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Article ; Online: Knowledge of Glasgow Coma Scale among Nurses in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Kc, Bidur / Adil, Mohamed Zaidan

JNMA; journal of the Nepal Medical Association

2022 Volume 60, Issue 252, Page(s) 723–726

Abstract: Introduction: Glasgow Coma Scale is a dependable and unprejudiced neurological evaluation kit applied for evaluating and recording the level of consciousness of a person. Evaluation of consciousness level using Glasgow Coma Scale is a tool necessitating ...

Abstract	Introduction: Glasgow Coma Scale is a dependable and unprejudiced neurological evaluation kit applied for evaluating and recording the level of consciousness of a person. Evaluation of consciousness level using Glasgow Coma Scale is a tool necessitating knowledge which is vital in identifying immediate worsening of level of consciousness. Critical thinking used with skill and knowledge in Glasgow Coma Scale is the groundwork of nursing practice to avoid delay in clinical worsening and treatment. The aim of this study was to find out the prevalence of inadequate knowledge of Glasgow Coma Scale among nurses working in a tertiary care centre. Methods: A descriptive cross-sectional study was performed among registered nurses working in different wards and Intensive Care Unit at tertiary care centre between 1 June 2022 and 30 June 2022 after receiving ethical approval from the Institutional Review Committee (Reference number: 2905202211). Convenience sampling was done. Self-administered structured questionnaires were used to collect data to assess the knowledge of Glasgow Coma Scale. Point estimate and 95% Confidence Interval were calculated. Results: Among 91 nurses, inadequate knowledge of the Glasgow Coma Scale was found in 48 nurses (52.70%) (42.30-63.10, 95 % Confidence Interval). Conclusions: The prevalence of inadequate knowledge of the Glasgow Coma Scale among nurses was found to be similar when compared to other studies done in similar settings. Keywords: glasgow coma scale; knowledge; nurses; tertiary care centre.
MeSH term(s)	Humans ; Cross-Sectional Studies ; Tertiary Care Centers ; Glasgow Coma Scale ; Surveys and Questionnaires ; Nurses
Language	English
Publishing date	2022-08-01
Publishing country	Nepal
Document type	Journal Article
ZDB-ID	2209910-4
ISSN	1815-672X ; 0028-2715
ISSN (online)	1815-672X
ISSN	0028-2715
DOI	10.31729/jnma.7673
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Article ; Online: Closely related reovirus lab strains induce opposite expression of RIG-I/IFN-dependent versus -independent host genes, via mechanisms of slow replication versus polymorphisms in dsRNA binding σ3 respectively.

Adil Mohamed / Prathyusha Konda / Heather E Eaton / Shashi Gujar / James R Smiley / Maya Shmulevitz

PLoS Pathogens, Vol 16, Iss 9, p e

2020 Volume 1008803

Abstract: The Dearing isolate of Mammalian orthoreovirus (T3D) is a prominent model of virus-host relationships and a candidate oncolytic virotherapy. Closely related laboratory strains of T3D, originating from the same ancestral T3D isolate, were recently found ... ...

Abstract	The Dearing isolate of Mammalian orthoreovirus (T3D) is a prominent model of virus-host relationships and a candidate oncolytic virotherapy. Closely related laboratory strains of T3D, originating from the same ancestral T3D isolate, were recently found to exhibit significantly different oncolytic properties. Specifically, the T3DPL strain had faster replication kinetics in a panel of cancer cells and improved tumor regression in an in vivo melanoma model, relative to T3DTD. In this study, we discover that T3DPL and T3DTD also differentially activate host signalling pathways and downstream gene transcription. At equivalent infectious dose, T3DTD induces higher IRF3 phosphorylation and expression of type I IFNs and IFN-stimulated genes (ISGs) than T3DPL. Using mono-reassortants with intermediate replication kinetics and pharmacological inhibitors of reovirus replication, IFN responses were found to inversely correlate with kinetics of virus replication. In other words, slow-replicating T3D strains induce more IFN signalling than fast-replicating T3D strains. Paradoxically, during co-infections by T3DPL and T3DTD, there was still high IRF3 phosphorylation indicating a phenodominant effect by the slow-replicating T3DTD. Using silencing and knock-out of RIG-I to impede IFN, we found that IFN induction does not affect the first round of reovirus replication but does prevent cell-cell spread in a paracrine fashion. Accordingly, during co-infections, T3DPL continues to replicate robustly despite activation of IFN by T3DTD. Using gene expression analysis, we discovered that reovirus can also induce a subset of genes in a RIG-I and IFN-independent manner; these genes were induced more by T3DPL than T3DTD. Polymorphisms in reovirus σ3 viral protein were found to control activation of RIG-I/ IFN-independent genes. Altogether, the study reveals that single amino acid polymorphisms in reovirus genomes can have large impact on host gene expression, by both changing replication kinetics and by modifying viral protein activity, ...
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Molecular phenotyping of small cell lung cancer using targeted cfDNA profiling of transcriptional regulatory regions.

Hiatt, Joseph B / Doebley, Anna-Lisa / Arnold, Henry U / Adil, Mohamed / Sandborg, Holly / Persse, Thomas W / Ko, Minjeong / Wu, Feinan / Quintanal Villalonga, Alvaro / Santana-Davila, Rafael / Eaton, Keith / Dive, Caroline / Rudin, Charles M / Thomas, Anish / Houghton, A McGarry / Ha, Gavin / MacPherson, David

Science advances

2024 Volume 10, Issue 15, Page(s) eadk2082

Abstract: We report an approach for cancer phenotyping based on targeted sequencing of cell-free DNA (cfDNA) for small cell lung cancer (SCLC). In SCLC, differential activation of transcription factors (TFs), such as ASCL1, NEUROD1, POU2F3, and REST defines ... ...

Abstract	We report an approach for cancer phenotyping based on targeted sequencing of cell-free DNA (cfDNA) for small cell lung cancer (SCLC). In SCLC, differential activation of transcription factors (TFs), such as ASCL1, NEUROD1, POU2F3, and REST defines molecular subtypes. We designed a targeted capture panel that identifies chromatin organization signatures at 1535 TF binding sites and 13,240 gene transcription start sites and detects exonic mutations in 842 genes. Sequencing of cfDNA from SCLC patient-derived xenograft models captured TF activity and gene expression and revealed individual highly informative loci. Prediction models of ASCL1 and NEUROD1 activity using informative loci achieved areas under the receiver operating characteristic curve (AUCs) from 0.84 to 0.88 in patients with SCLC. As non-SCLC (NSCLC) often transforms to SCLC following targeted therapy, we applied our framework to distinguish NSCLC from SCLC and achieved an AUC of 0.99. Our approach shows promising utility for SCLC subtyping and transformation monitoring, with potential applicability to diverse tumor types.
MeSH term(s)	Humans ; Small Cell Lung Carcinoma/metabolism ; Lung Neoplasms/metabolism ; Cell-Free Nucleic Acids ; Carcinoma, Non-Small-Cell Lung/pathology ; Regulatory Sequences, Nucleic Acid ; Gene Expression Regulation, Neoplastic
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adk2082
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Article ; Online: Development of Masitinib Derivatives with Enhanced M pro Ligand Efficiency and Reduced Cytotoxicity

Cintia A. Menendez / Adil Mohamed / Gustavo R. Perez-Lemus / Adam M. Weiss / Benjamin W. Rawe / Guancen Liu / Alex E. Crolais / Emma Kenna / Fabian Byléhn / Walter Alvarado / Dan Mendels / Stuart J. Rowan / Savaş Tay / Juan J. de Pablo

Molecules, Vol 28, Iss 6643, p

2023 Volume 6643

Abstract: Recently, a high-throughput screen of 1900 clinically used drugs identified masitinib, an orally bioavailable tyrosine kinase inhibitor, as a potential treatment for COVID-19. Masitinib acts as a broad-spectrum inhibitor for human coronaviruses, ... ...

Abstract	Recently, a high-throughput screen of 1900 clinically used drugs identified masitinib, an orally bioavailable tyrosine kinase inhibitor, as a potential treatment for COVID-19. Masitinib acts as a broad-spectrum inhibitor for human coronaviruses, including SARS-CoV-2 and several of its variants. In this work, we rely on atomistic molecular dynamics simulations with advanced sampling methods to develop a deeper understanding of masitinib’s mechanism of M pro inhibition. To improve the inhibitory efficiency and to increase the ligand selectivity for the viral target, we determined the minimal portion of the molecule (fragment) that is responsible for most of the interactions that arise within the masitinib-M pro complex. We found that masitinib forms highly stable and specific H-bond interactions with M pro through its pyridine and aminothiazole rings. Importantly, the interaction with His 163 is a key anchoring point of the inhibitor, and its perturbation leads to ligand unbinding within nanoseconds. Based on these observations, a small library of rationally designed masitinib derivatives ( M1 – M5 ) was proposed. Our results show increased inhibitory efficiency and highly reduced cytotoxicity for the M3 and M4 derivatives compared to masitinib.
Keywords	masitinib derivatives ; M pro inhibitors ; SARS-CoV-2 ; Organic chemistry ; QD241-441
Subject code	333
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Potential for Improving Potency and Specificity of Reovirus Oncolysis with Next-Generation Reovirus Variants

Adil Mohamed / Randal N. Johnston / Maya Shmulevitz

Viruses, Vol 7, Iss 12, Pp 6251-

2015 Volume 6278

Abstract: Viruses that specifically replicate in tumor over normal cells offer promising cancer therapies. Oncolytic viruses (OV) not only kill the tumor cells directly; they also promote anti-tumor immunotherapeutic responses. Other major advantages of OVs are ... ...

Abstract	Viruses that specifically replicate in tumor over normal cells offer promising cancer therapies. Oncolytic viruses (OV) not only kill the tumor cells directly; they also promote anti-tumor immunotherapeutic responses. Other major advantages of OVs are that they dose-escalate in tumors and can be genetically engineered to enhance potency and specificity. Unmodified wild type reovirus is a propitious OV currently in phase I–III clinical trials. This review summarizes modifications to reovirus that may improve potency and/or specificity during oncolysis. Classical genetics approaches have revealed reovirus variants with improved adaptation towards tumors or with enhanced ability to establish specific steps of virus replication and cell killing among transformed cells. The recent emergence of a reverse genetics system for reovirus has provided novel strategies to fine-tune reovirus proteins or introduce exogenous genes that could promote oncolytic activity. Over the next decade, these findings are likely to generate better-optimized second-generation reovirus vectors and improve the efficacy of oncolytic reotherapy.
Keywords	reovirus ; oncolytic virus ; cancer ; attachment ; uncoating ; replication ; reverse genetics ; Microbiology ; QR1-502 ; Science ; Q
Language	English
Publishing date	2015-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Serum Protein Exposure Activates a Core Regulatory Program Driving Human Proximal Tubule Injury.

Lidberg, Kevin A / Muthusamy, Selvaraj / Adil, Mohamed / Mahadeo, Anish / Yang, Jade / Patel, Ranita S / Wang, Lu / Bammler, Theo K / Reichel, Jonathan / Yeung, Catherine K / Himmelfarb, Jonathan / Kelly, Edward J / Akilesh, Shreeram

Journal of the American Society of Nephrology : JASN

2022 Volume 33, Issue 5, Page(s) 949–965

Abstract: Background: The kidneys efficiently filter waste products while retaining serum proteins in the circulation. However, numerous diseases compromise this barrier function, resulting in spillage of serum proteins into the urine (proteinuria). Some studies ... ...

Abstract	Background: The kidneys efficiently filter waste products while retaining serum proteins in the circulation. However, numerous diseases compromise this barrier function, resulting in spillage of serum proteins into the urine (proteinuria). Some studies of glomerular filtration suggest that tubules may be physiologically exposed to nephrotic-range protein levels. Therefore, whether serum components can directly injure the downstream tubular portions of the kidney, which in turn can lead to inflammation and fibrosis, remains controversial. Methods: We tested the effects of serum protein exposure in human kidney tubule microphysiologic systems and with orthogonal epigenomic approaches since animal models cannot directly assess the effect of serum components on tubules. Results: Serum, but not its major protein component albumin, induced tubular injury and secretion of proinflammatory cytokines. Epigenomic comparison of serum-injured tubules and intact kidney tissue revealed canonical stress-inducible regulation of injury-induced genes. Concordant transcriptional changes in microdissected tubulointerstitium were also observed in an independent cohort of patients with proteinuric kidney disease. Conclusions: Our results demonstrate a causal role for serum proteins in tubular injury and identify regulatory mechanisms and novel pathways for intervention.
MeSH term(s)	Animals ; Blood Proteins ; Female ; Humans ; Kidney Diseases/metabolism ; Kidney Tubules/metabolism ; Kidney Tubules, Proximal/metabolism ; Male ; Proteinuria/metabolism
Chemical Substances	Blood Proteins
Language	English
Publishing date	2022-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2021060751
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Article ; Online: Noninvasive Detection of Neuroendocrine Prostate Cancer through Targeted Cell-free DNA Methylation.

Franceschini, Gian Marco / Quaini, Orsetta / Mizuno, Kei / Orlando, Francesco / Ciani, Yari / Ku, Sheng-Yu / Sigouros, Michael / Rothmann, Emily / Alonso, Alicia / Benelli, Matteo / Nardella, Caterina / Auh, Joonghoon / Freeman, Dory / Hanratty, Brian / Adil, Mohamed / Elemento, Olivier / Tagawa, Scott T / Feng, Felix Y / Caffo, Orazio /

Buttigliero, Consuelo / Basso, Umberto / Nelson, Peter S / Corey, Eva / Haffner, Michael C / Attard, Gerhardt / Aparicio, Ana / Demichelis, Francesca / Beltran, Himisha

Cancer discovery

2024 Volume 14, Issue 3, Page(s) 424–445

Abstract: Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive therapy response and outcome differences. Histologic transformation to castration-resistant neuroendocrine prostate cancer (CRPC-NE) is ... ...

Abstract	Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive therapy response and outcome differences. Histologic transformation to castration-resistant neuroendocrine prostate cancer (CRPC-NE) is associated with distinct epigenetic alterations, including changes in DNA methylation. The current diagnosis of CRPC-NE is challenging and relies on metastatic biopsy. We developed a targeted DNA methylation assay to detect CRPC-NE using plasma cell-free DNA (cfDNA). The assay quantifies tumor content and provides a phenotype evidence score that captures diverse CRPC phenotypes, leveraging regions to inform transcriptional state. We tested the design in independent clinical cohorts (n = 222 plasma samples) and qualified it achieving an AUC > 0.93 for detecting pathology-confirmed CRPC-NE (n = 136). Methylation-defined cfDNA tumor content was associated with clinical outcomes in two prospective phase II clinical trials geared towards aggressive variant CRPC and CRPC-NE. These data support the application of targeted DNA methylation for CRPC-NE detection and patient stratification. Significance: Neuroendocrine prostate cancer is an aggressive subtype of treatment-resistant prostate cancer. Early detection is important, but the diagnosis currently relies on metastatic biopsy. We describe the development and validation of a plasma cell-free DNA targeted methylation panel that can quantify tumor fraction and identify patients with neuroendocrine prostate cancer noninvasively. This article is featured in Selected Articles from This Issue, p. 384.
MeSH term(s)	Male ; Humans ; DNA Methylation ; Prospective Studies ; Prostatic Neoplasms, Castration-Resistant/diagnosis ; Prostatic Neoplasms, Castration-Resistant/genetics ; Biopsy ; Cell-Free Nucleic Acids/genetics
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2024-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-23-0754
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Article ; Online: Author Correction: A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA.

Nature communications

2023 Volume 14, Issue 1, Page(s) 403

Language	English
Publishing date	2023-01-25
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-36187-8
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Article ; Online: Awareness about stroke among high and low risk individuals in Khartoum, Sudan

Ola Ahmed Abdulmjeed Mohammed / Fatima Abd Alraheem Osman Ahmed / Abubaker Emadeldin Adlan Koko / Sufian Elshafee Osman Khalifa / Hind Abdelaziz Mohamed Abdelaziz / Mohamed Elmojtaba Adil Mohamed / Francis Harrington / Sulaf Ibrahim Abdelaziz / Ihab Babiker Abdalrahman

The Pan African Medical Journal, Vol 36, Iss

a cross-sectional study

2020 Volume 318

Abstract: INTRODUCTION: Stroke causes 10.17% of all deaths in Sudan. Levels of stroke awareness amongst patients in Sudan are unknown. The aim of this study is to assess the level of awareness of stroke risk factors, symptoms and immediate management amongst high ... ...

Abstract	INTRODUCTION: Stroke causes 10.17% of all deaths in Sudan. Levels of stroke awareness amongst patients in Sudan are unknown. The aim of this study is to assess the level of awareness of stroke risk factors, symptoms and immediate management amongst high and low risk patients. METHODS: Using descriptive cross-sectional study, participants of high and low risk groups were recruited from the referral clinics of three tertiary hospitals in Khartoum. Data was collected through interviews using structured questionnaire. Knowledge score was devised to assess the awareness about stroke symptoms, risk factors, and management. RESULTS: Of the 286 participants, 150 were females. The mean age was 44.66 years. About 79.4% reported that stroke is preventable. Hypertension was the most identified risk factor (71.6%) while genetics (0.2%) and alcohol (0.2%) were the least identified risk factors. Twenty-seven percent (27.6%) did not know any stroke risk factors, while 32.9% did not know any warning symptoms. Paralysis of one side of the body was the most identified warning symptom (30.7%). The mean awareness score was 21.9± 3.4 among the high risk group vs. 22.1± 3.6 among the low risk group with no statistically significant difference between the two groups (p = .717). The mean awareness score was statistically associated with the level of education (p = 0.001). CONCLUSION: The awareness level was relatively low and not statistically different between high and low risk groups. We recommend the development of an effective educational program for the whole community.
Keywords	stroke ; awareness ; risk factors ; warning symptoms ; Medicine ; R
Subject code	150
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	The Pan African Medical Journal
Document type	Article ; Online
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Article ; Online: The Natural Occurrence, Weight and Length of the First and Second Adult Flight of the Wild Silkworm Epiphora Bauhiniae in Gedarif State, Sudan

Mohamedtom A.Eltayb, Talaat D. Abdel Magid and Adil Mohamed Ali Dirar

Journal of Forest Products and Industries, Vol 3, Iss 2, Pp 75-

2014 Volume 83

Abstract: This study was conducted in Gedarif town, Gedarif State, Sudan in (2012-2013). The objective was to test the hypothesis that, the wild silkworm Epiphora bauhiniae (Guerin-Meneville) has a great occurrence in its natural host Zizphus spina Christi trees, ... ...

Abstract	This study was conducted in Gedarif town, Gedarif State, Sudan in (2012-2013). The objective was to test the hypothesis that, the wild silkworm Epiphora bauhiniae (Guerin-Meneville) has a great occurrence in its natural host Zizphus spina Christi trees, which enable its cocoon to be collected outdoor, without distressing or disturbing the population dynamic of the insect. The study was conducted to determine the average number of the tree holding cocoons naturally and the average length and weight of the first and second flight of male and female moths. A field survey was carried out; it covered three localities viz, Showak, Galabat and Hawata in Gedarif state during the dry season 2012-2013. Four replicates were used, i.e. where 80 trees were selected per locality and cocoons holding per tree were recorded numerically in each locality. Data were recorded and analyzed. ANOVA was used for all replications in a randomized design. The study revealed that, the cocoons of E. bauhiniae, occurred naturally outdoors in a quantity suitable for commercial use, if managed in a careful manner. The average single tree holding of cocoons is significantly varied within trees and sites, it ranged from 90 to 150 cocoons per tree, which is estimated to give 180 to 300g of raw cocoons. The study proved that the first brood of the insect is lighter and shorter than the second ones, i.e. the analysis of variance showed a statistically significant (P<.0001) difference within sexes and flights. The study also revealed that, the potential of E. bauhiniae, as an important wild silkworm, to be a candidate as a commercial insect, for silk production in Sudan, because it is a bi-voltine racial (generate twice a year) beside that its products covers all quantitative and qualitative traits and accordingly this insect will have prominent concerns in the future. As sericulture activities in Sudan are quasi-absent, so these results will encourage sericulture industry, to enter this field in Sudan and consequently contribute in poverty alleviation and boost farmer income. This study claimed to be the first study that, shows the natural occurrence of E. bauhiniae in Sudan and open the door widely for the insect not to be placed out in the cold.
Keywords	Agriculture ; S ; Forestry ; SD1-669.5
Publishing date	2014-03-01T00:00:00Z
Document type	Article ; Online
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