Miracle-dz/UniFAR-FTUs huggingface dataset:
Syphilis at the Crossroad of Phylogenetics and Paleopathology

The origin of syphilis is still controversial. Different research avenues explore its fascinating history. Here we employed a new integrative approach, where paleopathology and molecular analyses are combined. As an exercise to test the validity of this approach we examined different hypotheses on the origin of syphilis and other human diseases caused by treponemes (treponematoses). Initially, we constructed a worldwide map containing all accessible reports on palaeopathological evidences of treponematoses before Columbus's return to Europe. Then, we selected the oldest ones to calibrate the time of the most recent common ancestor of Treponema pallidum subsp. pallidum, T. pallidum subsp. endemicum and T. pallidum subsp. pertenue in phylogenetic analyses with 21 genetic regions of different T. pallidum strains previously reported. Finally, we estimated the treponemes' evolutionary rate to test three scenarios: A) if treponematoses accompanied human evolution since Homo erectus; B) if venereal syphilis arose very recently from less virulent strains caught in the New World about 500 years ago, and C) if it emerged in the Americas between 16,500 and 5,000 years ago. Two of the resulting evolutionary rates were unlikely and do not explain the existent osseous evidence. Thus, treponematoses, as we know them today, did not emerge with H. erectus, nor did venereal syphilis appear only five centuries ago. However, considering 16,500 years before present (yBP) as the time of the first colonization of the Americas, and approximately 5,000 yBP as the oldest probable evidence of venereal syphilis in the world, we could not entirely reject hypothesis C. We confirm that syphilis seems to have emerged in this time span, since the resulting evolutionary rate is compatible with those observed in other bacteria. In contrast, if the claims of precolumbian venereal syphilis outside the Americas are taken into account, the place of origin remains unsolved. Finally, the endeavor of joining paleopathology and phylogenetics proved to be a fruitful and promising approach for the study of infectious diseases.
Trends of Outpatient Prescription Drug Utilization in US Children, 2002–2010

OBJECTIVE: To describe trends in outpatient prescription drug utilization in US children and the changes in major areas of pediatric therapeutic use for the years 2002 through 2010. METHODS: Large prescription databases (the IMS Vector One: National and Total Patient Tracker) were used to examine national drug utilization patterns for the US pediatric population (ages 0–17 years) from 2002 through 2010. RESULTS: In 2010, a total of 263.6 million prescriptions were dispensed to the US pediatric population, 7% lower than in 2002, while prescriptions dispensed to the adult population increased 22% during the same time. Analysis of pediatric drug utilization trends for the top 12 therapeutic areas in 2010 compared with 2002 showed decreases in systemic antibiotics (–14%), allergies (–61%), pain (–14%), depression (–5%), and cough/cold without expectorant (–42%) prescriptions, whereas asthma (14%), attention-deficit/hyperactivity disorder (46%), and contraceptive (93%) prescriptions increased. In 2010, amoxicillin was the most frequently dispensed prescription in infants (aged 0–23 months) and children (aged 2–11 years). Methylphenidate was the top prescription dispensed to adolescents (aged 12–17 years). Off-label use was identified, particularly for lansoprazole; ∼358 000 prescriptions were dispensed in 2010 for infants <1 year old. CONCLUSIONS: Changes in the patterns of pediatric drug utilization were observed from 2002 to 2010. Changes include a decrease in antibiotic use and an increase in attention-deficit/hyperactivity disorder medication use during the examined time. This article provides an overview of pediatric outpatient drug utilization, which could set the stage for further in-depth analyses.
An overview of variability management in cloud services

The Cloud Computing paradigm has enabled the multi-tenancy architectural approach in Cloud applications. In a multi-tenant application, one single instance is shared by many tenants (users). Since each client has its own and particular requirements and context, that are exposed to change in time, the process of realizing customizable and adaptable services becomes complex and difficult to handle. Handling variability has been subject of many research works in the domain of Service Oriented Computing, while less interest was given to variability in Cloud services. Therefore, managing variability in Cloud applications can take benefit from related works in service-oriented computing. In this paper, we present an overview of variability management in Cloud applications, in order to assess the pertinence of the different approaches proposed to tackle this issue.
UNDERLYING MECHANISM OF REGULATORY ACTIONS OF DICLOFENAC , A NONSTEROIDAL ANTI-INFLAMMATORY AGENT , ON NEURONAL POTASSIUM CHANNELS AND FIRING : AN EXPERIMENTAL AND THEORETICAL STUDY

Diclofenac (DIC), 2-[(2,6-diclorophenyl)amino]phenylacetate, is a nonsteroidal anti-inflammatory drug (NSAID) with antiinflammatory, antipyretic and analgesic activities. The treatment with this agent may be accompanied by deleterious effects including gastrointestinal damage and platelet dysfunction (1, 2). Notably, some of its pharmacological or toxicological effects might be linked to any modifications of ion channels caused by many types of NSAIDs. However, whether diclofenac produce any effects on ion currents inherent in neurons remains incompletely understood. There is emerging evidence showing that diclofenac can be a direct regulator of ion channels, especially the potassium channels, and those actions may have pharmacological or toxicological implications. For example, diclofenac was reported to activate voltage-gated K+ currents (3-5), while this compound effectively blocks K+ currents expressed in leukocytes (6). It was also shown to increase anti-nociceptive efficacy possibly through activation of ATP-sensitive K+ channels (3). Several investigators have recently demonstrated that diclofenac can bind to and modulate the amplitude and kinetics of voltage-gated K+ (Kv) channel subtypes 7.2–7.5 (Kv7.2-7.5 or KCNQ2-5) (7, 8). The increased activity of Kv7.2/7.3 channels generates the M-type K+ current (IK(M)) which is a slowly activating and deactivating current suppressed by stimulation of muscarinic receptors (9, 10). Agents known to activate IK(M) were reported to exert anticonvulsant activity (11-13). Flupirtine, an activator of IK(M), was intriguingly noted to be efficacious in suppressing or preventing repetitive febrile seizures (14). However, although previous findings seem to validate KCNQ2/Q3 channels as targets for diclofenac, it should be noted that this agent or other openers of Kv7 channels may exert some actions on other types of Kv channels (15). These experimental results with regard to the effects of diclofenac on different types of ion currents, remain controversial and are required to be further studied. The NSC-34 cell is a hybridoma cell line derived from the fusion of neuroblastoma cells with mice spinal cord cells. These cells have currently attracted growing interest as a useful cell line JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2013, 64, 3, 269-280 www.jpp. krakow.pl
The emergence of subcellular pacemaker sites for calcium waves and oscillations

• Calcium (Ca2+) is fundamental to biological cell function, and Ca2+ waves generating oscillatory Ca2+ signals are widely observed in many cell types. • Some experimental studies have shown that Ca2+ waves initiate from random locations within the cell, while other studies have shown that waves occur repetitively from preferred locations (pacemaker sites). • In both ventricular myocyte experiments and computer simulations of a heterogeneous model of coupled Ca2+ release units (CRUs), we show that Ca2+ waves occur randomly in space and time when the Ca2+ level is low, but as the Ca2+ level increases, waves occur repetitively from the same sites. • Ca2+ waves are self‐organized dynamics of the CRU network, and the wave frequency strongly depends on CRU coupling. • Using these results, we develop a theory for the entrainment of random oscillators, which provides a unified explanation for the experimental and computational observations.
Real-time Motion Control of a Nonholonomic Mobile Robot with Unknown Dynamics

In this paper, real-time fine motion control of a nonholonomic mobile robot is investigated, where the robot dynamics is completely unknown and is subject to significant uncertainties. A novel neural network based real-time controller is developed. The neural network assumes a single layer structure, by taking advantage of the robot regressor dynamics that express the highly nonlinear robot dynamics in a linear form in terms of the known and unknown robot dynamic parameters. The learning algorithm is computationally efficient. The system stability and the converge of tracking errors to zero are rigorously proved using a Lyapunov theory. The real-time fine control of mobile robot is achieved through the on-line learning of the neural network without any off-line learning procedures. In addition, the developed controller is capable of compensating sudden changes of robot dynamics or disturbance. The effectiveness and efficiency of the proposed controller is demonstrated by simulation studies.
Clinical, empirical, and developmental perspectives on the therapeutic relationship in child psychotherapy

Abstract Despite substantial interest in the therapeutic relationship by child clinicians, relationship processes in child therapy have been neglected by clinical researchers. In this paper, clinical and empirical perspectives on the therapeutic relationship in child treatment were reviewed. Initial findings indicated that the quality of the child's affective relationship with the therapist is associated with collaboration on therapy tasks. Given the recurrent finding of links between treatment collaboration and treatment outcome, research on factors that influence children's ability to form therapeutic relationships is recommended. To this end, a developmental social cognitive model of therapeutic alliance formation is proposed.
Psychological Treatment of Childhood Obesity: Main Principles and Pitfalls

The Ecological Systems Theory is an interesting framework that captures the multicausal interaction of hereditary, environmental and child characteristics that place a child at risk for overweight [1]. This theory serves as a guideline for the multidisciplinary assessment of obesity in childhood (see chapter X) and for the treatment. The benefits of a multidisciplinary approach focusing on healthy eating habits, moderate exercise and cognitive-behavioural modification are well established [2]. Several studies have shown positive and encouraging outcomes in short-term. This chapter will provide an overview of the main principles of the cognitive behavioural lifestyle program for obese children. Thereby, both working with children as well as how to involve parents will be addressed. However, also pitfalls in treatment need to be considered. To this day, obesity interventions, especially for adolescents and adults are also characterized by limited weight changes, relapse and a large drop-out (for adolescents, see [3]; for adults, see [4]). This chapter will focus on drop-out and will address some structural actions to overcome it.
Vocabularies of Motive for Illicit Drug Use: An Application of the Accounts Framework*

The importance of motives in the career of the user of illicit drugs has been stressed by researchers from the interactionist school. Users' “vocabularies of motive” or explanations for their behavior, however, were not systematically studied by the interactionists. Conversely, researchers who have studied drug motives systematically did not place their findings in an interactional context. The present report attempts to correct this imbalance. Data available in the literature on vocabularies of motive for illicit drug use were interpreted according to an interactionist framework—viz., Scott and Lyman's (1968) notion of “accounts,” the linguistic strategies adopted to explain deviance. The five major topics they covered are applied here to drug research data: (1) the different types of drug accounts users avow, (2) the situational contexts in which drug accounts are presented, (3) the strategies users employ to avoid giving accounts, (4) people's background expectancies for drugs and users, and their effe.
The major structural components of two cell surface filaments of Porphyromonas gingivalis are matured through lipoprotein precursors

Bacterial cell surface filaments play significant roles in adherence to and invasion of host cells. They are generated by the chaperone/usher pathway system (class I fimbriae), the type II secretion system (type IV pili) and the nucleation‐dependent polymerization system (Curli filaments) that are categorized by their modes of expression and assembly. In this study, we found that the periodontal pathogen Porphyromonas gingivalis expressed the major structural components of two cell surface filaments (fimbrilin and the 75 kDa protein) that had extremely long prosequences in their primary gene products. N‐terminal amino acid sequencing of the prosequences, treatment of P. gingivalis cells with globomycin, an inhibitor for lipoprotein‐specific signal peptidase, amino acid substitution of the cysteine residue of the prosequence of fimbrilin and [3H]‐palmitic acid labelling implied that fimbrilin and the 75 kDa protein were matured through their lipoprotein precursor forms. Accumulation of precursor forms of fimbrilin and the 75 kDa protein on the cell surface of the gingipain‐null mutant revealed that Arg‐gingipain processed these precursors on the surface to yield their mature forms, which subsequently assembled into the filamentous structures, suggesting that the transport and assembly of the major component proteins appear to be novel.
Visuospatial neglect and an ipsilesional bias during the start of performance in conventional tests of neglect

Abstract This study describes the relationship between an ipsilesional start of performance during conventional tests of neglect and the presence of visuospatial neglect. The validity of using ipsilesional bias as an indicator of neglect was examined in 60 patients with a single right hemisphere stroke, consecutively studied 1-8 weeks and 6-7 months poststroke. The spatial location of the start point within the tests was observed in four subtests from a modified version of the Behavioural Inattention Test. On the basis of defective performance in at least two of the measures used, 83 % of the patients with neglect in the test battery and 98% of the patients with no neglect were correctly identified (Phi = .84). At the follow-up, 50% of the patients with neglect and 98% of the patients with no neglect were correctly identified (Phi = .57). The use of only one measure resulted in a less satisfying outcome because of great variability of performance in the various subtests. It was concluded that a defective .
PI and Sliding Mode Control of a Multi-Input-Multi-Output Boost- Boost Converter

A proportional-integral (PI) controller and a sliding mode controller (SMC) are used to control a fourth-order Boost-Boost (BB) converter in continuous conduction mode with two input switches and two output voltages. Based on the equivalent control method, a closed-loop system is developed. The resultant PI gains have a nonlinear relationship with each other. The appropriate PI gains are obtained through the least squares method. The converter under the controller is stable and robust. The converter has voltage tracking accuracies within ±0.1 V for the first load and ±0.02 V for the second load. The maximum switching frequency is not greater than 100 KHz.
Frequent Contribution of T Cell Clonotypes with Public TCR Features to the Chronic Response Against a Dominant EBV-Derived Epitope: Application to Direct Detection of Their Molecular Imprint on the Human Peripheral T Cell Repertoire1

In an attempt to provide a global picture of the TCR repertoire diversity of a chronic T cell response against a common Ag, we performed an extensive TCR analysis of cells reactive against a dominant HLA-A2-restricted EBV epitope (hereafter referred to as GLC/A2), obtained after sorting PBL or synovial fluid lymphocytes from EBV-seropositive individuals using MHC/peptide multimers. Although TCR β-chain diversity of GLC/A2+ T cells was extensive and varied greatly from one donor to another, we identified in most cell lines several recurrent Vβ subsets (Vβ2, Vβ4, and Vβ16 positive) with highly conserved TCRβ complementarity-determining region 3 (CDR3) length and junctional motifs, which represented from 11 to 98% (mean, 50%) of GLC/A2-reactive cells. While TCR β-chains expressed by these subsets showed limited CDR1, CDR2, and CDR3 homology among themselves, their TCR α-chains comprised the same TCRAV region, thus suggesting hierarchical contribution of TCR α-chain vs TCR β-chain CDR to recognition of this particular MHC/peptide complex. The common occurrence of T cell clonotypes with public TCR features within GLC/A2-specific T cells allowed their direct detection within unsorted PBL using ad hoc clonotypic primers. These results, which suggest an unexpectedly high contribution of public clonotypes to the TCR repertoire against a dominant epitope, have several implications for the follow-up and modulation of T cell-mediated immunity.
Improvements in dizziness and imbalance results from using a multi disciplinary and multi sensory approach to Vestibular Physical Therapy – a case study

This paper discusses a case study of a 41-year-old active duty male service member who sustained head trauma from a motorcycle accident and underwent multidisciplinary vestibular physical therapy rehabilitation. He was initially treated with traditional physical therapy applications of treadmill walking and standing balance with some symptom improvements, but was not able to maintain a running speed that would allow him to return to full active duty status. Further treatment utilizing a Computer Assisted Rehabilitation Environment was performed in order to increase level of difficulty and further enhance function. This treatment is able to elicit vestibular deficits seen in the community as it requires subjects to walk and balance while performing tasks within a virtual scenario incorporating platform motion, visual surround and flow, and cognitive processing. After 6 weeks of therapy, twice weekly, improvements in clinical vestibular measures were observed as well as walking speed and patient confidence. The patient was able to return to full duty after treatment. This case study provides supportive evidence that multidimensional tasking in a virtual environment provides a safe but demanding form of vestibular therapy for patients needing more challenging tasks than those provided with traditional therapy techniques. Those persons requiring higher levels of performance before returning to full duty (e.g., pilots, special operators, etc.) may find this type of therapy beneficial.
The blind separation of non-stationary signals by only using the second order statistics

Lathauwer and Comon (see Signal Processing, vol.73, no.1-2, p.3-4, 1999) state that for the last 10 years, source separation has raised an increasing interest, partly because it has been discovered that space-time approaches will play an essential role in future radio communications. In the case of an instantaneous mixture (memoryless mixture or channel), many algorithms are proposed to solve the blind separation problem. In the general case (where no special assumption is assumed), the high order statistics (i.e. fourth order) are used. By adding special assumptions, algorithms and criteria can be simplified. In this paper, we discuss and present how the separation of a non-stationary signal can be done using only second order statistics.
Acceptance of clinical decision support surveillance technology in the clinical pharmacy

ABSTRACT Introduction: There are clinical and economic benefits to incorporating clinical decision support systems (CDSSs) in patient care interventions in the clinical pharmacy setting. However, user dissatisfaction and resistance to HIT can prevent optimal use of such systems, particularly when users employ system workarounds and overrides. Objectives: The present study applied a modified version of the unified theory of acceptance and use of technology (UTAUT) to evaluate the disposition and satisfaction with CDSS among clinical pharmacists who perform surveillance to identify potential medication therapy interventions on patients in the hospital setting. Methods: A survey of clinical pharmacists (N = 48) was conducted. Partial least squares (PLS) regression was used to analyze the influence of the UTAUT-related variables on behavioral intention and satisfaction with CDSS among clinical pharmacists. Results: While behavioral intention did not predict actual use of HIT, facilitating conditions had a direct effect on pharmacists’ use of CDSS. Likewise, satisfaction with CDSS was found to have a direct effect on use, with more satisfied users being less inclined to employ workarounds or overrides of the system. Conclusion: Based on the findings, organizational structures that facilitate CDSS use and user satisfaction affect the extent to which pharmacy and health care management maximize use in the clinical pharmacy setting.
The effects of emotion on attention: A review of attentional processing of emotional information

This review considers evidence from cognitive experimental investigations of attentional processing of emotional information. The review contrasts findings from the general population with those from populations selected for clinical disorder or vulnerability to it. Concepts critical for appreciation of this literature are presented and major cognitive theories are summarised, evaluated and compared. Empirical data are organised by type of attentional function, covering filtering (dichotic listening, emotional Stroop), search (visual search), cuing (attentional probe, spatial cuing) and multiple task (RSVP) paradigms. Conclusions are that, consistent with current models, differences in an “evaluative system” appear to lie at the heart of the phenomena reviewed and attentional biases to emotional material reflect the responsiveness of this system. If so, desensitising its over-reactivity would be the best approach to ameliorating the negative consequences of attentional biases in psychopathology. To do so requires greater understanding of how and on what basis the “evaluation” is conducted. A possible way forward is suggested.
Molecular quantum similarity measures as an alternative to log P values in QSAR studies

A new molecular descriptor of hydrophobicity based on molecular quantum similarity measures (MQSM), which can be used to replace the log P parameter in QSAR studies, is proposed. Unlike the majority of existing approaches for calculation of log P, the present methodology does not rely on the use of fragment additive contributions, but rather it is based on the comparison of quantum chemically calculated electron density distributions of a given molecule in water and in 1‐octanol, using MQSM. The method has been tested on a broad series of 58 molecules including such structural types as aliphatic hydrocarbons, alcohols, amines, halides, carboxylic acids, esters, amides, and ketones, as well as more complex systems with two functional groups. In all cases investigated, an excellent linear relationship between calculated MQSM and log P values was found. Additionally, an example of QSAR analysis is presented using MQSM instead of log P values, corresponding to predict the narcosis of tadpoles. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1575–1583, 1998