bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes in Sepsis and Inflammatory Tissue Injury
Authors: Park Eun J. , Appiah Michael G. , Myint Phyoe K. , Gaowa Arong , Kawamoto Eiji , Shimaoka Motomu 
Published: November 2019

:Sepsis is the leading cause of death in medical intensive care units, and thus represents a serious healthcare problem worldwide. Sepsis is often caused by the aberrant host responses to infection, which induce dysregulated inflammation that leads to life-threatening multiple organ failures. Mediators such as proinflammatory cytokines that drive the sepsis pathogenesis have been extensively studied. Exosomes, biological lipid bilayer nanoparticles secreted via the endosomal pathway of cells, have recently emerged as important cargos that carry multiple mediators critical for the pathogenesis of sepsis-associated organ dysfunctions. Here we will review current knowledge on the exosomes in sepsis and relevant inflammatory tissue injuries.
A Retrospective Look at Anti-EGFR Agents in Pancreatic Cancer Therapy
Authors: Verma Henu K. , Kampalli Praveen K. , Lakkakula Saikrishna , Chalikonda Gayathri , Bhaskar Lakkakula V.K.S. , Pattnaik Smaranika 
Published: November 2019

Background:The introduction of Monoclonal Antibodies (mAbs) and small-molecule Tyrosine Kinase Inhibitors (TKIs) that target the Epidermal Growth Factor Receptor (EGFR), marks a huge step forward in the Pancreatic Cancer (PC) therapy. However, anti-EGFR therapy is found to be successful only in a fraction of patients. Although anti-EGFR agents have shown considerable clinical promise, a serious adverse event associated with anti- EGFR therapy has been challenging. At this juncture, there is still more to be done in the search for effective predictive markers with therapeutic applicability.Methods:A focused literature search was conducted to summarize the existing evidence on anti-EGFR agents in pancreatic cancer therapy.Results:This review discusses various anti-EGFR agents currently in use for PC therapy and potential adverse effects associated with it. Existing evidence on EGFR TKIs demonstrated better tolerant effects and outcomes with multiple toxic regimens. Anti-EGFR therapy in combination with chemotherapy is necessary to achieve the best clinical outcomes.Conclusion:Future prospective studies on the identification of additional biological agents and novel anti-EGFR agents are warranted.
Antiplatelet Effect of a Pulaimab [Anti-GPIIb/IIIa F(ab)2 Injection] Evaluated by a Population Pharmacokinetic-pharmacodynamic Model
Authors: Liu Ya-Ou , Wang Zi-Ning , Chen Chao-Yang , Zhuang Xian-Han , Ruan Chang-Geng , Zhou Ying , Cui Yi-Min 
Published: November 2019

Background:
Cardiovascular disease has one of the highest mortality rates among all the diseases. Platelets
play an important role in the pathogenesis of cardiovascular diseases. Platelet membrane glycoprotein GPIIb/IIIa
antagonists are the most effective antiplatelet drugs, and pulaimab is one of these. The study aims to promote individual
medication of pulaimab [anti-GPIIb/IIIa F(ab)2 injection] by discovering the pharmacological relationship
among the dose, concentration, and effects. The goal of this study is to establish a population pharmacokineticpharmacodynamic
model to evaluate the antiplatelet effect of intravenous pulaimab injection.

Methods:
Data were collected from 59 healthy subjects who participated in a Phase-I clinical trial. Plasma concentration
was used as the pharmacokinetic index, and platelet aggregation inhibition rate was used as the pharmacodynamic
index. The basic pharmacokinetics model was a two-compartment model, whereas the basic pharmacodynamics
model was a sigmoid-EMAX model with a direct effect. The covariable model was established by a stepwise
method. The final model was verified by a goodness-of-fit method, and predictive performance was assessed by a
Bootstrap (BS) method.

Results:
In the final model, typical population values of the parameters were as follows: central distribution Volume
(V1), 183 L; peripheral distribution Volume (V2), 349 L; Central Clearance (CL), 31 L/h; peripheral clearance(Q),
204 L/h; effect compartment concentration reaching half of the maximum effect (EC50), 0.252 mg/L; maximum
effect value (EMAX), 54.0%; and shape factor (γ), 0.42. In the covariable model, thrombin time had significant
effects on CL and EMAX. Verification by the goodness-of-fit and BS methods showed that the final model was
stable and reliable.

Conclusion:
A model was successfully established to evaluate the antiplatelet effect of intravenous pulaimab injection
that could provide support for the clinical therapeutic regimen.
Ecofriendly Ethyl Cellulose Microsponges of Citronella Oil: Preparation, Characterization and Evaluation of Cytotoxicity and Larvicidal assay
Authors: Sharma Ruchi , Kumar Nitish , Singh Sompal P. , Kumar Sunil , Rao Rekha 
Published: November 2019

Background:
Citronella Oil (CO) was used by the Indian army as mosquito repellant to repel
mosquitoes at the beginning of the 20th century and later in 1948, it was registered in the USA for commercial
purposes. Due to its ecofriendly nature, CO possesses immense potential as a mosquito repellent.

Methods:
Citronella oil is a valuable alternative to synthetic mosquito repellents commonly used nowadays.
However, its volatile nature, poor stability in air and high temperature restrict its application. Its
direct application on skin may lead to skin irritation. To surmount the above-mentioned issues, the present
research aims to develop Microsponge (MS), a novel dosage form for enhancing the utility and
safety of CO. Quasi emulsion solvent diffusion method was chosen for crafting MS using ethyl cellulose
with various drug-polymer ratios and characterized. In vitro cytotoxicity evaluation was also carried
out to check the dermal safety of COMS.

Results:
The present results revealed that the size of all prepared formulation lies in the micro range
(20 ± 3 to 41 ± 4 μm), with good payload (42.09± 3.24 to 67.08± 6.43%). The results of FE-SEM depicted
that MS were spherical in shape with porous nature. Cytotoxicity results indicated that COMS
were safe on skin cells, when compared to pure CO. The optimized MS were also assessed for larvicidal
assay against larvae of Anopheles culicifacies.

Conclusion:
The CO micro-formulations were found to possess enhanced stability of this oil. Entrapment
of CO in MS resulted in a better vehicle system in terms of safety, stability and handling benefits
of this oil.
The Potential of PI3K/AKT/mTOR Signaling as a Druggable Target for Endometrial and Ovarian Carcinomas
Authors: Lengyel Csongor György , Altuna Sara Cecilia , Habeeb Baker Shalal , Trapani Dario , Khan Shah Zeb 
Published: November 2019

Aims:In this narrative review, we summarize the role and significance of PI3K-AKTmTOR (PAM) pathway in ovarian and endometrial cancers, providing the most recent and relevant literature on the topic and addressing options for targeting PAM along with future perspectives of drug development.Background:Alterations of the PAM-pathway are common in both endometrial and ovarian cancers, and are described in specific histology-defined subtypes. PAM seems to be involved in critical steps of endometrial and ovarian carcinogenesis, often mechanistically involved in the acquisition of a phenotype of treatment resistance, which could be targetable. However, early clinical trials with PAMinhibitors (PAMi) have provided disappointing results, particularly when non isoform-specific inhibitors were tested in unselected populations, accompanied by an adverse safety profile. Since then, more encouraging observations have been collected when targeting specific isoforms of PAM proteins with more selective drugs, resulting in encouraging activity and more manageable toxicity.Conclusion:Although the rationale of inhibiting the PAM-pathway has been demonstrated in several promising preclinical studies, no Phase III clinical trial is available to demonstrate a significant benefit of PAM-inhibitors. A way to manage targeted agents is to tailor their use to particular subpopulations most likely to obtain a considerable benefit, namely pursuing an individualized, precision-medicine approach.
Genome-wide Network-assisted Association and Enrichment Study of Amyloid Imaging Phenotype in Alzheimer’s Disease
Authors: Li Jin , Chen Feng , Zhang Qiushi , Meng Xianglian , Yao Xiaohui , Risacher Shannon L. , Yan Jingwen , Saykin Andrew J. , Liang Hong , Shen Li 
Published: November 2019

Background:
The etiology of Alzheimer’s disease remains poorly understood at the mechanistic
level, and genome-wide network-based genetics have the potential to provide new insights into the
disease mechanisms.

Objective:
The study aimed to explore the collective effects of multiple genetic association signals on an
AV-45 PET measure, which is a well-known Alzheimer’s disease biomarker, by employing a networ kassisted
strategy.

Method:
First, we took advantage of a dense module search algorithm to identify modules enriched by
genetic association signals in a protein-protein interaction network. Next, we performed statistical evaluation
to the modules identified by dense module search, including a normalization process to adjust the
topological bias in the network, a replication test to ensure the modules were not found randomly , and a
permutation test to evaluate unbiased associations between the modules and amyloid imaging phenotype.
Finally, topological analysis, module similarity tests and functional enrichment analysis were performed
for the identified modules.

Results:
We identified 24 consensus modules enriched by robust genetic signals in a genome-wide association
analysis. The results not only validated several previously reported AD genes (APOE, APP,
TOMM40, DDAH1, PARK2, ATP5C1, PVRL2, ELAVL1, ACTN1 and NRF1), but also nominated a few
novel genes (ABL1, ABLIM2) that have not been studied in Alzheimer’s disease but have shown associations
with other neurodegenerative diseases.

Conclusion:
The identified genes, consensus modules and enriched pathways may provide important
clues to future research on the neurobiology of Alzheimer’s disease and suggest potential therapeutic
targets.
Effects of Intermittent Hypoxia on Expression of Glucose Metabolism Genes in MCF7 Breast Cancer Cell Line
Authors: Jarrar Yazun , Zihlif Malek , Al Bawab Abdel Qader , Sharab Ahmad 
Published: November 2019

Background:
Hypoxic condition induces molecular alterations which affect the survival
rate and chemo-resistant phenotype of cancer cells.

Objective:
The aim of this study is to investigate the influence of intermittent hypoxic conditions on
the expression of glucose metabolism genes in breast cancer MCF7 cell line.

Methods:
The gene expression was analyzed using a polymerase chain reaction-array method. In
addition, the cell resistance, survival and migration rates were examined to assure the hypoxic influence
on the cells.

Results:
30 hypoxic episodes induced the Warburg effect through significant (p-value < 0.05)
upregulation of the expression of PCK2, PHKG1, ALDOC, G6PC, GYS2, ALDOB, HK3, PKLR,
PGK2, PDK2, ACO1 and H6PD genes that are involved in glycolysis, were obtained. Furthermore,
the expression of the major gluconeogenesis enzyme genes was significantly (ANOVA, p-value <
0.05) downregulated. These molecular alterations were associated with increased MCF7 cell division
and migration rate. However, molecular and phenotypic changes induced after 30 episodes were
normalized in MCF7 cells exposed to 60 hypoxic episodes.

Conclusion:
It is concluded, from this study, that 30 intermitted hypoxic episodes increased the survival
rate of MCF7 breast cancer cells and induced the Warburg effect through upregulation of the
expression of genes involved in the glycolysis pathway. These results may increase our understanding
of the molecular alterations of breast cancer cells under hypoxic conditions.
The Effect of ACT on Self-Esteem and Self-efficacy of Women with Breast Cancer in Iran
Authors: Daneshvar Masoumeh , Vakilian Katayon , Zadeh-Emran Akbar Hedayati , Zadeh Ramezan Hassan 
Published: November 2019

Background:Today, breast cancer is the second major cause of cancer deaths in women.Objective:The present study aimed to determine the effect of acceptance and commitment therapy (ACT) on self-esteem and self-efficacy of cancer adaptation behaviors in women.Methods:The present study was a randomized educational trial (IRCT Registration number: IRCT2016100430140N1) based on intervention and control groups including 30 patients with breast cancer who were referred to Cancer comprehensive center of Imam Khomeini Hospital in Sari 2017. The intervention group participated in ACT sessions for 8 weeks held as 8 sessions. In the control group, there was no intervention and only chemotherapy was carried out. Self-esteem and self-efficacy of cancer adaptation behaviors were assessed using Rosenberg Self-esteem Scale and Cancer Behavior Inventory before and after the intervention and one month later. Data analysis was tested by repeated measurement, ANOVA and Tukey post-hoc tests.Results:The mean of self-esteem before and after intervention and one month later was 13.46 ± 1.12, 16.86 ± 0.91, 15.86 ± 0.99 in ACT group, and 14 ± 1, 14.40 ± 0.98, 14.20 ± 1.08 in the control group, respectively (F(2,27)=11.90, P=0.001). The mean of self-efficacy of cancer adjustment behaviors before and after the intervention and one month later was 104.40 ± 20.19, 218.20 ± 15.32, 214.86 ± 16.97 in ACT group, and 96.86 ± 15.04, 97.06 ± 18.61, 94.53 ± 14.69 in the control group, respectively (F(2,27)=8.26, P=0.001).Conclusion:This counseling approach can be used as an easy, non-invasive and helpful method to increase self-esteem and self-efficacy among patients for adaptation to cancer.
One-Step Fabrication of Three Metals Zif and its Application for Adsorption of Levofloxacin in Aqueous Solution
Authors: Samadi-Maybodi Abdolraouf , Rahmati Afshin 
Published: November 2019

Background:
Zeolitic imidazolate frameworks with three metals Zn, Co and Ag (ZIF-3M)
and ZIF-67 were synthesized at room temperature and characterized with different techniques such as
FESEM, BET, EDX and XRD. Then, the synthesized nanoparticles were successfully applied for the
removal of levofloxacin from aqueous solutions.

Methods:
To optimize the significant factors (i.e., pH, adsorbent dose and contact time), the response
surface methodology (RSM) was implemented based on Box-Behnken design (BBD) in each step, an
appropriate amount of adsorbent was added to 30 ppm of a solution containing levofloxacin and the
pH was adjusted to the desired value with 0.1 M HCl or 0.1 M NaOH. The mixture was stirred at
room temperature and then centrifuged at 7500 rpm for 3 min.

Results:
The optimal conditions for each variable were performed using Box-Behnken design. Results
revealed that ZIF-3M nanoparticles more efficiently remove levofloxacin than ZIF-67 in aqueous
solution.

Conclusion:
In this research, new three metals ZIF (ZIF-3M) nanoparticles were synthesized with
Ag, Zn and Co in aqueous solution and characterized by different techniques. Results indicated successful
synthesis with preserving ZIF framework. Results indicated that ZIF-3M has more ability for
the removal of levofloxacin than ZIF-67. Isotherm studies showed that the most suitable model for
the adsorption of levofloxacin onto ZIF-3M has a good agreement with the Langmuier model.
Deglucohellebrin: A Potent Agent for Glioblastoma Treatment
Authors: Vartholomatos Evrysthenis , Alexiou George A. , Markopoulos Georgios S. , Lazari Diamanto , Tsiftsoglou Olga , Chousidis Ieremias , Leonardos Ioannis , Kyritsis Athanasios P. 
Published: November 2019

Background:
Glioblastoma is the most common primary brain tumor in adults with a dismal prognosis.
To date, several anticancer agents have been isolated from plants. Helleborus odorus subsp. Cyclophyllus is
an endemic plant of the Balcan flora. Herewith, we investigated for the first time, the anti-glioma effect of deglucohellebrin
(DGH) extracted from the roots of Helleborus.

Methods:
We investigated the effect of DGH in U251MG, T98G and U87G glioblastoma cell lines. We selected
the T98G cells because of their inherent temozolomide resistance.

Results:
The IC50 value of reduced viability for DGH was 7x10-5M in U251MG cells, 5x10-5M for the T98G
cells and 4x10-5M in U87G cells during 72h treatment. DGH induced G2/M cell cycle arrest, caspace-8 activation
and significant mitochondrial membrane depolarization, suggesting the activation of the intrinsic, mitochondrial-
dependent apoptotic pathway. DGH and temozolomide induced changes in CDs’ expression in
U251MG and T98G cells. In zebrafish, DGH did not induce toxicity or behavioral alterations.

Conclusion:
The present study is the first to determine the anti-glioma activity of DGH. DGH may be a potent
agent for glioblastoma treatment and further studies are needed.
Cracking in Reinforced Concrete Structures Damaged by Artificial Corrosion: An Overview
Authors: Imperatore Stefania , Rinaldi Zila 
Published: November 2019

Background:
Corrosion of the reinforcing steel is a significant issue in construction engineering. As the corrosive attack propagates, the oxides accumulated on the steel-concrete interface cause a radial internal pressure in the structural element and induce a tensile stress state in the concrete with the consequent cracking. Except for few cases, the main outcomes on the behavior of reinforced concrete structures damaged by corrosion come from experimental results on artificially corroded specimens. For many years, the scientific community has been discussing the feasibility of artificial techniques to simulate the corrosion process in structural element. Specifically, the most disputed method is the accelerated electrolytic corrosion test, often characterized by high current intensities in order to reduce the duration of the experimental surveys.

Objective:
In the paper the influence of the current density on the degradation of a reinforced concrete element is investigated with particular reference to the kind of formed oxides and to the crack width.

Methods:
An experimental survey on steel rebars embedded in concrete cylinders and subjected to an electrolytic corrosion has been performed, with different increasing current densities. Furthermore, an analytical model, based on the classical thick-walled cylinder theory already proposed by the authors, is applied for validating the experimental results.

Results:
The oxides produced by artificial corrosion with different current densities are analyzed with X-ray diffractometry measurements. The influence of the current density on the crack widths is also pointed out.

Conclusion:
The analyses of the obtained results show that for the analysed specimens and current density range, no significant differences are found for the oxides composition. On the contrary the influence of the current density on the crack width is pointed out, and an upper limit of this parameter is indicated.
A Novel FSK Generator Using a Second Generation Current Controlled Conveyor
Authors: Zahiruddin Syed , Srinivasulu Avireni , Sarada Musala 
Published: November 2019

Objective:The interest concern towards the development of enabling technology towards new current mode devices has forced the designers and researchers for the invention of devices, which has having the characteristics like such as low power, robustness, compactness, efficiency and scalability.Methods:Second Generation Current Controlled Conveyor (CCCII) is the prevailing current mode device of the times today. Since its invention by A. Fabre, it has prominent applications in the field of analog signal processing and in biomedical applications too. In this manuscript, CCCII is used as an enabling device to design a Frequency Shift Keying (FSK) Generator.Results:The proposed topology is designed using a single active device CCCII with least passive components. The circuit enjoys the features of like electronic tunability of frequency using the bias current.Conclusion:It can be concluded that the FSK generator circuit designed using single CCCII confers better results in contrast to the existing structures. The maximum power consumption is 0.196 mW. The proposed circuit has the benefit of simple configuration, which is very much proficient for IC fabrication.
Optimal Stochastic Gradient Descent with Multilayer Perceptron Based Student's Academic Performance Prediction Model
Authors: Ranjeeth S. , Latchoumi T.P. , Paul P. Victer 
Published: November 2019

Introduction:
Educational Data Mining and Machine Learning Models gained more interest
among researchers and academicians in recent years. These are used to extract meaningful data
from the educational database can be applied to predict the student academic performance.

Objective:
The main objective of this research shows the capability to predict the student's performance
and is highly beneficial to take remedial actions in the present educational system. It also offers
suitable student assistance, allows an educational institution or teacher to help the students in
gaining extra marks.

Methods:
The presented model operates in two stages, namely classification and outlier detection.
Initially, a multilayer perceptron is employed for data classification. Later, a stochastic gradient descent
classifier and multi-layer perceptron are integrated to effectively classify the data. For further
improvement in the classification, Student academic performance, outlier detection method namely
radial basis function is applied to remove the misclassified instances.

Results:
The proposed model achieves superior classification performance with the maximum precision
of 79.30, recall of 79.30, and accuracy of 79.30, F-score of 79.30 and kappa value of 52.40 respectively.
The simulation outcome exhibited that the multilayer perceptron and stochastic gradient
descentmodel offers better results over the other classifiers. However, the usage of outlier detection
using the radial basis function model takes the classifier results to the next level.

Conclusion:
Using classification techniques a new student academic performance model is proposed
by addressing some issues in the existing model which is used to predict the student academic
performance assist inproper time.
Educación Interprofesional: un desafío para dar visibilidad a la contribución de Enfermería en los equipos de salud
Authors: Pérez-Etchetto M. 
Published: November 2019

La Educación Interprofesional (EIP) en salud posee varias definiciones que se complementan y aportan diferentes enfoques. Según la OMS esta se define como: un enfoque de enseñanza y aprendizaje que reúne a estudiantes de dos o más profesiones para aprender juntos, con el fin de mejorar la colaboración y los resultados en salud.
La EIP surge como respuesta a los problemas actuales en los sistemas de salud y en la búsqueda de estrategias de enseñanza que regulen los cambios estructurales de los servicios y los procesos que implica el cuidado a la salud. Involucra una concepción integral y abarcativa del concepto salud que requiere la superación del modelo de formación de los silos profesionales y que conlleva a una reforma de la enseñanza en salud para la mejora del cuidado a la salud de la población; integra en ese concepto la necesaria conjunción entre la enseñanza, la investigación, así como el aporte a la sociedad a través del cuidado de la salud y la interacción con los equipos profesionales de los servicios sanitarios.