Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogenetic clustering of hepatitis C virus among people who inject drugs in Vancouver, Canada

Little is known about factors associated with hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Phylogenetic clustering and associated factors were evaluated among PWID in Vancouver, Canada. Data were derived from the Vancouver Injection Drug Users Study. Participants who were HCV antibody‐positive at enrolment and those with HCV antibody seroconversion during follow‐up (1996 to 2012) were tested for HCV RNA and sequenced (Core‐E2 region). Phylogenetic trees were inferred using maximum likelihood analysis and clusters were identified using ClusterPicker (90% bootstrap threshold, 0.05 genetic distance threshold). Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n = 313), G1b: 6% (n = 41), G2a: 3% (n = 20), G2b: 7% (n = 46), G3a: 33% (n = 213), G4a: <1% (n = 4), G6a: 1% (n = 8), G6e: <1% (n = 1), and unclassifiable: 1% (n = 9). The mean age was 36 years, 162 (25%) were female, and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n = 156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (versus age ≥40, adjusted odds ratio [AOR] = 1.64; 95% confidence interval [CI] 1.03, 2.63), human immunodeficiency virus (HIV) infection (AOR = 1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR = 3.05; 95% CI 1.40, 6.66), and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36). Conclusion: In this sample of PWID, one‐third demonstrated phylogenetic clustering. Factors independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these subpopulations. (Hepatology 2014;60:1571–1580)
A Method to Measure Perceptions of Food Among the Elderly

A method to measure food perceptions among the elderly was developed using focus group and Q-sort methodologies. The 78 elderly participants responded favorably to the method which resembled a card game. The strongest perceptions of food as quantified using factor analysis were the expense of the food and the health promoting qualities. Convenience and health promoting qualities of food were positively related to consumption while expense was negatively related to food consumption.
Unilateral vocal fold paralysis

The treatment of unilateral vocal fold paralysis continues to evolve; enhancement of vocal function and prevention of aspiration remain the principal goals. Voice therapy, vocal fold injection, laryngeal framework surgery, and laryngeal reinnervation or pacing techniques are currently employed or proposed tools in the armamentarium for treating this condition. The past year has seen advances in and refinements of treatment options for unilateral vocal fold paralysis, as well as further study into its pathophysiology and diagnosis. There is no current consensus on the optimum treatment because the ability to reconstitute normal physiologic function is not yet in hand.
Polymorphisms in melanoma differentiation‐associated gene 5 link protein function to clearance of hepatitis C virus

Among patients newly infected with hepatitis C virus (HCV), only 20‐30% clear the infection spontaneously. In the remaining 70% the infection persists, causing chronic liver inflammation and disease. It is well established that polymorphisms in host genes, especially in components of the innate immune response, contribute to the phenomenon of spontaneous HCV clearance. Retinoic acid inducible gene‐I (RIG‐I)‐like helicases such as melanoma differentiation‐associated gene 5 (MDA‐5) are cytoplasmic sensors of viral RNA that are critical for triggering innate immune responses after infection with RNA viruses. We analyzed 14 nonsynonymous single‐nucleotide polymorphisms in RIG‐I‐like helicase‐pathway‐genes comparing European patients who spontaneously cleared HCV (n = 285) or had persistent infection (n = 509). We found that polymorphic haplotypes in the MDA‐5 gene IFIH1 encoding histidine at position 843 and threonine at position 946 strongly correlate with the resolution of HCV infection (odds ratio [OR]: 16.23; 95% confidence interval [CI]: 3.67‐71.87; P = 1.1 × 10−6). Overexpression of MDA‐5 genetic variants in HEK 293 cells and in a tissue culture model of HCV infection revealed that the histidine 843/threonine 946 variant leads to increased baseline and ligand‐induced expression of interferon‐induced genes and confers an increased ability to suppress HCV replication. Conclusion: These data suggest that MDA‐5 plays a significant role in the defense against HCV and that polymorphisms in MDA‐5 can influence the outcome of HCV infection. (Hepatology 2015;61:460‐470)
Portal hypertension and the outcome of surgery for hepatocellular carcinoma in compensated cirrhosis: A systematic review and meta‐analysis

Whether preoperative clinically significant portal hypertension (CSPH) has or not an impact on the outcome of surgery for hepatocellular carcinoma (HCC) in patients with compensated cirrhosis is debated. This systematic review assesses the impact of CSPH on the outcome of HCC in patients with compensated cirrhosis treated with surgery. We performed a systematic search of the MEDLINE database (articles published in full in English language from 1996 to October 2013) and related bibliography for studies reporting on the postoperative outcomes (3‐ and 5‐year mortality and/or early clinical decompensation) of patients with HCC and compensated cirrhosis treated with surgery according to the presence or absence of CSPH. Independent extraction of articles by two authors using predefined data fields, including study quality indicators, was used; pooled analyses were based on random‐effects models. Eleven studies in total met our inclusion criteria (eight studies for 3‐ and 5‐year postoperative mortality and eight for postoperative clinical decompensation). Moderate heterogeneity among studies for both outcomes was observed, which disappeared after pooling studies using similar methods to assess CSPH. The presence of CSPH increased the risk of 3‐ and 5‐year mortality versus absence of CSPH (pooled odds ratio [OR] for 3‐year mortality: 2.09; 95% confidence interval [CI]: 1.52‐2.88; for 5‐year mortality: 2.07; 95% CI: 1.51‐2.84). CSPH also increased the risk of postoperative clinical decompensation (pooled OR: 3.04; 95% CI: 2.02‐4.59). Conclusions: CSPH (evaluated by any method) significantly increases the risk of 3‐ and 5‐year mortality and of clinical decompensation after surgery for HCC. (Hepatology 2015;61:526‐536)
Prospective validation of Baveno V definitions and criteria for failure to control bleeding in portal hypertension

New definitions and criteria were released at the Baveno V consensus meeting. The purposes of this study were to verify Baveno V definitions and criteria for failure to control bleeding and to determine the usefulness of the combined use of the Adjusted Blood Requirement Index [ABRI: (number of blood units)/(final hematocrit‐initial hematocrit)+0.01] with Baveno V criteria. In all, 246 consecutive liver cirrhosis patients with acute bleeding associated with portal hypertension were enrolled prospectively between January 2010 and October 2012. The treatment outcome on day 5 was assessed by endoscopy. For the ABRI calculation, two hematocrit levels were used as the initial hematocrit: the first level measured upon patient arrival (ABRI‐A) and the lowest level measured before transfusion (ABRI‐B). Treatment failures were identified in 53 patients, of whom 24 died. Based on repeated endoscopic findings, 29 patients were identified as treatment failures, while according to Baveno V criteria, 47 patients were regarded as treatment failures. The area under the receiver operating characteristic curve (AUROC) of Baveno V criteria was 0.906, and the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 83.0%, 98.4%, 93.6%, 95.5%, 53.41, and 0.17, respectively. The AUROC of Baveno V criteria was significantly greater than those of Baveno IV (P = 0.0001) and Baveno II/III (P < 0.0001) criteria. Adding ABRI‐A or ‐B to Baveno V criteria resulted in a significant reduction of the AUROC (P < 0.05). Conclusion: The Baveno V criteria are good predictors of treatment failure of early‐stage acute gastrointestinal bleeding in patients with portal hypertension, while the addition of ARBI does not improve the prediction accuracy of the outcome of bleeding. (Hepatology 2015;61:1033–1040)
Lipid-Lowering Effect and Efficacy After Switching to Etravirine in HIV-Infected Patients With Intolerance to Suppressive HAART

Abstract Purpose: Etravirine (ETR) has shown a good lipid profile in previous studies. The aim of this study was to determine the virologic, immunologic, and lipid outcome in HIV-infected patients switching to an ETR-based antiretroviral regimen due to intolerance or toxicity. Methods: Observational cohort study of 125 HIV-infected patients who switched therapy to an ETR-based regimen. The lipid profile, including total triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was compared after 24 weeks. Results: Patients changed from efavirenz (n = 34; 28%) and ritonavir-boosted protease inhibitors (PI/r; 67 cases: 21 atazanavir, 21 lopinavir, 11 fosamprenavir, 14 darunavir). Hyperlipidemia was the cause in only 22 patients (18%). At 24 weeks, a significant decrease was observed in mean TC level (-8%), LDL-C (-8%), TC:HDL ratio (-6%), and TG level (-20%). For patients receiving previously efavirenz, there was a significant reduction in TC (-23 mg/dL; -13%) and LDL-C (-25 mg/dL; -21%) levels and a trend to a better TG level (-38 mg/dL; -21%;P = .06). In the case of prior PI/r therapy, there was also a significant reduction in TC (-14 mg/dL; -6%) and TG levels (-58 mg/dL; -16%), mostly in prior lopinavir- or fosamprenavir-based therapy (TC -15%; TG -53%). Median CD4+ count increased from 513 to 621 cells/µL (P = .03), and there were only 3 cases of virologic failure (2%). Conclusions: In patients switching to an ETR-containing regimen, there is a significant improvement of lipids and maintenance of immunologic and virologic response. This lipid-lowering effect was irrespective of the presence of previous hyperlipidemia and for patients receiving different antiretroviral drugs.
The impairment of sexual function is less distressing for menopausal than for premenopausal women.

INTRODUCTION Menopause requires psychological and physical adjustments because of the occurring significant hormonal changes. Sexuality is one of the aspects that undergoes the most profound modifications. Preliminary data suggest that sometimes women do not regard sexual changes as problematic and often readjust their life and relationship according to their new physical status. AIM The aim of our study was to evaluate sexual function and the way women feel by comparing healthy postmenopausal and premenopausal women. METHODS One hundred menopausal (M) and 100 premenopausal (pM) healthy women were asked to complete anonymous questionnaires to assess sexual function and stress related to sexual activity. MAIN OUTCOME MEASURES Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS) were completed by M and pM women. Results. Medium FSFI score was 20.5 +/- 9.6 and 26.4 +/- 7.7 (P < 0.0005) and medium FSDS score was 12.1 +/- 11.7 (95% CI 9.7-14.4) and 11.3 +/- 10.2 (P = 0.917) for M and pM women, respectively. Twenty-five of the 69 M women and 20 of the 31 pM women with a pathological score in the FSFI questionnaire scored higher than 15 in the FSDS (P < 0.0005). The overall prevalence of sexual dysfunction was 20% and 25% (P = 0.5) in the M and pM women. CONCLUSIONS Our data confirm that menopause is associated with changes in sexual function that may be compatible with sexual dysfunction. However, personal distress caused by these changes in sexual life appears to be lower among menopausal women (36.2%) as compared with premenopausal women (64.5%). These data suggest that medical treatment for sexual health in menopause must be highly personalized and carefully prescribed.
Can oral contraceptives cause vestibulodynia?

AIM To describe the clinical course of a young woman who developed vestibulodynia with introital dyspareunia while on oral contraceptive (OCs) and to provide a possible explanation for the etiology of her symptoms as well as her recovery after treatment. METHODS A single case is presented including subjective reporting, laboratory evaluation, and quantitative sensory testing. RESULTS After topical hormonal therapy, the patient reported resolution of her dyspareunia and and her laboratory values normalized.
Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: A retrospective study

Recently, the beneficial effects of increased physical activity (PA) on nonalcoholic fatty liver disease (NAFLD) in obese subjects were reported. However, the optimal strength and volume of PA in lifestyle modification to improve NAFLD pathophysiology and be recommended as an appropriate management of this condition are unclear. The primary goal of this retrospective study was to estimate the beneficial effects of a varying volume of moderate to vigorous intensity PA (MVPA) on the improvement of NAFLD. A total of 169 obese, middle‐aged men were enrolled in a 12‐week weight reduction program through lifestyle modification consisting of dietary restrictions plus aerobic exercise. Among these obese subjects, 40 performed MVPA for <150 min·wk−1, 42 performed MVPA for 150‐250 min·wk−1, and 87 performed MVPA for >250 min·wk−1. The subjects in the MVPA ≥250 min·wk−1 group, in comparison with those in the MVPA <250 min·wk−1 group, showed significantly attenuated levels of hepatic steatosis (−31.8% versus −23.2%). This attenuation was likely independent of the detectable weight reduction. MVPA for ≥250 min·wk−1 in comparison with that for <150 min·wk−1 led to a significant decrease in the abdominal visceral adipose tissue severity (−40.6% versus −12.9%), levels of ferritin (−13.6% versus +1.5%), and lipid peroxidation (−15.1% versus −2.8%), and a significant increase in the adiponectin levels (+17.1% versus +5.6%). In association with these changes, the gene expression levels of sterol regulatory element‐binding protein‐1c and carnitine palmitoyltransferase‐1 in peripheral blood mononuclear cells also significantly decreased and increased, respectively. Conclusion: MVPA for ≥250 min·wk−1 as part of lifestyle management improves NAFLD pathophysiology in obese men. The benefits seem to be acquired through reducing inflammation and oxidative stress levels and altering fatty acid metabolism. (Hepatology 2015;61:1205–1215)
Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma

Radiofrequency ablation (RFA) is considered a curative treatment option for hepatocellular carcinoma (HCC). Growing data have demonstrated that cryoablation represents a safe and effective alternative therapy for HCC, but no randomized controlled trial (RCT) has been reported to compare cryoablation with RFA in HCC treatment. The present study was a multicenter RCT aimed to compare the outcomes of percutaneous cryoablation with RFA for the treatment of HCC. In all, 360 patients with Child‐Pugh class A or B cirrhosis and one or two HCC lesions ≤ 4 cm, treatment‐naïve, without metastasis were randomly assigned to cryoablation (n = 180) or RFA (n = 180). The primary endpoints were local tumor progression at 3 years after treatment and safety. Local tumor progression rates at 1, 2, and 3 years were 3%, 7%, and 7% for cryoablation and 9%, 11%, and 11% for RFA, respectively (P = 0.043). For lesions >3 cm in diameter, the local tumor progression rate was significantly lower in the cryoablation group versus the RFA group (7.7% versus 18.2%, P = 0.041). The 1‐, 3‐, and 5‐year overall survival rates were 97%, 67%, and 40% for cryoablation and 97%, 66%, and 38% for RFA, respectively (P = 0.747). The 1‐, 3‐, and 5‐year tumor‐free survival rates were 89%, 54%, and 35% in the cryoablation group and 84%, 50%, and 34% in the RFA group, respectively (P = 0.628). Multivariate analyses demonstrated that Child‐Pugh class B and distant intrahepatic recurrence were significant negative predictors for overall survival. Major complications occurred in seven patients (3.9%) following cryoablation and in six patients (3.3%) following RFA (P = 0.776). Conclusion: Cryoablation resulted in a significantly lower local tumor progression than RFA, although both cryoablation and RFA were equally safe and effective, with similar 5‐year survival rates. (Hepatology 2015;61:1579–1590)
Systematic analysis of berberine-induced signaling pathway between miRNA clusters and mRNAs and identification of mir-99a∼125b cluster function by seed-targeting inhibitors in multiple myeloma cells

Background: Berberine (BBR) is a natural alkaloid derived from a traditional Chinese herbal medicine. However, the exact mechanisms underlying the different effects of berberine on MM cells have not been fully elucidated. Methods: A systematic analysis assay integrated common signaling pathways modulated by the 3 miRNA clusters and mRNAs in MM cells after BBR treatment. The role of the mir-99a∼125b cluster, an important oncomir in MM, was identified by comparing the effects of t-anti-mirs with complete complementary antisense locked nucleic acids (LNAs) against mature mir-125b (anti-mir-125b). Results: Three miRNAs clusters (miR-99a∼125b, miR-17∼92 and miR-106∼25) were significantly down-regulated in BBR-treated MM cells and are involved in multiple cancer-related signaling pathways. Furthermore, the top 5 differentially regulated genes, RAC1, NFκB1, MYC, JUN and CCND1 might play key roles in the progression of MM. Systematic integration revealed that 3 common signaling pathways (TP53, Erb and MAPK) link the 3 miRNA clusters and the 5 key mRNAs. Meanwhile, both BBR and seed-targeting t-anti-mir-99a∼125b cluster LNAs significantly induced apoptosis, G2-phase cell cycle arrest and colony inhibition. Conclusions: our results suggest that BBR suppresses multiple myeloma cells, partly by down-regulating the 3 miRNA clusters and many mRNAs, possibly through TP53, Erb and MAPK signaling pathways. The mir-99a∼125b cluster might be a novel target for MM treatment. These findings provide new mechanistic insight into the anticancer effects of certain traditional Chinese herbal medicine compounds.
Noncoding regions of C. elegans mRNA undergo selective adenosine to inosine deamination and contain a small number of editing sites per transcript

ADARs (Adenosine deaminases that act on RNA) “edit” RNA by converting adenosines to inosines within double-stranded regions. The primary targets of ADARs are long duplexes present within noncoding regions of mRNAs, such as introns and 3′ untranslated regions (UTRs). Because adenosine and inosine have different base-pairing properties, editing within these regions can alter splicing and recognition by small RNAs. However, despite numerous studies identifying multiple editing sites in these genomic regions, little is known about the extent to which editing sites co-occur on individual transcripts or the functional output of these combinatorial editing events. To begin to address these questions, we performed an ultra-deep sequencing analysis of 4 Caenorhabditis elegans 3′ UTRs that are known ADAR targets. Synchronous editing events were determined for the long duplexes in vivo. Furthermore, the validity of each editing event was confirmed by sequencing the same regions of mRNA from worms that lack A-to-I editing. This analysis identified a large number of editing sites that can occur within each 3′ UTR, but interestingly, each individual transcript contained only a small fraction of these A-to-I editing events. In addition, editing patterns were not random, indicating that an editing event can affect the efficiency of editing at subsequent adenosines. Furthermore, we identified specific sites that can be both positively and negatively correlated with additional sites leading to mutually exclusive editing patterns. These results suggest that editing in noncoding regions is selective and hyper-editing of cellular RNAs is rare.
Headache as a Warning Symptom of Impending Aneurysmal Subarachnoid Haemorrhage

About half of the aneurysm patients admitted to neurosurgical departments experience warning symptoms in the form of minor bleeding episodes days or even several months before a major haemorrhage occurs. Headache is the most common symptom of this warning leak, occurring in 9 out of 10 patients. The onset of headache is sudden and is unusual in severity and location, being unlike any headache the patient has otherwise experienced. It is frequently accompanied by transient nausea, vomiting, visual disturbances or meningism. Medical advice may be sought by the patient but all too often the diagnostic importance of a warning headache is missed. It is misinterpreted as attacks of migraine, tension headache, the flu, sinuitis, or a “sprained neck”, A more vigilant attention to the presence of a warning headache probably offers the greatest opportunity for altering the otherwise serious natural history of aneurysmal sub-arachnoid haemorrhage. If a warning headache is suspected, lumbar puncture is the examination of choice, once CT scanning has ruled out an intracranial mass lesion.
Association of osteoprotegerin and rankl levels with insulin resistance in pubertal obese children

Osteoprotegerin (OPG)/“receptor activator of nuclear factor kappa B-ligand” (RANKL) system has an important role in the remodeling of bone through regulation of osteoclastogenesis. We aimed to detect OPG and RANKL levels, particularly in obese children in the pubertal period and to investigate whether these parameters correlate with insulin resistance in childhood. Our study included 66 obese children ranging in age from 9.1 to 16 years, and 22 non-obese children ranging in age from 10.5 to 16 years. Blood glucose, insulin, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured for all cases; HOMA-IR, Quicki index and atherogenic index were calculated. Serum OPG and RANKL levels were also measured. OPG and RANKL levels did not show any difference between obese and non-obese children (P>.05). No difference in these 2 parameters were observed among the children with and without insulin resistance (P>.05). No correlation could be established between the OPG, the HOMA-IR, Quick and atherogenic indices. Obesity and insulin resistance are believed to show their effect in the later period of life to become able to change some of the parameters.