bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parkinson's disease: Current assessment methods and wearable devices for evaluation of movement disorder motor symptoms - A patient and healthcare professional perspective
Authors: AlMahadin Ghayth , Lotfi Ahmad , Zysk Eva , Siena Francesco Luke , Carthy Marie Mc , Breedon Philip 
Published: April 2020

Abstract
Background Parkinson's disease is the second most common long-term chronic, progressive, neurodegenerative disease, affecting more than 10 million people worldwide. There has been a rising interest in wearable devices for evaluation of movement disorder diseases such as Parkinson's disease due to the limitations in current clinic assessment methods such as Unified Parkinson's Disease Rating Scale. However, there are only a few commercial wearable devices available, which, in addition, have had very limited adoption and implementation. This inconsistency may be due to a lack of users’ perspectives in terms of device design and implementation.Objectives This study aims to identify the perspectives of healthcare professionals and patients linked to current assessment methods and to identify preferences, needs, and requirements of wearable devices.Materials and Methods This was a qualitative study using semi-structured interviews followed by focus groups. Transcripts from sessions were analysed using a thematic approach.Results It was noted that the well-known assessment and monitoring process such as Unified Parkinson's Disease Rating Scale was not used routinely in clinics since it is time consuming, subjective, inaccurate, infrequent and dependent on patients’ memories. Participants suggested that objective diagnosis and assessment methods are needed to increase the chance of effective treatment. The participants’ perspectives were positive toward using wearable devices, particularly if they were involved in early design stages. Patients emphasized that the devices should be comfortable, but they did not have any concerns regarding device visibility or data privacy transmitted over the internet when it comes to their health. In terms of wearing a monitor, the preferable part of the body for all participants was the wrist. Healthcare professionals stated a need for an economical solution that is easy to interpret. Some design aspects identified by patients included clasps, material choice, and form factor.Conclusion The study concluded that current diagnosis and assessment methods are limited. Patients’ and healthcare professionals’ involvement in wearable devices design process has a pivotal role in terms of ultimate user acceptance. This includes the provision of additional functions to the wearable device, such as fall detection and medication reminders, which could be attractive features for patients.
A Dynamical Behavior of COVID-19 Virus Model with Carrier Effect to Outbreak Epidemic
Authors: AL-Husseiny Hassan Fadhil , Mohsen Ahmed A. , Zhou Xueyong 
Published: April 2020

Abstract
In this paper, COVID-19 virus model with effect the carrier to outbreak of epidemic is investigated. The outbreak of Covid-19 virus, is described by a mathematical model divided the population into four classes. The first class describes the susceptible unaware to disease, the second class the susceptible with has aware to disease by media coverage, the third class the carrier individuals and the last class is infected individuals. The existence, uniqueness and bounded-ness of the solutions of the model are discussed. All possible equilibrium points are determined. The locally asymptotically stable of the model is studied. Suitable Lyapunov functions are used to investigate the globally asymptotical stability of the model. Finally, numerical simulation is carried out to confirm the analytical results and understand the effect of varying the parameters on spread of disease.
Effect of Various Bulk Sweeteners on the Survivability of Lactobacillus casei 431 in Milk Chocolate: Rheological and Sensory Properties Analysis
Authors: Rad Aziz H. , Pirouzian Haniyeh R. , Toker Omer S. , Konar Nevzat 
Published: April 2020

Background:
Probiotics are the most widely consumed functional food. Consumers demand
the production of foods also in low-calorie forms.

Objective:
In this study, Lactobacillus casei 431 and various sweeteners were used in milk chocolate
as probiotic and bulking agents, respectively.

Methods:
Samples were prepared by using sucrose or optimum polyols combination. Chocolate samples
were stored at two temperatures (4°C and 20°C) for 180 days and the viability of probiotic cells
was controlled with the purpose of specifying the presented storage temperature.

Results:
The highest probiotic viability was determined in the samples produced with sucrose and
stored at 4°C. The cell counts were retained at the functional amount after maintenance for 6 months.
Probiotic sucrose-free chocolate was more viscous than control chocolate, although displayed satisfactory
sensory attributes.

Conclusion:
As a result, the sugared and sugar-free probiotic milk chocolates could be stored at room
temperature. Due to the acceptable number of probiotic cells, the sucrose-free chocolates containing
probiotics were considered as functional foods.
Genetic Editing and Pharmacogenetics in Current And Future Therapy Of Neurocognitive Disorders
Authors: Prendecki Michal , Kowalska Marta , Toton Ewa , Kozubski Wojciech 
Published: April 2020

:Dementia is an important issue in western societies, and in the following years, this problem will also rise in the developing regions, such as Africa and Asia. The most common types of dementia in adults are Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD) and Vascular Dementia (VaD), of which, AD accounts for more than half of the cases.:The most prominent symptom of AD is cognitive impairment, currently treated with four drugs: Donepezil, rivastigmine, and galantamine, enhancing cholinergic transmission; as well as memantine, protecting neurons against glutamate excitotoxicity. Despite ongoing efforts, no new drugs in the treatment of AD have been registered for the last ten years, thus multiple studies have been conducted on genetic factors affecting the efficacy of antidementia pharmacotherapy. The researchers investigate the effects of variants in multiple genes, such as ABCB1, ACE, CHAT, CHRNA7, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP3A7, NR1I2, NR1I3, POR, PPAR, RXR, SLC22A1/2/5, SLC47A1, UGT1A6, UGT1A9 and UGT2B7, associated with numerous pathways: the development of pathological proteins, formation and metabolism of acetylcholine, transport, metabolism and excretion of antidementia drugs and transcription factors regulating the expression of genes responsible for metabolism and transport of drugs. The most promising results have been demonstrated for APOE E4, dementia risk variant, BCHE-K, reduced butyrylcholinesterase activity variant, and CYP2D6 UM, ultrarapid hepatic metabolism. Further studies investigate the possibilities of the development of emerging drugs or genetic editing by CRISPR/Cas9 for causative treatment.:In conclusion, the pharmacogenetic studies on dementia diseases may improve the efficacy of pharmacotherapy in some patients with beneficial genetic variants, at the same time, identifying the carriers of unfavorable alleles, the potential group of novel approaches to the treatment and prevention of dementia.
L1CAM Beneficially Inhibits Histone Deacetylase 2 Expression under Conditions of Alzheimer’s Disease
Authors: Hu Chengliang , Hu Junkai , Meng Xianghe , Zhang Hongli , Shen Huifan , Huang Peizhi , Schachner Melitta , Zhao Weijiang 
Published: April 2020

Background:
Cognitive capacities in Alzheimer’s Disease (AD) are impaired by an epigenetic
blockade mediated by histone deacetylase 2 (HDAC2), which prevents the transcription of genes
that are important for synaptic plasticity.

Objective:
Investigation of the functional relationship between cell adhesion molecule L1 and HDAC2
in AD.

Methods:
Cultures of dissociated cortical and hippocampal neurons from wild-type or L1-deficient mice
were treated with Aβ1-42 for 24 h. After removal of Aβ1-42 cells were treated with the recombinant L1
extracellular domain (rL1) for 24 h followed by immunohistochemistry, western blotting, and reverse
transcription PCR to evaluate the interaction between L1 and HDAC2.

Results:
Aβ and HDAC2 protein levels were increased in APPSWE/L1+/- mutant brains compared to
APPSWE mutant brains. Administration of the recombinant extracellular domain of L1 to cultured cortical
and hippocampal neurons reduced HDAC2 mRNA and protein levels. In parallel, reduced phosphorylation
levels of glucocorticoid receptor 1 (GR1), which is implicated in regulating HDAC2 levels,
was observed in response to L1 administration. Application of a glucocorticoid receptor inhibitor reduced
Aβ-induced GR1 phosphorylation and prevented the increase in HDAC2 levels. HDAC2 protein
levels were increased in cultured cortical neurons from L1-deficient mice. This change could be reversed
by the administration of the recombinant extracellular domain of L1.

Conclusion:
Our results suggest that some functionally interdependent activities of L1 and HDAC2 contribute
to ameliorating the phenotype of AD by GR1 dephosphorylation, which leads to reduced HDAC2
expression. The combined findings encourage further investigations on the beneficial effects of L1 in the
treatment of AD.
Selenium Role in Reproduction, Pregnant/Postpartum Women and Neonates: A Current Study
Authors: Sattar Tabinda 
Published: April 2020

Background:
Selenium is a micronutrient, although required in low amounts, its importance
in male and female reproduction is well known.

Objectives:
The core purpose of this study is to evaluate the role of selenium in human reproduction,
during pregnancy/ lactation in women and newborns. The review explains side by side the sources of
selenium, required amounts of selenium in humans and during pregnancy or lactation.

Methods:
Selenium deficiency is a major cause of male infertility. Similarly, selenium deficiency,
both in pregnant and postpartum women, would greatly affect the health of the newborn baby in all
respects. The effect of maternal selenium upon the fetus and the neonates even one year after birth
has been explained with some recent examples.

Results:
The study elaborates the fact that the selenium deficiency in pregnancy and lactation is
common due to fetal/infant development, so selenium supplements must be provided in order to
overcome these deficiency symptoms.

Conclusions:
The better reproductive health in humans is possible due to the sufficient amounts of selenium
present both in males and females as well.
An Optimized Approach for Breast Cancer Classification for Histopathological Images Based on Hybrid Feature Set
Authors: Nasir Inzamam Mashood , Rashid Muhammad , Shah Jamal Hussain , Sharif Muhammad , Awan Muhammad Yahiya Haider , Alkinani Monagi H. 
Published: April 2020

Background:
Breast cancer is considered as one of the most perilous sickness among females
worldwide and the ratio of new cases is increasing yearly. Many researchers have proposed
efficient algorithms to diagnose breast cancer at early stages, which have increased the efficiency
and performance by utilizing the learned features of gold standard histopathological images.

Objective:
Most of these systems have either used traditional handcrafted or deep features, which
had a lot of noise and redundancy, and ultimately decrease the performance of the system.

Methods:
A hybrid approach is proposed by fusing and optimizing the properties of handcrafted
and deep features to classify the breast cancer images. HOG and LBP features are serially fused
with pre-trained models VGG19 and InceptionV3. PCR and ICR are used to evaluate the classification
performance of the proposed method.

Results:
The method concentrates on histopathological images to classify the breast cancer. The
performance is compared with the state-of-the-art techniques, where an overall patient-level accuracy
of 97.2% and image-level accuracy of 96.7% is recorded.

Conclusion:
The proposed hybrid method achieves the best performance as compared to previous
methods and it can be used for the intelligent healthcare systems and early breast cancer detection.
In Silico Design of Novel Sirtuin 1 Enzyme Activators for the Treatment of Age-related Diseases and Life Span
Authors: Ertan-Bolelli Tugba , Bolelli Kayhan 
Published: April 2020

Aims:
The aim of the study was to develop new SIRT1 activator compounds, for this aim,
we used virtual screening and molecular dynamics methods, which have been important tools for
new hit compound searches.

Background:
Recently, with the progress of computing technology, it has been possible to obtain
higher efficiency and lower costs for drug discovery. With in silico research and drug design, there
is a reduction in time-consuming and expensive experimental work. An NAD+ dependent histone
deacetylase enzyme, Sirtuin 1 (SIRT1), is involved in a variety of human disorders such as type II
diabetes, cancer, obesity, and aging. Activation of SIRT1 could be useful for longevity and treating
metabolic disorders.

Objective:
We used computational methods to develop new SIRT1 activator compounds.

Methods:
Firstly, virtual screening studies on the human SIRT1 enzyme were carried out. We used
approximately 150.000 commercially available compounds from the Zinc database, which include
FDA-approved drugs. According to virtual screening results, we selected seven potent activators.
Then we compared these hit compounds with known activators by using docking methods. One of
these hit compounds, acebutolol, is an FDA-approved drug, and was selected for additional studies
using molecular dynamics simulations.

Results:
Seven hit compounds were identified with database screening. Each showed strong interactions
with SIRT1, and acebutolol formed H-bonds with the important active site residues, Asn226
and/or Glu230 during the dynamics simulation.

Conclusion:
Based on our in silico studies, the seven most promising compounds, especially acebutolol,
showed promising SIRT1 activator potency. The results may be used to design new selective
and more potent SIRT1 activator drugs.
Establishment and Validation of an ICP-MS Method for Simultaneous Measurement of 24 Elemental Impurities in Ubenimex APIs According to USP/ICH guidelines
Authors: Zhao Ming-Juan , Cheng Lei , Huang Yu-Jia , Tao Ying , Gu Xiao , Zheng Jin-Qi 
Published: April 2020

Background:
To control the potential presence of heavy metals in pharmaceuticals, the United States
Pharmacopeia (USP) and International Conference on Harmonization (ICH) have put forth new requirements and
guidelines. USP <232> and ICH Q3D specify 24 elemental impurities and their concentration limits in consideration of
the permitted daily exposure (PDE) of different drug categories (oral, parenteral and inhalation). while USP <233>
describes more information about sample preparation and method validation procedure.

Objective:
To establish and verify an ICP-MS method for the determination of 24 elemental impurities (Cd, Pb, As, Hg,
Co, V, Ni, Tl, Au, Pd, Ir, Os, Ph, Ru, Se, Ag, Pt, Li, Sb, Ba, Mo, Cu, Sn, Cr) in ubenimex APIs according to USP/ICH
guidelines.

Method:
Samples were analyzed by ICP-MS after direct dissolution in diluted acid solution. All elements were detected
in He/HEHe mode (except for Li, which was in No gas mode).

Results:
The spiked recoveries were within 80-120% except Hg (79.4% at 0.5J level in HEHe mode) and Cd (121.9%
at 0.5J level in HE mode). The RSD of repeatability (N = 6) for all elements were < 7.0% and intermediate precision (N
= 12) were < 9.0%. The correlation coefficients of linear (R) for 24 elements were all > 0.998. The limits of detection
(LOD) were < 1 ng/mL except that Ni was 1.23 ng/mL in HEHe mode. The contents of 24 elements in 3 batches of
samples were significantly lower than the actual target limit of ICH, while the highest content of Pd did not exceed 10
μg/g.

Conclusion:
The established method was proved to be simple, sensitive and accurate. It successfully applied to the
elemental impurity determination in 3 batches of ubenimex APIs from different manufactories. This method also
provided technical guidance for determination of multiple elements in pharmaceutical products.
Using Bioinformatics to Quantify the Variability and Diversity of the Microbial Community Structure in Pond Ecosystems of a Subtropical Catchment
Authors: Zhou Jiaogen , Wang Yang , Lei Qiuliang 
Published: April 2020

Background:In rural China, many natural water bodies and farmlands have been converted into fish farming ponds as an economic developmental strategy. There is still a limited understanding of how the diversity and structure of microbial communities change in nature and become managed fish pond ecosystems.Objective:We aimed to identify the changes of the diversity and structure of microbial community and driving mechanism in pond ecosystems.Methods:The datasets of 16S rRNA amplicon sequencing and the concentrations of N and P fractions were achieved in water samples of pond ecosystems. Bioinformatics analysis was used to analyze the diversity and structure of the microbial communities.Results:Our results indicated that the diversity and structure of the microbial communities in the natural ponds were significantly different from ones in managed fish ponds. The nutrients of N and P and water environmental factors were responsible for 46.3% and 19.5% of the changes in the structure and diversity of the microbial community, respectively.Conclusion:The N and P fractions and water environmental factors influenced the microbial community structure and diversity in pond ecosystems. Fish farming indirectly affected the microbial community by altering the contents of N and P fractions in water bodies of ponds, when a natural pond was converted into a managed fish pond.
Targeting Breast Cancer Cells with G4 PAMAM Dendrimers and Valproic Acid Derivative Complexes
Authors: Muñoz Alberto M. , Fragoso-Vázquez Manuel J. , Martel Berenice P. , Chávez-Blanco Alma , Dueñas-González Alfonso , R.García-Sánchez José , Bello Martiniano , Romero-Castro Aurelio , Correa-Basurto José 
Published: April 2020

Background:Our research group has developed some Valproic Acid (VPA) derivatives employed as anti-proliferative compounds targeting the HDAC8 enzyme. However, some of these compounds are poorly soluble in water.Objective:Employed the four generations of Polyamidoamine (G4 PAMAM) dendrimers as drug carriers of these compounds to increase their water solubility for further in vitro evaluation.Methods:VPA derivatives were subjected to Docking and Molecular Dynamics (MD) simulations to evaluate their affinity on G4 PAMAM. Then, HPLC-UV/VIS, 1H NMR, MALDI-TOF and atomic force microscopy were employed to establish the formation of the drug-G4 PAMAM complexes.Results:The docking results showed that the amide groups of VPA derivatives make polar interactions with G4 PAMAM, whereas MD simulations corroborated the stability of the complexes. HPLC UV/VIS experiments showed an increase in the drug water solubility which was found to be directly proportional to the amount of G4 PAMAM. 1H NMR showed a disappearance of the proton amine group signals, correlating with docking results. MALDI-TOF and atomic force microscopy suggested the drug-G4 PAMAM dendrimer complexes formation.Discussion:In vitro studies showed that G4 PAMAM has toxicity in the micromolar concentration in MDAMB- 231, MCF7, and 3T3-L1 cell lines. VPA CF-G4 PAMAM dendrimer complex showed anti-proliferative properties in the micromolar concentration in MCF-7 and 3T3-L1, and in the milimolar concentration in MDAMB- 231, whereas VPA MF-G4 PAMAM dendrimer complex didn’t show effects on the three cell lines employed.Conclusion:These results demonstrate that G4 PAMAM dendrimers are capableof transporting poorly watersoluble aryl-VPA derivate compounds to increase its cytotoxic activity against neoplastic cell lines.
Brucella Pneumonia with Systemic Complications and Pancytopenia: A Case Report
Authors: Seyedpour Simin , Khodaei Behzad , Nezhad Malihe Hassan , SeyedAlinaghi SeyedAhmad , Ghiasvand Fereshteh 
Published: April 2020

Background::
Iran, which is regarded as an endemic region for brucellosis, ranks second
in brucella prevalence in the world. Pulmonary involvement is a rare complication of brucellosis.
In this article, we aimed to report a case of systemic brucellosis complicated with brucella pneumonia.

Case Presentation:
A 39-years-old man was referred to the emergency department with weakness,
productive coughs and severe weight loss during 8 months. Agglutination tests for brucellosis
showed high titers suggestive for brucella infection. After 6 days of treatment, the patients’ clinical
state improved significantly.

Conclusion::
The patient had systemic signs and bone marrow suppression with pulmonary involvement
that his diagnosis confirmed with delay after one year, but with treatment, he had a very good
outcome.
Remaining Useful life Estimation: A Review on Stochastic Process-based Approaches
Authors: Du Dangbo , Zhang Jianxun , Si Xiaosheng , Hu Changhua 
Published: April 2020

Background:
Remaining Useful Life (RUL) estimation is the central mission to the complex
systems’ prognostics and health management. During the last decades, numbers of developments
and applications of the RUL estimation have proliferated.

Objective:
As one of the most popular approaches, stochastic process-based approach has been widely
used for characterizing the degradation trajectories and estimating RULs. This paper aimed at reviewing
the latest methods and patents on this topic.

Methods:
The review is concentrated on four common stochastic processes for degradation modelling
and RUL estimation, i.e., Gamma process, Wiener process, inverse Gaussian process and Markov
chain.

Results:
After a brief review of these four models, we pointed out the pros and cons of them, as well
as the improvement direction of each method.

Conclusion:
For better implementation, the applications of these four approaches on maintenance and
decision-making are systematically introduced. Finally, possible future trends are concluded tentatively.