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  • 1
    Language: English
    In: BMJ open, 2020-10-21, Vol.10 (10), p.e038161-e038161
    Description: ObjectiveConcussions are the most frequent traumatic brain injuries. Yet, the socioeconomic impact of concussions remains unclear. Socioeconomic effects of concussions on working-age adults were studied on a population scale.DesignThis population-based, event time study uses administrative data as well as hospital and emergency room records for the population of Denmark.SettingWe study all Danish patients, aged 20–59 years, who were treated at a public hospital or at an emergency room between 2003 and 2017 after suffering a concussion without other intracranial or extracranial injuries (n=55 424 unique individuals). None of the patients had a prior diagnosis of intracranial or extracranial injuries within the past 10 years leading up to the incident.Primary and secondary outcome measuresAs primary endpoint, we investigate the mean effect of concussion on annual salaried income within a 5-year period after trauma. In an exploratory analysis, we study whether the potential impact of concussion on annual salaried income is driven by patient age, education or economic cycle.ResultsConcussion was associated with an average change in annual salary income of −€1223 (95% CI: −€1540 to −905, p〈0.001) corresponding to a salary change of −4.2% (95% CI: −5.2% to −3.1 %). People between 30 and 39 years and those without high school degrees suffered the largest salary decreases. Affected individuals leaving the workforce drove the main part of the decrease. Absolute annual effect sizes were countercyclical to the unemployment rate.ConclusionsConcussions have a large and long-lasting impact on salary and employment of working-age adults on a nationwide scale.
    Subject(s): Adult ; Age ; Athletic Injuries ; Bias ; Brain Concussion - epidemiology ; Concussion ; Emergency medical care ; Employment ; Humans ; Labor market ; Middle Aged ; Patients ; Productivity ; Research Design ; Salaries and Fringe Benefits ; Samhällsvetenskap ; Social Sciences ; Sociologi ; Sociology ; Time and Motion Studies ; Trends ; Young Adult
    ISSN: 2044-6055
    E-ISSN: 2044-6055
    Source: HighWire Press (Free Journals)
    Source: PubMed Central
    Source: SWEPUB Freely available online
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  • 2
    Language: English
    In: Clinical cancer research, 2008-01-01, Vol.14 (1), p.123-129
    Description: Purpose: The CD133 antigen has been identified as a putative stem cell marker in normal and malignant brain tissues. In gliomas, it is used to enrich a subpopulation of highly tumorigenic cancer cells. According to the cancer stem cell hypothesis, CD133-positive cells determine long-term tumor growth and, therefore, are suspected to influence clinical outcome. To date, a correlation between CD133 expression in primary tumor tissues and patients' prognosis has not been reported. Experimental Design: To address this question, we analyzed the expression of the CD133 stem cell antigen in a series of 95 gliomas of various grade and histology by immunohistochemistry on cryostat sections. Staining data were correlated with patient outcome. Results: By multivariate survival analysis, we found that both the proportion of CD133-positive cells and their topological organization in clusters were significant ( P 〈 0.001) prognostic factors for adverse progression-free survival and overall survival independent of tumor grade, extent of resection, or patient age. Furthermore, proportion of CD133-positive cells was an independent risk factor for tumor regrowth and time to malignant progression in WHO grade 2 and 3 tumors. Conclusions: These findings constitute the first conclusive evidence that CD133 stem cell antigen expression correlates with patient survival in gliomas, lending support to the current cancer stem cell hypothesis.
    Subject(s): AC133 Antigen ; Adult ; Antigens, CD - biosynthesis ; Antineoplastic agents ; Biological and medical sciences ; Brain Neoplasms - metabolism ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; CD133 ; Disease-Free Survival ; Female ; glioma ; Glioma - metabolism ; Glioma - mortality ; Glioma - pathology ; Glycoproteins - biosynthesis ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Medical sciences ; Middle Aged ; Neurology ; Peptides ; Pharmacology. Drug treatments ; Prognosis ; stem cells ; Stem Cells - metabolism ; Survival Analysis ; Tumors of the nervous system. Phacomatoses
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 3
    Language: English
    In: Nature medicine, 2013-07, Vol.19 (7), p.901-908
    Description: Here we show that glioblastoma express high levels of branched-chain amino acid transaminase 1 (BCAT1), the enzyme that initiates the catabolism of branched-chain amino acids (BCAAs). Expression of BCAT1 was exclusive to tumors carrying wild-type isocitrate dehydrogenase 1 (IDH1) and IDH2 genes and was highly correlated with methylation patterns in the BCAT1 promoter region. BCAT1 expression was dependent on the concentration of α-ketoglutarate substrate in glioma cell lines and could be suppressed by ectopic overexpression of mutant IDH1 in immortalized human astrocytes, providing a link between IDH1 function and BCAT1 expression. Suppression of BCAT1 in glioma cell lines blocked the excretion of glutamate and led to reduced proliferation and invasiveness in vitro, as well as significant decreases in tumor growth in a glioblastoma xenograft model. These findings suggest a central role for BCAT1 in glioma pathogenesis, making BCAT1 and BCAA metabolism attractive targets for the development of targeted therapeutic approaches to treat patients with glioblastoma.
    Subject(s): Amino acid metabolism ; Amino Acids, Branched-Chain - metabolism ; Animals ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Care and treatment ; Cell Line, Tumor ; Cell Proliferation ; Female ; Genetic aspects ; Glioma - genetics ; Glioma - metabolism ; Glioma - pathology ; Gliomas ; HEK293 Cells ; Humans ; Isocitrate Dehydrogenase - genetics ; Isocitrate Dehydrogenase - physiology ; Metabolism - genetics ; Methylation ; Mice ; Mice, Nude ; Models, Biological ; Physiological aspects ; Research ; Transaminases - genetics ; Transaminases - metabolism ; Transaminases - physiology
    ISSN: 1078-8956
    E-ISSN: 1546-170X
    Source: Single Journals
    Source: Academic Search Ultimate
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  • 4
    Language: English
    In: Neuromodulation (Malden, Mass.), 2021-04, Vol.24 (3), p.591-595
    Description: Objectives A new wireless spinal cord stimulation (SCS) technology, which was introduced in recent years, promises minimal invasive SCS as well as additional advantages such as a wide range of stimulation paradigms and 3‐T magnetic resonance imaging (MRI) conditionality. Materials and Methods We prospectively evaluated 12 patients suffering from therapy‐resistant neuropathic pain, who were implanted with a wireless SCS system from 2017 to 2019. Potential issues pertaining to handling and usability of the SCS device were evaluated from a patients' as well as from a surgeon's perspective. Results Mean follow‐up was 228.0 days (95% CI, 20.0–518.0 days). We did not record any handling issues nor did we record any relevant local discomfort associated with the implanted SCS device. N = 3/12 patients reported discomfort from wearing the SCS antenna and one patient complained about a short battery life of the controller device. There were no reported incidents during 3‐T MRI studies. After an average test period of 51.7 days (95% CI, 11.0–104.0 days), N = 9/12 patients (75%) had reached pain relief of 50% or more with an average pain relief (responders and partial responders) of 67.4% (95% CI, 50.0%–85.0%). On average, patients tested 2.2 different stimulation paradigms, with frequencies ranging from 60 Hz to 10 kHz, but there was no preferred stimulation paradigm. Conclusions Minimal invasive implantation of wireless SCS systems was feasible and safe. The device offered a broader range of stimulation paradigms compared to conventional SCS devices, an allowed for a prolonged testing phase and continuous adjustment of SCS programs.
    Subject(s): Antennas (Electronics) ; Batteries ; Care and treatment ; neuropathic pain ; Pain ; Patient satisfaction ; spinal cord stimulation ; wireless stimulation
    ISSN: 1094-7159
    E-ISSN: 1525-1403
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: Brain pathology (Zurich, Switzerland), 2013-01, Vol.23 (1), p.60-72
    Description: In various types of cancers including glioblastoma, accumulating evidence show the existence of cancer stem‐like cells (CSCs), characterized by stem cell marker expression, capability of differentiation and self‐renewal, and high potential for tumor propagation in vivo. LGR5, whose expression is positively regulated by the Wnt signaling pathway, is a stem cell marker in intestinal mucosa and hair follicle in the skin. As Wnt signaling is also involved in brain development, the function of LGR5 in the maintenance of brain CSCs is to be assessed. Our study showed that the LGR5 transcript level was increased in CSCs. Co‐immunofluorescence staining demonstrated the co‐localization of CD133‐ and LGR5‐positive cells in glioblastoma tissue sections. Functionally, silencing of LGR5 by lentiviral shRNA‐mediated knockdown induced apoptosis in brain CSCs. Moreover, LGR5 depletion led to a downregulation of L1 cell adhesion molecule expression. In line with an important function in glioma tumorigenesis, LGR5 expression increased with glioma progression and correlated with an adverse outcome. Our findings suggest that LGR5 plays a role in maintenance and/or survival of brain CSCs.
    Subject(s): AC133 Antigen ; Antigens, CD - metabolism ; Apoptosis ; Brain Neoplasms - diagnosis ; Brain Neoplasms - pathology ; Brain tumors ; Cancer ; cancer stem cell ; Cell Differentiation - genetics ; Cell Survival ; Cells, Cultured ; Development and progression ; Gene Expression Regulation, Neoplastic ; Genetic Vectors - physiology ; glioblastoma ; Glioblastoma - diagnosis ; Glioblastoma - pathology ; Glioblastoma multiforme ; glioma ; Glycoproteins - metabolism ; Humans ; Lentivirus - genetics ; LGR5 ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Neural Cell Adhesion Molecule L1 - genetics ; Neural Cell Adhesion Molecule L1 - metabolism ; Peptides - metabolism ; Prognosis ; Receptors, G-Protein-Coupled - metabolism ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Statistics as Topic ; Stem cells ; Tissue Array Analysis
    ISSN: 1015-6305
    E-ISSN: 1750-3639
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 6
    Language: English
    In: International journal of molecular sciences, 2021-03-15, Vol.22 (6), p.2960
    Description: MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models. Expression of candidate miRs with prognostic relevance (miR-221/222; miR-17-5p, miR-18a, miR-19b) was validated by qRT-PCR using Taqman technology on an independent validation cohort of GBM patients ( = 109) treated at Heidelberg University Hospital (HD cohort). In TCGA, 50 miRs showed significant association with survival. Among the top ranked prognostic miRs were members of the two miR families miR-221/222 and miR-17-92. Loss of miR-221/222 was correlated with improved prognosis in both cohorts (TCGA, HD) and was an independent prognostic marker in a multivariate analysis considering demographic characteristics (age, sex, Karnofsky performance index (KPI)), molecular markers (O-6-methylguanine-DNA methyltransferase (MGMT) methylation, IDH mutation status) and PORT as co-variables. The prognostic value of miR-17-92 family members was ambiguous and in part contradictory by direct comparison of the two cohorts, thus warranting further validation in larger prospective trials.
    Subject(s): Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - genetics ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic - genetics ; glioblastoma ; Glioblastoma - genetics ; Glioblastoma - pathology ; Glioblastoma - radiotherapy ; Glioblastoma - surgery ; Humans ; Male ; microRNA ; MicroRNAs - genetics ; Middle Aged ; miR-17-92 ; miR-221 ; miR-222 ; Prognosis ; Promoter Regions, Genetic - genetics ; radiochemotherapy ; RNA, Long Noncoding - genetics ; Tissue Array Analysis ; Transcriptome - genetics
    ISSN: 1422-0067
    ISSN: 1661-6596
    E-ISSN: 1422-0067
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 7
    Language: English
    In: PloS one, 2018, Vol.13 (10), p.e0205772-e0205772
    Description: Frame-based stereotactic biopsy (FBSB) is a minimally-invasive and effective procedure for the diagnosis of brain lesions and will likely gain clinical importance. Since FBSB procedures comprise a variety of imaging and sampling methods, it is necessary to compare the safety and effectiveness of individual techniques. To assess the safety and effectiveness of FBSB using 1.5T iMRI as a one-stop procedure under general anesthesia without intraoperative histological examination. In this single-center, retrospective analysis, 500 consecutive FBSBs using iMRI were compared to a historic control of 100 biopsies with traditional workflows (computed tomography (CT) with MRI image fusion). All procedures were performed under general anesthesia. Data on surgical procedures, pre- and postoperative neurologic patient status, complications and diagnostic yield were extracted from clinical records. Complication rates and diagnostic yield showed no significant differences between both groups. Mortality was 0.6%, 95% CI = [0.12%, 1.74%], in the iMRI and 0.0% [0.00%, 3.62%], in the control group with a morbidity of 5.4% [3.6%, 7.8%] and 6.0% [2.2%, 12.6%] and a diagnostic yield of 96.8% [94.9%, 98.2%] and 96.0% [90.1%, 98.9%]. Mean procedure duration was 124 [121, 127] minutes using iMRI and 112 [106, 118] minutes in the control group. FBSB using 1.5T iMRI under general anesthesia is a safe and effective procedure and is equivalent to traditional stereotactic workflows with respect to complication rate and diagnostic yield.
    Subject(s): Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anesthesia ; Biology and Life Sciences ; Biopsy ; Brain ; Brain - diagnostic imaging ; Brain - pathology ; Brain cancer ; Brain damage ; Brain diseases ; Brain Neoplasms - diagnosis ; Brain Neoplasms - pathology ; Child ; Child, Preschool ; Comparative analysis ; Complications ; Computed tomography ; Computer vision ; CT imaging ; Diagnosis ; Diagnostic systems ; Female ; Health aspects ; Humans ; Image processing ; Image-Guided Biopsy - adverse effects ; Image-Guided Biopsy - methods ; Infant ; Intraoperative Period ; Lesions ; Magnetic Resonance Imaging ; Male ; Medical imaging ; Medical records ; Medicine and Health Sciences ; Middle Aged ; Morbidity ; Neuroimaging ; Neurological complications ; Neuropathology ; Neurosurgery ; NMR ; Nuclear magnetic resonance ; Operative Time ; Patients ; People and Places ; Physical Sciences ; Postoperative Complications - epidemiology ; Postoperative Complications - etiology ; Postoperative Period ; Research and Analysis Methods ; Retrospective Studies ; Safety ; Sampling methods ; Scanners ; Stereotaxic Techniques - adverse effects ; Surgeons ; Surgery ; Tomography, X-Ray Computed - adverse effects ; Tomography, X-Ray Computed - methods ; Usage ; Yield ; Young Adult
    ISSN: 1932-6203
    E-ISSN: 1932-6203
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 8
    Language: English
    In: The Journal of pathology, 2014-09, Vol.234 (1), p.23-33
    Description: Cancer cells with enhanced self‐renewal capacity influence tumour growth in glioblastoma. So far, a variety of surrogate markers have been proposed to enrich these cells, emphasizing the need to devise new characterization methods. Here, we screen a large panel of glioblastoma cultures (n = 21) cultivated under stem cell‐permissive conditions and identify several cell lines with enhanced self‐renewal capacity. These cell lines are capable of matrix‐independent growth and form fast‐growing, orthotopic tumours in mice. Employing isolation, re‐plating, and label‐retention techniques, we show that self‐renewal potential of individual cells is partitioned asymmetrically between daughter cells in a robust and cell line‐specific fashion. This yields populations of fast‐ and slow‐cycling cells, which differ in the expression of cell cycle‐associated transcripts. Intriguingly, fast‐growing cells keep their slow‐cycling counterparts in a reversible state of quiescence associated with high chemoresistance. Our results suggest that two different subpopulations of tumour cells contribute to aberrant growth and tumour recurrence after therapy in glioblastoma. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Subject(s): Analysis ; Animals ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Cell Line, Tumor ; Cell Proliferation ; Comparative Genomic Hybridization ; Disease Models, Animal ; Gene Dosage - genetics ; Gene Expression Profiling ; glioblastoma ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Glioblastoma multiforme ; Humans ; label retention ; Mice ; Neoplasm Recurrence, Local - pathology ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Oligonucleotide Array Sequence Analysis ; quiescence ; self-renewal ; self‐renewal; glioblastoma; label retention; quiescence ; Stem cells
    ISSN: 0022-3417
    E-ISSN: 1096-9896
    Source: Alma/SFX Local Collection
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  • 9
    Language: English
    In: Trials, 2021-01-25, Vol.22 (1), p.87-87
    Description: Spinal cord stimulation (SCS) is an effective method to treat neuropathic pain; however, it is challenging to compare different stimulation modalities in an individual patient, and thus, it is largely unknown which of the many available SCS modalities is most effective. Specifically, electrodes leading out through the skin would have to be consecutively connected to different, incompatible SCS devices and be tested over a time period of several weeks or even months. The risk of wound infections for such a study would be unacceptably high and blinding of the trial difficult. The PARS-trial seizes the capacity of a new type of wireless SCS device, which enables a blinded and systematic intra-patient comparison of different SCS modalities over extended time periods and without increasing wound infection rates. The PARS-trial is designed as a double-blinded, randomized, and placebo-controlled multi-center crossover study. It will compare the clinical effectiveness of the three most relevant SCS paradigms in individual patients. The trial will recruit 60 patients suffering from intractable neuropathic pain of the lower extremities, who have been considered for SCS therapy and were already implanted with a wireless SCS device prior to study participation. Over a time period of 35 days, patients will be treated consecutively with three different SCS paradigms ("burst," "1 kHz," and "1.499 kHz") and placebo stimulation. Each SCS paradigm will be applied for 5 days with a washout period of 70 h between stimulation cycles. The primary endpoint of the study is the level of pain self-assessment on the visual analogue scale after 5 days of SCS. Secondary, exploratory endpoints include self-assessment of pain quality (as determined by painDETECT questionnaire), quality of life (as determined by Quality of Life EQ-5D-5L questionnaire), anxiety perception (as determined by the Hospital Anxiety and Depression Scale), and physical restriction (as determined by the Oswestry Disability Index). Combining paresthesia-free SCS modalities with wireless SCS offers a unique opportunity for a blinded and systematic comparison of different SCS modalities in individual patients. This trial will advance our understanding of the clinical effectiveness of the most relevant SCS paradigms. German Clinical Trials Register, DRKS00018929 . Registered on 14 January 2020.
    Subject(s): Adult ; Analysis ; Care and treatment ; Chronic Pain - diagnosis ; Chronic Pain - therapy ; Clinical trials ; Cross-Over Studies ; Diagnostic Self Evaluation ; Double-Blind Method ; Female ; Health aspects ; Humans ; Implantable Neurostimulators - adverse effects ; Infection ; Male ; Medical research ; Medicine, Experimental ; Multicenter Studies as Topic ; Neuralgia - diagnosis ; Neuralgia - therapy ; Neuropathic pain ; Pain ; Pain Measurement ; Physiological aspects ; Quality of Life ; Randomized controlled trial ; Randomized Controlled Trials as Topic ; Spinal cord ; Spinal cord stimulation ; Spinal Cord Stimulation - adverse effects ; Spinal Cord Stimulation - instrumentation ; Spinal Cord Stimulation - methods ; Study Protocol ; Treatment Outcome ; Wireless stimulation ; Wireless Technology - instrumentation
    ISSN: 1745-6215
    E-ISSN: 1745-6215
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 10
    Language: English
    In: British journal of neurosurgery, 2016-07-03, Vol.30 (4), p.397-400
    Description: Background: Intraoperative magnetic resonance imaging (io-MRI) improves the extent of glioma resection. Due to the magnetic field, patients have to be covered with sterile drape and are then transferred into an io-MRI chamber, where ferromagnetic anaesthesia monitors and machines must be kept at distance and can only be applied with limitations. Despite the development of specific paramagnetic equipment for io-MRI use, this method is suspected to carry a higher risk for anaesthesiological and surgical complications. Particularly, serial draping and un-draping cycles as well as the extended surgery duration might increase the risk of perioperative infection. Objective: Given the importance of io-MRI for glioma surgery, the question regarding io-MRI safety needs to be answered. Methods: We prospectively evaluate the perioperative anaesthesiological and surgical complications for 516 cases of brain tumour surgery involving io-MRI (MRI cohort). As a control group, we evaluate a cohort of 610 cases of brain tumour surgery, performed without io-MRI (control group). Results: The io-MRI procedure (including draping/undraping, transfer to and from the MRI cabinet and io-MRI scan) significantly extended surgery, defined as "skin to skin" time, by 57 min (SD = 16 min) (p ≤ 0.01). Still, we show low and comparable rates of surgical complications in the MRI cohort and the control group. Postoperative haemorrhage (3.7% versus 3.0% in MRI cohort versus control group; p = 0.49) and infections (2.2% versus 1.8% in MRI cohort versus control group; p = 0.69) were not significantly different between both groups. No anaesthesiological disturbances were reported. Conclusion: Despite prolonged surgery and serial draping and un-draping cycles, io-MRI was not linked to higher rates of infections and postoperative haemorrhage in this study.
    Subject(s): Adult ; Aged ; Aged, 80 and over ; Anesthesia ; Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - surgery ; Complications ; Female ; glioma ; Glioma - diagnostic imaging ; Glioma - surgery ; Humans ; Infections ; Intraoperative Complications - etiology ; intraoperative MRI ; Magnetic Resonance Imaging - methods ; Male ; Middle Aged ; Monitoring, Intraoperative - methods ; Neuronavigation - methods ; Neurosurgery ; Neurosurgical Procedures - methods ; Nuclear magnetic resonance--NMR ; Prospective Studies ; Risk assessment ; surgery ; Treatment Outcome
    ISSN: 0268-8697
    E-ISSN: 1360-046X
    Source: Academic Search Ultimate
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