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Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease
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作者 Ling-Xiao Yi Hui Ren Woon +3 位作者 Genevieve Saw Li Zeng Eng King Tan Zhi Dong Zhou 《Neural Regeneration Research》 SCIE CAS 2025年第11期3193-3206,共14页
The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed patho... The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease. 展开更多
关键词 dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches
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Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury
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作者 Mou Gao Qin Dong +3 位作者 Dan Zou Zhijun Yang Lili Guo Ruxiang Xu 《Neural Regeneration Research》 SCIE CAS 2025年第5期1416-1430,共15页
Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells ... Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury. 展开更多
关键词 Akt signaling cerebral edema closed head injury Crry CXCR4 induced neural stem cell MICROGLIA NEUROINFLAMMATION
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Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury
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作者 Stephen Vidman Yee Hang Ethan Ma +1 位作者 Nolan Fullenkamp Giles W.Plant 《Neural Regeneration Research》 SCIE CAS 2025年第11期3063-3075,共13页
In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the c... In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration. 展开更多
关键词 axon regeneration central nervous system regeneration induced pluripotent stem cells NEUROTRAUMA regenerative medicine spinal cord injury stem cell therapy
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Effectiveness of a novel, fixed dose combination of netupitant and palonosetron in prevention of chemotherapy induced nausea and vomiting: A real-life study from India
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作者 Bharat Vaswani Sagar Bhagat +1 位作者 Saiprasad Patil Hanmant Barkate 《World Journal of Clinical Oncology》 CAS 2020年第8期606-613,共8页
BACKGROUND A new,oral fixed dose combination of highly selective neurokinin-1 receptor antagonist,netupitant with 5HT3 receptor antagonist,netupitant and palonosetron(NEPA)was approved in India for prevention of chemo... BACKGROUND A new,oral fixed dose combination of highly selective neurokinin-1 receptor antagonist,netupitant with 5HT3 receptor antagonist,netupitant and palonosetron(NEPA)was approved in India for prevention of chemotherapy induced nausea and vomiting(CINV).AIM To assess effectiveness of NEPA in real-world scenario.METHODS We retrospectively assessed the medical records and patient dairies of adult patients who received highly emetogenic or moderately emetogenic chemotherapy(HEC/MEC)and treated with NEPA(Netupitant 300 mg+Palanosetron 0.50 mg)for prevention of CINV.Complete response(CR)was defined as no emesis or no requirement of rescue medication in overall phase(0 to 5 d),acute phase(0-24 h)and delayed phase(2 to 5 d).RESULTS In 403 patients included in the analysis,mean age was 56.24±11.11 years and 55.09%were females.Breast cancer(25.06%)was most common malignancy encountered.HEC and MEC were administered in 54.6%and 45.4%patients respectively.CR in overall phase was 93.79%whereas it was 98.01%in acute CINV and 93.79%in delayed CINV.Overall CR in HEC and MEC groups was 93.63%and 93.98%respectively.CR was more than 90%in different chemotherapy cycles except in group of patients of cycle 4 where CR was 88.88%.CONCLUSION NEPA is a novel combination that is effective in preventing CINV in up to 93%cases treated with highly emetogenic or moderately emetogenic chemotherapy.This study brings the first real-life evidence of its effectiveness in India population. 展开更多
关键词 Chemotherapy induced nausea vomiting Netupitant PALONOSETRON Cancer CHEMOTHERAPY
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基于能力的高职英语Real-life Skills教学探析
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作者 蒋晓雯 《江苏教育》 2019年第76期54-55,共2页
Real-life Skills是一种具有较强实践意义的教学活动,给学生创设了听说读写综合能力实践的情境。从Real-life Skills的教学现状出发,探讨了在教学时应重点考虑解决真实生活的问题、教学过程中教师的角色适时转换、“教法”基于“学法”... Real-life Skills是一种具有较强实践意义的教学活动,给学生创设了听说读写综合能力实践的情境。从Real-life Skills的教学现状出发,探讨了在教学时应重点考虑解决真实生活的问题、教学过程中教师的角色适时转换、“教法”基于“学法”、注重学生的多元评价等事项。 展开更多
关键词 高职英语 real-life Skills教学 学生能力
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Dried blood spots,valid screening for viral hepatitis and human immunodeficiency virus in real-life 被引量:2
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作者 Belinda K Mossner Benjamin Staugaard +3 位作者 Janne Jensen Soren Thue Lillevang Peer B Christensen Dorte Kinggaard Holm 《World Journal of Gastroenterology》 SCIE CAS 2016年第33期7604-7612,共9页
AIM To detect chronic hepatitis B(CHB),chronic hepatitis C(CHC) and human immunodeficiency virus(HIV) infections in dried blood spot(DBS) and compare these samples to venous blood sampling in real-life.METHODS We incl... AIM To detect chronic hepatitis B(CHB),chronic hepatitis C(CHC) and human immunodeficiency virus(HIV) infections in dried blood spot(DBS) and compare these samples to venous blood sampling in real-life.METHODS We included prospective patients with known viral infections from drug treatment centers,a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper,and a venous blood sample was obtained. The samples were analyzed for HBs Ag,antiHBc,anti-HBs,anti-HCV,and anti-HIV levels as well as subjected to a combined nucleic acid test(NAT) for HBV DNA,HCV RNA and HIV RNA.RESULTS Samples from 404 subjects were screened(85 CHB,116 CHC,114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity,but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS(68% and 42%).CONCLUSION DBS sampling,combined with an automated analysis system,is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system. 展开更多
关键词 Dried blood spot real-life SCREENING Hepatitis B Hepatitis C Human immunodeficiency virus People who inject drugs Drug-users PRISONERS
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Ecological footprint of Gansu Province,China between 1997 and 2002:changes and inducement 被引量:1
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作者 Shang Haiyang Chen Kegong +1 位作者 Xu Zhongmin Sam Garland-Renn 《Ecological Economy》 2009年第2期187-194,共8页
The calculation of Ecological Footprint (EF) on the basis of Input-Output model (I-O model) was advanced by Bicknell, and modified and improved hy Ferng who corrected the footprint's aggregation to each sectors. ... The calculation of Ecological Footprint (EF) on the basis of Input-Output model (I-O model) was advanced by Bicknell, and modified and improved hy Ferng who corrected the footprint's aggregation to each sectors. For the lack of sufficient teehnique to deal with the trade between the research areas and the rest of the world, it it necessary to improve this method. And a dynamic analysis of the change of footprint based on I-O model, which could explore the factor impacting the footprint using the ,special advantage of I-O model, ought to be put into practice. After introducing the new method in detail, we calculate and compare the EF and the change of Gansu Province in the northwest of China in 1997 and 2002. The result shows that there was an increase of EF in 2002 caused by final domestic demand. Further; the inerement in EF export was 2.0 × 10^5 ha and 1.6 × 10^6 ha in import. The out-of- region support dropped from 22.6% to 18. 6%. We introduce three factors causing the EF change based on the character of I-O model: the productivity of the resourve which is explained by the change of resource used to obtain one unit output in a sector, the improvement of the economics and the final demand. Finally, we find that the effects of the three factors on the EF change are not identical except the industry sectors and the change of factors in the agriculture and the industry sectors works notably. 展开更多
关键词 Ecological footprint Input-Output model inducement to change IhPAT
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Predictors of functional benefit of hepatitis C therapy in a‘real-life’cohort
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作者 Niels Steinebrunner Kerstin Stein +3 位作者 Catharina Sandig Thomas Bruckner Wolfgang Stremmel Anita Pathil 《World Journal of Gastroenterology》 SCIE CAS 2018年第7期852-861,共10页
AIM To define predictors of functional benefit of direct-acting antivirals(DAAs) in patients with chronic hepatitis C virus(HCV) infection and liver cirrhosis.METHODS We analysed a cohort of 199 patients with chronic ... AIM To define predictors of functional benefit of direct-acting antivirals(DAAs) in patients with chronic hepatitis C virus(HCV) infection and liver cirrhosis.METHODS We analysed a cohort of 199 patients with chronic HCV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated(76%) and decompensated(24%) liver cirrhosis at two tertiary centres in Germany. Patients were included withtreatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression analysis.RESULTS Viral clearance was achieved in 88%(175/199) of patients. Sustained virological response(SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90%(n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57%(n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87%(n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67%(n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37%(65/179) of patients, no change of MELD score in 41%(74/179) of patients, and an aggravation was observed in 22%(40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the Child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional benefit.CONCLUSION Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HCV and with advanced liver disease. 展开更多
关键词 FUNCTIONAL BENEFIT direct ACTING ANTIVIRAL hepatitis C cirrhosis real-life data
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Study on Bicoordination Chiral Inducement Catalysis of (R)-4-Thiazolidinecarboxylic Acid
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作者 Hui WANG Wei Wei PEI +1 位作者 Guo Bin SUN Wei Ping YE College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 《Chinese Chemical Letters》 SCIE CAS CSCD 2004年第12期1419-1422,共4页
The bicoordination chiral inducement catalysis of (R)-4-thiazolidinecarboxylic acid inthe enantioselective borane reduction of prochiral ketones has been studied. The fact that theabsolute configuration of the main pr... The bicoordination chiral inducement catalysis of (R)-4-thiazolidinecarboxylic acid inthe enantioselective borane reduction of prochiral ketones has been studied. The fact that theabsolute configuration of the main product can be changed by simply using different operationmethods was firstly verified. And the reason of bicoordination chiral inducement was discussed. 展开更多
关键词 Bicoordination chiral inducement (R)-4-thiazolidinecarboxylic acid.
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A combined treatment for patients with dry eye and associated laryngopharyngeal reflux:a real-life approach
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作者 Giorgio Ciprandi Stefano Bonini +2 位作者 Irene Schiavetti Valerio Damiani Study Group on Dry-Eye Pragmatical Management 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第10期1616-1622,共7页
AIM:To evaluate the efficacy and tolerability of administering a combined therapy in patients with dry eye syndrome(DES)and associated laryngopharyngeal reflux(LPR).METHODS:The study was retrospective,open,observation... AIM:To evaluate the efficacy and tolerability of administering a combined therapy in patients with dry eye syndrome(DES)and associated laryngopharyngeal reflux(LPR).METHODS:The study was retrospective,open,observational,and conducted in a real-life setting.Patients had pathological symptom assessment in dry eye(SANDE)and reflux symptom index(RSI)at baseline.Patients were re-assessed after 1mo and at the end of treatment.The treatment consisted of a three-month course based on the combined therapy:Gastroftal eye drops,one drop three times a day,and Gastroftal tablets,two tablets after lunch and two tablets after dinner.Tear break-up-time(TBUT)test,Schirmer test,RSI,and SANDE questionnaire were evaluated.RESULTS:The study included 253 patients.The mean age was 58±11.19y.TBUT test score and Schirmer’s test significantly increased(both P<0.001)after 1mo and at the end of treatment.The RSI score and SANDE scores significantly decreased(both P<0.001)after 1mo and at the end of treatment.CONCLUSION:The current,retrospective,and open study shows that combined therapy using Gastroftal eye drops and tablets could represent a valuable option in managing patients with DES associated with LPR. 展开更多
关键词 dry eye syndrome laryngopharyngeal reflux combined therapy hyaluronic acid ALGINATE Camelia sinensis real-life
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Integrated Electrode-Electrolyte Optimization to Manufacture a Real-Life Applicable Aqueous Supercapacitor with Record-Breaking Lifespan
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作者 Jichi Liu Chongchong Wu +3 位作者 Ian D.Gates Baohua Jia Zihang Huang Tianyi Ma 《Energy & Environmental Materials》 SCIE EI CAS CSCD 2023年第4期78-88,共11页
Aqueous supercapacitors(SCs)have been regarded as a promising candidate for commercial energy storage device due to their superior safety,low cost,and environmental benignity.Unfortunately,an age-old challenge of achi... Aqueous supercapacitors(SCs)have been regarded as a promising candidate for commercial energy storage device due to their superior safety,low cost,and environmental benignity.Unfortunately,an age-old challenge of achieving both long electrode lifespan and qualified energy-storage property blocks their practical application.Herein,we develop an electrode-electrolyte integrated optimization strategy to fulfill the real-life device requirements.Electrode optimization simultaneously regulates the nanomorphology and surface chemistry of the tungsten oxide anode,resulting in superior electrochemical performance given by an ideal“bird-nest”structure with optimal oxygen vacancy status;the anodes interact with and are protected from dissolution and structural collapse by the rationally designed hybrid electrolyte with optimized pH and facilitated cation desorption behavior.Collaboratively,a record-breaking durability of no capacitive decay after 250000 cycles is achieved.On the basis of this integrated optimization,the first aqueous pouch SCs with real-life practicability were manufactured by a soft-package encapsulation technique,which can steadily power commercial 3 C products such as tablets and smartphones and maintain safely working against extreme conditions.This work demonstrates the possibility of using aqueous energy storage devices with enhanced safety and lower cost to replace the commercial organic counterparts for wide range of daily applications. 展开更多
关键词 integrated electrode-electrolyte optimization real-life applicable supercapacitor record-breaking lifespan
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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment 被引量:2
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作者 Sumei Liu Baoguo Liu +4 位作者 Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期440-446,共7页
Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a... Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats. 展开更多
关键词 biomaterial FIBRINOGEN functional recovery induced neural stem cell transplantation MICROENVIRONMENT MICROGLIA spinal cord injury THROMBIN
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Sorafenib for advanced renal cell carcinoma in real-life practice: a literature review
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作者 Steven Simoens 《Health》 2011年第2期86-92,共7页
Sorafenib is a new treatment indicated for patients with advanced renal cell carcinoma who have failed prior cytokine-based therapy or are considered unsuitable for such therapy. Although treatment with sorafenib und... Sorafenib is a new treatment indicated for patients with advanced renal cell carcinoma who have failed prior cytokine-based therapy or are considered unsuitable for such therapy. Although treatment with sorafenib under ‘ideal trial conditions’ has been extensively studied, registration and reimbursement authorities are also interested in the behavior of sorafenib in real-life practice. This study aims to conduct a literature review of the dosage and treatment duration;safety, tolerability and effectiveness;costs and cost-effectiveness of sorafenib in routine clinical care. Studies were identified by searching PubMed, Embase, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, and EconLit up to November 2010. The literature search included articles published in peer-reviewed journals, congress abstracts, and internal studies of Bayer Schering Pharma. Eight studies were included. An open-label study observed stable disease for at least eight weeks in 80% of patients. The most common drug-related adverse events were hand-foot skin reaction, rash, hypertension, and fatigue. Although treatment with sorafenib led to fewer dose reductions, it was also associated with a shorter treatment duration, less time to pro-gression and a shorter survival time as compared to sunitinib. Monthly health care costs were lower with sorafenib as compared to sunitinib. A post-marketing surveillance study showed that patients rated the tolerability and effectiveness of sorafenib as very good, good or sufficient. In conclusion, the current evidence is too limited to derive conclusions and existing studies suffer from methodological shortcomings. 展开更多
关键词 SORAFENIB Advanced RENAL Cell CARCINOMA real-life Practice LITERATURE Review
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Real-life multi-center retrospective analysis on nivolumab in difficult-to-treat patients with advanced hepatocellular carcinoma
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作者 Nika De Wilde Luisa Vonghia +7 位作者 Sven Francque Thomas De Somer Ali Bagdadi Eva Staub Jasper Lambrechts Ana-Maria Bucalau Gontran Verset Christophe Van Steenkiste 《World Journal of Hepatology》 2022年第8期1608-1620,共13页
BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related death worldwide.The landscape of the systemic treatment for advanced HCC is changing quickly,and recently,the standard of care bec... BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related death worldwide.The landscape of the systemic treatment for advanced HCC is changing quickly,and recently,the standard of care became either atezolizumab plus bevacizumab or tremelimumab plus durvalumab in the single tremelimumab regular interval durvalumab regimen.Nivolumab monotherapy has proven to be effective sometimes for advanced HCC and could be a valuable treatment option for patients outside current treatment indications and reimbursement criteria for the standard of care.This is a particular population of interest.AIM To evaluate the real-world effectiveness of nivolumab monotherapy in patients with advanced HCC who are not eligible for other treatment.METHODS We conducted a retrospective,multicentric study including 29 patients with advanced HCC from 3 Belgian tertiary hospitals.All patients had had prior chemotherapy or were intolerant or ineligible for treatments.All study subjects received nivolumab 3 mg/kg in monotherapy,administered once every two weeks intravenously.Treatment continued until disease progression,severe adverse events or death.Data were retrieved from patients'medical records.The outcome parameters such as radiological response according to response evaluation criteria in solid tumors(RECIST)criteria,the biological response through the evolution of the alpha-fetoprotein(AFP)level,and clinical response considering both the Child–Pugh(CP)score and the World Health Organization(WHO)performance status(PS)were reported.A safety profile was also reported.Statistical analysis was performed using the SPSS Statistics 27 statistical software package.RESULTS The radiological overall response rate(defined as complete or partial response according to the immune RECIST and modified RECIST criteria)to nivolumab monotherapy was 24.1%.The biological overall response rate(defined as a decrease of≥25%in AFP blood level)was 20.7%.Radiological and biological responses were significantly associated both with each other(P<0.001)and with overall survival(P<0.005 for radiological response and P<0.001 for biological response).Overall survival was 14.5 mo(+/-2.1),and progression-free survival was 10.9 mo(+/-2.3).After 4 mo of treatment,78.3%of patients remained clinically stable or even showed improvement in WHO PS.Grade 3 adverse events occurred in 17.2%of patients,none had grade 4 adverse events,and no patients ceased nivolumab due to adverse events.CONCLUSION Nivolumab monotherapy is a good treatment choice in frail patients with HCC who are ineligible for the standard of care or other validated systemic treatments. 展开更多
关键词 Advanced hepatocellular carcinoma Systemic treatment Immunotherapy Nivolumab Difficult-to-treat patients real-life setting
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Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury 被引量:3
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作者 Mou Gao Qin Dong +4 位作者 Zhijun Yang Dan Zou Yajuan Han Zhanfeng Chen Ruxiang Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第4期872-880,共9页
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen... Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury. 展开更多
关键词 closed head injury Ctbp2 induced neural stem cell lncRNA H19 miR-325-3p NEUROGENESIS
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Linking Real-Life Situations with Classroom Assessment: Development of Real-Life Performance-Based Tasks in Business Mathematics
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作者 Sheena Mai A. Galman Jennalyn C. Del Rosario 《Journal of Applied Mathematics and Physics》 2021年第3期485-502,共18页
This study aimed to develop real-life performance-based tasks in Business Mathematics (RLPBTs) following the ADDIE’s model of instructional development. Using the descriptive-developmental research design, the study ... This study aimed to develop real-life performance-based tasks in Business Mathematics (RLPBTs) following the ADDIE’s model of instructional development. Using the descriptive-developmental research design, the study developed RLPBTS with mathematics experts, mathematics department head, bank manager, mathematics teachers, and students as respondents. The RLPBTs consist of instructional plans. Each instructional plan has these components: Introduction, Learning Competency, Learning Outcome, Task Execution, Scoring Guide, and Generalization. The design and content of the instructional plans were assessed as very good. On the other hand, the design and execution of the Tasks were assessed as favorable. Grade 11 students also agreed that real-life performance-based tasks helped them understand better concepts in business mathematics. They claimed that they enjoyed the tasks because of the inclusion of real-life situations that they simulated. The use of the RLPBTs provides another innovation in the teaching and learning concepts in Business Mathematics. 展开更多
关键词 ADDIE Model real-life Performance-Based Tasks Instructional Plans Business Mathematics
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Recent advances in the diagnosis of drug-induced liver injury 被引量:1
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作者 Taqwa Ahmed Jawad Ahmad 《World Journal of Hepatology》 2024年第2期186-192,共7页
Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between dr... Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI. 展开更多
关键词 Drug induced liver injury Liver biopsy DIAGNOSIS RUCAM RECAM
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Coupled multiphysical model for investigation of influence factors in the application of microbially induced calcite precipitation 被引量:1
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作者 Xuerui Wang Pavan Kumar Bhukya +1 位作者 Dali Naidu Arnepalli Shuang Chen 《Journal of Rock Mechanics and Geotechnical Engineering》 SCIE CSCD 2024年第6期2232-2249,共18页
The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiph... The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiphysics involved in MICP,such as bacterial ureolytic activities,biochemical reactions,multiphase and multicomponent transport,and alteration of the porosity and permeability.The model incorporates multiphysical coupling effects through well-established constitutive relations that connect parameters and variables from different physical fields.It was implemented in the open-source finite element code OpenGeoSys(OGS),and a semi-staggered solution strategy was designed to solve the couplings,allowing for flexible model settings.Therefore,the developed model can be easily adapted to simulate MICP applications in different scenarios.The numerical model was employed to analyze the effect of various factors,including temperature,injection strategies,and application scales.Besides,a TBCH modeling study was conducted on the laboratory-scale domain to analyze the effects of temperature on urease activity and precipitated calcium carbonate.To understand the scale dependency of MICP treatment,a large-scale heterogeneous domain was subjected to variable biochemical injection strategies.The simulations conducted at the field-scale guided the selection of an injection strategy to achieve the desired type and amount of precipitation.Additionally,the study emphasized the potential of numerical models as reliable tools for optimizing future developments in field-scale MICP treatment.The present study demonstrates the potential of this numerical framework for designing and optimizing the MICP applications in laboratory-,prototype-,and field-scale scenarios. 展开更多
关键词 MULTIPHYSICS Microbially induced calcite precipitation(MICP) Coupled thermo-bio-chemo-hydraulic(TBCH) model OpenGeoSys(OGS) Influence factors
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Prevalence of Induced Abortion among Female Students in Selected Tertiary Learning Institutions in Gaborone City, Botswana
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作者 Mabole Masweu Isaac Ogweno Owaka Rosebella Kipkalom 《International Journal of Clinical Medicine》 CAS 2024年第3期155-165,共11页
Induced abortion signifies that pregnancy has been tempered with. Abortion is the removal of an embryo or fetus weighing less than 500 grams from its mother. It can either be spontaneous (unprompted) or induced. Abort... Induced abortion signifies that pregnancy has been tempered with. Abortion is the removal of an embryo or fetus weighing less than 500 grams from its mother. It can either be spontaneous (unprompted) or induced. Abortion remains one of the leading causes of maternal deaths in developing countries with induced abortion being the key cause. In 2014 from January to August, 9 abortion related deaths occurred in Botswana. There are several reasons female students in tertiary institutions resort to seeking induced abortion which include the socio-demographics like age and socio-economic factors like financial instability. Parental fears, unintended pregnancy and pressure from the partner also force females to terminate pregnancy. Induced abortion has claimed many women’s lives especially in developing countries with very restrictive abortion laws like Botswana as women do not access safe abortion care services. The study intends to establish the determinants of induced abortion among female students in selected tertiary learning institutions in Gaborone City, Botswana. It concentrated primarily on determining the prevalence of induced abortion. This was a descriptive cross-sectional study using both quantitative and qualitative data collection techniques. Systematic random sampling technique was used to come up with 278 participants. Prior to commencement of data collection, all ethical and logistical prerequisites were satisfied. Informed consent was solicited from all the study participants and the purpose of the study was fully explained. A self-administered questionnaire was used to collect data. Microsoft Excel spread sheet was used to code, clean, and enter the data, which was then exported for analysis to the statistical package for social sciences version 24. Frequency distribution tables, percentages graphs, and pie charts were used to illustrate the descriptive information. The study revealed that prevalence of induced abortion among female students in Gaborone City is 7.9%. They even suggested that induced abortion be liberalized. Age was the only socio-demographic factor associated with induced abortion with p = 0.047 using Chi Square test χ<sup>2</sup> = 7.609, df = 3. The study findings concluded that female students resort to induced abortion as a result of pressure from both parents and male partners especially when the pregnancy is unintended. The study recommends that the abortion law in Botswana be made liberal to ease access to safe abortion care services. It also recommends that contraceptive commodities should consistently be available in public health facilities. 展开更多
关键词 induced Abortion Prevalence and Family Planning
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Numerical simulations of earthquake rupture induced by pressure perturbation
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作者 Bingquan Ren Caijun Xu +1 位作者 Guoyan Jiang Lei Yang 《Geodesy and Geodynamics》 EI CSCD 2024年第5期477-487,共11页
The subsurface fluid injection can cause pressure increase within faults,leading to earthquake occurrences.However,the factors controlling earthquake rupture due to pressure perturbation remain poorly understood.To re... The subsurface fluid injection can cause pressure increase within faults,leading to earthquake occurrences.However,the factors controlling earthquake rupture due to pressure perturbation remain poorly understood.To resolve this problem,we simulate the physical processes of earthquake nucleation and rupture on strike-slip faults perturbated by pressure migration based on the slip-weakening law.Multiple kinds of factors,including background stress,fluid injection rates,the area of the pressurized region,fault geometry,and fault friction coefficients,are considered in our simulations.Our simulation results reveal that the ratio of shear stress to normal stress rather than their absolute values controls the rupture behavior.With the large stress ratios,high injection rates,and large pressurized areas,earthquakes are prone to propagate as runaway ruptures.Additionally,faults with large aspect ratios of length to width are also favorable for causing runaway ruptures.In contrast,the factors of fault strike,dip angles and friction coefficients have minor influence on rupture behavior. 展开更多
关键词 induced seismicity Finite element simulation Rupture mode
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