bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the Circular Tandem Walk Test and Optimal Cutoff Score to Determine the Risk of Falls in Active Community-Dwelling Older Adults
Authors: Poncumhak Puttipong , Srithawong Arunrat , Duangsanjun Winut
Published: December 2021

This study was to develop and validate the circular tandem walk test (CTWT) by deriving an optimal cutoff score to indicate the fall risk in 89 active community-dwelling older individuals. The participants aged 65 years and older were assessed for their demographic data, fear of fall variables, and history of falls in the past 6 months. Subsequently, participants were randomized for the sequence of tests between the tandem walk test and the CTWT. The outcomes of CTWT showed the highest significant correlation with all the fall variables (ranging from .631 to .827, p < .001). Moreover, the time to perform the CTWT ≥ 14.6 s and ≥ two error scores had excellent and acceptable diagnostic accuracy to determine the risk of falls in the older individuals, respectively. The CTWT can be used as alternative screening tests for assessing the fall risk in active older adults in community settings.
Mechanosensitive Channels Mediate Hypoionic Shock-Induced Aminoglycoside Potentiation against Bacterial Persisters by Enhancing Antibiotic Uptake
Authors: Lv Boyan , Zeng Youhui , Zhang Huaidong , Li Zhongyan , Xu Zhaorong , Wang Yan , Gao Yuanyuan , Chen Yajuan , Fu Xinmiao
Published: December 2021

Improving the efficacy of existing antibiotics is a promising strategy for combating antibiotic-resistant/tolerant bacterial pathogens that have become a severe threat to human health. We previously reported that aminoglycoside antibiotics could be dramatically potentiated against stationary-phase
Escherichia coli
cells under hypoionic shock conditions (i.e., treatment with ion-free solutions), but the underlying molecular mechanism remains unknown.
The Ultrabroad-Spectrum Beta-Lactamase Inhibitor QPX7728 Restores the Potency of Multiple Oral Beta-Lactam Antibiotics against Beta-Lactamase-Producing Strains of Resistant
Enterobacterales
Authors: Lomovskaya Olga , Rubio-Aparicio Debora , Tsivkovski Ruslan , Loutit Jeff , Dudley Michael
Published: December 2021

QPX7728 is a cyclic boronate ultrabroad-spectrum beta-lactamase inhibitor, with potent activity against both serine beta-lactamases and metallo-beta-lactamases. QPX7728 can be delivered systemically by the intravenous (i.v.) or oral route of administration.
Host Defense Mechanisms Induce Genome Instability Leading to Rapid Evolution in an Opportunistic Fungal Pathogen
Authors: Smith Amanda C. , Morran Levi T. , Hickman Meleah A.
Published: December 2021

The ability to generate genetic variation facilitates rapid adaptation in stressful environments. The opportunistic fungal pathogen
Candida albicans
frequently undergoes large-scale genomic changes, including aneuploidy and loss of heterozygosity (LOH), following exposure to host environments.
Development of a Highly Sensitive Luciferase-Based Reporter System To Study Two-Step Protein Secretion in Cyanobacteria
Authors: Russo David A. , Zedler Julie A. Z. , Conradi Fabian D. , Schuergers Nils , Jensen Poul Erik , Mullineaux Conrad W. , Wilde Annegret , Pohnert Georg
Published: December 2021

Protein secretion allows bacteria to interact and communicate with the external environment. Secretion is also biotechnologically relevant, where it is often beneficial to target proteins to the extracellular space.
Increasing oxygen prescribing during the COVID-19 pandemic
Authors: Sahota Ramandeep , Kamieniarz Lukasz
Published: December 2021

Valid oxygen prescriptions for hospital inpatients have been a long-standing problem and have been described extensively inBMJ Open Qualitywith numerous quality improvement projects (QIPs) with the aim of improving compliance with oxygen prescribing.

The British Thoracic Society recommends that all inpatients should have oxygen target saturation set on admission: this is motivated by risks of both undertreatment and overtreatment with oxygen. The discrepancy between the recommendation and the reality produced a number of interventions studied in QIPs over the past years, all aiming at bringing the local ward teams closer to the target. This has become even more important during the COVID-19 pandemic, where non-standard oxygen saturation targets and oxygen scarcity led hospital systems to rethink their internal guidelines on the subject.

We propose three novel interventions to improve compliance: a remote, personally directed email communication to a ward pharmacist, a similar communication to ward nurses, and a remote, personally directed WhatsApp communication to junior ward doctors. We undertake a QIP which compares novel interventions developed in-house with the most successful interventions from oxygen prescribing initiatives that have previously been published byBMJ Open Quality. The main outcome measure was the proportion of patients with valid oxygen prescription on a ward.

The series of novel interventions in three plan, do study, act cycles led to improvement in the outcome measure from 0% at baseline to 70% at the end of the QIP. The successful interventions from previous QIPs were ran in parallel on a similar ward and achieved improvement from 17.9% at baseline to 55.6% at the end of the QIP.

This QIP demonstrates adapted interventions performed in context of social distancing aimed at members of multidisciplinary team which achieve superiority in increasing proportion of patients with a valid oxygen prescription, when compared with previously described methods fromBMJ Open Quality.
Predicting oncotype DX recurrence scores using locally available immunohistochemical markers: experience in a district general hospital
Authors: Humphris Katherine , Stephenson John , Kumaraswamy Vidya
Published: December 2021

Aims

Oncotype DX testing is a reliable widely used gene assay to determine whether chemotherapy is of additional value in oestrogen receptor (ER) positive Human Epidermal Growth Factor receptor 2 (HER2) negative, node negative breast cancer, but the high cost of the test can be a barrier for optimal therapy guidance for a substantial proportion of eligible patients around the world. We aimed to determine whether the commonly available immunohistochemical markers Ki67 and progesterone receptor (PR) can predict Oncotype DX Recurrence Score (RS) scores in a district general hospital setting.

Methods

The Oncotype DX RS scores from 58 tumours were regressed against corrected Ki67 values in a simple regression model, and against ER-derived and PR-derived indices and corrected Ki67 values in a multiple model. Model portability was assessed using leave-one-out cross-validation (LOOCV).

Results

All terms in both regression models were significantly associated with RS scores at the 5% significance level (p<0.001 for all parameters). The multiple model was a better fit to the data (adjusted R2=0.784), and performed better under LOOCV (root mean square error=7.26), suggesting good predictive capability and model portability.

Conclusions

Locally available, cheaper alternatives to multigene assays to determine therapy in ER positive HER2 negative patients is of benefit both from patient management and financial perspectives. A model has been derived with high capability to predict RS scores accurately from linear combinations of predictive biomarkers in a district general hospital setting, which should show good properties when applied to other samples.
Relationships among blueberry species within the section Cyanococcus of the Vaccinium genus based on EST-PCR markers
Authors: Rowland Lisa J. , Ogden Elizabeth L. , Ballington James R.
Published: December 2021

Commercial blueberry species of North America belong to the Vaccinium genus, section Cyanococcus. Phylogenetic relationships of 50 accessions of different ploidy levels within Cyanococcus were investigated using 249 expressed sequence tag-polymerase chain reaction markers and standard clustering methods. Of the commercial species, tetraploid V. corymbosum grouped most closely with the diploids, V. fuscatum and V. caesariense, followed by the diploid V. elliottii. Tetraploid V. angustifolium grouped with the diploids, V. boreale and V. myrtilloides. Hexaploid V. virgatum grouped most closely with the diploid V. tenellum, thus shedding light on the origins of these polyploid species.
Accounting Start-up Time of Parallel Processes in Amdahl’s Law
Authors: Eremin Evgeny
Published: December 2021

The conventional form of Amdahl’s law states that speedup of calculations in a multiprocessor machine is limited by the definite constant value just due to the existence of some non-parallelizable part in any algorithm. This brief paper considers one more general reason, which prevents a growth of parallel performance: processes that implement distributed task cannot start simultaneously and hence every process adds some start-up time, also reducing by that the gain from a parallel processing. The simple formula, proposed here to extend Amdahl’s law, leads to a less optimistic picture in comparison with classical results: for large amount of processor units the modified law does not approach to constant but vanishes. This is the result of competition between two factors: decreasing of calculation duty and increasing of start-up time when a number of parallel processes grows. The effect may be subdued by means of specific regularity in launching parallel processes.
Connected sum of virtual knots and F-polynomials
Authors: Ivanov Maxim
Published: December 2021

It is known that connected sum of two virtual knots is not uniquely determined and depends on knot diagrams and choosing the points to be connected. But different connected sums of the same virtual knots cannot be distinguished by Kauffman’s affine index polynomial. For any pair of virtual knots [Formula: see text] and [Formula: see text] with [Formula: see text]-dwrithe [Formula: see text] we construct an infinite family of different connected sums of [Formula: see text] and [Formula: see text] which can be distinguished by [Formula: see text]-polynomials.
Aspects of Force and Acceleration in Special Relativity
Authors: Riggs Peter J.
Published: December 2021

In relativistic dynamics, the direction of acceleration is not generally parallel to the direction of force. Both the magnitude and direction of an object’s three-acceleration can alter even when the magnitude of the applied three-force is constant. Graphs of the variation in acceleration and the angles between an object’s velocity, acceleration, and the applied force vectors are presented in order to illustrate the behavior at close to the speed of light.
Efficient Channel Attention Based Encoder–Decoder Approach for Image Captioning in Hindi
Authors: Mishra Santosh Kumar , Rai Gaurav , Saha Sriparna , Bhattacharyya Pushpak
Published: December 2021

Image captioning refers to the process of generating a textual description that describes objects and activities present in a given image. It connects two fields of artificial intelligence, computer vision, and natural language processing. Computer vision and natural language processing deal with image understanding and language modeling, respectively. In the existing literature, most of the works have been carried out for image captioning in the English language. This article presents a novel method for image captioning in the Hindi language using encoder–decoder based deep learning architecture with efficient channel attention. The key contribution of this work is the deployment of an efficient channel attention mechanism with bahdanau attention and a gated recurrent unit for developing an image captioning model in the Hindi language. Color images usually consist of three channels, namely red, green, and blue. The channel attention mechanism focuses on an image’s important channel while performing the convolution, which is basically to assign higher importance to specific channels over others. The channel attention mechanism has been shown to have great potential for improving the efficiency of deep convolution neural networks (CNNs). The proposed encoder–decoder architecture utilizes the recently introduced ECA-NET CNN to integrate the channel attention mechanism. Hindi is the fourth most spoken language globally, widely spoken in India and South Asia; it is India’s official language. By translating the well-known MSCOCO dataset from English to Hindi, a dataset for image captioning in Hindi is manually created. The efficiency of the proposed method is compared with other baselines in terms of Bilingual Evaluation Understudy (BLEU) scores, and the results obtained illustrate that the method proposed outperforms other baselines. The proposed method has attained improvements of 0.59%, 2.51%, 4.38%, and 3.30% in terms of BLEU-1, BLEU-2, BLEU-3, and BLEU-4 scores, respectively, with respect to the state-of-the-art. Qualities of the generated captions are further assessed manually in terms of adequacy and fluency to illustrate the proposed method’s efficacy.
Nitric oxide-dependent micro- and macrovascular dysfunction occurs early in adolescents with type 1 diabetes
Authors: Jahn Linda A. , Logan Brent , Love Kaitlin M. , Horton William B. , Eichner Natalie Z. , Hartline Lee M. , Weltman Arthur L. , Barrett Eugene J.
Published: December 2021

This is the first study to show that type 1 diabetes impairs multiple nitric oxide-dependent vascular functions.
A Multistep Prediction of Hydropower Station Inflow Based on Bagging-LSTM Model
Authors: Wang Lulu , Peng Hanmei , Tan Mao , Pan Rui
Published: December 2021

The inflow forecasting is one of the most important technologies for modern hydropower station. Under the joint influence of soil, upstream inflow, and precipitation, the inflow is often characterized by time lag, nonlinearity, and uncertainty and then results in the difficulty of accurate multistep prediction of inflow. To address the coupling relationship between inflow and the related factors, this paper proposes a long short-term memory deep learning model based on the Bagging algorithm (Bagging-LSTM) to predict the inflows of future 3 h, 12 h, and 24 h, respectively. To validate the proposed model, the inflow and related weather data come from a hydropower station in southern China. Compared with the classical time series models, the results show that the proposed model outperforms them on different accuracy metrics, especially in the scenario of multistep prediction.
Numerical Methods for Fractional-Order Fornberg-Whitham Equations in the Sense of Atangana-Baleanu Derivative
Authors: Iqbal Naveed , Yasmin Humaira , Ali Akbar , Bariq Abdul , Al-Sawalha M. Mossa , Mohammed Wael W.
Published: December 2021

In this paper, we investigate the numerical solution of the Fornberg-Whitham equations with the help of two powerful techniques: the modified decomposition technique and the modified variational iteration technique involving fractional-order derivatives with Mittag-Leffler kernel. To confirm and illustrate the accuracy of the proposed approach, we evaluated in terms of fractional order the projected models. Furthermore, the physical attitude of the results obtained has been acquired for the fractional-order different value graphs. The results demonstrated that the future method is easy to implement, highly methodical, and very effective in analyzing the behavior of complicated fractional-order linear and nonlinear differential equations existing in the related areas of applied science.
Clinical Nomogram to Predict Major Adverse Cardiac Events in Acute Myocardial Infarction Patients within 1 Year of Percutaneous Coronary Intervention
Authors: Pan Defeng , Xiao Shengjue , Hu Yue , Pan Qinyuan , Wu Qi , Wang Xiaotong , Liu Qiaozhi , Liu Ailin , Liu Jie , Zhu Hong , Zhou Yufei
Published: December 2021

The purpose of this study was to summarize the clinical characteristics and risk factors of major adverse cardiovascular events (MACEs) in patients who had had acute myocardial infarction (AMI) within 1 year of percutaneous coronary intervention (PCI). A total of 421 AMI patients who were treated with PCI and experienced MACEs within 1 year of their admission were included in this retrospective study. In addition, patients were matched for age, sex, and presentation with 561 patients after AMI who had not had MACEs. The clinical characteristics and risk factors for MACEs within 1 year in AMI patients were investigated, to develop a nomogram for MACEs based on univariate and multivariate analyses. The

C

statistic was used to assess the discriminative performance of the nomogram. In addition, calibration curve and decision curve analyses were conducted to validate the calibration performance and utility, respectively, of the nomogram. After univariate and multivariate analyses, a nomogram was constructed based on age (odds ratio (OR): 1.030; 95% confidence interval (CI): 1.014–1.047), diabetes mellitus (OR: 1.667; 95% CI: 1.151–2.415), low-density lipoprotein cholesterol (OR: 1.332; 95% CI: 1.134–1.565), uric acid (OR: 1.003; 95% CI: 1.001–1.005), lipoprotein (a) (OR: 1.003; 95% CI: 1.002–1.003), left ventricular ejection fraction (OR: 0.929; 95% CI: 0.905–0.954), Syntax score (OR: 1.075; 95% CI: 1.053–1.097), and hypersensitive troponin T (OR: 1.002; 95% CI: 1.002–1.003). The

C

statistic was 0.814. The calibration curve showed good concordance of the nomogram, while decision curve analysis demonstrated satisfactory positive net benefits. We developed a convenient, practical, and effective prediction model for predicting MACEs in AMI patients within 1 year of PCI. To ensure generalizability, this model requires external validation.
Safety Management of Civil Engineering Construction Based on Artificial Intelligence and Machine Vision Technology
Authors: Zhang Yuting
Published: December 2021

With the development of social economy and the progress of science and technology, the process of urbanization continues to deepen and the progress of the construction industry changes with each passing day. People are paying more and more attention to the safety of civil engineering. Accidents frequently occurred during the construction process, which exposed the lack of attention to safety issues during the construction process, the lack of effective supervision of safe construction, and the lack of safety awareness of construction personnel, which had an impact on the construction of civil engineering. In this article, a solution to the safety management system for construction personnel based on artificial intelligence machine vision technology is proposed for the study of the safety management of civil engineering structures. First of all, through the research and analysis of the problems in the safety management of construction workers, the types of safety accidents of construction workers are summarized and the effect of machine understanding of the construction scene is realized through target detection and description of the spatial interaction between the two. A real‐time detection and early warning platform is built, and early warnings are automatically sent out when a predefined dangerous scene occurs, so as to achieve the purpose of preventing construction accidents. The experimental results in this paper show that, in the use of artificial intelligence machine vision technology to manage the safety of civil engineering construction, the safety management of workers in the construction is realized, and the results show that the level of construction safety management has increased to 97.4%, ensuring the quality of civil engineering construction and safety.
Image Scale-Space Filtering Using Directional Local Variance Controlled Anisotropic Diffusion
Authors: Chen Yong , He Taoshun
Published: December 2021

The purpose of this paper is to develop an effective edge indicator and propose an image scale-space filter based on anisotropic diffusion equation for image denoising. We first develop an effective edge indicator named directional local variance (DLV) for detecting image features, which is anisotropic and robust and able to indicate the orientations of image features. We then combine two edge indicators (i.e., DLV and local spatial gradient) to formulate the desired image scale-space filter and incorporate the modulus of noise magnitude into the filter to trigger time-varying selective filtering. Moreover, we theoretically show that the proposed filter is robust to the outliers inherently. A series of experiments are conducted to demonstrate that the DLV metric is effective for detecting image features and the proposed filter yields promising results with higher quantitative indexes and better visual performance, which surpass those of some benchmark models.
The Equilibrium Time and Salt Expansion Characteristic of Sulfate Saline Soil upon Cooling
Authors: Ji Yanjie , Li Xu , Wang Wei , Liu Li
Published: December 2021

The salt expansion disease is severe for the soil containing sodium sulfate in cold regions. This paper carried out one‐dimensional salt expansion tests of saline soil, the crystallization test of saturated sodium sulfate solution, and the numerical cooling tests to explore the stability time of the salt expansion test and determine the standard procedure of salt expansion tests. The test results demonstrate that (i) the temperature equilibrium and the crystallization process are almost simultaneously completed in both sulfate saline soil and sulfate solution upon cooling; (ii) referring to the deformation equilibrium standard used in soil consolidation test, an expansion rate of less than 0.02 mm/h is suggested in the saline expansion test; and (iii) the equilibrium time is found to have a quadratic polynomial relationship to sample size and is much shorter under liquid bath conditions than under gas bath conditions. Based on these findings, a standard procedure of the one‐dimensional salt expansion test is proposed, in which the test equipment, the test process, the deformation stabilization time of salt expansion, and the data processing method are provided. As the deformation and the temperature are synchronized, the deformation stabilization time of samples with different sizes in different cooling media is recommended.
WGCNA‐Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease
Authors: Zeng Folai , Shi Meijie , Xiao Huanming , Chi Xiaoling
Published: December 2021

Background. The morbidity of nonalcoholic fatty liver disease (NAFLD) has been rising, but the pathogenesis of NAFLD is still elusive. This study is aimed at determining NAFLD‐related hub genes based on weighted gene coexpression network analysis (WGCNA). Methods. GSE126848 dataset based construction of coexpression networks was performed based on WGCNA. Database for Annotation, Visualization, and Integrated Discovery (DAVID) was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hub genes were identified and validated in independent datasets and mouse model. Results. We found that the steelblue module was most significantly correlated with NAFLD. Total 15 hub genes (NDUFA9, UQCRQ, NDUFB8, COPS5, RPS17, UBL5, PSMA3, PSMA1, SF3B5, MRPL27, RPL26, PDCD5, PFDN6, SNRPD2, PSMB3) were derived from both the coexpression and PPI networks and considered “true” hub genes. Functional enrichment analysis showed that the hub genes were related to NAFLD pathway and oxidative phosphorylation. Independent dataset‐based analysis and the establishment of NAFLD mouse model confirmed the involvement of two hub genes NDUFA9 and UQCRQ in the pathogenesis of NAFLD. Conclusions. Oxidative phosphorylation and NAFLD pathway may be crucially involved in the pathogenesis of NAFLD, and two hub genes NDUFA9 and UQCRQ might be diagnostic biomarkers and therapeutic targets for NAFLD.
Structure-Based Virtual Screening of Benzaldehyde Thiosemicarbazone Derivatives against DNA Gyrase B of Mycobacterium tuberculosis
Authors: Kistan Andiyappan , Anna Benedict Balakrishnan , Vasanthan Sundaramoorthy , PremKumar Alphonse , Kullappan Malathi , Ambrose Jenifer Mallavarpu , Veeraraghavan Vishnu Priya , Rengasamy Gayathri , Surapaneni Krishna Mohan
Published: December 2021

Emergence of antibiotic-resistant Mycobacterium tuberculosis (M. tuberculosis) restricts the availability of drugs for the treatment of tuberculosis, which leads to the increased morbidity and mortality of the disease worldwide. There are many intrinsic and extrinsic factors that have been reported for the resistance mechanism. To overcome such mechanisms, chemically synthesized benzaldehyde thiosemicarbazone derivatives were screened against M. tuberculosis to find potential inhibitor for tuberculosis. Such filtering process resulted in compound 13, compound 21, and compound 20 as the best binding energy compounds against DNA gyrase B, an important protein in the replication process. The ADMET prediction has shown the oral bioavailability of the novel compounds.
Comparing the Antifungal Effect of Sodium Hypochlorite Gel versus Different Types of Root Canal Medicaments at Different Time Intervals Using the Agar Diffusion Test: An In Vitro Study
Authors: El Sayed Mohamed , Ghanerad Nikta , Shabanpour Zeinab , Shabanpoor Mahin , Rahimi Fatemeh
Published: December 2021

Aims. The purpose of this study was to compare the antifungal activity of sodium hypochlorite gel to those of four intracanal medicaments at various time intervals. Materials and Methods. The agar well diffusion technique was utilized to test the antifungal activity of the following medicaments against Candida albinans (C. albicans): sodium hypochlorite gel, chlorhexidine gel, calcium hydroxide paste, Ledermix, and Diapex Plus. The inhibition zone related to each medicine was measured in millimeter after 24, 48, and 72 hours of incubation at 37°C. The data were analyzed using one-way ANOVA and Games–Howell tests, at a significance level of

P
<
0.05

. Results. Except for Ledermix and Diapex Plus, which had no antifungal action, all of the medicaments showed varied inhibitory zones for C. albicans. At all periods, the NaOCl gel had the most significant inhibition zones, followed by the CHX gel and calcium hydroxide. At all time intervals, the NaOCl gel demonstrated comparable antifungal efficacy. When compared to a 24-hour time interval, the CHX gel showed an increased antifungal activity at the 48-hour and 72-hour intervals. Calcium hydroxide, on the other hand, showed a decrease in its antifungal activity at the 72-hour interval. Conclusion. The antifungal activity of sodium hypochlorite gel was the highest among the investigated medicaments. Chlorhexidine gel's antifungal activity improved over time, whereas calcium hydroxide's antifungal activity declined. Diapex Plus and Ledermix did not have any antifungal properties.
Profitability vs. Stability: The Choice of Trading Strategies in a Capacity Sharing Supply Chain
Authors: Han Hongshuai , Yao Mengdi
Published: December 2021

Supported by a third-party capacity sharing platform, manufacturers can share capacities with others to match the rapidly changing demand. Both the capacity requestor and the capacity provider can choose to seek or wait for matches, forming different trading strategies (capacity- and demand-driven strategies). Based on the game and chaos theories, this paper analyzes the preference of the capacity provider, the capacity requestor, and the capacity platform operator on different trading strategies from the aspects of profitability and stability. It finds that the platform operator values stability much more than profitability, although the latter may reach higher optimal expected profits. The preference of each supply chain member is influenced by the production cost, potential market size, and the limited capacity of the capacity requestor. A stable system can result in higher long-run profits than a profitable system. We further propose the all-win situation for the capacity provider, capacity requestor, and platform operator.
Bearing Capacity of Concrete Filled Steel Tube Circular Arch under the Six‐Point Uniformly Distributed Loading and Its Engineering Application
Authors: Liu Keming , Sun Xizhen
Published: December 2021

The influence of rise‐span ratio on the bearing performance of concrete filled steel tube (CFST) circular arch was studied in this paper, three groups of CFST circular arch specimens with different rise‐span ratios (0.154, 0.207, and 0.26) were selected, the six‐point uniformly distributed loading was performed, and bearing performance experiments on CFST circular arch specimens with fixed ends were carried out. In this study, the ultimate bearing capacity and deformation failure characteristics of CFST circular arch specimens were obtained. The comparative analysis shows that the deformation evolution of CFST circular arch specimens has experienced compaction stage, elastic stage, elastic‐plastic stage, and plastic stage. In the elastic‐plastic and plastic deformation stages, the circular arch shows good ductility and bearing capacity. The bearing capacity of the circular arch is significantly affected by the rise‐span ratio. Compared with circular arch specimens with a rise‐span ratio of 0.154, the yield load of specimens with a rise‐span ratio of 0.207 and 0.26 is increased by 50.8% and 61.5%, and the ultimate bearing capacity is increased by 42.7% and 68.3%, respectively. The larger the rise‐span ratio, the greater the yield load and ultimate bearing capacity of the specimen and the stronger the deformation resistance of circular arch. The numerical simulation on the bending resistance process of circular arch was performed by ABAQUS to present the compression failure process of steel tube and core concrete. The simulation results are in good agreement with the experimental results. The experimental and simulation results show that the circular arch first yields at the inner side of the arch foot, and the curvature of different positions of the specimen is no longer consistent. When the ultimate bearing capacity is reached, the steel pipe at the arch foot obviously heaves, and the hooping effect of the steel pipe on the concrete is invalid. Based on the above research results, a closed composite support scheme of “bolt mesh shotcrete + vertical elliptical CFST support + steel fiber concrete shotcrete layer + reinforced anchor cable” was proposed for the extremely soft rock roadway and successfully applied in the Qingshuiying coal mine.
Overall Prevalence and Prevalence Compared among Psoriasis Treatments of Onychomycosis in Patients with Nail Psoriasis and Fungal Involvement
Authors: Chularojanamontri Leena , Pattanaprichakul Penvadee , Leeyaphan Charussri , Suphatsathienkul Panittra , Wongdama Supisara , Bunyaratavej Sumanas
Published: December 2021

Background. Whether nail psoriasis can increase the risk of onychomycosis is still being debated, and data relating to the prevalence of onychomycosis among psoriasis patients receiving different treatments is limited. Objectives. To investigate the overall prevalence and prevalence compared among psoriasis treatments of onychomycosis in patients with nail psoriasis and fungal involvement. Methods. A prospective study of three groups of nail psoriasis being treated with only topical medication, methotrexate, or biologics (25 patients per group, 150 nails) was conducted at Siriraj Hospital (Bangkok, Thailand) during November 2018 to September 2020. Demographic data, psoriasis severity, and nail psoriasis severity were recorded. The nail most severely affected with psoriasis on each hand was selected for mycological testing. Potassium hydroxide, periodic acid‐Schiff stain, and fungal culture were performed. Results. The prevalence of onychomycosis in nail psoriasis was 35.3%. Among the treatment groups, the prevalence of onychomycosis was significantly higher in the methotrexate group than in the topical treatment and biologic treatment groups (p = 0.014). Candida spp. was the main causative organism, followed by Trichophyton rubrum. Thumb was most commonly affected (59.3%). The most common abnormality of the nail matrix and the nail bed was pitted nail (71.3%) and onycholysis (91.3%), respectively. Multivariate analysis revealed diabetes, wet‐work exposure, and methotrexate treatment to be predictors of onychomycosis. Conclusions. Several factors, including psoriasis treatment, were shown to increase the risk of onychomycosis in nail psoriasis. Further research is needed to determine whether biologic agents, especially interleukin‐17 inhibitors, can increase risk of onychomycosis and Candida infection/colonization of the nails.
Ginsenoside CK Inhibits TGF‐β‐Induced Epithelial‐Mesenchymal Transition in A549 Cell via SIRT1
Authors: Sun Mingyang , Zhuang Xuefeng , Lv Guangfu , Lin Zhe , Huang Xiaowei , Zhao Jiarui , Lin He , Wang Yuchen
Published: December 2021

Ginsenoside CK is the main metabolite of protopanaxadiol saponins in intestinal bacteria. Previous studies have shown that ginsenoside CK can affect many aspects of tumor development through a variety of mechanisms. However, few studies have reported the antimetastatic effects of ginsenoside CK in non‐small‐cell lung cancer (NSCLC). In this study, we explored the effect of ginsenoside CK on epithelial‐mesenchymal transition (EMT) induced by TGF‐β in A549 cells and the potential molecular mechanisms. Our data showed that ginsenoside CK effectively prevented TGF‐β‐induced EMT, as indicated by the upregulation of E‐cadherin and downregulation of vimentin. Furthermore, ginsenoside CK inhibited the metastatic ability of A549 cells in the tail vein lung metastasis model of nude mice. Additionally, ginsenoside CK decreased the expression of silent information regulator 2 homolog 1 (SIRT1) in the inhibition of EMT induced by TGF‐β. Moreover, the antimetastatic effect of ginsenoside CK was reversed by SIRT1 overexpression. Generally, our results indicated the antimetastatic effect and underlying mechanism of ginsenoside CK on TGF‐β‐induced EMT in A549 cells, suggesting that ginsenoside CK can be used as an effective antineoplastic agent.
miRNA-144-5p/ITGA3 Suppressed the Tumor-Promoting Behaviors of Thyroid Cancer Cells by Downregulating ITGA3
Authors: Zhang Jizong , Zhong Yan , Sang Yiming , Ren Guanghui
Published: December 2021

Objective. To ascertain the mechanism of miRNA-144-5p and ITGA3 in thyroid cancer (TC). Methods. From The Cancer Genome Atlas (TCGA), RNA expression profiles were obtained for the expression analysis of miRNAs and mRNAs in TC. qRT-PCR and western blot were utilized to measure the expression of miRNA-144-5p and ITGA3 at RNA and protein levels, respectively. The association between miRNA-144-5p and ITGA3 was validated by the dual-luciferase assay. CCK-8, scratch healing, transwell, and flow cytometry assays were employed to evaluate tumor-related cell behaviors. Results. Low-expressed miRNA-144-5p and high-expressed ITGA3 were found in TC cells relative to normal cells. miRNA-144-5p expression was positively associated with suppressive effects on proliferative, invasive, and migratory ability of TC cells while negatively associated with cell apoptosis. miRNA-144-5p inhibited ITGA3 expression in TC, and its overexpression remarkably reversed the tumor-promoting effects of overexpressed ITGA3 on the biological functions of TC. Conclusion. It is verified in our study that cell growth of TC is inhibited by the miRNA-144-5p/ITGA3 axis, which represents an underlying target for TC. This research proposed a new insight into the strategy of TC treatment.
Neuroprotective Effect of Ceftriaxone on MPTP‐Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota
Authors: Zhou Xiaoting , Lu Jiachen , Wei Kehong , Wei Jing , Tian Puyuan , Yue Mengyun , Wang Yun , Hong Daojun , Li Fangjun , Wang Bo , Chen Tingtao , Fang Xin
Published: December 2021

Parkinson’s disease (PD) is a common degenerative disease of the central nervous system. Although some drugs can alleviate the progress of PD, their long‐term use will lead to complications, so it is still necessary to find new drugs to delay or cure PD effectively. In view of the difficulty in developing new drugs, it is imperative to discover new functions of existing compounds that could be used to treat PD. In this study, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) was used to induce PD symptoms in a mouse model. Subsequently, these mice were treated with the antibiotic ceftriaxone. Ceftriaxone alleviated the behavioural and neuropathological changes induced by MPTP, downregulated the expression of glial fibrillary acidic protein (GFAP) and ionised calcium‐binding adapter molecule 1 (Iba1) as markers of astroglia and microglia, respectively, and reduced the expression of neuroinflammation‐related Toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa‐B (p‐NF‐κB)/NF‐κB in the brain of PD mice. In addition, ceftriaxone reduced the abundance of pathogenic bacteria of the genus Proteus and increased the abundance of probiotic Akkermansia. Finally, ceftriaxone treatment increased the expression of the tight junction proteins zona occludens‐1(ZO‐1) and occludin in the colon, decreased the expression of the inflammation‐related proteins TLR4, MyD88, and NF‐κB in the colon, and decreased the serum concentration of the proinflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, and tumour necrosis factor‐α (TNF‐α). These results indicate that ceftriaxone had a neuroprotective effect on MPTP‐induced PD mice, and its neuroprotective effect could be through regulating inflammation and intestinal microbiota. While we showed that ceftriaxone exerts a neuroprotective effect in an MPTP‐induced PD mouse model, our findings are limited to the short‐term effects of ceftriaxone. Additional work using transgenic mice is required to determine the long‐term effects of ceftriaxone. In addition, the dose and frequency of ceftriaxone use should be evaluated.
Functional Analysis Identifies DamagingCHEK2Missense Variants Associated with Increased Cancer Risk
Authors: Boonen Rick A.C.M. , Wiegant Wouter W. , Celosse Nandi , Vroling Bas , Heijl Stephan , Kote-Jarai Zsofia , Mijuskovic Martina , Cristea Simona , Solleveld-Westerink Nienke , van Wezel Tom , Beerenwinkel Niko , Eeles Rosalind , Devilee Peter , Vreeswijk Maaike P.G. , Marra Giancarlo , van Attikum Haico
Published: December 2021

Heterozygous carriers of germline loss-of-function variants in the tumor suppressor gene checkpoint kinase 2 (CHEK2) are at an increased risk for developing breast and other cancers. While truncating variants in CHEK2 are known to be pathogenic, the interpretation of missense variants of uncertain significance (VUS) is challenging. Consequently, many VUS remain unclassified both functionally and clinically. Here we describe a mouse embryonic stem (mES) cell–based system to quantitatively determine the functional impact of 50 missense VUS in human CHEK2. By assessing the activity of human CHK2 to phosphorylate one of its main targets, Kap1, in Chek2 knockout mES cells, 31 missense VUS in CHEK2 were found to impair protein function to a similar extent as truncating variants, while 9 CHEK2 missense VUS resulted in intermediate functional defects. Mechanistically, most VUS impaired CHK2 kinase function by causing protein instability or by impairing activation through (auto)phosphorylation. Quantitative results showed that the degree of CHK2 kinase dysfunction correlates with an increased risk for breast cancer. Both damaging CHEK2 variants as a group [OR 2.23; 95% confidence interval (CI), 1.62–3.07; P < 0.0001] and intermediate variants (OR 1.63; 95% CI, 1.21–2.20; P = 0.0014) were associated with an increased breast cancer risk, while functional variants did not show this association (OR 1.13; 95% CI, 0.87–1.46; P = 0.378). Finally, a damaging VUS in CHEK2, c.486A>G/p.D162G, was also identified, which cosegregated with familial prostate cancer. Altogether, these functional assays efficiently and reliably identified VUS in CHEK2 that associate with cancer.

Significance:

Quantitative assessment of the functional consequences of CHEK2 variants of uncertain significance identifies damaging variants associated with increased cancer risk, which may aid in the clinical management of patients and carriers.
A Pan-Cancer Immunogenomic Atlas for Immune Checkpoint Blockade Immunotherapy
Authors: Yang Jing , Zhao Shilin , Wang Jing , Sheng Quanhu , Liu Qi , Shyr Yu
Published: December 2021

The ability to identify robust genomic signatures that predict response to immune checkpoint blockade is restricted by limited sample sizes and ungeneralizable performance across cohorts. To address these challenges, we established Cancer-Immu (http://bioinfo.vanderbilt.edu/database/Cancer-Immu/), a comprehensive platform that integrates large-scale multidimensional omics data, including genetic, bulk, and single-cell transcriptomic, proteomic, and dynamic genomic profiles, with clinical phenotypes to explore consistent and rare immunogenomic connections. Currently Cancer-Immu has incorporated data for 3,652 samples for 16 cancer types. It provides easy access to immunogenomic data and empowers researchers to translate omics datasets into biological insights and clinical applications.

Significance:

Cancer-Immu is a comprehensive functional portal for unraveling immune-genomic connections to improve immune checkpoint blockade–based cancer immunotherapy.
Exosomes Derived from Cancer-Associated Fibroblasts Regulate Cell Progression in Clear-Cell Renal-Cell Carcinoma
Authors: Fu Wenqiang , Zhao Haihong , Liu Yifei , Nie Honglin , Gao Bin , Yin Feng , Wang Baocun , Li Tengfei , Zhang Tingting , Wang Lijuan , Wu Xiaotang , Zhu Mengjiao , Xia Lianjie
Published: December 2021

Backgrounds: Exosomes from multiple sources function as regulatory factors in progression of various tumors. However, studies on the impact of exosomes from cancer-associated fibroblasts (CAFs) on tumor-cell proliferation, migration, invasion, and cycle regulation in clear-cell renal-cell carcinoma (ccRCC) are still lacking. Methods: A Western blot assay was performed to test the exosome-related marker protein level in exosomes derived from CAFs and normal fibroblasts (NFs). A confocal microscope was utilized to observe the internalization of CAF- and NF-derived exosomes after coculturing with cancer cells. MTT, EdU, colony formation, and transwell assays were conducted to detect progression of cancer cells incubated with CAF-derived exosomes. A Western blot assay was also conducted to test expression levels of metastasis-associated proteins. Changes in cell apoptosis and cell cycle were measured by flow cytometry. Results: Expression of CAF-derived exosome-related marker proteins was higher than that from NFs. Exosomes derived from CAFs and NFs could enter into cancer cells smoothly and be internalized by cancer cells. After cancer cells were cocultured with CAF-derived exosomes, cell proliferation, migration, and invasion were notably enhanced, and cell apoptosis was reduced. Moreover, expression of fibronectin, N-cadherin, vimentin, MMP9, and MMP2 in cancer cells increased, while E-cadherin was decreased. Besides, the proportion of cancer cells in the S phase increased. Conclusion: CAF-derived exosomes are internalized into ccRCC cells and promote the progression of ccRCC.
Multiple Colorectal Mucosa-Associated Lymphoid Tissue Lymphoma Successfully Treated with Chemotherapy
Authors: Saito Makoto , Tsukamoto Shihori , Ishio Takashi , Yokoyama Emi , Izumiyama Koh , Mori Akio , Morioka Masanobu , Kondo Takeshi , Sugino Hirokazu
Published: December 2021

The standard treatment for colorectal mucosa-associated lymphoid tissue (MALT) lymphoma has not yet been established due to the rarity of the disease. Here, we report a case of long-term response to chemotherapy for colorectal MALT lymphoma (stage I). A 77-year-old frail female patient with diabetes mellitus and dementia developed melena of unknown etiology, and a colonoscopy was performed at a nearby hospital. A biopsy suggested malignant lymphoma, and she was referred to our department. As a result of re-examination of colonoscopy, a total of 3 submucosal tumor-like lesions were confirmed. Of these, a biopsy of the lesions in the ascending colon and rectum was performed, and MALT lymphoma was diagnosed on the basis of the histopathological findings. Following close examination, no other lymphoma lesions were found, and the patient was diagnosed with primary colorectal MALT lymphoma, stage I. After 1 course of R-THP-COP chemotherapy (rituximab + cyclophosphamide, pirarubicin, vincristine, and prednisone), the rectal lesion was confirmed to have almost disappeared endoscopically, and lymphoma cells were not found histopathologically. The patient was determined to be in complete remission (CR). However, due to hematological toxicity and a slight worsening of glucose control, the second chemotherapy course was changed to the BR regimen (rituximab + bendamustine), and 4 courses were performed (5 total courses of chemotherapy). Currently, >3 years have passed since reaching CR, and the patient is alive without recurrence.
Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance
Authors: Aengevaeren Vincent L. , Baggish Aaron L. , Chung Eugene H. , George Keith , Kleiven Øyunn , Mingels Alma M.A. , Ørn Stein , Shave Rob E. , Thompson Paul D. , Eijsvogels Thijs M.H.
Published: December 2021

Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field.
The Inequitable Effects of Teacher Layoffs: What We Know and Can Do
Authors: Kraft Matthew A. , Bleiberg Joshua F.
Published: December 2021

Economic downturns can cause major funding shortfalls for U.S. public schools, often forcing districts to make difficult budget cuts, including teacher layoffs. In this brief, we synthesize the empirical literature on the widespread teacher layoffs caused by the Great Recession. Studies find that teacher layoffs harmed student achievement and were inequitably distributed across schools, teachers, and students. Research suggests that specific elements of the layoff process can exacerbate these negative effects. Seniority-based policies disproportionately concentrate layoffs among teachers of color, who are more likely to be early career teachers. These “last-in first-out” policies also disproportionately affect disadvantaged students because these students are more likely to be taught by early career teachers. The common practice of widely distributing pink slips warning about a potential job loss also appears to increase teacher churn and negatively impact teacher performance. Drawing on this evidence, we outline a set of policy recommendations to minimize the need for teacher layoffs during economic downturns and ensure that the burden of any unavoidable job cuts does not continue to be borne by students of color and students from low-income backgrounds.