Miracle-dz/UniFAR-FTUs huggingface dataset:
An open label trial of topiramate as adjunctive therapy in Asian patients with refractory partial epilepsy

Objectives: The study evaluated the efficacy and safety of topiramate as adjunctive therapy in patients with refractory partial seizures with or without secondarily generalization. Methods: A historical assessment of patients was performed before study. Topiramate was prescribed at target dosages of 200 – 1600 mg daily for 6 months. Primary efficacy variable was the percent reduction in the average monthly seizure rate in the core phase relative to the retrospective baseline phase. Secondary efficacy evaluation included percentage of patients with ≥ 50%, ≥ 75% and 100% reduction in seizure rate and clinical global evaluations. Safety evaluations were performed by monitoring of adverse events, vital signs and laboratory tests. Results: 103 patients with a mean age of 31 years were recruited. Median topiramate dosage at endpoint was about 300 mg daily (range: 100mg – 1200 mg). Fifty-three percent of patients had ≥ 50% seizure reduction, 31% had ≥ 75% seizure reduction and 12% became seizure free. Investigators’ global evaluation at endpoint indicated that 86% of patients improved compared to baseline, while patients’ own assessment of the treatment indicated good to excellent response in 53% of patients. The most common adverse events were central nervous system related. Conclusions: Topiramate appeared to be efficacious and safe in patients with refractory partial seizures.
Association between molecular subtypes and lymph node status in invasive breast cancer.

BACKGROUND The predictors for the involvement of lymph node (LN) have been widely studied. But the implication of the molecular type has not been well studied. Using the database of our institution, we investigated this relation. METHODS Patients with T1 and T2 primary breast cancer without distant metastasis were included in our study from 2012 Jan to 2013 Dec. All patients undertook the resection of the primary and the axillary lymph nodes (ALNs). We collected the clinical data including age at diagnosis, the status of ER, PR and HER2, tumor size, nodal status, and histological type. The relationship between demographic, tumor characteristics and lymph node status was evaluated. RESULTS 814 patients were included in our study. The number and the percentage (in parentheses) of each type of breast cancer is as follows: Luminal A 230 (28.3%), Luminal Her2- 284 (34.9%), Luminal Her2+ 104 (12.8%), HER2+ 72 (8.8%), TNBC 124 (15.2%). On univariate and multivariate analysis, tumor size and tumor subtype show statistical significance with LN involvement. Using TNBC as a reference, both Luminal B type (Luminal HER2-, Luminal HER2+) shows significant higher probability of LN involvement. CONCLUSIONS LN involvement is an intrinsic characteristic for molecular subtype of breast cancer. Triple positive and triple negative breast cancer accounts the most and least possibility of LN involvement.
Mutations of CEBPA in acute myeloid leukemia FAB types M1 and M2

CEBPA encodes the transcription factor C/EBPα and is specifically up‐regulated during granulocytic differentiation. The gene is mutated in approximately 20% of patients with acute myeloid leukemia (AML) FAB type M2 and occurs in the absence of the t(8;21). In much the same way as specific translocations are associated with a particular AML FAB type, the identification of non‐random associations of gene mutation with karyotype or FAB type may be helpful in elucidating the molecular basis of certain forms of leukemia. To confirm these initial findings, 99 patients with AML FAB type M1 or M2 were screened for CEBPA mutations by use of a PCR–single‐strand conformational polymorphism and sequencing approach. Nine CEBPA mutations were identified in eight patients. The mutations were clustered toward the COOH terminal of the protein and occurred exclusively in the intermediate cytogenetic risk group (8/64, 12.5%). Two patients with biallelic mutation, one homozygous for 1137Ins (57 bp) and another with two CEBPA mutations, 1096Ins (27 bp) and 363Ins (GGCC), were observed. There was no evidence for deletion of this region in the other six mutated samples analyzed by fluorescence in situ hybridization with a BAC clone spanning the CEBPA locus. CEBPA mutation status was not demonstrated to be of prognostic importance in this patient group, although this may reflect the selection and size of the AML population studied. In conclusion, mutation of CEBPA is a recurrent finding in AML and appears specific to the intermediate cytogenetic risk group patients. © 2003 Wiley‐Liss, Inc.
Multiple ways to switch platelet integrins on and off

Summary. In the classical concept of platelet integrin activation, it is considered that unidirectional conformational changes of αIIbβ3 and α2β1 regulate the adhesiveness of platelets for fibrin(ogen) and collagen, respectively. Here, we summarize recent evidence that these conformational changes: (i) can also occur in the reverse direction; and (ii) are not independent events. Platelet stimulation through the P2Y12 receptors provokes only transient αIIbβ3 activation via signaling routes involving phosphoinositide 3‐kinases and Rap1b. Furthermore, αIIbβ3 can be secondarily inactivated in platelets with prolonged high Ca2+ rises, which expose phosphatidylserine and bind coagulation factors. Thus, platelet stimulation with strong agonists (collagen and thrombin) also results in transient integrin activation. Integrin α2β1 is found to be activated by a mechanism that is directly linked to αIIbβ3 activation. Integrin α2β1 can adopt different activation states, depending on the trigger. Conclusively, reversibility and synchrony of platelet integrin activation are newly identified mechanisms to restrict thrombus growth and to allow optimal coagulation factor binding. Back‐shifting of activated integrins towards their resting state may be a novel goal of antithrombotic medication.
The status of anthropogenic threat at the people-park interface of Bwindi Impenetrable National Park, Uganda

SUMMARY Effective management of anthropogenic threats is key to sustaining biological diversity in protected areas. Types and distribution of threats to Bwindi Impenetrable National Park, Uganda were investigated to assess the Park's status 12 years after it was upgraded from a forest reserve to a national park. Bwindi, like many tropical forested parks, is surrounded by dense human populations. Threats were quantified in 104 1-km edge-interior transects set around the Park. The distribution of threats was patchy and was most common within 300–350 m of the edge. The commonest threat was harvesting of wood and poles. Other threats included occurrence of exotic species, degradation of adjacent habitat fragments and high impact of problem animals on some of the neighbouring communities. The fact that threats were primarily associated with the edges of the Park, when previously they were widespread throughout the Park, suggests that illegal resource harvesting has been reduced since the forest was upgraded to a national park. Park legislation, enforcement and related conservation efforts have been effective, and there should be increased effort to manage the people-park interface. Edge-based assessments appear to be useful for quantifying threats to protected areas and identifying areas in which they are concentrated.
Time Series Analysis of Surface Ozone Monitoring Records in Kemaman, Malaysia

Time series analysis and forecasting has become a major tool in many applications in air pollution and environmental management fields. Among the most effective approaches for analyzing time series data is the model introduced by Box and Jenkins, ARIMA (Autoregressive Integrated Moving Average). In this study we used Box-Jenkins methodology to build ARIMA model for monthly ozone data taken from an Automatic Air Quality Monitoring System in Kemaman station for the period from 1996 to 2007 with a total of 144 readings. Parametric seasonally adjusted ARIMA (0,1,1) (1,1,2)12 model was successfully applied to predict the long-term trend of ozone concentration. The detection of a steady statistical significant upward trend for ozone concentration in Kemaman is quite alarming. This is likely due to sources of ozone precursors related to industrial activities from nearby areas and the increase in road traffic volume.
Correlation of students' characteristics with their learning styles as they begin medical school.

PURPOSE To investigate the relationship between learning styles (surface, strategic, and deep learning) and admission data for an incoming class of medical students. METHOD In 1997, the Approaches and Study Skills Inventory (ASSIST) was administered to the University of Alberta Medical School's incoming class as part of their orientation. Ninety percent of the class completed the questionnaire, the results of which were correlated with prerequisite grade-point average (GPA), MCAT scores, number of years of premedical experience, and scores on autobiography, interview, and letters of reference. RESULTS Higher surface-learning scores correlated significantly with younger age at admission to medical school, as well as with higher GPA. There was a positive correlation between GPA and surface learning in the group of students with more than four years of premedical experience. CONCLUSIONS The need to compete for grades in prerequisite courses may be a factor contributing to surface learning in new medical students.
Successful treatment of recurrent Henoch–Schönlein purpura nephritis in a renal allograft with tonsillectomy and steroid pulse therapy

We report a case of recurrent Henoch–Schönlein purpura nephritis (HSPN) treated successfully with a tonsillectomy and steroid pulse therapy in a kidney transplant patient. A 29‐year‐old woman was admitted to our hospital for an episode biopsy; she had a serum creatinine (S‐Cr) of 1.0 mg/dL and 1.34 g/day proteinuria 26 months after kidney transplantation. Histological examination revealed increased amounts of mesangial matrix and mesangial hypercellularity with IgA deposition. Of note, one glomerulus showed focal endocapillary proliferation and tuft necrosis. We diagnosed active recurrent HSPN. Considering both the histological findings and refractory clinical course of the native kidney, she was treated for 3 consecutive days with steroid pulse therapy and a tonsillectomy. The patient's proteinuria decreased gradually to less than 150 mg/day 6 months later. A second biopsy 6 years after kidney transplantation showed an excellent response to treatment and revealed a marked reduction in both the mesangial matrix and mesangial hypercellularity, with trace IgA deposition. We conclude that a tonsillectomy and steroid pulse therapy appeared to be useful in this patient with active recurrent HSPN. This paper is the first to report a tonsillectomy and steroid pulse therapy as a therapeutic option for active recurrent HSPN. Further studies are needed to elucidate the efficacy and mechanisms of tonsillectomy with recurrent HSPN in kidney transplant patients.
Why Does Balanced News Produce Unbalanced Views?

Many studies find that presentation of balanced information, offering competing positions, can promote polarization and thus increase preexisting social divisions. We offer two explanations for this apparently puzzling phenomenon. The first involves what we call asymmetric Bayesianism: the same information can have diametrically opposite effects if those who receive it have opposing antecedent convictions. Recipients whose beliefs are buttressed by the message, or a relevant part, rationally believe that it is true, while recipients whose beliefs are at odds with that message, or a relevant part, rationally believe that the message is false (and may reflect desperation). The second explanation is that the same information can activate radically different memories and associated convictions, thus producing polarized responses to that information, or what we call a memory boomerang. An understanding of these explanations reveals when balanced news will produce unbalanced views. The explanations also account for the potential influence of "surprising validators. " Because such validators are credible to the relevant audience, they can reduce the likelihood of asymmetric Bayesianism, thus promoting agreement.
Do Better-Connected CEOs Innovate More?

We present evidence suggesting that chief executive officer (CEO) connections facilitate investments in corporate innovation. We find that firms with better-connected CEOs invest more in research and development and receive more and higher quality patents. Further tests suggest that this effect stems from two characteristics of personal networks that alleviate CEO risk aversion in investment decisions. First, personal connections increase the CEOâ€™s access to relevant network information, which encourages innovation by helping to identify, evaluate, and exploit innovative ideas. Second, personal connections provide the CEO with labor market insurance that facilitates investments in risky innovation by mitigating the career concerns inherent in such investments.
1 Innovative Glass-Box Approach : A Better Way to Enhance Learning of Complex Dynamic Systems

Due to increasing demand for simulation and modeling, efforts are needed to build up more powerful simulation and modeling methodologies that can help to facilitate learning complex dynamic systems. By learning we mean the acquisition of knowledge, skills and experience for better and faster learning of the various types of complex dynamic systems. System dynamics is one of the successful well formulated methodologies that provides a perfect framework for building highly interactive learning environments where learners involve in reasoning about the relationships between the structure and the dynamics of a complex system. In this paper, we address two recent well known approaches (Black-Box and Glass-Box) that enhance learning capabilities in a typical complex dynamic system and demonstrate the overall learning effectiveness by using their own methodologies. Furthermore, we present a critical comparison of traditional black-box approach and the innovative glass-box approach. In addition, we also present two experiments that are associated with the black-box approach.
Swedish Nurses' Experiences of Caring for Dying People: A Holistic Approach

Most people need to be cared for at the end of their lives by professionals. This study aimed to elucidate the meaning of nurses' experiences of caring for dying persons at home and in a special unit in a hospital. Four registered nurses working in private homes and 4 registered nurses working in a specific unit in a hospital setting were interviewed. The study was planned and carried out with a phenomenological hermeneutic approach. A naive reading guided a structural analysis, which resulted in 3 main themes: meeting patients and family members as unique persons, learning in a challenging environment, and gaining personal strength. The interpreted comprehensive understanding conveyed a meaning that caring for families with a member awaiting the end of life created a situation where the presence of an inevitable death demanded nurses to create close relationships with each unique person involved.
Lack of clinically significant pharmacological interactions between ticagrelor and enoxaparin or unfractionated heparin in healthy subjects

What is known and Objective: Patients with acute coronary syndromes (ACS) receive several pharmacological therapies concomitantly, including antiplatelet and anticoagulant agents. As unfractionated heparin (UFH) activates platelets in vitro and in vivo, co‐administration with an antiplatelet agent may lead to decreased clinical effectiveness of the latter. The aim was therefore to determine any potential drug–drug interactions between the new oral antiplatelet agent ticagrelor, and UFH or enoxaparin.
Prevalence and correlates of depression symptoms at 10 years after heart transplantation: continuous attention required

This study investigates the presence and correlates of symptoms of depression at 5 and 10 years after heart transplantation, with particular attention given to patients showing symptoms at both time points. Prevalence of depression symptoms were studied in 41 patients, prospectively, at 5 and 10 years after heart transplantation. We examined potential correlates of depression symptoms (i.e. worse functional capacity, inadequate coping mechanisms and lack of social contacts) 10 years after transplantation. The prevalence of depression symptoms was 30% at 5 years and 22% at 10 years. Of the 41 patients, 20% were depressed at both time points. Those patients had significantly higher scores on passive coping and had significantly lower club membership. They also tended to have more negative emotions (i.e. anger, hostility and irritability) and less engagement in sports activities. Functional capacity was not different. Depression symptoms were prevalent and persistent in the long-term after heart transplantation. This study opens perspectives for beyond-standard pharmacological and psychotherapeutic treatment for depression, i.e. training patients who are using passive coping to use problem-solving capacities instead and motivating them to engage in social life and sports activities.
Risk reduction and perceived collective efficacy and community support among female sex workers in Tamil Nadu and Maharashtra, India: the importance of context

Background Empowering sex workers to mobilise and influence the structural context that obstructs risk reduction efforts is now seen an essential component of successful HIV prevention programmes. However, success depends on local programme environments and history. Methods The authors analysed data from the Integrated Behavioural and Biological Assessment Round I cross-sectional survey among female sex workers in Tamil Nadu and Maharashtra. The authors used propensity score matching to estimate the impact of participation in intervention activities on reduction of risk (consistent condom use) and vulnerability (perceived collective efficacy and community support). Results Background levels of risk and vulnerability as well as intervention impact varied widely across the different settings. The effect size ATT of attending meetings/trainings on consistent condom use was as high as 21% in Tamil Nadu (outside of Chennai) where overall use was lowest at 51%. Overall, levels of perceived collective efficacy were low at the time of the survey; perceived community support was high in Tamil Nadu and especially in Chennai (93%) contrasting with 33% in Mumbai. Consistent with previous research, the context of Mumbai seems least conducive to vulnerability reduction, yet self-help groups had a significant impact on consistent condom use (ATT=10%) and were significantly associated with higher collective efficacy (ATT=31%). Conclusions Significant risk reduction can be achieved by large-scale female sex worker interventions, but the impact depends on the history of programming, the complexity of the context in which sex work happens and pre-existing levels of support sex workers perceive from their peers.
DUSP4 promotes doxorubicin resistance in gastric cancer through epithelial-mesenchymal transition

Chemoresistance limits treatment efficacy in gastric cancer and doxorubicin resistance is common in gastric cancer cells. Dual specificity phosphatase 4 (DUSP4) has been associated with tumor progression. This study aimed to investigate the mechanism of DUSP4 regulating doxorubicin resistance in gastric cancer cells. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay were used to measure cell viability and proliferation in gastric cancer cells treated with doxorubicin. The expression of DUSP4, E-cadherin and Vimentin protein was detected by Western blotting. Overexpression of DUSP4 was more resistant to doxorubicin in gastric cancer cells. Knockdown of DUSP4 increased the sensitivity of gastric cancer cells to doxorubicin. Moreover, up-regulation of DUSP4 promoted the Epithelial-Mesenchymal Transition (EMT) in gastric cancer cells, but blocking the EMT using a Twist siRNA increased the sensitivity of gastric cancer cells to doxorubicin and confirmed the EMT was involved in DUSP4-mediated doxorubicin resistance. These findings demonstrated that DUSP4 could enhance doxorubicin resistance by promoting EMT in gastric cancer cells.
Cloning, expression, and sequencing of squalene-hopene cyclase, a key enzyme in triterpenoid metabolism

The pentacyclic hopanoids, a class of eubacterial lipids, are synthesized by squalene-hopene cyclase and side chain-elongating enzymes. With the aid of DNA probes based on the amino-terminal sequence of purified squalene-hopene cyclase from Bacillus acidocaldarius, clones of Escherichia coli that express this enzyme in the cytoplasmic membrane were isolated. According to the DNA sequence, the cyclase contained 627 amino acids with a molecular mass of 69,473 Da. A high percentage of the amino acids were basic. No significant similarity to existing sequenced proteins was found.
Forensic Population Genetics - Original Research Development and assessment of an optimized next-generation DNA sequencing approach for the mtgenome using the Illumina MiSeq

A B S T R A C T The development of molecular tools to detect and report mitochondrial DNA (mtDNA) heteroplasmy will increase the discrimination potential of the testing method when applied to forensic cases. The inherent limitations of the current state-of-the-art, Sanger-based sequencing, including constrictions in speed, throughput, and resolution, have hindered progress in this area. With the advent of next-generation sequencing (NGS) approaches, it is now possible to clearly identify heteroplasmic variants, and at a much lower level than previously possible. However, in order to bring these approaches into forensic laboratories and subsequently as accepted scientific information in a court of law, validated methods will be required to produce and analyze NGS data. We report here on the development of an optimized approach to NGS analysis for the mtDNA genome (mtgenome) using the Illumina MiSeq instrument. This optimized protocol allows for the production of more than 5 gigabases of mtDNA sequence per run, sufficient for detection and reliable reporting of minor heteroplasmic variants down to approximately 0.5–1.0% when multiplexing twelve samples. Depending on sample throughput needs, sequence coverage rates can be set at various levels, but were optimized here for at least 5000 reads. In addition, analysis parameters are provided for a commercially available software package that identify the highest quality sequencing reads and effectively filter out sequencing-based noise. With this method it will be possible to measure the rates of low-level heteroplasmy across the mtgenome, evaluate the transmission of heteroplasmy between the generations of maternal lineages, and assess the drift of variant sequences between different tissue types within an individual.