Miracle-dz/UniFAR-FTUs huggingface dataset:
A Conserved N-capping Motif Contributes Significantly to the Stabilization and Dynamics of the C-terminal Region of Class Alpha Glutathione S-Transferases*

Helix 9, the major structural element in the C-terminal region of class Alpha glutathione transferases, forms part of the active site of these enzymes where its dynamic properties modulate both catalytic and ligandin functions. A conserved aspartic acid N-capping motif for helix 9 was identified by sequence alignments of the C-terminal regions of class Alpha glutathione S-transferases (GSTs) and an analysis by the helix-coil algorithm AGADIR. The contribution of the N-capping motif to the stability and dynamics of the region was investigated by replacing the N-cap residue Asp-209 with a glycine in human glutathione S-transferase A1-1 (hGST A1-1) and in a peptide corresponding to its C-terminal region. Far-UV circular dichroism and AGADIR analyses indicate that, in the absence of tertiary interactions, the wild-type peptide displays a low intrinsic tendency to form a helix and that this tendency is reduced significantly by the Asp-to-Gly mutation. Disruption of the N-capping motif of helix 9 in hGST A1-1 alters the conformational dynamics of the C-terminal region and, consequently, the features of the H-site to which hydrophobic substrates (e.g. 1-chloro-2,4-dinitrobenzene (CDNB)) and nonsubstrates (e.g. 8-anilino-1-naphthalene sulfonate (ANS)) bind. Isothermal calorimetric and fluorescence data for complex formation between ANS and protein suggest that the D209G-induced perturbation in the C-terminal region prevents normal ligand-induced localization of the region at the active site, resulting in a less hydrophobic and more solvent-exposed H-site. Therefore, the catalytic efficiency of the enzyme with CDNB is diminished due to a lowered affinity for the electrophilic substrate and a lower stabilization of the transition state.
Pharmacist-based antihypertensive medication review and assignment of morning versus evening dosing of once-daily antihypertensive medications: A pilot study to assess feasibility and efficacy in chronic kidney disease patients

ABSTRACT Evening dosing of antihypertensive medications lowers nighttime blood pressure, and in one large randomized trial, it reduced the risk for cardiovascular outcomes. However, the feasibility of nighttime dosing in routine clinical practice is unknown. The purpose of this pilot study was to evaluate the effect of a brief pharmacist intervention to assign patients to take antihypertensive medications at specific times of the day. In this pilot, randomized controlled trial, 79 patients with moderate to severe chronic kidney disease (CKD) taking one or more antihypertensive medications once daily were randomized to take one once-daily antihypertensive either in the morning or in the evening. A total of 79 patients were randomized (39 to morning dosing, 40 to evening dosing). Average (SD) age was 56.5 (14) years, 68% were male, and average (SD) estimated glomerular filtration rate (eGFR) was 36.6 (8.9) mL/min/1.73m2. Adherence, defined as taking the once-daily medication at the time indicated six or seven times in the last 7 days and not taking it at any other time during the day, was 91% in the morning arm and 95% in the evening arm (p = 0.57). This pilot demonstrates the feasibility and efficacy of a pharmacist–physician collaborative to assign once-daily antihypertensive medications to either morning or evening dosing.
Extrapyramidal and cognitive signs in amyotrophic lateral sclerosis: A population based cross-sectional study

Our objective was to assess the association between amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD) and Parkinson's disease (PD). From May 2007 through August 2012 we investigated 146 patients with newly diagnosed ALS and 146 age- and gender-matched controls. Each individual was screened for cardinal extrapyramidal signs (neurological examination) and cognitive dysfunction (Mini Mental State Examination, MMSE and Frontal Assessment Battery, FAB). Results demonstrated that rigidity was present in 8.2% of cases and 2.1% of controls (adjusted odds ratio, adjOR 5.7; 95% CI 1.5–22.0). The corresponding percentages for bradykinesia and postural instability were, respectively, 8.2 vs. 2.7% (adjOR 4.8; 95% CI 1.4–16.5) and 2.7 vs. 9.6% (adjOR 0.3; 95% CI 0.1–0.9). FAB ≤ 13.4 was recorded in 24.8 vs. 9.6%; adjOR 2.9; 95% CI 1.5–5.7). Tremor and abnormal FAB score were predicted by an older age at onset while an abnormal FAB score was associated with cramps and family history of neurodegenerative diseases. In conclusion, our data support the notion that newly diagnosed ALS carries a higher than expected risk of extrapyramidal signs and FTD.
Preladenant as an Adjunctive Therapy With Levodopa in Parkinson Disease: Two Randomized Clinical Trials and Lessons Learned.

IMPORTANCE Preladenant is an adenosine 2A receptor antagonist that reduced "off" time in a placebo-controlled phase 2b trial in patients with Parkinson disease (PD). We sought to confirm its efficacy in phase 3 trials. OBJECTIVE To evaluate preladenant as an adjunct to levodopa in patients with PD and motor fluctuations. DESIGN, SETTING, AND PARTICIPANTS Two 12-week, phase 3, randomized, placebo-controlled, double-blind trials performed from July 15, 2010, to April 16, 2013. The setting included neurology clinics, clinical research centers, and hospitals in the Americas, the European Union, Eastern Europe, India, and South Africa. Participants included patients with moderate to severe PD taking levodopa who were experiencing motor fluctuations. INTERVENTIONS In trial 1, a total of 778 eligible patients were randomized to the addition of preladenant (2 mg, 5 mg, or 10 mg twice daily), placebo, or rasagiline mesylate (1 mg/d) in a 1:1:1:1:1 ratio. In trial 2, a total of 476 eligible patients were randomized to the addition of preladenant (2 mg or 5 mg twice daily) or placebo in a 1:1:1 ratio. MAIN OUTCOMES AND MEASURES The primary outcome measure was change in off time from baseline to week 12. RESULTS In trial 1, neither preladenant nor rasagiline was superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.10 hour (95% CI, -0.69 to 0.46 hour) for preladenant 2 mg twice daily, -0.20 hour (95% CI, -0.75 to 0.41 hour) for preladenant 5 mg twice daily, -0.00 hour (95% CI, -0.62 to 0.53 hour) for preladenant 10 mg twice daily, and -0.30 hour (95% CI, -0.90 to 0.26 hour) for rasagiline mesylate 1 mg/d. In trial 2, preladenant was not superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.20 hour (95% CI, -0.72 to 0.35 hour) for preladenant 2 mg twice daily and -0.30 hour (95% CI, -0.86 to 0.21 hour) for preladenant 5 mg twice daily. Preladenant was well tolerated, with the most common adverse event that showed an increase over placebo in both trials being constipation (6%-8% for preladenant vs 1%-3% for placebo). CONCLUSIONS AND RELEVANCE In these phase 3 trials, preladenant did not significantly reduce off time compared with placebo. That the active control rasagiline also failed to demonstrate a significant reduction in off time suggests that issues of study design or conduct may have affected these trials. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01155466 and NCT01227265.
Internal Mammary Intercostal Perforators instead of the True Internal Mammary Vessels as the Recipient Vessels for Breast Reconstruction

Background: Free tissue transfer has become a mainstay in breast reconstruction, with the internal mammary system frequently used as the recipient vessels. Sacrificing the internal mammary artery, however, eliminates the potential to use this vessel as a coronary artery bypass conduit in the future and potentially increases recipient-site morbidity. The authors' goal was to evaluate the learning curve and effectiveness of their use of the internal mammary intercostal perforators for microsurgical breast reconstruction. Methods: The authors reviewed one surgeon's consecutive series of 100 abdominal adipocutaneous perforator flap breast reconstructions (72 patients) from July of 2005 through January of 2007. The internal mammary perforators were used as recipient vessels in 23 flaps, the traditional internal mammary vessels were used in 66, and the thoracodorsal vessels were used in 11. To see if there was a learning curve, flaps were analyzed in five consecutive cohorts of 20. Results: A learning curve was shown: internal mammary perforators were used in 5 percent of the first cohort and 45 percent of flaps in the final cohort. Flap survival was 99 percent; the one failure occurred in a traditional internal mammary flap reconstruction. Small palpable areas of fat necrosis were observed in one internal mammary perforator flap (4.3 percent) and in five traditional internal mammary or thoracodorsal flaps (6.5 percent). Conclusions: In all the authors' cohorts, internal mammary perforator vessels were used safely without increasing the incidence of flap failure or fat necrosis seen with the traditional approach. The learning curve for this technique resulted in increased use of these internal mammary perforators, indicating that operator experience is critical.
Definition of a critical spatiotemporal window within which primary cilia control midbrain dopaminergic neurogenesis

ABSTRACT Midbrain dopaminergic (mDA) neurons are generated in the ventral midbrain floor plate depending on Sonic Hedgehog (SHH) signaling for induction. Primary cilia transduce canonical SHH signals. Loss of intraflagellar transport protein IFT88, essential for ciliary function, disrupts SHH signaling in the ventral midbrain and results in the reduction in mDA progenitors and neurons. We investigate whether conditional inactivation of the kinesin motor protein KIF3A recapitulates phenotypes observed in conditional Ift88 mutants. Conditional Kif3a inactivation reduced the mDA progenitor domain size, but did not result in mDA neuron reduction, most likely because of a delayed loss of cilia and delayed inactivation of SHH signaling. We thereby define a precise spatiotemporal window within which primary cilia-dependent SHH signaling determines mDA fate.
THE COMPLEMENTARITY OF THE TWO PERSPECTIVES THE RESOURCE-BASED AND THE KNOWLEDGE-BASED VIEWS

The purpose of this paper is to explore the relationship between the two most important perspectives of the firm, the RBV and the KBV, by examining the relative impact of firm-specific assets and knowledge capabilities on the firm’s competitive advantage. A composite model is proposed which elaborates upon both perspectives causal logic with respect to the conditions relevant for the firm
The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis

The new stereological methods for correct and efficient sampling and sizing of cells and other particles are reviewed. There is a hierarchy of methods starting from the simplest where even the microscopic magnification may be unknown to the most complex where typically both section thickness and the magnification must be known. Opticalsections in suitably modified microscopes can be used to improve the ease and speed with which even the most demanding of these methods are performed. The methods are illustrated by practical examples of applications to a wide range of histological entities including synapses, neurons and cancer cells, glomerular corpuscles and ovarian follicles.
Dissection of Recombination Attributes for Multiple Maize Populations Using a Common SNP Assay

Recombination is a vital characteristic for quantitative trait loci mapping and breeding to enhance the yield potential of maize. However, recombination characteristics in globally used segregating populations have never been evaluated at similar genetic marker densities. This study aimed to divulge the characteristics of recombination events, recombinant chromosomal segments, and recombination frequency for four dissimilar populations. These populations were doubled haploid (DH), recombination inbred line (RIL), intermated B73xMo17 (IBM), and multi-parent advanced generation inter-cross (MAGIC), using the Illumina MaizeSNP50 BeadChip to provide markers. Our results revealed that the average number of recombination events was 16, 41, 72, and 86 per line in DH, RIL, IBM, and MAGIC populations, respectively. Accordingly, the average length of recombinant chromosomal segments was 84.8, 47.3, 29.2, and 20.4 Mb in DH, RIL, IBM, and MAGIC populations, respectively. Furtherly, the recombination frequency varied in different genomic regions and population types [DH (0–12.7 cM/Mb), RIL (0–15.5 cM/Mb), IBM (0–24.1 cM/Mb), MAGIC (0–42.3 cM/Mb)]. Utilizing different sub-sets of lines, the recombination bin number and size were analyzed in each population. Additionally, different sub-sets of markers and lines were employed to estimate the recombination bin number and size via formulas for relationship in these populations. The relationship between recombination events and recombination bin length was also examined. Our results contribute to determining the most suitable number of genetic markers, lines in each population, and population type for successful mapping and breeding.
A 300-kpixel Ultrahigh-Speed Charge-Coupled Device With a Dynamic Range of 48.6 dB at 1 Million Frames per Second

An ultrahigh-speed charge-coupled device (CCD) with an increased dynamic range at a frame rate above 200 kiloframes per second (kfps) was developed. The dynamic range of a CCD operating at extremely high speeds is reduced as a result of rounding of a sharp voltage waveform inside the device. The amount of rounding was estimated by using an equivalent circuit model of one kind of electrodes in a four-phase CCD memory. The simulation showed that the calculated voltage at a quarter period and the measured saturation signal level have similar dependence on the frame rate. To suppress the drop in voltage at a quarter period, the active pixels and the driving circuit were divided, and the resistance of the pixel wiring was reduced. A new ultrahigh-speed CCD, whose active pixels are divided into eight separately driven blocks and that employs dual wirings to each electrode of the four-phase CCD memory, was designed and fabricated. A driving evaluation experiment showed that the ultrahigh-speed CCD had a dynamic range of 48.6 dB at 1 000 000 fps. This range is equivalent to 8-bit digital and is 2.5 times higher than that of a previous ultrahigh-speed CCD.
Radiological Risk Factors of Pseudoarthrosis and/or Instrument Breakage After PLF With the Pedicle Screw System in Isthmic Spondylolisthesis

Objective Several studies have reported favorable results of posterolateral fusion (PLF) with pedicle screw systems (PSs) for isthmic spondylolisthesis. However, the best indication and limitations of this method still remain unclear. The present study aimed to analyze the radiological risk factors of pseudoarthrosis and/or instrumentation failure after PLF with PSs in isthmic spondylolisthesis, and to determine the limitations of this method. Methods The study group comprised of 101 patients with isthmic spondylolisthesis who underwent PLF with PSs. Follow-up was performed for more than 5 years. Statistical analyses with multivariate logistic regression models were used to identify risk factors of pseudoarthrosis and/or instrument failures associated with PLF with PSs. Results Average follow-up was 8 years. Fusion rate was 95%. There were instrument breakage in 6 patients, and pseudoarthrosis in 5. Statistical analysis with a logistic regression model revealed that preoperative % disc height (odds ratio: 3.60 per 10%, P<0.01) and slip angle (odds ratio : 4.48 per 10 degrees kyphosis, P<0.05) were the most crucial risk factors of pseudoarthrosis and/or instrument breakage when performing PLF for isthmic spondylolisthesis. Conclusions In conclusion, PLF with PSs provided satisfactory results with high fusion rate. However, there were complications including pseudoarthrosis or instrument breakage in specific conditions. Preserved disc height and presence of segmental kyphosis were risk factors of these complications. Statistically, % disc height within 20% without segmental kyphosis was the best indication for PLF with PSs.
Refractive Variation during Autorefraction: Multivariate Distribution of Refractive Status

The refractive variation of a sample of 106 university students (63 females and 43 males) studying optometry was examined by means of autorefraction. Stereo- pair scatter plots in Euclidean three-dimensional h-space are used to illustrate the nature of the spread or distribution of data measurements found in particular subjects. A wide variety of different distributions were observed ranging from tightly to loosely clustered arrangements of measurements. Some aspects of departure from multivariate normality, including outliers (atypical measurements in a sample) and polymodal or multimodal distributions, are demonstrated. Outliers appear to be possible anywhere in the space of the scatter plots, although outliers may be more common in the region of h-space corresponding to transitory increases in accommodation. Multimodal distributions may be indicative of changes in ocular fixation during autorefraction or may reflect accommodative or other anomalies. Other departures from multivariate normality such as kurtosis and skewness are also of importance when attempting to form an understanding of variation of refractive state. Measurements made on an artificial or test eye showed very tight clusters in h-space. This suggests that the autorefractor itself contributes little to the variation observed during autorefraction of an eye.
The ethnic prejudice of Flemish teachers: The role of ethnic school composition and of teachability.

OBJECTIVES The aim of this study is to investigate the association between ethnic composition in school and the ethnic prejudice of teachers, controlling for the individual characteristics of teachers and their perceptions of pupils' teachability. METHOD Multilevel analyses were carried out on data for 499 Flemish teachers in 44 Flemish (Belgian) secondary schools, collected through an online questionnaire. In this study, ethnic prejudice means a negative attitude to Moroccans, Turks, and Eastern Europeans. A scale was created by taking the mean scores for 18 items, with higher scores indicating greater ethnic prejudice (Quillian, 1995; Witte, 1999). RESULTS Teachers with long-term higher education or a university diploma are shown to be less ethnically prejudiced than teachers with a lower level of education. Moreover, teachers who work at a school with a greater number of ethnic minority pupils, and at the same time evaluate their pupils as more teachable, are less ethnically prejudiced. CONCLUSIONS These findings highlight the need for more research into the underlying processes, such as pupils' teachability, that influence the relationship between school characteristics and the ethnic prejudice of teachers. More knowledge about the context-specific factors and processes that mediate and/or moderate this relationship can increase the theoretical understanding of the development of ethnic prejudice. It can also highlight particular social characteristics, which can be the focus of social and organizational policy aimed at reducing ethnic prejudices. (PsycINFO Database Record
Effects of antitussive agents administered before bronchoalveolar lavage in horses.

OBJECTIVE To determine whether treatment of horses with antitussive agents before bronchoalveolar lavage (BAL) reduces the frequency and intensity of the cough reflex during BAL. ANIMALS 8 healthy horses. PROCEDURE Standard BAL was performed on each horse weekly for 6 weeks. Detomidine was used as a general sedative, and various antitussive agents were evaluated for their suitability to suppress undesirable coughing. Treatments administered prior to BAL consisted of saline (0.9% NaCl) solution (control treatment), codeine, butorphanol tartrate, glycopyrrolate, lidocaine hydrochloride (final concentration, 0.33%), and lidocaine hydrochloride at a final concentration of 0.66% (lidocaine 0.66%). Frequency and intensity of coughing were digitally recorded throughout the BAL procedure. The volume of BAL fluid collected was measured, and the fluid was cytologically examined to assess potential effects of the medications on composition. RESULTS Coughing frequency was significantly reduced after intratracheal administration of lidocaine 0.66%. Moreover, intratracheal administration of lidocaine 0.66% or IV administration of butorphanol resulted in a significant reduction in the intensity of coughing episodes. All other treatments failed to significantly suppress coughing frequency and intensity, compared with results for the saline treatment. Glycopyrrolate caused obvious adverse clinical effects. Treatments did not influence the volume of BAL fluid collected nor composition of the fluid. CONCLUSIONS AND CLINICAL RELEVANCE Intratracheal administration of lidocaine (final concentration, 0.66%) proved to be the most reliable method to reduce frequency and intensity of coughing in horses during BAL.
Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma.

BACKGROUND The association between dietary folate intake, two polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS), and survival in head and neck squamous cell carcinoma (HNSCC) patients is not clarified. PATIENTS AND METHODS We conducted a retrospective cohort study of 437 HNSCC patients treated at Aichi Cancer Center. We evaluated the survival impact of pretreatment dietary folate intake, which was estimated using a food-frequency questionnaire, and two polymorphisms, MTHFR C677T and a 6-bp insertion/deletion in the 3'-untranslated region of TYMS, using multivariate proportional hazard models. RESULTS Patients with high folate intake (≥320 μg/day; n=144) had significantly higher survival than patients with low or medium folate intake (<320 μg/day; n=278; 79.1% versus 68.2%, respectively, P=0.020). This association was consistent with multivariate analyses adjusted for established prognostic factors (hazard ratio 0.56; 95% confidence interval 0.37-0.84). MTHFR and TYMS polymorphisms did not show significant association with survival, although the TYMS 6-bp insertion allele showed potential association with a reduced risk of death. Notably, no significant interaction was observed between folate intake and the two examined polymorphisms. CONCLUSIONS High pretreatment dietary folate intake was identified as an independent prognostic factor associated with improved clinical outcomes in HNSCC patients. Further study is warranted.