Miracle-dz/UniFAR-FTUs huggingface dataset:
Not early drinking but early drunkenness is a risk factor for problem behaviors among adolescents from 38 European and North American countries.

BACKGROUND Many studies have reported that the earlier the age at first drink (AFDrink) the higher the later drinking levels and related problems. However, unless adolescents proceed into drunkenness, it is unclear why consuming small quantities at early age should lead to later problems. This study investigates the link between AFDrink and problem behaviors (smoking, cannabis use, injuries, fights, and low academic performance) among 15-year-olds who did and did not proceed into drunkenness. Among those with drunkenness experience, we tested whether AFDrink predicted problem behaviors over and above the age at first drunkenness (AFDrunk). METHODS Multilevel structural equation models were estimated based on a sample of 44,801 alcohol-experienced 15-year-olds from 38 North American and European countries and regions who participated in the Health Behaviour in School-aged Children cross-national survey. RESULTS Overall, there was a significant association between AFDrink and all 5 problem behaviors. However, this was the case only among those with drunkenness experiences but not among those never drunk. Among the former, AFDrunk was a strong predictor for all 5 problem behaviors, but time from first drink to first drunk did not predict problem behaviors. CONCLUSIONS Not early alcohol initiation but early drunkenness was a risk factor for various adolescent problem behaviors at the age of 15, that is, there was not consistent relationship for the time before the first drunkenness (i.e., since first drinking). Besides targeting early drinking, particular efforts are needed to impede early drunkenness to prevent associated harm in adolescence and beyond.
RETRACTED ARTICLE: Lidocaine gel vs lidocaine spray in reducing pain during insertion of the intrauterine contraceptive device

Abstract We, the Editor and Publisher of European Journal of Contraception and Reproductive Health Care, have retracted the following article: Haitham Torky, Asem Moussa, El-Sayed El-Desouky, Osama Dief & Ali Ahmed (2017) Lidocaine gel vs lidocaine spray in reducing pain during insertion of the intrauterine contraceptive device, The European Journal of Contraception & Reproductive Health Care, 22:2, 159-161, DOI: 10.1080/13625187.2017. 1285881 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors fully cooperated with the investigation and provided responses to our queries. However, they did not sufficiently address the concerns raised and they were unable to provide their original data for review. As we cannot verify the validity of the article, we are therefore retracting the article. The authors do not agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
Hardware performance counters for system reliability monitoring

As technology scaling reaches nanometre scales, the error rate due to variations in temperature and voltage, single event effects and component degradation increases, making components less reliable. In order to ensure a system continues to function correctly while facing known reliability issues, it is imperative that the system should have the means to detect the occurrence of errors due to the presence of faults. A system that behaves normally (no error detected in the system) exhibits a profile, and any deviations from this profile indicate that there is an anomaly in the system. In this paper, we propose to use hardware performance counters (HPCs) to measure events that occur during the execution of the program. We explore the various counters available which could be use to identify the anomalous behaviour in the system and develop a methodology to observe the anomalies using HPCs by creating a fault-free pattern and observing any subsequent changes in that pattern. We evaluate the proposed technique using GemFI, an architectural simulator based on Gem5 with additional fault injection capabilities. We compare the results obtained at the end of the execution with data collected during a time interval. Our results show that HPCs can be used to identify anomalous behaviour in a system that would lead to failure.
Associations of Acculturation With Self-Report and Objective Physical Activity and Sedentary Behaviors Among Latinas

Background. Less than 50% of Latinas meet physical activity (PA) recommendations. Acculturation is a complex cultural phenomenon that may influence health behaviors, but associations between acculturation and Latinas’ activity and sedentary levels are unclear. Aim. To examine associations of acculturation with Latinas’ domain-specific and total PA as well as sedentary time. Method. We analyzed baseline data collected between 2011 and 2013 among 410 Latinas (18-65 years) from a PA promotion intervention in San Diego, CA (Fe en Acción/Faith in Action). Participants wore an accelerometer to assess moderate-to-vigorous PA (MVPA) and sedentary time and completed a survey assessing domain-specific PA, sociodemographics, and acculturation as measured by length of residence in the United States and the Bidimensional Acculturation Scale (BAS) for Hispanics. Higher acculturation was defined as longer residence in the United States or being either assimilated or bicultural as per scores on the Hispanic and Anglo domains of the BAS. Results. Based on weekly averages from the accelerometer, Latinas spent 103 minutes in MVPA and 76% of total activity in sedentary time. Only 32% met MVPA recommendations via self-reported leisure-time and transportation PA. Longer residence in the United States was inversely associated with reporting any transportation or occupational PA and meeting MVPA recommendations. Assimilated/bicultural Latinas had significantly less accelerometer-based total MVPA and higher sedentary time than their lower acculturated counterparts. Conclusions. Overall, higher acculturation, based on either measure, was related to less activity. Our findings suggest interventions tailored to the acculturation levels of Latinas are needed to help reduce disparities in Latinas’ PA and sedentary behaviors.
Synapses between corticotropin‐releasing factor‐containing axon terminals and dopaminergic neurons in the ventral tegmental area are predominantly glutamatergic

Interactions between stress and the mesocorticolimbic dopamine (DA) system have been suggested from behavioral and electrophysiological studies. Because corticotropin‐releasing factor (CRF) plays a role in stress responses, we investigated possible interactions between neurons containing CRF and those producing DA in the ventral tegmental area (VTA). We first investigated the cellular distribution of CRF in the VTA by immunolabeling VTA sections with anti‐CRF antibodies and analyzing these sections by electron microscopy. We found CRF immunoreactivity present mostly in axon terminals establishing either symmetric or asymmetric synapses with VTA dendrites. We established that nearly all CRF asymmetric synapses are glutamatergic, insofar as the CRF‐immunolabeled axon terminals in these synapses coexpressed the vesicular glutamate transporter 2, and that the majority of CRF symmetric synapses are GABAergic, insofar as the CRF‐immunolabeled axon terminals in these synapses coexpressed glutamic acid decarboxylase, findings that are of functional importance. We then looked for synaptic interactions between CRF‐ and DA‐containing neurons, by using antibodies against CRF and tyrosine hydroxylase (TH; a marker for DA neurons). We found that most synapses between CRF‐immunoreactive axon terminals and TH neurons are asymmetric (in the majority likely to be glutamatergic) and suggest that glutamatergic neurons containing CRF may be part of the neuronal circuitry that mediates stress responses involving the mesocorticolimbic DA system. The presence of CRF synapses in the VTA offers a mechanism for interactions between the stress‐associated neuropeptide CRF and the mesocorticolimbic DA system. J. Comp. Neurol. 506:616–626, 2008. Published 2007 Wiley‐Liss, Inc.
American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.
Using the RxNorm Web Services API for Quality Assurance Purposes

Auditing large, rapidly evolving terminological systems is still a challenge. In the case of RxNorm, a standardized nomenclature for clinical drugs, we argue that quality assurance processes can benefit from the recently released application programming interface (API) provided by RxNav. We demonstrate the usefulness of the API by performing a systematic comparison of alternative paths in the RxNorm graph, over several thousands of drug entities. This study revealed potential errors in RxNorm, currently under review. The results also prompted us to modify the implementation of RxNav to navigate the RxNorm graph more accurately. The RxNav web services API used in this experiment is robust and fast.
Exclusion of West Nile Virus Superinfection through RNA Replication

ABSTRACT Superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. Using West Nile virus (WNV) as a model, we show that replicating replicons in BHK-21 cells suppress subsequent WNV infection. The WNV replicon also suppresses superinfections of other flaviviruses but not nonflaviviruses. Mode-of-action analysis indicates that the exclusion of WNV superinfection occurs at the step of RNA synthesis. The continuous culturing of WNV in the replicon-containing cells generated variants that could overcome the superinfection exclusion. The sequencing of the selected viruses revealed mutations in structural (prM S90R or envelope E138K) and nonstructural genes (NS4a K124R and peptide 2K V9M). Mutagenesis analysis showed that the mutations in structural genes nonselectively enhance viral infection in both naïve and replicon-containing BHK-21 cells; in contrast, the mutations in nonstructural genes more selectively enhance viral replication in the replicon-containing cells than in the naïve cells. Mechanistic analysis showed that the envelope mutation functions through the enhancement of virion attachment to BHK-21 cells, whereas the 2K mutation (and, to a lesser extent, the NS4a mutation) functions through the enhancement of viral RNA synthesis. Furthermore, we show that WNV superinfection exclusion is reversible by the treatment of the replicon cells with a flavivirus inhibitor. The preestablished replication of the replicon could be suppressed by infecting the cells with the 2K mutant WNV but not with the wild-type virus. These results suggest that WNV superinfection exclusion is a result of competition for intracellular host factors that are required for viral RNA synthesis.
Response inhibition in motor conversion disorder

Conversion disorders (CDs) are unexplained neurological symptoms presumed to be related to a psychological issue. Studies focusing on conversion paralysis have suggested potential impairments in motor initiation or execution. Here we studied CD patients with aberrant or excessive motor movements and focused on motor response inhibition. We also assessed cognitive measures in multiple domains. We compared 30 CD patients and 30 age‐, sex‐, and education‐matched healthy volunteers on a motor response inhibition task (go/no go), along with verbal motor response inhibition (color‐word interference) and measures of attention, sustained attention, processing speed, language, memory, visuospatial processing, and executive function including planning and verbal fluency. CD patients had greater impairments in commission errors on the go/no go task (P < .001) compared with healthy volunteers, which remained significant after Bonferroni correction for multiple comparisons and after controlling for attention, sustained attention, depression, and anxiety. There were no significant differences in other cognitive measures. We highlight a specific deficit in motor response inhibition that may play a role in impaired inhibition of unwanted movement such as the excessive and aberrant movements seen in motor conversion. Patients with nonepileptic seizures, a different form of conversion disorder, are commonly reported to have lower IQ and multiple cognitive deficits. Our results point toward potential differences between conversion disorder subgroups. © 2013 Movement Disorder Society
Genetic Simulation Tools for Post‐Genome Wide Association Studies of Complex Diseases

Genetic simulation programs are used to model data under specified assumptions to facilitate the understanding and study of complex genetic systems. Standardized data sets generated using genetic simulation are essential for the development and application of novel analytical tools in genetic epidemiology studies. With continuing advances in high‐throughput genomic technologies and generation and analysis of larger, more complex data sets, there is a need for updating current approaches in genetic simulation modeling. To provide a forum to address current and emerging challenges in this area, the National Cancer Institute (NCI) sponsored a workshop, entitled “Genetic Simulation Tools for Post‐Genome Wide Association Studies of Complex Diseases” at the National Institutes of Health (NIH) in Bethesda, Maryland on March 11–12, 2014. The goals of the workshop were to (1) identify opportunities, challenges, and resource needs for the development and application of genetic simulation models; (2) improve the integration of tools for modeling and analysis of simulated data; and (3) foster collaborations to facilitate development and applications of genetic simulation. During the course of the meeting, the group identified challenges and opportunities for the science of simulation, software and methods development, and collaboration. This paper summarizes key discussions at the meeting, and highlights important challenges and opportunities to advance the field of genetic simulation.
Heterotopic Ossification in Orthopaedic Trauma

Summary: Heterotopic ossification (HO) can be defined as the pathologic formation of bone in extraskeletal tissues. There has been a substantial amount of recent research on the pathophysiology, prophylaxis, and treatment of HO and traumatic conditions associated with the development of HO. This research has advanced our understanding of this disease and helped to clarify evidence-based approaches to both the prophylaxis and treatment of HO. This article reviews the literature on these topics with a focus on their application in orthopaedic trauma.
Evaluation of a multiplex panel of immune‐related markers in cervical secretions: A methodologic study

Although persistent carcinogenic human papillomavirus (HPV) infection is necessary for cervical carcinogenesis, the cofactors involved in HPV persistence and disease progression are poorly understood. Chronic cervical inflammation may increase risk, but few studies have measured immune markers (cytokines, chemokines and soluble receptors) in cervical secretions. We evaluated the performance of 74 multiplexed, bead‐based immune markers in cervical secretions from three groups of women with biopsy evaluation of cervical intraepithelial neoplasia (CIN), (i) 25% detectability and >80% interclass correlation coefficients (ICCs) acceptable for epidemiologic studies. Within‐batch coefficients of variation (CVs) of ≥25% indicated room for assay improvement. Secondarily, we explored associations between marker levels and CIN/HPV status adjusted for matching variables, assay batch, age and number of sexual partners. Sixty‐two markers (84%) had >25% detectability and ICCs > 80%. Of those, 53 (85%) had CVs < 25%. Using these preliminary data, we found that HPV positivity was associated with increased eotaxin‐1 [odds ratio (OR): 15.63, 95% confidence interval (CI): 1.26–200.00] and G‐CSF (OR: 12.99, 95% CI: 1.10–142.86) among CIN‐negative women. There was suggestive evidence that higher chemoattractant marker levels were associated with CIN2/3 (e.g., MIP‐1delta, OR: 4.48, 95% CI: 0.87–23.04 versus
Functional Replacement of a Retroviral Late Domain by Ubiquitin Fusion

Retroviral Gag polyprotein precursors are both necessary and sufficient for the assembly and release of virus‐like particles (VLPs) from infected cells. It is well established that small Gag‐encoded motifs, known as late domains, promote particle release by interacting with components of the cellular endosomal sorting and ubiquitination machinery. The Gag proteins of a number of different retroviruses are ubiquitinated; however, the role of Gag ubiquitination in particle egress remains undefined. In this study, we investigated this question by using a panel of equine infectious anemia virus (EIAV) Gag derivatives bearing the wild‐type EIAV late domain, heterologous retroviral late domains or no late domain. Ubiquitin was fused in cis to the C‐termini of these Gag polyproteins, and the effects on VLP budding were measured. Remarkably, fusion of ubiquitin to EIAV Gag lacking a late domain (EIAV/ΔYPDL‐Ub) largely rescued VLP release. We also determined the effects of ubiquitin fusion on the sensitivity of particle release to budding inhibitors and to depletion of key endosomal sorting factors. Ubiquitin fusion rendered EIAV/ΔYPDL‐Ub sensitive to depletion of cellular endosomal sorting factors Tsg101 and Alix and to overexpression of dominant‐negative fragments of Tsg101 and Alix. These findings demonstrate that ubiquitin can functionally compensate for the absence of a retroviral late domain and provide insights into the host‐cell machinery engaged by ubiquitin during particle egress.
Altered β-Catenin Accumulation in Hepatocellular Carcinomas of Diethylnitrosamine-Exposed Rhesus Macaques

Chemical exposures are important risks for development of hepatocellular carcinoma (HCC). One such chemical, diethylnitrosamine (DENA), is present in food products as well as in industrial and research settings. Further examination of tumors induced by DENA may yield clues to human risk. HCC from seven rhesus macaques exposed to DENA was selected from a tissue archive to examine for evidence of Wnt/β-catenin signaling events, which are frequently associated with HCC. DENA exposure durations ranged from 8 to 207 months, and total accumulated dose ranged from 0.7 to 4.08 mg. Unexposed colony breeder macaques served as controls. Previously unrecognized HCC metastases were discovered in lungs of three macaques. Overexpression of β-catenin and glutamine synthetase was detected by immunohistochemistry in six confirmed primary HCC and all metastatic HCC, which implicated Wnt/β-catenin activation. Concomitant β-catenin gene mutation was detected in one primary HCC; similar findings have been reported in human and rodent HCC. Neither β-catenin mutation nor β-catenin overexpression appeared to influence metastatic potential. Accumulation of intracellular proteins involved in Wnt/β-catenin signaling during HCC oncogenesis in rhesus macaques exposed to DENA appears to include other mechanisms, in addition to mutation of β-catenin gene.
TLR3 and Rig-Like Receptor on Myeloid Dendritic Cells and Rig-Like Receptor on Human NK Cells Are Both Mandatory for Production of IFN-γ in Response to Double-Stranded RNA

Cross-talk between NK cells and dendritic cells (DCs) is critical for the potent therapeutic response to dsRNA, but the receptors involved remained controversial. We show in this paper that two dsRNAs, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acid [poly(I:C)], similarly engaged human TLR3, whereas only poly(I:C) triggered human RIG-I and MDA5. Both dsRNA enhanced NK cell activation within PBMCs but only poly(I:C) induced IFN-γ. Although myeloid DCs (mDCs) were required for NK cell activation, induction of cytolytic potential and IFN-γ production did not require contact with mDCs but was dependent on type I IFN and IL-12, respectively. Poly(I:C) but not polyadenylic-polyuridylic acid synergized with mDC-derived IL-12 for IFN-γ production by acting directly on NK cells. Finally, the requirement of both TLR3 and Rig-like receptor (RLR) on mDCs and RLRs but not TLR3 on NK cells for IFN-γ production was demonstrated using TLR3- and Cardif-deficient mice and human RIG-I–specific activator. Thus, we report the requirement of cotriggering TLR3 and RLR on mDCs and RLRs on NK cells for a pathogen product to induce potent innate cell activation.
Acupuncture treatment for persistent hiccups in patients with cancer.

OBJECTIVE The objective of this study was to investigate the effects of acupuncture treatment for persistent hiccups in cancer patients. DESIGN The study design was a retrospective case series. SETTINGS/LOCATION The study setting was the Clinical Research Center of the National Institutes of Health. SUBJECTS The subjects were 16 adult male patients ages 27-71 with cancer, with persistent hiccups. INTERVENTIONS There were one to three acupuncture sessions over a 1-7-day period. OUTCOME MEASURES Treatment efficacy was measured using a hiccup assessment instrument pre- and post-treatment. The effects of acupuncture on common symptoms reported by all patients were also evaluated. RESULTS Thirteen (13) patients experienced complete remission of persistent hiccups (p < 0.0001); 3 patients experienced decreased hiccups severity. Significant improvement was observed in discomfort (p < 0.0001), distress (p < 0.0001), and fatigue (p = 0.0078). CONCLUSIONS This case series demonstrates that acupuncture may be a clinically useful, safe, and low-cost therapy for persistent hiccups in patients with cancer.