Miracle-dz/UniFAR-FTUs huggingface dataset:
Turning Digitised Material into a Diachronic Corpus: Metadata Challenges in the Nederlab Project

In this paper, we argue that exploitation of historical corpus data requires text metadata which metadata accompanying digital objects from digital libraries, archives or other electronic text collections, do not provide. Most text collections describe in their metadata the object (book, newspaper) containing the text. To do research on the style of an author, or study the language of a certain time period, or a phenomenon through time, correct metadata is needed for each word in the text, which leads to a very intricate metadata scheme for some text collections. We focus on the Nederlab corpus. Nederlab is a research environment that gives access to a large diachronic corpus of Dutch texts from the 6th - 21st century, of more than 10 billion words. The corpus has been compiled using existing digitised text material from researchers, research organisations, archives and libraries. The aim of Nederlab is to provide tools and data to enable researchers to trace long-term changes in Dutch language, culture and society. This type of research sets high-level requirements on the metadata accompanying the texts. Since the Nederlab corpus consists of different collections, each with their own metadata, the task of adding the appropriate metadata was not straightforward, all the more so because of the difference in perspective content providers and corpus builders have. We will describe the desired metadata scheme and how we tried to realize this for a corpus of the size of Nederlab.
Enhanced Reactive Oxygen Species Levels by Active Benzothiazole Complex mediated Fenton Reaction for Highly Effective Anti-tumor Therapy.

Breaking the threshold of intracellular reactive oxygen species (ROS) levels can cause non-specific oxidative damage to proteins, and lead to the Fenton reaction-mediated exogenous ROS production to be a new promising anticancer strategy. However, the problems including the inefficient transport of metal catalysts and insufficient endogenous hydrogen peroxide (H2O2) content in cells still need to be improved. In this study, functional nanosystem encapsulated with benzothiazole complexes (FeTB2) and the photosensitizer indocyanine green (ICG) was designed for highly effective antitumor therapy. The surface of the nanocarriers was modified with dihydroartemisinin (DHA)-grafted polyglutamic acid. The induced hyperthermia enables the lipid-polymer shell to depolymerize, releasing FeTB2. The released FeTB2 could kill tumor cells in two different ways by inhibiting DNA replication and catalyzing H2O2 to produce active •OH. Moreover, the conjugated DHA could increase the amount of peroxides in tumor cells and significantly enhance ROS yield. This work has provided solid evidence that the present nanosystem enables significant effect on tumor killing through the combined inhibition of DNA replication and ROS mediated oxidative damage by regulation of tumor microenvironment, providing a ROS-mediated high efficiency antitumor strategy.
Endoscopic management of iatrogenic gastrointestinal defects with the over-the-scope clip (OTSC) system: an updated systematic review

Abstract Background Management of iatrogenic gastrointestinal (GI) defects traditionally required surgical interventions. Recently, the over-the-scope-clip system (OTSC) has been reported to be effective for GI defects. So we aimed to conduct an updated systematic review to evaluate the clinical safety and efficacy of the OTSC system for the management of iatrogenic GI defects. Material and methods Studies published in PubMed, Embase and Cochrane library from January 2006 to December 2018 were searched. The literature was selected independently by two reviewers according to inclusion and exclusion criteria. The statistical analysis was carried out using Comprehensive Meta-Analysis software version 3.0. Results A total of 12 studies including 191 patients with iatrogenic GI defects were identified. The major causes for iatrogenic GI defects were endoscopic submucosal dissection (n = 79) and endoscopic mucosal resection (n = 31). Pooled technical success was achieved in 182 patients (89.1%; 95% confidence interval (CI), 81.6%-93.8%, I2 =41.06%), and the pooled clinical success was achieved in 170 patients (85.2%; 95% CI, 71.9%–92.8%, I2=58.92%). Two patients (1%) suffered complications after OTSC system procedures. Conclusions Our study revealed that endoscopic closure of iatrogenic GI defects by the OTSC system was a safe and effective approach. Further randomized controlled trials are warranted to compare the OTSC system to other treatment modalities.
Eficacia del indacaterol como broncodilatador en un grupo de pacientes asmáticos

La busqueda de nuevas opciones terapeuticas para tratar las enfermedades obstructivas bronquiales representa un reto permanente y los broncodilatadores constituyen unos de los farmacos mas empleados para la atencion de estos pacientes. En los ultimos anos han ido ganando fuerza los broncodilatadores de accion prolongada, pero el mayor efecto alcanzado era 12 h, superado por un broncodilatador nuevo salido al mercado en el ano 2011, denominado indacaterol, del grupo de los beta agonistas, se diferencia de estos por la duracion de su efecto que llega a alcanzar 24 h. Se realizo un estudio prospectivo, a ciego, tipo ensayo clinico, aleatorizado, con 90 pacientes asmaticos, entre 18 y 59 anos de edad, que acudieron al departamento de pruebas funcionales respiratorias para estudiarles la funcion pulmonar. Todos recibieron de manera aleatoria indacaterol, salbutamol o placebo, y se les repitio la espirometria a los 15 min y a las 24 h de aplicado cada medicamento. Se evidencio que la respuesta broncodilatadora obtenida en los que usaron indacaterol, a las 24 h, fue muy superior a la respuesta de los que usaron otros farmacos. Se muestra ademas un discreto aumento de la frecuencia cardiaca y de la tension arterial en los que usaron indacaterol y salbutamol, principalmente a los 15 min de empleados dichos medicamentos, pero dentro de los limites considerados como normales. No se evidenciaron efectos adversos(AU) The search for new therapeutic options to treat bronchial obstructive diseases represents a permanent challenge and bronchodilators constitute one of the most used drugs in the treatment of these patients. In recent years, long acting bronchodilators have grown importance, but the greatest effect has been 12 h, superseded by a new bronchodilator that came on to the market in the year 2011 named Indacaterol, which belongs to the group of s2-agonists and differentiates from the rest for its effect on the duration which lasts 24 hours. A randomized, essay-type, blind, prospective study was performed in 90 asthmatic patients, ranging from 18 to 59 years of age that presented to the department of respiratory functional tests for a study of their pulmonary functions. All the patients randomly received Indacaterol, Salbutamol or Placebo and spirometry was repeated 15 minutes and 24 hours after treatment. It was evidenced that the bronchodilator response obtained at the 24 hours in those patients that used Indacaterol, was higher than the response in the patients that used other drugs. The patients that used Indacterol and Salbutamol also showed a discrete increase of the cardiac frequency and blood pressure, mainly 15 minutes after receiving such drugs, but this increase is considered within the normal limits. Adverse effects were not evidenced(AU)
Expression patterns of intermediate filament proteins desmin and lamin A in the developing conduction system of early human embryonic hearts

Since embryonic heart development is a complex process and acquisition of human embryonic specimens is challenging, the mechanism by which the embryonic conduction system develops remains unclear. Herein, we attempt to gain insights into this developmental process through immunohistochemical staining and 3D reconstructions. Expression analysis of T‐box transcription factor 3, cytoskeleton desmin, and nucleoskeleton lamin A protein in human embryos in Carnegie stages 11–20 showed that desmin is preferentially expressed in the myocardium of the central conduction system compared with the peripheral conduction system, and is co‐expressed with T‐box transcription factor 3 in the central conduction system. Further, lamin A was first expressed in the embryonic ventricular trabeculations, where the terminal ramifications of the peripheral conduction system develop, and extended progressively to all parts of the central conduction system. The uncoupled spatiotemporal distribution pattern of lamin A and desmin indicated that the association of cytoskeleton desmin and nucleoskeleton lamin A may be a late event in human embryonic heart development. Compared with model animals, our data provide a direct morphological basis for understanding the arrhythmogenesis caused by mutations in human DES and LMNA genes.
Sinonasal Papillomas and Carcinomas: A Contemporary Update With Review of an Emerging Molecular Classification.

CONTEXT. — Sinonasal papillomas and carcinomas are uncommon head and neck neoplasms that comprise a broad clinicopathologic and morphologic spectrum, and thus frequently represent a diagnostic challenge for surgical pathologists. Recent molecular interrogation of these tumors has delineated a number of recurrent alterations that correspond to distinct entities with potential diagnostic and/or therapeutic clinical utility. OBJECTIVE. — To summarize the salient clinicopathologic, morphologic, and molecular features of sinonasal papillomas and carcinomas. DATA SOURCES. — Review of pertinent literature regarding sinonasal papillomas and sinonasal carcinomas. CONCLUSIONS. — Despite their relative rarity in many surgical pathology practices, sinonasal papillomas and carcinomas frequently demonstrate characteristic morphologic features that are important for accurate diagnosis. Given our emerging understanding of the molecular basis for these tumors, judicious use of available ancillary tools-including immunohistochemistry and in situ hybridization-may be helpful in subsets of cases, whereas additional molecular testing may be useful for diagnostically challenging and/or clinically aggressive sinonasal tumors.
Efficacy and safety of neuronox® for lateral canthal lines: a phase I/III, multicenter, randomized, double-blind, active-controlled study

Abstract Introduction Neuronox® has not yet been investigated for its efficacy and safety in the treatment of lateral canthal lines (LCL). Methods This study was a randomized, double-blind, active drug controlled, multicenter, 16 week, Phase I/III study designed to determine the non-inferiority of Neuronox® compared to onabotulinumtoxin A (ONA) in the treatment of moderate to severe LCL. Thirty subjects in Phase I and 220 subjects in Phase III were randomized in a 1:1 ratio to receive a single treatment (24 U) of either Neuronox® or ONA. The primary endpoint of the Phase III study was the responder rate according to the proportion of subjects achieving Grade 0 (none) or 1 (mild) from 2 (moderate) or 3 (severe) in LCL severity at maximum smile as assessed by the investigators at Week 4. Additional efficacy endpoints and safety endpoints (adverse events) were also evaluated. Results The primary endpoint was achieved as the proportion of responders was 83% for both Neuronox® and ONA, thus, supporting the non-inferiority of Neuronox® compare to ONA. The two groups also showed no statistical differences in safety analyses. Conclusion Treatment of moderate to severe LCL with Neuronox® was effective and well-tolerated.
Reticulocyte hemoglobin content as a function of iron stores at 35–36 weeks post menstrual age in very premature infants

Abstract Background Premature infants are born with lower iron stores and are at risk for iron deficiency during early infancy. To prevent iron deficiency, premature infants are routinely supplemented with 2 mg/kg/day oral elemental iron. Reticulocyte hemoglobin content (RET-He), a measure of iron deficiency, has not been well evaluated prior to discharge in premature infants. Objectives Our objectives were to evaluate RET-He and its correlation with serum ferritin (SF), an index of iron stores, at 35–36 weeks postmenstrual age (PMA) in ≤32 weeks gestational age (GA) infants. Methods We performed a prospective nested study involving 24–32 weeks GA infants who were receiving 2 mg/kg/day oral elemental iron with full enteral feedings at 35–36 weeks PMA. Infants with the following conditions were excluded: craniofacial malformation, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex), culture-proven sepsis, C-reactive protein >5 mg/l within 10 days of iron status assessment, or erythropoietin therapy. SF and RET-He were measured at 35–36 weeks PMA using chemiluminescence immunoassay and Sysmex XN hematology analyzer, respectively. RET-He <27 pg was deemed indicative of iron deficiency. Results Ninety-eight infants were studied, of which 21 infants had RET-He <27 pg. There was a positive correlation between RET-He and SF (coefficient 0.22, p = .03) that remained significant after controlling for GA (coefficient 0.21, p = .03) and frequency of prior erythrocyte transfusions (coefficient 0.21, p = .03). On stratified analysis, there was a positive correlation between SF and RET-He in females (N = 52, coefficient 0.23, p = .02), but not in males (N = 46, coefficient 0.05). Conclusions Most premature infants receiving 2 mg/kg/day oral elemental iron are iron replete for erythropoiesis at 35–36 weeks PMA. RET-He increases with an increase in iron stores, suggesting that additional iron supplementation prior to discharge to very premature infants with borderline low RET-He may help prevent iron deficiency during early infancy.
miR‐138 mediates sorafenib‐induced cell survival and is associated with poor prognosis in cholangiocarcinoma cells

Cholangiocarcinoma is an aggressive malignancy with rapid invasion, metastasis and poor prognosis, however, the mechanism mediating its cholangiocarcinoma development needs further investigation. Here, we demonstrate that decreased miR‐138 in tumor tissues is related to the poor prognosis in patients, and that miR‐138 mediates sorafenib‐induced cell survival in cholangiocarcinoma cells. Moreover, miR‐138 negatively regulates SOX4 expression by specifically targeting its 3′ untranslated region (3′ UTR). As per our results, overexpression of SOX4 reversed sorafenib‐induced changes in cell viability and apoptosis. Furthermore, the elevated levels of SOX4 in the tumor tissues that correlated with poor prognosis. Overall, the present study reveals that miR‐138/SOX4 is involved in sorafinib‐mediated cell survival in cholangiocarcinoma cells, and is associated with poor prognosis.
Clinical indicators of dry eye severity nursing outcome in intensive care unit*

Objective: to verify the extent of impairment of the clinical indicators of the nursing outcome Dry Eye Severity in patients admitted to the Intensive Care Unit. Method: cross-sectional, descriptive study developed with 206 patients. Based on the result listed, six indicators of the Classification of Nursing Results were evaluated with a questionnaire containing clinical variables and the Likert scale of the Classification of Nursing Results with constructed definitions, which varies from more impaired to non-impaired. The data were analyzed using descriptive and inferential statistics. Results: the decrease in lacrimal production and the presence of redness in the conjunctiva were more impaired. The other indicators were more frequent for the absence of impairment: incomplete eyelid closure 81% (167), excessive tearing 95.1%(196), excessive mucous secretion 78.7% (162) and decreased blinking mechanism 50.5% (104). The clinical characteristics of hospitalization for neurological disorders, invasive mechanical ventilation, chemosis, use of sedatives, vasoconstrictors, benzodiazepines, antibiotics and corticosteroids interfered in the impairment of the dry eye severity. Conclusion: the result indicators show that the clinical characteristics of patients in the intensive care unit interfere in the impairment and in the dry eyes severity. According to these results, the importance of assistance directed to the prevention of eye diseases is emphasized.
Design of a Repellent Against Aedes aegypti (Diptera: Culicidae) Using in silico Simulations With AaegOBP1 Protein

Abstract Skin irritation has been reported to be the main adverse effect of excessive use of N,N-diethyl-m-toluamide (DEET) and ethyl 3-acetyl(butyl)amino (IR3535) commercial repellents. Therefore, there is an interest in alternatives of natural origin such as essential oils (EOs) and major compounds, which have repellent effects but have no contraindications. The main purpose of the present study was to identify the repellent effect of selected terpenes on Aedes aegypti Linnaeus, 1762 (Diptera: Culicidae) by in silico analysis based on their affinity with the odorant protein AaegOBP1. The protein-metabolite interactions in 20 terpenes were analyzed using the SwissDock tool. Terpenes presenting the highest affinity compared with commercial repellents were selected to evaluate repellent activity at concentrations 0.1, 10, and 25% against Ae. aegypti. Different periods (0–2, 2–15, 15–60 min) were evaluated with DEET as a positive control. The toxicity of terpenes was verified through Osiris and Molinspiration Cheminformatics Software, and cytotoxicity assays in Vero and HepaRG cells were performed using the MTT method. Two formulations were prepared with polyethylene glycol to evaluate skin long-lasting in vivo assay. The results showed four terpenes: geranyl acetate, nerolidol, α-bisabolol, and nerol, with affinity to AaegOBP1 comparable with DEET and IR3535. Geranyl acetate, nerolidol, and their mixtures showed no cytotoxicity and protection percentages close to 100% during the test at concentrations 10 and 25%. Long-lasting assays with geranyl acetate and nerolidol formulate showed 3 h as maximum protection time with 100% protection percentage. These metabolites and their mixtures are candidates to repellent formulations with times and protection percentages similar to DEET.
GWAS to Identify Genetic Loci for Resistance to Yellow Rust in Wheat Pre-Breeding Lines Derived From Diverse Exotic Crosses

Yellow rust (YR) or stripe rust, caused by Puccinia striformis f. sp tritici Eriks (Pst), is a major challenge to resistance breeding in wheat. A genome wide association study (GWAS) was performed using 22,415 single nucleotide polymorphism (SNP) markers and 591 haplotypes to identify genomic regions associated with resistance to YR in a subset panel of 419 pre-breeding lines (PBLs) developed at International Center for Maize and Wheat Improvement (CIMMYT). The 419 PBLs were derived from an initial set of 984 PBLs generated by a three-way crossing scheme (exotic/elite1//elite2) among 25 best elites and 244 exotics (synthetics, landraces) from CIMMYT’s germplasm bank. For the study, 419 PBLs were characterized with 22,415 high-quality DArTseq-SNPs and phenotyped for severity of YR disease at five locations in Mexico. A population structure was evident in the panel with three distinct subpopulations, and a genome-wide linkage disequilibrium (LD) decay of 2.5 cM was obtained. Across all five locations, 14 SNPs and 7 haplotype blocks were significantly (P < 0.001) associated with the disease severity explaining 6.0 to 14.1% and 7.9 to 19.9% of variation, respectively. Based on average LD decay of 2.5 cM, identified 14 SNP–trait associations were delimited to seven quantitative trait loci in total. Seven SNPs were part of the two haplotype blocks on chromosome 2A identified in haplotypes-based GWAS. In silico analysis of the identified SNPs showed hits with interesting candidate genes, which are related to pathogenic process or known to regulate induction of genes related to pathogenesis such as those coding for glunolactone oxidase, quinate O-hydroxycinnamoyl transferase, or two-component histidine kinase. The two-component histidine kinase, for example, acts as a sensor in the perception of phytohormones ethylene and cytokinin. Ethylene plays a very important role in regulation of multiple metabolic processes of plants, including induction of defense mechanisms mediated by jasmonate. The SNPs linked to the promising genes identified in the study can be used for marker-assisted selection.
Desiccation-Driven Senescence in the Resurrection Plant Xerophyta schlechteri (Baker) N.L. Menezes: Comparison of Anatomical, Ultrastructural, and Metabolic Responses Between Senescent and Non-Senescent Tissues

Drought-induced senescence is a degenerative process that involves the degradation of cellular metabolites and photosynthetic pigments and uncontrolled dismantling of cellular membranes and organelles. Angiosperm resurrection plants display vegetative desiccation tolerance and avoid drought-induced senescence in most of their tissues. Developmentally older tissues, however, fail to recover during rehydration and ultimately senesce. Comparison of the desiccation-associated responses of older senescent tissues (ST) with non-ST (NST) will allow for understanding of mechanisms promoting senescence in the former and prevention of senescence in the latter. In the monocotyledonous resurrection plant Xerophyta schlechteri (Baker) N.L. Menezes*, leaf tips senesce following desiccation, whereas the rest of the leaf blade survives. We characterized structural and metabolic changes in ST and NST at varying water contents during desiccation and rehydration. Light and transmission electron microscopy was used to follow anatomical and subcellular responses, and metabolic differences were studied using gas chromatography-mass spectrometry and colorimetric metabolite assays. The results show that drying below 35% relative water content (0.7 gH2O/g dry mass) in ST resulted in the initiation of age-related senescence hallmarks and that these tissues continue this process after rehydration. We propose that an age-related desiccation sensitivity occurs in older tissues, in a process metabolically similar to that observed during age-related senescence in Arabidopsis thaliana.
Incontinence and psychological symptoms in Phelan‐McDermid syndrome

Phelan‐McDermid syndrome (PMD) is a congenital syndrome caused by a deletion on chromosome 22q13.3. About 600 cases have been identified worldwide. PMD is characterized by neonatal hypotonia, moderate/severe intellectual impairment, impaired expressive language, and typical dysmorphic features. Psychological symptoms as hyperactivity, attention problems, restlessness, and stereotyped‐repetitive behavior were reported. The aim of the study was to assess incontinence and associated psychological problems in PMD.