receptors that mediate the behavioral and physiologic effects of Δ9-tetrahydrocannabinol (Δ9-THC). This study examined the effects of SR 141716A on the rate-decreasing, hypothermic and discriminative stimulus effects of Δ9-THC in rhesus monkeys. In monkeys (n=4) responding under a multiple fixed ratio (FR-10:FR-10) schedule of food presentation and stimulus–shock termination, the potency of i.m. Δ9-THC to decrease responding in the food component (ED50=0.64 mg/kg) was threefold greater than its potency in the stimulus–shock termination component (ED50=2.14 mg/kg). In the same monkeys, hypothermia was induced by Δ9-THC at a dose (e.g. 0.32 mg/kg) that did not alter responding in either schedule component; the maximum decrease was 2.1°C at a dose of 3.2 mg/kg. A dose of 0.32 mg/kg of SR 141716A, significantly attenuated Δ9-THC-induced hypothermia without attenuating the rate-decreasing effects of Δ9-THC in either component of the multiple schedule. The largest dose of i.m. SR 141716A that was studied, 1.0 mg/kg, significantly decreased rectal temperature and responding in the food component but did not significantly decrease responding in the stimulus–shock termination component of the multiple schedule. In a separate group of monkeys (n=3) that discriminated i.v. Δ9-THC (0.1 mg/kg) while responding under an FR-5 schedule of stimulus–shock termination, SR 141716A (0.32 and 1 mg/kg) significantly increased the ED50 of the Δ9-THC by 2.3- and 3.7-fold, respectively. Collectively, these results demonstrate that the behavioral effects of Δ9-THC are not equally attenuated by SR 141716A.
Second Transmembrane Domains of ENaC Subunits Contribute to Ion Permeation and Selectivity*

Epithelial sodium channels (ENaC) are composed of three structurally related subunits (α, β, and γ). Each subunit has two transmembrane domains termed M1 and M2, and residues conferring cation selectivity have been shown to reside in a pore region immediately preceding the M2 domains of the three subunits. Negatively charged residues are interspersed within the M2 domains, and substitution of individual acidic residues within human α-ENaC with arginine essentially eliminated channel activity in oocytes, suggesting that these residues have a role in ion permeation. We examined the roles of M2 residues in contributing to the permeation pore by individually mutating residues within the M2 domain of mouse αENaC to cysteine and systematically characterizing functional properties of mutant channels expressed in Xenopus oocytes by two-electrode voltage clamp. The introduction of cysteine residues at selected sites, including negatively charged residues (αGlu595, αGlu598, and αAsp602) led to a significant reduction of expressed amiloride-sensitive Na+ currents. Two mutations (αE595C and αD602C) resulted in K+-permeable channels whereas multiple mutations altered Li+/Na+ current ratios. Channels containing αD602K or αD602A also conducted K+ whereas more conservative mutations (αD602E and αD602N) retained wild type selectivity. Cysteine substitution at the site equivalent to αAsp602 within β mENaC (βD544C) did not alter either Li+/Na+ or K+/Na+ current ratios, although mutation of the equivalent site within γ mENaC (γD562C) significantly increased the Li+/Na+ current ratio. Mutants containing introduced cysteine residues at αGlu595, αGlu598, αAsp602, or αThr607did not respond to externally applied sulfhydryl reagent with significant changes in macroscopic currents. Our results suggest that some residues within the M2 domain of αENaC contribute to the channel's conduction pore and that, in addition to the pore region, selected sites within M2 (αGlu595 and αAsp602) may have a role in conferring ion selectivity.
Craniofacial Morphology in Complete Unilateral Cleft Lip and Palate Patients Consecutively Treated With 1-Stage Repair of the Cleft

Objective:To retrospectively evaluate the craniofacial morphology of children with a complete unilateral cleft lip and palate treated with a 1-stage simultaneous cleft repair performed in the first year of life. Methods:Cephalograms and extraoral profile photographs of 61 consecutively treated patients (42 boys, 19 girls) who had been operated on at 9.2 (SD, 2.0) months by a single experienced surgeon were analyzed at 11.4 (SD, 1.5) years. The noncleft control group comprised 81 children (43 boys and 38 girls) of the same ethnicity at the age of 10.4 (SD, 0.5) years. Results:In children with cleft, the maxilla and mandible were retrusive; the palatal and mandibular planes were more open, and sagittal maxillomandibular relationship was less favorable in comparison to noncleft control subjects. Soft tissues in patients with cleft reflected retrusive morphology of hard tissues-subnasal and supramental regions were less convex, profile was flatter, and nasolabial angle was more acute relative to those of the control subjects. Conclusions:Craniofacial morphology after 1-stage repair was deviated in comparison with noncleft control subjects. However, the degree of deviation was comparable with that found after treatment with alternative surgical protocols.
Ionic effects on the motility of bull and chimpanzee spermatozoa.

Summary. The effects of potassium, sodium, chloride and calcium on the percentage progressive motility of samples of chimpanzee and bull spermatozoa were investigated. Inhibitors and stimulatory of motility were identified. Three parameters of chimpanzee sperm motility, velocity, frequency and amplitude, were measured. There was no consistent change related to ion concentration. The ionic constituents of chimpanzee and bull seminal plasma were also analysed.
Endogenous antiviral microRNAs determine permissiveness for hepatitis B virus replication in cultured human fetal and adult hepatocytes

Superior cell culture models for hepatitis B virus (HBV) will help advance insights into host‐virus interactions. To identify mechanisms regulating HBV replication, this study used cultured human HepG2 cells and adult or fetal hepatocytes transduced with adenoviral vector to express HBV upstream of green fluorescent protein. The vector efficiently transduced all cell types. In HepG2 cells, replicative viral intermediates, nucleocapsid‐associated HBcAg, and HBsAg were expressed. However, in fetal or adult hepatocytes, pregenomic HBV RNA and viral RNAs were expressed, but nucleocapsid‐associated HBcAg in cells or HBsAg in culture medium were absent, indicating interruptions in viral replication due to possible microRNA‐related interference. MicroRNA profiling demonstrated that a large number of microRNAs with antiviral potential were differentially expressed in hepatocytes after culture. In transfection assays using HepG2 cells, candidate antiviral microRNAs, e.g., hsa‐miR‐24 or hsa‐miR‐638 decreased the levels of HBV transcripts or HBV gene products. Since candidate microRNAs could have targeted interferon response genes as an alternative explanation interferon signaling was examined. However, HBV replication in cultured hepatocytes was not restored despite successful inhibition of JAK1/2‐STAT signaling by the inhibitor, ruxolitinib. Therefore, HBV was unable to complete replication in cultured hepatocytes due to expression of multiple antiviral microRNAs. This mechanism should help understand restrictions in HBV replication for developing HBV models in cultured cells while providing frameworks for pathophysiological studies of HBV replication in subsets of hepatocytes or stem/progenitor cells during hepatitis. J. Med. Virol. 87:1168–1183, 2015. © 2015 Wiley Periodicals, Inc.
Randomized trial of two schedules of low‐dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML‐19)

This study compared two schedules of low‐dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukaemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best supportive care or a course of GO according to one of two schedules: 3 mg/m2 on days 1, 3 and 5 (arm A), or GO 6 mg/m2 on day 1 and 3 mg/m2 on day 8 (arm B). Primary endpoint was the rate of disease non‐progression (DnP), defined as the proportion of patients either achieving a response or maintaining a stable disease following GO induction in each arm. Fifty‐six patients were randomized in the two GO arms (A, n = 29; B, n = 27). The rate of DnP was 38% [90% confidence interval (CI), 23–55] in arm A, and 63% (90% CI, 45–78) in arm B. Peripheral cytopenias were the most common adverse events for both regimens. The all‐cause early mortality rate was 14% in arm A and 11% in arm B. The day 1 + 8 schedule, which was associated with the highest rate of DnP, met the statistical criteria to be selected as the preferred regimen for phase III comparison with best supportive care.
Optimal timing of surgery for active infective endocarditis with cerebral complications: a Japanese multicentre study.

OBJECTIVES The aim of this study was to investigate the effect of the timing of valve surgery on the clinical outcomes of patients with active infective endocarditis (IE) accompanied by cerebral complications. METHODS We retrospectively analysed a cohort of 568 patients, comprising 118 with non-haemorrhagic cerebral infarction (CI), 54 with intracranial haemorrhage (ICH) and 396 without cerebral events (C; control), who underwent surgery for left-sided active IE in 15 Japanese institutes from 2000 to 2011. The mean age was 58.4 ± 16.9 years in the CI group; 54.5 ± 17.4 years in the ICH group and 56.9 ± 16.0 years in the C group. Clinical outcomes were analysed according to the timing of surgery after the diagnosis of CI or ICH was made. RESULTS In the CI group, there were 9 (7.6%) hospital deaths, 13 (11%) new cerebral events and 1 (0.8%) redo valve surgery. In the ICH group, there were 3 (5.6%) hospital deaths, 8 (14.8%) new cerebral events and 2 (3.7%) redo valve surgeries. In the C group, there were 36 (9.1%) hospital deaths, 23 (5.8%) new cerebral events and 9 (2.3%) redo valve surgeries. Risk factors for hospital death were prosthetic valve endocarditis (P = 0.045), high C-reactive protein (CRP; P < 0.001) and the elderly (P < 0.001) in the CI group. Delayed surgery (2 weeks after CI) seemed result in a higher incidence of hospital death in the CI group. Patients who had surgery between 15 and 28 days or after 29 days from the onset of CI had higher incidences of hospital death [odds ratio 5.90 (P = 0.107) and 4.92 (P = 0.137), respectively] compared with those who had surgery within 7 days. In the ICH group, risk factors for hospital death were high CRP (P = 0.002) and elderly (P < 0.001). Contrary to CI patients, patients who had surgery between 8 and 21 days or after 22 days after the onset of ICH had lower incidences of hospital death [odds ratio 0.79 (P = 0.843) and 0.12 (P = 0.200), respectively] compared with those who had surgery within 7 days. CONCLUSIONS Although statistically insignificant, early surgery in active IE patients with CI is safe, but very early surgery (within 7 days) should be avoided in patients with ICH.
Cangrelor for the treatment of arterial thrombosis: pharmacokinetics/pharmacodynamics and clinical data

Introduction: Dual antiplatelet therapy is the standard of care for patients with acute coronary syndromes or with recent coronary stents implantation. P2Y12 receptor antagonists have shown to reduce the risk of recurrent ischemic events among these patients, at the expense of an increased risk of bleeding. Cangrelor is a novel, intravenous, short-acting, reversible platelet P2Y12 inhibitor, which has been evaluated for the treatment of arterial thrombosis. Areas covered: Studies on the pharmacological characteristics of cangrelor and clinical trials were retrieved by a PubMed literature search. Expert opinion: Cangrelor has been tested in patients with coronary artery diseases undergoing percutaneous coronary intervention and as bridging therapy for patients undergoing coronary artery bypass graft. The rapid peak of action allows a fast and complete inhibition of platelet aggregation; the rapid offset is advantageous in case of bleeding complications; and finally, the intravenous administration also makes this drug suitable for patients unable to consume oral medications. Unfortunately, the large clinical trials evaluating cangrelor in percutaneous coronary intervention did not show superiority to the standard antiplatelet therapy, and its future use in this setting still needs to be better assessed. Conversely, when used as bridging therapy to coronary artery bypass graft, cangrelor showed promising results.
Class II MHCs In Silico Identification of Supertypes for

The development of epitope-based vaccines, which have wide population coverage, is greatly complicated by MHC polymorphism. The grouping of alleles into supertypes, on the basis of common structural and functional features, addresses this problem directly. In the present study we applied a combined bioinformatics approach, based on analysis of both protein sequence and structure, to identify similarities in the peptide binding sites of 2225 human class II MHC molecules, and thus deﬁne supertypes and supertype ﬁngerprints. Two chemometric techniques were used: hierarchical clustering using three-dimensional Comparative Similarity Indices Analysis ﬁelds and nonhierarchical k -means clustering using sequence-based z -descriptors. An average consensus of 84% was achieved, i.e., 1872 of 2225 class II molecules were classiﬁed in the same supertype by both techniques. Twelve class II supertypes were deﬁned: ﬁve DRs, three DQs, and four DPs. The HLA class II supertypes and their ﬁngerprints given in parenthesis are DR1 (Trp 9 (cid:1) ), DR3 (Glu 9 (cid:1) , Gln 70 (cid:1) , and Gln/Arg 74 (cid:1) ), DR4 (Glu 9 (cid:1) , Gln/Arg 70 (cid:1) , and Glu/Ala 74 (cid:1) ), DR5 (Glu 9 (cid:1) , Asp 70 (cid:1) ), and DR9 (Lys/Gln 9 (cid:1) ); DQ1 (Ala/Gly 86 (cid:1) ), DQ2 (Glu 86 (cid:1) , Lys 71 (cid:1) ), and DQ3 (Glu 86 (cid:1) , Thr/Asp 71 (cid:1) ); DPw1 (Asp 84 (cid:1) and Lys 69 (cid:1) ), DPw2 (Gly/Val 84 (cid:1) and Glu 69 (cid:1) principal component analysis and hierarchical clustering (18). We applied this approach to class I MHC molecules belonging to the HLA-A, HLA-B, and HLA-C loci and showed that only 1–3 aa are sufﬁcient for an allele to be classiﬁed within a particular supertype.
Characteristics of cancer blog users.

Blogs are a relatively new medium in computer-mediated health communication and are regarded as highly opinionated journals maintained by millions of users who read and write personal remarks on issues ranging from news stories to health care [1–3]. Of the 120 million US adults with Internet access, 7%, or 8 million people, have created blogs [4], and the increasing use of blogs has been reported in several studies [1,4,5]. Rainie found that the typical blogger is a young, male, Internet veteran; has a broadband connection; and is financially secure [5]. The gender of the blogger has also been a topic for research. Herring et al. found that even though women participate in blogging activities (focusing on emotional support), men are more likely to create filter blogs and k-logs (knowledge blogs) that are considered focused on information [1]. Blogs have been described as a new medium, one that shifts mainstream control of information into the hands of the audience. The potential use of blogs for cancer patients, basic scientists, clinical researchers, and practicing oncologists to discuss findings and suggestions has been envisioned in several cancer journals [6]. In addition, the use of online communication tools to share emotional support in all aspects of cancer-related issues has been frequently described [2,6]. While blogs are becoming more frequently researched, empirical studies regarding blogs and their users, especially cancer patients and their companions (defined for this study as patient family and friends), are noticeably lacking. Most research has been in the area of news media [7]. Some research has been reported in lexical (textual) analyses from studies designed to provide technological frameworks to classify blog messages for improved accessibility [8,9]. However, questions regarding motivation to post or comment on blogs and the perceived outcomes of using blogs still remain challenging research tasks [10,11]. Understanding how blogs are used can allow information providers to better understand the impact blogs can have on cancer patients, their friends, and families. This study used cluster analysis techniques to classify cancer blog users' demographics, as well as their use and perceptions of blogs.