Miracle-dz/UniFAR-FTUs huggingface dataset:
Hippocampal gray matter volume in bilateral vestibular failure

Bilateral vestibular failure (BVF) is a severe chronic disorder of the labyrinth or the eighth cranial nerve characterized by unsteadiness of gait and disabling oscillopsia during head movements. According to animal data, vestibular input to the hippocampus is proposed to contribute to spatial memory and spatial navigation. Except for one seminal study showing the association of impaired spatial navigation and hippocampal atrophy, patient data in BVF are lacking. Therefore, we performed a voxel‐wise comparison of the hippocampal gray matter volume (GMV) in a clinically representative sample of 27 patients with incomplete BVF and 29 age‐ and gender‐matched healthy controls to test the hypothesis of hippocampal atrophy in BVF. Although the two groups did not generally differ in their hippocampal GMV, a reduction of GMV in the bilateral hippocampal CA3 region was significantly correlated with increased vestibulopathy‐related clinical impairment. We propose that GMV reduction in the hippocampus of BVF patients is related to the severity of vestibular‐induced disability which is in line with combined hippocampal atrophy and disorders of spatial navigation in complete vestibular deafferentation due to bilateral nerve section. Clinically, however, the most frequent etiologies of BVF cause incomplete lesions. Accordingly, hippocampus atrophy and deficits in spatial navigation occur possibly less frequently than previously suspected. Hum Brain Mapp 37:1998–2006, 2016. © 2016 Wiley Periodicals, Inc.
von Willebrand Factor and Factor VIII: C in Acute Cerebrovascular Disease

Summary Background. Elevated von Willebrand factor (vWF) is a risk factor in the development of acute myocardial infarction. The importance of vWF and factor VIII :C in the pathogenesis of cerebrovascular disease (CVD) is poorly defined. Methods and results. We studied 208 cases of stroke whose pathological type was defined by cranial computed tomography. Cerebral infarcts were grouped according to the Oxfordshire Community Stroke Project (OCSP) clinical classification. The results in patients were compared with 184 healthy reference subjects. In patients, vWF and FVIII: C levels were determined initially and after three months. Patients were followed prospectively for six months or until death. Levels of vWF and FVIII :C were elevated initially (1.86 IU/ml and 2.20 U/ml respectively) and after 3 months (1.51 IU/ml and 1.90 U/ml) compared with a healthy reference population (1.26 IU/ml and 1.49 U/ml p = 0.0001). In the initial sample, vWF was associated with age (p = 0.01). FVIII: C was related to age (p = 0.04), gender (p = 0.007 higher for females) and a history of diabetes mellitus (2.56 U/ml vs. 2.16 U/ml in non-diabetics, p = 0.008). Initial vWF levels were higher in subjects with large vessel disease (TACI/PACI) group compared with the small vessel disease (LACI) group [2.12 IU/ml, (n = 112) vs. 1.48 IU/ml (n = 59) respectively, p = 0.0001] and similarly in initial FVIII :C levels (2.43 U/ml vs. 1.87 U/ml, p = 0.0001). Analysis of six-month case fatality, vWF levels were associated with risk of death [p = 0.01, OR 1.73 (1.12,2.66) for an increase of 1 U/ml], even after allowing for stroke type. Conclusion. The relationship of vWF with stroke mortality has not previously been described. Although we have not demonstrated a causal role for vWF in the pathogenesis of CVD, elevated circulating levels of vWF may be associated with increased risk of death following stroke. A prospective study would be required to establish whether vWF is predictive for the development of CVD.
Murine Oncostatin M Acts via Leukemia Inhibitory Factor Receptor to Phosphorylate Signal Transducer and Activator of Transcription 3 (STAT3) but Not STAT1, an Effect That Protects Bone Mass*

Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are IL-6 family members with a wide range of biological functions. Human OSM (hOSM) and murine LIF (mLIF) act in mouse cells via a LIF receptor (LIFR)-glycoprotein 130 (gp130) heterodimer. In contrast, murine OSM (mOSM) signals mainly via an OSM receptor (OSMR)-gp130 heterodimer and binds with only very low affinity to mLIFR. hOSM and mLIF stimulate bone remodeling by both reducing osteocytic sclerostin and up-regulating the pro-osteoclastic factor receptor activator of NF-κB ligand (RANKL) in osteoblasts. In the absence of OSMR, mOSM still strongly suppressed sclerostin and stimulated bone formation but did not induce RANKL, suggesting that intracellular signaling activated by the low affinity interaction of mOSM with mLIFR is different from the downstream effects when mLIF or hOSM interacts with the same receptor. Both STAT1 and STAT3 were activated by mOSM in wild type cells or by mLIF/hOSM in wild type and Osmr−/− cells. In contrast, in Osmr−/− primary osteocyte-like cells stimulated with mOSM (therefore acting through mLIFR), microarray expression profiling and Western blotting analysis identified preferential phosphorylation of STAT3 and induction of its target genes but not of STAT1 and its target genes; this correlated with reduced phosphorylation of both gp130 and LIFR. In a mouse model of spontaneous osteopenia caused by hyperactivation of STAT1/3 signaling downstream of gp130 (gp130Y757F/Y757F), STAT1 deletion rescued the osteopenic phenotype, indicating a beneficial effect of promoting STAT3 signaling over STAT1 downstream of gp130 in this low bone mass condition, and this may have therapeutic value.
Predicting bacterial essential genes using only sequence composition information.

Essential genes are those genes that are needed by organisms at any time and under any conditions. It is very important for us to identify essential genes from bacterial genomes because of their vital role in synthetic biology and biomedical practices. In this paper, we developed a support vector machine (SVM)-based method to predict essential genes of bacterial genomes using only compositional features. These features are all derived from the primary sequences, i.e., nucleotide sequences and protein sequences. After training on the multiple samplings of the labeled (essential or not essential) features using a library for SVM, we obtained an average area under the ROC curve (AUC) of about 0.82 in a 5-fold cross-validation for Escherichia coli and about 0.74 for Mycoplasma pulmonis. We further evaluated the performance of the method proposed using the dataset consisting of 16 bacterial genomes, and an average AUC of 0.76 was achieved. Based on this training dataset, a model for essential gene prediction was established. Another two independent genomes, Shewanella oneidensis RW1 and Salmonella enterica serovar Typhimurium SL1344 were used to evalutate the model. Results showed that the AUC sores were 0.77 and 0.81, respectively. For the convenience of the vast majority of experimental scientists, a web server has been constructed, which is freely available at http://cefg.uestc. edu.cn:9999/egp.
Development of a resilient wireless sensor network for real-time outdoor applications

Wireless sensor network deployed for any outdoor applications confronts link variations. The outdoor deployment can be appallingly affected by the precipitous change in the environmental conditions. The effect can vary accordingly with a single hop and a multi hop sensor network. In this paper, we analyze the impact of propagation factors such as shadowing, fading, foliage and rainfall on the link quality, received signal strength and packet reception rate. Then using a packet oriented simulation tool, Qualnet 5.0. 2 a simulation framework was created to analyze the aftermath of the aforementioned propagation factors' separate as well as integrated effect on the signal quality. The models developed from the simulation are tested and assessed with the data received from the real time wireless sensor network system for landslide monitoring, deployed at Munnar, India.
Randomized phase II study of two doses of gefitinib in hormone-refractory prostate cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group.

PURPOSE Overexpression of the epidermal growth factor receptor has been demonstrated in advanced prostate cancer and is associated with a poor outcome. A multi-institutional, randomized, phase II study was undertaken by the National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of two doses of oral gefitinib in patients with minimally symptomatic, hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS Between July and November 2001, 40 patients with HRPC and increasing prostate-specific antigen (PSA) or progression in measurable disease who had not received prior chemotherapy were randomly assigned to 250 mg (n = 19) or 500 mg (n = 21) oral gefitinib daily continuously. The primary end points were PSA response rate and objective measurable response. Functional Assessment of Cancer Therapy Prostate Cancer Subscale (FACT-P) quality-of-life questionnaires were completed at baseline and during treatment. RESULTS None of the patients demonstrated a PSA or objective measurable response. Five (14.3%) of 35 assessable patients had stable PSA (one patient at 250 mg and four patients at 500 mg), and five patients (14.3%) had a best response of stable disease (duration, 2.5 to 16.8 months). No significant effect on the rate of increase in PSA was seen. The most common drug-related nonhematologic toxicities observed were grade 1 to 2 diarrhea (250 mg, 65%; 500 mg, 56%), fatigue (250 mg, 29%; 500 mg, 33%), and grade 1 to 2 skin rash (250 mg, 24%; 500 mg, 39%). FACT-P scores decreased during treatment, indicating worsening of symptoms compared with baseline. CONCLUSION Gefitinib did not result in any responses in PSA or objective measurable disease at either dose level. Gefitinib has minimal single-agent activity in HRPC.
Prevalence and Risk Factors for HIV Among Sniffers, Short-Term Injectors, and Long-Term Injectors of Heroin

Abstract The prevalence of HIV and associated risk behaviors were assessed among three groups of heroin users: long term injection drug users (LTIDUs). new injection drug users (NIDUs), and heroin sniffers (HSs) with no history of injection. HIV seroprevalence was similar among NIDUs (13.3%) and HSs (12.7%). LTIDUs had almost twice as high a level of HIV infection (24.7%). A fter including drug use and sex behavior variables in logistic regression models, both drug and sexual risk factors remained in the models. Attributable risk percent (APR) from injection for HIV infection among injection drug users was estimated to be 55.7% for LTIDUs and 5.8% for NIDUs. High-risk sex behavior plays an important role in the prevalence of HIV among drug users and accounts for nearly all the infection among NIDUs. Both injection and sexual risk behaviors need to be stressed in HIV prevention and intervention programs aimed at drug users.
Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine

The present study assessed the effect of D-amphetamine on responding maintained by wheel-running and sucrose reinforcement. Six male albino Wistar rats were placed in running wheels and exposed to a fixed-interval 30-s schedule that produced either a drop of 5% sucrose solution or the opportunity to run for 15 s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D-amphetamine were administered by i.p. injection 20 min prior to a session. As the dose increased, index of curvature values decreased toward zero and rate-dependency plots revealed increases in lower rates early in the interval and decreases in higher rates toward the end of the interval. Effects were similar in the presence of both stimuli. However, an analysis of post-reinforcement pauses and local response rates broken down by transitions revealed a differential effect. As the dose increased, local response rates following a wheel-running reinforcer were affected more than those following a sucrose reinforcer.
OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial.

Importance Women with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information. Objective To assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence. Design, Setting, and Participants Multicenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence. Interventions Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189). Main Outcomes and Measures Primary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events. Results Of the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse effects (88.4 vs 85.1; mean difference, 3.3; 95% CI, -1.9 to 8.5; P = .22), and treatment preference (92.% vs 89%; risk difference, -3%; 95% CI, -16% to 10%; P = .49). Urinary tract infections were more frequent in the onabotulinumtoxinA group (35% vs 11%; risk difference, -23%; 95% CI, -33% to -13%; P < .001). The need for self-catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group. Neuromodulation device revisions and removals occurred in 3%. Conclusions and Relevance Among women with refractory urgency urinary incontinence, treatment with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance. In addition, it resulted in a higher risk of urinary tract infections and need for transient self-catheterizations.
Experimental hypoxia does not influence gene expression and protein synthesis of Eph receptors and ephrin ligands in human melanoma cells in vitro

Eph receptor tyrosine kinases and their ephrin ligands are considered to play important roles in melanoma progression and metastasis. Moreover, hypoxia is known to contribute to melanoma metastasis. In this study, the influence of experimental hypoxia on the expression and synthesis of EphA2 and EphB4, and their corresponding ligands ephrinA1, ephrinA5, and ephrinB2 was studied systematically in four human melanoma cell lines in vitro. Melanoma cell monolayer and spheroid cultures were used as both extrinsic and intrinsic hypoxia models. Hypoxic conditions were confirmed by analyzing hypoxia-inducible factors 1&agr; or 2&agr; expression, vascular endothelial growth factor expression, and cellular uptake of [18F]fluoromisonidazole. In normoxia, EphA2, EphB4, ephrinA1, ephrinA5, and ephrinB2 expression was detectable in all cell lines to varying extents. Considerable protein synthesis of EphA2 was detected in all cell lines. However, no effect of experimental hypoxia on both Eph/ephrin expression and protein synthesis was observed. This contributes critically to the debate on the hypothesis that hypoxia regulates the Eph/ephrin system in melanoma.
UK cost-utility analysis of rituximab in patients with rheumatoid arthritis that failed to respond adequately to a biologic disease-modifying antirheumatic drug.

OBJECTIVE To evaluate the incremental cost effectiveness of rituximab in patients with rheumatoid arthritis that failed to respond adequately to tumour necrosis factor-alpha inhibitors (biologic disease-modifying antirheumatic drugs; bDMARDs). A cost-utility model has been developed to simulate the long-term incremental cost and benefits of rituximab using data from clinical trials and registries. METHODS The model estimates the lifetime disease progression of up to 10,000 hypothetical rheumatoid arthritis (RA) patients that failed one bDMARD. It compares cost and outcomes of two treatment sequences, representing the current UK standard both with and without rituximab. The population characteristics match those of the Randomised Evaluation of Long-term Efficacy of rituximab in RA (REFLEX) phase III randomised control trial. Clinical outcomes were based on an indirect comparison of published American College of Rheumatology response rates, adjusted for differences in placebo. To estimate medical resource use, health assessment questionnaire (HAQ) scores were grouped into five categories with UK registry data informing the average cost for each category. Quality-adjusted life years (QALYs) gained were mapped from disease severity (HAQ scores). RESULTS Compared to a standard UK treatment sequence (assuming the sequential use of bDMARDs) the introduction of rituximab led to a QALY gain of 0.526 years. The incremental cost-effectiveness ratios (ICERs) based on total direct medical cost were 11,601 pounds. Adding rituximab to a treatment sequence with no sequential use of biologic generates an ICER of 14,690 pounds. CONCLUSION Rituximab has lower average annual treatment costs compared to other bDMARDs and is a highly cost-effective treatment option for patients who have failed to respond adequately to one bDMARD. The cost per QALY gained of rituximab falls well below commonly accepted thresholds within the UK. Potential weaknesses of the model include the paucity of data on the efficacy of bDMARDs or non-biologic DMARDs when used as second-line options; the lack of consensus about the most appropriate therapy in patients who fail all available bDMARDs; probable underestimation of the non-drug related medical costs; indirect measurement of QALY gains with rituximab therapy; and the necessity of synthesising data from a number of clinical trials with different populations and study drugs.
Soluble intercellular adhesion molecule‐1 in paediatric connective tissue diseases

The intercellular adhesion molecule‐1 (ICAM‐1) is a cytokine‐induced glycoprotein involved in the recruitment of cells into tissues undergoing inflammatory responses. The aim of this study was to compare the levels of soluble ICAM‐1 (s‐ICAM‐1) in children with juvenile chronic arthritis (JCA) and systemic lupus erythematosus (SLE) and to evaluate the usefulness of this molecule as marker of disease activity. Levels of s‐ICAM‐1 were measured in sera using a monoclonal antibody sandwich enzyme‐linked immunoassay. Serum levels (mean ± SD) of s‐ICAM‐1 in 37 children with JCA, 18 patients suffering from SLE and 25 healthy controls were 609 ± 184, 513 ± 139 and 210 ± 95 ng/ml, respectively. A significant difference could be demonstrated between the levels of s‐ICAM‐1 in sera from each disease, as a group, and those of healthy controls. Higher levels of s‐ICAM‐1 were recorded in JCA patients with systemic features and patients who had polyarthritis than in children who were pauciarticular. A positive correlation was observed between s‐ICAM‐1 levels and disease activity score in SLE patients. Moreover, s‐ICAM‐1 levels closely followed clinical conditions in five children with SLE during follow‐up. The data show that s‐ICAM‐1 levels are increased in children suffering from connective tissue diseases and reflect disease status or activity, suggesting the usefulness of this molecule in the follow‐up of these diseases.
The intrajudge reliability of the perceptual rating of cleft palate speech before and after pharyngeal flap surgery: the effect of judges and speech samples.

OBJECTIVE In this pilot study, the reliabilities of the perceptual ratings of four types of speech samples by six judges, with and without expertise in evaluating cleft palate speech, were studied. DESIGN Pre- and postoperative tape recordings of 15 patients with cleft lip and palate who had undergone a superiorly based pharyngeal flap operation were selected. Five speech-language pathologists and one oral and maxillofacial surgeon perceptually rated the following variables on separate 100-mm visual analog scales: hypernasality, audible nasal emission, intelligibility, misarticulations associated with velopharyngeal insufficiency, voice quality, and the presence or absence of hyponasality. These six variables were rated in four types of speech samples: reading of three sentences, repeating after the speech pathologist of three sentences, 10 sentences containing the aforementioned material, and the same 10 sentences in paired comparison. All speech samples were rerated after 3 months by the same judges. RESULTS Judges differed largely in the range they used in their rating. Intrajudge reliability of . 56 to . 78 was found for ratings of hypernasality. No significant differences in intrajudge reliability were found for the ratings with the different types of speech samples. The intrajudge reliability of a judge with expertise was not necessarily higher than of a judge without this expertise. CONCLUSIONS The improvement in speech is most reliably assessed with speech samples in paired comparison. A speech-language pathologist with expertise in evaluating cleft palate speech does not guarantee a high intrajudge reliability of the rating.
Increased glucose utilization and decreased fatty acid metabolism in myotubes from Glmpgt/gt mice

Abstract Glycosylated lysosomal membrane protein (GLMP) has been reported to enhance the expression from a peroxisome proliferator-activated receptor alpha (PPARα) responsive promoter, but also to be an integral lysosomal membrane protein. Using myotubes established from wild-type and Glmpgt/gt mice, the importance of GLMP in skeletal muscle was examined. Glmpgt/gt myotubes expressed a more glycolytic phenotype than wild-type myotubes. Myotubes from Glmpgt/gt mice metabolized glucose faster and had a larger pool of intracellular glycogen, while oleic acid uptake, storage and oxidation were significantly reduced. Gene expression analyses indicated lower expression of three PPAR-isoforms, a co-regulator of PPAR (PGC1α) and several genes important for lipid metabolism in Glmpgt/gt myotubes. However, ablation of GLMP did not seem to substantially impair the response to PPAR agonists. In conclusion, myotubes established from Glmpgt/gt mice were more glycolytic than myotubes from wild-type animals, in spite of no differences in muscle fiber types in vivo.