Miracle-dz/UniFAR-FTUs huggingface dataset:
Decoding the attended speech stream with multi-channel EEG: implications for online, daily-life applications

Objective. Recent studies have provided evidence that temporal envelope driven speech decoding from high-density electroencephalography (EEG) and magnetoencephalography recordings can identify the attended speech stream in a multi-speaker scenario. The present work replicated the previous high density EEG study and investigated the necessary technical requirements for practical attended speech decoding with EEG. Approach. Twelve normal hearing participants attended to one out of two simultaneously presented audiobook stories, while high density EEG was recorded. An offline iterative procedure eliminating those channels contributing the least to decoding provided insight into the necessary channel number and optimal cross-subject channel configuration. Aiming towards the future goal of near real-time classification with an individually trained decoder, the minimum duration of training data necessary for successful classification was determined by using a chronological cross-validation approach. Main results. Close replication of the previously reported results confirmed the method robustness. Decoder performance remained stable from 96 channels down to 25. Furthermore, for less than 15 min of training data, the subject-independent (pre-trained) decoder performed better than an individually trained decoder did. Significance. Our study complements previous research and provides information suggesting that efficient low-density EEG online decoding is within reach.
The generalizability of neurocognitive test/retest data derived from a nonclinical sample for detecting change among two HIV+ cohorts

Objective methods for determining clinically relevant neurocognitive change are useful for clinicians and researchers, but the utility of such methods requires validation studies in order to assess their accuracy among target populations. We examined the generalizability of regression equations and reliable change indexes (RCI) derived from a healthy sample to two HIV-infected samples, one similar in demographic makeup to the normative group and the other dissimilar. Measures administered at baseline and follow-up included the Trail Making Test, Controlled Oral Word Association Test (COWAT), Grooved Pegboard, and Digit Span. Frequencies of decline, improvement, or stability were determined for each measure. Among the demographically similar clinical cohort, elevated rates of decline among more immunologically impaired participants were indicated by simple regression method on measures of psychomotor speed and attention, while RCI addressing practice effects (RCI-PE) indicated improvement on most measures regardless of immunostatus. Conversely, among the demographically dissimilar cohort, simple regression indicated high rates of decline across all measures, while RCI-PE indicated elevated rates of decline on psychomotor and attention measures. Thus, the accuracy of the two methods examined for determining clinically significant change among HIV+ cohorts differs depending upon their similarity with the normative sample.
Unsuspected Diversity of Arsenite-Oxidizing Bacteria as Revealed by Widespread Distribution of the aoxB Gene in Prokaryotes

ABSTRACT In this study, new strains were isolated from an environment with elevated arsenic levels, Sainte-Marie-aux-Mines (France), and the diversity of aoxB genes encoding the arsenite oxidase large subunit was investigated. The distribution of bacterial aoxB genes is wider than what was previously thought. AoxB subfamilies characterized by specific signatures were identified. An exhaustive analysis of AoxB sequences from this study and from public databases shows that horizontal gene transfer has likely played a role in the spreading of aoxB in prokaryotic communities.
Differential Effects of the New Class III Agent Dofetilide on Potassium Currents in Guinea Pig Cardiomyocytes

The electrophysiologic effects of dofetilide (UK 68,798), a new class III antiarrhythmic drug were investigated on the following currents in guinea pig left ventricular cardiomyocytes by whole-cell patch-clamp technique: (a) delayed rectifier potassium current with its fast component (IKr) and its slow component (IKs), (b) inward rectifier potassium current (IK1), (c) fast sodium current (INa), and (d) L-type calcium current (ICa). Dofetilide in 10(-6) M reduced the amplitude of IKr to 61% of control currents, as measured by 200-ms test pulses and analysis of the deactivating tail currents of IKr. On the deactivating tail currents of IKs, dofetilide caused no significant amplitude change, but time constants of deactivation became 2.3 times slower, as measured by 2,000-ms test pulses and analysis of the deactivating tail currents of IKs. When the concentration of dofetilide was increased, these effects were more pronounced. Rapid application of the substance to the cells showed that IKr was reduced in the first minute to 60% of control currents. For complete current suppression, at least 3 min were necessary. The suppression effect remained unchanged during a 10-min washout phase. Dofetilide had no effect on IK1. Neither were amplitudes and Hodgkin-Huxley parameters of sodium current influenced by dofetilide. Calcium currents were not blocked by dofetilide. Dofetilide is not only a highly selective blocker of IKr, but also delays deactivation of IKs.
Analysis of the Potential Determinants of Foreign Direct Investment: Empirical Evidence from Thailand

This study analyze the main determinants of FDI in Thailand by applying the ordinary least square (OLS) technique to analyze the secondary time series data for a period of study which starts from the year 1988 to 2015 chosen basing on the data availability. The results obtained showed that the main determinants of FDI in Thailand are infrastructure development (lnINFRAR), Market size (lnRGDP), Corruption (lnCORUP) and GDP growth (lnGDPGR) which were all significant at 1 percent level and had the sign as expected basing on economic theories. These findings are in line with many other previous studies on the related subject. Therefore the Thai government is recommended to expand its market size, improve its infrastructure level, boost its economic growth and curb its level of corruption so that more FDI can enter in its economy. However it is also recommended that the results of this study should be interpreted with care until further studies are conducted with more variables and apply other reliable econometric techniques. Keywords: Foreign direct investment (FDI), Ordinary Least Square (OLS), unit root, Thailand.
REVIEW: Consilient research approaches in studying gene × environment interactions in alcohol research

This review article discusses the importance of identifying gene‐environment interactions for understanding the etiology and course of alcohol use disorders and related conditions. A number of critical challenges are discussed, including the fact that there is no organizing typology for classifying different types of environmental exposures, many key human environmental risk factors for alcohol dependence have no clear equivalents in other species, much of the genetic variance of alcohol dependence in human is not ‘alcohol specific’, and the potential range of gene‐environment interactions that could be considered is so vast that maintaining statistical control of Type 1 errors is a daunting task. Despite these and other challenges, there appears to be a number of promising approaches that could be taken in order to achieve consilience and ecologically valid translation between human alcohol dependence and animal models. Foremost among these is to distinguish environmental exposures that are thought to have enduring effects on alcohol use motivation (and self‐regulation) from situational environmental exposures that facilitate the expression of such motivations but do not, by themselves, have enduring effects. In order to enhance consilience, various domains of human approach motivation should be considered so that relevant environmental exposures can be sampled, as well as the appropriate species to study them in (i.e. where such motivations are ecologically relevant). Foremost among these are social environments, which are central to the initiation and escalation of human alcohol consumption. The value of twin studies, human laboratory studies and pharmacogenetic studies is also highlighted.
Myofibroblasts from salivary gland adenoid cystic carcinomas promote cancer invasion by expressing MMP2 and CXCL12

Salivary gland adenoid cystic carcinoma (ACC) is one of the most common malignant tumours in the oral and maxillofacial region, and has high aggressive potential. Tumour and stroma interactions are critical in determining the biological characteristics of malignancy. The aim of this study was to investigate the presence of myofibroblasts and their roles in the invasive characteristics of ACC.
Ki‐ras MUTATIONS IN ADENOMAS: A CHARACTERISTIC OF CANCER‐BEARING COLORECTAL MUCOSA

Activating mutations in the Ki‐ras2 oncogene are frequently observed in sporadic colorectal adenomas and their incidence is reported to rise in large and tubulovillous adenomas to values close to those in carcinomas. This study shows that this property is a feature of adenomas growing in large bowel that has already demonstrated its propensity to engender malignant tumours: i.e., bowel in which there is a synchronous carcinoma. Adenomas from cancer‐free bowel do not share this high incidence of Ki‐ras mutations. This difference in mutation incidence between adenomas from cancer‐free and cancer‐bearing patients does not appear to derive from sampling bias relative to adenoma size, site, or patient age, nor is it found in another gene (APC) known to be of importance in adenoma formation. Large, dysplastic adenomas from cancer‐bearing bowel, however, are particularly liable to carry Ki‐ras mutations when they arise in patients over 70 years old. The observations suggest that the role of Ki‐ras mutations may be more subtle than merely enhancing adenoma growth. Adenoma cells of cancer‐prone individuals may suffer more mutational events than those in persons selected as cancer‐free.
Comparison of the predictive abilities of pharmacogenetics-based warfarin dosing algorithms using seven mathematical models in Chinese patients.

AIM This study is aimed to find the best predictive model for warfarin stable dosage. MATERIALS & METHODS Seven models, namely multiple linear regression (MLR), artificial neural network, regression tree, boosted regression tree, support vector regression, multivariate adaptive regression spines and random forest regression, as well as the genetic and clinical data of two Chinese samples were employed. RESULTS The average predicted achievement ratio and mean absolute error of the algorithms were ranging from 52.31 to 58.08% and 4.25 to 4.84 mg/week in validation samples, respectively. The algorithm based on MLR showed the highest predicted achievement ratio and the lowest mean absolute error. CONCLUSION At present, MLR may be still the best model for warfarin stable dosage prediction in Chinese population. Original submitted 10 November 2014; Revision submitted 18 February 2015.
Disease specific quality of life instruments in multiple sclerosis: Validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS)

Quality of life (QoL) is discussed as an additional outcome measure in multiple sclerosis (MS). However, few questionnaires assessing disease specific QoL in MS have been published. On the basis of the literature and interviews with clinicians and MS patients, we have developed a disease specific QoL instrument and validated it in a broad range of patients with MS. In this study, a heterogeneous sample of n=237 MS patients completed the newly developed Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS, in German language) and a battery of already validated questionnaires. They further underwent neurological scoring and objective tests. By these means, we investigated its validity, appropriateness, internal consistency, and retest reliability. Internal consistency and retest coefficients were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlations with other health measures. HAQUAMS subscales and its total score distinguished between patient groups of varied disease severity, cognitive impairment, and affective symptomatology. No floor or ceiling effects were found in either of the HAQUAMS subscales. The HAQUAMS is a reliable, valid and appropriate instrument for QoL assessment in multiple sclerosis. Data of responsiveness are currently being obtained.
Effect of Seat Tube Angle and Exercise Intensity on Muscle Activity Patterns in Cyclists

Previous studies have reported improved efficiency at steeper seat tube angle (STA) during ergometer cycling; however, neuromuscular mechanisms have yet to be fully determined. The current study investigated effects of STA on lower limb EMG activity at varying exercise intensities. Cyclists (n=11) were tested at 2 workloads; 160W and an individualised workload (IWL) equivalent to lactate threshold (TLac) minus 10%δ (derived from maximal incremental data), using 3 STA (70, 75 and 80°). Electromyographic data from Vastus Medialis (VM), Rectus Femoris (RF), Vastus Lateralis (VL) and Biceps Femoris (BF) were assessed. The timing and magnitude of activation were quantified and analysed using a two-way ANOVA. STA had significant (P < 0.05) effects on timing of onset and offset of VM, timing of offset of VL, and angle at peak for RF, all occurring later at 80 vs. 70° STA at IWL. In RF, increased activity occurred during the first 108° of the crank cycle at 80 vs. 70° at IWL (P < 0.01). As most of the power in the pedal stroke is generated during the mid-section of the down-stroke, movement of the activation range of knee extensors into the predominantly power phase of the pedal stroke would potentially account for increased efficiency and decreased cardio-respiratory costs. Greater activity of bi-articular RF, in the first 108º of the crank cycle at IWL (80 vs. 70º) may more closely resemble the pelvic stabilising activity of RF in running biomechanics; and potentially explain the more effective transition from cycling to running reported in triathletes using steeper STA.
Ku86 is not required for protection of signal ends or for formation of nonstandard V(D)J recombination products

Ku, a heterodimer of 70- and 86-kDa subunits, serves as the DNA binding component of the DNA-dependent protein kinase (DNA-PK). Cells deficient for the 86-kDa subunit of Ku (Ku86-deficient cells) lack Ku DNA end-binding activity and are severely defective for formation of the standard V(D)J recombination products, i.e., signal and coding joints. It has been widely hypothesized that Ku is required for protection of broken DNA ends generated during V(D)J recombination. Here we report the first analysis of V(D)J recombination intermediates in a Ku-deficient cell line. We find that full-length, ligatable signal ends are abundant in these cells. These data show that Ku86 is not required for the protection or stabilization of signal ends, suggesting that other proteins may perform this function. The presence of high levels of signal ends in Ku-deficient cells prompted us to investigate whether these ends could participate in joining reactions. We show that nonstandard V(D)J recombination products (hybrid joints), which involve joining a signal end to a coding end, form with similar efficiencies in Ku-deficient and wild-type fibroblasts. These data support the surprising conclusion that Ku is not required for some types of V(D)J joining events. We propose a novel RAG-mediated joining mechanism, analogous to disintegration reactions performed by retroviral integrases, to explain how formation of hybrid joints can bypass the requirement for Ku and DNA-PK.
NIM811, a Mitochondrial Permeability Transition Inhibitor, Prevents Mitochondrial Depolarization in Small‐for‐Size Rat Liver Grafts

ATP decreases markedly in small‐for‐size liver grafts. This study tested if the mitochondrial permeability transition (MPT) underlies dysfunction of small‐for‐size livers. Half‐size livers were implanted into recipients of about twice the donor weight, resulting in quarter‐size liver grafts. NIM811 (5 μM), a nonimmunosuppressive MPT inhibitor was added to the storage solutions. Mitochondrial polarization and cell death were assessed by confocal microscopy of rhodamine 123 (Rh123) and propidium iodide (PI), respectively. After quarter‐size transplantation, alanine aminotransferase (ALT), serum bilirubin and necrosis all increased. NIM811 blocked these increases by >70%. After 38 h, BrdU labeling, a marker of cell proliferation and graft weight increase were 3% and 5%, respectively, which NIM811 increased to 30% and 42%. NIM811 also increased survival of quarter‐size grafts. In sham‐operated livers, hepatocytes exhibited punctate Rh123 fluorescence. By contrast, in quarter‐size grafts at 18 h after implantation, mitochondria of most hepatocytes did not take up Rh123, indicating mitochondrial depolarization. Nearly all hepatocytes not taking up Rh123 continued to exclude PI at 18 h, indicating that depolarization preceded cell death. NIM811 and free radical‐scavenging polyphenols strongly attenuated mitochondrial depolarization. In conclusion, mitochondria depolarized after quarter‐size liver transplantation. NIM811 decreased injury and stimulated regeneration, probably by inhibiting free radical‐dependent MPT onset.
Chronic Nicotine Consumption Does Not Influence 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis

Nicotine replacement therapy is often used to maintain smoking cessation. However, concerns exist about the safety of long-term nicotine replacement therapy use in ex-smokers and its concurrent use in smokers. In this study, we determined the effect of nicotine administration on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors in A/J mice. Female mice were administered a single dose of NNK (10 μmol) and 0.44 μmol/mL nicotine in the drinking water. Nicotine was administered 2 weeks prior to NNK, 44 weeks after NNK, throughout the experiment, or without NNK treatment. The average weekly consumption of nicotine-containing water was 15 ± 3 mL per mouse, resulting in an estimated daily nicotine dose of 0.9 μmol (0.15 mg) per mouse. Nicotine administration alone for 46 weeks did not increase lung tumor multiplicity (0.32 ± 0.1 vs. 0.53 ± 0.1 tumors per mouse). Lung tumor multiplicity in NNK-treated mice was 18.4 ± 4.5 and was not different for mice consuming nicotine before or after NNK administration, 21.9 ± 5.3 and 20.0 ± 5.4 tumors per mouse, respectively. Lung tumor multiplicity in animals consuming nicotine both before and after NNK administration was 20.4 ± 5.4. Tumor size and progression of adenomas to carcinomas was also not affected by nicotine consumption. In addition, nicotine consumption had no effect on the level of O6-methylguanine in the lung of NNK-treated mice. These negative findings in a commonly used model of human lung carcinogenesis should lead us to question the interpretation of the many in vitro studies that find that nicotine stimulates cancer cell growth. Cancer Prev Res; 4(11); 1752–60. ©2011 AACR.
2-day versus 5-day famciclovir as treatment of recurrences of genital herpes: results of the FaST study.

BACKGROUND The brief period of viral replication in recurrent genital herpes lesions suggests shorter therapeutic regimens may be as effective as standard 5-day courses. OBJECTIVE To demonstrate that a 2-day course of famciclovir 500 mg statim, then 250 mg twice daily was non-inferior to the standard 5-day course of 125 mg twice daily. METHODS Patients were randomly assigned either the 2-day or 5-day famciclovir course and initiated therapy within 12 h of onset of prodromal symptoms. They were instructed to complete daily questionnaires on herpes-related symptoms and functioning and to attend the clinic for assessment of healing 5.5 days after initiating therapy. RESULTS A total of 873 patients were randomised at least once and 1038 recurrences were treated. The proportion of evaluable recurrences with lesions present at 5.5 days was less in the 2-day arm (24%) than in the 5-day (28%) arm. The upper 97.5% confidence limit (CL) for this difference in favour of the 2-day arm was 2% in favour of the 5-day arm, well within the 10% predefined for non-inferiority. The upper 97.5% CL was similar in the intent-to-treat, evaluable and per-protocol recurrence populations and when adjusted for baseline differences (in gender, age, herpes history and HIV infection) or for clustering of recurrences within patients. Both treatments had similar side-effects; proportion of lesions aborted; time to next recurrence; patient-reported symptoms; and impact on daily functioning. CONCLUSIONS The 2-day course was as safe and effective as the standard 5-day course and can only enhance patient convenience and compliance.
Quantitative Coronary Arteriography and Its Assessment of Atherosclerosis

Background. Previous work has demonstrated that quantitative coronary arteriography (QCA) can accurately measure phantom images to within ±0.1 mm and has been accepted as a reliable and reproducible method of measuring human coronary artery disease (CAD). Assessment of CAD by QCA involves the measurement of numerous variables, which are currently required to calculate stenosis flow reserve (SFR). Methods and Results. In this study 1040 stenotic lesions were analyzed by two well- accepted methods with demonstrated accuracy and reproducibility. These methods measure percent diameter stenosis (%DS), absolute diameter, percent area stenosis, length, as well as entry and exit angles to and from a stenotic coronary artery lesion respectively Based upon these results, the mean ± standard deviations and range seen in CAD were determined for each of these independent variables. This study demonstrated that atherosclerotic coronary artery lesions do not appear to exceed an entry angle of -39°, an exit angle of +35°, or an absolute length of 4.84 cm when accurately measured by QCA. It was also noted that, once percent diameter stenosis exceeded 89% (regardless (continued on next page) of the visual estimate) or percent area stenosis exceeds 99%, coronary arteries become completely occluded as measured by QCA. Conclusions. While previously suspected that once certain critical limits are exceeded in the deposit of cholesterol and calcium within the coronary artery, the artery will close, this study demonstrated by QCA what the limitations in human coronary arteries appear to be. These limits may be in part due to turbulent factors resulting in platelet activation or local mediators from endothelium of the coronary artery. ABSTRACT Contemporary quantitative coronary arteriography (QCA) was used to measure the different variables present in atherosclerotic coronary arteries. While the interaction of each of the independent variables undoubtedly plays a role in the determination of coronary artery blood flow and closure, the limitations of each of these variables have not yet been defined in humans. This study, based on the results of human coronary arteri ograms as analyzed by QCA, demonstrates the limitations of each of these variables, after which coronary arteries close and blood flow equals zero.
Involvement of lysosomes in the pathogenesis of CAG repeat diseases

In CAG repeat diseases, affected neurons possess many cytoplasmic granules immunopositive for expanded polyglutamine stretches. Electron microscopic immunohistochemistry showed that the granules corresponded to lysosomes of primitive type. The results suggest that, in addition to the ubiquitin/proteasome pathway, mutant proteins with expanded polyglutamine stretches are involved in the lysosomal pathway for protein degradation and that this processing mechanism may serve as a target for a new therapeutic approach to CAG repeat diseases.