bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound guided minimally invasive autopsies: combining imaging and pathology to characterize the systemic involvement of COVID-19 infection
Authors: Monteiro Renata Aparecida de Almeida , Duarte-Neto Amaro Nunes , Silva Luiz Fernando Ferraz da , Mauad Thais , Theodoro-Filho Jair , Oliveira Ilka Regina Souza de , Saldiva Paulo Hilario do Nascimento , Dolhnikoff Marisa
Published: April 2020

Post mortem tissue sampling is of paramount importance to conduct in-situ and molecular studies of COVID-19. Ultrasound-based minimally invasive autopsies (MIA/US) is an inexpensive procedure to obtain tissue samples of several organs and, at the same time, reduce the risks of the autopsy procedure in situations of high contagiousness. The images obtained by ultrasound are good enough to localize and orient the sampling, and to select the most affected areas within each organ. The amount of tissue sampled is adequate for histological and molecular studies and microorganism identification, and delivers information within a rapid time window. The combination of the aforementioned aspects may extend the possibility of conducting autopsies in different parts of the world, perhaps helping to understand local characteristics of COVID-19 infections, within an extended range of genetic, social and economic diversity.
Articular cartilage and bone changes following treatment of focal osteochondral defects in the femoral head with polyether ether ketone implants versus cobalt chromium molybdenum alloy implants: assessment in a goat model
Authors: Yuan Zhiguo , Zhang Wei , Meng Xiangchao , Zhang Jue , TengLong Teng , Zhao Yaochao , Yang Chunxi , Lin Ruixin , Yue Bing , Wang You
Published: April 2020

Objective : This study aimed to investigate the feasibility of applying defect-size polyether ether ketone (PEEK) implant for the treatment of localized osteochondral defects in the femoral head and compared it with cobalt chromium molybdenum (CoCrMo) alloy implant. Methods : A femoral head osteochondral defect model was created in the left hips of goats (n=12). Defects were randomly treated by immediate placement of a PEEK (n=6) or CoCrMo implant (n=6). The un-operated right hip joints served as a control. Goats were sacrificed at 12 weeks. The hip joints were evaluated by gross appearance, computed tomography (CT), and magnetic resonance imaging(MRI). Periprosthetic cartilage quality and the opposing cartilage (at the acetabular) quality were analyzed macroscopically and microscopically. Implant osseointegration was measured by micro-CT and histomorphometry. Results : Radiography revealed that all implants had good overall placement, without loosening of the implant. The modified macroscopic articular evaluation score in the PEEK group was lower than that in the CoCrMo group (p<0.05), and the histological score of the periprosthetic and acetabular cartilage in the PEEK group was lower than that in the CoCrMo group (P<0.05). The mean bone-implant contact for PEEK implants was comparable with that for CoCrMo alloy implants at 12 weeks. Conclusions : A PEEK implant for the treatment of local osteochondral defect in the femoral head demonstrated effective fixation and superior in vivo cartilage protection compared with an identical CoCrMo alloy implant.
A transient CRISPR/Cas9 expression system for genome editing in Trypanosoma brucei
Authors: Shaw Sebastian , Knüsel Sebastian , Hoenner Sarah , Roditi Isabel
Published: April 2020

ObjectiveGeneration of knockouts and in situ tagging of genes in Trypanosoma brucei has been greatly facilitated by using CRISPR/Cas9 as a genome editing tool. To date, this has entailed using a limited number of cell lines that are stably transformed to express Cas9 and T7 RNA polymerase (T7RNAP). It would be desirable, however, to be able to use CRISPR/Cas9 for any cell line.ResultsWe describe a sequential transfection expression system that enables transient expression of the two proteins, followed by delivery of PCR products for gRNAs and repair templates. This procedure can be used for genome editing without the need for stable integration of the Cas9 and T7RNAP genes.
A Significant association between CXCL10 -1447 A>G and IL18 -607 C>A gene polymorphisms with Human T-cell lymphotropic virus type 1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM-TSP), a case-control report from city of Mashhad, Iran
Authors: Rafatpanah Houshang , Poursina Zohreh , Marzouni Hadi Zare , Atabaki Mahdi , Farid-Hosseini Reza , Tavakkol-Afshari Jalil , Mohammadi Mojgan
Published: April 2020

The authors have removed this preprint from Research Square.
Short-term Outcomes after High Tibial Osteotomy Aimed at Neutral Alignment Combined with Arthroscopic Centralization of Medial Meniscus in Osteoarthritis Patients
Authors: Katagiri Hiroki , Nakagawa Yusuke , Miyatake Kazumasa , Otabe Koji , Ohara Toshiyuki , Shioda Mikio , Sekiya Ichiro , Koga Hideyuki
Published: April 2020

Purpose To improve long-term outcomes of open-wedge high tibial osteotomy (OWHTO), procedures combining OWHTO aimed at neutral alignment and arthroscopic centralization for meniscal extrusion have been introduced. The purpose of the present study was to compare short-term clinical and radiological outcomes of medial joint space width (JSW) after the OWHTO aimed at neutral alignment with and without arthroscopic centralization for an extruded medial meniscus. Methods A retrospective review of 50 primary OWHTO patients was conducted. Thirty-five patients included for analysis after exclusion criteria was applied. Twenty-one knee osteoarthritis patients, who underwent the OWHTO with arthroscopic meniscal centralization, were included in the centralization group. Fourteen patients, who underwent solely OWHTO, were included in the control group. Lysholm knee scale, International Knee Documentation Committee (IKDC) subjective score, Knee Osteoarthritis Outcome Score (KOOS), and patient subjective satisfaction scores were recorded at the final follow-up. Radiographic changes of JSW and joint line congruence angle (JLCA) were measured 2 years postoperatively. Patient demographic data were also reviewed. Results IKDC subjective scores, KOOS subgroup scores, patient subjective satisfaction scores, and Lysholm score did not show significant differences between the two groups at the final follow-up. Change of the JSW in the centralization group was significantly greater than that in the control group 2 years postoperatively (Control group: -0.1 mm, Centralization group: 0.8 mm P =0.03). Conclusion Change of JSW after OWHTO aimed at neutral alignment with arthroscopic centralization for extruded medial meniscus was greater than solely OWHTO, and there was no significant difference in the short-term clinical outcomes between the 2 procedures at the final follow-up.
Clinical characteristics of COVID-19 and establishment of a disease risk prediction model
Authors: Fan Tao , Hao Bo , Yang Shuo , Shen Bo , Huang Zhixin , Lu Zilong , Xiong Rui , Shen Xiaokang , Jiang Wenyang , Zhang Lin , Li Donghang , He Ruyuan , Meng Heng , Lin Weichen , Feng Haojie , Geng Qing
Published: April 2020

Background: COVID-19 is spreading worldwide. No specific medicine has been used for the treatment of coronavirus infections. The aim of this study is to establish a new risk predictive model to screen potential critical patients for early intervention.Methods: In this study, Clinical characteristics were collected and analyzed from 317 confirmed cases of COVID-19. A total of 175 of the 317 cases with detailed examination results were included to establish models for predicting the risk of disease progression. Major independent risk factors were incorporated into MuLBSTA model to establish new models for predicting critical risk. We further tracked 25 mild or moderate patients with COVID-19 to research dynamic changes of the major independent risk factors in COVID-19 progression.Results: The average age of all of the 317 patients was 47.76 (SD 17.22). A total of 48 (15.14%) were diagnosed with mild disease with a median age of 34(39.29±13.04), 116(36.59%) were diagnosed with moderate disease with a median age of 34(38.78±12.32), 38(11.99%) were diagnosed as severe with a median age of 56(58.24±15.12), and 115(36.28) were diagnosed as critical with a median age of 59(56.89+17.09). The most common symptom at onset of illness were fever(211[66.56%] patients). Age>50, CK>64, CD4≤461, and CD8≤241 were predicted to be major independent risk factors that could promote COVID-19 progression. Compared with the MuLBSTA model, the predictive ability of the CD4-CD8-MuLBSTA model and the CD4-MuLBSTA model were improved by 11.87% and 11.79%, respectively. In the prospective study, CK value began to show significant differences from day13. The average CD4 in Severe Group began to decline significantly on the fourth day, and the CD8 maintained a relatively low level in the Severe Group after day13.Conclusions: Severe COVID-19 patients were significantly older than non-severe patients. Immune systems of severe COVID-19 patients were significantly suppressed, and advanced age(>50 years), low levels of CD4(≤461) or CD8(≤241) was important clinical manifestations of rapid deterioration. CK values in severe COVID-19 patients were significantly higher than in no severe patients. CD4 and CD8 were incorporated into the MuLBSTA to establish a new model, which is an ideal risk prediction model for COVID-19 patients.
DNA Methylation Data-based Molecular Subtype Classification Related to the Prognosis of Patients with Hepatocellular Carcinoma
Authors: He Hui , Chen Di , Yi Dehui , Cheng Ying , Wang Xun , Ye Peng , Jin Shi
Published: April 2020

Background: DNA methylation is one of most frequently occurring molecular behaviours that occurs early during the complicated carcinogenesis process of hepatocellular carcinoma (HCC).Methods: In this study, 348 samples were collected from The Cancer Genome Atlas (TCGA) database and analysed to mine the specific DNA methylation sites that affect the prognosis of HCC patients.Results: The 10699 selected CpG sites (CpGs) that were markedly correlated with patient prognosis were used for consistent clustering of the samples into 7 subgroups, and the samples in each subgroup varied in terms of race, age, tumour stage, receptor status, histological type, metastasis status and patient prognosis. In addition, the level of methylation sites in each subgroup were calculated, and 119 methylation sites (corresponding to 105 genes) were screened as the intra-subgroup-specific methylation sites. Moreover, genes in the corresponding promoter regions in which the above specific methylation sites were located were subjected to signalling pathway enrichment analysis, and it was discovered that these genes were enriched in the bio-logical pathways that were reported to be closely correlated with HCC. Additionally, the subsequent transcription factor enrichment analysis revealed that these genes were mainly enriched in the transcription factor KROX. A prognosis prediction mod-el for HCC patients was constructed using the naive Bayesian classification model, and the training and test datasets were used for independent verification and testing.Conclusions: This classification method based on specific DNA methylation sites can well reflect the heterogeneity of HCC tissues and contributes to developing individualized treatments and accurately predicting patient prognosis.
Identification of a costimulatory molecule-based signature for predicting prognosis risk and immunotherapy response in patients with lung adenocarcinoma
Authors: Zhang Chaoqi , Zhang Zhihui , Sun Nan , Zhang Zhen , Zhang Guochao , Wang Feng , Luo Yuejun , Che Yun , He Jie
Published: April 2020

Background Costimulatory molecules play significant roles in mounting anti-tumor immune responses, and antibodies targeting these molecules are recognized as promising adjunctive cancer immunotherapies. Here, we aim to conduct a first full-scale exploration of costimulatory molecules from the B7-CD28 and TNF families in patients with lung adenocarcinoma (LUAD) and generated a costimulatory molecule-based signature (CMS) to predict survival and response to immunotherapy. Methods We enrolled 1549 LUAD cases across 10 different cohorts and included 502 samples from TCGA for discovery. The validation set included 970 cases from eight different Gene Expression Omnibus (GEO) datasets and 77 frozen tumor tissues with qPCR data. The underlying mechanisms and predictive immunotherapy capabilities of the CMS were also explored. Results A five gene-based CMS (CD40LG, TNFRSF6B, TNFSF13, TNFRSF13C, and TNFRSF19) was initially constructed using the bioinformatics method from TCGA that classifies cases as high- vs. low-risk groups per OS. Multivariable Cox regression analysis confirmed that the CMS was an independent prognostic factor. As expected, CMS exhibited prognostic significance in the stratified cohorts and different validation cohorts. Additionally, the prognostic meta-analysis revealed that CMS was superior to the previous signature. Samples in high- and low-risk groups exhibited significantly different tumor-infiltrating leukocytes and inflammatory activities. Importantly, we found that signature high-risk patients were optimal candidates for immunotherapy. Conclusion We conducted the first and most comprehensive costimulatory molecule landscape analysis of patients with LUAD and built a clinically feasible CMS for prognosis and immunotherapy response prediction, which will be helpful for further optimize immunotherapies for cancer.
Ileal proteomic changes associated with IL-25-mediated resistance against intestinal trematode infections
Authors: Álvarez-Izquierdo María , Esteban J. Guillermo , Muñoz-Antoli Carla , Toledo Rafael
Published: April 2020

Background: Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been widely employed to investigate the factors determining the rejection of intestinal helminths. In this sense, several studies have shown that IL-25 is essential for the development of resistance against E. caproni in mice. In fact, treatment of mice with recombinant IL-25 generates resistance against primary E. caproni infection. However, the mechanisms by which IL-25 induces resistance remain unknown.Methods: To study the mechanisms responsible for resistance elicited by IL-25, we analyze the ileal proteomic changes induced by IL-25 in mice and their potential role in resistance. To this purpose, we compare the protein expression profiles in the ileum of four experimental groups of mice: naïve controls; E. caproni-infected mice; rIL-25-treated mice; and rIL-25-treated mice exposed to E. caproni metacercariae.Results: Quantitative comparison by 2D-DIGE showed significant changes in a total of 41 spots. Forty of those spots validated protein spots were were identified by mass spectrometry corresponding to 24 proteins.Conclusions: The analysis of differentially expressed proteins indicates that maintenance of the intestinal epithelial homeostasis and the regulation of proliferation and cell death are the most affected processes that appears to be related to the resistance to infection. These results provide new insights into the proteins involved in the regulation of tissue homeostasis after intestinal infection and its transcendence in resistance.
Cognitive remediation group therapy versus mutual aid group therapy: A pilot randomized, controlled trial to determine the feasibility and acceptability of group therapy for people aging with HIV facing cognitive challenges
Authors: Eaton Andrew David , Craig Shelley L. , Rourke Sean B. , Sota Teresa , McCullagh John W. , Fallon Barbara A. , Walmsley Sharon L.
Published: April 2020

Background: Cognitive impairment is an important comorbidity for people aging with HIV, yet we lack non-medical techniques to address the associated anxiety and stress. Combination psychosocial interventions may have better outcomes than single technique approaches. Mindfulness-Based Stress Reduction (MBSR) and tablet-based Brain Training Activities (BTA) are promising techniques. Using community-based participatory research, our objective was to determine the feasibility and acceptability of group therapy for HIV, aging, and cognition.Methods: A pilot, parallel design, two-arm RCT recruited from a Toronto neurobehavioural research unit. Eligibility criteria included: diagnoses with mild-to-moderate HIV-associated neurocognitive disorder (HAND), age ≥ 40 years, HIV-positive for 5+ years, and English fluency. Randomization was 1:1 concealed allocation to Cognitive Remediation Group Therapy (Experimental; combination of BTA and MBSR) or Mutual Aid Group Therapy (Control). Primary outcomes were feasibility, measured by recruitment and completion, and acceptability, determined by a satisfaction questionnaire. The secondary outcome was intervention fidelity, assessed via facilitator session reports. Exploratory outcomes were anxiety, stress, coping, and use of mindfulness and brain training activities. Facilitators and analysts were blinded, however participants were not.Results: From 1 April 2018 to 19 March 2019, forty eligible participants were contacted, 12 randomized, and 10 completed the study and were analyzed for outcomes. The trial met its a priori feasibility targets with 30% recruited and 25% completed. At post-intervention, acceptability was 90% in the novel and 85% in the control arm. Assessors confirmed intervention delivery with satisfactory fidelity, with no missing components or significant deviations. Anxiety decreased for all in the novel arm and half of the control. Stress decreased and coping increased for half in both arms. All participants increased and sustained BTA use and half with mindfulness activities. There were no reported study harms.Conclusions: Although the combination of BTA and MBSR proved equal or slightly better to mutual aid therapy on all outcomes, recruitment of people with a formal HAND diagnosis from a single site was challenging. We recommend that future exploration of these techniques broaden to those aging with HIV with cognitive challenges regardless of a formal HAND diagnosis.Trial registration: clinicaltrials.gov, NCT03483740. Registered 30 March 2018, https://clinicaltrials.gov/ct2/show/NCT03483740
Chest CT imaging characteristics of COVID-19 pneumonia in preschool children: a retrospective study
Authors: Li Yang , Cao Jianghui , Zhang Xiaolong , Liu Guangzhi , Wu Xiaxia , Wu Baolin
Published: April 2020

Background : Recently, the World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) outbreak a public health emergency of international concern. So far, however, limited data are available for children. Therefore, we aimed to investigate the clinical and chest CT imaging characteristics of COVID-19 in preschool children. Methods: From January 26, 2020 to February 20, 2020, the clinical and initial chest CT imaging data of eight preschool children with laboratory-confirmed COVID-19 from two hospitals were retrospectively collected. The chest CT imaging characteristics, including the distribution, shape, and density of lesions, and the pleural effusion, pleural changes, and enlarged lymph nodes were evaluated. Results: Two cases (25%) were classified as mild type, and they showed no obvious abnormal CT findings or minimal pleural thickening on the right side. Five cases (62.5%) were classified as moderate type. Among these patients, one case showed consolidation located in the subpleural region of the right upper lobe, with thickening in the adjacent pleura; one case showed multiple consolidation and ground-glass opacities (GGO) with blurry margins; one case displayed bronchial pneumonia-like changes in the left upper lobe; and two cases displayed asthmatic bronchitis-like changes. One case (12.5%) was classified as critical type and showed bronchial pneumonia-like changes in the bilateral lungs, presenting blurred and messy bilateral lung markings and multiple patchy shadows scattered along the lung markings with blurry margins. Conclusions: The chest CT findings of COVID-19 in preschool children are atypical and various. Accurate diagnosis requires a comprehensive evaluation of epidemiological, clinical, laboratory and CT imaging data.
First report of the root-knot nematode, Meloidogyne morocciensis infecting peach in Southern Brazil
Authors: Silva W. R. , Machaca-Calsin C. P. , Gomes C. B.
Published: April 2020

The peach tree (Prunus persica) is the third most cultivated temperate fruit species in Brazil. In August 2017, peach seedling plants showing symptoms of stunting and multiple galls in the roots were detected in the municipality of Pelotas, state of Rio Grande do Sul, Brazil. Samples of peach roots were collected and they were subsequently processed to obtain eggs and second-stage juveniles (J2), to determine the number of nematodes per gram of roots and to proceed with morphological studies. Additionally, individual females were extracted from the peach roots and submitted to Meloidogyne species identification by electrophoresis using α-esterase (Est) and malate dehydrogenase (Mdh) phenotypes and perineal pattern. The nematode population density in the samples was 283 eggs + J2s per gram of fresh roots. The polymorphism analysis revealed the A3N1 phenotype, typical to Meloidogyne morocciensis. Perineal patterns of females showed oval squared shapes, with moderately high to high dorsal arches, streaks widely separated, generally continuous, sometimes broken; the phasmids were separate by 29.3 μm (25.43-31.94 μm), similar to M. arenaria and M. incognita, as observed by Hammah and Hirschmann (1990). The second-stage juveniles had the following morphometric characters: L = 389.3 ± 3.8 (377.5-425.1) μm, stylet = 13.9 ± 0.2 (12.7-14.9) μm, DGO = 3.6 ± 0.1 (3.3-4.2) μm, tail length 47.5 ± 0.6 (45.3-48.9) µm, hyaline tail terminus = 14.1 ± 0.3 (12.5-17.0) µm, a = 25.6 ± 0.4 (23.8-28.8) µm and c = 8.6 ± 0.1 (8.0-9.3). The known SCAR marker obtained for M. arenaria is the same as that amplified for M. morocciensis. Under greenhouse conditions, peach plants seedlings inoculated with 1,000 eggs (Pi) with M. morocciensis were evaluated 28 days after inoculation compared to non-inoculated plants. The inoculated peach plants showed a mean of 338 galls per root system, and a nematode reproduction factor of 10.3. Besides this plants exhibited a reduction in fresh weight of shoots and roots compared to the non-inoculated plants. These results confirm M. morocciensis pathogenicity on P. persica.
Modeling total microcystin production by Microcystis aeruginosa using multiple regression
Authors: Aragão Marianna Correia , dos Reis Kelly Cristina , Souza Allan Clemente , Rocha Maria Aparecida Melo , Capelo Neto Jose
Published: April 2020

Microcystis sp. is one of the most studied genus of cyanobacteria worldwide. Once it has been identified in raw water, frequent analyses of cell density and toxic metabolites (microcystins) are recommended at the water treatment plants. However, both analytical procedures are highly time-consuming and labor-intensive, allowing the potentially contaminated finished water to reach customers. The identification of easily measurable parameters related to toxin production, preferably by on-line equipment, would mitigate this issue and help water companies to improve water safety and decrease operating costs. However, these devices still have precision limitations and need efficient mathematical models for converting light signals into cyanobacteria densities or cyanotoxin concentrations. In this scenario, this research aimed to develop a mathematical correlation between microcystin production and cell age and density, chlorophyll-a, pheophytin and phycocyanin in a Microcystis aeruginosa culture using a multiple linear regression model. Despite the significant correlation (p < 0.05) found between all the variables and total microcystin, a simplified and precise model (Adjusted R2 = 0.824) involving only phycocyanin and pheophytin concentrations was developed in order to provide an initial attempt to easily and cheaply predict microcystin concentration in raw water.
Development of GIS-based Python scripts to calculate a water surface profile on a landscape for wetlands decision-making
Authors: Wang Zhentao , Trauth Kathleen M.
Published: April 2020

Wetlands provide many benefits for humans and the natural environment, but land-use changes have reduced their number and areal extent. Interest has grown in examining the landscape to determine those locations where, with minimal effort, it might be possible to develop a mitigation wetland – a location with sufficient water over a sufficient period of time to develop and maintain wetland functioning. This paper proposes a methodology to support the examination of the landscape for mitigation purposes through the application of open channel hydraulics principles to flow over a landscape. The methodology is part of a larger research effort ultimately combining hydrology and hydraulics, along with the landscape processes of infiltration and evapotranspiration, to perform a water balance assessment. Specifically, the methodology is implemented through readily available geographic information system tools along with Python scripts written for this study. The Python scripts automatically extract landscape characteristics from a digital elevation model and calculate hydraulic parameters that are used to determine water surface profiles using the Modified Euler's method. Multiple tests show that the script accurately produces profiles of flow between depressions over a landscape. Such determinations are the first step in understanding where water might exist on the surface to support mitigation wetland functions.
Therapeutics and Research Related to Glioblastoma: Advancements and Future Targets
Authors: Chavda Vishal , Patel Vimal , Yadav Dhananjay , Shah Jigar , Patel Snehal , Jin Jun-O
Published: April 2020

Glioblastoma, the most common primary brain tumor, has been recognized as one of the most lethal and
fatal human tumors. It has a dismal prognosis, and survival after diagnosis is less than 15 months. Surgery and radiotherapy
are the only available treatment options at present. However, numerous approaches have been made to upgrade
in vivo and in vitro models with the primary goal of assessing abnormal molecular pathways that would be
suitable targets for novel therapeutic approaches. Novel drugs, delivery systems, and immunotherapy strategies to
establish new multimodal therapies that target the molecular pathways involved in tumor initiation and progression in
glioblastoma are being studied. The goal of this review was to describe the pathophysiology, neurodegeneration
mechanisms, signaling pathways, and future therapeutic targets associated with glioblastomas. The key features have
been detailed to provide an up-to-date summary of the advancement required in current diagnosis and therapeutics
for glioblastoma. The role of nanoparticulate system graphene quantum dots as suitable therapy for glioblastoma has
also been discussed.
Nifurtimox Hampered the Progression of Astroglioma In vivo Via Manipulating the AKT-GSK3β axis
Authors: Zhang Qiuxia , Chen Zhenshuai , Yuan Wei , Tang Yu-Qing , Zhu Jiangli , Wu Wentao , Ren Hongguang , Wang Hui , Zheng Weiyi , Zhang Zhongjian , Kong Eryan
Published: April 2020

Background:

Astroglioma, one major form of brain tumors, has remained principalAstroglioma, one major form of brain tumors, has remained
principally tough to handle for decades, due to the complexity of tumor pathology and
the poor response to chemo- and radio-therapies.ly tough
to handle for decades, due to the complexity of tumor pathology and the poor response
to chemo- and radio-therapies. Our previous study demonstrated that nifurtimox could
regulate the signaling axis of AKT-GSK3β in various tumor types including the
astroglioma U251 cells. Intriguingly, earlier case studies suggested that nifurtimox could
possibly permeate the blood brain barrier and arrest neuroblastoma in the brain. These
observations jointly encouraged us to explore whether nifurtimox would hinder the
growth of astroglioma in vivo. Our results exhibited that nifurtimox could competently
hinder the development of astroglioma in the mouse brain as compared to
temozolomide, the first line of drug for brain tumors. Meanwhile the surviving rate, as
well as the body-weight was dramatically upregulated upon nifurtimox treatment, as
compared to that of temozolomide. These findings offered nifurtimox as a better
alternative drug in treating astroglioma in vivo. Persistently, the manipulation of the
signaling axis of AKT-GSK3β in astroglioma was found in line with earlier findings in
neuroblastoma when treated with nifurtimox.

Methods:

Our previous study demonstrated that nifurtimox could regulate the signaling
axis of AKT-GSK3β in various tumor types including the astroglioma U251 cells.
Intriguingly, earlier case studies suggested that nifurtimox could possibly permeate the
blood brain barrier and arrest neuroblastoma in the brain. These observations jointly
encouraged us to explore whether nifurtimox would hinder the growth of astroglioma in
vivo.

Results:

Our results exhibited that nifurtimox could competently hinder the development
of astroglioma in the mouse brain as compared to temozolomide, the first line of drug for
brain tumors. Meanwhile the surviving rate, as well as the body-weight was dramatically
upregulated upon nifurtimox treatment, as compared to that of temozolomide. These
findings offered nifurtimox as a better alternative drug in treating astroglioma in vivo.

Conclusion:

Persistently, the manipulation of the signaling axis of AKT-GSK3β in
astroglioma was found in line with earlier findings in neuroblastoma when treated with
nifurtimox.
Cardiovascular Disease in Juvenile Idiopathic Arthritis
Authors: Arsenaki Elisavet , Georgakopoulos Panagiotis , Mitropoulou Panagiota , Koutli Evangelia , Thomas Konstantinos , Charakida Marietta , Georgiopoulos Georgios
Published: April 2020

Juvenile idiopathic arthritis (JIA), is a term used to describe a group of inflammatory disorders beginning before the age of 16 years. Although for the majority of children remission is achieved early, those with systemic or polyarticular form of the disease may present persistent symptoms in adulthood. Considering that there is overlap in the pathogenesis of JIA with adult rheumatic diseases, concerns have been raised as to whether JIA patients could be at increased cardiovascular (CV) risk in the long-term. In this review, we summarize evidence for CV involvement in JIA and present data on CV risk factors and surrogate markers of arterial disease. We also provide information on beneficial and harmful CV effects of anti-inflammatory medications in the context of JIA and suggest strategies for CV screening. Overall, patients with systemic forms of JIA demonstrate an adverse lipid profile and early arterial changes relevant to accelerated arterial disease progression. Although there is paucity of data on CV outcomes, we recommend a holistic approach in the management of JIA patients, which includes CV risk factor monitoring and lifestyle modification as well as use, when necessary, of antiinflammatory therapies with documented CV safety.
Polycystic Ovary Syndrome and Infertility: From Molecular Perspective
Authors: Ghafarzadeh Masoumeh
Published: April 2020

Polycystic ovary syndrome (PCOS) is one of the major endocrine abnormalities in
women. It is associated with the dysfunction of androgen metabolism, elevation in insulin resistance
and impaired fertility. In addition, it is characterized by polycystic ovaries, chronic anovulation,
hyperandrogenism, chronic low-grade inflammation and type 2 diabetes. Furthermore, the studies
have indicated that PCOS is associated with higher rates of obesity and central adiposity, which are
partly responsible for the clinical severity of PCOS. Over the years, PCOS has been associated with
infertility in women, as it is responsible for subfertility and increases the risk of pregnancy-related
complications like gestational diabetes, hypertensive disorders, and premature delivery. The pathogenesis
of PCOS remains ambiguous, however PI3K-Akt and retinoid signaling pathways are
known to be involved mechanisms. In this review, we will give a comprehensive summary based on
the possible association of PI3K-Akt and retinoid signaling pathways in PCOS-related infertility.
Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines
Authors: Baig Abdul M. , Rana Zohaib , Mannan Mohammad M. , Khaleeq Areeba , Nazim Fizza , Katyara Preet , Abbas Farhat
Published: April 2020

Background:

Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins
involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer
drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs.

Objectives:

We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved
in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1)
pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa).

Methods:

Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav,
CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa
cell lines.

Results:

We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects when
tested in DU145 and PC3 cell lines. Diphenhydramine, which shares its targets with promethazine, except the
CaM, failed to exhibit oncocidal effects.

Conclusion:

Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine
that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized, or these two drugs could
be re-purposed after human trials in PCa.
TIME SERIES ANALYSIS: FORECASTING SALES PERIODS IN WHOLESALE SYSTEMS
Authors: Predić Bratislav , Radosavljević Nevena , Stojčić Aleksandar
Published: April 2020

The main goal of time series analysis is explaining the correlation and the main features of the data in chronological order by using appropriate statistical models. It is being used in various aspects of life and work, as well as in forecasting future product demands, service demands, etc. The most common type of time series data is the one whose observations are taken in equally distributed time intervals (daily, weekly, monthly, etc.). However, in this paper, we analyze a different kind of time series which represents product purchase moments. Thus, since there are not any regular observation periods, this irregular time series must be transformed in some way before traditional methods of analysis can be applied.  After the data transformation is complete, the next step is modeling the nonstationary time series using commonly known models such as ARIMA and PNBD, which have been chosen for their fairly easy and successful forecasting processes. The goal of this analysis is timely product advertising to a customer in order to increase sales.Unlike some other models that consider the relationship between two or more different phenomena, time series models, including ARIMA, Pareto/NBD and Poisson models, examine the impact of historical values of a single phenomenon on its present and future value. This approach enables the study of the behavior of a given phenomenon over time and produces good results, especially if a large amount of historical data is available.
ANALISIS TERHADAP ISI MATERI PENDIDIKAN AGAMA ISLAM dalam Kurikulum 2006 (KTSP) Kelas VII, Memasuki Standar Nasional Pendidikan (SNP)
Authors: . Romlah
Published: April 2020

ANALISIS TERHADAP ISIMATERI PENDIDIKANAGAMA ISLAMdalamKurikulum 2006 (KTSP) Kelas VII,Memasuki Standar Nasional Pendidikan(SNP)Romlah *)Fai UMMABSTRACTThe title of our research is to foster "Content Analysis of Content of IslamicReligious Education in Curriculum 2006 (KTSP) Junior High School SeniorClass VII, entered the National Education Standards (SNP)". As a verybasic consideration making this title change of the curriculum is almostadjacent, from the curriculum in 2004 (KBK) with the curriculum in 2006(KTSP). If the observed substance or content of Islamic education in juniorhigh school level class VII, then the exact same between the standard andbasic competencies, as well as forms of learning are both more emphasizedcompetencies that each student is different from one another.Keyword:Materi Pendidikan Agama Islam,Kurikulum 2006 (KTSP)
DAMPAK SERTIFIKASI SEBAGAI PROGRAM PENINGKATAN PROFESIONALISME GURU TERHADAP KESEJAHTERAAN DAN KINERJA GURU
Authors: Masruroh Fita
Published: April 2020

Fita Masruroh *)Pasca Sarjana UMMABSTRACTProfesionalism is a process to increase the qualification or the ability’s members of aprofession to get the ideal criteria of the performance what the profession wanted.Professional teacher is one who to be able to validate their knowledge, by study their selfor used training from institution of government and public. Example: training, seminar,and training college. The prospect result is balance between output and input and givecontribution for government Indonesia, teachers and quality of education for younggeneration. UU No. 14 Tahun 2005 is one of government program to increase the qualityor professional teacher and to increase their safety life. Beside that, many modelsprepared from goverment to increase the profesional teacher. Example: long distencestudy model, long distence training college model, akreditasi model, sertifikasi, and ect.Kata Kunci : Profesionalisme Gurudan Dampak Sertifikasi
PEMBELAJARAN AL-QUR’AN MELALUI PENDEKATAN METODE TAFSIR TEMATIK BAGI GURU TPQ DI KOTA MALANG
Authors: Nur Taufiq Hadi
Published: April 2020

PEMBELAJARAN AL-QUR’ANMELALUI PENDEKATAN METODE TAFSIR TEMATIKBAGI GURU TPQ DI KOTA MALANGOleh :Hadi Nur Taufiq *)Fakultas Agama Islam UMMABSTRACTThematic interpretation approach was considerably new and unfamiliar in Al-Qur’an teachinglearning process due to a lack of expert and knowledge on the subject. However, the approachactually offered immediate and effective solution in Al Qur’an perspective. Hence, the approachwas worth applied to replace the old-fashioned one to provide Islamic education teachers and AlQur’an community with easier way to comprehend God’s revelation.Keywords : Teaching and Learning Process,Al-Qur’an, Thematic Interpretation
Central Asia as an area of China’s and Russia’s interests
Authors: Egorycheva Elena A.
Published: April 2020

Over the past decades, Russia and China have been steadily deepening their cooperation. It is seen in many fields: mutual trade agreements, investment and scientific cooperation, ecological and environment solutions to global issues. Russia is actively engaged in the Belt and Road Initiative proposed by China. Kazakhstan, Turkmenistan, Uzbekistan, Tajikistan, and Kyrgyzstan are engaged in it as well. Some of them are also members of the Eurasian Economic Union. The paper aimed to identify China’s and Russia’s current interests in these countries, as Central Asia (CA) is the area where Russia’s and China’s interests coincide. Trade relations between the analyzed countries are considered in it. The paper also addresses investment projects under Belt and Road Initiative, which China has been financing in CA countries.
Smart Tourism with Smart TVs
Authors: Camargo Ariza Luis Leonardo , Rivera Ospino Miguel José , Medina Delgado Byron
Published: April 2020

The use of ICT to promote tourism in the Colombian Caribbean is limited; however, applications for smart TVs are a viable alternative due to their multimedia capabilities. This paper presents the development of an app called SantaMartaTV, which is intended for Smart TVs and envisions the concept of tourism in a Smart City. The app offers photos, videos, maps and descriptions of the most ideal touristic places in Santa Marta; it allows users to share the content on Facebook, a social networking site. The content displayed on the site is stored on XML files which contain information about the resources. These files are hosted in the servers of freely available services, such as Facebook, YouTube, Google Maps and Dropbox. This feature reduces the cost of implementing new technological infrastructure and facilitates the editing of content. SantaMartaTV promotes the good name of the city as well as improves the visitors’ experience by providing them with interactive information at any time. This article further proposes a methodology for developing Smart TV apps. This new methodology is based on existing agile methodologies, usability concepts and the audiovisual capabilities of TV sets. The methodology satisfies the needs for the development of apps because it provides tools and diagrams which facilitate and guide the elaboration of these specific applications therefore ensuring a user-friendly and attractive app for potential users.
John Keats'in Lamia Şiiri ve Yaşar Kemal'in Yılanı Öldürseler Romanında Eril Kol
Authors: Karadaş Fırat
Published: April 2020

Bakış sadece bakma eylemini değil erkek egemen toplumsal söylemin kadınları kontrol etmesini ve onları belli bir şekilde temsil etmesini simgeler. Kültür tarihinde, mitolojide ve edebiyatta kadın sıkça yılanla (örn. Medusa, Lamia, Lilith) özdeşleştirilmiştir ve kötülük, cazibe ve büyü kaynağı olarak görülmüştür. Mitolojide ve kültür tarihinde yılansı kadının yaptığı kötülükler kem göz ile anlatılır ve koruyucu mavi göz (Türkçe’de nazarlık) veya bakış eril dünyayı bu kötülüklerden korumak için kullanılır. İngiliz Romantik şairi John Keats’in mitolojide üst tarafı kadın alt tarafı yılan olan Lamia’nın haberci tanrı Hermes tarafından insana dönüştürüldükten sonra Lycius adındaki genç bir adamla yaşadığı aşkı anlatan Lamia adlı şiiri, Corinth’in eril dünyasında Lamia’nın yokedilmesi konusunda kolektif bakışın işlevini yansıtmaktadır. Şiirde, bilge Apollonius’un öğrencisi Lycius’u yılanın kötülüklerinden koruma işlevi gören ‘mavi bakışı’ bu çalışmanın amacı bağlamında önemlidir. Yaşar Kemal’in Yılanı Öldürseler romanında eril/toplumsal bakış bu sefer kocası eski sevgilisi tarafından öldürülen ve çok güzel bir kadın olan Esme’ye odaklanmıştır. Roman başlığının gösterdiği gibi eril bakışın amacı yılanı ezmektir ve birçok karakter, özellikle de Esme’nin kaynanası, Hasan’ı annesini öldürmeğe ikna etmek için bir köy ortamındaki eril toplumsal söylemin bütün araçlarını kullanır. Makale, bakışın tarihi, dini ve mitolojik önemini, eril yönünü ve dişil olanla bağı veya mitik/tarihi çatışmasını ele almayı amaçlamaktadır. Makale, bu konuları Keats’in Lamia şiiri ve Yaşar Kemal’in Yılanı Öldürseler romanı bağlamında ele almaktadır.
Geopolitical thought of Saul Bernard Cohen: Between obsoletion and underutilization
Authors: Kopanja Mihajlo
Published: April 2020

At the time when geopolitics, after its half a century long downfal, is
reemerging and returning to the focus of academic considerations, varaities
of contemporary geopolitical thought is observed almost exclusively through
the prism of two entrenched positions: classical and critical geopolitics.
With such oversimplification, geopolitics may loose much, demanding
observation, understandment and requestioning of thoughts by those authors
that cannot be simply labeled as either classical or critical. In a desire
to contribute to the overcoming of such oversimplifications, this paper
observes the geopolitical though of Saul Bernard Cohen in the light of
determining its contemporary relevance. Starting from the question whether
his thoughts are obsolete or underutilized, the paper provides an overview
of authors that influenced Cohen, observation of the evolution of his
geopolitical thoughts through seven decade long career, and the conceptual
matrix he developed. Labeling Cohen?s thought as a specific geopolitical
approach, rather than a general theory, the paper identifies the limitations
of his approach with which the discrepancy between the possibilities it
provides and the lack of its usage in contemporary geopolitical literature
are explained. Yet, this paper points to the existence of considerations
within Cohen?s opus which can serve as the foundation for overcoming the
limitations of his geopolitical approach, concluding that, because of such
possibilities, Cohen?s geopolitical thought is to a greater extent
underutilized then it is obsolete.
CEO Tax Effects on Acquisition Structure and Value
Authors: Hanlon Michelle , Verdi Rodrigo S. , Yost Benjamin P.
Published: April 2020

We hypothesize that prior evidence of target shareholder capital gains tax liabilities affecting acquisition features is driven by the tax liabilities of the target firm CEO. To test this, we estimate CEOs' capital gains tax liabilities for a large sample of acquisitions and examine the effects of such liabilities on acquisition outcomes. Results indicate that the previously documented positive relations between shareholder-level capital gains tax rates and (1) the likelihood of a nontaxable acquisition (Ayers, Lefanowicz, and Robinson 2004), and (2) acquisition premiums (Ayers, Lefanowicz, and Robinson 2003) are largely driven by CEO tax effects. We also find evidence consistent with (1) CEOs' tax incentives leading to potential agency conflicts under certain conditions, and (2) acquisition structure or premium being adjusted in response to CEOs' taxes depending on the alternatives available to the acquirer. Our study contributes to our understanding of what and whose taxes affect acquisition structure and value.

JEL Classifications: G34:, H24; H32: J33; M52.
The Folly of Forecasting: The Effects of a Disaggregated Demand Forecasting System on Forecast Error, Forecast Positive Bias, and Inventory Levels
Authors: Brüggen Alexander , Grabner Isabella , Sedatole Karen L.
Published: April 2020

Periodic demand forecasts are the primary planning and coordination mechanism within organizations. Because most demand forecasts incorporate human judgment, they are subject to both unintentional error and intentional opportunistic bias. We examine whether a disaggregation of the forecast into various sources of demand reduces forecast error and bias. Using proprietary data from a manufacturing organization, we find that absolute demand forecast error declines following the implementation of a disaggregated forecast system. We also find a favorable effect of forecast disaggregation on finished goods inventory without a corresponding increase in costly production plan changes. We further document a decline in positive forecast bias, except for products whose production is limited owing to scarce production resources. This implies that disaggregation alone is not sufficient to overcome heightened incentives of self-interested sales managers to positively bias the forecast for the very products that an organization would like to avoid tying up in inventory.

Data Availability: Data are the property of the research partner and may not be redistributed by the authors.