The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules form...Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.展开更多
The dangerous Crimean-Congo hemorrhagic fever virus(CCHFV),an encapsulated negative-sense RNA virus of the family Nairoviridae,is transmitted from person to person via ticks.With a case fatality rate between 10%to 40%...The dangerous Crimean-Congo hemorrhagic fever virus(CCHFV),an encapsulated negative-sense RNA virus of the family Nairoviridae,is transmitted from person to person via ticks.With a case fatality rate between 10%to 40%,the most common ways that the disease may spread to humans are via tick bites or coming into touch with infected animals'blood or tissues.Furthermore,the transfer of bodily fluids between individuals is another potential route of infection.There is a wide range of symptoms experienced by patients throughout each stage,from myalgia and fever to extreme bruising and excess bleeding.Tick management measures include minimising the spread of ticks from one species to another and from people to animals via the use of protective clothing,repellents,and proper animal handling.In order to prevent the spread of illness,healthcare workers must adhere to stringent protocols.Despite the lack of an authorised vaccine,the main components of treatment now consist of preventative measures and supportive care,which may include the antiviral medicine ribavirin.We still don't know very much about the virus's mechanisms,even though advances in molecular virology and animal models have improved our understanding of the pathogenesis of CCHFV.A critical need for vaccination that is both safe and effective,as well as for quick diagnosis and efficient treatments to lessen the disease's impact in areas where it is most prevalent.Important steps towards lowering Crimean-Congo hemorrhagic fever mortality and morbidity rates were to anticipatethe future availability of immunoglobulin products.展开更多
Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning fr...Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning from the molecular mechanisms within cells to large-scale epidemiological patterns,has surpassed the capabilities of traditional analytical methods.In the era of artificial intelligence(AI)and big data,there is an urgent necessity for the optimization of these analytical methods to more effectively handle and utilize the information.Despite the rapid accumulation of data associated with viral infections,the lack of a comprehensive framework for integrating,selecting,and analyzing these datasets has left numerous researchers uncertain about which data to select,how to access it,and how to utilize it most effectively in their research.This review endeavors to fill these gaps by exploring the multifaceted nature of viral infectious diseases and summarizing relevant data across multiple levels,from the molecular details of pathogens to broad epidemiological trends.The scope extends from the micro-scale to the macro-scale,encompassing pathogens,hosts,and vectors.In addition to data summarization,this review thoroughly investigates various dataset sources.It also traces the historical evolution of data collection in the field of viral infectious diseases,highlighting the progress achieved over time.Simultaneously,it evaluates the current limitations that impede data utilization.Furthermore,we propose strategies to surmount these challenges,focusing on the development and application of advanced computational techniques,AI-driven models,and enhanced data integration practices.By providing a comprehensive synthesis of existing knowledge,this review is designed to guide future research and contribute to more informed approaches in the surveillance,prevention,and control of viral infectious diseases,particularly within the context of the expanding big-data landscape.展开更多
Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegment...Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.展开更多
The article"Secondary diabetes due to different etiologies:Four case reports"by Song et al,published in the World Journal of Clinical Cases,delves into the identi-fication of rare causes of secondary diabete...The article"Secondary diabetes due to different etiologies:Four case reports"by Song et al,published in the World Journal of Clinical Cases,delves into the identi-fication of rare causes of secondary diabetes and emphasizes the necessity for healthcare professionals to recognize these conditions.Failure to do so can result in treatment delays and compromised patient outcomes.The article discusses spe-cific types of diabetes,including maturity onset of diabetes in young,pancreas-related diseases,endocrinopathies,drug-induced diabetes,infections,and con-genital genetic syndromes associated with diabetes mellitus.Case summaries highlight how patients with secondary diabetes,stemming from conditions such as Williams-Beuren syndrome and pituitary adenoma,often exhibit distinct characteristics overlooked in clinical practice.The authors stress the importance of a holistic diagnostic approach and advocate for proactive management through early intervention,including genetic tests and antibody detection.Increased awa-reness and education are crucial for timely identification and proper management,ultimately improving patient well-being.These findings prompt a call to action for healthcare professionals to consider rare causes of secondary diabetes,facili-tating better glycemic control and overall patient care.展开更多
BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and afte...BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and after adoption of the Treat All policy among people living with HIV in Rwanda.METHODS Between 2014 and 2017,VL suppression[VL suppression(VLS)<200 copies/mL]was measured among people living with HIV from 28 healthcare facilities in Rwanda.Participant VL was measured at 6 months,18 months,and 30 months.The unit of analysis was visit-pair,with subjects across four visit-pair categories:(1)Sustained VL suppression(VL<200 copies/mL at two consecutive visits);(2)Persistent viremia(VL≥200 copies/mL at two consecutive visits);(3)Viral rebound(VL<200 copies/mL at prior visit only);and(4)Newly suppressed(VL<200 copies/mL at subsequent visit only).Poisson regression models with generalized estimating equations were used to estimate adjusted incidence risk ratio(aIRR)and 95%confidence intervals(CIs)for factors associated with sustained VLS.To handle missing data,multiple imputations was performed.RESULTS A total of 634 participants contributed 973 visit-pairs(295 single pairs and 339 double pairs).The median age was 37 years(interquartile range:32-43 years).The incidence rates of sustained VLS,persistent viremia,viral rebound,and new suppression were 85.2%,4.3%,4.6%,and 5.7%,respectively.Young individuals aged 18-24 years had higher incidence of viral rebound compared to those 25 years or older(14.8%vs 4.3%;P=0.011).Of the visit-pairs that had sustained VLS during the first two visits(49.8%;n=485),56.7%exhibited sustained VLS throughout follow-up.Compared to having no education,having at least primary education was associated with an increased likelihood of sustained VLS(aIRR=1.09;95%CI:1.01-1.17).Those who presented with advanced HIV disease at baseline had a 12%reduced likelihood of sustained VLS(aIRR=0.88;95%CI:0.79-0.99).Achieving sustained VLS did not differ before or after adoption of the Treat All policy.When the analysis was repeated on imputed datasets,similar results were found.CONCLUSION Although most people living with HIV have sustained VLS in Rwanda,individuals without formal education,those presenting with advanced HIV,and younger individuals were lagging on multiple outcomes.Interventions tailored to these individuals would improve treatment outcomes to achieve epidemic control.展开更多
The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough establ...The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough established a novel framework for site-specific gene delivery through repurposing ancient viral tools.展开更多
Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global populat...Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.展开更多
BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepat...BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections.Accurate prognostication is crucial for optimizing treatment and outcomes.Numerous staging systems exist,including the Barcelona Clinic Liver Cancer(BCLC),Hong Kong Liver Cancer(HKLC),cancer of the liver Italian Program(CLIP),Italian Liver Cancer(ITA.LI.CA),Japan Integrated Staging(JIS),Tokyo Score,and model to estimate survival in ambulatory HCC patients(MESIAH).However,their comparative performance in Vietnamese patients remains underexplored.AIM To compare the prognostic accuracy of seven HCC staging systems in predicting survival and identify the optimal model.METHODS This retrospective cohort study included 987 patients with HCC diagnosed at Nhan dan Gia Dinh Hospital,Vietnam,from January 2016 to December 2023.Patients were staged using BCLC,HKLC,CLIP,ITA.LI.CA,JIS,Tokyo score,and MESIAH.Overall survival was analyzed using Kaplan-Meier methods,and prognostic performance was evaluated via the area under the receiver operating characteristic(ROC)curve,Harrell’s concordance index,and calibration plots.RESULTS The HKLC and BCLC systems demonstrated the highest discriminatory ability,with area under the ROC curves of 0.834 and 0.830,respectively,at 12 months and 0.859 for both systems at 36 months.CLIP and ITA.LI.CA exhibited superior calibration,particularly at 36 months.The JIS system consistently showed the poorest discriminatory performance.Subgroup analyses revealed that HKLC maintained strong performance across different viral etiologies(HBV,HCV,non-B-non-C)and treatment modalities(transarterial chemoembolization,surgery,ablation).CONCLUSION The HKLC and BCLC systems showed superior prognostic performance for Vietnamese patients with HCC,supporting HKLC adoption in clinical practice.展开更多
Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by dir...Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA.Here,we examined the role of the host RNA-binding protein nucleophosmin-1(NPM1)in IAV replication.We found that,as a nucleolar phosphoprotein,NPM1 directly binds to viral RNA(vRNA)and inhibits the replication of various subtypes of IAV.NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity,thereby reducing the generation of progeny viral RNA and virions.The RNA-binding activity of NPM1,with the key residues T199,T219,T234,and T237,is essential for its anti-influenza function.Taken together,our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.展开更多
Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instea...Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instead integrate their genetic material into the host genome thus,affecting cell cycle and tumor suppression.This deregulation also leads to impaired immune function and promotes tumor progression by disrupting the removal of infected cells.Generally,innate immunity consists of two important members,including mitochondria and cell deaths,which impact each other as well.Due to the close correlation between viruses,cell death pathways(apoptosis,necroptosis,and pyroptosis),and mitochondria(mitochondrial antiviral-signaling protein and reactive oxygen species generation),targeting these immune system representatives may offer therapeutic strategies to control the progression of oncogenic viral infections.Some previous studies have covered the association of oncogenic viruses with mitochondria and cell death pathways,respectively,but mitochondria and cell death interact with each other,separately,and this interaction may play a role in the progression of cancer induced by oncogenic viruses.Hence,the purpose of this review is to discuss the relationship between cell death,mitochondria,and viral oncogenesis,focusing on the most surveyed oncogenic viruses’mechanisms of action.展开更多
Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacter...Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.展开更多
Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical c...Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients.This review examines the interaction between viral infections and SCD,highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population.Advances in antiviral therapies have significantly improved outcomes,yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions,altered pharmacokinetics,and the potential exacerbation of SCDrelated complications.Additionally,vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention.By focusing on both established and novel antiviral treatments,this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.展开更多
Pseudorabies virus(PRV,SuidAlphaherpesvirus 1)causes substantial economic losses in swine production.Here,we report the development of DNA aptamers targeting the PRV glycoprotein D(gD)through an optimized SELEX protoc...Pseudorabies virus(PRV,SuidAlphaherpesvirus 1)causes substantial economic losses in swine production.Here,we report the development of DNA aptamers targeting the PRV glycoprotein D(gD)through an optimized SELEX protocol.After 15 selection cycles,Apt-gD-2 demonstrated nanomolar affinity(Kd=6.107±0.476 nM)and high specificity for gD,as validated by an enzyme-linked aptamer-sorbent assay(ELASA)and fluorescence microscopy.Molecular docking revealed hydrogen bonding as the key interaction mechanism.The developed ic-ELASA achieved 83.3%concordance with qPCR in clinical samples,supporting its utility for on-farm PRV surveillance.These findings highlight the potential of aptamer-based diagnostic methods for rapid,sensitive,and onsite detection of PRV,offering a promising tool for disease control in the swine industry.展开更多
BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often dif...BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A(MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of Mx A to distinguish viral from bacterial infections.METHODS: We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic(ROC) curve analysis were used to determine the diagnostic value of Mx A, either alone or in combination with C-reactive protein(CRP) or procalcitonin(PCT), in patients with viral, bacterial, or co-infections.RESULTS: The value of MxA(ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections(82.3 [24.5–182.9] vs. 16.4 [10.8–26.5], P<0.0001)(82.3 [24.5–182.9] vs. 28.5 [10.2–106.8], P=0.0237). The area under the curve(AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799(95% confidence interval [95% CI] 0.696–0.903), with a sensitivity of 68.9%(95% CI 54.3%–80.5%) and specificity of 90.0%(95% CI 74.4%–96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus(15.8 [9.6–47.6] ng/mL) and Epstein-Barr virus(12.9 [8.5–21.0] ng/mL) infections.CONCLUSION: Our study showed the diagnostic efficacy of Mx A in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, EpsteinBarr virus and human cytomegalovirus infections did not elicit elevated Mx A expression.展开更多
A recent nationwide cohort study reported an increased incidence and altered seasonality of type 1 diabetes mellitus(T1DM)during the coronavirus disease 2019(COVID-19)pandemic.The study found that new-onset T1DM cases...A recent nationwide cohort study reported an increased incidence and altered seasonality of type 1 diabetes mellitus(T1DM)during the coronavirus disease 2019(COVID-19)pandemic.The study found that new-onset T1DM cases were significantly higher during the pandemic than in prior years,and the typical winter peak in T1DM diagnoses was blunted.This occurred alongside markedly reduced circulation of other respiratory viruses under lockdown measures.Carmon et al noted weak positive correlations between T1DM incidence and certain viruses(e.g.,influenza and respiratory syncytial virus),suggesting that reduced exposure to common infections-and possibly severe acute respiratory syndrome coronavirus 2 infection itself-might have contributed to the rise in T1DM.To highlight key methodological limitations of that study,which may affect the interpretation of the findings.We reviewed the study design and data of Carmon et al and discussed potential biases,including ecological inference,confounding factors,delayed diagnoses,lack of COVID-19-stratified analysis,and biases in viral surveillance data,supported by recent literature.The association observed by Carmon et al is at risk of ecological fallacy due to the absence of individual infection linkage.Uncontrolled confounders(healthcare access,socioeconomic changes)and not stratifying by COVID-19 infection status limit causal inference.Pandemic-related diagnostic delays likely inflated apparent T1DM incidence,as evidenced by higher rates of diabetic ketoacidosis in new cases.Biases in virological testing data(reduced testing and non-representative sampling)complicate conclusions about“reduced”viral circulation.The pandemic’s impact on T1DM incidence is important but requires cautious interpretation.Future studies should employ individual-level analyses,adjust for confounders,distinguish true incidence increases from diagnostic delays,stratify by infection status,and use comprehensive viral exposure data to draw more robust conclusions.展开更多
There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmi...There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmission are unknown.Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents.Air particles were collected from swine buildings using high-volume air samplers.Extracted DNA and RNA were used to perform specific RT-qPCR and qPCR and analyzed by highthroughput sequencing.Porcine astroviruses group 2 were common(from 102 to 105 genomic copies per cubic meter of air or gc/m^(3),93%positivity)while no norovirus genogroup II was recovered from air samples.Porcine torque teno sus virus were detected by qPCR in low concentrations(from 101 to 102 gc/m^(3),47%positivity).Among the identified viral families by metagenomics analysis,Herelleviridae,Microviridae,Myoviridae,Podoviridae,and Siphoviridae were dominant.The phage vB_AviM_AVP of Aerococcus was present in all air samples and a newly designed qPCR revealed between 101 and 105 gc/m^(3) among the samples taken for the present study(97%positivity)and banked samples from5-and 15-year old studies(89%positivity).According to the present study,both the porcine astrovirus group 2 and the phage vB_AviM_AVP of Aerococcus could be proxy for airborne viruses of swine buildings.展开更多
Viral hepatitis,including hepatitis B and hepatitis C(HCV),remains a significant global health burden,leading to liver fibrosis,cirrhosis,and hepatocellular car-cinoma.Traditional diagnostic methods,while effective,of...Viral hepatitis,including hepatitis B and hepatitis C(HCV),remains a significant global health burden,leading to liver fibrosis,cirrhosis,and hepatocellular car-cinoma.Traditional diagnostic methods,while effective,often face limitations in accuracy,accessibility,and timeliness.Artificial intelligence(AI)has emerged as a transformative tool in healthcare,enhancing the detection,diagnosis,and treat-ment of viral hepatitis.This review explores the role of AI in viral hepatitis mana-gement,focusing on early detection through image analysis,digital pathology,and machine learning algorithms.AI-driven image analysis tools,such as con-volutional neural networks,have demonstrated high accuracy in detecting HCV-related liver lesions from computed tomography scans.Supervised learning models such as support vector machines and hybrid quantum neural networks further enhance early risk stratification.AI also facilitates personalized treatment by predicting treatment responses,accelerating drug discovery,and advancing precision medicine.Furthermore,AI contributes to epidemiological surveillance by predicting disease spread and tracking treatment adherence.Despite its po-tential,challenges such as data privacy,algorithmic bias,and regulatory comp-liance must be addressed to ensure equitable and effective AI implementation.Future directions include integrating AI into clinical workflows and expanding AI applications in low-resource settings.AI-assisted diagnosis and management have the potential to revolutionize viral hepatitis care,improving patient outcomes and reducing the global disease burden.展开更多
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
基金supported by a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center(to PKS)the Rutgers University Startup Fund(to PKS).
文摘Stress granules are membraneless organelles that serve as a protective cellular response to external stressors by sequestering non-translating messenger RNAs(mRNAs)and regulating protein synthesis.Stress granules formation mechanism is conserved across species,from yeast to mammals,and they play a critical role in minimizing cellular damage during stress.Composed of heterogeneous ribonucleoprotein complexes,stress granules are enriched not only in mRNAs but also in noncoding RNAs and various proteins,including translation initiation factors and RNA-binding proteins.Genetic mutations affecting stress granule assembly and disassembly can lead to abnormal stress granule accumulation,contributing to the progression of several diseases.Recent research indicates that stress granule dynamics are pivotal in determining their physiological and pathological functions,with acute stress granule formation offering protection and chronic stress granule accumulation being detrimental.This review focuses on the multifaceted roles of stress granules under diverse physiological conditions,such as regulation of mRNA transport,mRNA translation,apoptosis,germ cell development,phase separation processes that govern stress granule formation,and their emerging implications in pathophysiological scenarios,such as viral infections,cancer,neurodevelopmental disorders,neurodegeneration,and neuronal trauma.
文摘The dangerous Crimean-Congo hemorrhagic fever virus(CCHFV),an encapsulated negative-sense RNA virus of the family Nairoviridae,is transmitted from person to person via ticks.With a case fatality rate between 10%to 40%,the most common ways that the disease may spread to humans are via tick bites or coming into touch with infected animals'blood or tissues.Furthermore,the transfer of bodily fluids between individuals is another potential route of infection.There is a wide range of symptoms experienced by patients throughout each stage,from myalgia and fever to extreme bruising and excess bleeding.Tick management measures include minimising the spread of ticks from one species to another and from people to animals via the use of protective clothing,repellents,and proper animal handling.In order to prevent the spread of illness,healthcare workers must adhere to stringent protocols.Despite the lack of an authorised vaccine,the main components of treatment now consist of preventative measures and supportive care,which may include the antiviral medicine ribavirin.We still don't know very much about the virus's mechanisms,even though advances in molecular virology and animal models have improved our understanding of the pathogenesis of CCHFV.A critical need for vaccination that is both safe and effective,as well as for quick diagnosis and efficient treatments to lessen the disease's impact in areas where it is most prevalent.Important steps towards lowering Crimean-Congo hemorrhagic fever mortality and morbidity rates were to anticipatethe future availability of immunoglobulin products.
基金supported by the National Natural Science Foundation of China(32370703)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M-1-021,2021-I2M-1-061)the Major Project of Guangzhou National Labora-tory(GZNL2024A01015).
文摘Viral infectious diseases,characterized by their intricate nature and wide-ranging diversity,pose substantial challenges in the domain of data management.The vast volume of data generated by these diseases,spanning from the molecular mechanisms within cells to large-scale epidemiological patterns,has surpassed the capabilities of traditional analytical methods.In the era of artificial intelligence(AI)and big data,there is an urgent necessity for the optimization of these analytical methods to more effectively handle and utilize the information.Despite the rapid accumulation of data associated with viral infections,the lack of a comprehensive framework for integrating,selecting,and analyzing these datasets has left numerous researchers uncertain about which data to select,how to access it,and how to utilize it most effectively in their research.This review endeavors to fill these gaps by exploring the multifaceted nature of viral infectious diseases and summarizing relevant data across multiple levels,from the molecular details of pathogens to broad epidemiological trends.The scope extends from the micro-scale to the macro-scale,encompassing pathogens,hosts,and vectors.In addition to data summarization,this review thoroughly investigates various dataset sources.It also traces the historical evolution of data collection in the field of viral infectious diseases,highlighting the progress achieved over time.Simultaneously,it evaluates the current limitations that impede data utilization.Furthermore,we propose strategies to surmount these challenges,focusing on the development and application of advanced computational techniques,AI-driven models,and enhanced data integration practices.By providing a comprehensive synthesis of existing knowledge,this review is designed to guide future research and contribute to more informed approaches in the surveillance,prevention,and control of viral infectious diseases,particularly within the context of the expanding big-data landscape.
基金supported by the National Key Research and Development Program of China(2022YFC2303300,2023YFC2605504)the National Natural Science Foundation of China(82172273 and 31670165)the Open Research Fund Program of the State Key Laboratory of Virology of China(2023JZZD-01).
文摘Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.
文摘The article"Secondary diabetes due to different etiologies:Four case reports"by Song et al,published in the World Journal of Clinical Cases,delves into the identi-fication of rare causes of secondary diabetes and emphasizes the necessity for healthcare professionals to recognize these conditions.Failure to do so can result in treatment delays and compromised patient outcomes.The article discusses spe-cific types of diabetes,including maturity onset of diabetes in young,pancreas-related diseases,endocrinopathies,drug-induced diabetes,infections,and con-genital genetic syndromes associated with diabetes mellitus.Case summaries highlight how patients with secondary diabetes,stemming from conditions such as Williams-Beuren syndrome and pituitary adenoma,often exhibit distinct characteristics overlooked in clinical practice.The authors stress the importance of a holistic diagnostic approach and advocate for proactive management through early intervention,including genetic tests and antibody detection.Increased awa-reness and education are crucial for timely identification and proper management,ultimately improving patient well-being.These findings prompt a call to action for healthcare professionals to consider rare causes of secondary diabetes,facili-tating better glycemic control and overall patient care.
文摘BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and after adoption of the Treat All policy among people living with HIV in Rwanda.METHODS Between 2014 and 2017,VL suppression[VL suppression(VLS)<200 copies/mL]was measured among people living with HIV from 28 healthcare facilities in Rwanda.Participant VL was measured at 6 months,18 months,and 30 months.The unit of analysis was visit-pair,with subjects across four visit-pair categories:(1)Sustained VL suppression(VL<200 copies/mL at two consecutive visits);(2)Persistent viremia(VL≥200 copies/mL at two consecutive visits);(3)Viral rebound(VL<200 copies/mL at prior visit only);and(4)Newly suppressed(VL<200 copies/mL at subsequent visit only).Poisson regression models with generalized estimating equations were used to estimate adjusted incidence risk ratio(aIRR)and 95%confidence intervals(CIs)for factors associated with sustained VLS.To handle missing data,multiple imputations was performed.RESULTS A total of 634 participants contributed 973 visit-pairs(295 single pairs and 339 double pairs).The median age was 37 years(interquartile range:32-43 years).The incidence rates of sustained VLS,persistent viremia,viral rebound,and new suppression were 85.2%,4.3%,4.6%,and 5.7%,respectively.Young individuals aged 18-24 years had higher incidence of viral rebound compared to those 25 years or older(14.8%vs 4.3%;P=0.011).Of the visit-pairs that had sustained VLS during the first two visits(49.8%;n=485),56.7%exhibited sustained VLS throughout follow-up.Compared to having no education,having at least primary education was associated with an increased likelihood of sustained VLS(aIRR=1.09;95%CI:1.01-1.17).Those who presented with advanced HIV disease at baseline had a 12%reduced likelihood of sustained VLS(aIRR=0.88;95%CI:0.79-0.99).Achieving sustained VLS did not differ before or after adoption of the Treat All policy.When the analysis was repeated on imputed datasets,similar results were found.CONCLUSION Although most people living with HIV have sustained VLS in Rwanda,individuals without formal education,those presenting with advanced HIV,and younger individuals were lagging on multiple outcomes.Interventions tailored to these individuals would improve treatment outcomes to achieve epidemic control.
文摘The 2024 development of a precision-engineered retrotransposon system marked a significant milestone in mammalian genome-editing research.As appeared in the July 8 issue of Cell,this methodological breakthrough established a novel framework for site-specific gene delivery through repurposing ancient viral tools.
基金supported by a grant from the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2019ZB101)。
文摘Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.
文摘BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections.Accurate prognostication is crucial for optimizing treatment and outcomes.Numerous staging systems exist,including the Barcelona Clinic Liver Cancer(BCLC),Hong Kong Liver Cancer(HKLC),cancer of the liver Italian Program(CLIP),Italian Liver Cancer(ITA.LI.CA),Japan Integrated Staging(JIS),Tokyo Score,and model to estimate survival in ambulatory HCC patients(MESIAH).However,their comparative performance in Vietnamese patients remains underexplored.AIM To compare the prognostic accuracy of seven HCC staging systems in predicting survival and identify the optimal model.METHODS This retrospective cohort study included 987 patients with HCC diagnosed at Nhan dan Gia Dinh Hospital,Vietnam,from January 2016 to December 2023.Patients were staged using BCLC,HKLC,CLIP,ITA.LI.CA,JIS,Tokyo score,and MESIAH.Overall survival was analyzed using Kaplan-Meier methods,and prognostic performance was evaluated via the area under the receiver operating characteristic(ROC)curve,Harrell’s concordance index,and calibration plots.RESULTS The HKLC and BCLC systems demonstrated the highest discriminatory ability,with area under the ROC curves of 0.834 and 0.830,respectively,at 12 months and 0.859 for both systems at 36 months.CLIP and ITA.LI.CA exhibited superior calibration,particularly at 36 months.The JIS system consistently showed the poorest discriminatory performance.Subgroup analyses revealed that HKLC maintained strong performance across different viral etiologies(HBV,HCV,non-B-non-C)and treatment modalities(transarterial chemoembolization,surgery,ablation).CONCLUSION The HKLC and BCLC systems showed superior prognostic performance for Vietnamese patients with HCC,supporting HKLC adoption in clinical practice.
基金supported by funding from the National Natural Science Foundation of China(U23A20243 and 32272972 to QZ,32172820 to SX)the Major Science and Technology Project of Gansu Province(22ZD6NA001 to SX)+1 种基金the Youth Innovation Program(Y2023QC30)the Agricultural Science and Technology Innovation Program(CAAS-ASTIP-JBGS-20210102 to SX)of the Chinese Academy of Agricultural Sciences.
文摘Influenza A viruses(IAVs)are single-stranded negative-sense RNA viruses that continually challenge animal and human health.In IAV-infected cells,host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA.Here,we examined the role of the host RNA-binding protein nucleophosmin-1(NPM1)in IAV replication.We found that,as a nucleolar phosphoprotein,NPM1 directly binds to viral RNA(vRNA)and inhibits the replication of various subtypes of IAV.NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity,thereby reducing the generation of progeny viral RNA and virions.The RNA-binding activity of NPM1,with the key residues T199,T219,T234,and T237,is essential for its anti-influenza function.Taken together,our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.
文摘Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instead integrate their genetic material into the host genome thus,affecting cell cycle and tumor suppression.This deregulation also leads to impaired immune function and promotes tumor progression by disrupting the removal of infected cells.Generally,innate immunity consists of two important members,including mitochondria and cell deaths,which impact each other as well.Due to the close correlation between viruses,cell death pathways(apoptosis,necroptosis,and pyroptosis),and mitochondria(mitochondrial antiviral-signaling protein and reactive oxygen species generation),targeting these immune system representatives may offer therapeutic strategies to control the progression of oncogenic viral infections.Some previous studies have covered the association of oncogenic viruses with mitochondria and cell death pathways,respectively,but mitochondria and cell death interact with each other,separately,and this interaction may play a role in the progression of cancer induced by oncogenic viruses.Hence,the purpose of this review is to discuss the relationship between cell death,mitochondria,and viral oncogenesis,focusing on the most surveyed oncogenic viruses’mechanisms of action.
基金supported by the National Natural Science Foundation of China(82372176,82272217,82002026,81971818)the Hubei Provincial Key Research and Development Program of China(2023BCB091)the National Key Research and Development Program of China(2021YFC2500802,2021YFC2300200).
文摘Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.
文摘Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients.This review examines the interaction between viral infections and SCD,highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population.Advances in antiviral therapies have significantly improved outcomes,yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions,altered pharmacokinetics,and the potential exacerbation of SCDrelated complications.Additionally,vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention.By focusing on both established and novel antiviral treatments,this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.
基金supported by the Henan Provincial Science and Technology Research Project(Grant No.242102110019)the National Natural Science Foundation of China(Grant No.31972672).
文摘Pseudorabies virus(PRV,SuidAlphaherpesvirus 1)causes substantial economic losses in swine production.Here,we report the development of DNA aptamers targeting the PRV glycoprotein D(gD)through an optimized SELEX protocol.After 15 selection cycles,Apt-gD-2 demonstrated nanomolar affinity(Kd=6.107±0.476 nM)and high specificity for gD,as validated by an enzyme-linked aptamer-sorbent assay(ELASA)and fluorescence microscopy.Molecular docking revealed hydrogen bonding as the key interaction mechanism.The developed ic-ELASA achieved 83.3%concordance with qPCR in clinical samples,supporting its utility for on-farm PRV surveillance.These findings highlight the potential of aptamer-based diagnostic methods for rapid,sensitive,and onsite detection of PRV,offering a promising tool for disease control in the swine industry.
基金supported by the National Natural Science Foundation of China (82272196 and 82272220)。
文摘BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A(MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of Mx A to distinguish viral from bacterial infections.METHODS: We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic(ROC) curve analysis were used to determine the diagnostic value of Mx A, either alone or in combination with C-reactive protein(CRP) or procalcitonin(PCT), in patients with viral, bacterial, or co-infections.RESULTS: The value of MxA(ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections(82.3 [24.5–182.9] vs. 16.4 [10.8–26.5], P<0.0001)(82.3 [24.5–182.9] vs. 28.5 [10.2–106.8], P=0.0237). The area under the curve(AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799(95% confidence interval [95% CI] 0.696–0.903), with a sensitivity of 68.9%(95% CI 54.3%–80.5%) and specificity of 90.0%(95% CI 74.4%–96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus(15.8 [9.6–47.6] ng/mL) and Epstein-Barr virus(12.9 [8.5–21.0] ng/mL) infections.CONCLUSION: Our study showed the diagnostic efficacy of Mx A in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, EpsteinBarr virus and human cytomegalovirus infections did not elicit elevated Mx A expression.
文摘A recent nationwide cohort study reported an increased incidence and altered seasonality of type 1 diabetes mellitus(T1DM)during the coronavirus disease 2019(COVID-19)pandemic.The study found that new-onset T1DM cases were significantly higher during the pandemic than in prior years,and the typical winter peak in T1DM diagnoses was blunted.This occurred alongside markedly reduced circulation of other respiratory viruses under lockdown measures.Carmon et al noted weak positive correlations between T1DM incidence and certain viruses(e.g.,influenza and respiratory syncytial virus),suggesting that reduced exposure to common infections-and possibly severe acute respiratory syndrome coronavirus 2 infection itself-might have contributed to the rise in T1DM.To highlight key methodological limitations of that study,which may affect the interpretation of the findings.We reviewed the study design and data of Carmon et al and discussed potential biases,including ecological inference,confounding factors,delayed diagnoses,lack of COVID-19-stratified analysis,and biases in viral surveillance data,supported by recent literature.The association observed by Carmon et al is at risk of ecological fallacy due to the absence of individual infection linkage.Uncontrolled confounders(healthcare access,socioeconomic changes)and not stratifying by COVID-19 infection status limit causal inference.Pandemic-related diagnostic delays likely inflated apparent T1DM incidence,as evidenced by higher rates of diabetic ketoacidosis in new cases.Biases in virological testing data(reduced testing and non-representative sampling)complicate conclusions about“reduced”viral circulation.The pandemic’s impact on T1DM incidence is important but requires cautious interpretation.Future studies should employ individual-level analyses,adjust for confounders,distinguish true incidence increases from diagnostic delays,stratify by infection status,and use comprehensive viral exposure data to draw more robust conclusions.
文摘There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmission are unknown.Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents.Air particles were collected from swine buildings using high-volume air samplers.Extracted DNA and RNA were used to perform specific RT-qPCR and qPCR and analyzed by highthroughput sequencing.Porcine astroviruses group 2 were common(from 102 to 105 genomic copies per cubic meter of air or gc/m^(3),93%positivity)while no norovirus genogroup II was recovered from air samples.Porcine torque teno sus virus were detected by qPCR in low concentrations(from 101 to 102 gc/m^(3),47%positivity).Among the identified viral families by metagenomics analysis,Herelleviridae,Microviridae,Myoviridae,Podoviridae,and Siphoviridae were dominant.The phage vB_AviM_AVP of Aerococcus was present in all air samples and a newly designed qPCR revealed between 101 and 105 gc/m^(3) among the samples taken for the present study(97%positivity)and banked samples from5-and 15-year old studies(89%positivity).According to the present study,both the porcine astrovirus group 2 and the phage vB_AviM_AVP of Aerococcus could be proxy for airborne viruses of swine buildings.
文摘Viral hepatitis,including hepatitis B and hepatitis C(HCV),remains a significant global health burden,leading to liver fibrosis,cirrhosis,and hepatocellular car-cinoma.Traditional diagnostic methods,while effective,often face limitations in accuracy,accessibility,and timeliness.Artificial intelligence(AI)has emerged as a transformative tool in healthcare,enhancing the detection,diagnosis,and treat-ment of viral hepatitis.This review explores the role of AI in viral hepatitis mana-gement,focusing on early detection through image analysis,digital pathology,and machine learning algorithms.AI-driven image analysis tools,such as con-volutional neural networks,have demonstrated high accuracy in detecting HCV-related liver lesions from computed tomography scans.Supervised learning models such as support vector machines and hybrid quantum neural networks further enhance early risk stratification.AI also facilitates personalized treatment by predicting treatment responses,accelerating drug discovery,and advancing precision medicine.Furthermore,AI contributes to epidemiological surveillance by predicting disease spread and tracking treatment adherence.Despite its po-tential,challenges such as data privacy,algorithmic bias,and regulatory comp-liance must be addressed to ensure equitable and effective AI implementation.Future directions include integrating AI into clinical workflows and expanding AI applications in low-resource settings.AI-assisted diagnosis and management have the potential to revolutionize viral hepatitis care,improving patient outcomes and reducing the global disease burden.
