Miracle-dz/UniFAR-FTUs huggingface dataset:
Alpha emitter radium-223 and survival in metastatic prostate cancer.

BACKGROUND Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. METHODS In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. RESULTS At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. CONCLUSIONS In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).
Bone Regeneration of Canine Skull Using Bone Marrow‐Derived Stromal Cells and β‐Tricalcium Phosphate

Objective: The aim of this study was to regenerate high‐quality cranial bone using tissue engineering techniques, with subsequent extension to clinical application. Our previous study with a 3‐month observation period indicated that a composite scaffold composed primarily of β‐tricalcium phosphate (TCP) had the potential for cranial bone regeneration. In this study, we investigated whether bone marrow derived stromal cells (BSCs) could promote the regeneration of cranial bone as determined after 3 and 6 months.
Reducing HIV infection among new injecting drug users in the China–Vietnam Cross Border Project

Objectives:To assess an HIV prevention programme for injecting drug users (IDU) in the crossborder area between China and Vietnam. Design:Serial cross-sectional surveys (0, 6, 12, 18, 24 and 36 months) of community-recruited current IDU. Methods:The project included peer educator outreach and the large-scale distribution of sterile injection equipment. Serial cross-sectional surveys with HIV testing of community recruited IDU were conducted at baseline (before implementation) and 6, 12, 18, 24 and 36 months post-baseline. HIV prevalence and estimated HIV incidence among new injectors (individuals injecting drugs for < 3 years) in each survey wave were the primary outcome measures. Results:The percentages of new injectors among all subjects declined across each survey waves in both Ning Ming and Lang Son. HIV prevalence and estimated incidence fell by approximately half at the 24-month survey and by approximately three quarters at the 36-month survey in both areas (all P < 0.01). Conclusion:The implementation of large-scale outreach and syringe access programmes was followed by substantial reductions in HIV infection among new injectors, with no evidence of any increase in individuals beginning to inject drugs. This project may serve as a model for large-scale HIV prevention programming for IDU in China, Vietnam, and other developing/transitional countries.
Integrative Analysis of Genomics and Transcriptome Data to Identify Potential Functional Genes of BMDs in Females

Osteoporosis is known to be highly heritable. However, to date, the findings from more than 20 genome‐wide association studies (GWASs) have explained less than 6% of genetic risks. Studies suggest that the missing heritability data may be because of joint effects among genes. To identify novel heritability for osteoporosis, we performed a system‐level study on bone mineral density (BMD) by weighted gene coexpression network analysis (WGCNA), using the largest GWAS data set for BMD in the field, Genetic Factors for Osteoporosis Consortium (GEFOS‐2), and a transcriptomic gene expression data set generated from transiliac bone biopsies in women. A weighted gene coexpression network was generated for 1574 genes with GWAS nominal evidence of association (p ≤ 0.05) based on dissimilarity measurement on the expression data. Twelve distinct gene modules were identified, and four modules showed nominally significant associations with BMD (p ≤ 0.05), but only one module, the yellow module, demonstrated a good correlation between module membership (MM) and gene significance (GS), suggesting that the yellow module serves an important biological role in bone regulation. Interestingly, through characterization of module content and topology, the yellow module was found to be significantly enriched with contractile fiber part (GO:044449), which is widely recognized as having a close relationship between muscle and bone. Furthermore, detailed submodule analyses of important candidate genes (HOMER1, SPTBN1) by all edges within the yellow module implied significant enrichment of functional connections between bone and cytoskeletal protein binding. Our study yielded novel information from system genetics analyses of GWAS data jointly with transcriptomic data. The findings highlighted a module and several genes in the model as playing important roles in the regulation of bone mass in females, which may yield novel insights into the genetic basis of osteoporosis. © 2016 American Society for Bone and Mineral Research.
Effect of nicotine, cotinine and cigarette smoke extract on the neutrophil respiratory burst.

AIMS To determine the effect of nicotine, cotinine and cigarette smoke extract (CSE) on the neutrophil respiratory burst and their effect on activation of the nuclear factor-κB (NFκB) pathway in oral epithelium. MATERIALS AND METHODS Neutrophils from periodontally healthy individuals were treated with nicotine, cotinine and CSE before stimulation with Fusobacterium nucleatum, IgG-opsonized Staphylococcus aureus and Escherichia coli lipopolysaccharide. Total and extracellular reactive oxygen species (ROS) generation was determined by luminol/isoluminol chemiluminescence. Activation of NFκB in oral epithelial cells was determined by immunocytochemistry. RESULTS Smoke extract alone caused increased neutrophil extracellular isoluminol-dependent chemiluminescence, not detectable with luminol. However, pre-treatment with smoke extract reduced both total and extracellular ROS generation in response to all stimuli. Nicotine and cotinine had no effect on the neutrophil respiratory burst. Smoke extract, nicotine and cotinine did not induce oral epithelial cell NFκB activation. CONCLUSIONS These data demonstrate that smoke extract reduces the ability of neutrophils to generate ROS after stimulation with F. nucleatum and IgG-opsonized S. aureus but, at high concentrations, stimulates extracellular ROS generation. During periodontitis, cigarette smoking may differentially affect neutrophil function, generally preventing elimination of periodontal pathogens but, in heavy smokers, also stimulating ROS release and oxidative stress mediated tissue damage.
Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor.

PURPOSE To evaluate the impact of photodynamic therapy (PDT) on expression and distribution of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-3, and pigment epithelium-derived factor (PEDF). METHODS Eyes of patients scheduled for enucleation due to untreatable malignancy served as study eyes (n = 4), age-matched donor eyes were used as the control (n = 4). PDT using verteporfin with the recommended standard parameters was applied to intact areas of the perimacular region. Lesions were classified by ophthalmoscopy, fluorescein angiography (FA), and indocyanine green angiography (ICGA), as well as light and electron microscopic (LM/EM) histology. Immunolabeling using specific antibodies against VEGF, VEGFR-3, and PEDF was performed in PDT-treated areas, untreated collateral areas in study eyes, and untreated areas of control eyes. Specimens were fixed in 4% paraformaldehyde and 1% glutaraldehyde and embedded in paraffin. Four-micrometer-thick sections were stained using the peroxidase-labeled streptavidin-biotin method. RESULTS All PDT-treated areas demonstrated characteristic choroidal hypofluorescence by FA and ICGA. LM/EM histology revealed selective damage of choriocapillary endothelial cells. VEGF was expressed in the endothelial layer of choriocapillaries and focally within larger choroidal vessels in treated areas, but not in untreated areas. Sites with positive VEGF labeling also demonstrated upregulation of VEGFR-3. PEDF expression was localized to retinas in all eyes; however, PEDF staining of choroidal endothelial cells was specific for treated areas of study eyes. CONCLUSIONS PDT using verteporfin induces a reproducible angiogenic response in elderly human eyes. VEGF, VEGFR-3, and PEDF expression is enhanced after PDT. Choroidal endothelial cells appear to be the primary site of angiogenic stimulation.
Mild sleep restriction acutely reduces plasma glucagon levels in healthy men.

BACKGROUND Sleep loss has repeatedly been suggested to affect glucose metabolism adversely, raising the question as to the impact of subtle forms of sleep loss. OBJECTIVE The aim of the study was to assess the effects of a single night of sleep restriction to 4.5 h on endocrine parameters of glucose metabolism. DESIGN We conducted crossover, balanced experiments including two conditions, i.e. one night of 4.5 h and one night of 7 h of sleep. SUBJECTS AND MEASUREMENTS In 10 healthy men, circulating concentrations of insulin, C-peptide, epinephrine, norepinephrine, GH, ACTH, cortisol, and glucagon were measured after sleep and sleep restriction, respectively, during basal rest and a subsequent stepwise hypoglycemic clamp. RESULTS Mild sleep restriction induced a robust reduction in basal plasma glucagon levels that persisted throughout the hypoglycemic clamp (P < 0.03). Basal glucose, insulin, and C-peptide levels were unaffected by sleep restriction. Also, basal and hypoglycemia-stimulated concentrations of epinephrine, norepinephrine, and GH were unchanged after sleep restriction. Concentrations of ACTH (P < 0.05) and cortisol (P < 0.001) were reduced after sleep loss during baseline and at the start of hypoglycemia, but reached roughly comparable levels in both conditions at the end of the clamp (ACTH, P > 0.06; cortisol, P > 0.93). CONCLUSION Our data show that mild restriction of nocturnal sleep to 4.5 h has a reducing effect on circulating glucagon levels. This finding provides further evidence for the notion that glucose homeostasis is sensitive to subtle changes in sleep duration.
Which patients are most likely to benefit from total joint arthroplasty?

OBJECTIVE To evaluate patient predictors of good outcome following total joint arthroplasty (TJA). METHODS A population cohort with hip/knee arthritis (osteoarthritis [OA] or inflammatory arthritis) ages ≥55 years was recruited between 1996 and 1998 (baseline) and assessed annually for demographics, troublesome joints, health status, and overall hip/knee arthritis severity using the Western Ontario and McMaster Universities OA Index (WOMAC). Survey data were linked with administrative databases to identify primary TJAs. Good outcome was defined as an improvement in WOMAC summary score greater than or equal to the minimal important difference (MID; 0.5 SD of the mean change). Logistic regression and Akaike's information criterion were used to determine the optimal number of predictors and the best model of that size. Log Poisson regression was used to determine the relative risk (RR) for a good outcome. RESULTS Primary TJA was performed in 202 patients (mean age 71.0 years; 79.7% female; 82.7% with >1 troublesome hip/knee; 65.8% knee replacements). Mean improvement in WOMAC summary score was 10.2 points (SD 18.05; MID 9 points). Of these patients, 53.5% experienced a good outcome. Four predictors were optimal. The best 4-variable model included pre-TJA WOMAC, comorbidity, number of troublesome hips/knees, and arthritis type (C statistic 0.80). The probability of a good outcome was greater with worse (higher) pre-TJA WOMAC summary scores (adjusted RR 1.32 per 10-point increase; P < 0.0001), fewer troublesome hips/knees (adjusted RR 0.82 per joint; P = 0.002), OA (adjusted RR for rheumatoid arthritis versus OA 0.33; P = 0.009), and fewer comorbidities (adjusted RR per condition 0.88; P = 0.01). CONCLUSION In an OA cohort with a high prevalence of multiple troublesome joints and comorbidity, only half achieved a good TJA outcome, defined as improved pain and disability. A more comprehensive assessment of the benefits and risks of TJA is warranted.
Verbal information-processing capabilities and cochlear implants: implications for preoperative predictors of speech understanding.

In this study, we examined preoperative verbal cognitive capacity in 11 deafened adults who were cochlear implant candidates and reexamined level of speech understanding after 6-8 months' experience with the implant. Verbal cognitive performance in the implant group was compared in a group of normal hearing subjects and in nonimplanted group of deafened adults. The three groups performed on par with each other with an exception: The individuals in the cochlear implant group and the nonimplanted group of deafened adults performed significatly worse than those of normal hearing in tasks in which use of internal speech is a key feature (i.e., rhyme judgement and lexical decision tasks). Postoperative observations of the implanted individuals' level of speech understanding suggest that it is possible to predict the level of speech understanding by means of a properative cognitive assessment. The characteristics of three verbal cognitive abilities prove to be critical indicators of 6 - 8 months' postoperative outcome: internal speech functioning, speed of verval information processing, and working memory capacity - the first factor proved the most decisive. We discuss the results with respect to direct versus indirect predictors of outcomes from cochlear implant operations and the effect of auditory deprivation on deafened adults' capability to process auditory information.
The EhADH112 recombinant polypeptide inhibits cell destruction and liver abscess formation by Entamoeba histolytica trophozoites

The Entamoeba histolytica EhCPADH complex, formed by a cysteine proteinase (EhCP112) and an adhesin (EhADH112), is involved in adherence, phagocytosis and cytolysis. This makes this complex an attractive candidate as a vaccine against amoebiasis. Here, we produced the recombinant polypeptide EhADH243, which includes the adherence epitope detected by a monoclonal antibody against the EhCPADH complex. EhADH243 was purified, and the effect of the polypeptide on in vitro and in vivo virulence was studied. Antibodies against EhADH243 reacted with the EhCPADH complex and with the recombinant polypeptide. EhADH243 and antibodies against this polypeptide inhibited adherence, phagocytosis and destruction of cell monolayers by live trophozoites, but had little effect on cell monolayer destruction by trophozoite extracts. EhADH243 recognized a 97 kDa protein in the MDCK membrane fraction that could be a putative receptor for E. histolytica trophozoites. Hamsters immunized with EhADH243 developed humoral response against EhCPADH, and animals were partially protected from amoebic liver abscess.
Machine translation of proper names from english and french into vietnamese : an error analysis and some proposed solutions

Machine translation (MT) has increasingly become an indispensable tool for decoding themeaning of a text from a source language into a target language in our current information and knowledgeera. In particular, MT of proper names (PN) plays a crucial role in providing the specific and preciseidentification of persons, places, organizations, and artefacts through the languages. Despite a largenumber of studies and significant achievements of named entity recognition in the NLP communityaround the world, there has been almost no research on PNMT for Vietnamese language. Due to the different features of PN writing, transliteration or transcription and translation from a variety of languages including English, French, Russian, Chinese, etc. into Vietnamese, the PNMT from those languages into Vietnamese is still challenging and problematic issue. This study focuses on theproblems of English-Vietnamese and French-Vietnamese PNMT arising from current MT engines. First,it proposes a corpus-based PN classification, then a detailed PNMT error analysis to conclude with somepre-processing solutions in order to improve the MT quality. Through the analysis and classification of PNMT errors from the two English-Vietnamese and French-Vietnamese parallel corpora of texts with PNs, we propose solutions concerning two major issues:(1)corpus annotation for preparing the pre-processing databases, and (2)design of the pre-processingprogram to be used on annotated corpora to reduce the PNMT errors and enhance the quality of MTsystems, including Google, Vietgle, Bing and EVTran. The efficacy of different annotation methods of English and French corpora of PNs and the results of PNMT errors before and after using the pre-processing program on the two annotated corporaare compared and discussed in this study. They prove that the pre-processing solution reducessignificantly PNMT errors and contributes to the improvement of the MT systems’ for Vietnameselanguage.
Enhancing Benefits or Increasing Harms: Community Responses for HIV Among Men Who Have Sex With Men, Transgender Women, Female Sex Workers, and People Who Inject Drugs

Abstract:Studies completed over the past 15 years have consistently demonstrated the importance of community-level determinants in potentiating or mitigating risks for the acquisition and transmission of HIV. Structural determinants are especially important in mediating HIV risk among key populations, including men who have sex with men, people who inject drugs, sex workers of all genders, and transgender women. The objective of this systematic review was to synthesize the evidence characterizing the community-level determinants that potentiate or mitigate HIV-related outcomes for key populations. The results of the review suggest that although health communication programs represent community-level strategies that have demonstrated the effectiveness in increasing the uptake of HIV testing and decreasing the experienced stigma among people living with HIV, there are limited studies focused on key populations in low- and middle-income settings. Moreover, interpretation from the 22 studies that met inclusion and exclusion criteria reinforce the importance of the continued measurement of community-level determinants of HIV risks and of the innovation in tools to effectively address these risks as components of the next generation of the HIV response. Consequently, the next generation of effective HIV prevention science research must improve our understanding of the multiple levels of HIV risk factors, while programming for key populations must address each of these risk levels. Failure to do so will cost lives, harm communities, and undermine the gains of the HIV response.
Vestibular response kinematics in posterior parietal cortex neurons of macaque monkeys

Perception of extrapersonal space is a fundamental requirement for accurate interaction with the environment and moving in it. Parietal cortical areas are thought to play an important role in this function. A significant sensory input to this area arrives from the vestibular system. We quantified neuronal responses in the ventral intraparietal area and the medial intraparietal area of awake head‐fixed macaque monkeys during classical vestibular sinusoidal stimulation protocols and with a newly developed random vestibular testing paradigm. The goal was to study more specifically the signal content of perietal vestibular neurons with respect to head movement kinematics. Traditional sinusoidal stimulation analysis revealed that about one‐third of the neurons responded in phase with either head position or head acceleration, besides classical head velocity tuning. Random vestibular stimulation revealed more complex signal profiles in the majority of neurons, although quantification of the kinematic variables that drove the neurons most effectively led to similar results to phase shift analysis. Thus, a majority of cells was principally driven by head velocity, and a minority by either acceleration or position. Nevertheless, random stimulation also revealed the simultaneous presence of all three kinematic response parameters (i.e. velocity, position and acceleration) in a majority of neurons. A minority of cells coded only two kinematic variables, i.e. head velocity coupled with either acceleration or position. Neurons coding only one kinematic variable were not found. We hereby demonstrate for the first time that central vestibular neurons carry several head movement kinematic variables simultaneously.
Differential effects of thyroid hormones on energy metabolism of rat slow‐ and fast‐twitch muscles

Thyroid hormone (TH) is an important regulator of mitochondrial content and activity. As mitochondrial content and properties differ depending on muscle‐type, we compared mitochondrial regulation and biogenesis by T3 in slow‐twitch oxidative (soleus) and fast‐twitch mixed muscle (plantaris). Male Wistar rats were treated for 21 to 27 days with T3 (200 μg/kg/day). Oxidative capacity, regulation of mitochondrial respiration by substrates and phosphate acceptors, and transcription factors were studied. In soleus, T3 treatment increased maximal oxygen consumption (Vmax) and the activities of citrate synthase (CS) and cytochrome oxidase (COX) by 100%, 45%, and 71%, respectively (P < 0.001), whereas in plantaris only Vmax increased, by 39% (P < 0.01). ADP‐independent respiration rate was increased in soleus muscle by 216% suggesting mitochondrial uncoupling. Mitochondrial substrate utilization in soleus was also influenced by T3, as were mitochondrial enzymes. Lactate dehydrogenase (LDH) activity was elevated in soleus and plantaris by 63% and 11%, respectively (P < 0.01), and soleus creatine kinase was increased by 48% (P < 0.001). T3 increased the mRNA content of the transcriptional co‐activator of mitochondrial genes, PGC‐1α, and the I and IV COX subunits in soleus. The muscle specific response to thyroid hormones could be explained by a lower content of TH receptors in plantaris than soleus. Moreover, TRα mRNA level decreased further after T3 treatment. These results demonstrate that TH has a major effect on mitochondrial content, regulation and coupling in slow oxidative muscle, but to a lesser extent in fast muscle, due to the high expression of TH receptors and PGC‐1α transcription factor. © 2004 Wiley‐Liss, Inc.