Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuropsychiatric events and dolutegravir in HIV patients: a worldwide issue involving a class effect.

We read with interest the work of Menard et al. [1] that brings additional knowledge on the neuropsychiatric tolerance of dolutegravir. They also provide pharmacokinetic data which is very welcomed as published works concerning the potential association between neuropsychiatric adverse drug reactions (ADRs) and dolutegravir concentrations are scarce. Their data are in line with other studies that recently reported neuropsychiatric adverse effects in patients receiving dolutegravir-containing regimen in other countries in Europe [2–4].
Statistical strategies to reveal potential vibrational markers for in vivo analysis by confocal Raman spectroscopy

Abstract. The analysis of biological systems by spectroscopic techniques involves the evaluation of hundreds to thousands of variables. Hence, different statistical approaches are used to elucidate regions that discriminate classes of samples and to propose new vibrational markers for explaining various phenomena like disease monitoring, mechanisms of action of drugs, food, and so on. However, the technical statistics are not always widely discussed in applied sciences. In this context, this work presents a detailed discussion including the various steps necessary for proper statistical analysis. It includes univariate parametric and nonparametric tests, as well as multivariate unsupervised and supervised approaches. The main objective of this study is to promote proper understanding of the application of various statistical tools in these spectroscopic methods used for the analysis of biological samples. The discussion of these methods is performed on a set of in vivo confocal Raman spectra of human skin analysis that aims to identify skin aging markers. In the Appendix, a complete routine of data analysis is executed in a free software that can be used by the scientific community involved in these studies.
Characterization of human monoclonal antibodies specific to the hepatitis C virus glycoprotein E2 with in vitro binding neutralization properties.

Both linear and conformational determinants of hepatitis C virus (HCV) are believed to be involved in viral neutralization. After immortalization of B cells from HCV chronically infected patients with Epstein-Barr virus, we obtained two polyclonal lymphoblastoid cell lines (LCL) secreting human monoclonal antibodies (HMabs). One clone was derived from a patient infected with a genotype 4 isolate while the second was isolated from a genotype 1b-infected patient. Immunoprecipitation studies, Western blot, and immunofluorescence analysis, peptide scanning, and ELISA studies indicated that the HMabs (1) recognized conformation-dependent determinant(s), (2) were capable of recognizing genotype 1a and 1b derived antigens, and (3) were able to precipitate noncovalently associated E1E2 complexes believed to exist on the surface of virion particles. The HMab derived from the genotype 4-infected patient was in addition shown to neutralize the in vitro binding of recombinant E2 protein onto susceptible cells suggesting a potential for in vivo neutralization. These data indicate that anti-E2 antibodies directed at conserved conformational-dependent determinant(s) exist in chronic HCV infection.
Adaptive Evolution and Antiviral Activity of the Conserved Mammalian Cytidine Deaminase APOBEC3H

ABSTRACT The APOBEC3 genes encode cytidine deaminases that act as components of an intrinsic immune defense that have potent activity against a variety of retroelements. This family of genes has undergone a rapid expansion from one or two genes in nonprimate mammals to at least seven members in primates. Here we describe the evolution and function of an uncharacterized antiviral effector, APOBEC3H, which represents the most evolutionarily divergent APOBEC3 gene found in primates. We found that APOBEC3H has undergone significant adaptive evolution in primates. Consistent with our previous findings implicating adaptively evolving APOBEC3 genes as antiviral effectors, APOBEC3H from Old World monkeys (OWMs) has efficient antiviral activity against primate lentiviruses, is sensitive to inactivation by the simian immunodeficiency virus Vif protein, and is capable of hypermutating retroviral genomes. In contrast, human APOBEC3H is inherently poorly expressed in primate cells and is ineffective at inhibiting retroviral replication. Both OWM and human APOBEC3H proteins can be expressed in bacteria, where they display significant DNA mutator activity. Thus, humans have retained an APOBEC3H gene that encodes a functional, but poorly expressed, cytidine deaminase with no apparent antiviral activity. The consequences of the lack of antiviral activity of human APOBEC3H are likely to be relevant to the current-day abilities of humans to combat retroviral challenges.
In Vitro Translation of Uukuniemi Virus-Specific RNAs: Identification of a Nonstructural Protein and a Precursor to the Membrane Glycoproteins

We isolated the virus-specific RNA species from Uukuniemi virus-infected chicken embryo cells and fractionated them by sucrose gradient centrifugation. In addition to three RNA species cosedimenting with the three viral RNA segments L (29S), M (23S), and S (17S), a fourth major RNA species, sedimenting at about 12S (S2), was found early in the infection. Annealing experiments indicated that the cytoplasmic L and M RNA species consisted of both plus and minus strands, with the plus strands in slight excess. Most of the S1 RNA was of negative polarity, whereas S2 was of positive polarity. The S2 RNA specifically annealed to the virion S RNA segment, indicating that it is transcribed from this segment. In vitro translation of the individual RNA species in micrococcal nuclease-treated cell-free reticulocyte extracts showed that an mRNA cosedimenting with the virion M RNA directed the synthesis of a virus-specific 110,000-dalton polypeptide (p110). This polypeptide could be immunoprecipitated with antiserum prepared against purified virions. When translation was carried out in the presence of dog pancreas microsomes, p110 was absent. Instead, an immunoprecipitable polypeptide band, with a molecular weight of about 70,000 and migrating between the virion surface glycoproteins G1 and G2, was observed. It is thus likely that the glycoproteins are synthesized as a precursor (p110), which during translation is cleaved roughly in the middle to yield G1 and G2. The 12S RNA species directed the synthesis of the nucleocapsid protein and a novel polypeptide with an apparent molecular weight of about 30,000. The latter was not precipitated with antivirion serum and was absent from lysates programmed with the corresponding RNA fraction from a mock-infected extract. Since, in addition, it was not found in purified virions and was present in the cytoplasm of infected cells but not in uninfected cells, it probably represents a nonstructural polypeptide.
The Southampton Consensus Guidelines for Laparoscopic Liver Surgery: From Indication to Implementation

Objective: The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery. Background: The exponential growth of laparoscopic liver surgery in recent years mandates the development of clinical practice guidelines to direct the speciality's continued safe progression and dissemination. Methods: A unique approach to the development of clinical guidelines was adopted. Three well-validated methods were integrated: the Scottish Intercollegiate Guidelines Network methodology for the assessment of evidence and development of guideline statements; the Delphi method of establishing expert consensus, and the AGREE II-GRS Instrument for the assessment of the methodological quality and external validation of the final statements. Results: Along with the committee chairman, 22 European experts; 7 junior experts and an independent validation committee of 11 international surgeons produced 67 guideline statements for the safe progression and dissemination of laparoscopic liver surgery. Each of the statements reached at least a 95% consensus among the experts and were endorsed by the independent validation committee. Conclusion: The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts’ knowledge taking in consideration the relevant stakeholders’ opinions and complying with the international methodology standards.
The effect of chloroquine on the pharmacokinetics and metabolism of praziquantel in rats and in humans

It is likely that a proportion of people treated with the anti‐schistosomicidal drug praziquantel (PZQ) is also taking other drugs such as chloroquine (CHQ), a widely used anti‐malarial. The effect of CHQ on the pharmacokinetics and metabolism of PZQ in rats and in humans was therefore studied. CHQ decreased the bioavailability of PZQ and reduced its maximum serum concentrations to a significant extent in rats and in humans. The clearance was increased to a statistically significant extent in rats but not in humans because of the wide interindividual variation. The effect of CHQ on PZQ pharmacokinetics was unexpected since drugs that inhibit hepatic drug metabolism usually increase the bioavailability of PZQ. We found that CHQ inhibits non‐competitively the metabolism of PZQ to its major metabolite, 4‐hydroxy‐praziquantel, with a Ki of 1.65 mM in rat hepatic microsomes. Maximum concentrations attained by CHQ in serum, however, are low compared to the Ki value and significant inhibition is therefore unlikely in vivo. The explanation for CHQ's effect on the pharmacokinetics of PZQ may be due to other effects of CHQ rather than to a direct effect on drug‐metabolizing enzymes.
Fuzzy Control in Power Electronics Converters for Smart Power Systems

During the last decade, power systems have experienced continuous challenges due to the increasing of demanded energy and the integration with different Renewable Energy Sources (RES) as a possible reduction option to the pollution around the world, for this reason it is necessary the transition to the new power concept known as “Smart Grid”, which has been conceived as the integration of different engineering fields and looks for the application of intelligent controllers with adaptability and interoperability with other systems (Bose, 2010; Momoh, 2009).
Platelet‐derived growth factor‐responsive neural precursors give rise to myelinating oligodendrocytes after transplantation into the spinal cords of contused rats and dysmyelinated mice

Spinal cord injury (SCI) results in substantial oligodendrocyte death and subsequent demyelination leading to white‐matter defects. Cell replacement strategies to promote remyelination are under intense investigation; however, the optimal cell for transplantation remains to be determined. We previously isolated a platelet‐derived growth factor (PDGF)‐responsive neural precursor (PRP) from the ventral forebrain of fetal mice that primarily generates oligodendrocytes, but also astrocytes and neurons. Importantly, human PRPs were found to possess a greater capacity for oligodendrogenesis than human epidermal growth factor‐ and/or fibroblast growth factor‐responsive neural stem cells. Therefore, we tested the potential of PRPs isolated from green fluorescent protein (GFP)‐expressing transgenic mice to remyelinate axons in the injured rat spinal cord. PRPs were transplanted 1 week after a moderate thoracic (T9) spinal cord contusion in adult male rats. After initial losses, PRP numbers remained stable from 2 weeks posttransplantation onward and those surviving cells integrated into host tissue. Approximately one‐third of the surviving cells developed the typical branched phenotype of mature oligodendrocytes, expressing the marker APC‐CC1. The close association of GFP cells with myelin basic protein as well as with Kv1.2 and Caspr in the paranodal and juxtaparanodal regions of nodes of Ranvier indicated that the transplanted cells successfully formed mature myelin sheaths. Transplantation of PRPs into dysmyelinated Shiverer mice confirmed the ability of PRP‐derived cells to produce compact myelin sheaths with normal periodicity. These findings indicate that PRPs are a novel candidate for CNS myelin repair, although PRP‐derived myelinating oligodendrocytes were insufficient to produce behavioral improvements in our model of SCI. © 2011 Wiley‐Liss, Inc.
Sleep quality, chronotype and metabolic syndrome components in bipolar disorders during the remission period: Results from the FACE-BD cohort

ABSTRACT Data on sleep or circadian abnormalities and metabolic disturbances in euthymic bipolar disorders are scarce and based on small sample sizes. The aim of this study was to explore the associations between sleep disturbances, chronotype and metabolic components in a large sample of euthymic patients with bipolar disorders (BD). From 2009 to 2015, 752 individuals with bipolar disorders from the FACE-BD cohort were included and assessed for sleep quality, chronotype and metabolic components. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to confirm the diagnosis of BD. Subjective sleep quality was measured with the Pittsburgh Sleep Quality Index and chronotype with the Composite Scale of Morningness. Sociodemographic and clinical characteristics, psychotropic treatment, psychiatric comorbidities and blood samples were collected. In our sample, 22.4% of individuals with BD presented with a metabolic syndrome, 53.7% had sleep disturbances, 25.4% were considered as having an evening chronotype and 12.6% as having a morning chronotype. Independently of potential confounders, euthymic patients with sleep disturbances had a higher abdominal circumference, and patients with evening chronotype had a significantly higher level of triglycerides. There was an association between evening chronotype and an increased atherogenic index of plasma (OR = 4.8, 95%CI = 1.6–14.7). Our findings contribute the scant literature on the relationship between sleep quality, chronotype and cardiometabolic components in euthymic individuals with BD and highlight the need to improve quality of sleep and patient education about healthier sleep-hygiene practices.
Citation frequency and journal impact: valid indicators of scientific quality?

Evaluation of scientific quality has never been an easy matter. It requires highly qualified scientific expertise (the peer review principle) and is, if properly performed, a time-consuming business. Were it not for the unique willingness of scientists to work for honours rather than for pennies, the costs of evaluation would have been prohibitive. No wonder many researchers have searched for eva! uation -methods that are quicker, cheaper and more objective. Some believe that the answer is to be found in bibliometric indicators, which are based on article citation frequencies published in the Science Citation Zndex (SCI) . Intuitively, most scientists would feel that the more frequently an article is cited, the better it must be. However, this is true only with qualifications: a citation is primarily a measure of utility rather than of quality, and the selection of article references can be both haphazard and highly biased [l]. Reputation, marketing, persuasion, competition, camaraderie, neglect, reference copying and self-citation all enter the picture. In addition, there are numerous problems of database coverage and registration (including 2 5 % misprinting) which may easily reduce the recovery of citations to below 50%
SURGICAL AND POST-SURGICAL BLEEDING

It is of critical importance that clinicians who provide care to surgical patients understand the dynamic interplay of the coagulation and fibrinolytic systems. An appreciation for the relevant underlying biologic mechanisms is central to the diagnosis and appropriate management of patients who present with bleeding diatheses in both the operative and the postoperative setting. Surgery provides the most significant challenge to the integrity of the hemostatic system, and the fidelity of the coagulation system serves as the homeostatic defense mechanism that abrogates the proclivity for bleeding in this context.
And now for something completely different

This article presents a critical analysis of Kamp and Rohrer's (1983) proposal to distinguish two different types of temporal perspective points within the temporal structure of a text. They claim that such a distinction is needed to account for different types of deictic temporal adverbs, when used in narrative discourse. Their analysis seems to account for the difference between the deictic adverbs maintenant 'now' and aujourd'hui 'today'. I will show that the difference between these two adverbs can be explained more adequately in another way. My analysis points out the specific character of maintenant, already observed in Nef (1986). I will argue that the difference between maintenant and aujourd'hui is best accounted for by admitting, on the one hand, that maintenant has two distinct discourse functions and, on the other hand, by adopting the view that there are different time levels, each level corresponding to a particular entity in the narrative: a narrator or a protagonist. In the first part of this paper (sections 1 and 2), I will give a short sketch of how temporal expressions, i.e. tense forms and temporal adverbs, are dealt with in a Reichenbachian framework. I will also justify the introduction of the notion of perspective point as part of the temporal structure of a text. In the second part of the paper (sections 3 and 4), it will be shown that the different functions of maintenant in present tense contexts also apply to the use of this adverb in past tense contexts. The difference between maintenant and aujourd'hui will then turn out to be a question of the more or less deictic value of the adverb.
Activation‐induced CD137 is a fast assay for identification and multi‐parameter flow cytometric analysis of alloreactive T cells

Detection and isolation of viable alloreactive T cells at the single‐cell level requires a cell surface marker induced specifically upon T cell receptor activation. In this study, a member of the tumour necrosis factor receptor (TNFR)‐family, CD137 (4‐1BB) was investigated for its potential to identify the total pool of circulating alloreactive T cells. Optimal conditions for sensitive and specific detection of allogeneic‐induced CD137 expression on circulating T cells were established. Thereafter, CD137+ alloreactive T cells were phenotypically and functionally characterized by multi‐parameter flow cytometry. Alloantigen‐induced CD137 expression identified both alloreactive CD8+ T cells (mean ± standard error of the mean: 0·21 ± 0·07%) and alloreactive CD4+ T cells (0·21 ± 0·05%). CD137+ alloreactive T cells were detected in different T cell subsets, including naive T cells, but were found preferentially in CD28+ T cells and not in the terminally differentiated T cell subset. Upon allogeneic (re‐)stimulation, the cytokine‐producing as well as proliferative capacity of T cells resided mainly within the CD137‐expressing fraction. About 10% of the CD137+ alloreactive T cells produced any combination of interferon (IFN)‐γ, interleukin (IL)‐2 and TNF‐α. Polyfunctional alloreactive T cells, defined by multiple cytokine expression, were observed infrequently. In conclusion, activation‐induced CD137 expression is a fast assay allowing for detection and functional analysis of the total alloreactive T cell compartment at the single‐cell level by multi‐parameter flow cytometry.
Design of an Intelligent Location Identification Scheme Based On LANDMARC and BPNs

— Radio frequency identification (RFID) applications have grown rapidly in many industries, especially in indoor location identification. The advantage of using received signal strength indicator (RSSI) values as an indoor location measurement method is a cost-effective approach without installing extra hardware. Because the accuracy of many positioning schemes using RSSI values is limited by interference factors and the environment, thus it is challenging to use RFID location techniques based on integrating positioning algorithm design. This study proposes the location estimation approach and analyzes a scheme relying on RSSI values to minimize location errors. In addition, this paper examines different factors that affect location accuracy by integrating the backpropagation neural network (BPN) with the LANDMARC algorithm in a training phase and an online phase. First, the training phase computes coordinates obtained from the LANDMARC algorithm, which uses RSSI values and the real coordinates of reference tags as training data for constructing an appropriate BPN architecture and training length. Second, in the online phase, the LANDMARC algorithm calculates the coordinates of tracking tags, which are then used as BPN inputs to obtain location estimates. The results show that the proposed scheme can estimate locations more accurately compared to LANDMARC without extra devices.
The impact of recreational music-making for long-term care workers.

ADVANCES Fall/Winter 2003, VOL. 19, NO. 3/4 The Impact of Recreational Music-Making for Long-Term Care Workers The featured article in this issue, Recreational MusicMaking: A Cost-Effective Group Interdisciplinary Strategy for Reducing Burnout and Improving Mood States in Long-Term Care Workers—Insights and Potential Economic Impact, represents an outstanding research contribution. This paper provides for a new, innovative approach outside the realm of direct patient impact. Bittman and his research team present a compelling comprehensive rationale for directly addressing and developing effective programs to meet the needs of the often-overlooked healthcare worker. This study not only introduces recreational music-making as an effective interdisciplinary group mind-body wellness strategy, but also serves to document impressive, statisticallysignificant improvements in burnout and mood parameters in a stressed healthcare workforce serving one of society’s most challenged areas—long-term care. The authors explore the multidimensional impact of a unique recreational music-making program in the context of diminishing long-term care employee turnover rates that are currently estimated at over 60% per year in the US. The process of reducing turnover and thereby fostering enhanced continuity of care impacts not only healthcare workers, but also their families, long-term care centers, and ultimately residents and their loved ones alike. In addition, Bittman and colleagues present a post hoc economic-impact analysis performed by an independent healthcare financial consulting firm. A potential savings of $89,100 based upon reduced employee turnover was projected for each typical 100-bed long-term care facility that uses this innovative music strategy. Based upon these results and the economic impact projections, this editor subsequently contacted the long-term care center where this study was performed for additional information. During a telephone interview, Donald Clawson, president of Wesbury United Methodist Retirement Community in Meadville, Pa, reported that a marked behavioral shift in greater tolerance and team-building had indeed occurred in his workforce since the inception of this intervention. In addition, he noted a significant improvement in employee morale, as well as a dramatic and concomitant reduction of employee complaints during this period. Clawson also referred to data recently compiled by the center’s human resources department, which concluded that a substantial reduction in the employee turnover rate had occurred, comparing 2002 (the year of the study) with the The Impact of Recreational Music-making for Long-Term Care Workers