bluuebunny/crossref_metadata_2025 huggingface dataset:
OsGATA16, a GATA Transcription Factor, Confers Cold Tolerance by Repressing OsWRKY45-1 at the Seedling Stage in Rice
Authors: Zhang Hongjia , Wu Tao , Li Zhao , Huang Kai , Kim Na-Eun , Ma Ziming , Kwon Soon-Wook , Jiang Wenzhu , Du Xinglin
Published: February 2021

BackgroundCold stress in rice is a major abiotic stress that adversely affects growth and substantially reduces rice yield. Identification of cold-related functional rice genes is important for breeding programs aimed at increasing resilience and yield in rice crops. GATA-family transcription factors involve diverse function in rice, however, their roles in the response to low-temperature stress remain unclear.ResultsA GATA-type zinc finger transcription factor, OsGATA16, that increases cold tolerance in rice. OsGATA16 is an OsGATA subfamily-II protein and contains eleven putative phosphorylation sites, NLS, and several conserved domains. Overexpression of OsGATA16 increased tolerance to cold stress at seedling stage. Transcriptional analysis showed that OsGATA16 was induced by cold and ABA treatments, but was repressed by drought, cytokinin, and JA. OsGATA16 was expressed in all plant tissues, with highest expression in panicles. Subcellular localization and transcriptional analysis indicated that OsGATA16 acted as a nuclear-targeted transcriptional suppressor. Four cold-related genes (OsWRKY45-1, OsSRFP1, OsCYL4, and OsMYB30) were repressed in OsGATA16-overexpression lines compared with wild type after low-temperature exposure. Yeast one-hybrid and Dual-luciferase reporter assays showed that OsGATA16 bound to the promoter of OsWRKY45-1 and repressed its expression. Eleven SNPs within OsGATA16 were identified and haplotype analysis showed a polarization between Japonica and Indicia subspecies. A non-synonymous SNP was identified that explained differences in cold tolerance among the 137 rice accessions.ConclusionA novel GATA transcription factor, OsGATA16, plays a positive role in cold tolerance at the seedling stage in rice by direct repression of OsWRKY45-1 expression. One SNP was identified that explained cold tolerance differences among rice accessions. These results support future breeding programs to improve cold tolerance in commercial rice crops.
Dim Target Detection Method Based on Deep Learning in Complex Traffic Environment
Authors: Zheng Hao , Liu Jianfang , Ren Xiaogang
Published: February 2021

Although the current vehicle detection and recognition framework based on deep learning has its own characteristics and advantages, it is difficult to effectively combine multi-scale and multi category vehicle features, and there is still room for improvement in vehicle detection and recognition performance. Based on this, an improved fast R-CNN convolutional neural network is proposed to detect dim targets in complex traffic environment. The deep learning model of fast R-CNN convolutional neural network is introduced into the image recognition of complex traffic environment, and a structure optimization method is proposed, which replaces vgg16 in fast RCNN with RESNET to make it suitable for small target recognition in complex background. Max pooling is the down sampling method, and then feature pyramid network is introduced into RPN to generate target candidate box to optimize the structure of convolutional neural network. After training with 1497 images, the complex traffic environment images are identified and tested.
Normative Data on Spontaneous Stride Velocity, Stride Length, and Walking Activity in a Non-controlled Environment.
Authors: Poleur Margaux , Ulinici Ana , Daron Aurore , Schneider Olivier , Farra Fabian Dal , Demonceau Marie , Annoussamy Mélanie , Vissière David , Eggenspieler Damien , Servais Laurent
Published: February 2021

BACKGROUND Normative data are necessary for validation of new outcome measures. Recently, the 95th centile of stride speed was qualified by the European Medicines Agency as a valid secondary outcome for clinical trials in subjects with Duchenne muscular dystrophy. This study aims to obtain normative data on spontaneous stride velocity and length in a non-controlled environment and their evolution over a 1-year period.METHOD 91 Healthy volunteers (50 females, 41 males), mean age 16 years 11 months, were recruited and assessed at baseline and 12 months later. 4-stair climb, 6-minute walk test, 10-metre walk test and rise from floor were performed. Stride length, stride velocity, and the distance walked per hour were studied in daily living for one month after each evaluation.RESULTS We observed significant positive correlations of the stride length with age and height of participants, and a significant increase of the median stride length over 1-year in children. In children, the 95th centile stride velocity was not correlated with age and was stable over a 1-year period.CONCLUSION This study provides with data on the influence of age, height, and gender on stride velocity and length as well as the natural change over 1-year in controls.
Evaluating the Covalent Binding of Carbapenems on BlaC Using Noncovalent Interactions
Authors: Sun Lu , Fan Hongjun , Zhong Shijun
Published: February 2021

Carbapenems, as irreversible covalent binders and slow substrates to the Class A β-lactamase (BlaC) of Mycobacterium tuberculosis, can inhibit BlaC to hydrolyze the β-lactam drugs which are used to control tuberculosis. Their binding on BlaC involves covalent bonding and noncovalent interaction. We introduce a hypothesis that the noncovalent interactions dominate the difference of binding free energies for covalent ligands based on the assumption that their covalent bonding energies are same. MM/GBSA binding free energies calculated from the noncovalent interactions, provided a threshold with respect to the experimental kinetic data, to select slow carbapenem substrates which were either constructed using the structural units of experimentally identified carbapenems or obtained from the similarity search over the ZINC15 database. Combining molecular docking with consensus scoring and molecular dynamics simulation with MM/GBSA binding free energy calculations, a computational protocol was developed from which several new tight-binding carbapenems were theoretically identified.
IL17A (rs2275913 G>A) and IL17F (rs2397084 T>C) Gene Polymorphisms: Relation to Psoriasis Risk and Response to Methotrexate.
Authors: Hamza Ashraf , Elwafa Reham AbdelHaleem Abo , Ramadan Nasren , Omar Salma Samir
Published: February 2021

Background The relation of IL17 polymorphisms to psoriasis risk and response to methotrexate has not been previously studied in Egyptians. Objectives To study the relation of IL17A (rs2275913 G>A) and IL17F (rs2397084 T>C) polymorphisms to psoriasis risk and assess their predictive role as regards response to methotrexate.Patients & Methods IL17A (rs 2275913) and IL17F (rs 2397084) polymorphisms were evaluated in 100 healthy subjects and 100 patients with chronic plaque psoriasis by real time-PCR. Patients were given methotrexate weekly intramuscularly (0.6mg/kg) for 12 weeks. Results IL17F TT genotype was more frequent in patients (87%) than controls (68%), while TC genotype was more frequent in controls (32%) than patients (13%). TT genotype was associated with increased risk of psoriasis whereas the TC allele was associated with a decreased risk. There was no significant difference regarding IL17A GG, GA and AA genotype frequencies between patients and controls. PASI ≥75% was achieved in 22 patients (73.3%) with the TT genotype and 8 patients (26.7%) with TC genotype (p=0.019). Conclusion IL17F (rs2397084 T>C) TT genotype could be considered a susceptibility marker in Egyptian patients. Psoriatic patients with TT genotype and T allele of IL17F (rs2397084 T>C) are likely to show a better response to methotrexate.
Microbiomes of Clownfish and Their Symbiotic Host Anemone Converge Before Their First Physical Contact.
Authors: Audet-Gilbert Émie , Sylvain François-Étienne , Bouslama Sidki , Derome Nicolas
Published: February 2021

BackgroundOne of the most charismatic, and yet not completely resolved example of mutualistic interaction is the partnership of clownfish and its symbiotic sea anemone. The mechanism explaining this tolerance currently relies on the molecular mimicry of clownfish epithelial mucus, which could serve as camouflage, preventing the anemone's nematocysts' discharge. Resident bacteria are known as key drivers of epithelial mucus chemical signature in vertebrates. A recent study has proposed a restructuration of the skin microbiota in a generalist clown fish when first contacting its symbiotic anemone. We explored a novel hypothesis by testing the effect of remote interaction on epithelial microbiota restructuration in both partners. MethodsWith metataxonomics, we investigated the epithelial microbiota dynamic of 18 pairs of percula clownfish (Amphiprion percula) and their symbiotic anemone Heteractis magnifica in remote interaction, physical interaction and control groups for both partners during a four weeks trial.ResultsPhysical and Remote Interaction groups’ results evidence gradual epithelial microbiota convergence between both partners when fish and anemone were placed in the same water system. This convergence occurred preceding any physical contact between partners, and was maintained during the two-weeks interaction period in both contact groups. After the interaction period, community structure of both fish and anemone’s epthelial community structures maintained the interaction signature two weeks after fish-anemone pairs separation. Furthermore, the interaction signature persistence was observed both in Physical and Remote Interaction groups, thus suggesting that water-mediated chemical communication between symbiotic partners was strong enough to shift the skin microbiota durably, even after the separation of fish-anemone pairs. Finally, our results suggest that fish-anemone convergent microbiota restructuration was increasingly associated with the parallel recruitment of three Flavobacteriaceae strains closely related to a tyrosinase-producing Cellulophaga tyrosinoxydans. ConclusionsOur study shows that bacterial community restructuration, in the acclimation process, does not only rely on direct physical contact. Furthermore, our results challenge, for the first time, the traditional unidirectional chemical camouflage hypothesis, as we argue that convergence of the epithelial microbiota of both partners may play essential roles in establishing mutual acceptance.
Identification of Two Novel Mutations of ABCD1 Gene in Pedigrees With X‐linked Adrenoleukodystrophy and Review of the Literatures
Authors: Dong Bingzi , Lv Wenshan , Xu Lili , Zhao Yuhang , Sun Xiaofang , Cheng Bingfei , Wang Yangang
Published: February 2021

BackgroundX-linked adrenoleukodysrophy (ALD) is an inherited peroxisomal metabolism disorder, results from the loss-of-function mutation of ATP-binding cassette protein subfamily D1 ( ABCD1 ) gene. The dysfunction of ALD protein, a peroxisomal ATP-binding cassette transporter, results in the excessive saturated very long chain fatty acids (VLCFAs) accumulation in organs including brain, spine and adrenal cortex. X-ALD is characterized as the childhood, adolescent, adult cerebral ALD, adrenomyeloneuropathy (AMN), adrenal insufficiency, and asymptomatic phenotypes, exhibiting a high variety of clinical neurological manifestations with or without adrenocortical insufficiency. ResultsIn this study, we reported two cases of X-ALD, which were firstly diagnosed as adrenal insufficiency (Addison’s disease) and treated with adrenocortical supplement. However, both of the cases progressed as neurological symptoms and signs after decades. Elevated VLCFAs level, brain MRI scan and genetic analysis confirmed final diagnosis. In addition, we identified two novel mutations of ABCD1 gene, c.874_876delGAG (p.Glu292del) and c.96_97delCT (p.Tyr33Profs*161) in exon 1 of ABCD1 gene. Sanger sequencing confirmed that the proband’s mother of the first case was hemizygous carrying the same variant. Adrenal insufficiency-only type is very rare, however, it may be the starting performance of X-ALD. In addition, we summarized reported mutation sites and clinical manifestations to investigate the correlationship of phenotype-genotype of X-ALD. ConclusionsThe early warning manifestations should be noticed, and the probability of X-ALD should be considered. This report could be beneficial for the early diagnosis and genetic counseling for patients with X-ALD.
Multivariate Analysis of Prognostic Factors in Patients With Nodular Melanoma
Authors: Susok Laura , Stücker Markus , Bechara Falk G. , Stockfleth Eggert , Gambichler Thilo
Published: February 2021

Purpose Nodular melanoma (NM) is associated with worse disease outcome when compared to superficial spreading melanoma (SSM). We aimed to perform a single center analysis of prognostic factors in patients with NM and compare the data with SSM patients. Methods We studied 228 patients with NN and 396 patients with SSM. Patients with in-situ melanomas or stage IV at diagnosis were not included in the study. Data were analyzed using the Mann-Whitney test, Chi² test, Kaplan-Meier curves including the log-rank test, and logistic regression model.Results When compared to patients with SSM, patients with NM had less likely lower Clark level, higher tumor thickness, less likely tumor regression, more often ulcerated tumors, and less likely a history of precursor lesions such as a nevus. Within a 5-year follow-up we observed significantly more disease relapses and deaths in NM patients than in SSM patients. On multivariate analysis, disease relapse in NM patients was independently predicted by tumor thickness and positive SLNB, whereas melanom-specific death of NM patients was independently predicted by male sex and tumor thickness. Histologic regression also remained in the logistic regression model as a significant independent negative predictor of NM death.Conclusions We did not observe that NM subtype was a significant independent predictor for disease relapse or melanoma-specific death. Among the well-known prognostic factors such as tumor thickness and male sex, NM is also associated with other unfavorable factors such as absence of regression.
Molecular Characterization of Mouse CREB3 Regulatory Factor in Neuro2a Cells
Authors: Oh-hashi Kentaro , Hasegawa Tomoyuki , Naruse Yoshihisa , Hirata Yoko
Published: February 2021

We performed expression and functional analysis of mouse CREB3 regulatory factor (CREBRF) in Neuro2a cells by constructing several expression vectors. Overexpressed full-length CREBRF protein was stabilized by MG132; however, the intrinsic CREBRF expression in Neuro2a cells was negligible under all conditions. On the other hand, N- or C-terminal deletion of CREBRF influenced its stability. Cotransfection of CREBRF together with GAL4-tagged full-length CREB3 increased luciferase reporter activity, and only the N-terminal region of CREBRF was sufficient to potentiate luciferase activity. Furthermore, this positive effect of CREBRF was also observed in cells expressing GAL4-tagged cleaved CREB3, although CREBRF hardly influenced the protein stability of NanoLuc-tagged cleaved CREB3 or intracellular localization of EGFP-tagged one. In conclusion, this study suggests that CREBRF, a quite unstable proteasome substrate, positively regulates the CREB3 pathway, which is distinct from the canonical ER stress pathway in Neuro2a cells.
A missense Variant in IFT122 Associated with a Canine Model of Retinitis Pigmentosa
Authors: Kaukonen Maria , Pettinen Inka-Tuulevi , Wickström Kaisa , Arumilli Meharji , Donner Jonas , Juhola Ida-Julia , Holopainen Saila , Turunen Joni A. , Yoshihara Masahito , Kere Juha , Lohi Hannes
Published: February 2021

Retinitis pigmentosa (RP) is a blinding eye disease affecting nearly two million people worldwide. Dogs are affected with a similar illness termed progressive retinal atrophy (PRA). Lapponian Herders (LHs) are affected with several types of inherited retinal dystrophies, and variants in PRCD and BEST1 genes have been associated with generalized PRA and canine multifocal retinopathy 3 (cmr3), respectively. However, all retinal dystrophy cases in LHs are not explained by these variants, indicating additional genetic causes of disease in the breed. We collected DNA samples from 10 PRA-affected LHs, with known PRCD and BEST1 variants excluded, and 34 unaffected LHs. A genome-wide association study identified a locus on CFA20 (praw=2.4x10-7, pBonf=0.035), and subsequent whole-genome sequencing of an affected LH revealed a missense variant, c.3176G>A, in the intraflagellar transport 122 (IFT122) gene. The variant was also found in Finnish Lapphunds, in which its clinical relevancy needs to be studied further. The variant interrupts a highly conserved residue, p.(R1059H), in IFT122 and likely impairs its function. Variants in IFT122 have not been associated with retinal degeneration in mammals, but the loss of ift122 in zebrafish larvae impaired opsin transport and resulted in progressive photoreceptor degeneration. Our study establishes a new spontaneous dog model to study the role of IFT122 in RP biology, while the affected breed will benefit from a genetic test for a recessive condition.
α -Lipoic Acid-Plus Ameliorates Endothelial Injury via Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in Vivo and Vitro Endothelial Injury Model
Authors: Wang Yang , Kong Xiangqian , Bao Dejun , xu Bin , Dong Yongfei , Wei Xiangping , Niu Chaoshi
Published: February 2021

PurposeWe tried to explore the potential role of the α-Lipoic acid-plus (LAP) in endothelial injury in vitro and vivo models. Simultaneously, possible endovascular protective mechanisms of LAP were also investigated further. MethodsIn vitro, oxyhemoglobin (OxyHb) stimulating human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, carotid artery angioplasty injury was used to generate a model of rat carotid artery intimal injury (CAII). HUVECs and rats were treated with desferrioxamine (DFO) and LAP. ResultsIn experiment 1, we found that the expressions of Cathepsin B/D in endothelial tissue increased and reached peak point in 48 hours post rat CAII. In experiment 2, firstly, the protein levels of Cathepsin B/D, cleaved-caspase-3, Bax, Ferritin, Transferrin Receptor (TfR) markedly increased after CAII and reversed by DFO and LAP treatments. Besides, DFO and LAP treatments also reduced oxidative stress level and endothelial cells (ECs) necrosis of the damaged endometrium. In experiment 3, firstly, the protein levels of Cathepsin B/D, cleaved-caspase-3, Bax, Ferritin and TfR apparently increased post OxyHb stimulation, which were further aggravated by the addition of iron and decreased by DFO and LAP treatments. Moreover, DFO and LAP significantly ameliorated oxidative stress level, HUVECs injury, iron level, mitochondrial damage and were beneficial to maintain lysosomal integrity. Finally, LAP may have exerted more significant endovascular protective effects than DFO.Conclusions﻿LAP probably exerted endovascular protective effects via inhibiting the apoptosis pathway mediated by intralysosomal Cathepsins by chelating excessive iron in endothelial lysosomes post intimal injury.
Transcriptomic Phases of Periodontitis Lesions Using the Nonhuman Primate Model
Authors: Ebersole Jeffrey , Nagarajan Radhakrishnan , Kirakodu Sreenatha , Gonzalez Octavio A.
Published: February 2021

We used a nonhuman primate model of ligature-induced periodontitis to identify patterns of gingival transcriptomic changes demarcating phases of periodontitis lesions (initiation, progression, resolution). 18 adult Mulatta macaca (12-22 years) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained (baseline, 2 weeks, 1 and 3 months during periodontitis and at 5 months resolution). Gene expression was analyzed by microarray [Rhesus Gene 1.0 ST Array (Affymetrix)]. Compared to baseline, a large array of genes were significantly altered at initiation (n=6049), early progression (n=4893), and late progression (n=5078) of disease, with the preponderance being up-regulated. Additionally, 1918 genes were altered in expression with disease resolution, skewed towards down-regulation. Assessment of the genes demonstrated specific profiles of epithelial, bone/connective tissue, apoptosis/autophagy, metabolism, regulatory, immune, and inflammatory responses that were related to health, stages of disease, and tissues with resolved lesions. Unique transcriptomic profiles occured during the kinetics of the periodontitis lesion exacerbation and remission. We delineated phase specific gene expression profiles of the disease lesion. Detection of these gene products in gingival crevicular fluid samples from human disease may contribute to a better understanding of the biological dynamics of the disease to improve patient management.
Targeting Several Biologically Reported Targets of Glioblastoma Multiforme by Assaying 2D and 3D Cultured Cells
Authors: Sixto-López Yudibeth , Marhuenda Emilie , García-Vazquez Juan Benjamin , Fragoso-Vazquez Jonathan , Rosales-Hernández Martha Cecilia , Zacarías-Lara Oscar , Méndez-Luna David , Gómez-Vidal José Antonio , Cornu David , Bakalara Norbert , Basurto Jose Correa Correa
Published: February 2021

Glioblastoma multiforme (GBM) is account for 70% of all primary malignancies of the central nervous system. Median The survival of human patients after treatment is around 15 months. There are However, several biological targets which have been reported that can be pursued using ligands with varied structures to treat this disease. In our group, we have developed several ligands that target a wide range of proteins involved in anticancer effects, such as histone deacetylase (HDACs), G protein-coupled estrogen receptor 1 (GPER), estrogen receptor-beta (ERβ), and NADPH oxidase (NOX), that were screened on bidimensional (2D) and tridimensional (3D) GBM stem cells like (GSC). Our results show that some HDAC inhibitors show antiproliferative properties at 21-32 µM as well as . These results suggest that in this 3D culture, HDACs could be the most relevant targets that are modulated to induce the antiproliferative effects that require in the future further experimental studies.
Levels, Daily Exposures, and Health Risk Assessment of Pesticides and Toxic Metals in Fruits of Lycium Barbarum L. (Goji berries) Sourced from Different Locations in Ningxia, China
Authors: Zhang Yahong , Qin Jiaqi , Wang Yan , Zhou Tongning , Feng Ningchuan , Ma Caihong , Zhu Meilin
Published: February 2021

Background: The berries of Lycium barbarum L. (Goji) are widely used as a Chinese traditional herbal medicine and functional food because of their reported beneficial pharmacological effects. However, there are reports of Goji berries being contaminated by chemical residues that could pose a hazard to humans. Methods: In this study, samples of L. barbarum L. berries were collected from plantations in a genuine production area and supermarkets in Ningxia, China. The major hazardous chemicals, including pesticides (dichlorvos, omethoate, cypermethrin, fenvalerate, malathion, and deltamethrin) and toxic metals (lead, cadmium, copper, nickel, zinc, and arsenic), were quantified by gas chromatography and inductively coupled plasma-optical emission spectrometry. In addition, associated daily exposures and health risks were determined using deterministic and probabilistic assessments. Results: The levels of five pesticides from the plantation samples were considerably lower than the maximum residue limits; only dichlorvos was detected in the supermarket samples, and deltamethrin was not detected in any samples. Copper, zinc, arsenic, lead, nickel and cadmium were detected in samples from both sources. The hazard quotient values of individual hazardous chemicals and the hazard index of combined hazardous chemicals were considerably less than 1, indicating the absence of a non-carcinogenic effect of hazardous chemical exposures through Goji berry consumption. The R value of arsenic was much less than 10-6, which shows that consumption of the Goji berries had no obvious carcinogenic risks. Conclusions: The potentially harmful effects of the L. barbarum L. are more likely from berries obtained from plantations than those from supermarkets, and heavy metal exposure is more dangerous than pesticide exposure. However, on the basis of our analysis, no population would be exposed hazardous chemicals exceeding existing standards, and the factors most affecting the health risk were exposure frequency and arsenic content.
Surgery Alone, Adjuvant Tegafur/gimeracil/octeracil (S-1), or Platinum-based Chemotherapies For Resectable Gastric Cancer: Real-world Experience and A Propensity Score Matching Analysis
Authors: Yen Chih-Chieh , Shan Yan-Shen , Chao Yin-Jui , Liao Ting-Kai , Huang Hsuan-Yi , Liu I-Ting , Yen Chia-Jui
Published: February 2021

Background: Adjuvant chemotherapy has changed the paradigm in resectable gastric cancer. S-1 is an oral chemotherapeutic with promising efficacy in Asia. However, comparisons with close observation or platinum-based doublets post D2 gastrectomy have been less reported.Methods: We retrospectively evaluated patients with D2-dissected stage IB-III gastric cancer who received S-1 (S-1, n=64), platinum-based doublets (P, n=95) and operation with close observation (OBS, n=110) from Jan 2013 to Oct 2018. A propensity score matching was used to compare for recurrence-free (RFS) and overall survivals (OS). Adverse reactions, dosage, and associated factors for S-1 are also discussed.Results: In a median follow-up of 42.5 months, Group S-1 had a comparable survival to that of P and OBS. (median RFS/OS: S-1 vs. P, 24.4/37.4 vs. 39.1/62.1 months, HR=1.12/1.22, p=0.667/0.514; S-1 vs. OBS, 23.6/37.4 vs. 24.0/64.6 months, HR=1.17/1.23, p=0.554/0.499). However, in patients with N2-3 or stage IIIB/IIIC disease, P significantly improved survival as compared with S-1. Conversely, S-1 was comparable to P and superior to OBS in stage IB-IIIA or N0-1 disease. S-1 was well-tolerated with a relative dose intensity of 73.6%, a median duration of 8.3 months and associated with less adverse reactions as compared with P. In the subgroup analysis, P was favored in stage III, N2-3 or T3-4 disease wherase patients with Helicobacter Pylori infection had a better survival when treated with S-1.Conclusions: Adjuvant S-1 correlated with comparable survival rates but fewer adverse reactions as compared with platinum-based doublets. Patients with low to moderate risk of recurrence and Helicobacter pylori infection derived benefits from S-1 while platinum-based doublets were favored in advanced cases. The study provides additional information about adjuvant S-1 in patients with selected risk of recurrence.
A Comprehensive Bioinformatics Analysis of TIMP2 in Multiple Malignancies
Authors: Wang Dan-Dan , Xu Wen-Xiu , Chen Wen-Quan , Yang Su-Jin , Zhang Jian , Tang Jinhai
Published: February 2021

Background: Tissue inhibitor of metalloproteinase-2 (TIMP2), an endogenous inhibitor of matrix metalloproteinases, has been disclosed to participate in the development and carcinogenesis of multiple malignancies. However, the prognosis of TIMP2 in different cancers and its correlation with tumor microenvironment and immunity have not been clarified.Methods: In this study, we conducted a comprehensive bioinformatics analysis to evaluate the prognostic and therapeutic value of TIMP2 in cancer patients by utilizing a series of databases, including ONCOMINE, GEPIA, cBioPortal, GeneMANIA, Metascape, and Sangerbox online tool. The expression of TIMP2 in different cancers were analyzed by Oncomine, TCGA and GTEx databases and mutation status of TIMP2 in cancers was then verified using cBioportal database. The protein-protein interaction (PPI) network of the TIMP family was exhibited by GeneMANIA. The prognosis of TIMP2 in cancers was performed though GEPIA database and cox regression. Additionally, the correlations between TIMP2 expression and immunity (immune cells, gene markers of immune cells, TMB, MSI, and neoantigen) were explored using Sangerbox online tool.Results: The transcriptional level of TIMP2 in most cancerous tissues were significantly elevated. Survival analysis revealed that elevated expression of TIMP2 was associated with unfavorable survival outcome in multiple cancers. Enrichment analysis demonstrated the possible mechanisms of TIMPs and their associated genes mainly involved in pathways including extracellular matrix (ECM) regulators, degradation of ECM and ECM disassembly, and several other signaling pathways. Conclusions: Our findings systematically dissected that TIMP2 was a potential prognostic maker in various cancers and use the inhibitor of TIMP2 may be an effective strategy for cancer therapy to improve the poor cancer survival and prognostic accuracy, but concrete mechanisms need to be validated by subsequent experiments.
Breast Cancer Incidence by Age at Finding of Mammographic Abnormality in Women Participating in French Organized Screening Campaigns.
Authors: KOÏVOGUI AKOÏ , BALAMOU CHRISTIAN , RYMZHANOVA Raushan , CORNELIS STEPHANE , RODRIGUE-MOULINIE CHRISTELLE , SELLIER NICOLAS
Published: February 2021

Purpose: Using reduced samples, statistical modelling was already predicted the occurrence of Breast-cancer or its prognosis from previous radiological findings. This study aims to predict breast-cancer risk by mammographic abnormalities finding age in the French breast-cancer screening campaign. Methods: The study involved 261,083 women aged 50-74 living in French Departments (Ain, Doubs, Haute-Saône, Jura, Territoire-de-Belfort, Yonne). These women had at least two screening mammograms between Jan-1999 and Dec-2017 of which the first was classified as “normal/benign”. The incidence of mammographic-abnormality (microcalcification, spiculated-mass, obscured-mass, architectural-distortion, asymmetric-density) and the incidence of breast-cancer after abnormality detection were estimated abnormalities finding age, using an actuarial life-table method. Breast-cancer risk was predicted in a Cox multivariate model.Results: The incidence of mammographic-abnormality was 95.4[94.9; 95.9]/1000 person-years. Breast-cancer (6,326 cases) incidence was 3.3[3.0; 3.1]/1000 person-years. That incidence was 5 times higher in women who showed a speculated-mass vs. those who did not (6.9[6.4; 7.4] vs. 1.3[1.2; 1.3]). Whatever the abnormality, the incidence of cancer was higher when it was present in only one breast. Depending on the spiculated-mass finding age, the risk increased by at least 40% between the age groups 55-59years (1.4[1.0; 1.8]) and ≥70years (2.4[1.9; 3.3]).Conclusion: The study showed the increased risk of cancer with the abnormalities finding age and the low risk related to the presence of the same mammographic-abnormality in both breasts compared to the isolated mammographic-abnormality in one of the breasts. This should alert radiologists to the relevance of certain diagnostic procedures in the management of a bilateral mammographic abnormality.
Correlation Between Semen Examination Based on the WHO Criteria and Sperm DNA Fragmentation Test
Authors: Okubo Tsuyoshi , Onda Noriyuki , Hayashi Teruaki , omi Kenji , Segawa Tomoya
Published: February 2021

Purpose: We performed and analyzed the DFI test and semen test based on the WHO criteria and compared the two using semen factors. Methods: DFI tests and general semen tests were conducted in accordance with the WHO criteria, and correlations between the two tests were investigated. The WHO criteria were set as the cutoff value for each of the following factors: fluid volume, concentration, motility, and normal morphology, and compared with the DFI results.Results: The subjects had a mean DFI of 15.6±11.5% and the DFI increased with age. In contrast, the concentration, motility, and normal morphology decreased as the DFI increased. Patients who satisfied the WHO criteria in terms of sperm concentration, motility, and normal morphology had a significantly lower DFI than the group that did not satisfy the criteria. Therefore, evaluation with a general semen test based on the WHO criteria should be regarded as a qualitative evaluation of all factors other than fluid volume.Conclusions: Male infertility due to sperm DNA fragmentation should be suspected when in vitro fertilization (IVF) results are poor despite normal semen findings based on the WHO criteria. The results of this study suggest that the DFI test may be an important evaluation in follow-up semen analyses.
Challenging collaboration of general practitioners and specialists for patients with complex chronic conditions: A scoping review to identify improvement strategies
Authors: Tomaschek Rebecca , Lampart Patricia , Scheel-Sailer Anke , Gemperli Armin , Merlo Christoph , Essig Stefan
Published: February 2021

BackgroundCollaboration between medical specialists and general practitioners (GPs) is well known from daily practice, but research on the topic is rather scarce. This scoping review summarizes role distributions and components of this collaboration that have potential for improvement for the care of patients with complex chronic conditions. Methods Scoping review as a knowledge synthesis for components of collaboration and role distributions between medical specialists and GPs in intervention studies. The PubMed database was searched for literature from 2010-2020.ResultsLiterature search and reference screening generated 2,174 articles. Of these, 30 articles originating from 22 unique projects were included in our synthesis. These projects focus on different patient populations and take diverse approaches to improve collaboration within an intervention. The GP is most commonly in charge of patient management and extends the scope of practice. The specialist provides support when needed. Clear definition of roles and responsibilities, resources for knowledge exchange and raising awareness through education from specialists for specific health conditions are commonly utilized interventions. Typically, combinations of process and system changes that address communication and coordination issues are applied. Most interventions improve provider and patient satisfaction, health outcomes, and reduce fragmentation of patient care.ConclusionInterventions to improve collaboration between GPs and medical specialists seem promising. Further efforts should be made to test and apply the findings in broad clinical practice.
Seizure After Cardiopulmonary bypass Surgery: A Retrospective Study
Authors: Kim Jean Hee , Jang Jinhee , Kim Hwan Wook , Kim Woojun
Published: February 2021

Background: We are to investigate prognostic factors of seizure after cardiopulmonary bypass surgery based on the incidence, the operation parameters, and the outcomes of seizure.Methods: Consecutive patients presented a seizure after a cardiac or aortic surgery using a cardiopulmonary bypass (CPB) during the admission between January 2006 and January 2019 were retrospectively enrolled. Patients with a previous seizure history were excluded. The medical records were reviewed on the demographics, associated medical conditions, laboratory, electroencephalography (EEG), and imaging findings, cardiopulmonary bypass parameters, types of seizure, and prognosis.Results: Among the 488 patients who received cardiopulmonary surgery using CPB, 29 patients were diagnosed with seizure during admission. There were nine cases of aortic valve replacement, six of mitral valve replacement, four of aorta graft, two of patent ductus arteriosus closure, coronary artery bypass graft, tricuspid annuloplasty, and tumor resection for each. The average durations of the operation and of cardiopulmonary bypass were 278±119 and 108±55 minutes, respectively. The average aortic cross clamping time was 72±41 minutes. The median detection time of a seizure was 34.38±83.37 hours after surgery. Twenty-three patients (79.3%) did not show recovery of mental status after surgery until the seizure was detected. Seventeen patients were diagnosed with status epilepticus, and two of them had nonconvulsive status epilepticus. Nine showed repetitive seizures and three presented a single seizure. EEG analysis showed five cases of spike-and-wave, four of periodic discharges, four of rhythmic delta, and one of burst suppression. From the image studies, sixteen patients showed stroke, two revealed posterior reversible encephalopathy syndrome, and two showed seizure related changes. Nine (31.0%) expired in 25±27 postoperative day. For the survived patients, the average duration of ICU admission was 9±7 days.Conclusions: Due to its difficulty of detecting preclinical seizure after the surgery, evaluation including performance of EEG in early postoperative phase should be considered.
Global Stability and Backward Bifurcation for a Lymphatic filariasis model
Authors: Iyare Egberanmwen Barry , Okuonghae Daniel , Osagiede Francis
Published: February 2021

An ODE model of Lymphatic filariasis is proposed with eight mutually disjoint compartments. The model is proven to be mathematically and epidemiologically well posed. Epidemiological interpretation of the effective reproduction number is presented. A special case is considered where the death rate due to the disease is negligible. An endemic equilibrium under this special scenario is explicitly computed and the presence of backward bifurcation under this condition is suggested. Bifurcation analysis is performed using the Castillo-Chavez and Song theorem in the special case where death due to disease is zero. When the re-infection rate is zero, backward bifurcation is shown not to be present. In such a situation, global asymptotic stability of the endemic equilibrium is established.
Clinical Effect of Partial Sensory Root Rhizotomy on Recurrence of Multiple Sclerosing Trigeminal Neuralgia After Percutaneous Balloon Compression
Authors: Li Yuanchao , Zhang Guodong , Zhang Jiaqi , Cheng Zhenguo , Lan Yanping
Published: February 2021

Objective To investigate the Clinical effect of partial sensory root rhizotomy(PSR) on recurrence of multiple sclerosing trigeminal neuralgia(TN-MS) after percutaneous balloon compression(PBC). Methods A retrospective analysis of the clinical data of 21 cases of recurrent multiple sclerosis trigeminal neuralgia after PBC who were treated with PSR in the Department of Neurosurgery of Xinxiang Central Hospital from January 2012 to July 2018; The diagnosis of MS was made by McDonald criteria, and using MRI to exclude REZ Regional blood vessels compress nerves; analysis of patients' preoperative and postoperative Visual Analogue Score (VAS), VAS 0-3 points means effective, 4 points and above means invalid or recurrence.Results Preoperative VAS: 8 -10 points in 21 cases, 1 day and 6 months after surgery VAS: 0-3 points in 21 cases, effective rate 100%; 12 months after surgery: 4 points in 2case, effective rate 95%, recurrence rate 5%; 18 months after surgery, 4 cases scored above 4, the effective rate was 81%, and the recurrence rate was 19%. The average point of VAS after PSR at 1 day, 6M, 12M, and 18M were lower than PBC, P<0.05, and the difference was statistically significant. The postoperative recurrence rate of PSR at 6M, 12M, and 18M is lower than that of PBC, P<0.05, and the difference is statistically significant. All 21 patients had facial sensation loss after surgery without major complications such as intracranial hemorrhage, facial palsy, and cerebrospinal fluid leakage. 1 case of intracranial infection. Conclusion PSR is effective in the treatment of TN-MS and can be used as a treatment for recurrence after PBC.
Multifocal Papillary Thyroid Carcinoma，Hashimoto's Thyroiditis and Lymph Node Metastasis：A Retrospective Cohort Study
Authors: Wang Denghui , Zhu Jiang , Deng Chang , Yang Zhixin , Hu Daixing , Shu Xiujie , Yu Ping , Su Xinliang
Published: February 2021

Objective: Few studies have evaluated the influence of HT and Multifocality on central lymph node metastases(CLNM) and lateral lymph node metastases(LLNM) of PTC. The present study focused on risk factors for lymph node metastasis in PTC according to the presence of HT or multifocality. Materials and methods:1413 patients were identified.The relationship between HT or multifocality and lymph nodemetastasis was analyzed by univariate and multivariate logistic regression, ROC curves were constructed to show the predictive effect of each variable on the target outcome.Results: The PTCs with HT were more likely to be multifocal.(40.0% versus 17.5%,P ＜0.001). Compared to MPTC without HT, MPTC with HT showed a lower number of metastatic CLNs and LLNs (P < 0.05). HT was identifified as an independent protective factor for CLNM in all PTC patients (OR, 0.480; 95% CI, 0.359-0.643; P< .001) and in MPTC patients (OR, 0.094; 95% CI, 0.044-0.204; P < 0.001), the multicocality was independent risk factors for CLNM(OR, 2.316; 95% CI, 1.667-3.217; P< 0.001) and LLNM(OR, 2.004; 95% CI, 1.469-2.733; P< 0.001).The variables concluded HT or MPTC were screened to predict CLNM in all patients, CLNM in patients with MPTC and LLNM in all patients (AUCs: 0.731, 0.843 and 0.696, respectively, P < 0.0001). The two type of diseases existed concurrently may result in the decrease of CLNM and LLNM, AUCs of ROC to predict CLNM and LLNM are 0.696 and 0.63(P<0.0001). Conclusions: Our study identified multifocality as an independent risk factor predicting CLNM and LLNM in PTC patients. HT was proven to be a protective factor that reduced the CLNM risk in all patients and in patients with MPTC. The existence of both type of diseases can result in the reduction of CLNM and LLNM.
Environmental Protection and Energy Efficiency Improvement by using Marine Alternative fuels in Maritime Transportation
Authors: Elkafas Ahmed Gamal , Khalil Mohamed , Shouman Mohamed R. , Elgohary Mohamed M.
Published: February 2021

Emissions from vessels are a major environmental concern because of their impacts on the deterioration of the environment, especially global warming of the atmosphere. Therefore, the International Maritime Organization (IMO) concern significant care to environmental protection through the reduction of exhaust emission and improvement of energy efficiency through technical and operational measures. Among the suggested measures from IMO, the alternative fuel such as Liquefied Natural Gas (LNG) has the priority to be used instead of fossil fuels. The present paper calculates the effect of using LNG in a dual fuel engine from Environmental and Energy efficiency perspectives. As a case study, a Container Ship has been investigated. The results of the analysis show that percent of CO2, NOx and SOx emissions reduction corresponding to using a dual-fuel engine operating by LNG instead of a diesel engine operating by Heavy Fuel Oil is about 30.1%,81.44%, and 96.94%, respectively. Also, the attained Energy Efficiency Index Value in the case of using the dual-fuel engine is lower than its value by using diesel engine by about 30% and this value will be 77.18%, 86.84%, and 99.27% of the required value of the first, second and third phases, respectively as recommended by IMO.
Heparin Induced Thrombocytopenia in Patients with COVID-19
Authors: Warrior Surbhi , Behrens Elizabeth , Gezer Sefer , Venugopal Parameswaran , Jain Shivi
Published: February 2021

Background
Acute respiratory and renal failure as well as systemic coagulopathy are critical aspects of the morbidity and mortality in patients with COVID-19. Heparin Induced Thrombocytopenia (HIT) occurs when IgG antibodies form against platelet factor 4-Heparin complex, resulting in platelet activation and removal, leading to a prothrombotic state. Studies have shown that only 6% who are investigated serologically for HIT actually have the diagnosis.
Methods
A retrospective analysis was performed on all COVID-19 positive patients hospitalized between March and June 2020. Patients with suspicion for HIT were tested for HIT antibodies with IgG-specific platelet factor 4(PF4)-dependent enzyme immunoassay (EIA). Confirmatory testing with serotonin release assay (SRA) and heparin-induced platelet aggregation were used in cases with intermediate or low optical density (OD) with EIA positivity (EIA+). Due to rarity of disease, a through literature review on HIT in COVID-19 patients was also analyzed.
Results
Incidence of EIA + in COVID-19 patients was 0.6%, significantly higher than in the general population 0.2% (p < 0.0001). The incidence of thromboembolic events in EIA + patients was 87.5%, significantly higher than the rate of 10.90% in all COVID-19 patients (p < 0.0001). The mortality rate in EIA + patients was 50%, significantly greater than the mortality rate of 12% in all hospitalized COVID-19 patients (p = 0.0011). Serological confirmation of HIT diagnosis was 37.5% which is significantly higher than confirmation of HIT in nonCOVID-19 patients 6% (p < 0.0001). Of 39 HIT antibody positive patients in the literature, 23.07% had positive confirmatory testing (6 SRA, 3 HIPAA) which is significantly higher than 5.6% in the general population (p = 0.00001). The incidence of thrombosis in EIA + COVID-19 patients in the literature was 56.4% which is significantly higher than reported rates of thrombotic events in in all COVID-19 patients in the literature at 4.8%1 (p = 0.00001).
Conclusion
Our study indicates incidence of HIT is higher in the COVID-19 population. This can be attributed to the cytokine storm and severe sepsis seen in critically ill COVID-19 patients. Our study also suggests that development of HIT can contribute to increased risk for thromboembolic events as well as mortality of COVID-19 patients, however, our study is limited due to small sample size.
Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Uterosacral Ligament Suspension: a Pilot Study of 35 Caseswith Severe Pelvic Organ Prolapse
Authors: Lu Zhiying , Chen Yisong , Wang Xiaojuan , Li Junwei , Hua Keqin , Hu Changdong
Published: February 2021

Background To describe the short-term outcomes of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) for uterosacral ligament suspension (USLS) in patients with severe prolapse.Methods This is a retrospective study conducted for patients with severe prolapsed (≥stage 3) who underwent vNOTES USLS between May 2019 and July 2020. The Pelvic Organ Prolapse Quantification (POP-Q) score, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form (PISQ-12) and Pelvic Floor Inventory-20 (PFDI-20) were used to evaluate physical prolapse and quality of life before and after vNOTES USLS.Results A total of 35 patients were included. The mean operative time was 111.7±39.4 minutes. The mean blood loss was 67.9±35.8 ml. Statistically significant differences were observed before and after vNOTES USLS in regard to Aa (+0.6±1.7 versus −2.9±0.2), Ba (+1.9±2.2 versus −2.9±0.3), C (+1.5±2.2 versus -6.9±0.9), Ap (-1.4±1.0 versus −3.0±0.1) and Bp (-1.1±1.4 versus −2.9±0.1) (P < 0.05 for all). The mean pre- and post-operative PFDI-20 score was 19.9±6.7 versus 3.2±5.4, and the PISQ-12 score was 24.8±2.3 versus 38.3±4.1 (P < 0.05 for both). During 1–13 months of follow-up, no severe complications or recurrence.Conclusions vNOTES USLS may be a feasible technique to manage severe prolapse, with promising short-term efficacy and safety data. However, a study with a larger number of patients and a longer follow-up period should be conducted.