Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta‐analysis of the Influence of UGT Genetic Polymorphisms on Lamotrigine Concentration

Uridine 5′‐diphospho‐glucuronosyltransferases (UGTs) are involved in the metabolism of lamotrigine, but whether the UGT1A4 and UGT2B7 genetic polymorphisms affect lamotrigine concentration remains controversial. Thus, the objective of this meta‐analysis was to analyse the influence of UGT1A4 and UGT2B7 genetic polymorphisms on lamotrigine concentration. Through searching, screening, selection, data extraction and quantitative analyses, the influence of UGT1A4 and UGT2B7 genetic polymorphisms on lamotrigine concentration‐to‐dose ratio (CDR) was assessed by meta‐analysis of nine studies. Neither UGT1A4 70C>A nor 142T>G significantly affected lamotrigine CDR values (standardized difference in means [SDM] = 0.433, 95% confidence interval [CI] = −0.380‐1.302; SDM = −0.458, 95% CI = −1.141‐0.224, respectively). Only the UGT2B7 ‐161C>T homozygous variant had significantly higher CDR values than the wild‐type (WT) and heterozygous variant (SDM = 0.634, 95% CI = 0.056‐1.222). In conclusion, CDR of lamotrigine was significantly higher for the UGT2B7 ‐161C>T homozygous variant than for the WT and heterozygous variant. Thus, UGT2B7 ‐161C>T homozygous variant needs to receive reduced dose.
Resistance to complement activation, cell membrane hypersialylation and relapses in chronic lymphocytic leukemia patients treated with rituximab and chemotherapy

The anti-CD20-specific monoclonal antibody rituximab (RTX), in combination with chemotherapy, is commonly used for primary treatment in chronic lymphocytic leukemia (CLL). However, relapses remain important and activation of the complement pathway is one of the mechanisms by which RTX generates the destruction of B cells directly by complement-dependent cytotoxicity (CDC), or indirectly by antibody-dependent cellular phagocytosis. In this study, the RTX capacity to induce CDC was established in 69 untreated CLL patients, this cohort including 34 patients tested before the initiation of RTX-chemotherapy. In vitro CDC-resistance to RTX predicts lower response rates to RTX-chemotherapy and shorter treatment free survival. Furthermore, the predictive value of CDC-resistance was independent from the clinical, cytogenetic and FcγR3A V158F polymorphism status. In contrast, CLL cell resistance to CDC predominates in IGHV unmutated patients and was related to an important α2-6 sialyl transferase activity, which in turn increases cell surface α2-6 hypersialylation. Suspected factors associated with resistance to CDC (CD20, CD55, CD59, factor H, GM1, and sphingomyelin) were not differentially expressed or recruited between the two CLL groups. Altogether, results provide evidence that testing RTX capacity to induce CDC in vitro represents an independent predictive factor of therapeutic effects of RTX, and that α2-6 hypersialylation in CLL cells controls RTX response through the control of the complement pathway. At a time when CLL therapy is moving towards chemo-free treatments, further experiments are required to determine whether performing an initial in vitro assay to appreciate CLL CDC resistance might be useful to select patients.
Missing Link?: Alachlor and Semen Quality

Frumkin’s editorial in the May 2005 issue of EHP (Frumkin 2005) was very interesting and enlightening. On page A291, Frumkin cited several studies that endorse the “broken windows theory,” noting that Part of this effect may well be due to the disorder and squalor of the environment. Poor people and people of color are disproportionately exposed to “broken windows. ” It is interesting that the “broken windows” are considered to cause disease and health inequity. What happened first: the “broken windows,” or the lack of social skills and the abandonment of the population who live in such places? As a scientist, I find it very difficult to accept that “broken windows” are associated with the number of cases of gonorrhea and are associated with causality. The cases of venereal diseases (VD) are more related to the social skills and social behaviors of the people living in the community. They also have a lack of respect for property, and destruction of property often occurs. If we say the reverse is plausible, what would happen if we got a grant and fixed all of the “broken windows” in a particular community, with no other intervention, and observed the trend of VD? With the assumptions and inferences made in Frumkin’s editorial, this would have a positive effect in reducing cases of VD. My instincts tell me that this would not be the case. The “broken windows” are a consequence of the behaviors of that particular community and they are not the cause of the behaviors. The “broken windows” are what I consider “collateral damage” of people lacking the necessary social skills to overcome certain challenges, such as socioeconomic stress and the lack of maintenance provided by building owners. These people show their frustration and anger many times against property, as well as other people.
Dixon-VIBE Deep Learning (DIVIDE) Pseudo-CT Synthesis for Pelvis PET/MR Attenuation Correction

Whole-body attenuation correction (AC) is still challenging in combined PET/MR scanners. We describe Dixon-VIBE Deep Learning (DIVIDE), a deep-learning network that allows synthesizing pelvis pseudo-CT maps based only on the standard Dixon volumetric interpolated breath-hold examination (Dixon-VIBE) images currently acquired for AC in some commercial scanners. Methods: We propose a network that maps between the four 2-dimensional (2D) Dixon MR images (water, fat, in-phase, and out-of-phase) and their corresponding 2D CT image. In contrast to previous methods, we used transposed convolutions to learn the up-sampling parameters, we used whole 2D slices to provide context information, and we pretrained the network with brain images. Twenty-eight datasets obtained from 19 patients who underwent PET/CT and PET/MR examinations were used to evaluate the proposed method. We assessed the accuracy of the μ-maps and reconstructed PET images by performing voxel- and region-based analysis comparing the SUVs (in g/mL) obtained after AC using the Dixon-VIBE (PETDixon), DIVIDE (PETDIVIDE), and CT-based (PETCT) methods. Additionally, the bias in quantification was estimated in synthetic lesions defined in the prostate, rectum, pelvis, and spine. Results: Absolute mean relative change values relative to CT AC were lower than 2% on average for the DIVIDE method in every region of interest except for bone tissue, where it was lower than 4% and 6.75 times smaller than the relative change of the Dixon method. There was an excellent voxel-by-voxel correlation between PETCT and PETDIVIDE (R2 = 0.9998, P < 0.01). The Bland–Altman plot between PETCT and PETDIVIDE showed that the average of the differences and the variability were lower (mean PETCT–PETDIVIDE SUV, 0.0003; PETCT–PETDIVIDE SD, 0.0094; 95% confidence interval, [−0.0180,0.0188]) than the average of differences between PETCT and PETDixon (mean PETCT–PETDixon SUV, 0.0006; PETCT–PETDixon SD, 0.0264; 95% confidence interval, [−0.0510,0.0524]). Statistically significant changes in PET data quantification were observed between the 2 methods in the synthetic lesions, with the largest improvement in femur and spine lesions. Conclusion: The DIVIDE method can accurately synthesize a pelvis pseudo-CT scan from standard Dixon-VIBE images, allowing for accurate AC in combined PET/MR scanners. Additionally, our implementation allows rapid pseudo-CT synthesis, making it suitable for routine applications and even allowing retrospective processing of Dixon-VIBE data.
Content Security and Privacy Preservation in Social Networks through Text Mining

Due to their huge popularity, Social Networks are increasingly being used as malware, spam and phishing propagation applications. Moreover, Social Networks are being widely recognized as a source of private (either corporate or personal) information leaks. Within the project Segur@, Optenet has developed a number of prototypes that deal with these problems, based on several techniques that share text mining as the underlying approach. These prototypes include a malware detection system based on Information Retrieval techniques, a compression-based spam filter, and a Data Leak Prevention system that makes use of Named Entity Recognition techniques.
Specializing a meta-interpreter: JIT compilation of dynsem specifications on the graal VM

DynSem is a domain-specific language for concise specification of the dynamic semantics of programming languages, aimed at rapid experimentation and evolution of language designs. DynSem specifications can be executed to interpret programs in the language under development. To enable fast turnaround during language development, we have developed a meta-interpreter for DynSem specifications, which requires minimal processing of the specification. In addition to fast development time, we also aim to achieve fast run times for interpreted programs. In this paper we present the design of a meta-interpreter for DynSem and report on experiments with JIT compiling the application of the meta-interpreter on the Graal VM. By interpreting specifications directly, we have minimal compilation overhead. By specializing pattern matches, maintaining call-site dispatch chains and using native control-flow constructs we gain significant run-time performance. We evaluate the performance of the meta-interpreter when applied to the Tiger language specification running a set of common benchmark programs. Specialization enables the Graal VM to JIT compile the meta-interpreter giving speedups of up to factor 15 over running on the standard Oracle Java VM.
Generalized Sub-Array-Connected Hybrid Precoding Improves the Energy-Efficiency of Millimeter-Wave Massive MIMO Systems

In this paper, we propose a generalized sub-array-connected architecture for arbitrary radio frequency (RF) chain and antenna configurations, where the number of RF chains connected to a sub-array and the number of antennas in each sub-array can be arbitrary. Our design objective is to improve the energy efficiency of the hybrid precoder of millimeter-wave massive multiple input multiple output (MIMO) systems. We also propose a successive interference cancellation based hybrid precoding scheme for any given RF chain and antenna configuration. This scheme firstly decomposes the total achievable rate optimization problem into multiple sub-rate optimization problems, each of which is only related to a single sub-array and then it successively maximizes these sub-rates. Our simulation results demonstrate that the proposed scheme achieves a similar rate as the corresponding optimal unconstrained precoding scheme. Furthermore, we show that the energy-efficiency of the proposed scheme is better than that of the existing schemes in the fully-connected and sub-array-connected architectures.
Hemolysis, tocopherol, and lipid oxidation in erythrocytes and muscle tissue in chickens, ducks, and turkeys

&NA; Muscle from turkeys is more sensitive to lipid oxidation during post mortem storage compared with that of chicken and duck which may involve increased lysis of turkey erythrocytes that releases hemoglobin oxidant. Three separate experiments were conducted to study characteristics of chicken, duck, and turkey erythrocytes in which dietary tocopherols were standardized. In Experiment I, tocopherol, fatty acid composition, and lipid oxidation capacity were measured in erythrocytes from chickens, ducks, and turkeys. Tocopherol content was greater in chicken erythrocytes compared with that of duck and turkey (P < 0.05). Oleic and linoleic acid content was higher in chicken erythrocytes compared with that of turkey (P < 0.05). Lipid oxidation capacity of erythrocytes in washed turkey muscle (WTM) at pH 5.8 ranked chicken > duck > turkey (P < 0.05). In Experiment II, hemolysis was measured in erythrocytes from turkeys and chickens. Detergent‐induced hemolysis (pH 7.4) was on average 12‐fold greater for turkey erythrocytes compared with that of chicken (P < 0.05). In Experiment III, the ability of lysed and non‐lysed erythrocytes to promote lipid oxidation was examined. Lysed erythrocytes promoted lipid oxidation in WTM more effectively than intact erythrocytes (P < 0.05). Reasons that turkey erythrocytes were more labile to detergent‐induced hemolysis whereas chicken erythrocytes more effectively promoted lipid oxidation in the WTM model system are discussed. These studies describe variation in chemical and physical properties of erythrocytes from chickens, ducks, and turkeys that can influence progression of lipid oxidation in poultry muscle.
Effect of an antimitotic agent colchicine on thioacetamide hepatotoxicity.

In an earlier study we established that timely and adequate tissue repair response following the administration of a six-fold dose-range of thioacetamide (TA; 50, 150, and 300 mg/kg) prevented progression of injury and led to recovery and animal survival. Delayed and attenuated repair response after the 600 mg/kg TA dose resulted in a marked progression of injury and 100% lethality. The objective of the present study was to further scrutinize this concept in an experimental protocol in which we hypothesized that a selective ablation of the tissue repair response should lead to lethality from the nonlethal, moderately toxic doses of 150 and 300 mg/kg TA. In this study we investigated the effect of the antimitotic agent colchicine (CLC, 1 mg/kg) on the outcome of TA hepatotoxicity. Male Sprague-Dawley rats (175-225 g) were injected intraperitoneally (ip) with 150 and 300 mg/kg TA. We assessed liver injury by serum enzyme elevations and histopathology. Tissue regeneration response was measured by 3H-thymidine incorporation into hepatonuclear DNA and by proliferating cell nuclear antigen (PCNA) assay. S-Phase stimulation, as indicated by 3H-thymidine incorporation, was noted at 36 and 48 hr following the administration of 150 mg/kg TA, whereas with the 300 mg/kg TA S-phase stimulation was elicited at 48 hr following treatment. Therefore, two doses of CLC (30 hr and 42 hr, 1 mg/kg, ip) were administered to the 150 mg/kg treated group while a single dose of CLC (42 hr, 1 mg/kg, ip) was administered to the 300 mg/kg group. CLC treatment resulted in 100% lethality in both groups. Thus, CLC administration converted nonlethal doses into lethal doses. The 150 mg/kg TA dose was then chosen to further investigate the underlying mechanism. Rats treated with TA alone recovered from injury by 36-48 hr while CLC treatment resulted in a progression of injury as indicated by serum enzyme elevation and histopathology. Tissue repair, as evidenced by 3H-thymidine incorporation and PCNA studies explained this dichotomy. Antimitotic intervention with CLC resulted in a significantly diminished repair response leading to unrestrained progression of injury and lethality even from nonlethal doses. This model demonstrates the critical role of tissue repair response in determining the final outcome of toxicity. ImagesFigure 1.Figure 2.Figure 3.Figure 3.Figure 3.Figure 3.Figure 3.Figure 3.Figure 5.Figure 5.Figure 5.Figure 5.Figure 5.Figure 5.Figure 4.Figure 6.
Physiological background of the remarkably high Cd2+ tolerance of the Aspergillus fumigatus Af293 strain

The physiological background of the unusually high cadmium tolerance (MIC50 > 2 mM) of Aspergillus fumigatus Af293 was investigated. The cadmium tolerance of the tested environmental and clinical A. fumigatus strains varied over a wide range (0.25 mM < MIC50 < 1 mM). Only the Af293 strain showed a MIC50 value of >2 mM, and this phenotype was accompanied by increased in vivo virulence in mice. A strong correlation was found between the cadmium tolerance and the transcription of the pcaA gene, which encodes a putative cadmium efflux pump. The cadmium tolerance also correlated with the iron tolerance and the extracellular siderophore production of the strains. In addition to these findings, Af293 did not show the synergism between iron toxicity and cadmium toxicity that was detected in the other strains. Based on these results, we suggest that the primary function of PcaA should be acting as a ferrous iron pump and protecting cells from iron overload. Nevertheless, the heterologous expression of pcaA may represent an attractive strain improvement strategy to construct fungal strains for use in biosorption or biomining processes or to prevent accumulation of this toxic metal in crops.
NOP receptor pharmacological profile – A dynamic mass redistribution study

The Nociceptin/Orphanin FQ (N/OFQ) peptide NOP receptor is coupled to pertussis toxin (PTX)-sensitive G proteins (Gi/o) whose activation leads to the inhibition of both cAMP production and calcium channel activity, and to the stimulation of potassium currents. The label free dynamic mass redistribution (DMR) approach has been demonstrated useful for investigating the pharmacological profile of G protein-coupled receptors. Herein, we employ DMR technology to systematically characterize the pharmacology of a large panel of NOP receptor ligands. These are of peptide and non-peptide nature and display varying degrees of receptor efficacy, ranging from full agonism to pure antagonism. Using Chinese hamster ovary (CHO) cells expressing the human NOP receptor we provide rank orders of potency for full and partial agonists as well as apparent affinities for selective antagonists. We find the pharmacological profile of NOP receptor ligands to be similar but not identical to values reported in the literature using canonical assays for Gi/o-coupled receptors. Our data demonstrate that holistic label-free DMR detection can be successfully used to investigate the pharmacology of the NOP receptor and to characterize the cellular effects of novel NOP receptor ligands.
Long‐term outcomes of catheter ablation in patients with longstanding persistent atrial fibrillation lasting less than 2 years

Outcome data after catheter ablation (CA) for longstanding persistent atrial fibrillation (LSPAF) lasting less than 2 years are limited and highly variable with different ablation approaches. We aimed to assess the long‐term outcomes in patients with LSPAF lasting less than 2 years undergoing extended pulmonary vein antrum isolation (PVAI) versus those with additional non‐pulmonary vein (PV) trigger ablation.
Dissociable psychosocial profiles of adolescent substance users

Objective Alcohol, tobacco and cannabis use in adolescence is associated with adverse outcomes. Characterizing adolescent substance misusers, however, is difficult due to the wide range of risk and protective factors linked to substance use. The aim of the present study was to examine the role of the Individual, Family, School, Peer, and Social Environment on alcohol (lifetime and risky), tobacco (risky only), and cannabis use (lifetime and riskiness). Method Data were analyzed from a national sample of 5,680 adolescents, capturing substance use behavior alongside risk and protective factors across Individual, Family, School, Peer and Social domains. We applied a sophisticated machine learning classifier to develop models of alcohol, tobacco and cannabis initiation and misuse. Results We found highly accurate (area under curve of receiver-operator-characteristic for out-of-sample performance was > .88) and replicable (over multiple iterations and in comparison with permuted outcomes) dissociable psychosocial profiles of alcohol, tobacco and cannabis use. Alongside common predictors (peer relations and externalizing behavior), dissociable risk and resilience factors were observed. Adolescent profiles of alcohol use were distinguished by the contribution of multiple domains. In contrast, tobacco use was characterized by a small number of individual variables, including female gender and poor perceived academic position. Cannabis use was differentiated by the distinct contribution of Individual risk factors, in particular male gender and feelings of anger. Differential associations were also evident, with the strength and direction of association differing substantially across substances. Conclusion This study indicates that the relationship between the environment and substance use is more complex than previously thought.
Semen Arousal: Its Prevalence, Relationship to HIV Risk Practices, and Predictors among Men Using the Internet to Find Male Partners for Unprotected Sex

Purpose: This paper examines the extent to which men who use the Internet to find other men for unprotected sex are aroused by semen. It also looks at the relationship between semen arousal and involvement in HIV risk practices, and the factors associated with higher levels of semen arousal. Methods: 332 men who used any of 16 websites targeting unprotected sex completed 90-minute telephone interviews. Both quantitative and qualitative data were collected. A random sampling strategy was used. Semen arousal was assessed by four questions asking men how much they were turned on by the way that semen smelled, tasted, looked, and felt. Results: 65.1 % of the men found at least one sensory aspect of semen to be “fairly” or “very” arousing, compared to 10.2% being “not very” or “not at all” aroused by all four sensory aspects of semen. Multivariate analysis revealed that semen arousal was related to greater involvement in HIV risk practices, even when the impact of other salient factors such as demographic characteristics, HIV serostatus, and psychological functioning was taken into account. Five factors were found to underlie greater levels of semen arousal: not being African American, self-identification as a sexual “bottom,” being better educated, being HIV-positive, and being more depressed. Conclusions: Being aroused by the sensory aspects of giving or receiving semen is commonplace amongst men in this high-risk population. Semen arousal was related closely to involvement in risk practices, indicating a need for HIV intervention programs to address this phenomenon in this population.
Clustered domestic model of residential care is associated with better consumer rated quality of care

Abstract Objective To compare consumer rated quality of care among individuals living long-term in homelike clustered domestic and standard models of residential care in Australia. Design Cross-sectional study. Setting Seventeen residential aged care facilities in four Australian states providing alternative models of care. Study participants A sample of individuals with high prevalence of cognitive impairment living in residential care for 12 months or longer, not immediately in palliative care and having a proxy available to provide consent and assist with data collection. Of 901 eligible participants, 541 consented and participated in the study. Main outcome measure Consumer rated quality of care was measured using the Consumer Choice Index–6 Dimension instrument (CCI-6D) providing a preference weighted summary score ranging from 0 to 1. The six dimensions of care time, shared-spaces, own-room, outside and gardens, meaningful activities and care flexibility were individually evaluated. Results Overall consumer rated quality of care (Mean ∆: 0.138, 95% CI 0.073–0.203 P < 0.001) was higher in clustered domestic models after adjusting for potential confounders. Individually, the dimensions of access to outside and gardens (P < 0.001) and flexibility of care (P < 0.001) were rated significantly better compared to those living in standard model of care. Conclusions Homelike, clustered domestic models of care are associated with better consumer rated quality of care, specifically the domains of access to outdoors and care flexibility, in a sample of individuals with cognitive impairment. Including consumer views on quality of care is feasible and should be standard in future evaluations of residential care.