Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA polymerase kappa counteracts inflammation‐induced mutagenesis in multiple organs of mice

In vitro studies indicate that DNA polymerase kappa (Polκ) is able to accurately and efficiently perform DNA synthesis using templates containing various types of DNA damage, including benzo[a]pyrene (BP)‐induced N2‐deoxyguanosine adducts. In this study, we examined sensitivity of inactivated Polk knock‐in (Polk−/−) mice to BP carcinogenicity in the colon by administering an oral dose of BP plus dextran sulfate sodium (DSS), an inflammation causing promoter of carcinogenesis. Although colon cancer was successfully induced by BP plus DSS, there was no significant difference in tumor incidence or multiplicity between Polk−/− and Polk+/+ mice. Malignant lymphoma was induced in thymus by the treatment only in Polk−/− mice, but it lacked statistical significance. Mutant frequencies (MFs) in the gpt reporter gene were strongly enhanced in colon; almost to the same extent in both types of mice. Micronucleus formation in bone marrow at the high dose of BP and DNA adducts in colon and lung was not significantly different between two types of mice. Surprisingly, however, Polk−/− mice exhibited significantly higher MFs in colon and lung than did Polk+/+ mice when they were treated with DSS alone. The most prominent mutation induced by DSS treatment was G:C to C:G transversion, whose specific MF in proximal colon was 30 times higher in Polk−/− than in Polk+/+ mice. DSS alone did not enhance MF at all in Polk+/+ mice. The results indicate that Polκ does not suppress BP‐induced mutagenesis and carcinogenesis in the colon, but counteracts inflammation‐induced mutagenesis in multiple organs. Environ. Mol. Mutagen. 60:320–330, 2019. © 2019 Wiley Periodicals, Inc.
Measles-vectored vaccine approaches against viral infections: a focus on Chikungunya

ABSTRACT Introduction: The large global burden of viral infections and especially the rapidly spreading vector-borne diseases and other emerging viral diseases show the need for new approaches in vaccine development. Several new vaccine technology platforms have been developed and are under evaluation. Areas covered: This article discusses the measles vector platform technology derived from the safe and highly efficacious measles virus vaccine. The pipeline of measles-vectored vaccine candidates against viral diseases is reviewed. Particular focus is given to the Chikungunya vaccine candidate as the first measles-vectored vaccine that demonstrated safety, immunogenicity, and functionality of the technology in humans even in the presence of pre-existing anti-measles immunity and thus achieved proof of concept for the technology. Expert commentary: Demonstrating no impact of pre-existing anti-measles immunity in humans on the response to the transgene was fundamental for the technology and indicates that the technology is suitable for large-scale immunization in measles pre-immune populations. The proof of concept in humans combined with a large preclinical track record of safety, immunogenicity, and efficacy for a variety of pathogens suggest the measles vector platform as promising plug-and-play vaccine platform technology for rapid development of effective preventive vaccines against viral and other infectious diseases.
No-reference image quality assessment algorithm based on weibull statistics of log-derivatives of natural scenes

A blind/no-reference (NR) image quality assessment (IQA) algorithm based on natural scenes is developed. The proposed algorithm does not need training on databases of human judgments of distorted images or even prior knowledge about expected distortions (as is the case in most general NR IQA algorithms). To measure the image quality, the introduced approach uses a set of novel features in a spatial domain. The devised features are formed using the Weibull statistics of log-derivatives. When testing the proposed algorithm on the LIVE database, experiments showed that it correlates well with subjective opinion scores. In addition, they indicated that the new method has a good performance when compared with the state-of-the-art methods.
Is mindfulness associated with interpersonal forgiveness?

Using a multimethod approach, the current research tested the basic prediction that mindfulness is associated with interpersonal forgiveness. Across 5 studies, we found that mindfulness meditation, trait mindfulness, and an experimental induction of mindfulness, were positively associated with indicators of both dispositional forgiving tendencies, state levels of forgiveness regarding a past offense, and levels of perceived forgiving tendencies as rated by the romantic partner. Two studies examined the roles of perspective taking and rumination as potential mechanisms; results provided most consistent support for the role of perspective taking. The findings are discussed in light of the broader theoretical questions of when and how people forgive and how mindfulness may promote interpersonal functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Prevalence of serum markers of infection and naturally acquired immunity to hepatitis B virus in transfused children treated at a children’s hospital in Salvador, Bahia: A cross-sectional study

Abstract The artificially acquired humoral immunity against hepatitis B virus (HBV) apparently may decline over the years. This study aimed to investigate the prevalence of naturally occurring serological markers of infection and active immunity to HBV in severely ill children and adolescents treated at the Martagão Gesteira Pediatric Hospital who received blood transfusions. The serum samples of 353 children who received poly-transfusions between August 2016 and March 2017 were tested for HBV surface antigen (HBsAg) markers, anti-HBc antibodies (IgG and IgM isotypes), and IgG anti-HBs. None of the children presented an outcome compatible with HBV infection. Three patients were seroreactive to markers of past infection, tested positive for anti-HBc IgG and negative for anti-HBc IgM, and were seropositive for anti-HBs, with antibody titers of >150.00 mIU/mL. Only 52.4% of the patients in the study were protected against HBV, with anti-HBs antibody titers of >10 mIU/mL. Children aged 5 years had lower titers of anti-HBs. The results indicated that the older children were more likely to be unprotected from HBV; this suggests the need to evaluate the vaccine response in children, especially those who received blood transfusions.
Predictive utility of an adapted Marshall head CT classification scheme after traumatic brain injury

ABSTRACT Objective: To study the predictive relationship among persons with traumatic brain injury (TBI) between an objective indicator of injury severity (the adapted Marshall computed tomography [CT] classification scheme) and clinical indicators of injury severity in the acute phase, functional outcomes at inpatient rehabilitation discharge, and functional and participation outcomes at 1 year after injury, including death. Participants: The sample involved 4895 individuals who received inpatient rehabilitation following acute hospitalization for TBI and were enrolled in the Traumatic Brain Injury Model Systems National Database between 1989 and 2014. Design: Head CT variables for each person were fit into adapted Marshall CT classification categories I through IV. Main Measures: Prediction models were developed to determine the amount of variability explained by the CT classification categories compared with commonly used predictors, including a clinical indicator of injury severity. Results: The adapted Marshall classification categories aided only in the prediction of craniotomy or craniectomy during acute hospitalization, otherwise making no meaningful contribution to variance in the multivariable models predicting outcomes at any time point after injury. Conclusion: Results suggest that head CT findings classified in this manner do not inform clinical discussions related to functional prognosis or rehabilitation planning after TBI.Abbreviations: CT: computed tomography; DRS: disability rating scale; EGOS: extended Glasgow outcome scale; FIM: functional independence measure; NDB: National Data Base; PTA: posttraumatic amnesia; RLOS: rehabilitation length of stay; SPOS: semipartial omega squared statistic; TBI: traumatic brain injury; TBIMS: Traumatic Brain Injury Model Systems
Ethanol Conditioned Taste Aversion in High Drinking in the Dark Mice

Two independent lines of High Drinking in the Dark (HDID-1, HDID-2) mice have been bred to reach high blood alcohol levels after a short period of binge-like ethanol drinking. Male mice of both lines were shown to have reduced sensitivity to develop a taste aversion to a novel flavor conditioned by ethanol injections as compared with their unselected HS/NPT founder stock. We have subsequently developed inbred variants of each line. The current experiments established that reduced ethanol-conditioned taste aversion is also seen in the inbred variants, in both males and females. In other experiments, we asked whether HDID mice would ingest sufficient doses of ethanol to lead to a conditioned taste aversion upon retest. Different manipulations were used to elevate consumption of ethanol on initial exposure. Access to increased ethanol concentrations, to multiple tubes of ethanol, and fluid restriction to increase thirst motivation all enhanced initial drinking of ethanol. Each condition led to reduced intake the next day, consistent with a mild conditioned taste aversion. These experiments support the conclusion that one reason contributing to the willingness of HDID mice to drink to the point of intoxication is a genetic insensitivity to the aversive effects of ethanol.
Event-related potentials in the odd-ball paradigm and behavioral scales for the assessment of children and adolescents with disorders of consciousness: A proof of concept study

Abstract Objective: Quantification of signatures of conscious processing in children with disorders of consciousness (DoC) using odd-ball paradigms in multiple modalities. Method: We review the diagnostic approaches available in the field, from clinical scales to neuroimaging methods, and concentrate upon measures derived from electroencephalographic event related potentials. Results: Evoked potentials were recorded in five procedures, encompassing visual, auditory and tactile modalities, from ten pediatric DoC patients—six in a minimally conscious state (MCS), three in unresponsive wakefulness syndrome (UWS) and one who emerged from MCS (eMCS)—and the control group of 10 healthy children. In almost all the eMCS and MCS patients, higher amplitude of P300 was observed and the effect was statistically significant in at least one out of the five performed procedures. Additionally, signs of conscious information processing were detected in one UWS patient. Conclusion: The presented results provide a proof of concept for the possibility of applying ERP-derived electrophysiological measures as an aid in the assessment of children and adolescents in DoC.
Generation of a function affect model for residents with advanced dementia

AIMS AND OBJECTIVES This article presents the generation of a model of care encompassing "function" and "affect" based on findings from a 2011 research project aimed at improving care delivery for people with advanced dementia. Objectives were to provide comprehensive and sustainable care, honouring and respecting the person. BACKGROUND Dementia is a debilitating, progressive, and terminal disease with a trajectory ranging from approximately 3 to 16 years, yet attention to end-of-life care, promoting comfort, alleviating suffering, and maximizing quality of life is frequently overlooked for people living in the advanced stages of the disease. METHODS The research project from which the model was drawn used a three-phase mixed methods approach at three residential aged care facilities (nursing homes) providing high care in New South Wales, Australia. Thematic analysis was elicited from focus group discussions with staff, family members, and carers of residents. FINDINGS Themes describe distinct dimensions of a model of care: "function" (dedication, designation, and deliberation) and "affect" (the personal outcomes revealed in relaxation, stimulation, and transformation). CONCLUSION Reframing nursing practice from task and disease orientation to person centred and relationship focused is essential in meeting the complete needs of people with advanced dementia. This transformational model of care may be useful in adapting to other end-of-life care settings.
Magnesium controls aptamer-expression platform switching in the SAM-I riboswitch

Abstract Investigations of most riboswitches remain confined to the ligand-binding aptamer domain. However, during the riboswitch mediated transcription regulation process, the aptamer domain and the expression platform compete for a shared strand. If the expression platform dominates, an anti-terminator helix is formed, and the transcription process is active (ON state). When the aptamer dominates, transcription is terminated (OFF state). Here, we use an expression platform switching experimental assay and structure-based electrostatic simulations to investigate this ON-OFF transition of the full length SAM-I riboswitch and its magnesium concentration dependence. Interestingly, we find the ratio of the OFF population to the ON population to vary non-monotonically as magnesium concentration increases. Upon addition of magnesium, the aptamer domain pre-organizes, populating the OFF state, but only up to an intermediate magnesium concentration level. Higher magnesium concentration preferentially stabilizes the anti-terminator helix, populating the ON state, relatively destabilizing the OFF state. Magnesium mediated aptamer-expression platform domain closure explains this relative destabilization of the OFF state at higher magnesium concentration. Our study reveals the functional potential of magnesium in controlling transcription of its downstream genes and underscores the importance of a narrow concentration regime near the physiological magnesium concentration ranges, striking a balance between the OFF and ON states in bacterial gene regulation.
The role of offspring’s birthweight on the association between pre-pregnancy obesity and offspring’s childhood anthropometrics: a mediation analysis

Abstract While birthweight of offspring is associated with pre-pregnancy body mass index (BMI) and later risk of obesity, its mediating effect between the association of maternal pre-pregnancy BMI and offspring’s childhood anthropometrics has rarely been investigated. This study aimed to examine whether offspring birthweight is a mediator in the association between pre-pregnancy BMI and offspring’s childhood anthropometrics. The study included 1,618 mother–child pairs from the Australian Longitudinal Study on Women’s Health and Mothers and their Children’s Health Study. Children’s anthropometrics [mean age 8.6 (s.d. =3.0) years] were calculated from the mothers’ self-reported child weight and height measures. G-computation was used to estimate the natural direct and indirect (via birthweight) effects of pre-pregnancy BMI. In the fully adjusted model for maternal sociodemographic and lifestyle factors, the natural direct effects of pre-pregnancy obesity on child BMI-for-age, height-for-age, weight-for-age and weight-for-height outcomes were, β (95% confidence interval, CI), 0.75 (0.55, 0.95), 0.13 (−0.07, 0.32), 0.62 (0.44, 0.80) and 0.57 (0.24, 0.90), respectively. The corresponding natural indirect effects were 0.04 (−0.04, 0.12), −0.01 (−0.09, 0.07), −0.01 (−0.08, 0.07) and 0.09 (−0.05, 0.23). Similar results were observed for pre-pregnancy overweight and pre-pregnancy BMI as a continuous scale. Most of the effect of pre-pregnancy obesity on childhood weight-related anthropometric outcomes appears to be via a direct effect, not mediated through offspring’s birthweight.
Specification and formation of the neural crest: Perspectives on lineage segregation

The neural crest is a fascinating embryonic population unique to vertebrates that is endowed with remarkable differentiation capacity. Thought to originate from ectodermal tissue, neural crest cells generate neurons and glia of the peripheral nervous system, and melanocytes throughout the body. However, the neural crest also generates many ectomesenchymal derivatives in the cranial region, including cell types considered to be of mesodermal origin such as cartilage, bone, and adipose tissue. These ectomesenchymal derivatives play a critical role in the formation of the vertebrate head, and are thought to be a key attribute at the center of vertebrate evolution and diversity. Further, aberrant neural crest cell development and differentiation is the root cause of many human pathologies, including cancers, rare syndromes, and birth malformations. In this review, we discuss the current findings of neural crest cell ontogeny, and consider tissue, cell, and molecular contributions toward neural crest formation. We further provide current perspectives into the molecular network involved during the segregation of the neural crest lineage.
Relation between Chlamydia trachomatis infection and pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility in a Dutch cohort of women previously tested for chlamydia in a chlamydia screening trial

Objectives A better understanding of Chlamydia trachomatis infection (chlamydia)–related sequelae can provide a framework for effective chlamydia control strategies. The objective of this study was to estimate risks and risk factors of pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility (TFI) with a follow-up time of up until 8 years in women previously tested for chlamydia in the Chlamydia Screening Implementation study (CSI) and participating in the Netherlands Chlamydia Cohort Study (NECCST). Methods Women who participated in the CSI 2008–2011 (n=13 498) were invited in 2015–2016 for NECCST. Chlamydia positive was defined as a positive CSI-PCR test, positive chlamydia serology and/or self-reported infection (time dependent). Data on PID, ectopic pregnancy and TFI were collected by self-completed questionnaires. Incidence rates and HRs were compared between chlamydia-positive and chlamydia-negative women corrected for confounders. Results Of 5704 women included, 29.5% (95% CI 28.3 to 30.7) were chlamydia positive. The incidence rate of PID was 1.8 per 1000 person-years (py) (1.6 to 2.2) overall, 4.4 per 1000 py (3.3 to 5.7) among chlamydia positives compared with 1.4 per 1000 py (1.1 to 1.7) for chlamydia negatives. For TFI, this was 0.4 per 1000 py (0.3 to 0.5) overall, 1.3 per 1000 py (0.8 to 2.1) and 0.2 per 1000 py (0.1 to 0.4) among chlamydia positives and negatives, respectively. And for ectopic pregnancy, this was 0.6 per 1000 py (0.5 to 0.8) overall, 0.8 per 1000 py (0.4 to 1.5) and 0.6 per 1000 py (0.4 to 0.8) for chlamydia negatives. Among chlamydia-positive women, the strongest risk factor for PID was symptomatic versus asymptomatic infection (adjusted HR 2.88, 1.4 to 4.5) and for TFI age <20 versus >24 years at first infection (HR 4.35, 1.1 to 16.8). Conclusion We found a considerably higher risk for PID and TFI in chlamydia-positive women, but the incidence for ectopic pregnancy was comparable between chlamydia-positive and chlamydia-negative women. Overall, the incidence rates of sequelae remained low. Trial registration NTR-5597.
On-chip adaptive components for balanced computing

The demand for more on-chip computing resources to effectively execute compute-intensive functions is ever increasing. On the other hand, design of an effective register file architecture is becoming a bottleneck for meeting the memory-bandwidth demand of modern wide-issue superscalar processors. A need for a balance in the memory-bandwidth and the computing rate is significant to achieve a higher processor throughput. Further, at the advent of mobile and ad-hoc computing, processors are being expected to consume lesser amounts of energy even while delivering higher performance. This dissertation aims to address the above issues in the context of reconfigurable architectures, by exploiting the possibility of using on-chip memory elements as computing units. This enables an efficient utilization of silicon real-estate on the chip. First, this dissertation proposes TriBank Register file architecture, a novel register file organization for wide-issue superscalar processors. The organization exploits long latencies in the lifetime of a register to meet the two requirements of a small register access time and a large memory bandwidth. Next, the dissertation proposes Adaptive Register File Computing (ARC) unit, a novel on-chip processing element that leverages application-specific processing capabilities. The ARC unit supplements a conventional register file to provide large memory bandwidth, or acts as a configurable computing unit to provide higher on-chip computing capacity; depending on the requirement of a specific application. The dissertation also explores the ability of the reconfigurable computing models in delivering high performance while providing with significant savings in the energy dissipation in the various on-chip components of the processor. For the Reconfigurable Computing Cache (RFC) based processor, developed earlier to utilize a module of an L1 data cache is used as a coprocessor to process compute intensive multimedia applications, the impact of RFC on cache access time and energy dissipation has been explored. It also gives a detailed analysis on the performance of the RFC based processor in terms of the execution time of application for various configuration schemes, including the study of the effect of the percentage of the core function in an entire application over the management of RFC modules.
Ataluren Pharmacokinetics in Healthy Japanese and Caucasian Subjects

To evaluate the potential for ethnicity‐related differences in ataluren pharmacokinetics (PK) and safety, a phase 1 single‐dose study was conducted in 48 healthy (24 Japanese and 24 Caucasian subjects), nonsmoking male volunteers who were equally divided into 3 cohorts of oral doses at 5, 10, and 20 mg/kg. Blood samples were collected until 48 hours postdose. PK results demonstrated rapid absorption of ataluren, with peak plasma levels (Cmax) being attained between 0.875 and 2.5 hours after dosing. The mean Cmax and area under the concentration‐time curve (AUC(0‐last)) increased with each increasing dose level in both Japanese and Caucasian subjects. Although the Cmax was similar across all subjects at each dose regardless of ethnicity, Japanese subjects had a mean AUC(0‐last) approximately 14% to 34% lower than that of Caucasian subjects across the 3 dose levels. This difference was likely due to the higher variability of AUC values in Caucasian subjects and the relatively small study population. In conclusion, similar ataluren PK profiles were observed in healthy Japanese and Caucasian subjects following single oral administration of ataluren at all dose levels.