Miracle-dz/UniFAR-FTUs huggingface dataset:
Impairment of Oligodendroglia Maturation Leads to Aberrantly Increased Cortical Glutamate and Anxiety-Like Behaviors in Juvenile Mice

Adolescence is the critical time for developing proper oligodendrocyte (OL)-neuron interaction and the peak of onset for many cognitive diseases, among which anxiety disorders display the highest prevalence. However, whether impairment of de novo OL development causes neuronal abnormalities and contributes to the early onset of anxiety phenotype in childhood still remains unexplored. In this study, we tested the hypothesis that defects in OL maturation manifests cortical neuron function and leads to anxiety-like behaviors in juvenile mice. We report here that conditional knockout of the Olig2 gene (Olig2 cKO) specifically in differentiating OLs in the mouse brain preferentially impaired OL maturation in the gray matter of cerebral cortex. Interestingly, localized proton magnetic resonance spectroscopy revealed that Olig2 cKO mice displayed abnormally elevated cortical glutamate levels. In addition, transmission electron microscopy demonstrated increased vesicle density in excitatory glutamatergic synapses in the cortex of the Olig2 cKO mice. Moreover, juvenile Olig2 cKO mice exhibited anxiety-like behaviors and impairment in behavioral inhibition. Taken together, our results suggest that impaired OL development affects glutamatergic neuron function in the cortex and causes anxiety-related behaviors in juvenile mice. These discoveries raise an intriguing possibility that OL defects may be a contributing mechanism for the onset of anxiety in childhood.
Improving PBLs in the International Medical University: defining the ‘good’ PBL facilitator

Students’ perception of the role and characteristics of a good problem-based learning (PBL) facilitator were assessed in the same study in which students were exposed to the ‘Flying a Kite Approach’ to PBL. A pre-tested anonymous questionnaire addressed the good qualities of a facilitator as well as the negative aspects. Although faculty and students’ perceptions of ‘good ‘and ‘bad’ attributes generally agreed, it is clear that students still prefer facilitators who talk more, i.e. explain unclear facts or correct them when their facts are wrong. Content experts are also preferred over non-content experts.
Using GMM and SVM-Based Techniques for the Classification of SSH-Encrypted Traffic

When employing cryptographic tunnels such as the ones provided by Secure Shell (SSH) to protect their privacy on the Internet, users expect two forms of protection. First, they aim at preserving the privacy of their data. Second, they expect that their behavior, e.g., the type of applications they use, also remains private. In this paper we report on two statistical traffic analysis techniques that can be used to break the second type of protection when applied to SSH tunnels, at least under some restricting hypothesis. Experimental results show how current implementations of SSH can be susceptible to this type of analysis, and illustrate the effectiveness of our two classifiers both in terms of their capabilities in analyzing encrypted traffic and in terms of their relative computational complexity.
A clinical update on the role of carfilzomib in the treatment of relapsed or refractory multiple myeloma

Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015. Furthermore carfilzomib showed superiority over bortezomib on both efficacy and toxicity profiles, especially a profoundly lower incidence in polyneuropathy. Carfilzomib has been shown to partially overcome the negative effects of high-risk cytogenetics. Promising combinations of carfilzomib with histone deacetylase (HDAC) inhibitors, pomalidomide and several other novel therapeutics have been presented in early studies. The optimal dosing regimen and sequence of treatment regimens remain important questions for the future.
Blood volumes in cardiac surgery with cardiopulmonary bypass

Purpose: Total blood volume (TBV) estimation potentially impacts various aspects of cardiac surgical care, including pharmacological and transfusion interventions, hemodynamic and volume management and perfusion equipment selection. TBV is commonly computed during cardiopulmonary bypass (CPB), using standardized formulae. We hypothesized that these equations fail to accurately predict individual blood volume variability. The aim of this study was to determine TBV with a dilution technique and compare the results to commonly utilized TBV calculations. Methods: After institutional review board approval, data was prospectively collected and analyzed for 101 patients undergoing open-heart surgery. Hematocrits (Hct) just prior to and immediately after the initiation of CPB were used to calculate the TBV. Results were compared to (1) the Allen formula and (2) weight-based standards (70 ml/kg for males (SM); 65 ml/kg for females (SF)). Results: The average dilution TBV (male: 4684 ± 1641 ml; female: 3027 ± 1067 ml; total: 4175 ± 1617 ml) was significantly smaller (p<0.05) than TBV estimated by Allen’s formula (male: 6328 ± 973 ml; female: 4167 ± 643 ml; total: 5665 ± 1134 ml) and weight-based standards (male: 6278 ± 1256 ml; female: 4924 ± 1064 ml; total: 5862 ± 1350 ml). Allen’s formula and the weight-based standards correlated strongly (R2 = 0.821, p<0.001), suggesting similar estimates of TBV when using these methods. In contrast, hemodilution correlated poorly with the estimates by Allen (R2 = 0.221, p<0.001) and weight-based formulae (R2 = 0.122, p<0.001), suggesting different TBV computation. Conclusions: The dilution method during CPB for TBV estimation is applicable and reproducible in the cardiac surgical arena and can be utilized to calculate TBV. Our results suggest that traditional TBV assessment in cardiac surgical patients by Allen’s and weight-based formulae lacks the desired accuracy in estimating true TBV.
TH ANNIVERSARY Low-voltage ferroelectric – paraelectric superlattices as gate materials for field-effect transistors

The demand for new materials to be used in field-effect transistors and similar devices with low energy loss is more than ever before as integrated circuits have become a considerable source of energy consumption. One of the challenges in designing such energy efficient logic devices is finding suitable dielectric materials systems for the gate that controls the drain current in a p-type channel. A fundamental limit for energy efficiency exists in such devices imposed by the polarizability of conventional linear gate dielectrics. Generating on/off states in the channel that differ by at least a million times in the magnitude of the drain current near saturation requires several volts of gate bias for the case of a linear dielectric material in a submicron device. In this study, we demonstrate that ferroelectric–paraelectric superlattice heterostructures can generate the same effect in a p-type channel for bias voltages much lower than in a linear high dielectric constant gate. We consider a metal/superlattice/p-type semiconductor stack for this purpose. Using a thermodynamic model, we show that the multi-domain state of the ferroelectric layers can be tailored and distinct on/off states of the channel are possible for gate bias voltages below 1 V. The origins of such functionality of ferroelectric–paraelectric superlattices are discussed with respect to material characteristics such as the phase transition temperature of the ferroelectric, total polarization, and the dielectric response.
Maternal late-pregnancy serum 25-hydroxyvitamin D in relation to childhood wheeze and atopic outcomes

Background Studies exploring the relationship between prenatal vitamin D exposure and childhood asthma have yielded conflicting results. Higher vitamin D intake during pregnancy has been shown to lower the risk of childhood wheeze, yet a study of maternal late-pregnancy serum 25-hydroxyvitamin D suggested higher serum concentrations may be associated with increased childhood asthma. Objective To assess the relationship between mothers' serum 25-hydroxyvitamin D status and asthma and wheeze phenotypes in their children at age 6 years. Also to explore the relationship between maternal 25-hydroxyvitamin D status and objective measures of childhood atopy and lung function. Methods Serum 25-hydroxyvitamin D was measured at 34 weeks' gestation in the mothers of 860 children born at term. Wheeze was classified as either transient or persistent/late using questionnaire data collated from 6, 12, 24 and 36 months and 6 years. At 6 years spirometry was performed and atopic status was determined by skin prick testing, exhaled nitric oxide was measured in 451 children and bronchial hyperresponsiveness in 216 children. Results There were no significant associations between maternal late-pregnancy 25-hydroxyvitamin D status and either asthma or wheeze at age 6 years. Maternal vitamin D status was not associated with transient or persistent/late wheeze; no significant association was found between persistent/late wheeze when subdivided according to atopic status. No associations were found with skin sensitisation or lung function. Conclusions This study provides no evidence that exposure to higher concentrations of 25-hydroxyvitamin D in maternal serum during late pregnancy increases the risk of childhood asthma, wheeze or atopy.
Use of Transporter Knockdown Caco-2 Cells to Investigate the In Vitro Efflux of Statin Drugs

The objective of the present study was to determine the efflux transporters responsible for acid and lactone statin drug efflux using transporter knockdown Caco-2 cells. The bidirectional transport was determined in Caco-2 cell monolayers in which the expression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), or multidrug resistance associated protein 2 (MRP2) was knocked down by transduction with lentivirus containing human transporter-targeted small hairpin RNAs (shRNAs). Cells transduced with lentivirus containing nontargeted shRNA served as the vector control. Atorvastatin, lovastatin, and rosuvastatin displayed extremely low apical-to-basolateral (A-to-B) transport, which made the Papp,A-B values too unreliable to calculate the efflux ratio. Thus, transport comparisons were performed using the B-to-A permeability (Papp,B-A) values. Presented in the order of vector control, P-gp, BCRP, and MRP2 knockdown Caco-2 cells, the Papp,B-A values (×10−6, cm/s) were 28.1 ± 1.3, 8.6 ± 2.9, 20.3 ± 1.8, and 21.5 ± 1.6 for atorvastatin; 96.1 ± 7.1, 25.3 ± 3.5, 57.3 ± 9.8, and 48.2 ± 2.3 for fluvastatin; and 14.1 ± 1.9, 4.6 ± 1.7, 5.8 ± 0.7, and 6.6 ± 1.8 for rosuvastatin, respectively. Lovastatin and simvastatin showed no efflux in the vector control or knockdown cell monolayers in either lactone or acid forms. Results indicate that atorvastatin, fluvastatin, and rosuvastatin were transported by P-gp, BCRP, and MRP2. On the other hand, neither the lactone nor the resulting acid of lovastatin and simvastatin was transported by P-gp, BCRP, or MRP2. The current study demonstrated that the transporter knockdown Caco-2 cells are useful tools for studying drug-transporter interactions and should help eliminate some of the ambiguity associated with the identification of drug-transporter interactions based on chemical inhibitors alone.
The proto‐oncogene C‐myc is involved in cell differentiation as well as cell proliferation: Studies on growth plate chondrocytes in situ

A combination of immunocytochemistry and microdensitometry has been used to localize and quantify the expression of the proto‐oncogene c‐myc within chondrocytes of the proximal growth plates of rat and chick long bones. Although the c‐myc protein was localized in all chondrocytes of the growth plate of both species the most intense staining was restricted to the proliferating and differentiating chondrocytes. These were identified by their ability to synthesize DNA (bromodeoxyuridine positive) and the presence of alkaline phosphatase activity, respectively. Species differences did exist with the c‐myc concentration of the chick proliferating and differentiating chondrocytes being higher (128% and 240%, respectively) than the respective chondrocytes of the rat. The higher c‐myc concentration in the chick proliferating chondrocytes paralleled the differences in the bromodeoxyuridine labelling index between the two species. In the rat, the concentration of c‐myc protein present in the differentiating chondrocytes was 74% higher than in the respective proliferating chondrocytes, while in the chick it was 146% higher. The data not only provides further evidence for a role of the c‐myc protein in cell proliferation but also suggests involvement of this protein in chondrocyte differentiation and/or hypertrophy. © 1992 Wiley‐Liss, Inc.
Investment Recommendation using Investor Opinions in Social Media

Investor social media, such as StockTwist, are gaining increasing popularity. These sites allow users to post their investing opinions and suggestions in the form of microblogs. Given the growth of the posted data, a significant and challenging research problem is how to utilize the personal wisdom and different viewpoints in these opinions to help investment. Previous work aggregates sentiments related to stocks and generates buy or hold recommendations for stocks obtaining favorable votes while suggesting sell or short actions for stocks with negative votes. However, considering the fact that there always exist unreasonable or misleading posts, sentiment aggregation should be improved to be robust to noise. In this paper, we improve investment recommendation by modeling and using the quality of each investment opinion. To model the quality of an opinion, we use multiple categories of features generated from the author information, opinion content and the characteristics of stocks to which the opinion refers. Then, we discuss how to perform investment recommendation (including opinion recommendation and portfolio recommendation) with predicted qualities of investor opinions. Experimental results on real datasets demonstrate effectiveness of our work in recommending high-quality opinions and generating profitable investment decisions.
Uncemented and cemented primary total hip arthroplasty in the Swedish Hip Arthroplasty Register

Background and purpose Since the introduction of total hip arthroplasty (THA) in Sweden, both components have most commonly been cemented. A decade ago the frequency of uncemented fixation started to increase, and this change in practice has continued. We therefore analyzed implant survival of cemented and uncemented THA, and whether the modes of failure differ between the two methods of fixation. Patients and methods All patients registered in the Swedish Hip Arthroplasty Register between 1992 and 2007 who received either totally cemented or totally uncemented THA were identified (n = 170,413). Kaplan-Meier survival analysis with revision of any component, and for any reason, as the endpoints was performed. Cox regression models were used to calculate risk ratios (RRs) for revision for various reasons, adjusted for sex, age, and primary diagnosis. Results Revision-free 10-year survival of uncemented THA was lower than that of cemented THA (85% vs. 94%, p < 0.001). No age or diagnosis groups benefited from the use of uncemented fixation. Cox regression analysis confirmed that uncemented THA had a higher risk of revision for any reason (RR = 1.5, 95% CI: 1.4–1.6) and for aseptic loosening (RR = 1.5, CI: 1.3–1.6). Uncemented cup components had a higher risk of cup revision due to aseptic loosening (RR = 1.8, CI: 1.6–2.0), whereas uncemented stem components had a lower risk of stem revision due to aseptic loosening (RR = 0.4, CI: 0.3–0.5) when compared to cemented components. Uncemented stems were more frequently revised due to periprosthetic fracture during the first 2 postoperative years than cemented stems (RR = 8, CI: 5–14). The 5 most common uncemented cups had no increased risk of revision for any reason when compared with the 5 most commonly used cemented cups (RR = 0.9, CI: 0.6–1.1). There was no significant difference in the risk of revision due to infection between cemented and uncemented THA. Interpretation Survival of uncemented THA is inferior to that of cemented THA, and this appears to be mainly related to poorer performance of uncemented cups. Uncemented stems perform better than cemented stems; however, unrecognized intraoperative femoral fractures may be an important reason for early failure of uncemented stems. The risk of revision of the most common uncemented cup designs is similar to that of cemented cups, indicating that some of the problems with uncemented cup fixation may have been solved.
Correlates and Causes of Death in Patients With Severe Symptomatic Aortic Stenosis Who Are Not Eligible to Participate in a Clinical Trial of Transcatheter Aortic Valve Implantation

Background— Transcatheter aortic valve implantation is currently being evaluated in patients with severe aortic stenosis who are considered high-risk surgical candidates. This study aimed to detect incidences, causes, and correlates of mortality in patients ineligible to participate in transcatheter aortic valve implantation studies. Methods and Results— From April 2007 to July 2009, a cohort of 362 patients with severe aortic stenosis were screened and did not meet the inclusion/exclusion criteria necessary to participate in a transcatheter aortic valve implantation trial. These patients were classified into 2 groups: group 1 (medical): 274 (75.7%): 97 (35.4%) treated medically and 177 (64.6%) treated with balloon aortic valvuloplasty; and group 2 (surgical): 88 (24.3%). The medical/balloon aortic valvuloplasty group had significantly higher clinical risk compared with the surgical group, with significantly higher Society of Thoracic Surgeons score (12.8±7.0 versus 8.5±5.1; P<0.001) and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (42.4±22.8 versus 24.4±18.1; P<0.001). The medical/balloon aortic valvuloplasty group had a higher New York Heart Association functional class, incidence of renal failure, and lower ejection fraction. During median follow-up of 377.5 days, mortality in the medical/balloon aortic valvuloplasty group was 102 (37.2%), and during median follow-up of 386 days, mortality in the surgical group was 19 (21.5%). Multivariable adjustment analysis identified renal failure (hazard ratio [HR]: 5.60), New York Heart Association class IV (HR: 5.88), and aortic systolic pressure (HR: 0.99) as independent correlates for mortality in the medical group, whereas renal failure (HR: 7.45), Society of Thoracic Surgeons score (STS; HR: 1.09) and logistic EuroSCORE (HR: 1.45) were correlates of mortality in the in the surgical group. Conclusion— Patients with severe symptomatic aortic stenosis not included in transcatheter aortic valve implantation trials do poorly and have extremely high mortality rates, especially in nonsurgical groups, and loss of quality of life in surgical groups.
In vivo inhibition of lipopolysaccharide-induced lethality and tumor necrosis factor synthesis by Rhodobacter sphaeroides diphosphoryl lipid A is dependent on corticosterone induction

Diphosphoryl lipid A from the lipopolysaccharide (LPS) of Rhodobacter sphaeroides (Rs-DPLA) has been demonstrated to block in mice and guinea pigs the increase in the serum tumor necrosis factor (TNF) response induced by highly purified deep rough chemotype LPS from Escherichia coli D31m4 (ReLPS). The present study was designed to determine the role of corticosterone induction by Rs-DPLA and its effect on TNF regulation and survival in lethal endotoxin shock models and to evaluate the ability of Rs-DPLA to induce endotoxin tolerance. Administration of a 100-fold excess of Rs-DPLA 1 h prior to ReLPS administration inhibited the characteristic peak in serum TNF levels induced by LPS. Inhibition was apparent in normal and D-galactosamine (GalN)-sensitized mice and occurred at the pretranslational level, as splenic TNF and interleukin-1 beta mRNAs were present in lower amounts in LPS-stimulated mice pretreated with Rs-DPLA. Consistent with its effects in reducing serum TNF levels, Rs-DPLA pretreatment protected GalN-sensitized mice from a lethal ReLPS challenge. In contrast, Rs-DPLA did not inhibit the increase in the serum TNF response or protect against a lethal ReLPS challenge in parallel experiments with adrenalectomized (Adrex) mice, for which the 50% lethal dose of ReLPS was comparable to that for GalN-sensitized mice. Furthermore, Rs-DPLA appeared to prime Adrex animals and increase the magnitude of the serum TNF response to a suboptimal LPS stimulus. Priming by Rs-DPLA, however, was not observed in normal or GalN-sensitized mice. Although Rs-DPLA by itself was nontoxic and unable to elevate serum TNF levels in any of the models investigated, it did induce a significant increase in the serum corticosterone response and was capable of inducing endotoxin tolerance in normal mice. The inability of Rs-DPLA to protect Adrex mice from a lethal ReLPS stimulus or to inhibit the increase in the serum TNF response suggests that the protective effect of Rs-DPLA in normal or GalN-sensitized animals occurs through corticosterone induction. These results support the concept that endogenous glucocorticoids can modulate the endotoxic effects of LPS by inhibiting the synthesis of inflammatory cytokines.
Ecstasy (MDMA) in Recreational Users: Self‐Reported Psychological and Physiological Effects

Twenty recreational drug users were asked to describe the psychological and physiological effects they experienced under MDMA (3,4‐methylenedioxymethamphetamine). The subjects comprised 11 males and nine females, in the age range 18–31 years. Five subjects had taken MDMA once, nine had taken it 2–9 times, while six subjects had taken it +10 times. Each subject completed a modified Profile of Mood States Questionnaire (POMS), an Ecstasy Effect Questionnaire, and a structured interview, covering past experience with MDMA. Increased feelings of elation, agreeableness, energy, and mental confusion were reported on‐drug (p < 0·001), together with faster heart rate, feeling hot, increased sweating and dehydration, dilated pupils, and tight jaw (trismus). Coming off‐Ecstasy led to feelings of lethargy, moodiness, insomnia, depression, irritability, and paranoia. Bad MDMA trips were reported by 25 per cent of the sample, following a variety of unpleasant experiences. Chronic pharmacodynamic tolerance was not apparent, since although regular users all described their first MDMA experience as ‘the most intense’, later trips were affected by knowledge and expectancy, rather than any diminution in drug response. Acute pharmacodynamic tolerance was, however, evident, with a period between drugs being described as necessary in order to maintain drug effectiveness. This may help explain the low addiction potential of MDMA. © 1997 John Wiley & Sons, Ltd.
Chemoselection combined with alternating chemoradiotherapy or surgery for hypopharyngeal cancer

In order to make possible organ preservation, since 2007 our hospital has performed induction chemotherapy (ICT) with cisplatin and 5‐fluorouracil (PF) for hypopharyngeal cancer as chemoselection, followed by alternating chemoradiotherapy (ACRT) with docetaxel, cisplatin, and 5‐fluorouracil in (TPF) good responders and curative surgery was used in poor responders.