bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human APOE ɛ3 and APOE ɛ4 Alleles Have Differential Effects on Mouse Olfactory Epithelium
Authors: Khan Naazneen , Alimova Yelena , Clark Sophie J. , Vekaria Hemendra J. , Walsh Adeline E. , Williams Holden C. , Hawk Gregory S. , Sullivan Patrick G. , Johnson Lance A. , McClintock Timothy S. 
Published: December 2021

Background: Alzheimer’s disease (AD) is a progressive age-dependent disorder whose risk is affected by genetic factors. Better models for investigating early effects of risk factors such as apolipoprotein E ( APOE) genotype are needed. Objective: To determine whether APOE genotype produces neuropathologies in an AD-susceptible neural system, we compared effects of human APOE ɛ3 (E3) and APOE ɛ4 (E4) alleles on the mouse olfactory epithelium. Methods: RNA-Seq using the STAR aligner and DESeq2, immunohistochemistry for activated caspase-3 and phosphorylated histone H3, glucose uptake after oral gavage of 2-[1,2-3H (N)]-deoxy-D-glucose, and Seahorse Mito Stress tests on dissociated olfactory mucosal cells. Results: E3 and E4 olfactory mucosae show 121 differentially abundant mRNAs at age 6 months. These do not indicate differences in cell type proportions, but effects on 17 odorant receptor mRNAs suggest small differences in tissue development. Ten oxidoreductases mRNAs important for cellular metabolism and mitochondria are less abundant in E4 olfactory mucosae but this does not translate into differences in cellular respiration. E4 olfactory mucosae show lower glucose uptake, characteristic of AD susceptibility and consistent with greater expression of the glucose-sensitive gene, Asns. Olfactory sensory neuron apoptosis is unaffected at age 6 months but is greater in E4 mice at 10 months. Conclusion: Effects of human APOE alleles on mouse olfactory epithelium phenotype are apparent in early adulthood, and neuronal loss begins to increase by middle age (10 months). The olfactory epithelium is an appropriate model for the ability of human APOE alleles to modulate age-dependent effects associated with the progression of AD.
Depression and Dementia: The Role of Cortisol and Vascular Brain Lesions. AGES-Reykjavik Study
Authors: Gerritsen Lotte , Twait Emma L. , Jonsson Palmi V. , Gudnason Vilmundur , Launer Lenore J. , Geerlings Mirjam I. 
Published: December 2021

Background: Late-life depression (LLD) is related to an increased risk of developing dementia; however, the biological mechanisms explaining this relationship remain unclear. Objective: To determine whether the relationship between LLD and dementia can be best explained by the glucocorticoid cascade or vascular hypothesis. Methods: Data are from 4,354 persons (mean age 76±5 years) without dementia at baseline from the AGES-Reykjavik Study. LLD was assessed with the MINI diagnostic interview (current and remitted major depressive disorder [MDD]) and the Geriatric Depression Scale-15. Morning and evening salivary cortisol were collected (glucocorticoid cascade hypothesis). White matter hyperintensities (WMH; vascular hypothesis) volume was assessed using 1.5T brain MRI. Using Cox proportional hazard models, we estimated the associations of LLD, cortisol levels, and WMH volume with incident all-cause dementia, AD, and non-AD dementia. Results: During 8.8±3.2 years of follow-up, 843 persons developed dementia, including 397 with AD. Current MDD was associated with an increased risk of developing all-cause dementia (HR = 2.17; 95% CI 1.66–2.67), with risks similar for AD and non-AD, while remitted MDD was not (HR = 1.02; 95% CI 0.55–1.49). Depressive symptoms were also associated with increased risk of dementia, in particular non-AD dementias. Higher levels of evening cortisol increased risk of dementia, but this was independent of MDD. WMH partially explained the relation between current MDD and dementia risk but remained increased (HR = 1.71; 95% CI 1.34–2.08). Conclusion: The current study highlights the importance of LLD in developing dementia. However, neither the glucocorticoid cascade nor the vascular hypotheses fully explained the relation between depression and dementia.
Functional Neural Correlates of Semantic Fluency Task Performance in Mild Cognitive Impairment and Alzheimer’s Disease: An FDG-PET Study
Authors: Ahn Hyejin , Yi Dahyun , Chu Kyungjin , Joung Haejung , Lee Younghwa , Jung Gijung , Sung Kiyoung , Han Dongkyun , Lee Jun Ho , Byun Min Soo , Lee Dong Young 
Published: December 2021

Background: Total score (TS) of semantic verbal fluency test (SVFT) is generally used to interpret results, but it is ambiguous as to specific neural functions it reflects. Different SVFT strategy scores reflecting qualitative aspects are proposed to identify specific cognitive functions to overcome limitations of using the TS. Objective: Functional neural correlates of the TS as well as the other strategy scores in subjects with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia using Fluorine-18-Fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Correlations between various SVFT scores (i.e., TS, mean cluster size, switching (SW), hard switching, cluster switching (CSW)) and cerebral glucose metabolism were explored using voxelwise whole-brain approach. Subgroup analyses were also performed based on the diagnosis and investigated the effects of disease severity on the associations. Results: Significant positive correlation between TS and cerebral glucose metabolism was found in prefrontal, parietal, cingulate, temporal cortex, and subcortical regions. Significantly increased glucose metabolism associated with the SW were found in similar but smaller regions, mainly in the fronto-parieto-temporal regions. CSW was only correlated with the caudate. In the subgroup analysis conducted to assess different contribution of clinical severity, differential associations between the strategy scores and regional glucose metabolism were found. Conclusion: SW and CSW may reflect specific language and executive functions better than the TS. The SVFT is influenced by brain dysfunction due to the progression of AD, as demonstrated by the SW with larger involvement of temporal lobe for the AD, and CSW with significant association only for the MCI.
The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study
Authors: Zhang Heng , Lyu Diyang , Jia Jianping ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2021

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.
Parkinson’s Disease Motor Subtypes Change with the Progression of the Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up
Authors: Santos García Diego , Canfield Hector , de Deus Fonticoba Teresa , Cores Bartolomé Carlos , Naya Ríos Lucía , García Roca Lucía , Martínez Miró Cristina , Jesús Silvia , Aguilar Miquel , Pastor Pau , Cosgaya Marina , García Caldentey Juan , Caballol Nuria , Legarda Inés , Hernández Vara Jorge , Cabo Iria , López Manzanares Lydia , González Aramburu Isabel , Ávila Rivera María A. , Gómez Mayordomo Víctor , Nogueira Víctor , Puente Víctor , Dotor Julio , Borrué Carmen , Solano Vila Berta , Álvarez Sauco María , Vela Lydia , Escalante Sonia , Cubo Esther , Carrillo Padilla Francisco , Martínez Castrillo Juan C. , Sánchez Alonso Pilar , Alonso Losada Maria G. , López Ariztegui Nuria , Gastón Itziar , Kulisevsky Jaime , Blázquez Estrada Marta , Seijo Manuel , Rúiz Martínez Javier , Valero Caridad , Kurtis Mónica , de Fábregues Oriol , González Ardura Jessica , Alonso Redondo Ruben , Ordás Carlos , López Díaz Luis M. , McAfee Darrian , Martinez-Martin Pablo , Mir Pablo ,   COPPADIS Study Group
Published: December 2021

Background: Motor phenotype (MP) can be associated with a different prognosis in Parkinson’s disease (PD), but it is not fixed and can change over time. Objective: Our aim was to analyze how the MP changed over time and to identify factors associated with the changes in PD patients from a multicenter Spanish PD cohort. Methods: PD patients who were recruited from January-2016 to November-2017 (baseline visit; V0) and evaluated again at a 2-year±30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this study.MP was calculated at both visits based on Jankovic classification in TD (tremor dominant), IND (indeterminate), or PIGD (postural instability and gait difficulty). Sociodemographic and clinical data were collected, including serum biomarkers. Results: Five hundred eleven patients (62.57±8.59 years old; 59.2%males) were included in the study. At V0, MP was: 47.4%(242/511) TD; 36.6%(187/511) PIGD; 16%(82/511) IND. Up to 38%(194/511) of the patients changed their phenotype from V0 to V2, being the most frequent from TD to IND (8.4%) and from TD to PIGD (6.7%). A worse cognitive status (OR = 0.966) and less autonomy for activities of daily living (OR  =  0.937) at V0 and a greater increase in the globalNMS burden (OR  =  1.011) from V0 to V2 were associated with changing from TD to another phenotype after 2-year follow-up. Conclusion: The MP in PD can change over time. With disease progression, the percentage of cases with non-tremoric MP increases. PD patients who changed from TD to postural instability and gait difficulty increased NMS burden significantly.
Intraperitoneal Administration of Forskolin Reverses Motor Symptoms and Loss of Midbrain Dopamine Neurons in PINK1 Knockout Rats
Authors: Vazquez-Mayorga Emmanuel , Grigoruta Mariana , Dagda Raul , Martinez Bridget , Dagda Ruben K. 
Published: December 2021

Background: Parkinson’s disease (PD) is a relentless, chronic neurodegenerative disease characterized by the progressive loss of substantia nigra (SN) neurons that leads to the onset of motor and non-motor symptoms. Standard of care for PD consists of replenishing the loss of dopamine through oral administration of Levodopa; however, this treatment is not disease-modifying and often induces intolerable side effects. While the etiology that contributes to PD is largely unknown, emerging evidence in animal models suggests that a significant reduction in neuroprotective Protein Kinase A (PKA) signaling in the SN contributes to PD pathogenesis, suggesting that restoring PKA signaling in the midbrain may be a new anti-PD therapeutic alternative. Objective: We surmised that pharmacological activation of PKA via intraperitoneal administration of Forskolin exerts anti-PD effects in symptomatic PTEN-induced kinase 1 knockout (PINK1-KO), a bona fide in vivo model of PD. Methods: By using a beam balance and a grip strength analyzer, we show that Forskolin reverses motor symptoms and loss of hindlimb strength with long-lasting therapeutic effects (> 5 weeks) following the last dose. Results: In comparison, intraperitoneal treatment with Levodopa temporarily (24 h) reduces motor symptoms but unable to restore hindlimb strength in PINK1-KO rats. By using immunohistochemistry and an XF24e BioAnalyzer, Forskolin treatment reverses SN neurons loss, elevates brain energy production and restores PKA activity in SN in symptomatic PINK1-KO rats. Conclusion: Overall, our collective in vivo data suggest that Forskolin is a promising disease-modifying therapeutic alternative for PD and is superior to Levodopa because it confers long-lasting therapeutic effects.
Effects of in vitro short- and long-term treatment with telomerase inhibitor in U-251 glioma cells
Authors: Andrade da Mota Tales Henrique , Reis Guimarães Ana Flávia , Silva de Carvalho Amandda Évelin , Saldanha- de Araujo Felipe , Pinto de Faria Lopes Giselle , Pittella-Silva Fábio , do Amaral Rabello Doralina , Madureira de Oliveira Diêgo 
Published: December 2021

BACKGROUND: The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. OBJECTIVE: Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. METHODS: Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. RESULTS: We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. CONCLUSIONS: Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications.
Analysis of serum HE4 levels in various histologic subtypes of epithelial ovarian cancer and other malignant tumors
Authors: Blackman Alexandra , Mitchell Jessica , Rowswell-Turner Rachael , Singh Rakesh , Kim Kyu Kwang , Eklund Elizabeth , Skates Steven , Bast Robert C. , Messerlian Geralyn , Miller M. Craig , Moore Richard G. 
Published: December 2021

BACKGROUND: The measurement of serum HE4 levels has emerged as a sensitive and specific biomarker for epithelial ovarian cancers (EOCs). However, serum levels in women diagnosed with various histologic subtypes of EOC and in women with metastatic non-ovarian primary malignancies have not been widely reported. OBJECTIVE: The goal of this study was to identify how serum HE4 levels vary in women diagnosed with different histologic subtypes of EOC and non-ovarian malignancies. METHODS: Data from six prospective pelvic mass clinical trials was combined and an evaluation of serum HE4 levels in women diagnosed with a malignancy was performed. For all patients, serum was obtained prior to surgery and final pathology, including primary tumor site, histologic subtype, grade and stage, were recorded. The mean, median, standard deviation, maximum, and minimum HE4 levels were determined for each group. RESULTS: A total of 984 patients were included in this study, with the average patient age being 60 years old. There were 230 premenopausal and 754 postmenopausal patients. Serum HE4 levels were elevated (≥70.0 pMol) in 85%of EOCs, 40%of LMP tumors, 21%of non-EOCs (germ cell tumors), 25%of cervical cancers, and 47%of non-gynecologic metastatic cancers. Analysis of histologic subtypes revealed 90%( n = 391) of serous, 85%( n = 73) of endometrioid, 45%( n = 42) of mucinous, 86%( n = 51) of mixed tumors, and 69%( n = 36) of clear cell tumors had elevated serum HE4 levels. CONCLUSIONS: Serum HE4 levels are most often elevated in women with high grade serous and endometrioid EOCs, and though serum elevations are seen more often with advanced stage disease, HE4 is also often elevated in early stage disease and lower grade tumors.
The Great Pechersk Church’ Mural Paintings of the Late 19th Century as the Interpretation of Its Old Russian Image
Authors: Bardik Maryna 
Published: December 2021

The purpose of the article is to discover the mural paintings of the Great Pechersk Church as the version of theology and academic sacred mural painting of the late 19th century. The research methodology is based on complex using historical and cultural analysis, art study analysis, and biographical method. Scientific novelty. It is determined that the process of creating the Old Russian image in the Great Pechersk Church (the Dormition Cathedral) began in 1880. The photo of the drawing of the ancient part of the Church made by the order of A. Prakhov in 1893, has been introduced into scientific circulation. The author studied the painting decoration as a synthesis of the academic theological thought and academic sacred mural painting, discovered its implementation in choosing topics, plots, and placement of compositions. The author gave a characteristic of the source corps on the paintings from the collection of the National Preserve “Kyiv-Pechersk Lavra”. The author researched the transformation of painting preliminary design and Byzantine Canon of the 11–12th centuries on behalf of the Holy Mother of God theme and observed the connection of the composition “Ascension of Panagia” on the tradition of monastic life in the Kyiv-Pechersk Lavra. The topical and plotlines have been improved namely Christianize Old Russian is determined by one more leading topic. Conclusions. The process of creating a new mural painting in the Great Pechersk Church began still yet 1880. The detection of the ancient part of the Church contributed to the change in its painting decoration. This change was the result of the academic theological program implemented by means of academic sacred mural painting. The tradition of previous painting decoration preserved in the preliminary design end reflected one of the traditions of monastic life in the Kyiv-Pechersk Lavra. The witness in Pechersk Paterikon of the compositions in the Great Church has been implemented in mural paintings. However, the academic theological opinion of the late 19th century was subordinated to the canon of 11–12th centuries not complete. The theme of the introduction of Christianity was presented in mural painting as one of the leading topics.
Performance evaluation of various deployment scenarios of the 3-replicated Cassandra NoSQL cluster on AWS
Authors: Gorbenko Anatoliy , Karpenko Andrii , Tarasyuk Olga 
Published: December 2021

A concept of distributed replicated NoSQL data storages Cassandra-like, HBase, MongoDB has been proposed to effectively manage Big Data set whose volume, velocity and variability are difficult to deal with by using the traditional Relational Database Management Systems. Tradeoffs between consistency, availability, partition tolerance and latency is intrinsic to such systems. Although relations between these properties have been previously identified by the well-known CAP and PACELC theorems in qualitative terms, it is still necessary to quantify how different consistency settings, deployment patterns and other properties affect system performance.This experience report analysis performance of the Cassandra NoSQL database cluster and studies the tradeoff between data consistency guaranties and performance in distributed data storages. The primary focus is on investigating the quantitative interplay between Cassandra response time, throughput and its consistency settings considering different single- and multi-region deployment scenarios. The study uses the YCSB benchmarking framework and reports the results of the read and write performance tests of the three-replicated Cassandra cluster deployed in the Amazon AWS. In this paper, we also put forward a notation which can be used to formally describe distributed deployment of Cassandra cluster and its nodes relative to each other and to a client application. We present quantitative results showing how different consistency settings and deployment patterns affect Cassandra performance under different workloads. In particular, our experiments show that strong consistency costs up to 22 % of performance in case of the centralized Cassandra cluster deployment and can cause a 600 % increase in the read/write requests if Cassandra replicas and its clients are globally distributed across different AWS Regions.
ANALISIS KUALITAS PLATFORM E-MARKETPLACE TERHADAP LOYALITAS PELANGGAN (Studi Kasus: Pengguna Zilingo)
Authors: Ferdinand Erfina , Aransyah Muhammad Fikry , Bharata Wira 
Published: December 2021

Penelitian ini bertujuan untuk menganalisis kualitas suatu platform e-marketplace Zilingo terhadap loyalitas pelanggannya, apakah sudah sesuai dengan kaidah penyajian platform e-marketplace yang baik dan benar serta melakukan evaluasi untuk mengukur dan meningkatkan serta memperbaiki kualitas layanannya yang masih kurang guna meningkatkan loyalitas pelanggan. Metode yang digunakan adalah metode Structural Equation Modelling melalui pendekatan Partial Least Square atau SEM-PLS. Data primer didapat dari penyebaran kuesioner secara online melalui Google Form dengan dukungan oleh data sekunder yaitu diantaranya buku, e-journal, dan website. Hasil dari penelitian ini menyatakan bahwa variabel e-service quality berpengaruh positif dan signifikan terhadap e-loyalty dengan dimensi yang paling berpengaruh yaitu dimensi reliabilitas. Dimensi ini berkaitan dengan fungsionalitas fitur-fitur yang ditawarkan oleh platform e-marketplace Zilingo. Fitur-fitur yang berfungsi sebagaimana mestinya menjadi indikator yang penting untuk meningkatkan e-loyalty pengguna Zilingo. Lalu didapati dalam penelitian ini bahwa variabel e-satisfaction berpengaruh negatif dan tidak signifikan terhadap e-loyalty. Dapat disimpulkan bahwa semakin baik suatu e-satisfaction maka tidak akan meningkatkan suatu e-loyalty.
Kata Kunci: SEM-PLS, Platform E-Marketplace, E-Service Quality, E-Satisfaction, E-Trust, E-Loyalty.
AULAS DE MODELAGEM MATEMÁTICA EM TEMPO DE PANDEMIA: UM RELATO DA EXPERIÊNCIA VIVIDA
Authors: Ramon Rosangela , Klüber Tiago Emanuel 
Published: December 2021

Este relato busca apresentar reflexões sobre a experiência vivida ao ministrarmos a disciplina Resolução de Problemas e Modelagem Matemática alocada no terceiro ano do curso de Licenciatura em Matemática. As aulas foram realizadas no período de isolamento social devido à pandemia ocasionada pela COVID-19, de forma remota por meio da plataforma Teams. No texto, descrevemos um modo de trabalho que, partindo de tarefas de Modelagem explora aspectos teóricos da produção acadêmica da área da Modelagem, prática já realizada em aulas presenciais e que foi transposta para o ensino remoto, bem como os procedimentos de condução das aulas, as tarefas de Modelagem realizadas e algumas reflexões sobre como a prática foi realizada. Com isso, compreendemos que a abordagem adotada na disciplina se mostrou como um importante modo de proporcionar aos estudantes uma visão e uma vivência da articulação entre a teoria produzida pela comunidade acadêmica da área da Modelagem Matemática na Educação Matemática e a implementação de tarefas de Modelagem. Por outro lado, apresentamos os anseios e as dificuldades ao ministrar uma disciplina de Modelagem em aulas remotas.