bluuebunny/crossref_metadata_2025 huggingface dataset:
Universidades peruanas y su producción científica en el área de turismo
Authors: Vargas-Arana Gabriel , Utia-Shapiama Dorcas
Published: December 2020

Teniendo en cuenta la creciente importancia que adquiere el turismo para el desarrollo del Perú, y que en la actualidad todo modelo de desarrollo turístico se debe alimentar de la investigación turística, es evidente la necesidad de analizar la producción de las universidades peruanas que han realizado en el campo del turismo. La presente investigación analiza los artículos publicados relacionados al turismo por docentes afiliados a universidades peruanas en revistas científicas indizadas, tanto de ámbito nacional como internacional. La búsqueda se realizó utilizando las bases de datos de Scopus y Scielo durante el periodo de 2008 a 2018. El análisis nos permitió identificar aquellas universidades y autores que han realizado un mayor esfuerzo de investigación y difusión en turismo, las revistas en las que se publican estos trabajos, las citas e impacto internacional de los artículos y autores. Según lo analizado, a pesar que hace buen tiempo el Perú es un destino turístico recomendado internacionalmente, la investigación en turismo por parte de las universidades peruanas ha sido bajo y tienen un crecimiento lento, siendo inferior al crecimiento de los países de nuestro entorno.
Az immunválasz néhány újonnan felismert hatásmechanizmusa és az immunológia szemléleti átalakulása
Authors: Falus András
Published: December 2020

Az immunológia az egészséges és kóros immunválaszt tanulmányozó komplex tu­domány. Ez az élettani, patofiziológiai tu­dományág az egyes mechanizmusok megértését elsősorban sejt- és molekuláris biológiai, genetikai, epigenetikai és (neu­ro)­en­do­kri­nológiai megközelítéssel, illetve a patológiás folyamatok részleteinek feltárásával vég­zi. Az immunológia egyike a na­gyon gyorsan fejlődő tudományoknak, eredményei visszahatnak más diszciplínákra is el­mé­leti (például hálózattudományok, rend­szer-biológia) és módszertani (monoklonális ellenanyagok, biomarkerek, immunoassay-ek) szinten egyaránt. Az immunológusok az elmúlt évtizedekben számos szemléleti változást értek meg, és sok, a hatásmechanizmusokban megnyilvánuló lényegi részletkérdés érvényesülését ismerték fel.
Exploratory case study difficulty of junior high school students in resolving problems of the pyramids surface area
Authors: Sudirman Sudirman , Martadiputra Bambang Avip Priatna
Published: December 2020

Penelitian ini bertujuan untuk mengeksplorasi kesulitan-kesulitan siswa sekolah menengah pertama dalam menyelesaikan permasalahan luas permukaan limas. Penelitian ini merupakan penelitian kualitatif dengan desain exploratory case study. Proses eksplorasi pada penelitian ini dilakukan pada partisipan yang berjumlah 13 siswa kelas VIII pada salah satu SMP Swasta di Kabupaten Indramayu.  Pengumpulan data dalam penelitian ini menggunakan tes, wawancara, dokumentasi, dan catatan lapangan. Sedangkan teknik analisis data yang digunakan mengadopsi modifikasi analisis data dari Miles dan Huberman yang terdiri dari pengumpulan data, pengodean (coding), reduksi data (data reduction), penyajian data (data display), dan penarikan kesimpulan (verification). Berdasarkan temuan penelitian, didapat bahwa kesulitan belajar yang dialami siswa pada saat menyelesaikan soal materi luas permukaan limas yaitu: (1) kesulitan dalam mengidentifikasi masalah yang terdapat pada soal; (2) kesulitan dalam mengoneksikan konsep luas permukaan dengan konsep materi prasyarat; (3) kesulitan dalam menentukan strategi penyelesaian soal tersebut; (4) kesulitan dalam menggunakan operasi yang melibatkan perkalian bilangan pecahan atau bentuk akar; (5) kesulitan dalam menggunakan formula konsep luas permukaan limas. Selain itu hasil temuan ini memberikan implikasi kepada guru untuk dapat mempersiapkan desain bahan ajar atau pembelajaran untuk mengatasi kesulitan tersebut.
Performance assessment of reform in the field of ensuring Ukraine’s tax security
Authors:   SESE “The Academy of Financial Management”, KUSHNERUK Oleksandr , ALEKSEIENKO Nataliia ,   SESE “The Academy of Financial Management”
Published: December 2020

During the period of 2014-2019 Ukraine experienced many tax changes, which concerned the optimization of the tax system to overcome threats to tax security in the field of tax payment, filling of the state budget and tax administration. Changes in the tax system have significantly affected the amount of tax revenues, but there is uncertainty about their effectiveness in ensuring tax security. The purpose of the article is to quantify the level of effectiveness of tax reforms in order to ensure tax security. Based on the analysis of publications in 2016-2019, major tax reforms in Ukraine were studied and the indicators that assess the effectiveness of reforms in the field of tax security were selected. The analysis of indicators of efficiency of administration and tax burden in Ukraine, Georgia and Poland in 2008-2019 is carried out. It is determined that there has been a reduction in the risks of tax evasion and the risks of non-payment of taxes due to improved tax administration. In general, the time for tax administration in Ukraine was significantly reduced and this was the most drastic change. In 10 years, the time of preparation and payment of taxes (hours) has been reduced from 860 hours to 328 hours! As a result, the risks of tax evasion in Ukraine have decreased due to the reduction of the tax burden on business; the administration of taxes and contributions has become more efficient, which reduces the risks of tax evasion. These indicators affected the amount of tax revenues and relative indicators of the tax burden. Tax revenues (% of GDP) in Ukraine increased by 2.27% of GDP. This means that the efficiency of tax revenue administration has improved, which has a positive effect on the level of tax security. As a result, the tax system has become more transparent.
Prime Harmonics and Twin Prime Distribution
Authors: Dolgikh Serge
Published: December 2020

Distribution of twin primes is a long standing problem in the number theory. As of present, it is not known if the set of twin primes is ﬁnite, the problem known as twin prime conjecture. An analysis of prime modulo cycles, or prime harmonics in this work allowed to deﬁne approaches in estimation of twin prime distributions with good accuracy of approximation and establish constraints on gaps between consecutive twin prime pairs. With technical effort, the bounds on the distance between consecutive prime pairs obtained in this work can prove sufﬁcient to establish that the next twin prime exists within the estimated distance, leading to the conclusion that the set of twin primes is unlimited and reducing the inﬁnitely repeating distance between consecutive primes to two. The methods developed in the study can be instrumental in future analysis of prime distributions
Re-thinking COVID-19's causation narrative
Authors: Campbell Junior
Published: December 2020

The COVID-19 narrative has been the story of a pathogen, probably created in a Chinese wet market, somehow jumping from the animal kingdom into the human population and basically destroying our bodies from within by virtue of its reproductive rapacity or viral "virility". However, given COVID-19's well documented impact on the mind, inducing delirium, feelings of exhaustion and other psychosomatic manifestations, might it be worth considering the possibility that SARS-CoV-2's virility and reproductive efficacy is interdependent with a radical change in human bio-psychology? In other words, might some seismic alteration in human bio-psychology and psychosocial relations have occurred that predisposes human beings to infection with the SARS-CoV-2 virus, of which the delusions and other neurological or bio-psychological disease insults are "atypical" symptoms? Might the much noted higher covid-19 death rates among males point to or reflect a distinct, possibly "new" phase in humanity's perennial, existential battle of the sexes?
Modification of in situ Biofilm Formation on Titanium by a Hydroxyapatite Nanoparticle-Based Solution
Authors: Nobre Cíntia M. G. , Pütz Norbert , König Belinda , Rupf Stefan , Hannig Matthias
Published: December 2020

Oral biofilms play an essential role on peri-implant disease development. Synthetic hydroxyapatite nanoparticles (nHAP) are a bioinspired material that has structural and functional similarities to dental enamel apatite and may provide preventive properties against biofilm formation. This study aimed to investigate the effects of an experimental nHAP solution on biofilm formation on polished and non-polished titanium under oral conditions. Five volunteers carried maxillary splints with non-polished and polished titanium and followed a 48 h rinsing protocol with the proposed nHAP solution, and with chlorhexidine 0.2% (CHX) and water, as controls. Samples were analyzed by fluorescence microscopy (FM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). FM showed a significant reduction of biofilms on polished samples treated with nHAP (p = 0.0485) compared with water, without differences between nHAP and CHX (p > 0.9999). Analyzing biofilm viability, polished samples rinsed with nHAP showed significantly fewer dead bacteria than CHX (p = 0.0079), but there was no significant difference in viability between polished samples rinsed with water and nHAP (p = 0.9268). A significantly higher biofilm coverage was observed on the non-polished surfaces compared to the polished surfaces when nHAP was applied (p = 0.0317). This difference between polished and non-polished surfaces was not significant when water (p = 0.1587) or CHX (p = 0.3413) rinsing were applied. SEM and TEM analysis supported the FM findings, that polished samples rinsed with nHAP presented fewer biofilm coverage compared to samples rinsed with water. In conclusion, the nHAP solution reduced the biofilm formation on polished Ti surfaces without altering bacterial viability, providing a novel approach for the management of biofilm formation on biomaterials.
Reliability Based Life Cycle Management of Bridge Subjected to Fatigue Damage
Authors: Stipanovic Irina , Connolly Lorcan , Skaric Palic Sandra , Duranovic Marko , Donnelly Róisín , Bernardini Ilaria , Bakker Jaap
Published: December 2020

In recent times, there has been an increase in transport infrastructure failure. This increase is due to aging infrastructure, increased number of extreme weather events caused by climate change, and increased traffic loading. Accordingly, the need for planned and unplanned maintenance interventions is rising. Associated costs do not only involve direct maintenance or reconstruction costs, but also secondary effects experienced by users of the transport network as well as the environment and society in general. Infrastructure managers require tools for accurate quantification of infrastructure resilience that will enable rational adaptation investment strategies, so as to maintain high level of safety of transport networks. Through the development of a Global Safety Framework, at the core of which is a Multi-modal Network Decision Support Tool, the SAFE-10-T project (Safety of Transport Infrastructure on the TEN-T Network) is providing integrated solutions to issues related to infrastructure safety and planning. The paper presents a reliability-based whole life cycle model developed within this project enabling strategic investment decisions that maximize safety, minimize disruption, and environmental impacts and allow for the best use of limited resources. The model is applied on a case study of a bridge in the Port of Rotterdam in the Netherlands.
Benchmarking Adaptive Variational Quantum Eigensolvers
Authors: Claudino Daniel , Wright Jerimiah , McCaskey Alexander J. , Humble Travis S.
Published: December 2020

By design, the variational quantum eigensolver (VQE) strives to recover the lowest-energy eigenvalue of a given Hamiltonian by preparing quantum states guided by the variational principle. In practice, the prepared quantum state is indirectly assessed by the value of the associated energy. Novel adaptive derivative-assembled pseudo-trotter (ADAPT) ansatz approaches and recent formal advances now establish a clear connection between the theory of quantum chemistry and the quantum state ansatz used to solve the electronic structure problem. Here we benchmark the accuracy of VQE and ADAPT-VQE to calculate the electronic ground states and potential energy curves for a few selected diatomic molecules, namely H2, NaH, and KH. Using numerical simulation, we find both methods provide good estimates of the energy and ground state, but only ADAPT-VQE proves to be robust to particularities in optimization methods. Another relevant finding is that gradient-based optimization is overall more economical and delivers superior performance than analogous simulations carried out with gradient-free optimizers. The results also identify small errors in the prepared state fidelity which show an increasing trend with molecular size.
Electrically Enhanced Transition Metal Dichalcogenides as Charge Transport Layers in Metallophthalocyanine-Based Solar Cells
Authors: Manamela Lebogang , Fru Juvet N. , Kyesmen Pannan I. , Diale Mmantsae , Nombona Nolwazi
Published: December 2020

Transitional metal dichalcogenides (TMDs), such as molybdenum disulfide (MoS2) have found application in photovoltaic cells as a charge transporting layer due to their high carrier mobility, chemical stability, and flexibility. In this research, a photovoltaic device was fabricated consisting of copper phthalocyanine (CuPc) as the active layer, exfoliated and Au-doped MoS2, which are n-type and p-type as electron and hole transport layers, respectively. XRD studies showed prominent peaks at (002) and other weak reflections at (100), (103), (006), and (105) planes corresponding to those of bulky MoS2. The only maintained reflection at (002) was weakened for the exfoliated MoS2 compared to the bulk, which confirmed that the material was highly exfoliated. Additional peaks at (111) and (200) planes were observed for the Au doped MoS2. The interlayer spacing (d002) was calculated to be 0.62 nm for the trigonal prismatic MoS2 with the space group P6m2. Raman spectroscopy showed that the E21g (393 cm−1) and A1g (409 cm−1) peaks for exfoliated MoS2 are closer to each other compared to their bulk counterparts (378 and 408 cm−1, respectively) hence confirming exfoliation. Raman spectroscopy also confirmed doping of MoS2 by Au as the Au-S peak was observed at 320 cm−1. Exfoliation was further confirmed by SEM as when moving from bulky to exfoliated MoS2, a single nanosheet was observed. Doping was further proven by EDS, which detected Au in the sample suggesting the yield of a p-type Au-MoS2. The fabricated device had the architecture: Glass/FTO/Au-MoS2/CuPc/MoS2/Au. A quadratic relationship between I-V was observed suggesting little rectification from the device. Illuminated I-V characterization verified that the device was sensitive and absorbed visible light. Upon illumination, the device was able to absorb photons to create electron-hole pairs and it was evident that semipermeable junctions were formed between Au-MoS2/CuPc and CuPc/MoS2 as holes and electrons were extracted and separated at respective junctions generating current from light. This study indicates that the exfoliated and Au-MoS2 could be employed as an electron transporting layer (ETL) and hole transporting layer (HTL), respectively in fabricating photovoltaic devices.
Progesterone Intramuscularly or Vaginally Administration May Not Change Live Birth Rate or Neonatal Outcomes in Artificial Frozen-Thawed Embryo Transfer Cycles
Authors: Liu Yuan , Wu Yu
Published: December 2020

Backgrounds

Previous studies suggested that singletons from frozen-thawed embryo transfer (FET) were associated with higher risk of large, post-date babies and adverse obstetrical outcomes compared to fresh transfer and natural pregnancy. No data available revealed whether the adverse perinatal outcomes were associated with aberrantly high progesterone level from different endometrium preparations in HRT-FET cycle. This study aimed to compare the impact of progesterone intramuscularly and vaginally regimens on neonatal outcomes in HRT-FET cycles.

Methods

A total of 856 HRT-FET cycles from a fertility center from 2015 to 2018 were retrospectively analyzed. All patients had their first FET with two cleavage-staged embryos transferred. Endometrial preparation was performed with sequential administration of estrogen followed by progesterone intramuscularly 60 mg per day or vaginal gel Crinone 90 mg per day. Pregnancy outcomes including live birth rate, singleton birthweight, large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm delivery rate were analyzed. Student’s t test, Mann-Whitney U-test, Chi square analysis, and multivariable logistic regression were used where appropriate. Differences were considered significant if p < 0.05.

Results

No significant difference of live birth rate was found between different progesterone regimens (Adjusted OR 1.128, 95% CI 0.842, 1.511, p = 0.420). Neonatal outcomes like singleton birthweight (p = 0.744), preterm delivery rate (Adjusted OR 1.920, 95% CI 0.603, 6.11, p = 0.269), SGA (Adjusted OR 0.227, 95% CI 0.027, 1.934, p = 0.175), and LGA rate (Adjusted OR 0.862, 95% CI 0.425, 1.749, p=0.681) were not different between two progesterone regimens. Serum P level >41.82 pmol/L at 14 day post-FET was associated with higher live birth rate than serum P level ≤41.82 pmol/L in HRT-FET cycles when progesterone was intramuscularly delivered (Adjusted OR 1.690, 95% CI 1.002, 2.849, p = 0.049). But singleton birthweight, preterm delivery rate, SGA and LGA rate were not different between these two groups.

Conclusions

Relatively higher serum progesterone level induced by intramuscular regimen did not change live birth rate or neonatal outcomes compared to vaginal regimen. Monitoring serum progesterone level and optimizing progesterone dose of intramuscular progesterone as needed in HRT-FET cycles has a role in improving live birth rate without impact on neonatal outcomes.
The Human Microbiota in Endocrinology: Implications for Pathophysiology, Treatment, and Prognosis in Thyroid Diseases
Authors: Docimo Giovanni , Cangiano Angelo , Romano Roberto Maria , Pignatelli Marcello Filograna , Offi Chiara , Paglionico Vanda Amoresano , Galdiero Marilena , Donnarumma Giovanna , Nigro Vincenzo , Esposito Daniela , Rotondi Mario , Candela Giancarlo , Pasquali Daniela
Published: December 2020

The human microbiota is an integral component in the maintenance of health and of the immune system. Microbiome-wide association studies have found numerous diseases associated to dysbiosis. Studies are needed to move beyond correlations and begin to address causation. Autoimmune thyroid diseases (ATD) are one of the most common organ-specific autoimmune disorders with an increasing prevalence, higher than 5% worldwide. Most frequent manifestations of ATD are Hashimoto’s thyroiditis and Graves’ disease. The exact etiology of ATD remains unknown. Until now it is not clear whether bacterial infections can trigger ATD or modulate the efficacy of treatment and prognosis. The aim of our review is to characterize the microbiota and in ATD and to evaluate the impact of dysbiosis on treatment and prognosis. Moreover, variation of gut microbiome has been associated with thyroid cancer and benign nodules. Here we will characterize the microbioma in benign thyroid nodules, and papillary thyroid cancer to evaluate their implications in the pathophysiology and progression.
The Identification of Critical m6A RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma
Authors: Xu Jiaju , Liu Yuenan , Liu Jingchong , Xu Tianbo , Cheng Gong , Shou Yi , Tong Junwei , Liu Lilong , Zhou Lijie , Xiao Wen , Xiong Zhiyong , Yuan Changfei , Chen Zhixian , Liu Di , Yang Hongmei , Liang Huageng , Chen Ke , Zhang Xiaoping
Published: December 2020

RNA methylation accounts for over 60% of all RNA modifications, and N6-methyladenosine (m6A) is the most common modification on mRNA and lncRNA of human beings. It has been found that m6A modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The m6A modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of m6A RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 m6A RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of p < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed m6A RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of m6A RNA methylation regulators in prostate cancer and determined a m6A gene expression classifier that well predicted the prognosis of prostate cancer.
Construction of CII-Specific CAR-T to Explore the Cytokine Cascades Between Cartilage-Reactive T Cells and Chondrocytes
Authors: Liu Xiaolong , Zhao Jun , Shi Ce , Liu Zhiyu , Shen Hongtao , Dang Junlong , Li Yang , Yang Dongguang , Wei Jia , Kang Liqing , Zhou Jin , Cao Fenglin , Zheng Song Guo , Wang Zhenkun
Published: December 2020

Cytokine cascades exist in many autoimmune disorders which amplify and sustain the autoimmune process and lead to chronic inflammatory injury to the host tissues. Increasing evidence indicates that chondrocytes can interact with T cells, which may be a crucial event in inflammatory arthritis. To address the reciprocal influences of cartilage-reactive T cells and chondrocytes, we constructed cartilage-reactive T cells by developing a type II collagen-specific chimeric antigen receptor (CII-CAR). Anin vitroco-culture model of CII-CAR-T cells and fresh cartilage was developed, in which CII-CAR-T displayed specific proliferative capacity and cytokine release against fresh cartilage samples, and chondrocytes could respond to CII-CAR-T cells by secreting IL-6. The proposed model will help us to explore the possible cytokine cascades between cartilage-reactive T cells and cartilage.
The JAK1 Selective Inhibitor ABT 317 Blocks Signaling Through Interferon-γ and Common γ Chain Cytokine Receptors to Reverse Autoimmune Diabetes in NOD Mice
Authors: Ge Tingting , Jhala Gaurang , Fynch Stacey , Akazawa Satoru , Litwak Sara , Pappas Evan G. , Catterall Tara , Vakil Ishan , Long Andrew J. , Olson Lisa M. , Krishnamurthy Balasubramanian , Kay Thomas W. , Thomas Helen E.
Published: December 2020

Cytokines that signal through the JAK-STAT pathway, such as interferon-γ (IFN-γ) and common γ chain cytokines, contribute to the destruction of insulin-secreting β cells by CD8+T cells in type 1 diabetes (T1D). We previously showed that JAK1/JAK2 inhibitors reversed autoimmune insulitis in non-obese diabetic (NOD) mice and also blocked IFN-γ mediated MHC class I upregulation on β cells. Blocking interferons on their own does not prevent diabetes in knockout NOD mice, so we tested whether JAK inhibitor action on signaling downstream of common γ chain cytokines, including IL-2, IL-7 IL-15, and IL-21, may also affect the progression of diabetes in NOD mice. Common γ chain cytokines activate JAK1 and JAK3 to regulate T cell proliferation. We used a JAK1-selective inhibitor, ABT 317, to better understand the specific role of JAK1 signaling in autoimmune diabetes. ABT 317 reduced IL-21, IL-2, IL-15 and IL-7 signaling in T cells and IFN-γ signaling in β cells, but ABT 317 did not affect GM-CSF signaling in granulocytes. When givenin vivoto NOD mice, ABT 317 reduced CD8+T cell proliferation as well as the number of KLRG+effector and CD44hiCD62Lloeffector memory CD8+T cells in spleen. ABT 317 also prevented MHC class I upregulation on β cells. Newly diagnosed diabetes was reversed in 94% NOD mice treated twice daily with ABT 317 while still on treatment at 40 days and 44% remained normoglycemic after a further 60 days from discontinuing the drug. Our results indicate that ABT 317 blocks common γ chain cytokines in lymphocytes and interferons in lymphocytes and β cells and are thus more effective against diabetes pathogenesis than IFN-γ receptor deficiency alone. Our studies suggest use of this class of drug for the treatment of type 1 diabetes.
Inhibition of Glycogen Synthase Kinase 3β Increases the Proportion and Suppressive Function of CD19+CD24hiCD27+ Breg Cells
Authors: Li Jinyang , Gao Ji , Zhou Haoming , Zhou Jinren , Deng Zhenghua , Lu Yunjie , Rao Jianhua , Ji Guwei , Gu Jian , Yang Xinxiang , Xia Yongxiang , Wang Xuehao
Published: December 2020

CD19+CD24hiCD27+ memory Breg cells exhibit decreased abundance in patients with chronic graft-versus-host disease (cGVHD) after liver transplantation and produce less IL-10 than those from patients without cGVHD and healthy donors. Due to the lack of Breg cells and the difficulty in expanding them in vitro, in mouse models and early human clinical trials, the adoptive transfer of Breg cells to autoimmune diseases is greatly restricted. Glycogen synthase kinase 3β (GSK-3β) is a multifunctional serine/threonine (ser/thr) protein kinase that can participate in B cell growth, metabolic activity, and proliferation. Phosphoprotein array analysis showed that p-GSK-3β-s9 was highly expressed in mBreg cells. Furthermore, here, we demonstrated that GSK-3β expression in mBreg cells is lower than that observed in B cells by flow cytometry. We found that the treatment of B cells with the specific GSK-3β inhibitor SB216763 can significantly increase the proportion and immunosuppressive function of mBreg cells in vitro. Nuclear factor of activated T cells (NFAT) is one of a pivotal regulator of gene expression in adaptive immune system. Here, we observed that inhibition of GSK-3β by SB216763 results in enhanced expression of NFATc1 in B cells, which is essential in regulating the ability of B cells to secrete IL-10. By constructing a xGVHD mouse model, we observed that SB216763-treated mBreg cells effectively prevent xenogeneic GVHD. Here we propose a novel strategy using SB216763 to inhibit GSK-3β and then enhance the proportion and immunosuppressive function of mBreg cells by increasing the expression of NFATc1. This approach may be used as a therapy to ameliorate GVHD and inflammatory diseases.
The Prevalence of Pulmonary Hypertension Among Maintenance Dialysis Patients With ESRD and Its Associated Factors: A Retrospective Study
Authors: Zhang Ying , Ding Xiao-Han , Rao Rongsheng , Wang Yiqin , Pang Fang , Tang Sha , Nie Ling , Bian Shi-Zhu
Published: December 2020

Aim: To determine the prevalence of pulmonary hypertension (PH) and its associated factors among end-stage renal disease (ESRD) patients who underwent maintenance dialysis.

Methods: A total of 491 patients received echocardiography examinations and underwent pulmonary artery systolic pressure (PASP) assessments. A subgroup of 283 patients were subjected to plasma creatinine (Cr) and blood urea nitrogen concentration (BUN) tests, routine blood examinations and electrolyte analysis. First, we compared the differences in echocardiographic, Cr and BUN, blood routine and electrolyte parameters between PH and non-PH groups. The correlations between PASP and the parameters mentioned above were also analyzed. Furthermore, univariate and adjusted logistic regression analyses were performed to identify the independent associated factors.

Results: The incidence of PH among ESRD patients who were treated with maintenance dialysis was 34.6%. Most of the echocardiographic parameters, including end-diastolic internal diameters of the left atrium, left ventricle, right atrium, and pulmonary artery, as well as interventricular septum mobility, left ventricular posterior wall mobility, fractional shortening, stroke volume and left ventricle ejection fraction (LVEF), were associated with PH. Furthermore, Mg2+ (p = 0.037) and Cl− (p = 0.043) were significantly associated with PASP. However, after adjustments were made in the regression analysis, only internal diameters of the left atrium, right atrium, and LVEF were independently associated with PH.

Conclusion: PH is prevalent, with a relatively high incidence among ESRD patients who undergo maintenance dialysis. The sizes of the left and right atria as well as LVEF were independently associated with PH, but further cohort and basic mechanistic studies are needed to confirm this finding.
COVID-19 Chest Computed Tomography to Stratify Severity and Disease Extension by Artificial Neural Network Computer-Aided Diagnosis
Authors: Carvalho Alysson Roncally S. , Guimarães Alan , Werberich Gabriel Madeira , de Castro Stephane Nery , Pinto Joana Sofia F. , Schmitt Willian Rebouças , França Manuela , Bozza Fernando Augusto , Guimarães Bruno Leonardo da Silva , Zin Walter Araujo , Rodrigues Rosana Souza
Published: December 2020

Purpose: This work aims to develop a computer-aided diagnosis (CAD) to quantify the extent of pulmonary involvement (PI) in COVID-19 as well as the radiological patterns referred to as lung opacities in chest computer tomography (CT).

Methods: One hundred thirty subjects with COVID-19 pneumonia who underwent chest CT at hospital admission were retrospectively studied (141 sets of CT scan images). Eighty-eight healthy individuals without radiological evidence of acute lung disease served as controls. Two radiologists selected up to four regions of interest (ROI) per patient (totaling 1,475 ROIs) visually regarded as well-aerated regions (472), ground-glass opacity (GGO, 413), crazy paving and linear opacities (CP/LO, 340), and consolidation (250). After balancing with 250 ROIs for each class, the density quantiles (2.5, 25, 50, 75, and 97.5%) of 1,000 ROIs were used to train (700), validate (150), and test (150 ROIs) an artificial neural network (ANN) classifier (60 neurons in a single-hidden-layer architecture). Pulmonary involvement was defined as the sum of GGO, CP/LO, and consolidation volumes divided by total lung volume (TLV), and the cutoff of normality between controls and COVID-19 patients was determined with a receiver operator characteristic (ROC) curve. The severity of pulmonary involvement in COVID-19 patients was also assessed by calculating Z scores relative to the average volume of parenchymal opacities in controls. Thus, COVID-19 cases were classified as mild (<cutoff of normality), moderate (cutoff of normality ≤ pulmonary involvement < Z score 3), and severe pulmonary involvement (Z score ≥3).

Results: Cohen's kappa agreement between CAD and radiologist classification was 81% (79–84%, 95% CI). The ROC curve of PI by the ANN presented a threshold of 21.5%, sensitivity of 0.80, specificity of 0.86, AUC of 0.90, accuracy of 0.82, F score of 0.85, and 0.65 Matthews' correlation coefficient. Accordingly, 77 patients were classified as having severe pulmonary involvement reaching 55 ± 13% of the TLV (Z score related to controls ≥3) and presented significantly higher lung weight, serum C-reactive protein concentration, proportion of hospitalization in intensive care units, instances of mechanical ventilation, and case fatality.

Conclusion: The proposed CAD aided in detecting and quantifying the extent of pulmonary involvement, helping to phenotype patients with COVID-19 pneumonia.
Assessment of Hypertension Using Clinical Electrocardiogram Features: A First-Ever Review
Authors: Bird Kathleen , Chan Gabriel , Lu Huiqi , Greeff Heloise , Allen John , Abbott Derek , Menon Carlo , Lovell Nigel H. , Howard Newton , Chan Wee-Shian , Fletcher Richard Ribon , Alian Aymen , Ward Rabab , Elgendi Mohamed
Published: December 2020

Hypertension affects an estimated 1.4 billion people and is a major cause of morbidity and mortality worldwide. Early diagnosis and intervention can potentially decrease cardiovascular events later in life. However, blood pressure (BP) measurements take time and require training for health care professionals. The measurements are also inconvenient for patients to access, numerous daily variables affect BP values, and only a few BP readings can be collected per session. This leads to an unmet need for an accurate, 24-h continuous, and portable BP measurement system. Electrocardiograms (ECGs) have been considered as an alternative way to measure BP and may meet this need. This review summarizes the literature published from January 1, 2010, to January 1, 2020, on the use of only ECG wave morphology to monitor BP or identify hypertension. From 35 articles analyzed (9 of those with no listed comorbidities and confounders), the P wave, QTc intervals and TpTe intervals may be promising for this purpose. Unfortunately, with the limited number of articles and the variety of participant populations, we are unable to make conclusions about the effectiveness of ECG-only BP monitoring. We provide 13 recommendations for future ECG-only BP monitoring studies and highlight the limited findings in pregnant and pediatric populations. With the advent of convenient and portable ECG signal recording in smart devices and wearables such as watches, understanding how to apply ECG-only findings to identify hypertension early is crucial to improving health outcomes worldwide.
FAM83A as a Potential Biological Marker Is Regulated by miR-206 to Promote Cervical Cancer Progression Through PI3K/AKT/mTOR Pathway
Authors: Rong Li , Li Haiyu , Li Zhaodong , Ouyang Jing , Ma Yongping , Song Fangzhou , Chen Yaokai
Published: December 2020

Background and Objective: Chemotherapy and radiotherapy are effective treatment options for cervical cancer (CC), but their efficacy is limited by short survival rate of about 5 years particularly for advance stage CC. Bioinformatics analysis combined with experimental in vivo and in vitro data can identify potential markers of tumorigenesis and cancer progression to improve CC prognosis and survival rate of the patients. This study aims to investigate the prognostic value of family with sequence similarity 83, member A (FAM83A) gene and miR-206 in promoting CC progression and the involved genetic signaling pathways.

Method: This was a bioinformatic analysis study based on RNA sequencing data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and verification by in vivo and in vitro experimental data. It was designed to evaluate whether the aberrantly expressed gene signatures could serve as new potential biomarker to improve prognosis prediction in CC. The TCGA RNA sequencing data [306 cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma samples and 13 adjacent samples] and GEO data (GSE9750 and GSE52903 datasets) were integrated and performed a bioinformatics analysis.

Results: The results showed that CC-associated FAM83A gene serves as a key regulator of CC development and progression. Functionally, we observed that FAM83A is significantly overexpressed in CC, which is linked to poor overall survival as well as disease-free survival in CC patients. The in-vitro and in-vivo assessments performed after silencing FAM83A revealed that cell proliferation was significantly inhibited and the S-phase cell cycle arrest was induced. Mechanistically, FAM83A plays a role in PI3K/AKT signaling, and its downstream molecules could promote CC cell proliferation. Furthermore, functionality assessments by in-vitro luciferase reporter system and immunoblot analysis showed that miR-206 was the upstream of FAM83A and negatively correlated with FAM83A.

Conclusion: The miR-206/FAM83A/PI3K/AKT signaling pathway possibly serves as a critical effector in CC progression indicating the potential prognostic value of FAM83A gene as a novel biomarker for CC progression.
Non-surface Attached Bacterial Aggregates: A Ubiquitous Third Lifestyle
Authors: Cai Yu-Ming
Published: December 2020

Bacteria are now generally believed to adopt two main lifestyles: planktonic individuals, or surface-attached biofilms. However, in recent years medical microbiologists started to stress that suspended bacterial aggregates are a major form of bacterial communities in chronic infection sites. Despite sharing many similarities with surface-attached biofilms and are thus generally defined as biofilm-like aggregates, these non-attached clumps of cells in vivo show much smaller sizes and different formation mechanisms. Furthermore, ex vivo clinical isolates were frequently reported to be less attached to abiotic surfaces when compared to standard type strains. While this third lifestyle is starting to draw heavy attention in clinical studies, it has a long history in natural and environmental sciences. For example, marine gel particles formed by bacteria attachment to phytoplankton exopolymers have been well documented in oceans; large river and lake snows loaded with bacterial aggregates are frequently found in freshwater systems; multispecies bacterial “flocs” have long been used in wastewater treatment. This review focuses on non-attached aggregates found in a variety of natural and clinical settings, as well as some recent technical developments facilitating aggregate research. The aim is to summarise the characteristics of different types of bacterial aggregates, bridging the knowledge gap, provoking new perspectives for researchers from different fields, and highlighting the importance of more research input in this third lifestyle of bacteria closely relevant to our daily life.
From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1
Authors: Ramdas Pavitra , Sahu Amit Kumar , Mishra Tarun , Bhardwaj Vipin , Chande Ajit
Published: December 2020

HIV-1 employs a rich arsenal of viral factors throughout its life cycle and co-opts intracellular trafficking pathways. This exquisitely coordinated process requires precise manipulation of the host microenvironment, most often within defined subcellular compartments. The virus capitalizes on the host by modulating cell-surface proteins and cleverly exploiting nuclear import pathways for post entry events, among other key processes. Successful virus–cell interactions are indeed crucial in determining the extent of infection. By evolving defenses against host restriction factors, while simultaneously exploiting host dependency factors, the life cycle of HIV-1 presents a fascinating montage of an ongoing host–virus arms race. Herein, we provide an overview of how HIV-1 exploits native functions of the host cell and discuss recent findings that fundamentally change our understanding of the post-entry replication events.
The Bio-Synthesis of Three Metal Oxide Nanoparticles (ZnO, MnO2, and MgO) and Their Antibacterial Activity Against the Bacterial Leaf Blight Pathogen
Authors: Ogunyemi Solabomi Olaitan , Zhang Muchen , Abdallah Yasmine , Ahmed Temoor , Qiu Wen , Ali Md. Arshad , Yan Chengqi , Yang Yong , Chen Jianping , Li Bin
Published: December 2020

Xanthomonas oryzae pv. oryzae (Xoo) is the most infectious pathogen of rice, which causes bacterial leaf blight (BLB) disease. However, the accumulation of chemical or antibiotic resistance of Xoo necessitate the development of its alternative control. In this study, we biologically synthesize three metal oxide nanoparticles (ZnO, MnO2, and MgO) using rhizophytic bacteria Paenibacillus polymyxa strain Sx3 as reducing agent. The biosynthesis of nanoparticles was confirmed and characterized by using UV-vis spectroscopy, XRD, FTIR, EDS, SEM, and TEM analysis. The UV Vis reflectance of the nanoparticle had peaks at 385, 230, and 230 nm with an average crystallite particle size 62.8, 18.8, and 10.9 nm for ZnO, MnO2, and MgO, respectively. Biogenic ZnO, MnO2, and MgO nanoparticles showed substantial significant inhibition effects against Xoo strain GZ 0006 at a concentration of 16.0 μg/ml, for which the antagonized area was 17, 13, and 13 mm and the biofilm formation was decreased by 74.5, 74.4, and 80.2%, respectively. Moreover, the underlining mechanism of nanoparticles was inferred to be in relation to the reactive oxygen species based on their antibacterial efficiency and the deformity in the cell wall phenomenon. Overall, an attractive and eco-friendly biogenic ZnO, MnO2, and MgO nanoparticles were successfully produced. Altogether, the results suggest that the nanoparticles had an excellent antibacterial efficacy against BLB disease in rice plants, together with the increase in growth parameter and rice biomass. In conclusion, the synthesized nanoparticles could serve as an alternative safe measure in combatting the antibiotic-resistant of Xoo.
Penicillium italicum: An Underexplored Postharvest Pathogen
Authors: Kanashiro Aline Midori , Akiyama Daniel Yuri , Kupper Katia Cristina , Fill Taícia Pacheco
Published: December 2020

In the agricultural sector, citrus is one of the most important fruit genus in the world. In this scenario, Brazil is the largest producer of oranges; 34% of the global production, and exporter of concentrated orange juice; 76% of the juice consumed in the planet, summing up US$ 6.5 billion to Brazilian GDP. However, the orange production has been considerable decreasing due to unfavorable weather conditions in recent years and the increasing number of pathogen infections. One of the main citrus post-harvest phytopathogen is Penicillium italicum, responsible for the blue mold disease, which is currently controlled by pesticides, such as Imazalil, Pyrimethanil, Fludioxonil, and Tiabendazole, which are toxic chemicals harmful to the environment and also to human health. In addition, P. italicum has developed considerable resistance to these chemicals as a result of widespread applications. To address this growing problem, the search for new control methods of citrus post-harvest phytopathogens is being extensively explored, resulting in promising new approaches such as biocontrol methods as “killer” yeasts, application of essential oils, and antimicrobial volatile substances. The alternative methodologies to control P. italicum are reviewed here, as well as the fungal virulence factors and infection strategies. Therefore, this review will focus on a general overview of recent research carried out regarding the phytopathological interaction of P. italicum and its citrus host.
Antimicrobial Activity of Soil Clostridium Enriched Conditioned Media Against Bacillus mycoides, Bacillus cereus, and Pseudomonas aeruginosa
Authors: Pahalagedara Amila Srilal Nawarathna Weligala , Flint Steve , Palmer Jon , Subbaraj Arvind , Brightwell Gale , Gupta Tanushree Barua
Published: December 2020

The rise of antimicrobial resistant bacteria has fast-tracked the exploration for novel antimicrobial compounds. Reports on antimicrobial producing soil anaerobes such as Clostridium spp. are very limited. In the present study, the antimicrobial activity of soil Clostridium enriched conditioned/spent media (CMs) against Bacillus mycoides, Bacillus cereus and Pseudomonas aeruginosa was assessed by turbidimetric growth inhibition assay. Our results highlighted the antimicrobial potential of soil Clostridium enriched conditioned media against pathogenic and spoilage bacteria. Farm 4 soil conditioned medium (F4SCM) demonstrated a greater growth inhibition activity against all three tested microorganisms in comparison to other soil conditioned media. Non-targeted metabolite profiling of all soil conditioned media revealed distinctive polar and intermediate-polar metabolites in F4SCM, consistent with its strong antimicrobial property. Moreover, 539 significantly abundant metabolites including some unique features were detected in F4SCM suggesting its substantial and specialized chemical diversity. This study putatively identified seven significantly high metabolites in F4SCM; 3-hydroxyphenylacetic acid, γ-aminobutyric acid, creatine, tryptamine, and 2-hydroxyisocaproic acid. Tryptamine and 2-hydroxyisocaproic acid were previously reported to have antimicrobial properties. The present study shows that soil Clostridium spp. are a promising group of bacteria producing metabolites with antimicrobial activity and provides future prospects for clostridial antimicrobial discovery within their metabolic diversity.
Identification of Tamoxifen-Resistant Breast Cancer Cell Lines and Drug Response Signature
Authors: Guan Qingzhou , Song Xuekun , Zhang Zhenzhen , Zhang Yizhi , Chen Yating , Li Jing
Published: December 2020

Breast cancer cell lines are frequently used to elucidate the molecular mechanisms of the disease. However, a large proportion of cell lines are affected by problems such as mislabeling and cross-contamination. Therefore, it is of great clinical significance to select optimal breast cancer cell lines models. Using tamoxifen survival-related genes from breast cancer tissues as the gold standard, we selected the optimal cell line model to represent the characteristics of clinical tissue samples. Moreover, using relative expression orderings of gene pairs, we developed a gene pair signature that could predict tamoxifen therapy outcomes. Based on 235 consistently identified survival-related genes from datasets GSE17705 and GSE6532, we found that only the differentially expressed genes (DEGs) from the cell line dataset GSE26459 were significantly reproducible in tissue samples (binomial test, p = 2.13E-07). Finally, using the consistent DEGs from cell line dataset GSE26459 and tissue samples, we used the transcriptional qualitative feature to develop a two-gene pair (TOP2A, SLC7A5; NMU, PDSS1) for predicting clinical tamoxifen resistance in the training data (logrank p = 1.98E-07); this signature was verified using an independent dataset (logrank p = 0.009909). Our results indicate that the cell line model from dataset GSE26459 provides a good representation of the characteristics of clinical tissue samples; thus, it will be a good choice for the selection of drug-resistant and drug-sensitive breast cancer cell lines in the future. Moreover, our signature could predict tamoxifen treatment outcomes in breast cancer patients.