Subsequent Events Research Articles

Integrating Relational Knowledge With Text Sequences for Script Event Prediction.

Script event prediction aims to infer subsequent events given an incomplete script. It requires a deep understanding of events, and can provide support for a variety of tasks. Existing models rarely consider the relational knowledge between events, they regard scripts as sequences or graphs, which cannot capture the relational information between events and the semantic information of script sequences jointly. To address this issue, we propose a new script form, relational event chain, that combines event chains and relational graphs. We also introduce a new model, relational-transformer, to learn embeddings based on this new script form. In particular, we first extract the relationship between events from an event knowledge graph to formalize scripts as relational event chains, then use the relational-transformer to calculate the likelihood of different candidate events, where the model learns event embeddings that encode both semantic and relational knowledge by combining transformers and graph neural networks (GNNs). Experimental results on both one-step inference and multistep inference tasks show that our model can outperform existing baselines, indicating the validity of encoding relational knowledge into event embeddings. The influence of using different model structures and different types of relational knowledge is analyzed as well.

Complete revascularization based on angiography derived fractional flow reserve versus incomplete revascularization in patients with ST-segment elevation myocardial infarction.

Nearly half of ST-segment elevation myocardial infarction (STEMI) patients present with significant multivessel coronary artery disease, they are at high risk of subsequent adverse events. Whether complete revascularization guided by coronary angiography-derived fractional flow reserve (caFFR) further reduces such events risk is not fully investigated. In this study, 367 consecutive STEMI patients who underwent successful primary percutaneous coronary intervention (PCI) were enrolled. caFFR of all three coronary vessels were measured, including 367 culprit vessels and 703 non-culprit vessels. Complete revascularization was defined as post-PCI caFFR > 0.8 of all three coronary vessels. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal recurrent myocardial infarction, ischemia-driven revascularization and non-fatal stroke/transient ischemic attacks) during follow-up. At a median follow-up of 3.8 years, MACE had occurred in 39 patients of the 220 (17.7%) in the complete revascularization group as compared with 49 patients of the 131 (37.4%) in the incomplete revascularization group (hazard ratio [HR] 1.9; 95% confidence interval [CI] 1.2-3.0; p = 0.005). The incomplete revascularization in culprit vessels evaluated by caFFR showed the highest risk for MACE occurrence. In STEMI patients with multivessel coronary artery disease, incomplete revascularization based on caFFR might contribute to identifying patients at high-risk.

Could persistent organic pollutants affect future generations of sea turtles by maternal transfer? First results for Caretta caretta nests along the North-Western coast of Italy

Since 2013, loggerhead sea turtle (Caretta caretta, Linnaeus 1758) nesting has been observed further north along the Italian coast, reaching the Tuscan coast (NW Mediterranean Sea). The four nesting events that occurred in Tuscany in the summer of 2019 spurred the scientific community to monitor these occurrences more carefully, following them from egg deposition to hatching. This provided an opportunity to collect samples for conducting multidisciplinary investigations, including the toxicological investigations of the biological material collected from the four nests. The aim of this study was to conduct an initial assessment of persistent organic pollutants in the eggs laid in Tuscany, aiming to establish a baseline on this topic for subsequent nesting events that have occurred until today. Organochlorine compounds (OCs), specifically polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and its metabolites, and hexachlorobenzene (HCB), were analyzed and detected in unhatched eggs, embryos, and chorio-allantoic membranes (CAMs). OCs were detected in all samples, with PCBs > DDTs ≫ HCB. A significant spatial variation in pollutant levels and profiles among sea turtle nesting locations was found. Embryos showed higher levels of contamination than egg contents regardless of the developmental stages. Depth of the laying chamber and egg mass were not significant factors in OC bioaccumulation. For the first time in the Mediterranean Sea, this study assessed the role of CAM in the transfer of contaminants to the embryo. Overall, the OC levels found were lower compared to the results from other studies conducted worldwide on loggerhead sea turtle biological material. This was the first assessment of nest biological material for the North-Western coast of Italy.

Новая коронавирусная инфекция (COVID-19) и нозологическая структура больных ревматологического отделения. Взгляд из региона

Based on the analysis of 670 archival patients' case histories of the disease, patients discharges in 2021 from the rheumatological department (there are excluded cases of repeated short-term hospitalizations in order to conduct supporting therapy of genetically engineering biological drugs), the question of the connection of rheumatic pathology with coronaviral infection and its influence on the formation of the characteristics of clinical clinicals forms of this pathology. Coronavirus infection, which occurred in the period of 6 months before hospitalization, is registered in every tenth (76–11.3 %). Three groups are highlighted: I. Patients with the diagnosis of Covid diagnosed/verified in the department and who later transferred to the specialized infectious department – 18 people (2.7 %). II. Patients who have clinical features of the disease can be interpreted as part of the so -called post-covid syndrome – 35 people (5.2 %). A clear chronological relationship of post-covid asthenia and other symptoms with subsequent (after 4 weeks) events make the role of the virus in the induction of this pathology undoubted. III. Patients with a previously established rheumatic diagnosis, and the exacerbation of a previously diagnosed disease was undoubtedly induced by coronavirus infection – 23 people (3.4 %) among those patients. The relationship of the development and exacerbation of chronic rheumatic pathology with coronavirus is actually much more often than the numbers cited in this study, but many cases of light infection were not recorded as COVID. Post-covid syndromes in rheumatology, developing at different times from the beginning of the infection, from the so called long-covid is up to six months, have a wide range of clinical manifestations. It can be assumed that the most characteristic feature of patients with post-covid syndromes who find themselves in the hospital is their uncertainty in terms of specification of the nosological form. It is significant that in 80 % of patients in whom the clinical features can be considered as part of the post-covid syndrome, such “transitional” diagnoses as inflammatory arthropathy, undifferentiated or mixed connective tissue syndrome, RS3PE syndrome and others, and only less than a smaller part of the patients examined had more outlined signs of a specific rheumatic disease.

Impact of post-procedure stenosis on outcomes of patients with severe intracranial stenosis treated with intracranial stent placement

BackgroundThe optimal target post-procedure stenosis after percutaneous angioplasty and stent placement (PTAS) for intracranial stenosis is unknown. We determined the effect of post-procedure stenosis after intracranial PTAS on subsequent clinical...

Elevated factor XI is associated with recurrent left ventricular thrombus of unknown origin.

Elevated factor XI (FXI) has been shown to predispose to thromboembolism. We investigated whether it is associated with left ventricular thrombus (LVT) formation, its recurrence and subsequent thromboembolic events. In 54 patients with prior LVT of unknown origin, who stopped anticoagulation and 54 controls, we determined FXI, along with plasma clot permeability (Ks), fibrinolysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (vWF) and fibrinolysis proteins. During follow-up, the primary endpoint involving the recurrence of LVT a symptomatic ischemic stroke or systemic embolism was recorded. Elevated (>120%) FXI levels were more often observed in LVT patients when compared to the control group (14 [25.9%] vs. 6 [11.1%], p = .048) in association with the presence of active FXI. FXI correlated with age (r = .406, p = .002), Ks (r = -.542, p < .001) and CLT (r = .406, p = .002), also after adjustment for age, but not with ETP, vWF or fibrinolysis proteins. During follow-up of 77.6 ± 18.5 months the primary endpoint occurred in 17 (31.5%) LVT patients, including 11 (20.4%) recurrent LVT, and in 4 (7.4%) controls (annual incidence rate 4.9% vs. 1.1%, respectively; p = .002). On multivariate logistic regression analysis, elevated FXI was independently associated with the primary endpoint (OR 1.18; 95% CI 1.09-1.28). Elevated FXI in association with a prothrombotic state characterizes patients with prior LVT of unknown origin and predisposes to its recurrence and/or ischemic stroke during follow-up. It might be speculated that the measurement of FXI helps identify patients who could benefit from prolonged anticoagulation and FXI inhibitors in the future.

Disruption of gonadotropin hormone biosynthesis by parabens: A potential development and reproduction-associated adverse outcome pathway

Parabens are widely used as antibacterial preservatives in foods and personal care products. The knowledge about the modes of toxic action of parabens on development and reproduction remain very limited. The present study attempted to establish a development and reproduction-associated adverse outcome pathway (AOP) by evaluating the effects of methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) on the biosynthesis of gonadotropins, which are key hormones for development and reproduction. MP and BP significantly upregulated the mRNA and protein levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in pituitary gonadotropic cells in a concentration-dependent manner. Activation of gonadotropin-releasing hormone receptor (GnRHR) was required for gonadotropin biosynthesis induced by BP, but not MP. Molecular docking data further demonstrated the higher binding efficiency of BP to human GnRHR than that of MP, suggesting GnRHR as a potential molecular initiative event (MIE) for BP-induced gonadotropin production. L-type voltage-gated calcium channels (VGCCs) were found to be another candidate for MIE in gonadotropic cells response to both MP and BP exposure. The calcium-dependent activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2 was subsequently required for MP- and BP-induced activation of GnRHR and L-type VGCCs pathways. In summary, MP and BP promoted gonadotropin biosynthesis through their interactions with cellular macromolecules GnRHR, L-type VGCCs, and subsequent key event ERK1/2. This is the first study to report the direct interference of parabens with gonadotropin biosynthesis and establish a potential AOP based on pathway-specific mechanism, which contributes to the effective screening of environmental chemicals with developmental and reproductive health risks.

Estimation and reduction of bias in self-controlled case series with non-rare event dependent outcomes and heterogeneous populations.

The self-controlled case series (SCCS) is a commonly adopted study design in the assessment of vaccine and drug safety. Recurrent event data collected from SCCS studies are typically analyzed using the conditional Poisson model which assumes event times are independent within-cases. This assumption is violated in the presence of event dependence, where the occurrence of an event influences the probability and timing of subsequent events. When event dependence is suspected in an SCCS study, the standard recommendation is to include only the first event from each case in the analysis. However, first event analysis can still yield biased estimates of the exposure relative incidence if the outcome event is not rare. We first demonstrate that the bias in first event analysis can be even higher than previously assumed when subpopulations with different baseline incidence rates are present and describe an improved method for estimating this bias. Subsequently, we propose a novel partitioned analysis method and demonstrate how it can reduce this bias. We provide a recommendation to guide the number of partitions to use with the partitioned analysis, illustrate this recommendation with an example SCCS study of the association between beta-blockers and acute myocardial infarction, and compare the partitioned analysis against other SCCS analysis methods by simulation.

San Albino, Nicaragua: A Low-Angle, Thrust-Controlled Orogenic Gold Deposit

Abstract The San Albino deposit is an orogenic gold occurrence hosted by a low-angle thrust that is the site of a new open-pit mine in northern Nicaragua. The deposit is hosted in greenschist facies rocks of the Jurassic metasedimentary Neuvo Segovia Formation. The schist was uplifted and exposed during arc accretion and Cretaceous thin-skin deformation, forming the NE-striking Colon fold-and-thrust belt. Deformation included emplacement of the 119 to 113 Ma NE-trending Dipilto batholith into the regionally metamorphosed clastic rocks about 5 km northwest of the San Albino deposit. Mineralization is dominated by three laminated quartz vein systems (i.e., San Albino, Naranjo, Arras) that broadly follow shallowly dipping (approx. 30°) carbonaceous shears roughly concordant to schistosity along the limbs of a doubly plunging antiform. The three main parallel shears are each separated by about 90 m and individually reach a maximum thickness of about 8 m. Maximum thickness of ore zones is where post-ore local folding and reverse motion along the shallow shears has duplicated the laminated low-angle gold-bearing veins (D2 and early D3). Additional gold was added to the veins, with abundant sulfides, during a subsequent brecciation event of the early formed quartz veins that accompanied progressive thrusting (late D3). This predated boudinage of the veins during continued compression and thrust loading (D4); high gold grades are particularly notable along pyrite- and arsenopyrite-bearing stylolites formed during D4 pressure solution. The D2 to D3 gold event is likely coeval with Albian uplift of the Dipilto batholith and with back thrusting in the schist aided by the stress inhomogeneities provided by the igneous complex. Low-angle thrust-controlled orogenic gold deposits may represent world-class exploration targets because of their large linear footprints, although they are traditionally looked at as less favorable exploration targets relative to gold systems developed more commonly along high-angle reverse faults. Our case study of the San Albino deposit shows that although low-angle deposits are not inherently misoriented for failure like the more common subvertical reverse fault-related deposits, they may be sites of significant pressure buildup due to hydrothermal mineral precipitation during initial water-rock interaction or slight temperature decreases along the low-angle flow path. Resulting fluid cycling may lead to thick laminated vein development, such as seen at San Albino, where especially high-grade zones may be associated with local steepening and/or dilational zones within the broader, low-angle vein-hosting shear system.

Cost-Effectiveness Analysis of Denosumab in the Prevention of Skeletal-Related Events Among Patients With Breast Cancer With Bone Metastasis in India.

Denosumab is clinically superior to zoledronic acid (ZA) for preventing and delaying time to first and subsequent skeletal-related events (SREs) among patients with breast cancer (BC) with bone metastases. We evaluated the cost and health benefits of denosumab and ZA (once every 4 weeks and once every 12 weeks) among four different molecular subtypes of BC with bone metastases in India. A Markov model was developed in Microsoft Excel to estimate lifetime health consequences and resulting costs among cohort of 1,000 patients with BC with bone metastasis, for three intervention scenarios, namely denosumab (once every 4 weeks), ZA (once every 4 weeks), and ZA (once every 12 weeks). The health outcomes were measured in terms of SREs averted and quality-adjusted life-years (QALYs) gained. The cost of each intervention scenario was measured using both the health system and the patient's perspectives. Indirect costs because of lost productivity were not included. The future costs and outcomes were discounted at the standard rate of 3%. Over a lifetime, the incremental number of SREs averted with use of denosumab once every 4 weeks (compared with ZA once every 4 weeks and once every 12 weeks) among patients with luminal A, luminal B, human epidermal growth factor receptor 2-enriched, and triple negative breast cancer were estimated as 0.39, 0.26, 0.25, and 0.19, respectively. The number of QALYs lived were slightly higher in the denosumab arm (1.45-2.80) compared with ZA once every 4 weeks and once every 12 weeks arms (1.44-2.78). However, denosumab once every 4 weeks was not found to be a cost-effective alternative for either of the four molecular subtypes of breast cancer. ZA once every 12 weeks was found to be a cost-effective option with an average cost-effectiveness ratio ranging between ₹68,254 and ₹73,636. ZA once every 12 weeks is the cost-effective treatment option for BC with bone metastases in India. The present study findings hold significance for standard treatment guidelines under India's government-funded health insurance program.

Galactoseismology in cosmological simulations

Context. Complex models recently became available for studying the dynamics of disk galaxies such as the Milky Way (MW). These models include the global dynamics from dwarf satellite galaxies, dark matter halo structure, gas infall, and stellar disks in a cosmological context. Aims. We use a MW model from a suite of high-resolution hydrodynamical cosmological simulations named GARROTXA to establish the relationship between the vertical disturbances seen in its galactic disk and multiple perturbations from the dark matter halo, satellites, and gas. Methods. We calculated the bending modes in the galactic disk in the last 6 Gyr of evolution. We computed the vertical acceleration exerted by dark matter and gas in order to quantify the impact of these components on the disk, and compared this with the bending behavior with Fourier analysis. Results. We find complex bending patterns at different radii and times, such as an inner retrograde mode with high frequency and an outer slower retrograde mode excited at different times. The amplitudes of these bending modes are highest during the early stages of formation of the thin disk (20 km s−1) and reach up to 8.5 km s−1 in the late disk evolution. We find that the infall of satellite galaxies leads to a tilt of the disk, and produces strong anisotropic gas accretion with a misalignment of 8° with subsequent star formation events and supernovae, creating significant vertical accelerations on the disk plane. The misalignment between the disk and the inner stellar and dark matter triaxial structure, which formed during the ancient assembly of the galaxy, also leads to a strong vertical acceleration of the stars. We also find dark matter subhalos that temporally coincide with the appearance of bending waves in certain periods. Conclusions. We conclude that several agents trigger the bending of the stellar disk and its phase spirals in this simulation, including satellite galaxies, dark subhalos, misaligned gaseous structures, and the inner dark matter profile. These phenomena coexist and influence each other, sometimes making it challenging to establish direct causality.

Setting S&T perspective priorities in an era of complexity and uncertainty: a case for megacities

PurposeThe purpose of this study is to create a methodological approach for identifying priority areas for science and technology (S&T) development and its empirical application within the city of Moscow. This research uncovers a wide range of multicultural and multidisciplinary global trends that will affect the development of major cities in an era of complexity and uncertainty, including the inherent complexity of urban contexts, demographic and socioeconomic trends, as well as scientific and ecological factors.Design/methodology/approachThe methodological approach is based on classic foresight instruments. Its novelty lays in the blending of qualitative and quantitative methods specially selected as the most appropriate for the identification of S&T areas in an era of complexity and uncertainty, including horizon scanning, bibliometric analysis, expert surveys and the construction of composite indexes with respect to the scope and resources of the research and the selected object for empirical application – Moscow, which is one of the world’s largest megacities. The analysis was performed for the period of 2009–2018 and expert procedures took place in 2019.FindingsAs a result, 25 global trends were identified, evaluated and discussed over the course of an expert survey and subsequent expert events. Ten priority areas of S&T development were determined, including 62 technological sub-areas within them and the most important market niches for all identified technological sub-areas, which could be useful for the world’s megacities. The results of this study are illustrated using the construction sector. Based on the conducted research and results, a list of recommendations on S&T policy measures and instruments were suggested, including the creation of the Moscow Innovation Cluster, which by the end of 2023 contained more than 6,000 projects and initiatives, selected using the findings of this investigation.Originality/valueThis research contributes to the existing literature and research agenda of setting priorities for S&T development and shows how it can be done for a megacity. The blended foresight methodology that was created within the study satisfies the criteria of scientific originality, is repeatable for any interested researcher, is applicable to any other city in the world and demonstrates its high efficiency in empirical application. It could be used for creating new agenda items in S&T policy, setting S&T priorities for a megacity and integrating the results into decision-making processes. This study provides recommendations on the further implementation of the designed methodology and results into a policymaking system. Moreover, the example of the Moscow Innovation Cluster, which was created based on the results of our research, demonstrates these recommendations’ practical significance in real life, which is quite valuable. The limitation of this study is that it is not devoted to urban planning issues directly or the promotion of R&D areas; it is about setting promising S&T priorities in an era of complexity and uncertainty for megacities.

Sex Differences in the Relationship Between Schizophrenia and the Development of Cardiovascular Disease.

There are few data on sex differences in the association between schizophrenia and the development of cardiovascular disease (CVD). We sought to clarify the relationship of schizophrenia with the risk of developing CVDs and to explore the potential modification effect of sex differences. We conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4 124 508 individuals aged 18 to 75 years without a history of CVD or renal replacement therapy. The primary end point is defined as a composite end point that includes myocardial infarction, angina pectoris, stroke, heart failure, atrial fibrillation, and pulmonary thromboembolism. During a mean follow-up of 1288±1001 days, we observed 182 158 composite end points. We found a significant relationship of schizophrenia with a greater risk of developing composite CVD events in both men and women, with a stronger association observed in women. The hazard ratio for the composite end point was 1.63 (95% CI, 1.52-1.74) in women and 1.42 (95% CI, 1.33-1.52) in men after multivariable adjustment (P for interaction=0.0049). This sex-specific difference in the association between schizophrenia and incident CVD was consistent for angina pectoris, heart failure, and atrial fibrillation. Our analysis using a large-scale epidemiologic cohort demonstrated that the association between schizophrenia and subsequent CVD events was more pronounced in women than in men, suggesting the clinical importance of addressing schizophrenia and tailoring the CVD prevention strategy based on sex-specific factors.

In Utero Exposure to Antibiotics and Risk of Serious Infections in the First Year of Life.

Given the high prevalence of antibiotic prescription during pregnancy in France and previous studies suggesting an increased risk of infection in offspring with such exposures, our study aimed to investigate the association between prenatal exposure to systemic antibiotics and serious infections in full-term infants during their first year of life. We conducted a retrospective population-based cohort study on singleton, full-term liveborn non-immunocompromised infants, using the French National Health Data System (SNDS) between 2012 and 2021. Systemic antibiotic dispensing in ambulatory care settings during pregnancy defined the exposure. Outcomes concerned serious infections (i.e., infections requiring hospitalization) in offspring identified between 3 and 12 months of life, hence excluding infections of maternal origin. Adjusted odds ratios (aORs) were estimated using logistic regression with multivariate models to control for potential confounders. Of 2,836,630 infants included, 39.6% were prenatally exposed to systemic antibiotics. Infants prenatally exposed to antibiotics had a higher incidence of serious infections compared with unexposed infants {aOR 1.12 [95% confidence interval (95% CI) 1.11-1.13]}. Similar associations were observed according to the timing of exposure during pregnancy, antibiotic class, and site of infections. The strongest association was observed when infants were prenatally exposed to three or more antibiotic courses during pregnancy [aOR 1.21 (95% CI 1.19-1.24)]. Limitations include residual confounders, such as genetic susceptibility to infections and the role of the underlying pathogen agent. Prenatal exposure to systemic antibiotics is very common and is associated with a weak yet significant associations with subsequent serious infectious events during the first year of life. While our study revealed associations, it is important to note that causation cannot be established, given the acknowledged limitations, including potential confounding by indication.

Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Associations between air pollution and the risk of first admission and multiple readmissions for cardiovascular diseases

ObjectivesWe aimed to investigate the associations between air pollutants and the risk of admission and multiple readmission events for cardiovascular disease (CVD).MethodsA total of 285 009 participants free of CVD...

Microvascular rarefaction caused by the NOTCH signaling pathway is a key cause of TKI-apatinib-induced hypertension and cardiac damage.

With the advancement of tumour-targeted therapy technology, the survival of cancer patients has continued to increase, and cardiovascular events have gradually become an important cause of death in cancer patients. This phenomenon occurs due to adverse cardiovascular reactions caused by the cardiovascular toxicity of antitumour therapy. Moreover, the increase in the proportion of elderly patients with cancer and cardiovascular diseases is due to the extension of life expectancy. Hypertension is the most common cardiovascular side effect of small molecule tyrosine kinase inhibitors (TKIs). The increase in blood pressure induced by TKIs and subsequent cardiovascular complications and events affect the survival and quality of life of patients and partly offset the benefits of antitumour therapy. Many studies have confirmed that in the pathogenesis of hypertension, arterioles and capillary thinness are involved in its occurrence and development. Our previous findings showing that apatinib causes microcirculation rarefaction of the superior mesenteric artery and impaired microvascular growth may inspire new therapeutic strategies for treating hypertension. Thus, by restoring microvascular development and branching patterns, total peripheral resistance and blood pressure are reduced. Therefore, exploring the key molecular targets of TKIs that inhibit the expression of angiogenic factors and elucidating the specific molecular mechanism involved are key scientific avenues for effectively promoting endothelial cell angiogenesis and achieving accurate repair of microcirculation injury in hypertension patients.

Advances in risk predictive performance of pre-symptomatic type 1 diabetes via the multiplex Antibody-Detection-by-Agglutination-PCR assay.

Achieving early diagnosis of pre-symptomatic type 1 diabetes is critical to reduce potentially life-threatening diabetic ketoacidosis (DKA) at symptom onset, link patients to FDA approved therapeutics that can delay disease progression and support novel interventional drugs development. The presence of two or more islet autoantibodies in pre-symptomatic type 1 diabetes patients indicates high-risk of progression to clinical manifestation. Herein, we characterized the capability of multiplex ADAP assay to predict type 1 diabetes progression. We obtained retrospective coded sera from a cohort of 48 progressors and 44 non-progressors from the NIDDK DPT-1 study. The multiplex ADAP assay and radiobinding assays had positive predictive value (PPV)/negative predictive value (NPV) of 68%/92% and 67%/66% respectively. The improved NPV stemmed from 12 progressors tested positive for multiple islet autoantibodies by multiplex ADAP assay but not by RBA. Furthermore, 6 out of these 12 patients tested positive for multiple islet autoantibodies by RBA in subsequent sampling events with a median delay of 2.8 years compared to multiplex ADAP assay. In summary, multiplex ADAP assay could be an ideal tool for type 1 diabetes risk testing due to its sample-sparing nature (4µL), non-radioactiveness, compatibility with widely available real-time qPCR instruments and favorable risk prediction capability.

COVID-19-related accounting disclosures in the financial statements: evidence from an emerging economy

PurposeThis study aims to explore COVID-19-related accounting disclosures using sociological disclosure analysis (SDA) within the context of the developing economy of Bangladesh.Design/methodology/approachCOVID-19-related accounting disclosures from listed banks’ annual reports have been examined using three levels of SDA: textual, contextual and sociological interpretations. Data were gathered from the banks’ 2019 and 2020 annual reports. The study uses the legitimacy theory as its theoretical framework.FindingsThe research reveals a substantial shift in corporate disclosures due to COVID-19, marked by a significant increase from 2019 to 2020. Despite regulatory and professional directives for COVID-19-specific disclosures, notable non-compliance is evident in subsequent events, going concern, fair value, financial instruments and more. Instead of assessing the implications of COVID-19 and making disclosures, companies used positive, vague and subjective wording to legitimize non-disclosure.Practical implicationsThe study’s insights can inform regulators and policymakers in crafting effective guidelines for future crisis-related reporting like COVID-19. The research adds to the literature by methodologically using SDA to explore pandemic-specific disclosures, uncovering the interplay between disclosures, legitimacy and stakeholder engagement.Originality/valueThis study represents a pioneering effort in investigating COVID-19-specific disclosures. Moreover, it uses the SDA methodology along with the legitimacy theory to analyze accounting disclosures associated with COVID-19.

The impacts of the transmission line length in an interconnected micro-grid on its performance and protection at different fault levels

Power systems, in recent years, have been experiencing a dynamic rise in the amount of power obtained from distributed renewable energy sources leading to the concept of microgrids to address the distributed power grid integration issues. Microgrids, a promising means of facilitating the green transformation of power systems, allow the union operation of distributed energy resources (DER) such as combined heat and power (CHP), renewables like photovoltaic (PV), wind and fuel cells (FC), energy storage systems, diesel generators, and controllable loads, either individually or in combination. The protection of DERs within microgrids can be considered as one of the main challenges associated with such phenomenon. Short and Long power transmission lines, in case of a fault, both have particular impacts on system parameters and may result into subsequent events threatening the microgrid and renewable generation units. On the other hand, The high penetration of microgrids not only can change the power flow within the power network, but it can also affect the fault current levels and may lead to their islanding in case of a fault. Before investing in microgrids, especially those in far places, this paper develops a tool to be used in investigating the influence of the interconnecting transmission line length as well as the type/severity of fault on the microgrid performance. The toolbox was developed using MATLAB/Simulink Toolbox. The developed tool was then validated on a case study microgrid and results show that the length of the interconnecting transmission line and the fault severity directly impact the microgrid performance (i.e. voltage and power deviations). In that case, interconnection or islanded mode is contingent upon the decision of the utility operator which also depends on the sensitivity of the equipment used in the microgrid.