bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of MRI‐Based Radiomics in Preoperative T Staging of Rectal Cancer: Comparison between Minimum and Maximum Delineation Methods
Authors: Lu Haidi , Yuan Yuan , Zhou Zhen , Ma Xiaolu , Shen Fu , Xia Yuwei , Lu Jianping
Published: July 2021

The manual delineation of the lesion is mainly used as a conventional segmentation method, but it is subjective and has poor stability and repeatability. The purpose of this study is to validate the effect of a radiomics model based on MRI derived from two delineation methods in the preoperative T staging of patients with rectal cancer (RC). A total of 454 consecutive patients with pathologically confirmed RC who underwent preoperative MRI between January 2018 and December 2019 were retrospectively analyzed. RC patients were grouped according to whether the muscularis propria was penetrated. Two radiologists segmented lesions, respectively, by minimum delineation (Method 1) and maximum delineation (Method 2), after which radiomics features were extracted. Inter‐ and intraclass correlation coefficient (ICC) of all features was evaluated. After feature reduction, the support vector machine (SVM) was trained to build a prediction model. The diagnostic performances of models were determined by receiver operating characteristic (ROC) curves. Then, the areas under the curve (AUCs) were compared by the DeLong test. Decision curve analysis (DCA) was performed to evaluate clinical benefit. Finally, 317 patients were assessed, including 152 cases in the training set and 165 cases in the validation set. Moreover, 1288/1409 (91.4%) features of Method 1 and 1273/1409 (90.3%) features of Method 2 had good robustness (P < 0.05). The AUCs of Model 1 and Model 2 were 0.808 and 0.903 in the validation set, respectively (P = 0.035). DCA showed that the maximum delineation yielded more net benefit. MRI‐based radiomics models derived from two segmentation methods demonstrated good performance in the preoperative T staging of RC. The minimum delineation had better stability in feature selection, while the maximum delineation method was more clinically beneficial.
Satellite and Scene Image Classification Based on Transfer Learning and Fine Tuning of ResNet50
Authors: Shabbir Amsa , Ali Nouman , Ahmed Jameel , Zafar Bushra , Rasheed Aqsa , Sajid Muhammad , Ahmed Afzal , Dar Saadat Hanif
Published: July 2021

Image classification has gained lot of attention due to its application in different computer vision tasks such as remote sensing, scene analysis, surveillance, object detection, and image retrieval. The primary goal of image classification is to assign the class labels to images according to the image contents. The applications of image classification and image analysis in remote sensing are important as they are used in various applied domains such as military and civil fields. Earlier approaches for remote sensing images and scene analysis are based on low-level feature representations such as color- and texture-based features. Vector of Locally Aggregated Descriptors (VLAD) and orderless Bag-of-Features (BoF) representations are the examples of mid-level approaches for remote sensing image classification. Recent trends for remote sensing and scene classification are focused on the use of Convolutional Neural Network (CNN). Keeping in view the success of CNN models, in this research, we aim to fine-tune ResNet50 by using network surgery and creation of network head along with the fine-tuning of hyperparameters. The learning of hyperparameters is tuned by using a linear decay learning rate scheduler known as piecewise scheduler. To tune the optimizer hyperparameter, Stochastic Gradient Descent with Momentum (SGDM) is used with the usage of weight learn and bias learn rate factor. Experiments and analysis are conducted on five different datasets, that is, UC Merced Land Use Dataset (UCM), RSSCN (the remote sensing scene classification image dataset), SIRI-WHU, Corel-1K, and Corel-1.5K. The analysis and competitive results exemplify that our proposed image classification-based model can classify the images in a more effective and efficient manner as compared to the state-of-the-art research.
Torsades de Pointes due to Excessive Marijuana Use in a Susceptible Patient
Authors: Shah Vivek D. , Mohammad Adeba , Nandkeolyar Shuktika , Stoletniy Liset , Contractor Tahmeed
Published: July 2021

There are several recent reports of tetrahydrocannabinol vaping-related sudden cardiac arrest, and the mechanisms are unclear. We report a unique case of a 19-year-old female who suffered documented prolonged QTc leading to Torsades de pointes and cardiac arrest in the setting of frequent marijuana wax vaping. While she demonstrated normal baseline QTc measurements years earlier, she was found to have a genetic predisposition to QTc prolongation (genetic mutation, family history of prolonged QTc), suggesting that specific patient populations are at higher risk of these adverse events. The patient was acutely managed with isoproterenol to increase the heart rate and was discharged on nadolol after placement of an implantable cardioverter-defibrillator. Marijuana wax vaping and dabbing may cause fatal Torsades de pointes in susceptible patients, and further research is required to identify these patients a priori.
Experimental Investigation and Load Capacity of Slender Cold‐Formed Lipped Channel Sections with Holes in Compression
Authors: Yao Xingyou
Published: July 2021

The use of cold‐formed steel (CFS) channels with circular or rectangular web holes is becoming increasingly popular in building structures. However, such holes can result in sections becoming more susceptible to buckle and display lower load‐carrying capacities. This paper presents a total of 42 axial compression tests of CFS lipped channel slender columns with and without circular and rectangular web holes, including different hole sizes and cross sections. The test results show that the axial members with a small ratio of width to thickness were governed by global buckling, while the members with a large ratio of width to thickness were controlled by the interaction of local, distortional, and global buckling. The axial strength decreased maximum by 20.48% and 22.98% for the member with circular holes and rectangular holes, compared to a member without a web hole. Then, a nonlinear elastoplastic finite element model (FEM) was developed, and the analysis results showed good agreement with the test results. The validated FE model was used to conduct a parametric study involving 36 FEMs to investigate the effects of column slenderness, dimension of the hole, and the number of holes on the axial strength of such channels. Furthermore, the formulas to predict the global buckling coefficient and the effective area were modified for such sections with holes by using the verified FEM. Finally, the tests and parametric study results were compared against the design strengths calculated in accordance with the developed method. The comparison results show that the proposed design method closely predicts the axial capacity of CFS channels with circular or rectangular web holes.
National and Subnational Cancer Incidence for 22 Cancer Groups, 2000 to 2016: A Study Based on Cancer Registration Data of Iran
Authors: Khanali Javad , Kolahi Ali-Asghar
Published: July 2021

Background. Cancer is an increasing public health concern, and detailed knowledge of the cancer incidence is required for developing effective cancer control plans. The objective of this study is to present the cancer incidence of 22 cancer groups in Iran and all 31 provinces of the country from 2000 to 2016, for both sexes across different age groups. Method. To study the national and provincial cancer incidence in Iran, we extracted data from the Cancer Project, which collects the Iranian cancer registry data and visualizes it in the VIZIT data visualization system. The methodology and statistical analysis that is used in this study follow the cancer project study protocol. Joinpoint analysis was performed to calculate the average annual percent change of the crude rates and age-standardized rates from 2000 to 2016. Results. Cancer incidence was 126,982 patients in 2016, and the crude rate (CR) of cancer in both sexes and all ages was 155 per 100,000 people. Cancer incidence approximately doubled between 2000 and 2016; however, the age-standardized rate (ASR) had a less drastic increase. The most incident cancers in 2016 were breast, skin, and colorectal cancers; however, the ranking of cancer groups by incidence was different in different age and sex groups and provinces. Some cancers exhibited a unique distribution pattern in the country with high-incidence local areas. Discussion. The study showed that cancer incidence, crude rate, and age-standardized rate (ASR) in Iran had increased in 2000-2016 with vast heterogeneity by cancer type, province, and sex. Moreover, it was shown that the crude rate of cancer in Iran was much less than the global cancer crude rate. Providing such data helps to allocate resources and develop effective national cancer control plans appropriately.
Aralia armata (Wall.) Seem Improves Intimal Hyperplasia after Vascular Injury by Downregulating the Wnt3α/Dvl‐1/β‐Catenin Pathway
Authors: Zhao Xiangpei , Huang Jinchang , Mo Zhenyu , Wei Jiangcun , Zhong Chuanmei , Teng Hongli
Published: July 2021

The aim of the study is to examine the mechanism of Aralia armata (Wall.) Seem (AAS) in improving intimal hyperplasia after vascular injury in rats. Rats with femoral artery injury were randomly divided into three groups: the model group, AAS low‐dose group (40 mg/kg), and AAS high‐dose group (80 mg/kg). The sham operation group was used as a control group. HE staining was used to observe the changes in femoral artery vessels. Immunohistochemistry was adopted to detect α‐SMA, PCNA, GSK‐3β, and β‐catenin proteins in femoral artery tissue. The CCK‐8 test and wound healing assay were employed to analyze the effect of AAS on proliferation and migration of vascular smooth muscle cells (VSMCs) cultured in vitro. Western blotting (WB) and polymerase chain reaction (PCR) assays were used to evaluate the molecular mechanism. AAS reduced the stenosis of blood vessels and the protein expressions of α‐SMA, PCNA, GSK‐3β, and β‐catenin compared to the model group. In addition, AAS (0‐15 μg/mL) effectively inhibited the proliferation and migration of VSMCs. Moreover, the results of WB and PCR showed that AAS could inhibit the activation of β‐catenin induced by 15% FBS and significantly decrease the expression levels of Wnt3α, Dvl‐1, GSK‐3β, β‐catenin, and cyclin D1 in the upstream and downstream of the pathway. AAS could effectively inhibit the proliferation and migration of neointima after vascular injury in rats by regulating the Wnt/β‐catenin signaling pathway.
Traumatic J-Pouch Perforation following a Blunt Abdominal Injury
Authors: Drober Leonid , Hochstein David , Bahouth Hany
Published: July 2021

A 46-year-old male was admitted to the trauma department after a motor vehicle accident. He presented with severe abdominal pain and a distended abdomen with peritonitis. His past surgical history included total proctocolectomy with ileal J-pouch anal anastomosis for ulcerative colitis 20 years previously. Computed tomography showed free peritoneal air and fluid in the abdomen mandating an exploratory laparotomy. A perforation at the ileal J-pouch blind end was found. Primary closure with diverting loop ileostomy was performed. The patient had an uneventful recovery and underwent closure of the ileostomy two months later. The case and management are discussed after reviewing the literature.
Flipped Classroom Design of College Ideological and Political Courses Based on Long Short-Term Memory Networks
Authors: Su Fei , Fan Zhe
Published: July 2021

The advancement and rising of information technology have promoted the flipped classroom in an effective way. It flips knowledge transfer and knowledge internalization from two levels of teaching structure and teaching process, reversing the traditional teaching knowledge transfer in class and knowledge deepening after class from time and space. Although the use of flipped classrooms in ideological and political theory courses is relatively uncommon in colleges and universities, realistic teaching and related study findings in some colleges and universities provide some reference value for the use of flipped classrooms in ideological and political theory courses. As a result, the short- and long-time memory network-based flipped classroom design algorithm for ideological and political courses in colleges and universities has a wide range of applications. A neural network prediction model based on a hybrid genetic algorithm is developed in this paper. The hybrid genetic algorithm is used in this model to determine the optimal dropout probability and the number of cells in the hidden layer of the neural network. The hybrid genetic algorithm will lengthen the memory neural network to predict the teaching quality of root mean square error between real value and predictive value as a fitness function, in the process of optimization, genetic algorithm convergence to the local optimal solution of the area.
Mitochondrial ATP-Sensitive K+ Channel Opening Increased the Airway Smooth Muscle Cell Proliferation by Activating the PI3K/AKT Signaling Pathway in a Rat Model of Asthma
Authors: Gao Min , Sun Qinran , Liu Qingfa
Published: July 2021

Abnormal proliferation of airway smooth muscle cells (ASMCs) leads to airway remodeling and the development of asthma. This study aimed to assess whether mitochondrial ATP-sensitive K+ (mitoKATP) channels regulated the proliferation of ASMCs by regulating the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway in asthmatic rats. Forty-eight Sprague Dawley rats were immunized with ovalbumin-containing alum to establish the asthma models. The ASMCs were isolated and identified by phase-contrast microscopic images and immunohistochemical staining for α-smooth muscle actin. The ASMCs were treated with a potent activator of mitoKATP, diazoxide, or an inhibitor of mitoKATP, 5-hydroxydecanoate (5-HD). Rhodamine-123 (R-123) was used for detecting the mitochondrial membrane potential (Δψm). The proliferation of ASMCs was examined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The protein and mRNA expressions of AKT and p-AKT were detected using western blotting and quantitative real-time PCR. The results showed that diazoxide enhanced the mitoKATP channel opening in ASMCs in the rat model of asthma, while 5-HD impeded it. Diazoxide also increased ASMC proliferation in the rat model of asthma, whereas 5-HD alleviated it. However, LY294002, a PI3K/AKT pathway inhibitor, reversed the functional roles of diazoxide in the proliferation ability of ASMCs in the rat model of asthma. Furthermore, treatment with diazoxide induced the phosphorylation of AKT, and treatment with 5-HD decreased the phosphorylation of AKT in ASMCs in the rat model of asthma. In conclusion, the mitoKATP channel opening increased the proliferation of ASMCs by activating the PI3K/AKT signaling pathway in a rat model of asthma.
Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin‐Mediated Renal Oxidative Injury and Inflammation
Authors: An Lingyue , Wu Weizhou , Li Shujue , Lai Yongchang , Chen Dong , He Zhican , Chang Zhenglin , Xu Peng , Huang Yapeng , Lei Min , Jiang Zheng , Zeng Tao , Sun Xinyuan , Sun Xuan , Duan Xiaolu , Wu Wenqi
Published: July 2021

Escherichia coli (E. coli) is closely associated with the formation of kidney stones. However, the role of E. coli in CaOx stone formation is not well understood. We explored whether E. coli facilitate CaOx stone formation and its mechanism. Stone and urine cultures were reviewed from kidney stone formers. The ability of calcium oxalate monohydrate (COM) aggregation was detected to evaluate the influence of uropathogenic E. coli, then gel electrophoresis and nanoLC‐MS/MS to detect the crystal‐adhered protein. Flagellin (Flic) and polyphosphate kinase 1 (PPK1) were screened out following detection of their role on crystal aggregation, oxidative injury, and inflammation of HK‐2 cell in vitro. By transurethral injection of wild‐type, Ppk1 mutant and Flic mutant strains of E. coli and intraperitoneally injected with glyoxylate in C57BL/6J female mice to establish an animal model. We found that E. coli was the most common bacterial species in patients with CaOx stone. It could enhance CaOx crystal aggregation both in vitro and in vivo. Flagellin was identified as the key molecules regulated by PPK1, and both of them could facilitate the crystal aggregation and mediated HK‐2 cell oxidative injury and activated the inflammation‐related NF‐κB/P38 signaling pathway. Wild‐type strain of E. coli injection significantly increased CaOx deposition and enhanced oxidative injury and inflammation‐related protein expression, and this effect could be reversed by Ppk1 or Flic mutation. In conclusion, E. coli promotes CaOx stone formation via enhancing oxidative injury and inflammation regulated by the PPK1/flagellin, which activated NF‐κB/P38 pathways, providing new potential drug targets for the renal CaOx calculus precaution and treatment.
Cardioprotective Effect of Nec-1 in Rats Subjected to MI/R: Downregulation of Autophagy-Like Cell Death
Authors: Wang Liang , Lv Xuebai , Tian Jue , Wang Xiaoliang , Wu Ye , Liu Hui Rong
Published: July 2021

Objective. Necrostatin-1 (Nec-1), an inhibitor of necroptosis, has been reported to protect against myocardial ischemia-reperfusion (MI/R) injury. However, the contribution of the potential antinecroptotic effect of Nec-1 on its infarct limitation and cardiac function improvement effects after MI/R has not been investigated. Methods. The present study investigated the effect of Nec-1 on myocardial infarct size, necroptosis, and cardiac functional recovery in rats subjected to myocardial ischemia-reperfusion (MI/R 30 min/12, 24, 48, and 72 h). Results. The study showed that Nec-1 might reduce myocardial cell death and maintain myoarchitectonic integrity, consequently inhibiting the reactive fibrosis process in rats in myocardial ischemia/late reperfusion. Moreover, the administration of Nec-1 (0.6 mg/kg) at the onset of reperfusion significantly reduced the release of creatine kinase and downregulation of autophagy within 24 h after reperfusion, and there was a significantly positive correlation between them. Conclusion. These results suggest that antinecroptosis treatment may improve the clinical outcomes of patients with ischemic heart disease.
Sky Image-Based Localized, Short-Term Solar Irradiance Forecasting for Multiple PV Sites via Cloud Motion Tracking
Authors: Dissawa Lasanthika H. , Godaliyadda Roshan I. , Ekanayake Parakrama B. , Agalgaonkar Ashish P. , Robinson Duane , Ekanayake Janaka B. , Perera Sarath
Published: July 2021

Power generation through solar photovoltaics has shown significant growth in recent years. However, high penetration of solar PV creates power system operational issues as a result of solar PV variability and uncertainty. Short-term PV variability mainly occurs due to the intermittency of cloud cover. Therefore, to mitigate the effects of PV variability, a sky-image-based, localized, global horizontal irradiance forecasting model was introduced considering the individual cloud motion, cloud thicknesses, and the elevations of clouds above the ground level. The proposed forecasting model works independently of any historical irradiance measurements. Two inexpensive sky camera systems were developed and placed in two different locations to obtain sky images for cloud tracking and cloud-based heights. Then, irradiance values for onsite and for a PV site located with a distance of 2 km from the main camera were forecasted for 1 minute, 5 minutes, and 15 minutes ahead of real-time. Results show that the three-level cloud categorization and the individual cloud movement tracking method introduced in this paper increase the forecasting accuracy. For partially cloudy and sunny days, the forecasting model for 15 min forecasting time interval achieved a positive skill factor concerning the persistent model. The accuracy of determining the correct irradiance state for a 1 min forecasting time interval using the proposed model is 81%. The average measures of RMSE, MAE, and SF obtained using the proposed method for 15 min forecasting time horizon are 101 Wm-2, 64 Wm-2, and 0.26, respectively. These forecasting accuracy levels are much higher than the other benchmarks considered in this paper.
Correlation between Family RB1 Gene Pathogenic Variant with Clinical Features and Prognosis of Retinoblastoma under 5 Years Old
Authors: Zhang Yi , Wang Yizhuo , Huang Dongsheng , Ma Jianmin , Zhang Weiling , Gu Huali , Zhou Yan , Yi You , Zhang Pinwei
Published: July 2021

Retinoblastoma (RB) is the most common primary intraocular malignant tumor in infants and the prototype of human hereditary tumors. Its occurrence and development are closely related to the pathogenic variant of tumor suppressor RB1 gene. We aim to analyze the characteristics of RB1 gene pathogenic variant and clinical phenotype in retinoblastoma patients and their relatives. Children with RB were recruited from August 2007 to November 2017. QT-PCR, probing, and gene sequencing were used to analyze the sequence of RB1 gene in RB children, their parents, or grandparents with a clear history of illness. The SPSS20.0 software was used to analyze the correlation between polymorphisms of RB1 gene and the incidence and prognosis of the enrolled children and relatives. 40 RB children (20 males and 20 females) were recruited, unilateral RB accounted for 52.5% (21/40), bilateral RB accounted for 42.5% (17/40), and trilateral RB accounted for 5.0% (2/40). 6 patients had a clear family history (15.0%, 6/40). It had been verified that 19 probands (47.5%) have RB1 gene pathogenic variants (11 frameshift and 8 missense pathogenic variants), of which germline inheritance accounted for 47.4% (9/19) and nongermline heredity accounted for 52.6% (10/19). Pathogenic variants of 10 nucleic acid sites without reported were found, among which c.2455C>G (p.L819V) was confirmed to have heterozygous pathogenic variants in both a bilateral RB patient and his mother with unilateral RB. Family genetic high-risk factors, bilateral/trilateral RB, >12-month-onset RB have a higher proportion of RB1 gene pathogenic variant than children with no family history, unilateral RB, and ≤12-month (P=0.021, 0.001,0.034). The proportion of pedigree inheritance of infantile retinoblastoma with bilateral disease is high. There was a certain proportion of RB1 gene pathogenic variant in 3-5-year-old children with bilateral RB, even if they had no family genetic history. Therefore, the detection of RB1 gene pathogenic variant should not only focus on infants but also on the phenotype of RB1 gene pathogenic variant in children over 3 years old with bilateral eye disease.
Warm Footbaths with Sinapis nigra or Zingiber officinale Enhance Self-Reported Vitality in Healthy Adults More than Footbaths with Warm Water Only: A Randomized, Controlled Trial
Authors: Vagedes Jan , Kuderer Silja , Helmert Eduard , Kohl Matthias , Beissner Florian , Szöke Henrik , Joos Stefanie , Wolf Ursula
Published: July 2021

Objectives. To examine the effects of warm footbaths with thermogenic medicinal powders on vitality and heart rate variability in healthy adults. Intervention and Outcome. Seventeen healthy young adults (22.1 ± 2.4 years, 11 females) received three footbaths (WA: warm water only; GI: warm water and ginger; MU: warm water and mustard) in randomized order with a crossover design. We assessed vitality with the Basler Befindlichkeit questionnaire (BBS) and heart rate variability (HRV) before (t0), immediately after (t1), and 10 minutes following footbaths (t2). The primary outcome measure was self-reported vitality, measured via the BBS, at t1. Results. The primary outcome measure, self-reported vitality, was higher after GI and tended to be higher after MU compared to WA with medium effect sizes (GI vs. WA, mean difference −2.47 (95% CI −5.28 to 0.34),padj=0.048, dadj = 0.74), MU vs. WA, −2.35 (−5.32 to 0.61),padj=0.30, dadj = 0.50). At t2, the standard deviation of beat-to-beat intervals (SDNN) of HRV increased, and the stress index tended to decrease after all three footbath conditions with small to medium effect sizes (0.42–0.66). Conclusion. There is preliminary evidence that footbaths with thermogenic agents GI and MU may increase self-reported vitality during a short-time period with a more pronounced effect with GI. After a short follow-up, all three conditions tended to shift the autonomic balance towards relaxation. Future research should investigate these effects in clinical samples with a larger, more diverse sample size.
Single Pick Cutting Rock Load Identification Based on Improved Regularization Method
Authors: Dong Lei , Zhai Siyu , Wang Bukang , Dong Liang , Wang Junyuan , Shi Ruimin
Published: July 2021

To explore the relationship between the cutting vibration and the cutting load of a single pick, this paper studied a new method for a single pick cutting rock load identification. This paper improved the low accuracy problem of the regularization method in the inverse process of frequency response function in the traditional load identification method by introducing a filter operator. By combining the inverse pseudoexcitation method and the improved regularization method, the identification of the load dependent on the vibration signal was realized. A single pick cutting rock test equipment was built, which could simulate the actual working conditions of pick cutting rock in the underground or tunnel. By changing cutting speed, cutting angle, cutting spacing, and cutting depth of the single pick, the change trends of real cutting load and identification load were obtained. The load identification method proposed in this paper was consistent with the change trend of the real load under the single pick cutting state. Therefore, the method had good recognition accuracy and the maximum load recognition error was 17.35%. Compared with other traditional load identification methods, the identification error was reduced by a maximum of 1.98%. This method can identify the cutting load of single pick and modify the morbidity problem of frequency response function matrix. The method has a better recognition effect on the cutting load of the pick than the traditional recognition methods. The research could benefit the design of the cutting system and the arrangement of the pick on the coal mine or tunneling machinery.
Complexity of Some Generalized Operations on Networks
Authors: Javaid Muhammad , Afzal Hafiz Usman , Wang Shaohui
Published: July 2021

The number of spanning trees in a network determines the totality of acyclic and connected components present within. This number is termed as complexity of the network. In this article, we address the closed formulae of the complexity of networks’ operations such as duplication (split, shadow, and vortex networks of Sn), sum (Sn + W3, Sn + K2, and (Cn∘K2) + K1), product (Sn⊠K2 and Wn∘K2), semitotal networks (Q(Sn) and R(Sn)), and edge subdivision of the wheel. All our findings in this article have been obtained by applying the methods from linear algebra, matrix theory, and Chebyshev polynomials. Our results shall also be summarized with the help of individual plots and relative comparison at the end of this article.
MicroRNA-324-5p–CUEDC2 Axis Mediates Gain-of-Function Mutant p53-Driven Cancer Stemness
Authors: Ghatak Dishari , Datta Arindam , Roychowdhury Tanaya , Chattopadhyay Samit , Roychoudhury Susanta
Published: July 2021

Regulation of cancer stemness has recently emerged as a new gain-of-function (GOF) property of mutant p53. In this study, we identify miR-324-5p as a critical epigenetic regulator of cancer stemness and demonstrate its role in mediating GOF-mutant p53-driven stemness phenotypes. We report that miR-324–5p is upregulated in human cancer cell lines and non–small cell lung carcinoma (NSCLC) tumors carrying TP53 GOF mutations. Mechanistically, we show that GOF mutant p53 upregulates miR-324–5p expression via c-Myc, an oncogenic transcription factor in cancer cells. Our experimental results suggest that miR-324–5p–induced CSC phenotypes stem from the downregulation of CUEDC2, a downstream target gene of miR-324–5p. Accordingly, CUEDC2 complementation diminishes elevated CSC marker expression in miR-324–5p–overexpressing cancer cells. We further demonstrate that mutant p53 cancer cells maintain a low level of CUEDC2 that is rescued upon miR-324–5p inhibition. Importantly, we identify CUEDC2 downregulation as a novel characteristic feature of TP53-mutated human cancers. We show that activation of NF-κB due to downregulation of CUEDC2 by miR-324–5p imparts stemness in GOF mutant p53 cancer cells. Finally, we provide evidence that TP53 mutations coupled with high miR-324–5p expression predict poor prognosis in patients with lung adenocarcinoma. Thus, our study delineates an altered miR-324–5p-CUEDC2-NF-κB pathway as a novel regulator of GOF mutant p53-driven cancer stemness.

Implications:

Our findings implicate miRNA-324–5p as a novel epigenetic modifier of human cancer stemness.
Mice Deficient in the RNA-Binding Protein Zfp871 Are Prone to Early Death and Steatohepatitis in Part through the p53–Mdm2 Axis
Authors: Mohibi Shakur , Zhang Jin , Chen Mingyi , Chen Xinbin
Published: July 2021

p53 transcription factor is activated upon exposure to various cellular stresses, leading to growth suppression. However, aberrant activation of p53 can lead to defects in embryonic development and other abnormalities. Here, we identified zinc finger protein Zfp871 as a p53 target gene. We showed that as an RNA-binding protein, Zfp871 binds to Mdm2 3′UTR and stabilizes Mdm2 mRNA, which in turn suppresses p53 expression through increased expression of Mdm2 E3 ubiquitin ligase. Consistently, Zfp871 deficiency increases p53 expression, leading to growth suppression in a p53-dependent manner. To determine the role of Zfp871 in the p53 pathway, we used Zfp871-deficient mouse model and found that Zfp871-null mice were prone to embryonic/pre-weaning lethality, which can be partially rescued by simultaneous deletion of Trp53. We also found that mice heterozygous for Zfp871 had a short lifespan and were susceptible to steatohepatitis but not to spontaneous tumors. To determine the underlying mechanism, RNA-seq analysis was performed and showed that an array of genes involved in development, lipid metabolism, and inflammation is regulated by Zfp871 in conjunction with p53. Taken together, we conclude that the Zfp871–Mdm2–p53 pathway plays a critical role in tumor-free survival and development.

Implications:

A fine equilibrium of p53 is required for preventing damaging effects of aberrant p53 expression. We identify the Zfp871–Mdm2–p53 pathway that plays a critical role in development of mice and steatohepatitis.
Supraclavicular Scrofuloderma: A Diagnostic Challenge without Apparent Clinical Manifestations of Tuberculosis
Authors: Yoshioka Yusuke , Namiki Takeshi , Ugajin Tsukasa , Miura Keiko , Yokozeki Hiroo
Published: July 2021

Scrofuloderma is one of the cutaneous manifestations of tuberculosis and usually occurs when underlying tuberculosis such as lymphadenitis directly involves the skin. However, the diagnosis of scrofuloderma without other apparent clinical manifestations of tuberculosis is sometimes challenging. A 27-year-old male from Bangladesh presented with a dome-shaped tumor on his right clavicle. MRI showed a high-density area that expanded from the lymph nodes between the internal jugular vein and the common carotid artery into the tumor on his right clavicle. Bacterial examinations of cultures from the tumor detected Mycobacterium tuberculosis. Further examinations for pulmonary tuberculosis including chest X-ray and computed tomography did not detect any lesions suggestive of pulmonary tuberculosis. From those examinations, the diagnosis of scrofuloderma was made. We emphasize the importance of recognizing a variety of clinical manifestations of tuberculosis including scrofuloderma due to the recent increase of immigrants from developing countries.
Intrahepatic Bile Duct Injury as a Hepatic Immune-Related Adverse Event after Immune-Checkpoint Inhibitor Treatment
Authors: Murayama Aiko , Tajiri Kazuto , Nakaya Atsuko , Ito Hiroyuki , Hayashi Yuka , Entani Toshiki , Nagata Kohei , Tanaka Shinichi , Hamashima Takeru , Yasuda Ichiro
Published: July 2021

The increased use of immune-checkpoint inhibitors to treat various types of cancer has increased the incidence of immune-related adverse events (irAEs). Hepatic irAEs are frequent and can lead to serious conditions. Among the various types of hepatic irAEs reported to date, bile duct injury has been shown refractory to steroid treatment. This study describes 2 patients with hepatic irAEs manifesting as intrahepatic bile duct injury. Immunostaining with antibodies to both CD8 and cytokeratin-7 was useful for the diagnosis, and both patients were refractory to steroid treatment. Prompt diagnosis and active immunosuppressive therapies are required in such cases.
Subkutane Allergen-Immuntherapie bei Hausstaubmilbenallergie – die Anwendung kann auch bei Kindern unter 5 Jahren sicher erfolgen
Authors: Jorczyk Maximilian
Published: July 2021

Background: Allergen immunotherapy (AIT) is the only causal therapy for IgE-mediated allergy. There is less evidence about the safety and efficacy of AIT especially subcutaneous immunotherapy (SCIT) in children under 5 years old. We aimed to investigate the side effects and associated risk factors of house dust mite (HDM) SCIT in preschool children with respiratory allergic diseases. Methods: The preschool children who had HDM-related allergic rhinitis with/without asthma were enrolled and undergone standardized HDM SCIT in our department from June 2013 to December 2019. Local reactions (LRs) and systemic reactions (SRs) were recorded and categorized according to World Allergy Organization recommendations. Demographic data and other therapeutic-related parameters were also recorded to investigate potential risk factors for these side effects. Results: A total of 91 children (60 boys, 65.93%; 31 girls, 34.07%; mean age 4.13 years old) were included in the study. Among the 91 patients, 3109 SCIT injections were recorded, 62/91 (68.13%) experienced 186 immediate LRs, 4 /91(4.40%) experienced 6 delayed LRs, 11/91 (12.09%) children experienced 44 immediate SRs, 21/44 (47.73%) were grade 1 SRs, 21/44 (47.73%) were grade 2, 2/44 (4.55%) were grade 3, no grade 4 or 5 SRs occurred. Furthermore, 1/91 (1.10%) experienced 1 delayed SRs, manifested by urticaria 2 days later after allergen injection. 9/91 (9.89%) experienced 2 or more times SRs. Multivariable logistic regression analysis showed BMI (OR 1.506; 95%CI 1.091 to 2.079; p < 0.05) and sIgE against HDM (OR 1.497; 95%CI 1.082 to 2.071; p < 0.05) were risk factors for LRs. No variable was found to correlate with SRs (all p > 0.05). Conclusions: HDM subcutaneous immunotherapy is considered to be safe in preschool children with respiratory allergic diseases. Higher BMI and HDM sIgE level in children are risk factors for developing LRs. The incidence of SRs and the rate of severe SRs are low in preschool children.
Fusidic Acid Resistance Determinants in Methicillin-Resistant Staphylococcus aureus Isolated in Kuwait Hospitals
Authors: Boloki Halimah A. , Al-Musaileem Wasmiyah F. , AlFouzan Wadha , Verghese Tina , Udo Edet E.
Published: July 2021

Objective: The aim of this study was to investigate the genetic determinants of fusidic acid (FA) resistance in MRSA isolated from patients in Kuwait hospitals. Methods: The minimum inhibitory concentration (MIC) of FA was tested with E-test strips. Genetic determinants of FA were determined by PCR and DNA microarray. Staphylococcal protein A gene (spa) typing and DNA microarray analysis were used to study their genetic backgrounds. Results: The FA MIC ranged from 2 mg/L to >256 mg/L. Of the 97 isolates, 79 (81.4%) harbored fusC, 14 isolates harbored fusA mutations (fusA), and 4 isolates harbored fusB. Isolates with fusA mutations expressed high FA MIC (MIC >256 mg/L), whereas those with fusC and fusB expressed low FA MIC (MIC 2–16 mg/L). The isolates belonged to 23 spa types and 12 clonal complexes (CCs). The major spa types were t688 (n = 25), t311 (n = 14), t860 (n = 8), and t127 (n = 6) which constituted 54.6% of the isolates. The 12 CCs were CC1, CC5, CC8, CC15, CC22, CC80, CC88, and CC97 with CC5 (45.6%) and CC97 (13.2%) as the dominant CCs. Conclusions: The MRSA isolates belonged to diverse genetic backgrounds with the majority carrying the fusC resistance determinants. The high prevalence of FA resistance belonging to diverse genetic backgrounds warrants a review of FA usage in the country to preserve its therapeutic benefits.
Ankle-Brachial Index for Risk Stratification in Patients With Symptomatic Peripheral Artery Disease With and Without Prior Lower Extremity Revascularization: Observations From the EUCLID Trial
Authors: Hiatt William R. , Hess Connie N. , Bonaca Marc P. , Kavanagh Sarah , Patel Manesh R. , Baumgartner Iris , Berger Jeffrey S. , Blomster Juuso I. , Jones W. Schuyler , Katona Brian G. , Mahaffey Kenneth W. , Norgren Lars , Rockhold Frank W. , Fowkes F. Gerry R.
Published: July 2021

Background:

A reduced ankle-brachial index (ABI) is a measure of atherosclerosis and is associated with ischemic risk in the general population. Whether this relationship is maintained in peripheral artery disease after lower extremity revascularization (LER), which can modify ABI, is unknown.

Methods:

The EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) enrolled 13 885 patients with symptomatic peripheral artery disease; 57% with prior LER, and 43% with ABI ≤0.80. The primary major adverse cardiovascular events (MACE) outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Major adverse limb events (MALE) included acute limb ischemia and major amputation. An adjusted Cox proportional hazards model demonstrated a nonlinear relationship between ABI and outcomes. A restricted cubic spline model with 4 knots was developed to identify the best fitting model to describe the relationship between ABI and MACE and MALE risk.

Results:

Baseline ABI (mean±SD) was 0.77±0.21 in participants with prior LER and 0.63±0.14 in those without prior LER (
P
<0.0001). There was no statistical interaction between prior LER and ABI, meaning the shapes of the cubic spline models were similar between groups. In those with prior LER, for every 0.10 unit lower ABI below an ABI of 1.00, the hazard ratio for MACE was 1.08 (95% CI, 1.04–1.12;
P
<0.0001), below an ABI of 0.80 the hazard ratio for MALE was 1.32 (95% CI, 1.21–1.43;
P
<0.0001). In patients without prior LER, every 0.10 unit lower ABI below an ABI of 0.70 was associated with increased risk for MACE (hazard ratio, 1.14 [95% CI, 1.06–1.23];
P
=0.0004) and MALE (hazard ratio, 1.27 [95% CI, 1.08–1.49];
P
=0.003).

Conclusions:

Patients with established peripheral artery disease, particularly those with prior LER, have an increased risk of MACE and MALE. The ABI remains a strong predictor of MACE and MALE ischemic events with an inverse relationship below an ABI threshold for patients with and without prior LER.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01732822.
ALTIN, FAİZ, İŞSİZLİK, PARA ARZI İLE BORSA ARASINDAKİ EŞBÜTÜNLEŞME İLİŞKİSİNİN ARAŞTIRILMASI
Authors: YEŞİLDAĞ Eser
Published: July 2021

Hisse senedi fiyatlarının hangi faktörlerden etkilendiği konusu hem kurumsal hem de bireysel yatırımcılar açısından her zaman en önemli konulardan olmuştur. Bu çalışmanın temel amacı, Türkiye’deki hisse fiyatları ile altın fiyatları, faiz oranları, işsizlik oranları ve para arzı arasındaki eşbütünleşme ilişkisinin analiz edilmesidir. Bunun için 2009:01-2019:01 dönemleri arasındaki aylık BIST100 endeks değerleri ile altın, faiz, işsizlik ve para arzı makroekonomik faktörlerinin değerleri analize dâhil edilmiştir. Hisse senetleri, altın, faiz, işsizlik ve para arzı arasında bir eşbütünleşme ilişkisinin olup olmadığı ARDL sınır testi kullanılarak araştırılmıştır. Analiz sonuçları hisse senediyle altın, faiz, işsizlik ve para arzı değişkenleri arasında bir eşbütünleşme olduğunu göstermiştir. Buna göre hisse fiyatları ile faiz oranları ve para arzı arasında uzun ve kısa vadeli anlamlı bir ilişki bulunmuştur. Bu ilişkide faiz oranları hisse senedi fiyatlarını negatif, para arzı ise pozitif yönde etkilemektedir. Altın fiyatları ve işsizlik oranı ile hisse fiyatları arasında herhangi bir anlamlı ilişki bulunamamıştır.
Industrial Designs Protection in Qatar: An Analytical Study of Industrial Designs and Models Law No. 10 of 2020
Authors: El-Farag Mohamed Salem Abou , Al-Muraikhi Shaikha Jaber S.H.
Published: July 2021

For the industrial development of national economic industries in any given country, designs for products and goods need to be created and developed. In 2020, Qatar issued a new law on Industrial Designs and Models (Law No. 10 of 2020) as a means of enhancing and strengthening Intellectual Property Rights and their protection, which is regarded as a part of Qatar’s National Vision 2030. In this article, the provisions of the new law will be critically examined. The discussion starts by highlighting the definition of, and the requirements for, protection. The rights granted to the owner of the design will also be explored. A comparison between the Qatari provisions and those from a number of other countries will be made throughout. The main purpose of this paper is to provide a comprehensive analysis of the new law on industrial designs, taking into consideration the legal development of those jurisdictions.
Ubuntu Apologetics in Faith Formation
Authors: Ndereba Kevin Muriithi
Published: July 2021

Faith formation is a crucial area in youth ministry. Although the area of apologetics may be a helpful bridge, the theory and praxis of apologetics in the African context is scanty. The work of apologists such as William Lane Craig, John Frame, Ravi Zacharias, and John Lennox has responded to the post-Christian context of Europe and North America. Much needs to be done in light of the African contextual realities. Using a practical theological methodology, this paper considers how ubuntu apologetics – which honors both the cognitive and affective development of adolescents – can lead to holistic faith formation of African youth. This research paper will 1) consider youth ministry contextual realities in Kenya and Africa; 2) analyze foundational methods of apologetics; 3) utilize an ethnographic methodology in analyzing the data and 4) offer recommendations for youth ministry education and practice in Nairobi and Africa at large.
Controversies about Religious Organisations within an Evolving Taiwan Civil Society
Authors: Madsen Richard
Published: July 2021

A staple of political theory is that democracy depends on a vibrant civil society. What are the indicators of such a society? Is it the number of voluntary associations, their relative independence from government, the content of their activities, their systemic relationships with one another—and/or the way the relationships among these variables are evolving over time? In this paper, I place special emphasis on the systemic relationships among civil society organisations and their evolution over time, and I revisit some of the findings from the book Democracy’s Dharma to show how this emphasis might offer a new perspective on the development of Taiwan’s civil society today.
A new species of Dune Cricket from China (Orthoptera: Ensifera: Schizodactylidae)
Authors: HE ZHU-QING , LIU YI-JIAO
Published: July 2021

A new species, Schizodactylus jimo He sp. nov., is described from Yunnan, China. The Schizodactylidae is recorded from China for the first time. The new species is similar to S. salweenensis, but different based on the shape of epiproct and other characters. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).
Designation of a neotype for Orchestoidea tuberculata Nicolet, 1849 (Amphipoda: Senticaudata: Talitridae), a monotypic sandhopper endemic to the southeastern Pacific coast
Authors: PÉREZ-SCHULTHEISS JORGE , FERNÁNDEZ LEONARDO D. , RIBEIRO FELIPE BEZERRA
Published: July 2021

The genus Orchestoidea Nicolet, 1849 is geographically restricted to sandy beaches of the southeastern Pacific coast of Chile, being found from 23°S (Antofagasta, northern Chile) to 45°S (Guamblin Island, southern Chile), along a latitudinal gradient of ca. 2,400 km. Orchestoidea tuberculata Nicolet, 1849, the only known species for the genus, was originally described from Valparaíso Bay, central Chile (33°S). However, the published morphological descriptions are incomplete and a comparison with populations along the entire distributional range is difficult, because the type material is considered lost. In this paper, we selected a male specimen recently obtained from a site close to the type locality, to designate a neotype for O. tuberculata. A detailed description and illustrations of this specimen are also provided to establish a basis for further analysis of Orchestoidea.
Updates on the Fixator—Facilitating the investigation, mounting, and photography of structures and specimens in liquid
Authors: WANKE DOMINIC , ULMER JONAH M , WENDT INGO , RAJAEI HOSSEIN
Published: July 2021

N/A
Diurnal variability of frontal dynamics, instability, and turbulence in a submesoscale upwelling filament
Authors: Peng Jen-Ping , Umlauf Lars , Dräger-Dietel Julia , North Ryan P.
Published: July 2021

Recent high-resolution numerical simulations have shown that the diurnal variability in the atmospheric forcing strongly affects the dynamics, stability, and turbulence of submesoscale structures in the surface boundary layer (SBL). Field observations supporting the real-ocean relevance of these studies are, however, largely lacking at the moment. Here, the impact of large diurnal variations in the surface heat flux on a dense submesoscale upwelling filament in the Benguela upwelling system is investigated, based on a combination of densely-spaced turbulence microstructure observations and surface drifter data. Our data show that during nighttime and early-morning conditions, when solar radiation is still weak, frontal turbulence is generated by a mix of symmetric and shear instability. In this situation, turbulent diapycnal mixing is approximately balanced by frontal restratification associated with the cross-front secondary circulation. During daytime, when solar radiation is close to its peak value, the SBL quickly restratifies, the conditions for frontal instability are no longer fulfilled, and SBL turbulence collapses except for a thin wind-driven layer near the surface. The drifter data suggest that inertial oscillations periodically modulate the stability characteristics and energetics of the submesoscale fronts bounding the filament.