bluuebunny/crossref_metadata_2025 huggingface dataset:
STRESS CONCENTRATION IN THE VICINITY OF A CRACK IN THE ROAD COATING UNDER TRANSPORT LOADS
Authors:   National Transport University, Kyiv, Ukraine, L Shevchuk
Published: November 2021

The problem of stress concentration in the vicinity of a crack under the action of transport loads is posed. Its analysis takes place in an elastic (thermoelastic) formulation using the given modules that correspond to a given state of the system at a given load level. Cases where the coating has no cracks and has them in the upper and inner layers are considered. The effect of transverse cracks on the redistribution of stress fields under the action of transport loads is analyzed. In the case where the coating has no cracks, the greatest compressive stresses occur on the top plane of the coating. Tensile stresses predominate in the zone of the third layer. They increase as they approach the contact plane of the third and fourth layers. The maximum values of the tangent stresses are realized at the boundary of the second and third layers, thus being a potential cause of the coating delamination in this zone. If the crack penetrates the first two upper layers, then the greatest compression stress has moved to the fracture mouth, and the tensile stress remains almost unchanged. In the case where a vertical crack penetrates the inner layer, the maximum values of the normal and tangent values occur in the central and edge zones of the load distribution. A finite element analysis of the effect of the crack on the stress-strain state of the multilayer system is performed. The stress concentration in the crack zones depends largely on the geometry of the crack and its structure at its mouth. KEYWORDS: AUTOMOBILE ROAD, ROAD COATING STRUCTURE, TRANSPORT LOADS, NORMAL VOLTAGE, TENSION VOLTAGE, TENSION-DEFORMED CONDITION
SINGULARLY PERTURBED PROBLEMS OF THERMO-MECHANICS OF LAYERED ROAD COATINGS
Authors:   National Transport University, Kyiv, Ukraine, N Shlyun , O Bilobrytska ,   National Transport University, Kyiv, Ukraine
Published: November 2021

The problem of singular perturbation of the equations of elastic bending of layered pavements and thermal conductivity is discussed. It is shown that the complexity of solving these equations significantly exceeds the complexity of singularly perturbed equations known in the scientific literature. First, this is due to the fact that in the problems of road construction, the mechanics of elastic bending are described by the partial differential equations, and the integration domain reaches large dimensions. The problem of thermal deformation of the pavement and distribution in its array of temperature, displacement, and stress fields is also considered. It is proved that thesolution of the problemof thermal conductivity has the appearance of a boundary effect, localized in the elements of the coating adjacent to its free surface.Also is noted that high-gradient temperature distribution deep in the soil leads to large values of normal and tangential stresses that provoke cracking and delamination of the upper layers of the coating. They are confirmed by the results of computer simulation. KEYWORDS: SINGULARLY PERTURBED PROBLEM, LAYERED ROAD COVERING, TEMPERATURE FIELD, TRANSPORT LOAD, STRESS FIELD, THERMAL STRAIN STATE
A Simple Critical Response Evaluation Method for Base-Isolation Building-Connection Hybrid System Under Double Impulse as Representative of Near-Fault Ground Motion
Authors: Nakamura Tomoya , Fujita Kohei , Takewaki Izuru
Published: November 2021

We revisit a unique building system including a base-isolation, building-connection hybrid control system. The base-isolation system withstands pulse-type earthquake ground motions effectively and the building-connection system resists long-duration earthquake ground motions efficiently. A simple smart critical response evaluation method without nonlinear time-history response analysis is proposed for this hybrid building system under near-fault ground motions. An analytical expression of the maximum elastic-plastic deformation of a damped bilinear hysteretic single-degree-of-freedom (SDOF) model under critical double impulse as a representative of pulse-type ground motions derived in our previous paper plays an important role in the development of the simple critical response evaluation method. A two-step transformation procedure into an SDOF model is proposed. The first step is the transformation of the main base-isolated building into an SDOF system and the second step is the reduction of the connecting dampers supported on a sub building to a damper with a sophisticated compensation factor on an assumed rigid wall. The evaluation of damping coefficients with the consideration of yielding of the base-isolation story is a key step in this paper. Different from the previous work, the equivalent damping coefficient is derived depending on the response range before and after yielding of the base-isolation story. This treatment enhances the accuracy of the proposed method. The accuracy and reliability of the proposed response evaluation method is demonstrated by the time-history response analysis of the multi-degree-of-freedom (MDOF) model.
Forest Steppe-Like Vegetation Near Cherskiy (West Beringia) During the Early Pleistocene Olyorian Period Reconstructed Using Plant Macrofossils
Authors: Kienast Frank , Davydov Sergei P.
Published: November 2021

The lower Kolyma region is known for rich Early Olyorian large mammal assemblages including plesiomorphic musk ox, reindeer, horse, broad-fronted moose, steppe mammoth and cave bear. Data on the vegetation in zonal habitats from the Olyorian period are, in contrast, scarce. Earlier palynological results from classical Olyorian sites indicated predominant grassland vegetation with scattered larch occurrences but are, due to limited taxonomical resolution, uncertain. Plant macrofossil data were, so far, only available from azonal, aquatic habitats. Here, we describe Olyorian palaeo-vegetation from an exposure near Cherskiy, Nizhnekolymsky District, Sakha Republic, Russia. The macrofossil-based reconstruction of palaeo-vegetation revealed the existence of an open forest steppe comprising a mosaic of sparse larch groves in a dry grassland composed of tundra steppes, degraded meadow steppes and saline meadows. In the larch groves, light demanding shrubs and dwarf shrubs such as shrub birch (Betula cf. fruticosa, B. nana ssp. exilis), raspberry (Rubus idaeus), cowberry (Vaccinium vitis-idaea), and crowberry (Empetrum nigrum) formed the understory. Ruderal pioneer plants point to open ground as result of disturbances, possibly due to the activity of large herbivores. The nitrophytic ruderal species Urtica dioica, in particular, suggests locally increased nutrient supply from animal excretions. Also, the abundant remains of Chenopodium cf. prostratum might be explained by disturbances and nutrient enrichment, but Chenopodium is also characteristic of salt accumulation in the soil owing to high evaporation under arid conditions, which are also indicated by alkali grass (Puccinellia sp.). The presence of trees and shrubs indicates interglacial-like temperature conditions but the dominance of dry grassland species and the occurrence of facultatively halophytic plants (Chenopodium prostratum, Puccinellia sp.) suggests aridity, which is more typical of cold stages. During the early Pleistocene, i.e., prior to the Early-Middle Pleistocene transition (EMPT) culminating around 900 ka ago, the duration of climate cycles was shorter and the amplitude of climate fluctuations was smaller. Ice-rich permafrost formed only after the EMPT during increasingly extreme cold stages, and, during warm stages, its thawing resulted in paludification of the active layer. Prior to the EMPT, the climate in West Beringia was constantly relatively dry, more or less moderate and more stable than thereafter. In contrast to modern tundra and northern taiga in the study region, dry habitats apparently prevailed during the time of deposition of the plant macro-remains.
Orbital Signaling in Graves’ Orbitopathy
Authors: Draman Mohd Shazli , Zhang Lei , Dayan Colin , Ludgate Marian
Published: November 2021

Graves’ orbitopathy (GO) is a complex and poorly understood disease in which extensive remodeling of orbital tissue is dominated by adipogenesis and hyaluronan production. The resulting proptosis is disfiguring and underpins the majority of GO signs and symptoms. While there is strong evidence for the thyrotropin receptor (TSHR) being a thyroid/orbit shared autoantigen, the insulin-like growth factor 1 receptor (IGF1R) is also likely to play a key role in the disease. The pathogenesis of GO has been investigated extensively in the last decade with further understanding of some aspects of the disease. This is mainly derived by using in vitro and ex vivo analysis of the orbital tissues. Here, we have summarized the features of GO pathogenesis involving target autoantigens and their signaling pathways.
Genomic Analysis of Multidrug-Resistant Mycobacterium tuberculosis Strains From Patients in Kazakhstan
Authors: Daniyarov Asset , Molkenov Askhat , Rakhimova Saule , Akhmetova Ainur , Yerezhepov Dauren , Chingissova Lyailya , Bismilda Venera , Toksanbayeva Bekzat , Rakisheva Anar , Akilzhanova Ainur , Kozhamkulov Ulan , Kairov Ulykbek
Published: November 2021

Tuberculosis (TB) is an infectious disease that remains an essential public health problem in many countries. Despite decreasing numbers of new cases worldwide, the incidence of antibiotic-resistant forms (multidrug resistant and extensively drug-resistant) of TB is increasing. Next-generation sequencing technologies provide a high-throughput approach to identify known and novel potential genetic variants that are associated with drug resistance inMycobacterium tuberculosis(Mtb). There are limited reports and data related to whole-genome characteristics of drug-resistantMtbstrains circulating in Kazakhstan. Here, we report whole-genome sequencing and analysis results of eight multidrug-resistant strains collected from TB patients in Kazakhstan. Genotyping and validation of all strains by MIRU-VNTR and spoligotyping methodologies revealed that these strains belong to the Beijing family. The spectrum of specific and potentially novel genomic variants (single-nucleotide polymorphisms, insertions, and deletions) related to drug resistance was identified and annotated. ResFinder, CARD, and CASTB antibiotic resistance databases were used for the characterization of genetic variants in genes associated with drug resistance. Our results provide reference data and genomic profiles of multidrug-resistant isolates for further comparative studies and investigations of genetic patterns in drug-resistantMtbstrains.
Genome-wide Identification and Evolutionary Analysis of NBS-LRR Genes From Secale cereale
Authors: Qian Lan-Hua , Wang Yue , Chen Min , Liu Jia , Lu Rui-Sen , Zou Xin , Sun Xiao-Qin , Zhang Yan-Mei
Published: November 2021

Secale cereale is an important crop in the Triticeae tribe of the Poaceae family, and it has unique agronomic characteristics and genome properties. It possesses resistance to many diseases and serves as an important resource for the breeding of other Triticeae crops. We performed a genome-wide study on S. cereale to identify the largest group of plant disease resistance genes (R genes), the nucleotide-binding site-leucine-rich repeat receptor (NBS-LRR) genes. In its genome, 582 NBS-LRR genes were identified, including one from the RNL subclass and 581 from the CNL subclass. The NBS-LRR gene number in the S. cereale genome is greater than that in barley and the diploid wheat genomes. S. cereale chromosome 4 contains the largest number of NBS-LRR genes among the seven chromosomes, which is different from the pattern in barley and the genomes B and D of wheat but similar to that in the genome A of wheat. Further synteny analysis suggests that more NBS-LRR genes on chromosome 4 have been inherited from a common ancestor by S. cereale and the wheat genome A than the wheat genomes B and D. Phylogenetic analysis revealed that at least 740 NBS-LRR lineages are present in the common ancestor of S. cereale, Hordeum vulgare and Triticum urartu. However, most of them have only been inherited by one or two species, with only 65 of them preserved in all three species. The S. cereale genome inherited 382 of these ancestral NBS-LRR lineages, but 120 of them have been lost in both H. vulgare and T. urartu. This study provides the full NBS-LRR profile of the S. cereale genome, which is a resource for S. cereale breeding and indicates that S. cereale can be an important material for the molecular breeding of other Triticeae crops.
Associations of Serum Resistin With the Severity and Prognosis in Patients With Community-Acquired Pneumonia
Authors: Feng Chun-Mei , Cheng Jia-Yi , Xu Zheng , Liu Hong-Yan , Xu De-Xiang , Fu Lin , Zhao Hui
Published: November 2021

Background

Resistin is an endogenous ligand of Toll-like receptor 4 that activates several inflammatory signals. But the physiological function of resistin in community-acquired pneumonia (CAP) remains unknown. The goal of this research was to explore the associations between serum resistin and the severity and prognosis in CAP patients through a retrospective cohort study.

Methods

All 212 CAP patients and 106 healthy cases were enrolled. Demographic characteristics were extracted. Serum resistin was determined via enzyme-linked immunosorbent assay. The prognosis was tracked in CAP patients.

Results

Serum resistin on admission was raised in CAP patients compared with control cases. The level of resistin was gradually increased in parallel with CAP severity scores in CAP patients. Pearson and Spearman analyses revealed that serum resistin was positively correlated with CAP severity scores, white blood cells, urea nitrogen, creatinine, and inflammatory cytokines among CAP patients. There were negative relationships between resistin and hematocrit and albumin in CAP patients. Besides, linear and logistic regression analyses further indicated that serum resistin on admission was positively associated with CAP severity scores among CAP patients. Follow-up research revealed that serum resistin elevation on admission prolonged hospital stay in CAP patients.

Conclusion

Serum resistin on admission is positively correlated with the severity and hospital stay in CAP patients, indicating that resistin may be involved in the physiological process of CAP. Serum resistin may be a potential biomarker in the diagnosis and prognosis for CAP.
Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response
Authors: Song Jing , Tang Yongyao , Luo Xiaoyong , Shi Xinpeng , Song Fangzhou , Ran Longke
Published: November 2021

Transmembrane Channel-like (TMC) genes are critical in the carcinogenesis, proliferation, and cell cycle of human cancers. However, the multi-omics features of TMCs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We discovered that TMCs 4-8 were commonly deregulated and correlated with patient survival in a variety of cancers. For example, TMC5 and TMC8 were correlated with the relapse and overall survival rates of breast cancer and skin melanoma, respectively. These results were validated by multiple independent cohorts. TMCs were regulated by DNA methylation and somatic alterations, such as TMC5 amplification in breast cancer (523/1062, 49.2%). Six algorithms concordantly uncovered the critical role of TMCs in the tumor microenvironment, potentially regulating immune cell toxicity and lymphocytes infiltration. Moreover, TMCs 4-8 were correlated with tumor mutation burden and expression of PD-1/PD-L1/CTLA4 in 33 cancers. Thus, we established an immunotherapy response prediction (IRP) score based on the signature of TMCs 4-8. Patients with higher IRP scores showed higher immunotherapeutic responses in five cohorts of skin melanoma (area under curve [AUC] = 0.90 in the training cohort, AUCs range from 0.70 to 0.83 in the validation cohorts). Together, our study highlights the great potential of TMCs as biomarkers for prognosis and immunotherapeutic response, which can pave the way for further investigation of the tumor-infiltrating mechanisms and therapeutic potentials of TMCs in cancer.
Targeting TBK1 Attenuates LPS-Induced NLRP3 Inflammasome Activation by Regulating of mTORC1 Pathways in Trophoblasts
Authors: Lee Sohee , Shin Jiha , Kim Jong-Seok , Shin Jongdae , Lee Sung Ki , Park Hwan-Woo
Published: November 2021

Pathological maternal inflammation and abnormal placentation contribute to several pregnancy-related disorders, including preterm birth, intrauterine growth restriction, and preeclampsia. TANK-binding kinase 1 (TBK1), a serine/threonine kinase, has been implicated in the regulation of various physiological processes, including innate immune response, autophagy, and cell growth. However, the relevance of TBK1 in the placental pro-inflammatory environment has not been investigated. In this study, we assessed the effect of TBK1 inhibition on lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation and its underlying mechanisms in human trophoblast cell lines and mouse placenta. TBK1 phosphorylation was upregulated in the trophoblasts and placenta in response to LPS. Pharmacological and genetic inhibition of TBK1 in trophoblasts ameliorated LPS-induced NLRP3 inflammasome activation, placental inflammation, and subsequent interleukin (IL)-1 production. Moreover, maternal administration of amlexanox, a TBK1 inhibitor, reversed LPS-induced adverse pregnancy outcomes. Notably, TBK1 inhibition prevented LPS-induced NLRP3 inflammasome activation by targeting the mammalian target of rapamycin complex 1 (mTORC1). Thus, this study provides evidence for the biological significance of TBK1 in placental inflammation, suggesting that amlexanox may be a potential therapeutic candidate for treating inflammation-associated pregnancy-related complications.
Dopamine Circuit Mechanisms of Addiction-Like Behaviors
Authors: Poisson Carli L. , Engel Liv , Saunders Benjamin T.
Published: November 2021

Addiction is a complex disease that impacts millions of people around the world. Clinically, addiction is formalized as substance use disorder (SUD), with three primary symptom categories: exaggerated substance use, social or lifestyle impairment, and risky substance use. Considerable efforts have been made to model features of these criteria in non-human animal research subjects, for insight into the underlying neurobiological mechanisms. Here we review evidence from rodent models of SUD-inspired criteria, focusing on the role of the striatal dopamine system. We identify distinct mesostriatal and nigrostriatal dopamine circuit functions in behavioral outcomes that are relevant to addictions and SUDs. This work suggests that striatal dopamine is essential for not only positive symptom features of SUDs, such as elevated intake and craving, but also for impairments in decision making that underlie compulsive behavior, reduced sociality, and risk taking. Understanding the functional heterogeneity of the dopamine system and related networks can offer insight into this complex symptomatology and may lead to more targeted treatments.
Proteome Analysis of Camellia nitidissima Chi Revealed Its Role in Colon Cancer Through the Apoptosis and Ferroptosis Pathway
Authors: Chen Yiwei , Zhang Fan , Du Zhengcai , Xie Jinling , Xia Lei , Hou Xiaotao , Hao Erwei , Deng Jiagang
Published: November 2021

Colon cancer is the third most common cancer in the world with a high mortality rate. At present, surgery combined with radiotherapy and chemotherapy is the primary treatment, but patient prognosis remains poor. Traditional Chinese medicine (TCM) has become a complementary and alternative source of anti-cancer drugs. Camellia nitidissima Chi (CNC) is a TCM used to treat a variety of cancers. However, the role of CNC in cancer remains elusive, and its effect and mechanism on colon cancer have not been reported. Here, we show that CNC exerts an excellent inhibitory effect on colon cancer proliferation and apoptosis induction in vitro and in vivo. We performed label free-based quantitative proteomic analysis to evaluate the HCT116 cells treated with CNC. Our data revealed a total of 363 differentially expressed proteins, of which 157 were up-regulated and 206 down-regulated. Gene Ontology enrichment analysis showed that these proteins were involved in tumor occurrence and development through multiple biological processes such as cell proliferation, cell apoptosis, cell cycle, and cell death. Interestingly, we also found significant changes in ferroptosis pathways. The role of essential proteins glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HMOX1) were verified. CNC decreased the expression of GPX4 and increased the expression of HMOX1 at the mRNA and protein levels in vivo and in vitro. Collectively, these findings reveal that CNC regulates colon cancer progression via the ferroptosis pathway and could be an attractive treatment for colon cancer.
Disparities in Reported Testing for 1p/19q Codeletion in Oligodendroglioma and Oligoastrocytoma Patients: An Analysis of the National Cancer Database
Authors: Zreik Jad , Kerezoudis Panagiotis , Alvi Mohammed Ali , Yolcu Yagiz U. , Kizilbash Sani H.
Published: November 2021

Purpose

A chromosomal 1p/19q codeletion was included as a required diagnostic component of oligodendrogliomas in the 2016 World Health Organization (WHO) classification of central nervous system tumors. We sought to evaluate disparities in reported testing for 1p/19q codeletion among oligodendroglioma and oligoastrocytoma patients before and after the guidelines.

Methods

The National Cancer Database (NCDB) was queried for patients with histologically-confirmed WHO grade II/III oligodendroglioma or oligoastrocytoma from 2011-2017. Adjusted odds of having a reported 1p/19q codeletion test for patient- and hospital-level factors were calculated before (2011-2015) and after (2017) the guidelines. The adjusted likelihood of receiving adjuvant treatment (chemotherapy and/or radiotherapy) based on reported testing was also evaluated.

Results

Overall, 6,404 patients were identified. The reported 1p/19q codeletion testing rate increased from 45.8% in 2011 to 59.8% in 2017. From 2011-2015, lack of insurance (OR 0.77; 95% CI 0.62-0.97;p=0.025), lower zip code-level educational attainment (OR 0.62; 95% CI 0.49-0.78;p<0.001), and Northeast (OR 0.68; 95% CI 0.57-0.82;p<0.001) or Southern (OR 0.62; 95% CI 0.49-0.79;p<0.001) facility geographic region were negatively associated with reported testing. In 2017, Black race (OR 0.49; 95% CI 0.26-0.91;p=0.024) and Northeast (OR 0.50; 95% CI 0.30-0.84;p=0.009) or Southern (OR 0.42; 95% CI 0.22-0.78;p=0.007) region were negatively associated with reported testing. Patients with a reported test were more likely to receive adjuvant treatment (OR 1.73; 95% CI 1.46-2.04;p<0.001).

Conclusion

Despite the 2016 WHO guidelines, disparities in reported 1p/19q codeletion testing by geographic region persisted while new disparities in race/ethnicity were identified, which may influence oligodendroglioma and oligoastrocytoma patient management.
Safety Profile of Immunotherapy Combined With Antiangiogenic Therapy in Patients With Melanoma: Analysis of Three Clinical Studies
Authors: Tian Hui , Wang Xuan , Lian Bin , Yan Xieqiao , Si Lu , Chi Zhihong , Sheng Xinan , Kong Yan , Mao Lili , Bai Xue , Tang Bixia , Li Siming , Zhou Li , Cui Chuanliang , Guo Jun
Published: November 2021

Objective: To describe the frequency and spectrum of treatment-related adverse events (TRAEs) of immunotherapy combined with antiangiogenic therapy in patients with melanoma.

Methods: This retrospective cohort study included three clinical trials on patients with stage III/IV melanoma treated with anti–PD 1 and antiangiogenic therapy.

Results: We analyzed data from 72 patients with a median follow-up time of 25.9 months (95% CI, 9.1–42.7 m). The median treatment duration was 7.5 months (range, 0.7–42.8 m), and the median of treatment cycles was 11.0 (range, 1–90). Most patients (70 of 72 or 97.2%) experienced TRAEs (mostly grades 1 or 2). No drug-related deaths were reported. Most TRAEs were hepatic (75%), endocrine (72.2%), skin (65.3%), and gastrointestinal tract (59.7%) manifestations, followed by myelosuppression (55.6%), renal dysfunction (55.6%), and dyslipidaemia (54.2%). The adverse event (AE) spectra were similar between regimens. Using multivariate Cox proportional risk models showed that hypertension was associated with a long PFS. According to our multivariable logistic regression models, TRAEs were not associated with ORR.

Conclusion: We found that the prevalence of AEs was higher than that of anti–PD-1 monotherapy. Most of the AEs were mild. The AE spectra were similar to those seen after anti–PD-1 or antiangiogenic therapy monotherapy, without unexpected AEs. Immunotherapy combined with antiangiogenic therapy was well tolerated.

Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03955354.
Caveolin-1/Endothelial Nitric Oxide Synthase Interaction Is Reduced in Arteries From Pregnant Spontaneously Hypertensive Rats
Authors: Troiano Jéssica A. , Potje Simone R. , Graton Murilo E. , Gonçalves Emily T. , Tostes Rita C. , Antoniali Cristina
Published: November 2021

We have investigated the role caveolae/caveolin-1 (Cav-1) plays in endothelial nitric oxide synthase (eNOS) activation and how it impacts pregnancy-induced decreased vascular reactivity in normotensive (Wistar rats) and spontaneously hypertensive rats (SHR). Wistar rats and SHR were divided into non-pregnant (NP) and pregnant (P). Nitrite levels were assessed by the Griess method in the aorta and mesenteric vascular bed. In functional studies, arteries were incubated with methyl-β-cyclodextrin (dextrin, 10mmol/L), which disrupts caveolae by depleting cholesterol, and concentration-response curves to phenylephrine (PE) and acetylcholine (ACh) were constructed. Electronic microscopy was used to determine endothelial caveolae density in the aorta and resistance mesenteric artery in the presence of vehicle or dextrin (10mmol/L). Western blot was performed to evaluate Cav-1, p-Cav-1, calmodulin (CaM), and heat shock protein 90 (Hsp90) expression. Cav-1/eNOS interaction in the aorta and mesenteric vascular bed was assessed by co-immunoprecipitation. Nitric oxide (NO) generation was greater in arteries from P groups compared to NP groups. Dextrin did not change vascular responses in the aorta from P groups or the number of caveolae in P groups compared to NP groups. Compared to NP Wistar rats, NP SHR showed smaller number of caveolae and reduced Cav-1 expression. Pregnancy did not alter Cav-1, CaM, or Hsp90 expression in the aorta or mesenteric vascular bed from Wistar rats or SHR. These results suggest that pregnancy does not alter expression of the main eNOS regulatory proteins, but it decreases Cav-1/eNOS interaction. Reduced Cav-1/eNOS interaction in the aorta and mesenteric vascular bed seems to be an important mechanism to increase eNOS activity and nitric oxide production in pregnant normotensive and hypertensive rats.
Factors Influencing Technical Efficiency in the EU Dairy Farms
Authors: Náglová Zdeňka , Rudinskaya Tamara
Published: November 2021

This paper aims to analyse the technical efficiency (TE) of dairy farms and find its determinants. To accomplish this problem, the Stochastic Frontier Analysis was applied. The data were obtained from the Farm Accountancy Data Network database for dairy farms (TF15-45—Specialist dairying) for 2004–2019. Dairy farms were divided into four clusters according to their physical size (number of livestock units per farm) and economic size (standard output per farm). The largest farms by physical and economic size are located in Denmark and Cyprus. The smallest, in comparison, are in Bulgaria, Croatia, Latvia, Lithuania, Austria, Poland, Romania, and Slovenia. Farms in the EU are relatively technically efficient, i.e., they use their resources efficiently to produce maximum output (production). However, they have the potential to achieve better economic results and be more competitive, as the size of farms’ is not fully optimised. The abolition of the milk quota can be considered a factor in improving technical efficiency, as the indicator is higher after the abolition. New and old member states have almost comparable technical efficiency levels (the p-value of the t-test is 0.463), with old members having slightly higher level TE. Subsidies have contradictory effects on TE. Farm efficiency with higher subsidies per cow is higher for farms with €51–100/cow. However, as subsidies increase, TE decreases. Only the group of farms with the highest subsidies has a higher TE. More diversified farms are more technically efficient than specialised farms. Milk yield did not influence the analysed indicator. The analysis results can serve the stakeholders as a tool for modelling future agricultural policy, as the European farms are very heterogenous and show different conditions and economic outcomes.
The Use of Temperate Tannin Containing Forage Legumes to Improve Sustainability in Forage–Livestock Production
Authors: Lagrange Sebastian P. , MacAdam Jennifer W. , Villalba Juan J.
Published: November 2021

Greenhouse gas emissions from ruminant livestock production systems contribute significantly to the environmental footprint of agriculture. Emissions are lower for feedlot systems than for grass-based systems primarily because of the extra time required for grass-finished cattle to reach slaughter weight. In contrast, legume forages are of greater quality than grasses, which enhances intake and food conversion efficiencies, leading to improvements in production and reductions in environmental impacts compared with forage grasses. In addition, the presence of certain bioactives in legumes such as condensed tannins (CT) enhance the efficiency of energy and protein use in ruminants relative to grasses and other feeds and forages. Grazing tannin-containing legumes also reduce the incidence of bloat and improve meat quality. Synergies among nutrients and bioactives when animals graze diverse legume pastures have the potential to enhance these benefits. Thus, a diversity of legumes in feeding systems may lead to more economically, environmentally, and socially sustainable beef production than grass monocultures or feedlot rations.
Comparison of MicroRNA Profiles in Extracellular Vesicles from Small and Large Goat Follicular Fluid
Authors: Ding Qiang , Jin Miaohan , Kalds Peter , Meng Chunhua , Wang Huili , Zhong Jifeng , Wang Xiaolong , Chen Yulin
Published: November 2021

Extracellular vesicles (EVs), which exist in the follicular fluid of ruminant ovaries, are considered as cargo carriers for the transfer of biomolecules to recipient cells. However, the functions and changes in EVs in antral follicles remain ambiguous. In the present study, we isolated and characterized EVs from goat follicular fluid by means of differential ultracentrifugation and Western blotting of marker proteins. Bioinformatics tools were used to detect miRNA expression levels in EVs. Different miRNA expression patterns of EVs exist in small to large follicles. Thirteen differentially expressed miRNAs (seven upregulated and six downregulated) were identified and used for analysis. A total of 1948 predicted target genes of 13 miRNAs were mapped to signaling pathways, and three significantly enriched pathways (FoxO, MAPK, and PI3K-AKT signaling pathways) were involved in follicular development, as revealed by KEGG enrichment analysis. Our findings suggest that EVs in follicular fluid play biofunctional roles during follicular development in goats.
Use of Antimicrobials in a French Veterinary Teaching Hospital: A Retrospective Study
Authors: Prouillac Caroline
Published: November 2021

Antibiotic resistance has become a major concern for not only human health, but also for animal health. To preserve the efficacy of antibiotics, it has become essential to establish measures to regulate the prescription of antibiotics to ensure their prudent use. In France, these measures have been translated into regulations for animal health since 2015, with the publication of three important regulatory texts. The results obtained on a national scale in terms of reducing the use of antibiotics have been satisfactory. The aim of our study was to evaluate the differences related to the prescription of antimicrobials at the veterinary teaching hospital of the Veterinary School of Lyon (CHUV) before and after the implementation of French regulations. Prescriptions and consumption of antimicrobials were examined, along with bacteriological analyses, for the period of 2014–2020, for companion animals and horses. The most frequently prescribed compounds were broad-spectrum antimicrobials, including penicillins with β-lactamase inhibitors, as well as first-generation cephalosporins tetracyclines and sulfamides. The prescription and consumption of critically important antibiotics (CIA) strongly decreased during the study period, with an increase of bacteriological analyses. This study shows the interest of having computerized tools to monitor the use of antimicrobials to implement corrective measures if needed.
Multi-Mode Active Suspension Control Based on a Genetic K-Means Clustering Linear Quadratic Algorithm
Authors: Wu Kun , Liu Jiang , Li Min , Liu Jianze , Wang Yushun
Published: November 2021

The traditional Linear quadratic regulator (LQR) control algorithm depends too much on expert experience during the selection of weighting coefficients. To solve this problem, we proposed a Genetic K-means clustering Linear quadratic (GKL) algorithm. Firstly, a 2-DOF 1/4 vehicle model and road input model are established. The weights of an LQR controller are optimized using a genetic algorithm. Then, a possible weighting space is constructed based on this optimal solution. Random weighting coefficients of each performance index are generated in this space. Next, LQR control for the 1/4 vehicle model is performed, and the simulation data are recorded automatically, with these random weighting values, different road classes, and driving speed. A machine learning dataset is built from these simulations. Finally, a K-means clustering algorithm is used to classify the LQR control active suspension into three performance modes: safety mode, comprehensive mode, and comfort mode. The optimal weighting matrix of each performance mode is determined to satisfy requirements for different types of drivers. The results show that the new GKL algorithm not only improves the suspension control effect but also realizes different performance modes. It can better adapt to the changes in driving conditions and drivers.
Efficient Position Change Algorithms for Prolonging Driving Range of a Truck Platoon
Authors: Srisomboon Issaree , Lee Sanghwan
Published: November 2021

Cooperative automated driving technology has emerged as a potential way to increase the efficiency of transportation systems and enhance traffic safety by allowing vehicles to exchange relevant information via wireless communication. Truck platooning utilizes this technology and achieves synchronized braking and acceleration, controlling two or more trucks simultaneously. This synchronized control makes driving with a very short inter-vehicle distance among trucks possible and reduces aerodynamic drag. This provides significant fuel consumption reduction, both in leading and trailing trucks, and achieves fuel-saving improvement. However, the static positioning sacrifices trucks in the front since they consume more fuel energy because of more air resistance than the rears. To solve this in-equivalent fuel consumption reduction benefit, this paper presents several heuristic algorithms to balance fuel consumption reduction and prolong the driving ranges by exploiting position changes among trucks in a platoon. Furthermore, the proposed algorithms try to reduce the number of position changes as much as possible to prevent any fuel waste caused by the unnecessary position change operations. In this manner, each truck in the platoon is likely to share a similar fuel consumption reduction with fewer position change counts, thus addressing the challenge of in-equivalent fuel savings distribution and obtaining optimal fuel efficiency. Our extensive simulation results show that the proposed algorithms can prolong the total distance by approximately 3% increased in two-truck platooning and even higher in six-trucks platooning of approximately 8%. Moreover, our proposed algorithms can decrease the position change count and ensure that trucks only switch to position arrangement once with no duplicate. Therefore, truck platooning obtains the maximum driving range with fewer position change counts, thus achieving efficient fuel saving.
Petrogenesis of Neoproterozoic Ultramafic Rocks, Wadi Ibib–Wadi Shani, South Eastern Desert, Egypt: Constraints from Whole Rock and Mineral Chemistry
Authors: Lasheen El Saeed R. , Saleh Gehad M. , Khaleal Farrage M. , Alwetaishi Mamdooh
Published: November 2021

This contribution deals with new geology, petrography, and bulk-rock/mineral chemistry of the poorly studied ultramafics of Wadi Ibib–Wadi Shani (WI–WS) district, South Eastern Desert, Egypt. These ultramafics are dismembered ophiolitic rocks that can be subdivided into serpentinites and serpentinized peridotites. Primary minerals such as olivine and pyroxene are absent in serpentinites, but relics of them occur in serpentinized peridotites. Pseudomorph after olivine is indicated by common hourglass textures with less mesh, whilst schistose bastites reflect a pyroxene pseudomorph. Chromite can be subdivided into Cr-spinel and Al-spinel. Cr-spinel ranges from chromite to magnesochromite in composition, whereas Al-spinel belongs to the spinel field. Cr-spinel includes YCr (Cr/(Cr+Al+Fe+3), YAl (Al/(Al+Cr+Fe+3), and YFe+3 (Fe+3/(Fe+3+Al+Cr), similar to forearc peridotite, whilst Al-spinel is more similar to abyssal peridotite, and may be formed during inanition of subduction processes in proto forearc environments. The main secondary minerals are tremolite, talc, and chlorite—which is subdivided into pycnochlorite and diabantite—and their temperature ranges from 174 to 224 °C. The examined rocks had undergone high partial melting degrees (>25%), as indicated by the Cr# of their unaltered cores (Cr-spinel, >0.6), whole rocks (Al2O3, SiO2, CaO, and MgO), trace and REEs, depleted Na2O, Al2O3, and Cr2O3 of clinopyroxene, and high forsterite content ((Fo = 100 Mg/Mg + Fe), av. 95.23 mol%), consistent with forearc settings.
Seasonal Variations in the Daily Mortality Associated with Exposure to Particles, Nitrogen Dioxide, and Ozone in Stockholm, Sweden, from 2000 to 2016
Authors: Olstrup Henrik , Johansson Christer , Forsberg Bertil , Åström Christofer , Orru Hans
Published: November 2021

Urban air pollutant emissions and concentrations vary throughout the year due to various factors, e.g., meteorological conditions and human activities. In this study, seasonal variations in daily mortality associated with increases in the concentrations of PM10 (particulate matter), PM2.5–10 (coarse particles), BC (black carbon), NO2 (nitrogen dioxide), and O3 (ozone) were calculated for Stockholm during the period from 2000 to 2016. The excess risks in daily mortality are presented in single and multi-pollutant models during the whole year and divided into four different seasons, i.e., winter (December–February), spring (March–May), summer (June–August), and autumn (September–November). The excess risks in the single-pollutant models associated with an interquartile range (IQR) increase for a lag 02 during the whole year were 0.8% (95% CI: 0.1–1.4) for PM10, 1.1% (95% CI: 0.4–1.8) for PM2.5–10, 0.5% (95% CI: −0.5–1.5) for BC, −1.5% (95% CI: −0.5–−2.5) for NO2, and 1.9% (95% CI: 1.0–2.9) for O3. When divided into different seasons, the excess risks for PM10 and PM2.5–10 showed a clear pattern, with the strongest associations during spring and autumn, but with weaker associations during summer and winter, indicating increased risks associated with road dust particles during these seasons. For BC, which represents combustion-generated particles, the pattern was not very clear, but the strongest positive excess risks were found during autumn. The excess risks for NO2 were negative during all seasons, and in several cases even statistically significantly negative, indicating that NO2 in itself was not harmful at the concentrations prevailing during the measurement period (mean values < 20 µg m−3). For O3, the excess risks were statistically significantly positive during “all year” in both the single and the multi-pollutant models. The excess risks for O3 in the single-pollutant models were also statistically significantly positive during all seasons.
Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers
Authors: Kisoh Keishi , Sugahara Go , Ogawa Yuko , Furukawa Suzue , Ishida Yuji , Okanoue Takeshi , Kohara Michinori , Tateno Chise
Published: November 2021

Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is the most common liver disorder in developed countries. Although many new therapeutics for NASH are present in the drug development pipeline, there are still no approved drugs. One of the reasons that makes NASH drug development challenging is the lack of appropriate animal NASH models that resolve issues arising from inter-species differences between humans and rodents. In the present study, we developed a choline-deficient, L-amino-acid-defined, high-fat-diet (CDAHFD)-induced human NASH model using human liver chimeric mice. We demonstrated human hepatocyte injury by an elevation of plasma human alanine aminotransferase 1 in mice fed CDAHFD. Histological analysis showed that CDAHFD feeding induced similar histological changes to human NASH patients, including ballooning, inflammation, apoptosis, regeneration of human hepatocytes, and pericellular and perisinusoidal fibrosis. The chimeric mice fed CDAHFD were treated with a peroxisome-proliferator-activated receptor α/δ agonist, Elafibranor. Elafibranor ameliorated steatosis, ballooning of hepatocytes, and preserved fibrosis progression. We developed a novel humanized NASH model that can elucidate pathophysiological mechanisms and predict therapeutic efficacy in human NASH. This model will be useful in exploring new drugs and biomarkers in the early stages of human NASH.
Prediction of Radiation-Induced Hypothyroidism Using Radiomic Data Analysis Does Not Show Superiority over Standard Normal Tissue Complication Models
Authors: Smyczynska Urszula , Grabia Szymon , Nowicka Zuzanna , Papis-Ubych Anna , Bibik Robert , Latusek Tomasz , Rutkowski Tomasz , Fijuth Jacek , Fendler Wojciech , Tomasik Bartlomiej
Published: November 2021

State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33–35 fractions). During the 28-month (median) follow-up 27 patients (28%) developed RIHT. For each patient, we extracted 1316 radiomic features from original and transformed images using manually contoured thyroid masks. Creating models based on clinical, radiomic features or a combination thereof, we considered 3 variants of data preprocessing. Based on their performance metrics (sensitivity, specificity), we picked best models for each variant ((0.8, 0.96), (0.9, 0.93), (0.9, 0.89) variant-wise) and compared them with external NTCP models ((0.82, 0.88), (0.82, 0.88), (0.76, 0.91)). We showed that radiomic-based models did not outperform state-of-art NTCP models (p > 0.05). The potential benefit of radiomic-based approach is that it is dose-independent, and models can be used prior to treatment planning allowing faster selection of susceptible population.
Impact of Serum γ-Glutamyltransferase on Overall Survival in Men with Metastatic Castration-Resistant Prostate Cancer Treated with Docetaxel
Authors: Une Minami , Takemura Kosuke , Inamura Kentaro , Fukushima Hiroshi , Ito Masaya , Kobayashi Shuichiro , Yuasa Takeshi , Yonese Junji , Board Philip G. , Koga Fumitaka
Published: November 2021

Background: Reports on the prognostic significance of serum γ-glutamyltransferase (GGT) in men with metastatic castration-resistant prostate cancer (mCRPC) are limited. In addition, GGT expression status in cancer tissues has not been well characterized regardless of cancer types. Methods: This retrospective study included 107 consecutive men with mCRPC receiving docetaxel therapy. The primary endpoints were associations of serum GGT with overall survival (OS) and prostate-specific antigen (PSA) response. The secondary endpoint was an association of serum GGT with progression-free survival (PFS). Additionally, GGT expression status was immunohistochemically semi-quantified using tissue microarrays. Results: A total of 67 (63%) men died during follow-up periods (median 22.5 months for survivors). On multivariable analysis, high Log GGT was independently associated with adverse OS (HR 1.49, p = 0.006) as were low hemoglobin (HR 0.79, p = 0.002) and high PSA (HR 1.40, p < 0.001). In contrast, serum GGT was not significantly associated with PSA response or PFS. Moreover, incorporation of serum GGT into established prognostic models (i.e., Halabi and Smaletz models) increased their C-indices for predicting OS from 0.772 to 0.787 (p = 0.066) and from 0.777 to 0.785 (p = 0.118), respectively. Furthermore, there was a positive correlation between serum and tissue GGT levels (ρ = 0.53, p = 0.003). Conclusions: Serum GGT may be a prognostic biomarker in men with mCRPC receiving docetaxel therapy. GGT overexpression by prostate cancer cells appears to be responsible for the elevation of GGT in the serum.
ERAS, a Member of the Ras Superfamily, Acts as an Oncoprotein in the Mammary Gland
Authors: Suarez-Cabrera Cristian , Ojeda-Perez Isabel , Sanchez-Baltasar Raquel , Page Angustias , Bravo Ana , Navarro Manuel , Ramirez Angel
Published: November 2021

ERAS is a relatively uncharacterized gene of the Ras superfamily. It is expressed in ES cells and in the first stages of embryonic development; later on, it is silenced in the majority of cell types and tissues. Although there are several reports showing ERAS expression in tumoral cell lines and human tumor samples, it is unknown if ERAS deregulated expression is enough to drive tumor development. In this report, we have generated transgenic mice expressing ERAS in myoepithelial basal cells of the mammary gland and in basal cells of stratified epithelia. In spite of the low level of ERAS expression, these transgenic mice showed phenotypic alterations resembling overgrowth syndromes caused by the activation of the AKT-PI3K pathway. In addition, their mammary glands present developmental and functional disabilities accompanied by morphological and biochemical alterations in the myoepithelial cells. These mice suffer from tumoral transformation in the mammary glands with high incidence. These mammary tumors resemble, both histologically and by the expression of differentiation markers, malignant adenomyoepitheliomas. In sum, our results highlight the importance of ERAS silencing in adult tissues and define a truly oncogenic role for ERAS in mammary gland cells when inappropriately expressed.