Annotating an Arabic Learner Corpus for Error

This paper describes an ongoing project in which we are collecting a learner corpus of Arabic, developing a tagset for error annotation and performing Computer-aided Error Analysis (CEA) on the data. We adapted the French Interlanguage Database FRIDA tagset (Granger, 2003a) to the data. We chose FRIDA in order to follow a known standard and to see whether the changes needed to move from a French to an Arabic tagset would give us a measure of the distance between the two languages with respect to learner difficulty. The current collection of texts, which is constantly growing, contains intermediate and advanced-level student writings. We describe the need for such corpora, the learner data we have collected and the tagset we have developed. We also describe the error frequency distribution of both proficiency levels and the ongoing work

Prevention of ear‐looped face mask‐induced pressure injury on ears: A Technical report with review of literature

In modern times, protective masks with flexible loops are commonly used to prevent the spread of microorganisms during surgical procedure the constant contact of the stretching bands caused by wearing a mask for several hours’ daily causes pressure on this cartilage, leading to painful and erythematous lesions on the skin behind the auricles. Patients and the public now wear masks for extended periods of time. Over time, wearing this mask frequently can cause damage to the ear. Consequently, people regularly switch out their masks to alleviate pressure, increasing their chances of getting infected. Doctors and other healthcare professionals should be aware that continued use may cause damage to the ears and auricles. This article addresses a novel method to alleviate stress on the ear loops of surgical masks and examines the typical ear injuries or pressure injuries on the ear mentioned in literature regarding prolonged mask usage and ways to prevent them.Keywords: Pressure injury; Ear injury; Pinna injury; Surgical masks; Elastic ear loops 

Pulmonary Endothelial Mechanical Sensing and Signaling, a Story of Focal Adhesions and Integrins in Ventilator Induced Lung Injury

Patients with critical illness such as acute lung injury often undergo mechanical ventilation in the intensive care unit. Though lifesaving in many instances, mechanical ventilation often results in ventilator induced lung injury (VILI), characterized by overdistension of lung tissue leading to release of edemagenic agents, which further damage the lung and contribute to the mortality and progression of pulmonary inflammation. The endothelium is particularly sensitive, as VILI associated mechanical stress results in endothelial cytoskeletal rearrangement, stress fiber formation, and integrity loss. At the heart of these changes are integrin tethered focal adhesions (FAs) which participate in mechanosensing, structure, and signaling. Here, we present the known roles of FA proteins including c-Src, talin, FAK, paxillin, vinculin, and integrins in the sensing and response to cyclic stretch and VILI associated stress. Attention is given to how stretch is propagated from the extracellular matrix through integrins to talin and other FA proteins, as well as signaling cascades that include FA proteins, leading to stress fiber formation and other cellular responses. This unifying picture of FAs aids our understanding in an effort to prevent and treat VILI

METTL3-METTL14 Inhibition: A Novel Therapeutic Target for Acute Lung Injury

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are acute, inflammatory clinical syndromes characterized by poor oxygenation and diffuse pulmonary infiltrates. This syndrome is associated with microvascular endothelial dysfunction and subsequent pulmonary hypertension and may ultimately lead to mortality without rigorous and acute clinical intervention. Over the years, many attempts have been made to detect novel therapeutic avenues for research without much success. The urgency for the discovery of novel therapeutic agents has become more pronounced recently given the current pandemic infection of coronavirus disease 2019 (COVID-2019), still ongoing at the time that this dissertation is being written. N6-methyladenosine (m6A) is the most common methylation modification in mammalian messenger RNA (mRNA) and noncoding RNAs that plays a role in the regulation of gene expression. Deregulation of m6A methylation has been implicated in many human diseases and exploitation of the methylation process may possess utility against ALI. In chapter I, we review the current landscape of literature regarding ALI and ARDS etiology, pathophysiology, and therapeutics and present a potential role of m6A methylation. Additionally, we will establish the axiomatic principles of m6A methylation to provide a framework for chapters II-IV. In chapter II, we explore gene expression in response to ALI-related stimuli. We confirmed METTL3 as a vital component of m6A up-regulation following LPS treatment and demonstrated alleviation of endothelial barrier dysfunction by METTL3 knockdown-suggesting that METTL3 inhibition may possess therapeutic utility for ALI. We used a known METTL3 inhibitor (STM) to selectively inhibit METTL3’s demethylation which induced the increase of m6A mRNA methylation level in human pulmonary artery endothelial cells (HPAECs). METTL3 inhibition reduced m6A methylation levels following LPS treatment and reduced ICAM1 levels. Additionally, LPS-induced responses in endothelial barrier regulation were attenuated by METTL3 knockdown. In chapter III, we continue exploring gene expression deregulation in response to ALI-related stimuli. We present our findings from a similar m6A methylation project focusing on the effects of particulate matter and airway epithelium. Our group has experience studying the effects of PM2.5 on cardiopulmonary systems and decided to pursue a side project using our m6A methylation platform to examine whether PM2.5 can produce this functional and robust post-transcriptional regulation. We confirmed an increase in m6A methylation activity following PM2.5 treatment which correlated with increased METTL3 and METTL14 protein expression. METTL3 knockdown greatly attenuated PM2.5 -induced m6A methylation and decreased protein expression of ICAM1. Moreover, METTL3 knockdown decreased the protein expression of ERK and up-regulated protein expression of p-JNK and JNK, highlighting a potential link between m6A methylation and the MAPK signaling pathway. Lastly, we observed that PM2.5 increased mRNA expression of both MAP3k8 and CXCL5 in A549 cells and that TNF-α secretion increased in PM2.5-treated cells. In chapter IV, we sought to identify a small molecule inhibitor of METTL3 using a novel virtual drug discovery campaign. Our strategy was to identify ligands by virtually screening molecular libraries for modulators of the RNA methyltransferase METTL3-14-WTAP complex and then to characterize their binding properties as well as effects on enzymatic activity with the intention of ultimately choosing a lead compound for animal studies of ALI. Using the crystal structure of the METTL3-METTL14 complex, we searched databases compromising of almost 8 million compounds to identify a small molecule compound with favorable docking to the SAM binding pocket. Ultimately, 24 compounds passed visual inspection following our cluster-based selection. Twenty-three small molecule compounds with favorable glide scores were procured and chosen to undergo METTL3-14 binding affinity and kinetics studies using surface plasmon resonance (SPR). Of the 23 compounds, 6 demonstrated favorable binding to the METTL3-14 complex and underwent a bioluminescence methyltransferase activity assay to determine whether any compounds contained METTL3-14 inhibitory activity. Two compounds, ZRF001 and Z70895572, exhibited concentration-dependent methyltransferase inhibitory activity with ZRF001 demonstrating IC50 value in the low uM range. Compound ZRF001 was ultimately chosen as our lead compound for in vitro studies of ALI. In conclusion, METTL3 is a hub of pro-inflammatory gene expression regulation in ALI, and using a modern drug discovery strategy will identify new and effective ALI drug candidates targeting METTTL3

Synthesizing Titania Based Catalysts for Water Splitting and CO2 Conversion

Recently, blackening titanium dioxide has attracted attention as a promising catalyst for improving photoelectrochemical activity. It has been investigated for hydrogen production, and it is expected to have enhanced carbon dioxide conversion ability. In this study, a new generation of the titanium oxide catalysts referred to as the black titanium dioxide nanotube (BTNT) is tested to produce hydrogen from water splitting and carbon monoxide from carbon dioxide conversion. BTNT synthesis is optimized through electrochemical anodization and reduction in an ethylene glycol electrolyte. The synthesized material is also compared with the white titanium dioxide nanotube (TNT). The surface morphology, phase crystallinity, and oxidation states are confirmed by characterization using scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). SEM shows a uniform nanotube structure with an average pore diameter of 65nm, while XRD indicated anatase crystallinity phase. The photoelectrochemical performance is investigated using the BTNT as a photoanode and a platinum wire as a cathode, where hydrogen was detected online via a residual gas analyzer (RGA). The highest performance is achieved in acidic conditions as the maximum percentage based on the gas sample volume reached 5.15% at an average current density of 1.75 mA/cm2. BTNT is then tested in an electrochemical system to produce a mixture of CO/H2 with a gold cathode. A qualitative model is developed for product analysis based on Fourier-Transform Infrared Spectroscopy (FTIR) and RGA for CO and H2 detection, respectively. BTNT, compared to Pt, requires higher voltages to reach the same current densities and generate an equivalent amount of the product. The final part of this work covers a detailed sustainability analysis of our developed system compared to other electrochemical and conventional CO/H2 production routes. This analysis shows that the developed system needs to achieve higher CO2 conversion to lower the CO2 emissions and operating cost. Comparison with conventional routes showed that the electrochemical path needs further technological advancements that facilitates significant increase in energy efficiency such as lowering the overpotential, combined with substantial decrease in the renewable electricity price that could be achieved as well by new policies that provides incentives for this technology to be economically viable

Exploring m6A‐RNA methylation as a potential therapeutic strategy for acute lung injury and acute respiratory distress syndrome

Abstract N6‐methyladenosine (m6A) is the most common methylation modification in mammalian messenger RNA (mRNA) and noncoding RNAs. m6A modification plays a role in the regulation of gene expression and deregulation of m6A methylation has been implicated in many human diseases. Recent publications suggest that exploitation of this methylation process may possess utility against acute lung injury (ALI). ALI and its more severe form, acute respiratory distress syndrome (ARDS) are acute, inflammatory clinical syndromes characterized by poor oxygenation and diffuse pulmonary infiltrates. This syndrome is associated with microvascular endothelial dysfunction, subsequent pulmonary hypertension and may ultimately lead to mortality without rigorous and acute clinical intervention. Over the years, many attempts have been made to detect novel therapeutic avenues for research without much success. The urgency for the discovery of novel therapeutic agents has become more pronounced recently given the current pandemic infection of coronavirus disease 2019 (COVID‐2019), still ongoing at the time that this review is being written. We review the current landscape of literature regarding ALI and ARDS etiology, pathophysiology, and therapeutics and present a potential role of m6A methylation. Additionally, we will establish the axiomatic principles of m6A methylation to provide a framework. In conclusion, METTL3, or methyltransferase‐like 3, the selective RNA methyltransferase for m6A, is a hub of proinflammatory gene expression regulation in ALI, and using a modern drug discovery strategy will identify new and effective ALI drug candidates targeting METTTL3

The Factors Affecting CO Emission in the European Union Countries: A Statistical Approach to Sustainability across the Food Industry

The research investigates four prime factors influencing CO2 emission levels associated with the food production industry in the European Union (EU) member states. The prime factors, namely population size, percentage of urbanization, percentage of agricultural land, and average years of schooling, were used in the analysis. The research further examines the existing policies that regulate carbon emission in EU states. The analysis covers 25 EU member countries for the years from 2000 till 2019. The relationship between the prime factors and CO2 emissions were identified using a simple linear regression model, confirming the significance of this relation. The strength of these relations was numerically measured using a clustered analysis. The results indicate that a negative impact on CO2 emission was found in relation to the increase in population and urbanization based on the survival requirements and sustainability in social and urban settings. The effect of the factor 'average years of schooling' on CO2 emission is relatively negligible when compared to the other chosen factors. The findings provide sufficient information to develop and support suggestions for enhancing the available policies in EU member states

Identification of S1PR3 gene signature involved in survival of sepsis patients

Background: Sepsis is a life-threatening complication of infection that rapidly triggers tissue damage in multiple organ systems and leads to multi-organ deterioration. Up to date, prognostic biomarkers still have limitations in predicting the survival of patients with sepsis. We need to discover more prognostic biomarkers to improve the sensitivity and specificity of the prognosis of sepsis patients. Sphingosine-1-phosphate (S1P) receptor 3 (S1PR3), as one of the S1P receptors, is a prospective prognostic biomarker regulating sepsis-relevant events, including compromised vascular integrity, antigen presentation, and cytokine secretion. Until now, no S1PR3-related prognostic gene signatures for sepsis patients have been found. Methods: This study intends to obtain an S1PR3-associated gene signature from whole blood samples to be utilized as a probable prognostic tool for patients with sepsis. Results: We obtained an 18-gene S1PR3-related molecular signature (S3MS) from the intersection of S1PR3-associated genes and survival-associated genes. Numerous important immunity pathways that regulate the progression of sepsis are enriched among our 18 genes. Significantly, S3MS functions greatly in both the discovery and validation cohort. Furthermore, we demonstrated that S3MS obtains significantly better classification performance than random 18-gene signatures. Conclusions: Our results confirm the key role of S1PR3-associated genes in the development of sepsis, which will be a potential prognostic biomarker for patients with sepsis. Our results also focus on the classification performance of our S3MS as biomarkers for sepsis, which could also provide an early warning system for patients with sepsis. © 2021, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally