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  • 1
    Online Resource
    Online Resource
    Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries
    Elsevier BV ; 2022
    In:  The Lancet Vol. 400, No. 10363 ( 2022-11), p. 1607-1617
    Details
    In: The Lancet, Elsevier BV, Vol. 400, No. 10363 ( 2022-11), p. 1607-1617
    Type of Medium: Online Resource
    ISSN: 0140-6736
    URL: Article
    DOI: 10.1016/S0140-6736(22)01846-3
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 2
    Online Resource
    Online Resource
    PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK
    Oxford University Press (OUP) ; 2023
    In:  BJS Open Vol. 7, No. 3 ( 2023-05-05)
    Details
    In: BJS Open, Oxford University Press (OUP), Vol. 7, No. 3 ( 2023-05-05)
    Abstract: Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions.
    Type of Medium: Online Resource
    ISSN: 2474-9842
    URL: Article
    DOI: 10.1093/bjsopen/zrad008
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2902033-5
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  • 3
    Online Resource
    Online Resource
    Whole-genome sequencing reveals host factors underlying critical COVID-19
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 607, No. 7917 ( 2022-07-07), p. 97-103
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 607, No. 7917 ( 2022-07-07), p. 97-103
    Abstract: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care 1 or hospitalization 2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling ( IL10RB and PLSCR1 ), leucocyte differentiation ( BCL11A ) and blood-type antigen secretor status ( FUT2 ). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase ( ATP11A ), and increased expression of a mucin ( MUC1 )—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules ( SELE , ICAM5 and CD209 ) and the coagulation factor F8 , all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-04576-6
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 4
    Online Resource
    Online Resource
    Epidermal growth factor receptor expression as a molecular determinant of glioblastoma response to the dopamine receptor D2 antagonist, ONC201.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e14552-e14552
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e14552-e14552
    Abstract: e14552 Background: Durable response in glioblastoma patients have been reported in phase I/II clinical trials for the blood-brain penetrant dopamine receptor D2 (DRD2) antagonist, ONC201. Here we examine potential molecular determinants of response to DRD2 inhibition. Methods: The Cancer Genome Atlas (TCGA) glioblastoma database and other published mRNA profiles were used to analyze the DRD2 expression pattern. In vitro and in vivo responses to ONC201 were determined using patient derived xenograft glioblastoma models. Immunohistochemical studies were performed on clinically annotated glioblastoma samples derived from phase I/II clinical trials involving ONC201. Results: For the majority of clinical glioblastoma specimens in both the TCGA and non-TCGA dataset, epidermal growth factor receptor (EGFR) expression was inversely correlated with DRD2. This observation was recapitulated in a panel of patient-derived glioblastoma lines. In this panel of DRD2 expressing lines, high EGFR expression was associated with poor response to ONC201 in vitro and in vivo. Moreover, ectopic expression of EGFR reduced DRD2 expression and ONC201 sensitivity, suggesting functional redundancy between DRD2 and EGFR. In cell lines and clinical glioblastoma samples, DRD2 expression closely associated with the expression of rate-limiting enzymes for dopamine synthesis, suggesting dependency of a subset of glioblastomas on autocrine DRD2 signaling. Analysis of specimens from patients treated with ONC201 (n = 15) showed an inverse correlation between the intensity of EGFR staining and clinical response. The median overall survival for patients with high and low EGFR staining was 162 and 373 days, respectively (p = 0.037). All patients who exhibited progression free survival beyond 200 days showed low to no EGFR expression. Conclusions: Our results suggest EGFR expression as a determinant of response to ONC201 in glioblastoma patients and should inform the design of future clinical trials.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e14552
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells
    IOS Press ; 2017
    In:  Tumor Biology Vol. 39, No. 3 ( 2017-03), p. 101042831769502-
    Details
    In: Tumor Biology, IOS Press, Vol. 39, No. 3 ( 2017-03), p. 101042831769502-
    Abstract: Despite an overall good prognosis, a significant proportion of patients with hormone receptor positive human epidermal growth factor receptor 2 negative breast cancers develop distant metastases. The metastatic potential of epithelial cells is known to be regulated by tumor–stromal interaction and mediated by epithelial-to-mesenchymal transition. Hormone receptor positive human epidermal growth factor receptor 2 negative tumors were used to estimate markers of epithelial-to-mesenchymal transition, and the luminal breast cancer cell line MCF-7 was used to examine the interactions between integrins and growth factor receptors in causation of epithelial-to-mesenchymal transition. A total of 140 primary tumors were sub-divided into groups enriched for the markers of epithelial-to-mesenchymal transition (snail family transcriptional repressor 2 and integrin β6) versus those with low levels. Within the epithelial-to-mesenchymal transition+ tumors, there was a positive correlation between the transcripts of integrin β6 and growth factor receptors—human epidermal growth factor receptor 2 and epidermal growth factor receptor. In tumors enriched for epithelial-to-mesenchymal transition markers, patients with tumors with the highest quartile of growth factor receptor transcripts had a shorter disease-free survival compared to patients with low growth factor receptor expression by Kaplan–Meier analysis (log rank, p = 0.03). Epithelial-to-mesenchymal transition was induced in MCF-7 cells by treatment with transforming growth factor beta 1 and confirmed by upregulation of SNAI1 and SNAI2 transcripts, increase of vimentin and integrin β6 protein, and repression of E-cadherin. Treatment of these cells with the dual-specificity tyrosine-kinase inhibitor lapatinib led to downregulation of epithelial-to-mesenchymal transition as indicated by lower levels of SNAI1 and SNAI2 transcripts, integrin αvβ6, and matrix metalloproteinase 9 protein. The results suggest that synergistic interactions between growth factor receptors and integrin β6 could mediate epithelial-to-mesenchymal transition and migration in a subset of luminal breast cancers and lapatinib might be effective in disrupting this interaction.
    Type of Medium: Online Resource
    ISSN: 1010-4283 , 1423-0380
    URL: Article
    DOI: 10.1177/1010428317695028
    Language: English
    Publisher: IOS Press
    Publication Date: 2017
    detail.hit.zdb_id: 605825-5
    detail.hit.zdb_id: 1483579-4
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    ONC201 and imipridones: Anti-cancer compounds with clinical efficacy
    Elsevier BV ; 2020
    In:  Neoplasia Vol. 22, No. 12 ( 2020-12), p. 725-744
    Details
    In: Neoplasia, Elsevier BV, Vol. 22, No. 12 ( 2020-12), p. 725-744
    Type of Medium: Online Resource
    ISSN: 1476-5586
    URL: Article
    DOI: 10.1016/j.neo.2020.09.005
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2008231-9
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  • 7
    Online Resource
    Online Resource
    Utility of Neutrophil-Lymphocyte Ratio (NLR) as an Indicator of Disease Severity and Prognostic Marker among Patients with Covid-19 Infection in a Tertiary Care Centre in Bangalore – A Retrospective Study
    Level Up Business Center ; 2021
    In:  Journal of Evidence Based Medicine and Healthcare Vol. 8, No. 16 ( 2021-04-19), p. 1020-1024
    Details
    In: Journal of Evidence Based Medicine and Healthcare, Level Up Business Center, Vol. 8, No. 16 ( 2021-04-19), p. 1020-1024
    Abstract: BACKGROUND The infection caused due to novel coronavirus 2 can cause wide spectrum of disease from asymptomatic mild disease to life threatening disease. The widespread inflammation is most likely the cause of the adverse outcomes. There are numerous markers of the inflammation which are used to identify the severity and prognosis of the disease. Neutrophil lymphocyte ratio (NLR) is one such marker which is easily available and feasible in all the hospital settings. This study intended to evaluate the NLR as a marker of disease severity and prognosis, in those with Covid-19. METHODS This was a retrospective study to determine the utility of NLR as a marker of severity and prognosis among patients with Covid disease. Medical records of 60 patients admitted with mild to moderate Covid-19 disease were reviewed and relevant data was retrieved. The NLR at admission and 72 hours later was noted. High resolution computerised tomography was done and computerised tomography severity score (CT-SS) was calculated. The outcomes of these patients were noted. RESULTS Mean NLR at admission in mild disease was 5.6 and in moderate disease was 9.2. This difference was found to be statistically significant. It was also seen that NLR had a positive co-relation with CT severity score, duration of hospital stay, Creactive protein (CRP) and D-dimer. For predicting mortality, NLR with cut off of 6.6 had a sensitivity of 100 % and a specificity of 66.07 %. CRP with cut off of 6.8 had sensitivity of 100 %, specificity of 76.79 %. D-dimer with cut off of 1.6 had specificity of 78.58 %. For predicting severity, NLR with cut off of 6.6 had sensitivity of 75 % and specificity of 80 %. CRP with cut off of 7.9 had sensitivity of 65 % and specificity of 100 %. D-dimer with cut off of 1.3, had sensitivity of 90 % and specificity of 97.5 %. CONCLUSIONS The study shows that neutrophil–lymphocyte ratio is a good indicator of disease severity and has prognostic significance in Covid-19. There is a positive correlation with high-resolution computed tomography (HRCT) chest score and other markers of inflammation among patients with Covid-19. Serial monitoring of NLR can be utilised as a surrogate to HRCT chest to determine disease severity whenever the latter is not available. This can ensure early intervention and help prevent mortality. KEYWORDS Neutrophil-Lymphocyte Ratio, Severity of Covid
    Type of Medium: Online Resource
    ISSN: 2349-2562 , 2349-2570
    Uniform Title: English
    URL: Journal
    URL: Article
    DOI: 10.18410/jebmh
    DOI: 10.18410/jebmh/2021/197
    Language: Unknown
    Publisher: Level Up Business Center
    Publication Date: 2021
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  • 8
    Online Resource
    Online Resource
    Potent Anti-Leukemic Effects of Small Molecule ONC212, a Member of the Imipridone Class of Anti-Cancer Compounds
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 5133-5133
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5133-5133
    Abstract: ONC201, the founding member of the imipridone class of anti-cancer compounds, is a highly selective small molecule GPCR antagonist that is in Phase I/II advanced cancer clinical trials. In this study, we evaluated the anti-cancer effects of ONC212, an ONC201 analogue that possess the same unique core chemical structure shared by imipridones. The in vitro efficacy of ONC212 was assessed in the Genomics of Drug Sensitivity in Cancer collection of cell lines ( 〉 1,000 cell lines). Cell viability assays were performed to generate dose responses curves at concentrations from 78nM upto 20uM and at 72 hours post-treatment. ONC212 was broadly efficacious across most solid tumors and hematological malignancies in the low nanomolar range. Ranking the ONC212 sensitivity dataset revealed that leukemia is the most responsive tumor type based on completeness of response (area under the dose-response curve, AUC). ONC212 was tested in 65 leukemia cell lines in this study that is comprised of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML) and hairy cell leukemia. ONC212 demonstrated broad spectrum anti-leukemic activity and was equally efficacious across all leukemia subtypes tested, in terms of AUC. Most cell lines (63/65) were responsive to ONC212 with GI50 ranging from 〈 78nM to 312nM. Within ALL, both B-cell and T-cell ALL were highly sensitive to ONC212. ONC212 reduced cell viability in AML independent of complex karyotypes that are associated with poor clinical prognoses. Thus, ONC212 possesses robust anti-leukemic activity irrespective of subtype and provides further validation of the anti-cancer efficacy of the novel imipridone class of small molecules. Disclosures Prabhu: Oncoceutics: Employment. Tarapore:Oncoceutics: Employment, Equity Ownership. El-Deiry:Oncoceutics: Equity Ownership. Stogniew:Oncoceutics Inc.: Employment, Equity Ownership. Oster:Oncoceutics: Employment, Equity Ownership. Allen:Oncoceutics: Employment, Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.5133.5133
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    Online Resource
    Online Resource
    Screen of Small Molecule ONC201/TIC10 Identifies Single Agent Activity and Combinatorial Efficacy with Bortezomib, Rituximab or Dexamethasone in Killing of Acute Lymphoblastic Leukemia Cells
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 5233-5233
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5233-5233
    Abstract: The antitumor protein recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anticancer therapy although it has notable shortcomings that have limited its clinical development. Our lab previously identified a novel use for TRAIL-inducing compound 10 (ONC201/TIC10) as an efficacious antitumor therapeutic that induces TRAIL pathway activation through dual blockade of Akt and ERK that releases Foxo3a to transcriptionally activate the TRAIL and its death receptor DR5 genes. ONC201/TIC10 is being developed by Oncoceutics for the clinical therapy of cancer. Acute lymphoblastic leukemia (ALL) is a heterogeneous disease with an increasing rate of refractory/relapsed population of patients, making it a challenging disease to treat. Therefore, new therapeutic options as single dose or combinational treatments are required. Therapeutic agonist TRAIL antibodies have been investigated as a therapy for solid tumors; however, the biologic agents have not been explored extensively as a potential single or combinational therapy for the treatment of ALL. The aim of this study was to begin to characterize ONC201/TIC10 as a single agent for ALL therapy and in combination with bortezomib to increase induction of tumor cell death. Single agent ONC201/TIC10 decreased ALL cell viability at IC50 values ranging from 2.5-5 µM after a 48 hour treatment. ONC201/TIC10 was combined with various accepted clinical treatments of ALL to determine if a synergistic or additive effect exists. Treatments of compounds at doses below their IC50, including the proteasome inhibitor bortezomib and monoclonal antibody-based rituximab therapy, showed synergistic or additive anti-leukemic effects when treated mutually with ONC201/TIC10 in ALL and T-cell ALL. TRAIL and Foxo3a expression was monitored by western blot analysis and apoptosis was indicated by both subG1 and caspase activity to investigate the effect of these combination treatments. Bortezomib-ONC201/TIC10 combinational treatments decreased cell viability by approximately 30% in MALT-4 cells and 20% in Jurkat compared to single dose bortezomib treatments. Rituximab and the steroid compound dexamethasone were administered both below their IC50 in combination with ONC201/TIC10 and exhibited 20-40% cell viability decrease in ALL in vitro beyond the monoagent effects. Pharmacological enhancement by the addition of ONC201/TIC10 increased apoptotic efficacy and significantly decreased cell viability during combination treatments as compared to single agent therapy. The formation of the TRAIL death-inducing signaling complex could provide a rationale for further investigation into ONC201/TIC10 combinational treatment in ALL. These preclinical results suggest that there may be a clinical therapeutic advantage to modifying current ALL patient therapies to include the addition of ONC201/TIC10. Disclosures Allen: Oncoceutics, Inc.: Employment, Equity Ownership, Patents & Royalties. El-Deiry:Oncoceutics, Inc.: Equity Ownership, Patents & Royalties.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.5233.5233
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    Online Resource
    Online Resource
    HOG Neural Network Based Student Attendance System
    ISROSET: International Scientific Research Organization for Science, Engineering and Technology ; 2019
    In:  International Journal of Computer Sciences and Engineering Vol. 7, No. 5 ( 2019-05-31), p. 1701-1705
    Details
    In: International Journal of Computer Sciences and Engineering, ISROSET: International Scientific Research Organization for Science, Engineering and Technology, Vol. 7, No. 5 ( 2019-05-31), p. 1701-1705
    Type of Medium: Online Resource
    ISSN: 2347-2693
    URL: Journal
    URL: Article
    DOI: 10.26438/ijcse
    DOI: 10.26438/ijcse/v7i5.17011705
    Language: Unknown
    Publisher: ISROSET: International Scientific Research Organization for Science, Engineering and Technology
    Publication Date: 2019
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