The original online version https://doi.org/10.1007/s11629-024-9130-x has wrong title.The correct title for this article should be“Reactivation mechanisms of the ancient Dahekou landslide in Hanzhong City,Shaanxi Pro...The original online version https://doi.org/10.1007/s11629-024-9130-x has wrong title.The correct title for this article should be“Reactivation mechanisms of the ancient Dahekou landslide in Hanzhong City,Shaanxi Province,China”.展开更多
Toxoplasma gondii(T.gondii)is an obligate intracellular parasite with a wide range of hosts,including humans and many warm-blooded animals.The parasite exists in two interconvertible forms,namely tachyzoites and brady...Toxoplasma gondii(T.gondii)is an obligate intracellular parasite with a wide range of hosts,including humans and many warm-blooded animals.The parasite exists in two interconvertible forms,namely tachyzoites and bradyzoites in intermediate hosts that are responsible for acute and chronic infections respectively.Mature bradyzoites accumulate large amounts of amylopectin granules but their roles have not been fully characterized.In this study,the predicted key enzymes involved in amylopectin synthesis(UDP-sugar pyrophospharylase,USP)and degradation(alpha-glucan water dikinase,GWD)of ME49 strain were individually knocked out,and then bradyzoite-related phenotyping experiments in vitro and in vivo were performed to dissect their roles during parasite growth and development.Deletion of the usp or gwd gene in the type II strain ME49 reduced the replication rates of tachyzoites in vitro and parasite virulence in vivo,suggesting that amylopectin metabolism is important for optimal tachyzoite growth.Interestingly,the Δusp mutant grew slightly faster than the parental strain under stress conditions that induced bradyzoite transition,which was likely due to the decreased efficiency of bradyzoite formation of theΔusp mutant.Although theΔgwd mutant could convert to bradyzoite robustly in vitro,it was significantly impaired in establishing chronic infection in vivo.Both the Δusp and Δgwd mutants showed a dramatic reduction in the reactivation of chronic infection in an in vitro model.Together,these results suggest that USP and GWD,which are involved in amylopectin synthesis and degradation have important roles in tachyzoite growth,as well as in the formation and reactivation of bradyzoites in T.gondii.展开更多
Objective:The role of non-alcoholic steatohepatitis(NASH)in hepatitis B virus(HBV)reactivation following liver transplantation for hepatocellular carcinoma(HCC)remains unclear,and the metabolic differences between pat...Objective:The role of non-alcoholic steatohepatitis(NASH)in hepatitis B virus(HBV)reactivation following liver transplantation for hepatocellular carcinoma(HCC)remains unclear,and the metabolic differences between patients with NASH and those with HBV reactivation are also yet to be elucidated.This study is to investigate the impact of NASH on HBV reactivation risk and prognosis following liver transplantation for HCC,and to develop a predictive model and identify therapeutic targets.Methods:This study included 274 patients who underwent liver transplantation for HCC.The HBV reactivation status of patients with NASH was analyzed,and the metabolic characteristics of peripheral blood were examined to compare NASH and non-NASH patients with or without HBV reactivation.Results:The HBV reactivation free survival was better in non-NASH patients(P<0.0001).Furthermore,NASH patients with HBV reactivation had worse recurrence-free survival(RFS)than non-NASH patients with HBV reactivation(P=0.016).In contrast,the RFS of NASH patients without HBV reactivation was comparable to that of non-NASH patients without HBV reactivation(P=0.810).Subsequently,we constructed a model to predict HBV reactivation by incorporating 7 clinical indicators using the Least Absolute Shrinkage and Selection Operator-Cox(LASSO-Cox)approach.The area under the receiver operating characteristic curve(AUROC)values for predictions at 500,1,000,and 1,500 d were 0.759,0.809,and 0.814,respectively.Finally,metabolic pathway analysis identified key pathways involved in HBV reactivation,and glutamine was found to be an independent protective factor against HBV reactivation following liver transplantation for HCC.Conclusions:NASH patients are more prone to HBV reactivation following liver transplantation for HCC and exhibit worse recurrence-free survival.Glutamine may serve as a potential therapeutic target or predictive biomarker for HBV reactivation.展开更多
With the advancement of fracturing technologies in deeper and more geologically complex formations,fault reactivation and induced seismicity have attracted increasing attention.The increasing frequency and magnitude o...With the advancement of fracturing technologies in deeper and more geologically complex formations,fault reactivation and induced seismicity have attracted increasing attention.The increasing frequency and magnitude of these events underscore the need for a robust understanding of the governing physical mechanisms.Elevated pore pressure,modified fault-loading conditions,and aseismic slip are widely acknowledged as the primary drivers.Recent studies have explored these mechanisms under varying factors,including fluid properties,rock ductility,poroelastic responses,and evolving fault stress states,thereby offering critical insights into model refinement.Probabilistic forecasting approaches,which combine statistical analyses of historical data with real-time monitoring,are being increasingly adopted in seismic risk assessments.In parallel,machine learning techniques are employed to process large seismic datasets and identify key patterns.However,their predictive capabilities remain limited by geological heterogeneity,subsurface complexity,and scarce observational data.Moreover,fluid–rock interactions further complicate the development of universally applicable models,thereby constraining the generalizability of mitigation strategies.This review synthesizes the current understanding of induced seismicity mechanisms,evaluates the prevailing prediction and mitigation methods,and identifies major challenges and future research directions.Advancements in these areas are essential to enhancing seismic risk management and ensuring the safe,sustainable development of deep-subsurface energy resources.展开更多
BACKGROUND Cytomegalovirus(CMV)reactivation is a potentially severe complication in immunocompromised patients,yet its incidence and impact in recipients of autologous hematopoietic stem cell transplantation(AHSCT)rem...BACKGROUND Cytomegalovirus(CMV)reactivation is a potentially severe complication in immunocompromised patients,yet its incidence and impact in recipients of autologous hematopoietic stem cell transplantation(AHSCT)remain insufficiently documented.AIM To assess the frequency,timing,and outcomes of CMV reactivation in patients undergoing AHSCT at Aziza Othmana Hospital.METHODS We conducted a retrospective descriptive study of all patients who underwent AHSCT between January 2022 and December 2024 and had at least one posttransplant plasma viral load(VL)assessment.CMV VL was quantified by realtime polymerase chain reaction using TaqMan probes(GeneProof®)with a sensitivity threshold of 150 IU/mL.RESULTS Among 277 AHSCT recipients,17(6.1%)experienced CMV reactivation.Their median age was 43 years,with a sex ratio of 0.46(male/female).Underlying diseases included large B-cell lymphoma(n=5),multiple myeloma(n=3),and Hodgkin’s lymphoma(n=4).The median time to reactivation was 26 days post transplant(11 days after neutrophil recovery).Median peak VL was 1325 IU/mL(range:150-641000 IU/mL).Six patients required antiviral therapy(median peak VL:30150 IU/mL),while 11 had spontaneous resolution(median peak VL:1320 IU/mL).Two patients died in the context of CMV reactivation.CONCLUSION CMV reactivation occurs in a noteworthy proportion of AHSCT recipients and may lead to severe outcomes.Routine VL monitoring in the early post-transplant period is crucial,and preemptive therapy should be initiated once clinically relevant VL thresholds are reached to prevent progression to CMV disease and associated mortality.展开更多
Ancient landslides with platform geomorphology occasionally reactivate,posing serious geohazards.On September 9,2021,persistent heavy rainfall triggered the reactivation of the Dahekou ancient landslide within a gentl...Ancient landslides with platform geomorphology occasionally reactivate,posing serious geohazards.On September 9,2021,persistent heavy rainfall triggered the reactivation of the Dahekou ancient landslide within a gently sloping geomorphology at the core of Zhangjiantan syncline in China's western Qinling-Daba Mountains.This event caused one death,damaged 80 houses,and blocked the Yushui River.This study reconstructs the sliding process of the Dahekou landslide and deciphers the complex landslide initiation mechanisms through field surveys,unmanned aerial vehicle(UAV)imagery analysis,drilling,electrical resistivity tomography(ERT)and small baseline subset–interferometric synthetic aperture radar(SBAS–InSAR)monitoring.We divide the sliding process of the Dahekou landslide into three stages.Two new landslides(#1 and#2)occurred at 18:30 on September 9,2021.Subsequently,the ancient landslide(#3)slid in the 230°direction at approximately 20:30 on September 9,2021,then changed the direction to 170°–240°at 22:30 on the same day,and moved in the direction of 300°at 10:00 the next day.Finally,the reactivated ancient landslide(#3)formed two partially sliding masses,with volumes of approximately 158×10^(4)m^(3)and 160×10~4 m^(3),along the directions of 170°–240°and 300°,respectively,damaging 80 houses and blocking the Yushui River.Field surveys suggest that new landslides#1 and#2 are rock landslides and soil landslides,respectively,with volumes of approximately 230×10^(4)m^(3)and 7.49×10~4 m^(3).Compared with the InSAR data,the new landslide#1 thrust the ancient landslide#3,with an uplift velocity rate of 22.68 mm/a at the rear edge,from September 2020–September 2021.An analysis of drill hole data reveals that the bedding in the landslide area has complex geological conditions,comprising mudstone prone to slipping with different degrees of weathering.Notably,the core of the Zhangjiatan syncline sits on the sliding bedding of the ancient landslide,contributing to a change in the sliding direction.This comprehensive study reveals that the landslide#1 loading and thrusting,the persistent and heavy rainfall,and the complex geological conditions influenced the reactivated ancient landslide.Considering the intricacies of landslide failure mechanisms,we advocate for giving more attention in the future to the zone of potentially slip-prone strata located at the edge of ancient landslides.展开更多
Elsberg syndrome, or HSV-2 lumbosacral radiculitis, is a rare and underrecognized neurologic condition that mimics cauda equina syndrome (CES). It typically presents with symptoms such as urinary retention, saddle ane...Elsberg syndrome, or HSV-2 lumbosacral radiculitis, is a rare and underrecognized neurologic condition that mimics cauda equina syndrome (CES). It typically presents with symptoms such as urinary retention, saddle anesthesia, and bowel incontinence. This case report describes a 59-year-old immunosuppressed male with idiopathic pulmonary fibrosis who developed Elsberg syndrome due to re-activation of latent HSV-2. The patient experienced progressive lower extremity sensory deficits and genitourinary dysfunction, culminating in a vesiculopustular rash. Diagnosis was confirmed via cerebrospinal fluid analysis and PCR testing of skin lesions. Despite early imaging findings being unremarkable, subsequent MRI revealed enhancement of the conus medullaris and cauda equina. Treatment with intravenous acyclovir, corticosteroids, and supportive therapy led to gradual functional improvement, though sensory deficits and neuropathy persisted. This case highlights the diagnostic challenges and importance of clinical suspicion for HSV-2 reactivation in immunosuppressed patients, as well as considerations for long-term symptom management.展开更多
Indonesia is facing severe congestion and high accident rates as motor vehicle growth continues to outpace road capacity,underscoring the urgent need for alternative mass transportation.A promising solution is the rea...Indonesia is facing severe congestion and high accident rates as motor vehicle growth continues to outpace road capacity,underscoring the urgent need for alternative mass transportation.A promising solution is the reactivation of the Surabaya–Madura railway,an abandoned infrastructure with significant potential to enhance regional connectivity and urban mobility.However,academic studies on railway reactivation remain limited,particularly in the Madura context where dependence on road-based transport persists.This research gap highlights the importance of examining reactivation not only as a transportation alternative but also as a catalyst for regional development.This study adopts a qualitative approach through descriptive surveys to evaluate infrastructure conditions,identify feasible routes,and analyze broader spatial implications.Findings reveal that railway reactivation could strengthen multimodal integration,reduce congestion,and support sustainable growth.This study provides the first empirical evidence of the strategic value of the Surabaya–Madura railway within Indonesia’s transport and regional development discourse.展开更多
Fracture(fault)reactivation can lead to dynamic geological hazards including earthquakes,rock collapses,landslides,and rock bursts.True triaxial compression tests were conducted to analyze the fracture reactivation pr...Fracture(fault)reactivation can lead to dynamic geological hazards including earthquakes,rock collapses,landslides,and rock bursts.True triaxial compression tests were conducted to analyze the fracture reactivation process under two different orientations of σ_(2),i.e.σ_(2) parallel to the fracture plane(Scheme 2)and σ_(2) cutting through the fracture plane(Scheme 3),under varying σ_(3) from 10 MPa to 40 MPa.The peak or fracture reactivation strength,deformation,failure mode,and post-peak mechanical behavior of intact(Scheme 1)and pre-fractured(Schemes 2 and 3)specimens were also compared.Results show that for intact specimens,the stress remains nearly constant in the residual sliding stage with no stick-slip,and the newly formed fracture surface only propagates along the σ_(2) direction when σ_(3) ranges from 10 MPa to 30 MPa,while it extends along both σ_(2) and σ_(3) directions when σ_(3) increases to 40 MPa;for the pre-fractured specimens,the fractures are usually reactivated under all the σ_(3) levels in Scheme 2,but fracture reactivation only occurs when σ_(3) is greater than 25 MPa in Scheme 3,below which new faulting traversing the original macro fracture occurs.In all the test schemes,both ε_(2) and ε_(3) experience an accumulative process of elongation,after which an abrupt change occurs at the point of the final failure;the degree of this change is dependent on the orientation of the new faulting or the slip direction of the original fracture,and it is generally more than 10 times larger in the slip direction of the original fracture than in the non-slip direction.Besides,the differential stress(peak stress)required for reactivation and the post-peak stress drop increase with increasing σ_(3).Post-peak stress drop and residual strength in Scheme 3 are generally greater than those in Scheme 2 at the same σ_(3) value.Our study clearly shows that intermediate principal stress orientation not only affects the fracture reactivation strength but also influences the slip deformation and failure modes.These new findings facilitate the mitigation of dynamic geological hazards associated with fracture and fault slip.展开更多
Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately charac...Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately characterized.Herein,we retrospectively analyzed our cohort(NCT06114251)comprising 453 patients with an HBV background.Propensity score matching(PSM)and sensitivity analyses were employed to assess the influence of ALD on surgical outcomes.Benchmark analysis compared the predictive performance of 21 models for post-transplant HBV reactivation.The Shapley additive explanation(SHAP)algorithm facilitated feature ranking and model interpretation.Patients were stratified into three subgroups based on the alcohol-modified HBV reactivation index(AMBRI).Among the cohort,113 patients(24.9%)had concurrent pre-transplant diagnoses of ALD and HBV infection,while 340(75.1%)had HBV infection alone.The presence of ALD was associated with an elevated risk of HBV reactivation and liver metastasis.PSM and sensitivity analyses revealed significantly lower five-year HBV reactivation-free survival(74.9%vs 85.4%),overall survival(OS,56.2%vs 70.5%),and tumor recurrence-free survival(RFS,47.8%vs 63.3%)in the ALD cohort.In recipients without HBV reactivation,hepatocellular carcinomas(HCCs)arising from both ALD and HBV exhibited inferior RFS(log-rank P=0.026)and OS beyond one year(landmark P=0.032)compared to HBV-related HCC alone.Benchmark analysis identified the surv.cforest model as the optimal predictor,achieving an area under the receiver operating characteristic(AUC)curve of 0.914 in internal validation and 0.884 in external validation,outperforming the published Cox model(AUC=0.78).AMBRI-based stratification delineated three distinct risk subgroups,with the intermediate-and high-risk groups exhibiting significantly worse OS and RFS than the low-risk group.In this study,stratification by AMBRI identified intermediate-and high-risk groups with poorer post-transplant outcomes,underscoring the necessity for intensified surveillance and enhanced HBV treatment regimens,particularly in recipients with pre-transplant ALD.展开更多
In recent years,a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive drugs....In recent years,a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive drugs.The cases of viral hepatitis reactivation that have been reported are characterized by a wide range of clinical manifestations,from viremia without clinically relevant manifestations to fulminant life-threatening hepatitis.The development and dissemination of biological immunosuppressive drugs have led to a significant increase in the number of reports of interest to physicians in a variety of clinical settings.On this topic,there have been a number of published guidelines and reviews that have collected the available evidence,providing recommendations on prophylactic and therapeutic strategies and methods for monitoring patients at risk.However,it should be noted that,to date,very few clinical studies have been published,and most of the recommendations have been borrowed from otherclinical settings.The published studies are mostly retrospective and are based on very heterogeneous populations,using different therapeutic and prophylactic regimens and obtaining conflicting results.Thus,it seems clear that it is desirable to concentrate our efforts on prospective studies,not conducting further reviews of the literature in the continued absence of new evidence.展开更多
Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a...Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.展开更多
Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus(HBV) replication,often accompanied by an increase in serum transaminase levels,and both events occurring in a patient wit...Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus(HBV) replication,often accompanied by an increase in serum transaminase levels,and both events occurring in a patient with a previous inactive hepatitis B infection.This reactivation can occur in situations in which the ratio of HBV replication and immune response is altered.It can happen during the treatment of hemato-oncological malignancies with chemotherapy and in immunosuppression of autoimmune diseases.Clinical manifestations of hepatitis B reactivation are variable and can range from asymptomatic to acute hepatitis,which are sometimes serious and result in acute liver failure with risk of death,and usually occur in the periods between cycles or at the end of chemotherapy.Immunosuppressive drugs such as corticosteroids or azathioprine can induce HBV reactivation in patients carrying hepatitis B virus surface antigen(HBsAg) or anti-HBc,but much less frequently than chemotherapy treatments.The tumor necrosis factorαinhibitors infliximab,etanercept and adalimumab may cause reactivation of hepatitis B,and the overall frequency with infliximab may be similar(50%-66%) to that caused by chemotherapy.Baseline HBV serology is recommended for all patients receiving chemotherapy and immunosuppressive drugs,and HBsAg positive patients should receive anti-HBV prophylaxis to decrease virus reactivation and death rates.展开更多
Due to the inherent relationship between the immune system and the hepatitis B virus(HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignanci...Due to the inherent relationship between the immune system and the hepatitis B virus(HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation(HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations' guidelines and the best available evidence to date.展开更多
Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascul...Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.展开更多
Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabc...Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.展开更多
Disinfection of reclaimed water prior to reuse is important to prevent the transmission of pathogens. Chlorine is a widely utilized disinfectant and as such is a leading contender for disinfection of reclaimed water. ...Disinfection of reclaimed water prior to reuse is important to prevent the transmission of pathogens. Chlorine is a widely utilized disinfectant and as such is a leading contender for disinfection of reclaimed water. To understand the risks of chlorination resulting from the potential selection of pathogenic bacteria, the inactivation, reactivation and regrowth rates of indigenous bacteria were investigated in reclaimed water after chlorine disinfection. Inactivation of total coliforms, Enterococcus and Salmonella showed linear correlations, with constants of 0.1384, 0.1624 and 0.057 L/（mg·min） and R 2 of 0.7617, 0.8316 and 0.845, respectively. However, inactivation of total viable cells by measurement of metabolic activity typically showed a linear correlation at lower chlorine dose （0-22 （mg·min）/L）, and a trailing region with chlorine dose increasing from 22 to 69 （mg·min）/L. Reactivation and regrowth of bacteria were most likely to occur after exposure to lower chlorine doses, and extents of reactivation decreased gradually with increasing chlorine dose. In contrast to total coliforms and Enterococcus, Salmonella had a high level of regrowth and reactivation, and still had 2% regrowth even after chlorination of 69 （mg·min）/L and 24 hr storage. The bacterial compositions were also significantly altered by chlorination and storage of reclaimed water, and the ratio of Salmonella was significantly increased from 0.001% to 0.045% after chlorination of 69 （mg·min）/L and 24 hr storage. These trends indicated that chlorination contributes to the selection of chlorine-resistant pathogenic bacteria, and regrowth of pathogenic bacteria after chlorination in reclaimed water with a long retention time could threaten public health security during wastewater reuse.展开更多
AIM:To investigate characteristics of hepatitis B virus(HBV)implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.METHODS:Serum samples were collected from 53 p...AIM:To investigate characteristics of hepatitis B virus(HBV)implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.METHODS:Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen(HBsAg)before the start of and throughout the chemotherapy course.HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by realtime detection polymerase chain reaction(RTD-PCR).For detecting the serological markers of HBV infection,HBsAg as well as antibodies to the core antigen(antiHBc)and to the surface antigen were measured in the sera by CEIA.Nucleic acids were extracted from sera,and HBV DNA sequences spanning the S gene were amplified by RTD-PCR.The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancerⅡ/core promoter/pre-core/core regions(nt1628-2364).Amplicons were sequenced directly.RESULTS:Thirty-five(66%)of the 53 HBsAg-negative patients were found to be negative serologically for antiHBc,and the remaining 18(34%)patients were positive for anti-HBc.Five of the 53(9.4%)patients with hematologic malignancies experienced HBV reactivation.Genotype D1 was detected in all five patients.Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation:T/S120,L143,and I126.HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation.In this patient,sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100%homology.Furthermore,in the phylogenetic tree,the sequences were clustered together,thereby indicating that this patient developed reactivation from an occult HBV infection.CONCLUSION:Past infection with HBV is a risk factor for HBV reactivation in Egypt.Mandatory anti-HBc screening prior to chemotherapy in patients with hematological malignancies is recommended.展开更多
AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preem...AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.展开更多
This paper presents a three-dimensional fully hydro-mechanical coupled distinct element study on fault reactivation and induced seismicity due to hydraulic fracturing injection and subsequent backflow process,based on...This paper presents a three-dimensional fully hydro-mechanical coupled distinct element study on fault reactivation and induced seismicity due to hydraulic fracturing injection and subsequent backflow process,based on the geological data in Horn River Basin,Northeast British Columbia,Canada.The modeling results indicate that the maximum magnitude of seismic events appears at the fracturing stage.The increment of fluid volume in the fault determines the cumulative moment and maximum fault slippage,both of which are essentially proportional to the fluid volume.After backflow starts,the fluid near the joint intersection keeps flowing into the critically stressed fault,rather than backflows to the wellbore.Although fault slippage is affected by the changes of both pore pressure and ambient rock stress,their contributions are different at fracturing and backflow stages.At fracturing stage,pore pressure change shows a dominant effect on induced fault slippage.While at backflow stage,because the fault plane is under a critical stress state,any minor disturbance would trigger a fault slippage.The energy analysis indicates that aseismic deformation takes up a majority of the total deformation energy during hydraulic fracturing.A common regularity is found in both fracturing-and backflow-induced seismicity that the cumulative moment and maximum fault slippage are nearly proportional to the injected fluid volume.This study shows some novel insights into interpreting fracturing-and backflowinduced seismicity,and provides useful information for controlling and mitigating seismic hazards due to hydraulic fracturing.展开更多
文摘The original online version https://doi.org/10.1007/s11629-024-9130-x has wrong title.The correct title for this article should be“Reactivation mechanisms of the ancient Dahekou landslide in Hanzhong City,Shaanxi Province,China”.
基金supported by the Fundamental Research Funds for the Central Universities in China(Grant no.2662022DKPY003)the HZAU-AGIS Cooperation Fund(Grant no.SZYJY2022015).
文摘Toxoplasma gondii(T.gondii)is an obligate intracellular parasite with a wide range of hosts,including humans and many warm-blooded animals.The parasite exists in two interconvertible forms,namely tachyzoites and bradyzoites in intermediate hosts that are responsible for acute and chronic infections respectively.Mature bradyzoites accumulate large amounts of amylopectin granules but their roles have not been fully characterized.In this study,the predicted key enzymes involved in amylopectin synthesis(UDP-sugar pyrophospharylase,USP)and degradation(alpha-glucan water dikinase,GWD)of ME49 strain were individually knocked out,and then bradyzoite-related phenotyping experiments in vitro and in vivo were performed to dissect their roles during parasite growth and development.Deletion of the usp or gwd gene in the type II strain ME49 reduced the replication rates of tachyzoites in vitro and parasite virulence in vivo,suggesting that amylopectin metabolism is important for optimal tachyzoite growth.Interestingly,the Δusp mutant grew slightly faster than the parental strain under stress conditions that induced bradyzoite transition,which was likely due to the decreased efficiency of bradyzoite formation of theΔusp mutant.Although theΔgwd mutant could convert to bradyzoite robustly in vitro,it was significantly impaired in establishing chronic infection in vivo.Both the Δusp and Δgwd mutants showed a dramatic reduction in the reactivation of chronic infection in an in vitro model.Together,these results suggest that USP and GWD,which are involved in amylopectin synthesis and degradation have important roles in tachyzoite growth,as well as in the formation and reactivation of bradyzoites in T.gondii.
基金supported by the Major Research Plan of the National Natural Science Foundation of China(No.92159202)the National Key Research and Development Program of China(No.2021YFA1100500)+2 种基金the Key Research&Development Plan of Zhejiang Province(No.2019C03050)National S&T Major Project(No.2017ZX10203205)the Health Science&Technology Plan of Zhejiang Province(No.2022RC060)。
文摘Objective:The role of non-alcoholic steatohepatitis(NASH)in hepatitis B virus(HBV)reactivation following liver transplantation for hepatocellular carcinoma(HCC)remains unclear,and the metabolic differences between patients with NASH and those with HBV reactivation are also yet to be elucidated.This study is to investigate the impact of NASH on HBV reactivation risk and prognosis following liver transplantation for HCC,and to develop a predictive model and identify therapeutic targets.Methods:This study included 274 patients who underwent liver transplantation for HCC.The HBV reactivation status of patients with NASH was analyzed,and the metabolic characteristics of peripheral blood were examined to compare NASH and non-NASH patients with or without HBV reactivation.Results:The HBV reactivation free survival was better in non-NASH patients(P<0.0001).Furthermore,NASH patients with HBV reactivation had worse recurrence-free survival(RFS)than non-NASH patients with HBV reactivation(P=0.016).In contrast,the RFS of NASH patients without HBV reactivation was comparable to that of non-NASH patients without HBV reactivation(P=0.810).Subsequently,we constructed a model to predict HBV reactivation by incorporating 7 clinical indicators using the Least Absolute Shrinkage and Selection Operator-Cox(LASSO-Cox)approach.The area under the receiver operating characteristic curve(AUROC)values for predictions at 500,1,000,and 1,500 d were 0.759,0.809,and 0.814,respectively.Finally,metabolic pathway analysis identified key pathways involved in HBV reactivation,and glutamine was found to be an independent protective factor against HBV reactivation following liver transplantation for HCC.Conclusions:NASH patients are more prone to HBV reactivation following liver transplantation for HCC and exhibit worse recurrence-free survival.Glutamine may serve as a potential therapeutic target or predictive biomarker for HBV reactivation.
基金supported in part by the National Key Research and Development Project of China(No.2022YFC3004602)in part by the National Natural Science Foundation of China(Nos.52121003 and 52442406)。
文摘With the advancement of fracturing technologies in deeper and more geologically complex formations,fault reactivation and induced seismicity have attracted increasing attention.The increasing frequency and magnitude of these events underscore the need for a robust understanding of the governing physical mechanisms.Elevated pore pressure,modified fault-loading conditions,and aseismic slip are widely acknowledged as the primary drivers.Recent studies have explored these mechanisms under varying factors,including fluid properties,rock ductility,poroelastic responses,and evolving fault stress states,thereby offering critical insights into model refinement.Probabilistic forecasting approaches,which combine statistical analyses of historical data with real-time monitoring,are being increasingly adopted in seismic risk assessments.In parallel,machine learning techniques are employed to process large seismic datasets and identify key patterns.However,their predictive capabilities remain limited by geological heterogeneity,subsurface complexity,and scarce observational data.Moreover,fluid–rock interactions further complicate the development of universally applicable models,thereby constraining the generalizability of mitigation strategies.This review synthesizes the current understanding of induced seismicity mechanisms,evaluates the prevailing prediction and mitigation methods,and identifies major challenges and future research directions.Advancements in these areas are essential to enhancing seismic risk management and ensuring the safe,sustainable development of deep-subsurface energy resources.
文摘BACKGROUND Cytomegalovirus(CMV)reactivation is a potentially severe complication in immunocompromised patients,yet its incidence and impact in recipients of autologous hematopoietic stem cell transplantation(AHSCT)remain insufficiently documented.AIM To assess the frequency,timing,and outcomes of CMV reactivation in patients undergoing AHSCT at Aziza Othmana Hospital.METHODS We conducted a retrospective descriptive study of all patients who underwent AHSCT between January 2022 and December 2024 and had at least one posttransplant plasma viral load(VL)assessment.CMV VL was quantified by realtime polymerase chain reaction using TaqMan probes(GeneProof®)with a sensitivity threshold of 150 IU/mL.RESULTS Among 277 AHSCT recipients,17(6.1%)experienced CMV reactivation.Their median age was 43 years,with a sex ratio of 0.46(male/female).Underlying diseases included large B-cell lymphoma(n=5),multiple myeloma(n=3),and Hodgkin’s lymphoma(n=4).The median time to reactivation was 26 days post transplant(11 days after neutrophil recovery).Median peak VL was 1325 IU/mL(range:150-641000 IU/mL).Six patients required antiviral therapy(median peak VL:30150 IU/mL),while 11 had spontaneous resolution(median peak VL:1320 IU/mL).Two patients died in the context of CMV reactivation.CONCLUSION CMV reactivation occurs in a noteworthy proportion of AHSCT recipients and may lead to severe outcomes.Routine VL monitoring in the early post-transplant period is crucial,and preemptive therapy should be initiated once clinically relevant VL thresholds are reached to prevent progression to CMV disease and associated mortality.
基金funded by the National Natural Science Foundation of China(Grant No.42077257)。
文摘Ancient landslides with platform geomorphology occasionally reactivate,posing serious geohazards.On September 9,2021,persistent heavy rainfall triggered the reactivation of the Dahekou ancient landslide within a gently sloping geomorphology at the core of Zhangjiantan syncline in China's western Qinling-Daba Mountains.This event caused one death,damaged 80 houses,and blocked the Yushui River.This study reconstructs the sliding process of the Dahekou landslide and deciphers the complex landslide initiation mechanisms through field surveys,unmanned aerial vehicle(UAV)imagery analysis,drilling,electrical resistivity tomography(ERT)and small baseline subset–interferometric synthetic aperture radar(SBAS–InSAR)monitoring.We divide the sliding process of the Dahekou landslide into three stages.Two new landslides(#1 and#2)occurred at 18:30 on September 9,2021.Subsequently,the ancient landslide(#3)slid in the 230°direction at approximately 20:30 on September 9,2021,then changed the direction to 170°–240°at 22:30 on the same day,and moved in the direction of 300°at 10:00 the next day.Finally,the reactivated ancient landslide(#3)formed two partially sliding masses,with volumes of approximately 158×10^(4)m^(3)and 160×10~4 m^(3),along the directions of 170°–240°and 300°,respectively,damaging 80 houses and blocking the Yushui River.Field surveys suggest that new landslides#1 and#2 are rock landslides and soil landslides,respectively,with volumes of approximately 230×10^(4)m^(3)and 7.49×10~4 m^(3).Compared with the InSAR data,the new landslide#1 thrust the ancient landslide#3,with an uplift velocity rate of 22.68 mm/a at the rear edge,from September 2020–September 2021.An analysis of drill hole data reveals that the bedding in the landslide area has complex geological conditions,comprising mudstone prone to slipping with different degrees of weathering.Notably,the core of the Zhangjiatan syncline sits on the sliding bedding of the ancient landslide,contributing to a change in the sliding direction.This comprehensive study reveals that the landslide#1 loading and thrusting,the persistent and heavy rainfall,and the complex geological conditions influenced the reactivated ancient landslide.Considering the intricacies of landslide failure mechanisms,we advocate for giving more attention in the future to the zone of potentially slip-prone strata located at the edge of ancient landslides.
文摘Elsberg syndrome, or HSV-2 lumbosacral radiculitis, is a rare and underrecognized neurologic condition that mimics cauda equina syndrome (CES). It typically presents with symptoms such as urinary retention, saddle anesthesia, and bowel incontinence. This case report describes a 59-year-old immunosuppressed male with idiopathic pulmonary fibrosis who developed Elsberg syndrome due to re-activation of latent HSV-2. The patient experienced progressive lower extremity sensory deficits and genitourinary dysfunction, culminating in a vesiculopustular rash. Diagnosis was confirmed via cerebrospinal fluid analysis and PCR testing of skin lesions. Despite early imaging findings being unremarkable, subsequent MRI revealed enhancement of the conus medullaris and cauda equina. Treatment with intravenous acyclovir, corticosteroids, and supportive therapy led to gradual functional improvement, though sensory deficits and neuropathy persisted. This case highlights the diagnostic challenges and importance of clinical suspicion for HSV-2 reactivation in immunosuppressed patients, as well as considerations for long-term symptom management.
文摘Indonesia is facing severe congestion and high accident rates as motor vehicle growth continues to outpace road capacity,underscoring the urgent need for alternative mass transportation.A promising solution is the reactivation of the Surabaya–Madura railway,an abandoned infrastructure with significant potential to enhance regional connectivity and urban mobility.However,academic studies on railway reactivation remain limited,particularly in the Madura context where dependence on road-based transport persists.This research gap highlights the importance of examining reactivation not only as a transportation alternative but also as a catalyst for regional development.This study adopts a qualitative approach through descriptive surveys to evaluate infrastructure conditions,identify feasible routes,and analyze broader spatial implications.Findings reveal that railway reactivation could strengthen multimodal integration,reduce congestion,and support sustainable growth.This study provides the first empirical evidence of the strategic value of the Surabaya–Madura railway within Indonesia’s transport and regional development discourse.
基金funding support from the National Nature Science Foundation of China(Grant No.42272334)the National Key Research and Development Program of China(Grant No.2022YFE0137200)the Taishan Scholars Program(Grant No.2019RKB01083).
文摘Fracture(fault)reactivation can lead to dynamic geological hazards including earthquakes,rock collapses,landslides,and rock bursts.True triaxial compression tests were conducted to analyze the fracture reactivation process under two different orientations of σ_(2),i.e.σ_(2) parallel to the fracture plane(Scheme 2)and σ_(2) cutting through the fracture plane(Scheme 3),under varying σ_(3) from 10 MPa to 40 MPa.The peak or fracture reactivation strength,deformation,failure mode,and post-peak mechanical behavior of intact(Scheme 1)and pre-fractured(Schemes 2 and 3)specimens were also compared.Results show that for intact specimens,the stress remains nearly constant in the residual sliding stage with no stick-slip,and the newly formed fracture surface only propagates along the σ_(2) direction when σ_(3) ranges from 10 MPa to 30 MPa,while it extends along both σ_(2) and σ_(3) directions when σ_(3) increases to 40 MPa;for the pre-fractured specimens,the fractures are usually reactivated under all the σ_(3) levels in Scheme 2,but fracture reactivation only occurs when σ_(3) is greater than 25 MPa in Scheme 3,below which new faulting traversing the original macro fracture occurs.In all the test schemes,both ε_(2) and ε_(3) experience an accumulative process of elongation,after which an abrupt change occurs at the point of the final failure;the degree of this change is dependent on the orientation of the new faulting or the slip direction of the original fracture,and it is generally more than 10 times larger in the slip direction of the original fracture than in the non-slip direction.Besides,the differential stress(peak stress)required for reactivation and the post-peak stress drop increase with increasing σ_(3).Post-peak stress drop and residual strength in Scheme 3 are generally greater than those in Scheme 2 at the same σ_(3) value.Our study clearly shows that intermediate principal stress orientation not only affects the fracture reactivation strength but also influences the slip deformation and failure modes.These new findings facilitate the mitigation of dynamic geological hazards associated with fracture and fault slip.
基金supported by the National Natural Science Foun-dation of China(92159202)the National Science and Technology Major Project of China(2017ZX10203205)+4 种基金the Fundamental Research Funds for the Central Universities(2022ZFJH003)the Major Research Plan of Key Research and Development Project of Zhejiang Province(2024C03149 and 2023C03046)the National Key Research and Development Program of China(2021YFF1200404 and 2021YFA1201200)the Zhejiang Provincial Natural Science Foundation of China(LQ24C050005 and LQ22H160052)the Medical and Health Technology Program Project of Zhejiang Province(2021434810).
文摘Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately characterized.Herein,we retrospectively analyzed our cohort(NCT06114251)comprising 453 patients with an HBV background.Propensity score matching(PSM)and sensitivity analyses were employed to assess the influence of ALD on surgical outcomes.Benchmark analysis compared the predictive performance of 21 models for post-transplant HBV reactivation.The Shapley additive explanation(SHAP)algorithm facilitated feature ranking and model interpretation.Patients were stratified into three subgroups based on the alcohol-modified HBV reactivation index(AMBRI).Among the cohort,113 patients(24.9%)had concurrent pre-transplant diagnoses of ALD and HBV infection,while 340(75.1%)had HBV infection alone.The presence of ALD was associated with an elevated risk of HBV reactivation and liver metastasis.PSM and sensitivity analyses revealed significantly lower five-year HBV reactivation-free survival(74.9%vs 85.4%),overall survival(OS,56.2%vs 70.5%),and tumor recurrence-free survival(RFS,47.8%vs 63.3%)in the ALD cohort.In recipients without HBV reactivation,hepatocellular carcinomas(HCCs)arising from both ALD and HBV exhibited inferior RFS(log-rank P=0.026)and OS beyond one year(landmark P=0.032)compared to HBV-related HCC alone.Benchmark analysis identified the surv.cforest model as the optimal predictor,achieving an area under the receiver operating characteristic(AUC)curve of 0.914 in internal validation and 0.884 in external validation,outperforming the published Cox model(AUC=0.78).AMBRI-based stratification delineated three distinct risk subgroups,with the intermediate-and high-risk groups exhibiting significantly worse OS and RFS than the low-risk group.In this study,stratification by AMBRI identified intermediate-and high-risk groups with poorer post-transplant outcomes,underscoring the necessity for intensified surveillance and enhanced HBV treatment regimens,particularly in recipients with pre-transplant ALD.
文摘In recent years,a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive drugs.The cases of viral hepatitis reactivation that have been reported are characterized by a wide range of clinical manifestations,from viremia without clinically relevant manifestations to fulminant life-threatening hepatitis.The development and dissemination of biological immunosuppressive drugs have led to a significant increase in the number of reports of interest to physicians in a variety of clinical settings.On this topic,there have been a number of published guidelines and reviews that have collected the available evidence,providing recommendations on prophylactic and therapeutic strategies and methods for monitoring patients at risk.However,it should be noted that,to date,very few clinical studies have been published,and most of the recommendations have been borrowed from otherclinical settings.The published studies are mostly retrospective and are based on very heterogeneous populations,using different therapeutic and prophylactic regimens and obtaining conflicting results.Thus,it seems clear that it is desirable to concentrate our efforts on prospective studies,not conducting further reviews of the literature in the continued absence of new evidence.
文摘Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.
文摘Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus(HBV) replication,often accompanied by an increase in serum transaminase levels,and both events occurring in a patient with a previous inactive hepatitis B infection.This reactivation can occur in situations in which the ratio of HBV replication and immune response is altered.It can happen during the treatment of hemato-oncological malignancies with chemotherapy and in immunosuppression of autoimmune diseases.Clinical manifestations of hepatitis B reactivation are variable and can range from asymptomatic to acute hepatitis,which are sometimes serious and result in acute liver failure with risk of death,and usually occur in the periods between cycles or at the end of chemotherapy.Immunosuppressive drugs such as corticosteroids or azathioprine can induce HBV reactivation in patients carrying hepatitis B virus surface antigen(HBsAg) or anti-HBc,but much less frequently than chemotherapy treatments.The tumor necrosis factorαinhibitors infliximab,etanercept and adalimumab may cause reactivation of hepatitis B,and the overall frequency with infliximab may be similar(50%-66%) to that caused by chemotherapy.Baseline HBV serology is recommended for all patients receiving chemotherapy and immunosuppressive drugs,and HBsAg positive patients should receive anti-HBV prophylaxis to decrease virus reactivation and death rates.
文摘Due to the inherent relationship between the immune system and the hepatitis B virus(HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation(HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations' guidelines and the best available evidence to date.
文摘Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.
文摘Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
基金supported by the National Natural Science Foundation of China(No.51178242)the National Post-doctoral Research Foundation of China(No.023203010)
文摘Disinfection of reclaimed water prior to reuse is important to prevent the transmission of pathogens. Chlorine is a widely utilized disinfectant and as such is a leading contender for disinfection of reclaimed water. To understand the risks of chlorination resulting from the potential selection of pathogenic bacteria, the inactivation, reactivation and regrowth rates of indigenous bacteria were investigated in reclaimed water after chlorine disinfection. Inactivation of total coliforms, Enterococcus and Salmonella showed linear correlations, with constants of 0.1384, 0.1624 and 0.057 L/（mg·min） and R 2 of 0.7617, 0.8316 and 0.845, respectively. However, inactivation of total viable cells by measurement of metabolic activity typically showed a linear correlation at lower chlorine dose （0-22 （mg·min）/L）, and a trailing region with chlorine dose increasing from 22 to 69 （mg·min）/L. Reactivation and regrowth of bacteria were most likely to occur after exposure to lower chlorine doses, and extents of reactivation decreased gradually with increasing chlorine dose. In contrast to total coliforms and Enterococcus, Salmonella had a high level of regrowth and reactivation, and still had 2% regrowth even after chlorination of 69 （mg·min）/L and 24 hr storage. The bacterial compositions were also significantly altered by chlorination and storage of reclaimed water, and the ratio of Salmonella was significantly increased from 0.001% to 0.045% after chlorination of 69 （mg·min）/L and 24 hr storage. These trends indicated that chlorination contributes to the selection of chlorine-resistant pathogenic bacteria, and regrowth of pathogenic bacteria after chlorination in reclaimed water with a long retention time could threaten public health security during wastewater reuse.
基金Supported by The Grant for National Center For Global Health and Medicine(22A-9)a Grant-in-Aid form Japan Society for the Promotion of Science(JSPS) Fellows(21.09355)a Grant-in-Aid form the Ministry of Health,Labour and Welfare of Japan
文摘AIM:To investigate characteristics of hepatitis B virus(HBV)implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.METHODS:Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen(HBsAg)before the start of and throughout the chemotherapy course.HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by realtime detection polymerase chain reaction(RTD-PCR).For detecting the serological markers of HBV infection,HBsAg as well as antibodies to the core antigen(antiHBc)and to the surface antigen were measured in the sera by CEIA.Nucleic acids were extracted from sera,and HBV DNA sequences spanning the S gene were amplified by RTD-PCR.The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancerⅡ/core promoter/pre-core/core regions(nt1628-2364).Amplicons were sequenced directly.RESULTS:Thirty-five(66%)of the 53 HBsAg-negative patients were found to be negative serologically for antiHBc,and the remaining 18(34%)patients were positive for anti-HBc.Five of the 53(9.4%)patients with hematologic malignancies experienced HBV reactivation.Genotype D1 was detected in all five patients.Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation:T/S120,L143,and I126.HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation.In this patient,sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100%homology.Furthermore,in the phylogenetic tree,the sequences were clustered together,thereby indicating that this patient developed reactivation from an occult HBV infection.CONCLUSION:Past infection with HBV is a risk factor for HBV reactivation in Egypt.Mandatory anti-HBc screening prior to chemotherapy in patients with hematological malignancies is recommended.
文摘AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.
基金supported by the Key Innovation Team Program of Innovation Talents Promotion Plan by Ministry of Science and Technology of China(Grant No.2016RA4059)National Natural Science Foundation of China(Grant Nos.41672268 and 41772286)。
文摘This paper presents a three-dimensional fully hydro-mechanical coupled distinct element study on fault reactivation and induced seismicity due to hydraulic fracturing injection and subsequent backflow process,based on the geological data in Horn River Basin,Northeast British Columbia,Canada.The modeling results indicate that the maximum magnitude of seismic events appears at the fracturing stage.The increment of fluid volume in the fault determines the cumulative moment and maximum fault slippage,both of which are essentially proportional to the fluid volume.After backflow starts,the fluid near the joint intersection keeps flowing into the critically stressed fault,rather than backflows to the wellbore.Although fault slippage is affected by the changes of both pore pressure and ambient rock stress,their contributions are different at fracturing and backflow stages.At fracturing stage,pore pressure change shows a dominant effect on induced fault slippage.While at backflow stage,because the fault plane is under a critical stress state,any minor disturbance would trigger a fault slippage.The energy analysis indicates that aseismic deformation takes up a majority of the total deformation energy during hydraulic fracturing.A common regularity is found in both fracturing-and backflow-induced seismicity that the cumulative moment and maximum fault slippage are nearly proportional to the injected fluid volume.This study shows some novel insights into interpreting fracturing-and backflowinduced seismicity,and provides useful information for controlling and mitigating seismic hazards due to hydraulic fracturing.
