Clinical outcomes of COVID-19 in hemodialysis patients

BackgroundThe coronavirus disease 2019 (COVID-19) is known for its effects on the respiratory system. Three years after the pandemic morbid and mortal consequences, growing evidence is showing that the disease also has adverse outcomes and complications on additional organs including the kidneys. This study aims at investigating the effects of COVID-19 on hemodialysis patients receiving services at Palestine Medical Complex (PMC) kidney dialysis department, and to identify mortality related risk factors.MethodsIn April 2022, data was collected using the electronic medical records system for the dialysis department at PMC. The study included all PMC hemodialysis patients that were infected with COVID-19 between January 2020–April 2022. The collected data included patient demographics, clinical features, laboratory tests, dialysis frequency and the disease outcome.ResultsThe results showed that the patients’ outcomes and dialysis frequency were impacted by their blood urea nitrogen (BUN), serum creatinine (SCr) and calcium levels. About one third of the study population died after being infected with COVID-19. The frequency of dialysis was also affected by the presence of comorbidities like hypertension, diabetes mellitus (DM) and myocardial infarction (MI).ConclusionThis study found that there was a high mortality rate within the hemodialysis patients infected with COVID-19. Having comorbidities affected the frequency of dialysis following COVID-19 infection. Dialysis patients should be protected from infections such as COVID-19 and their comorbidities should be monitored and kept under control as much as possible

Examining the moderating effect of individual-level cultural values on users’ acceptance of E-learning in developing countries: a structural equation modeling of an extended technology acceptance model

In this study, we examine the effects of individual-level culture on the adoption and acceptance of e-learning tools by students in Lebanon using a theoretical framework based on the Technology Acceptance Model (TAM). To overcome possible limitations of using TAM in developing countries, we extend TAM to include subjective norms (SN) and quality of work life constructs as additional constructs and a number of cultural variables as moderators. The four cultural dimensions of masculinity/femininity (MF), individualism/collectivism, power distance and uncertainty avoidance were measured at the individual level to enable them to be integrated into the extended TAM as moderators and a research model was developed based on previous literature. To test the hypothesised model, data were collected from 569 undergraduate and postgraduate students using e-learning tools in Lebanon via questionnaire. The collected data were analysed using the structural equation modelling technique in conjunction with multi-group analysis. As hypothesised, the results of the study revealed perceived usefulness (PU), perceived ease of use (PEOU), SN and quality of work life to be significant determinants of students’ behavioural intention (BI) towards e-learning. The empirical results also demonstrated that the relationship between SN and BI was particularly sensitive to differences in individual-cultural values, with significant moderating effects observed for all four of the cultural dimensions studied. Some moderating effects of culture were also found for both PU and PEOU, however, contrary to expectations the effect of quality of work life was not found to be moderated by MF as some previous authors have predicted. The implications of these results to both theory and practice are explored in the paper

Multi-Method Diagnosis of CT Images for Rapid Detection of Intracranial Hemorrhages Based on Deep and Hybrid Learning

Intracranial hemorrhaging is considered a type of disease that affects the brain and is very dangerous, with high-mortality cases if there is no rapid diagnosis and prompt treatment. CT images are one of the most important methods of diagnosing intracranial hemorrhages. CT images contain huge amounts of information, requiring a lot of experience and taking a long time for proper analysis and diagnosis. Thus, artificial intelligence techniques provide an automatic mechanism for evaluating CT images to make a diagnosis with high accuracy and help radiologists make their diagnostic decisions. In this study, CT images for rapid detection of intracranial hemorrhages are diagnosed by three proposed systems with various methodologies and materials, where each system contains more than one network. The first system is proposed by three pretrained deep learning models, which are GoogLeNet, ResNet-50 and AlexNet. The second proposed system using a hybrid technology consists of two parts: the first part is the GoogLeNet, ResNet-50 and AlexNet models for extracting feature maps, while the second part is the SVM algorithm for classifying feature maps. The third proposed system uses artificial neural networks (ANNs) based on the features of the GoogLeNet, ResNet-50 and AlexNet models, whose dimensions are reduced by a principal component analysis (PCA) algorithm, and then the low-dimensional features are combined with the features of the GLCM and LBP algorithms. All the proposed systems achieved promising results in the diagnosis of CT images for the rapid detection of intracranial hemorrhages. The ANN network based on fusion of the deep feature of AlexNet with the features of GLCM and LBP reached an accuracy of 99.3%, precision of 99.36%, sensitivity of 99.5%, specificity of 99.57% and AUC of 99.84

Inequalities in higher education in low‐ and middle‐income countries:A scoping review of the literature

Motivation:  Higher  education  is  regarded  as  a  key  instrument  to  enhance  socioeconomic  mobility  andreduce inequalities. Recent literature reviews have examined inequalities in the higher education systemsof  high-income  countries,  but  less  is  known  about  the  situation  in  low-  and  middle-income  countries,where higher education is expanding fast.Purpose:  The  article  reviews  the  academic  literature  on  higher  education  in  low-  and  middle-incomecountries using a research framework inspired by social justice and capability approaches. It considers the financial,  socio-cultural,  human,  and  political  resource  domains  on  which  people  draw,  and  how  they relate to access, participation, and outcomes in higher education.Methods: A literature search for studies explicitly discussing in-country  inequalities  in  higher  education revealed  22  publications. Substantial  knowledge  gaps remain,  especially  regarding  the  political  (and decision-making)  side  of  inequalities;  the  ideologies  and  philosophies  underpinning  higher  education systems; and the linkages between resource domains, both micro and macro.Findings:  The  review  highlights  key  elements  for  policy-makers  and  researchers:  (1)  the  financial  lens alone  is  insufficient  to  understand  and  tackle  inequalities,  since  these  are  also  shaped  by  human  and other non-financial factors; (2) socio-cultural constructs are central in explaining unequal outcomes; and (3) inequalities develop throughout one’s life and need to be considered during, but also before and afterhigher education.  The scope  of  inequalities  is  wide, and  the literature  offers a  few ideas  for short-term fixes such as part-time and online education.Policy implications: Inclusive policy frameworks for higher education should include explicit goals related to (in)equality,  which  are  best  measured in  terms  of  the  extent  to  which  certain  actions  or  choices are feasible for all. Policies in these frameworks, we argue, should go beyond providing financial support, and also address socio-cultural and human resource constraints and challenges in retention, performance, and labour market outcomes. Finally, they should consider relevant contextual determinants of inequalities.</p

Deletion of the thrombin cleavage domain of osteopontin mediates breast cancer cell adhesion, proteolytic activity, tumorgenicity, and metastasis

<p>Abstract</p> <p>Background</p> <p>Osteopontin (OPN) is a secreted phosphoprotein often overexpressed at high levels in the blood and primary tumors of breast cancer patients. OPN contains two integrin-binding sites and a thrombin cleavage domain located in close proximity to each other.</p> <p>Methods</p> <p>To study the role of the thrombin cleavage site of OPN, MDA-MB-468 human breast cancer cells were stably transfected with either wildtype OPN (468-OPN), mutant OPN lacking the thrombin cleavage domain (468-ΔTC) or an empty vector (468-CON) and assessed for <it>in vitro </it>and <it>in vivo </it>functional differences in malignant/metastatic behavior.</p> <p>Results</p> <p>All three cell lines were found to equivalently express thrombin, tissue factor, CD44, αvβ5 integrin and β1 integrin. Relative to 468-OPN and 468-CON cells, 468-ΔTC cells expressing OPN with a deleted thrombin cleavage domain demonstrated decreased cell adhesion (p < 0.001), decreased mRNA expression of MCAM, maspin and TRAIL (p < 0.01), and increased uPA expression and activity (p < 0.01) <it>in vitro</it>. Furthermore, injection of 468-ΔTC cells into the mammary fat pad of nude mice resulted in decreased primary tumor latency time (p < 0.01) and increased primary tumor growth and lymph node metastatic burden (p < 0.001) compared to 468-OPN and 468-CON cells.</p> <p>Conclusions</p> <p>The results presented here suggest that expression of thrombin-uncleavable OPN imparts an early tumor formation advantage as well as a metastatic advantage for breast cancer cells, possibly due to increased proteolytic activity and decreased adhesion and apoptosis. Clarification of the mechanisms responsible for these observations and the translation of this knowledge into the clinic could ultimately provide new therapeutic opportunities for combating breast cancer.</p

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.This study was funded by NIH grant NS073976 to TKH and a John Sealy Grant to PSS