Miracle-dz/UniFAR-FTUs huggingface dataset:
Findings of the 2018 Conference on Machine Translation (WMT18)

This paper presents the results of the premier shared task organized alongside the Conference on Machine Translation (WMT) 2018. Participants were asked to build machine translation systems for any of 7 language pairs in both directions, to be evaluated on a test set of news stories. The main metric for this task is human judgment of translation quality. This year, we also opened up the task to additional test sets to probe specific aspects of translation.
Projection of Future Extreme Precipitation and Flood Changes of the Jinsha River Basin in China Based on CMIP5 Climate Models

Projecting future changes in extreme flood is critical for risk management. This paper presented an analysis of the implications of the Fifth Coupled Model Intercomparison Project Phase (CMIP5) climate models on the future flood in the Jinsha River Basin (JRB) in Southwest China, using the Xinanjiang (XAJ) hydrologic model. The bias-corrected and resampled results of the multimodel dataset came from the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP). Relatively optimal general circulation models (GCMs) were selected with probability density functions (PDFs)-based assessment. These GCMs were coupled with the XAJ model to evaluate the impact of climate change on future extreme flood changes in the JRB. Two scenarios were chosen, namely: a midrange mitigation scenario (Representative Concentration Pathway 4.5, RCP4.5) and a high scenario (RCP8.5). Results show that: (1) The XAJ model performed well in simulating daily discharge and was suitable for the study area, with ENS and R2 higher than 0.8; (2) IPSL-CM5A-LR and MIROC-ESM-CHEM showed considerable skill in representing the observed PDFs of extreme precipitation. The average skill scores across the total area of the JRB were 0.41 to 0.66 and 0.53 to 0.67, respectively. Therefore, these two GCMs can be chosen to analyze the changes in extreme precipitation and flood in the future; (3) The average extreme precipitation under 20- and 50-year return period across the JRB were projected to increase by 1.0–33.7% under RCP4.5 and RCP8.5 during 2020 to 2050. The Upper basin is projected to experience the largest increase in extreme precipitation indices, possibly caused by a warmer climate. The extreme flood under 20- and 50-year return period will change by 0.8 to 23.8% and −6.2 to 28.2%, respectively, over this same future period. Most of scenarios projected an increase during the near future periods, implying the JRB would be likely to undergo more flooding in the future.
A Systematic Review and Meta-Analysis on the Prevalence of Dementia in Europe: Estimates from the Highest-Quality Studies Adopting the DSM IV Diagnostic Criteria

Background: Dementia, including Alzheimer’s disease (AD), is one of the most burdensome medical conditions. Usually, the reviews that aim at calculating the prevalence of dementia include estimates from studies without assessing their methodological quality. Alzheimer’s Disease International (ADI) proposed a score to assess the methodological quality of population-based studies aimed at estimating the prevalence of dementia. During the last three years, the European Commission has funded three projects (Eurodem, EuroCoDe, and ALCOVE) in order to estimate the prevalence of dementia in Europe. Objective: The aim of this study was to perform a systematic review and meta-analysis of data on the prevalence of dementia in Europe derived from studies that included only subjects with a diagnosis of dementia according to the DSM IV criteria, and that had a high quality score according to ADI criteria. Methods: We considered the studies selected by the two projects EuroCoDe (1993–2007) and Alcove (2008–2011), and we performed a new bibliographic search. For the systematic review, we only selected the subset of articles that included subjects with a diagnosis of dementia according to the DSM IV criteria. The studies were qualitatively assessed using the ADI tool. Results: The meta-analysis considered 9 studies that were carried out in Europe between 1993 and 2018 including a total of 18,263 participants, of which 2,137 were diagnosed with dementia. The prevalence rate standardized for age and sex resulted 7.1%. Discussion: This is the first systematic review on the prevalence of dementia in Europe considering only high-quality studies adopting the same diagnostic criteria (i.e., DSM IV).
The effect of media exposure on body satisfaction and drive for muscularity in women

The purpose of this study was to determine if exposure to media’s “ideal body types” influences women’s eating patterns, body satisfaction and drive for muscularity. A primary objective of this study was to examine the difference in drive for muscularity and the risk for the development of muscle dysmorphia (MD) between female athletes and non-athletes. A series of magazine covers were viewed, ranging from thin to muscular and toned, either before or after the Body Appreciation Scale (BAS) was administered. It was hypothesized that exposure to images of what society defines as “ideal” body types before an assessment of self-perception and body appreciation will result in a stronger level of body dissatisfaction. It was also hypothesized that a drive for muscularity would be present in female competitive athletes, more so than non-athletes. Surveys were administered to measure body satisfaction, eating patterns, drive for muscularity and susceptibility for the development of MD. These surveys included the Intuitive Eating Scale (IES), Drive for Muscularity Scale (DMS) and the Muscle Dysmorphia Index (MDI). The results suggest that a higher Body Mass Index (BMI) is correlated with non-athletes striving for thinness, while a lower BMI is correlated with competitive athletes developing a drive for muscularity and risking the development of MD. This research is important to determine the effects of media on female body appreciation and drive for muscularity. Furthermore, this study indicates that competitive female athletes may exhibit a higher level of drive for muscularity and thus, more characteristics of muscle dysmorphia. *Correspondence to: Karen M Skemp, Department of Health Education Health Promotion, University Wisconsin-La Crosse, 1725 State Street, La Crosse, WI 54601, USA, Tel: 608-785-8187; Fax: 608-785-6792; E-mail: kskemp@uwlax.edu
DIG-seq: a genome-wide CRISPR off-target profiling method using chromatin DNA

To investigate whether and how CRISPR-Cas9 on-target and off-target activities are affected by chromatin in eukaryotic cells, we first identified a series of identical endogenous DNA sequences present in both open and closed chromatin regions and then measured mutation frequencies at these sites in human cells using Cas9 complexed with matched or mismatched sgRNAs. Unlike matched sgRNAs, mismatched sgRNAs were highly sensitive to chromatin states, suggesting that off-target but not on-target DNA cleavage is hindered by chromatin. We next performed Digenome-seq using cell-free chromatin DNA (now termed DIG-seq) and histone-free genomic DNA in parallel and found that only a subset of sites, cleaved in histone-free DNA, were cut in chromatin DNA, suggesting that chromatin can inhibit Cas9 off-target effects in favor of its genome-wide specificity in cells.
Hypoxia Restrains Lipid Utilization via Protein Kinase A and Adipose Triglyceride Lipase Downregulation through Hypoxia-Inducible Factor

Oxygen is a key molecule for efficient energy production in living organisms. Although aerobic organisms have adaptive processes to survive in low-oxygen environments, it is poorly understood how lipolysis, the first step of energy production from stored lipid metabolites, would be modulated during hypoxia. ABSTRACT Oxygen is a key molecule for efficient energy production in living organisms. Although aerobic organisms have adaptive processes to survive in low-oxygen environments, it is poorly understood how lipolysis, the first step of energy production from stored lipid metabolites, would be modulated during hypoxia. Here, we demonstrate that fasting-induced lipolysis is downregulated by hypoxia through the hypoxia-inducible factor (HIF) signaling pathway. In Caenorhabditis elegans and mammalian adipocytes, hypoxia suppressed protein kinase A (PKA)-stimulated lipolysis, which is evolutionarily well conserved. During hypoxia, the levels of PKA activity and adipose triglyceride lipase (ATGL) protein were downregulated, resulting in attenuated fasting-induced lipolysis. In worms, HIF stabilization was sufficient to moderate the suppressive effect of hypoxia on lipolysis through ATGL and PKA inhibition. These data suggest that HIF activation under hypoxia plays key roles in the suppression of lipolysis, which might preserve energy resources in both C. elegans and mammalian adipocytes.
The influence of nuclear interactions on ionization chamber perturbation factors in proton beams: FLUKA simulations supported by a Fano test

PURPOSE In all recent protocols for the reference dosimetry of clinical proton beams, ionization chamber perturbation factors are assumed to be unity. In this work, such factors were computed using the FLUKA Monte Carlo code for three ionization chamber types, with particular attention to the influence of nuclear interactions. METHODS The accuracy of the transport algorithms implemented in FLUKA was first evaluated by performing a Fano cavity test. Ionization chamber perturbation factors were computed for the PTW-34001 Roos® and the PTW-34070 and PTW-34073 Bragg peak® chambers for proton beams of 60-250 MeV using the same transport parameters that were needed to pass the Fano test. RESULTS FLUKA was found to pass the Fano test within 0.15%. Ionization chamber simulation results show that the presence of the air cavity and the wall results in dose perturbations of the order of 0.6% and 0.8%, respectively. The perturbation factors are shown to be energy dependent and nuclear interactions must be taken into account for accurate calculation of the ionization chamber's response. CONCLUSION Ionization chamber perturbations can amount to 1% in high-energy proton beams and therefore need to be considered in dosimetry procedures.
Management of in‐transit melanoma metastases: a review

In‐transit metastases (ITM) of cutaneous melanoma are locoregional recurrences confined to the superficial lymphatics that occur in 3.4–6.2% of patients diagnosed with melanoma. ITM are a heterogeneous disease that poses a therapeutic dilemma. Patients may have a prolonged disease trajectory involving multiple or repeat treatment modalities for frequent recurrences. The management of ITM has evolved without the development of a standardized protocol. Owing to the variability of the disease course there are few dedicated clinical trials, with a number of key trials in stage III melanoma excluding ITM patients. Thus, there is a paucity of quality data on the efficacy of the treatment modalities available for ITM and even fewer studies directly comparing modalities. At present the mainstay of ITM treatment is surgical resection, with intralesional therapies, isolated limb infusion and radiotherapy utilized as second‐line measures. The developing role of targeted therapies and immunotherapy has yet to be explored completely in these patients. This review addresses the evidence base of the efficacy of the various treatment modalities available and those factors that have impacted their clinical uptake.
Towards Further Verification of Physiologically-Based Kidney Models: Predictability of the Effects of Urine-Flow and Urine-pH on Renal Clearance

In vitro-in vivo extrapolation (IVIVE) of renal excretory clearance (CLR) using the physiologically based kidney models can provide mechanistic insight into the interplay of multiple processes occurring in the renal tubule; however, the ability of these models to capture quantitatively the impact of perturbed conditions (e.g., urine flow, urine pH changes) on CLR has not been fully evaluated. In this work, we aimed to assess the predictability of the effect of urine flow and urine pH on CLR and tubular drug concentrations (selected examples). Passive diffusion clearance across the nephron tubule membrane was scaled from in vitro human epithelial cell line Caco-2 permeability data by nephron tubular surface area to predict the fraction reabsorbed and the CLR of caffeine, chloramphenicol, creatinine, dextroamphetamine, nicotine, sulfamethoxazole, and theophylline. CLR values predicted using mechanistic kidney model at a urinary pH of 6.2 and 7.4 resulted in prediction bias of 2.87- and 3.62-fold, respectively. Model simulations captured urine flow–dependent CLR, albeit with minor underprediction of the observed magnitude of change. The relationship between drug solubility, urine flow, and urine pH, illustrated in simulated intratubular concentrations of acyclovir and sulfamethoxazole, agreed with clinical data on tubular precipitation and crystal-induced acute kidney injury. This study represents the first systematic evaluation of the ability of the mechanistic kidney model to capture the impact of urine flow and urine pH on CLR and drug tubular concentrations with the aim of facilitating refinement of IVIVE-based mechanistic prediction of renal excretion.
Does early linear growth failure influence later school performance? A cohort study in Karonga district, northern Malawi

Introduction Stunting or linear growth retardation in childhood is associated with delayed cognitive development due to related causes (malnutrition, illness, poor stimulation), which leads to poor school outcomes at later ages, although evidence of the association between the timing and persistence of stunting and school outcomes within the sub-Saharan African context is limited. Methods Anthropometric data around birth (0–4 months), early (11–16 months) and late childhood (ages 4–8 years) along with school outcomes up until the age of 11 were analysed for a cohort of 1,044 respondents, born between 2002–2004 in Karonga district, northern Malawi. The schooling outcomes were age at school enrolment, grade repetition in Standard 1 and age-for-grade by age 11. Height-for-Age Z-scores (HAZ) and growth trajectories were examined as predictors, based on stunting (<-2SD HAZ) and on trajectories between early and late childhood (never stunted, improvers, decliners or persistently stunted). Multinomial and logistic regression were used to estimate the association between stunting/trajectories and schooling, adjusted for socioeconomic confounders. Results The effects of stunting on schooling were evident in early childhood but were more pronounced in late childhood. Children who were stunted in early childhood (9.3%) were less likely to be underage at enrolment, more likely to repeat Standard 1 and were 2–3 times more likely to be overage for their grade by the age of 11, compared to their non-stunted peers. Those persistently stunted between early and late childhood (7.3%) faced the worst consequences on schooling, being three times as likely to enrol late and 3–5 times more likely to be overage for their grade by the age of 11, compared to those never stunted. Compared to improvers, those persistently stunted were three times as likely to be overage by two or more years by the age of 11, with no effect on enrolment or repetition. Conclusion Our findings confirm the importance of early childhood stunting on schooling outcomes and suggest some mitigation by improvements in growth by the age of starting school. The nutritional and learning needs of those persistently stunted may need to be prioritised in future interventions.
Interaction capture and synthesis

A major challenge in motion capture research is how to modify a motion to satisfy the constraints of new animation. Motion transformation becomes difficult when contact is involved because physical interaction involves energy or power transfer between the system of interest and the environment (for example, an animated hand and a grasped object). Although contact force measurements provide a means of monitoring this transfer, motion capture as used for creating animation in movies and computer games has largely ignored contact forces. Our approach is based on the hypothesis that for many motions, human motor control is similar to impedance based control. That is, humans plan both the motion and stiffness of their joints, which allows interaction motions, such as grasping, to accommodate uncertainty in the actual position of objects or surfaces. Impedance control algorithms have previously been proposed as models for human motor control [Hogan 1984]. From synchronized capture of both force and motion we estimate the impedance, which relates the two during contact. We call this interaction capture. Using impedance estimates has real advantages over arbitrarily selected values since stiffness depends on both pose and task [Milner and Franklin 1998]. Our goal is the synthesis of new motion, which is both natural and physically valid, from captured interaction. In this sketch we describe how we achieve this using a Vicon motion capture system augmented with inexpensive force sensors, combined with a technique for retargeting interaction through simulation. Although the ideas used in our approach are general, this work focuses on hands since grasping and manipulation are arguably the most important forms of interaction.
Impact and longevity of measles-associated immune suppression: a matched cohort study using data from the THIN general practice database in the UK

Objective To test the hypothesis that measles infection increases the incidence of non-measles infectious diseases over a prolonged period of time. Design A population-based matched cohort study. Data sources This study examined children aged 1–15 years in The Health Improvement Network UK general practice medical records database. Participants included 2228 patients diagnosed with measles between 1990 and 2014, which were matched on age, sex, general practitioner practice and calendar year with 19 930 children without measles. All controls had received at least one measles vaccination. Children with a history of immune-compromising conditions or with immune-suppressive treatment were excluded. Primary outcome measures Incidence rate ratio (IRR) of infections, anti-infective prescriptions and all-cause hospitalisations following measles in predetermined periods using multivariate analysis to adjust for confounding variables. Results In children with measles, the incidence rate for non-measles infectious disease was significantly increased in each time period assessed up to 5 years postmeasles: 43% in the first month (IRR: 1.43; 95% CI 1.22 to 1.68), 22% from month one to the first year (IRR: 1.22; 95% CI 1.14 to 1.31), 10% from year 1 to 2.5 years (IRR: 1.10; 95% CI 1.02 to 1.19) and 15% (IRR: 1.15; 95% CI 1.06 to 1.25) in years 2.5 to 5 years of follow-up. Children with measles were more than three times as likely to receive an anti-infective prescription in the first month and 15%–24% more likely between the first month and 5 years. The rate of hospitalisation in children with measles was increased only in the month following diagnosis but not thereafter (IRR: 2.83; 95% CI 1.72 to 4.67). Conclusion Following measles, children had increased rates of diagnosed infections, requiring increased prescribing of antimicrobial therapies. This population-based matched cohort study supports the hypothesis that measles has a prolonged impact on host resistance to non-measles infectious diseases.
Histamine H1 Receptor Contributes to Vestibular Compensation

Vestibular compensation is responsible for the spontaneous recovery of postural, locomotor, and oculomotor dysfunctions in patients with peripheral vestibular lesion or posterior circulation stroke. Mechanism investigation of vestibular compensation is of great importance in both facilitating recovery of vestibular function and understanding the postlesion functional plasticity in the adult CNS. Here, we report that postsynaptic histamine H1 receptor contributes greatly to facilitating vestibular compensation. The expression of H1 receptor is restrictedly increased in the ipsilesional rather than contralesional GABAergic projection neurons in the medial vestibular nucleus (MVN), one of the most important centers for vestibular compensation, in unilateral labyrinthectomized male rats. Furthermore, H1 receptor mediates an asymmetric excitation of the commissural GABAergic but not glutamatergic neurons in the ipsilesional MVN, which may help to rebalance bilateral vestibular systems and promote vestibular compensation. Selective blockage of H1 receptor in the MVN significantly retards the recovery of both static and dynamic vestibular symptoms following unilateral labyrinthectomy, and remarkably attenuates the facilitation of betahistine, whose effect has traditionally been attributed to its antagonistic action on the presynaptic H3 receptor, on vestibular compensation. These results reveal a previously unknown role for histamine H1 receptor in vestibular compensation and amelioration of vestibular motor deficits, as well as an involvement of H1 receptor in potential therapeutic effects of betahistine. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery in the CNS, but also a novel potential therapeutic target for vestibular disorders. SIGNIFICANCE STATEMENT Vestibular disorders manifest postural imbalance, nystagmus, and vertigo. Vestibular compensation is critical for facilitating recovery from vestibular disorders, and of great importance in understanding the postlesion functional plasticity in the adult CNS. Here, we show that postsynaptic H1 receptor in the medial vestibular nucleus (MVN) contributes greatly to the recovery of both static and dynamic symptoms following unilateral vestibular lesion. H1 receptor selectively mediates the asymmetric activation of commissural inhibitory system in the ipsilesional MVN and actively promotes vestibular compensation. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery of CNS, but also a novel potential therapeutic target for promoting vestibular compensation and ameliorating vestibular disorders.
Kidney Transplantation in C3 Glomerulopathy: A Case Series.

RATIONALE & OBJECTIVE C3 glomerulopathy (C3G), a form of glomerulonephritis associated with dysregulation of the alternative complement pathway, occurs either as dense deposit disease (DDD) or C3 glomerulonephritis (C3GN). Few studies have reported outcomes of patients with C3G after transplantation since its formal classification and the advent of complement-targeting therapies such as eculizumab. STUDY DESIGN Case series of C3G. SETTING & PARTICIPANTS We reviewed laboratory testing, native and allograft biopsy reports, and clinical charts of the 19 patients (12, C3GN; and 7, DDD) from our C3G registry who underwent transplantation between 1999 and 2016. RESULTS During a median follow-up of 76 months, 16 patients had recurrent disease (10 of 12, C3GN; and 6 of 7, DDD), with median time to recurrence of 14 months in C3GN versus 15 months in DDD. Graft failure was more frequent in patients with DDD (6 of 7) than in patients with C3GN (3 of 12), occurred at a median time of 42 months posttransplantation, and was attributed to recurrent disease in half the failures. A rare genetic variant or autoantibody associated with alternative complement pathway abnormalities was detected in 9 of 10 screened patients. Treatment of 7 patients (8 allografts) with eculizumab was associated with variable clinical outcomes. LIMITATIONS Incomplete testing for complement pathway abnormalities and genetic defects, incomplete records of HLA antigen matching, lack of centralized biopsy review, and limited sample size. CONCLUSIONS In a case series of C3G transplant recipients, the proportion of disease recurrence was high in both C3GN and DDD, although graft loss appeared to occur more frequently in DDD. In a small subset of study patients, eculizumab therapy was not consistently followed by salutary outcomes.