In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of ...In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death(DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease(CKD). Acute kidney injury(AKI) post-LT has been recently recognized as an important risk factor for the occurrence of denovo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome(PRS) that can influence recipient's morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since preLT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A Pub Med search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on Pub Med search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in l展开更多
Mobile ad-hoc networks （MANETs） and wireless sensor networks （WSNs） have gained remarkable apprecia- tion and technological development over the last few years. Despite ease of deployment, tremendous applications ...Mobile ad-hoc networks （MANETs） and wireless sensor networks （WSNs） have gained remarkable apprecia- tion and technological development over the last few years. Despite ease of deployment, tremendous applications and significant advantages, security has always been a challeng- ing issue due to the nature of environments in which nodes operate. Nodes＇ physical capture, malicious or selfish behav- ior cannot be detected by traditional security schemes. Trust and reputation based approaches have gained global recog- nition in providing additional means of security for decision making in sensor and ad-hoc networks. This paper provides an extensive literature review of trust and reputation based models both in sensor and ad-hoc networks. Based on the mechanism of trust establishment, we categorize the state- of-the-art into two groups namely node-centric trust mod- els and system-centric trust models. Based on trust evidence, initialization, computation, propagation and weight assign- ments, we evaluate the efficacy of the existing schemes. Fi- nally, we conclude our discussion with identification of some unresolved issues in pursuit of trust and reputation manage- ment.展开更多
Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent causes of chronic liver disease worldwide.In the last decade it has become the third most common indication for liver transplantation in the United ...Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent causes of chronic liver disease worldwide.In the last decade it has become the third most common indication for liver transplantation in the United States.Increasing prevalence of NAFLD in the general population also poses a risk to organ donation,as allograft steatosis can be associated with non-function of the graft.Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease,although long term outcomes beyond 10 year are lacking.NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted.De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease.Predictors for NAFLD post-transplant recurrence include obesity,hyperlipidemia and diabetes as well as steroid dose after liver transplantation.A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk.Although immunosuppression side effects potentiate obesity and the metabolic syndrome,studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population.Based on pre-transplant data,sustained weight loss through diet and exercise is the most effective therapy for NAFLD.Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents.Studies of these therapies are lacking in the post-transplant population.A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD.展开更多
Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying,enhancing,and restoring immune function.Thymosin alpha 1 has been utilized in the treatment of immunocompromi...Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying,enhancing,and restoring immune function.Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies,as an enhancer of vaccine response,and as a means of curbing morbidity and mortality in sepsis and numerous infections.Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells.In this review,we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1.Considering the known biochemical properties including antibacterial and antiviral properties,timehonored applications,and the new promising findings regarding the use of thymosin,we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.展开更多
Drug-resistant tuberculosis （TB） poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insigh...Drug-resistant tuberculosis （TB） poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug- resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuber- culosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.展开更多
AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolizati...AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) + sorafenib vs TACE alone. METHODS: In this retrospective cohort study we collected data on all consecutive patients with a diagnosis of unresectable HCC between 2007 and 2011 who had been treated with TACE + sorafenib or TACE alone. We hypothesized that the combination therapy is superior to TACE alone in improving the survival in these patients. Data extracted included patient's demographics, etiology of liver disease, histology of HCC, stage of liver disease with respect to model of end stage liverdisease score and Child-Turcotte-Pugh (CTP) classification and Barcelona Clinic Liver Cancer (BCLC) staging for HCC. Computed tomography scan findings, alpha fetoprotein levels, number of treatments and related AE were also recorded and analyzed. RESULTS: Of the 43 patients who met inclusion criteria, 13 were treated with TACE + sorafenib and 30 with TACE alone. There was no significant difference in median survival: 20.6 mo (95%CI: 13.4-38.4) for the TACE + sorafenib and 18.3 mo (95%CI: 11.8-32.9) for the TACE alone (P = 0.72). There were also no statistically significant differences between groups in OS (HR = 0.82, 95%CI: 0.38-1.77; P = 0.61), PFS (HR = 0.93, 95%CI: 0.45-1.89; P = 0.83), and treatment-related toxicities (P = 0.554). CTP classification and BCLC staging for HCC were statistically significant (P = 0.001, P = 0.04 respectively) in predicting the survival in patients with HCC. The common AE observed were abdominal pain, nausea, vomiting and mild elevation of liver enzymes. CONCLUSION: Combination therapy with TACE + sorafenib is safe and equally effective as TACE alone in patients with unresectable HCC. CTP classification and BCLC staging were the significant predictors of survival. Future trials with large number of patients are needed to further validate this observation.展开更多
Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur w...Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.展开更多
Self-referenced dissipative Kerr solitons (DKSs) based on optical microresonators offer prominent characteristics allowing for various applications from precision measurement to astronomical spectrometer calibration. ...Self-referenced dissipative Kerr solitons (DKSs) based on optical microresonators offer prominent characteristics allowing for various applications from precision measurement to astronomical spectrometer calibration. To date,direct octave-spanning DKS generation has been achieved only in ultrahigh-Q silicon nitride microresonators under optimized laser tuning speed or bi-directional tuning. Here we propose a simple method to easily access the octave-spanning DKS in an aluminum nitride (AlN) microresonator. In the design,two modes that belong to different families but with the same polarization are nearly degenerate and act as a pump and an auxiliary resonance,respectively. The presence of the auxiliary resonance can balance the thermal dragging effect,crucially simplifying the DKS generation with a single pump and leading to an enhanced soliton access window. We experimentally demonstrate the long-lived DKS operation with a record single-soliton step (10.4 GHz or83 pm) and an octave-spanning bandwidth (1100–2300 nm) through adiabatic pump tuning. Our scheme also allows for direct creation of the DKS state with high probability and without elaborate wavelength or power schemes being required to stabilize the soliton behavior.展开更多
AIM:To determine antibiotic resistance of Helicobacter pylori(H.pylori) in Pakistan and its correlation with host and pathogen associated factors.METHODS:A total of 178 strains of H.pylori were isolated from gastric b...AIM:To determine antibiotic resistance of Helicobacter pylori(H.pylori) in Pakistan and its correlation with host and pathogen associated factors.METHODS:A total of 178 strains of H.pylori were isolated from gastric biopsies of dyspeptic patients.Susceptibility patterns against first and second-line antibiotics were determined and trends of resistance were analyzed in relation to the sampling period,gastric conditions and cagA gene carriage.The effect of cagA gene on the acquisition of resistance was investigated by mutant selection assay.RESULTS:The observations showed that monoresistant strains were prevalent with rates of 89% for metronidazole,36% for clarithromycin,37% for amoxicillin,18.5% for ofloxacin and 12% for tetracycline.Furthermore,clarithromycin resistance was on the rise from 2005 to 2008(32% vs 38%,P = 0.004) and it is significantly observed in non ulcerative dyspeptic patients compared to gastritis,gastric ulcer and duodenal ulcer cases(53% vs 20%,18% and 19%,P = 0.000).On the contrary,metronidazole and ofloxacin resistance were more common in gastritis and gastric ulcer cases.Distribution analysis and frequencies of resistant mutants in vitro correlated with the absence of cagA gene with metronidazole and ofloxacin resistance.CONCLUSION:The study confirms the alarming levels of antibiotic resistance associated with the degree of gastric inflammation and cagA gene carriage in H.pylori strains.展开更多
An epidemic is a quick and widespread disease that threatens many lives and damages the economy.The epidemic lifetime should be accurate so that timely and remedial steps are determined.These include the closing of bo...An epidemic is a quick and widespread disease that threatens many lives and damages the economy.The epidemic lifetime should be accurate so that timely and remedial steps are determined.These include the closing of borders schools,suspension of community and commuting services.The forecast of an outbreak effectively is a very necessary but difficult task.A predictive model that provides the best possible forecast is a great challenge for machine learning with only a few samples of training available.This work proposes and examines a prediction model based on a deep extreme learning machine(DELM).This methodology is used to carry out an experiment based on the recent Wuhan coronavirus outbreak.An optimized prediction model that has been developed,namely DELM,is demonstrated to be able to make a prediction that is fairly best.The results show that the new methodology is useful in developing an appropriate forecast when the samples are far from abundant during the critical period of the disease.During the investigation,it is shown that the proposed approach has the highest accuracy rate of 97.59%with 70%of training,30%of test and validation.Simulation results validate the prediction effectiveness of the proposed scheme.展开更多
Congenital abnormalities of the kidney and urinary tract(CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis(bilateral). Many of them are detected ...Congenital abnormalities of the kidney and urinary tract(CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis(bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number(agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography(US) is typically the first imaging performed as it is easily available, noninvasive and radiation free used both antenatally and postnatally. Computed tomography(CT) and magnetic resonance imaging(MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management.展开更多
Iron deficiency anemia(IDA)is common and often under recognized problem in the elderly.It may be the result of multiple factors including a bleeding lesion in the gastrointestinal tract.Twenty percent of elderly patie...Iron deficiency anemia(IDA)is common and often under recognized problem in the elderly.It may be the result of multiple factors including a bleeding lesion in the gastrointestinal tract.Twenty percent of elderly patients with IDA have a negative upper and lower endoscopy and two-thirds of these have a lesion in the small bowel(SB).Capsule endoscopy(CE)provides direct visualization of entire SB mucosa,which was not possible before.It is superior to push enteroscopy,enteroclysis and barium radiography for diagnosing clinically significant SB pathology resulting in IDA.Angioectasia is one of the commonest lesions seen on the CE in elderly with IDA.The diagnostic yield of CE for IDA progressively increases with advancing age,and is highest among patients over 85 years of age.Balloon assisted enteroscopy is used to treat the lesions seen on CE.CE has some limitations mainly lack of therapeutic capability,inability to provide precise location of the lesion and false positive results.Overall CE is a very safe and effective procedure for the evaluation of IDA in elderly.展开更多
Visible-light-responsive ternary metal tungstate(MWO_4) photocatalysts are being increasingly investigated for energy conversion and environmental purification applications owing to their striking features, including ...Visible-light-responsive ternary metal tungstate(MWO_4) photocatalysts are being increasingly investigated for energy conversion and environmental purification applications owing to their striking features, including low cost,eco-friendliness, and high stability under acidic and oxidative conditions. However, rapid recombination of photoinduced electron–hole pairs and a narrow light response range to the solar spectrum lead to low photocatalytic activity of MWO_4-based materials, thus significantly hampering their wide usage in practice. To enable their widespread practical usage, significant efforts have been devoted, by developing new concepts and innovative strategies. In this review, we aim to provide an integrated overview of the fundamentals and recent progress of MWO_4-based photocatalysts. Furthermore, different strategies, including morphological control, surface modification, heteroatom doping, and heterojunction fabrication, which are employed to promote the photocatalyticactivities of MWO_4-based materials, are systematically summarized and discussed. Finally, existing challenges and a future perspective are also provided to shed light on the development of highly efficient MWO_4-based photocatalysts.展开更多
Metabolic diseases such as nonalcoholic fatty liver disease(NAFLD)are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma(HCC).The gut microbiome is closely connected to ...Metabolic diseases such as nonalcoholic fatty liver disease(NAFLD)are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma(HCC).The gut microbiome is closely connected to the liver via the portal vein,and has recently been identified as a predictor of liver disease state.Studies in NAFLD,cirrhosis and HCC have identified certain microbial signatures associated with these diseases,with the disease-associated microbiome changes collectively referred to as dysbiosis.The pathophysiologic underpinnings of these observations are an area of ongoing investigation,with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability(leaky gut)and activation of the innate immune system.In the innate immune system,pathogen recognition receptors(Toll like receptors)on resident liver cells and macrophages cause liver inflammation,fibrosis,hepatocyte proliferation and reduced antitumor immunity,leading to chronic liver disease and carcinogenesis.Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR(nuclear receptor),which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease.Longitudinal experimental and clinical studies are needed in different populations to examine these questions further.The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet,probiotics,fecal microbiota transplantation and prebiotics in improving liver disease in experimental models.Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis.The microbial profile is different in responders to cancer immunotherapy including liver cancer,but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.展开更多
基金Supported by An international research grant 2014 of the Italian Society of NephrologyThe study sponsor provided logistic support but had no role in the collection and analysis of data or in the writing of the review and in the decision to submit the paper for publication+1 种基金The study also received support from the NIHR Birmingham Liver Biomedical Research UnitThe opinions expressed are those of the authors and not necessarily those of the NHS,the NIHR or the Department of Health
文摘In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death(DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease(CKD). Acute kidney injury(AKI) post-LT has been recently recognized as an important risk factor for the occurrence of denovo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome(PRS) that can influence recipient's morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since preLT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A Pub Med search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on Pub Med search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in l
文摘Mobile ad-hoc networks （MANETs） and wireless sensor networks （WSNs） have gained remarkable apprecia- tion and technological development over the last few years. Despite ease of deployment, tremendous applications and significant advantages, security has always been a challeng- ing issue due to the nature of environments in which nodes operate. Nodes＇ physical capture, malicious or selfish behav- ior cannot be detected by traditional security schemes. Trust and reputation based approaches have gained global recog- nition in providing additional means of security for decision making in sensor and ad-hoc networks. This paper provides an extensive literature review of trust and reputation based models both in sensor and ad-hoc networks. Based on the mechanism of trust establishment, we categorize the state- of-the-art into two groups namely node-centric trust mod- els and system-centric trust models. Based on trust evidence, initialization, computation, propagation and weight assign- ments, we evaluate the efficacy of the existing schemes. Fi- nally, we conclude our discussion with identification of some unresolved issues in pursuit of trust and reputation manage- ment.
文摘Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent causes of chronic liver disease worldwide.In the last decade it has become the third most common indication for liver transplantation in the United States.Increasing prevalence of NAFLD in the general population also poses a risk to organ donation,as allograft steatosis can be associated with non-function of the graft.Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease,although long term outcomes beyond 10 year are lacking.NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted.De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease.Predictors for NAFLD post-transplant recurrence include obesity,hyperlipidemia and diabetes as well as steroid dose after liver transplantation.A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk.Although immunosuppression side effects potentiate obesity and the metabolic syndrome,studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population.Based on pre-transplant data,sustained weight loss through diet and exercise is the most effective therapy for NAFLD.Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents.Studies of these therapies are lacking in the post-transplant population.A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD.
文摘Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying,enhancing,and restoring immune function.Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies,as an enhancer of vaccine response,and as a means of curbing morbidity and mortality in sepsis and numerous infections.Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells.In this review,we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1.Considering the known biochemical properties including antibacterial and antiviral properties,timehonored applications,and the new promising findings regarding the use of thymosin,we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.
基金supported by the National Natural Science Foundation of China(No.81572037)the One Hundred Talents Program of the Chinese Academy of Sciences(Category A,to T.Z.)+8 种基金the Open Project Grant(No.2014SKLRD-006)the Key Project Grant(No.SKLRD2016ZJ003)the State Key Laboratory of Respiratory Diseases,Guangzhou Institute of Respiratory Disease,First Allied Hospital of Guangzhou Medical Universitythe PhD Start-up Fund of Natural Science Foundation,Guangdong Province, China(No.2016A030310123 to J.G.)the Chinese Academy of Sciences-Commonwealth Scientific and Industrial Research Organization Mutual Grant(No.154144KYSB20150045)partially financed by Guangzhou Municipal Industry and Research Collaborative Innovation Program(Nos.201508020248 and 201604020019)Guangzhou Municipal Clinical Medical Center Program(No.155700012)sponsored by CASTWAS President's PhD Fellowship Program(to M.M.I,and C.C.)UCAS Fellowship Program(to H.M.A.H.and J.M.) for international PhD students
文摘Drug-resistant tuberculosis （TB） poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug- resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuber- culosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.
文摘AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) + sorafenib vs TACE alone. METHODS: In this retrospective cohort study we collected data on all consecutive patients with a diagnosis of unresectable HCC between 2007 and 2011 who had been treated with TACE + sorafenib or TACE alone. We hypothesized that the combination therapy is superior to TACE alone in improving the survival in these patients. Data extracted included patient's demographics, etiology of liver disease, histology of HCC, stage of liver disease with respect to model of end stage liverdisease score and Child-Turcotte-Pugh (CTP) classification and Barcelona Clinic Liver Cancer (BCLC) staging for HCC. Computed tomography scan findings, alpha fetoprotein levels, number of treatments and related AE were also recorded and analyzed. RESULTS: Of the 43 patients who met inclusion criteria, 13 were treated with TACE + sorafenib and 30 with TACE alone. There was no significant difference in median survival: 20.6 mo (95%CI: 13.4-38.4) for the TACE + sorafenib and 18.3 mo (95%CI: 11.8-32.9) for the TACE alone (P = 0.72). There were also no statistically significant differences between groups in OS (HR = 0.82, 95%CI: 0.38-1.77; P = 0.61), PFS (HR = 0.93, 95%CI: 0.45-1.89; P = 0.83), and treatment-related toxicities (P = 0.554). CTP classification and BCLC staging for HCC were statistically significant (P = 0.001, P = 0.04 respectively) in predicting the survival in patients with HCC. The common AE observed were abdominal pain, nausea, vomiting and mild elevation of liver enzymes. CONCLUSION: Combination therapy with TACE + sorafenib is safe and equally effective as TACE alone in patients with unresectable HCC. CTP classification and BCLC staging were the significant predictors of survival. Future trials with large number of patients are needed to further validate this observation.
文摘Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.
基金Science Foundation Ireland (17/NSFC/4918)National Natural Science Foundation of China(61861136001)。
文摘Self-referenced dissipative Kerr solitons (DKSs) based on optical microresonators offer prominent characteristics allowing for various applications from precision measurement to astronomical spectrometer calibration. To date,direct octave-spanning DKS generation has been achieved only in ultrahigh-Q silicon nitride microresonators under optimized laser tuning speed or bi-directional tuning. Here we propose a simple method to easily access the octave-spanning DKS in an aluminum nitride (AlN) microresonator. In the design,two modes that belong to different families but with the same polarization are nearly degenerate and act as a pump and an auxiliary resonance,respectively. The presence of the auxiliary resonance can balance the thermal dragging effect,crucially simplifying the DKS generation with a single pump and leading to an enhanced soliton access window. We experimentally demonstrate the long-lived DKS operation with a record single-soliton step (10.4 GHz or83 pm) and an octave-spanning bandwidth (1100–2300 nm) through adiabatic pump tuning. Our scheme also allows for direct creation of the DKS state with high probability and without elaborate wavelength or power schemes being required to stabilize the soliton behavior.
基金Supported by The grants of Higher Education Commission of Pakistan and University of Karachi awarded to Adnan Khan
文摘AIM:To determine antibiotic resistance of Helicobacter pylori(H.pylori) in Pakistan and its correlation with host and pathogen associated factors.METHODS:A total of 178 strains of H.pylori were isolated from gastric biopsies of dyspeptic patients.Susceptibility patterns against first and second-line antibiotics were determined and trends of resistance were analyzed in relation to the sampling period,gastric conditions and cagA gene carriage.The effect of cagA gene on the acquisition of resistance was investigated by mutant selection assay.RESULTS:The observations showed that monoresistant strains were prevalent with rates of 89% for metronidazole,36% for clarithromycin,37% for amoxicillin,18.5% for ofloxacin and 12% for tetracycline.Furthermore,clarithromycin resistance was on the rise from 2005 to 2008(32% vs 38%,P = 0.004) and it is significantly observed in non ulcerative dyspeptic patients compared to gastritis,gastric ulcer and duodenal ulcer cases(53% vs 20%,18% and 19%,P = 0.000).On the contrary,metronidazole and ofloxacin resistance were more common in gastritis and gastric ulcer cases.Distribution analysis and frequencies of resistant mutants in vitro correlated with the absence of cagA gene with metronidazole and ofloxacin resistance.CONCLUSION:The study confirms the alarming levels of antibiotic resistance associated with the degree of gastric inflammation and cagA gene carriage in H.pylori strains.
文摘An epidemic is a quick and widespread disease that threatens many lives and damages the economy.The epidemic lifetime should be accurate so that timely and remedial steps are determined.These include the closing of borders schools,suspension of community and commuting services.The forecast of an outbreak effectively is a very necessary but difficult task.A predictive model that provides the best possible forecast is a great challenge for machine learning with only a few samples of training available.This work proposes and examines a prediction model based on a deep extreme learning machine(DELM).This methodology is used to carry out an experiment based on the recent Wuhan coronavirus outbreak.An optimized prediction model that has been developed,namely DELM,is demonstrated to be able to make a prediction that is fairly best.The results show that the new methodology is useful in developing an appropriate forecast when the samples are far from abundant during the critical period of the disease.During the investigation,it is shown that the proposed approach has the highest accuracy rate of 97.59%with 70%of training,30%of test and validation.Simulation results validate the prediction effectiveness of the proposed scheme.
文摘Congenital abnormalities of the kidney and urinary tract(CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis(bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number(agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography(US) is typically the first imaging performed as it is easily available, noninvasive and radiation free used both antenatally and postnatally. Computed tomography(CT) and magnetic resonance imaging(MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management.
文摘Iron deficiency anemia(IDA)is common and often under recognized problem in the elderly.It may be the result of multiple factors including a bleeding lesion in the gastrointestinal tract.Twenty percent of elderly patients with IDA have a negative upper and lower endoscopy and two-thirds of these have a lesion in the small bowel(SB).Capsule endoscopy(CE)provides direct visualization of entire SB mucosa,which was not possible before.It is superior to push enteroscopy,enteroclysis and barium radiography for diagnosing clinically significant SB pathology resulting in IDA.Angioectasia is one of the commonest lesions seen on the CE in elderly with IDA.The diagnostic yield of CE for IDA progressively increases with advancing age,and is highest among patients over 85 years of age.Balloon assisted enteroscopy is used to treat the lesions seen on CE.CE has some limitations mainly lack of therapeutic capability,inability to provide precise location of the lesion and false positive results.Overall CE is a very safe and effective procedure for the evaluation of IDA in elderly.
基金support of NSFC 51702284Fundamental Research Funds for the Central Universities (112109*172210171)+2 种基金the Startup Foundation for Hundred-Talent Program of Zhejiang University (112100-193820101/001/022)support of the NSFC 21501138the Science Research Foundation of Wuhan Institute of Technology (K201513)
文摘Visible-light-responsive ternary metal tungstate(MWO_4) photocatalysts are being increasingly investigated for energy conversion and environmental purification applications owing to their striking features, including low cost,eco-friendliness, and high stability under acidic and oxidative conditions. However, rapid recombination of photoinduced electron–hole pairs and a narrow light response range to the solar spectrum lead to low photocatalytic activity of MWO_4-based materials, thus significantly hampering their wide usage in practice. To enable their widespread practical usage, significant efforts have been devoted, by developing new concepts and innovative strategies. In this review, we aim to provide an integrated overview of the fundamentals and recent progress of MWO_4-based photocatalysts. Furthermore, different strategies, including morphological control, surface modification, heteroatom doping, and heterojunction fabrication, which are employed to promote the photocatalyticactivities of MWO_4-based materials, are systematically summarized and discussed. Finally, existing challenges and a future perspective are also provided to shed light on the development of highly efficient MWO_4-based photocatalysts.
文摘Metabolic diseases such as nonalcoholic fatty liver disease(NAFLD)are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma(HCC).The gut microbiome is closely connected to the liver via the portal vein,and has recently been identified as a predictor of liver disease state.Studies in NAFLD,cirrhosis and HCC have identified certain microbial signatures associated with these diseases,with the disease-associated microbiome changes collectively referred to as dysbiosis.The pathophysiologic underpinnings of these observations are an area of ongoing investigation,with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability(leaky gut)and activation of the innate immune system.In the innate immune system,pathogen recognition receptors(Toll like receptors)on resident liver cells and macrophages cause liver inflammation,fibrosis,hepatocyte proliferation and reduced antitumor immunity,leading to chronic liver disease and carcinogenesis.Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR(nuclear receptor),which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease.Longitudinal experimental and clinical studies are needed in different populations to examine these questions further.The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet,probiotics,fecal microbiota transplantation and prebiotics in improving liver disease in experimental models.Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis.The microbial profile is different in responders to cancer immunotherapy including liver cancer,but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.
