bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Differences in the Cardiometabolic Risk Profile of Patients with Psoriatic Disease according to Their HLA‐C∗06 Status
Authors: Queiro Rubén , Coto-Segura Pablo , Braña Ignacio , Pino Marina , Burger Stefanie
Published: January 2022

The human leukocyte antigen‐C∗06 (HLA‐C∗06, formerly HLA‐Cw6) is the main genetic biomarker in psoriatic disease. It has been related to several phenotypic traits in psoriatic disease, but its role in relation to cardiometabolic comorbidities is unknown at present. Here, we analyze the potential connections between this biomarker and the cardiometabolic profile of these patients. We carried out a cross‐sectional observational study including 400 patients recruited at a single university hospital. Clinical and classical cardiometabolic factors were compared between HLA‐C∗06‐positive and HLA‐C∗06‐negative individuals (OR with 95% CI). Multivariate regression analyses were carried out to check for disease traits associated with different cardiometabolic risk factors. The study population included 215 men (53.8%) and 185 women (46.2%), mean age of 46 ± 15 years, and an average disease evolution of 17 ± 12.6 years. Ninety‐three (23.3%) patients met CASPAR criteria for psoriatic arthritis. HLA‐C∗06 carriers (n: 160, 40%) showed an earlier age at disease onset, psoriasis family history, and more severe skin disease (type I disease). After correcting for age, sex, and disease duration, they also showed less hypertension (13.8% vs. 24.2%, OR 0.7 (95% CI: 0.42‐0.78), p = 0.025), lower waist circumference (94.4 ± 13.7 vs. 98.3 ± 13.8 cm), and lower BMI (27 ± 4.4 vs. 28.1 ± 4.8, p < 0.05). We confirmed the well‐known association between HLA‐C∗06 and type I psoriatic disease. As a novel finding, patients carrying HLA‐C∗06 showed a better cardiometabolic profile. In any case, these findings need further confirmation.
Application of Porcine Kidney‐Derived Extracellular Matrix as Coating, Hydrogel, and Scaffold Material for Renal Proximal Tubular Epithelial Cell
Authors: Lee Eun Hye , Chun So Young , Yoon Bo Hyun , Kim Hyun Tae , Chung Jae-Wook , Lee Jun Nyung , Ha Yun-Sok , Kwon Tae Gyun , Byeon Kyeong-Hyeon , Kim Bum Soo
Published: January 2022

Background. Human renal proximal tubular epithelial (RPTE) cell is a very useful tool for kidney‐related experiments in vitro/ex vivo. However, only a few primary RPTE cells can be obtained through kidney biopsy, the proliferation rate of primary cell is very low, and the cultured cell properties are easily altered in artificial conditions. Thus, RPTE cell usage is very tricky; we applied porcine kidney‐derived extracellular matrix (renal ECM) as coating, hydrogel, and scaffold material to increase cell proliferation and maintain cellular properties providing three‐dimensional (3D) niche, which can be a valuable cell delivery vehicle. Methods. Porcine renal ECM was prepared by decellularization using 1% Triton X‐100, solubilized with 0.5 M acetic acid. The final protein concentration was adjusted to 10 μg/μL (pH 7.0). The efficacies as coating, hydrogel, and scaffold materials were analyzed through cell morphology, proliferation rate, renal‐associated gene expressions, chemical composition, and microstructure evaluation. The efficacies as a coating material were compared with Matrigel, collagen type 1 (col1), gelatin, fibrinogen, and thrombin. After confirmation of coating effects, the effective concentration range was decided. The efficacies as hydrogel and scaffold materials were compared with hyaluronic acid (HA) and col1, respectively. Results. As the coating material, renal ECM showed a higher cell proliferation rate compared to other materials, except for Matrigel. Renal‐associated gene expressions were significantly enhanced in the renal ECM than other materials. Coating effect on cell proliferation was dependent on the renal ECM concentration, and the effective concentration ranged from 30 to 100 μg. As the hydrogel material, renal ECM showed a distinct inner cell network morphology and significantly increased renal‐associated gene expressions, compared to HA hydrogel. As the scaffold material, renal ECM showed specific amide peaks, enhanced internal porosity, cell proliferation rate, and renal‐associated gene expression compared to the col1 scaffold. Conclusions. We concluded that renal ECM can be a suitable material for RPTE cell culture and usage. More practically, the coated renal ECM stimulates RPTE cell proliferation, and the hydrogel and scaffold of renal ECM provide useful 3D culture niche and cell delivery vehicles maintaining renal cell properties.
Contralateral Effect following Intravitreal Brolucizumab Injection in Diabetic Macular Edema
Authors: Chakraborty Somnath , Sheth Jay Umed
Published: January 2022

The authors describe a novel case of a 48-year-old male with bilateral diabetic macular edema (DME) who underwent intravitreal injection (IVI) of brolucizumab in the left eye. At four weeks, the patient demonstrated a bilateral response by way of improvement in the best-corrected visual acuity (BCVA) and reduction in the central macular thickness (CMT) in both eyes. Further studies on the ocular and systemic assays of the brolucizumab molecule are warranted to evaluate its systemic escape and to better understand the pharmacokinetics behind the bilateral effect.
The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway
Authors: Wang Kaifang , Sun Meiyan , Juan Zhaodong , Zhang Jianxin , Sun Yingui , Wang Guizhi , Wang Chunling , Li Yanjing , Kong Wenwen , Fan Lulu , Zhang Yue , Zhao Hongxiang , Zhao Xiaoyong
Published: January 2022

The pathogenesis of sepsis-associated encephalopathy (SAE) involves many aspects, including intracellular peroxidative stress damage, mitochondrial dysfunction, and cell apoptosis. In this study, we mainly explored the influence of P2X7R on the cognitive function of SAE and its molecular mechanism. We established a sepsis model using lipopolysaccharide (LPS) stimulation, followed by an assessment of cognitive function using Morris water maze, and then Western Blot was used to analyze the expression of tight junction proteins ZO-1 and Occludin in the hippocampus of mice. TUNEL assay was used to analyze the apoptosis of brain cells in frozen brain slices of mice during sepsis. Human brain microvascular endothelial cells (HBMECs) were used to research the molecular mechanism of brain cell damage induced by P2X7R. The results showed that P2X7R inhibitors dramatically improved the survival rate of mice, relieved the cognitive dysfunction caused by LPS stimulation, and significantly reduced the brain cell apoptosis caused by LPS. In addition, the inhibition of P2X7R can also reduce the production and accumulation of reactive oxygen species (ROS) in HBMECs in vitro and inhibit the apoptosis signaling pathway associated with mitochondrial serine protease Omi/HtrA2 in HBMECs in vitro. These results suggest that P2X7R has strong value as a potential target for the treatment of SAE.
Preparation and Study of Folate Modified Albumin Targeting Microspheres
Authors: Zha Quanbin , Zhang Ling , Guo Yuhua , Bao Rui , Shi Feng , Shi Yongkang
Published: January 2022

In this study, folate modified bovine serum albumin was successfully synthesized, while preparation of Nintedanib albumin microspheres (ND-FSA NPs) as a carrier was carried out via electrospinning technology. Folate modified albumin was used to enhance the targeting potential of the prepared microspheres. The prepared microspheres had spherical appearance and smooth outer surface. The diameters of microspheres (764.68 ± 88.46 nm) and zeta potential (- 18.38 ± 0.41 mV) were acceptable. The prepared ND-FSA NPs demonstrated a good degree of modification, wherein the modification rate was 28.1%. In vitro release was significantly increased in three different media (double deionized water-DDW, HCl-pH 1.2, and phosphate buffered solution containing 0.5% Tween 80). It is worth noting that incorporation of Nintedanib into folic acid modified albumin microspheres resulted in an enhanced uptake of the drug into MCF-7 breast cancer cells coupled with higher inhibition rate. Altogether, incorporation of Nintedanib into folate modified albumin microspheres is a new approach to improve water solubility and targeting effect of the drug.
Influence of Foundation Pit Excavation on Tunnels at Different Locations
Authors: Wang Chengwu , Sun Huasheng , Zhang Jihua , Lu Yu
Published: January 2022

To evaluate the tunnel deformation law and soil stress distribution between foundation pit excavation and tunnel in different locations, numerical analyses using the hypoplastic model are conducted based on reported centrifuge model tests. Two cases are designed to investigate the effects of the foundation pit excavation on the deformation of existing tunnels. In case C, an existing tunnel is directly located underneath the foundation pit; in case S, the tunnel is located at one side of the foundation pit. Three-dimensional tunnel deformation mechanisms along the tunnel axis are observed through the variation of stresses change in the soil circumambient tunnel. It is found that compared with case C, there are minor Earth pressure changes in case S. The different Earth pressure changes around the tunnel lead to different modes of tunnel deformation. The maximum additional tunnel bending strain appears at the crown and invert, while the minimum value appears at the spring lines in case C. In case S, the maximum values appear in the right shoulder and left knee, while the minimum values appear on the left shoulder and right knee. The additional tunnel bending strain and stress reduction at different tunnel cross sections in case S is much smaller than those in case C. In case C, after the excavation, lateral Earth pressure coefficient changes ΔKxz and ΔKyz rise to 70% and 150%, respectively, of their initial value at shoulders, while little changes can be found at spring lines. However, in case S, the maximum absolute value of both ΔKxz/(Kxz)0 and (ΔKyz/(Kyz)0) is no more than 10%.
UAV-Based Physical-Layer Intelligent Technologies for 5G-Enabled Internet of Things: A Survey
Authors: Wang Changyu , Yu Weili , Lu Jinrong , Zhu Fusheng , Fan Lihua , Li Shengping
Published: January 2022

In recent years, the utilization and application of unmanned aerial vehicle (UAV) have attracted much attention, both from academy and industry. UAVs have been widely used in many practical communication scenarios, due to its high flexibility, high mobility, and low cost. Therefore, this paper addresses the key technologies of UAV communication and reviews the current research status, from various aspects including UAV communication transmission, UAV formation control and networking, UAV resource allocation, and intelligent communication from artificial intelligence algorithms. Then, artificial intelligence is introduced into multiple aspects of UAV communication, including channel transmission, control and networking, and resource scheduling, to organically integrate artificial intelligence into UAV communication, which can help reduce the complexity of communication algorithms and improve system spectrum efficiency. This paper will help improve the efficiency of UAV communication and promote the development of UAV-related industries.
Construction of a Hybrid Teaching Model System Based on Promoting Deep Learning
Authors: Sun Yingjie , Li Yang , Tian Yuan , Qi Wanqiang
Published: January 2022

The rapid development of computer network technology in today’s society has also brought new opportunities for the transformation of the teaching management mode of colleges and universities. Nowadays, most colleges and universities are gradually improving the construction of campus informatization projects, further integrating school teaching resources, centralizing the work related to the work process, and carrying out platform management to improve the daily work efficiency of various departments of the school, which is also prominent from the user experience. Humanized management out of school. This paper designs and develops a set of online teaching management system suitable for colleges and universities, realizes the informatization of college teaching management, and solves the traditional teaching methods, such as the inability of offline correspondence students to take classes in time and the limited teaching venues. Through comparison and analysis, in order to ensure that the system has better portability, this article will mainly adopt the MVC architecture model to develop and design the entire school hybrid teaching management system. The MVC architecture model is mainly developed based on the abstract design model. Strong reusability, combined with the system architecture, the main choice for database selection is development based on Oracle database technology. In the specific development process, the detailed business requirements and functional requirements of the entire school online teaching management system will be analyzed in detail. Based on this, by adopting an object-oriented approach, the system management included in the school's hybrid teaching management system will be further analyzed. Detailed analysis and design of the specific functional structure, work flow, work sequence diagram and class diagram of the online learning management and article management functional modules, and finally complete the implementation and testing of the various functional modules of the system.
Higher Prevalence of Diabetes in Pontine Infarction than in Other Posterior Circulation Strokes
Authors: Zhu Jinmao , Li Youfu , Wang Yanxia , Zhu Shuanggen , Jiang Yongjun
Published: January 2022

Background. Pontine infarction is the major subtype of posterior circulation stroke, and diabetes is more common in pontine infarction patients than in anterior circulation stroke patients. Whether the prevalence of diabetes remains homogenous within the posterior circulation stroke population is unclear. The present study is aimed at investigating the prevalence of diabetes in pontine infarction and comparing it to other subtypes of posterior circulation stroke. Methods. We conducted a multicenter case-control study. Patients with posterior circulation stroke were screened. The subjects were divided into pontine infarction and nonpontine infarction groups. Results. From November 1, 2018, to February 28, 2021, a total of 6145 stroke patients were screened and 2627 patients had posterior circulation strokes. After excluding cardioembolic stroke, as well as its other determined and undetermined causes, 1549 patients with 754 pontine infarctions were included in the analysis. The prevalence of diabetes in the pontine infarction group was higher than that in the nonpontine infarction group (42.7% vs. 31.4%,

P
<
0.05

). After adjusting for confounding factors, diabetes was an independent risk factor for pontine infarction (OR 1.63, 95% CI 1.27-2.09,

P
<
0.05

). For small vessel occlusion, diabetes was also more common in the pontine infarction group (43.2% vs. 30.0%,

P
<
0.05

). Multivariate analysis also showed that diabetes was an independent risk factor for pontine infarction (OR 1.80, 95% CI 1.32-2.46,

P
<
0.05

). Conclusion. In comparison with the nonpontine infarction subtype of posterior circulation stroke, patients with pontine infarction had a higher prevalence of diabetes, and diabetes was an independent risk factor for pontine infarction.
[Retracted] Transcriptome Comparison of Brain and Kidney Endothelial Cells in Homeostasis
Authors: Huang Xiaohua , Huang Zhongshi , Wei Zhongheng , Feng Yun , Li Xuebin , Xu Anding , Jian Chongdong
Published: January 2022

Endothelial cells are heterogeneous, stemming from multiple organs, but there is still little known about the connection between the brain and kidney endothelial cells, especially in homeostasis. In this study, scRNA‐seq results were obtained to compare genetic profiles and biological features of tissue‐specific endothelial cells. On this basis, seven endothelial cell subpopulations were identified, two of which were upregulated genes in pathways related to stroke and/or depression, as characterized by neuroinflammation. This study revealed the similarities and distinctions between brain and kidney endothelial cells, providing baseline information needed to fully understand the relationship between renal diseases and neuroinflammation, such as stroke and depression.
Model Test and Numerical Simulation Analysis on Freezing Effect of Different Freezers in Freeze-Sealing Pipe-Roof Method
Authors: Cai Haibing , Liu Yujie , Hong Rongbao , Li Mengkai , Wang Zongjin , Ding Hanglong
Published: January 2022

The Gongbei Tunnel Project is a key phased project of the Zhuhai Connection Line of the Hong Kong–Zhuhai–Macao Bridge, and the freeze-sealing pipe-roof (SFPR) method was first applied successfully. During this period, in order to obtain the best arrangement of freezers, three configurations, that is, solid pipe with circular freezer (SCF), empty pipe with double circular freezer (EDCF), and empty pipe with special-shaped freezer (ESF), were designed to analyze their freezing effects. The model test results show that the freezing temperature fields excited by different arrangements of freezers are obviously different, and the freezing effect of ESF is the best. The numerical simulation results indicate that the temperature cloud diagram of SCF at 42 h is butterfly-shaped after opening the limit pipes, and the temperature cloud diagrams of ESF and EDCF are the same as the model test results. However, the processing method of ESF is relatively complex, which adopts arc angle steel welding requiring a lot of reverse welding and high welding quality. Eventually, EDCF is recommended to ensure the quality of frozen walls due to its lower cost and better freezing effect. This research plays a basic role in the implementation of the freeze-sealing pipe-roof method.
Connectivity of Drones in FANETs Using Biologically Inspired Dragonfly Algorithm (DA) through Machine Learning
Authors: Hameed Shahzad , Minhas Qurratul-Ain , Ahmad Sheeraz , Ullah Fasee , Khan Arshad , Khan Atif , Uddin M. Irfan , Hua Qiaozhi
Published: January 2022

Flying Ad hoc Network (FANET) presents various challenges during communication due to the dynamic nature of network and ever-changing topology. Owing to high mobility, it is difficult to ensure a well-connected network and link stability. Thus, flying nodes have a higher chance of becoming disconnected from the network. In order to overcome these discrepancies, this work provides a well-connected network, reducing the number of isolated nodes in FANETs utilizing the depth of machine learning by taking inspiration from biology. Every biological species is innately intelligent and has strong learning ability. Moreover, they can also learn from existing active events and can take decision based on previous experience. There may be some unusual events such as attack of predator or when it may become isolated from the rest of the community. This ability helps them to maintain connectivity and concentrate on target. In this work, we take inspiration from dragonflies, which provide novel swarming behaviors of dynamic swarming and static swarming. The nodes in FANETs learn from the dragonflies and use this learning to search for a neighbor, ensuring connectivity. Moreover, to avoid collision and establish larger coverage area, they employ separation and alignment. In case a drone is isolated, it strives to become part of the network using machine learning (ML) via the dragonfly algorithm (DA). The proposed scheme results in larger coverage area with reduced number of isolated drones. This improves the connectivity in FANETs adding to the network intelligence via learning through DA, allowing communication despite the complexity of mobility and dynamic network topology.
Performance and Genetic Variability of Okra (Abelmoschus esculentus (L.) Moench) Genotypes in Ethiopia for Agromorphology and Biochemical Traits
Authors: Mohammed Jemal , Mohammed Wassu , Shiferaw Eleni
Published: January 2022

No research has been done to assess the genetic diversity of Okra (Abelmoschus esculentus) genotypes in Ethiopia based on the combination of agromorphology and biochemical traits of the crop. Such an assessment would assist in the development of high fruit yield and nutritionally good cultivars. Therefore, 36 okra genotypes were evaluated for 29 agromorphological and biochemical traits at the Melkassa Agricultural Research Center (Ethiopia) during the 2018 main rainy season, using a 6 × 6 simple lattice design. Analysis of variance showed significant differences among genotypes for all the studied traits, except number of flower epicalyxes and fruit diameter. Genotypic coefficients of variation and phenotypic coefficient of variation were high for number of branches, internode length, fresh fruit weight, number of mature pods, fruit yield per plant, fruit yield per hectare, seed yield per plant, seed yield per hectare, and seed protein content. Heritability values ranged between 33.63 and 99.81%, while the genetic advance as percentage of mean ranged between 4.29 and 95.45%. High broad sense heritability was coupled with high GAM for plant height, branch, internod length, fruit length, panicle length, fresh fruit weight, number of fruits per plant, number of mature pods, seed yield per plant, seed yield per hectare, and fibre and protein content. In conclusion, this study showed the presence of genetic variation among genotypes for fruit yield, seed yield, and nutritional content, indicating the potential success of developing okra varieties for high fruit yielding and good nutritional content.
Mathematical Model and Simulated Annealing Algorithm for the Two-Dimensional Loading Heterogeneous Fixed Fleet Vehicle Routing Problem
Authors: Candido Lilian Caroline Xavier , de Souza Luzia Vidal
Published: January 2022

This paper addresses the two-dimensional loading heterogeneous fixed fleet vehicle routing problem, which is a complex and unstudied variant of the classical vehicle routing problem and has a wide range of applications in transportation and logistics fields. In this problem, each customer demands a set of rectangular two-dimensional items, and the objective is to find the minimum cost delivery routes for a limited set of vehicles with different capacities, fixed and variable operating costs, and rectangular two-dimensional loading surfaces. We formulate a mixed integer linear programming model to obtain optimal solutions for small-scale problems. To obtain solutions for large-scale problems, we develop an algorithm based on simulated annealing and local search, which uses a collection of packing heuristics to address the loading constraints, and we also propose three new heuristics. We conduct experiments on benchmark instances derived from the two-dimensional loading heterogeneous fleet vehicle routing problem. The results indicate that the proposed model correctly describes the problem and can solve small-scale problems, that the new packing heuristics are effective in improving the collection of packing heuristics, and that the proposed simulated annealing algorithm can find good solutions to large-scale problems within an acceptable computational time. Hence, it can be used by logistic companies using a heterogeneous fixed fleet in the integrated planning of vehicle loading and routing.
Input-to-State Stability Analysis for Stochastic Mixed Time-Delayed Neural Networks with Hybrid Impulses
Authors: Zhao Chi , Song Yinfang , Zhu Quanxin , Shi Kaibo
Published: January 2022

This paper investigates the mean-square exponential input-to-state stability (MEISS) of stochastic mixed time-delayed neural networks with hybrid impulses. A generalized comparison principle is introduced and a new inequality about the solution of an impulsive differential equation is established. Moreover, by utilizing the proposed inequality and average impulsive interval approach based on different kinds of impulsive sequences, some novel criteria on MEISS are established. When the external input is removed, several conclusions on mean-square exponential stability (MES) are also derived. Unusually, the hybrid impulses including destabilizing and stabilizing impulses have been taken into account in the presented system. Finally, two simulation examples are provided to demonstrate the validity of our theoretical results.
Colchicine Ameliorates 5-Fluorouracil-Induced Cardiotoxicity in Rats
Authors: Safarpour Soheila , Safarpour Samaneh , Pirzadeh Marzieh , Moghadamnia Ali Akbar , Ebrahimpour Anahita , Shirafkan Fatemeh , Mansoori Razieh , Kazemi Sohrab , Hosseini Mohammad
Published: January 2022

Background and Objective. 5-Fluorouracil is one of the most common chemotherapeutic agents used in the treatment of solid tumors. 5-Fluorouracil-associated cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Colchicine is a strong anti-inflammatory drug used to prevent and treat acute gout and treat familial Mediterranean fever. And also, its protective effects on cardiovascular disease have been reported in various studies. The current study is aimed at appraising the effect of colchicine on 5-fluorouracil-induced cardiotoxicity in rats. Methods. Twenty male Wistar rats were divided into four groups as follows: control, 5-fluorouracil, colchicine (5 mg/kg), and 5-fluorouracil+5 mg/kg colchicine. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-fluorouracil (100 mg/kg). The control group received normal saline, and the treatment groups received colchicine with an intraperitoneal injection for 14 days. Findings. 5-Fluorouracil resulted in significant cardiotoxicity represented by an increase in cardiac enzymes, malondialdehyde levels, cyclooxygenase-2 and tumor necrosis factor-alpha expression, cardiac enzymes, and histopathological degenerations. 5-Fluorouracil treatment also decreased body weight, total antioxidant capacity and catalase values, blood cells, and hemoglobin levels. In addition, 5-fluorouracil disrupted electrocardiographic parameters, including increased elevation in the ST segment and increased QRS duration. Treatment with colchicine reduced oxidative stress, cardiac enzymes, histopathological degenerations, and cyclooxygenase-2 expression in cardiac tissue, improved electrocardiographic disorders, and enhanced the number of blood cells and total antioxidant capacity levels. Moreover, body weight loss was hampered after treatment with colchicine. Our results demonstrated that treatment with colchicine significantly improved cardiotoxicity induced by 5-fluorouracil in rats.
Development of Educational Communication Path of Journalism in Colleges and Universities in the Era of Mobile Communication
Authors: Xu Xiaoman , Liu Chunxia
Published: January 2022

The development of journalism has a huge impact on mobile communication technology and media ecology. Especially in terms of information dissemination, it not only allows people to better obtain the content they are interested in but also provides media workers with more ways to understand their own needs, meet the needs of audiences, and enhance competitiveness. Therefore, in order to enhance the development space of the journalism major, this article studies the communication development path of this major in colleges and universities in the era of mobile communications. This article mainly uses case analysis method, data method, and investigation method to study the development of journalism education in colleges and universities. The survey results show that 21 people believe that the authenticity of news is an indispensable item in teaching. Therefore, the education and communication development of journalism majors in colleges and universities cannot ignore the principle of authenticity. There are 18 people who think it is necessary to tie their majors with the Internet, indicating that colleges and universities can use the Internet platform to teach journalism.
Epidemiology of Avian Tuberculosis in Selected Districts of Oromia Region, Ethiopia
Authors: Debelu Tesfaye , Abunna Fufa , Mamo Kassa Gezahegne , Ameni Gobena
Published: January 2022

Avian tuberculosis is a growing public health concern and a significant impediment to socioeconomic development, especially in developing countries, where the risk of infection is high. The disease is predominantly caused by Mycobacterium avium belonging to serotypes 1, 2, 3, and 6 (genotypes IS901 and IS1245) and Mycobacterium genavense. It mostly occurs in older birds and immunocompromised individuals due to the greater opportunity for infection with age and host immunity. A cross-sectional study anticipated to generate epidemiological information on avian tuberculosis was carried out from November 2016 to June 2017 at highland areas of Gerar Jarso, Ada’a (midland), and Boset (lowland) districts of Oromia region, Ethiopia. Two hundred seventy-three village chickens comprising local breeds, exotic breeds, and crossbreeds of both sexes were used in the study. Single intradermal avian tuberculin test, postmortem inspection of positive reactors, mycobacteriological culturing, and histopathological examination were used to assess information on the epidemiology of the disease. Subsequently, avian tuberculin test revealed an overall apparent prevalence of 11.4% (31/273) and a specific prevalence of 6.8% (6/88) in the highland, 13.4% (13/97) in the midland, and 13.6% (12/88) in the lowland study districts. Besides, it signified a higher odd of exposure in crossbreeds and females as compared to locals and males. In addition, greater odd of exposure was observed in chickens at mid- and low altitudes as compared to those at the highland. Moreover, 40.9% (9/22) of positive reactor chickens sacrificed for necropsy showed gross pathological lesions. Similarly, histopathological examination revealed a granuloma characterized by central necrosis and peripheral mononuclear lymphocytes. Nevertheless, only 0.02% (2/120) of the cultured tissues had shown colonial growth up to 12 weeks of incubation, and both were seen on sodium pyruvate-enriched Lowenstein–Jensen medium slants. Generally, the study revealed an overall increment of the apparent prevalence of avian tuberculosis with decreasing altitude. Besides, it signified a relative breed and sex variation in the risk of acquiring the disease, with crossbreeds and female chickens having higher odds of exposure.
ALDH1A1 Gene Expression and Cellular Copper Levels between Low and Highly Metastatic Osteosarcoma Provide a Case for Novel Repurposing with Disulfiram and Copper
Authors: Mandell Jonathan B. , Douglas Nerone , Ukani Vrutika , Beumer Jan H. , Guo Jianxia , Payne John , Newman Rebecca , Mancinelli Luigi , Intini Giuseppe , Anderson Carolyn J. , Watters Rebecca , Weiss Kurt
Published: January 2022

Aldehyde dehydrogenase 1A1 (ALDH) is a cancer stem cell marker highly expressed in metastatic cells. Disulfiram (Dis) is an FDA-approved antialcoholism drug that inhibits ALDH and has been studied as a candidate for drug repurposing in multiple neoplasia. Dis cytotoxicity in cancer cells has been shown to be copper-dependent, in part due to Dis’s ability to function as a bivalent metal ion chelator of copper (Cu). The objectives of this research were to test ALDH expression levels and Cu concentrations in sarcoma patient tumors and human osteosarcoma (OS) cell lines with differing metastatic phenotypes. We also sought to evaluate Dis + Cu combination therapy in human OS cells. Intracellular Cu was inversely proportional to the metastatic phenotype in human OS cell lines (SaOS2 > LM2 > LM7). Nonmetastatic human sarcoma tumors demonstrated increased Cu concentrations compared with metastatic tumors. qPCR demonstrated that ALDH expression was significantly increased in highly metastatic LM2 and LM7 human OS cell lines compared with low metastatic SaOS2. Tumor cells from sarcoma patients with metastatic disease displayed significantly increased ALDH expression compared with tumor cells from patients without metastatic disease. Serum Cu concentration in canine OS versus normal canine patients demonstrated similar trends. Dis demonstrated selective cytotoxicity compared with human multipotential stromal cells (MSCs): Dis-treated OS cells demonstrated increased apoptosis, whereas MSCs did not. CuCl2 combined with Dis and low-dose doxorubicin resulted in a superior cytotoxic effect in both SaOS2 and LM7 cell lines. In summary, ALDH gene expression and Cu levels are altered between low and highly metastatic human OS cells, canine samples, and patient tumors. Our findings support the feasibility of a repurposed drug strategy for Dis and Cu in combination with low-dose anthracycline to specifically target metastatic OS cells.
Blind Crosstalk Correction for Color Fringe Projection Profilometry Combining the Sine and Cosine Phase-Shifting Patterns
Authors: Yang Jun , Li Guoliang , Zhang Yang , Wu Jun , Zhang Min , Li Jin , Liu Wenxiang
Published: January 2022

Color crosstalk is challenging for color fringe projection profilometry, which will cause color imbalance and phase-shift deviation, thus resulting in phase error. To address this challenge, this paper presents a blind crosstalk correction method for color phase-shifting fringe projection profilometry without crosstalk calibration. Three channels of the color fringe are firstly normalized to resolve color imbalance. The phase error induced by phase-shift deviation between three channels doubles the frequency of the color fringe. Therefore, the original cosine color fringe is shifted by quarter period to generate another sine color fringe to compensate the periodic phase error. Both simulations and experiments were carried out, and their results confirmed the effectiveness and accuracy of the proposed method.
A Study of Network Negative News Based on Behavioral Finance Analysis of Abnormal Fluctuation of Stock Price
Authors: Wu Cheng Chung , Yan Ye , Yuan Tiantong , Huang Chih Chiang , Tsai Ya Ju
Published: January 2022

This article studies the model of the impact of real negative news on stock prices and provides evidence using China’s A‐share listed companies as an example. It first defines the negative news of the network. Then, it constructs the negative news to the stock price influence model, from the perspective of the theory of behavioral finance, the relationship between stock market and investor sentiment is systematically analyzed, and the theoretical support for the research of this paper is provided according to the definition of network negative news concept using the event study, abnormal returns test, regression analysis of the sample selected out of the study, observation of negative news before and after the abnormal returns, and excess returns changes. Studies have shown that negative news before 1 day and after 4 days makes stock price volatility larger, resulting in excess returns. The network negative news on the listed company’s stock price fluctuations can cause a certain degree of impact; in the short term, the fluctuation of the stock price of listed companies is more active. This article finds that when online media disclose negative information on listed companies from one day before to four days later, stock prices will fluctuate greatly, generate excess returns, and continue to make stock fluctuations more active in the short term. In addition, when studying the influencing factors of the stock price fluctuations of listed companies, we found that stock price fluctuations are affected by the company’s performance. The better the company’s performance is, the smaller the stock price fluctuations will be when it is affected by negative news. Finally, we find that the higher the shareholding ratio of institutional investors in listed companies, the more stable the stock price.
Impact of Implementing Teleophthalmology Referral Guidelines Using the eyeSmart EMR App in 63,703 Patients from India
Authors: Das Anthony Vipin , Khanna Rohit C. , Kumar Niranjan , Rani Padmaja Kumari
Published: January 2022

Objective. To describe the clinical indications and the impact of implementation of specific teleophthalmology referral guidelines in a large rural village vision centre network in India. Methods. This cross-sectional vision centre-based study included 1,016,284 patients presenting between January 2017 and March 2020. Patients who were referred for a teleophthalmology opinion were included as cases. The data were collected using the eyeSmart EMR app on a smart tablet. A training intervention was done to reinforce the implementation of targeted teleophthalmology referral guidelines. Results. Overall, 63,703 (6.3%) patients were referred for a teleophthalmology opinion and were included for analysis. The median age was 41 (IQR: 26-59) years, and adults (88.4%) were commonly referred for a consult. The two most common age groups were between 31-40 years (17.4%) and 21-30 years (16.3%), and the majority of patients were male (59.1%). The most common clinical indication was cornea and anterior segment disorders (71.05%). The most common queries for teleophthalmology referral before versus after the reinforcement of implementation of guidelines were red eye (33.4% vs. 45.6%) followed by cataract (21.2% vs. 8.1%). There was an increase in the red eye (<0.001) and a decrease in cataract (<0.001) which was statistically significant. The proportion of patients for whom a teleophthalmology consult could have been requested but not sent was minimal (2.3%). Conclusion. Implementation of targeted teleophthalmology referral guidelines enables an effective triage to seek opinion for more pertinent ocular diseases that require care. Adult male patients with cornea and anterior segment disorders are most commonly referred for a teleophthalmology opinion.
An Improved Strategy for Task Scheduling in the Parallel Computational Alignment of Multiple Sequences
Authors: Ishaq Muhammad , Khan Asfandyar , Su’ud Mazliham Mohd , Alam Muhammad Mansoor , Bangash Javed Iqbal , Khan Abdullah
Published: January 2022

Task scheduling in parallel multiple sequence alignment (MSA) through improved dynamic programming optimization speeds up alignment processing. The increased importance of multiple matching sequences also needs the utilization of parallel processor systems. This dynamic algorithm proposes improved task scheduling in case of parallel MSA. Specifically, the alignment of several tertiary structured proteins is computationally complex than simple word-based MSA. Parallel task processing is computationally more efficient for protein-structured based superposition. The basic condition for the application of dynamic programming is also fulfilled, because the task scheduling problem has multiple possible solutions or options. Search space reduction for speedy processing of this algorithm is carried out through greedy strategy. Performance in terms of better results is ensured through computationally expensive recursive and iterative greedy approaches. Any optimal scheduling schemes show better performance in heterogeneous resources using CPU or GPU.
The Partial Least Squares Spline Model for Public Health Surveillance Data
Authors: Sadiq Maryam , Alnagar Dalia Kamal Fathi , Abdulrahman Alanazi Talal , Alharbi Randa
Published: January 2022

Factor discovery of public health surveillance data is a crucial problem and extremely challenging from a scientific viewpoint with enormous applications in research studies. In this study, the main focus is to introduce the improved survival regression technique in the presence of multicollinearity, and hence, the partial least squares spline modeling approach is proposed. The proposed method is compared with the benchmark partial least squares Cox regression model in terms of accuracy based on the Akaike information criterion. Further, the optimal model is practiced on a real data set of infant mortality obtained from the Pakistan Demographic and Health Survey. This model is implemented to assess the significant risk factors of infant mortality. The recommended features contain key information about infant survival and could be useful in public health surveillance-related research.
Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer
Authors: Pan Ruijun , Yu Chaoran , Shao Yanfei , Hong Hiju , Sun Jing , Zhang Zhou , Li Peiyong , Zheng Minhua
Published: January 2022

Background. Characterization of the features associated with circulating tumor cells (CTCs) is one of major interests for predicting clinical outcome of colorectal cancer (CRC) patients. However, the molecular features of CTCs remain largely unclear. Methods. For identification of key genes and pathways, GSE31023, contained CTCs from six metastatic CRC patients and three controls, was retrieved for differentially expressed gene (DEG) analysis. Protein-protein interaction networks of DEGs were constructed. Hub genes from the network were prognostic analyzed, as well as the association with tumor-infiltrating immune cells. Results. 1353 DEGs were identified between the CTC and control groups, with 403 genes upregulated and 950 downregulated. 32 pathways were significantly enriched in KEGG, with ribosome pathway as top. The top 10 hub genes were included, including eukaryotic translation elongation factor 2 (EEF2), ribosomal protein S2 (RPS2), ribosomal protein S5 (RPS5), ribosomal protein L3 (RPL3), ribosomal protein S3 (RPS3), ribosomal protein S14 (RPS14), ribosomal protein SA (RPSA), eukaryotic translation elongation factor 1 alpha 1 (EEF1A1), ribosomal protein S15a (RPS15A), and ribosomal protein L4 (RPL4). The correlation between CD4+ T cells and RPS14 (

correlation
=
−
0.5

) was the highest in colon cancer while CD8+ T and RPS2 (

correlation
=
−
0.53

) was the highest in rectal cancer. Conclusion. This study identified potential role of ribosome pathway in CTC, providing further insightful therapeutic targets and biomarkers for CRC.
Phase II Study of Ponatinib in Advanced Gastrointestinal Stromal Tumors: Efficacy, Safety, and Impact of Liquid Biopsy and Other Biomarkers
Authors: George Suzanne , von Mehren Margaret , Fletcher Jonathan A. , Sun Jichao , Zhang Sen , Pritchard Justin R. , Hodgson John Graeme , Kerstein David , Rivera Victor M. , Haluska Frank G. , Heinrich Michael C.
Published: January 2022

Purpose:

The purpose of this study is to evaluate ponatinib for advanced gastrointestinal stromal tumors (GIST).

Patients and Methods:

This single-arm phase II trial enrolled patients with metastatic and/or unresectable GIST with failure of prior tyrosine kinase inhibitor (TKI) treatment into two cohorts based on presence or absence of KIT exon 11 (ex11) primary mutations. Patients initially received ponatinib 45 mg once daily. Following a temporary clinical hold in October 2013, dose reductions were implemented to reduce risk of arterial occlusive events (AOE). Primary endpoint was 16-week clinical benefit rate (CBR) in KIT ex11–positive cohort. KIT mutations in circulating tumor DNA (ctDNA) were assessed.

Results:

Forty-five patients enrolled (30 KIT ex11–positive and 15 KIT ex11–negative); median follow-up was 14.7 and 13.6 months, respectively, as of August 1, 2016. Sixteen-week CBR was 36% (KIT ex11–positive; primary endpoint) and 20% (KIT ex11–negative). ctDNA analyses (n = 37) demonstrated strong concordance of primary KIT mutations between plasma and tumor. At least two secondary mutations were detected in 35% of patients overall and 54% of KIT ex11–positive patients. Changes from baseline in mutated ctDNA levels were consistent with clinical activity. Ponatinib was ineffective in patients with KIT exon 9 primary mutations. Resistance was associated with emergence of V654A. AOEs and venous thromboembolic events occurred in three and two patients, respectively. Six patients died; two deaths (pneumonia and pulmonary embolism) were considered possibly ponatinib-related.

Conclusions:

Ponatinib demonstrated activity in advanced GIST, particularly in KIT ex11–positive disease. ctDNA analysis confirmed heterogeneous resistance mutations in TKI-pretreated advanced GIST. Safety was consistent with previous studies.
Expanding Therapeutic Opportunities for Extrapulmonary Neuroendocrine Carcinoma
Authors: Frizziero Melissa , Kilgour Elaine , Simpson Kathryn L. , Rothwell Dominic G. , Moore David A. , Frese Kristopher K. , Galvin Melanie , Lamarca Angela , Hubner Richard A. , Valle Juan W. , McNamara Mairéad G. , Dive Caroline
Published: January 2022

Poorly differentiated neuroendocrine carcinomas (PD-NEC) are rare cancers garnering interest as they become more commonly encountered in the clinic. This is due to improved diagnostic methods and the increasingly observed phenomenon of “NE lineage plasticity,” whereby nonneuroendocrine (non-NE) epithelial cancers transition to aggressive NE phenotypes after targeted treatment. Effective treatment options for patients with PD-NEC are challenging for several reasons. This includes a lack of targetable, recurrent molecular drivers, a paucity of patient-relevant preclinical models to study biology and test novel therapeutics, and the absence of validated biomarkers to guide clinical management. Although advances have been made pertaining to molecular subtyping of small cell lung cancer (SCLC), a PD-NEC of lung origin, extrapulmonary (EP)-PD-NECs remain understudied. This review will address emerging SCLC-like, same-organ non-NE cancer-like and tumor-type–agnostic biological vulnerabilities of EP-PD-NECs, with the potential for therapeutic exploitation. The hypotheses surrounding the origin of these cancers and how “NE lineage plasticity” can be leveraged for therapeutic purposes are discussed. SCLC is herein proposed as a paradigm for supporting progress toward precision medicine in EP-PD-NECs. The aim of this review is to provide a thorough portrait of the current knowledge of EP-PD-NEC biology, with a view to informing new avenues for research and future therapeutic opportunities in these cancers of unmet need.
Estimating Long-Term Survival Outcomes for Tumor-Agnostic Therapies: Larotrectinib Case Study
Authors: Briggs Andrew , Paracha Noman , Rosettie Katherine , Upton Alexander , Bokemeyer Carsten , Lassen Ulrik , Sullivan Sean D.
Published: January 2022

Background: Larotrectinib is a precision oncology treatment for solid tumors with neurotrophic tyrosine receptor kinase (NTRK) gene fusions. Larotrectinib efficacy has been evaluated in single-arm basket trials with limited follow-up and sample sizes at the initial regulatory approval due to the rarity of solid tumors with NTRK gene fusion. Objectives: We aim to demonstrate that trends in progression-free survival (PFS) and overall survival (OS) in survival data with longer follow-up may be predicted from long-term survival estimates from survival data with shorter follow-up, including predictions for median survival when it is not observed in the trial. Methods: Patient-level data were pooled from 3 clinical trials (NCT02122913, NCT02576431, and NCT02637687) using the 2018 and 2020 data cuts for the same subset of pediatric and adult patients. The Weibull distribution was selected for survival models. Survival predictions using 2018 data were compared to 2020 Kaplan-Meier (KM) curves. Results: A total of 102 patients representing 15 tumor types were included in the analysis, with a mean age of 37 years. When comparing PFS from the 2018 survival prediction to observed 2020 KM data, the 12-month PFS rate was identical (66.6%). The 36-month PFS rate was lower for the 2018 prediction (35.3%) compared to 2020 KM data (44.4%). The median OS had not yet been reached in either data cut but was predicted to be 90 months using the 2018 data. When comparing OS from the 2018 survival prediction to the observed 2020 KM data, the 12-month OS rate was 89.0% and 86.6% and the 48-month OS rate was 67.2% and 63.0%, respectively. Conclusion: Long-term PFS predictions deviated from observed PFS rates due to response differences across tumor types and heavy censoring towards the end of the survival curve. However, for OS, the 48-month survival prediction was consistent with the observed 2020 KM estimate.