Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

Biomarkers associated with immune-related adverse events induced by immune checkpoint inhibitors

Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irAEs),significantly affecting the efficacy and survival rates of patients undergoing ICI therapy.While conventional hematological and imaging tests are adept at detecting organ-specific toxicities,distinguishing adverse reactions from those induced by viruses,bacteria,or immune diseases remains a formidable challenge.Consequently,there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs.Thus,a thorough review of existing studies on irAEs biomarkers is indispensable.Our review commences by providing a succinct over-view of major irAEs,followed by a comprehensive summary of irAEs biomarkers across various dimensions.Furthermore,we delve into innovative methodologies such as machine learning,single-cell RNA sequencing,multiomics analysis,and gut microbiota profiling to identify novel,robust biomarkers that can facilitate precise irAEs diagnosis or prediction.Lastly,this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction,diagnosis,and treatment strategies.

Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma:A retrospective study

BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.AIM To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.METHODS From March 2019 to February 2021,a total of 190 unresectable HCC(Barcelona Clinic Liver Cancer C)patients receiving pembrolizumab treatment were retrospectively reviewed.Overall survival(OS)was the primary endpoint,while objective response rate(ORR),disease control rate(DCR),and time to progression(TTP)were secondary evaluation indexes.We assessed demographics,irAEs,and outcomes by retrospective review.RESULTS One hundred and forty-three males and 47 females were included in the study.The ORR and DCR were 12.1%(23/190)and 52.1%(99/190),respectively.The median OS was 376 d[95%confidence interval(CI):340-411 d]and the median TTP was 98 d(95%CI:75-124 d).The overall incidence of treatment-related adverse events was 72.6%(138/190)and 10.0%of them were severe irAEs(grade≥3).Child-Pugh B class,portal vein tumor thrombus,extrahepatic metastasis,and hypothyroidism were the independent risk factors for survival.Patients with hypothyroidism showed a longer OS[517 d(95%CI:423-562)vs 431 d(95%CI:412-485),P=0.011]and TTP[125 d(95%CI:89-154)vs 87 d(95%CI:61-98),P=0.004]than those without irAEs.CONCLUSION Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response.Hypothyroidism,an irAE,may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.

Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy

Lymphoma,which is highly malignant,stems from lymph nodes and lymphoid tissue.Lymphoma cells express programmed death-ligand 1/2(PD-L1/PD-L2),which binds with programmed cell death 1 protein(PD-1)to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance.Recently,immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors(nivolumab and pembrolizumab)have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients.Accordingly,the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually,which results in an increasing number of patients developing immune-related adverse events(irAEs).The occurrence of irAEs inevitably affects the benefits provided by immunotherapy,particularly when PD-1 inhibitors are applied.However,the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation.This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors.A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.

Projecting Spring Consecutive Rainfall Events in the Three Gorges Reservoir Based on Triple-Nested Dynamical Downscaling

Spring consecutive rainfall events(CREs) are key triggers of geological hazards in the Three Gorges Reservoir area(TGR), China. However, previous projections of CREs based on the direct outputs of global climate models(GCMs) are subject to considerable uncertainties, largely caused by their coarse resolution. This study applies a triple-nested WRF(Weather Research and Forecasting) model dynamical downscaling, driven by a GCM, MIROC6(Model for Interdisciplinary Research on Climate, version 6), to improve the historical simulation and reduce the uncertainties in the future projection of CREs in the TGR. Results indicate that WRF has better performances in reproducing the observed rainfall in terms of the daily probability distribution, monthly evolution and duration of rainfall events, demonstrating the ability of WRF in simulating CREs. Thus, the triple-nested WRF is applied to project the future changes of CREs under the middle-of-the-road and fossil-fueled development scenarios. It is indicated that light and moderate rainfall and the duration of continuous rainfall spells will decrease in the TGR, leading to a decrease in the frequency of CREs. Meanwhile, the duration, rainfall amount, and intensity of CREs is projected to regional increase in the central-west TGR. These results are inconsistent with the raw projection of MIROC6. Observational diagnosis implies that CREs are mainly contributed by the vertical moisture advection. Such a synoptic contribution is captured well by WRF, which is not the case in MIROC6,indicating larger uncertainties in the CREs projected by MIROC6.

Anthropogenic Influence on Decadal Changes in Concurrent Hot and Dry Events over China around the Mid-1990s

The frequency and duration of observed concurrent hot and dry events(HDEs) over China during the growing season(April–September) exhibit significant decadal changes across the mid-1990s. These changes are characterized by increases in HDE frequency and duration over most of China, with relatively large increases over southeastern China(SEC), northern China(NC), and northeastern China(NEC). The frequency of HDEs averaged over China in the present day(PD,1994–2011) is double that in the early period(EP, 1964–81);the duration of HDEs increases by 60%. Climate experiments with the Met Office Unified Model(MetUM-GOML2) are used to estimate the contributions of anthropogenic forcing to HDE decadal changes over China. Anthropogenic forcing changes can explain 60%–70% of the observed decadal changes,suggesting an important anthropogenic influence on HDE changes over China across the mid-1990s. Single-forcing experiments indicate that the increase in greenhouse gas(GHG) concentrations dominates the simulated decadal changes,increasing the frequency and duration of HDEs throughout China. The change in anthropogenic aerosol(AA) emissions significantly decreases the frequency and duration of HDEs over SEC and NC, but the magnitude of the decrease is much smaller than the increase induced by GHGs. The changes in HDEs in response to anthropogenic forcing are mainly due to the response of climatological mean surface air temperatures. The contributions from changes in variability and changes in climatological mean soil moisture and evapotranspiration are relatively small. The physical processes associated with the response of HDEs to GHG and AA changes are also revealed.

Prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

BACKGROUND Prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively studied.Therefore,this study aimed to establish a link between prediabetes and MACCE in AF patients.AIM To investigate a link between prediabetes and MACCE in AF patients.METHODS We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding diabetics.The primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related hospitalizations.RESULTS Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with prediabetes.The prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(P<0.001).The prediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all P<0.05).The prediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher costs.After adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,P<0.001].On subgroup analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This population-based study found a significant association between prediabetes and MACCE in AF patients.Therefore,there is a need for further research to actively screen and manage prediabetes in AF to prevent MACCE.

Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events:a prospective observational study

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy populations.However,the ability of retinal vasculature changes,specifically focusing on retinal vessel diameter,to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined comprehensively.While previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events,they have not incorporated this information into a predictive model.Therefore,this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic stroke.Additionally,we sought to establish a predictive model by combining retinal veessel diameter with traditional risk factors.We performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan University.All of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 years.We found that,after adjusting for related risk factors,patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin(MAD_(0.5-1.0DD))of≥74.14μm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin(MVD_(0.5-1.0DD))of≥83.91μm tended to experience recurrent cerebrovascular events.We established three multivariate Cox proportional hazard regression models:model 1 included traditional risk factors,model 2 added MAD_(0.5-1.0DD)to model 1,and model 3 added MVD0.5-1.0DD to model 1.Model 3 had the greatest potential to predict subsequent cerebrovascular events,followed by model 2,and finally model 1.These findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke,and that retinal imaging could be a useful and non-invasive method for identifying high-risk patients who require closer monitoring and more aggressive management.

Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019)

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases cardiovascular disease(CVD)risk irrespective of other risk factors.However,large-scale cardiovascular sex and race differences are poorly understood.AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events(MACCE)in subgroups using a nationally representative United States inpatient sample.METHODS We examined National Inpatient Sample(2019)to identify adult hospitalizations with NAFLD by age,sex,and race using ICD-10-CM codes.Clinical and demographic characteristics,comorbidities,and MACCE-related mortality,acute myocardial infarction(AMI),cardiac arrest,and stroke were compared in NAFLD cohorts by sex and race.Multivariable regression analyses were adjusted for sociodemographic characteristics,hospitalization features,and comorbidities.RESULTS We examined 409130 hospitalizations[median 55(IQR 43-66)years]with NFALD.NAFLD was more common in females(1.2%),Hispanics(2%),and Native Americans(1.9%)than whites.Females often reported non-elective admissions,Medicare enrolment,the median age of 55(IQR 42-67),and poor income.Females had higher obesity and uncomplicated diabetes but lower hypertension,hyperlipidemia,and complicated diabetes than males.Hispanics had a median age of 48(IQR 37-60),were Medicaid enrollees,and had non-elective admissions.Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia.MACCE,all-cause mortality,AMI,cardiac arrest,and stroke were all greater in elderly individuals(P<0.001).MACCE,AMI,and cardiac arrest were more common in men(P<0.001).Native Americans(aOR 1.64)and Asian Pacific Islanders(aOR 1.18)had higher all-cause death risks than whites.CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes;Native Americans and Asian Pacific Islanders face higher mortality,highlighting a need for tailored interventions and care.

Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

BACKGROUND Liver transplant(LT)patients have become older and sicker.The rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT mortality.Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.AIM To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.METHODS This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center.We developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning model.We addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each case.The modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac assessments.Model performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature impacts.The dataset was split into training(75%)and testing(25%)sets.Calibration was evaluated using the Brier score.We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting.Scikit-learn and SHAP in Python 3 were used for all analyses.The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.RESULTS Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 years.The majority,66.1%,were male.The XGBoost model achieved an impressive AUROC of 0.89 during the training stage.This model exhibited accuracy,precision,recall,and F1-score values of 0.84,0.85,0.80,and 0.79,respectively.Calibration,as assessed by the Brier score,indicated excellent model calibration with a score of 0.07.Furthermore,SHAP values highlighted the significance of certain variables in predicting postoperative MACE,with negative noninvasive cardiac stress testing,use of nonselective beta-blockers,direct bilirubin levels,blood type O,and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level.These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE,making it a valuable tool for clinical practice.CONCLUSION Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE,using both cardiovascular and hepatic variables.The model demonstrated impressive performance,aligning with literature findings,and exhibited excellent calibration.Notably,our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data,reinforcing the model’s value as a reliable tool for predicting post-LT MACE in clinical practice.

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei

Pseudomyxoma peritonei(PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy(CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit(GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radioimmunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

Grassland-type ecosystem stability in China differs under the influence of drought and wet events

Ecological stability is a core issue in ecological research and holds significant implications forhumanity. The increased frequency and intensity of drought and wet climate events resulting from climatechange pose a major threat to global ecological stability. Variations in stability among different ecosystemshave been confirmed, but it remains unclear whether there are differences in stability within the sameterrestrial vegetation ecosystem under the influence of climate events in different directions and intensities.China's grassland ecosystem includes most grassland types and is a good choice for studying this issue.This study used the Standardized Precipitation Evapotranspiration Index-12 (SPEI-12) to identify thedirections and intensities of different types of climate events, and based on Normalized DifferenceVegetation Index (NDVI), calculated the resistance and resilience of different grassland types for 30consecutive years from 1990 to 2019 (resistance and resilience are important indicators to measurestability). Based on a traditional regression model, standardized methods were integrated to analyze theimpacts of the intensity and duration of drought and wet events on vegetation stability. The resultsshowed that meadow steppe exhibited the highest stability, while alpine steppe and desert steppe had thelowest overall stability. The stability of typical steppe, alpine meadow, temperate meadow was at anintermediate level. Regarding the impact of the duration and intensity of climate events on vegetationecosystem stability for the same grassland type, the resilience of desert steppe during drought was mainlyaffected by the duration. In contrast, the impact of intensity was not significant. However, alpine steppewas mainly affected by intensity in wet environments, and duration had no significant impact. Ourconclusions can provide decision support for the future grassland ecosystem governance.

Immune-related gene characteristics:A new chapter in precision treatment of gastric cancer

Gastric cancer ranks as the sixth most prevalent cancer worldwide.In recent research within the realm of gastric cancer treatment,the identification and application of immune-related genetic features have emerged as groundbreaking advancements.The study by Ma et al,which developed a prognostic model based on 10 genes,categorizes patients into high and low-risk groups to predict their responsiveness to immune checkpoint inhibitor therapy.This research underscores the potential of immune-related genes as biomarkers for personalized treatment,offering insights into tumor mutation burden and immune phenotype scores.We advocate for further validation,understanding of biological mechanisms,and integration of diverse datasets to enhance the model's predictive accuracy and clinical application,marking a significant step towards personalized and precise treatment for gastric cancer.

Predictive Effect of CA125 on Adverse Cardiovascular Events in Patients with Chronic Heart Failure

Objective: To study the expression of CA125 in the serum of patients with CHF and the relationship between CA125 level and the occurrence of adverse cardiovascular events. Methods: The clinical data of 132 patients with CHF admitted to Shizuishan Second People’s Hospital from January 2023 to December 2023 were collected and divided into heart function II group, heart function III group, heart function IV group according to cardiac function. 44 healthy subjects who underwent physical examination during the same period were selected as the control group. The clinical data of CA125, NT-proBNP, echocardiography and other clinical data of the four groups were compared, and the incidence of major adverse cardiovascular events was followed up for 12 months. Results: Compared with the control group, the CA125 level in the CHF group was significantly increased (P Conclusion: Serum CA125 level is related to the cardiac function level in CHF patients and increases with the deterioration of cardiac function. The increase of the index is related to the mortality rate and re-hospitalization rate, suggesting that CA125 can be used as an indicator to reflect the severity of heart failure and prognosis monitoring.

Potential morphological responses of an artificial beach to a flood in extreme events: field observation and numerical modelling

Conch Island is a typical artificial island at the Tanghe Estuary in Bohai Sea,China.To improve natural environment and boost local tourism,beach nourishment will be applied to its north-western shore.The projected beach is landward and opposite to the Jinmeng Bay Beach.Nowadays,with climate changes,frequent heavy rainfalls in Hebei Province rise flood hazards at the Tanghe Estuary.Under this circumstance,potential influences on the projected beach of a flood are investigated for sustainable managements.A multi-coupled model is established and based on the data from field observations,where wave model,flow model and multifraction sediment transport model are included.In addition,the impacts on the projected beach of different components in extreme events are discussed,including the spring tides,storm winds,storm waves,and sediment inputs.The numerical results indicate the following result.(1)Artificial islands protect the coasts from erosion by obstructing landward waves,but rise the deposition risks along the target shore.(2)Flood brings massive sediment inputs and leads to scours at the estuary,but the currents with high sediment concentration contribute to the accretions along the target shore.(3)The projected beach mitigates flood actions and reduces the maximum mean sediment concentration along the target shore by 20%.(4)The storm winds restrict the flood and decrease the maximum mean sediment concentration by 21%.With the combined actions of storm winds and waves,the maximum value further declines by 38%.(5)A quadratic polynomial relationship between the deposition depths and the maximum sediment inputs with flood is established for estimations on the potential morphological changes after the flood process in extreme events.For the uncertainty of estuarine floods,continuous monitoring on local hydrodynamic variations and sediment characteristics at Tanghe Estuary is necessary.

Adverse Events following AstraZeneca COVID-19 Vaccination: A Case Study in Abidjan, Côte d’Ivoire

Introduction: Pharmaceutical companies have boosted vaccine production following the global COVID-19 pandemic. In Côte d’Ivoire, the first vaccination campaign with the AstraZeneca vaccine began on March 1, 2021, as part of the Covax program. Despite the positive benefit/risk balance, the adverse effects of vaccination should not be minimized. Objective: To identify adverse events of AstraZeneca’s COVID-19 vaccination for better management. Materials and Methods: This is a case of a 57-year-old obese (BMI = 39 kg/m2) female health care worker who experienced adverse events in March 2021 after the second dose of AstraZeneca vaccine administered 4 weeks apart. These were subject to mandatory case reporting. Results: Major post-vaccination events occurred in a noisy systemic picture with parameters showing significant disturbances. Biological surveillance remains costly and makes the accountability of the vaccine complex. Conclusion: Vaccination remains the ultimate weapon in the fight against endemic diseases but should not overshadow the reporting of adverse events.

Evaluation of the Impact of Driver Behavior on Back of Queues Events in Work Zones Using the SHRP2 Naturalistic Driving Study Data

The SHRP2 Naturalistic Driving Study was used to evaluate the impact of various work zone and driver characteristics on back of queue safety critical events (crash, near-crash, or conflicts) The model included 43 SCE and 209 “normal” events which were used as controls. The traces included representing 209 unique drivers. A Mixed-Effects Logistic Regression model was developed with probability of a SCE as the response variable and driver and work zone characteristics as predictor variables. The final model indicated glances over 1 second away from the driving task and following closely increased risk of an SCE by 3.8 times and 2.9 times, respectively. Average speed was negatively correlated to crash risk. This is counterintuitive since in most cases, it is expected that higher speeds are related to back of queue crashes. However, most queues form under congested conditions. As a result, vehicles encountering a back of queue would be more likely to be traveling at lower speeds.

Prothrombotic state and thrombotic events in COVID-19 pandemic period,including portal vein and splenic artery thromboses

This editorial article is intended to perform a discussion on the manuscript entitled“Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient:A case report and review of literature”written by Abramowitz et al.The article focuses on the diagnostic processes in a 77-year-old-male patient with a simultaneous portal vein and splenic artery thrombosis accompanying coronavirus disease 2019(COVID-19).The authors postulated that splanchnic thrombosis should be on the list of differential diagnoses in a patient presenting with abdominal pain in presence of a COVID-19 infection.The tendency for venous and arterial thrombosis in COVID-19 patients is encountered,largely attributed to hypercoagulopathy.In general,venous thromboembolism mostly manifest as deep vein thrombosis(DVT),pulmonary embolism(PE)or catheterrelated thromboembolic events.Acute PE,DVT,cerebrovascular events and myocardial infarction are seen as the most common thromboembolic complications in COVID-19 patients.COVID-19-associated hemostatic abnormalities include mild thrombocytopenia and increased D-dimer level.Similar to other coagulopathies,the treatment of the underlying condition is the mainstay.Addition of antiplatelet agents can be considered in critically ill patients at low bleeding risk,not on therapeutic anticoagulation,and receiving gastric acid suppression Early administration of antithrombotic drugs will have a beneficial effect in both the prevention and treatment of thrombotic events,especially in non-ambulatory patients.Low molecular weight heparin(LMWH)should be started if there is no contraindication,including in non-critical patients who are at risk of hospitalization LMWH(enoxaparin)is preferred to standard heparin.

Characteristics and Mechanisms of Persistent Wet–Cold Events with Different Cold-air Paths in South China

We investigate the characteristics and mechanisms of persistent wet–cold events(PWCEs)with different types of coldair paths.Results show that the cumulative single-station frequency of the PWCEs in the western part of South China is higher than that in the eastern part.The pattern of single-station frequency of the PWCEs are“Yangtze River(YR)uniform”and“east–west inverse”.The YR uniform pattern is the dominant mode,so we focus on this pattern.The cold-air paths for PWCEs of the YR uniform pattern are divided into three types—namely,the west,northwest and north types—among which the west type accounts for the largest proportion.The differences in atmospheric circulation of the PWCEs under the three types of paths are obvious.The thermal inversion layer in the lower troposphere is favorable for precipitation during the PWCEs.The positive water vapor budget for the three types of PWCEs mainly appears at the southern boundary.