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  1. Article ; Online: Disease patterns among Saudi children undergoing colonoscopy for lower gastrointestinal bleeding: Single tertiary care center experience.

    Alrashidi, Sami / AlAmery, Tarig / Alshanbary, Abdullah / Aljohani, Eman / Bashir, Salman M / Alsaleem, Bader / Asery, Ali / Al-Hussaini, Abdulrahman

    Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association

    2023  Volume 29, Issue 6, Page(s) 388–395

    Abstract: Background: : The yield of colonoscopy in cases presenting with lower gastrointestinal bleeding (LGIB) in previously published studies varies according to several factors, including endoscopic skills, histopathological experience, and pattern of colonic ...

    Abstract Background: : The yield of colonoscopy in cases presenting with lower gastrointestinal bleeding (LGIB) in previously published studies varies according to several factors, including endoscopic skills, histopathological experience, and pattern of colonic pathology in different countries. The local literature is limited to a single small 20-year-old study. Our objective was to provide updated data on the diagnostic yield of colonoscopy in Saudi children with LGIB in Saudi Arabia.
    Methods: : This was a retrospective analysis of pediatric patients (0-14 years of age) who underwent colonoscopy for LGIB at the King Fahad Medical City (KFMC), from 2008 to 2018. LGIB was defined as fresh or dark blood per rectum.
    Results: : During the study period, 175 children underwent colonoscopy for LGIB (99 males, mean age 7.05 ± 3.81 years), which constituted 53.5% of indications for colonoscopy procedures (n = 327) in our center. The terminal ileum was intubated in 81% of the procedures. Overall, inflammatory bowel disease (IBD) was the most commonly identified cause of LGIB (32% ) followed by colonic lymphonodular hyperplasia (CLNH) in 17% and juvenile polyp and rectal mucosal prolapse syndrome (RMPS), 11% each. On sub-analysis, cow's milk protein allergy (CMPA) and CLNH were the most common causes in infants and toddlers, 35% each; IBD (26.5%) and polyps (22.4%) in young children (2-6 years), and IBD (36%), CLNH (14.9%) and RMPS (14%) in older children (6-14 years). In comparing the IBD to the non-IBD group, IBD patients were older (mean 8.37 vs. 6.46 years, P = 0.002) and more likely to have diarrhea, weight loss, high erythrocyte sedimentation rate, anemia, and hypoalbuminemia (odds ratio 24, 11, 10.7, 6.5, and 4, respectively). Colonoscopy had a sensitivity of 97%, specificity of 100%, positive predictive value of 100%, negative predictive value of 81.4%, and accuracy of 97% in diagnosing LGIB.
    Conclusion: : Colonoscopy is an effective diagnostic tool in children with LGIB with a high diagnostic yield. Besides IBD, CLNH and RMPS are two other important pathologic entities that need to be considered in a child with LGIB.
    MeSH term(s) Male ; Infant ; Female ; Animals ; Cattle ; Humans ; Child ; Child, Preschool ; Young Adult ; Adult ; Retrospective Studies ; Saudi Arabia/epidemiology ; Tertiary Care Centers ; Gastrointestinal Hemorrhage/diagnosis ; Gastrointestinal Hemorrhage/epidemiology ; Gastrointestinal Hemorrhage/etiology ; Colonoscopy/adverse effects ; Colonoscopy/methods ; Inflammatory Bowel Diseases/complications
    Language English
    Publishing date 2023-09-13
    Publishing country India
    Document type Journal Article
    ZDB-ID 2299174-8
    ISSN 1998-4049 ; 1319-3767
    ISSN (online) 1998-4049
    ISSN 1319-3767
    DOI 10.4103/sjg.sjg_130_23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Topological Indices of Novel Drugs Used in Cardiovascular Disease Treatment and Its QSPR Modeling

    Fozia Bashir Farooq / Nadeem Ul Hassan Awan / Saima Parveen / Nazeran Idrees / Salma Kanwal / Tarig A. Abdelhaleem

    Journal of Chemistry, Vol

    2022  Volume 2022

    Abstract: A topological index is a score function that changes each molecular structure to a unique real number. It aids in determining the physicochemical and biological properties of a wide range of drugs, and it more accurately reflects the theoretical ... ...

    Abstract A topological index is a score function that changes each molecular structure to a unique real number. It aids in determining the physicochemical and biological properties of a wide range of drugs, and it more accurately reflects the theoretical properties of drugs. The task is accomplished through the use of degree-based topological indices (TIs). Heart disease refers to a group of disorders that affect our hearts. Heart diseases include blood vessel disorders such as irregular heartbeat and heart muscle disease. In this article, Eliquis, metoprolol, valsartan, etc., and other drugs employed to treat cardiovascular disease are studied and the QSPR analysis goal will probe the mathematical relationship of properties such as (polarity, boiling point, enthalpy, etc.) and assorted descriptors associated to drug’s structure. The present study on TIs imposed on drugs was found to have a good correlation with physical properties.
    Keywords Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Potential Therapeutic Target and Vaccines for SARS-CoV-2.

    Hussain, Mohamed A / Hassan, Mohamed M / Bashir, Bashir Abdrhman / Gamar, Tarig A / Gasmalbari, Elmuaiz / Mohamed, Ahmed Osman / Osman, Wadah / Sherif, Asmaa E / Elgaml, Abdelaziz / Alhaddad, Aisha A / Ghazawi, Kholoud F / Miski, Samar F / Ainousah, Bayan E / Andijani, Yusra Saleh / Ibrahim, Sabrin R M / Mohamed, Gamal A / Ashour, Ahmed

    Pathogens (Basel, Switzerland)

    2023  Volume 12, Issue 7

    Abstract: The coronavirus has become the most interesting virus for scientists because of the recently emerging deadly SARS-CoV-2. This study aimed to understand the behavior of SARS-CoV-2 through the comparative genomic analysis with the closest one among the ... ...

    Abstract The coronavirus has become the most interesting virus for scientists because of the recently emerging deadly SARS-CoV-2. This study aimed to understand the behavior of SARS-CoV-2 through the comparative genomic analysis with the closest one among the seven species of coronavirus that infect humans. The genomes of coronavirus species that infect humans were retrieved from NCBI, and then subjected to comparative genomic analysis using different bioinformatics tools. The study revealed that SARS-CoV-2 is the most similar to SARS-CoV among the coronavirus species. The core genes were shared by the two genomes, but there were some genes, found in one of them but not in both, such as ORF8, which is found in SARS-CoV-2. The ORF8 protein of SARS-CoV-2 could be considered as a good therapeutic target for stopping viral transmission, as it was predicted to be a transmembrane protein, which is responsible for interspecies transmission. This is supported by the molecular interaction of ORF8 with both the ORF7 protein, which contains a transmembrane domain that is essential to retaining the protein in the Golgi compartment, and the S protein, which facilitates the entry of the coronavirus into host cells. ORF1ab, ORF1a, ORF8, and S proteins of SARS-CoV-2 could be immunogenic and capable of evoking an immune response, which means that these four proteins could be considered a potential vaccine source. Overall, SARS-CoV-2 is most related to SARS-CoV. ORF8 could be considered a potential therapeutic target for stopping viral transmission, and ORF1ab, ORF1a, ORF8, and the S proteins of SARS-CoV-2 could be utilized as a potential vaccine source.
    Language English
    Publishing date 2023-07-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens12070926
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: External Validation and Recalibration of the CURB-65 and PSI for Predicting 30-Day Mortality and Critical Care Intervention in Multiethnic Patients with COVID-19.

    Elmoheen, Amr / Abdelhafez, Ibrahim / Salem, Waleed / Bahgat, Mohamed / Elkandow, Ali / Tarig, Amina / Arshad, Nauman / Mohamed, Khoulod / Al-Hitmi, Maryam / Saad, Mona / Emam, Fatima / Taha, Samah / Bashir, Khalid / Azad, Aftab

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

    2021  Volume 111, Page(s) 108–116

    Abstract: Objectives: To validate and recalibrate the CURB-65 and pneumonia severity index (PSI) in predicting 30-day mortality and critical care intervention (CCI) in a multiethnic population with COVID-19, along with evaluating both models in predicting CCI.: ...

    Abstract Objectives: To validate and recalibrate the CURB-65 and pneumonia severity index (PSI) in predicting 30-day mortality and critical care intervention (CCI) in a multiethnic population with COVID-19, along with evaluating both models in predicting CCI.
    Methods: Retrospective data was collected for 1181 patients admitted to the largest hospital in Qatar with COVID-19 pneumonia. The area under the curve (AUC), calibration curves, and other metrics were bootstrapped to examine the performance of the models. Variables constituting the CURB-65 and PSI scores underwent further analysis using the Least Absolute Shrinkage and Selection Operator (LASSO) along with logistic regression to develop a model predicting CCI. Complex machine learning models were built for comparative analysis.
    Results: The PSI performed better than CURB-65 in predicting 30-day mortality (AUC 0.83, 0.78 respectively), while CURB-65 outperformed PSI in predicting CCI (AUC 0.78, 0.70 respectively). The modified PSI/CURB-65 model (respiratory rate, oxygen saturation, hematocrit, age, sodium, and glucose) predicting CCI had excellent accuracy (AUC 0.823) and good calibration.
    Conclusions: Our study recalibrated, externally validated the PSI and CURB-65 for predicting 30-day mortality and CCI, and developed a model for predicting CCI. Our tool can potentially guide clinicians in Qatar to stratify patients with COVID-19 pneumonia.
    MeSH term(s) COVID-19 ; Community-Acquired Infections ; Critical Care ; Hospital Mortality ; Humans ; Pneumonia/diagnosis ; Pneumonia/therapy ; Prognosis ; Retrospective Studies ; SARS-CoV-2 ; Severity of Illness Index
    Language English
    Publishing date 2021-08-18
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 1331197-9
    ISSN 1878-3511 ; 1201-9712
    ISSN (online) 1878-3511
    ISSN 1201-9712
    DOI 10.1016/j.ijid.2021.08.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Identification of Two Non-Peptidergic Small Molecule Inhibitors of CBX2 Binding to K27 Trimethylated Oligonucleosomes.

    Lercher, Lukas / Simon, Nina / Bergmann, Andreas / Tauchert, Marcel / Bochmann, David / Bashir, Tarig / Neuefeind, Torsten / Riley, Daniel / Danna, Ben / Krawczuk, Paul / Pande, Vineet / Patrick, Aaron / Steele, Ruth / Wang, Weixue / Rupnow, Brent / Tummino, Peter / Sharma, Sujata / Finley, Michael

    SLAS discovery : advancing life sciences R & D

    2022  Volume 27, Issue 5, Page(s) 306–313

    Abstract: The dysregulation of the PRC1/2 complex plays a key role in lineage plasticity in prostate cancer and may be required to maintain neuroendocrine phenotype. [1] CBX2, a key component of the canonical PRC1 complex, is an epigenetic reader, recognizing ... ...

    Abstract The dysregulation of the PRC1/2 complex plays a key role in lineage plasticity in prostate cancer and may be required to maintain neuroendocrine phenotype. [1] CBX2, a key component of the canonical PRC1 complex, is an epigenetic reader, recognizing trimethylated lysine on histone 3 (H3K27me3) [2] and is overexpressed in metastatic neuroendocrine prostate cancer. [3,4] We implemented a screening strategy using nucleosome substrates to identify inhibitors of CBX2 binding to chromatin. Construct design and phosphorylation state of CBX2 were critical for successful implementation and execution of an HTS library screen. A rigorous screening funnel including counter and selectivity assays allowed us to quickly focus on true positive hit matter. Two distinct non-peptide-like chemotypes were identified and confirmed in orthogonal biochemical and biophysical assays demonstrating disruption of CBX2 binding to nucleosomes and direct binding to purified CBX2, respectively.
    MeSH term(s) Cell Nucleus/metabolism ; Chromatin ; Histones/metabolism ; Humans ; Male ; Polycomb Repressive Complex 1/genetics ; Prostatic Neoplasms/metabolism
    Chemical Substances CBX2 protein, human ; Chromatin ; Histones ; Polycomb Repressive Complex 1 (EC 2.3.2.27)
    Language English
    Publishing date 2022-05-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1016/j.slasd.2022.04.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Identification of Two Non-Peptidergic Small Molecule Inhibitors of CBX2 Binding to K27 Trimethylated Oligonucleosomes

    Lukas Lercher / Nina Simon / Andreas Bergmann / Marcel Tauchert / David Bochmann / Tarig Bashir / Torsten Neuefeind / Daniel Riley / Ben Danna / Paul Krawczuk / Vineet Pande / Aaron Patrick / Ruth Steele / Weixue Wang / Brent Rupnow / Peter Tummino / Sujata Sharma / Michael Finley

    SLAS Discovery, Vol 27, Iss 5, Pp 306-

    2022  Volume 313

    Abstract: The dysregulation of the PRC1/2 complex plays a key role in lineage plasticity in prostate cancer and may be required to maintain neuroendocrine phenotype. [1] CBX2, a key component of the canonical PRC1 complex, is an epigenetic reader, recognizing ... ...

    Abstract The dysregulation of the PRC1/2 complex plays a key role in lineage plasticity in prostate cancer and may be required to maintain neuroendocrine phenotype. [1] CBX2, a key component of the canonical PRC1 complex, is an epigenetic reader, recognizing trimethylated lysine on histone 3 (H3K27me3) [2] and is overexpressed in metastatic neuroendocrine prostate cancer. [3,4] We implemented a screening strategy using nucleosome substrates to identify inhibitors of CBX2 binding to chromatin. Construct design and phosphorylation state of CBX2 were critical for successful implementation and execution of an HTS library screen. A rigorous screening funnel including counter and selectivity assays allowed us to quickly focus on true positive hit matter. Two distinct non-peptide-like chemotypes were identified and confirmed in orthogonal biochemical and biophysical assays demonstrating disruption of CBX2 binding to nucleosomes and direct binding to purified CBX2, respectively.
    Keywords Medicine (General) ; R5-920 ; Biotechnology ; TP248.13-248.65
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Structural insights reveal a recognition feature for tailoring hydrocarbon stapled-peptides against the eukaryotic translation initiation factor 4E protein.

    Lama, Dilraj / Liberatore, Anne-Marie / Frosi, Yuri / Nakhle, Jessica / Tsomaia, Natia / Bashir, Tarig / Lane, David P / Brown, Christopher J / Verma, Chandra S / Auvin, Serge

    Chemical science

    2019  Volume 10, Issue 8, Page(s) 2489–2500

    Abstract: Stapled-peptides have emerged as an exciting class of molecules which can modulate protein-protein interactions. We have used a structure-guided approach to rationally develop a set of hydrocarbon stapled-peptides with high binding affinities and ... ...

    Abstract Stapled-peptides have emerged as an exciting class of molecules which can modulate protein-protein interactions. We have used a structure-guided approach to rationally develop a set of hydrocarbon stapled-peptides with high binding affinities and residence times against the oncogenic eukaryotic translation initiation factor 4E (eIF4E) protein. Crystal structures of these peptides in complex with eIF4E show that they form specific interactions with a region on the protein-binding interface of eIF4E which is distinct from the other well-established canonical interactions. This recognition element is a major molecular determinant underlying the improved binding kinetics of these peptides with eIF4E. The interactions were further exploited by designing features in the peptides to attenuate disorder and increase helicity which collectively resulted in the generation of a distinct class of hydrocarbon stapled-peptides targeting eIF4E. This study details new insights into the molecular basis of stapled-peptide: eIF4E interactions and their exploitation to enhance promising lead molecules for the development of stapled-peptide compounds for oncology.
    Language English
    Publishing date 2019-01-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2559110-1
    ISSN 2041-6539 ; 2041-6520
    ISSN (online) 2041-6539
    ISSN 2041-6520
    DOI 10.1039/c8sc03759k
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Correction: MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage tolerance in proliferating cancer cells.

    Beke, Lijs / Kig, Cenk / Linders, Joannes T M / Boens, Shannah / Boeckx, An / van Heerde, Erika / Parade, Marc / De Bondt, An / Van den Wyngaert, Ilse / Bashir, Tarig / Ogata, Souichi / Meerpoel, Lieven / Van Eynde, Aleyde / Johnson, Christopher N / Beullens, Monique / Brehmer, Dirk / Bollen, Mathieu

    Bioscience reports

    2018  Volume 38, Issue 6

    Language English
    Publishing date 2018-11-30
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 764946-0
    ISSN 1573-4935 ; 0144-8463
    ISSN (online) 1573-4935
    ISSN 0144-8463
    DOI 10.1042/BSR-20150194_COR
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cells.

    Auvin, Serge / Öztürk, Harun / Abaci, Yusuf T / Mautino, Gisele / Meyer-Losic, Florence / Jollivet, Florence / Bashir, Tarig / de Thé, Hugues / Sahin, Umut

    Life science alliance

    2019  Volume 2, Issue 4

    Abstract: Aberrant androgen signaling drives prostate cancer and is targeted by drugs that diminish androgen production or impede androgen-androgen receptor (AR) interaction. Clinical resistance arises from AR overexpression or ligand-independent constitutive ... ...

    Abstract Aberrant androgen signaling drives prostate cancer and is targeted by drugs that diminish androgen production or impede androgen-androgen receptor (AR) interaction. Clinical resistance arises from AR overexpression or ligand-independent constitutive activation, suggesting that complete AR elimination could be a novel therapeutic strategy in prostate cancers. IRC117539 is a new molecule that targets AR for proteasomal degradation. Exposure to IRC117539 promotes AR sumoylation and ubiquitination, reminiscent of therapy-induced PML/RARA degradation in acute promyelocytic leukemia. Critically, ex vivo, IRC117539-mediated AR degradation induces prostate cancer cell viability loss by inhibiting AR signaling, even in androgen-insensitive cells. This approach may be beneficial for castration-resistant prostate cancer, which remains a clinical issue. In xenograft models, IRC117539 is as potent as enzalutamide in impeding growth, albeit less efficient than expected from ex vivo studies. Unexpectedly, IRC117539 also behaves as a weak proteasome inhibitor, likely explaining its suboptimal efficacy in vivo. Our studies highlight the feasibility of AR targeting for degradation and off-target effects' importance in modulating drug activity in vivo.
    MeSH term(s) Androgen Antagonists/metabolism ; Androgen Receptor Antagonists/metabolism ; Androgen Receptor Antagonists/pharmacology ; Androgens/metabolism ; Animals ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Prostate/metabolism ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/metabolism ; Receptors, Androgen/metabolism ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays
    Chemical Substances Androgen Antagonists ; Androgen Receptor Antagonists ; Androgens ; Receptors, Androgen
    Language English
    Publishing date 2019-08-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.201800213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Cdk1: the dominant sibling of Cdk2.

    Bashir, Tarig / Pagano, Michele

    Nature cell biology

    2005  Volume 7, Issue 8, Page(s) 779–781

    MeSH term(s) Animals ; CDC2 Protein Kinase/metabolism ; CDC2-CDC28 Kinases/genetics ; CDC2-CDC28 Kinases/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; G1 Phase/physiology ; Interphase/physiology ; Mice ; Mice, Knockout ; Mitosis/physiology ; S Phase/physiology ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
    Chemical Substances Cdkn1a protein, mouse ; Cdkn1b protein, mouse ; Cell Cycle Proteins ; Cyclin-Dependent Kinase Inhibitor p21 ; Tumor Suppressor Proteins ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; CDC2 Protein Kinase (EC 2.7.11.22) ; CDC2-CDC28 Kinases (EC 2.7.11.22) ; Cdk2 protein, mouse (EC 2.7.11.22) ; Cyclin-Dependent Kinase 2 (EC 2.7.11.22)
    Language English
    Publishing date 2005-08
    Publishing country England
    Document type Comment ; News
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/ncb0805-779
    Database MEDical Literature Analysis and Retrieval System OnLINE

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