bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Peak Inspiratory Flow and Hand Grip Strength Measurement in Men with Mild Chronic Obstructive Pulmonary Disease
Authors: Tsuburai Takahiro , Komase Yuko , Tsuruoka Hajime , Oyama Baku , Muraoka Hiromi , Hida Naoya , Kobayashi Takayuki , Matsushima Shinya
Published: August 2021

Backgrounds: Chronic obstructive pulmonary disease (COPD) decreases quality of life and muscular strength. Inspiratory flow is important for inhalants in the bronchi but is complicated to measure in routine practice. We hypothesized that hand grip strength (HGS) would correlate with inhalation rate in patients with mild COPD.Methods: The COPD patients were recruited at the St. Marianna University School of Medicine, Yokohama Seibu Hospital, from 2015 to 2018. We measured peak inspiratory flow (PIF) through an In-Check flow meter attached with Diskus [PIF(D)] and Turbuhaler [PIF(T)] inhalers. The 6-minute walking test (6MWT), and the fraction of exhaled nitric oxide (FENO), spirometry, HGS, or forced oscillation technique (FOT) parameters were measured.Results: Forty-four subjects were enrolled. All were men, with a mean age (± SD) of 77.8 ± 9.36 years. Thirty-nine patients had mild COPD. PIF(D) was 110 (80, 140) L/min (median, interquartile range), PIF(T) was 80 (70, 90) L/min, and HGS was 28.7 (13.8, 43.6) kgf. PIF(D) and PIF(T) were significantly correlated (r = 0.443, p = 0.003). PIF(D) was significantly correlated with age (r = − 0.327, p = 0.030) and HGS (r = 0.326, p = 0.031). PIF(T) was significantly correlated with age (r = − 0.328, p = 0.030), FVC (r = 0.351, p = 0.019), 6MWT distance (r = 0.392, p = 0.011), and HGS (r = 0.328, p = 0.030).Conclusion: HGS might be more useful for predicting PIF than other parameters. Also, elderly COPD patients need to be taught inhaled methods carefully.
Design of Broadband Infrared Photodetectors Enhanced by Dual-Mode Plasmonic Resonant Cavities
Authors: Du Jiayuan , Zhao Xinyu , Sun Xiaodong , Zeng Jinyao , Hu Xinhua
Published: August 2021

The signal-to-noise ratio of infrared photodetectors can be improved by using resonant cavities, whereas the enhancement effect usually occurs in a narrow wavelength range. Here, we propose a dual-mode plasmonic resonant cavity which can enhance the performance of infrared photodetectors in a wide range of wavelengths from 3.5 μm to 5.5 μm. The optical cavity consists of an Au grating, an ultrathin (310 nm) detective layer of mercury cadmium telluride, and an Au film, which can exhibit nearly perfect absorption at resonant wavelengths with using optimal parameters. For the target wavelength range, the wavelength-averaged absorption in the detective layer can also be 62%, about 12 times of that without the resonant cavity. Such a high enhancement of absorption can occur for incident light in a broad range of angle (θ < 45⁰) and with different polarizations.
KCNQ1OT1 Knock Down Alleviates Hyperosmlity Induced Dry Eye Disease via Inhibiting NLRP3 Inflammsome Activation and IL-1β Release
Authors: Li Xuran , Zhang Yanyan , Li Xinyue , Yu Yu , Jin Xin , Zhang Hong
Published: August 2021

Background. Long noncoding RNAs (lncRNAs) have been indicated that participate in inflammatory diaeases and age related diseases by regulating physiological and pathological processes directly or indirectly. Evidences have indicated lncRNAs might be involving in dry eye disease which can cause pathological changes of cornea and conjunctiva in ocular surface though inflammatory response. KCNQ1OT1 is a novel lncRNA, whose function remains totally unclear.Methods. qRT-PCR was performed to detect the expression of KCNQ1OT1, miR-214 and inflammasome-related genes NLRP3, caspase1 and IL-1β. Western blotting was carried out to detect inflammasome-related markers. The dry eye disease (DED) model was set up by scopolamine hydrobromide though subcutaneous injection. Bioinformatics was used to predict and validate the interaction between KCNQ1OT1 and miR-214 as well caspase1 and miR-214.Results. KCNQ1OT1 was significantly up-regulated during the process of DED while miR-214 was contrarily down-regulated. Knockdown of KCNQ1OT1 promoted cornea epithelial cells migration and down-regulated inflammasome-related genes. It was also confirmed that KCNQ1OT1 directly interacted with miR-214. Meanwhile, miR-214 could bind to 3'UTR of caspase1 and therefore inhibited its expression. Furthermore, co-transfection of miR-214 inhibitor could rescue the down-regulation of cell migration induced by KCNQ1OT1 knockdown.
Construction and Validation of an Immune-related lncRNA Prognosis Model in Thyroid Cancer
Authors: Li Zheng , Wang Hui , Deng Xia , Zhang Jing , Tang Wanyan , Wang Ling , You Wenxin , Nian Weiqi
Published: August 2021

Background A growing number of studies have shown that immune-related long non-coding RNAs (lncRNAs) play an important role in the development of cancer. The aim of this study was to identify immune-related lncRNAs in thyroid cancer (THCA) and to develop a prognostic model for THCA. Methods We downloaded immune-associated gene sets from the Gene Set Enrichment Analysis (GSEA) website and obtained THCA gene expression and clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were then obtained by performing a correlation analysis of the expression of lncRNAs and immune-related genes. Prognostic models for THCA immune-related lncRNAs were developed by univariate Cox regression and multiple Cox regression analysis. We confirmed the results in clinical samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results26 immune-related lncRNAs in THCA were obtained. Then we constructed a prognosis model composed of 7 lncRNAs (LINC01614, AC017074.1, LINC01184, LINC00667, ACVR2B-AS1, AC090673.1, LINC00900). Our model could be used as an independent prognostic factor. Principal component analysis displayed that the lncRNAs in the model can distinguish between high-risk and low-risk groups. Clinical correlation analysis showed that the expression levels of AC090673.1 (P<0.05), LINC01184 (P<0.001), LINC01614 (P<0.001) were related to disease stage, LINC00900 (P<0.001), LINC01614 (P<0.001) were related to the T stage of THCA. We validated this model in the cancer and paracancerous tissues from 24 THCA patients.ConclusionsWe identified seven immune-related lncRNAs as potential biomarkers for the prognosis of THCA.
Identification of Key Genes and Pathways in Hypertrophic Cardiomyopathy via Weighted Gene Co-Expression Network Analysis
Authors: Hua Yang , Sun Jin-Yu , Xin Ziling , Sun Wei , Sheng Yanhui , Kong Xiang-Qing
Published: August 2021

BackgroundHypertrophic cardiomyopathy (HCM) is a prevalent cardiovascular disease characterized as asymmetric hypertrophy of ventricular muscles. Cardiac morphological abnormality may result in slight or severe cardiopulmonary symptoms, arrhythmia, heart failure, and even sudden death. Previous studies have shown that HCM was an inherited disease where sixty percent carry mutations in genes encoding sarcomere proteins. However, considering heterogeneous phenotype or prognosis, the underlying mechanisms remain unclear.MethodsThe gene expression profiles of GSE36961 and GSE160997 were analyzed by ‘limma’ and ‘weighted gene co-expression network analysis (WGCNA)’ package in R to identify differentially expressed genes (DEGs) and key modules, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Protein-protein interaction network was constructed based on the overlapped genes of DEGs and key modules, and we identified the top 4 hub genes using ‘cytohubba’ according to inner connectivity.ResultsWe identified the red and brown modules as the key modules. Enrichment analysis showed that cellular divalent inorganic cation homeostasis, collagen−containing extracellular matrix, and actin binding were significantly enriched. VSIG4, CD163, FCER1G, and LAPTM5 were identified as hub genes.ConclusionsThis study suggested that VSIG4, CD163, FCER1G, and LAPTM5 might be hub genes associated with the progression of HCM. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.
Investigation Into the Optical Emission of Features for Powder-bed Fusion Am Process Monitoring
Authors: Zhang Yingjie , Yan Wentao , Peng Xiaojun , Chen Zhangdong , Jiang Zimeng , Wang Di
Published: August 2021

Process monitoring and control is an essential approach to improve additive manufacturing (AM) built quality. For the development of powder bed fusion (PBF) AM monitoring system, sensing process optical emission is a popular approach, as it provides rich information on melt pool condition which directly determines final part quality. However, the optical emission information is convoluted. And the lack of full understanding of it limits the further development of an optimal monitoring system. Therefore, the aim of this study is to explore the correlations between the optical emission and the processing condition to help enhance PBF process monitoring. A high-speed camera was used to acquire the images of the optical emission in the waveband of 800 nm – 1,000 nm. Several typical features were extracted and analyzed with the increase of laser power. The K-means clustering method was used to identify the hidden patterns of these features. The SVM model was built for quality identification. Five process patterns have been identified and therefore the collected dataset was partitioned into five subsets. The extracted features in each subset was characterized. It is found that plume area and plume orientation are the two most crucial features for processing condition monitoring. Number of spatters and spatter dispersion index are sensitive to some minor process vibrations which have little effect on built quality. Additionally, the time sequence information of the features can help improve the quality identification performance.
Ultrasound Gray Scale Ratio for the Differential Diagnosis of Papillary Thyroid Microcarcinoma and Benign Micronodule in Patients with Hashimoto’s Thyroiditis
Authors: Han Zhijiang , Xie Lesi , Wei Peiying , Lei Zhikai , Ding Zhongxiang , Zhang Ming
Published: August 2021

Purpose To investigate the diagnostic value of ultrasound gray scale ratio (UGSR) for differentiating papillary thyroid microcarcinomas (PTMCs) and benign micronodules (BMNs) in patients with HT.Methods The ultrasound images of 285 PTMCs (in 247 patients) and 173 BMNs (in 140 patients) in the HT group, as well as 461 PTMCs (in 417 patients) and 234 BMNs (in 197 patients) in the non-HT group were retrospectively analyzed. All cases were confirmed by histological examinations. The gray scale values of the nodules and surrounding thyroid tissues were measured and subsequently the UGSR was calculated. Receiver operating characteristic curve was used for determining the area under the curve (AUC), optimal UGSR threshold, sensitivity and specificity in differentiating PTMCs and BMNs in the two groups.Results The UGSRs of PTMCs and BMNs were 0.52±0.12 and 0.85±0.24 (P<0.001) in the HT group and 0.57±0.13 and 0.87±0.20 (P<0.001) in the non-HT group, respectively. The differences in the UGSRs of PTMCs were significantly different between the two groups (P<0.001), whereas the difference in the UGSRs of BMNs was not significantly different between the two groups (P=0.416). The AUC, optimal UGSR threshold, sensitivity and specificity of UGSR for differentiating PTMCs and BMNs in the HT and non-HT groups were 0.901 and 0.890, 0.727 and 0.687, 82.05% and 77.46% and 90.67% and 91.23%, respectively.Conclusions UGSR exhibits important diagnostic value for differentiating PTMCs from BMNs in both HT and non-HT groups, and the USGR was lower in the HT group compared with that in the non-HT group.
Identification of Potential Crucial Immune-related Genes and Key Pathways in Oral Lichen Planus
Authors: Geng Lou , Zhang Xingming , Tang Yi , Gu Wenli
Published: August 2021

Oral lichen planus (OLP) is a chronic autoimmune oral mucosal disease which seriously affect the life quality of the patients. But till now, the exact etiology and pathogenesis of OLP still remains unclear. The aim of our study was to find the key molecules and pathway involved in the pathogenesis mechanisms of OLP, therefore, provide reference for identifying more effective therapeutic strategies for OLP. Data from GSE52130 were downloaded from GEO data sets for analysis, and a total of 255 differentially expressed genes were selected out. Then by means of a series of gene enrichment analysis, we illustrated that most of these important genes were enriched in the focal adhesion pathway and metabolism pathways. In addition, we also constructed a protein-protein interaction (PPI) network and identified 8 hub genes which may play the important role in the development of OLP, including THBS2, COL3A1, IGFBP3, COL1A2, COL1A1, PTGS2, IL1B, ARG1. Lastly, we also predicted transcription factors of these hub genes, then constructed the corresponding transcription regulatory network. Taken together, our data indicated that the focal adhesion pathway and metabolism pathways, as well as 8 crucial immune-related genes might be most likely involved in the development of OLP, which would provide important information and objective basis for elucidating the pathogenesis of OLP and providing more effective targeted immunotherapy strategies for OLP.
WITHDRAWN: Distance-Based Performance Evaluation of Two-Ray Ground and Free Space Propagation Models in Mobile Ad-hoc NETwork (MANET)
Authors: HUSSAIN ALTAF
Published: August 2021

Mobile Ad-hoc NETwork (MANET) is a decentralized type of wireless network. The network is ad hoc because it does not rely on a pre-existing infrastructure, such as routers in wired networks or access points in managed wireless networks. One of the major issue and challenging area in MANET is the process of routing due to dynamic topologies and high mobility of mobile nodes. The efficiency and accuracy of a protocol depend on many parameters in these networks. In addition to other parameters node velocity and propagation models are among them. Calculating signal strength at the receiver is the responsibility of a propagation model while the mobility of nodes is responsible for the topology of the network. A huge amount of loss in performance is occurred due to the variation of signal strength at the receiver while increasing and decreasing the distance of nodes. In this paper, a novel approach is identified and portrayed of the said propagation models based on distance from each other. It has been analyzed to check distance based performance evaluation of Two Ray Ground and Free Space Radio Wave Propagation Models on the performance of Ad-hoc On-demand Distance Vector (AODV) Routing Protocol in MANET. The simulation has been carried out in (Network Simulator-2) NS-2 by using performance metrics that are Average Throughput (kpbs), Average Latency (milliseconds) and Average Packet Drop (packets). The results predicted that propagation models and mobility have a strong influence on the performance of AODV in considered distance based scenario.
Endogenous microRNA Triggered Enzyme-free DNA Logic Self-assembly for Amplified Bioimaging and Enhanced Gene Therapy via in Situ Generation of siRNAs
Authors: Jiang Qinghua , Yue Shuzhen , Yu Kaixin , Tian Tian , Zhang Jian , Chu Huijun , Cui Zhumei , Bi Sai
Published: August 2021

BackgroundSmall interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma.MethodsThis strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded “AND” gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma. ResultsThe proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs.ConclusionThe endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation.
Corneal Densitometry in Bilateral Keratoconus Patients with Unilateral Corneal Vogt's Striae: A Contralateral Eye Study
Authors: Wei Shengsheng , Li Jing , Li Yong , Zhang Yaohua , Cai Yan , Du Jing , Liu Jianguo , Wang Yan
Published: August 2021

BackgroundWe aimed to investigate corneal densitometry and correlations with corneal morphological parameters in bilateral keratoconus (KCN) patients with unilateral Vogt's striae.MethodsOne hundred and-twelve patients (224 eyes) with bilateral KCN and unilateral Vogt's striae were enrolled in this cross-sectional contralateral eye study. Corneal densitometry and morphological parameters were measured using Pentacam HR.ResultsOur study revealed that corneal densitometry values of the anterior 0–2 mm and 2–6 mm, intermediate 0–2 mm and 2–6 mm, posterior 2–6 mm, and total cornea 2–6 mm in eyes with Vogt’s striae were significantly higher than those in eyes without Vogt's striae (P < 0.05). The corneal densitometry values of the anterior 6–10 mm, posterior 0–2 mm, and total cornea 6–10 mm were significantly lower in eyes with Vogt's striae (P < 0.05). The corneal densitometry values in the anterior 0–2 mm and total cornea 2–6 mm were positively correlated with K1, K2, Km, Kmax, ACE, and PCE (P < 0.05) and negatively correlated with CCT and TCT in eyes with Vogt's striae (P < 0.05). K2, Km, and Kmax were significantly correlated with densitometry values of the anterior 0–2 mm and the intermediate 0–2 mm in eyes without Vogt’s striae (P < 0.05). Corneal densitometry values of the anterior and intermediate layers in the central cornea were higher in KCN eyes with Vogt's striae than in eyes without Vogt's striae, and the densitometry values of the anterior corneal stroma in the central region of the cornea were higher than those of the peripheral cornea in KCN eyes with and without Vogt's striae.ConclusionsIn conclusion, these results indicate that Vogt's striae mainly occur on the anterior and intermediate layers during the progression of KCN.
Exosomal Mir-21 Derived from Umbilical Cord Mesenchymal Stem Cells Promotes Angiogenesis by Activating SPRY1/PI3K/AKT Pathway and Contributes New Bone Formation in a Rat Model.
Authors: Zhang Yuntong , Li Xiaoqun , Xie Yang , Xia Yan , Wang Panfeng , Hao Zichen , Fang Shuo , Xu Shuogui
Published: August 2021

Background: Delayed atrophic healing and non-union remain the most difficult types of complications to treat and can lead to numerous re-operations and high socioeconomic cost. Exosome derived from MSCs is a promising strategy in the treatment of fracture. However, it’s still not fully clear in the underlying mechanisms. Methods: In this study, we first elucidated the underlying mechanism of umbilical cord MSC (uMSC)-Exo-induced angiogenesis in bone regeneration and fracture repair. RT-PCR, luciferase reporter, western blot and immunofluorescence in situ hybridization assay were performed to identify the expression of related genes and pathways in uMSC-Exo. Proliferation, tube formation and transwell migration assay were used to evaluated the effects of uMSC-Exo in vitro. A rat calvarial defect model was used to evaluated the effects of uMSC-Exo in vivo.Results: We found that, miR-21 was the most abundant miRNA in the uMSC-Exos. In vivo and in vitro experiments demonstrated that, the uMSC-Exo could promote the migration, angiogenic and capacity of HUVECs via miR-21, inhibition of miR-21 could attenuate the effects of uMSC-Exos. For mechanical study, we found that, exosomal miR-21 derived from uMSCs activates PI3K/AKT signalling by targeting SPRY1 in HUVECs, SPRY1 knockdown could promote the PI3K/AKT activation and HUVEC proliferation, migration and angiogenesis. In addition, exosomal miR-21 derived from uMSCs enhanced local microvascular network formation and bone regeneration in vivo. ConclusionIn: In conclusion, we firstly reported that uMSC-derived exosomes as a ready-made regenerative medicine therapy to bone healing.
Assesment of Origin of Inflammation in the Destruction of the Vascular Wall in the Form of Outside-in or Inside-out in Amputated Diabetic Limbs
Authors: saberianpour shirin , Modaghegh Mohammad hadi saeed , Amoueian sakineh , shahri Jamal Jalili
Published: August 2021

Introduction and aimsThe traditional thought of vascular inflammation has been an “inside-out” reaction, concentrated on the monocyte adherence to the intima of blood vessels and the oxidative lipid hypotheses. The relevancy of the “outside-in” procedure in vascular disorders will be better clarified in future investigations. In this study, we tried to investigate the origin of inflammation in the form of outside-in and inside-out in the vascular wall of diabetic patients.Material and MethodsA random sampling technique was used to enroll patients in this pilot study (10 Samples). Specimens were prepared when the diabetic foot with lesion was mainly amputated from the tissue, comprising the dermal layer and muscle from the lesion site and the transitory site with a minimal 1 cm length, width, and height. The specimens were placed in pathology battles containing 10% formalin for pathological tests. Slides were stained based on the Hematoxylin and Eosin Staining Protocol, Elastin staining and Trichrome staining. Immunohistochemistry was performed for IL-1, IL-6, VECAM-1, PECAM-1 and 4-HNE markers.ResultsAccording to the results of pathological studies and the level of inflammatory markers, it was shown that in diabetic tissues with vascular damage, the source of inflammation is more from the wound and from outside the body than internal factors such as hyperglycemia. On the other hand, the same inflammation the wound can spread from the outer vascular layers of the adventitia to the inner layers of the intima vascular in the form of outside-in.ConclusionIt is concluded that the source of vascular wall-destroying inflammation is from the outside to the inside and according to the (outside- in) assumption in patients with diabetic foot, ulceration leads to limb amputation.
A 8-gene-methylation-based Signature for Head and Neck Squamous Cell Carcinoma Prognosis
Authors: Wang Zihui , Yang Jingrun , Liu Lihong
Published: August 2021

Background Head and neck squamous cell carcinoma (HNSCC), accounting for 6% of systemic malignant tumors, has an increasing incidence rate year by year worldwide. A large number of studies have investigated the tumor markers to determine clinical stage, prognosis, treatment evaluation, predict relapses, and overall survival of HNSCC patients, with controversial results. Methods In this paper, we comprehensively analyzed gene expression and DNA methylation data sets of HNSCC and adjacent non-tumor samples from The Cancer Genome Atlas (TCGA). Univariate cox regression analysis followed by sure independence screening (SIS) were used for identifying differential methylation signatures to stratify patients with significantly different prognosis. Results We identified methylation levels of HS3ST1，TOMM34，RPL26L1，MTHFD2，ORC1，MYOSLID，UHRF1 and AL357033.3 as potential HNSCC prognosis signatures, and verified the correlation between their gene expression and the corresponding methylation. Their reliability for predicting the prognosis of HNSCC was confirmed in an independent dataset. Conclusions In conclusion, we built a 8-gene-methylation-based signature which can well assess the prognosis of HNSCC patients.
Towards Next Generation of High-Performance Radio Frequency Passive Components for Beyond-5G, 6G and Super-IoT – Application of Response Surface Method to the Optimization of RF-MEMS Reconfigurable Power Attenuators
Authors: Iannacci Jacopo , Tagliapietra Girolamo , Bucciarelli Alessio
Published: August 2021

The emerging paradigms of Beyond-5G, 6G and Super-IoT will demand for Radio Frequency (RF) passive components with pronounced performance, and RF-MEMS technology, i.e. Microsystem-based RF passives, is a good candidate to meet such a challenge. As known, RF-MEMS have a complex behavior, that crosses different physical domains (mechanical; electrical; electromagnetic), making the whole design optimization and trimming phases particularly articulated and time consuming. In this work, we propose a novel design optimization approach based on the Response Surface Method (RSM) statistical methodology, focusing the attention on a class of RF-MEMS-based programmable step power attenuators. The proposed method is validated both against physical simulations, performed with Finite Element Method (FEM) commercial software tools, as well as experimental measurements of physical devices. The case study here discussed features 3 DoFs (Degrees of Freedom), comprising both geometrical and material parameters, and aims at optimizing the RF performance of the MEMS attenuator in terms of attenuation (S21 Scattering parameter) and reflection (VSWR – Voltage Standing Wave Ratio). When validate, the proposed RSM-based method allows avoiding physical FEM simulations, thus making the design optimization considerably faster and less complex, both in terms of time and computational load.
Selection Stability in High Dimensional Statistical Modelling: Defining a Threshold for Robust Model Inference
Authors: Green Martin , Lima Eliana , Hyde Robert
Published: August 2021

Epidemiological research commonly involves identification of causal factors from within high dimensional (wide) data, where predictor variables outnumber observations. In this situation, however, conventional stepwise selection procedures perform poorly. Selection stability is one method to aid robust variable selection, by refitting a model to repeated resamples of the data and calculating the proportion of times each covariate is selected. A key problem when applying selection stability is to determine a threshold of stability above which a covariate is deemed ‘important’. In this research we describe and illustrate a two-step process to implement a stability threshold for covariate selection. Firstly, covariate stability distributions were established with a permuted model (randomly reordering the outcome to sever the relationship with predictors) using a cumulative distribution function. Subsequently, covariate stability was estimated using the true model outcome and covariates with a stability above a threshold defined from the permuted model, were selected in a final model. The proposed method performed well across 22 varied, simulated datasets with known outcomes; selection error rates were consistently lower than conventional implementation of equivalent models. This method of covariate selection appears to offer substantial advantages over current methods, to accurately identify the correct covariates from within a large, complex parameter space.
Patients with Chromosome 11q-abberations are Characterized by a Combined Primary Immunodeficiency Involving Both B- and T-lymphocytes
Authors: Huisman Elisabeth Janneke , Brooimans A. Rick , Mayer Samone , Joosten Marieke , de Bont Louis , Dekker Mariëlle , Rammeloo Elisabeth L.M. , Smiers Frans J. , Hagen P. Martin Van , Zwaan C Michel , de Haas Masja , Cnossen Marjon H. , Dalm Virgil A.S.H.
Published: August 2021

Disorders of the long arm of chromosome 11 (11q) are rare and involve various chromosomal regions. Patients with 11q-disorders, including Jacobsen syndrome, often present with a susceptibility for bacterial, prolonged viral and fungal infections partially explained by hypogammaglobulinemia. Additional T-lymphocyte or granular neutrophil dysfunction may also be present. In order to evaluate infectious burden and immunological function in patients with 11q-disorders, we prospectively studied a cohort of 14 patients with various 11q aberrations. Clinically, 12 patients exhibited prolonged and repetitive respiratory tract infections, frequently requiring (prophylactic) antibiotic treatment (n=7), ear-tube placement (n=9) or use of inhalers (n=5). Complicated varicella infections (n=5), chronic eczema (n=6), warts and chronic fungal infections (n=4) were reported. Six patients were on immunoglobulin replacement therapy. We observed a high prevalence of low B-lymphocyte counts (n=8), decreased T-lymphocyte counts (n=5) and abnormal T-lymphocyte function (n=12). Granulocyte function was abnormal in 29% without an aberrant clinical phenotype. Immunodeficiency was found in patients with terminal and interstitial 11q-deletions and in one patient with 11q trisomy. Genetically, FLI1 and ETS1 are seen as causative for the immunodeficiency, but these genes were deleted nor duplicated in 5 of our 14 patients. Alternative candidate genes on 11q such as ATM, CD3-cluster, CBL and THYN1 may have a role in immune dysregulation in our patients. In conclusion, we present evidence that a combined primary immune deficiency may be present in patients with 11q-disorders leading to clinically relevant infections. Therefore, broad immunological screening and necessary treatment is of importance in this patient group.
CAV1 and VCL are Downregulated in Atherosclerotic Aortic Endothelial
Authors: zhang wei , Wu Jianping , Dong Jinyun , Li Wenwen , Wang Xinjie
Published: August 2021

Background: Atherosclerosis (AS) is a common atherosclerotic vascular disease, and is one of the important factors leading to cardiovascular and cerebrovascular diseases.So far, the specific etiology and pathogenesis of AS have not been clarified, and further research is needed.Methods: Bioinformatics methods were used to analyze the data set of GSE57691 and GSE137578 in normal and atherosclerotic arterial endothelial cells from Gene Expression Omnibus (GEO).Results: There are a total of 300 differentially expressed genes (DEGs) in the GSE57691 and GSE137578 datasets, which are mainly enriched in the focal adhesion signaling pathway (adj P<0.05).We identified 10 hub genes (ACTG2, CAV1, CALD1, CDC42, CCT2, CCT3, VCL, PPARG, POLR2F and TPM3) in the protein-protein interaction (PPI) network, of which 3 ( CAV1, CDC42 and VCL) Significantly enriched in the adhesion signaling pathway.In addition, a search in the BIOGPS database found that CAV1 and VCL are highly expressed in coronary arteries.Conclusions: In conclusion, bioinformatics technology has proved to be useful for screening and identifying novel biomarkers of diseases.300 DEGs and 10 hub genes were significantly enriched in atherosclerotic aortic endothelial cells, especially CAV1 and VCL genes.
Rikkunshito for Upper Gastrointestinal Syndrome in Patients With Cancer: A Systematic Review and Meta-analysis Protocol
Authors: Liu Hong , Ren Yifeng , Wang Yuting , Yang Yu , Zheng Chuan , You Fengming
Published: August 2021

BackgroundUpper gastrointestinal syndrome including nausea, vomiting, and anorexia is a common side effect of chemotherapy, which are associated with treatment interruptions, reduced food intake, decreased functionality and a worse quality of life. Rikkunshito is a traditional herbal medicine that has gained increasing attention in recent years for its effect on relieving gastrointestinal disorders in various digestive diseases, while its efficacy for upper gastrointestinal syndrome induced by chemotherapy remains uncertain. MethodsDatabases including PubMed, EMBASE, MEDLINE, Cochrane Library, Chinese databases, and Japanese database will be systematically searched from their inception onwards. Randomized controlled trials will be assessed. The primary outcome parameters are the complete control (CC) rate, complete response (CR) rate, and complete protection (CP) rate in the overall phase (0–120 hours). The secondary outcomes include: (I) the CC rate, CR rate and CP rate during the acute phase (0–24 hours) and delayed phase (24–120 hours); (II) the score and frequency of vomiting, nausea, and anorexia occurring; (III) the daily dietary intake and body weight; (IV) plasma ghrelin level; (V) quality of life; (VI) incidence of adverse events. The overall quality of the data will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation guidelines. Risk of bias will be evaluated by the Cochrane tool. Reporting bias will be estimated using Begg and Egger tests. Heterogeneity will be evaluated by the I2 statistic and Q test. If I2 > 50%, sensitivity analysis and subgroup analysis of different items will be performed. DiscussionFrom the study, we will ascertain the efficacy and safety of rikkunshito in chemotherapy-induced upper gastrointestinal syndrome. This review may provide evidence for rikkunshito as an adjuvant to treat upper gastrointestinal symptoms in patients with cancer. Systematic review registration﻿CRD42020214299 in PROSPERO.
Worry and Perceived Risk of COVID-19 Among Government Employees in Ethiopia
Authors: Deressa Wakgari , Worku Alemayehu , Getachew Sefonias , Amogne Wondwossen , Abebe Workeabeba
Published: August 2021

Background

Worry and perceived risk have been identified as important factors that affect people’s attitude to adopt preventive behaviors against infectious diseases outbreaks and pandemics. However, very few recent studies investigated the worry and perceived risk aspects of the COVID-19 pandemic. This study aimed to assess the level of worry and perceived risk of COVID-19 among government employees working in 46 public institutions in Addis Ababa, Ethiopia.
Methods

This cross-sectional study used a sample of 1,573 respondents selected by systematic random sampling technique. Data on socio-demographics, worry and perceived risks of COVID-19 were collected using a self-administered questionnaire between 8th and 19th June 2020. Summary statistics were used to summarize the data. Mixed-effects linear regression analyses were performed to identify predictors of COVID-19 worry and perceived risk.
Results

The mean (± SD) age was 35 (± 8.5) years, with 58.3% aged between 30 to 49 years. About 63% were male and 87% had bachelor’s degree or above. Almost all (98%) respondents were worried about the economic crisis due to COVID-19, followed by worries related to limited access to food supplies (97%), and losing loved one’s (95%). Majority (81%) reported they were being susceptible to coronavirus, and 79% indicated they had a chance of acquiring the virus. About 61% reported their personal health’s increased risk of COVID-19 due to their work characteristics. Predictors of COVID-19 worry were increased year of service (β = 0.09, p = 0.001), being from Oromia (β = 3.93, p < 0.001), younger age (β = -0.07, p < 0.001), having bachelor’s degree (β = -1.58, p = 0.001), and master’s degree or above β = -1.84, p < 0.001). COVID-19 level of worry (β = 0.07, p < 0.001), being men (β = 0.34, p = 0.010) and self-reported chronic illness (β = 0.45, p = 0.047) were significant predictors of perceived risk.
Conclusions

This study demonstrated higher level of COVID-19 related worry and perceived risk. COVID-19 worry correlated significantly with perceived risk. The findings highlight the importance of considering public reactions such as worry and risk perceptions towards COVID-19 to inform the ongoing public health interventions and health promotion programs.
DIVIS: A Semantic Distance to Improve the Visualization of Incomplete Heterogeneous Phenotypic Datasets
Authors: Eid Rayan , Landès Claudine , Pernet Alix , Benoît Emmanuel , Santagostini Pierre , Ghaziri Angélina El , Bourbeillon Julie
Published: August 2021

BackgroundThanks to the wider spread of high-throughput experimental techniques, biologists are accumulating large amounts of datasets which often mix quantitative and qualitative variables and are not always complete, in particular when they regard phenotypic traits. In order to get a first insight into these datasets and reduce the data matrices size scientists often rely on multivariate analyses. However such approaches are not always easily practicable in particular when faced with mixed datasets with missing values. Moreover displaying large numbers of individuals leads to cluttered visualizations which are difficult to interpret. ResultsWe introduce a new methodology to overcome these limits. The underlying principle consists in (i) grouping similar individuals, (ii) representing each group by emblematic individuals we call archetypes and (iii) build sparse visualizations based on these archetypes. As a preliminary step to the clustering we design a new semantic distance tailored for both quantitative and qualitative variables which allows a realistic representation of the relationships between individuals. This semantic distance is based on ontologies which are engineered to represent real life knowledge regarding the underlying variables. Our approach is implemented as a Python pipeline and illustrated by a rosebush dataset including passport and phenotypic data. ConclusionsThe introduction of our new semantic distance and of the archetype concept allows us to build a comprehensive representation of an incomplete dataset characterized by large proportion of qualitative data. The methodology described here could have wider use beyond information characterizing organisms or species and beyond plant science. Indeed we could apply the same approach to any incomplete mixed dataset.
Carbon Monoxide Modulation of Microglia-Neuron Communication: Anti-Neuroinflammatory and Neurotrophic Role
Authors: Soares Nuno L. , Paiva Inês , Bravo Joana , Queiroga Claudia S.F. , Melo Bernadete F. , Conde Silvia V. , Romão Carlos C. , Summavielle Teresa , Vieira Helena L.A.
Published: August 2021

Background Microglia, the ‘resident immunocompetent cells’ of the central nervous system (CNS), are key players in innate immunity, synaptic refinement and homeostasis. Dysfunctional microglia contribute heavily to the creation of a toxic inflammatory milieu, a driving factor in the pathophysiology of several CNS disorders. Strategies for modulation of microglial function are required to tackle exacerbated tissue inflammation. Carbon monoxide (CO) is an endogenous gaseous molecule, produced by the degradation of haem, which presents several biological functions, namely anti-inflammatory, anti-apoptotic, pro-homeostatic and cytoprotective.Methods A novel molybdenum based CO-releasing molecule ALF826 was used for the assessment of neuron-microglia remote communication. Primary cultures of rat microglia and neurons, or BV-2 microglial mouse cell line and CAD neuronal mouse cell line were used to study microglia to neuron interaction. An approach based on microglial derived conditioned media in neuronal culture was applied.Results Medium derived from CO-treated microglia provided indirect neuroprotection against inflammation by limiting lipopolysaccharide (LPS)-induced expression of reactivity markers (CD11b), production of reactive oxygen species (ROS) and secretion of inflammatory factors (TNF-α, nitrites). This consequently prevented neuronal cell death and maintained neuronal morphology. In contrast, in the absence of inflammatory stimulus, conditioned media from CO-treated microglia improved neuronal morphological complexity, which is an indirect manner of assessing neuronal function. Likewise, microglial medium also prevented neuronal cell death induced by pro-oxidant tert-Butyl hydroperoxide (t-BHP). ALF826 treatment reinforced microglia secretion of Interleukin-10 (IL-10) and adenosine, mediators which may be involved in providing protection against t-BHP stress in this remote communication model. Chemical inhibition of adenosine receptors A2A and A1 reverted CO-derived neuroprotective effect, further highlighting a role for CO in regulating neuron-microglia communication via purinergic signalling.Conclusions Our findings indicate that CO has a modulatory role on microglia-to-neuron communication, promoting neuroprotection in a non-cell autonomous manner. In conclusion, CO-induced neuroprotection is afforded (i) by blocking exacerbated microglial inflammation and (ii) by the microglial release of neurotrophic factors. For the first time it is described CO improvement of microglial neurotrophism under non-inflammatory conditions.
Association Between Base Excess and Mortality Among Patients in ICU with Acute Kidney Injury
Authors: Cheng Yi , Tang Yuanjun , Tu Boxiang , Cheng Xin , Qi Ran , Guo Wei , Li Dongdong , Wu Shengyong , Zhu Ronghui , Zhao Yanfang , Qin Yingyi , Wu Cheng
Published: August 2021

Objective This study aimed to explore the association between base excess (BE) and risk of 30-day mortality among patients with acute kidney injury (AKI) in ICU.Methods This retrospective study including ICU patients with AKI from Medical Information Mart for Intensive Care (MIMIC)-IV database. We used multivariate Cox proportional-hazards model to calculate the hazard ratio (HR) for risk of 30-day mortality among patients with AKI. Furthermore, we utilized Cox proportional-hazard model with restrict cubic splines (RCS) to explore the potential no-linear association. Results Of all the 14238 ICU patients with AKI, BE showed U-shaped relationship with risk of 30-day mortality for patients with AKI, and higher or lower BE value could increase the risk. Compared with normal base excess (-3~3 mmol/L), patients with difference groups (BE ≤ -9mmol/L, -9 mmol/L <BE≤-3 mmol/L, 3 mmol/L <BE≤9 mmol/L and BE＞9 mmol/L) had different HR for mortality: 1.57(1.40,1.76), 1.26(1.14,1.39), 0.97(0.83,1.12), 1.53(1.17,2.02) respectively. And the RCS analyses also showed U-shaped curve between BE and 30-day mortality risk.Conclusion Our results suggest both higher and lower BE in patients with AKI would increase the risk of 30-day mortality. BE measured at administration could be a critical prognostic indicator for ICU patients with AIK and provide guidance for clinicians.
Combination of Synovial Fluid IL-4 and Polymorphonuclear Cell Percentage Improves the Diagnostic Accuracy of Chronic Periprosthetic Joint Infection
Authors: Huang Jiaxing , wang Jiawei , Qin Lei lei , Zhu Bo , Zhu Sizheng , yang Jianye , Huang Wei , Hu Ning
Published: August 2021

Background: Synovial fluid biomarkers have been confirmed with promising diagnostic value for chronic periprosthetic joint infection (PJI), even there was still no “gold standard”. Interleukin-4 (IL-4) and polymorphonuclear cells (neutrophil) count in synovial fluid play a crucial role in mediating local inflammation of bacterial infections and therefore could be valuable biomarkers for PJI. Methods: The purpose of this study was to investigate the diagnostic capacity of synovial fluid IL4 (SF-IL4) and polymorphonuclear cell percentage(SF-PMN%) for chronic PJI. According to the 2013 Musculoskeletal Infections Society(MSIS 2013) criteria, chronic PJI is defined as occurred more than 6 weeks after the primary arthroplasty. A total of 110 patients who scheduled to undergo revision arthroplasty from January 2019 to October 2020 were enrolled. 11 patients were eliminated by exclusion criteria. 43 of 99 patients were classified as infected and 56 as not infected. In all patients, SF-IL4 and SF-PMN% were measured in synovial fluid, serum CRP, ESR levels were measured preoperatively. The area under the curve(AUC) for each biomarker was analyzed, the diagnostic value and optimal cutoff values were calculated. Results: The demographic data was not statistically different. The SF-IL4 and SF-PMN% showed a great diagnostic accuracy of chronic PJI from aseptic failure patients with AUC of 0.97(95% confidence interval (CI), 0.92-0.99) and 0.89(95%CI, 0.82-0.95) separately, which was higher than the serum ESR (0.72), and serum CRP (0.83). We set 1.7 pg/mL and 75% as the optimal cut-off values of SF-IL4 and SF-PMN% individually. Combination of SF-IL4 and SF-PMN% improved the diagnostic ability for chronic PJI with a specificity of 97.0%, and 96.0% accuracy.Conclusion: Synovial fluid IL-4 was a valuable biomarker for chronic PJI detection. Combination of SF-IL4 and SF-PMN% provided higher specificity and accuracy when met the cut-off values of 1.7 pg/mL and 75% simultaneously.
Pharmacological Inhibition of Cryptochrome and REV-ERB Promotes DNA Repair and Cell Cycle Arrest in Cisplatin-Treated Human Cells
Authors: Anabtawi Nadeen , Cvammen William , Kemp Michael G.
Published: July 2021

Nucleotide excision repair (NER) and cell cycle checkpoints impact the ability of the anti-cancer drug cisplatin to inhibit cell proliferation and induce cell death. Genetic studies have shown that both NER and cell cycle progression are impacted by the circadian clock, which has emerged as a novel pharmacological target for the treatment of various disease states. In this study, cultured human cell lines were treated with combinations of cisplatin and the circadian clock modulating compounds KS15 and SR8278, which enhance circadian clock transcriptional output by inhibiting the activities of the cryptochrome and REV-ERB proteins, respectively. Treatment of cells with KS15 and SR8278 protected cells against the anti-proliferative effects of cisplatin and increased the expression of NER factor XPA and cell cycle regulators Wee1 and p21 at the mRNA and protein level. Correlated with these molecular changes, KS15 and SR8278 treatment resulted in fewer unrepaired cisplatin-DNA adducts in genomic DNA and a higher fraction of cells in the G1 phase of the cell cycle. Thus, the use of pharmacological agents targeting the circadian clock could be a novel approach to modulate the responses of normal and cancer cells to cisplatin chemotherapy regimens.
UHMK1 Dependent Phosphorylation of Cajal Body Protein Coilin Altered 5-FU Sensitivity in Colon Cancer Cells
Authors: Niu Huan , Zhao Meng , Huang Jing , Wang Jing , Si Yang , Cheng Shan , Ding Wei
Published: August 2021

Background: Resistance to 5-fluorouracil (5-FU) in chemotherapy and recurrence of colorectal tumors is a serious problem to be resolved for the improvement of clinical outcomes.Methods: In the present study, the effects of conditioned medium (CM) derived from 5-FU-resistant HCT-8/FU on cell functions were evaluated. The methods of immunofluorescence and RNA-seq analyses were used to investigate the molecular mechanism underlining the roles of CM from resistant cells.Results: we found that CM derived from 5-FU-resistant HCT-8/FU was able to reduce 5-FU chemosensitivity of HCT-8 colon cancer cells, with correlating changes in the number and morphology of the Cajal bodies (CBs) as observable nuclear structures. We identified UHMK1 was able to change the disassembly and reassembly of CBs regulated by the phosphorylation of coilin, a major component of CBs, and subsequently resulted in a large number of variations of RNA alternative splicing, affecting the cell survival following 5-FU treatment through changes in intracellular phenotype and transmitted preadaptive signals to adjacent cells in tumor microenvironment (TME).Conclusion: Our finding provided evidence to demonstrate CBs of their disassembling/reassembling dynamics to indicate drug sensitivity or resistance in tumor cells in response to stress signal. The results also suggested that UHMK1 could be an important factor to maintain CB structure and morphology with its possible roles in the regulation of splicing events, especially when cells exposed to cytotoxic drugs.