The TALP-UPC System for the WMT Similar Language Task: Statistical vs Neural Machine Translation

Although the problem of similar language translation has been an area of research interest for many years, yet it is still far from being solved. In this paper, we study the performance of two popular approaches: statistical and neural. We conclude that both methods yield similar results; however, the performance varies depending on the language pair. While the statistical approach outperforms the neural one by a difference of 6 BLEU points for the Spanish-Portuguese language pair, the proposed neural model surpasses the statistical one by a difference of 2 BLEU points for Czech-Polish. In the former case, the language similarity (based on perplexity) is much higher than in the latter case. Additionally, we report negative results for the system combination with back-translation. Our TALP-UPC system submission won 1st place for Czech-to-Polish and 2nd place for Spanish-to-Portuguese in the official evaluation of the 1st WMT Similar Language Translation task.Comment: WMT 2019 Shared Task pape

A Slc38a8 Mouse Model of FHONDA Syndrome Faithfully Recapitulates the Visual Deficits of Albinism Without Pigmentation Defects

Purpose: We aimed to generate and phenotype a mouse model of foveal hypoplasia, optic nerve decussation defects, and anterior segment dysgenesis (FHONDA), a rare disease associated with mutations in Slc38a8 that causes severe visual alterations similar to albinism without affecting pigmentation. Methods: The FHONDA mouse model was generated with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology using an RNA guide targeting the Scl38a8 murine locus. The resulting mice were backcrossed to C57BL/6J. Melanin content was measured using spectrophotometry. Retinal cell architecture was analyzed through light and electron microscopy. Retinal projections to the brain were evaluated with anterograde labelling in embryos and adults. Visual function was assessed by electroretinography (ERG) and the optomotor test (OT). Results: From numerous Slc38a8 mouse mutant alleles generated, we selected one that encodes a truncated protein (p.196Pro*, equivalent to p.199Pro* in the human protein) closely resembling a mutant allele described in patients (p.200Gln*). Slc38a8 mutant mice exhibit wild-type eye and coat pigmentation with comparable melanin content. Subcellular abnormalities were observed in retinal pigment epithelium cells of Slc38a8 mutant mice. Anterograde labeling experiments of retinal projections in embryos and adults showed a reduction of ipsilateral fibers. Functional visual analyses revealed a decreased ERG response in scotopic conditions and a reduction of visual acuity in mutant mice measured by OT. Conclusions: Slc38a8 mutant mice recapitulate the phenotype of patients with FHONDA concerning their normal pigmentation and their abnormal visual system, in the latter being a hallmark of all types of albinism. These mice will be helpful in better understanding the pathophysiology of this genetic condition.Funded by the Spanish Ministry of Economy and Competitiveness under BIO2015-70978-R, the Spanish Ministry of Science and Innovation under RTI2018-101223-B-I00, CIBERER and Fundación Ramón Areces to L.M. Additionally, Spanish Ministry of Science and Innovation (FEDER-PID2019-106230RB-I00, 2019) and Generalitat Valenciana IDIFEDER/2017/064, 2017, PROMETEO/2021/024, 2021 supported the work of N.C. Funds from INSERM, Sorbonne Université, Retina France and Genespoir supported the work of A.R., as well as LabEx LIFESENSES (ANR-10-LABX-65) and IHU FOReSIGHT (ANR-18-IAHU-01) for the Institut de la Vision, a doctoral fellowship from the French Ministry of Education and Research to V.C

High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods

HepatitisCvirus(HCV)is classified into seven major genotypesand67 subtypes. Recent studies haveshownthat inHCVgenotype 1-infected patients, response rates to regimens containingdirect-acting antivirals(DAAs)are subtype dependent. Currently available genotypingmethods have limited subtyping accuracy.Wehave evaluated theperformanceof adeep-sequencing-basedHCVsubtyping assay, developed for the 454/GS-Junior platform, in comparisonwith thoseof two commercial assays (VersantHCVgenotype 2.0andAbbott Real-timeHCVGenotype II)andusingdirectNS5Bsequencing as a gold standard (direct sequencing), in 114 clinical specimenspreviously tested by first-generation hybridization assay (82 genotype 1and32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 callingbypopulation Sanger sequencing(69%1b,31%1a) in 81 specimensandidentified amixed-subtype infection (1b/3a/1a) in one sample. Similarly,amongthe 32previously indeterminate specimens, identical genotypeandsubtype results were obtained by directanddeep sequencing in all but four samples with dual infection. In contrast, both VersantHCVGenotype 2.0andAbbott Real-timeHCVGenotype II failed subtype 1 calling in 13 (16%) samples eachandwere unable to identify theHCVgenotype and/or subtype inmore than half of the nongenotype 1 samples.Weconcluded that deep sequencing ismore efficient forHCVsubtyping than currently available methodsandallows qualitative identificationofmixed infectionsandmay bemorehelpfulwith respect to informing treatment strategies withnewDAA-containing regimens across allHCVsubtypesThis study has been supported by CDTI (Centro para el Desarrollo Tecnológico Industrial), Spanish Ministry of Economics and Competitiveness (MINECO), IDI-20110115; MINECO projects SAF 2009-10403; and also by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS) projects PI10/01505, PI12/01893, and PI13/00456. CIBERehd is funded by the Instituto de Salud Carlos III, Madrid, Spain. Work at CBMSO was supported by grant MINECO-BFU2011-23604, FIPSE, and Fundación Ramón Areces. X. Forns received unrestricted grant support from Roche and has acted as advisor for MSD, Gilead, and Abbvie. M. Alvarez-Tejado, J. Gregori, and J. M. Muñoz work in Roche Diagnostic

Bispectral index in hypercapnic encephalopathy associated with COPD exacerbation : a pilot study

Altres ajuts: We are thankful to Jonathan McFarland for his editing aid and to Mireia Admetllo and Camino Fernández for their help in collecting clinical data. This project was funded in part by SAF, CIBERES, BRN-Pla Armengol 2014, SEPAR 2015, and SEPAR Becario 2015.Hypercapnic encephalopathy is relatively frequent in severe exacerbations of COPD (ECOPDs), with its intensity usually being evaluated through clinical scales. Bispectral index (BIS) is a relatively new technique, based on the analysis of the electroencephalographic signal, which provides a good approximation to the level of consciousness, having already been validated in anesthesia. The objective of the study was to evaluate the utility of BIS in the assessment of the intensity of hypercapnic encephalopathy in ECOPD patients. A total of ten ECOPD patients were included, and the level of brain activity was assessed using BIS and different scales: Glasgow Coma Scale, Ramsay Sedation Scale (RSS), and Richmond Agitation-Sedation Scale. The evaluation was performed both in the acute phase and 3 months after discharge. BIS was recorded for a total of about 600 minutes. During ECOPD, BIS values ranged from 58.8 (95% CI: 48.6-69) for RSS score of 4 to 92.2 (95% CI: 90.1-94.3) for RSS score of 2. A significant correlation was observed between values obtained with BIS and those from the three scales, although the best fit was for RSS, followed by Glasgow and Richmond (r =−0.757, r =0.701, and r =0.615, respectively; P <0.001 for all). In the stable phase after discharge, BIS showed values considered as normal for a wake state (94.6; 95% CI: 91.7-97.9). BIS may be useful for the objective early detection and automatic monitoring of the intensity of hypercapnic encephalopathy in ECOPD, facilitating the early detection and follow-up of this condition, which may avoid management problems in these patients

Outcome of early vs. deferred antiviral treatment for recurrent hepatitis C in liver transplant recipients

The optimal timing to treat recurrent hepatitis-C virus (HCV) after liver transplantation (LT) remains uncertain. We compared the outcome of early (acute phase) and deferred (chronic phase) antiviral treatment for recurrent HCV infection in this population. Consecutive HCV genotype-1 infected LT patients receiving antiviral therapy between 2001-2010 were retrospectively classified according to histology at treatment start into the early or deferred treatment group. Measured endpoints included sustained virological response (SVR) rates and long-term survival. The study cohort comprised 105 patients: 60 (57%) received early treatment (ET) and 45 (43%) deferred treatment (DT). The median interval from LT to antiviral start was 3 (1-9) and 18 months (11-74) in ET and DT respectively. The SVR rate was similar in both treatment groups (23% ET and 36% DT; p = 0.27). After a median follow-up of 5.8 years, all-cause and liver-related mortality were similar in both groups. Variables independently associated with mortality included pre-treatment bilirubin > 2 mg/dL (HR 6.1, 95%CI: 2.8-13.7; p 60 (HR 3.1, 95%CI: 1.4-6.7; p = 0.01), and failure to achieve SVR (HR 10.3, 95%CI: 1.3-18.3; p = 0.03). In conclusion, early treatment of recurrent HCV is safe, but does not lead to higher SVR rates. In HCV-infected LT recipients, elevated bilirubin, older donor age, and failure to achieve SVR are independently associated with increased mortality

Sulfate-Decorated Amorphous-Crystalline Cobalt-Iron Oxide Nanosheets to Enhance O-O Coupling in the Oxygen Evolution Reaction

The electrochemical oxygen evolution reaction (OER) plays a fundamental role in several energy technologies, which performance and cost-effectiveness are in large part related to the used OER electrocatalyst. Herein, we detail the synthesis of cobalt-iron oxide nanosheets containing controlled amounts of well-anchored SO42- anionic groups (CoFexOy-SO4). We use a cobalt-based zeolitic imidazolate framework (ZIF-67) as the structural template and a cobalt source and Mohr's salt ((NH4)2Fe(SO4)2·6H2O) as the source of iron and sulfate. When combining the ZIF-67 with ammonium iron sulfate, the protons produced by the ammonium ion hydrolysis (NH4+ + H2O = NH3·H2O + H+) etch the ZIF-67, dissociating its polyhedron structure, and form porous assemblies of two-dimensional nanostructures through a diffusion-controlled process. At the same time, iron ions partially replace cobalt within the structure, and SO42- ions are anchored on the material surface by exchange with organic ligands. As a result, ultrathin CoFexOy-SO4 nanosheets are obtained. The proposed synthetic procedure enables controlling the amount of Fe and SO4 ions and analyzing the effect of each element on the electrocatalytic activity. The optimized CoFexOy-SO4 material displays outstanding OER activity with a 10 mA cm-2 overpotential of 268 mV, a Tafel slope of 46.5 mV dec-1, and excellent stability during 62 h. This excellent performance is correlated to the material's structural and chemical parameters. The assembled nanosheet structure is characterized by a large electrochemically active surface area, a high density of reaction sites, and fast electron transportation. Meanwhile, the introduction of iron increases the electrical conductivity of the catalysts and provides fast reaction sites with optimum bond energy and spin state for the adsorption of OER intermediates. The presence of sulfate ions at the catalyst surface modifies the electronic energy level of active sites, regulates the adsorption of intermediates to reduce the OER overpotential, and promotes the surface charge transfer, which accelerates the formation of oxygenated intermediates. Overall, the present work details the synthesis of a high-efficiency OER electrocatalyst and demonstrates the introduction of nonmetallic anionic groups as an excellent strategy to promote electrocatalytic activity in energy conversion technologies.The authors thank the support from the projects Combenergy (PID2019-105490RB-C32) from the Spanish Ministerio de Ciencia e Innovación, ENE2016-77798-C4-3-R and NANOGEN (PID2020-116093RB-C43), funded by MCIN/AEI/10.13039/501100011033/ and by “ERDF A way of making Europe”, by the “European Union”. The authors also thank the Spanish Ministry of Science and Innovation through the Severo Ochoa (CEX2019-000917-S) and OXISOT (PID2021- 128410OB-I00) projects. X.W., X.H., C.X., and R.D. thank the China Scholarship Council (CSC) for the scholarship support. The authors acknowledge funding from Generalitat de Catalunya 2017 SGR 327 and 2017 SGR 1246. ICN2 is supported by the Severo Ochoa program from Spanish MCIN / AEI (Grant No.: CEX2021-001214-S). IREC and ICN2 are funded by the CERCA Programme/Generalitat de Catalunya. Z.L. acknowledges funding from MINECO SO-FPT Ph.D. grant (SEV-2013-0295-17-1). J.L. is a Serra Húnter Fellow and is grateful to MICINN/FEDER PID2021-124572OB-C31, GC 2017 SGR 128 and ICREA Academia program. Part of the present work has been performed in the frameworks of Universitat de Barcelona Nanoscience Ph.D. program and Universitat Autònoma de Barcelona Materials Science Ph.D. program.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

A Focused Screen Identifies Antifolates with Activity on Mycobacterium tuberculosis

Antifolates are widely used to treat several diseases but are not currently used in the first-line treatment of tuberculosis, despite evidence that some of these molecules can target Mycobacterium tuberculosis (Mtb) bacilli in vitro. To identify new antifolate candidates for animal-model efficacy studies of tuberculosis, we paired knowledge and tools developed in academia with the infrastructure and chemistry resources of a large pharmaceutical company. Together we curated a focused library of 2508 potential antifolates, which were then tested for activity against live Mtb. We identified 210 primary hits, confirmed the on-target activity of potent compounds, and now report the identification and characterization of 5 hit compounds, representative of 5 different chemical scaffolds. These antifolates have potent activity against Mtb and represent good starting points for improvement that could lead to in vivo efficacy studies