Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients.

BACKGROUND Liver transplant recipients at high risk for serious fungal infections frequently receive fluconazole or an amphotericin B preparation for antifungal prophylaxis. Because of concerns about fungal resistance with fluconazole, safety with amphotericin B, and the cost of lipid formulations of amphotericin, alternative prophylactic regimens are needed. In this randomized, controlled trial, we compared the efficacy and safety of oral itraconazole solution with intravenous/oral fluconazole for prevention of fungal infections. METHODS Adult liver transplant recipients were randomized to receive either oral itraconazole solution (200 mg every 12 hr) or intravenous/oral fluconazole (400 mg every 24 hr). Each study drug was started immediately before transplant surgery and continued for 10 weeks after transplantation. Patients were evaluated for fungal colonization, proven invasive or superficial fungal infection, drug-related side effects, and death. RESULTS Fungal colonization decreased from baseline to week 8 after transplantation in both the itraconazole patients (67% to 25%, P<0.001) and the fluconazole patients (77% to 30%, P<0.001). Proven fungal infection developed in 9 (9%) of 97 itraconazole patients and in 4 (4%) of 91 fluconazole patients (P =0.25). The number of proven invasive fungal infections (seven with itraconazole [7%], three with fluconazole [3%]) and proven superficial fungal infections (two with itraconazole [2%], one with fluconazole [1%]) were also similar in both groups of patients. Organisms causing infection were (four patients), (three patients), and species (two patients) in the itraconazole group and (two patients), (one patient), and species (one patient) in the fluconazole group. Mortality from fungal infection was very low and occurred in only 1 (0.5%) of 188 patients. Except for more frequent gastrointestinal side effects (nausea, vomiting, diarrhea) with itraconazole, both itraconazole and fluconazole were well tolerated and not associated with any hepatotoxicity. Mean trough plasma concentrations of itraconazole were greater than 250 ng/mL throughout the study and were not affected by H -receptor antagonists or antacids. CONCLUSION Oral itraconazole solution has adequate bioavailability in liver transplant recipients for effective antifungal prophylaxis. Similar to fluconazole, prophylactic oral itraconazole decreases fungal colonization and is associated with a low incidence of serious or fatal fungal infections. Except for gastrointestinal side effects, oral itraconazole solution is well tolerated and has no significant hepatotoxicity.
Using G6PD tests to enable the safe treatment of Plasmodium vivax infections with primaquine on the Thailand-Myanmar border: A cost-effectiveness analysis

Background Primaquine is the only licensed antimalarial for the radical cure of Plasmodium vivax infections. Many countries, however, do not administer primaquine due to fear of hemolysis in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In other settings, primaquine is given without G6PD testing, putting patients at risk of hemolysis. New rapid diagnostic tests (RDTs) offer the opportunity to screen for G6PD deficiency prior to treatment with primaquine. Here we assessed the cost-effectiveness of using G6PD RDTs on the Thailand-Myanmar border and provide the model as an online tool for use in other settings. Methods/Principal findings Decision tree models for the management of P. vivax malaria evaluated the costs and disability-adjusted life-years (DALYs) associated with recurrences and primaquine-induced hemolysis from a health care provider perspective. Screening with G6PD RDTs before primaquine use was compared to (1) giving chloroquine alone and (2) giving primaquine without screening. Data were taken from a recent study on the impact of primaquine on P. vivax recurrences and a literature review. Compared to the use of chloroquine alone, the screening strategy had similar costs while averting 0.026 and 0.024 DALYs per primary infection in males and females respectively. Compared to primaquine administered without screening, the screening strategy provided modest cost savings while averting 0.011 and 0.004 DALYs in males and females respectively. The probabilistic sensitivity analyses resulted in a greater than 75% certainty that the screening strategy was cost-effective at a willingness to pay threshold of US$500, which is well below the common benchmark of per capita gross domestic product for Myanmar. Conclusions/Significance In this setting G6PD RDTs could avert DALYs by reducing recurrences and reducing hemolytic risk in G6PD deficient patients at low costs or cost savings. The model results are limited by the paucity of data available in the literature for some parameter values, including the mortality rates for both primaquine-induced hemolysis and P. vivax. The online model provides an opportunity to use different parameter estimates to examine the validity of these findings in other settings.
Reversion to methionine independence in simian virus 40-transformed human and malignant rat fibroblasts is associated with altered ploidy and altered properties of transformation.

Many transformed and malignant cells, unlike normal cells, do not grow when methionine in the growth medium is replaced by its immediate precursor homocysteine [Chello, P. & Bertino, J. (1973) Cancer Res. 33, 1898-1904 and Hoffman, R. & Erbe, R. (1976) Proc. Natl. Acad. Sci. USA 73, 1523-1527]. Rare cells from those populations revert to methionine independence [Hoffman, R. , Jacobsen, S. & Erbe, R. (1978) Biochem. Biophys. Res. Commun. 82, 228-234]. We report here that methionine-independent revertants of both human fibroblasts transformed by simian virus 40 and malignant rat fibroblasts concomitantly revert for some of the properties associated with the transformed state. Of the 13 methionine-independent revertants described here, 5 showed increased anchorage dependence as reflected by reduced cloning efficiences in methylcellulose; 8 showed an increased serum requirement for optimal growth; 8 showed decreased cell density in medium containing high serum; and 3 altered their cell morphology significantly. Eight of the 13 have increased chromosome numbers. All lines tested contained immunologically identifiable tumor antigen of simian virus 40. Thus by selecting for methionine independence it is possible to select for heterogeneous transformation revertants, indicating further a relationship between altered methionine metabolism and oncogenic transformation. Therefore a positive metabolic method to select for transformation revertants has been developed, and its use has resulted in selection of human transformation revertants.
Inflammatory bowel disease therapies discontinued between 2009 and 2014

Introduction: New therapeutic approaches are currently under development, which consider the fundamental mechanisms involved in the pathogenesis of inflammatory bowel disease (IBD). The disease is associated with inflamed intestinal and colonic mucosa in response to the dysregulated immune system. Areas covered: The aim of this article is to review drugs that have been designed for the treatment of IBD and discontinued between 2009 and 2014. Herein, nine molecules with different mechanisms of action are under review. Brodalumab, daclizumab, elubrixin and vatelizumab were withdrawn from the Phase II trial due to the lack of efficacy. Abatacept was not significantly superior to the placebo in the rate of remission and its Phase III trials were stopped. CNDO-210 and Catridecacog were discontinued due to safety concerns and lack of efficacy, respectively. Finally, NU-206 and alkaline phosphatase also ceased in development during Phase I and II tests. Expert opinion: The development in our knowledge and understanding of the pathophysiology of IBD and the identification of key objectives for the future play significant roles in IBD therapeutic development. Furthermore, well-planned clinical trials with concise measures of efficacy and safety are required to better decide whether to extend or terminate the development process. Some anti-inflammatory cytokines such as IL-2, IL-12, IL-17, IL-18, IL-23 and INF-γ could garner more attention in the future.
Analysis of ‘driver’ and ‘passenger’ CD8+ T-cell responses against variable viruses

Variable viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV), persist despite host immune responses directed against them. Numerous lines of evidence have suggested that antiviral CD8+ T–cell responses are key among these immune responses, but these vary widely in their ability to contain virus. We propose that only a proportion of responses may exert significant antiviral pressure (‘driver’ responses), leading to control over viral replication (protection) and/or, ultimately, selection of escape mutants. Another set of responses may exert only weak pressure on the virus (‘passenger’ responses): these neither protect nor select. To examine this we have analysed (using established databases of HIV and HCV sequences and cytotoxic T–lymphocyte (CTL) epitopes, and published experimental datasets) two important features—predicted binding of the epitope to major histocompatibility complex molecule and observed variability of the epitope—that might distinguish such responses. We find that a high predicted binding estimate could only explain a limited set of ‘driver’ responses associated with protection or selection. There is statistical evidence that readily defined (and non–protective) CTL responses target regions associated with lower levels of viral variability. Taken together, this suggests that a large number of well–documented responses may represent ‘passengers’ and we propose a mechanism that might explain their presence.
Characteristic Factor Structures of the Japanese Version of the State-Trait Anxiety Inventory: Coexistence of Positive-Negative and State-Trait Factor Structures

Previous factor studies of the State-Trait Anxiety Inventory (STAI; Spielberger, Gorsuch, & Lushene, 1970) have reported certain typical factors that are state-trait (S-T) 2-factor solutions and positively-negatively (P-N) worded item 2-factor solutions in addition to 4-factor solutions (positively and negatively worded state factors, positively and negatively worded trait factors). We explored the possibility that these factor structures are included in a factor space. Responses to the Japanese version of the STAI in a sample of 848 male workers were factor analyzed. The first-order factors obtained from principal-component analysis were almost equal to the previous 4 factors, except for a minor factor, and their second-order factors were the P-N factors. However, the S-T factors were also obtained from the same first-order factors by the oblique Procrustes rotation. Moreover, coexistence of these two 2-factor structures was determined in the same factor space by the orthogonal Procrustes rotation.
Patient Satisfaction Survey of Outpatient-Based Topical Local Anesthetic KTP Laser Inferior Turbinectomy: A Prospective Study

Background The aim of this study was to determine patient satisfaction and feasibility of performing KTP laser inferior turbinectomy under topical anesthetic/decongestant spray. A prospective survey study was performed in the Outpatients’ Department of a District General Hospital. Methods Thirty-nine consecutive patients suffering from allergic or nonallergic vasomotor rhinitis were prospectively entered into the study. Preoperative details were gathered including current nasal obstruction score as indicated on a visual analog score (VAS). Lidocaine hydrochloride 5% w/v and phenylephrine hydrochloride 0.5% w/v was applied via topical spray to anesthetize and decongest the nose. The inferior turbinates (ITs) were reduced by parallel mucosal cuts using the KTP laser. Intraoperative details were recorded included pain experienced and bleeding. We studied the subjective clinical effectiveness and patient satisfaction. Results All patients were followed up at standard intervals by telephone over a 6-month period. At each interval, current nasal obstruction, pain, bleeding, and crusting on VAS were collected. Morbidity was determined in terms of return to work, return to hospital, or recurrence of symptoms. At the end of 6 months all patients were asked if they would have the procedure repeated again and/or recommend it to a friend. Reduction of ITs under topical anesthesia was acceptable to 83% of all patients. Eighty-seven percent of all patients felt they would recommend the procedure and mode of anesthesia to a friend. Our patients obtained the maximum subjective benefit at 6 weeks postoperatively. A significant improvement in nasal obstruction was achieved. There was subjective improvement in associated symptoms including hyposmia/anosmia, rhinorrhea, and sneezing. Only 28% of all patients required medication again to aid symptom control. Postoperative bleeding was insignificant. The return to a ward or clinic was minimal and 82% of all employed patients were back at work within a week. Conclusion Our study showed that KTP laser inferior turbinectomy is suitable to be performed in the outpatient department under topical anesthetic/decongestant spray and provides excellent relief for nasal obstruction and high patient compliance and satisfaction.
The impact of different spirometric definitions on the prevalence of airway obstruction and their association with respiratory symptoms

The fixed ratio criterion of forced expiratory volume in 1 s/forced vital capacity <0.70 for diagnosing airway obstruction may overdiagnose the condition, particularly in the elderly, so the lower limit of normal (LLN) is recommended as the most appropriate criterion. Our aim was to compare LLN versus fixed ratio on the prevalence of chronic obstructive pulmonary disease (COPD) and examine the association between respiratory symptoms and airway obstruction defined by LLN and fixed ratio. 12 449 twins aged 40–80 years participated in a nationwide survey using the Danish Twin Registry. They completed a questionnaire, underwent clinical examination and recorded prebronchodilator spirometry. Individuals with self-reported asthma were excluded. Clinical COPD was defined by respiratory symptoms together with airway obstruction. 10 329 individuals were included, with a mean±sd age of 58.4±9.6 years and mean body mass index of 26.6±4.4 kg·m−2; 20% were current smokers, 37% former smokers and 43% never-smokers; and 48% were male. The prevalence of LLN airway obstruction (LLN-AO) and fixed ratio airway obstruction (FR-AO) was 5.6% and 18.0%, respectively (p<0.001). Overall, 26% reported current respiratory symptoms, but 50% of those with LLN-AO had respiratory symptoms compared to 39% with FR-AO, p<0.001. The prevalence of clinical LLN-COPD and fixed ratio COPD was 2.6% and 6.3%, respectively (p<0.001). Individuals with LLN-AO had a significantly higher probability of reporting respiratory symptoms compared with both healthy individuals and FR-AO when adjusted for sex, age and ever-smoking. The use of fixed ratio more than doubled the prevalence of clinical COPD compared with LLN, this being more pronounced with increased age, and identified subjects with a lower prevalence of respiratory symptoms than LLN-AO. Prevalence of airway obstruction in a nationwide twin population http://ow.ly/x4QR30g1rId
Preoperative serum cystatin-C as a potential biomarker for prognosis of renal cell carcinoma

Purpose The prognostic value of serum cystatin-C (Cys-C) in renal cell carcinoma (RCC) remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients. Patients and methods The levels of preoperative Cys-C, creatinine (CRE) and estimated glomerular filtration rate (e-GFR) were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC) curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC. Results Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L) was significantly associated with shorter overall survival (OS) in all RCC patients (hazard ratio [HR], 1.59; P = 0.012), patients at pT1-2 (P<0.001), pN0 (P<0.001) and pM0 stages (P<0.001). Moreover, Multivariate Cox regression analyses also showed that in the 306 patients without metastasis, high preoperative Cys-C was also associated with shorter disease-free survival (DFS) (HR, 3.50; P = 0.013). Conclusions An elevated preoperative Cys-C level was demonstrated to be related with worse survival in patients with RCC. Measuring preoperative serum Cys-C might be a simple way for finding poor prognostic patients and patients with elevated preoperative Cys-C level should be more closely followed up.
Twenty-Year Outcome of a Longitudinal Prospective Evaluation of Isolated Endoscopic Anterior Cruciate Ligament Reconstruction With Patellar Tendon or Hamstring Autograft

Background: Long-term prospective studies of isolated endoscopic anterior cruciate ligament (ACL) reconstruction are limited and may include confounding factors. Purpose: This study aimed to compare the outcomes of isolated ACL reconstruction using the patellar tendon (PT) autograft and the hamstring (HT) autograft in 180 patients over 20 years. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 180 participants undergoing isolated ACL reconstruction between 1993 and 1994 were prospectively recruited. Evaluation was performed at 1, 2, 5, 7, 10, 15, and 20 years after surgery and included the International Knee Documentation Committee (IKDC) knee ligament evaluation with radiographic evaluation, KT-1000 arthrometer side-to-side difference, and subjective scores. Results: Over 20 years, there were 16 patients (18%) and 9 patients (10%) with an ACL graft rupture in the HT and PT groups, respectively (P = .13). ACL graft rupture was associated with male sex (odds ratio [OR], 3.9; P = .007), nonideal tunnel position (OR, 3.6; P = .019), and age <18 years at the time of surgery (OR, 4.6; P = .003). The odds of a contralateral ACL rupture were increased in patients with the PT graft compared with patients with the HT graft (OR, 2.2; P = .02) and those aged <18 years at the time of surgery (OR, 3.4; P = .001). The mean IKDC scores at 20-year follow-up were 86 and 89 for the PT and HT groups, respectively (P = .18). At 20 years, 53% and 57% of the PT and HT groups participated in strenuous or very strenuous activities (P = .55), kneeling pain was present in 63% and 20% of the PT and HT groups (P = .018), and radiographic osteoarthritic change was found in 61% and 41% of the PT and HT groups (P = .008), respectively. Conclusion: Compared with patients who received the HT graft, patients who received the PT graft had significantly worse outcomes with regard to radiologically detectable osteoarthritis, kneeling pain, and contralateral ACL injury. At 20-year follow-up, both HT and PT autografts continued to provide good subjective outcomes and objective stability. However, further ACL injury is common, particularly in male individuals, younger patients, and those with tunnel malposition.
Serum lipid and lipoprotein parameters of Turkman horses.

BACKGROUND Lipid transport systems in animals have been evaluated both as experimental models for lipid and lipoprotein metabolism in humans and to gain insight into the lipid metabolism of specific breeds. The Turkman horse is a pure-blooded horse that lives on the margins of the Caspian Basin; information about serum lipids and lipoproteins in this breed is lacking. OBJECTIVE The purpose of this study was to evaluate serum lipid and lipoprotein concentrations in clinically healthy Turkman horses. METHODS Concentrations of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C), and lipoprotein electrophoretic patterns were determined in serum samples from 48 Turkman horses of both sexes and 0-12 years of age. Results were analyzed by 1-way ANOVA. RESULTS In both sexes and all age groups, the relative percentages of LDL-C (44.2-64.3%) were higher than those of HDL-C (29.7-47.1%) and VLDL-C (5.9-9.0%). Serum concentrations of TG and TC were significantly higher in male (0.45 +/- 0.12 mmol/L; 2.70 +/- 0.45 mmol/L) than in female (0.34 +/- 0.1 mmol/L; 2.15 +/- 0.3 mmol/L) horses in most age groups. The relative percentages of alpha- and beta-lipoproteins in electrophoretic tracings were 62.77 +/- 5.05% and 36.67 +/- 4.29%, respectively. CONCLUSION Serum lipid and lipoprotein values in Turkman horses differ from those of other equine breeds, and may be useful for evaluating metabolic diseases in this species.
Expression analysis of regulatory microRNAs in bovine cumulus oocyte complex and preimplantation embryos

Summary MicroRNAs (miRNAs) are small endogenous molecules that are involved in a diverse of cellular process. However, little is known about their abundance in bovine oocytes and their surrounding cumulus cells during oocyte development. To elucidate this situation, we investigated the relative expression pattern of sets of miRNAs between bovine oocyte and the surrounding cumulus cells during in vitro maturation using miRNA polymerase chain reaction (PCR) array. Results revealed that a total of 47 and 51 miRNAs were highly abundant in immature and matured oocytes, respectively, compared with their surrounding cumulus cells. Furthermore, expression analysis of six miRNAs enriched in oocyte miR-205, miR-150, miR-122, miR-96, miR-146a and miR-146b-5p at different maturation times showed a dramatic decrease in abundance from 0 h to 22 h of maturation. The expression of the same miRNAs in preimplantation stage embryos was found to be highly abundant in early stages of embryo development and decreased after the 8-cell stage to the blastocyst stage following a typical maternal transcript profile. Similar results were obtained by localization of miR-205 in preimplantation stage embryos, in which signals were higher up to the 4-cell stage and reduced thereafter. miR-205 and miR-210 were localized in situ in ovarian follicles and revealed a spatio-temporal expression during follicular development. Interestingly, the presence or absence of oocytes or cumulus cells during maturation was found to affect the expression of miRNAs in each of the two cell types. Hence, our results showed the presence of distinct sets of miRNAs in oocytes or cumulus cells and the presence of their dynamic degradation during bovine oocyte maturation.