AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer.METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out usin...AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer.METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and Pub Med until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out.RESULTS: Fourteen studies reported the prevalence of extramural venous invasion(EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26(0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395(0.29, 0.51)].CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future.展开更多
Colorectal cancer (CRC) is the 3<sup>rd</sup> most common cancer in the United States with more than 10000 new cases diagnosed annually. Approximately 20% of patients with CRC will have distant metastasis ...Colorectal cancer (CRC) is the 3<sup>rd</sup> most common cancer in the United States with more than 10000 new cases diagnosed annually. Approximately 20% of patients with CRC will have distant metastasis at time of diagnosis, making them poor candidates for primary surgical resection. Similarly, 8%-25% of patients with CRC will present with bowel obstruction and will require palliative therapy. Emergent surgical decompression has a high mortality and morbidity, and often leads to a colostomy which impairs the patient’s quality of life. In the last decade, there has been an increasing use of colonic stents for palliative therapy to relieve malignant colonic obstruction. Colonic stents have been shown to be effective and safe to treat obstruction from CRC, and are now the therapy of choice in this scenario. In the setting of an acute bowel obstruction in patients with potentially resectable colon cancer, stents may be used to delay surgery and thus allow for decompression, adequate bowel preparation, and optimization of the patient’s condition for curative surgical intervention. An overall complication rate (major and minor) of up to 25% has been associated with the procedure. Long term failure of stents may result from stent migration and tumor ingrowth. In the majority of cases, repeat stenting or surgical intervention can successfully overcome these adverse effects.展开更多
BACKGROUND Hemorrhoidal disease is the most common anorectal disorder.Hemorrhoids can be classified as external or internal,according to their relation to the dentate line.External hemorrhoids originate below the dent...BACKGROUND Hemorrhoidal disease is the most common anorectal disorder.Hemorrhoids can be classified as external or internal,according to their relation to the dentate line.External hemorrhoids originate below the dentate line and are managed conservatively unless the patient cannot keep the perianal region clean,or they cause significant discomfort.Internal hemorrhoids originate above the dentate line and can be managed according to the graded degree of prolapse,as described by Goligher.Generally,low-grade internal hemorrhoids are effectively treated conservatively,by non-operative measures,while high-grade internal hemorrhoids warrant procedural intervention.AIM To determine the application of clinical practice guidelines for the current management of hemorrhoids and colorectal surgeon consensus in Australia and New Zealand.METHODS An online survey was distributed to 206 colorectal surgeons in Australia and New Zealand using 17 guideline-based hypothetical clinical scenarios.RESULTS There were 82 respondents(40%)to 17 guideline-based scenarios.Nine(53%)reached consensus,of which only 1(6%)disagreed with the guidelines.This was based on low quality evidence for the management of acutely thrombosed external hemorrhoids.There were 8 scenarios which showed community equipoise(47%)and they were equally divided for agreeing or disagreeing with the guidelines.These topics were based on low and moderate levels of evidence.They included the initial management of grade I internal hemorrhoids,grade III internal hemorrhoids when initial management had failed and the patient had recognised risks factors for septic complications;and finally,the decision-making when considering patient preferences,including a prompt return to work,or minimal post-operative pain.CONCLUSION Although there are areas of consensus in the management of hemorrhoids,there are many areas of community equipoise which would benefit from further research.展开更多
Objective Intracerebral hemorrhage(ICH)refers to predominant,sporadic,and non-traumatic bleeding in the brain parenchyma.The PI3K/AKT/mTOR signaling pathway is an important signal transduction pathway regulated by enz...Objective Intracerebral hemorrhage(ICH)refers to predominant,sporadic,and non-traumatic bleeding in the brain parenchyma.The PI3K/AKT/mTOR signaling pathway is an important signal transduction pathway regulated by enzyme-linked receptors and has many biological functions in mammals.It plays a key role in neuronal metabolism,gene expression regulation,and tissue homeostasis in the healthy and diseased brain.Methods In the present study,the role of the PI3K/AKT/mTOR pathway inhibitor chrysophanol(CPH)(10 mg/kg and 20 mg/kg,orally)in the improvement of ICH-associated neurological defects in rats was investigated.Autologous blood(20µL/5 min/unilateral/intracerebroventricular)mimics ICH-like defects involving cellular and molecular dysfunction and neurotransmitter imbalance.The current study also included various behavioral assessments to examine cognition,memory,and motor and neuromuscular coordination.The protein expression levels of PI3K,AKT,and mTOR as well as myelin basic protein and apoptotic markers,such as Bax,Bcl-2,and caspase-3,were examined using ELISA kits.Furthermore,the levels of various neuroinflammatory cytokines and oxidative stress markers were assessed.Additionally,the neurological severity score,brain water content,gross brain pathology,and hematoma size were used to indicate neurological function and brain edema.Results CPH was found to be neuroprotective by restoring neurobehavioral alterations and significantly reducing the elevated PI3K,AKT,and mTOR protein levels,and modulating the apoptotic markers such as Bax,Bcl-2,and caspase-3 in rat brain homogenate.CPH substantially reduced the inflammatory cytokines like interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.CPH administration restored the neurotransmitters GABA,glutamate,acetylcholine,dopamine,and various oxidative stress markers.Conclusion Our results show that CPH may be a promising therapeutic approach for overcoming neuronal damage caused by the overexpression of the PI3K/AKT/mTOR signaling pathway in ICH-induced neurological dysfu展开更多
Pyricularia oryzae anamorph of Magnaporthe oryzae is one of the most notorious fungal pathogens causing severe economic loss in rice production worldwide. Various methods, viz. cultural, biological and molecular appro...Pyricularia oryzae anamorph of Magnaporthe oryzae is one of the most notorious fungal pathogens causing severe economic loss in rice production worldwide. Various methods, viz. cultural, biological and molecular approaches, are utilized to counteract this pathogen. Moreover, some tolerant or resistant rice varieties have been developed with the help of breeding programmes. Isolation and molecular characterization of different blast resistance genes now open the gate for new possibilities to elucidate the actual allelic variants of these genes via various molecular breeding and transgenic approaches. However, the behavioral pattern of this fungus breakups the resistance barriers in the resistant or tolerant rice varieties. This host-pathogen barrier will be possibly countered in future research by comparative genomics data from available genome sequence data of rice and M. oryzae for durable resistance. Present review emphasized fascinating recent updates, new molecular breeding approaches, transgenic and genomics approaches(i.e. mi RNA and genome editing) for the management of blast disease in rice. The updated information will be helpful for the durable, resistance breeding programme in rice against blast pathogen.展开更多
We investigated the composition of plant communities to quantify their relationships with environmental parameters in the Chitral Hindukush range of Pakistan. We sampled tree vegetation using the Point Centered Quart...We investigated the composition of plant communities to quantify their relationships with environmental parameters in the Chitral Hindukush range of Pakistan. We sampled tree vegetation using the Point Centered Quarter （PCQ） method while understory vegetation was sampled in 1.5-m circular quadrats. Cedrus deodara is the national symbol of Pakistan and was dominant in the sampled communities. Because environmental variables determine vegetation types, we analyzed and evaluated edaphic and topographic factors. DCA-Ordination showed the major gradient as an amalgam of elevation （p〈0.05） and slope （p〈0.01） as the topographic factors correlated with species distribution. Soil variables were the factors of environmental significance along DCA axes. However, among these factors, Mg2＋ , K ＋ and N2＋ contributed not more than 0.054% 0.20% and 0.073%, respectively, to variation along the first ordination axis. We conclude that the principal reason for weak or no correlation with many edaphic variables was the anthropogenic disturbance of vegetation. The understory vegetation was composed of perennial herbs in most communities and was most dense under the tree canopy. The understory vegetation strongly regulates tree seedling growth and regeneration patterns. We recommend further study of the understory vegetation using permanent plots to aid development of forest regeneration strategies.展开更多
Use of composite structures is exponentially growing in different fields due to their higher strength-to-weight ratio. This application trend requires that accurate theoretical explanations and their finite element mo...Use of composite structures is exponentially growing in different fields due to their higher strength-to-weight ratio. This application trend requires that accurate theoretical explanations and their finite element models be developed for analyzing sandwich plates before finalizing the designs. This paper reviews the recent research trends of finite element formulations developed for analyzing sandwich plates. This paper reviews the finite element models developed after the year 2000. Initially, the finite element formulations based on first order shear deformation theory, higher order shear deformation theories, mixed solid-shell elements, zig-zag theories and global–local theories are presented. Then, some finite element formulations developed to analyze a very new class of structures called piezoelectric structures are presented. At the end, some formulations to analyze a very critical phenomenon called buckling are presented.展开更多
Multi-pass TIG welding was conducted on plates(15×300×180 mm^(3))of aluminum alloy Al-5083 that usually serves as the component material in structural applications such as cryogenics and chemical processing ...Multi-pass TIG welding was conducted on plates(15×300×180 mm^(3))of aluminum alloy Al-5083 that usually serves as the component material in structural applications such as cryogenics and chemical processing industries.Porosity formation and solidification cracking are the most common defects when TIG welding Al-5083 alloy,which is sensitive to the welding heat input.In the experiment,the heat input was varied from 0.89 kJ/mm to 5 kJ/mm designed by the combination of welding torch travel speed and welding current.Tensile,micro-Vicker hardness and Charpy impact tests were executed to witness the impetus response of heat input on the mechanical properties of the joints.Radiographic inspection was performed to assess the joint’s quality and welding defects.The results show that all the specimens displayed inferior mechanical properties as compared to the base alloy.It was established that porosity was progressively abridged by the increase of heat input.The results also clinched that the use of medium heat input(1-2 kJ/mm)offered the best mechanical properties by eradicating welding defects,in which only about 18.26% of strength was lost.The yield strength of all the welded specimens remained unaffected indica ted no influence of heat input.Partially melted zone(PMZ)width also affected by heat input,which became widened with the increase of heat input.The grain size of PMZ was found to be coarser than the respective grain size in the fusion zone.Charpy impact testing revealed that the absorbed energy by low heat input specimen(welded at high speed)was greater than that of high heat input(welded at low speed)because of low porosity and the formation of equiaxed grains which induce better impact toughness.Cryogenic(-196℃)impact testing was also performed and the results corroborate that impact properties under the cryogenic environment revealed no appreciable change after welding at designated heat input.Finally,Macro and micro fractured surfaces of tensile and impact specimens were analyzed using Stereo and Scan展开更多
The American College of Cardiology/American Heart Association defines resistant hypertension(RH)as a clinical blood pressure(BP)reading of>130/80 mmHg in patients taking three antihypertensive drugs,including a re...The American College of Cardiology/American Heart Association defines resistant hypertension(RH)as a clinical blood pressure(BP)reading of>130/80 mmHg in patients taking three antihypertensive drugs,including a renin–angiotensin system inhibitor,a calcium channel blocker(CCB),and a diuretic at well-tolerated doses.1,2 It is reported from multiple population-based surveys that in the United States,there is an approximately 12%–15%prevalence of RH among adults diagnosed with hypertension.2 A prospective study demonstrates that 20%of people diagnosed with RH had primary hyperaldosteronism.3,4 In addition to the classic three antihypertensive drugs,spironolactone and mineralocorticoid are also administered for RH.However,with respect to the safety profile of spironolactone,it has been reported to have several side effects such as low testosterone production,menstrual irregularities,and excessively raised serum potassium levels,leaving the drug unfit for the longitudinal therapeutic purpose of treating RH.展开更多
Traumatic brain injury(TBI)impacts over 3.17 million Americans.Management of hemorrhage and coagulation caused by vascular disruption after TBI is critical for the recovery of patients.Cerebrovascular pathologies play...Traumatic brain injury(TBI)impacts over 3.17 million Americans.Management of hemorrhage and coagulation caused by vascular disruption after TBI is critical for the recovery of patients.Cerebrovascular pathologies play an important role in the underlying mechanisms of TBI.The objective of this study is to evaluate a novel regenerative medicine for the injured tissue after brain injury.We utilized a recently described synthetic growth factor with angiogenic potential to facilitate vascular growth in situ at the injury site.Previous work has shown how this injectable self-assembling peptide-based hydrogel(SAPH)creates a regenerative microenvironment for neovascularization at the injury site.Supramolecular assembly allows for thixotropy;the injectable drug delivery system provides sustained in vivo efficacy.In this study,a moderate blunt injury model was used to cause physical vascular damage and hemorrhage.The angiogenic SAPH was then applied directly on the injured rat brain.At day 7 post-TBI,significantly more blood vessels were observed than the sham and injury control group,as well as activation of VEGF-receptor 2,demonstrating the robust angiogenic response elicited by the angiogenic SAPH.Vascular markers von-Willebrand factor(vWF)andα-smooth muscle actin(α-SMA)showed a concomitant increase with blood vessel density in response to the angiogenic SAPH.Moreover,blood brain barrier integrity and blood coagulation were also examined as the parameters to indicate wound recovery post TBI.Neuronal rescue examination by NeuN and myelin basic protein staining showed that the angiogenic SAPH may provide and neuroprotective benefit in the long-term recovery.展开更多
Many nanoparticles have been created over the last few decades using a variety of techniques and used to develop environmental technology, including water treatment, the detection of persistent contaminants, and soil ...Many nanoparticles have been created over the last few decades using a variety of techniques and used to develop environmental technology, including water treatment, the detection of persistent contaminants, and soil and water remediation. The studies of alternative inputs for nanoparticle production as well as the use of green synthesis techniques are driven by the field of materials science and engineering’s growing interest in increasing the sustainability of the processes involved in their production. In this paper, we begin by providing an overview of the fundamental principles of producing nanoparticles from different sources, such as plastic, electronic, metal, and industrial waste. We elaborate on key facts of waste identification as a workable input for the treatment and recovery of metal and carbon-based nanoparticles. We next go over several controlling factors that play a role in creating nanoparticles, pointing out probable conclusions as we go. Then, we show some instances of waste-derived nanoparticles used in a proof-of-concept experiment of technology for applications in water quality and safety. Before scaling up production and implementing waste-derived nanoparticles, there are several present problems from the toxicological and life-cycle perspectives that must be taken into account.展开更多
Most forest fires in the Margalla Hills are related to human activities and socioeconomic factors are essential to assess their likelihood of occurrence.This study considers both environmental(altitude,precipitation,f...Most forest fires in the Margalla Hills are related to human activities and socioeconomic factors are essential to assess their likelihood of occurrence.This study considers both environmental(altitude,precipitation,forest type,terrain and humidity index)and socioeconomic(population density,distance from roads and urban areas)factors to analyze how human behavior affects the risk of forest fires.Maximum entropy(Maxent)modelling and random forest(RF)machine learning methods were used to predict the probability and spatial diffusion patterns of forest fires in the Margalla Hills.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to compare the models.We studied the fire history from 1990 to 2019 to establish the relationship between the probability of forest fire and environmental and socioeconomic changes.Using Maxent,the AUC fire probability values for the 1999 s,2009 s,and 2019 s were 0.532,0.569,and 0.518,respectively;using RF,they were 0.782,0.825,and 0.789,respectively.Fires were mainly distributed in urban areas and their probability of occurrence was related to accessibility and human behaviour/activity.AUC principles for validation were greater in the random forest models than in the Maxent models.Our results can be used to establish preventive measures to reduce risks of forest fires by considering socio-economic and environmental conditions.展开更多
Artificial intelligence(AI),a branch of machine learning(ML)has been increasingly employed in the research of trauma in various aspects.Hemorrhage is the most common cause of trauma-related death.To better elucidate t...Artificial intelligence(AI),a branch of machine learning(ML)has been increasingly employed in the research of trauma in various aspects.Hemorrhage is the most common cause of trauma-related death.To better elucidate the current role of AI and contribute to future development of ML in trauma care,we conducted a review focused on the use of ML in the diagnosis or treatment strategy of traumatic hemorrhage.A literature search was carried out on PubMed and Google scholar.Titles and abstracts were screened and,if deemed appropriate,the full articles were reviewed.We included 89 studies in the review.These studies could be grouped into five areas:(1)prediction of outcomes;(2)risk assessment and injury severity for triage;(3)prediction of transfusions;(4)detection of hemorrhage;and(5)prediction of coagulopathy.Performance analysis of ML in comparison with current standards for trauma care showed that most studies demonstrated the benefits of ML models.However,most studies were retrospective,focused on prediction of mortality,and development of patient outcome scoring systems.Few studies performed model assessment via test datasets obtained from different sources.Prediction models for transfusions and coagulopathy have been developed,but none is in widespread use.AI-enabled ML-driven technology is becoming integral part of the whole course of trauma care.Comparison and application of ML algorithms using different datasets from initial training,testing and validation in prospective and randomized controlled trials are warranted for provision of decision support for individualized patient care as far forward as possible.展开更多
Cancer is a major stress for public well-being and is the most dreadful disease.The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies.Cancer m...Cancer is a major stress for public well-being and is the most dreadful disease.The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies.Cancer models are either naturally existing or artificially prepared experimental systems that show similar features with human tumors though the heterogeneous nature of the tumor is very familiar.The choice of the most fitting model to best reflect the given tumor system is one of the real difficulties for cancer examination.Therefore,vast studies have been conducted on the cancer models for developing a better understanding of cancer invasion,progression,and early detection.These models give an insight into cancer etiology,molecular basis,host tumor interaction,the role of microenvironment,and tumor heterogeneity in tumor metastasis.These models are also used to predict novel can-cer markers,targeted therapies,and are extremely helpful in drug development.In this review,the potential of cancer models to be used as a platform for drug screening and therapeutic discoveries are highlighted.Although none of the cancer models is regarded as ideal because each is associated with essential caveats that restraint its application yet by bridging the gap between preliminary cancer research and transla-tional medicine.However,they promise a brighter future for cancer treatment.展开更多
AIM To investigate indications and outcomes of endoscopic retrograde cholangiopancreatography(ERCP) in cirrhotics, especially adverse events. Patients with cirrhosis undergoing ERCP are believed to have increased risk...AIM To investigate indications and outcomes of endoscopic retrograde cholangiopancreatography(ERCP) in cirrhotics, especially adverse events. Patients with cirrhosis undergoing ERCP are believed to have increased risk. However, there is a paucity of literature describing the indications and outcomes of ERCP procedures in patients with cirrhosis, especially focusing on adverse events.METHODS We performed a systematic appraisal of major literature databases, including PubMed and EMBASE, with a manual search of literature from their inception until April 2017.RESULTS A total of 6,505 patients from 15 studies were analyzed(male ratio 59%, mean age 59 years), 11% with alcoholic and 89% with non-alcoholic cirrhosis, with 56.2% Child-Pugh class A, and 43.8% class B or C. Indications for ERCP included choledocholithiasis 60.9%, biliary strictures 26.2%, gallstone pancreatitis 21.1% and cholangitis 15.5%. Types of interventions included endoscopic sphincterotomy 52.7%, biliary stenting 16.7% and biliary dilation 4.6%. Individual adverse events included hemorrhage in 4.58%(95%CI: 2.77-6.75%, I^2 = 85.9%), post-ERCP pancreatitis(PEP) in 3.68%(95%CI: 1.83-6.00%, I^2 = 89.5%), cholangitis in 1.93%(95%CI: 0.63-3.71%, I^2 = 87.1%) and perforation in 0.00%(95%CI: 0.00-0.23%, I^2 = 37.8%). Six studies were used for comparison of ERCPrelated complications in cirrhosis vs non-cirrhosis, which showed higher overall rates of complications in cirrhosis patients with pooled OR of 1.63(95%CI: 1.27-2.09, I2 = 65%): higher rates of hemorrhage with OR of 2.05(95%CI: 1.62-2.58, I^2 = 2.1%) and PEP with OR of 1.33(95%CI: 1.04-1.70, I2=65%), but similar cholangitis rates with OR of 1.23(95%CI: 0.67-2.26, I^2 = 44.3%).CONCLUSION There is an overall higher rate of adverse events related to ERCP in patients with cirrhosis, especially hemorrhage and PEP. A thorough risk/benefit assessment should be performed prior to undertaking ERCP in patients with cirrhosis.展开更多
The presence of invasive plant species poses a substantial ecological impact,thus comprehensive evaluation of their potential range and risk under the influence of climate change is necessary.This study uses maximum e...The presence of invasive plant species poses a substantial ecological impact,thus comprehensive evaluation of their potential range and risk under the influence of climate change is necessary.This study uses maximum entropy(MaxEnt)modeling to forecast the likelihood of Leucaena leucocephala(Lam.)de Wit invasion in Saudi Arabia under present and future climate change scenarios.Utilizing the MaxEnt modeling,we integrated climatic and soil data to predict habitat suitability for the invasive species.We conducted a detailed analysis of the distribution patterns of the species,using climate variables and ecological factors.We focused on the important influence of temperature seasonality,temperature annual range,and precipitation seasonality.The distribution modeling used robust measures of area under the curve(AUC)and receiver-operator characteristic(ROC)curves,to map the invasion extent,which has a high level of accuracy in identifying appropriate habitats.The complex interaction that influenced the invasion of L.leucocephala was highlighted by the environmental parameters using Jackknife test.Presently,the actual geographic area where L.leucocephala was found in Saudi Arabia was considerably smaller than the theoretical maximum range,suggesting that it had the capacity to expand further.The MaxEnt model exhibited excellent prediction accuracy and produced reliable results based on the data from the ROC curve.Precipitation and temperature were the primary factors influencing the potential distribution of L.leucocephala.Currently,an estimated area of 216,342 km^(2)in Saudi Arabia was at a high probability of invasion by L.leucocephala.We investigated the potential for increased invasion hazards in the future due to climate change scenarios(Shared Socioeconomic Pathways(SSPs)245 and 585).The analysis of key climatic variables,including temperature seasonality and annual range,along with soil properties such as clay composition and nitrogen content,unveiled their substantial influence on the distribution dynamic of L.le展开更多
Malnutrition is a highly prevalent and under recognized condition in developing countries of South Asia.The presence of malnutrition causes a severe impact on patients with liver cirrhosis.The etiology of cirrhosis di...Malnutrition is a highly prevalent and under recognized condition in developing countries of South Asia.The presence of malnutrition causes a severe impact on patients with liver cirrhosis.The etiology of cirrhosis differs in the South Asian region compared to the West,with hepatitis B and C still being the leading causes and the prevalence of nonalcoholic fatty liver disease increasing over time.Comorbid malnutrition worsens outcomes for cirrhosis patients.Urgent attention to address malnutrition is needed to improve patient outcomes.The etiology and pathophysiology of malnutrition in liver diseases is multifactorial,as reduction in liver function affects both macronutrients and micronutrients.A need for nutritional status assessment for liver disease patients exists in all parts of the world.There are many widely studied tools in use to perform a thorough nutritional assessment,of which some tools are low cost and do not require extensive training.These tools can be studied and evaluated for use in the resource limited setting of a country like Pakistan.Treatment guidelines for proper nutrition maintenance in chronic liver disease exist for all parts of the world,but the knowledge and practice of nutritional counseling in Pakistan is poor,both amongst patients and physicians.Emphasis on assessment for nutritional status at the initial visit with recording of vital signs is needed.Simultaneously,treating physicians need to be made aware of the misconceptions surrounding nutritional restrictions in cirrhosis so that patient education is done correctly based on proper scientific evidence.展开更多
Autophagy is a self-eating process,in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular microenvironment.Autophagy is generally thought of as a pro-survival m...Autophagy is a self-eating process,in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular microenvironment.Autophagy is generally thought of as a pro-survival mechanism which is not only important for balancing energy supply at times of nutrient deprivation but also in the removal of various stress stimuli to ensure homeostasis.In addition to the target materials of“self”origin,autophagy can also eliminate intracellular pathogens and acts as a defense mechanism to curb infections.In addition,autophagy is linked to the host cell's innate immune response.However,viruses have evolved various strategies to manipulate and overtake host cell machinery to establish productive replication and maintain infectious process.In fact,replication of many viruses has been found to be autophagy-dependent and suppression of autophagy can potentially affect the viral replication.Thus,autophagy can either serve as an anti-viral defense mechanism or a pro-viral process that supports viral replication.Hepatitis B virus(HBV)and hepatitis C virus(HCV)are known to co-opt cellular autophagy process as a pro-viral tool.Both viruses also induce mitophagy,which contributes to the establishment of chronic hepatitis.This review focuses on the roles of autophagy and mitophagy in the chronic liver disease pathogenesis associated with HBV and HCV infections.展开更多
文摘AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer.METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and Pub Med until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out.RESULTS: Fourteen studies reported the prevalence of extramural venous invasion(EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26(0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395(0.29, 0.51)].CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future.
基金Supported by(Entirely)Thomas Jefferson University HospitalUniversity of Utah through existing intramural funds and salary support
文摘Colorectal cancer (CRC) is the 3<sup>rd</sup> most common cancer in the United States with more than 10000 new cases diagnosed annually. Approximately 20% of patients with CRC will have distant metastasis at time of diagnosis, making them poor candidates for primary surgical resection. Similarly, 8%-25% of patients with CRC will present with bowel obstruction and will require palliative therapy. Emergent surgical decompression has a high mortality and morbidity, and often leads to a colostomy which impairs the patient’s quality of life. In the last decade, there has been an increasing use of colonic stents for palliative therapy to relieve malignant colonic obstruction. Colonic stents have been shown to be effective and safe to treat obstruction from CRC, and are now the therapy of choice in this scenario. In the setting of an acute bowel obstruction in patients with potentially resectable colon cancer, stents may be used to delay surgery and thus allow for decompression, adequate bowel preparation, and optimization of the patient’s condition for curative surgical intervention. An overall complication rate (major and minor) of up to 25% has been associated with the procedure. Long term failure of stents may result from stent migration and tumor ingrowth. In the majority of cases, repeat stenting or surgical intervention can successfully overcome these adverse effects.
文摘BACKGROUND Hemorrhoidal disease is the most common anorectal disorder.Hemorrhoids can be classified as external or internal,according to their relation to the dentate line.External hemorrhoids originate below the dentate line and are managed conservatively unless the patient cannot keep the perianal region clean,or they cause significant discomfort.Internal hemorrhoids originate above the dentate line and can be managed according to the graded degree of prolapse,as described by Goligher.Generally,low-grade internal hemorrhoids are effectively treated conservatively,by non-operative measures,while high-grade internal hemorrhoids warrant procedural intervention.AIM To determine the application of clinical practice guidelines for the current management of hemorrhoids and colorectal surgeon consensus in Australia and New Zealand.METHODS An online survey was distributed to 206 colorectal surgeons in Australia and New Zealand using 17 guideline-based hypothetical clinical scenarios.RESULTS There were 82 respondents(40%)to 17 guideline-based scenarios.Nine(53%)reached consensus,of which only 1(6%)disagreed with the guidelines.This was based on low quality evidence for the management of acutely thrombosed external hemorrhoids.There were 8 scenarios which showed community equipoise(47%)and they were equally divided for agreeing or disagreeing with the guidelines.These topics were based on low and moderate levels of evidence.They included the initial management of grade I internal hemorrhoids,grade III internal hemorrhoids when initial management had failed and the patient had recognised risks factors for septic complications;and finally,the decision-making when considering patient preferences,including a prompt return to work,or minimal post-operative pain.CONCLUSION Although there are areas of consensus in the management of hemorrhoids,there are many areas of community equipoise which would benefit from further research.
基金The authors express their gratitude to Chairman,Mr.Parveen Garg and Director,Dr.G.D.Gupta,ISF College of Pharmacy,Moga(Punjab),India,for their great support.
文摘Objective Intracerebral hemorrhage(ICH)refers to predominant,sporadic,and non-traumatic bleeding in the brain parenchyma.The PI3K/AKT/mTOR signaling pathway is an important signal transduction pathway regulated by enzyme-linked receptors and has many biological functions in mammals.It plays a key role in neuronal metabolism,gene expression regulation,and tissue homeostasis in the healthy and diseased brain.Methods In the present study,the role of the PI3K/AKT/mTOR pathway inhibitor chrysophanol(CPH)(10 mg/kg and 20 mg/kg,orally)in the improvement of ICH-associated neurological defects in rats was investigated.Autologous blood(20µL/5 min/unilateral/intracerebroventricular)mimics ICH-like defects involving cellular and molecular dysfunction and neurotransmitter imbalance.The current study also included various behavioral assessments to examine cognition,memory,and motor and neuromuscular coordination.The protein expression levels of PI3K,AKT,and mTOR as well as myelin basic protein and apoptotic markers,such as Bax,Bcl-2,and caspase-3,were examined using ELISA kits.Furthermore,the levels of various neuroinflammatory cytokines and oxidative stress markers were assessed.Additionally,the neurological severity score,brain water content,gross brain pathology,and hematoma size were used to indicate neurological function and brain edema.Results CPH was found to be neuroprotective by restoring neurobehavioral alterations and significantly reducing the elevated PI3K,AKT,and mTOR protein levels,and modulating the apoptotic markers such as Bax,Bcl-2,and caspase-3 in rat brain homogenate.CPH substantially reduced the inflammatory cytokines like interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.CPH administration restored the neurotransmitters GABA,glutamate,acetylcholine,dopamine,and various oxidative stress markers.Conclusion Our results show that CPH may be a promising therapeutic approach for overcoming neuronal damage caused by the overexpression of the PI3K/AKT/mTOR signaling pathway in ICH-induced neurological dysfu
文摘Pyricularia oryzae anamorph of Magnaporthe oryzae is one of the most notorious fungal pathogens causing severe economic loss in rice production worldwide. Various methods, viz. cultural, biological and molecular approaches, are utilized to counteract this pathogen. Moreover, some tolerant or resistant rice varieties have been developed with the help of breeding programmes. Isolation and molecular characterization of different blast resistance genes now open the gate for new possibilities to elucidate the actual allelic variants of these genes via various molecular breeding and transgenic approaches. However, the behavioral pattern of this fungus breakups the resistance barriers in the resistant or tolerant rice varieties. This host-pathogen barrier will be possibly countered in future research by comparative genomics data from available genome sequence data of rice and M. oryzae for durable resistance. Present review emphasized fascinating recent updates, new molecular breeding approaches, transgenic and genomics approaches(i.e. mi RNA and genome editing) for the management of blast disease in rice. The updated information will be helpful for the durable, resistance breeding programme in rice against blast pathogen.
基金supported by the Higher Education Commission of Pakistan
文摘We investigated the composition of plant communities to quantify their relationships with environmental parameters in the Chitral Hindukush range of Pakistan. We sampled tree vegetation using the Point Centered Quarter （PCQ） method while understory vegetation was sampled in 1.5-m circular quadrats. Cedrus deodara is the national symbol of Pakistan and was dominant in the sampled communities. Because environmental variables determine vegetation types, we analyzed and evaluated edaphic and topographic factors. DCA-Ordination showed the major gradient as an amalgam of elevation （p〈0.05） and slope （p〈0.01） as the topographic factors correlated with species distribution. Soil variables were the factors of environmental significance along DCA axes. However, among these factors, Mg2＋ , K ＋ and N2＋ contributed not more than 0.054% 0.20% and 0.073%, respectively, to variation along the first ordination axis. We conclude that the principal reason for weak or no correlation with many edaphic variables was the anthropogenic disturbance of vegetation. The understory vegetation was composed of perennial herbs in most communities and was most dense under the tree canopy. The understory vegetation strongly regulates tree seedling growth and regeneration patterns. We recommend further study of the understory vegetation using permanent plots to aid development of forest regeneration strategies.
文摘Use of composite structures is exponentially growing in different fields due to their higher strength-to-weight ratio. This application trend requires that accurate theoretical explanations and their finite element models be developed for analyzing sandwich plates before finalizing the designs. This paper reviews the recent research trends of finite element formulations developed for analyzing sandwich plates. This paper reviews the finite element models developed after the year 2000. Initially, the finite element formulations based on first order shear deformation theory, higher order shear deformation theories, mixed solid-shell elements, zig-zag theories and global–local theories are presented. Then, some finite element formulations developed to analyze a very new class of structures called piezoelectric structures are presented. At the end, some formulations to analyze a very critical phenomenon called buckling are presented.
文摘Multi-pass TIG welding was conducted on plates(15×300×180 mm^(3))of aluminum alloy Al-5083 that usually serves as the component material in structural applications such as cryogenics and chemical processing industries.Porosity formation and solidification cracking are the most common defects when TIG welding Al-5083 alloy,which is sensitive to the welding heat input.In the experiment,the heat input was varied from 0.89 kJ/mm to 5 kJ/mm designed by the combination of welding torch travel speed and welding current.Tensile,micro-Vicker hardness and Charpy impact tests were executed to witness the impetus response of heat input on the mechanical properties of the joints.Radiographic inspection was performed to assess the joint’s quality and welding defects.The results show that all the specimens displayed inferior mechanical properties as compared to the base alloy.It was established that porosity was progressively abridged by the increase of heat input.The results also clinched that the use of medium heat input(1-2 kJ/mm)offered the best mechanical properties by eradicating welding defects,in which only about 18.26% of strength was lost.The yield strength of all the welded specimens remained unaffected indica ted no influence of heat input.Partially melted zone(PMZ)width also affected by heat input,which became widened with the increase of heat input.The grain size of PMZ was found to be coarser than the respective grain size in the fusion zone.Charpy impact testing revealed that the absorbed energy by low heat input specimen(welded at high speed)was greater than that of high heat input(welded at low speed)because of low porosity and the formation of equiaxed grains which induce better impact toughness.Cryogenic(-196℃)impact testing was also performed and the results corroborate that impact properties under the cryogenic environment revealed no appreciable change after welding at designated heat input.Finally,Macro and micro fractured surfaces of tensile and impact specimens were analyzed using Stereo and Scan
文摘The American College of Cardiology/American Heart Association defines resistant hypertension(RH)as a clinical blood pressure(BP)reading of>130/80 mmHg in patients taking three antihypertensive drugs,including a renin–angiotensin system inhibitor,a calcium channel blocker(CCB),and a diuretic at well-tolerated doses.1,2 It is reported from multiple population-based surveys that in the United States,there is an approximately 12%–15%prevalence of RH among adults diagnosed with hypertension.2 A prospective study demonstrates that 20%of people diagnosed with RH had primary hyperaldosteronism.3,4 In addition to the classic three antihypertensive drugs,spironolactone and mineralocorticoid are also administered for RH.However,with respect to the safety profile of spironolactone,it has been reported to have several side effects such as low testosterone production,menstrual irregularities,and excessively raised serum potassium levels,leaving the drug unfit for the longitudinal therapeutic purpose of treating RH.
基金This work was supported by grant 1R21AA022734-01A1(to JH)from National Institutes of Health,and NIH R15 EY029504,NSF IIP 1903617,the NJIT Undergraduate Research and Innovation(URI)Program and NJIT Startup funds(to V.A.K.).
文摘Traumatic brain injury(TBI)impacts over 3.17 million Americans.Management of hemorrhage and coagulation caused by vascular disruption after TBI is critical for the recovery of patients.Cerebrovascular pathologies play an important role in the underlying mechanisms of TBI.The objective of this study is to evaluate a novel regenerative medicine for the injured tissue after brain injury.We utilized a recently described synthetic growth factor with angiogenic potential to facilitate vascular growth in situ at the injury site.Previous work has shown how this injectable self-assembling peptide-based hydrogel(SAPH)creates a regenerative microenvironment for neovascularization at the injury site.Supramolecular assembly allows for thixotropy;the injectable drug delivery system provides sustained in vivo efficacy.In this study,a moderate blunt injury model was used to cause physical vascular damage and hemorrhage.The angiogenic SAPH was then applied directly on the injured rat brain.At day 7 post-TBI,significantly more blood vessels were observed than the sham and injury control group,as well as activation of VEGF-receptor 2,demonstrating the robust angiogenic response elicited by the angiogenic SAPH.Vascular markers von-Willebrand factor(vWF)andα-smooth muscle actin(α-SMA)showed a concomitant increase with blood vessel density in response to the angiogenic SAPH.Moreover,blood brain barrier integrity and blood coagulation were also examined as the parameters to indicate wound recovery post TBI.Neuronal rescue examination by NeuN and myelin basic protein staining showed that the angiogenic SAPH may provide and neuroprotective benefit in the long-term recovery.
文摘Many nanoparticles have been created over the last few decades using a variety of techniques and used to develop environmental technology, including water treatment, the detection of persistent contaminants, and soil and water remediation. The studies of alternative inputs for nanoparticle production as well as the use of green synthesis techniques are driven by the field of materials science and engineering’s growing interest in increasing the sustainability of the processes involved in their production. In this paper, we begin by providing an overview of the fundamental principles of producing nanoparticles from different sources, such as plastic, electronic, metal, and industrial waste. We elaborate on key facts of waste identification as a workable input for the treatment and recovery of metal and carbon-based nanoparticles. We next go over several controlling factors that play a role in creating nanoparticles, pointing out probable conclusions as we go. Then, we show some instances of waste-derived nanoparticles used in a proof-of-concept experiment of technology for applications in water quality and safety. Before scaling up production and implementing waste-derived nanoparticles, there are several present problems from the toxicological and life-cycle perspectives that must be taken into account.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFE0127700)。
文摘Most forest fires in the Margalla Hills are related to human activities and socioeconomic factors are essential to assess their likelihood of occurrence.This study considers both environmental(altitude,precipitation,forest type,terrain and humidity index)and socioeconomic(population density,distance from roads and urban areas)factors to analyze how human behavior affects the risk of forest fires.Maximum entropy(Maxent)modelling and random forest(RF)machine learning methods were used to predict the probability and spatial diffusion patterns of forest fires in the Margalla Hills.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to compare the models.We studied the fire history from 1990 to 2019 to establish the relationship between the probability of forest fire and environmental and socioeconomic changes.Using Maxent,the AUC fire probability values for the 1999 s,2009 s,and 2019 s were 0.532,0.569,and 0.518,respectively;using RF,they were 0.782,0.825,and 0.789,respectively.Fires were mainly distributed in urban areas and their probability of occurrence was related to accessibility and human behaviour/activity.AUC principles for validation were greater in the random forest models than in the Maxent models.Our results can be used to establish preventive measures to reduce risks of forest fires by considering socio-economic and environmental conditions.
基金Defence Research and Development Canada,Program Activity PEOPLE_014.
文摘Artificial intelligence(AI),a branch of machine learning(ML)has been increasingly employed in the research of trauma in various aspects.Hemorrhage is the most common cause of trauma-related death.To better elucidate the current role of AI and contribute to future development of ML in trauma care,we conducted a review focused on the use of ML in the diagnosis or treatment strategy of traumatic hemorrhage.A literature search was carried out on PubMed and Google scholar.Titles and abstracts were screened and,if deemed appropriate,the full articles were reviewed.We included 89 studies in the review.These studies could be grouped into five areas:(1)prediction of outcomes;(2)risk assessment and injury severity for triage;(3)prediction of transfusions;(4)detection of hemorrhage;and(5)prediction of coagulopathy.Performance analysis of ML in comparison with current standards for trauma care showed that most studies demonstrated the benefits of ML models.However,most studies were retrospective,focused on prediction of mortality,and development of patient outcome scoring systems.Few studies performed model assessment via test datasets obtained from different sources.Prediction models for transfusions and coagulopathy have been developed,but none is in widespread use.AI-enabled ML-driven technology is becoming integral part of the whole course of trauma care.Comparison and application of ML algorithms using different datasets from initial training,testing and validation in prospective and randomized controlled trials are warranted for provision of decision support for individualized patient care as far forward as possible.
文摘Cancer is a major stress for public well-being and is the most dreadful disease.The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies.Cancer models are either naturally existing or artificially prepared experimental systems that show similar features with human tumors though the heterogeneous nature of the tumor is very familiar.The choice of the most fitting model to best reflect the given tumor system is one of the real difficulties for cancer examination.Therefore,vast studies have been conducted on the cancer models for developing a better understanding of cancer invasion,progression,and early detection.These models give an insight into cancer etiology,molecular basis,host tumor interaction,the role of microenvironment,and tumor heterogeneity in tumor metastasis.These models are also used to predict novel can-cer markers,targeted therapies,and are extremely helpful in drug development.In this review,the potential of cancer models to be used as a platform for drug screening and therapeutic discoveries are highlighted.Although none of the cancer models is regarded as ideal because each is associated with essential caveats that restraint its application yet by bridging the gap between preliminary cancer research and transla-tional medicine.However,they promise a brighter future for cancer treatment.
文摘AIM To investigate indications and outcomes of endoscopic retrograde cholangiopancreatography(ERCP) in cirrhotics, especially adverse events. Patients with cirrhosis undergoing ERCP are believed to have increased risk. However, there is a paucity of literature describing the indications and outcomes of ERCP procedures in patients with cirrhosis, especially focusing on adverse events.METHODS We performed a systematic appraisal of major literature databases, including PubMed and EMBASE, with a manual search of literature from their inception until April 2017.RESULTS A total of 6,505 patients from 15 studies were analyzed(male ratio 59%, mean age 59 years), 11% with alcoholic and 89% with non-alcoholic cirrhosis, with 56.2% Child-Pugh class A, and 43.8% class B or C. Indications for ERCP included choledocholithiasis 60.9%, biliary strictures 26.2%, gallstone pancreatitis 21.1% and cholangitis 15.5%. Types of interventions included endoscopic sphincterotomy 52.7%, biliary stenting 16.7% and biliary dilation 4.6%. Individual adverse events included hemorrhage in 4.58%(95%CI: 2.77-6.75%, I^2 = 85.9%), post-ERCP pancreatitis(PEP) in 3.68%(95%CI: 1.83-6.00%, I^2 = 89.5%), cholangitis in 1.93%(95%CI: 0.63-3.71%, I^2 = 87.1%) and perforation in 0.00%(95%CI: 0.00-0.23%, I^2 = 37.8%). Six studies were used for comparison of ERCPrelated complications in cirrhosis vs non-cirrhosis, which showed higher overall rates of complications in cirrhosis patients with pooled OR of 1.63(95%CI: 1.27-2.09, I2 = 65%): higher rates of hemorrhage with OR of 2.05(95%CI: 1.62-2.58, I^2 = 2.1%) and PEP with OR of 1.33(95%CI: 1.04-1.70, I2=65%), but similar cholangitis rates with OR of 1.23(95%CI: 0.67-2.26, I^2 = 44.3%).CONCLUSION There is an overall higher rate of adverse events related to ERCP in patients with cirrhosis, especially hemorrhage and PEP. A thorough risk/benefit assessment should be performed prior to undertaking ERCP in patients with cirrhosis.
基金the Researchers Supporting Project(RSP2024R347),King Saud University,Riyadh,Saudi Arabia.
文摘The presence of invasive plant species poses a substantial ecological impact,thus comprehensive evaluation of their potential range and risk under the influence of climate change is necessary.This study uses maximum entropy(MaxEnt)modeling to forecast the likelihood of Leucaena leucocephala(Lam.)de Wit invasion in Saudi Arabia under present and future climate change scenarios.Utilizing the MaxEnt modeling,we integrated climatic and soil data to predict habitat suitability for the invasive species.We conducted a detailed analysis of the distribution patterns of the species,using climate variables and ecological factors.We focused on the important influence of temperature seasonality,temperature annual range,and precipitation seasonality.The distribution modeling used robust measures of area under the curve(AUC)and receiver-operator characteristic(ROC)curves,to map the invasion extent,which has a high level of accuracy in identifying appropriate habitats.The complex interaction that influenced the invasion of L.leucocephala was highlighted by the environmental parameters using Jackknife test.Presently,the actual geographic area where L.leucocephala was found in Saudi Arabia was considerably smaller than the theoretical maximum range,suggesting that it had the capacity to expand further.The MaxEnt model exhibited excellent prediction accuracy and produced reliable results based on the data from the ROC curve.Precipitation and temperature were the primary factors influencing the potential distribution of L.leucocephala.Currently,an estimated area of 216,342 km^(2)in Saudi Arabia was at a high probability of invasion by L.leucocephala.We investigated the potential for increased invasion hazards in the future due to climate change scenarios(Shared Socioeconomic Pathways(SSPs)245 and 585).The analysis of key climatic variables,including temperature seasonality and annual range,along with soil properties such as clay composition and nitrogen content,unveiled their substantial influence on the distribution dynamic of L.le
文摘Malnutrition is a highly prevalent and under recognized condition in developing countries of South Asia.The presence of malnutrition causes a severe impact on patients with liver cirrhosis.The etiology of cirrhosis differs in the South Asian region compared to the West,with hepatitis B and C still being the leading causes and the prevalence of nonalcoholic fatty liver disease increasing over time.Comorbid malnutrition worsens outcomes for cirrhosis patients.Urgent attention to address malnutrition is needed to improve patient outcomes.The etiology and pathophysiology of malnutrition in liver diseases is multifactorial,as reduction in liver function affects both macronutrients and micronutrients.A need for nutritional status assessment for liver disease patients exists in all parts of the world.There are many widely studied tools in use to perform a thorough nutritional assessment,of which some tools are low cost and do not require extensive training.These tools can be studied and evaluated for use in the resource limited setting of a country like Pakistan.Treatment guidelines for proper nutrition maintenance in chronic liver disease exist for all parts of the world,but the knowledge and practice of nutritional counseling in Pakistan is poor,both amongst patients and physicians.Emphasis on assessment for nutritional status at the initial visit with recording of vital signs is needed.Simultaneously,treating physicians need to be made aware of the misconceptions surrounding nutritional restrictions in cirrhosis so that patient education is done correctly based on proper scientific evidence.
基金This work was supported by USA National Institutes of Health(NIH)grants AI125350,AI085087 and AI139234 to A.Siddiqui.
文摘Autophagy is a self-eating process,in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular microenvironment.Autophagy is generally thought of as a pro-survival mechanism which is not only important for balancing energy supply at times of nutrient deprivation but also in the removal of various stress stimuli to ensure homeostasis.In addition to the target materials of“self”origin,autophagy can also eliminate intracellular pathogens and acts as a defense mechanism to curb infections.In addition,autophagy is linked to the host cell's innate immune response.However,viruses have evolved various strategies to manipulate and overtake host cell machinery to establish productive replication and maintain infectious process.In fact,replication of many viruses has been found to be autophagy-dependent and suppression of autophagy can potentially affect the viral replication.Thus,autophagy can either serve as an anti-viral defense mechanism or a pro-viral process that supports viral replication.Hepatitis B virus(HBV)and hepatitis C virus(HCV)are known to co-opt cellular autophagy process as a pro-viral tool.Both viruses also induce mitophagy,which contributes to the establishment of chronic hepatitis.This review focuses on the roles of autophagy and mitophagy in the chronic liver disease pathogenesis associated with HBV and HCV infections.
