Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacotherapy of conduct disorder: Challenges, options and future directions

There is a critical need for evaluation of the pharmacotherapies used in conduct disorder (CD), due to the high incidence of off-label prescribing. The aim of this review was to identify concerns associated with the safety, efficacy and impact on quality of life (QOL) that pharmacotherapy has in children and adolescents with CD. A systematic review was undertaken using pre-defined search criteria and four databases, including reference searches. We assessed these studies using the Strength of Recommendation Taxonomy, Grading of Recommendations Assessment, Development and Evaluation, and Review Manager Risk of Bias (RevMan®) tools. There were 12 randomised controlled trials that met our inclusion criteria. Studies included: antipsychotics, atomoxetine, lithium, clonidine, divalproex sodium and psychostimulants. The antipsychotics demonstrated efficacy, but were associated with adverse effects. Other agents demonstrated mixed responses, highlighting the lack of clinical significance and increased incidence of adverse effects. The management of related adverse effects was addressed to assist with clinical gaps. Overall, there is limited evidence regarding the role of pharmacotherapy in CD. More research is needed that takes into account the heterogeneity of CD and analysis of pharmacotherapy in pure CD.
Setting the pace: examining cognitive processing in MOOC discussion forums with automatic text analysis

ABSTRACT Learning analytics focuses on extracting meaning from large amounts of data. One of the largest datasets in education comes from Massive Open Online Courses (MOOCs) that typically feature enrollments in the tens of thousands. Analyzing MOOC discussion forums presents logistical issues, resulting chiefly from the size of the dataset, which can create challenges for understanding and adequately describing student behaviors. Utilizing automatic text analysis, this study built a hierarchical linear model that examines the influence of the pacing condition of a massive open online course (MOOC), whether it is self-paced or instructor-paced, on the demonstration of cognitive processing in a HarvardX MOOC. The analysis of 2,423 discussion posts generated by 671 students revealed the number of dictionary words used were positively associated with cognitive processing while analytical thinking and clout was negatively associated. We found that none of the student background information (gender, education), status of the course engagement (explored or completed), or the course pace (self-paced versus instructor paced) significantly influenced the cognitive processing of the postings.
Mechanisms of Recombination between Diverged Sequences in Wild-Type and BLM-Deficient Mouse and Human Cells

ABSTRACT Double-strand breaks (DSBs) are particularly deleterious DNA lesions for which cells have developed multiple mechanisms of repair. One major mechanism of DSB repair in mammalian cells is homologous recombination (HR), whereby a homologous donor sequence is used as a template for repair. For this reason, HR repair of DSBs is also being exploited for gene modification in possible therapeutic approaches. HR is sensitive to sequence divergence, such that the cell has developed ways to suppress recombination between diverged (“homeologous”) sequences. In this report, we have examined several aspects of HR between homeologous sequences in mouse and human cells. We found that gene conversion tracts are similar for mouse and human cells and are generally ≤100 bp, even in Msh2−/− cells which fail to suppress homeologous recombination. Gene conversion tracts are mostly unidirectional, with no observed mutations. Additionally, no alterations were observed in the donor sequences. While both mouse and human cells suppress homeologous recombination, the suppression is substantially less in the transformed human cells, despite similarities in the gene conversion tracts. BLM-deficient mouse and human cells suppress homeologous recombination to a similar extent as wild-type cells, unlike Sgs1-deficient Saccharomyces cerevisiae.
Protection of MV Converters in the Grid: The Case of MV/LV Solid-State Transformers

Solid-state transformers (SSTs) are a promising technology as they provide new functionalities and services enabling future smart grids. An SST establishes the interface between an MV ac grid and an LV (ac or dc) grid or load. The SST must provide high reliability even in the event of certain grid faults, where the SST is subject to exceptional electrical stresses. In addition, the MV and LV grids are exposed to failures of the SSTs. Spurred by such challenging requirements, this paper defines the different relevant stresses, identifies the corresponding protection needs, and proposes adequate protection circuitries and devices. The protection mechanisms that are currently used for low-frequency transformers are analyzed and an adapted version is proposed for SSTs. MV short circuits and overvoltages are identified as the most critical situations and are analyzed in detail. From the presented in-depth investigation, guidelines are extracted for designing robust SSTs and are applied to a 1 MVA, 10 kV SST.
Cerebral Blood Volume and Blood Flow Responses to Hyperventilation in Brain Tumors During Isoflurane or Propofol Anesthesia

Using computerized tomography, we measured absolute cerebral blood flow (CBF) and cerebral blood volume (CBV) in tumor, peri-tumor, and contralateral normal regions, at normocapnia and hypocapnia, in 16 rabbits with brain tumors (VX2 carcinoma), under isoflurane or propofol anesthesia. In both anesthetic groups, CBV and CBF were highest in the tumor region and lowest in the contralateral normal tissue. For isoflurane, a significant decrease in both CBV and CBF was observed in all tissue regions with hyperventilation (P < 0.05), but without accompanying changes in intracranial pressure. However, the percent reduction in regional CBF with hypocapnia was two times larger than that observed in the CBV response (P < 0.01). In contrast, there were no significant changes in CBV and CBF in the Propofol group with hyperventilation for all regions (P > 0.10). In addition, there were no differences between CBV values for isoflurane at hypocapnia when compared with CBV values for propofol at normo- or hypocapnia (P > 0.34 and P > 0.35, respectively, in the tumor regions). Our results indicate that propofol increases cerebral vascular tone in both neoplastic and normal tissue vessels compared with isoflurane. CBV and CBF during normocapnia were significantly greater in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol. CBV and CBF remained responsive to hyperventilation only with isoflurane.
Interaction of Heat with Chemotherapy in Vitro: Effect on Cell Viability and Protein Synthesis in Human and Murine Cell Lines

Cell survival in response to doxorubicin (Dx) and cis-diammine-dichloroplatinum (cis-Pt) administration, either alone or combined with hyperthermic treatment, was analyzed in human osteosarcoma (U-2-OS), murine melanoma (B16V) and murine leukemia (P388) cell lines and in Dx-resistant sublines derived from B16V and P388. In all cell lines tested there was an enhancement of drug toxicity by hyperthermia. In U-2-OS, the increase was more pronounced for cis-Pt than for Dx. In B16V and in P388, the increase in Dx toxicity was of the same degree in Dx-senstitive and Dx-resistant sublines, whereas heat-induced sensitization to cis-Pt was higher in Dx-resistant sublines than in their Dx-sensitive counterpart. Analysis of the protein pattern in the various cell lines showed that the synthesis of heat-shock proteins induced by heat was not influenced by the combined use of drugs and heat. Moreover, in spite of some differences in the overall protein pattern, no significant differences in the basal levels of heat-shock protein synthesis or in the extent of its induction after heat shock were observed between murine cell lines relatively sensitive to Dx and their corresponding selected resistant cells.
Phosphorylation motifs in the nonhelical domains of myosin heavy chain and paramyosin may negatively regulate assembly in Caenorhabditis elegans striated muscle

We are interested in mechanisms that establish and maintain the highly ordered contractile apparatus of striated muscle. The homologous proteins myosin and paramyosin are the major structural components of thick filaments in invertebrate animals. In Caenorhabditis elegans, both proteins contain a homologous, small nonhelical domain that is known to be phosphorylated in paramyosin. In this report, we show that a proposed phosphorylation motif (S_S_A), which is present in several copies in the nonhelical regions of both myosin and paramyosin, is highly conserved among nematodes. We used in vivo assays to examine the assembly properties of proteins in which one or more motifs were targeted by point mutagenesis or deletion. In all cases, expression of mutant proteins improved the phenotype of the corresponding null mutant animals, but produced variable structural defects, including birefringent aggregates in adults and abnormal localization in embryos. Point mutation, but not deletion, of the myosin A nonhelical tailpiece produced ectopic structures that appeared as masses of jumbled filaments by TEM. Antibody labeling showed that aggregates of either mutant protein did not recruit the endogenous version of the other. Analysis of mutant embryos lacking either paramyosin or myosin A (the essential isoform at the thick filament center) indicated that both wild‐type proteins can independently localize and initiate assembly, although the structures produced are abnormal. Our results suggest that muscle cells actively restrict myosin and paramyosin assembly through phosphorylation of the S_S_A motifs and that each protein is regulated independently. © 2010 Wiley‐Liss, Inc.
Toxicity assessment of manganese oxide micro and nanoparticles in Wistar rats after 28 days of repeated oral exposure

In the near future, nanotechnology is envisaged for large‐scale use. Hence health and safety issues of nanoparticles (NPs) should be promptly addressed. Twenty‐eight‐day oral toxicity, genotoxicity, biochemical alterations, histopathological changes and tissue distribution of nano and microparticles (MPs) of manganese oxide (MnO2) in Wistar rats was studied. Genotoxicity was assessed using comet, micronucleus and chromosomal aberration assays. The results demonstrated a significant increase in DNA damage in leukocytes, micronuclei and chromosomal aberrations in bone marrow cells after exposure of MnO2‐NPs at 1000, 300 mg kg–1 bw per day and MnO2‐MPs at the dose of 1000 mg kg–1 bw per day. Our findings showed acetylcholinestrase inhibition at 1000 as well as at 300 mg kg–1 bw per day in blood and with all the doses in the brain indicating the toxicity of MnO2‐NPs. Further, the doses significantly inhibited different ATPases in the brain P2 fraction. Significant changes were observed in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in the liver, kidney and serum in a dose‐dependent manner. MnO2‐MPs at 1000 mg kg–1 bw per day were found to induce significant alterations in biochemical enzymes. A significant distribution was found in all the tissues in a dose‐dependent manner. MnO2‐NPs showed a much higher absorptivity and tissue distribution as compared with MnO2‐MPs. A large fraction of MnO2‐NPs and MnO2‐MPs was cleared by urine and feces. Histopathological analysis revealed that MnO2‐NPs caused alterations in liver, spleen, kidney and brain. The MnO2‐NPs induced toxicity at lower doses compared with MnO2‐MPs. Further, this study did not display gender differences after exposure to MnO2‐NPs and MnO2‐MPs. Therefore, the results suggested that prolonged exposure to MnO2 has the potential to cause genetic damage, biochemical alterations and histological changes. Copyright © 2013 John Wiley & Sons, Ltd.
Malignant Peripheral Nerve Sheath Tumors: A Single Institution’s Experience Using Combined Surgery and Radiation Therapy

Purpose: The purpose of this study is to investigate local control (LC), survival outcomes, and associated prognostic factors for patients with malignant peripheral nerve sheath tumors (MPNSTs) treated with combined surgery and radiation therapy (RT). Methods: We reviewed the medical records of 71 consecutive patients treated with surgery and RT for localized MPNST between 1965 and 2012. Preoperative RT was used to treat 23 patients (32%) to a median dose of 50 Gy (range, 50 to 60 Gy), whereas 48 (68%) received postoperative RT to a median dose of 64 Gy (range, 45 to 70 Gy). Results: Median follow-up for living patients was 118 months (range, 21 to 512 mo). The 5-year LC, distant metastatic free survival, and disease-specific survival rates were 84%, 62%, and 66%, respectively. To identify predictors of outcome, several multivariate models were constructed: (1) positive/uncertain surgical margin status was the only factor adversely associated local relapse at 5 years (28% vs. 5% for negative margins; P=0.02; hazard ratios 5.92; 95% confidence interval, 1.3-27.4). (2) No factors were significantly associated with distant metastatic free survival. Of the 35 patients (49%) who sustained disease relapse, only 3 were ultimately salvaged. Only 2 patients had grade 2 late toxicities (necrosis, fibrosis) based on Common Terminology Criteria for Adverse Events version 4.03 criteria, and 1 patient had grade 1 edema. Conclusions: Combination therapy with surgery and RT provides favorable LC. Distant recurrences, however, continue to be challenging with limited salvage success at the time of relapse.
Work–Life Balance, Burnout, and Satisfaction of Early Career Pediatricians

BACKGROUND AND OBJECTIVE: Data describing factors associated with work–life balance, burnout, and career and life satisfaction for early career pediatricians are limited. We sought to identify personal and work factors related to these outcomes. METHODS: We analyzed 2013 survey data of pediatricians who graduated residency between 2002 and 2004. Dependent variables included: (1) balance between personal and professional commitments, (2) current burnout in work, (3) career satisfaction, and (4) life satisfaction. Multivariable logistic regression examined associations of personal and work characteristics with each of the 4 dependent variables. RESULTS: A total of 93% of participants completed the survey (n = 840). A majority reported career (83%) and life (71%) satisfaction. Fewer reported current appropriate work–life balance (43%) or burnout (30%). In multivariable modeling, excellent/very good health, having support from physician colleagues, and adequate resources for patient care were all found to be associated with a lower prevalence of burnout and a higher likelihood of work–life balance and career and life satisfaction. Having children, race, and clinical specialty were not found to be significantly associated with any of the 4 outcome measures. Female gender was associated with a lower likelihood of balance and career satisfaction but did not have an association with burnout or life satisfaction. CONCLUSIONS: Burnout and struggles with work–life balance are common; dissatisfaction with life and career are a concern for some early career pediatricians. Efforts to minimize these outcomes should focus on encouragement of modifiable factors, including health supervision, peer support, and ensuring sufficient patient care resources.
Co-integration Analysis between the Turkish Stock Market and its Balkan Hinterland Equivalents: Proof From the 2010-2015 Period

Abstract: The purpose of this study is to investigate whether there is a co-integration amongst (3) three Balkan countries; Bosnia Herzegovina, Macedonia and Turkey in relation to the German stock market (important for the Europe scale). For this purpose, the relevant stock market’s weekly closing values (in the time series) were analyzed between the periods of September 2010 and August 2015. The long-term co-integrated relationship is analyzed by the Johansen Juselius Co-integration Test. The empirical results show that these three Balkan countries have a meaningful, but moderate relationship in reference to the stock markets. In addition, the German stock market has a more powerful effect on the Turkish stock exchange in comparison to the Bosnia Herzegovinian and Macedonian stock exchanges. This paper suggests that international investors can diversify their portfolios in these (3) three Balkan stock markets. Keywords: the Balkans, emerging stock markets, indexes, market linkages, co-integration analysis
A Study on Lead Lag Relationship between Selected Index in Indian Financial Markets

The area of derivates was a recent financial security introduced in the Indian financial system which witnessed a phenomenal growth. The theory emphasis that, the main function of futures market is Price discovery function, i.e., futures market plays a dominant role when compared to spot market. The futures market senses the information rapidly than the spot market. This study investigates the Lead lag Relationship between the Spot and Futures market in Indian Financial market. Even though many studies were done on the Nifty Index and Stocks, fewer studies were conducted on the specific index which was available on the futures and spot market. The purpose of the study is to identify whether the futures market leads or lags when compared to the spot market. Granger Causality test and Johansen Co integration test were conducted to find out the relationship on the three selected indexes namely Bank Nifty, Cnx IT and Minifty. The empirical analysis was conducted on the daily data from its inception to 9th February 2012 collected from NSE Website. The Analysis shows that futures markets leads to spot markets in the selected indexes.
Identification of infants at risk for autism spectrum disorder and developmental language delay prior to 12 months

Studies have shown an increased head circumference and the absence of the head tilt reflex as possible risk factors for autism spectrum disorder, allowing for early detection at 12 months in typically developing population of infants. Our aim was to develop a screening tool to identify infants prior to 12 months at risk for autism spectrum disorder and developmental learning delay, not affected by literacy or primary parental language, and provide immediate determination of risk for autism spectrum disorder. An abrupt head circumference acceleration and the absence of head tilt reflex by 9 months were used to identify infants at risk for autism spectrum disorder. Stability of early findings was then investigated when compared to comprehensive standardized neurodevelopmental assessment results and complete neurological and genetics evaluations. A total of 1024 typically developing infants were enrolled by 9 months, with 14 identified as at risk for autism spectrum disorder and 33 for developmental learning delay. There was a good positive predictive value for the identification of autism spectrum disorder prior to 12 months. This study demonstrates an efficient means to identify infants at risk for autism spectrum disorder by 9 months of age and serves to alert primary care providers of infants who are vulnerable for autism spectrum disorder before symptoms are discernible by clinical judgment of primary care providers, parental concerns, or by screening questionnaires.
The Aspergillus niger MADS‐box transcription factor RlmA is required for cell wall reinforcement in response to cell wall stress

In Aspergillus niger, the genes coding for glutamine:fructose‐6‐phosphate amidotransferase (gfaA) and α‐1,3‐glucan synthase (agsA) are induced in response to cell wall stress. In silico analysis of the promoter region of the two genes revealed the presence of putative DNA binding sites for transcription factors involved in stress responses, including sites identical to the Saccharomyces cerevisiae Rlm1p and Msn2p/Msn4p transcription factors. Promoter analysis indicated that the induction of the agsA gene in response to cell wall stress is fully dependent on a putative Rlm1p binding site in its promoter region. Database searches revealed the presence of S. cerevisiae Rlm1p homologues in most filamentous fungi examined, including A. niger. Deletion of the RLM1 homologue, named rlmA in A. niger, completely eliminated the induction of agsA and resulted in a twofold reduced induction of gfaA during Calcofluor White‐induced cell wall stress. The rise in cell wall chitin in the presence of Calcofluor White was also affected in the rlmA deletion strain. In addition, the deletion strain was more sensitive towards cell wall stress agents. Our results indicate that A. niger responds to cell wall stress by transcriptional activation of cell wall reinforcing genes including agsA and gfaA through an Rlm1p‐like transcription factor. We propose that such a cell wall salvage mechanism is wide spread in filamentous fungi.
Femtocell power control by discrimination of indoor and outdoor users

Femtocells are usually deployed in an indoor environment to provide in-building coverage enhancements. However, femtocells get to provide services for not only indoor users but also outdoor users in vicinity. Without the knowledge from the femtocell of whether the serviced users are located indoor or outdoor, the outdoor users are likely to experience low Quality of Service (QoS) due to inefficient coverage management and power control from the femtocells. To resolve such problem, this paper provides a method of discriminating indoor and outdoor users in a simplified way. Also, based on such discrimination, a downlink power control scheme is provided. Through simulations, we show that the discrimination procedure achieves 97.48% of correct determination in environment with low shadowing effect, and 89.41% of correct determination with high shadowing effects. Also based on the proposed discrimination procedure, power control exploiting such information provides a 31.96% reduction of outage probability, and a 8dB performance gain for cell-edge HUEs, compared to a power control with random discrimination.
Rheumatoid Arthritis and Fibromyalgia: A Frequent Unrelated Association Complicating Disease Management

Objective To assess the value of the 28-joint Disease Activity Score (DAS28) in evaluating disease activity in rheumatoid arthritis (RA) associated with fibromyalgia (FM). In this situation, because of the weight of the subjective measures included in the DAS28 equation, the patient’s status may be overestimated, leading to inappropriate treatment. We analyze the relationship between RA and FM and discuss whether the association is random or a marker of poor prognosis. Methods A questionnaire, developed when biologic therapies were introduced, was administered and the results analyzed in a consecutive, female outpatient population including 105 patients with RA, 49 with RA and FM (RAF), and 28 with FM. Psychosocial characteristics, disease presentation, and radiographic joint destruction evaluation were compared in the 3 populations. Results The presentation of RA was the same in patients with RA and RAF, but the 2 populations differed by socioprofessional characteristics, significantly higher disease activity in patients with RAF, and significantly more severe joint destruction in patients with RA. The RAF group was similar to the FM control population in socioprofessional and some physical characteristics. Regression analysis using the DAS28 measures differed significantly in the weight allowed to 28-joint counts for pain and swelling, but the constant factor was higher in patients with RAF. Conclusion DAS28 overestimated objective RA severity in patients who also had FM. The association between RA and FM does not appear to be a marker of worse prognosis, but rather a fortuitous association between the 2 diseases and one that may afford these patients some protection against joint destruction.