Miracle-dz/UniFAR-FTUs huggingface dataset:
Vigabatrin Retinopathy in an Irish Cohort: Lack of Correlation with Dose

Summary: Purpose: The anticonvulsant vigabatrin (VGB) causes irreversible visual‐field constriction in 19–92% of patients. It is unclear whether this correlates with dosing, and the natural history of the retinopathy remains obscure. We conducted a retrospective analysis of patients receiving long‐term VGB to examine whether toxicity is related to the daily dose, duration of therapy, or cumulative dose.
HIV, Tuberculosis, and Noncommunicable Diseases: What Is Known About the Costs, Effects, and Cost-effectiveness of Integrated Care?

Abstract:Unprecedented investments in health systems in low- and middle-income countries (LMICs) have resulted in more than 8 million individuals on antiretroviral therapy. Such individuals experience dramatically increased survival but are increasingly at risk of developing common noncommunicable diseases (NCDs). Integrating clinical care for HIV, other infectious diseases, and NCDs could make health services more effective and provide greater value. Cost-effectiveness analysis is a method to evaluate the clinical benefits and costs associated with different health care interventions and offers guidance for prioritization of investments and scale-up, especially as resources are increasingly constrained. We first examine tuberculosis and HIV as 1 example of integrated care already successfully implemented in several LMICs; we then review the published literature regarding cervical cancer and depression as 2 examples of NCDs for which integrating care with HIV services could offer excellent value. Direct evidence of the benefits of integrated services generally remains scarce; however, data suggest that improved effectiveness and reduced costs may be attained by integrating additional services with existing HIV clinical care. Further investigation into clinical outcomes and costs of care for NCDs among people living with HIV in LMICs will help to prioritize specific health care services by contributing to an understanding of the affordability and implementation of an integrated approach.
PTEN Is Fundamental for Elimination of Leukemia Stem Cells Mediated by GSK126 Targeting EZH2 in Chronic Myelogenous Leukemia

Purpose: Leukemia stem cells (LSCs) are an important source of tyrosine kinase inhibitor resistance and disease relapse in patients with chronic myelogenous leukemia (CML). Targeting LSCs may be an attractive strategy to override this thorny problem. Given that EZH2 was overexpressed in primary CML CD34+ cells, our purpose in this study was to evaluate the effects of targeting EZH2 on CML LSCs and clarify its underlying mechanism. Experimental Design: Human primary CML CD34+ cells and retrovirally BCR–ABL-driven CML mouse models were employed to evaluate the effects of suppression of EZH2 by GSK126- or EZH2-specific shRNA in vitro and in vivo. Recruitment of EZH2 and H3K27me3 on the promoter of tumor-suppressor gene PTEN in CML cells was measured by chromatin immunoprecipitation assay. Results: Our results showed that pharmacologic inhibition of EZH2 by GSK126 not only elicited apoptosis and restricted cell growth in CML bulk leukemia cells, but also decreased LSCs in CML CD34+ cells while sparing those from normal bone marrow CD34+ cells. Suppression of EZH2 by GSK126 or specific shRNA prolonged survival of CML mice and reduced the number of LSCs in mice. EZH2 knockdown resulted in elevation of PTEN and led to impaired recruitment of EZH2 and H3K27me3 on the promoter of PTEN gene. The effect of EZH2 knockdown in the CML mice was at least partially reversed by PTEN knockdown. Conclusions: These findings improve the understanding of the epigenetic regulation of stemness in CML LSCs and warrant clinical trial of GSK126 in refractory patients with CML. Clin Cancer Res; 24(1); 145–57. ©2017 AACR.
Parenting behaviors and the occurrence and co-occurrence of depressive symptoms and conduct problems among african american children.

The occurrence and co-occurrence of depressive symptoms and conduct problems were examined in the context of parenting behaviors in a community-based sample of 897 African American children and their primary caregivers using a multi-informant, longitudinal design. Parenting behaviors and clinical symptoms were assessed in 2 waves, when the children averaged 10.5 and 12.3 years of age. Parenting behaviors differed significantly according to a child's symptomatology; (a) that is, when a child exhibited no depressive or conduct problems, (b) depressive problems only, (c) conduct problems only, or (d) co-occurring depressive and conduct problems. When parenting behaviors were examined according to changes in children's symptom levels, children whose symptoms increased over time reported increases in hostility and harsh-inconsistent parenting and decreases in warmth and nurturant-involved parenting.
Maximum likelihood estimation in the joint analysis of time‐to‐event and multiple longitudinal variables

Joint modelling of longitudinal and survival data has received much attention in recent years. Most have concentrated on a single longitudinal variable. This paper considers joint modelling in the presence of multiple longitudinal variables. We explore direct association of time‐to‐event and multiple longitudinal processes through a frailty model and use a mixed effects model for each of the longitudinal variables. Correlations among the longitudinal variables are induced through correlated random effects. We allow effects of categorical and continuous covariates on both longitudinal and time‐to‐event responses and explore interactions between the longtudinal variables and other covariates on time‐to‐event. Estimates of the parameters are obtained by maximizing the joint likelihood for the longitudinal variable processes and the event process. We use a one‐step‐late EM algorithm to handle the direct dependence of the event process on the modelled longitudinal variables along with the presence of other fixed covariates in both processes. We argue that such a joint analysis with multiple longitudinal variables is advantageous to one with only a single longitudinal variable in revealing interplay among multiple longitudinal variables and the time‐to‐event. Copyright © 2002 John Wiley & Sons, Ltd.
"Dopamine-dependent" side effects of selective serotonin reuptake inhibitors: a clinical review.

OBJECTIVE Neurophysiologic findings indicate an inhibition of dopaminergic neurotransmission by selective serotonin reuptake inhibitors (SSRIs). This article highlights the relationships between changes in dopaminergic neurotrans-mission induced by SSRIs and the occurrence of certain side effects such as hyperprolactinemia, extrapyramidal symptoms, sexual and cognitive dysfunction, galactorrhea, mammary hypertrophy, and, more rarely, gynecomastia. DATA SOURCES AND SELECTION A systematic search of the literature in English, French, and German from 1980 to 2004 was performed in MEDLINE, EMBASE, and the Cochrane Library using the keywords SSRI, dopamine, serotonin, side effects, antidepressants, citalopram, escitalopram, sertraline, paroxetine, fluoxetine, fluvoxamine, and nefazodone. References cited in all trials were searched iteratively to identify missing studies. All studies concerning inhibition of dopaminergic neurotransmission by SSRIs and SSRI-related side effects were considered. We retained 62 significant articles debating the subject. DATA EXTRACTION AND SYNTHESIS We critically reviewed the studies, depending on the methodologies (case reports, clinical reports, randomized studies), and assessed the pertinence of "dopamine-dependent" SSRI-related side effects. The analytic review of these articles suggests that some specific SSRI-related side effects be classified as dopamine-dependent. CONCLUSIONS At a clinical level, it could be useful to underline dopamine-dependent characteristics of some SSRI-related side effects. This approach would allow clinicians the opportunity to search other dopamine-dependent side effects systematically. At a pharmacologic level, this approach could stimulate the development of molecules with a "corrective" function on dopamine-dependent side effects of SSRIs by facilitating dopaminergic neurotransmission.
Realtime Ray Tracing

Realtime ray tracing produces high quality images at interactive frame rates. While the realtime rendering domain is still dominated by raster graphics, realtime ray tracing recently has become much more powerful. This paper addresses the essence of realtime ray tracing: the various acceleration techniques which yield interactive performance, how coherence between rays can be exploited and effective parallelization. In addition to that, a comprehensive comparison of realtime ray tracing versus modern raster graphics hardware is given. Compared to raster graphics, ray tracing allows highly realistic image synthesis and most importantly, it scales well for massively complex scenes. Considering those advantages and the fact that realtime ray tracing software performance on PCs has finally surpassed the performance of dedicated rasterization hardware for highly complex models, all indications are that ray tracing may replace rasterization based realtime rendering for scientific visualization and games in the near future. CR Categories: I.3. 7 [Computer Graphics]: Ray Tracing—ThreeDimensional Graphics and Realism;
A Jones slopes characterization of adequate knots

We establish a characterization of adequate knots in terms of the degree of their colored Jones polynomial. We show that, assuming the Strong Slope conjecture, our characterization can be reformulated in terms of "Jones slopes" of knots and the essential surfaces that realize the slopes . For alternating knots the reformulated characterization follows by recent work of J. Greene and J. Howie.
Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale—supportive analyses from a Phase 3 study

Objective Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints. Methods Patients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression–Improvement (CGI-I) scale score, was also analyzed. Results Of 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92–94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo. Conclusion AL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.
Persistence of Neuropsychological Testing Deficits in Mild Cognitive Impairment

Background: The significant variability across studies of mild cognitive impairment (MCI) in rates of progression to Alzheimer’s disease (AD) and reversion to normal cognition may be due to differences in specific neuropsychological tests and thresholds used to define MCI. Methods: We assessed 115 subjects with amnestic (AMN) or non-amnestic (NON) MCI on a standardized neuropsychological battery at baseline and after a mean follow-up of 16.4 months to determine the prevalence and persistence of deficits identified with specific tests. Results: The prevalence of impaired performance varied widely across tests. Deficits were more persistent in the AMN group than in the NON group. Baseline deficits in Visual Reproduction II and the California Verbal Learning Test were the best predictors of persistent memory impairment. Subjects who at baseline were impaired on multiple memory tests or had poorer overall memory performance were more likely to exhibit persistent memory deficits. Conclusions: The use of different neuropsychological tests and thresholds to diagnose MCI identified subsets of subjects with different rates of persistence of cognitive impairment. Standardization of the operational definition of cognitive impairment in MCI may result in more consistent predictions of progression to AD.
Paternity assessment in rhesus macaques (Macaca mulatta): Multilocus DNA fingerprinting and PCR marker typing

Establishing kinship relations in primates using modern molecular genetic techniques has enhanced the ability to scrutinize a number of fundamental biological issues. We screened 51 human short tandem repeats (STRs) for cross‐species PCR amplification in rhesus macaques (Macaca mulatta) and identified 11 polymorphic loci with heterozygosity rates of at least 0.6. These markers were used for paternity testing in three social groups (M, R, and S) of rhesus macaques from Cayo Santiago, Puerto Rico. Several consecutive birth cohorts were analyzed in which approximately 200 males were tested for paternity against more than 100 mother/infant pairs. Despite a combined exclusion rate of more than 99.9% in all three groups, some cases could not be solved unequivocally with the STR markers and additional testing of the MHC‐associated DQB1 polymorphism. A final decision became possible through multilocus DNA fingerprinting with one or more of the oligonucleotide probes (GATA)4, (CA)8, and (CAC)5. Paternity assessment by multilocus DNA analysis with probe (CAC)5 alone was found to have limitations in rhesus macaques as regards the number of potential sires which might be involved in a given case. Multilocus DNA fingerprinting requires large amounts of DNA, and the ensuing autoradiographic patterns present difficulties in comparisons across gels and even within the same gel across remote lanes. Computer‐assisted image analysis was incapable of eliminating this problem. Therefore, a dual approach to DNA typing has been adopted, using STR markers to reduce the number of potential sires to a level where all remaining candidates can be tested by multilocus DNA fingerprinting on a single gel, preferably in lanes adjacent to the mother/infant pair. Am. J. Primatol. 44:1–18, 1998. © 1998 Wiley‐Liss, Inc.
Hereditary Spastic Paraplegia Clinical Genetic Study of 15 Families

Results: Nine families with ADHSP were linked to the SPG4 locus at 2p21-p24. Sequence analysis of SPG4 showed a novel N386S mutation in all 9 of these families. Expression of mutant spastin showed aberrant distribution in cultured cells. Haplotype analysis suggested the existence of a common founder. Clinical examination of the affected members carrying the mutation showed phenotypic variations including broad range of age at onset and disease duration and additional neurologic features such as mental retardation. Magnetic resonance imaging demonstrated unique features, including thin corpus callosum and atrophy of the cerebellum in 2 patients. Linkage and sequence analyses showed no evidence of linkage to the currently known ADHSP loci in the remaining 6 families.
Convergent Actor Critic by Humans

Programming robot behavior can be painstaking: for a layperson, this path is unavailable without investing significant effort in building up proficiency in coding. In contrast, nearly half of American households have a pet dog and at least some exposure to animal training, suggesting an alternative path for customizing robot behavior. Unfortunately, most existing reinforcement-learning (RL) algorithms are not well suited to learning from human-delivered reinforcement. This paper introduces a framework for incorporating humandelivered rewards into RL algorithms and preliminary results demonstrating feasibility.
Report in the Thyroid Hormone Signaling Pathway in the Stickleback Radiation

Jun Kitano,1,2,3,* Sean C. Lema,4,5 J. Adam Luckenbach,5 Seiichi Mori,6 Yui Kawagishi,1 Makoto Kusakabe,7,8 Penny Swanson,5 and Catherine L. Peichel3 1Department of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan 2PRESTO, Japan Science and Technology Agency (JST), Honcho Kawaguchi, Saitama 332-0012, Japan 3Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA 4Department of Biology and Marine Biology, University of North Carolina-Wilmington, Wilmington, NC 28403, USA 5Northwest Fisheries Science Center, National Marine Fisheries Service, Seattle, WA 98112, USA 6Biological Laboratory, Gifu-keizai University, Ogaki, Gifu 503-8550, Japan 7School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195-5020, USA 8Department of Marine Bioscience, Atmosphere and Ocean Research Institute, The University of Tokyo, Kashiwanoha, Chiba 277-8564, Japan
A method for automatic extraction of F/sub 0/ contour generation process model parameters for Mandarin

The model of F/sub 0/ contour generation has been successfully applied to Mandarin, which is a typical tone language with a distinct feature that both positive and negative tone commands are required. In this paper, a method is proposed for automatic extraction of parameters of the F/sub 0/ contour model for Mandarin. With the same framework as that proposed for Japanese and English, the method presented here for Mandarin is focused on the first-order estimation of tone command parameters. In order to distinguish between positive and negative tone commands, the information on syllable timing and tone labels is employed, and a set of rules are constructed to recognize the tone command patterns within each syllable. A preliminary experiment indicates that the method works effectively and gives results comparable with those obtained by manual analysis.
Galanin receptor subtypes and ligand binding

Galanin is a neuropeptide initiating its multiple biological effects by binding to different subtypes of seven transmembrane spanning galanin receptors, thus transducing the extracellular signal to G-proteins. There is a wide range of galanin receptor ligands available today, and some of the ligands have been shown to act as antagonists in galaninergic signal transduction systems at tissue level and in vivo. Subtype-specific galanin receptor ligands could be used selectively to initiate or block the effects of galanin in order to provide insights into the role of galanin both at normal and pathophysiological conditions, and in the development of compounds with therapeutical values. This review highlights the recent reports on the binding affinities of GalR in CNS and transfected cell lines.
Effect of the codon 72 polymorphism (c.215G>C, p.Arg72Pro) in combination with somatic sequence variants in the TP53 gene on survival in patients with advanced ovarian carcinoma

This study was conducted to evaluate the frequency and prognostic impact of TP53 alterations stratified for the TP53 codon 72 polymorphism (c.215G>C, p.Arg72Pro) in a cohort of 109 patients with advanced ovarian carcinomas. TP53 sequence variants were observed in 80 of the 109 (73.4%) tumors and were significantly associated with grade of differentiation (P=0.001). A tendency towards higher frequency of sequence variants in tumors with higher FIGO stages was seen (P=0.05). The type of TP53 sequence variant (transition A:T>G:C vs. G:C>A:T at CpG dinucleotides, and transversion G:C>T:A) had significant correlation with patients' age (P=0.04) with more A:T>G:C in patients over 60 years old. No significant associations were found between frequency of sequence variants and age at diagnosis, histological type, size of residual tumor after primary surgery, or long‐term survival. Analyses of the codon 72 polymorphism in tumor DNA gave a higher frequency of homozygosity/hemizygosity than expected from the population frequency, particularly for the Pro allele. Tumors homozygous or hemizygous for the Pro allele had significantly higher frequency of TP53 sequence variants, particularly of the nonmissense type (P=0.002), and patients with these types of alterations had significantly shorter survival (P=0.04). TP53 protein accumulation, determined by immunohistochemistry (IHC), was found in 67.9% (74 out of 109) of the tumors, was significantly more common among serous than nonserous ovarian carcinomas (P=0.008), and had a significant effect on progression‐free survival (P=0.03). p63 (TP73L; formerly TP63) and p73 (TP73) protein accumulation detected by IHC was seen in 67.9 and 0% of the tumors, respectively. A significantly higher frequency of p63‐positive cases was seen among serous tumors (P=0.008) and tended to increase with increasing FIGO stages (P=0.05), but had no significant effect on survival. No association between p63 protein accumulation and TP53 protein accumulation was seen. Hum Mutat 24:21–34, 2004. © 2004 Wiley‐Liss, Inc.
USING BAGGING AND MAPREDUCE IN K-MEANS CLUSTERING FOR DETECTION OF CANCER

Cancer is a group of diseases which involves abnormal growth of cell and spread to other body parts. As the cause of the disease is unknown, it is leading to the cause of death of many people. Early detection of cancer is a challenging thing. Many methods of detection have been developed and are being used, but the selection of a proper method of detection helps in early treatment and recovery of a patient. This paper proposes the clustering of k-means using MBK Algorithm, MapReduce technique. So that large data sets will run efficiently and also it will help in early detection of cancer.
Acrosomal Status Quantitation in Human Sperm

Acceptable methods are currently available for the rapid quantitation of acrosomal status in human sperm. Application of these methods to human sperm has led to the concept that spontaneous acrosomal loss occurs infrequently during capacitation. Induced loss occurs following sperm exposure to human follicular fluid, to zonae- or cumulus-enclosed eggs, or to calcium ionophores or other agents that modulate intracellular calcium levels. Acrosomal status quantitation may be helpful in sperm morphologic characterization or in evaluating cryodamage but has not yet been established in fertility potential measurement.
Non-Significance of Early Speech Delay in Children with Autism and Normal Intelligence and Implications for DSM-IV Asperger’s Disorder

According to the DSM-IV, children with Asperger’s disorder do not have significant cognitive or speech delays, whereas children with autistic disorder may or may not. In our study, children with normal intelligence who had clinical diagnoses of autism or Asperger syndrome were divided into two groups: those with and without a significant speech delay. The purpose was to determine if clinically meaningful differences existed between the two groups that would support absence of speech delay as a DSM-IV criterion for Asperger’s disorder. No significant differences were found between the 23 children with a speech delay and the 24 children without a speech delay on any of the 71 variables analyzed, including autistic symptoms and expressive language. Results suggest that early speech delay may be irrelevant to later functioning in children who have normal intelligence and clinical diagnoses of autism or Asperger syndrome and that speech delay as a DSM-IV distinction between Asperger’s disorder and autism may not be justified.