bluuebunny/crossref_metadata_2025 huggingface dataset:
O teatro para o desenvolvimento humano nas organizações empresairais
Authors: Renaud Carla Helaine , Rosseto Robson
Published: March 2023

Com o avanço da tecnologia, a partir da década de 1990, o padrão profissional antes apreciado mudou: exigia, agora, um trabalhador mais dinâmico, proativo e flexível. A tecnologia, que veio para auxiliar no processo de produção das organizações, também resultou em uma baixa nesta produtividade. O homem tornou-se completamente dependente dela e isto o adoeceu. O estresse apareceu como um obstáculo no crescimento das organizações, uma vez que as doenças derivadas deste problema causam um bloqueio físico e mental do profissional, provocando, assim, perda em qualidade de vida. O artigo a seguir propõe o teatro, em suas diversas formas, como uma maneira de amenizar este sintoma e auxiliar no desenvolvimento organizacional.
Entrevista com a Professora de Musicoterapeuta Eulide Jazar Weibel.
Authors: InCantare Revista
Published: March 2023

Nossa revista continua perseguindo o objetivo de publicar as histórias e opiniões de pessoas que colaboraram com a construção do curso de Musicoterapia e que, com empenho e perseverança, abriram caminhos para a colocação da profissão em diferentes instituições no Paraná. A Professora e Musicoterapeuta Eulide Jazar Weibelfoi a entrevistada desta edição. Professora da Faculdade de Artes do Paraná-FAP, aposentou-se no ano de 2012, quando exercia o cargo de vice-diretora. Musicoterapeuta atuante e sempre envolvida com o processo de divulgação do curso e da profissão, o entusiasmo com que desenvolveu seu trabalho foi marcante.Com a espontaneidade que lhe é característica, ela relatou dados de sua biografia musical e os caminhos que a levaram a trabalhar no âmbito musicoterapêutico
IMPACTOS DA QUARTA REVOLUÇÃO INDUSTRIAL NA EDUCAÇÃO
Authors: Camargo Leonardo Nunes , Da Luz Lara Emanuele
Published: March 2023

É evidente que a tecnologia assumiu na contemporaneidade um poder autônomo que influencia de maneira decisiva a existência humana. A cada momento ficamos mais familiarizados com novas tecnologias como: robótica, inteligência artificial, big data, biotecnologia, internet das coisas, impressão 3D, nanotecnologia, etc., tudo isso, faz parte daquilo que chamamos de quarta revolução industrial. O objetivo desse artigo é analisar, a partir de um ponto de vista filosófico, as influências desta revolução na sociedade, principalmente em relação à educação. Por isso, primeiramente analisaremos o contexto histórico desta nova revolução industrial; posteriormente analisaremos sob a ótica de Byung-Chul Han os impactos produzidos na sociedade tecnológica diante da exposição que esta quarta revolução industrial provoca. Ou seja, abordaremos que em uma sociedade transparente e aberta, precisamos da educação como elemento de reflexão e guia para nossas ações.
Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C
Authors: Maltz-Matyschsyk Michele , Melchiorre Clare K. , Herbst Katherine W. , Hogan Alexander H. , Dibble Kristina , O’Sullivan Brandon , Graf Joerg , Jadhav Aishwarya , Lawrence David A. , Lee William T. , Carson Kyle J. , Radolf Justin D. , Salazar Juan C. , Lynes Michael A. ,   Connecticut Children’s COVID Collaborative
Published: March 2023

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4–6 weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5–13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19. Unfortunately, diagnosis of MIS-C is difficult, and delayed diagnosis can lead to cardiogenic shock, intensive care admission, and prolonged hospitalization. There is no validated biomarker for the rapid diagnosis of MIS-C. In this study, we used Grating-coupled Fluorescence Plasmonic (GCFP) microarray technology to develop biomarker signatures in pediatric salvia and serum samples from patients with MIS-C in the United States and Colombia. GCFP measures antibody-antigen interactions at individual regions of interest (ROIs) on a gold-coated diffraction grating sensor chip in a sandwich immunoassay to generate a fluorescent signal based on analyte presence within a sample. Using a microarray printer, we designed a first-generation biosensor chip with the capability of capturing 33 different analytes from 80 μL of sample (saliva or serum). Here, we show potential biomarker signatures in both saliva and serum samples in six patient cohorts. In saliva samples, we noted occasional analyte outliers on the chip within individual samples and were able to compare those samples to 16S RNA microbiome data. These comparisons indicate differences in relative abundance of oral pathogens within those patients. Microsphere Immunoassay (MIA) of immunoglobulin isotypes was also performed on serum samples and revealed MIS-C patients had several COVID antigen-specific immunoglobulins that were significantly higher than other cohorts, thus identifying potential new targets for the second-generation biosensor chip. MIA also identified additional biomarkers for our second-generation chip, verified biomarker signatures generated on the first-generation chip, and aided in second-generation chip optimization. Interestingly, MIS-C samples from the United States had a more diverse and robust signature than the Colombian samples, which was also illustrated in the MIA cytokine data. These observations identify new MIS-C biomarkers and biomarker signatures for each of the cohorts. Ultimately, these tools may represent a potential diagnostic tool for use in the rapid identification of MIS-C.
The phosphoproteome of choroid plexus epithelial cells following infection with Neisseria meningitidis
Authors: Herold Rosanna , Denzer Lea , Muranyi Walter , Stump-Guthier Carolin , Ishikawa Hiroshi , Schroten Horst , Schwerk Christian
Published: March 2023

The Gram-negative bacterium Neisseria meningitidis, which causes meningitis in humans, has been demonstrated to manipulate or alter host signalling pathways during infection of the central nervous system (CNS). However, these complex signalling networks are not completely understood. We investigate the phosphoproteome of an in vitro model of the blood-cerebrospinal fluid barrier (BCSFB) based on human epithelial choroid plexus (CP) papilloma (HIBCPP) cells during infection with the N. meningitidis serogroup B strain MC58 in presence and absence of the bacterial capsule. Interestingly, our data demonstrates a stronger impact on the phosphoproteome of the cells by the capsule-deficient mutant of MC58. Using enrichment analyses, potential pathways, molecular processes, biological processes, cellular components and kinases were determined to be regulated as a consequence of N. meningitidis infection of the BCSFB. Our data highlight a variety of protein regulations that are altered during infection of CP epithelial cells with N. meningitidis, with the regulation of several pathways and molecular events only being detected after infection with the capsule-deficient mutant. Mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD038560.
Helicobacter pylori infection increases the risk of thyroid nodules in adults of Northwest China
Authors: Di Jia , Ge Zhuang , Xie Qingwei , Kong Danfeng , Liu Sha , Wang Pengwei , Li Jie , Ning Ning , Qu Wei , Guo Rong , Chang Danyan , Zhang Jun , Zheng Xiang-hong
Published: March 2023

Background

Thyroid nodules (TNs) are very common in the adults of Northwest China. The role of Helicobacter pylori (H. pylori) infection in TNs is poorly investigated and even with controversial conclusions. Our study aimed at highlighting the relationship between H. pylori infection and the risk of TNs.

Methods

9,042 individuals were enrolled with thyroid ultrasonography and 14C-urea breath test (14C-UBT). Baseline characteristics and relevant covariates were obtained, including basic and laboratory indicators. After applying the exclusion criteria, 8,839 patients were included and divided into 2 groups: a cross-sectional study of single follow-up (n=8,711) and a retrospective cohort study of multiple follow-ups for 5 years (n=139).

Results

The prevalence of H. pylori infection and TNs was 39.58% and 47.94% in the adults of Northwest China, respectively. The prevalence of TNs was significantly higher among H. pylori-positive individuals than those without infection (52.55% vs. 44.92%, p<0.01). The result of binary logistic regression revealed that the crude odds ratio (OR) was 1.624 (95% CI 1.242~2.123) in Model 1 without adjustment compared to H. pylori-negative group, and was also positive in Model 2, 3, and 4 (Model 2: OR=1.731, 95% CI 1.294~2.316; Model 3: OR=2.287, 95% CI 1.633~3.205; Model 4: OR=2.016, 95% CI 1.390~2.922) after the adjustment. The data of 5-year follow-up showed that the annual incidence of TNs was significantly higher in individuals with persistent H. pylori infection than non-infected counterparts (all p<0.05).

Conclusions

H. pylori is an independent risk factor for TNs in the adults of Northwest China.
Research progress on complications of Brucellosis
Authors: Jin Min , Fan Zixu , Gao Ruifang , Li Xingnan , Gao Zhixiang , Wang Zhanli
Published: March 2023

Brucellosis is a common zoonotic disease that is widely spread worldwide and poses a major threat to human health. Clinically, it often presents with non-specific symptoms such as fever, excessive sweating, malaise, myalgia, arthralgia, loss of appetite, weight loss, and enlarged liver, spleen and lymph nodes. The disease has a long and recurrent course, often accumulating in multiple systems and organs. Of these, osteoarticular involvement is the most common complication, with a prevalence of approximately 2-77%, usually manifesting as spondylitis, sacroiliac arthritis and peripheral arthritis. Hepatosplenomegaly is seen in about 50% of patients with brucellosis, and gastrointestinal disturbances such as abdominal pain, nausea, and vomiting are common. Although respiratory involvement is less common, pneumonia, pleurisy, pleural effusion, and pulmonary nodules have been reported. Besides, approximately 2-20% of cases involve infections of the male genitourinary system, mainly manifesting as unilateral epididymal-orchitis and orchitis. The most serious complication facing brucellosis is cardiovascular involvement, and although the overall mortality rate of brucellosis is about 1% and the incidence of brucellosis endocarditis is less than 2%, more than 80% of deaths are associated with endocarditis. Furthermore, brucellosis is complicated by hematologic disease, with anemia occurring in approximately 20-53% of children during the acute phase. In addition, the neurological incidence of brucellosis is about 0.5-25%, mainly manifested as meningitis. In this study, we review the multisystem complications of brucellosis with the aim of improving early diagnosis, timely treatment and prevention of long-term complications.
Statistical optimization of a podoviral anti-MRSA phage CCASU-L10 generated from an under sampled repository: Chicken rinse
Authors: Abd-Allah Israa M. , El-Housseiny Ghadir S. , Al-Agamy Mohamed H. , Radwan Hesham H. , Aboshanab Khaled M. , Hassouna Nadia A.
Published: March 2023

Introduction

The insurgence of antimicrobial resistance is an imminent health danger globally. A wide range of challenging diseases are attributed to methicillin-resistant Staphylococcus aureus (MRSA) as it is weaponized with a unique array of virulence factors, and most importantly, the resistance it develops to most of the antibiotics used clinically. On that account, the present study targeted the optimization of the production of a bacteriophage active against MRSA, and evaluating some of its characters.

Methods and results

The bacteriophage originated from a quite peculiar environmental source, raw chicken rinse and was suggested to belong to Podoviridae, order Caudovirales. It withstood a variety of extreme conditions and yield optimization was accomplished via the D-optimal design by response surface methodology (RSM). A reduced quadratic model was generated, and the ideal production conditions recommended were pH 8, glycerol 0.9% v/v, peptone 0.08% w/v, and 107 CFU/ml as the host inoculum size. These conditions led to a two-log fold increase in the phage titer (1.17x10¹² PFU/ml), as compared to the regular conditions.

Discussion

To conclude, statistical optimization successfully enhanced the output of the podoviral phage titer by two-log fold and therefore, can be regarded as a potential scale-up strategy. The produced phage was able to tolerate extreme environmental condition making it suitable for topical pharmaceutical preparations. Further preclinical and clinical studies are required to ensure its suitability for use in human.
Long-term variations in trophic groups of coral reef fishes in the lagoon of Meiji Reef in the South China Sea
Authors: Zhang Jun , Gong Yuyan , Cai Yancong , Yang Yutao , Chen Zuozhi
Published: March 2023

Fishes play significant ecological functions though many ways in coral reef, and feeding process is one of the most important. To understand responses of reef fish communities to external disturbances, we studied variations in trophic groups of fishes in the lagoon of Meiji Reef in the South China Sea based on fish specimens collected by hand-line and gillnet in 1998—2018, databases and literatures. Differences in species richness, abundance, weight and size of fish in different trophic groups among years were analysed, especially herbivorous and high-economy fish. The results indicated that the percentages of species number and weight of herbivores, piscivores and detritivores decreased significantly from 1998—1999/2016—2018. Herbivorous fishes saw the biggest decline. In the gillnet surveys, the percentages of species number and weight of herbivorous fishes in 1999 were 33.33% and 56.14%, respectively, while the percentages in 2016—2018 were all zero. The species number percentage of large-sized fishes (maximum total length ≥ 65 cm) in 1998—1999 was significantly larger than that in 2016—2018. Thirty-two fish species being found in the lagoon of Meiji Reef during 1998—1999 were not discovered during 2012—2018. Contingency table analysis showed that the disappearance of fish was not significantly related to the vulnerability or resilience of fish rather than economic value. The mean body weight of very high & high-value fish in 1998—1999 was significantly larger than that in 2016—2018. Simple linear regression showed that coral cover had the greater effect on the species number and weight of herbivorous fishes as compare to fishing power. Both fishing power and coral cover had significant effects on the mean body weight. To protect fish on Meiji Reef, we propose to strengthen the conservation initiatives (e.g., creating protected areas, prohibiting fishing, and reconstructing habitat).
Evidencing subtle faults in deep seismic reflection profiles: Data pre-conditioning and seismic attribute analysis of the legacy CROP-04 profile
Authors: Ercoli Maurizio , Carboni Filippo , Akimbekova Assel , Carbonell Ramon Bertran , Barchi Massimiliano Rinaldo
Published: March 2023

Legacy seismic reflection data constitute infrastructure of tremendous value for basic research. This is especially relevant in seismically hazardous areas, as such datasets can significantly contribute to the seismotectonic characterization of the region. The quality of the data and the resulting image can be effectively improved by using modern tools, such as pre-conditioning techniques and seismic attributes. The latter are extensively used by the hydrocarbon exploration industry, but are still only poorly applied to the study of active faults. Pre-conditioning filters are effective in removing random noise, which hampers the detection of subtle geologic structures (i.e., normal faults). In this study, a workflow including pre-conditioning and extraction of seismic attributes is used to improve the quality of the CROP-04 deep seismic reflection profile. CROP-04 was acquired in the 1980s across the Southern Apennines mountain range, one of the most hazardous seismically active regions in Italy. The results show the capacity of this method to extract, from low-resolution legacy data, subtle seismic fabrics that correspond to a dense network of fault sets. These seismic signatures and the enhanced discontinuities disrupting the reflections, which were invisible in the original data, correlate well with the main regional normal faults outcropping at the surface. Moreover, the data reveal higher structural complexity, due to many secondary synthetic and antithetic structures, knowledge of which is useful in modeling of the local and regional distribution of the deformation and potentially in guiding future field mapping of active faults. This proposed approach and workflow can be extended to seismotectonic studies of other high-hazard regions worldwide, where seismic reflection data are available.
Adverse cardiovascular effect following gonadotropin-releasing hormone antagonist versus GnRH agonist for prostate cancer treatment: A systematic review and meta-analysis
Authors: Gu Li , Li Xurui , Liu Wentao
Published: March 2023

Background

Androgen deprivation therapy is the mainstay of medical treatment for prostate cancer (Pca); however, it is associated with an increased risk of adverse cardiovascular (CV) events and death. To date, CV death has been the leading noncancer cause of death in Pca patients. Both GnRH antagonists (an emerging class of drugs) and GnRH agonists (most frequently prescribed) are efficacious against Pca. However, the adverse effects, especially the adverse CV effect between them remain unclear.

Methods

Through a literature search using MEDLINE, EMBASE and the Cochrane Library, all available studies comparing the safety of CV risk between GnRH antagonists and GnRH agonists in Pca patients were extracted. Comparisons of outcomes of interest between these two classes of drugs were calculated using the risk ratio (RR). Subgroup analyses were performed depending on the study design and preexisting CV disease at baseline.

Results

Nine randomized controlled clinical trials (RCTs) and five real-world observational studies comprising 62160 Pca patients were included in our meta-analysis. Patients receiving GnRH antagonists experienced fewer CV events (RR: 0.66, 95% CI:0.53-0.82, P<0.001), CV death (RR:0.4, 95% CI: 0.24-0.67, P<0.001) and myocardial infarctions (RR: 0.71, 95% CI: 0.52-0.96, P=0.03). No difference was found in the incidence of stroke and heart failure. Moreover, GnRH antagonists were associated with fewer CV events in patients with preexisting CV disease but not in those without preexisting CV disease in the RCT series.

Conclusion

GnRH antagonists appear to offer favorable safety in terms of adverse CV events and CV death compared with GnRH agonists among men diagnosed with Pca, especially those who had established CV disease at baseline.

Systematic review registration

https://inplasy.com/inplasy-2023-2-0009/, identifier INPLASY202320009.
Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy
Authors: Cheng Yanan , Wang Yan , Yin Ruili , Xu Yongsong , Zhang Lijie , Zhang Yuanyuan , Yang Longyan , Zhao Dong
Published: March 2023

Diabetic cardiomyopathy (DCM), a main cardiovascular complication of diabetes, can eventually develop into heart failure and affect the prognosis of patients. Myocardial fibrosis is the main factor causing ventricular wall stiffness and heart failure in DCM. Early control of myocardial fibrosis in DCM is of great significance to prevent or postpone the progression of DCM to heart failure. A growing body of evidence suggests that cardiomyocytes, immunocytes, and endothelial cells involve fibrogenic actions, however, cardiac fibroblasts, the main participants in collagen production, are situated in the most central position in cardiac fibrosis. In this review, we systematically elaborate the source and physiological role of myocardial fibroblasts in the context of DCM, and we also discuss the potential action and mechanism of cardiac fibroblasts in promoting fibrosis, so as to provide guidance for formulating strategies for prevention and treatment of cardiac fibrosis in DCM.
Recent advances of long non-coding RNAs in control of hepatic gluconeogenesis
Authors: Wang Zhe , Ma Jinyu , Wu Runze , Kong Yinghong , Sun Cheng
Published: March 2023

Gluconeogenesis is the main process for endogenous glucose production during prolonged fasting, or certain pathological conditions, which occurs primarily in the liver. Hepatic gluconeogenesis is a biochemical process that is finely controlled by hormones such as insulin and glucagon, and it is of great importance for maintaining normal physiological blood glucose levels. Dysregulated gluconeogenesis induced by obesity is often associated with hyperglycemia, hyperinsulinemia, and type 2 diabetes (T2D). Long noncoding RNAs (lncRNAs) are involved in various cellular events, from gene transcription to protein translation, stability, and function. In recent years, a growing number of evidences has shown that lncRNAs play a key role in hepatic gluconeogenesis and thereby, affect the pathogenesis of T2D. Here we summarized the recent progress in lncRNAs and hepatic gluconeogenesis.
Uncovering a novel role of focal adhesion and interferon-gamma in cellular rejection of kidney allografts at single cell resolution
Authors: Halawi Ahmad , El Kurdi Abdullah B. , Vernon Katherine A. , Solhjou Zhabiz , Choi John Y. , Saad Anis J. , Younis Nour K. , Elfekih Rania , Mohammed Mostafa Tawfeek , Deban Christa A. , Weins Astrid , Abdi Reza , Riella Leonardo V. , De Serres Sasha A. , Cravedi Paolo , Greka Anna , Khoueiry Pierre , Azzi Jamil R.
Published: March 2023

Background

Kidney transplant recipients are currently treated with nonspecific immunosuppressants that cause severe systemic side effects. Current immunosuppressants were developed based on their effect on T-cell activation rather than the underlying mechanisms driving alloimmune responses. Thus, understanding the role of the intragraft microenvironment will help us identify more directed therapies with lower side effects.

Methods

To understand the role of the alloimmune response and the intragraft microenvironment in cellular rejection progression, we conducted a Single nucleus RNA sequencing (snRNA-seq) on one human non-rejecting kidney allograft sample, one borderline sample, and T-cell mediated rejection (TCMR) sample (Banff IIa). We studied the differential gene expression and enriched pathways in different conditions, in addition to ligand-receptor (L-R) interactions.

Results

Pathway analysis of T-cells in borderline sample showed enrichment for allograft rejection pathway, suggesting that the borderline sample reflects an early rejection. Hence, this allows for studying the early stages of cellular rejection. Moreover, we showed that focal adhesion (FA), IFNg pathways, and endomucin (EMCN) were significantly upregulated in endothelial cell clusters (ECs) of borderline compared to ECs TCMR. Furthermore, we found that pericytes in TCMR seem to favor endothelial permeability compared to borderline. Similarly, T-cells interaction with ECs in borderline differs from TCMR by involving DAMPS-TLRs interactions.

Conclusion

Our data revealed novel roles of T-cells, ECs, and pericytes in cellular rejection progression, providing new clues on the pathophysiology of allograft rejection.
Three-dimensional and single-cell sequencing of liver cancer reveals comprehensive host-virus interactions in HBV infection
Authors: Guo Mengbiao , Yao Zhicheng , Jiang Chen , Songyang Zhou , Gan Lian , Xiong Yuanyan
Published: March 2023

Backgrounds

Hepatitis B virus (HBV) infection is a major risk factor for chronic liver diseases and liver cancer (mainly hepatocellular carcinoma, HCC), while the underlying mechanisms and host-virus interactions are still largely elusive.

Methods

We applied HiC sequencing to HepG2 (HBV-) and HepG2-2.2.15 (HBV+) cell lines and combined them with public HCC single-cell RNA-seq data, HCC bulk RNA-seq data, and both genomic and epigenomic ChIP-seq data to reveal potential disease mechanisms of HBV infection and host-virus interactions reflected by 3D genome organization.

Results

We found that HBV enhanced overall proximal chromatin interactions (CIs) of liver cells and primarily affected regional CIs on chromosomes 13, 14, 17, and 22. Interestingly, HBV altered the boundaries of many topologically associating domains (TADs), and genes nearby these boundaries showed functional enrichment in cell adhesion which may promote cancer metastasis. Moreover, A/B compartment analysis revealed dramatic changes on chromosomes 9, 13 and 21, with more B compartments (inactive or closed) shifting to A compartments (active or open). The A-to-B regions (closing) harbored enhancers enriched in the regulation of inflammatory responses, whereas B-to-A regions (opening) were enriched for transposable elements (TE). Furthermore, we identified large HBV-induced structural variations (SVs) that disrupted tumor suppressors, NLGN4Y and PROS1. Finally, we examined differentially expressed genes and TEs in single hepatocytes with or without HBV infection, by using single-cell RNA-seq data. Consistent with our HiC sequencing findings, two upregulated genes that promote HBV replication, HNF4A and NR5A2, were located in regions with HBV-enhanced CIs, and five TEs were located in HBV-activated regions. Therefore, HBV may promote liver diseases by affecting the human 3D genome structure.

Conclusion

Our work promotes mechanistic understanding of HBV infection and host-virus interactions related to liver diseases that affect billions of people worldwide. Our findings may also have implications for novel immunotherapeutic strategies targeting HBV infection.
Thioredoxin VdTrx1, an unconventional secreted protein, is a virulence factor in Verticillium dahliae
Authors: Tian Li , Zhuang Jing , Li Jun-Jiao , Zhu He , Klosterman Steven J. , Dai Xiao-Feng , Chen Jie-Yin , Subbarao Krishna V. , Zhang Dan-Dan
Published: March 2023

Understanding how plant pathogenic fungi adapt to their hosts is of critical importance to securing optimal crop productivity. In response to pathogenic attack, plants produce reactive oxygen species (ROS) as part of a multipronged defense response. Pathogens, in turn, have evolved ROS scavenging mechanisms to undermine host defense. Thioredoxins (Trx) are highly conserved oxidoreductase enzymes with a dithiol-disulfide active site, and function as antioxidants to protect cells against free radicals, such as ROS. However, the roles of thioredoxins in Verticillium dahliae, an important vascular pathogen, are not clear. Through proteomics analyses, we identified a putative thioredoxin (VdTrx1) lacking a signal peptide. VdTrx1 was present in the exoproteome of V. dahliae cultured in the presence of host tissues, a finding that suggested that it plays a role in host-pathogen interactions. We constructed a VdTrx1 deletion mutant ΔVdTrx1 that exhibited significantly higher sensitivity to ROS stress, H2O2, and tert-butyl hydroperoxide (t-BOOH). In vivo assays by live-cell imaging and in vitro assays by western blotting revealed that while VdTrx1 lacking the signal peptide can be localized within V. dahliae cells, VdTrx1 can also be secreted unconventionally depending on VdVps36, a member of the ESCRT-II protein complex. The ΔVdTrx1 strain was unable to scavenge host-generated extracellular ROS fully during host invasion. Deletion of VdTrx1 resulted in higher intracellular ROS levels of V. dahliae mycelium, displayed impaired conidial production, and showed significantly reduced virulence on Gossypium hirsutum, and model plants, Arabidopsis thaliana and Nicotiana benthamiana. Thus, we conclude that VdTrx1 acts as a virulence factor in V. dahliae.
Effects of fertilizer reduction coupled with straw returning on soil fertility, wheat root endophytic bacteria, and the occurrence of wheat crown rot
Authors: Wang Yajiao , Wu Yuxing , Cao Caiyun , Han Sen , Zhao Weisong , Li Qiusheng , Liu Xuetong , Kong Lingxiao
Published: March 2023

Excessive fertilization is associated with nutrient loss, soil compaction, and weak plant resistance. Straw returning can increase soil fertility with a consequent reduction in fertilizer, but the effects of fertilizer reduction coupled with straw returning on crop endophytic microbes and crop disease are poorly understood. Therefore, using metagenomic sequencing methods we investigated the responses of soil fertility, diversity, the function of root endophytic bacteria, and the occurrence of wheat crown rot due to the application of fertilizer (no, moderate and excessive fertilizer) coupled with or without straw returning after 7 years of treatments. The results showed that, after excessive fertilization, the wheat crown rot became severe, registering a disease index of 23. Compared with excessive fertilization, moderate fertilization coupled with straw returning significantly reduced the incidence of wheat crown rot, the disease index was reduced by 38.50%, and the richness and diversity of endophytic bacteria were increased by 61.20 and 11.93%, respectively, but the soil fertility was not significantly affected. In addition, moderate fertilization coupled with straw returning changed the community structure of endophytic bacteria and increased the relative abundance of carbohydrate metabolism and nitrogen fixation-related genes by 4.72 and 9.32%, respectively. Our results indicated that fertilizer reduction coupled with straw returning reduced the occurrence of wheat crown rot, increased the diversity of endophytic bacteria, and changed the community structure and function of endophytic bacteria, which will provide a better understanding of the interaction of fertilization coupled with straw returning, endophytic bacteria and wheat crown rot.
Gene therapy and genome editing for type I glycogen storage diseases
Authors: Chou Janice Y. , Mansfield Brian C.
Published: March 2023

Type I glycogen storage diseases (GSD-I) consist of two major autosomal recessive disorders, GSD-Ia, caused by a reduction of glucose-6-phosphatase-α (G6Pase-α or G6PC) activity and GSD-Ib, caused by a reduction in the glucose-6-phosphate transporter (G6PT or SLC37A4) activity. The G6Pase-α and G6PT are functionally co-dependent. Together, the G6Pase-α/G6PT complex catalyzes the translocation of G6P from the cytoplasm into the endoplasmic reticulum lumen and its subsequent hydrolysis to glucose that is released into the blood to maintain euglycemia. Consequently, all GSD-I patients share a metabolic phenotype that includes a loss of glucose homeostasis and long-term risks of hepatocellular adenoma/carcinoma and renal disease. A rigorous dietary therapy has enabled GSD-I patients to maintain a normalized metabolic phenotype, but adherence is challenging. Moreover, dietary therapies do not address the underlying pathological processes, and long-term complications still occur in metabolically compensated patients. Animal models of GSD-Ia and GSD-Ib have delineated the disease biology and pathophysiology, and guided development of effective gene therapy strategies for both disorders. Preclinical studies of GSD-I have established that recombinant adeno-associated virus vector-mediated gene therapy for GSD-Ia and GSD-Ib are safe, and efficacious. A phase III clinical trial of rAAV-mediated gene augmentation therapy for GSD-Ia (NCT05139316) is in progress as of 2023. A phase I clinical trial of mRNA augmentation for GSD-Ia was initiated in 2022 (NCT05095727). Alternative genetic technologies for GSD-I therapies, such as gene editing, are also being examined for their potential to improve further long-term outcomes.
Online breath analysis with SESI/HRMS for metabolic signatures in children with allergic asthma
Authors: Weber Ronja , Streckenbach Bettina , Welti Lara , Inci Demet , Kohler Malcolm , Perkins Nathan , Zenobi Renato , Micic Srdjan , Moeller Alexander
Published: March 2023

Introduction: There is a need to improve the diagnosis and management of pediatric asthma. Breath analysis aims to address this by non-invasively assessing altered metabolism and disease-associated processes. Our goal was to identify exhaled metabolic signatures that distinguish children with allergic asthma from healthy controls using secondary electrospray ionization high-resolution mass spectrometry (SESI/HRMS) in a cross-sectional observational study.

Methods: Breath analysis was performed with SESI/HRMS. Significant differentially expressed mass-to-charge features in breath were extracted using the empirical Bayes moderated t-statistics test. Corresponding molecules were putatively annotated by tandem mass spectrometry database matching and pathway analysis.

Results: 48 allergic asthmatics and 56 healthy controls were included in the study. Among 375 significant mass-to-charge features, 134 were putatively identified. Many of these could be grouped to metabolites of common pathways or chemical families. We found several pathways that are well-represented by the significant metabolites, for example, lysine degradation elevated and two arginine pathways downregulated in the asthmatic group. Assessing the ability of breath profiles to classify samples as asthmatic or healthy with supervised machine learning in a 10 times repeated 10-fold cross-validation revealed an area under the receiver operating characteristic curve of 0.83.

Discussion: For the first time, a large number of breath-derived metabolites that discriminate children with allergic asthma from healthy controls were identified by online breath analysis. Many are linked to well-described metabolic pathways and chemical families involved in pathophysiological processes of asthma. Furthermore, a subset of these volatile organic compounds showed high potential for clinical diagnostic applications.
Efficiency measurement based on novel performance measures in total productive maintenance (TPM) using a fuzzy integrated COPRAS and DEA method
Authors: Turanoglu Bekar Ebru
Published: March 2023

Total Productive Maintenance (TPM) has been widely recognized as a strategic tool and lean manufacturing practice for improving manufacturing performance and sustainability, and therefore it has been successfully implemented in many organizations. The evaluation of TPM efficiency can assist companies in improving their operations across a variety of dimensions. This paper aims to propose a comprehensive and systematic framework for the evaluation of TPM performance. The proposed total productive maintenance performance measurement system (TPM PMS) is divided into four phases (e.g., design, evaluate, implement, and review): i) the design of new performance measures, ii) the evaluation of the new performance measures, iii) the implementation of the new performance measures to evaluate TPM performance, and iv) the reviewing of the TPM PMS. In the design phase, different types of performance measures impacting TPM are defined and analyzed by decision-makers. In the evaluation phase, novel performance measures are evaluated using the Fuzzy COmplex Proportional Assessment (FCOPRAS) method. In the implementation phase, a modified fuzzy data envelopment analysis (FDEA) is used to determine efficient and inefficient TPM performance with novel performance measures. In the review phase, TPM performance is periodically monitored, and the proposed TPM PMS is reviewed for successful implementation of TPM. A real-world case study from an international manufacturing company operating in the automotive industry is presented to demonstrate the applicability of the proposed TPM PMS. The main findings from the real-world case study showed that the proposed TPM PMS allows measuring TPM performance with different indicators especially soft ones, e.g., human-related, and supports decision makers by comparing the TPM performances of production lines and so prioritizing the most important preventive/predictive decisions and actions according to production lines, especially the ineffective ones in TPM program implementation. Therefore, this system can be considered a powerful monitoring tool and reliable evidence to make the implementation process of TPM more efficient in the real-world production environment.
Association of APOE ε4/ε4 with fluid biomarkers in patients from the PUMCH dementia cohort
Authors: Shang Li , Dong Liling , Huang Xinying , Wang Tianyi , Mao Chenhui , Li Jie , Wang Jie , Liu Caiyan , Gao Jing
Published: March 2023

Background

Apolipoprotein-E (APOE) ε4 is a major genetic risk factor for Alzheimer’s disease (AD). Current studies, which were mainly based on the clinical diagnosis rather than biomarkers, come to inconsistent conclusions regarding the associations of APOE ε4 homozygotes (APOE ε4/ε4) and cerebrospinal fluid (CSF) biomarkers of AD. In addition, few studies have explored the associations of APOE ε4/ε4 with plasma biomarkers. Therefore, we aimed to investigate the associations of APOE ε4/ε4 with fluid biomarkers in dementia and biomarker-diagnosed AD.

Methods

A total of 297 patients were enrolled. They were classified into Alzheimer’s continuum, AD, and non-AD, according to CSF biomarkers and/or β amyloid PET results. AD was a subgroup of the AD continuum. Plasma Amyloid β (Aβ) 40, Aβ42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and phosphorylated tau (P-tau)181 were quantified in 144 of the total population using an ultra-sensitive Simoa technology. We analyzed the associations of APOE ε4/ε4 on CSF and plasma biomarkers in dementia and biomarker diagnosed AD.

Results

Based on the biomarker diagnostic criteria, 169 participants were diagnosed with Alzheimer’s continuum and 128 individuals with non-AD, and among the former, 120 patients with AD. The APOE ε4/ε4 frequencies were 11.8% (20/169), 14.2% (17/120), and 0.8% (1/128) in Alzheimer’s continuum, AD and non-AD, respectively. Only CSF Aβ42 was shown to be decreased in APOE ε4/ε4 carriers than in non-carriers for patients with AD (p = 0.024). Furthermore, we did not find any associations of APOE ε4 with plasma biomarkers of AD and non-AD. Interestingly, we found that in non-AD patients, APOE ε4 carriers had lower CSF Aβ42 (p = 0.018) and higher T-tau/Aβ42 ratios (p < 0.001) and P-tau181/Aβ42 ratios (p = 0.002) than non-carriers.

Conclusion

Our data confirmed that of the three groups (AD continuum, AD, and non-AD), those with AD had the highest frequency of APOE ɛ4/ɛ4 genotypes. The APOE ɛ4/ɛ4 was associated with CSF levels of Aβ42 but not tau for AD and non-AD, suggesting that APOE ɛ4/ɛ4 affected the Aβ metabolism of both. No associations between APOE ε4/ɛ4 and plasma biomarkers of AD and non-AD were found.
Lateral septal nucleus, dorsal part, and dentate gyrus are necessary for spatial and object recognition memory, respectively, in mice
Authors: Jiang Ying-Ke , Dong Fei-Yuan , Dong Yi-Bei , Zhu Xin-Yi , Pan Lu-Hui , Hu Lin-Bo , Xu Le , Xu Xiao-Fan , Xu Li-Min , Zhang Xiao-Qin
Published: March 2023

Introduction

Cognitive impairment includes the abnormality of learning, memory and judgment, resulting in severe learning and memory impairment and social activity impairment, which greatly affects the life quality of individuals. However, the specific mechanisms underlying cognitive impairment in different behavioral paradigms remain to be elucidated.

Methods

The study utilized two behavioral paradigms, novel location recognition (NLR) and novel object recognition (NOR), to investigate the brain regions involved in cognitive function. These tests comprised two phases: mice were presented with two identical objects for familiarization during the training phase, and a novel (experiment) or familiar (control) object/location was presented during testing. Immunostaining quantification of c-Fos, an immediate early gene used as a neuronal activity marker, was performed in eight different brain regions after the NLR or NOR test.

Results

The number of c-Fos-positive cells was significantly higher in the dorsal part of the lateral septal nucleus (LSD) in the NLR and dentate gyrus (DG) in the NOR experiment group than in the control group. We further bilaterally lesioned these regions using excitotoxic ibotenic acid and replenished the damaged areas using an antisense oligonucleotide (ASO) strategy.

Discussion

These data reinforced the importance of LSD and DG in regulating spatial and object recognition memory, respectively. Thus, the study provides insight into the roles of these brain regions and suggests potential intervention targets for impaired spatial and object recognition memory.
Eye movement characteristics and visual fatigue assessment of virtual reality games with different interaction modes
Authors: Fan Lei , Wang Junjie , Li Qi , Song Zhenhao , Dong Jinhui , Bao Fangjun , Wang Xiaofei
Published: March 2023

This study aimed to investigate the eye movement characteristics and visual fatigue of virtual reality games with different interaction modes. Eye movement data were recorded using the built-in eye tracker of the VR device and eye movement parameters were calculated from the recorded raw data. The Visual Fatigue Scales and Simulator Sickness Questionnaire were used to subjectively assess visual fatigue and overall discomfort of the VR experience. Sixteen male and 17 female students were recruited for this study. Results showed that both the primary and 360 mode of VR could cause visual fatigue after 30 min of gameplay, with significant differences observed in eye movement behavior between the two modes. The primary mode was more likely to cause visual fatigue, as shown by objective measurements of blinking and pupil diameter. Fixation and saccade parameters also showed significant differences between the two modes, possibly due to the different interaction modes employed in the 360 mode. Further research is required to examine the effects of different content and interactive modes of VR on visual fatigue, as well as to develop more objective measures for assessing it.
Investigating the causal association between branched-chain amino acids and Alzheimer's disease: A bidirectional Mendelian randomized study
Authors: Qian Xiao-hang , Liu Xiao-li , Zhang Bin , Lin Yuan , Xu Jian-hua , Ding Gang-yu , Tang Hui-dong
Published: March 2023

Background

There are many metabolic pathway abnormalities in Alzheimer's disease (AD). Several studies have linked branched-chain amino acid (BCAA) metabolism disorders with AD but have not obtained consistent results. The purpose of this study is to explore the causal association between BCAA concentration and the risk of AD.

Methods

A bidirectional Mendelian randomized (MR) study was applied to explore the causal effect between BCAA level and the risk of AD. Genetic instrumental variables from the genome-wide association study (GWAS) of serum BCAA levels [total BCAAs (115,047 participants), valine (115,048 participants), leucine (115,074 participants), and isoleucine (115,075 participants)] from the UK Biobank and AD (21,982 AD cases and 41,944 controls) from the International Genomics of Alzheimer's Project were applied to explore the causal effect through the inverse variance-weighted (IVW) method, MR-Egger, and weighted median, accompanied by multiple pluripotency and heterogeneity tests.

Results

The forward MR analysis showed that there was no causal effect of total BCAAs (OR: 1.067, 95% CI: 0.838–1.358; p = 0.838), valine (OR: 1.106, 95% CI: 0.917–1.333; p = 0.292), leucine (OR: 1.096, 95% CI: 0.861–1.396; p = 0.659), and isoleucine (OR: 1.457, 95% CI: 1.024–2.742; p = 0.037) levels on the risk of AD. The reverse analysis showed that AD was related to reduced levels of total BCAAs (OR: 0.979, 95% CI: 0.989–0.990; p < 0.001), valine (OR: 0.977, 95% CI: 0.963–0.991; p = 0.001), leucine (OR: 0.983, 95% CI: 0.973–0.994; p = 0.002), and isoleucine (OR: 0.982, 95% CI: 0.971–0.992; p = 0.001).

Conclusion

We provide robust evidence that AD was associated with a decreased level of BCAAs, which can serve as a marker for early diagnosis of AD.
Success rate of the treatment of early childhood caries under general anesthesia: A retrospective cohort study in different periods
Authors: Zhang Baize , Wang Junhui , Han Xinxin , Fang Ruohao , Wang Zirui , Hui Zeming , Chen Yujiang , Liu Jiajia , Wang Xiaojing
Published: March 2023

Instruction

The purpose of this study was to evaluate the three-year success rate of the treatment for early childhood caries (ECC) under general anesthesia in different periods (2011 and 2018).

Methods

Children (<6 years old) who had severe caries and were treated under general anesthesia in 2011 and 2018 were selected and followed up by telephone appointment and clinical examination. Success rate of each treatment was determined and possible factors associated with treatment failure were evaluated.

Results

There were 153 patients (with an average age of 48.55 ± 13.37 months) and a total of 2,018 teeth included in the 2011 group. In the 2018 group, there were 273 patients with an average age of 49.01 ± 12.42 months and a total of 3,796 teeth. The success rate in the 2011 group was significantly lower than that in the 2018 group. Teeth with mineral trioxide aggregate (MTA)-capped pulp survived significantly longer than those with calcium hydroxide-capped pulp. The utilization rate of preformed crown restoration was higher than that of resin restoration, and the survival time of dental restorations with preformed crown was prolonged. For posterior teeth, the success rate of indirect pulp capping and pulpotomy was also significantly higher than those without preformed crowns.

Discussion

General anesthesia is a safe and effective behavioral management method for uncooperative children's dental treatment. The use of biocompatible pulp capping materials and preformed crowns improved the success rate of treatment and prolonged the survival time of affected teeth.
Transplacental passage of hyperforin, hypericin, and valerenic acid
Authors: Spiess Deborah , Abegg Vanessa Fabienne , Chauveau Antoine , Rath Joshua , Treyer Andrea , Reinehr Michael , Kuoni Sabrina , Oufir Mouhssin , Potterat Olivier , Hamburger Matthias , Simões-Wüst Ana Paula
Published: March 2023

Safe medications for mild mental diseases in pregnancy are needed. Phytomedicines from St. John’s wort and valerian are valid candidates, but safety data in pregnancy are lacking. The transplacental transport of hyperforin and hypericin (from St. John’s wort), and valerenic acid (from valerian) was evaluated using the ex vivo cotyledon perfusion model (4 h perfusions, term placentae) and, in part, the in vitro Transwell assay with BeWo b30 cells. Antipyrine was used for comparison in both models. U(H)PLC-MS/MS bioanalytical methods were developed to quantify the compounds. Perfusion data obtained with term placentae showed that only minor amounts of hyperforin passed into the fetal circuit, while hypericin did not cross the placental barrier and valerenic acid equilibrated between the maternal and fetal compartments. None of the investigated compounds affected metabolic, functional, and histopathological parameters of the placenta during the perfusion experiments. Data from the Transwell model suggested that valerenic acid does not cross the placental cell layer. Taken together, our data suggest that throughout the pregnancy the potential fetal exposure to hypericin and hyperforin – but not to valerenic acid – is likely to be minimal.