bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Vitamin D Binding Protein Gene Polymorphism (rs7041), Vitamin D Receptor, and 25-Hydroxyvitamin D Serum Levels With Prostate Cancer in Kurdish Population in West of Iran
Authors: Amiri Mohammad , Elieh Ali Komi Daniel , Vaisi-Raygani Asad , Kiani Amir , Moradi Mahmoudreza , Aliyari Mahdieh , Rahimi Zohreh , Mohammadi-Noori Ehsan , Bashiri Homayoon
Published: August 2022

Prostate cancer (PCa) pathology has been linked to vitamin D, vitamin D receptors (VDRs), and vitamin D binding proteins (VDBPs). We sought to investigate the association between VDR rs2228570 and rs1544410 as well as VDBP rs7041 polymorphisms and serum 25-hydroxyvitamin D (25(OH)-vitamin D) levels in PCa patients. Blood samples were collected from 111 PCa patients and 150 age-matched healthy volunteers. The VDR rs2228570 T/C, rs1544410 G/A, and VDBP rs7041 T/G genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). 25(OH)-vitamin D and PSA (Total and Free) serum levels were measured. The frequencies of VDBP genotypes T/G vs. T/T (56.5% vs. 44.5%, p = 0.01) according to the dominant model T/G + G/G vs. T/T (84.3% vs. 71.5%, p = 0.01) were significantly higher in PCa patients when compared to control group and considerably increased the risk of disease by 2.29, 1.44, and 2.13 folds respectively. Interestingly, the results demonstrated that PCa patients with the dominant model (T/G + G/G vs. T/T) of VDBP had significantly lower serum levels of vitamin D and higher serum levels of total and free PSA in comparison to the controls. Furthermore, when compared to controls, PCa patients with the dominant model T allele (T/G + G/G vs. TT) of VDBP had significantly higher vitamin D, total PSA, and free PSA concentrations. Serum levels of 25(OH)-vitamin D and rs7041 T/G polymorphism of the VDBP gene could be potential risk factors for PCa.
Design, Modeling, Testing, and Control of a Novel Fully Flexure-Based Displacement Reduction Mechanism Driven by Voice Coil Motor
Authors: Chen Yunzhuang , Lai Leijie
Published: August 2022

This paper presents a flexure-based displacement reduction mechanism driven by a voice coil motor to improve the motion resolution and eliminate the hysteresis nonlinearity of the traditional piezo-actuated micropositioning/nanopositioning stages. The mechanism is composed of three groups of compound bridge-type displacement reduction mechanisms, which adopt distributed-compliance rectangular beams to reduce the concentration of stress and improve the dynamic performance of the mechanism. The symmetrical distribution of the structure can eliminate the parasitic displacement of the mechanism and avoid the bending moment and lateral stress applied to the voice coil motor. Firstly, the analytical model of the mechanism is obtained by the stiffness matrix method. The theoretical displacement reduction ratio, input stiffness, and natural frequency of the displacement reduction mechanism are obtained by solving the analytical model. Then, through the static analysis and modal analysis of the mechanism with the Ansys software, the accuracy of the analytical model is verified, and the experimental prototype is also constructed for performance tests. The results show that the maximum stroke of the mechanism is 197.43 μm with motion resolution of 40 nm. The natural frequency is 291 Hz, and the input stiffness is 28.50 N/mm. Finally, the trajectory tracking experiment is carried out to verify the positioning performance of the mechanism. The experimental results show that the designed feedback controller has good stability, and the introduction of the feedforward controller and disturbance observer can greatly reduce the tracking errors.
Coordinate Inheritance of Seed Isoflavone and Protein in Soybean
Authors: Zhao Qingsong , Qin Jun , Li Xinxin , Liu Bingqiang , Liu Yang , Yang Qing , Liu Song , Zhao Xin , Ma Niannian , Yan Long , Zhang Mengchen , Yang Chunyan , Liao Hong
Published: August 2022

Soybean (Glycine max (L.) Merr.) is an important nutritional crop, not only as a rich source of protein and oil, but also for the production of isoflavones. There is a demand to breed soybean cultivars bearing consistently high protein, oil and isoflavone yields, yet this requires a clear heritable genetic relationship among isoflavone, protein and oil production. Here, two soybean genotypes contrasting in terms of protein, oil and isoflavone contents and their 185 F8:10 recombinant inbred lines (RILs) were employed to characterize seed protein, oil and isoflavone contents over two years of field trials. In this population, protein, but not oil, was significantly correlated with isoflavone content. A high-density genetic linkage map containing 3943 SNP markers identified through genotyping-by-sequencing (GBS) technology was constructed for further genetic analysis, whereby a total of 25 integrated isoflavone loci were identified, including qISO1, qISO 6.1, qISO 6.3 and qISO 6.4, which are newly identified QTLs. Two major QTLs identified in this study, qISO5 and qISO6.2, were fine-mapped for production of daidzein and genistein derivatives, as well as for glycitein derivatives, in the sequences between nucleotide positions 41042159 and 42098680 on chromosome 5 and between 18449510 and 19395795 on chromosome 6, which, respectively, explain 9.3–20.4% and 7.8–24.8% of the phenotypic variation in these traits. Further combination of qISO5 and qISO6.2 resulted in additive impacts on isoflavone production. Among the 13 QTLs linked with seed protein content in this study, three also colocated with QTLs for isoflavone content, indicating that seed isoflavone and protein content may be coordinately inherited. These results contribute to understanding the relationships between isoflavone and protein or oil content in soybean seeds. This knowledge could be valuable for soybean breeding programs aiming to combine consistently high isoflavone production with high protein or oil content.
Home Range and Movement Patterns of Reintroduced White Lions (Panthera leo melanochaita) in the Kruger to Canyons Biosphere Reserve, South Africa
Authors: Turner Jason A. , Dunston-Clarke Emma J. , Fabris-Rotelli Inger , de Iongh Hans
Published: August 2022

White lions are a colour variant of the African lion Panthera leo melanochaita and disappeared from the wild due to anthropogenic factors until their reintroduction to the Greater Kruger Park Region of South Africa in 2006. Natural home range behaviour is an index of reintroduction success. Therefore, the home range and movement of a pride of reintroduced white lions and a constructed pride consisting of reintroduced white lions and translocated wild tawny lionesses in small, fenced reserves was assessed. GPS data from collared adults were collected for the white lion pride between 2010–2011 and 2018–2020 for the constructed pride. Home ranges were estimated using kernel density estimation and minimum convex polygon, with minimum daily distance tested for differences between sex, season, and pride. Home ranges were small and average daily movements restricted for both prides (white lion pride: 5.41 km2 and 10.44 ± 4.82 km; constructed pride: 5.50 km2, 11.37 ± 4.72 km) due to the small reserve size of 7 km2. There was no difference between prides for annual and seasonal home range size, male and female home ranges, minimum daily distance travelled, or habitat selection. White lions from both prides established territories and displayed natural home ranging behaviour, suggesting that their reintroduction was successful, in the absence of anthropogenic threats.
De Novo Whole-Genome Sequencing and Assembly of the Yellow-Throated Bunting (Emberiza elegans) Provides Insights into Its Evolutionary Adaptation
Authors: Hu Tingli , Chen Guotao , Xu Zhen , Luo Site , Wang Hui , Li Chunlin , Shan Lei , Zhang Baowei
Published: August 2022

Yellow-throated bunting is a small migratory songbird unique to the Palearctic region. However, the genetic studies of this species remain limited, with no nuclear genomic sequence reported to date. In this study, the genomic DNA from the bird was sequenced in long reads using Nanopore sequencing technology. Combining short-read sequencing, the genome was well-assembled and annotated. The final length of the assembly is approximately 1.14 Gb, with a scaffold N50 of 28.94 Mb. About 15,868 protein-coding genes were predicted, and 16.62% of the genome was identified as having repetitive elements. Comparative genomic analysis showed numerous expanded gene families and positively selected genes significantly enriched in those KEGG pathways that are associated with migratory behavior adaptation and immune response. Here, this newly generated de novo genome of the yellow-throated bunting using long reads provide the research community with a valuable resource for further studies of population genetic diversity and genome evolution in this species.
Effects of Long-Term Protein Restriction on Meat Quality and Muscle Metabolites of Shaziling Pigs
Authors: Zheng Jie , Duan Yehui , Yu Jiayi , Li Fengna , Guo Qiuping , Li Tiejun , Yin Yulong
Published: August 2022

Background: It has been demonstrated that low-protein diets can improve the meat quality of pork. This study aimed to investigate the effects of long-term protein restriction from piglets to finishing pigs for 24 weeks on meat quality and muscle metabolites of Shaziling pigs. Results: Compared to the control group, reducing dietary protein levels by 20% reduced the L* value (p < 0.05), increased the a* value (p < 0.01), and tended to decrease pressing loss (p = 0.06) of longissimus thoracis muscle (LTM). Furthermore, compared to the control group, the −20% group had significantly lower levels of muscular danazol, N,N-dimethyl-Safingol, and cer(d18:0/14:0) (p < 0.05), all of which were positively associated with the L* value and negatively associated with the a* value (p < 0.05). Therefore, danazol, N,N-dimethyl-Safingol, and cer(d18:0/14:0) might be potential biomarkers for meat color. Conclusions: These results indicated that reducing dietary crude protein by 20% for 24 weeks could improve meat quality and alter muscular metabolites of Shaziling pigs, and the improvement in meat quality might be ascribable to decreased danazol, N,N-dimethyl-Safingol and cer(d18:0/14:0).
Antimicrobial and Cytotoxic Cyathane-Xylosides from Cultures of the Basidiomycete Dentipellis fragilis
Authors: Sum Winnie Chemutai , Mitschke Nico , Schrey Hedda , Wittstein Kathrin , Kellner Harald , Stadler Marc , Matasyoh Josphat Clement
Published: August 2022

In our continued search for biologically active metabolites from cultures of rare Basidiomycota species, we found eight previously undescribed cyathane-xylosides from submerged cultures of Dentipellis fragilis, which were named dentifragilins A–H. In addition, the known cyathane derivatives striatal D and laxitextine A were isolated. All compounds were characterized by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) as well as by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Several of the compounds exhibited significant activities in standardized cell-based assays for the determination of antimicrobial and cytotoxic effects. The discovery of cyathanes in the genus Dentipellis has chemotaxonomic implications, as this class of diterpenoids has already been shown to be characteristic for mycelial cultures of the related genera Hericium and Laxitextum, which are classified as Dentipellis in the family Hericiaceae.
Analysis of Antioxidant Lipids in Five Species of Dietary Seaweeds by Liquid Chromatography/Mass Spectrometry
Authors: Gowda Siddabasave Gowda B. , Yifan Chen , Gowda Divyavani , Tsuboi Yui , Chiba Hitoshi , Hui Shu-Ping
Published: August 2022

Seaweeds are a good source of bioactive lipids and are known for their nutritional benefits, making them a valuable food source. Despite their dietary significance and nutritional importance, there are limited reports on comprehensive lipidome analysis of lipids with antioxidant properties. Therefore, this study aimed to compare the lipid profiles of five commonly consumed Japanese dietary seaweeds using non-targeted liquid chromatography/mass spectrometry (LC/MS). A total, of 304 molecular species from four major lipid classes were detected and characterized by MS/MS analysis. Multivariate statistical analysis revealed distinct lipid molecular compositions in kombu and sea mustard compared to hijiki, mozuku, and laver seaweeds. Kombu has been shown to contain large amounts of antioxidants, such as polyunsaturated fatty acids (PUFAs), and a high health promotion index compared to other seaweeds. Hierarchical cluster correlations indicated the predominance of glycerophospholipids (GPs) and glycerolipids (GLs) in sea mustard and kombu. As a result, dietary seaweeds have great potential as antioxidants and health-promoting foods for human consumption due to their high levels of PUFA-rich GPs and GLs. Unsaturated triacylglycerols are predominant in hijiki, whereas other health-beneficial lipids, such as monogalactosyldiacylglycerol and sulfoquinovosyl diacylglycerols, are predominant in sea mustard. This study provides a detailed characterization of lipids and their comparative fingerprints in seaweeds, demonstrating the potential use of dietary seaweeds in biotechnological and industrial applications involving the development of functional food products.
Improving Adversarial Robustness of CNNs via Maximum Margin
Authors: Wu Jiaping , Xia Zhaoqiang , Feng Xiaoyi
Published: August 2022

In recent years, adversarial examples have aroused widespread research interest and raised concerns about the safety of CNNs. We study adversarial machine learning inspired by a support vector machine (SVM), where the decision boundary with maximum margin is only determined by examples close to it. From the perspective of margin, the adversarial examples are the clean examples perturbed in the margin direction and adversarial training (AT) is equivalent to a data augmentation method that moves the input toward the decision boundary, the purpose also being to increase the margin. So we propose adversarial training with supported vector machine (AT-SVM) to improve the standard AT by inserting an SVM auxiliary classifier to learn a larger margin. In addition, we select examples close to the decision boundary through the SVM auxiliary classifier and train only on these more important examples. We prove that the SVM auxiliary classifier can constrain the high-layer feature map of the original network to make its margin larger, thereby improving the inter-class separability and intra-class compactness of the network. Experiments indicate that our proposed method can effectively improve the robustness against adversarial examples.
Numerical Investigation of Slurry Fracturing during Shield Tunneling under a Reservoir
Authors: Han Bingyu , Yuan Dajun , Wang Teng , Wang Zhongxin
Published: August 2022

The Jinan Jiluo Road Crossing the Yellow River Tunnel North Extension Project will intersect the Queshan reservoir, which currently supplies 60% of the domestic water in Jinan City. During the excavation process of the large-diameter slurry type shield used in this project, it may lead to slurry fracturing of the stratum in front of the excavation face and slurry blow-out from the surface if the slurry support pressure is too high. The leakage of shield slurry will pollute the reservoir water, and the safety of domestic water in Jinan will be threatened. Shield slurry blow-out may also lead to water inrush accidents. It is difficult to prevent slurry blow-out during shallow shield tunnel construction due to an insufficient understanding of the shield slurry fracturing mechanism. The initiation and extension of shield slurry fracturing are very complex and difficult to observe in the stratum. Currently, there is no effective method to study the slurry fracturing mechanism of shield tunneling. This paper presents a numerical simulation method of shield tunneling slurry fracturing based on the extended finite element method (XFEM). The risk of slurry blow-out in shield tunnel crossing reservoir engineering is analyzed. The advantages of the XFEM for simulating crack propagation are fully exploited. Considering the coexistence of tensile and shear failures in soft soils, embedding the combined tensile and shear failure criterion is realized in the XFEM by the secondary development of the ABAQUS extended finite element. Compared with the slurry fracturing test of blind-hole clay samples, the rationality of the simulation method for slurry fracturing in cohesive soil is verified. Through the establishment of the slurry fracturing extension model, the slurry fracturing process of shield tunneling in cohesive soil layer is simulated. The variation law of slurry pressure in the process of fracture extension is studied, and the influence of shield slurry support pressure, overburden thickness, formation shear strength, and slurry viscosity on fracture extension pressure and extension path is analyzed. Based on this numerical simulation method, the risk of slurry blow-out is analyzed in the shield tunneling intersecting the Queshan Reservoir of the Jinan Jiluo Road Crossing the Yellow River Tunnel North Extension Project.
Tensile Test Analysis of Tire Tread Rubber’s Tendency to Resist Cracks
Authors: Noh Ingyu , Hong Sangyeop , Kim Jaehoon
Published: August 2022

Among the various components of a tire, this study explores the tread portion, which has the longest contact with the ground during the summer, all-weather, and in the winter. The mechanical properties of three types of tread crack specimens were measured, and a stress–strain diagram for each specimen at low and high speeds was derived. Through the digital image correlation method, the crack tip opening displacement and angle were considered as fracture parameters and derived through equations. Subsequently, the different fracture progression regions were compared and analyzed to confirm the characteristics of the elastic displacement field. It was found that under both low- and high-speed conditions, the maximum elastic strains for the tread specimens were attained in the following order: summer, all-weather, and winter.
Damping Behavior of Hybrid Composite Structures by Aeronautical Technologies
Authors: Proietti Alice , Gallo Nicola , Bellisario Denise , Quadrini Fabrizio , Santo Loredana
Published: August 2022

Hybrid composite laminates are manufactured by using technologies and raw materials of the aeronautic sector with the aim to improve the damping behavior of composite structures. Matrix hybridization was achieved by laminating carbon fiber reinforced (CFR) plies with elastomer interlayers. Up to 10 different composite sandwich architectures were investigated by changing the stacking sequence, the thickness of the elastomer layers, and the elastomer typology, whereas the total number of the CFR plies was fixed to six for all the hybrid composites. Square panels with the size of 300 × 300 mm2 were autoclave molded with vacuum bagging, and rectangular samples were extracted for static and dynamic tests. Dynamic mechanical analyses were performed to measure the storage modulus and loss factor of hybrid materials, which were compared with static and dynamic performances of the composite structures under bending. Repeated loading–unloading cycles and free oscillation tests allowed us to the energy loss per unit of volume, and the acceleration damping, respectively. Results show that softest elastomer interlayers lead to big loss of stiffness without any positive effect in the damping behavior, which worsens as well. By using soft elastomers, complex architectures do not provide any additional benefit in comparison with the traditional sandwich structure with soft core and hard skins.
Birotons and “Dark” Quantum Hall Hierarchies
Authors: Grigorev Oleg A. , Musina Liliya I. , Van’kov Alexander B. , Volkov Oleg V. , Kulik Leonid V.
Published: August 2022

A computational scheme is suggested to estimate neutral excitation energies in the fractional quantum Hall effect (FQHE) states. The FQHE states are systematized according to the Farey-number hierarchy structure. We show that besides the widely known Laughlin–Jain hierarchy of fractional states, there exist other “dark” hierarchies. Although hardly observed in the highest mobility samples, they can significantly affect the thermodynamics and spectral characteristics of the FQHE states. The known problems in the interpretation of the FQHE’s experimental results are explained in terms of the coexistence of two fundamentally different transformations of the electron system, one of which is a neutral excitation in the FQHE state, whereas the other is a transition between two FQHE ground states, one of which represents the Laughlin–Jain FQHE hierarchy and the other a state of “dark” hierarchies.
Accelerated Glacier Mass Loss over Svalbard Derived from ICESat-2 in 2019–2021
Authors: Wang Junhao , Yang Yuande , Wang Chuya , Li Leiyu
Published: August 2022

The glaciers in Arctic Archipelago of Svalbard, located in the hotspot of global warming, are sensitive to climate change. The assessment of glacier mass balance in Svalbard is one of the hotspots in Arctic research. In this study, we use the laser altimetry ICESat-2 data to investigate the elevation and mass change of Svalbard from 2019 to 2021 by a hypsometric approach. It is shown that the Svalbard-wide elevation change rate is −0.775 ± 0.225 m yr−1 in 2019–2021, corresponding to the mass change of −14.843 ± 4.024 Gt yr−1. All regions exhibit a negative mass balance, and the highest mass loss rates are observed at Northwestern Spitsbergen. Compared with ICESat/ICESat-2 (2003–2008 to 2019) and Cryosat-2 (2011–2017) periods, the elevation change from 2019 to 2021 has accelerated, with an increase by 158.3% and 31.5%, respectively, leading to equilibrium line altitude increasing to 750 m. Among the seven subregions, four are accelerated. It is shown that the overall accelerated glacier mass loss in Svalbard is expected to be caused by increasing surge events and temperature rise.
Anthropogenic Vehicular Heat and Its Influence on Urban Planning
Authors: Grajeda-Rosado Ruth M. , Alonso-Guzmán Elia M. , Escobar-Del Pozo Carlos , Esparza-López Carlos J. , Sotelo-Salas Cristina , Martínez-Molina Wilfrido , Mondragon-Olan Max , Cabrera-Macedo Alfonso
Published: August 2022

Anthropogenic heat (QF) is one of the parameters that contributes to the urban heat island (UHI) phenomenon. Usually, this variable is studied holistically, among other anthropogenic flux such as industrial, vehicular, buildings, and human metabolism, due to the complexity of data collection through field measurements. The aim of this paper was to weigh vehicular anthropogenic heat and its impact on the thermal profile of an urban canyon. A total of 108 simulations were carried out, using the ANSYS Fluent® software, incorporating variables such as the number of vehicles, wind speed, urban canyon orientation, and urban canyon aspect ratio. The results were compared with a database of 61 American cities in 2015 and showed that orientation is the main factor of alteration in vehicular heat flow, increasing it in a range of 2 °C to 6.5 °C, followed by the wind speed (1.2 to 2.2 m/s), which allows for decreases of 1 to 3.8 °C. The exploration of these variables and their weighing in the definition of urban street canyon temperature profiles at the canopy level of urban structures provides valuable information on the hygrothermal comfort of its inhabitants; its appropriate quantification can be an example of many urban energy balances altering processes.
A Novel Investigation of Non-Periodic Snap BVP in the G-Caputo Sense
Authors: Wang Xiaofeng , Berhail Amel , Tabouche Nora , Matar Mohammed M. , Samei Mohammad Esmael , Kaabar Mohammed K. A. , Yue Xiao-Guang
Published: August 2022

In the present paper, we consider a nonlinear fractional snap model with respect to a G-Caputo derivative and subject to non-periodic boundary conditions. Some qualitative analysis of the solution, such as existence and uniqueness, are investigated in view of fixed-point theorems. Moreover, the stabilities of Ulam–Hyers and Ulam–Hyers–Rassias criterions are considered and investigated. Some numerical simulations were performed using MATLAB for understanding the theoretical results. All results in this work play an important role in understanding ocean engineering phenomena due to the huge applicability of jerk and snap in seakeeping, ride comfort, and shock response spectrum.
Effect of Ghrelin on the Cardiovascular System
Authors: Hosoda Hiroshi
Published: August 2022

Ghrelin, an n-octanoyl-modified 28-amino-acid-peptide, was first discovered in the human and rat stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Ghrelin-GHS-R1a signaling regulates feeding behavior and energy balance, promotes vascular activity and angiogenesis, improves arrhythmia and heart failure, and also protects against cardiovascular disease by suppressing cardiac remodeling after myocardial infarction. Ghrelin’s cardiovascular protective effects are mediated by the suppression of sympathetic activity; activation of parasympathetic activity; alleviation of vascular endothelial dysfunction; and regulation of inflammation, apoptosis, and autophagy. The physiological functions of ghrelin should be clarified to determine its pharmacological potential as a cardiovascular medication.
The Cell Autonomous and Non-Cell Autonomous Aspects of Neuronal Vulnerability and Resilience in Amyotrophic Lateral Sclerosis
Authors: Schweingruber Christoph , Hedlund Eva
Published: August 2022

Amyotrophic lateral sclerosis (ALS) is defined by the loss of upper motor neurons (MNs) that project from the cerebral cortex to the brain stem and spinal cord and of lower MNs in the brain stem and spinal cord which innervate skeletal muscles, leading to spasticity, muscle atrophy, and paralysis. ALS involves several disease stages, and multiple cell types show dysfunction and play important roles during distinct phases of disease initiation and progression, subsequently leading to selective MN loss. Why MNs are particularly vulnerable in this lethal disease is still not entirely clear. Neither is it fully understood why certain MNs are more resilient to degeneration in ALS than others. Brain stem MNs of cranial nerves III, IV, and VI, which innervate our eye muscles, are highly resistant and persist until the end-stage of the disease, enabling paralyzed patients to communicate through ocular tracking devices. MNs of the Onuf’s nucleus in the sacral spinal cord, that innervate sphincter muscles and control urogenital functions, are also spared throughout the disease. There is also a differential vulnerability among MNs that are intermingled throughout the spinal cord, that directly relate to their physiological properties. Here, fast-twitch fatigable (FF) MNs, which innervate type IIb muscle fibers, are affected early, before onset of clinical symptoms, while slow-twitch (S) MNs, that innervate type I muscle fibers, remain longer throughout the disease progression. The resilience of particular MN subpopulations has been attributed to intrinsic determinants and multiple studies have demonstrated their unique gene regulation and protein content in health and in response to disease. Identified factors within resilient MNs have been utilized to protect more vulnerable cells. Selective vulnerability may also, in part, be driven by non-cell autonomous processes and the unique surroundings and constantly changing environment close to particular MN groups. In this article, we review in detail the cell intrinsic properties of resilient and vulnerable MN groups, as well as multiple additional cell types involved in disease initiation and progression and explain how these may contribute to the selective MN resilience and vulnerability in ALS.
Cerebral Toxoplasmosis as an Uncommon Complication of Biologic Therapy for Rheumatoid Arthritis: Case Report and Review of the Literature
Authors: de Almeida Gonçalo Borges , Cristóvão Miguel , Pontinha Carlos , Januário Gonçalo
Published: August 2022

Toxoplasmosis is one of the most common opportunistic infections, mainly reported in patients with acquired immunodeficiency syndrome (AIDS). Patients with rheumatoid arthritis (RA) have also been linked to reactivation of toxoplasmosis due to immunosuppressive treatment, although biologic drugs have seldom been implicated. We present a case of cerebral toxoplasmosis in a 62-year-old female patient with RA after initiation of biologic therapy (adalimumab). The patient had detectable serum IgG antibodies to toxoplasma gondii, was also on chronic treatment with other non-biologic drugs and presented with worsening disorientation, unsteady gait and left hemiparesis. Imaging studies showed a space-occupying lesion in the right basal ganglia with ring-enhancement. Brain biopsy confirmed the diagnosis of toxoplasmosis and the patient was treated with pyrimethamine and sulfadiazine for 6 weeks, showing complete recovery on follow-up. A review of the literature yielded other four case reports of cerebral toxoplasmosis implying biologic drugs; however, data concerning toxoplasmosis serologic testing, prophylaxis and treatment in these patients are lacking. Each case must be carefully evaluated prior to treatment and a high-index of suspicion in seropositive patients is warranted. Since the use of biologic drugs is increasing, further research is needed to establish practical guidelines for seropositive patients receiving immunosuppressive treatment.
Paraneoplastic Amyotrophic Lateral Sclerosis: Case Series and Literature Review
Authors: Yang Zhao , He Lu , Ren Manli , Lu Yizhou , Meng Huanyu , Yin Dou , Chen Sheng , Zhou Qinming
Published: August 2022

Paraneoplastic amyotrophic lateral sclerosis (ALS) is a rare and special type of ALS. The pathogenesis, clinical presentation, treatment and prognosis remain poorly understood. We herein presented three cases of paraneoplastic ALS. In case 1, we first reported an ALS patient with the positive serum antibodies against both Sry-like high mobility group box 1 (SOX1) and glutamic acid decarboxylase 65 (GAD65). However, immunotherapy did not improve his neurological symptoms. We also reported two ALS patients with renal clear cell carcinoma and chronic myelogenous leukemia. No positive paraneoplastic antibodies were detected in either the serum or the cerebrospinal fluid of the two patients, and their clinical symptoms progressed slowly after tumor treatment. The three cases enriched the existing case pool of this rare disorder. In addition, we have comprehensively reviewed the literature of paraneoplastic ALS. The clinical features, treatment effect and prognosis were summarized to broaden our understanding of paraneoplastic ALS.
Seismic Damage Assessment for Isolated Buildings with a Substructure Method
Authors: Guo Lina , Ding Yong , Zhang Yifei
Published: August 2022

A seismic damage detection method for isolated buildings is proposed based on substructure identification with incomplete contaminated measurements. A concept of a pseudo substructure with virtual conditions is constructed for the proof of the proposed substructure identification method. This identification method is implemented in a two-stage procedure. The interface forces of the target substructure are identified in the first stage and the parameter of the target substructure is updated in the second stage, which can enable the parameter identification of substructures with unknown input. Two computational methods are also proposed to improve the two-stage identification algorithm. A sub-time zone identification method is utilized to reduce the computation effort and the simultaneous identification of the unknown force and initial structural responses is presented in the first-stage identification for a general case in practical engineering. Numerical studies of a shear frame with nonlinear base isolation subject to earthquake ground motion are investigated to validate the proposed seismic damage detection method. A fourteen-storey concrete shear wall building with a two-storey steel frame on top connected by isolation is studied experimentally with shaking table tests to further validate the proposed method. The shear wall structure is taken as the target substructure for damage assessment. The interface force and parameter of the concrete shear wall building are estimated with the proposed method. Results from both the numerical simulations and laboratory tests indicate that the proposed method can estimate seismic isolated structures and detect damage effectively based on only a few accelerometers. It is also demonstrated that the parameter identification results based on the structure response measurement during the earthquake are more accurate than the identification with post-earthquake structural response measurement.
Evidence from Clinical Studies Related to Dermatologic Surgeries for Skin Cancer
Authors: Ishizuki Shoichiro , Nakamura Yoshiyuki
Published: August 2022

Despite the significant progress made in the past several years in pharmacotherapies for skin cancer, such as BRAF/MEK inhibitors, immune checkpoint inhibitors, and Hedgehog pathway inhibitors, surgical removal of primary skin cancer is still the first choice of treatment unless distant metastases are evident. In cases of lymph node metastases with clinically palpable lymphadenopathy, lymph node dissection (LND) is typically performed for most skin cancers. In the surgical treatment of primary skin tumors, the surgical margin is critical not only for reducing the possibility of tumor recurrence but also for minimizing the cosmetic and functional complications associated with wide local excision. In contrast, dermatologic surgery can cause various complications. Although skin graft is frequently used for reconstruction of the surgical defect, extensive graft necrosis may develop if optimal stabilization of the graft is not obtained. LND also sometimes causes complications such as intraoperative or postoperative bleeding and postoperative lymphoceles. Moreover, as in other types of surgery, surgical site infection, intraoperative anxiety, and intraoperative and postoperative pain may also develop. These complications are frequently associated with significant morbidity and discomfort. In this review, we summarize the evidence from previous clinical studies regarding the optimal surgical margin for skin cancer and the methods for diminishing the complications associated with dermatologic surgery.
Detection of Microsatellite Instability in Colonoscopic Biopsies and Postal Urine Samples from Lynch Syndrome Cancer Patients Using a Multiplex PCR Assay
Authors: Phelps Rachel , Gallon Richard , Hayes Christine , Glover Eli , Gibson Philip , Edidi Ibrahim , Lee Tom , Mills Sarah , Shaw Adam , Heer Rakesh , Ralte Angela , McAnulty Ciaron , Santibanez-Koref Mauro , Burn John , Jackson Michael S.
Published: August 2022

Identification of mismatch repair (MMR)-deficient colorectal cancers (CRCs) is recommended for Lynch syndrome (LS) screening, and supports targeting of immune checkpoint inhibitors. Microsatellite instability (MSI) analysis is commonly used to test for MMR deficiency. Testing biopsies prior to tumour resection can inform surgical and therapeutic decisions, but can be limited by DNA quantity. MSI analysis of voided urine could also provide much needed surveillance for genitourinary tract cancers in LS. Here, we reconfigure an existing molecular inversion probe-based MSI and BRAF c.1799T > A assay to a multiplex PCR (mPCR) format, and demonstrate that it can sample >140 unique molecules per marker from <1 ng of DNA and classify CRCs with 96–100% sensitivity and specificity. We also show that it can detect increased MSI within individual and composite CRC biopsies from LS patients, and within preoperative urine cell free DNA (cfDNA) from two LS patients, one with an upper tract urothelial cancer, the other an undiagnosed endometrial cancer. Approximately 60–70% of the urine cfDNAs were tumour-derived. Our results suggest that mPCR sequence-based analysis of MSI and mutation hotspots in CRC biopsies could facilitate presurgery decision making, and could enable postal-based screening for urinary tract and endometrial tumours in LS patients.
CAR-NK Cells: A Chimeric Hope or a Promising Therapy?
Authors: Sabbah Mohamad , Jondreville Ludovic , Lacan Claire , Norol Francoise , Vieillard Vincent , Roos-Weil Damien , Nguyen Stéphanie
Published: August 2022

Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable quality and quantity of collected effector T cells, extended time of cell processing, limited number of available CAR cells, toxicities, and a high cost. Thanks to their powerful cytotoxic capabilities, with proven antitumor effects in both haploidentical hematopoietic stem cell transplantation and adoptive cell therapy against solid tumors and hematological malignancies, Natural Killer cells could be a promising alternative. Different sources of NK cells can be used, including cellular lines, cord blood, peripheral blood, and induced pluripotent stem cells. Their biggest advantage is the possibility of using them in an allogeneic context without major toxic side effects. However, the majority of the reports on CAR-NK cells concern preclinical or early clinical trials. Indeed, NK cells might be more difficult to engineer, and the optimization and standardization of expansion and transfection protocols need to be defined. Furthermore, their short persistence after infusion is also a major setback. However, with recent advances in manufacturing engineered CAR-NK cells exploiting their cytolytic capacities, antibody-dependent cellular cytotoxicity (ADCC), and cytokine production, “off-the-shelf” allogeneic CAR-NK cells can provide a great potential in cancer treatments.
Theranostics Using Indocyanine Green Lactosomes
Authors: Kaibori Masaki , Matsui Kosuke , Hayashi Mikio
Published: August 2022

Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled in the range of 20 to 100 nm. Lactosomes can also be loaded with hydrophobic imaging probes and photosensitizers, such as indocyanine green. Indocyanine green-loaded lactosomes are stable for long-term circulation in the blood, allowing for accumulation in cancer tissues. Such lactosomes function as a photosensitizer, which simultaneously enables fluorescence diagnosis and photodynamic therapy. This review provides an overview of lactosomes with respect to molecular design, accumulation in cancer tissue, and theranostics applications. The use of lactosomes can facilitate the treatment of cancers in unresectable tissues, such as glioblastoma and head and neck cancers, which can lead to improved quality of life for patients with recurrent and unresectable cancers. We conclude by describing some outstanding questions and future directions for cancer theranostics with respect to clinical applications.
Nanovaccines for Cancer Prevention and Immunotherapy: An Update Review
Authors: Fang Xingliang , Lan Huanrong , Jin Ketao , Gong Daojun , Qian Jun
Published: August 2022

Cancer immunotherapy has received more and more attention from cancer researchers over the past few decades. Various methods such as cell therapy, immune checkpoint blockers, and cancer vaccines alone or in combination therapies have achieved relatively satisfactory results in cancer therapy. Among these immunotherapy-based methods, cancer vaccines alone have not yet had the necessary efficacy in the clinic. Therefore, nanomaterials have increased the efficacy and ef-fectiveness of cancer vaccines by increasing their half-life and durability, promoting tumor mi-croenvironment (TME) reprogramming, and enhancing their anti-tumor immunity with minimal toxicity. In this review, according to the latest studies, the structure and different types of nanovaccines, the mechanisms of these vaccines in cancer treatment, as well as the advantages and disadvantages of these nanovaccines are discussed.
A Heterogeneous Bifunctional Carbon Nanocatalyst from Plastic Waste to Efficiently Catalyze Waste Cooking Oil into Biodiesel
Authors: Hazmi Balkis , Rashid Umer , Kawi Sibudjing , Mokhtar Wan Nur Aini Wan , Ahangar Firdous Ahmad , Yaw Thomas Choong Shean , Tsubota Toshiki , Alharthi Fahad A. , Ngamcharussrivichai Chawalit
Published: August 2022

In this study, black carbon derived from polyethylene terephthalate (PET) wastes was utilized as the precursor for heterogeneous bifunctional nanocatalyst, which successively catalyzed waste cooking oil into biodiesel. The nano-sized catalysts were prepared by impregnation method with different heat treatment techniques, such as reflux, hydrothermal, and microwave solvothermal, to provide good distribution of K2O and NiO particles on PET activated carbon mesoporous surface. The sample treated with microwave solvothermal technique (MAC-K2O-NiO) exhibited a high surface area of 120 m2/g with good dispersion of nanoparticles, as shown by FESEM image, large crystallite size of 62.2 nm, and consisted of a highest density of basicity (2.58 mmol/g) and acidity (1.79 mmol/g) for improving transesterification to a maximum yield. The catalytic transesterification of MAC-K2O-NiO was optimized with 3 wt.% of catalyst loading, 18: 1 methanol-oil molar ratio, 65 °C for 3 h of reaction, with a maximum yield of 97.2%. The catalyst reusability was performed, and it was found to maintain the catalytic activity up to six reaction cycles, with a yield of 72.9%. The physiochemical quality of the optimized biodiesel was examined in accordance with the American Society for Testing and Materials, ASTM D6751 testing method.
Identification of SOX18 as a New Gene Predisposing to Congenital Heart Disease
Authors: Shi Hong-Yu , Xie Meng-Shi , Yang Chen-Xi , Huang Ri-Tai , Xue Song , Liu Xing-Yuan , Xu Ying-Jia , Yang Yi-Qing
Published: August 2022

Congenital heart disease (CHD) is the most frequent kind of birth deformity in human beings and the leading cause of neonatal mortality worldwide. Although genetic etiologies encompassing aneuploidy, copy number variations, and mutations in over 100 genes have been uncovered to be involved in the pathogenesis of CHD, the genetic components predisposing to CHD in most cases remain unclear. We recruited a family with CHD from the Chinese Han population in the present investigation. Through whole-exome sequencing analysis of selected family members, a new SOX18 variation, namely NM_018419.3:c.349A>T; p.(Lys117*), was identified and confirmed to co-segregate with the CHD phenotype in the entire family by Sanger sequencing analysis. The heterozygous variant was absent from the 384 healthy volunteers enlisted as control individuals. Functional exploration via luciferase reporter analysis in cultivated HeLa cells revealed that Lys117*-mutant SOX18 lost transactivation on its target genes NR2F2 and GATA4, two genes responsible for CHD. Moreover, the genetic variation terminated the synergistic activation between SOX18 and NKX2.5, another gene accountable for CHD. The findings strongly indicate SOX18 as a novel gene contributing to CHD, which helps address challenges in the clinical genetic diagnosis and prenatal prophylaxis of CHD.
Integrated Analysis of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma
Authors: Zhao Yulan , Huang Ting , Huang Pintong
Published: August 2022

Tumor mutation burdens (TMBs) act as an indicator of immunotherapeutic responsiveness in various tumors. However, the relationship between TMBs and immune cell infiltrates in hepatocellular carcinoma (HCC) is still obscure. The present study aimed to explore the potential diagnostic markers of TMBs for HCC and analyze the role of immune cell infiltration in this pathology. We used OA datasets from The Cancer Genome Atlas database. First, the “maftools” package was used to screen the highest mutation frequency in all samples. R software was used to identify differentially expressed genes (DEGs) according to mutation frequency and perform functional correlation analysis. Then, the gene ontology (GO) enrichment analysis was performed with “clusterProfiler”, “enrichplot”, and “ggplot2” packages. Finally, the correlations between diagnostic markers and infiltrating immune cells were analyzed, and CIBERSORT was used to evaluate the infiltration of immune cells in HCC tissues. As a result, we identified a total of 359 DEGs in this study. These DEGs may affect HCC prognosis by regulating fatty acid metabolism, hypoxia, and the P53 pathway. The top 15 genes were selected as the hub genes through PPI network analysis. SRSF1, SNRPA1, and SRSF3 showed strong similarities in biological effects, NCBP2 was demonstrated as a diagnostic marker of HCC, and high NCBP2 expression was significantly correlated with poor over survival (OS) in HCC. In addition, NCBP2 expression was correlated with the infiltration of B cells (r = 0.364, p = 3.30 × 10−12), CD8+ T cells (r = 0.295, p = 2.71 × 10−8), CD4+ T cells, (r = 0.484, p = 1.37 × 10−21), macrophages (r = 0.551, p = 1.97 × 10−28), neutrophils (r = 0.457, p = 3.26 × 10−19), and dendritic cells (r = 0.453, p = 1.97 × 10−18). Immune cell infiltration analysis revealed that the degree of central memory T-cell (Tcm) infiltration may be correlated with the HCC process. In conclusion, NCBP2 can be used as diagnostic markers of HCC, and immune cell infiltration plays an important role in the occurrence and progression of HCC.
Real and Pseudo Pedestrian Detection Method with CA-YOLOv5s Based on Stereo Image Fusion
Authors: Song Xiaowei , Li Gaoyang , Yang Lei , Zhu Luxiao , Hou Chunping , Xiong Zixiang
Published: August 2022

With the development of convolutional neural networks, the effect of pedestrian detection has been greatly improved by deep learning models. However, the presence of pseudo pedestrians will lead to accuracy reduction in pedestrian detection. To solve the problem that the existing pedestrian detection algorithms cannot distinguish pseudo pedestrians from real pedestrians, a real and pseudo pedestrian detection method with CA-YOLOv5s based on stereo image fusion is proposed in this paper. Firstly, the two-view images of the pedestrian are captured by a binocular stereo camera. Then, a proposed CA-YOLOv5s pedestrian detection algorithm is used for the left-view and right-view images, respectively, to detect the respective pedestrian regions. Afterwards, the detected left-view and right-view pedestrian regions are matched to obtain the feature point set, and the 3D spatial coordinates of the feature point set are calculated with Zhengyou Zhang’s calibration method. Finally, the RANSAC plane-fitting algorithm is adopted to extract the 3D features of the feature point set, and the real and pseudo pedestrian detection is achieved by the trained SVM. The proposed real and pseudo pedestrian detection method with CA-YOLOv5s based on stereo image fusion effectively solves the pseudo pedestrian detection problem and efficiently improves the accuracy. Experimental results also show that for the dataset with real and pseudo pedestrians, the proposed method significantly outperforms other existing pedestrian detection algorithms in terms of accuracy and precision.