Miracle-dz/UniFAR-FTUs huggingface dataset:
Computerized Cognitive Testing for Use in Clinical Trials: A Comparison of the NIH Toolbox and Cogstate C3 Batteries.

BACKGROUND As prevention trials for Alzheimer's disease move into asymptomatic populations, identifying older individuals who manifest the earliest cognitive signs of Alzheimer's disease is critical. Computerized cognitive testing has the potential to replace current gold standard paper and pencil measures and may be a more efficient means of assessing cognition. However, more empirical evidence about the comparability of novel computerized batteries to paper and pencil measures is required. OBJECTIVES To determine whether two computerized IPad batteries, the NIH Toolbox Cognition Battery and Cogstate-C3, similarly predict subtle cognitive impairment identified using the Preclinical Alzheimer Cognitive Composite (PACC). DESIGN, SETTING, PARTICIPANTS A pilot sample of 50 clinically normal older adults (Mage=68.5 years±7.6, 45% non-Caucasian) completed the PACC assessment, and the NIH Toolbox and Cogstate-C3 at research centers of Massachusetts General and Brigham and Women's Hospitals. Participants made 3-4 in-clinic visits, receiving the PACC first, then the NIH Toolbox, and finally the Cogstate-C3. >= 0.5SD), versus subtle cognitive impairment (<0.5SD). Composites for each computerized battery were created using principle components analysis, and compared with the PACC using non-parametric Spearman correlations. Logistic regression analyses were used to determine which composite was best able to classify subtle cognitive impairment from typical performance. RESULTS The NIH Toolbox formed one composite and exhibited the strongest within-battery alignment, while the Cogstate-C3 formed two distinct composites (Learning-Memory and Processing Speed-Attention). The NIH Toolbox and C3 Learning-Memory composites exhibited positive correlations with the PACC (ρ=0.49, p<0.001; ρ=0.58, p<0.001, respectively), but not the C3 Processing Speed-Attention composite, ρ=-0.18, p=0.22. The C3 Learning-Memory was the only composite that classified subtle cognitive impairment, and demonstrated the greatest sensitivity (62%) and specificity (81%) for that subtle cognitive impairment. CONCLUSIONS Preliminary findings suggest that the NIH Toolbox has the advantage of showing the strongest overall clustering and alignment with standardized paper-and-pencil tasks. By contrast, Learning-Memory tasks within the Cogstate-C3 battery have the greatest potential to identify cross-sectional, subtle cognitive impairment as defined by the PACC.
An Optimal Zero-Forcing PIC Group Decoding for Two-User Layered Alamouti Code

The decoding complexity of the layered Alamouti code with the maximum-likelihood (ML) receiver is high. Partial interference cancellation (PIC) group decoding is an attractive method to reduce the ML decoding complexity. However, different grouping schemes for the PIC group decoding may have different performances. In this letter, by fully taking advantage of the Alamouti code structure, we analytically calculate the power gains of the information symbols after the PIC for a grouping scheme, where the zero-forcing (ZF) operator is used for the PIC. We then propose an optimal grouping scheme for the PIC group decoding by proposing a criterion to choose the grouping schemes adaptively so that the power gains of the information symbols are maximized after the PIC.
Antibody-mediated growth of infectious salmon anaemia virus in macrophage-like fish cell lines.

Infectious salmon anaemia virus (ISAV), a pathogen in marine aquaculture, belongs to the genus Isavirus, family Orthomyxoviridae. There is limited information on how ISAV interacts with host defences. To study ISAV-antibody interactions, virus neutralization (VN) assays were performed in the cell lines CHSE-214, SHK-1 and TO using three strains of ISAV and rabbit or fish anti-ISAV sera. Homologous VN titres of >1 : 1280 in CHSE-214 cells corresponded to titres of only 1 : 80 in the macrophage-like fish cell lines SHK-1 and TO, despite using 1000 and 2000 times less virus, respectively. However, rabbit antiserum to infectious pancreatic necrosis virus (IPNV) had a VN titre of 1 : 10,260 against IPNV in both CHSE-214 and TO cells. Poor ISAV neutralization in TO cells was attributed to Fc receptors mediating virus infectivity, because (1) neutralization by rabbit antiserum to ISAV was increased 48-fold in the presence of staphylococcal Protein A and (2) when using FITC-labelled virus and spectrofluorometry, a significant increase (P=0.018) in the intensity of fluorescence of intracellular virus was observed in assays of virus-antiserum mixtures in the absence of Protein A as compared to those in the presence of Protein A. Neutralization of ISAV with fish antisera was observed only in CHSE-214 cells, as Protein A could not restore neutralization in TO cells. These findings demonstrate for the first time antibody-mediated infection of macrophage-like fish cell lines by a fish virus, ISAV, and, as ISAV in Atlantic salmon targets leukocytic and endothelial cells, this may have implications for ISA pathogenesis and vaccination.
Arterio‐venous fistula for automated red blood cells exchange in patients with sickle cell disease: Complications and outcomes

Erythrocytapheresis (ER) can improve outcome in patients with sickle cell disease (SCD). A good vascular access is required but frequently it can be difficult to obtain for sickle cell patients. Arterio‐venous fistulas (AVFs) have been suggested for ER in SCD supported by limited evidence. We report the largest cohort of ER performed with AVFs from three French SCD reference centers. Data of SCD patients undergoing ER with AVFs in the French SCD reference center were retrospectively collected. The inclusion criteria were: SS or Sβ‐Thalassemia and AVF surgery for ER. SCD‐related complications, transfusion history, details about AVF surgical procedure, echocardiographic data before and after AVF, AVF‐related surgical and hemodynamical complications were collected. Twenty‐six patients (mean age 20.5 years, mean follow‐up 68 months [11–279]) were included. Twenty‐three patients (88.5%) required central vascular access before AVF. Fifteen AVFs (58%) were created on the forearm and 11 (42%) on the arm. Nineteen patients (73%) had stenotic, thrombotic or infectious AVF complications. A total of 0.36 stenosis per 1,000 AVF days, 0.37 thrombosis per 1,000 AVF days and 0.078 infections per 1.000 AVF days were observed. The mean AVF lifespan was 51 months [13–218]. One patient with severe pulmonary hypertension worsened after AVF creation and died. We report the first series of SCD patients with AVF for ER, demonstrating that AVFs could be considered as a potential vascular access for ER. Patients with increased risk for hemodynamic intolerance of AVFs must be carefully identified, so that alternative vascular accesses can be considered. Am. J. Hematol. 92:136–140, 2017. © 2016 Wiley Periodicals, Inc.
Arabidopsis thaliana Plants Lacking the PSI-D Subunit of Photosystem I Suffer Severe Photoinhibition, Have Unstable Photosystem I Complexes, and Altered Redox Homeostasis in the Chloroplast Stroma*

The PSI-D subunit of photosystem I is a hydrophilic subunit of about 18 kDa, which is exposed to the stroma and has an important function in the docking of ferredoxin to photosystem I. We have used an antisense approach to obtain Arabidopsis thaliana plants with only 5–60% of PSI-D. No plants were recovered completely lacking PSI-D, suggesting that PSI-D is essential for a functional PSI in plants. Plants with reduced amounts of PSI-D showed a similar decrease in all other subunits of PSI including the light harvesting complex, suggesting that in the absence of PSI-D, PSI cannot be properly assembled and becomes degraded. Plants with reduced amounts of PSI-D became light-stressed even in low light although they exhibited high non-photochemical quenching (NPQ). The high NPQ was generated by upregulating the level of violaxanthin de-epoxidase and PsbS, which are both essential components of NPQ. Interestingly, the lack of PSI-D affected the redox state of thioredoxin. During the normal light cycle thioredoxin became increasingly oxidized, which was observed as decreasing malate dehydrogenase activity over a 4-h light period. This result shows that photosynthesis was close to normal the first 15 min, but after 2–4 h photoinhibition dominated as the stroma progressively became less reduced. The change in the thiol disulfide redox state might be fatal for the PSI-D-less plants, because reduction of thioredoxin is one of the main switches for the initiation of CO2 assimilation and photoprotection upon light exposure.
Performance of AEP Monitor/2‐derived composite index as an indicator for depth of sedation with midazolam and alfentanil during gastrointestinal endoscopy

Background and objective: The A‐Line® auditory evoked potential index (AAI) (AEP Monitor/2, Danmeter A/S, Odense, Denmark) is a newly developed composite parameter representing the degree of hypnosis. We conducted a prospective, observational study to explore the performance and validity of the AAI during conventional sedation for gastrointestinal (GI) endoscopy. Methods: Thirty adults of either sex, age <65, scheduled for combined oesophagogastroduodenoscopy (OGD) and colonoscopy under sedation with intravenous (i.v.) midazolam and alfentanil were enrolled. The sedative end‐point was set at the Observer’s Assessment of Alertness/Sedation (OAA/S) score less than 4. An AEP Monitor/2 was used in all patients. AAI, sedation scores, heart rate (HR), blood pressure (BP) and SPO2 were recorded every 2 min up to the end of the procedure. Receiver operator characteristic analysis was used to test validity and to select optimal sedation. Results: There was a significantly positive correlation between AAI and OAA/S scores (&rgr; = 0.886; P < 0.001). The AAI also showed significant differences between subsequent levels of sedation scores (P < 0.001). AAI greater than 54 indicated fully awake or minimal sedation and values between 54 and 42 were suggestive of moderate sedation. Values between 42 and 34 were associated with moderate to deep sedation and readings below 34 were associated with deep sedation. The relative risk of SPO2 < 95% for OAA/S = 2 compared with 3 was 15.98 (95% confidence interval (CI): 3.94–64.81). Conclusions: AAI is an effective tool for monitoring sedation during GI endoscopy induced by i.v. midazolam and alfentanil.
p16INK4A Expression Is Related to Grade of CIN and High-risk Human Papillomavirus but Does not Predict Virus Clearance After Conization or Disease Outcome

The role of p16INK4a as a marker of HR-HPV and in the diagnosis of CIN has been well established, but its predictive value in the clearance of the virus after CIN treatment and its use as a prognostic marker of cervical cancer has not been studied. A series of 302 archival samples, including 150 squamous cell carcinomas (SCCs) and 152 CIN lesions, were subjected to immunohistochemical staining for p16INK4a and HPV testing using PCR with three primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available of 88 SCC patients, and 67 of the CIN lesions had been followed-up with serial PCR after conization. HR-HPV types were closely associated with CIN (OR 19.12; 95%CI 2.31–157.81) and SCC (OR 27.25; 95%CI 3.28–226.09). There was a significant linear relationship between the lesion grade and intensity of p16INK4a staining (p = 0.0001). The expression of p16INK4a was also closely related to HR-HPV (p = 0.0001). p16INK4a staining was a 100% specific indicator of CIN, with 100% PPV, and showed 83.5% sensitivity and 80.1% PPV in detecting HR-HPV. However, p16INK4a staining did not predict clearance/persistence of HR-HPV after treatment of CIN. Similarly, despite a slightly more favorable survival in women with strong/intense p16INK4a staining in univariate analysis, p16INK4a expression was not an independent prognostic predictor in multivariate survival (Cox) analysis. After adjustment for p16INK4a staining, HR-HPV, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and age, only the last two were significant prognostic predictors (p = 0.0001 and p = 0.003, respectively). The present data confirm the role of p16INK4a as a highly specific marker of CIN and HR-HPV type, but expression of this protein does not seem to be of any prognostic value in cervical cancer or in predicting the clearance of HR-HPV after treatment of CIN. We speculate that different subgroups of cervical cancer are characterized by aberrant p16INK4a/cyclin D/Rb pathways that are due to different mechanisms that can be mutually exclusive.
Association between allergic rhinitis and hospital resource use among asthmatic children in Norway

Background: Preliminary evidence suggests that inadequately controlled allergic rhinitis in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. The objective of this study was therefore to assess the effect of concomitant allergic rhinitis on asthma‐related hospital resource utilization among children below 15 years of age with asthma in Norway.
The ubiquitin‐mediated proteolytic pathway: mechanisms of recognition of the proteolytic substrate and involvement in the degradation of native cellular proteins

Ubiquitin modification of a variety of protein targets within the cell plays important roles in many cellular processes. Among these are regulation of gene expression, regulation of cell cycle and division, involvement in the cellular stress response, modification of cell surface receptors, DNA repair, import of proteins into mitochondria, uptake of precursors into neurons, and biogenesis of mitochondria, ribosomes, and peroxisomes. The best studied modification occurs in the ubiquitin‐mediated proteolytic pathway. Degradation of a protein via the ubiquitin system involves two discrete steps. Initially, multiple ubiquitin molecules are covalently linked in an ATP‐dependent mode to the protein substrate. The targeted protein is then degraded by a specific and energy‐dependent high molecular mass protease into free amino acids, and free and reutilizable ubiquitin is released. In addition, stable mono‐ubiquitin adducts are also found in the cell, for example, those involving nucleosomal histones. Despite the considerable progress that has been made in elucidating the mode of action and roles of the ubiquitin system, many problems remain unsolved. For example, little is known on the signals that target proteins for degradation. Although mechanistic aspects of recognition via the N‐terminal residue have been studied thoroughly, it is clear that the vast majority of cellular proteins are targeted by other signals. The identity of the native cellular substrates of the system is another important, yet unresolved, problem: only few proteins have been recognized so far as substrates of the system in vivo. The scope of this review is to discuss the mechanisms involved in ubiquitin activation, selection of substrates for conjugation, and degradation of ubiquitin‐conjugated proteins in the cell‐free system. In addition, we shall summarize what is currently known of the physiological roles of ubiquitin‐mediated proteolysis in vivo. —Ciechanover, A. ; Schwartz, A. L. The ubiquitin‐mediated proteolytice pathway: mechanisms of recognition of the proteolytic substrate and involvement in the degradation of native cellular proteins. FASEB J. 8: 182‐191; 1994.
Circadian fluctuations of contrast sensitivity in Parkinson's disease

Spontaneous circadian fluctuations of motor symptoms in Parkinson's disease (PD) often occur, with dysfunction typically less severe in the early morning than in the afternoon. In 23 PD patients with or without a history of circadian motor fluctuations, we studied contrast sensitivity (CS), a non-motor function, considered to be dependent on dopaminergic transmission to see if it exhibits similar circadian variability. We tested CS throughout the day at 2-hour intervals beginning at 8:30 am. To facilitate multiple testing sessions, we used a rapid, printed, forced choice test of CS not requiring a motor response. We tested CS in 43 eyes in the PD patients and 23 eyes in 12 controls at spatial frequencies of 1.5,3,6,12, and 18 cycles per degree (cpd). At 8:30 am, CS in PD did not differ from that of controls, but at all other testing times it was significantly worse at 3 or more spatial frequencies. In PD, CS was significantly worse at 2:30 pm than at 8:30 am at 3 and 6 cpd, but in controls it was unchanged throughout the day. Separate analysis of CS in PD patients, with and without a history of circadian change in motor symptoms, revealed no significant difference between the groups. These results suggest that in PD a non-motor dopaminergic function can exhibit circadian variability and that this pattern can exist in the absence of similar variability in motor symptoms. Circadian variability which parallels the most common pattern of motor variability in PD supports the notion that the CS abnormality in this condition is related to dopamine deficiency.
Enhancement of Anandamide-Mediated Endocannabinoid Signaling Corrects Autism-Related Social Impairment

Abstract Introduction: We recently uncovered a signaling mechanism by which the endocannabinoid anandamide mediates the action of oxytocin, a neuropeptide that is crucial for social behavior, to control social reward. Oxytocin signaling has been implicated in autism spectrum disorder (ASD), and social reward is a key aspect of social functioning that is thought to be disrupted in ASD. Therefore, as a proof of principle for the core component of ASD—social impairment—we tested an endocannabinoid-enhancing compound on two widely studied mouse models of ASD, the BTBR and fmr1−/− (model of Fragile X Syndrome). Methods: We used the established three-chambered social approach test. We specifically increased the activity of anandamide by administering the compound URB597, a selective inhibitor of fatty acid amide hydrolase (FAAH), the hydrolytic enzyme for anandamide. Results: Remarkably, we found that FAAH blockade completely reversed the social impairment in both mouse models. CB1 receptor blockade prevented the prosocial action of FAAH inhibition in BTBR mice. These results were likely independent of effects on anxiety, as FAAH inhibition did not alter the performance of BTBR mice in the elevated plus maze. Conclusions: The results suggest that increasing anandamide activity at CB1 receptors improves ASD-related social impairment and identify FAAH as a novel therapeutic target for ASD.
Antitubercular pharmacodynamics of phenothiazines.

OBJECTIVES Phenothiazines have been shown to exhibit in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb) and multidrug-resistant Mtb. They are predicted to target the genetically validated respiratory chain component type II NADH:quinone oxidoreductase (Ndh). Using a set of compounds containing the phenothiazine pharmacophore, we have (i) investigated whether chemical validation data support the molecular target and (ii) evaluated pharmacophore tractability for further drug development. METHODS Recombinant Mtb Ndh was generated and its functionality confirmed by steady-state kinetics. Pharmacodynamic profiling of the phenothiazines, including antitubercular efficacy in aerobic and O2-limited conditions, time-kill assays and isobole analyses against first-line antituberculars, was performed. Potential mitochondrial toxicity was assessed in a modified HepG2 cell-line assay and against bovine cytochrome bc1. RESULTS Steady-state kinetic analyses revealed a substrate preference for coenzyme Q2 and an inability to utilize NADPH. A positive correlation between recombinant Ndh inhibition and kill of aerobically cultured Mtb was observed, whilst enhanced potency was demonstrated in a hypoxic model. Time-kill studies revealed the phenothiazines to be bactericidal whilst isobolograms exposed antagonism with isoniazid, indicative of intracellular NADH/NAD(+) couple perturbation. At therapeutic levels, phenothiazine-mediated toxicity was appreciable; however, specific mitochondrial targeting was excluded. CONCLUSIONS Data generated support the hypothesis that Ndh is the molecular target of phenothiazines. The favourable pharmacodynamic properties of the phenothiazines are consistent with a target product profile that includes activity against dormant/persistent bacilli, rapid bactericidal activity and activity against drug-resistant Mtb by a previously unexploited mode of action. These properties warrant further medicinal chemistry to improve potency and safety.
Responses to mental stress and physical provocations before and during long term treatment of hypertensive patients with beta-adrenoceptor blockers or hydrochlorothiazide.

1 Cardiovascular and sympatho-adrenal responsiveness to mental stress (CWT; a colour word test), orthostatic testing (ORT) and a cold pressor test (CPT) were examined in three groups of hypertensive patients (n = 14-16) before and after 6 months treatment with metoprolol (243 +/- 26 mg daily), propranolol (149 +/- 16 mg daily) or hydrochlorothiazide (50 +/- 8 mg daily) in an open trial design. 2 Treatment reduced outpatient blood pressures in the three groups similarly (from approximately 155/102 to 135/90 mm Hg). During treatment resting blood pressures in the laboratory were clearly reduced by beta-adrenoceptor blockade but not by thiazide treatment. Metoprolol and propranolol caused similar reductions of basal heart rates and plasma glycerol levels, whereas only propranolol reduced cyclic AMP concentrations in plasma. 3 Before treatment CWT and CPT increased systolic and diastolic blood pressures by about 30%. Heart rate increased by about 30 beats min-1 during CWT and 10-15 beats min-1 during CPT and ORT. Small venous plasma adrenaline responses were evoked by all tests, whereas noradrenaline was elevated mainly by CPT and ORT. Dopamine levels did not change. 4 Heart rate responses to all stressors were markedly and similarly reduced, whereas blood pressure responses were essentially unchanged during metoprolol or propranolol treatment. In the thiazide group circulatory responses to CWT were slightly attenuated, whereas responses to ORT and CPT were unchanged. 5 The systolic blood pressure levels were reduced throughout the test session in all three groups, although less so in the hydrochlorothiazide group. Both beta-adrenoceptor antagonists clearly reduced diastolic blood pressure and heart rate levels at rest and during stress, whereas thiazide treatment caused no significant changes in these respects. 6 The rate pressure product, which increased by 80-100% in response to CWT before treatment, was more markedly reduced by beta-adrenoceptor blockade than by thiazide treatment both at rest and during stress. 7 Self ratings (visual analogue scales) of stress and irritation were increased by CWT in a similar fashion before and during treatment in all groups. beta-adrenoceptor blockade was associated with higher subjective ratings of tiredness at rest, but not after CWT. Performance in the CWT increased slightly more in the thiazide group. The physiological responses to CWT were not correlated to the subjective responses. (ABSTRACT TRUNCATED AT 400 WORDS)