bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole Exome Sequencing Uncovered the Genetic Architecture of Growth Hormone Deficiency Patients
Authors: Yu Chenxi , Xie Bobo , Zhao Zhengye , Zhao Sen , Liu Lian , Cheng Xi , Li Xiaoxin , Cao Bingyan , Shao Jiashen , Chen Jiajia , Zhao Hengqiang , Yan Zihui , Su Chang , Niu Yuchen , Song Yanning , Wei Liya , Wang Yi , Ren Xiaoya , Fan Lijun , Zhang Beibei , Li Chuan , Gui Baoheng , Zhang Yuanqiang , Wang Lianlei , Chen Shaoke , Zhang Jianguo , Wu Zhihong , Gong Chunxiu , Fan Xin , Wu Nan
Published: September 2021

Purpose

Congenital growth hormone deficiency (GHD) is a rare and etiologically heterogeneous disease. We aim to screen disease-causing mutations of GHD in a relatively sizable cohort and discover underlying mechanisms via a candidate gene-based mutational burden analysis.

Methods

We retrospectively analyzed 109 short stature patients associated with hormone deficiency. All patients were classified into two groups: Group I (n=45) with definitive GHD and Group II (n=64) with possible GHD. We analyzed correlation consistency between clinical criteria and molecular findings by whole exome sequencing (WES) in two groups. The patients without a molecular diagnosis (n=90) were compared with 942 in-house controls for the mutational burden of rare mutations in 259 genes biologically related with the GH axis.

Results

In 19 patients with molecular diagnosis, we found 5 possible GHD patients received known molecular diagnosis associated with GHD (NF1 [c.2329T>A, c.7131C>G], GHRHR [c.731G>A], STAT5B [c.1102delC], HRAS [c.187_207dup]). By mutational burden analysis of predicted deleterious variants in 90 patients without molecular diagnosis, we found that POLR3A (p = 0.005), SUFU (p = 0.006), LHX3 (p = 0.021) and CREB3L4 (p = 0.040) represented top genes enriched in GHD patients.

Conclusion

Our study revealed the discrepancies between the laboratory testing and molecular diagnosis of GHD. These differences should be considered when for an accurate diagnosis of GHD. We also identified four candidate genes that might be associated with GHD.
Combining High-Resolution Land Use Data With Crowdsourced Air Temperature to Investigate Intra-Urban Microclimate
Authors: Potgieter Julia , Nazarian Negin , Lipson Mathew J. , Hart Melissa A. , Ulpiani Giulia , Morrison William , Benjamin Kit
Published: September 2021

The spatial variability of land cover in cities results in a heterogeneous urban microclimate, which is often not represented with regulatory meteorological sensor networks. Crowdsourced sensor networks have the potential to address this shortcoming with real-time and fine-grained temperature measurements across cities. We use crowdsourced data from over 500 citizen weather stations during summer in Sydney, Australia, combined with 100-m land use and Local Climate Zone (LCZ) maps to explore intra-urban variabilities in air temperature. Sydney presents unique drivers for spatio-temporal variability, with its climate influenced by the ocean, mountainous topography, and diverse urban land use. Here, we explore the interplay of geography with urban form and fabric on spatial variability in urban temperatures. The crowdsourced data consists of 2.3 million data points that were quality controlled and compared with reference data from five synoptic weather stations. Crowdsourced stations measured higher night-time temperatures, higher maximum temperatures on warm days, and cooler maximum temperatures on cool days compared to the reference stations. These differences are likely due to siting, with crowdsourced weather stations closer to anthropogenic heat emissions, urban materials with high thermal inertia, and in areas of reduced sky view factor. Distance from the coast was found to be the dominant factor impacting the spatial variability in urban temperatures, with diurnal temperature range greater for sensors located inland. Further differences in urban temperature could be explained by spatial variability in urban land-use and land-cover. Temperature varied both within and between LCZs across the city. Crowdsourced nocturnal temperatures were particularly sensitive to surrounding land cover, with lower temperatures in regions with higher vegetation cover, and higher temperatures in regions with more impervious surfaces. Crowdsourced weather stations provide highly relevant data for health monitoring and urban planning, however, there are several challenges to overcome to interpret this data including a lack of metadata and an uneven distribution of stations with a possible socio-economic bias. The sheer number of crowdsourced weather stations available can provide a high-resolution understanding of the variability of urban heat that is not possible to obtain via traditional networks.
The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy
Authors: Wang Zeyu , Liu Yuze , Mo Yuyao , Zhang Hao , Dai Ziyu , Zhang Xun , Ye Weijie , Cao Hui , Liu Zhixiong , Cheng Quan
Published: September 2021

Gliomas are a type of malignant central nervous system tumor with poor prognosis. Molecular biomarkers of gliomas can predict glioma patient’s clinical outcome, but their limitations are also emerging. C-X-C motif chemokine ligand family plays a critical role in shaping tumor immune landscape and modulating tumor progression, but its role in gliomas is elusive. In this work, samples of TCGA were treated as the training cohort, and as for validation cohort, two CGGA datasets, four datasets from GEO database, and our own clinical samples were enrolled. Consensus clustering analysis was first introduced to classify samples based on CXCL expression profile, and the support vector machine was applied to construct the cluster model in validation cohort based on training cohort. Next, the elastic net analysis was applied to calculate the risk score of each sample based on CXCL expression. High-risk samples associated with more malignant clinical features, worse survival outcome, and more complicated immune landscape than low-risk samples. Besides, higher immune checkpoint gene expression was also noticed in high-risk samples, suggesting CXCL may participate in tumor evasion from immune surveillance. Notably, high-risk samples also manifested higher chemotherapy resistance than low-risk samples. Therefore, we predicted potential compounds that target high-risk samples. Two novel drugs, LCL-161 and ADZ5582, were firstly identified as gliomas’ potential compounds, and five compounds from PubChem database were filtered out. Taken together, we constructed a prognostic model based on CXCL expression, and predicted that CXCL may affect tumor progression by modulating tumor immune landscape and tumor immune escape. Novel potential compounds were also proposed, which may improve malignant glioma prognosis.
Evidence of Deep DOC Enrichment via Particle Export Beneath Subarctic and Northern Subtropical Fronts in the North Pacific
Authors: Lopez Chelsea Nicole , Hansell Dennis Arthur
Published: September 2021

Here we provide compelling evidence that deep particle export enhanced dissolved organic carbon (DOC) concentrations beneath the Pacific’s Subarctic Front (SA, ∼42°N) and Northern Subtropical Front (NST, ∼34°N). We report three main findings: First, deep export of subjectively small particles (128–512 μm) was apparent throughout the frontal zone in which the SA resides. However, export of large particles was specifically associated with the SA, rather than the entire frontal zone, and appeared to exclusively transfer DOC into the bathypelagic water column. Second, a similar DOC enrichment existed beneath the NST, though this signal was curiously not accompanied by observable particles (>128 μm). We conclude that export occurring previously in winter left this DOC behind as a residue, though the associated particles were no longer present by spring. Third, the presence of strong hydrographic fronts was not the only control on export that resulted in these unique DOC distributions. Deep export and DOC enrichment was also controlled by latitude-specific biogeochemical and hydrographic conditions, such as depth of the nutricline and seasonal mixed layer shoaling. Given these observations, the fronts within the transitional region of the North Pacific are clearly special locations for deep carbon sequestration and for providing uncommon DOC enrichment that ultimately supports the deep microbial community.
Experimental Study on the Piezoresistivity of Concrete Containing Steel Fibers, Carbon Black, and Graphene
Authors: Wang Shijun , Singh Amardeep , Liu Qiong
Published: September 2021

Adding conductive materials to cement-based composites can lead to pressure-sensitive properties. In this study, different scales of conductive materials were incorporated, including macro-scale steel fibers, micro-scale carbon black powder, and nano-scale graphene. The coupling effect of three scales of materials ensured that the intelligent concrete had improved strength, lower cost, and comparable pressure-sensitive performance. The results show that the strength of intelligent concrete with multi-scale conductive materials is higher than that of the contrast group of ordinary concrete and intelligent concrete when adding nano-scale graphene alone. Especially, the addition of steel fibers significantly improved the crack resistance of the intelligent concrete. In the elastic stage, the resistivity of intelligent concrete of multi-scale conductive materials decreases with the increase in compression, and the decrease range of resistivity is approximately proportional to the external force. After reaching the peak load, the resistivity of the intelligent concrete gradually increases and can illustrate the damage evolution. This study lays a foundation for the application of intelligent concrete in deformation and damage monitoring.
Seismic Performance of Ni-Ti SMA Wires Equipped in the Spatial Skeletal Structure
Authors: Liu Yang , Yang Tao , Li Binbin , Liu Bo , Wang Wentao , Wang Sheliang
Published: September 2021

Nickel Titanium (Ni-Ti) Shape Memory Alloy (SMA) can be used to limit response of structure during external disturbances such as large seismic events. This paper presents a seismic performance study of Ni-Ti SMA wires equipped in the spatial skeletal structure. First, an improved Graesser-Cozzarelli (G-C) numerical constitutive model of the Austenitic phase of NiTi SMA wire is established. By contrast, the model based on uniaxial cyclic loading experimental tests is demonstrated as feasibility and validity. Next, a method consisting of a three-layer steel spatial skeletal structure model equipped with SMA wires is employed for simulation and experimental tests. According to the obtained constitutive numerical model, the simulation program of vibration control is written to simulate the effect of vibration control of seismic EL-centro wave. Furthermore, a shaking table experimental test was designed to verify the vibration control effect under the same action of seismic EL-centro wave. By comparison of the results of the numerical simulation and shaking table test, dynamic responses of the displacement and acceleration for different floors with control and without control was concluded. The superior superelastic properties of SMA wires used in passive control are investigated and the correctness of the constitutive numerical model are verified as well. The results show that such a comprehensive analysis integrates seismic-resistant behavior of Ni-Ti SMA wires in this type of structure. Besides, proposed method has broad application prospects to address the issues in passive control field of building structures.
Interprofessional Communication Team for Caregivers of Patients Hospitalized in the COVID-19 Wards: Results From an Italian Experience
Authors: Carletto Sara , Corezzi Michele , Furmenti Maria Francesca , Olivero Elena , Rapicavoli Paola , Rossello Paola , Stanizzo Maria Rosa , Bovero Andrea
Published: September 2021

Background: During the COVID-19 pandemic, emergency restrictions did not allow clinician family meetings and relatives' visits. In Molinette Hospital, a new communication model between healthcare providers and families of COVID-19 affected patients was developed by a team of physicians and psychologists. The study's aims were to investigate caregivers' distress and to analyse their satisfaction with the communications provided.

Methods: A cross-sectional study was conducted among caregivers of patients of Molinette Hospital COVID wards. Between April and June 2020, all caregivers were contacted 2 weeks after the patient's discharge/death to assess their satisfaction with the communications received through an online survey.

Results: A total of 155 caregivers completed the survey. Caregivers' distress level was found to be higher in women than men (p = 0.048) and in caregivers whose relative died compared to the caregivers whose relative was discharged (p < 0.001). More than 85% of caregivers defined communication “excellent”/“very good”; being male was associated with higher satisfaction levels than women (β = −0.165, p = 0.046). Besides daily communication, 63 caregivers (40.6%) received additional support from a psychologist of the team.

Conclusions: To our knowledge, this is the first study presenting, in an emergency, a new model of communication provided by a team of physicians and psychologists, and analyzing satisfaction with it. This model was highly appreciated by caregivers and it limited the discomfort caused by the restrictions on relatives' visits. It would be interesting to further evaluate the possibility of extending a communication model that includes doctors and psychologists in routine clinical practice.
Repurposing Candesartan Cilexetil as Antibacterial Agent for MRSA Infection
Authors: Xu Lanlan , She Pengfei , Chen Lihua , Li Shijia , Zhou Linying , Hussain Zubair , Liu Yaqian , Wu Yong
Published: September 2021

Staphylococcus aureus is an important pathogen causing hospital-acquired infections. Methicillin-resistant S. aureus (MRSA), biofilms, and persisters are highly tolerant to traditional antibiotics and make it difficult to treat. Therefore, new antimicrobial agents are urgently needed to treat hard-to-eradicate diseases caused by this bacterium. In this study, candesartan cilexetil (CC), an angiotensin hypertension drug, had strong antimicrobial activity against S. aureus with minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 8–16 μg/ml and 16–32 μg/ml. CC exhibited limited cytotoxicity and low potential to induce drug resistance. In addition, it showed a synergistic antibacterial effect when combined with gentamicin and tobramycin. The effective concentrations to inhibit MRSA biofilm formation were 16–64 μg/ml, and intractable persisters were killed at 4–8 × MIC. Through the analysis of its mechanism of action, it was evident that the membrane permeability was disrupted as well as the cell structure was damaged. Furthermore, we demonstrated that CC had antibacterial effects in vivo in MRSA-infected murine skin abscess models. In conclusion, these results imply that CC might be a potential antibacterial agent for the treatment of S. aureus-associated infections.
Comparison of the Intestinal Microbiota During the Different Growth Stages of Red Swamp Crayfish (Procambarus clarkii)
Authors: Xie Mengqi , Zhang Shiyu , Xu Lili , Wu Zhixin , Yuan Junfa , Chen Xiaoxuan
Published: September 2021

This study aimed to determine the effect of the growth stage of Procambarus clarkii on their intestinal microbiota. Intestinal samples of five different growth stages of P. clarkii (first instar, second instar, third instar, juvenile, and adult) from laboratory culture were analyzed through the Illumina MiSeq high-throughput sequencing platform to determine the intestinal microbiome of crayfish. The alpha diversity decreased along with the growth of the crayfish, with the relative abundance of the microbiota changing among stages; crayfish at closer development stages had a more comparable intestinal microbiota composition. A comparative analysis by principal component analysis and principal coordinate analysis showed that there were significant differences in the intestinal microbiota of crayfish among the different growth stages, except for the first two stages of larval crayfish, and the intestinal microbiota showed a consistent progression pattern from the larval stage to the juvenile stage. Some microbiota showed stage specificity, which might be the characteristic microbiota of different stages of growth. According to FAPROTAX functional clustering analysis, the three stages of larvae were clustered together, while the juvenile and adult stages were clustered separately according to the growth stage, indicating that, in the early stages of larval development, the function of the intestinal flora was similar; as the body grew and developed, the composition and function of the intestinal microbiota also changed.
Genomic and Physiological Characterization of Bacilli Isolated From Salt-Pans With Plant Growth Promoting Features
Authors: Petrillo Claudia , Castaldi Stefany , Lanzilli Mariamichela , Selci Matteo , Cordone Angelina , Giovannelli Donato , Isticato Rachele
Published: September 2021

Massive application of chemical fertilizers and pesticides has been the main strategy used to cope with the rising crop demands in the last decades. The indiscriminate use of chemicals while providing a temporary solution to food demand has led to a decrease in crop productivity and an increase in the environmental impact of modern agriculture. A sustainable alternative to the use of agrochemicals is the use of microorganisms naturally capable of enhancing plant growth and protecting crops from pests known as Plant-Growth-Promoting Bacteria (PGPB). Aim of the present study was to isolate and characterize PGPB from salt-pans sand samples with activities associated to plant fitness increase. To survive high salinity, salt-tolerant microbes produce a broad range of compounds with heterogeneous biological activities that are potentially beneficial for plant growth. A total of 20 halophilic spore-forming bacteria have been screened in vitro for phyto-beneficial traits and compared with other two members of Bacillus genus recently isolated from the rhizosphere of the same collection site and characterized as potential biocontrol agents. Whole-genome analysis on seven selected strains confirmed the presence of numerous gene clusters with PGP and biocontrol functions and of novel secondary-metabolite biosynthetic genes, which could exert beneficial impacts on plant growth and protection. The predicted biocontrol potential was confirmed in dual culture assays against several phytopathogenic fungi and bacteria. Interestingly, the presence of predicted gene clusters with known biocontrol functions in some of the isolates was not predictive of the in vitro results, supporting the need of combining laboratory assays and genome mining in PGPB identification for future applications.
SUN-Family Protein UvSUN1 Regulates the Development and Virulence of Ustilaginoidea virens
Authors: Yu Mina , Yu Junjie , Cao Huijuan , Song Tianqiao , Pan Xiayan , Qi Zhongqiang , Du Yan , Zhang Rongsheng , Huang Shiwen , Liu Wende , Liu Yongfeng
Published: September 2021

Ustilaginoidea virens, the causal agent of rice false smut disease, is an important plant pathogen that causes severe quantitative and qualitative losses in rice worldwide. UvSUN1 is the only member of Group-I SUN family proteins in U. virens. In this work, the role of UvSUN1 in different aspects of the U. virens biology was studied by phenotypic analysis of Uvsun1 knockout strains. We identified that UvSUN1 was expressed during both conidial germination and the infection of rice. Disruption of the Uvsun1 gene affected the hyphal growth, conidiation, morphology of hyphae and conidia, adhesion and virulence. We also found that UvSUN1 is involved in the production of toxic compounds, which are able to inhibit elongation of the germinated seeds. Moreover, RNA-seq data showed that knockout of Uvsun1 resulted in misregulation of a subset of genes involved in signal recognition and transduction system, glycometabolism, cell wall integrity, and secondary metabolism. Collectively, this study reveals that Uvsun1 is required for growth, cell wall integrity and pathogenicity of U. virens, thereby providing new insights into the function of SUN family proteins in the growth and pathogenesis of this pathogen.
Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction
Authors: Takata Fuyuko , Nakagawa Shinsuke , Matsumoto Junichi , Dohgu Shinya
Published: September 2021

Neuroinflammation is involved in the onset or progression of various neurodegenerative diseases. Initiation of neuroinflammation is triggered by endogenous substances (damage-associated molecular patterns) and/or exogenous pathogens. Activation of glial cells (microglia and astrocytes) is widely recognized as a hallmark of neuroinflammation and triggers the release of proinflammatory cytokines, leading to neurotoxicity and neuronal dysfunction. Another feature associated with neuroinflammatory diseases is impairment of the blood-brain barrier (BBB). The BBB, which is composed of brain endothelial cells connected by tight junctions, maintains brain homeostasis and protects neurons. Impairment of this barrier allows trafficking of immune cells or plasma proteins into the brain parenchyma and subsequent inflammatory processes in the brain. Besides neurons, activated glial cells also affect BBB integrity. Therefore, BBB dysfunction can amplify neuroinflammation and act as a key process in the development of neuroinflammation. BBB integrity is determined by the integration of multiple signaling pathways within brain endothelial cells through intercellular communication between brain endothelial cells and brain perivascular cells (pericytes, astrocytes, microglia, and oligodendrocytes). For prevention of BBB disruption, both cellular components, such as signaling molecules in brain endothelial cells, and non-cellular components, such as inflammatory mediators released by perivascular cells, should be considered. Thus, understanding of intracellular signaling pathways that disrupt the BBB can provide novel treatments for neurological diseases associated with neuroinflammation. In this review, we discuss current knowledge regarding the underlying mechanisms involved in BBB impairment by inflammatory mediators released by perivascular cells.
RETRACTED: Multiple Sclerosis Recognition by Biorthogonal Wavelet Features and Fitness-Scaled Adaptive Genetic Algorithm
Authors: Wang Shui-Hua , Jiang Xianwei , Zhang Yu-Dong
Published: September 2021

Aim: Multiple sclerosis (MS) is a disease, which can affect the brain and/or spinal cord, leading to a wide range of potential symptoms. This method aims to propose a novel MS recognition method.

Methods: First, the bior4.4 wavelet is used to extract multiscale coefficients. Second, three types of biorthogonal wavelet features are proposed and calculated. Third, fitness-scaled adaptive genetic algorithm (FAGA)—a combination of standard genetic algorithm, adaptive mechanism, and power-rank fitness scaling—is harnessed as the optimization algorithm. Fourth, multiple-way data augmentation is utilized on the training set under the setting of 10 runs of 10-fold cross-validation. Our method is abbreviated as BWF-FAGA.

Results: Our method achieves a sensitivity of 98.00 ± 0.95%, a specificity of 97.78 ± 0.95%, and an accuracy of 97.89 ± 0.94%. The area under the curve of our method is 0.9876.

Conclusion: The results show that the proposed BWF-FAGA method is better than 10 state-of-the-art MS recognition methods, including eight artificial intelligence-based methods, and two deep learning-based methods.
Gut Microbiota Disorders Promote Inflammation and Aggravate Spinal Cord Injury Through the TLR4/MyD88 Signaling Pathway
Authors: Rong Zijie , Huang Yuliang , Cai Honghua , Chen Min , Wang Hao , Liu Guihua , Zhang Zhiwen , Wu Jiawen
Published: September 2021

Background: In spinal cord injury (SCI), systemic inflammation and the death of nerve cells in the spinal cord are life threatening. The connection between gut microbiota and signaling pathways has been a hot research topic in recent years. The Toll-like receptor 4/Myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway is closely related to the inflammatory response. This study explored whether the gut microbiota imbalance could affect the TLR4/MyD88 signaling pathway to regulate SCI to provide a new basis for SCI research and treatment.

Methods: An SCI model was constructed to study the influence on the injury of gut microbiota. 16S amplicon sequencing was used to identify the diversity and abundance of gut microbes. Fecal microbiota transplantation was performed in mice with SCI. ELISA was used to detect the serum levels of pro-inflammatory and anti-inflammatory factors in mice. Hematoxylin and eosin staining was used to observe SCI in mice. Immunofluorescence was used to detect the rates of loss glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN), and ionized calcium-binding adapter molecule 1 (IBA1) in the spinal cord as indicators of apoptosis. The expression of the TLR4/MyD88 signaling pathway was detected by qRT-PCR and western blotting.

Results: Significant differences were observed in the gut microbiota of SCI mice and normal mice. The gut microbiota of SCI mice was imbalanced. The levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in SCI mice were increased, as was the level of the toxic induced nitric oxide synthase. The levels of anti-inflammatory factors IL-4, transforming growth factor-β, and IL-10 were decreased, as was the level of arginase-1. The apoptosis rates of GFAP, NeuN, and IBA1 were increased. The TLR4/MyD88 signaling pathway was activated. In the SCI group, inflammation increased after fecal transplantation, apoptosis of GFAP, NeuN, and IBA1 increased, and SCI was more serious.

Conclusion: The TLR4/MyD88 signaling pathway promotes the death of nerve cells by inducing inflammation. Gut microbiota dysregulation can lead to aggravated SCI by activating the TLR4/MyD88 signaling pathway.
B4GALNT2 Gene Promotes Proliferation, and Invasiveness and Migration Abilities of Model Triple Negative Breast Cancer (TNBC) Cells by Interacting With HLA-B Protein
Authors: Yu Pu , Zhu Lili , Cui Kang , Du Yabing , Zhang Chaojie , Ma Wang , Guo Jia
Published: September 2021

B4GALNT2 gene encodes the enzyme β1,4-N-acetylgalactosaminyltransferase 2 that biosynthesizes the histo-blood group antigen Sda, which is expressed on the surface of erythrocytes and in body secretions. Analysis of The Cancer Genome Atlas (TCGA) database revealed that this gene was highly expressed in breast cancer tissues in comparison with adjacent healthy ones. In-vitro lentivirus-assisted B4GALNT2 gene knockdown experiments in model triple negative breast cancer (TNBC) cell lines (HCC1937 and MDA-MB-231) showed inhibition in cell proliferation, decrease in cell viability, promotion of cell apoptosis and inhibitions in cell migration and invasiveness abilities in comparison with empty lentivirus transfectant controls. Also, in cell cycle tests, the number of cells in the G1 phase increased, in the S phase decreased and did not change in the G2/M phase (indicative of the presence of a block in the G1 phase). In-vivo tumor formation experiments in mice revealed that knockdown of the B4GALNT2 gene in MDA-MB-231 cells inhibited their proliferation. Using co-immunoprecipitation (Co-IP) mass spectroscopy-assisted analysis, it was found that HLA-B protein [a product of the human leukocyte antigen (HLA) class I gene] interacts with B4GALNT2 protein. In-vitro overexpression of HLA-B in B4GALNT2-knocked down MDA-MB-231 cell lines significantly recovered the cell proliferation, viability and migration ability of B4GALNT2 gene. These indicate that HLA-B is one of the interaction proteins in the downstream pathway of the B4GALNT2 gene.
Neoadjuvant Chemotherapy Followed by Surgery Versus Abdominal Radical Hysterectomy Alone for Oncological Outcomes of Stage IB3 Cervical Cancer—A Propensity Score Matching Analysis
Authors: Li Weili , Zhang Wenling , Sun Lixin , Wang Li , Cui Zhumei , Zhao Hongwei , Wang Danbo , Zhang Yi , Guo Jianxin , Yang Ying , Wang Wuliang , Bin Xiaonong , Lang Jinghe , Liu Ping , Chen Chunlin
Published: September 2021

Objective

To compare the 5-year overall survival (OS) and disease-free survival (DFS) of patients with cervical cancer who received neoadjuvant chemotherapy followed by surgery (NACT) with those who received abdominal radical hysterectomy alone (ARH).

Methods

We retrospectively compared the oncological outcomes of 1410 patients with stage IB3 cervical cancer who received NACT (n=583) or ARH (n=827). The patients in the NACT group were divided into an NACT-sensitive group and an NACT-insensitive group according to their response to chemotherapy.

Results

The 5-year oncological outcomes were significantly better in the NACT group than in the ARH group (OS: 96.2% vs. 91.2%, respectively, p=0.002; DFS: 92.2% vs. 87.5%, respectively, p=0.016). Cox multivariate analysis suggested that NACT was independently associated with a better 5-year OS (HR=0.496; 95% CI, 0.281-0.875; p=0.015), but it was not an independent factor for 5-year DFS (HR=0.760; 95% CI, 0.505-1.145; p=0.189). After matching, the 5-year oncological outcomes of the NACT group were better than those of the ARH group. Cox multivariate analysis suggested that NACT was still an independent protective factor for 5-year OS (HR=0.503; 95% CI, 0.275-0.918; p=0.025). The proportion of patients in the NACT group who received postoperative radiotherapy was significantly lower than that in the ARH group (p<0.001). Compared to the ARH group, the NACT-sensitive group had similar results as the NACT group. The NACT-insensitive group and the ARH group had similar 5-year oncological outcomes and proportions of patients receiving postoperative radiotherapy.

Conclusion

Among patients with stage IB3 cervical cancer, NACT improved 5-year OS and was associated with a reduction in the proportion of patients receiving postoperative radiotherapy. These findings suggest that patients with stage IB3 cervical cancer, especially those who are sensitive to chemotherapy, might consider NACT followed by surgery.
Radiotherapy for Vaginal Recurrences of Cervical Cancer in Patients After Prior Surgery: Analysis of Effect and Prognostic Factors
Authors: Yan Junfang , Zheng Ziye , Zhu Jiawei , Hu Ke , Hou Xiaorong , Shen Jie , Lian Xin , Sun Shuai , Miao Zheng , Shen Jing , Guan Hui , Meng Qingyu , Zhang Fuquan
Published: September 2021

Objective

The role of salvage radiotherapy (RT) in the treatment for vaginal recurrence of cervical cancer in patients after prior surgery remains controversial. The aim of this study was to evaluate the efficacy and toxicity of salvage RT and explore prognostic factors associated with the survival after recurrence.

Methods

Patients with cervical cancer, treated for vaginal recurrences at Peking Union Medical College Hospital between July 2011 and November 2019, were identified. All the patients underwent prior surgery for primary tumor and received salvage RT including external beam radiotherapy (EBRT), brachytherapy (BT), or both. The irradiation field and dose depended on the conditions of patients. Recurrence patterns were classified into four categories according to the site of recurrence. Prognostic factors on the overall survival (OS), progression-free survival (PFS), and local control (LC) were analyzed, and late toxicity was evaluated.

Results

A total of 141 patients were included in the analysis, with a median follow-up time of 40.8 months. The estimated 5-year OS, PFS, and LC rates were 81%, 75%, and 87%, respectively. In multivariate analysis, endovaginal recurrence and no irradiation history were favorable prognostic factors associated with OS (all p < 0.05), PFS (all p < 0.05), and LC (all p < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of the recurrence pattern is larger than the stage of primary tumor (0.734 vs. 0.670).

Conclusions

RT was an effective treatment with tolerable toxicity for vaginal recurrences of cervical cancer in patients with prior surgery. Recurrence pattern and irradiation history were important prognostic factors.
Case Report: The Genetic Diagnosis of Duchenne Muscular Dystrophy in the Middle East
Authors: Alghamdi Fouad , Al-Tawari Asmaa , Alrohaif Hadil , Alshuaibi Walaa , Mansour Hicham , Aartsma-Rus Annemieke , Mégarbané André
Published: September 2021

The timely and accurate genetic diagnosis of Duchenne muscular dystrophy (DMD) enables prompt initiation of disease management and genetic counseling and optimal patient care. Despite the existence of best practice guidelines for the diagnosis of DMD, implementation of these recommendations in different parts of the world is challenging. Here, we present 4 unique case studies which illustrate the different diagnostic pathways of patients with DMD in Middle Eastern countries and highlight region-specific challenges to achieving timely and accurate genetic diagnosis of DMD. A lack of disease awareness and consequential failure to recognize the signs and symptoms of DMD significantly contributed to the delayed diagnoses of these patients. Additional challenges included limited available funding for genetic testing and a lack of local specialist and genetic testing centers, causing patients and their families to travel vast distances for appointments in some countries. Earlier and more accurate genetic diagnosis of DMD in this region would allow patients to benefit from effective disease management, leading to improvements in health-related quality of life.
Efficacy and Safety of Fospropofol Disodium for Injection in General Anesthesia Induction for Adult Patients: A Phase 3 Trial
Authors: Wu Chao-Meng , Zhang Wen-Sheng , Liu Jin , Zhang Wei-Yi , Ke Bo-Wen
Published: September 2021

Background:Fospropofol disodium for injection (FospropofolFD) is a prodrug that is metabolized into propofol to produce a general anesthesia effect when administered intravenously.

Objective:This study aimed to assess the efficacy and safety of FospropofolFDin comparison with propofol medium/long-chain fat emulsion injections (propofol-MCT/LCT) for general anesthesia induction in adult patients undergoing elective surgeries.

Setting:Nine academic medical centers in China.

Method:This multicenter, randomized, double-blind, double-simulated, controlled, and non-inferiority trial evaluated 540 eligible adult patients randomly assigned (2:1) to the intervention (20 mg/kg FospropofolFD) or control (2 mg/kg propofol-MCT/LCT) groups.

Main Outcome Measure:The primary efficacy endpoint was the success rate, defined as a Modified Observer’s Assessment of Alertness/Sedation Scale score of 1 within 5 min after study drug administration. The safety endpoints consisted of adverse events (AEs) related to consciousness, cognitive function, hemodynamic status, liver and kidney function, and blood tests.

Results:A total of 347 (96.3%) and 175 (97.2%) patients in the intervention and control groups, respectively, completed the study. The success rate for the primary outcome was 97.7% for both study drugs. The most frequent AEs in the intervention group were abnormal feeling (62.0%), blood pressure reduction (13.5%), and injection site pain (13.3%). No AEs related to consciousness and mental and cognitive functions or serious adverse events were reported.

Conclusion:FospropofolFD(20 mg/kg) is not inferior to propofol-MCT/LCT (2 mg/kg) in general anesthesia induction for American Society of Anesthesiologists (ASA) physical status I-II adult patients undergoing elective surgeries. It is safe and effective for clinical use under anesthesiologist monitoring.

Impact on Practice Statement:FospropofolFDcan produce a general anesthesia effect and reduce the incidence of pain at the site of injection.
HDAC6 and CXCL13 Mediate Atopic Dermatitis by Regulating Cellular Interactions and Expression Levels of miR-9 and SIRT1
Authors: Kwon Yoojung , Choi Yunji , Kim Misun , Jeong Myeong Seon , Jung Hyun Suk , Jeoung Dooil
Published: September 2021

Histone deacetylase 6 (HDAC6) has been known to regulate inflammatory diseases. The role of HDAC6 in allergic skin inflammation has not been studied. We studied the role of HDAC6 in atopic dermatitis (AD) and the mechanisms associated with it. The decreased expression or chemical inhibition of HDAC6 suppressed AD by decreasing autophagic flux and cellular features of AD. AD increased expression levels of the Th1 and Th2 cytokines, but decreased expression levels of forkhead box P3 (FoxP3) and interleukin-10 (IL-10) in an HDAC6-dependent manner. CXC chemokine ligand 13 (CXCL13), which was increased in an HDAC6-depenednt manner, mediated AD. MiR-9, negatively regulated by HDAC6, suppressed AD by directly regulating the expression of sirtuin 1 (SIRT1). The downregulation or inhibition of SIRT1 suppressed AD. Experiments employing culture medium and transwell suggested that cellular interactions involving mast cells, keratinocytes, and dermal fibroblast cells could promote AD; HDAC6 and CXCL13 were found to be necessary for these cellular interactions. Mouse recombinant CXCL13 protein increased HDAC6 expression in skin mast cells and dermal fibroblast cells. CXCL13 protein was found to be present in the exosomes of DNCB-treated skin mast cells. Exosomes of DNCB-treated skin mast cells enhanced invasion potentials of keratinocytes and dermal fibroblast cells and increased expression levels of HDAC6, SIRT1 and CXCL13 in keratinocytes and dermal fibroblast cells. These results indicate that HDAC6 and CXCL13 may serve as targets for the developing anti-atopic drugs.
Ion Homeostasis and Metabolome Analysis of Arabidopsis 14-3-3 Quadruple Mutants to Salt Stress
Authors: Gao Jing , van Kleeff Paula J. M. , de Boer Mark H. , Erban Alexander , Kopka Joachim , Hincha Dirk K. , de Boer Albertus H.
Published: September 2021

Salinity is one of the major abiotic stresses that limits agricultural productivity worldwide. Many proteins with defined functions in salt stress adaptation are controlled through interactions with members of the 14-3-3 family. In the present study, we generated three 14-3-3 quadruple knockout mutants (qKOs: klpc, klun, and unpc) to study the role of six non-epsilon group 14-3-3 proteins for salt stress adaptation. The relative growth inhibition under 100 mM of NaCl stress was the same for wild-type (Wt) and qKOs, but the accumulation of Na+ in the shoots of klpc was significantly lower than that in Wt. This difference correlated with the higher expression of the HKT1 gene in klpc. Considering the regulatory role of 14-3-3 proteins in metabolism and the effect of salt stress on metabolite accumulation, we analyzed the effect of a 24-h salt treatment on the root metabolome of nutrient solution-grown genotypes. The results indicated that the klpc mutant had metabolome responses that were different from those of Wt. Notably, the reducing sugars, glucose and fructose, were lower in klpc under control and salt stress. On the other hand, their phosphorylated forms, glucose-6P and fructose-6P, were lower under salt stress as compared to Wt. This study provided insight into the functions of the 14-3-3 proteins from non-epsilon group members. In summary, it was found that these proteins control ion homeostasis and metabolite composition under salt stress conditions and non-stressed conditions. The analyses of single, double, and triple mutants that modify subsets from the most effective qKO mutant (klpc) may also reveal the potential redundancy for the observed phenotypes.
Transcriptomic and Metabolomic Analyses Provide Insights Into an Aberrant Tissue of Tea Plant (Camellia sinensis)
Authors: Liu Ding-Ding , Wang Jun-Ya , Tang Rong-Jin , Chen Jie-Dan , Liu Zhen , Chen Liang , Yao Ming-Zhe , Ma Chun-Lei
Published: September 2021

Tea plant (Camellia sinensis (L.) O. Kuntze) is one of the most important economic crops with multiple mutants. Recently, we found a special tea germplasm that has an aberrant tissue on its branches. To figure out whether this aberrant tissue is associated with floral bud (FB) or dormant bud (DB), we performed tissue section, transcriptome sequencing, and metabolomic analysis of these tissues. Longitudinal sections indicated the aberrant tissue internal structure was more like a special bud (SB), but was similar to that of DB. Transcriptome data analysis showed that the number of heterozygous and homozygous SNPs was significantly different in the aberrant tissue compared with FB and DB. Further, by aligning the unmapped sequences of the aberrant tissue to the Non-Redundant Protein Sequences (NR) database, we observed that 36.13% of unmapped sequences were insect sequences, which suggested that the aberrant tissue might be a variation of dormant bud tissue influenced by the interaction of tea plants and insects or pathogens. Metabolomic analysis showed that the differentially expressed metabolites (DEMs) between the aberrant tissue and DB were significantly enriched in the metabolic pathways of biosynthesis of plant hormones and biosynthesis of phenylpropanoids. Subsequently, we analyzed the differentially expressed genes (DEGs) in the above mentioned two tissues, and the results indicated that photosynthetic capacity in the aberrant tissue was reduced, whereas the ethylene, salicylic acid and jasmonic acid signaling pathways were activated. We speculated that exogenous infection induced programmed cell death (PCD) and increased the lignin content in dormant buds of tea plants, leading to the formation of this aberrant tissue. This study advanced our understanding of the interaction between plants and insects or pathogens, providing important clues about biotic stress factors and key genes that lead to mutations and formation of the aberrant tissue.
How Do We Perceive a Humorous Manager? Manager Humor, Impression Management, and Employee Willingness to Work With the Manager
Authors: Brender-Ilan Yael , Reizer Abira
Published: September 2021

Humor is a form of communication that is intended to be entertaining and produce positive affective and cognitive responses from receivers. Nonetheless, humor in the workplace is a complicated matter. It has been recognized as a valuable tool for managers because it can activate various favorable outcomes and alter employees’ perception of the manager’s warmth and competence (impression management), but not always to the benefit of the manager. In our studies, the use of humor showed changed attitudes toward a manager’s warmth and competence, and eventually influenced the employee’s behavioral intentions. In Study 1, we tested the use of managerial humor in two emails. The humorous manager was perceived as warm, but not competent. Impression management mediated the employee’s willingness to work with the manager. In Study 2, we tested the use of managerial humor with one introductory email. In this study, we also monitored the gender of both the manager and the employee. Once again, the humorous manager was perceived as warm and humor mediated employees’ behavioral intentions. As for competence, gender moderated the results, such that male employees perceived humorous female managers as more competent, while female employees perceived humorous male managers as less competent. Practical implications are presented.
Nurturing Grandchildren With Down Syndrome: A Qualitative Study on Grandparents’ Needs Using Digital Tools†
Authors: Sánchez Gómez María C. , Martín-Sevillano Rocío , Martín-Cilleros María V. , Marcos J. J. Mena , García-Peñalvo Francisco J.
Published: September 2021

Grandparents who have grandchildren with disabilities are an underrepresented group in existing research related to the field. This qualitative phenomenological study’s general purpose is to analyze, from a personal perspective, the situations and needs of grandparents who have grandchildren with Down syndrome. The participants’ ages range from 65 to 85, and the ages of their grandchildren with Down syndrome range from 3 to 21 years. All participants had one grandchild with a disability, except for two, who each had two. A sociodemographic questionnaire was administered, and individual interviews were conducted, using open questions, through phone and/or video calls. An analysis of the participants’ speech was carried out, which implied the development of a system of meta-categories and categories. This analysis was developed manually, given the COVID-19 environment. The results indicate a substantial change from negative feelings caused by the knowledge of the diagnosis to feelings related to positive experiences expressed currently. The participants see themselves as a fundamental source of support (informal, instrumental, practical, social, emotional, and economic) for their families and, mainly, for their grandchildren with Down syndrome. A need for information and training was observed when the grandparents talked about first being informed of the diagnosis and their concerns about the future of these grandchildren and their siblings. They made social demands, such as greater government involvement or more significant opportunities to access resources and rights for their grandchildren. The results are discussed, as are possible future research directions.
An Empirical Investigation of the Relationship Between Spirituality, Work Culture, and Burnout: The Need for an Extended Health and Disease Model
Authors: Listopad Ian W. , Esch Tobias , Michaelsen Maren M.
Published: September 2021

Apart from biological, psychological, and social factors, recent studies indicate that spirituality and work culture also play an important role in the onset of burnout. Hence, the commonly applied bio-psycho-social model of health and disease might not be sufficient to comprehensively explain and describe burnout. This study empirically investigates the relationship between spirituality (operationalized by perceived meaningfulness of work) and work culture (operationalized by sense of homeliness of the working environment) with burnout risk and work engagement. For this purpose, an anonymous cross-sectional data collection with fully standardized questionnaires and selected socio-demographic and work-related items was conducted among working adults (n= 439) from different industriesviasocial media and local health service centers. For all scales and subscales, we found significant moderate to strong correlations. Furthermore, positive meaning within the perceived meaningfulness of work scale was the largest beta coefficient for burnout (β = −0.65) and work engagement (β = 0.62). Within sense of homeliness, the largest beta coefficient for burnout was needs fulfillment (β = −0.34) and work engagement emotional connection (β = 0.36). The strong associations suggest that the current health and disease model needs to be expanded to a bio-psycho-socio-spirito-cultural model to be able to sufficiently describe burnout. The perceived meaningfulness of work and a sense of homeliness should be adequately considered when examining the onset of burnout, describing burnout as a concept, and explaining work engagement.