bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcatheter aortic valve replacement in patients with quadricuspid aortic valve in a single center
Authors: Liu Yang , Zhai Mengen , Mao Yu , Xu Chennian , Ma Yanyan , Li Lanlan , Jin Ping , Yang Jian
Published: September 2022

Background

Quadricuspid aortic valve (QAV) is a rare congenital malformation that can present with aortic regurgitation or aortic stenosis (AS)), requiring surgical treatment. Transcatheter aortic valve replacement (TAVR) is an alternative treatment for older patients and its prognosis for QAV therapy remains challenging. We sought to examine our early experience with TAVR in patients with QAV.

Materials and methods

Prospectively collected data were retrospectively reviewed in patients with QAV undergoing TAVR in our institution.

Results

Five patients with QAV and AR or AS were treated with TAVR between January 2016 and January 2022. The mean age was 73.8 years (range 69–82 years), and the median Society of Thoracic Surgeons score was 7.51% (range 2.668–18.138%). Two patients had type B and three had either type A, D, or F according to the Hurwitz and Roberts classification for QAV. Four patients with pure aortic regurgitation underwent transapical TAVR using the J-Valve system, and the patient with severe AS underwent transfemoral TAVR using the Venus-A system. Procedural success was achieved in all five patients. Trivial paravalvular leak was only detected in one case after the procedure, and one patient received a permanent pacemaker due to high-degree atrioventricular block three days later. The median follow-up period was 18 (12–56) months. After discharge, no deaths occurred during the 1 year follow-up. All patients improved by ≥1 New York Heart Association functional class at 30 days; four patients were in functional class ≤II later in the follow-up period. All patients’ heart failure symptoms improved considerably.

Conclusion

Our early experience with TAVR in QAV demonstrates these procedures to be feasible with acceptable early results. Further follow-up is necessary to determine the long-term outcomes of this modality.

Clinical trial registration

[ClinicalTrials.gov], identifier [NCT02917980].
Comparison of terrain corrections based on the point source and line source DC methods
Authors: Xie Haijun , Li Lu , Li Zhiqiang , Li Jingrui , Li Gang , Li Wanlu
Published: September 2022

In the direct current (DC) exploration method, topographic relief distorts the apparent resistivity curve. To eliminate effects of terrain fluctuations, two undulating terrains comprising valleys and ridges were investigated in the present study. An unstructured triangular mesh method in which the wave number k and its coefficient g were obtained using the integral method and the point and line source surveys were conducted using comsol multiphysics. Current sources were evaluated using two-dimensional (2-D) finite element forward modeling, whereas terrain correction was performed using both the comparison and conformal transformation methods. The results reveal comparable theoretical curves for the line and point sources, but quantitative characteristics of the curves differ. The comparison method is suitable for both curves, whereas the conformal transformation method is only applicable to the line source. Even though electric fields associated with the line and point sources differ, the comparison method that is based on the electrical cross-section curve of the line source and the electric profile curve of the point source remains effective.
Typical site seismic response analysis with reinforcement under earthquake and rainfall in the mountainous areas of China
Authors: Zhang Jian , Cao Licong , Shen Hao
Published: September 2022

Multi-tilted layered soil is widespread in the mountainous areas of China, and pile systems are widely applied to foundation support and repair. In order to investigate the seismic response of pile systems in multi-tilted layered soils under earthquake and rainfall, two models were built and tested through a large 1-g shaking table. The interlayer was tilted and highly weathered, and it was saturated during rainfall. The piles were embedded in the bedrock with different lengths. The results showed that: 1) The acceleration response was weakened in the interlayer, and it diminished as the earthquake amplitude increased. The structures showed the maximum acceleration response. 2) The existence of water in the tilted interlayer led to a greater response of the superstructure. The bending moment of piles varied under different containers, which was mainly due to the inertial force of the container and the potential sliding force of the covering layer. The water in the interlayer from rainfall promoted the bending moment caused by the potential sliding force, increasing the potential risk of instability of the system. 3) The motion mode of the container under rainfall was translation. The rotation angle of the container with saturated moisture content was significant and it increased with the increase of the earthquake amplitude.
The determinant factors of medical students' learning behavior in the national medical competency examination in Indonesia: A qualitative study
Authors: Firmansyah Marindra , Suhoyo Yoyo , Rahayu Gandes Retno
Published: September 2022

Indonesia has applied for a national competency exit examination for medical graduates since 2014. This examination has an impact on students. There is limited literature that describes the impact mechanism of the national examination. This study aimed to identify the determinant factors of the learning behavior of medical students in the national medical competency examination during the COVID-19 pandemic in Indonesia. This qualitative study was conducted using semi-structured in-depth face-to-face interviews with 13 medical students from the Faculty of Medicine Universitas Islam Malang and online interviews with 13 medical students from the Faculty of Medicine Universitas Gadjah Mada, Indonesia. Theoretical sampling was carried out by including three medical students from a faculty of medicine in east Indonesia. Semi-structured in-depth interviews with respondents from FK Unisma were conducted offline with strict health protocols. Meanwhile, communications with respondents from FK-KMK UGM and the eastern Indonesia medical faculty were conducted online by telephone or through Zoom meetings. Transcribed interviews were coded openly. Themes were finalized through discussion to reach a consensus. The extracted concepts from our study were classified into 10 categories that describe the determinant factors of learning behavior and two categories of learning behavior. These categories include task value, goal orientation, weakness, impact failure, benefits of passing the examination, self-efficacy, beliefs, barriers to learning, environment factors, and test anxiety. The learning behavior itself consists of two categories: quality of learning and regulation of learning. The conclusion is determinant factors consisting of internal and external factors. Internal factors include task value, goal orientation, weakness, benefits of passing the examination, self-efficacy, belief, and test anxiety. The external factor includes the environmental factor. These factors determine the medical student learning behavior in the national medical competency examination during the COVID-19 pandemic in Indonesia, both in quality and regulation of learning. The impact of failure only determines the regulation of learning, while the barrier to learn only determines the quality of learning.
Employability competences through short-term intensive PBL-events in higher education
Authors: Wyke Simon , Jensen Annie Aarup , Krogh Lone , Ravn Ole , Svidt Kjeld
Published: September 2022

The article presents a three-day problem based learning (PBL) event taking place as an interdisciplinary, cross-institution, and cross-sector digital learning activity in architecture, engineering, and construction (AEC). Students were given an overall realistic task by a builder to solve in interdisciplinary teams consisting of members from the involved institutions, i.e., a university college, a university, and a vocational school. Representatives from the AEC industry acted as consultants and teachers from the involved institutions acted as supervisors. Besides drawing on and enhancing students’ existing disciplinary knowledge and skills, their skills in project management, collaboration, and communication were challenged during the event. Coming from a university with a PBL-model of semester-long project work, our main research interest focused on the university students’ learning experience during this very short PBL learning activity. When studying the event from a work-based learning (WBL) perspective we found that the students’ experiences and competences developed during the course of the event to a large extent could be interpreted as employability competences, thus placing the event as a “transitional” activity between education and a future work-place. Furthermore, we found that the gain from the event was mutual—the industry representatives learned about new digital solutions and programs used in the event. The empirical research was based on qualitative methods involving semi structured interviews (students as well as industry representatives), supplemented with informal conversations, observations, and photo documentation.
Does attending preschool in an economically advantaged or disadvantaged neighborhood moderate the effects of the preschool edition of promoting alternative thinking strategies®?
Authors: Kapetanovic Sabina , Ginner Hau Hanna , Eichas Kyle , Olsson Tina M. , Ferrer-Wreder Laura , Eninger Lilianne
Published: September 2022

Early interventions that foster the participation, engagement, and development of children attending preschools, including those in economically disadvantaged (low-income) neighborhoods, are of high priority. One such intervention is a universal socioemotional learning (SEL) program called Promoting Alternative Thinking Strategies (PATHS®) which aims to promote social emotional competence and positive adjustment in children, in general, and may have unique benefits for children attending preschool in low incomes areas. In the SEL field, areas in need of exploration include the possible role that neighborhood income level (i.e., all residents’ income in a postal code that a preschool is located in) could have for children’s social emotional competence and positive adjustment and how neighborhood income level may relate to benefits of an intervention such as PATHS. The study aims were to investigate 1) the baseline group differences in social emotional competence and adjustment depending on the neighborhood income level and 2) to determine if neighborhood income level moderated the effects of PATHS on children’s social emotional competence and adjustment from pre to posttest. Participants were 275 children aged four to five years old, from the preschools randomized into an immediate intervention (n= 145 children) or a wait-list control group (n= 130 children). Overall, 42.9% (n= 118) of the children attended preschools in economically disadvantaged neighborhoods and 57.1% (n= 157) of the children attended preschools in economically advantaged neighborhoods. Children’s social emotional competence and adjustment were assessed through child tasks, child observations and teacher reports. The moderation of intervention effects by the preschools’ neighborhood income was tested in a series of just-identified structural equation models (SEM) that explored interaction effects (income*PATHS interactions). At baseline, relative to children attending preschool in economically advantaged preschools, children attending preschool in economically disadvantaged neighborhoods showed lower levels of inhibitory control, working memory, task orientation and higher levels of inattention. Children attending preschools in economically disadvantaged neighborhoods participating in PATHS also showed reductions in inattention, social withdrawal and anxiety compared to control group children also attending preschool in disadvantaged neighborhoods. Additionally, PATHS children from advantaged neighborhoods improved their prosocial behavior, but not their social independence, relative to control group children who also attended preschool in advantaged neighborhoods. Offering PATHS as an SEL intervention in early childhood education and care settings could help to reduce disparities among children in a number of key outcomes.
Developing a web-based system for coordinating school-based care for students with social, emotional, and behavioral problems
Authors: Evans Steven W. , Brockstein Hannah , Allan Darcey M. , Girton Sam L. , Owens Julie Sarno , Everly Elise L.
Published: September 2022

Many students with social, emotional, and behavioral problems receive school-based services. Multi-Tiered System of Support (MTSS) is the one most frequently referenced systems for coordinating services. The goal of this framework is to effectively match assessment and services to the needs of individual students. In many schools this process is limited by a lack of an overall coordinating system. As a result, many students receive services for social, emotional and behavioral problems that are unlikely to be effective, are not guided by progress monitoring, and not adequately informed by current and historical data. The Beacon System is a web-based tool created to enhance the quality of service provision for students with social, emotional, and behavioral problems by supporting continuous progress monitoring, helping educators know what services are likely to be helpful for a particular student according to their age and presenting problems, and providing educators and school mental health professionals with information to help them implement both familiar and unfamiliar interventions. Additionally, the Beacon system will enhance educators’ abilities to coordinate with a student’s entire intervention team and allow for continuity as a child changes grades, teachers, or schools. Enhancing these parts of the overall process can improve educators’ efforts to achieve the goals of MTSS to provide effective interventions matched to the students’ needs. The purpose of this manuscript is to describe the iterative development process used to create Beacon and highlight specific examples of some of the methods. In addition, we will describe how feedback from stakeholders (e.g., teachers, school mental health professionals) was used to inform decisions about design. Finally, we will describe the final development steps taken prior to pilot implementation studies and our plans for additional data collection to inform continued development of Beacon. This includes the strategies being used to measure outcomes at multiple levels including assessing a variety of behaviors of the professionals in the schools as well as student outcomes. These data will inform continuous development work that will keep us moving toward our goal of enhancing the outcomes of students with social, emotional and behavioral problems.
Obesity is associated with a higher Torque Teno viral load compared to leanness
Authors: Herz Carsten T. , Kulterer Oana C. , Kulifaj Dorian , Gelas Fanny , Franzke Bernhard , Haupenthal Frederik , Prager Gerhard , Langer Felix B. , Marculescu Rodrig , Haug Alexander R. , Kiefer Florian W. , Bond Gregor
Published: September 2022

Introduction

Obesity affects a rising proportion of the population and is an important risk factor for unfavorable outcomes in viral disease including severe acute respiratory syndrome coronavirus 2- associated diseases. Torque Teno virus (TTV) is a ubiquitous and apathogenic virus which reflects the immune function of its host. The aim of this study was to investigate the association between obesity and TTV load - an indirect marker of compromised viral immune response.

Methods

TTV was quantified by TTV R-GENE® PCR in a total of 89 participants of which 30 were lean (BMI <25 kg/m2) and 59 were obese (BMI >30 kg/m2). For 38 subjects, follow-up was available after bariatric surgery.

Results

TTV load was higher in individuals with obesity (median 2.39, IQR: 1.69–3.33 vs. 1.88, IQR 1.08–2.43 log10 copies/mL; p = 0.027). Multivariable linear modeling revealed an independent association between TTV load and obesity. TTV was positively correlated with waist-to-hip ratio and inversely with 25OH vitamin D levels. Interleukin 6 and fasting insulin resistance were confounders of the association between TTV and obesity, while age was an effect modifier. TTV load increased by 87% (95% CI 2–243%) in the year following bariatric surgery.

Discussion

A higher TTV load in obese individuals may reflect compromised immune function and thus might serve for risk stratification of unfavorable outcomes during infectious disease, including coronavirus disease 2019, in this population. Our data warrant further analysis of TTV-based risk assessment in obese individuals in the context of infectious disease-associated outcomes.
Load shedding for frequency and voltage control in the multimachine system using a heuristic knowledge discovery method
Authors: Karn Amrendra Kumar , Hameed Salman , Sarfraz Mohammad , Ro Jong Suk , Khalid Mohd Rizwan
Published: September 2022

The voltage profile of different buses and the rotor dynamics of generators are adversely affected by a generator outage. Generator outages can be minimized using a variety of strategies and algorithms. An AI-based knowledge discovery approach has been reported in this article. This article proposes a technique for identifying sensitive loads and the amount of active and reactive power curtailment for rotor speed regulation and voltage management at the terminals. The MATLAB®/Simulink environment verifies and tests the method’s practicality on an IEEE-10-machine-39-bus system. Active power shedding is considered for rotor angle stability, while reactive power is also shedded for maintaining the terminal voltage at the loads. A sequential outage is considered to simulate a scenario where the two generators with the highest active and reactive power are taken out of service. The generator’s rotor speed, terminal voltage, and load are measured with and without load restriction. In all situations, the rotor and center of inertia speed are 1 p.u. The average steady-state load terminal voltage is 0.967 V. The average terminal voltage of all load buses improves from 0.933 to 0.972 and 0.936 to 0.971, case-wise. The reported results confirm and validate the effectiveness and applicability of the proposed technique.
Privacy-preserving deep learning for electricity consumer characteristics identification
Authors: Zhang Zhixiang , Lu Qian , Xu Hansong , Xu Guobin , Kong Fanyu , Yu You
Published: September 2022

Deep learning models trained from smart meter data have proven to be effective in predicting socio-demographic characteristics of electricity consumers, which can help retailers provide personalized service to electricity customers. Traditionally, deep learning models are trained in a centralized manner to gather large amounts of data to ensure effectiveness and efficiency. However, gathering smart meter data in plaintext may raise privacy concerns since the data is privately owned by different retailers. This indicates an imminent need for privacy-preserving deep learning. This paper proposes several secure multi-party computation (MPC) protocols that enable deep learning training and inference for electricity consumer characteristics identification while keeping the retailer’s raw data confidential. In our protocols, the retailers secret-share their raw data to three computational servers, which implement deep learning training and inference through lightweight replicated secret sharing techniques. We implement and benchmark multiple neural network models and optimization strategies. Comprehensive experiments are conducted on the Irish Commission for Energy Regulation (CER) dataset to verify that our MPC-based protocols have comparable performance.
Evaluation of regional environmental carrying capacity and its obstacle indicators diagnosis: Evidence from three major urban agglomerations in China
Authors: Cui Zhe , Wang Zhi-guo , Zhang Xue-rong , Wang Yu-yu , Zhang Miao
Published: September 2022

With rapid population growth and productivity development, the contradiction between economic and social development and resource and environmental protection is becoming increasingly prominent, so it is important to study the regional environmental carrying capacity to protect the environment and promote high-quality economic development. This study takes the three major urban agglomerations of Beijing-Tianjin-Hebei, Yangtze River Delta and Pearl River Delta as the research objects, and uses the entropy-weighted topsis model and the obstacle diagnosis model to evaluate the comprehensive environmental carrying capacity levels of the three major urban agglomerations and analyse their main obstacle factors. The results show that: 1) the average environmental carrying capacity level scores of the three major urban agglomerations during the study period were Beijing-Tianjin-Hebei (0.23103) > Yangtze River Delta (0.17687) > Pearl River Delta (0.16); 2) the degree of synergy between subsystems affects the environmental carrying capacity level; 3) China has still not achieved harmony between the environment and economic growth, and economic development is the main influencing factor for the level of environmental carrying capacity. In the future, it is recommended that each city cluster adhere to the construction of ecological civilization and vigorously develop high-tech and green industries; at the same time, give full play to the radiation-driven role of the regional core cities, make use of the synergistic effect of resource agglomeration and maximize the efficiency of resource utilization, so as to ultimately achieve the coordinated development of economic society and regional resources and environment.
Airborne small-footprint full-waveform LiDAR data for urban land cover classification
Authors: Qin Haiming , Zhou Weiqi , Zhao Wenhui
Published: September 2022

Airborne small-footprint full-waveform LiDAR data have a unique ability to characterize the landscape because it contains rich horizontal and vertical information. However, a few studies have fully explored its role in distinguishing different objects in the urban area. In this study, we examined the efficacy of small-footprint full-waveform LiDAR data on urban land cover classification. The study area is located in a suburban area in Beijing, China. Eight land cover classes were included: impervious ground, bare soil, grass, crop, tree, low building, high building, and water. We first decomposed waveform LiDAR data, from which a set of features were extracted. These features were related to amplitude, echo width, mixed ratio, height, symmetry, and vertical distribution. Then, we used a random forest classifier to evaluate the importance of these features and conduct the urban land cover classification. Finally, we assessed the classification accuracy based on a confusion matrix. Results showed that Afirst was the most important feature for urban land cover classification, and the other seven features, namely, ωfirst, HEavg, nHEavg, RAω, SYMS, Srise, and ωRf_fl, also played important roles in classification. The random forest classifier yielded an overall classification accuracy of 94.7%, which was higher than those from previous LiDAR-derived classifications. The results indicated that full-waveform LiDAR data could be used for high-precision urban land cover classification, and the proposed features could help improve the classification accuracy.
Machine learning-based transcriptome analysis of lipid metabolism biomarkers for the survival prediction in hepatocellular carcinoma
Authors: Xiong Ronghong , Wang Hui , Li Ying , Zheng Jingpeng , Cheng Yating , Liu Shunfang , Yang Guohua
Published: September 2022

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a very high fatality rate. Our goal in this study is to find a reliable lipid metabolism-related signature associated with prognostic significance for HCC. In this study, HCC lipid metabolism-related molecular subtype analysis was conducted based on the 243 lipid metabolism genes collected from the Molecular Signatures Database. Several significant disparities in prognosis, clinicopathological characteristics, and immune and ferroptosis-related status were found across the three subtypes, especially between C1 and C3 subgroups. Differential expression analysis yielded 57 differentially expressed genes (DEGs) between C1 and C3 subtypes. GO and KEGG analysis was employed for functional annotation. Three of 21 prognostic DEGs (CXCL8, SLC10A1, and ADH4) were finally selected through machine-learning-based discovery and validation strategy. The risk score = (0.103) × expression value of CXCL8 + (−0.0333) × expression value of SLC10A1 + (−0.0812) × expression value of ADH4. We used these three to construct a HCC prognostic risk model, which stratified the patients of the validation cohort into two risk subtypes with significantly different overall survival. Our work provides possible significance of the lipid metabolism-associated model in stratifying patient prognosis and its feasibility to guide therapeutic selection.
Frequent cleft lip and palate in families with pathogenic germline CDH1 variants
Authors: Green Benjamin L. , Fasaye Grace-Ann , Samaranayake Sarah G. , Duemler Anna , Gamble Lauren A. , Davis Jeremy L.
Published: September 2022

Pathogenic and likely pathogenic (P/LP) germline variants in the tumor suppressor gene CDH1 (E-cadherin) result in increased lifetime risk of diffuse-type gastric cancer and lobular breast cancer. CDH1 variants are also associated with hereditary cleft lip and palate (CLP), the mechanism of which is not well understood. We sought to determine the prevalence of CLP in families who carry P/LP CDH1 variants. Patients with P/LP CDH1 variants who were enrolled in a prospective clinical trial were reviewed (NCT03030404). The cohort included 299 individuals from 153 families that had 80 unique P/LP variants in CDH1. The rate of CLP was 19% (29/153) in families reporting CLP in at least one family member, and 2.7% (8/299) among individuals with confirmed germline CDH1 P/LP variants. There were 22 unique variants in CDH1 among the 29 families that reported CLP, or a CLP rate of 27.5% per variant (22/80). 10 of the variants were not previously reported to be associated with CLP. We observed that 24% (7/29) of CLP-associated gene variants involved large-scale (≥1 exon) deletions. Among families with CLP, 69% (20/29) had a member diagnosed with gastric cancer, and 79% (23/29) had a member with breast cancer, which were similar to rates observed in non-CLP families (p >0.3 for both). Our analysis suggests that the prevalence of CLP in families with germline CDH1 P/LP variants was high in this large cohort, and there was no genotype-phenotype pattern. Genetic testing for CDH1 variants should be considered in families with CLP and history of either diffuse-type gastric or lobular breast cancer.
A novel risk score model based on fourteen chromatin regulators-based genes for predicting overall survival of patients with lower-grade gliomas
Authors: Zhang Yongfeng , Yu Beibei , Tian Yunze , Ren Pengyu , Lyu Boqiang , Fu Longhui , Chen Huangtao , Li Jianzhong , Gong Shouping
Published: September 2022

Background: Low grade gliomas(LGGs) present vexatious management issues for neurosurgeons. Chromatin regulators (CRs) are emerging as a focus of tumor research due to their pivotal role in tumorigenesis and progression. Hence, the goal of the current work was to unveil the function and value of CRs in patients with LGGs.

Methods: RNA-Sequencing and corresponding clinical data were extracted from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) database. A single-cell RNA-seq dataset was sourced from the Gene Expression Omnibus (GEO) database. Altogether 870 CRs were retrieved from the published articles in top academic journals. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were applied to construct the prognostic risk model. Patients were then assigned into high- and low-risk groups based on the median risk score. The Kaplan–Meier (K-M) survival curve and receiver operating characteristic curve (ROC) were performed to assess the prognostic value. Sequentially, functional enrichment, tumor immune microenvironment, tumor mutation burden, drug prediction, single cell analysis and so on were analyzed to further explore the value of CR-based signature. Finally, the expression of signature genes were validated by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR).

Results: We successfully constructed and validated a 14 CRs-based model for predicting the prognosis of patients with LGGs. Moreover, we also found 14 CRs-based model was an independent prognostic factor. Functional analysis revealed that the differentially expressed genes were mainly enriched in tumor and immune related pathways. Subsequently, our research uncovered that LGGs patients with higher risk scores exhibited a higher TMB and were less likely to be responsive to immunotherapy. Meanwhile, the results of drug analysis offered several potential drug candidates. Furthermore, tSNE plots highlighting the magnitude of expression of the genes of interest in the cells from the scRNA-seq assay. Ultimately, transcription expression of six representative signature genes at the mRNA level was consistent with their protein expression changes.

Conclusion: Our findings provided a reliable biomarker for predicting the prognosis, which is expected to offer new insight into LGGs management and would hopefully become a promising target for future research.
Cutaneous kinase activity correlates with treatment outcomes following PI3K delta inhibition in mice with experimental pemphigoid diseases
Authors: Ghorbanalipoor Saeedeh , Emtenani Shirin , Parker Melissa , Kamaguchi Mayumi , Osterloh Colin , Pigors Manuela , Gross Natalie , Khil’chenko Stanislav , Kasprick Anika , Patzelt Sabrina , Wortmann Diana , Ibrahim Ibrahim O. , Izumi Kentaro , Goletz Stephanie , Boch Katharina , Kalies Kathrin , Bieber Katja , Smith Paul , Schmidt Enno , Ludwig Ralf J.
Published: September 2022

Chronic blistering at the skin and/or mucous membranes, accompanied by a varying degree of inflammation, is the clinical hallmark of pemphigoid diseases that impose a major medical burden. Pemphigoid diseases are caused by autoantibodies targeting structural proteins of the epithelial basement membrane. One major pathogenic pathway of skin blistering and inflammation is activation of myeloid cells following Fc gamma receptor-dependent binding to the skin-bound immune complexes. This process requires activation of specific kinases, such as PI3Kδ, which have emerged as potential targets for the treatment of pemphigoid diseases. Yet, it is unknown if global cutaneous kinase activity present in lesional pemphigoid disease correlates with therapeutic effects following treatment with a given target-selective kinase inhibitor. To address this, we here first determined the kinase activity in three different mouse models of pemphigoid diseases: Antibody transfer-induced mucous membrane pemphigoid (MMP), antibody transfer-induced epidermolysis bullosa acquisita (EBA) and immunization-induced EBA. Interestingly, the kinome signatures were different among the three models. More specifically, PI3Kδ was within the kinome activation network of antibody transfer-induced MMP and immunization-induced EBA, but not in antibody transfer-induced EBA. Next, the therapeutic impact of the PI3Kδ-selective inhibitor parsaclisib was evaluated in the three model systems. In line with the kinome signatures, parsaclisib had therapeutic effects in antibody transfer-induced MMP and immunization-induced EBA, but not in autoantibody-induced EBA. In conclusion, kinase activation signatures of inflamed skin, herein exemplified by pemphigoid diseases, correlate with the therapeutic outcomes following kinase inhibition, demonstrated here by the PI3Kδ inhibitor parsaclisib.
Skin-to-blood pH shift triggers metabolome and proteome global remodelling in Staphylococcus epidermidis
Authors: Gonçalves Luis Gafeira , Santos Susana , Gomes Laidson Paes , Armengaud Jean , Miragaia Maria , Coelho Ana Varela
Published: September 2022

Staphylococcus epidermidisis one of the most common bacteria of the human skin microbiota. Despite its role as a commensal,S. epidermidishas emerged as an opportunistic pathogen, associated with 80% of medical devices related infections. Moreover, these bacteria are extremely difficult to treat due to their ability to form biofilms and accumulate resistance to almost all classes of antimicrobials. Thus new preventive and therapeutic strategies are urgently needed. However, the molecular mechanisms associated withS. epidermidiscolonisation and disease are still poorly understood. A deeper understanding of the metabolic and cellular processes associated with response to environmental factors characteristic of SE ecological niches in health and disease might provide new clues on colonisation and disease processes. Here we studied the impact of pH conditions, mimicking the skin pH (5.5) and blood pH (7.4), in aS. epidermidiscommensal strain by means of next-generation proteomics and1H NMR-based metabolomics. Moreover, we evaluated the metabolic changes occurring during a sudden pH change, simulating the skin barrier break produced by a catheter. We found that exposure ofS. epidermidisto skin pH induced oxidative phosphorylation and biosynthesis of peptidoglycan, lipoteichoic acids and betaine. In contrast, at blood pH, the bacterial assimilation of monosaccharides and its oxidation by glycolysis and fermentation was promoted. Additionally, several proteins related to virulence and immune evasion, namely extracellular proteases and membrane iron transporters were more abundant at blood pH. In the situation of an abrupt skin-to-blood pH shift we observed the decrease in the osmolyte betaine and changes in the levels of several metabolites and proteins involved in cellular redoxl homeostasis. Our results suggest that at the skin pHS. epidermidiscells are metabolically more active and adhesion is promoted, while at blood pH, metabolism is tuned down and cells have a more virulent profile. pH increase during commensal-to-pathogen conversion appears to be a critical environmental signal to the remodelling of theS. epidermidismetabolism toward a more pathogenic state. TargetingS. epidermidisproteins induced by pH 7.4 and promoting the acidification of the medical device surface or surrounding environment might be new strategies to treat and preventS. epidermidisinfections.
Phenotypic and molecular characterization of IMP-producing Enterobacterales in Spain: Predominance of IMP-8 in Klebsiella pneumoniae and IMP-22 in Enterobacter roggenkampii
Authors: Cañada-García Javier E. , Grippo Natalin , de Arellano Eva Ramírez , Bautista Verónica , Lara Noelia , Navarro Ana María , Cabezas Teresa , Martínez-Ramírez Nora Mariela , García-Cobos Silvia , Calvo Jorge , Cercenado Emilia , Aracil Belén , Pérez-Vázquez María , Oteo-Iglesias Jesús ,   the Spanish IMP Study Group
Published: September 2022

Objectives

Little is known about IMP-producing Enterobacterales (IMP-Ent) in Europe. We analyzed at genomic and phenotypic level IMP-Ent isolates circulating in Spain in a 9-year period.

Materials and methods

IMP-Ent isolates submitted to our reference laboratory were included. Antibiotic susceptibility was performed using microdilution method (EUCAST), and IMP-carbapenemase activity was measured with carbapenemase inhibitors, the β-CARBA method, the modified Hodge test (MHT), and the modified carbapenemase inhibition method (mCIM). All isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.

Results

Fifty IMP-Ent isolates, collected from 19 hospitals in 13 Spanish provinces, were detected: Klebsiella pneumoniae (IMP-Kpn) (24; 48%), Enterobacter roggenkampii (13; 26%), Enterobacter hormaechei (8, 16%), Klebsiella oxytoca (two; 4%), Enterobacter asburiae (one, 2%), Serratia marcescens (one; 2%) and Escherichia coli (one; 2%). All isolates were positive by the MHT and β-CARBA tests; 48 (96%) were mCIM positive; 12 (24%) and 26 (52%) displayed positive inhibition with dipicolinic (meropenem) and EDTA (ertapenem), respectively. Five IMP-carbapenemase types were identified: IMP-8 (22; 44%), IMP-22 (17; 34%), IMP-13 (7; 14%), IMP-28 (two; 4%), and IMP-15 (two; 4%), predominating IMP-8 in K. pneumoniae and IMP-22 in E. roggenkampii. IMP-28 was exclusively identified in K. oxytoca and IMP-15 in E. hormaechei. Predominant STs were ST405 (29.2%), ST15 (25%) and ST464 (20.8%) in IMP-Kpn; ST96 (100%) in E. roggenkampii and ST182 (62.5%) in E. hormachei. Colistin and amikacin were the most active non-carbapenem antibiotics against IMP-Ent.

Conclusion

IMP-Ent isolates remain infrequent in Spain, although in recent years have been circulating causing nosocomial outbreaks, being IMP-8-producing K. pneumoniae and IMP-22-producing E. roggenkampii the most frequently detected in this study. Inhibition with EDTA or dipicolinic acid presented false negative results in some IMP-producing strains. Active microbiological and molecular surveillance is essential for a better comprehension and control of IMP-Ent dissemination.
Invasive group B Streptococcus strains and clinical characteristics in Danish infants from 1999 to 2009
Authors: Andersen Mads , Smith Birgitte , Murra May , Nielsen Stine Yde , Slotved Hans-Christian , Henriksen Tine Brink
Published: September 2022

Background

Group B Streptococcus (GBS) infection in infants may result in both respiratory, cardiovascular, and neurological dysfunction and ultimately death of the infant. Surveillance of GBS strains in infants and their clinical characteristics guide development of effective vaccines and other potential treatments and may have implications for future prognostics and infant care. Therefore, we aimed to study GBS serotypes and clonal complexes (CC) in Danish infants with early onset infection (EOD) (0–6 days of life) and late-onset infection (LOD) (7–89 days of life) and to estimate the association between GBS strain and different clinical outcomes.

Methods

We included Danish infants less than 3 months of age with GBS isolates from blood or cerebrospinal fluid between 1999 and 2009. GBS isolates were analyzed by serotyping and multilocus sequence typing with classification of isolates into clonal complexes. Clinical characteristics were obtained by questionnaires completed by tending pediatrician including gestational age, Apgar scores, age at onset, meningitis, symptom severity, treatment duration, and mortality. Symptom severities were reported within neurological symptoms, need for respiratory or circulatory support, and treatment of disseminated intravascular coagulation.

Results

A total of 212 GBS isolates were collected with 129 from EOD and 83 from LOD. The dominating GBS strains were III/CC17 (41%), Ia/CC23 (17%), III/CC19 (15%), Ib/CC8-10 (7%), and V/CC1 (6%). Strain Ia/CC23 was mostly found in EOD, while III/CC17 was widespread in LOD, though being the most common in both EOD and LOD. Strain III/CC17 and Ia/CC23 had highest percentage of samples from cerebrospinal fluid (26%), while III/CC19 had the least (8%). Strain III/CC19 had highest mortality with about one fifth of infected infants dying (22%) followed by Ia/CC23 (16%), Ib/CC8-10 (9%), and then III/CC17 (6%). The symptom severity varied between strains, but with no strain consistently resulting in more severe symptoms.

Conclusion

Some potential differences in disease severity were observed between the different strains. These findings emphasize the continuous need for multimodal surveillance of infant GBS strains and their clinical characteristics to optimize development of GBS vaccines and other potential treatments.
Plant NLRs: Evolving with pathogen effectors and engineerable to improve resistance
Authors: Zhang Biaoming , Liu Mengting , Wang Yanchao , Yuan Wenya , Zhang Haitao
Published: September 2022

Pathogens are important threats to many plants throughout their lifetimes. Plants have developed different strategies to overcome them. In the plant immunity system, nucleotide-binding domain and leucine-rich repeat-containing proteins (NLRs) are the most common components. And recent studies have greatly expanded our understanding of how NLRs function in plants. In this review, we summarize the studies on the mechanism of NLRs in the processes of effector recognition, resistosome formation, and defense activation. Typical NLRs are divided into three groups according to the different domains at their N termini and function in interrelated ways in immunity. Atypical NLRs contain additional integrated domains (IDs), some of which directly interact with pathogen effectors. Plant NLRs evolve with pathogen effectors and exhibit specific recognition. Meanwhile, some NLRs have been successfully engineered to confer resistance to new pathogens based on accumulated studies. In summary, some pioneering processes have been obtained in NLR researches, though more questions arise as a result of the huge number of NLRs. However, with a broadened understanding of the mechanism, NLRs will be important components for engineering in plant resistance improvement.
The microbiome of the dinoflagellate Prorocentrum cordatum in laboratory culture and its changes at higher temperatures
Authors: Sanchez-Garcia Selene , Wang Hui , Wagner-Döbler Irene
Published: September 2022

In the ocean, phytoplankton are dependent on communities of bacteria living in the phycosphere, a hot spot of metabolic and genetic exchange. Many types of interactions between phytoplankton and phycosphere bacteria have been shown, but it is unclear if the microbial communities associated with microalgae strains in culture collections are beneficial or harmful to the host strain. Here, we studied the microbial communities associated with four strains of the dinoflagellate Prorocentrum cordatum that had been isolated from distant geographical locations and maintained in culture collection for hundreds of generations. Community composition was determined by 16S rRNA gene amplicon sequencing. The dinoflagellate host strain was the strongest parameter separating communities, while growth phase, lifestyle (particle-attached versus free-living) and temperature had only a modulating effect. Although the strains had been isolated from distant locations in the Atlantic and Pacific Ocean, 14 ASVs were shared among all strains, the most abundant ones being Gilvibacter, Marivita, uncultivated Rhodobacteraceae, Marinobacter, Hyphomonadaceae, Cupriavidus, Variovorax, and Paucibacter. Adaptation to higher temperatures resulted in specific changes in each phycosphere microbiome, including increased abundance of rare community members. We then compared the growth of the four xenic cultures to that of the axenic P. cordatum CCMP1329. At 20°C, growth of the xenic cultures was similar or slower than that of CCMP1329. At 26°C, all four xenic cultures experienced a death phase, while the axenic culture stably remained in the stationary phase. At 30°C, only two of the xenic cultures were able to grow. A shift of dinoflagellate metabolism from autotrophy to mixotrophy and competition between dinoflagellate and bacteria for limiting nutrients, including essential vitamins, may contribute to these differences in growth patterns.
Prelimbic cortex responds to male ultrasonic vocalizations in the presence of a male pheromone in female mice
Authors: Asaba Akari , Nomoto Kensaku , Osakada Takuya , Matsuo Tomohiko , Kobayakawa Ko , Kobayakawa Reiko , Touhara Kazushige , Mogi Kazutaka , Kikusui Takefumi
Published: September 2022

Sensory signals are critical to perform adaptive social behavior. During copulation, male mice emit ultrasonic vocalizations (USVs). Our previous studies have shown that female mice exhibit approach behavior toward sound sources of male USVs and that, after being exposed to a male pheromone, exocrine gland-secreting peptide 1 (ESP1), female mice exhibited a preference toward a particular type of male USVs. These findings suggest that male USVs modulate female courtship behavior. However, it remains unclear which brain regions and what cell types of neurons are involved in neuronal processing of male USVs. To clarify this issue, immediate early gene analysis, behavioral analysis, and neurochemical analysis were performed. The in situ hybridization analysis of c-fos mRNA in multiple brain regions showed that neurons in the prelimbic cortex were responsive to presentation of male USVs in the presence of ESP1. Furthermore, this study found that activity of prelimbic cortex was correlated with the duration of female exploration behavior toward a sound source of the USVs. Finally, by using double immunohistochemistry, the present study showed that the prelimbic neurons responding to the presentation of male USVs were presumably excitatory glutamatergic neurons. These results suggest that the prelimbic cortex may facilitate female courtship behavior in response to male USVs.
Case report: IgG4-related intracranial lesions mimicking multiple sclerosis in a 14-year-old girl
Authors: Qing Pingying , Lu Chenyang , Yan Bing , Liu Chang , Fox David A. , Zhao Yi , Liu Yi , Tan Chunyu
Published: September 2022

Objectives

IgG4-related disease (IgG4-RD) is distinguished by the infiltration of IgG4-positive plasma cells in a variety of tissues and organs. Even so, central nervous system lesions associated with IgG4-RD are scarce. We present a case of IgG4-related brain parenchymal lesions that mimics multiple sclerosis in a young girl.

Methods

The patient was followed by our neurology and rheumatology teams. Clinical information was recorded, and the brain was screened using magnetic resonance imaging (MRI). During follow-up, we examined serum IgE, IgG and IgG4 and lymph node biopsy.

Results

Here, we presented details of a 14-year-old Chinese girl suffering from diplopia, left eyelid ptosis, right facial numbness, and right lower limb weakness admitted to our institute. Brain MRI revealed multiple sclerosis-like lesions in the brain parenchyma and spinal cord. During the follow-up, she developed lymphadenopathy. Elevation of serum, IgG, IgG4 and IgE and lymph node biopsy favors a diagnosis of IgG4-RD. The patient had a good response to glucocorticoids and mycophenolate mofetil. The literature review summarized eight previously reported IgG4-RD involving brain parenchyma.

Discussion

Our case expands the known age spectrum of IgG4-RD. The intracranial IgG4-RD is rare and could mimic multiple sclerosis. Careful examination and dynamic review of disease history are crucial in the differential diagnosis.