bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Characterization of the Nsp2 and ORF5 (ORF5a) Genes of PRRSV Strains in Nine Provinces of China During 2016–2018
Authors: Yin Baishuang , Qi Shanshan , Sha Wanli , Qin Hongyu , Liu Liming , Yun Jinyan , Zhu Jinhai , Li Guojiang , Sun Dongbo
Published: March 2021

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease and brings huge economic losses to commercial pork production worldwide. PRRSV causes severe reproductive failure in sows and respiratory distress in piglets. To trace the evolution of PRRSV in pigs with respiratory diseases in some regions of China, 112 samples were collected from nine provinces in China during 2016–2018. All samples were detected by RT-PCR and analyzed by the Nsp2/ORF5 (ORF5a)-genes-phylogeny. Sequence analysis and recombination analysis were conducted on the Nsp2/ORF5 (ORF5a) genes of the identified strain in the study. The RT-PCR result shown that the positive rate of PRRSV was 50.89% (57/112). Phylogenetic analysis showed that the identified PRRSV strains were all NA genotype and belonged to lineage 1, 3, and 8. The Nsp2 gene of identified PRRSV strains exhibited nucleotide homologies of 53.0 ~ 99.8%, and amino acid homologies of 46.8 ~ 99.7%. The ORF5 gene of identified PRRSV strains exhibited nucleotide homologies of 82.4 ~ 100%, and amino acid homologies of 79.6 ~ 100%. Sequence analysis revealed that a discontinuous 30-amino-acid deletion (positions 481 and 533–561) and a 131-amino-acid discontinuity deletion (positions 323–433, 481, and 533–551) in Nsp2 of PPRSV isolates; all identified strains in this study may be wild strains, and most identified strains may be highly virulent strains. Sequence analysis of ORF5 and ORF5a revealed that the mutation sites of GP5 were mainly concentrated in the signal peptide and epitopes region, while the mutation sites of ORF5a were mainly concentrated in the transmembrane and the intramembrane region. The recombination analysis indicated that there may be multiple recombination regions in identified strains, and the recombination pattern was more complex. This study showed that the prevalent PRRSV strain in some regions of China was still HP-PRRSV, while NADC30 strain also occupied a certain proportion; different types of PRRSV strains showed different patterns and variation in China. This study suggested that the monitoring of PRRSV prevalence and genetic variation should be further strengthened.
Diagnostic Accuracy of Delayed Phase Post Contrast Computed Tomographic Images in the Diagnosis of Focal Liver Lesions in Dogs: 69 Cases
Authors: Burti Silvia , Zotti Alessandro , Bonsembiante Federico , Contiero Barbara , Banzato Tommaso
Published: March 2021

To describe the computed tomographic (CT) features of focal liver lesions (FLLs) in dogs, that could enable predicting lesion histotype. Dogs diagnosed with FLLs through both CT and cytopathology and/or histopathology were retrospectively collected. Ten qualitative and 6 quantitative CT features have been described for each case. Lastly, a machine learning-based decision tree was developed to predict the lesion histotype. Four categories of FLLs - hepatocellular carcinoma (HCC, n = 13), nodular hyperplasia (NH, n = 19), other benign lesions (OBL, n = 18), and other malignant lesions (OML, n = 19) - were evaluated in 69 dogs. Five of the observed qualitative CT features resulted to be statistically significant in the distinction between the 4 categories: surface, appearance, lymph-node appearance, capsule formation, and homogeneity of contrast medium distribution. Three of the observed quantitative CT features were significantly different between the 4 categories: the Hounsfield Units (HU) of the radiologically normal liver parenchyma during the pre-contrast scan, the maximum dimension, and the ellipsoid volume of the lesion. Using the machine learning-based decision tree, it was possible to correctly classify NHs, OBLs, HCCs, and OMLs with an accuracy of 0.74, 0.88, 0.87, and 0.75, respectively. The developed decision tree could be an easy-to-use tool to predict the histotype of different FLLs in dogs. Cytology and histology are necessary to obtain the final diagnosis of the lesions.
Changes in Oviductal Cells and Small Extracellular Vesicles miRNAs in Pregnant Cows
Authors: Mazzarella Rosane , Bastos Natália Marins , Bridi Alessandra , del Collado Maite , Andrade Gabriella Mamede , Pinzon Jorge , Prado Cibele Maria , Silva Luciano Andrade , Meirelles Flávio Vieira , Pugliesi Guilherme , Perecin Felipe , da Silveira Juliano Coelho
Published: March 2021

Early embryonic development occurs in the oviduct, where an ideal microenvironment is provided by the epithelial cells and by the oviductal fluid produced by these cells. The oviductal fluid contains small extracellular vesicles (sEVs), which through their contents, including microRNAs (miRNAs), can ensure proper cell communication between the mother and the embryo. However, little is known about the modulation of miRNAs within oviductal epithelial cells (OECs) and sEVs from the oviductal fluid in pregnant cows. In this study, we evaluate the miRNAs profile in sEVs from the oviductal flushing (OF-sEVs) and OECs from pregnant cows compared to non-pregnant, at 120 h after ovulation induction. In OF-sEVs, eight miRNAs (bta-miR-126-5p, bta-miR-129, bta-miR-140, bta-miR-188, bta-miR-219, bta-miR-345-3p, bta-miR-4523, and bta-miR-760-3p) were up-regulated in pregnant and one miRNA (bta-miR-331-5p) was up-regulated in non-pregnant cows. In OECs, six miRNAs (bta-miR-133b, bta-miR-205, bta-miR-584, bta-miR-551a, bta-miR-1193, and bta-miR-1225-3p) were up-regulated in non-pregnant and none was up-regulated in pregnant cows. Our results suggest that embryonic maternal communication mediated by sEVs initiates in the oviduct, and the passage of gametes and the embryo presence modulate miRNAs contents of sEVs and OECs. Furthermore, we demonstrated the transcriptional levels modulation of selected genes in OECs in pregnant cows. Therefore, the embryonic-maternal crosstalk potentially begins during early embryonic development in the oviduct through the modulation of miRNAs in OECs and sEVs in pregnant cows.
Chemokine Therapy in Cats With Experimental Renal Fibrosis and in a Kidney Disease Pilot Study
Authors: Bennington Julie , Lankford Shannon , Magalhaes Renata S. , Shankle Douglas , Fanning Jason , Kartini Cucu , Suparto Irma , Kusumawardhani Winda , Putra M. ArRaniri , Mariya Silmi , Badlani Gopal , Williams J. Koudy
Published: March 2021

Background: Chronic tubulointerstitial fibrosis is a common final pathway leading to end stage kidney disease in cats and has no effective treatment. The use of cell-based molecules to treat kidney fibrosis may be a promising approach. The objectives were to test the effects of intra-renal chemokine CXCL12 injection in a pre-clinical cat model of unilateral ischemia/reperfusion (I/R)-induced kidney fibrosis and then, within a clinical pilot study, test the safety/feasibility of CXCL12 injection in cats that might have early chronic kidney disease (CKD).

Methods:Pre-clinical: Thirty cats received intra-renal injection of 100, 200, or 400 ng of recombinant human CXCL12, or sterile saline, into the I/R kidney 70 days post-injury, or were non-injured, non-injected controls (n = 6/group). Kidney collagen content was quantified 4 months post-treatment using Masson's Trichrome and Picrosirius Red (PSR) stained tissues. In a separate study (n = 2) exploring short-term effects of CXCL12, 200 ng CXCL12 was injected into I/R kidneys and then harvested either 30 min (n = 1) or 1 month (n = 1) post-injection. Kidney concentrations of CXCL12, matrix metalloproteinase 1 (MMP-1), and lysyl oxidase-like enzyme 2 (LOXL-2) were quantified via ELISA. Clinical Pilot: 14 client-owned cats with potential early kidney disease received a single-treatment, bilateral intra-renal injection of 200 ng CXCL12 (n = 7), or received no injection (n = 7). Blood/urine samples were collected monthly for 9 months to assess renal function and CKD staging.

Results:Pre-clinical: I/R increased the affected kidney collagen content, which both mid and high doses of CXCL12 restored to normal (ps < 0.05 vs. untreated). I/R increased collagen fiber width, which both mid and high doses of CXCL12 restored to normal (p < 0.001 vs. untreated). Early changes in kidney MMP-1, associated with collagen breakdown, and subsequent decreases in LOXL-2, associated with collagen cross-linking, in response to CXCL12 treatment may contribute to these findings. Clinical Pilot: Bilateral intra-renal injection of CXCL12 using ultrasound guidance in cats with CKD was feasible and safe in a general practice clinical setting with no obvious side effects noted during the 9-month follow-up period.

Conclusions: Intra-renal injection of CXCL12 may prove to be an effective treatment for kidney fibrosis in cats with CKD. Additional mechanistic and clinical evaluations are needed.
RNA-Seq Analysis Reveals the Role of Omp16 in Brucella-Infected RAW264.7 Cells
Authors: Zhou Dong , Zhi Feijie , Fang Jiaoyang , Zheng Weifang , Li Junmei , Zhang Guangdong , Chen Lei , Jin Yaping , Wang Aihua
Published: March 2021

Brucellosis is an endemic zoonotic infectious disease in the majority of developing countries, which causes huge economic losses. As immunogenic and protective antigens at the surface of Brucella spp., outer membrane proteins (Omps) are particularly attractive for developing vaccine and could have more relevant role in host–pathogen interactions. Omp16, a homolog to peptidoglycan-associated lipoproteins (Pals), is essential for Brucella survival in vitro. At present, the functions of Omp16 have been poorly studied. Here, the gene expression profile of RAW264.7 cells infected with Brucella suis vaccine strain 2 (B. suis S2) and ΔOmp16 was analyzed by RNA-seq to investigate the cellular response immediately after Brucella entry. The RNA-sequence analysis revealed that a total of 303 genes were significantly regulated by B. suis S2 24 h post-infection. Of these, 273 differentially expressed genes (DEGs) were upregulated, and 30 DEGs were downregulated. These DEGs were mainly involved in innate immune signaling pathways, including pattern recognition receptors (PRRs), proinflammatory cytokines, and chemokines by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In ΔOmp16-infected cells, the expression of 52 total cells genes was significantly upregulated and that of 9 total cells genes were downregulated compared to B. suis S2-infected RAW264.7 cells. The KEGG pathway analysis showed that several upregulated genes were proinflammatory cytokines and chemokines, such as interleukin (IL)-6, IL-11, IL-12β, C–C motif chemokine (CCL2), and CCL22. All together, we clearly demonstrate that ΔOmp16 can alter macrophage immune-related pathways to increase proinflammatory cytokines and chemokines, which provide insights into illuminating the Brucella pathogenic strategies.
The Lack of Light-Dark and Feeding-Fasting Cycles Alters Temporal Events in the Goldfish (Carassius auratus) Stress Axis
Authors: Saiz Nuria , Gómez-Boronat Miguel , De Pedro Nuria , Delgado María Jesús , Isorna Esther
Published: March 2021

Vertebrates possess circadian clocks, driven by transcriptional–translational loops of clock genes, to orchestrate anticipatory physiological adaptations to cyclic environmental changes. This work aims to investigate how the absence of a light-dark cycle and a feeding schedule impacts the oscillators in the hypothalamus-pituitary-interrenal axis of goldfish. Fish were maintained under 12L:12D feeding at ZT 2; 12L:12D feeding at random times; and constant darkness feeding at ZT 2. After 30 days, fish were sampled to measure daily variations in plasma cortisol and clock gene expression in the hypothalamus-pituitary-interrenal (HPI) axis. Clock gene rhythms in the HPI were synchronic in the presence of a light-dark cycle but were lost in its absence, while in randomly fed fish, only the interrenal clock was disrupted. The highest cortisol levels were found in the randomly fed group, suggesting that uncertainty of food availability could be as stressful as the absence of a light-dark cycle. Cortisol daily rhythms seem to depend on central clocks, as a disruption in the adrenal clock did not impede rhythmic cortisol release, although it could sensitize the tissue to stress.
Research on the Effects of Gender and Feeding Geese Oats and Hybrid Rye on Their Slaughter Traits and Meat Quality
Authors: Lisiak Dariusz , Janiszewski Piotr , Grześkowiak Eugenia , Borzuta Karol , Lisiak Beata , Samardakiewicz Łukasz , Schwarz Tomasz , Powałowski Krzysztof , Andres Krzysztof
Published: March 2021

The aim of the study was to determine the effect of feeding Zatorska variety geese hybrid rye, oats, or a mixture of both grains (1:1) on slaughter value and meat quality. At 14 weeks old, the birds were separated into three feeding groups (n = 12) and were fed between 15 and 17 weeks of age with hybrid rye, oats, or a mixture of these two grains. The research proved the effect of gender and feeding on some slaughter value traits and meat quality of the goslings’ breast meat. It was found that the ganders had a 10% to 15% higher body and carcass weight than the females. No significant differences were observed between the genders within the majority of the physical and chemical characteristics as well as the sensory traits. The feeding type did not have a significant effect on the goslings’ body weight and carcass element share. The birds fed hybrid rye had a 2 percentage points lower slaughter yield than those birds fed oats which was combined with a lower share of subcutaneous fat (measured as the weight of the tissue coming from dissection) in birds fed hybrid rye. The meat of the birds fed hybrid rye had some better physical, chemical characteristics and, in the female goslings, also better sensory quality. The results indicated that hybrid rye may be used in feeding goslings at the end of the growing period, because it did not cause any negative effects on the pre-slaughter body weight and had a positive effect on some meat quality traits, such as better sensory estimation results, higher protein content, and lower drip losses.
Transcriptome Profiling of the Retained Fetal Membranes—An Insight in the Possible Pathogenesis of the Disease
Authors: Jaworska Joanna , Ropka-Molik Katarzyna , Piórkowska Katarzyna , Szmatoła Tomasz , Kowalczyk-Zięba Ilona , Wocławek-Potocka Izabela , Siemieniuch Marta
Published: March 2021

Retained fetal membranes (RFM) is one of the most common post-partum diseases of a complex etiology. Moreover, its pathogenesis is still not elucidated. Detailed transcriptomic analysis of physiological and retained placenta may bring profound insight in the pathogenesis of the disease. The aim of the study was to compare the transcriptome of the retained and physiologically released placenta as well as biological pathways and processes in order to determine the possible pathogenesis of the disease. Samples of the endometrium and the allantochorion were taken within 2 h after parturition from control mares (n = 3) and mares with RFM (n = 3). RNA sequencing was performed with the use of all samples and mRNA expression of chosen genes was validated with Real Time PCR. Analysis of RNA-seq identified 487 differentially expressed genes in the allantochorion and 261 in the endometrium of control and RFM mares (p < 0.0001). Within genes that may be important in the release of fetal membranes and were differentially expressed, our report pinpointed BGN, TIMP1, DRB, CD3E, C3, FCN3, CASP3, BCL2L1. Gene ontology analysis showed possible processes which were altered in RFM that are apoptosis, inflammatory-related processes, and extracellular matrix metabolism and might be involved in the pathogenesis of RFM. This is the first report on the transcriptome of RFM and physiologically released placenta in mares.
Comparative Study on the Essential Oils from Five Wild Egyptian Centaurea Species: Effective Extraction Techniques, Antimicrobial Activity and In-Silico Analyses
Authors: Reda Eman H. , Shakour Zienab T. Abdel , El-Halawany Ali M. , El-Kashoury El-Sayeda A. , Shams Khaled A. , Mohamed Tarik A. , Saleh Ibrahim , Elshamy Abdelsamed I. , Atia Mohamed A. M. , El-Beih Ahmed A. , Abdel-Azim Nahla S. , El-Seedi Hesham R. , Hegazy Mohamed-Elamir F.
Published: March 2021

The genus Centaurea is recognized in folk medicine for anti-inflammatory, anti-itch, antitussive, purgative, astringent, and tonic activities. To study the chemical determinant for antimicrobial activity essential oils (EOs), five Centaurea species were analyzed including: C. scoparia, C. calcitrapa, C. glomerata, C. lipii and C. alexandrina. Conventional hydro-distillation (HD) and microwave-assisted extraction (MAE), as new green technologies, were compared for the extraction of essential oils. GC/MS analysis identified 120 EOs including mostly terpenoid except from C. lipii and C. alexandrina in which nonterpenoids were the major constituents. Major terpenoids included spathulenol, caryophyllene oxide and alloaromadendrene oxide-2. To probe antibacterial activity, potential EO inhibitors of a bacterial type II DNA topoisomerase, DNA gyrase B were screened via an in silico molecular docking approach. Spathulenol and alloaromadendrene oxide-2 possessed the best binding affinity in the ATP- binding pocket of Gyrase B enzyme. Principal component analysis and agglomerative hierarchical clustering were used for sample classification and revealed that sesquiterpenes contributed the most for accessions classification. In vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli and Aspergillus niger for all EOs were also evaluated. EOs from C. lipii, C. glomerata and C. calcitrapa exhibited significant MIC against S. aureus with an MIC value of 31.25 µg/mL.
Rain Streak Removal for Single Images Using Conditional Generative Adversarial Networks
Authors: Hettiarachchi Prasad , Nawaratne Rashmika , Alahakoon Damminda , De Silva Daswin , Chilamkurti Naveen
Published: March 2021

Rapid developments in urbanization and smart city environments have accelerated the need to deliver safe, sustainable, and effective resource utilization and service provision and have thereby enhanced the need for intelligent, real-time video surveillance. Recent advances in machine learning and deep learning have the capability to detect and localize salient objects in surveillance video streams; however, several practical issues remain unaddressed, such as diverse weather conditions, recording conditions, and motion blur. In this context, image de-raining is an important issue that has been investigated extensively in recent years to provide accurate and quality surveillance in the smart city domain. Existing deep convolutional neural networks have obtained great success in image translation and other computer vision tasks; however, image de-raining is ill posed and has not been addressed in real-time, intelligent video surveillance systems. In this work, we propose to utilize the generative capabilities of recently introduced conditional generative adversarial networks (cGANs) as an image de-raining approach. We utilize the adversarial loss in GANs that provides an additional component to the loss function, which in turn regulates the final output and helps to yield better results. Experiments on both real and synthetic data show that the proposed method outperforms most of the existing state-of-the-art models in terms of quantitative evaluations and visual appearance.
Modified Ankle Joint Neuromechanics during One-Legged Heel Raise Test after an Achilles Rupture and Its Associations with Jumping
Authors: Shih Kao-Shang , Chen Pei-Yu , Yeh Wen-Ling , Ma Hsiao-Li , Farn Chui-Jia , Hou Chun-Han , Peng Wei-Chen , Wang Hsing-Kuo
Published: March 2021

This study had two purposes. The first purpose of the study was to compare the electromyographic(EMG) and dynamic characteristics in injured and non-injured legs during the one-legged heel-raise test after a unilateral Achilles repair. The second purpose was to determine the correlations between the EMG results and the dynamic characteristics and between the characteristics in the eccentric phase and jumping distance. Twenty-six participants who underwent an Achilles repair between 4 and 12 months prior to the measurement were recruited to perform the following bilateral tests: (1) one-legged heel-raise test with measurements of muscle activation, kinematics, and kinetics and (2) one-legged forward jumping. During the heel-raise exercise, there were increases of the EMG amplitudes in the soleus and tibialis anterior muscles, lower ankle joint angle and angular velocity, lower normalized ground reaction force, and mechanical work in the repaired legs in comparison to the non-injured legs. The EMG results of the medial gastrocnemius and soleus muscles correlated with the dynamic results (rs = 0.467 and −0.537). Furthermore, the dynamic data in the eccentric phase were correlated with the jumping performance (rs = 0.575 and −0.471). It is concluded the soleus muscle undergoes neuromechanical changes, including changes in EMG and dynamic characteristics, and changes affecting jumping performance.
Physical Activity and Redox Balance in the Elderly: Signal Transduction Mechanisms
Authors: Galli Daniela , Carubbi Cecilia , Masselli Elena , Vaccarezza Mauro , Presta Valentina , Pozzi Giulia , Ambrosini Luca , Gobbi Giuliana , Vitale Marco , Mirandola Prisco
Published: March 2021

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy.
Design and Experimental Evaluation of a Form Trimming Machine for Horticultural Plants
Authors: Li Mao , Ma Lina , Zong Wangyuan , Luo Chengming , Huang Muchang , Song Yang
Published: March 2021

Form trimming is an important practice in horticulture. Currently, handheld trimming tools are the most commonly used in China, which presents certain disadvantages including high human labor input, low productivity and inconsistent performance. In this work, a wheeled form trimming machine was designed for shrub plants with the aim of reducing labor input, increasing efficiency and improving trimming performance. The machine was mainly composed of three parts: a supporting frame, a rotary base and a knife system. The design and construction of the key components of the machine were introduced. The knife system was a combination of multiple cutter units with reciprocating motions. The number of units and their connecting angles could be adjusted to realize different trimming shapes. The knife system was carried by the rotary base and could realize 360° rotations to cut the plants into a desired form. Experiments were performed to determine the optimal working parameters (cutting frequency of the cutter unit and rotating speed of the rotary base). The similarity between the plant profile after trimming and the profile of the knife system and the consumed time in each operation were chosen as two evaluation indexes. Results showed that when the cutting frequency was 16.7 Hz and the rotating speed of the rotary base was 13.5 r/min, the trimming operation could be completed by two circles, and the time consumption was 8.89 s. Furthermore, to test the adaptability of the machine, five different shrub plants were chosen and trimmed by the machine, and results showed that the overall similarity was above 93%. Therefore, the form trimming machine developed could meet the requirements of shrub trimming in horticulture with desirable precision and adaptability.
A Low-Profile HF Meandered Dipole Antenna with a Ferrite-Loaded Artificial Magnetic Conductor
Authors: Kwon Oh Heon , Park Won Bin , Yun Juho , Lim Hong Jun , Hwang Keum Cheol
Published: March 2021

In this paper, a low-profile HF (high-frequency) meandered dipole antenna with a ferrite-loaded artificial magnetic conductor (AMC) is proposed. To operate in the HF band while retaining a compact size, ferrite with high permeability is applied to the unit cell of the AMC. The operating frequency bandwidth of the designed unit cell of the AMC is 1.89:1 (19–36 MHz). Thereafter, a meandered dipole antenna is designed by implementing a binary genetic algorithm and is combined with the AMC. The overall size of the designed antenna is 0.06×0.06×0.002 λ3 at the lowest operating frequency. The proposed dipole antenna with a ferrite-loaded AMC is fabricated and measured. The measured VSWR bandwidth (<3) covers 20–30 MHz on the HF band. To confirm the performance of the antenna, a reference monopole antenna which operates on the HF band was selected, and the measured receiving power is compared with the result of the proposed antenna with the AMC.
Stress and Fatigue Analysis of Picking Device Gears for a 2.6 kW Automatic Pepper Transplanter
Authors: Islam Md Nafiul , Iqbal Md Zafar , Chowdhury Milon , Ali Mohammod , Shafik Kiraga , Kabir Md Shaha Nur , Lee Dae-Hyun , Chung Sun-Ok
Published: March 2021

A seedling picking device is an essential component for an automatic transplanter to automatically convey the seedling to the dibbling part. It is necessary to find the appropriate material and dimensions for the picking device gears to avoid mechanical damage and increase their durability. Therefore, the objectives of this research were to analyze the stress of a picking device gear mechanism in order to select suitable materials and dimensions, and to predict the fatigue life by considering the damage level. The picking device gear shaft divided the input power into two categories, i.e., crank and cam gear sets. Finite element analysis simulation and American Gear Manufacturers Association standard stress analysis theory tests were conducted on both of the crank and cam gear sets for different materials and dimensions. A test bench was fabricated to collect the load (torque) data at different gear operating speeds. The torque data were analyzed using the load duration distribution method to observe the cyclic load patterns. The Palmgren–Miner cumulative damage rule was used to determine the damage level of the picking mechanism gears with respect to the operating speed. The desired lifespan of the transplanter was 255 h to meet the real field service life requirement. Predicted fatigue life range of the picking mechanism gears was recorded as from 436.65 to 4635.97 h, making it higher (by approximately 2 to 18 times) than the lifespan of the transplanter. According to the analyses, the “Steel Composite Material 420H carbon steel” material with a 5 mm face width gear was suitable to operate the picking device for a 10-year transplanter service life. The analysis of stress and fatigue presented in this study will guide the design of picking device gears with effective material properties to maintain the recommended service life of the pepper transplanter.
A New Switching Adaptive Fuzzy Controller with an Application to Vibration Control of a Vehicle Seat Suspension Subjected to Disturbances
Authors: Phu Do Xuan , Mien Van , Choi Seung-Bok
Published: March 2021

This paper proposes a new switching adaptive fuzzy controller and applies it to vibration control of a vehicle seat suspension equipped with a semi-active magnetorheological (MR) damper. The proposed control system consists of three functioned filters: (1) Filter 1: a model of interval type 2 fuzzy to compensate disturbances; (2) Filter 2: a ‘switching term’ to evaluate the magnitude of disturbance; and (3) Filter 3: a group of adaptation laws to enhance the robustness of control input. These filters play a role of powerful shields to improve control performance and guarantee the stability of the applied system subjected to external disturbances. After embedding a PID (proportional-integral-derivative) model into Riccati-like equation, main control parameters are updated based on the adaptation laws. The proposed controller is then synthesized in two different cases: high disturbance and small disturbance. For the high disturbance, a special type of sliding surface function, which relates to an exponential function and its t-norm, is used to increase the energy of control system. For the small disturbance, the energy from the modified t-norm of the sliding surface is neglected to reduce the energy consumption with maintaining the desired performance. To demonstrate the effectiveness of the proposed controller, a vehicle seat suspension installed with controllable MR damper is adopted to reflect the robustness against external disturbances corresponding to road excitations. It is validated from computer simulation that the proposed controller can provide better vibration control performance than other existing robust controllers showing excellent control stability with well-reduced displacement and velocity at the position of the seat.
Antimicrobial Cocktail Combining Specific Peptide Extracts from Native Probiotic Bacteria Hamper Adulteration of Ready-to-Eat Mango Wedges
Authors: Tenea Gabriela N. , Olmedo Daniela
Published: March 2021

Consumption of ready-to-eat chopped fruits sold in the streets is a concern, as such activities are outside the regulation and protection in most developing countries. Ready-to-eat mangos are commonly sold as wedges in plastic cups at ambient temperature by mobile vendors in Ecuador, thus they are prone to contamination by bacteria, which poses a safety issue of concern. This work aimed to evaluate the effect of several antimicrobial cocktails consisting of previously designed specific peptide extract combinations from two probiotic bacteria Lactobacillus plantarum UTNCys5-4 and Lactococcus lactis subsp. lactis UTNGt28, along with nisin, a commercial food additive, on mango wedges artificially inoculated with a logarithmic phase culture of a five-strain bacterial mixture (FSBM). Preliminary bacteriological analysis of mango wedges purchased from mobile vendors showed the presence of multiple antibiotic-resistant isolates such E. coli spp., Enterobacter spp., Shigella spp., Salmonella spp., along with yeasts and molds, indicating non-compliance with the food safety standards. The results revealed that two antimicrobial cocktails, T2 and T5, containing cell-free supernatant based (CFS) and precipitated peptides (PP) based cocktails from UTNCys5-4 and UTNGt28 strains applied at dose 1:3 (v/v), were the most efficient combinations that inhibited the colonization of total bacterial counts with 56.03% and 55.61% in mango wedges stored with refrigeration. The reduction of total E. coli counts was 64.93%, while Salmonella and Shigella counts were reduced by 98.09% and 97.93%, respectively, when mango wedges were treated with T5-cocktail. The commercial nisin inhibited total Salmonella spp. counts by 40.13%, while E. coli spp. and Shigella spp. diminished by 28.20% and 37.22%, respectively. Moreover, we showed that T5 but not T7 (nisin) damaged the target cell integrity, thereby eventually inhibiting their growth and reproduction. The selected antimicrobial cocktails exerted a bacteriolytic effect by killing the FSBM simultaneously in a fruit matrix and preventing their accumulation in mango wedges. Furthermore, there is a possibility of using peptide combinatorial treatments to combat drug-resistant bacteria in ready-to-eat fruits.
In Silico Drug Repurposing by Structural Alteration after Induced Fit: Discovery of a Candidate Agent for Recovery of Nucleotide Excision Repair in Xeroderma Pigmentosum Group D Mutant (R683W)
Authors: Takaoka Yutaka , Ohta Mika , Tateishi Satoshi , Sugano Aki , Nakano Eiji , Miura Kenji , Suzuki Takashi , Nishigori Chikako
Published: March 2021

Xeroderma pigmentosum complementation group D (XPD) is a UV-sensitive syndrome and a rare incurable genetic disease which is caused by the genetic mutation of the excision repair cross-complementation group 2 gene (ERCC2). Patients who harbor only XPD R683W mutant protein develop severe photosensitivity and progressive neurological symptoms. Cultured cells derived from patients with XPD (XPD R683W cells) demonstrate a reduced nucleotide excision repair (NER) ability. We hope to ameliorate clinical symptoms if we can identify candidate agents that would aid recovery of the cells’ NER ability. To investigate such candidates, we created in silico methods of drug repurposing (in silico DR), a strategy that utilizes the recovery of ATP-binding in the XPD R683W protein after the induced fit. We chose 4E1RCat and aprepitant as the candidates for our in silico DR, and evaluated them by using the UV-induced unscheduled DNA synthesis (UDS) assay to verify the recovery of NER in XPD R683W cells. UDS values of the cells improved about 1.4–1.7 times after 4E1RCat treatment compared with solvent-only controls; aprepitant showed no positive effect. In this study, therefore, we succeeded in finding the candidate agent 4E1RCat for XPD R683W. We also demonstrated that our in silico DR method is a cost-effective approach for drug candidate discovery.
Facilitatory rTMS over the Supplementary Motor Cortex Impedes Gait Performance in Parkinson Patients with Freezing of Gait
Authors: Brugger Florian , Wegener Regina , Baty Florent , Walch Julia , Krüger Marie T. , Hägele-Link Stefan , Bohlhalter Stephan , Kägi Georg
Published: March 2021

Freezing of gait (FOG) in Parkinson’s disease (PD) occurs frequently in situations with high environmental complexity. The supplementary motor cortex (SMC) is regarded as a major network node that exerts cortical input for motor control in these situations. We aimed at assessing the impact of single-session (excitatory) intermittent theta burst stimulation (iTBS) of the SMC on established walking during FOG provoking situations such as passing through narrow spaces and turning for directional changes. Twelve PD patients with FOG underwent two visits in the off-medication state with either iTBS or sham stimulation. At each visit, spatiotemporal gait parameters were measured during walking without obstacles and in FOG-provoking situations before and after stimulation. When patients passed through narrow spaces, decreased stride time along with increased stride length and walking speed (i.e., improved gait) was observed after both sham stimulation and iTBS. These effects, particularly on stride time, were attenuated by real iTBS. During turning, iTBS resulted in decreased stride time along with unchanged stride length, a constellation compatible with increased stepping frequency. The observed iTBS effects are regarded as relative gait deterioration. We conclude that iTBS over the SMC increases stepping frequency in PD patients with FOG, particularly in FOG provoking situations.
Glioma biopsies Classification Using Raman Spectroscopy and Machine Learning Models on Fresh Tissue Samples
Authors: Riva Marco , Sciortino Tommaso , Secoli Riccardo , D’Amico Ester , Moccia Sara , Fernandes Bethania , Conti Nibali Marco , Gay Lorenzo , Rossi Marco , De Momi Elena , Bello Lorenzo
Published: March 2021

Identifying tumor cells infiltrating normal-appearing brain tissue is critical to achieve a total glioma resection. Raman spectroscopy (RS) is an optical technique with potential for real-time glioma detection. Most RS reports are based on formalin-fixed or frozen samples, with only a few studies deployed on fresh untreated tissue. We aimed to probe RS on untreated brain biopsies exploring novel Raman bands useful in distinguishing glioma and normal brain tissue. Sixty-three fresh tissue biopsies were analyzed within few minutes after resection. A total of 3450 spectra were collected, with 1377 labelled as Healthy and 2073 as Tumor. Machine learning methods were used to classify spectra compared to the histo-pathological standard. The algorithms extracted information from 60 different Raman peaks identified as the most representative among 135 peaks screened. We were able to distinguish between tumor and healthy brain tissue with accuracy and precision of 83% and 82%, respectively. We identified 19 new Raman shifts with known biological significance. Raman spectroscopy was effective and accurate in discriminating glioma tissue from healthy brain ex-vivo in fresh samples. This study added new spectroscopic data that can contribute to further develop Raman Spectroscopy as an intraoperative tool for in-vivo glioma detection.
Tumor Growth Rate Estimates Are Independently Predictive of Therapy Response and Survival in Recurrent High-Grade Serous Ovarian Cancer Patients
Authors: Bartl Thomas , Karacs Jasmine , Kreuzinger Caroline , Pfaffinger Stephanie , Kendler Jonatan , Ciocsirescu Cristina , Wolf Andrea , Reinthaller Alexander , Meyer Elias , Brandstetter Maximilian , Postl Magdalena , Langthaler Eva , Braicu Elena , Vergote Ignace , Cunnea Paula , Gourley Charlie , Schmitt Wolfgang , Cacsire Castillo-Tong Dan , Grimm Christoph
Published: March 2021

This study aimed to assess the predictive value of tumor growth rate estimates based on serial cancer antigen-125 (CA-125) levels on therapy response and survival of patients with recurrent high-grade serous ovarian cancer (HGSOC). In total, 301 consecutive patients with advanced HGSOC (exploratory cohort: n = 155, treated at the Medical University of Vienna; external validation cohort: n = 146, from the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) consortium) were enrolled. Tumor growth estimates were obtained using a validated two-phase equation model involving serial CA-125 levels, and their predictive value with respect to treatment response to the next chemotherapy and the prognostic value with respect to disease-specific survival and overall survival were assessed. Tumor growth estimates were an independent predictor for response to second-line chemotherapy and an independent prognostic factor for second-line chemotherapy use in both univariate and multivariable analyses, outperforming both the predictive (second line: p = 0.003, HR 5.19 [1.73–15.58] vs. p = 0.453, HR 1.95 [0.34–11.17]) and prognostic values (second line: p = 0.042, HR 1.53 [1.02–2.31] vs. p = 0.331, HR 1.39 [0.71–2.27]) of a therapy-free interval (TFI) < 6 months. Tumor growth estimates were a predictive factor for response to third- and fourth-line chemotherapy and a prognostic factor for third- and fourth-line chemotherapy use in the univariate analysis. The CA-125-derived tumor growth rate estimate may be a quantifiable and easily assessable surrogate to TFI in treatment decision making for patients with recurrent HGSOC.
EphB6 Regulates TFEB-Lysosomal Pathway and Survival of Disseminated Indolent Breast Cancer Cells
Authors: Zangrossi Manuela , Romani Patrizia , Chakravarty Probir , Ratcliffe Colin D.H. , Hooper Steven , Dori Martina , Forcato Mattia , Bicciato Silvio , Dupont Sirio , Sahai Erik , Montagner Marco
Published: March 2021

Late relapse of disseminated cancer cells is a common feature of breast and prostate tumors. Several intrinsic and extrinsic factors have been shown to affect quiescence and reawakening of disseminated dormant cancer cells (DDCCs); however, the signals and processes sustaining the survival of DDCCs in a foreign environment are still poorly understood. We have recently shown that crosstalk with lung epithelial cells promotes survival of DDCCs of estrogen receptor-positive (ER+) breast tumors. By using a lung organotypic system and in vivo dissemination assays, here we show that the TFEB-lysosomal axis is activated in DDCCs and that it is modulated by the pro-survival ephrin receptor EphB6. TFEB lysosomal direct targets are enriched in DDCCs in vivo and correlate with relapse in ER+ breast cancer patients. Direct coculture of DDCCs with alveolar type I-like lung epithelial cells and dissemination in the lung drive lysosomal accumulation and EphB6 induction. EphB6 contributes to survival, TFEB transcriptional activity, and lysosome formation in DDCCs in vitro and in vivo. Furthermore, signaling from EphB6 promotes the proliferation of surrounding lung parenchymal cells in vivo. Our data provide evidence that EphB6 is a key factor in the crosstalk between disseminated dormant cancer cells and the lung parenchyma and that the TFEB-lysosomal pathway plays an important role in the persistence of DDCCs.
Dosimetric Validation of a GAN-Based Pseudo-CT Generation for MRI-Only Stereotactic Brain Radiotherapy
Authors: Bourbonne Vincent , Jaouen Vincent , Hognon Clément , Boussion Nicolas , Lucia François , Pradier Olivier , Bert Julien , Visvikis Dimitris , Schick Ulrike
Published: March 2021

Purpose: Stereotactic radiotherapy (SRT) has become widely accepted as a treatment of choice for patients with a small number of brain metastases that are of an acceptable size, allowing for better target dose conformity, resulting in high local control rates and better sparing of organs at risk. An MRI-only workflow could reduce the risk of misalignment between magnetic resonance imaging (MRI) brain studies and computed tomography (CT) scanning for SRT planning, while shortening delays in planning. Given the absence of a calibrated electronic density in MRI, we aimed to assess the equivalence of synthetic CTs generated by a generative adversarial network (GAN) for planning in the brain SRT setting. Methods: All patients with available MRIs and treated with intra-cranial SRT for brain metastases from 2014 to 2018 in our institution were included. After co-registration between the diagnostic MRI and the planning CT, a synthetic CT was generated using a 2D-GAN (2D U-Net). Using the initial treatment plan (Pinnacle v9.10, Philips Healthcare), dosimetric comparison was performed using main dose-volume histogram (DVH) endpoints in respect to ICRU 91 guidelines (Dmax, Dmean, D2%, D50%, D98%) as well as local and global gamma analysis with 1%/1 mm, 2%/1 mm and 2%/2 mm criteria and a 10% threshold to the maximum dose. t-test analysis was used for comparison between the two cohorts (initial and synthetic dose maps). Results: 184 patients were included, with 290 treated brain metastases. The mean number of treated lesions per patient was 1 (range 1–6) and the median planning target volume (PTV) was 6.44 cc (range 0.12–45.41). Local and global gamma passing rates (2%/2 mm) were 99.1 CI95% (98.1–99.4) and 99.7 CI95% (99.6–99.7) respectively (CI: confidence interval). DVHs were comparable, with no significant statistical differences regarding ICRU 91′s endpoints. Conclusions: Our study is the first to compare GAN-generated CT scans from diagnostic brain MRIs with initial CT scans for the planning of brain stereotactic radiotherapy. We found high similarity between the planning CT and the synthetic CT for both the organs at risk and the target volumes. Prospective validation is under investigation at our institution.
Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study
Authors: Adjei Araba A. , Lopez Camden L. , Schaid Daniel J. , Sloan Jeff A. , Le-Rademacher Jennifer G. , Loprinzi Charles L. , Norman Aaron D. , Olson Janet E. , Couch Fergus J. , Beutler Andreas S. , Vachon Celine M. , Ruddy Kathryn J.
Published: March 2021

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially permanent adverse effect of chemotherapeutic agents including taxanes such as paclitaxel and platinum-based compounds such as oxaliplatin and carboplatin. Previous studies have suggested that genetics may impact the risk of CIPN. We conducted genome-wide association studies (GWASs) for CIPN in two independent populations who had completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-CIPN20 assessments (a CIPN-specific 20-item questionnaire which includes three scales that evaluate sensory, autonomic, and motor symptoms). The study population N08Cx included 692 participants from three clinical trials (North Central Cancer Treatment Group (NCCTG) N08C1, N08CA, and N08CB) who had been treated with paclitaxel, paclitaxel plus carboplatin, or oxaliplatin. The primary endpoint for the GWAS was the change from pre-chemotherapy CIPN20 sensory score to the worse score over the following 18 weeks. Study population The Mayo Clinic Breast Disease Registry (MCBDR) consisted of 381 Mayo Clinic Breast Disease Registry enrollees who had been treated with taxane or platinum-based chemotherapy. The primary endpoint for the GWAS assessed was the earliest CIPN20 sensory score available after the completion of chemotherapy. In multivariate model analyses, chemotherapy regimen (p = 3.0 × 10−8) and genetic ancestry (p = 0.007) were significantly associated with CIPN in the N08Cx population. Only age (p = 0.0004) was significantly associated with CIPN in the MCBDR population. The SNP most associated with CIPN was rs56360211 near PDE6C (p =7.92 × 10−8) in N08Cx and rs113807868 near TMEM150C in the MCBDR (p = 1.27 × 10−8). Due to a lack of replication, we cannot conclude that we identified any genetic predictors of CIPN.
Small Non-Coding-RNA in Gynecological Malignancies
Authors: Dwivedi Shailendra Kumar Dhar , Rao Geeta , Dey Anindya , Mukherjee Priyabrata , Wren Jonathan D. , Bhattacharya Resham
Published: March 2021

Gynecologic malignancies, which include cancers of the cervix, ovary, uterus, vulva, vagina, and fallopian tube, are among the leading causes of female mortality worldwide, with the most prevalent being endometrial, ovarian, and cervical cancer. Gynecologic malignancies are complex, heterogeneous diseases, and despite extensive research efforts, the molecular mechanisms underlying their development and pathology remain largely unclear. Currently, mechanistic and therapeutic research in cancer is largely focused on protein targets that are encoded by about 1% of the human genome. Our current understanding of 99% of the genome, which includes noncoding RNA, is limited. The discovery of tens of thousands of noncoding RNAs (ncRNAs), possessing either structural or regulatory functions, has fundamentally altered our understanding of genetics, physiology, pathophysiology, and disease treatment as they relate to gynecologic malignancies. In recent years, it has become clear that ncRNAs are relatively stable, and can serve as biomarkers for cancer diagnosis and prognosis, as well as guide therapy choices. Here we discuss the role of small non-coding RNAs, i.e., microRNAs (miRs), P-Element induced wimpy testis interacting (PIWI) RNAs (piRNAs), and tRNA-derived small RNAs in gynecological malignancies, specifically focusing on ovarian, endometrial, and cervical cancer.