Background： Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting （CINV） at a national level in China or to assess how treatment regimens adhere to current...Background： Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting （CINV） at a national level in China or to assess how treatment regimens adhere to current guidelines. Methods： We searched the China Health Insurance Research Association （CHIRA） Database to identify patients with cancer who were 〉 18 years old and received either moderately or highly emetogenie chemotherapy （MEC and HEC, respectively） between 2008 and 2012. Patients＇ characteristics as well as usage of specific antiemetic regimens were analyzed using descriptive statistics. Results： Of the 14,548 patients included in the study, 6,477 received HEC while 8,071 were treated with MEC. Approximately 89.9% used antiemetics prophylactically to prevent acute CINV and 71.5% for delayed CINV while 9.0% were prescribed antiemetics as rescue therapy. A significantly lower proportion of patients treated with HEC received prophylactic antiemetic therapy for delayed CINV as compared to those treated with MEC （59.4% vs. 81.3 %; P〈0.001）. The HEC group had a slightly lower proportion of patients using a mixed regimen containing a 5-HT3 antagonist to prevent both acute and delayed CINV than the MEC group （P〈0.012）; however, a higher proportion received a mixed regimen containing eorticosteroids （P≤0.007）. Although more than half of the patients in the HEC group took three antiemeties to prevent acute and delayed CINV, these rates were significantly lower than those of the MEC group （both P〈0.001）. Finally, analysis of the regimens used revealed that there is over-utilization of drugs within the same class of antiemetic. Conclusions： These findings indicate that more attention is needed for treatment of delayed CINV, in terms of both overall use and the components of a typical treatment regimen.展开更多
Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summa...Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summarize the published literature on the clinical outcome and response to therapy of pediatric CG including two new cases. We performed a search in Pubmed, OVID for related terms; articles including management and clinical and/or endo-histologic follow up information were included and abstracted. Reported findings were pooled in a dedicated database including the corresponding data extracted from chart review in our patients with CG. Twenty-four patients were included (17 females) with a mean age of 11.7 years. The clinical presentation included iron deficiency anemia and dyspepsia. The reported duration of follow up (in 18 patients) ranged between 0.2-14 years. Despite most subjects presenting with anemia including one requiring blood transfusion, oral iron therapy was only documented in 12 patients. Other treatment modalities were antisecretory measures in 13 patients; proton pump inhibitors (12), or histamine-2 blockers (3), sucralfate (5), prednisolone (6), oral budesonide in 3 patients where one received it in fish oil and triple therapy (3). Three (13%) patients showed no clinical improvement despite therapy; conversely 19 out of 22 were reported with improved symptoms including 8 with complete symptom resolution. Spontaneous clinical resolution without antisecretory, anti-inflammatory or gastroprotective agents was noted in 5 patients (4 received only supplemental iron). Follow up endohistopathologic data (17 patients) included persistent collagen band and stable Mononuclear cell infiltrate in 12 patients with histopathologic improvement in 5 patients. Neither collagen band thickness nor mononuclear cell infiltrate correlated with clinical course. Intestinal metaplasia and endocrine cell hyperplasia were reported (1) raising the concern of long term malignant transformation. In summary, CG in chil展开更多
Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluoro...Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be les展开更多
The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) proj...The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) projects: 1) Strategy;2) Infrastructure;3) Technology;4) Processes & Procedures;5) Governance;6) Culture;7) People;8) Goals & Metrics and selected six critical success factors from these categories: 1) Operational Efficiency;2) Time Savings;3) Timeframe to Realize Value;4) Employee Engagement;5) Participation;6) Number of Sponsored Ideas. End users of the digital transformation efforts through Citizen Development were asked to assess the six critical success measures in terms of performance and importance criteria. The research results identified that focus should be applied to improving “Timeframe to Realize Value”, on “Operational Efficiency”, and on “Time Savings” to deliver success.展开更多
BACKGROUND The introduction of biologics has revolutionized the management of the chronic inflammatory bowel disease,ulcerative colitis(UC),with many patients experiencing significant improvements not only in their sy...BACKGROUND The introduction of biologics has revolutionized the management of the chronic inflammatory bowel disease,ulcerative colitis(UC),with many patients experiencing significant improvements not only in their symptoms but in other outcomes relevant to individuals and society as a whole.In Germany,there are no prospective data>3 mo that assess the work productivity,daily activities and quality of life(QoL)of patients with moderate-to-severe UC treated with golimumab.AIM To assess change in work productivity,capacity for daily activities and QoL in UC patients treated with golimumab in Germany.METHODS The validated Work Productivity Activity Impairment(WPAI)Questionnaire was used to analyze the change in work productivity,the capacity for daily activities after three months(primary endpoint)and disease specific and health related QoL(HRQoL)up to 1 year(secondary endpoints).The changes in work productivity and activity impairment were evaluated every three months until month twelve compared to baseline.Disease-specific and health-related QoL were assessed with the inflammatory bowel disease questionnaire and with the short-form 12 health survey questionnaire(SF-12).RESULTS This prospective non-interventional study included 287 patients.The analysis population was comprised of 282 patients who had completed at least two visits.At baseline,61%of patients had moderate UC and 18%had severe UC.Furthermore,75%of patients worked full-time or part-time at baseline.A total of 212 patients who were employed at the start of the study(employed population)were evaluated for the primary endpoint.Golimumab significantly reduced all WPAI sub-scores compared to baseline after three,six,nine and twelve months after the start of treatment(P<0.0001).In addition,disease-specific QoL and HRQoL,as measured by the SF-12 questionnaire,improved significantly with golimumab at all evaluation times(P<0.0001 in each case vs baseline).CONCLUSION Treatment of moderate-to-severe UC with golimumab leads to significant improvements in patient�展开更多
Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,cont...Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,contribute to maintaining healthy cognitive functions throughout life.The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues.The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has,however,not been established.This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans.While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease,consensual results have yet to be reached to fully explore this hypothesis.In this review,we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases,especially in Alzheimer’s disease.We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease.In particular,we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems,as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues,could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.展开更多
Background There have been no mortality/morbidity endpoint studies with Iosartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose Iosartan on clinical outcomes in ...Background There have been no mortality/morbidity endpoint studies with Iosartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose Iosartan on clinical outcomes in Chinese subjects with heart failure.展开更多
Objective To provide an update on the evidence of the effectiveness of acupuncture in treating chronic non-specific low back pain(CNSLBP)based on randomized controlled trials(RCTs)of acupuncture for CNSLBP published b...Objective To provide an update on the evidence of the effectiveness of acupuncture in treating chronic non-specific low back pain(CNSLBP)based on randomized controlled trials(RCTs)of acupuncture for CNSLBP published between 2006 and 2020.Methods A comprehensive literature search was conducted through the University of Malta website,using the HyDi search engine.The‘Advanced Search’option was chosen in order to search for articles that were published in English,and associated with the key words,‘Chronic’,‘Acupuncture’,‘Needle’,‘Needling’,‘Non-specific’and‘Low Back Pain’,which were entered in their‘Subject’field,from the year 2006 till 2020.A comprehensive reading and analysis was done for the search result.Results Through the use of the HyDi search engine,accessible through the University of Malta,eighteen randomized controlled trials that met the criteria of this study were selected.Conclusion Through the analysis and comparison of the studies selected for this literature review,there is evidence providing that acupuncture is significantly more effective than current conservative treatment modalities for patients with CNSLBP in reducing pain and improving function.展开更多
Programming errors in Ethereum smart contracts can result in catastrophic financial losses from stolen cryptocurrency.While vulnerability detectors can prevent vulnerable contracts from being deployed,this does not me...Programming errors in Ethereum smart contracts can result in catastrophic financial losses from stolen cryptocurrency.While vulnerability detectors can prevent vulnerable contracts from being deployed,this does not mean that such contracts will not be deployed.Once a vulnerable contract is instantiated on the blockchain and becomes the target of attacks,the identification of exploit transactions becomes indispensable in assessing whether it has been actually exploited and identifying which malicious or subverted accounts were involved.In this work,we study the problem of post-factum investigation of Ethereum attacks using Indicators of Compromise(IoC)specially crafted for use in the blockchain.IoC definitions need to capture the side-effects of successful exploitation in the context of the Ethereum blockchain.Therefore,we define a model for smart contract execution,comprising multiple abstraction levels that mirror the multiple views of code execution on a blockchain.Subsequently,we compare IoCs defined across the different levels in terms of their effectiveness and practicality through EtherClue,a prototype tool for investigating Ethereum security incidents.Our results illustrate that coarse-grained IoCs defined over blocks of transactions can detect exploit transactions with less computation.However,they are contract-specific and suffer from false negatives.On the other hand,fine-grained IoCs defined over virtual machine instructions can avoid these pitfalls at the expense of increased computation,which is nevertheless applicable for practical use.展开更多
Japanese encephalitis（JE）is a serious public health issue.This study was undertaken to better understand the relationship between JE distribution and environmental factors in China.JE data from 2005 to 2010 were ret...Japanese encephalitis（JE）is a serious public health issue.This study was undertaken to better understand the relationship between JE distribution and environmental factors in China.JE data from 2005 to 2010 were retrieved from National Notifiable Disease Report System.展开更多
Superoxide dismutase (SOD)-deficient Escherichia coli OX326Acells are protected against chemically-induced oxidative stress by expression of the chaperonin GroESL. This protection is equivalent to expression of supero...Superoxide dismutase (SOD)-deficient Escherichia coli OX326Acells are protected against chemically-induced oxidative stress by expression of the chaperonin GroESL. This protection is equivalent to expression of superoxide dismutase even though GroESL has no inherent SOD activity. Co-overexpression of GroESL and SOD in the same cells results in higher protein yields of SOD and greater metallation of SOD when compared with expression of SOD alone. Greater metallation results in the higher specific activity of SOD that is observed in heat shock, and is not due to increased synthesis of SOD mRNA or protein.展开更多
According to various worldwide statistics,most car accidents occur solely due to human error.The person driving a car needs to be alert,especially when travelling through high traffic volumes that permit high-speed tr...According to various worldwide statistics,most car accidents occur solely due to human error.The person driving a car needs to be alert,especially when travelling through high traffic volumes that permit high-speed transit since a slight distraction can cause a fatal accident.Even though semiautomated checks,such as speed detecting cameras and speed barriers,are deployed,controlling human errors is an arduous task.The key causes of driver’s distraction include drunken driving,conversing with co-passengers,fatigue,and operating gadgets while driving.If these distractions are accurately predicted,the drivers can be alerted through an alarm system.Further,this research develops a deep convolutional neural network(deep CNN)models for predicting the reason behind the driver’s distraction.The deep CNN models are trained using numerous images of distracted drivers.The performance of deep CNN models,namely the VGG16,ResNet,and Xception network,is assessed based on the evaluation metrics,such as the precision score,the recall/sensitivity score,the F1 score,and the specificity score.The ResNet model outperformed all other models as the best detection model for predicting and accurately determining the drivers’activities.展开更多
Penile urethral strictures have been managed by a staged surgical approach.In selected cases,spongiofibrosis can be excised,a neo-urethral plate created using buccal mucosa graft(BMG)and tubularized during the same pr...Penile urethral strictures have been managed by a staged surgical approach.In selected cases,spongiofibrosis can be excised,a neo-urethral plate created using buccal mucosa graft(BMG)and tubularized during the same procedure,performing a“twoin-one”stage approach.We aim to identify stricture factors which indicate suitability for this two-in-one stage approach.We assess surgical outcome and compare with staged reconstruction.We conducted an observational descriptive study.The data were prospectively collected from two-in-one stage and staged penile urethroplasties using BMG in a single center between 2007 and 2017.The minimum follow-up was 6 months.Outcomes were assessed clinically,radiologically,and by flow-rate analysis.Failure was defined as recurrent stricture or any subsequent surgical or endoscopic intervention.Descriptive analysis of stricture characteristics and statistical comparison was made between groups.Of 425 penile urethroplasties,139 met the inclusion criteria:59 two-in-one stage and 80 staged.The mean stricture length was 2.8 cm(single stage)and 4.5 cm(staged).Etiology was lichen sclerosus(LS)52.5%(single stage)and 73.8%hypospadias related(staged).40.7%of patients had previous failed urethroplasties in the single-stage group and 81.2%in the staged.The most common stricture locations were navicular fossa(39.0%)and distal penile urethra(59.3%)in the single-stage group and mid or proximal penile urethra(58.7%)in the staged group.Success rates were 89.8%(single stage)and 81.3%(staged).A trend toward a single-stage approach for select penile urethral strictures was noted.We conclude that a single-stage substitution penile urethroplasty using BMG as a“two-in-one”approach is associated with excellent functional outcomes.The most suitable strictures for this approach are distal,primary,and LS-related strictures.展开更多
Twitter sentiment has been shown to be useful in predicting whether Bitcoin’s price will increase or decrease.Yet the state-of-the-art is limited to predicting the price direction and not the magnitude of increase/de...Twitter sentiment has been shown to be useful in predicting whether Bitcoin’s price will increase or decrease.Yet the state-of-the-art is limited to predicting the price direction and not the magnitude of increase/decrease.In this paper,we seek to build on the state-of-the-art to not only predict the direction yet to also predict the magnitude of increase/decrease.We utilise not only sentiment extracted from tweets,but also the volume of tweets.We present results from experiments exploring the relation between sentiment and future price at different temporal granularities,with the goal of discovering the optimal time interval at which the sentiment expressed becomes a reliable indicator of price change.Two different neural network models are explored and evaluated,one based on recurrent nets and one based on convolutional networks.An additional model is presented to predict the magnitude of change,which is framed as a multi-class classification problem.It is shown that this model yields more reliable predictions when used alongside a price trend prediction model.The main research contribution from this paper is that we demonstrate that not only can price direction prediction be made but the magnitude in price change can be predicted with relative accuracy(63%).展开更多
Aneurysmal dilatation of the aortic sinuses of Valsalva has been most extensively documented in the setting of aortopathies, particularly Marfan syndrome. On the other hand, there is limited data in the literature abo...Aneurysmal dilatation of the aortic sinuses of Valsalva has been most extensively documented in the setting of aortopathies, particularly Marfan syndrome. On the other hand, there is limited data in the literature about congenital sinus of Valsalva aneurysms outside this context. For the purpose of this review, we carried out a literature search on aneurysmal dilatation of the sinuses of Valsalva in Marfan syndrome, and compared this with congenital sinus of Valsaiva aneurysms, also including data from a case series from our institution. In conclusion, there are differences in management of aortic dilatation in Marfan syndrome and congenital sinus of Valsalva aneurysms. Though less weil-recognised, congenital aneurysms are often associated with significant morbidity and mortality and timely intervention is necessary.展开更多
This study reports that the carbon star CGCS 673 is a semi-regular(SR)variable star with a period of 135 d and an amplitude of 0.18mag in the V-band.The light curve obtained by this study correlates well with the SR c...This study reports that the carbon star CGCS 673 is a semi-regular(SR)variable star with a period of 135 d and an amplitude of 0.18mag in the V-band.The light curve obtained by this study correlates well with the SR classification as the photometric data obtained show noticeable periodicity in the light changes of CGCS 673 that is occasionally interrupted by a period of irregular variability.The derived period and colour index obtained from our data and those from professional databases indicate that the attributes of this star fall within the parameters of the SR class of variable stars.Following our notification of the discovery that this star is a variable source,CGCS 673 has received the AAVSO Unique Identifier of(AAVSO UID)000-BMZ-492.展开更多
Purpose: This epidemiological retrospective survey aims to provide population-based estimates of the burden of hospitalisation for herpes zoster ophthalmicus in Spain during a twelve-year period (1997-2008). Methods: ...Purpose: This epidemiological retrospective survey aims to provide population-based estimates of the burden of hospitalisation for herpes zoster ophthalmicus in Spain during a twelve-year period (1997-2008). Methods: All hospital discharges and deaths related to herpes zoster ophthalmicus in patients older than 30 years old from 1997 to 2008 in Spain were obtained. Differences in proportions were assessed by the Chi-square test. ANOVA was used for multiple comparisons. Poisson regression was used to assess differences in the rates. Results: A total of 3029 hospital discharges in patients older than 30 years old were coded as herpes zoster ophthalmicus. Of those, 1009 were coded as primary cause of hospitalization. This corresponds to a hospitalization rate of 0.94 and 0.31 hospitalizations per 100,000 for any position and first diagnostic position, respectively. The 75% of the total discharges were in immunocompetent patients. The herpes zoster ophthalmicus hospitalization rate increased significantly during the study period. This increase was also observed for immunocompetent patients. A total of 127 and 21 deaths occurred in patients ≥ 30 year-old hospitalized with herpes zoster ophthalmicus in any diagnostic position and principal diagnostic code, respectively during the 12-year study period. Of them, 70 (53.4%) were in immunocompetent patients, and, of those 11 were in patients with HZO in the first diagnosis position. The hospitalization rate and case-fatality rate increase significantly with age from 50 years old onwards. Conclusion: HZO, a vaccine preventable disease, still causes hospitalization and death in adults in Spain.展开更多
Tourism is becoming a vital component for economic development in South Africa. The income generated by the tourism industry is about 6% of the GDP, which is significant but still falls short of the goal set by the Wh...Tourism is becoming a vital component for economic development in South Africa. The income generated by the tourism industry is about 6% of the GDP, which is significant but still falls short of the goal set by the White Paper on Tourism in 2000. In the light of South Africa hosting the 2010 Football World Cup, it is important to identify ways of sustainable tourism development that would continue to increase the benefits to the economy long after the event＇s over. The main objective of the research was to explore an idea for increasing the level of tourist income generated in the Port Elizabeth （Eastern Cape） area. The idea was researched by means of conducting a cost-benefit analysis of two tourist related projects. These projects would introduce Charter airline services between Europe and Port Elizabeth. A second objective was to identify constraints on the project or market failures which would prevent their implementation. The economic theory behind the operation of an airline showed that lease costs and aeroplane operating costs are the two most important factors determine Charter airline＇s profitability. In order to offset these costs, airlines must achieve high passenger load factors. Charter airlines have the advantage over scheduled airlines, in that they will only fly if a minimum level of people has pre-booked seats. Two aeroplanes were chosen for comparison purpose： an Airbus A 340-300 and a Boeing 767-300ER. The private benefits calculated were based on load factors between 80 and 95 percent for ticket prices of USD 667 and USD 773. In addition, to private costs and benefits, social benefits were also estimated in the form of additional secondary revenue generated. With the introduction of net social benefits, both projects become profitable. A 50 percent substitution of revenue generated by the Charter tourists reduces the profits for the both projects drastically. A project based on a Boeing 767-300ER is the most efficient project as it has the highest NPV and BCR values. A reduction in 展开更多
基金supported by MSD Holding Co.,Ltd.The funding was only for the payment of using CHIRA database
文摘Background： Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting （CINV） at a national level in China or to assess how treatment regimens adhere to current guidelines. Methods： We searched the China Health Insurance Research Association （CHIRA） Database to identify patients with cancer who were 〉 18 years old and received either moderately or highly emetogenie chemotherapy （MEC and HEC, respectively） between 2008 and 2012. Patients＇ characteristics as well as usage of specific antiemetic regimens were analyzed using descriptive statistics. Results： Of the 14,548 patients included in the study, 6,477 received HEC while 8,071 were treated with MEC. Approximately 89.9% used antiemetics prophylactically to prevent acute CINV and 71.5% for delayed CINV while 9.0% were prescribed antiemetics as rescue therapy. A significantly lower proportion of patients treated with HEC received prophylactic antiemetic therapy for delayed CINV as compared to those treated with MEC （59.4% vs. 81.3 %; P〈0.001）. The HEC group had a slightly lower proportion of patients using a mixed regimen containing a 5-HT3 antagonist to prevent both acute and delayed CINV than the MEC group （P〈0.012）; however, a higher proportion received a mixed regimen containing eorticosteroids （P≤0.007）. Although more than half of the patients in the HEC group took three antiemeties to prevent acute and delayed CINV, these rates were significantly lower than those of the MEC group （both P〈0.001）. Finally, analysis of the regimens used revealed that there is over-utilization of drugs within the same class of antiemetic. Conclusions： These findings indicate that more attention is needed for treatment of delayed CINV, in terms of both overall use and the components of a typical treatment regimen.
文摘Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summarize the published literature on the clinical outcome and response to therapy of pediatric CG including two new cases. We performed a search in Pubmed, OVID for related terms; articles including management and clinical and/or endo-histologic follow up information were included and abstracted. Reported findings were pooled in a dedicated database including the corresponding data extracted from chart review in our patients with CG. Twenty-four patients were included (17 females) with a mean age of 11.7 years. The clinical presentation included iron deficiency anemia and dyspepsia. The reported duration of follow up (in 18 patients) ranged between 0.2-14 years. Despite most subjects presenting with anemia including one requiring blood transfusion, oral iron therapy was only documented in 12 patients. Other treatment modalities were antisecretory measures in 13 patients; proton pump inhibitors (12), or histamine-2 blockers (3), sucralfate (5), prednisolone (6), oral budesonide in 3 patients where one received it in fish oil and triple therapy (3). Three (13%) patients showed no clinical improvement despite therapy; conversely 19 out of 22 were reported with improved symptoms including 8 with complete symptom resolution. Spontaneous clinical resolution without antisecretory, anti-inflammatory or gastroprotective agents was noted in 5 patients (4 received only supplemental iron). Follow up endohistopathologic data (17 patients) included persistent collagen band and stable Mononuclear cell infiltrate in 12 patients with histopathologic improvement in 5 patients. Neither collagen band thickness nor mononuclear cell infiltrate correlated with clinical course. Intestinal metaplasia and endocrine cell hyperplasia were reported (1) raising the concern of long term malignant transformation. In summary, CG in chil
基金supported through the Faculty of Medicine and Surgery Award 2021 University of Malta(awarded to K.F).
文摘Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be les
文摘The purpose of the research was to assess the impact of Citizen Development activities on digital transformation. The research identified eight categories that contribute to the success of Low-code No-code (LCNC) projects: 1) Strategy;2) Infrastructure;3) Technology;4) Processes & Procedures;5) Governance;6) Culture;7) People;8) Goals & Metrics and selected six critical success factors from these categories: 1) Operational Efficiency;2) Time Savings;3) Timeframe to Realize Value;4) Employee Engagement;5) Participation;6) Number of Sponsored Ideas. End users of the digital transformation efforts through Citizen Development were asked to assess the six critical success measures in terms of performance and importance criteria. The research results identified that focus should be applied to improving “Timeframe to Realize Value”, on “Operational Efficiency”, and on “Time Savings” to deliver success.
基金Supported by MSD Sharp and Dohme GmbH,Haar,Germany。
文摘BACKGROUND The introduction of biologics has revolutionized the management of the chronic inflammatory bowel disease,ulcerative colitis(UC),with many patients experiencing significant improvements not only in their symptoms but in other outcomes relevant to individuals and society as a whole.In Germany,there are no prospective data>3 mo that assess the work productivity,daily activities and quality of life(QoL)of patients with moderate-to-severe UC treated with golimumab.AIM To assess change in work productivity,capacity for daily activities and QoL in UC patients treated with golimumab in Germany.METHODS The validated Work Productivity Activity Impairment(WPAI)Questionnaire was used to analyze the change in work productivity,the capacity for daily activities after three months(primary endpoint)and disease specific and health related QoL(HRQoL)up to 1 year(secondary endpoints).The changes in work productivity and activity impairment were evaluated every three months until month twelve compared to baseline.Disease-specific and health-related QoL were assessed with the inflammatory bowel disease questionnaire and with the short-form 12 health survey questionnaire(SF-12).RESULTS This prospective non-interventional study included 287 patients.The analysis population was comprised of 282 patients who had completed at least two visits.At baseline,61%of patients had moderate UC and 18%had severe UC.Furthermore,75%of patients worked full-time or part-time at baseline.A total of 212 patients who were employed at the start of the study(employed population)were evaluated for the primary endpoint.Golimumab significantly reduced all WPAI sub-scores compared to baseline after three,six,nine and twelve months after the start of treatment(P<0.0001).In addition,disease-specific QoL and HRQoL,as measured by the SF-12 questionnaire,improved significantly with golimumab at all evaluation times(P<0.0001 in each case vs baseline).CONCLUSION Treatment of moderate-to-severe UC with golimumab leads to significant improvements in patient�
文摘Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,contribute to maintaining healthy cognitive functions throughout life.The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues.The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has,however,not been established.This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans.While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease,consensual results have yet to be reached to fully explore this hypothesis.In this review,we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases,especially in Alzheimer’s disease.We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease.In particular,we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems,as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues,could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.
文摘Background There have been no mortality/morbidity endpoint studies with Iosartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose Iosartan on clinical outcomes in Chinese subjects with heart failure.
基金国家中医药管理局中医药国际合作专项中医药国际化发展研究中心项目,No.GZYYGJ2020003University of Maltaand the Centre of Traditional Chinese Medicine and Culture,University of Malta.
文摘Objective To provide an update on the evidence of the effectiveness of acupuncture in treating chronic non-specific low back pain(CNSLBP)based on randomized controlled trials(RCTs)of acupuncture for CNSLBP published between 2006 and 2020.Methods A comprehensive literature search was conducted through the University of Malta website,using the HyDi search engine.The‘Advanced Search’option was chosen in order to search for articles that were published in English,and associated with the key words,‘Chronic’,‘Acupuncture’,‘Needle’,‘Needling’,‘Non-specific’and‘Low Back Pain’,which were entered in their‘Subject’field,from the year 2006 till 2020.A comprehensive reading and analysis was done for the search result.Results Through the use of the HyDi search engine,accessible through the University of Malta,eighteen randomized controlled trials that met the criteria of this study were selected.Conclusion Through the analysis and comparison of the studies selected for this literature review,there is evidence providing that acupuncture is significantly more effective than current conservative treatment modalities for patients with CNSLBP in reducing pain and improving function.
基金supported by the European Commission under the Horizon 2020 Programme(H2020)part of the LOCARD(https://locard.eu)(Grant Agreement No.832735)project.
文摘Programming errors in Ethereum smart contracts can result in catastrophic financial losses from stolen cryptocurrency.While vulnerability detectors can prevent vulnerable contracts from being deployed,this does not mean that such contracts will not be deployed.Once a vulnerable contract is instantiated on the blockchain and becomes the target of attacks,the identification of exploit transactions becomes indispensable in assessing whether it has been actually exploited and identifying which malicious or subverted accounts were involved.In this work,we study the problem of post-factum investigation of Ethereum attacks using Indicators of Compromise(IoC)specially crafted for use in the blockchain.IoC definitions need to capture the side-effects of successful exploitation in the context of the Ethereum blockchain.Therefore,we define a model for smart contract execution,comprising multiple abstraction levels that mirror the multiple views of code execution on a blockchain.Subsequently,we compare IoCs defined across the different levels in terms of their effectiveness and practicality through EtherClue,a prototype tool for investigating Ethereum security incidents.Our results illustrate that coarse-grained IoCs defined over blocks of transactions can detect exploit transactions with less computation.However,they are contract-specific and suffer from false negatives.On the other hand,fine-grained IoCs defined over virtual machine instructions can avoid these pitfalls at the expense of increased computation,which is nevertheless applicable for practical use.
基金supported by the National Key Research and Development Program[2016YFD0500401]National Science and Technology Support Program[2014BAI13B05]the Development Grant of State Key Laboratory for Infectious Disease Prevention and Control[2015SKLID505]
文摘Japanese encephalitis（JE）is a serious public health issue.This study was undertaken to better understand the relationship between JE distribution and environmental factors in China.JE data from 2005 to 2010 were retrieved from National Notifiable Disease Report System.
文摘Superoxide dismutase (SOD)-deficient Escherichia coli OX326Acells are protected against chemically-induced oxidative stress by expression of the chaperonin GroESL. This protection is equivalent to expression of superoxide dismutase even though GroESL has no inherent SOD activity. Co-overexpression of GroESL and SOD in the same cells results in higher protein yields of SOD and greater metallation of SOD when compared with expression of SOD alone. Greater metallation results in the higher specific activity of SOD that is observed in heat shock, and is not due to increased synthesis of SOD mRNA or protein.
文摘According to various worldwide statistics,most car accidents occur solely due to human error.The person driving a car needs to be alert,especially when travelling through high traffic volumes that permit high-speed transit since a slight distraction can cause a fatal accident.Even though semiautomated checks,such as speed detecting cameras and speed barriers,are deployed,controlling human errors is an arduous task.The key causes of driver’s distraction include drunken driving,conversing with co-passengers,fatigue,and operating gadgets while driving.If these distractions are accurately predicted,the drivers can be alerted through an alarm system.Further,this research develops a deep convolutional neural network(deep CNN)models for predicting the reason behind the driver’s distraction.The deep CNN models are trained using numerous images of distracted drivers.The performance of deep CNN models,namely the VGG16,ResNet,and Xception network,is assessed based on the evaluation metrics,such as the precision score,the recall/sensitivity score,the F1 score,and the specificity score.The ResNet model outperformed all other models as the best detection model for predicting and accurately determining the drivers’activities.
文摘Penile urethral strictures have been managed by a staged surgical approach.In selected cases,spongiofibrosis can be excised,a neo-urethral plate created using buccal mucosa graft(BMG)and tubularized during the same procedure,performing a“twoin-one”stage approach.We aim to identify stricture factors which indicate suitability for this two-in-one stage approach.We assess surgical outcome and compare with staged reconstruction.We conducted an observational descriptive study.The data were prospectively collected from two-in-one stage and staged penile urethroplasties using BMG in a single center between 2007 and 2017.The minimum follow-up was 6 months.Outcomes were assessed clinically,radiologically,and by flow-rate analysis.Failure was defined as recurrent stricture or any subsequent surgical or endoscopic intervention.Descriptive analysis of stricture characteristics and statistical comparison was made between groups.Of 425 penile urethroplasties,139 met the inclusion criteria:59 two-in-one stage and 80 staged.The mean stricture length was 2.8 cm(single stage)and 4.5 cm(staged).Etiology was lichen sclerosus(LS)52.5%(single stage)and 73.8%hypospadias related(staged).40.7%of patients had previous failed urethroplasties in the single-stage group and 81.2%in the staged.The most common stricture locations were navicular fossa(39.0%)and distal penile urethra(59.3%)in the single-stage group and mid or proximal penile urethra(58.7%)in the staged group.Success rates were 89.8%(single stage)and 81.3%(staged).A trend toward a single-stage approach for select penile urethral strictures was noted.We conclude that a single-stage substitution penile urethroplasty using BMG as a“two-in-one”approach is associated with excellent functional outcomes.The most suitable strictures for this approach are distal,primary,and LS-related strictures.
文摘Twitter sentiment has been shown to be useful in predicting whether Bitcoin’s price will increase or decrease.Yet the state-of-the-art is limited to predicting the price direction and not the magnitude of increase/decrease.In this paper,we seek to build on the state-of-the-art to not only predict the direction yet to also predict the magnitude of increase/decrease.We utilise not only sentiment extracted from tweets,but also the volume of tweets.We present results from experiments exploring the relation between sentiment and future price at different temporal granularities,with the goal of discovering the optimal time interval at which the sentiment expressed becomes a reliable indicator of price change.Two different neural network models are explored and evaluated,one based on recurrent nets and one based on convolutional networks.An additional model is presented to predict the magnitude of change,which is framed as a multi-class classification problem.It is shown that this model yields more reliable predictions when used alongside a price trend prediction model.The main research contribution from this paper is that we demonstrate that not only can price direction prediction be made but the magnitude in price change can be predicted with relative accuracy(63%).
文摘Aneurysmal dilatation of the aortic sinuses of Valsalva has been most extensively documented in the setting of aortopathies, particularly Marfan syndrome. On the other hand, there is limited data in the literature about congenital sinus of Valsalva aneurysms outside this context. For the purpose of this review, we carried out a literature search on aneurysmal dilatation of the sinuses of Valsalva in Marfan syndrome, and compared this with congenital sinus of Valsaiva aneurysms, also including data from a case series from our institution. In conclusion, there are differences in management of aortic dilatation in Marfan syndrome and congenital sinus of Valsalva aneurysms. Though less weil-recognised, congenital aneurysms are often associated with significant morbidity and mortality and timely intervention is necessary.
基金This research was made possible through the use of the AAVSO Photometric All-Sky Survey(APASS),funded by the Robert Martin Ayers Sciences Fund and NSF AST-1412587.
文摘This study reports that the carbon star CGCS 673 is a semi-regular(SR)variable star with a period of 135 d and an amplitude of 0.18mag in the V-band.The light curve obtained by this study correlates well with the SR classification as the photometric data obtained show noticeable periodicity in the light changes of CGCS 673 that is occasionally interrupted by a period of irregular variability.The derived period and colour index obtained from our data and those from professional databases indicate that the attributes of this star fall within the parameters of the SR class of variable stars.Following our notification of the discovery that this star is a variable source,CGCS 673 has received the AAVSO Unique Identifier of(AAVSO UID)000-BMZ-492.
文摘Purpose: This epidemiological retrospective survey aims to provide population-based estimates of the burden of hospitalisation for herpes zoster ophthalmicus in Spain during a twelve-year period (1997-2008). Methods: All hospital discharges and deaths related to herpes zoster ophthalmicus in patients older than 30 years old from 1997 to 2008 in Spain were obtained. Differences in proportions were assessed by the Chi-square test. ANOVA was used for multiple comparisons. Poisson regression was used to assess differences in the rates. Results: A total of 3029 hospital discharges in patients older than 30 years old were coded as herpes zoster ophthalmicus. Of those, 1009 were coded as primary cause of hospitalization. This corresponds to a hospitalization rate of 0.94 and 0.31 hospitalizations per 100,000 for any position and first diagnostic position, respectively. The 75% of the total discharges were in immunocompetent patients. The herpes zoster ophthalmicus hospitalization rate increased significantly during the study period. This increase was also observed for immunocompetent patients. A total of 127 and 21 deaths occurred in patients ≥ 30 year-old hospitalized with herpes zoster ophthalmicus in any diagnostic position and principal diagnostic code, respectively during the 12-year study period. Of them, 70 (53.4%) were in immunocompetent patients, and, of those 11 were in patients with HZO in the first diagnosis position. The hospitalization rate and case-fatality rate increase significantly with age from 50 years old onwards. Conclusion: HZO, a vaccine preventable disease, still causes hospitalization and death in adults in Spain.
文摘Tourism is becoming a vital component for economic development in South Africa. The income generated by the tourism industry is about 6% of the GDP, which is significant but still falls short of the goal set by the White Paper on Tourism in 2000. In the light of South Africa hosting the 2010 Football World Cup, it is important to identify ways of sustainable tourism development that would continue to increase the benefits to the economy long after the event＇s over. The main objective of the research was to explore an idea for increasing the level of tourist income generated in the Port Elizabeth （Eastern Cape） area. The idea was researched by means of conducting a cost-benefit analysis of two tourist related projects. These projects would introduce Charter airline services between Europe and Port Elizabeth. A second objective was to identify constraints on the project or market failures which would prevent their implementation. The economic theory behind the operation of an airline showed that lease costs and aeroplane operating costs are the two most important factors determine Charter airline＇s profitability. In order to offset these costs, airlines must achieve high passenger load factors. Charter airlines have the advantage over scheduled airlines, in that they will only fly if a minimum level of people has pre-booked seats. Two aeroplanes were chosen for comparison purpose： an Airbus A 340-300 and a Boeing 767-300ER. The private benefits calculated were based on load factors between 80 and 95 percent for ticket prices of USD 667 and USD 773. In addition, to private costs and benefits, social benefits were also estimated in the form of additional secondary revenue generated. With the introduction of net social benefits, both projects become profitable. A 50 percent substitution of revenue generated by the Charter tourists reduces the profits for the both projects drastically. A project based on a Boeing 767-300ER is the most efficient project as it has the highest NPV and BCR values. A reduction in
