bluuebunny/crossref_metadata_2025 huggingface dataset:
Algebraic Properties of Intuitionistic L-fuzzy Multiset Finite Automata
Authors: Wang Yongbing , Zhang Lixia
Published: June 2021

Algrbraic properties and structures of intuitionistic L -fuzzy multiset finite automata (ILFMA) are discussed through congruences on a semigroup in this paper. Firstly,we put forward the notion of the intuitionistic L -fuzzy compatible relation, the compatible monoid associated to the intuitionistic L- fuzzy compatible relation can be effectively constructed, and we construct two finite monoids through two different congruence relations on a given ILFMA, then we also prove that they are isomorphic. Furthermore, using the quotient structure of ILFMA, algebraic properties of intuitionistic L -fuzzy multiset transformation semigroup are discussed. According to intuitionistic L -admissible relation and homomorphism of ILFMA, we show that there is a bijective correspondence between an ILFMA and the quotient structure of another ILFMA.
Managing Water Supply and Demand to Achieve Economic and Environmental Objectives: Application of Mathematical Programming and ANFIS Models
Authors: Najafabadi Mostafa Mardani , Mirzaei Abbas , Azarm Hassan , Nikmehr Siyamak
Published: June 2021

Integrated management of water supply and demand has been considered by many policymakers and due to its complexity, the decision makers have faced many challenges. In this study, we proposed an efficient framework for managing water supply and demand in line with the economic and environmental objectives of the basin. To design this framework, a combination of ANFIS and multi-objective augmented ε-constraint programming models and TOPSIS were used. First, using hydrological data from 2001 to 2017, the rate of water release from the dam reservoir was estimated with the ANFIS model; afterwards, its allocation to agricultural areas was performed by combining multi-objective augmented ε-constraint models and TOPSIS. To prove the reliability of the proposed model, the southern Karkheh basin in Khuzestan province, Iran, was considered as a case study. The results showed that this model is able to reduce irrigation water consumption and improve its economic productivity in the basin.
Physicochemical And Antioxidant Activity of Fruit Harvested From Eight Jujube (Ziziphus Jujuba Mill.) Cultivars At Different Development Stages
Authors: Yan Min , Wang Yan , Watharkar Ritesh Balaso , Pu Yunfeng , Wu Cuiyun , Lin Minjuan , Lu Dengyang , Liu Mingzhe , Bao Jingkai , Xia Yilei
Published: June 2021

Jujube is a crop highly resistant to drought and salinity, making it the main fruit tree in Xinjiang. The present study was to investigate the effect of development stage on physicochemical and antioxidant activity of fruit harvested from eight jujube cultivars situated in Xinjiang, China. The content of water, ascorbic acid, total polyphenols, catechin, epicatechin, proanthocyanidin and rutin decreased during development of jujube fruit harvested from the eight cultivars, while the contents of fructose, glucose, sucrose, cAMP, and cGMP greatly increased. The antioxidant activity determined by DPPH and ABTS radical scavenging decreased through the whole growth phase. After the early stages of development, a regular trend in changes of physicochemical and antioxidant characteristic was identified, while the differences among jujube cultivars gradually reduced with complete fruit development. This work contributes to understanding the changes that take place during the development of jujube fruit, indicating that development stage influenced the change in physicochemical and antioxidant activity more than cultivar, and the initial development stage was found to be rich in AA, phenolic compounds, and antioxidant activity, whereas the red maturity stage was rich in sugars, cAMP, and cGMP.
Home-Based Cardiac Rehabilitation During COVID-19: A Qualitative Study
Authors: Ganeshan Smitha , Tse Crystal , Beatty Alexis
Published: June 2021

Background: Cardiac rehabilitation (CR) has been shown to reduce mortality, morbidity, and hospitalizations. Increasingly, digital tools have augmented the ease of delivering programs outside of the traditional rehabilitation center setting. Because of the need for distancing during the COVID-19 pandemic, many cardiac rehabilitation (CR) centers suspended in-person services and pivoted to home-based CR (HBCR). In this study, we qualitatively evaluated implementation of HBCR, which included weekly phone or video visits for individualized exercise plans, nutrition and health education counseling, wellness sessions, and optional mobile phone applications.Methods: Patient participants and staff members (physician, nurses, exercise physiologists, dietician, administrative staff) participated in semi-structured interviews. Two independent reviewers coded interview transcripts for emergent themes and pre-specified themes from the Theory of Planned Behavior, Unified Theory of Acceptance and Use of Technology, and the Consolidated Framework for Implementation Research.Results: A total of 12 patients and 7 staff were interviewed. Narrative descriptions highlighted the isolation, fear, and disruption of life activities during COVID-19. Key facilitators of the HBCR patient experience included strong relationships with staff who served as coaches and sources of accountability and the ability of HBCR to deliver an individually tailored experience within a patient’s home. Important organizational factors for implementation included leadership buy-in, culture of change, and support for staff. Though technology tools facilitated communication and accountability, not all participants embraced technology and some reported challenges with use.Conclusions: Individually tailored HBCR can facilitate access for patients to participate outside of a CR center. Ongoing research is needed to understand the long-term outcomes of flexible delivery models that may include both in-person and remote visits, and the role of technology in these models.
Magnetic Resonance Imaging Measurement of Entorhinal Cortex in the Diagnosis and Differential Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease
Authors: Li Qianqian , Wang Junkai , Liu Jianghong , Wang Yumeng , Liang Peipeng , Li Kuncheng
Published: June 2021

Background: Several Magnetic Resonance Imaging (MRI) studies have shown that the entorhinal cortex (ERC) is the first brain area related to pathologic changes of Alzheimer's disease (AD), even before atrophy of hippocampus (HP). However, Change of ERC morphology (thickness, surface area and volume) in the progression from aMCI to AD, especially in the subtypes of aMCI (single domain and multiple domain, aMCI-s and aMCI-m), however, is still unclear. Methods: ERC thickness, surface area and volume were measured in 29 people with aMCI-s, 22 people with aMCI-m, 18 patients with AD and 26 age-/sex-matched healthy controls. Group comparisons of the ERC geometry measurements (including thickness, volume and surface area) were performed using analyses of covariance (ANCOVA). Furthermore, receiver operator characteristic (ROC) analysis and the area under the curve (AUC) were employed to investigate the classification ability (HC, aMCI-s, aMCI-m and AD from each other).Results: There was a significant ERC thickness decreasing tendency from HC to aMCI-s to aMCI-m to finally AD in both left and right hemispheres (left hemisphere: HC > aMCI-s > AD; right hemisphere: aMCI-s > aMCI-m > AD). For ERC volume, both the AD group and the aMCI-m group showed significantly decreased volume in both sides compared with the HC group. Besides, the AD group also had significantly decreased volume in both sides compared with the aMCI-s group. As for the ERC surface area, no significant difference was identified among the four groups. Furthermore, the AUC results demonstrated that combined ERC parameters (thickness and volume) can better discriminate the four groups from each other than ERC thickness alone. Finally, and most importantly, relative to HP volume, the capacity of combined ERC parameters was better at discriminating between HC and aMCI-s, as well as aMCI-m and AD.Conclusion: ERC atrophy, particularly combination of ERC thickness and volume, might be regarded as a promising candidate biomarker in the early diagnosis of aMCI.
Same Total Normal Forms Sperm Counts of Males From Lhasa and Shanghai, China
Authors: GU Benhong , WANG Shangren , LIU Feng , SONG Yuxuan , LI Jun , NI Yongtao , CHEN Min , HU Jianlin , Ouzhu Luobu , LI Zheng , LIU Li , LI Xia , LIU Xiaoqiang
Published: June 2021

Male infertility may be caused by genetic and/or environmental factors that impair spermatogenesis and sperm maturation. High-altitude (HA) hypoxic environments represent one of the most serious challenges faced by humans that reside in these areas. To assess the influence of the plateau environment on semen parameters, 2,798 males, including 1,111 native Tibetans and 1,687 Han Chinese individuals living in the plains(HCILP) who underwent pre-pregnancy checkups, were enrolled in this study. The semen samples of males were evaluated to determine conventional sperm parameters, sperm morphology, and sperm movement. Reproductive endocrine hormones (REHs) were detected in 474 males, including 221 Tibetans and 253 HCILP. Due to recurrent abortions in partners, the DNA fragmentation index (DFI) of 133 native Tibetans and 393 HCILP individuals was further compared. Luteinizing hormone (LH) (4.94 ± 2.12 vs. 3.29 ± 1.43 U/L), prolactin (11.34 ± 3.87 vs. 8.97 ± 3.48 nmol/L), E2/T (0.22 ± 0.11 vs 0.11 ± 0.05), median total sperm motility (61.20% vs. 51.56%), and DFI (23.11% vs. 7.22%) were higher in males from plateau areas while median progressive motility (PR) (35.60% vs. 41.12%), total number of PR sperms (51.61 vs. 59.63 mil/ejaculate), percentage of normal form sperms (3.70% vs. 6.00%), curvilinear velocity (36.10 vs. 48.97 μm/s), straight-line (rectilinear) velocity (14.70 vs. 31.52 μm/s), estradiol (103.82 ± 45.92 vs. 146.01 ± 39.73 pmol/L), progesterone (0.29 ± 0.27 vs. 2.22 ± 0.84 nmol/L), testosterone (4.90 ± 1.96 vs. 14.36 ± 5.24 nmol/L), and testosterone secretion index (ratio of testosterone to LH) (33.45 ± 22.86 vs 145.78 ± 73.41) were lower than those in males from the plains. There was no difference in median total sperm number (157.76 vs. 151.65 mil/mL), sperm concentration (52.40 vs. 51.79 mil/mL), volume (3.10 vs. 3.10 mL), total normal form sperms (5.91 vs. 6.58 mil/ejaculate, p50), and follicle-stimulating hormone (FSH) levels (4.13 ± 2.55 U/L vs 3.82 ± 2.35 U/L) between the two groups of males. The REH and sperm parameters of males from HA hypoxic environments were adaptively altered. Although the total number of PR sperm decreased and DFI increased, the Tibetan population that lives at HAs has been found to grown continuously and rapidly. These results supplement prior findings regarding the impact of HA on male reproductive function.
Macrovascular Complications in Patients with Diabetes Mellitus: Incidence and Impact on Survival in Kazakhstan
Authors: Sarría-Santamera Antonio , Orazumbekova Binur , Maulenkul Tilektes , Salustri Alessandro , Glushkova Natalya , Makashev Daniyar , Gaipov Abuzhappar
Published: June 2021

Background and aim: Diabetic patients are at an increased risk for the development of macrovascular complications such as acute myocardial infarction (AMI), stroke and lower-limb amputations (LLA). This study aimed to explore a. the incidence of hospital admission for macrovascular complications (AMI, stroke, and LLA); b. to assess the impact of hospital admission on survival in a large population with diabetes mellitus living in Kazakhstan. Materials and methods: Retrospective observational study using a nationwide anonymized electronic database of 98.469 hospitalized diabetic patients from Kazakhstan between November 2013 and December 2019. The incidence of hospital admissions for AMI, stroke and LLA were obtained to calculate their all-time cumulative incidence, and survival rate at follow-up. Results: The all-time cumulative incidence of hospital admissions was 1.30% for AMI, 1.94% for stroke and 2.94% for LLA. The incidence of macrovascular complications was statistically significantly higher in males compared to females (p-value<0.05). 29.03% of diabetic patients with AMI, 25.16% with stroke and 29.80% with LLA died during the follow-up period. Individuals with AMI had 3.58 (95% CI 3.20; 4.01) times, with stroke 3.86 (95% CI 3.52; 4.24) times and with LLA 3.63 (95% CI 3.38; 3.88) times higher hazard of 6-year death compared to diabetic patients free of these complications. The stratified survival analysis by sex indicated the lower survival in women than in men, and the lower survival in older age groups. Conclusion: The results from this study shows that cumulative incidence of AMI and stroke among diabetic patients admitted in the hospitals in Kazakhstan between 2013-2019 years was similar to the estimates from other countries, but the incidence of LLA was significantly higher in Kazakhstan. Patients with diabetes mellitus (DM) in Kazakhstan are at high risk of excess mortality if they suffer from macro-vascular complications. More research is required to explore the reasons for the high incidence of those complications, in order to propose systematic solutions for lowering the incidence and improve survival.
Inter-Laboratory Validation Of An ISO Test Method For Measuring Enzyme Activities In Soil Samples Using Colorimetric Substrates
Authors: Cheviron Nathalie , Grondin Virginie , Marrauld Christelle , Poiroux Francoise , Bertrand Isabelle , Abadie Josiane , Pandard Pascal , Riah-Anglet Wassila , Dubois Caroline , Maly Stanislav , Marques Catarina R , Asenjo Inmaculada Valverde , Alonso Alejandro , Diaz Domingo Marquina , Mougin Christian
Published: June 2021

The evaluation of soil quality requires the use of robust methods to assess biologically based-indicators. Among them, enzyme activities are used for several decades, but there is a clear need to update their measurement methods for routine use, in combining feasibility, accuracy and reliability. To this end, the platform Biochem-Env optimised a miniaturised method to measure enzyme activities in soils using colorimetric substrates in micro-well plates. The standardization of the method was carried out within the framework of ISO/TC 190/SC 4/WG 4 "Soil quality – Biological methods” workgroup, recommending an inter-laboratory evaluation for the publication of a full ISO standard.That evaluation, managed by the platform, was based on the measurement, in six soils of contrasted physicochemical properties, of the ten soil enzyme activities described in the standard. Eight laboratories were involved in the validation study. Only 2.7% of outliers were identified from the analyses of the whole dataset. The repeatability and reproducibility of the method were determined by computing, respectively, the intra-laboratory (CVr,) and inter-laboratory (CVR) coefficients of variation for each soil and enzyme. The mean CVr ranged from 4.5% (Phosphatase) to 9.9% (αGlucosidase), illustrating a reduced variability of enzyme activities within laboratories. The mean CVR ranged from 13.8% (Alkaline Phosphatase) to 30.9% (Phosphatase).Nevertheless, the method was repeatable, reproducible and sensitive. It also proved to be applicable for measuring enzyme activities in different types of soils. These results have been found successful by ISO/TC 190/SC4 and resulted in the publication of ISO 20130:2018 standard.
Analysis of Eddy Effect for Cu and CNT Bundle Based Through-Silicon Vias: Impact on Crosstalk and Power
Authors: Sahu Chopali Chanchal , Anand Shubham , Majumder Manoj Kumar
Published: June 2021

The performance of a three dimensional integrated circuit primarily depends on the filler material used in through silicon via (TSV). The mostly used filler material Cu is primarily facing severe reliability issues due to the skin effect and electromugration related problems at high frequencies. Therefore, in recent, single- and multi-walled carbon nanotubes (SWCNT and MWCNT) have been emerged as suitable filler materials in TSV. Additionally, at high frequencies, an electrmagetic force primarly induces to an eddy current that adversely affects the overall performance of a TSV. This paper for the first time demonstrates the impact of eddy current on Cu, bundled SWCNT and MWCNT based TSVs. An accurate RLGC circuit model is proposed by considering the eddy effect at the depletion layer and the silicon substrate region. The equivalent circuit parameters are modelled at 7 nm technology using a three line driver-via-load setup. Using the proposed setup, crosstalk and power disspation are analyzed with and without considering the eddy effect. Irrespective of TSV heights, the MWCNT bundle demonstrates substantially lower crosstalk delay, peak noise and power dissipation in comparison to the Cu and SWCNT bundle based TSVs.
Low Complexity Single Carrier Frequency Domain Detectors for Internet of Underwater Things (IoUT)s
Authors: Aljanabi Amer , Alluhaibi Osama , Ahmed Qasim Zeeshan Zeeshan , Khan Fahd Ahmed , Abbas Waqas Bin , Lazaridis Pavlos
Published: June 2021

This paper proposes low complexity detection for internet of underwater things (IoUT)s communication. The signal is transmitted from the source to the destination using several sensors. To simplify the computational operations at the transmitter and the sensory nodes, a single carrier frequency domain equalizer (SC-FDE) is proposed and amplify-and-forward (AF) protocols are employed. Fast Fourier transform (FFT) and use of cyclic prefix (CP) are also proposed to simplify these algorithms when compared to time-domain equalization. As precise channel data is difficult to capture in underwater communications, the adaptive implementation of FDE is proposed as a solution that can be employed when the channel experiences a fast doppler shift. The two adaptive detectors are based on the least mean-square (LMS) and recursive least square (RLS) principles. Numerical simulations show that the performance of the bit error rate (BER) performance of the proposed detectors is close to that of the ideal minimum mean square error (MMSE).
Transcriptional landscape of human microglia reveals robust gene expression signatures that implicates age, sex and APOE-related immunometabolic pathway perturbations
Authors: Patel Tulsi , Carnwath Troy , Wang Xue , Allen Mariet , Lincoln Sarah , Lewis-Tuffin Laura , Quicksall Zachary , Lin Shu , Tutor-New Frederick , Ho Charlotte , Min Yuhao , Malphrus Kimberly , Nguyen Thuy , Martin Elizabeth , Garcia Cesar , Alkharboosh Rawan , Grewal Sanjeet , Chaichana Kaisorn , Wharen Robert , Guerrero-Cazares Hugo , Quinones-Hinojosa Alfredo , Ertekin-Taner Nilufer
Published: June 2021

Microglia have fundamental roles in health and disease, however effects of age, sex and genetic factors on human microglia have not been fully explored. We applied bulk and single cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex and APOE. We identified a novel microglial signature, characterized its expression in bulk data from 1,306 brain samples across 6 regions and in single cell microglia transcriptome. We discovered microglial co-expression network modules associated with age, sex and APOE-ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single cell transcriptomes revealed significant overlap between age-associated module genes and both pro-inflammatory and disease-associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2 and BIN1. These data represent a well-characterized human microglial transcriptome resource; and highlight age, sex and APOE-related microglial immunometabolism perturbations with potential relevance in neurodegeneration.
A High-Fish Oil Diet Can Significantly Reshape The Gut Microbiota In Mice
Authors: Sun Han , Chen Dan , Yang Yingyun , Tan Bei , Huang Changzhi , Li Yue , Qian Jiaming
Published: June 2021

Background: Gut microbiota plays an essential role for human health and recent evidence has revealed the beneficial effects of fish oil supplements on the gut microbiota. The present study was to investigate the influence of fish oil on diet-based gut microbiota changes and colitis in mice and whether pyroptosis plays a role in this process.Results: A high-fish oil diet alleviated colitis, resulted in less weight loss and improved pathological scores. Caspase-1, activated in the dextran sulphate sodium (DSS) group, was suppressed by a high-fish oil diet. AIN-93M significantly decreased the gut microbial diversity of mice, increasing the abundances of Bacteroides and Parabacteroides and decreasing the abundance of Odoribacter. In contrast, gut microbial diversity was maintained in mice fed a high-fish oil diet; the Firmicutes: Bacteroidetes ratio was increased, the abundance of Parabacteroides was increased, and that the abundance of Odoribacter was decreased.Conclusion: AIN-93M can decrease gut microbiota diversity, which may be associated with a potential proinflammatory effect. Fish oil has anti-inflammatory effects. It can also restore and maintain microbial diversity and suppress pyroptosis activation.
Expression Profiles of Plasma IFN Signaling-Related miRNAs (ISR-miRNAs) at the Acute and Recovery Phase of COVID-19
Authors: Wu Jing , Liu Xingxiang , Shao Jianguo , Zhang Yuanyuan , Lu Renfei , Xue Hong , Xu Yunfang , Wang Lijuan , Zhou Hui , Yu Lugang , Yue Ming , Dong Chen
Published: June 2021

BackgroundCoronavirus disease 2019 (COVID-19) has brought major harm and challenges to the world. Although many studies have suggested that IFN-I could affect the life cycle of the virus by regulating the expression level of microRNAs, the expression characteristics of plasma IFN-I signaling-related miRNAs at the acute and recovery phase of COVID-19 remain unclear.MethodsDemographic characteristics and fasting blood samples were collected from the acute and recovery phases of 29 COVID-19 patients and 29 healthy controls matched by age (± 5years) and gender (1:1). Expression levels of 12 IFN signaling-related miRNAs were analyzed using RT-qPCR. The receptor-binding domain (RBD) IgG antibody in the convalescent plasma samples was detected using competitive ELISA.ResultsCompared with healthy controls, patients with COVID-19 presented increased levels of miR-29b-3p (~ 5.91-fold), miR-497-5p (~ 2.28-fold), and miR-1246 (~ 7.97-fold), and decreased expression levels of miR-186-5p (~ 6.39-fold) and miR-15a-5p (~ 3.26-fold) at the acute phase of infection. However, the expression levels of miR-29b-3p and miR-1246, which significantly elevated at the acute phase, were not different between individuals at the recovery phase and healthy controls. The expression levels of miR-30b-5p, miR-497-5p, miR-409-3p and miR-548c-5p in convalescent plasma samples were significantly lower than those in healthy controls. However, the concentration of miR-186-5p in the convalescent plasma samples was significantly higher than that in healthy controls and patients with acute infection. Furthermore, competitive ELISA results showed that the plasma level of miR-497-5p at the acute phase positively correlated with RBD-IgG antibody response (r=0.48, P=0.038).ConclusionsThe present study firstly reported that timely and appropriate regulation of IFN signaling-related miRNA expression plays a critical role during both acute and recovery phase of SARS-CoV-2 infection. Furthermore, the circulating miR-497-5p level was positively correlated to RBD-IgG antibody response in COVID-19 patients.
Platinum Layers Sandwiched between Black Phosphorous and Graphene for Enhanced SPR Sensor Performance
Authors: Pandaram Maheswari , Santhanakumar Subanya , Veeran Ravi , Balasundaram Rajesh Karuppaiya , Jha Rajan , Jaroszewicz Zbigniew
Published: June 2021

Highly sensitivity Surface Plasmon resonance (SPR) sensor consisting of Ag-Pt bimetallic films sandwiched with 2D materials Black Phosphorus (BP) and Graphene over Pt layer in Kretschmann configuration is analyzed theoretically using the Transfer Matrix Method. Numerical results shows that upon suitable optimization of thickness of Ag-Pt and number of layers of BP & graphene, sensitivity as high as 412º/RIU can be achieved for p-polarized light of wavelength 633 nm. This performance can be tuned and controlled by changing the number of layers of BP and graphene. Further, the addition of graphene and heterostructures of black phosphorus not only improved the sensitivity of the sensor but keep the FWHM of the resonance curve much smaller than the conventional sensor utilizing Au as plasmon metal and hence improved the resolution to a significant extent. We expect that this new proposed design will be useful for medical diagnosis, biomolecular detection and chemical examination.
Co-expression of Mesothelin and CA125/MUC16 Is a Prognostic Factor for Breast Cancer
Authors: Einama Takahiro , Yamagishi Yoji , Takihata Yasuhiro , Suzuki Takafumi , Yamasaki Tamio , Hirose Yuichi , Kobayashi Kazuki , Yonamine Naoto , Fujinuma Ibuki , Tsunenari Takazumi , Koga Makiko , Ishibashi Yusuke , Nagata Ken , Shiraishi Takehiro , Nakazawa Akiko , Iwasaki Toshimitsu , Shinto Eiji , Kato Kimi , Sato Kimiya , Ueno Hideki , Kishi Yoji , Tsuda Hitoshi
Published: June 2021

Background: The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the clinicopathological significance and prognostic implications of the co-expression of mesothelin and CA125 in breast cancer. Methods: The expression of mesothelin and CA125 was immunohistochemically examined in tissue samples collected from 478 breast cancer patients. The expression of these two molecules in more than 1% of tumor cells was defined as positive. The relationships between the co-expression of mesothelin and CA125, clinicopathological parameters, and clinical outcomes were analyzed by the chi-squared test and Cox’s univariate and multivariate proportional hazard model analyses. Results: Among 478 patients, mesothelin and CA125 were co-expressed in 48 (10%), mesothelin only in 75 (16%), CA125 only in 217 (45%), and neither in 234 (49%). A strong correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with unfavorable patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox’s multivariate analysis. Conclusion: This is the first study to demonstrate the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of these two molecules may play a significant role in the acquisition of aggressive clinical behavior.
A Hybrid CNN- GLCM Classifier for Detection and Grade Classification of Brain Tumor
Authors: gurunathan Akila , Krishnan Batri
Published: June 2021

Early identification and diagnosis of brain tumor using a supervised approach plays an essential role in the field of medicine. In this paper, an automated computer-aided method using deep learning architecture named CNN Deep net is proposed for the detection, classification and diagnosis of meningioma brain tumor. This proposed method includes preprocessing, classification, and segmentation of the primary occurring brain tumor in adults. The proposed CNN Deep Net architecture extracts the features internally from enhanced image and classifies them into normal and abnormal tumor images. The segmentation of tumor region is performed by the global thresholding with area morphological function method. This proposed method of fully automated classification and segmentation of brain tumor preserves the spatial invariance and inheritance. Furthermore, based on its feature attributes the proposed CNN Deep net classifier, classifies the detected tumor image belongs either to (low grade)benign or (high grade)malignant. This proposed CNN Deep net classification methodology approach with grading system is evaluated both quantitatively and qualitatively. The quantitative measures such as sensitivity, specificity, accuracy, Dice similarity coefficient, precision, F-score of the proposed classification and segmentation methodology states a better segmentation accuracy and classification rate of 99.4% and 99.5% with respect to ground truth images.
Chemotherapy Choice in Neoadjuvant Dual Her2 Blockade; is it Really Necessary to add Anthracycline?
Authors: ozveren ahmet , Erdogan Atike Pinar , Ekinci Ferhat , Kirdok Kutay , Almuradova Elvina , Karabulut Bulent
Published: June 2021

1. BackgroundAddition of trastuzumab and pertuzumab to neoadjuvant chemotherapy in human epidermal growth factor receptor 2(HER-2) positive patients is the current clinical standard today. In studies on neoadjuvant chemotherapy, the primary endpoint is pathological complete response (pCR). More real-life data are needed to answer whether the presence of anthracycline in the chemotherapy regimen enhances complete response with neoadjuvant dual HER-2 blockade, and whether cardiotoxicity increases with dual HER-2 blockade after anthracycline.2. Methods52 patients with HER-2 positive breast cancer who received neoadjuvant chemotherapy were retrospectively evaluated. Three centers participated in the study (İzmir Kent Hospital, Manisa Celal Bayar University, Ege University). The effects of chemotherapy regimen and several other factors such as age, stage, menopause status, lymph node positivity, hormone receptor positivity on pCR were evaluated. Also presence of cardiotoxicity was evaluated.3. ResultsThe mean age of diagnosis was 46 ± 9 (range: 26-67), and 50% (26) of the patients were postmenopausal. The pCR rate was 71.2% (37) in the entire study group. In terms of pCR, there was no significant difference between those who use an anthracycline containing and non-anthracycline containing regimens (71.4% vs 70%, p=1.000), those with negative and positive hormone receptors (64.7% vs 74.3%, p=0.525), those with Ki67 levels of %20 or less and those over 20% (60% vs 73.8%, p=0.447), premenopausal and postmenopausal ones (76.9% vs 65.4%, p=0.054). 4. ConclusionsAs a result of the data we obtained, it was concluded that adding anthracycline regimen to dual HER-2 blockade in the neoadjuvant period did not bring additional benefits in terms of pCR. Additional studies are needed on whether the use of anthracycline-containing regimen contributes additionally in patients who will use the neoadjuvant pertuzumab-trastuzumab combination.
N-Acetylcysteine Attenuates Monocrotophos-induced Toxicity by Mitigating Oxidative Stress and Structural Changes in Rat Liver
Authors: Singh Jagjeet , Phogat Annu , Prakash Chandra , Kumar Vijay , Malik Vinay
Published: June 2021

The present study evaluated the effect of N-acetylcysteine (NAC) against sub chronic monocrotophos (MCP) exposure induced oxidative stress in rat liver. Albino wistar rats were divided into control, NAC treated, MCP and MCP treated groups. An oral dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) was administered for 28 days. We observed high oxidative stress generation on MCP exposure in liver tissue as evident by significant increase in lipid peroxidation, protein oxidation and decreased glutathione content followed by altered activities of superoxide dismutase, catalase and acetylcholinesterase. Sub chronic MCP exposure caused an array of cellular and structural alternations in lipids and proteins of liver tissue as depicted by the FTIR, histopathological and electron microscopic analysis. N-acetylcysteine attenuated the loss of glutathione and prevented lipid peroxidation and protein oxidation. Pre-treatment of NAC also restored histological and ultra space structural alternations. So NAC protects oxidative stress and tissue damage induced by sub chronic MCP exposure in rat liver; suggesting the therapeutic and antioxidant potential of NAC.
Accelerated Hypofractionated Radiotherapy With Simultaneous Integrated Boost With Volumetric Modulated Arc Technique in Patients With Breast Cancer: a Phase 2 Study.
Authors: Yadav Budhi Singh , Gupta Shipra , Dahiya Divya , Gupta Ankita , Oinam Arun
Published: June 2021

PurposeTo assess feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) with volumetric modulated arc technique (VMAT) in patients with breast cancer.Methods Total 27 patients after breast conserving surgery (BCS) were included in this study. Patients were planned on 4-dimensional computerized tomogram (4D-CT) and contouring was done using RTOG guidelines. Dose delivered was 34 Gy/10#/2wk to the breast and 40 Gy/10#/2wk to the tumor bed as SIB with VMAT technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs at risk were calculated. Toxicities and cosmesis were assessed using RTOG LENT-SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) was calculated with Kaplan Meier curves.ResultsMean age of the patients was 42 years. Left and right breast cancer was seen in 17 (63%) and 10 (37%) patients, respectively. Ipsilateral lung mean V16 and contralateral lung V5 was 16.01% and 3.73%, respectively. Mean heart dose from the left and right breast was 7.25Gy and 4.37Gy, respectively. Mean dose to the contralateral breast, oesophagus and spinal cord was 2.64Gy, 3.69Gy and 3.15Gy, respectively. Thyroid V25 mean was 19.69%.Grade 1 and 2 acute skin toxicity was observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema and induration were observed in 1 (3.7%), 2 (7.4%) and 4(14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient each. Median follow-up was 48 months (range 12-58 months). At 4 years breast induration, edema and fibrosis each were observed in 1(3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred 1(3.7%) and 2(7.4%) patients, respectively. DFS and OS at 3-years was 88% and 92%, respectively.ConclusionWith this RT schedule acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS and OS were good.
Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves.
Authors: Quaresima Virginia , Scarpazza Cristina , Sottini Alessandra , Fiorini Chiara , Signorini Simona , Delmonte Ottavia Maria , Signorini Liana , Quiros-Roldan Eugenia , Imberti Luisa
Published: June 2021

Background: Coronavirus Disease 2019 (COVID-19) severity seems to be influenced by genetic background, sex, age, and presence of specific comorbidities. So far, little attention has been paid to sex-specific variations of demographic, clinical and laboratory features of COVID-19 patients referred to the same hospital in the two consecutive pandemic waves.Methods: Demographic, clinical and laboratory data were collected in 1,000 COVID-19 patients (367 females and 633 males), 500 hospitalized in the first wave and 500 in the second one, at the ASST Spedali Civili of Brescia from March to December 2020. Statistical analyses have been employed to compare data obtained in females and males, taking into account their age, and during the first and second COVID-19 waves. Results: The mean age at the time of hospitalization was similar in females and males but was significantly higher for both in the second wave; the time elapsed from symptoms onset to hospital admission did not differ between sexes in the two waves and no correlation was observed between delayed hospital admission and length of hospitalization. The number of multi-symptomatic males was higher than that of females and patients with a higher number of comorbidities were more frequently admitted to intensive care unit (ICU) and more frequently died. Older males remained in ICU longer than females and showed a longer disease duration, mainly the first wave. The highest levels of white blood cells, neutrophils, C-reactive protein and fibrinogen were significantly higher in males and in the first, and along with higher levels of D-dimer, ferritin, lactate dehydrogenase and procalcitonin which were preferentially documented in patients requiring ICU or died. While the ICU death rate was higher in males, the overall death rate did not differ between the sexes; however, the deceased women were older.Conclusions: These data indicate that once patients were hospitalized, the risk of dying was similar between females and males. Therefore, future studies should aim at understanding the reasons why, for a given number of SARS-CoV-2 infection, less females develop the disease requiring hospitalization.
Role of APOA1 in the Resistance to Platinum-Based Chemotherapy in Squamous Cervical Cancer
Authors: He Yue , Han Su-Bin , Liu Yang , Zhang Jing-Jing , Wu Yu-Mei
Published: June 2021

Introduction: To investigate the mechanism by which apolipoprotein A1 (APOA1) enhances the resistance of cervical squamous carcinoma to platinum-based chemotherapy.Methods: Two cervical squamous carcinoma cell lines (SiHa and Caski) overexpressing APOA1 (OE) were constructed, treated with carboplatin (CBP), and compared to normal control (NC) cells.Results: In both cell lines, the clone-forming ability of CBP-treated cells was lower than that of untreated cells, and the clone formation rate of OE cells was lower than that of NC cells (p < 0.05), indicating that APOA1 overexpression enhanced chemoresistance. A screen for APOA1 downstream proteins affecting platinum-based chemoresistance using TMT revealed 64 differentially expressed proteins, which were subjected to GO annotation, KEGG enrichment, subcellular localization, structural domain annotation and enrichment, clustering, and interaction network analyses. Twenty-nine differentially expressed proteins matching cancer-relavent association terms were screened and parallel response monitoring identified 21 as possibly involved in the mechanism of platinum-based chemoresistance.Conclusions: Our analysis suggested that the mechanism may involve numerous regulatory pathways, including promoting tumor growth via the P38 MAPK signaling pathway through STAT1, promoting tumor progression via the PI3K signaling pathway through CD81 and C3, and promoting resistance to platinum-based chemotherapy resistance through TOP2A.
Elucidating Multiple Negative Differential Resistance and Rectification Ratio Through L-Aspartic Acid at Nanometre Scale Using Symmetrical Metal Electrodes
Authors: Sikri Gaurav , Sawhney Ravinder Singh
Published: June 2021

Protein-based electronics is one of the growing areas of bio-nanoelectronics, where novel electronic devices possessing distinctive properties, are being fabricated using specific proteins. Furthermore, if the bio-molecule is analysed amidst different electrodes, intriguing properties are elucidated. This research article investigates the electron transport properties of L-aspartic acid (i.e., L-amino acid) bound to symmetrical electrodes of gold, silver, copper, platinum and palladium employing NEGF-DFT approach using self-consistent function. The theoretical work function of different electrodes is calculated using local density approximation and generalized gradient approximation approach. The calculated work function correlates well with the hole tunnelling barrier and conductance of the molecular device, which further authenticate the coupling strength between molecule and electrode. Molecule under consideration also exhibits the multiple negative differential resistance and rectification ratio with all the different electrodes, due to its asymmetrical structure. The molecular device using platinum electrodes exhibits the highest peak to valley ratio of 1.38 and rectification ratio of 3.20, at finite bias. The switching characteristics of different molecular device are justified with detailed transmission spectra and MPSH. These results indicate that L-aspartic acid and similar biomolecule can be vital to the growth of Proteotronics.
Neohesperidin Protects Hypertension-induced Endothelial Injury by Intervening Oxidative Stress
Authors: Zhang Jingsi , Hui Yuanshu , Liu Fengyi , Yang Qian , Lu Yi , Chang Yeting , Liu Qinlong , Ding Yanchun
Published: June 2021

Background: Currently, vascular endothelial damage caused by hypertension is one of the major health challenges facing countries around the world. Neohesperidin has been shown to play an important role in tumorigenesis and tumorigenesis, cardiac hypertrophy and remodeling, and oxidative stress. However, whether Nehesperidin plays an important role in endothelial injury induced by hypertension has not been clarified.Results: In this study, Angiotensin II was used to induce hypertension in mice. Blood pressure and vasoconstrictor function were measured, vascular thickness and fibrosis were detected by H&E and Masson tricolor staining, vascular inflammation was detected by immunofluorescence, oxidative stress was detected by DHE staining, and markers such as fibrosis, hypertrophy and oxidative stress were detected by qPCR. At the same time, we observed the effect of Nehesperidin on Ang II-induced HUVECs. The results showed that neohesperidin can significantly inhibit Ang II-induced hypertension, vascular thickness, fibrosis, oxidative stress and inflammation in vivo and in vitro. Conclusions: The results suggested that Nehesperidin could act as an antioxidant to significantly inhibit Ang II-induced hypertension and endothelial injury in HUVECs in mice by inhibiting oxidative stress response.
NAT10 as a Potential Prognostic Biomarker and Therapeutic Target for HNSCC
Authors: Tao Wenjie , Tian Guocai , Xu Shengming , Li Jiayi , Zhang Zhiyuan , Li Jiang
Published: June 2021

Background. Increasing evidence has demonstrated the critical roles of mRNA modification regulators on multiple types of cancers. However, it is still poorly known about the prognostic and therapeutic value of mRNA modification regulators in HNSCC.Methods. The gene expression profile of 36 mRNA modification regulators and their corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Stepwise regression in R with both directions was used to construct a model for the prognosis of HNSCC. Univariate Cox regression survival analysis was performed to find the most significant risk gene. Gene set enrichment analysis (GSEA) was applied to identify the cancer-associated pathways with NAT10. Immunohistochemistry (IHC) staining was performed to evaluate the expression of NAT10 in formalin fixed paraffin-embedded (FFPE) samples of HNSCC. Univariate and multivariate Cox regression survival analysis performed to identify the independent risk factors associated with the OS of patients with HNSCC. HNSCC cell lines (Cal-27, FaDu, and Detroit-562) were transfected with short interfering RNA (siRNA) targeting NAT10 or treated with Remodelin, a small-molecule inhibitor of NAT10. Knockdown efficiency of siRNA was assessed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. In addition, CCK-8 assay, scratch assay and transwell assay were used to examine the proliferation, migration, and invasion abilities of the three HNSCC cell lines after NAT10 was inhibited genetically and pharmaceutically. Cell cycle and cell apoptosis assays were performed by flow cytometry. Finally, the therapeutic value of Remodelin in HNSCC was evaluated via a patient-derived xenograft (PDX) model. The statistical analysis was performed with SPSS 23.0.Results. A risk prediction model containing ten mRNA modification regulators was constructed and showed prognostic value in HNSCC. NAT10 was further identified as a key risk gene and independent prognostic factor in TCGA HNSCC dataset. The GSEA analysis suggested that high NAT10 expression was associated with MYC, E2F, G2M checkpoint, mTORC1, DNA repair and oxidative phosphorylation pathways. NAT10 protein expression was significantly up-regulated in tumour cells compared to normal epithelial cells in FFPE samples and increased NAT10 protein expression was correlated with poor overall survival of 267 HNSCC patients. Genetic depletion of NAT10 using siRNA or chemical inhibition of NAT10 using Remodelin resulted in reduced cell proliferation, migration and invasion abilities in Cal-27, FaDu and Detroit-562 cells. Knockdown of NAT10 using siRNA significantly increased cell cycle arrest in S/G2-phase. Remodelin significantly inhibited tumour growth and tumour cell proliferation in the PDX model of HNSCC.Conclusions. NAT10 could be a potential prognostic marker and a therapeutic target for HNSCC.
Contrast-enhanced Mammographic Features of In-situ and Invasive Ductal Carcinoma Manifesting Microcalcifications Only: Feasibility for Predicting Underestimation
Authors: Cheung Yun-chung , Chen Kueian , Yu Chi-Chang , Ueng Shir-Hwa , Lee Chia-Wei , Chen Shin-Cheh
Published: June 2021

Background:The contrast-enhanced mammographic features of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) manifesting microcalcifications only on mammograms were evaluated to determine whether they could predict DCIS underestimation.Methods:We reviewed the records of patients who underwent mammography-guided breast biopsy with vacuum-assisted core needle biopsy to enrol patients meeting the following inclusion criteria: (1) mammographic microcalcifications only; (2) contrast-enhanced spectral mammography within 2 weeks before biopsy; (3) mammography-guided biopsy-proven cancer (including DCIS and IDC); and (4) subsequent surgical treatment in our hospital. The presence or absence, size, morphology and texture of enhancement on contrast-enhanced spectral mammography were compared to determine any significant differences.Results:A total of 49 patients (27 DCIS, 22 IDC) were enrolled. Forty patients (81.6%) showed enhancement, including 18 (45%) DCIS and 22 (55%) IDC patients. All 9 unenhanced cancers were DCIS. DCIS showed 72.22% nonmass enhancement and 83.33% pure ground glass enhancement. IDC showed more mass (72.2% to 27.8%) and solid enhancements (83.33% to 16.67%). The cancer and texture of enhancement were significantly different, with moderate diagnostic performance for the former (p value <0.01, AUC= 0.66, sensitivity= 93%, specificity= 39%) and the latter (p value <0.01, AUC= 0.74, sensitivity= 0.65, specificity= 83%). DCIS showed a significant difference in enhanced texture compared with upgraded IDC and IDC (p=0.0226 and 0.0018, respectively).Conclusions:CESM-enhanced features can feasibly predict DCIS underestimation. Biopsy-proven DCIS without associated enhancement has a low DCIS upgrade rate.Nonmass and pure ground glass enhancements were closely related to DCIS, and cases showing mass and unpurified solid enhancements should be suspected as IDC.
HOXB9 Promotes Laryngeal Squamous Cell Carcinoma Progression by Upregulating MMP12
Authors: Sun Chuanhui , Wang Peng , Chen Yujiang , Li Qiuying , Deng Hua , Han Changsong , Sun Yanan
Published: June 2021

Background：The HOX family transcription factor HOXB9 is a crucial element in the progression of various cancers. In the previous study conducted by the investigators, a drastically higher HOXB9 expression was reported in laryngeal squamous cell cancer (LSCC), when compared to adjacent normal laryngeal squamous tissues. Furthermore, a high level of HOXB9 was closely correlated with histological grade and overall survival in LSCC patients. However, the underlying molecular mechanisms have not been fully elucidated.Results: The present study explored the molecular mechanisms of HOXB9 in LSCC progression. Furthermore, the in vitro and in vivo studies revealed that the gene knockout of HOXB9 using the CRISPR/CAS9 system inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. Mechanistic studies in LSCC cell lines and human LSCC specimens demonstrated that HOXB9 promotes LSCC progression by directly upregulating the MMP12 expression at the level of its transcription.Conclusions: Collectively, the present study is the first to demonstrate the role of HOXB9 in the regulation of LSCC progression by enhancing the upregulation of MMP12.