bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel framework to study community-level social and physical impacts of hurricane-induced winds through synthetic scenario analysis
Authors: Mazumder Ram Krishna , Enderami S. Amin , Sutley Elaina J.
Published: February 2023

Strong hurricane winds often cause severe infrastructure damage and pose social and economic consequences in coastal communities. In the context of community resilience planning, estimating such impacts can facilitate developing more risk-informed mitigation plans in the community of interest. This study presents a new framework for synthetically simulating scenario-hurricane winds using a parametric wind field model for predicting community-level building damage, direct economic loss, and social consequences. The proposed synthetic scenario approach uses historical hurricane data and adjusts its original trajectory to create synthetic change scenarios and estimates peak gust wind speed at the location of each building. In this research, a stochastic damage simulation algorithm is applied to assess the buildings’ physical damage. The algorithm assigns a damage level to each building using the corresponding damage-based fragility functions, predicted maximum gust speed at the building’s location, and a randomly generated number. The monetary loss to the building inventory due to its physical damage is determined using FEMA’s direct loss ratios and buildings’ replacement costs considering uncertainty. To assess the social impacts of the physical damage exposure, three likely post-disaster social disruptions are measured, including household dislocation, employment disruption, and school closures. The framework is demonstrated by its application to the hurricane-prone community of Onslow County, North Carolina. The novel contribution of the developed framework, aside from the introduced approach for spatial predicting hurricane-induced wind hazards, is its ability to illuminate some aspects of the social consequences of substantial physical damages to the building inventory in a coastal community due to the hurricane-induced winds. These advancements enable community planners and decision-makers to make more risk-informed decisions for improving coastal community resilience.
Genetics and pathophysiology of mitral valve prolapse
Authors: Delwarde Constance , Capoulade Romain , Mérot Jean , Le Scouarnec Solena , Bouatia-Naji Nabila , Yu Mengyao , Huttin Olivier , Selton-Suty Christine , Sellal Jean-Marc , Piriou Nicolas , Schott Jean-Jacques , Dina Christian , Le Tourneau Thierry
Published: February 2023

Mitral valve prolapse (MVP) is a common condition affecting 2–3% of the general population, and the most complex form of valve pathology, with a complication rate up to 10–15% per year in advanced stages. Complications include mitral regurgitation which can lead to heart failure and atrial fibrillation, but also life-threatening ventricular arrhythmia and cardiovascular death. Sudden death has been recently brought to the forefront of MVP disease, increasing the complexity of management and suggesting that MVP condition is not properly understood. MVP can occur as part of syndromic conditions such as Marfan syndrome, but the most common form is non-syndromic, isolated or familial. Although a specific X-linked form of MVP was initially identified, autosomal dominant inheritance appears to be the primary mode of transmission. MVP can be stratified into myxomatous degeneration (Barlow), fibroelastic deficiency, and Filamin A-related MVP. While FED is still considered a degenerative disease associated with aging, myxomatous MVP and FlnA-MVP are recognized as familial pathologies. Deciphering genetic defects associated to MVP is still a work in progress; although FLNA, DCHS1, and DZIP1 have been identified as causative genes in myxomatous forms of MVP thanks to familial approaches, they explain only a small proportion of MVP. In addition, genome-wide association studies have revealed the important role of common variants in the development of MVP, in agreement with the high prevalence of this condition in the population. Furthermore, a potential genetic link between MVP and ventricular arrhythmia or a specific type of cardiomyopathy is considered. Animal models that allow to advance in the genetic and pathophysiological knowledge of MVP, and in particular those that can be easily manipulated to express a genetic defect identified in humans are detailed. Corroborated by genetic data and animal models, the main pathophysiological pathways of MVP are briefly addressed. Finally, genetic counseling is considered in the context of MVP.
Development and validation of a nomogram to predict mortality risk in patients with ischemic heart disease
Authors: Yang Long , Dong Xia , Abuduaini Baiheremujiang , Jiamali Nueraihemaiti , Seyiti Zulihuma , Shan Xue-Feng , Gao Xiao-Ming
Published: February 2023

Background

Ischemic Heart Disease (IHD) is the leading cause of death from cardiovascular disease. Currently, most studies have focused on factors influencing IDH or mortality risk, while few predictive models have been used for mortality risk in IHD patients. In this study, we constructed an effective nomogram prediction model to predict the risk of death in IHD patients by machine learning.

Methods

We conducted a retrospective study of 1,663 patients with IHD. The data were divided into training and validation sets in a 3:1 ratio. The least absolute shrinkage and selection operator (LASSO) regression method was used to screen the variables to test the accuracy of the risk prediction model. Data from the training and validation sets were used to calculate receiver operating characteristic (ROC) curves, C-index, calibration plots, and dynamic component analysis (DCA), respectively.

Results

Using LASSO regression, we selected six representative features, age, uric acid, serum total bilirubin, albumin, alkaline phosphatase, and left ventricular ejection fraction, from 31 variables to predict the risk of death at 1, 3, and 5 years in patients with IHD, and constructed the nomogram model. In the reliability of the validated model, the C-index at 1, 3, and 5 years was 0.705 (0.658–0.751), 0.705 (0.671–0.739), and 0.694 (0.656–0.733) for the training set, respectively; the C-index at 1, 3, and 5 years based on the validation set was 0.720 (0.654–0.786), 0.708 (0.650–0.765), and 0.683 (0.613–0.754), respectively. Both the calibration plot and the DCA curve are well-behaved.

Conclusion

Age, uric acid, total serum bilirubin, serum albumin, alkaline phosphatase, and left ventricular ejection fraction were significantly associated with the risk of death in patients with IHD. We constructed a simple nomogram model to predict the risk of death at 1, 3, and 5 years for patients with IHD. Clinicians can use this simple model to assess the prognosis of patients at the time of admission to make better clinical decisions in tertiary prevention of the disease.
Hazard assessment of potential debris flow: A case study of Shaling Gully, Lingshou County, Hebei Province, China
Authors: Wang Zhong Fu , Zhang Xu Sheng , Zhang Xu Zhu , Wu Ming Tang , Wu Bo
Published: February 2023

The debris flows in the Taihang Mountain region in North China are basically triggered by rainstorms. Firstly, the debris flow susceptibility of the Shaling Gully, Lingshou County, Hebei Province, China was analyzed in this paper to evaluate its hazard and effect on the downstream proposed structures. Secondly, the maximum flow depth and velocity of the potential debris flow in Shaling Gully were numerically simulated based on the FLO-2D model, and the simulation results indicate that the flow depths under the 50-year and 100-year rainstorms will have some effect on the downstream proposed structures. With debris flow intensity classification, the hazard of potential debris flow in Shaling Gully was classified. According to the flow depths and velocities simulated by FLO-2D model, the ARCGIS10.8 software was adopted to optimize the hazard zones, and therefore the hazard zonation map was established. With consideration of simulation results under natural conditions and other factors such as gully feature, a 4 m high and 40 m wide retaining dam was designed. The numerical simulation results show that the retaining dam may decrease the debris flow hazard to a negligible level, which offers some beneficial reference to the subsequent engineering design for Shaling Gully.
Prestack seismic random noise attenuation using the wavelet-inspired invertible network with atrous convolutions spatial pyramid
Authors: He Liangsheng , Wu Hao , Wen Xiaotao
Published: February 2023

Convolutional Neural Network (CNN) is widely used in seismic data denoising due to its simplicity and effectiveness. However, traditional seismic denoising methods based on CNN ignore multi-scale features of seismic data in the wavelet domain. The lack of these features will decrease the accuracy of denoising results. To address this barrier, a seismic denoise method based on the wavelet-inspired invertible network with atrous convolutions spatial pyramid (WINNet_ACSP) is proposed. WINNet_ACSP follows the principle of lifting wavelet transform. The proposed method utilizes the redundant orthogonal wavelet transform to obtain frequency multi-scale information from noisy seismic data. Then predict update network (PUNet) extracts spatial multi-scale features of approximate and detailed parts. The sparse driven network (SDN) learns the complex multi-scale information and obtains sparse features. These sparse features are processed to eliminate random noise. Compared to standard convolution, the atrous convolutions spatial pyramid (ACSP) can extract more features. The redundant features are the key to ensure the precision of multi-scale information. Therefore, the introduction of ACSP in PUNet can guarantee the denoising effect of the network. WINNet_ASCP combines the characteristics of wavelet transform and neural network and has a high generalization. Besides, transfer learning is used to overcome the difficulty caused by the training sample size of seismic data. The training process includes pre-training and post-training. The former is trained to obtain the initial denoising network by natural image samples. The latter is trained with a small sample of seismic data to enhance stratigraphic continuity. Finally, the proposed method is tested with synthetic and field data. The experimental results show that the proposed method can effectively remove random noise and reduce the loss of detailed information in prestack seismic data. In the future, we will make further improvements on this basis and conduct experiments on 3D prestack data.
Implementation of an early childhood mental health consultation pilot in Virginia: Critical tensions and implications for scale-up
Authors: Partee Ann M. , Sachdeva Shubhi , Bivona Marissa A. , Clayback Kelsey A. , Miller-Marshall Sasha , Parker Kyra , Alamos Pilar , Frank Cloe , Downer Jason T. , Williford Amanda P.
Published: February 2023

Early childhood mental health consultation (ECMHC) is a targeted prevention service that aims to build the capacity of early care and education (ECE) professionals and foster supportive environments that promote children’s social–emotional competence and improve mental health and well-being. A key challenge to delivering ECMHC at scale is navigating complex multi-level factors to maximize successful implementation and program benefits at scale. The current study describes the implementation tensions arising during the first year of a pilot ECMHC program conducted in partnership across multiple agencies and a state’s department of education. In the 2021–2022 pilot year, ECMHC was offered as a free service to ECE programs in one large region of Virginia, with the goal of examining feasibility to scale statewide in future years. Consultation was implemented in 45 preschool classrooms across 30 programs. Implementation data were collected using consultation logs and participant surveys, and 20 participants (educators, families, program directors) participated in focus groups. Three implementation tensions are highlighted in this paper: (1) ideal plans versus reality of a new ECMHC roll-out; (2) how to support ECE professionals’ practice as it relates to children’s behavior, without contributing to a deficit view that children need to be “fixed;” and (3) systemic factors in the early childhood field that undermine the implementation and effectiveness of ECMHC. For each tension, we provide context from the larger literature on ECMHC, describe relevant decision points from Virginia’s pilot ECMHC program, and present implementation data to illustrate these tensions in practice. We conclude with reflections on lessons learned that have implications for other ECMHC and SEL intervention scale-up efforts.
Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells
Authors: Liu Jiatong , Lin Xi , McDavid Andrew , Yang Yutiancheng , Zhang Hengwei , Boyce Brendan F. , Xing Lianping
Published: February 2023

Cellular senescence plays important roles in age-related diseases, including musculoskeletal disorders. Senescent cells (SCs) exert a senescence-associated secretory phenotype (SASP) by producing SASP factors, some of which overlap with factors produced by inflammatory cells (Inf-Cs). However, the differences between SCs and Inf-Cs and how they interact with each other during fracture repair have not been well studied. Here, we analyzed single cell RNA sequencing data of aged mouse fracture callus stromal cells. We defined Inf-Cs as cells that express NF-κB Rela/Relb, SCs as cells that express the senescence genes, Cdkn1a, Cdkn2a or Cdkn2c, and inflammatory SCs (Inf-SCs) as cells that express both NF-κB and senescence genes. Differentially expressed genes and pathway analyses revealed that Inf-SCs and SCs had a similar gene expression profile and upregulated pathways that are related to DNA damage/oxidation-reduction and cellular senescence, while Inf-Cs expressed different gene signatures and pathways from SCs and Inf-SCs, mainly related to inflammation. Cellchat software analysis indicated that SCs and Inf-SCs are potential ligand-producing cells that affect Inf-Cs as target cells. Cell culture experiments demonstrated that SC conditioned medium promoted inflammatory gene expression by callus-derived mesenchymal progenitor cells, and Inf-Cs had reduced osteoblast differentiation capacity. In summary, we have identified three cell subclusters associated with inflammation and senescence in callus stromal cells, predicted potential effects of Inf-SCs and SCs on Inf-Cs by production of active ligands, and demonstrated that when mesenchymal progenitors acquire inflammatory phenotypes their osteogenic potential is reduced.
Harmonic analysis on direct-current side of tokamak power supply under asymmetrical triggering
Authors: He Rui , Wu Yanan , Lu Jing , Li Jun , Zhang Junmin , Tian Yunxiang , Wang Pengfei
Published: February 2023

Tokamak is a promising device for using nuclear fusion energy, and the triggering of Tokamak power supply has the characteristics of extreme asymmetry and drastic instantaneous change, which bring spectrum-rich harmonics to the DC side of the power supply, threatening the operational safety of the device. Although the harmonic analysis method of the DC side already exists, however, it still has the problem of cumbersome and inaccurate calculation when it is oriented to fusion power systems with complex operation modes. Based on the three-phase unified switching function, this paper introduces delay factor, and establishes a non-linear function model of converter suitable for the case of asymmetrical triggering. According to the principle of the switching function method, the frequency domain equation of the proposed model is obtained, then combined with power grid parameters, the harmonic analysis of the DC side can be derived. The correctness of the theoretical analysis is verified by comparing the calculation results with the harmonic frequency spectrum data obtained by direct Fourier decomposition of the DC side voltage.
Study on gas injection development effect of tight reservoir based on fluid occurrence state
Authors: Yishan Liu , Lin Zu , An Sheng , Yanan Hou , Yuqi Liu , Changbing Tian , Xiaohu Dong , Zhengdong Lei
Published: February 2023

Based on the tight oil reservoir conditions of Lucaogou Formation in Jimusar Sag, Xinjiang, this paper conducts a full-scale characterization experiment of pore structure and designs the optimization numerical simulation of the development scheme based on the geological model combination with the fluid occurrence state. A comparative study on the development methods of tight reservoirs shows that the enhanced oil recovery effect of CO2 flooding is obviously better than that of CH4 flooding and water flooding. When the production bottom hole pressure is lower than the formation fluid saturation pressure, changing the production bottom hole pressure has little impact on the productivity of CO2 flooding in tight reservoirs. The recovery factor increases with the increase of injection rate, but when the injection rate is higher than 15,000 m³/d, the increase of oil recovery and the oil change rate decrease obviously; The complex fractures near the well can help to increase the swept volume of CO2 flooding, while the complex fractures far away from the well will cause channeling, which is not conducive to production. Combined with the occurrence state of the fluid, it is obtained that in the process of CO2 displacement, when the adsorption is considered, when the adsorption components are the same, with the increase of the adsorption capacity, the recovery factor decreases; When the adsorption capacity is constant, the higher the proportion of heavy components is, the lower the recovery factor is; With the increase of adsorption capacity, the permeability decreases more. The fluid occurrence state in tight oil reservoirs is very different from that in conventional reservoirs, and the adsorption phase accounts for a larger proportion, which seriously affects the flow capacity of the fluid during the development process. However, conventional numerical simulation rarely considers the influence of fluid occurrence state.
Faecal sludge emptying in Sub-Saharan Africa, South and Southeast Asia: A systematic review of emptying technology choices, challenges, and improvement initiatives
Authors: Muoghalu Chimdi , Semiyaga Swaib , Manga Musa
Published: February 2023

The emptying and transport of faecal sludge (FS) is a fundamental aspect of the sanitation service chain and is mostly carried out by private operators who usually face a lot of challenges. Our review assessed how influencing factors and challenges FS emptiers face are linked and in turn how they act as barriers to improvement initiatives. We conducted a systematic review of peer-reviewed journals on FS emptying in sub-Saharan Africa, South and Southeast Asia published between January 2002 and December 2021. Amongst the 37 journals reviewed, accessibility was mostly documented (n = 18) as a factor which affected choice of emptying method, followed by cost (n = 14), quality of service (n = 13) and then sludge thickness (n = 8). We grouped the types of challenges identified from the publications into five categories of financial, technical and institutional (n = 14, each), followed by health (n = 12) and then social challenges (n = 8). Discussions on initiatives (n = 13) used to improve the emptying business were limited to Cost/affordability of sanitation services and access to finance by FS emptiers, which were noted to be the major barriers to effective implementation of these strategies. This review identified the need for sensitizing the public on FS emptying, financial modelling of manual emptying business and a need to study the relationship between perceptions and emptying behavior of users.
Redox-associated messenger RNAs identify novel prognostic values and influence the tumor immune microenvironment of lung adenocarcinoma
Authors: Zhao Chen , Xiong Kewei , Bi Dong , Zhao Fangrui , Lan Yanfang , Jin Xiaorui , Li Xiangpan
Published: February 2023

Background: An imbalance of redox homeostasis participates in tumorigenesis, proliferation, and metastasis, which results from the production of reactive oxygen species (ROS). However, the biological mechanism and prognostic significance of redox-associated messenger RNAs (ramRNAs) in lung adenocarcinoma (LUAD) still remain unclear.

Methods: Transcriptional profiles and clinicopathological information were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) of LUAD patients. A total of 31 overlapped ramRNAs were determined, and patients were separated into three subtypes by unsupervised consensus clustering. Biological functions and tumor immune-infiltrating levels were analyzed, and then, differentially expressed genes (DEGs) were identified. The TCGA cohort was divided into a training set and an internal validation set at a ratio of 6:4. Least absolute shrinkage and selection operator regression were used to compute the risk score and determine the risk cutoff in the training set. Both TCGA and GEO cohort were distinguished into a high-risk or low-risk group at the median cutoff, and then, relationships of mutation characteristics, tumor stemness, immune differences, and drug sensitivity were investigated.

Results: Five optimal signatures (ANLN, HLA-DQA1, RHOV, TLR2, and TYMS) were selected. Patients in the high-risk group had poorer prognosis, higher tumor mutational burden, overexpression of PD-L1, and lower immune dysfunction and exclusion score compared with the low-risk group. Cisplatin, docetaxel, and gemcitabine had significantly lower IC50 in the high-risk group.

Conclusion: This study constructed a novel predictive signature of LUAD based on redox-associated genes. Risk score based on ramRNAs served as a promising biomarker for prognosis, TME, and anti-cancer therapies of LUAD.
In silico analysis to identify novel ceRNA regulatory axes associated with gallbladder cancer
Authors: Saklani Neeraj , Chauhan Varnit , Akhtar Javed , Upadhyay Santosh Kumar , Sirdeshmukh Ravi , Gautam Poonam
Published: February 2023

Competitive endogenous RNA (ceRNA) networks are reported to play a crucial role in regulating cancer-associated genes. Identification of novel ceRNA networks in gallbladder cancer (GBC) may improve the understanding of its pathogenesis and might yield useful leads on potential therapeutic targets for GBC. For this, a literature survey was done to identify differentially expressed lncRNAs (DELs), miRNAs (DEMs), mRNAs (DEGs) and proteins (DEPs) in GBC. Ingenuity pathway analysis (IPA) using DEMs, DEGs and DEPs in GBC identified 242 experimentally observed miRNA-mRNA interactions with 183 miRNA targets, of these 9 (CDX2, MTDH, TAGLN, TOP2A, TSPAN8, EZH2, TAGLN2, LMNB1, and PTMA) were reported at both mRNA and protein levels. Pathway analysis of 183 targets revealed p53 signaling among the top pathway. Protein-protein interaction (PPI) analysis of 183 targets using the STRING database and cytoHubba plug-in of Cytoscape software revealed 5 hub molecules, of which 3 of them (TP53, CCND1 and CTNNB1) were associated with the p53 signaling pathway. Further, using Diana tools and Cytoscape software, novel lncRNA-miRNA-mRNA networks regulating the expression of TP53, CCND1, CTNNB1, CDX2, MTDH, TOP2A, TSPAN8, EZH2, TAGLN2, LMNB1, and PTMA were constructed. These regulatory networks may be experimentally validated in GBC and explored for therapeutic applications.
Review the progression of ovarian clear cell carcinoma from the perspective of genomics and epigenomics
Authors: Tong An , Di Xiangjie , Zhao Xia , Liang Xiao
Published: February 2023

Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer with unique molecular characteristics, specific biological and clinical behavior, poor prognosis and high resistance to chemotherapy. Pushed by the development of genome-wide technologies, our knowledge about the molecular features of OCCC has been considerably advanced. Numerous studies are emerging as groundbreaking, and many of them are promising treatment strategies. In this article, we reviewed studies about the genomics and epigenetics of OCCC, including gene mutation, copy number variations, DNA methylation and histone modifications.
Enhancing structural balance theory and measurement to analyze signed digraphs of real-world social networks
Authors: Dinh Ly , Rezapour Rezvaneh , Jiang Lan , Diesner Jana
Published: February 2023

Structural balance theory assumes triads in networks to gravitate toward stable configurations. The theory has been verified for undirected graphs. Since real-world social networks are often directed, we introduce a novel method for considering both transitivity and sign consistency for calculating balance in signed digraphs. We test our approach on graphs that we constructed by using different methods for identifying edge signs: natural language processing to infer signs from underlying text data, and self-reported survey data. Our results show that for various social contexts and edge sign detection methods, balance is moderately high, ranging from 61% to 96%. This paper makes three contributions: First, we extend the theory of structural balance to include signed digraphs where both transitivity and sign consistency are required and considered for calculating balance in triads with signed and directed edges. This improves the modeling of communication networks and other organizational networks where ties might be directed. Second, we show how to construct and analyze email networks from unstructured text data, using natural language processing methods to infer two different types of edge signs from emails authored by nodes. Third, we empirically assess balance in two different and contemporary contexts, namely remote communication in two business organizations, and team-based interactions in a virtual environment. We find empirical evidence in support of structural balance theory across these contexts.
The epidemic of the multiresistant dermatophyte Trichophyton indotineae has reached China
Authors: Jia Songgan , Long Xuemei , Hu Wei , Zhu Jiali , Jiang Yinhui , Ahmed Sarah , de Hoog G. Sybren , Liu Weida , Jiang Yanping
Published: February 2023

Due to its high degree of natural resistance to terbinafine in vitro and its tendency to spread globally from the Indian subcontinent, the emerging dermatophyte Trichophyton indotineae has become a major concern in dermatology. Herein, we present the first report of T. indotineae from mainland China. The transmission of the fungus to Guizhou Province in central China and eventual host susceptibilities were investigated. We studied 31 strains of the T. mentagrophytes complex from outpatient clinics of our hospital collected during the past 5 years. The set comprised four ITS genotypes, two of which were T. mentagrophytes genotype VIII, now known as Trichophyton indotineae; the earliest isolation in the Guiyang area appeared to date back to 2018. The isolate was derived from an Indian patient, while local Chinese patients had no dermatophytosis caused by this genotype. Reports from around the world indicated that almost all of the globally reported T. indotineae cases originated from the Indian subcontinent and surrounding countries without transmission among native populations, suggesting deviating local conditions or racial differences in immunity against this fungus.
A tool for evaluating heterogeneity in avidity of polyclonal antibodies
Authors: Li Kan , Dodds Michael , Spreng Rachel L. , Abraha Milite , Huntwork Richard H. C. , Dahora Lindsay C. , Nyanhete Tinashe , Dutta Sheetij , Wille-Reece Ulrike , Jongert Erik , Ewer Katie J. , Hill Adrian V. S. , Jin Celina , Hill Jennifer , Pollard Andrew J. , Munir Alam S. , Tomaras Georgia D. , Dennison S. Moses
Published: February 2023

Diversity in specificity of polyclonal antibody (pAb) responses is extensively investigated in vaccine efficacy or immunological evaluations, but the heterogeneity in antibody avidity is rarely probed as convenient tools are lacking. Here we have developed a polyclonal antibodies avidity resolution tool (PAART) for use with label-free techniques, such as surface plasmon resonance and biolayer interferometry, that can monitor pAb-antigen interactions in real time to measure dissociation rate constant (kd) for defining avidity. PAART utilizes a sum of exponentials model to fit the dissociation time-courses of pAb-antigens interactions and resolve multiple kd contributing to the overall dissociation. Each kd value of pAb dissociation resolved by PAART corresponds to a group of antibodies with similar avidity. PAART is designed to identify the minimum number of exponentials required to explain the dissociation course and guards against overfitting of data by parsimony selection of best model using Akaike information criterion. Validation of PAART was performed using binary mixtures of monoclonal antibodies of same specificity but differing in kd of the interaction with their epitope. We applied PAART to examine the heterogeneity in avidities of pAb from malaria and typhoid vaccinees, and individuals living with HIV-1 that naturally control the viral load. In many cases, two to three kd were dissected indicating the heterogeneity of pAb avidities. We showcase examples of affinity maturation of vaccine induced pAb responses at component level and enhanced resolution of heterogeneity in avidity when antigen-binding fragments (Fab) are used instead of polyclonal IgG antibodies. The utility of PAART can be manifold in examining circulating pAb characteristics and could inform vaccine strategies aimed to guide the host humoral immune response.
Primate liver tissue substrate in indirect immunofluorescence diagnostics for patients with dermatitis herpetiformis and celiac disease
Authors: Schauer Franziska , Tasiopoulou Georgia , Schuster Daniel , Behrens Max , Müller Sabine , Kiritsi Dimitra
Published: February 2023

Introduction

Dermatitis herpetiformis (DH) is a rare autoimmune, polymorphous blistering disorder, characterized by severe itch or burning sensation, which represents the cutaneous manifestation of celiac disease (CD). The current estimation of DH versus CD is around 1:8 and the affected individuals have a genetic predisposition. Pathogenetically, IgA autoantibodies against the epidermal transglutaminase, an essential constituent of the epidermis, cause DH and are reported to develop through cross-reaction with the tissue transglutaminase, with IgA auto-antibodies causing CD. Immunofluorescence techniques allow for a rapid diagnostics of the disease using patient sera. Evaluation of IgA endomysial deposition with indirect immunofluorescence on monkey oesophagus is highly specific, but moderately sensitive, with some operator-dependent variability. Recently, indirect immunofluorescence with monkey liver as a substrate has been proposed as an alternative, well-functioning diagnostic approach with higher sensitivity in CD.

Methods

The objective of our study was to evaluate whether monkey oesophagus or liver tissue shows advantage for diagnostics in patients with DH, compared to CD. To that end, sera of 103 patients with DH (n=16), CD (n=67) and 20 controls ere compared by 4 blinded experienced raters.

Results

For DH, we found a sensitivity of 94.2% for monkey liver (ML) compared to 96.2% in monkey oesophagus (ME), while specificity in ML was superior (91.6% versus 75%) to ME. In CD, ML had a sensitivity of 76.9% (ME 89.1%) and specificity of 98.3% (ME 94.1%).

Discussion

Our data show that ML substrate is well suitable for DH diagnostics.
Lung T cell response in COVID-19
Authors: Shakiba Mehrnoush Hadaddzadeh , Gemünd Ioanna , Beyer Marc , Bonaguro Lorenzo
Published: February 2023

The COVID-19 pandemic has shown the potentially devastating impact of novel respiratory infections worldwide. Insightful data obtained in the last years have shed light on the pathophysiology of SARS-CoV-2 infection and the role of the inflammatory response in driving both the resolution of the disease and uncontrolled deleterious inflammatory status in severe cases. In this mini-review, we cover some important aspects of the role of T cells in COVID-19 with a special focus on the local response in the lung. We focus on the reported T cell phenotypes in mild, moderate, and severe COVID-19, focusing on lung inflammation and on both the protective and damaging roles of the T cell response, also highlighting the open questions in the field.
Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma
Authors: Chintala Navin K. , Choe Jennie K. , McGee Erin , Bellis Rebecca , Saini Jasmeen K. , Banerjee Srijita , Moreira Andre L. , Zauderer Marjorie G. , Adusumilli Prasad S. , Rusch Valerie W.
Published: February 2023

Background

The attenuated, genetically engineered vaccinia virus has been shown to be a promising oncolytic virus for the treatment of patients with solid tumors, through both direct cytotoxic and immune-activating effects. Whereas systemically administered oncolytic viruses can be neutralized by pre-existing antibodies, locoregionally administered viruses can infect tumor cells and generate immune responses. We conducted a phase I clinical trial to investigate the safety, feasibility and immune activating effects of intrapleural administration of oncolytic vaccinia virus (NCT01766739).

Methods

Eighteen patients with malignant pleural effusion due to either malignant pleural mesothelioma or metastatic disease (non-small cell lung cancer or breast cancer) underwent intrapleural administration of the oncolytic vaccinia virus using a dose-escalating method, following drainage of malignant pleural effusion. The primary objective of this trial was to determine a recommended dose of attenuated vaccinia virus. The secondary objectives were to assess feasibility, safety and tolerability; evaluate viral presence in the tumor and serum as well as viral shedding in pleural fluid, sputum, and urine; and evaluate anti-vaccinia virus immune response. Correlative analyses were performed on body fluids, peripheral blood, and tumor specimens obtained from pre- and post-treatment timepoints.

Results

Treatment with attenuated vaccinia virus at the dose of 1.00E+07 plaque-forming units (PFU) to 6.00E+09 PFU was feasible and safe, with no treatment-associated mortalities or dose-limiting toxicities. Vaccinia virus was detectable in tumor cells 2-5 days post-treatment, and treatment was associated with a decrease in tumor cell density and an increase in immune cell density as assessed by a pathologist blinded to the clinical observations. An increase in both effector (CD8+, NK, cytotoxic cells) and suppressor (Tregs) immune cell populations was observed following treatment. Dendritic cell and neutrophil populations were also increased, and immune effector and immune checkpoint proteins (granzyme B, perforin, PD-1, PD-L1, and PD-L2) and cytokines (IFN-γ, TNF-α, TGFβ1 and RANTES) were upregulated.

Conclusion

The intrapleural administration of oncolytic vaccinia viral therapy is safe and feasible and generates regional immune response without overt systemic symptoms.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT01766739, identifier NCT01766739.
Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment
Authors: Zhang Nana , Yao Huimin , Zhang Zhixuan , Li Zhuoqun , Chen Xue , Zhao Yan , Ju Ran , He Jiayi , Pan Heli , Liu Xiaoli , Lv Yi
Published: February 2023

Hepatic fibrosis is often secondary to chronic inflammatory liver injury. During the development of hepatic fibrosis, the damaged hepatocytes and activated hepatic stellate cells (HSCs) caused by the pathogenic injury could secrete a variety of cytokines and chemokines, which will chemotactic innate and adaptive immune cells of liver tissue and peripheral circulation infiltrating into the injury site, mediating the immune response against injury and promoting tissue reparation. However, the continuous release of persistent injurious stimulus-induced inflammatory cytokines will promote HSCs-mediated fibrous tissue hyperproliferation and excessive repair, which will cause hepatic fibrosis development and progression to cirrhosis even liver cancer. And the activated HSCs can secrete various cytokines and chemokines, which directly interact with immune cells and actively participate in liver disease progression. Therefore, analyzing the changes in local immune homeostasis caused by immune response under different pathological states will greatly enrich our understanding of liver diseases’ reversal, chronicity, progression, and even deterioration of liver cancer. In this review, we summarized the critical components of the hepatic immune microenvironment (HIME), different sub-type immune cells, and their released cytokines, according to their effect on the development of progression of hepatic fibrosis. And we also reviewed and analyzed the specific changes and the related mechanisms of the immune microenvironment in different chronic liver diseases.Moreover, we retrospectively analyzed whether the progression of hepatic fibrosis could be alleviated by modulating the HIME.We aimed to elucidate the pathogenesis of hepatic fibrosis and provide the possibility for exploring the therapeutic targets for hepatic fibrosis.
Transcriptome profiling reveals a global response in harmful dinoflagellate Karlodinium veneficum to naturally-occurring bacterial algicides
Authors: Wang Yanfei , Coyne Kathryn J.
Published: February 2023

Dinoflagellates are among the most toxigenic phytoplankton that cause harmful algal blooms; they can produce toxins that accumulate through the aquatic food chains to cause illness and even death in marine animals and humans. Shewanella sp. IRI-160 is a naturally-occurring bacterium that secretes a suite of algicidal compounds (collectively designated as IRI-160AA) specifically targeting dinoflagellates. Studies revealed IRI-160AA inhibited photosynthesis, while inducing cell cycle arrest, DNA damage, and reactive oxygen species (ROS) production, as well as other markers associated with programmed cell death (PCD). Recent research indicated that IRI-160AA contains ammonium and other compounds as active ingredients for its algicidal activity, while impacts by ammonium differed from the algicide with respect to photobiology. Here, transcriptomic analysis was conducted on the toxic dinoflagellate Karlodinium veneficum exposed to IRI-160AA to investigate the effects of this algicide at the molecular level. Transcriptomic analysis was also conducted on K. veneficum treated with ammonium to further differentiate its effects from IRI-160AA. Results demonstrated differential impacts by IRI-160AA and ammonium on K. veneficum at the molecular level and revealed a global response of K. veneficum to algicide exposure, supported by the enriched biological processes involved in regulating gene expression, protein activity, and morphology. Differentially expressed genes associated with stress and ROS response, DNA damage response, cell cycle checkpoint activation, and PCD were also identified in K. veneficum exposed to IRI-160AA. The potential involvement of a recovery mechanism from photodamage in K. veneficum induced by IRI-160AA was identified. Overall, results of this study further differentiated the impacts of ammonium from IRI-160AA on K. veneficum and illustrated the cellular mechanisms behind the algicidal effect. This research provided insights on algal response to bacterial derivatives in nature.
Statistical modelling of voluntary feed intake in individual Atlantic salmon (Salmo salar L.)
Authors: Gomes Ana S. , Zimmermann Fabian , Hevrøy Ernst M. , Søyland Marcus A. L. , Hansen Tom J. , Nilsen Tom Ole , Rønnestad Ivar
Published: February 2023

Precision feeding aims to provide the correct amount of feed to farmed animals for optimal growth and performance and to avoid feed waste. However, knowledge underlying the meal-to-meal variability in voluntary feed intake of farmed species is still limited. This study examined the relationship between meals, feed deprivation time and the feed (pellets) consumed by Atlantic salmon post smolts. The data was collected from individual fish handfed to satiety without social interaction in three independent short-term (6-12 days) experiments. The fixed variables of our model (feed deprivation time (i.e., time between meals), number of pellets provided, day, previous meal size, and fish growth) explained most of the feed intake (number of pellets ingested) (R2 0.68). Results show that fish ingested more pellets over the course of the trials as they grew, resulting in a positive correlation between feed intake and fish growth (final minus initial fish weight). The time between meals and prior meal size (the number of pellets ingested in the previous meal) significantly affected feed intake in the following meal. Our results suggest that it is possible to optimise meal size by considering the size of the previous meal and the time since it was given.
Review and reflections of legislation and policies on shipping decarbonization under China’s “dual carbon” target
Authors: Yang Weiming , Chen Xidi , Liu Yu
Published: February 2023

Although shipping is a relatively energy-saving and environmentally friendly mode of transportation, the growth rate of its energy consumption and carbon emissions far exceeds that of other industries. As an important response to climate change, shipping decarbonization is not only an important part of achieving the temperature control goal of the Paris Agreement but is also an important direction for the future development of China’s ecological civilization construction. China has formulated and promulgated legislation and policies on shipping decarbonization both at the national and local levels. The proposal in 2020 of the goal of carbon peaking and carbon neutrality has accelerated this process. In this context, this paper aims at reflecting on legislation and policies for decarbonization of shipping under China’s “double carbon” target, and proposing suggestions for improvement. Firstly, we systematically review China’s legislation and policies on shipping decarbonization to outline the normative system of China’s shipping carbon reduction. Secondly, this paper evaluates China’s legislation and policies on shipping decarbonization from the perspective of both achievements and challenges. Finally, this paper proposes that China’s legislation and policies for decarbonization of shipping should be further improved from two aspects: enhancing mandatory force and expanding normative content.
The association between vitamin D deficiency and risk of renal event: Results from the Korean cohort study for outcomes in patients with chronic kidney disease (KNOW-CKD)
Authors: Lee Juyeon , Bae Eun Hui , Kim Soo Wan , Chung Wookyung , Kim Yeong Hoon , Oh Yun Kyu , Kim Yong-Soo , Oh Kook-Hwan , Park Sue K.
Published: February 2023

Backgrounds

Some observational studies have suggested a possible association between vitamin D deficiency and CKD. However, in most studies, the causality between low levels of vitamin D and risk of renal events could not be explained. We investigated the relationship between vitamin D deficiency and risk of severe CKD stage and renal event in a large-scale prospective cohort study.

Methods

We used data from a prospective cohort of 2,144 patients with available information on serum 25-hydroxyvitamin D (25(OH)D) levels at baseline from KNOW-CKD, 2011-2015 were included. Vitamin D deficiency was defined as serum 25(OH)D levels < 15 ng/mL. We performed a cross-sectional analysis to elucidate the relationship between 25(OH)D and CKD stage using baseline CKD patient data. We further examined a cohort analysis to clarify the association between 25(OH)D and risk of renal event. Renal event was a composite of the first occurrence of a 50% decline in eGFR from the baseline value or the onset of CKD stage 5 (initiation of dialysis or kidney transplantation) across the follow-up period. We also investigated the associations of vitamin D deficiency with risk of renal event according to diabetes and overweight status.

Results

Vitamin D deficiency were significantly associated with an increased risk of severe CKD stage – 1.30-fold (95% CI: 1.10-1.69) for 25(OH)D. Deficiency of 25(OH)D with 1.64-fold (95% CI: 1.32-2.65) was related to renal event compared with the reference. Furthermore, vitamin D deficiency patients with presence of DM and overweight status also displayed higher risk than non-deficient patients for risk of renal event.

Conclusion

Vitamin D deficiency is associated with significantly increased risk of severe CKD stage and renal event.
The influencing factors of health–related quality of life of the general population of Iran during the COVID-19 Pandemic
Authors: Shirvani Shiri Maryam , Karami Hassan , Ameri Hosein , Akbari Sari Ali , Tatari Maryam , Emamgholipour Sara , Afshari Somayeh
Published: February 2023

COVID-19 is a global challenge that negatively affects the health–related quality of life (HRQoL) of the general population. The current study aimed to evaluate HRQoL and its associated factors among the Iranian general population during the COVID-19 pandemic. The data were collected in 2021 using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) and EQ-5D Visual Analog Scale (EQ VAS) questionnaires through an online survey. Participants were recruited via social media from the Fars province. The multiple binary logistic regression model was used to identify factors influencing participants' HRQoL. Kolmogorov-Smirnov, the t-test, ANOVA, and the chi-square test were used. All tests were conducted at a significance level of 5% using Stata 14.2 and SPSS 16. A total of 1,198 participants were involved in this cross-sectional study. The mean age of participants was 33.3 (SD:10.2), and more than half were women (55.6%). The mean EQ-5D-3L index value and EQ-VAS of the respondents were 0.80 and 77.53, respectively. The maximum scores of the EQ-5D-3L and EQ-VAS in the present study were 1 and 100, respectively. The most frequently reported problems were anxiety/depression (A/D) (53.7%), followed by pain/discomfort (P/D) (44.2%). Logistic regression models showed that the odds of reporting problems on the A/D dimension increased significantly with supplementary insurance, including concern about getting COVID-19, hypertension, and asthma, by 35% (OR = 1.35; P = 0.03), 2% (OR = 1.02; P = 0.02), 83% (OR = 1.83; P = 0.02), and 6.52 times (OR = 6.52; P = 0.01), respectively. The odds of having problems on the A/D dimension were significantly lower among male respondents, those in the housewives + students category, and employed individuals by 54% (OR = 0.46; P = 0.04), 38% (OR = 0.62; P = 0.02) and 41% (OR = 0.59; P = 0.03), respectively. Moreover, the odds of reporting a problem on the P/D dimension decreased significantly in those belonging in a lower age group and with people who were not worried about getting COVID-19 by 71% (OR = 0.29; P = 0.03) and 65% (OR = 0.35; P = 0.01), respectively. The findings of this study could be helpful for policy-making and economic evaluations. A significant percentage of participants (53.7%) experienced psychological problems during the pandemic. Therefore, effective interventions to improve the quality of life of these vulnerable groups in society are essential.