Miracle-dz/UniFAR-FTUs huggingface dataset:
Relation between DNA double-strand breaks and energy spectra of secondary electrons produced by different X-ray energies

Abstract Purpose: In a radiological examination, low-energy X-radiation is used (<100 keV). For other radiological procedures, the energy used is several MeV. ICRP in publication 103 has currently considered that photons irrespective of their energy have the same radiation weighting factor. Nevertheless, there are topological differences at the nanoscale of X-ray energy deposition as a function of its energy spectrum, meaning that the different interactions with living matter could vary in biological efficacy. Materials and methods: To study these differences, we characterized our irradiation conditions in terms of initial photon energies, but especially in terms of energy spectra of secondary electrons at the cell nucleus level, using Monte Carlo simulations. We evaluated signaling of DNA damage by monitoring a large number of γH2A. X foci after exposure of G0/G1-phase synchronized human primary endothelial cells from 0.25 to 5 Gy at 40 kV, 220 kV and 4 MV X-rays. Number and spatial distribution of γH2A. X foci were explored. In parallel, we investigated cell behavior through cell death and ability of a mother cell to produce two daughter cells. We also studied the missegregation rate after cell division. Results: We report a higher number of DNA double-strand breaks signaled by γH2A. X for 40 kVp and/or 220 kVp compared to 4 MVp for the highest tested doses of 2 and 5 Gy. We observed no difference between the biological endpoint studies with 40 kVp and 220 kVp X-ray spectra. This lack of difference could be explained by the relative similarity of the calculated energy spectra of secondary electrons at the cell monolayer. Conclusion: The energy spectrum of secondary electrons seems to be more closely related to the level of DNA damage measured by γH2A. X than the initial spectrum of photon energy or voltage settings. Our results indicate that as the energy spectrum of secondary electrons increases, the DNA damage signaled by γH2A. X decreases and this effect is observable beyond 220 kVp.
Clozapine Monotherapy as a Treatment for Antipsychotic-Induced Tardive Dyskinesia: A Meta-Analysis.

OBJECTIVE Tardive dyskinesia (TD) is an antipsychotic-induced movement disorder that typically occurs after long-term exposure to antipsychotic drugs. There is evidence that switching to clozapine reduces TD. This meta-analysis reviews the effect of switching to clozapine on the severity of TD. DATA SOURCES The PubMed, PsycINFO, and Embase databases were searched for clozapine, tardive dyskinesia, and related keywords. The search was restricted to articles written in English and Dutch, and it was last updated on October 13, 2015. STUDY SELECTION Sixteen studies were included in the meta-analysis. Inclusion criteria were a diagnosis of schizophrenia or a related disorder, a switch to clozapine monotherapy, and reports of scores on a TD rating scale before and after the switch to clozapine. DATA EXTRACTION Two independent investigators extracted the data. Data were converted to standardized mean change scores and analyzed in a random-effects model. RESULTS A random-effects model showed that the overall effect of switching to clozapine was a significant reduction in TD (npatients = 1,060, d = -0.40, P < .01), especially in the 4 studies that investigated the severity of TD as a primary outcome (npatients = 48, d = -2.56, P = .02). CONCLUSIONS The overall results show that clozapine treatment can yield a slight reduction in TD. The severity of TD was reduced greatly in patients with moderate to severe TD. In patients with minimal to mild TD, switching to clozapine seldom worsens TD and a trend toward reduction is seen. These results support that a switch to clozapine should be considered for patients with moderate to severe TD and/or patients who experience substantial discomfort due to TD.
A Novel Setup and Protocol to Measure the Range of Motion of the Wrist and the Hand

The human hand is important for the performance of activities of daily living which are directly related to quality of life. Various conditions, such as Duchenne muscular dystrophy (DMD) can affect the function of the human hand and wrist. The ability to assess the impairment in the hand and the wrist by measuring the range of motion (ROM), is essential for the development of effective rehabilitation protocols. Currently the clinical standard is the goniometer. In this study we explore the feasibility and reliability of an optical sensor (Leap motion sensor) in measuring active hand/wrist ROM. We measured the hand/wrist ROM of 20 healthy adults with the goniometer and the Leap motion sensor, in order to check the agreement between the two methods and additionally, we performed a test-retest of the Leap motion sensor with 12 of them, to assess its reliability. The results suggest low agreement between the goniometer and the leap motion sensor, yet showing a large decrease in measurement time and high reliability when using the later. Despite the low agreement between the two methods, we believe that the Leap motion sensor shows potential to contribute to the development of hand rehabilitation protocols and be used with patients in a clinical setting.
Evaluation of the Rosemary Extract Effect on the Properties of Polylactic Acid-Based Materials

New multifunctional materials containing additives derived from natural resources as powdered rosemary ethanolic extract were obtained by melt mixing and processed in good conditions without degradation and loss of additives. Incorporation of powdered rosemary ethanolic extract (R) into poly(lactic acid) (PLA) improved elongation at break, rheological properties, antibacterial and antioxidant activities, in addition to the biocompatibility. The good accordance between results of the chemiluminescence method and radical scavenging activity determination by chemical method evidenced the increased thermoxidative stability of the PLA biocomposites with respect to neat PLA, with R acting as an antioxidant. PLA/R biocomposites also showed low permeability to gases and migration rates of the bioactive compounds and could be considered as high-performance materials for food packaging. In vitro biocompatibility based on the determination of surface properties demonstrated a good hydrophilicity, better spreading and division of fibroblasts, and increased platelet cohesion. The implantation of PLA/R pellets, was proven to possess a good in vivo biocompatibility, and resulted in similar changes in blood parameters and biochemical responses with the control group, suggesting that these PLA-based materials demonstrate very desirable properties as potential biomaterials, useful in human medicine for tissue engineering, wound management, orthopedic devices, scaffolds, drug delivery systems, etc. Therefore, PLA/R-based materials show promising properties for applications both in food packaging and as bioactive biomaterials.
Socioeconomic Differences In Smoking And Cessation Across a Period Of Rapid Economic Growth in an Upper-Middle-Income Country.

Introduction Higher smoking rates and lower cessation rates among the poor compared to the rich are evident in high-income countries. In low and middle-income countries (LMICs), many of which are in the early stages of tackling the tobacco epidemic, more knowledge is required of the socioeconomic inequalities in smoking. This is especially the case for upper-middle-income countries, where smoking prevalence is highest. This study examines trends in the socioeconomic gradient in smoking and cessation among adults across a period of rapid economic development in Malaysia, an LMIC with an upper-middle-income economy. Methods The socioeconomic trends in smoking were analysed using data from cross-sectional National Health and Morbidity Surveys (NHMS) for the years 1996, 2006 and 2011. Household per-capita income was used as a measure of socioeconomic position. As a measure of inequality, the concentration index which quantified the degree of socioeconomic inequality in a health outcome was computed. Smoking was assessed in current and former smokers. The study population was examined by gender, region and age group. Results This study found a trend of an increasingly higher smoking prevalence among the poor and higher cessation rates among the rich. With the exception of younger women in Peninsular Malaysia, the socioeconomic gradient in current smoking is concentrated among the poor. For former smokers, especially men, distributions across the years were mostly concentrated among the rich. Conclusion It is important to ensure that health policies, programmes and interventions consider the potential impact of the socioeconomic patterning in smoking on equity in health.
Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review

Background: Nephrotoxicity is a notable adverse effect in cisplatin treated patients characterized by tubular injury and/or increased serum creatinine (SCr) with incidence varying from 20 to 70%. Pharmacogenomics has been shown to identify strongly predictive genetic markers to help determine which patients are more likely to experience, for example, a serious adverse drug reaction or receive optimal benefit through enhanced efficacy. Genetic variations have been reported to influence the risk of cisplatin nephrotoxicity; however, a comprehensive overview is lacking. Methods: A systematic review was performed using Pubmed, Embase and Web of Science on clinical studies that used cisplatin-based chemotherapy as treatment, had available genotyping data, and evaluated nephrotoxicity as an outcome. The quality of reporting was assessed using the STrengthening the REporting of Genetic Association Studies (STREGA) checklist. Results: Twenty-eight eligible studies were included; all were candidate gene studies. Over 300 SNPs across 135 genes were studied; 29 SNPs in 14 genes were significantly associated with cisplatin-induced nephrotoxicity. A variation in SLC22A2 rs316019, a gene involved in platinum uptake by the kidney, was associated with different measures of nephrotoxicity in four independent studies. Further, variants of ERCC1 (rs11615 and rs3212986) and ERCC2 (rs13181), two genes involved in DNA repair, were found to be positively associated with increased risks of nephrotoxicity in two independent studies. Conclusion: Three genes consistently associated with cisplatin-induced nephrotoxicity. Further research is needed to assess the biological mechanism and the clinical value of modifying treatment based on SLCC22A2 and ERCC1/2 genotypes.
Rab17 regulates apical delivery of hepatic transcytotic vesicles

A major focus for our laboratory is identifying the molecules and mechanisms that regulate basolateral-to-apical transcytosis in polarized hepatocytes. Our most recent studies have focused on characterizing the biochemical and functional properties of the small rab17 GTPase. We determined that rab17 is a monosumoylated protein and that this modification likely mediates selective interactions with the apically located syntaxin 2. Using polarized hepatic WIF-B cells exogenously expressing wild-type, dominant active/guanosine triphosphate (GTP)-bound, dominant negative/guanosine diphosphate (GDP)-bound, or sumoylation-deficient/K68R rab17 proteins, we confirmed that rab17 regulates basolateral-to-apical transcytotic vesicle docking and fusion with the apical surface. We further confirmed that transcytosis is impaired from the subapical compartment to the apical surface and that GTP-bound and sumoylated rab17 are likely required for apical vesicle docking. Because expression of the GTP-bound rab17 led to impaired transcytosis, whereas wild type had no effect, we further propose that rab17 GTP hydrolysis is required for vesicle delivery. We also determined that transcytosis of three classes of newly synthesized apical residents showed similar responses to rab17 mutant expression, indicating that rab17 is a general component of the transcytotic machinery required for apically destined vesicle docking and fusion.
All common bipedal gaits emerge from a single passive model

In this paper, we systematically investigate passive gaits that emerge from the natural mechanical dynamics of a bipedal system. We use an energetically conservative model of a simple spring-leg biped that exhibits well-defined swing leg dynamics. Through a targeted continuation of periodic motions of this model, we systematically identify different gaits that emerge from simple bouncing in place. We show that these gaits arise along one-dimensional manifolds that bifurcate into different branches with distinctly different motions. The branching is associated with repeated breaks in symmetry of the motion. Among others, the resulting passive dynamic gaits include walking, running, hopping, skipping and galloping. Our work establishes that the most common bipedal gaits can be obtained as different oscillatory motions (or nonlinear modes) of a single mechanical system with a single set of parameter values. For each of these gaits, the timing of swing leg motion and vertical motion is matched. This work thus supports the notion that different gaits are primarily a manifestation of the underlying natural mechanical dynamics of a legged system. Our results might explain the prevalence of certain gaits in nature, and may provide a blueprint for the design and control of energetically economical legged robots.
Synthesis of adaptive gain robust model-following/tracking controllers for a class of uncertain linear systems

This paper proposes a new adaptive gain robust model-following/tracking controller for a class of uncertain linear systems. The proposed adaptive gain robust controller is composed of state feedback laws with fixed gains, feedfoward inputs for the reference model and nonlinear compensation inputs with adjustable time-varying parameters. Moreover, the proposed control strategy can achieve good transient performance and avoid the excessive control input by means of the design parameter. In this paper, linear matrix inequality-based sufficient conditions for the existence of the proposed adaptive gain controller are given, and two design strategies are presented. Finally, simple illustrative examples are included to show the effectiveness of the proposed adaptive gain robust controller.
Diagnostic Outcomes of Childhood ADHD in Chinese Adults

Objective: We examined adulthood diagnostic, functioning, and social outcomes of childhood ADHD in a Hong Kong Chinese clinical sample. Method: We identified from the central registry 499 Chinese adults clinically diagnosed with ADHD aged 6 to 12 in 2002-2005 in four Hong Kong child psychiatric centers. Assessments included ADHD Clinical Diagnostic Scale (ACDS), Structured Clinical Interview for DSM Disorders (SCID), and World Health Organization Disability Assessment Schedule (WHO-DAS). Results: Eligible participants = 499. One hundred forty-five completed assessments, two deceased, six incarcerated, 100 had invalid contact, 83 declined, 34 emigrated, and 129 unable to attend. Mean follow-up duration = 14.9 years. Nonrespondents were slightly younger (19.78 vs. 20.53, p < .001). In all, 83.1% of all participants currently met Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD criteria (36.8% inattentive subtype (IA), 43% combined, 3.3% hyperactive/impulsive subtype (H/I) ). One third of persistent ADHD participants currently received care. ADHD persistence was associated with significantly increased psychiatric comorbidity (49.5% vs. 22.7%, p = .02) and poor academic and social outcomes. ADHD persistence and comorbidity independently predicted impairment. Conclusion: Adulthood-persistence of clinically presented childhood ADHD is common and impairing in Hong Kong Chinese.
Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease

While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS. For example, anti-programmed cell death-1 (PD-1) monotherapy with pembrolizumab has shown intracranial response rates of 20–30% in patients with melanoma or non-small cell lung cancer (NSCLC) brain metastases. The combination of nivolumab and ipilimumab [anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)] showed an intracranial response rate of 55% in patients with melanoma brain metastases. More data are needed to confirm these response rates and to determine mechanisms of efficacy and resistance. While local therapies such as stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and surgery remain current mainstays, ICIS offer potential decreased neurotoxicity. This review summarizes the biological rationale for systemic immunotherapy to treat CNS metastatic disease, existing clinical data on ICIs in this setting and ongoing clinical trials exploring areas of unmet need.
Prevalence and pattern of genital injuries among adolescent rape victims attending Enugu State University Teaching Hospital, South East Nigeria

Abstract The study aimed to determine the prevalence and pattern of genital injuries among the female adolescents alleged to have been raped that presented at the Enugu State University Teaching Hospital (ESUTH) from January 1 2013 to August 31 2014. All of the adolescents alleged to have been raped that presented within the study period were studied, and the relevant data were extracted from their records. The data were analysed using the Epi info statistical software, Version 7. There were 78 adolescents alleged to have been raped within the study period. They were all female, with a mean age of 14.12 ± 5.6 years. The majority of them were virgins (n = 47, 60.3%). Five of them (6.4%) had multiple perpetrators. The prevalence of genital injuries was 44.9%, while the genital injury frequency rate was 1.2. Laceration was the commonest injury type, while the hymen was the most affected site (n = 15; 35.7%). Being a virgin at the time of the rape was significantly associated with the presence of genital injury (p < .001). This suggests that the absence of genital injury is not sufficient evidence to rule out the possibility of rape. Impact Statement What is already known on this subject? Rape is a global problem with a severe negative impact on the victim. Apart from the associated psychological and emotional trauma, a genital injury could result. However, it appears that so much emphasis are usually placed on the presence of a genital injury in establishing an incident of rape in the developing world. Genital injuries seem to be the main substantive evidence of rape in the developing world including Nigeria. Convicting the perpetrator of rape in law court is usually difficult in the absence of genital injuries after medical examination. What the results of this study add? The result of this study shows that a genital injury is not be found in all cases of an alleged rape, especially among the adolescents. In fact, more than half of the rape survivors had no genital injury. What the implications are of these findings for clinical practice and/or further research? The absence of a genital injury does not exclude the possibility of a rape, neither does its presence confirm a rape, as genital injuries can occur even in consensual sex. Adopting a modern method of establishing a rape case is very important for the provision of concrete evidence in court that will enable the proper and sound dispensation of justice.
PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice

Significance Engineered mouse models of acute leukemia are critical to understanding the biological mechanisms by which a primary oncogene induces disease. While PAX5 fusion proteins are considered primary oncogenic events in B-ALL, their role in leukemia development is ill-known due to the lack of animal models. This report provides a novel and accurate in vivo model for B-ALL induced by PAX5-ELN fusion protein that establishes a preleukemic phase and recapitulates the key features of human disease, including acquired mutations in genes of the JAK/STAT and RAS/MAPK pathways. This study is of general interest, as it allows a better understanding of the biological mechanism by which an oncoprotein perturbs normal B-cell development and leads to pathological B-ALL. PAX5 is a well-known haploinsufficient tumor suppressor gene in human B-cell precursor acute lymphoblastic leukemia (B-ALL) and is involved in various chromosomal translocations that fuse a part of PAX5 with other partners. However, the role of PAX5 fusion proteins in B-ALL initiation and transformation is ill-known. We previously reported a new recurrent t(7;9)(q11;p13) chromosomal translocation in human B-ALL that juxtaposed PAX5 to the coding sequence of elastin (ELN). To study the function of the resulting PAX5-ELN fusion protein in B-ALL development, we generated a knockin mouse model in which the PAX5-ELN transgene is expressed specifically in B cells. PAX5-ELN–expressing mice efficiently developed B-ALL with an incidence of 80%. Leukemic transformation was associated with recurrent secondary mutations on Ptpn11, Kras, Pax5, and Jak3 genes affecting key signaling pathways required for cell proliferation. Our functional studies demonstrate that PAX5-ELN affected B-cell development in vitro and in vivo featuring an aberrant expansion of the pro-B cell compartment at the preleukemic stage. Finally, our molecular and computational approaches identified PAX5-ELN–regulated gene candidates that establish the molecular bases of the preleukemic state to drive B-ALL initiation. Hence, our study provides a new in vivo model of human B-ALL and strongly implicates PAX5 fusion proteins as potent oncoproteins in leukemia development.
Reduced dorsal striatal gray matter volume predicts implicit suicidal ideation in adolescents

Abstract Suicidal ideation (SI), a potent risk factor for suicide attempts, increases in adolescence. While alterations in dopaminergic functioning have been implicated in suicidal acts—particularly in adults—we do not know whether morphological alterations in dopamine‐rich regions of the brain, such as the striatum, are vulnerability factors for the emergence of SI in adolescents. At baseline, a community sample of 152 adolescents (89 female; mean age: 11.41 ± 1.01 years) completed a magnetic resonance imaging (MRI) scan that was used to estimate gray matter volumes (GMVs) of three striatal structures: caudate, nucleus accumbens and putamen. At a 24 month follow‐up session, participants completed a self‐report measure of SI frequency [Suicidal Ideation Questionnaire (SIQ)] and the death version of the Implicit Association Test (IAT). Robust linear regression models were conducted to predict SIQ and IAT scores from striatal GMV. Bilateral putamen and left caudate GMV significantly predicted IAT scores (all Ps < 0.03). No other associations were significant (all Ps > 0.05). Our finding of reduced dorsal striatal GMV predicting implicit SI may indicate that downstream dopaminergic dysfunction is implicated in the development of overt suicidal behaviors. Self‐reported SI was not associated with striatal GMV, suggesting that biological correlates of suicide risk may correlate specifically with objective measurements of SI in adolescents.