Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and tolerability of intravenous busulfan in hematopoietic stem cell transplantation

Abstract: Intravenous (IV) busulfan has been developed to overcome variable absorption of oral busulfan and tested in several trials. We tested its pharmacological properties and tolerability in 16 Korean stem cell transplantation (SCT) patients. IV busulfan was administered at 0.8 mg/kg every six h for a total of 16 doses (days −7 to −4), which was followed by cyclophosphamide administration at 60 mg/kg every 24 h for two d (days −3 and −2). The median AUCinf values (at the first dose) and AUCss (at the steady state) were 1060.4 μM·min (range: 511.1–1812.7) and 1092.5 μM·min (range: 539.7–1560.8) respectively. All patients had an AUCinf of <1500 μM·min at the first dose, and 13 of the 16 (81.3%) maintained AUCss levels between 800 and 1500 μM·min. Thirteen of 16 patients showed successful engraftments but four patients (25%) developed hepatic VOD (two of which were fatal), three of whom had advanced disease at the time of SCT. Overall, pharmacokinetics of IV busulfan in our SCT patients appeared comparable with those observed in other study. However, hepatic VOD was a major morbidity in patients with advanced disease.
Volatility Mean-Reversion on the Zimbabwe Stock Exchange (ZSE)

Prediction of volatility is to a larger extent anchored on the properties of a volatility time series i.e. mean-reversion or random-walk. The consistency of mean-reversion or random-walk on the ZSE stock price and return volatility remain unexplored. This study therefore attempts to investigate the behavior of ZSE stock price and return volatility using the class of Generalised Autoregressive Conditional heteroskedasticity (GARCH) models under a no distribution assumption. Stock price data has been differenced once and tested for stationarity using the Augmented Dickey Fuller test and the PP test. An appropriate GARCH (2.1) t model has been selected using Akaike and Schwarz Information criteria. Testing for mean-reversion and random-walk on stock price and return volatilities, the study concludes that both time series tend to mean-revert to their long-run averages with stock return volatility reverting faster than stock price volatility. We therefore recommend the need for dealing with liquidity challenges, ZSE automation as well as use of volatility as a leading indicator.
Endothelial Progenitor Cells: Therapeutic Perspective for Ischemic Stroke

Endothelial progenitor cells (EPCs), which can be cultured in vitro from mononuclear cells in peripheral blood or bone marrow, express both hematopoietic stem cell and endothelial cell markers on their surface. They are believed to participate in endothelial repair and postnatal angiogenesis due to their abilities of differentiating into endothelial cells and secreting protective cytokines and growth factors. Mounting evidence suggests that circulating EPCs are reduced and dysfunctional in various diseases including hypertension, diabetes, coronary heart disease, and ischemic stroke. Therefore, EPCs have been documented to be a potential biomarker for vascular diseases and a hopeful candidate for regenerative medicine. Ischemic stroke, as the major cause of disability and death, still has limited therapeutics based on the approaches of vascular recanalization or neuronal protection. Emerging evidence indicates that transplantation of EPCs is beneficial for the recovery of ischemic cerebral injury. EPC‐based therapy could open a new avenue for ischemic cerebrovascular disease. Currently, clinical trials for evaluating EPC transfusion in treating ischemic stroke are underway. In this review, we summarize the general conceptions and the characteristics of EPCs, and highlight the recent research developments on EPCs. More importantly, the rationale, perspectives, and strategies for using them to treat ischemic stroke will be discussed.
School problems in Tourette's syndrome.

BACKGROUND A retrospective study of 138 children with Tourette's syndrome for associated school problems revealed that at the time of initial evaluation, 64 subjects (46%) experienced a school-related problem. OBJECTIVE To survey a childhood population with Tourette's syndrome to explore the contributions of neurobehavioral concomitants to academic difficulties. RESULTS A diagnosis of a specific learning disorder had previously been made in 30 (22%) of 138 children. Among the 108 without a diagnosis of learning disorder, 36 (33%) experienced school difficulties defined as grade retention (16 [15%]) and/or special education placement (41 [38%]). Regression analysis of subjects without a diagnosis of learning disability revealed that the presence of attention-deficit hyperactivity disorder served as a significant predictor of school problems. CONCLUSIONS Tics represented the primary reason for referral, but did not emerge as a significant predictor of academic problems. Rather, school-related difficulties appeared to be strongly associated with comorbid attention-deficit hyperactivity disorder.
Cognitive Function and Psychiatric Symptoms in Early- and Late-Onset Frontotemporal Dementia

Background/Aim: Some recent studies mentioned that late-onset frontotemporal dementia (FTD) is more common than previously assumed. Although much research has been done in the field, there are no systematic studies which have compared clinical characteristics of early- and late-onset FTD. The aim of this study was to compare cognitive function and psychiatric symptoms in patients with early- and late-onset FTD. Methods: Study participants were consecutive outpatients. There were 35 FTD patients; their mean age at onset was 63.0 years. We studied sex, education, duration from onset to consultation, Clinical Dementia Rating (CDR) scores, Mini-Mental State Examination (MMSE) scores, Raven’s Coloured Progressive Matrices (RCPM) scores, and Neuropsychiatric Inventory (NPI) scores at first consultation of early- and late-onset FTD patients. Results: There were no significant differences in sex ratio, education, CDR scores, and duration from onset to consultation. There were significant differences in the total MMSE scores, ‘three-word recall task’, ‘construction task’, and RCPM scores; late-onset groups scored significantly lower than early-onset groups. There were significant differences in the apathy domain of NPI and total NPI scores; late-onset groups scored significantly higher than early-onset groups. Conclusion: Late-onset FTD patients may have memory and visuospatial deficits in addition to their behavioural changes, even if they are clinically diagnosed according to consensus diagnostic criteria. They also present more apathy, and they may have a different histolopathological background.
Platelet‐activating factor (PAF) induces activation of matrix metalloproteinase 2 activity and vascular endothelial cell invasion and migration

Tumor‐induced angiogenic responses lead to complex phenotypic changes in vascular endothelial cells, which must coordinate the expression of both proteases and protease inhibitors prior to the proliferation and invasion of surrounding stroma. Matrix metalloproteinase 2 (MMP2), which degrades Type IV collagen, is produced as proMMP2. proMMP2 is activated in part through its interactions with membrane Type 1 MMP (MT1‐MMP) and tissue inhibitor of matrix metalloproteinase 2 (TIMP2). In this study, we demonstrate that platelet‐activating factor (PAF) is a potent inducer of human umbilical vein endothelial cell (HUVEC) migration and invasion, which is attenuated by PAF receptor antagonists, and that PAF receptor antagonists inhibit the migration and invasion of HUVEC mediated by medium conditioned by a prostatic carcinoma cell line. We confirm that PAF receptor antagonists inhibit proliferation of HUVEC grown in rich growth medium. We show that PAF increases mRNA levels for MT1‐MMP and TIMP2, followed by increased temporal conversion of latent proMMP2 to MMP2. Finally, we demonstrate that the ratio of MT1‐MMP to TIMP2 in membrane preparations from PAF‐stimulated HUVEC is 1.6:1, approximating the hypothesized ideal ratio of 2:1 necessary for the conversion of proMMP2 to MMP2. Our data support the involvement of PAF in vascular endothelial cell migration and invasion.
Mast Cells Contribute to the Mucosal Adjuvant Effect of CTA1–DD after IgG-Complex Formation

Mast cell activation is one of the most dramatic immune-mediated responses the body can encounter. In the worst scenario (i.e., anaphylaxis), this response is fatal. However, the importance of mast cells as initiators and effectors of both innate and adaptive immunity in healthy individuals has recently been appreciated. It was reported that mast cell activation can be used as an adjuvant to promote Ag-specific humoral immune responses upon vaccination. In this study, we have used a clinically relevant mucosal adjuvant, cholera toxin A1 subunit (CTA1)–DD, which is a fusion protein composed of CTA1, the ADP-ribosylating part of cholera toxin, and DD, two Ig-binding domains derived from Staphylococcus aureus protein A. CTA1–DD in combination with polyclonal IgG induced degranulation and production of TNF-α from mouse mast cells. Furthermore, CTA1–DD and polyclonal IgG complex induced mast cell degranulation in mouse skin tissue and nasal mucosa. We also found that intranasal immunization with hapten (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to chicken gammaglobulin admixed with CTA1–DD complexed with polyclonal IgG greatly enhanced serum IgG anti-NP Ab responses and stimulated higher numbers of NP-specific plasma cells in the bone marrow as compared with that observed in mice immunized with NP-chicken gammaglobulin with CTA1–DD alone. This CTA1–DD/IgG complex-mediated enhancement was mast cell dependent because it was absent in mast cell-deficient KitW-sh/W-sh mice. In conclusion, our data suggest that a clinically relevant adjuvant, CTA1–DD, exerts additional augmenting effects through activation of mucosal mast cells, clearly demonstrating that mast cells could be further exploited for improving the efficacy of mucosal vaccines.
A Course Assessment Process for Curricular Quality Improvement

Objective. To describe a systematic assessment process that provides continuous improvement in the curriculum, supports faculty development, and enhances student learning outcomes. Design. Teams of faculty members, students, and course instructors conducted course assessments, which consisted of monitoring the delivered instruction for agreement with planned content and course integration within the curriculum, and providing ongoing feedback for improving course content, course management, faculty teaching, and student learning experiences. Assessment. Areas needing improvement were identified and appropriate changes were made. Improvements were achieved in course policy standardization, course integration within the curriculum, faculty teaching behaviors, and student experiences. Conclusion. The curriculum assessment plan provides a structured method of monitoring and delivering continuous quality improvement.
Nosocomial Bacteremia due to Acinetobacter baumannii: Clinical Features, Epidemiology, and Predictors of Mortality

To study the possible predisposing factors, clinical features, molecular epidemiology, and factors affecting mortality associated with bacteremia due to Acinetobacter baumannii, we reviewed 87 episodes of A. baumannii bacteremia occurring in 79 patients hospitalized at 2 university tertiary care centers and 4 community-based hospitals during a recent 18-month period. Plasmid DNA analysis and analysis of genomic DNA with pulsed-field gel electrophoresis was performed to investigate possible epidemiologic relationship. All patients acquired their infections in the hospital, and no seasonal variation was observed. Among patients with A. baumannii bacteremia, 91% were hospitalized in an intensive care unit, 99% had indwelling vascular catheters, 81% received prior broad spectrum antimicrobial therapy, 70% were mechanically ventilated, and 47% had major surgical procedures. In 39 cases (45%) the infection was related to indwelling vascular access devices. Other infections included pneumonia (9%), tracheobronchitis (22%), meningitis (2%), and burn wound infections (4%). Septic shock occurred in 30% of patients. All isolates were multidrug resistant. Polymicrobial bacteremia was observed in 35% of cases. The crude mortality rate was 44%. Death was considered attributable to A. baumannii bacteremia in 15 (19%) patients. All patients with pneumonia as the primary site of infection died. Using multivariate analysis, we identified 3 independent predictors of mortality: the presence of a rapidly or ultimately fatal underlying disease (p = 0.0009), septic shock at the onset of bacteremia (p = 0.0013), and mechanical ventilation (p = 0.016). Epidemiologic typing revealed that 82 episodes were associated with different hospital outbreaks of infection, and only 7 episodes were due to epidemiologically unrelated strains.
β-Amyloid Stimulates Murine Postnatal and Adult Microglia Cultures in a Unique Manner

Reactive microglia are commonly observed in association with the β-amyloid (Aβ) plaques of Alzheimer's disease brains. This localization supports the hypothesis that Aβ is a specific activating stimulus for microglia. A variety of in vitro studies have used postnatal derived rodent microglia cultures to characterize the ability of Aβ to stimulate these cells. However, it is unclear whether this paradigm accurately models conditions in aged animals. To determine whether Aβ stimulatory phenotypes differ between young and adult microglia, we established cultures of acutely isolated adult murine cortical microglia to compare with postnatal derived microglial cultures. Although cells from both ages expressed robust immunoreactivity for CD68 and CD11b, their responses to activating stimuli differed. Fibrillar Aβ was rapidly phagocytosed by postnatal microglia and both oligomeric and fibrillar peptide stimulated increased tumor necrosis factor α (TNFα) secretion. However, Aβ oligomers but not fibrils stimulated TNFα secretion from adult microglia. More importantly, adult microglia had diminished ability to phagocytose Aβ fibrils. These findings demonstrate that adult microglia respond to Aβ fibril stimulation uniquely from postnatal cells and suggest that adult rather than postnatal microglia cultures are more appropriate for modeling proinflammatory changes in the aged CNS.
Psychometric properties of the Fear of Cancer Recurrence Inventory: an item response theory approach

Classical psychometric methods have been used to demonstrate the validity and reliability of the 42‐item Fear of Cancer Recurrence Inventory (FCRI). Our aim was to expand on this evidence with information on the discriminative value of the individual items when administered to people with a personal history of melanoma, using an item response theory (IRT) approach.
Diffusion Induced Chaos in a Closed Loop Thermosyphon

The dynamics of a closed loop thermosyphon are considered. The model assumes a prescribed heat flux along the loop wall and the contribution of axial diusion. The well-posedness of the model which consists of a coupled ODE and PDE is shown for both the case with diusion and without diusion. Boundedness of solutions, the existence of an attractor, and an inertial manifold is proven, and an exact reduction to a low-dimensional model is obtained for the diusion case. The reduced systems may have far fewer degrees of freedom than the reduction to the inertial manifold. For the three mode models, equivalence with the classical Lorenz equations is shown. Numerical results are presented for ve mode models.
Drug resistance of Mycobacterium tuberculosis strains in southern Brazil.

INTRODUCTION The aim of this work was to evaluate the prevalence of Mycobacterium tuberculosis (MT) strains with mutations that could result in resistance to the main drugs used in treatment in a region with one of the highest numbers of tuberculosis (TB) cases in southern Brazil. METHODS Deoxyribonucleic acid (DNA) from 120 sputum samples from different patients suspicious of pulmonary tuberculosis who attended the Municipal Public Laboratory for Mycobacterium sp. diagnosis was directly amplified and analyzed by PCR-SSCP. The DNA was amplified in known hotspot mutation regions of the genes rpoB, ahpC, embB, katG, inhA, and pncA. RESULTS The percentage of samples positive by culture was 9.2% (11/120); 5% (6/120) were positive by bacilloscopy and MT-PCR, and DNA fragments of the aforementioned resistance genes could be amplified from seven (7) of the eleven (11) samples with positive results, either by culture or PCR/bacilloscopy. All presented a SSCP pattern similar to a native, nonresistant genotype, with the ATCC strain 25177 as control, except for one sample (0.01%), which presented a SSCP profile demonstrating mutation at the embB gene. CONCLUSIONS These results are consistent with the empirical observations by physicians treating TB patients in our region of a low occurrence of cases that are refractory to conventional treatment schemes, in contrast to other parts of the country. Continued surveillance, especially molecular, is essential to detect and monitor the outbreak of MT-resistant strains.
A Magnetic Microbead Occlusion Model to Induce Ocular Hypertension-Dependent Glaucoma in Mice

The use of rodent models of glaucoma has been essential to understand the molecular mechanisms that underlie the pathophysiology of this multifactorial neurodegenerative disease. With the advent of numerous transgenic mouse lines, there is increasing interest in inducible murine models of ocular hypertension. Here, we present an occlusion model of glaucoma based on the injection of magnetic microbeads into the anterior chamber of the eye using a modified microneedle with a facetted bevel. The magnetic microbeads are attracted to the iridocorneal angle using a handheld magnet to block the drainage of aqueous humour from the anterior chamber. This disruption in aqueous dynamics results in a steady elevation of intraocular pressure, which subsequently leads to the loss of retinal ganglion cells, as observed in human glaucoma patients. The microbead occlusion model presented in this manuscript is simple compared to other inducible models of glaucoma and also highly effective and reproducible. Importantly, the modifications presented here minimize common issues that often arise in occlusion models. First, the use of a bevelled glass microneedle prevents backflow of microbeads and ensures that minimal damage occurs to the cornea during the injection, thus reducing injury-related effects. Second, the use of magnetic microbeads ensures the ability to attract most beads to the iridocorneal angle, effectively reducing the number of beads floating in the anterior chamber avoiding contact with other structures (e.g., iris, lens). Lastly, the use of a handheld magnet allows flexibility when handling the small mouse eye to efficiently direct the magnetic microbeads and ensure that there is little reflux of the microbeads from the eye when the microneedle is withdrawn. In summary, the microbead occlusion mouse model presented here is a powerful investigative tool to study neurodegenerative changes that occur during the onset and progression of glaucoma.
Power of Words: When Terrorism Goes Viral

In recent years, the actors of terrorism quickly learned how to adapt to the new communication and media environment. From face-to-face communication, localized propaganda, and direct recruitments methods, terrorist cells and organizations started moving their activities to online forums, social networks, and social media. The impact is huge and widespread: not only has their primary reach extended, but also, thanks to the overall globalization of communication methods, they are being given secondary “advertisement” through exposure in world media. This is becoming more than evident in the case of ISIS, whose reach and communication methods are unprecedented. This paper concentrates not only on ISIS, however, as it introduces when and how terrorism started turning viral and what particular forms this communication, propaganda as well as recruitment shift takes, together with what primary and what secondary threats it poses. Moreover, emphasis is put on both the technical aspects of the aforementioned changes as well as on the analysis of the new means of communication as such, namely on its linguistic, psychological, imagery, and security content. The outcome of the paper is the identification of the methods and analysis of the current state of affairs in terrorist communication, together with overall evaluation of their contemporary recruitment and propaganda practices.
SOCIAL CAPITAL DEVELOPMENT STRATEGY AND COLLABORATIVE KNOWLEDGE CREATION IN HIGHER EDUCATION: THE UK AND TURKEY

The paper presents the second phase of international (three countries) study that explores the influence of social capital and personal learning networks (PLN) development approaches utilized by international students in the multicultural learning environment and the types of the social and academic networks they develop. It also addresses the influence of learners choice on their collaborative knowledge increase, in particular, the knowledge related to preparation for international careers. A comparative analysis has been conducted within three international programs (in Turkey, Ecuador, and the UK) that offer international education in the English language. The paper presents the preliminary results of a comparison in two locations – Turkey and the UK. The study applies the concepts of collaborative knowledge development, social capital, and social networks. It uses the constructivist grounded theory [1] to uncover the process of social capital and collaborative knowledge creation. Based on the data, collected through semi-structured interviews and analyzed through dımensıonal analysis [2]; [3], an updated process model is developed. The model takes into account the core social identity of the learner, and the stability of this identity, as well as the existing and emergent social, personal and institutional learning ties, built on social capital. An additional goal of the study is to uncover the overlapping social and personal learning networks International and local students participate in and develop, to trace the knowledge sharing routes and to pinpoint knowledge creation hubs in these networks. While we are not proposing the final theoretical model until the completion of the full cycle of the continuous comparison analysis process, it appears that the learners who are engaged in multi-dimensional and loosely connected [4] personal earning networks (PLN) [5] characterized by multiple networks consisted of weak ties and who utilize problem-solving models of knowledge creation are more likely to become cross/interculturally competent and are more likely to be prepared for global careers.