bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Basis for the Understanding of Entry Inhibitors against
SARS Viruses
Authors: Kushwaha Prem Kumar , Kumari Neha , Nayak Sneha , Kishor Keshav , Sharon Ashoke
Published: May 2021

Outbreaks due to Severe Acute Respiratory Syndrome-Corona virus 2 (SARSCoV-
2) initiated in Wuhan city, China, in December 2019 and continued to spread Internationally,
posing a pandemic threat as declared by WHO and as of March 10, 2021, confirmed
cases reached 118 million along with 2.6 million deaths worldwide. In the
absence of specific antiviral medication, symptomatic treatment and physical isolation remain
the options to control the disease and contagion. The recent clinical trials on antiviral
drugs highlighted some promising compounds such as umifenovir (haemagglutininand
has only 70% similarity to SAmediated fusion inhibitor), remdesivir (RdRp nucleoside
inhibitor), and favipiravir (RdRp Inhibitor). WHO launched a multinational clinical
trial on several promising analogs as a potential treatment to combat SARS infection.
This situation urges a holistic approach to invent safe and specific drugs as a prophylactic
and therapeutic cure for SARS-related viral diseases, including COVID-19.
It is significant to note that researchers worldwide have been doing their best to handle
the crisis and have produced an extensive and promising literature body. It opens a scope
and allows understanding the viral entry at the molecular level. A structure-based approach
can reveal the molecular-level understanding of viral entry interaction. The ligand
profiling and non-covalent interactions among participating amino-acid residues are critical
information to delineate a structural interpretation. The structural investigation of
SARS virus entry into host cells will reveal the possible strategy for designing drugs like
entry inhibitors.
The structure-based approach demonstrates details at the 3D molecular level. It shows
specificity about SARS-CoV-2 spike interaction, which uses human angiotensin-converting
enzyme 2 (ACE2) as a receptor for entry, and the human protease completes the process
of viral fusion and infection.
The 3D structural studies reveal the existence of two units, namely S1 and S2. S1 is
called a receptor-binding domain (RBD) and responsible for interacting with the host
(ACE2), and the S2 unit participates in the fusion of viral and cellular membranes. TMPRSS2
mediates the cleavage at the S1/S2 subunit interface in the S-protein of SARS
CoV-2, leading to viral fusion. Conformational difference associated with S1 binding alters
ACE2 interaction and inhibits viral fusion. Overall, the detailed 3D structural studies
help understand the 3D structural basis of interaction between viruses with host factors
and open scope for the new drug discovery process targeting SARS-related virus entry into
the host cell.
An Updated Review of the Cross-talk Between MicroRNAs and Epigenetic
Factors in Cancers
Authors: Dastmalchi Narges , Safaralizadeh Reza , Banan Khojasteh Seyed Mahdi , Sam Mohammad Reza , Latifi-Navid Saeid , Hussen Bashdar Mahmud , Shadbad Mahdi Abdoli , Baradaran Behzad
Published: May 2021

Background:

Growing evidence indicates that miRs have critical activities in
adjusting cellular processes, e.g., cell death, proliferation, and cell-cycle.

Introduction:

This study aimed to provide a concise review of the recent findings regarding
tumoral miRs and the cross-talk between miRs and epigenetic factors.

Results:

Like the protein-coding genes, the expression levels of miRs are mediated by
various transcriptional networks. Indeed, the expression of miRs could be epigenetically
modulated by DNA methylation factors and histone modifiers. Furthermore, miRs can
suppress critical factors, which mediate epigenetic modifications. Besides, miRs have
been implicated in cancer development, metastasis, and chemo-resistance. The aberrant
expression of miRs and dysregulated modulatory circuits between miRs and epigenetic
factors participate in tumor progression.

Conclusion:

Identifying tumoral miRs can provide ample opportunity to overcome chemo-
resistance and bring a forefront treatment for affected patients.
Role of γ-Secretase Inhibitors for the Treatment of Diverse Disease Conditions through Inhibition of Notch Signaling Pathway
Authors: Mondal Arijit , Bose Sankhadip , Banerjee Sabyasachi , Pal Dilipkumar
Published: May 2021

γ-secretase is an intramembrane protease sub-assembly that sunders transmembrane proteins.
It is involved in intramembrane proteolysis and also contributes to the regeneration of transmembrane
protein. The amyloid precursor proteins (APPs) are typical γ-secretase substrates. These
proteins are cleaved to produce 36-43 amyloid-beta (Aβ) amino acid peptides. Abnormal folding of
these proteins fragments leads to amyloid plaques, which are frequently encountered in
Alzheimer’s disease. Some Type I class of integral membrane proteins is processed under the influence
of γ-secretase, such as receptor tyrosine-protein kinase erbB4 and CD44 glycoprotein. γ-Secretase
is being explored in several diseases as a clinical goal. Both γ-secretase inhibitors (GSIs) and
γ-secretase modulators (GSMs) are being evaluated for this purpose. A large amount of γ-secretase
inhibitors (GSIs) from peptide to non-peptide have been disclosed, offering several lead compounds
for the design and optimization of γ-secretase targets, but most GSIs lack sufficient potency,
exhibit low penetration in the brain, and manifest low selectiveness. γ-secretase inhibitors are
obliquely a regulator of a γ-secretase substrate Notch, and valuable in the development of β-amyloid
peptide (Aβ). These γ-secretase inhibitors block the Notch signaling pathway in autoimmune
and lymphoproliferative disorders, like autoimmune lymphoproliferative syndrome (ALPS) and
systemic lupus erythematosus (SLE), and perhaps even in cancerous cell proliferation, angiogenesis,
and cellular differentiation of human-induced pluripotent stem cells (hiPSC). The current review
portrays the mechanism, regulation, and inhibition of γ-secretase in the management of a
wide assortment of diseases.
COVID-19 and Children’s Mental Health: Identifying Challenges and the New Normal
Authors: Behere Aniruddh , Barber Garcia Brittany N.
Published: May 2021

The novel coronavirus disease COVID-19 has had a clear and direct impact on the physical
health of human beings. However, the mental health toll associated with this global pandemic is
only beginning to be understood. Although children and adolescents have been largely spared from
the more severe symptoms associated with the disease, global health organizations such as the United
Nations have suggested that COVID-19 may have the longest and most severe impact on children
and adolescents due to the socioeconomic, physical, psychological impacts associated with
the disease itself and the measures taken to stop transmission, such as physical distancing. This paper
provides an overview of the evolutionary basis for community and the ways that social and
physical distancing measures to contain COVID-19 threaten the important social learning and support
that community provides. It then discusses how this pandemic is likely to impact the mental
health of children and adolescents, based on research from prior pandemics, recommendations
from global health authorities, and emerging data on the impacts of COVID-19. Finally, we offer
evidence-based suggestions on how to mitigate the effects of physical and social distancing.
Safety and Efficacy of Intermittent Hypoxia Conditioning as a New Rehabilitation/
Secondary Prevention Strategy for Patients with Cardiovascular
Diseases: A Systematic Review and Meta-analysis
Authors: Glazachev Oleg S. , Kryzhanovskaya Svetlana Yu , Zapara Maxim A. , Dudnik Elena N. , Samartseva Vlada G. , Susta Davide
Published: May 2021

Background:

Once used by mountaineers to facilitate rapid adaptations to altitude and
by athletes to improve their aerobic capacity, exposure to hypoxia has been proven to affect various
physiological, clinically relevant parameters. A form of conditioning known as Intermittent Hypoxia
Conditioning (IHC) consists of repeated exposures to intermittent hypoxia, combined with
normoxia and hyperoxia, which has been shown to have potential as a treatment to improve cardio-
metabolic risks profile in cardiac patients but results across studies are inconsistent. This systematic
review and meta-analysis aimed to evaluate the clinical effectiveness of IHC.

Methods:

Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register
of Controlled Trials) were searched (from inception to December 2019) to retrieve all studies
focused on IHC in elderly patients with cardiovascular disease. A meta-analysis of functional, efficacy
and safety outcomes in cardiac patients was completed to compare IHC to sham treatments.

Results:

Fourteen studies with 320 patients in the Interval Hypoxia-normoxia Group (IHNG) or Interval
Hypoxia-hyperoxia training Group (IHHG) and 111 patients in the control group were included
in our meta-analysis. IHNT and IHHT were associated with significant reduction in heart rate,
SBP, and DBP at rest after treatment [MD= -5.35 beat/min, 95% CI (-9.19 to -1.50), p=0.006],
[MD= -13.72 mmHg, 95% CI (-18.31 to -9.132), p<0.001], and [MD= -7.882 mmHg, 95% CI
(-13.163 to -2.601), p=0.003], respectively. There were no significant complications or serious adverse
events related to IHNT/IHHT.

Conclusion:

The current evidence suggested that the use of the IHNT/IHHT program in elderly patients
with CVDs can be safe and effective in terms of heart rate and elevated blood pressure. However,
currently, there is no supporting evidence that IHNT/IHHT can significantly improve hematological
parameters or lipid profile. Exercise tolerance increased at the end of the course of hypoxic
conditioning within IHC group, but did not differ from controls. Further research is needed.
Ankylosing Spondylitis and Risk of Cardiac Arrhythmia and Conduction Disorders: A Systematic Review and Meta-analysis
Authors: Morovatdar Negar , Watts Gerald F. , Bondarsahebi Yones , Goldani Fatemeh , Rahmanipour Elham , Rezaee Ramin , Sahebkar Amirhossein
Published: May 2021

Objective:

The objective of this study isto assess the association between ankylosing
spondylitis (AS) and risk of heart conduction disorders and arrhythmia.

Methods:

PubMed, Embase, and Web of Science databases were systematically searched for observational
studies that investigated the association between AS and risk of heart conduction disorders
and arrhythmia with no language or date restrictions until September 16, 2019. We used randomand
fixed-effects models to pool the results of the studies. Publication bias was assessed by Egger’s
test. Subgroup analysis was carried out based on the study design. A p-value less than 0.05 was considered
significant. Comprehensive Meta-Analysis (CMA) software was used to perform meta-analysis.

Results:

After removing duplicates, we reviewed 135 articles. Finally, we included seven articles
in our meta-analysis, of which four studies reported AV block and any conductive abnormality and
three focused on atrial fibrillation and any arrhythmia. Based on our meta-analysis, an increased
risk of atrial fibrillation (RR: 1.85, 95%CI: 1.15-2.98) and atrioventricular block (OR: 3.46, 95%-
CI: 1.09-10.93) was found in AS subjects compared to the general population. In a subgroup analysis
based on study design, we found a greater association between AS and atrioventricular block in
cohort studies (RR: 5.14, 95%CI: 1.001-26.50) compared to cross-sectional ones. However, we did
not find any association between AS and any arrhythmia (OR=3.36, 95% CI: 0.93-12.15), or conduction
disorders (OR: 0.64, 95%CI: 0.38-1.06). No publication bias was found.

Conclusion:

Our results support an association between AS and a higher risk of atrial fibrillation
and atrioventricular block.
Primary Tumors of the Sacrum: Imaging Findings
Authors: Sambri Andrea , Fiore Michele , Giannini Claudio , Pipola Valerio , Zucchini Riccardo , Aparisi Gomez Maria Pilar , Aguiar Paula Musa , Gasbarrini Alessandro , De Paolis Massimiliano
Published: May 2021

The diagnosis of sacral neoplasms is often delayed because they tend to remain clinically silent for a long time. Imaging is useful at all stages of the management of sacral bone tumors, i.e., from the detection of the neoplasm to the long-term follow-up. Radiographs are recommended as the modality of choice to begin the imaging workup of a patient with known or suspected sacral pathology. More sensitive examinations, such as Computerized Tomography (CT), magnetic resonance (MRI), or scintigraphy, are often necessary. The morphological features of the lesions on CT and MRI help orientate the diagnosis. Although some imaging characteristics are helpful to limit the differential diagnosis, an imaging-guided biopsy is often ultimately required to establish a specific diagnosis. Imaging is of paramount importance even in the long-term follow-up, in order to assess any residual tumor when surgical resection remains incomplete, to assess the efficacy of adjuvant chemotherapy and radiotherapy, and to detect recurrence.
The Photodynamic Anti-Tumor Effects of New PPa-CDs Conjugate with pH Sensitivity and Improved Biocompatibility
Authors: Sajjad Faiza , Liu Xu-Ying , Yan Yi-Jia , Zhou Xing-Ping , Chen Zhi-Long
Published: May 2021

Background:

Photodynamic therapy has been increasingly used to cope with the alarming problem of cancer. Porphyrins and their derivatives are widely used as Potent Photosensitizers (PS) for PDT. However, the hydrophobicity of porphyrins poses a challenge for their use in clinics, while most of the carbon dots (CDs) are known for good biocompatibility, solubility, and pH sensitivity.

Objective:

This study aimed to improve the properties/biocompatibility of the pyropheophorbide-α for PDT.

Methods::

The PPa-CD conjugate was synthesized through covalent interaction using amide condensation. The structure of synthesized conjugate was confirmed by TEM, 1HNMR, and FTIR. The absorption and emission spectra were studied. In vitro, cytotoxicity of the conjugate was examined in human esophageal cancer cell line (Eca-109).

Results:

The results showed that the fluorescence of the drug was increased compared to its precursor. CDbased conjugate could generate ROS as well as enhanced biocompatibility by decreasing cytotoxicity. The conjugated drug also showed pH sensitivity in different solutions.

Conclusion:

The dark toxicity, as well as hemocompatibility, was improved.
Probiotics for the Chemoprotective Role against the Toxic Effect of Cancer Chemotherapy
Authors: Waziri Aafrin , Bharti Charu , Aslam Mohammed , Jamil Parween , Mirza Mohd. Aamir , Javed Md Noushad , Pottoo Uzma , Ahmadi Amirhossein , Alam Md Sabir
Published: May 2021

Background:

Chemo- and radiation therapy-based clinical management of different types of cancers is associated with toxicity and several side effects. Therefore, there is always an unmet need to explore agents that reduce such risk factors. Among these, natural products have attracted much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer.

Methods:

Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics.

Results:

Apart from excellent anti-cancer abilities, probiotics alleviate toxicity & side effects of chemotherapeutics, with a high degree of safety and efficiency.

Conclusion:

Preclinical and clinical evidence suggests that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.
Effects of Xenogen Mesenchymal Stem Cells and Cryo-Platelet Gel on
Intractable Wound Healing in Animal Model (Rat)
Authors: Alavi-Farzaneh Babak , Shojaeian Ali , Banitalebi-Dehkordi Mehdi , Mirahmadi Fatemeh , Mehri-Ghahfarrokhi Ameneh , Ghorbanpour Alireza , Rahmati-Dehkordi Shima , Yazdani Farshad
Published: May 2021

Background:

Today, the effects of growth factors and mesenchymal stem cells (MSCs)
in promoting wound healing has been confirmed.

Objective:

This study aimed to investigate the effect of MSCs and platelet cryogel on wound healing.

Methods:

40 male wistar rats were randomly divided into five groups (n=8). The control group
was just dressed, the second group received platelet cryogel, the third group received platelet cryogel
containing MSCs, the fourth group received plasma, and the fifth group received plasma plus
MSCs. The biopsy was obtained from the wounds in the 2, 4, 6, and 8 days of the treatment. Then,
pathological evaluation was conducted. Finally, qRT-PCR was performed to determine angiogenesis.

Results:

The intervention groups had faster wound healing and lower wound area than the control
group (p<0.05). The highest wound healing rate and the smallest wound area was observed in the
group receiving platelet cryogel plus MSCs. Angiogenesis, fibrosis, myoepithelial and epithelialization
in the pathologic examination using H & E staining were not significantly different between
the groups. The expression of Ang-1 in the intervention groups was higher than the control group
and the highest expression was observed in the platelet cryogel plus MSCs, followed by the
platelet cryogel group. The expression of VEGF in the plasma plus MSCs was higher than in the
other groups.

Conclusion:

Further studies require to determine the effects of combined use of platelet cryogel
plus MSCs on other types of wound and evaluate mechanisms involved in wound healing like collagenesis
and inflammatory factors.
Chronic Cannabis Users: A New Special Population to Consider for Drug
Development
Authors: Pastino Gina , Shuster Diana
Published: May 2021

The use and acceptance of cannabis, either medically or recreationally, has substantially
outpaced the collection of data necessary to evaluate it’s use in any population. However, the mere
widespread availability does not imply the absence of risk or confirmation of efficacy and should not
be treated as such. There is enough data to suggest that not only does the potential for pharmacokinetic
and metabolic interactions exist, but also that baseline characteristics for a given population could be
different in chronic cannabis users. Either or both of these may impact the safety and efficacy profile
for any new drug in development. As such, we encourage drug developers to consider that the cannabis
user may very well be a special population that warrants its own clinical pharmacology evaluation.
Synonymy in modern pharmaceutical terminology of Uzbek and English languages
Authors: Khudoyqulova Dilafruz Kabildjanovna
Published: May 2021

The main goal of the article deals with descriptions and analyzes of synonyms, polysemy and neologisms in the terminology of the pharmaceutical industry in a comparative aspect. The place and role of synonymous and polysemantic words and neologisms in the pharmaceutical lexicon, the semantics and ambiguity of words when translating documents and literature on the practice of the field are given in practical forms.
Source characteristics of Ayyub’s work “sharhi masnaviyi mawlavi”
Authors: Umarova Iroda Amanullayevna
Published: May 2021

Manuscript No. 2225 is kept in the fund of the Institute of Oriental Studies named after Abu Rayhon Beruni of the Academy of Sciences of the Republic of Uzbekistan. This manuscript is an excellent commentary on Jalaliddin Rumi's “Masnaviyi Manaviy” and contains six books. The commentary is called “Sharhi Masnaviyi Mawlavi” by Ayyub. The commentary explains some of Masnavi's words, as well as stories about Rumi's life and teachings. Some of the stories are narrated by the narrator himself. At the beginning of each comment or story that Ayyub gave, he noted the source from which that information was obtained. In interpreting the Masnavi, the commentator used the following works: Abdurahman Jami's Naynama, Yusuf and Zulayha, Nafahotu-l-uns, Ahmad Afloki's “Manoqibu-l-Arifin”, Sheikh Abdurahim Bihari's “Kashfu-l-lugat va -l istilohot”. In some verses of the Masnavi, a word or phrase from the verses of the Qur'an is quoted. The commentator explains this verse in full in the commentary, sometimes after giving a sentence of the verse. In his Masnavi, Rumi refers to the Hadiths or any event in the history of the prophets. Ayyub gives that Hadith or incident in full and then goes on to comment on it.
Paraphrases related to the language of advertising
Authors: Yunusova Shakhnoza Mukhamedumarovna
Published: May 2021

The article deals with the language of advertising in Uzbek Language. The objective of the work is to provide the analysis of language of advertising from linguistic point of view and specify linguistic means used in advertising texts.  The format of the advertising text is a certain difference compared to other functional properties of the text style. This is one of the distinguishing features mentioned are used in the title of any kind of short news reports in newspapers. The title of the advertising is important to the composition of the advertising creation relevant information. It’s the most important and interesting part of the target audience to attract attention. Text title, in general, does not explain all the details. We have the scientific language of the advertising text in a statement issued through the media; we will focus on the style characteristics of scientific and scholarly texts.
Context-aware architecture for Industry 4.0-ready manufacturing facility
Authors:   Department of Computer Science, College of Science and Humanities at Rumah, Majmaah University, AlMajmaah, Saudi Arabia, Alharbi Olayan , Alharbi Mafawez ,   Department of Natural and Applied Science, Community College Buraydah, Qassim University, Buraydah, Saudi Arabia
Published: May 2021

The industry 4.0 revolution is empowering the manufacturing sector with several advantages from the production to consumption stage of products, or beyond that. Recently, operators in factories have been accumulating extensive data from machine sensors and other organizational and operational technologies such as company enterprise and planning systems. Notably, having access to extensive data is a double-edged sword. To the best of our knowledge, there is not any work in the literature that proposed architecture for industry 4.0 based on a context-aware system. The aim of this research is to provide the context-aware architecture to enhance decision-making in factories and reduce the exposure of operators to the necessary and related findings. The proposed system is contextually aware of three aspects, operator feedback for previous similar findings, specifications of products under production, and historical data of manufacturing machines. The proposed system is proactive which attracted operator attention only when the findings were contextually related, based on the aforementioned aspects. The contributions of this research an intelligent architecture, a case study, and a mathematical model.
Differences of sodium consumption pattern hypertension sufferer in coastal and highland communities in Wakatobi islands
Authors: Alifariki La Ode , Tukatman Tukatman, , Bangu Bangu, , Siagian HeriviyatnoJulika
Published: May 2021

Available data indicate that food sodium (such as salt) is directly related to blood pressure (BP). The research aims to look at the different sodium consumption patterns of hypertension sufferers in two different coastal areas and highland areas in the Wakatobi Islands. The type of research is observational analytic research using a cross-sectional design. This study has been carried out in the District of Wangi-Wangi, especially in the MolaSamaturu villages and Waginopo Village in October 2019. The number of research samples is 100 people (50 respondents in Mola Samaturu Village and 50 people in Waginopo Village). The results showed the differences between sodium consumption patterns in hypertensive sufferers in Mola Samaturu Village and Waginopo Village with a p-value = 0,000 <α 0.05. Sodium consumption patterns in coastal communities are higher than in highlands community.
Identification of maize kernel resistance proteins against Aspergillus flavus by a statistical approach: A predictive model of resistance capacity.
Authors: Balzano Leandro , Alezones Jesús , Diez García Nardy
Published: May 2021

Although kernel infection by Aspergillus flavus and pre-harvest aflatoxin contamination of Zea mays grain is a significant crop production problem, not only in Venezuela but also around the world, little progress has been made in identifying proteins and metabolic pathways associated with this pathogen resistance. Usually, a protein with a two-fold expression between control and condition is considered a biomarker of some phenomena, but we think it is essential to evaluate its contribution to resistance. That is why we decided to determine the behavior's resistance capacity in terms of expression levels of an identified protein of maize kernels infected with A. flavus by using a multivariate approach. In this work, we identify 47 of 66 differentially expressed spots with a remarkable contribution to resistance against the fungus Aspergillus flavus. We finally test this approach to know if it can be used as a predictive resistance model and probe it by including theoretical and experimental protein expression profiles of other inoculated maize lines.
Assimilation of natural Radionuclides in the wheat plant from cultivated soil
Authors: Alsaedi Suad A. , Alsaadie Naseer A. , Mouhamad Raghad S. , Yass Nibras A.
Published: May 2021

The intake of naturally nuclides 238U, 232Th, and 40K by wheat crop from two different fertilization soils of Iraq was studied under natural farm conditions. The overall mean of soil to wheat cereal transfer factors (TF) was studied and observed to be in the range of 0.6 × 10-3 to 0.70 × 10-3 for 238U, 0.11 × 10-3 to 0.13 × 10-3 for 232Th and 0.054 to 0.055 for 40K. The calculated values of TF for wheat grain denote that 40K are the significant radionuclides that are transferred in grain. This evaluation is most important for the production of foodstuffs with low contents of radionuclides. The assimilation of radionuclides by consuming wheat cereals from the farms studied gives a small fraction to the total annual ingestion dose received by a person due to naturally existent radioactivity material in the environment. This study proves that the natural radioactivity and Ingestion effective dose was lower than the safe, which the total of the dose received from 238U and 232Th due to consumption of wheat grains alone from fertilized field 0.056 and 0.045 mSv y-1 from the unfertilized field total ingestion dose, the dose received from 40K due to the consumption from the unfertilized and fertilized field was 0.0102 and 0.0137 respectively. The dose values were less than the limit value of 0.30 mSv y-1. Therefore, the consumption of these foods has no health risks. This process may help to obtain basics on radiological health regulations
The activity concentration of natural radionuclides 238U, 232Th, and 40K in fertilized and unfertilized soil and wheat plants growing into is statistically significant at 1% level of significance using an independent t-test.
Upregulation of miR-206 is a potential diagnostic biomarker in breast cancer
Authors: Karami Faezeh , Maleki Narges , Monfared Arefeh Khazraei , Marandi Sayeh Jafari
Published: May 2021

Breast cancer is one of the most common malignancies, and like most cancers, most cases are caused by somatic mutations. Due to estrogen's role in the growth, differentiation, and division of breast and endometrial cancer cells, tamoxifen is used as an estrogen receptor antagonist in breast cancer cells with estrogen receptor (ER +) has a special place, which unfortunately in one-third of the Cases are resisted. This study aimed to investigate the effect of tamoxifen-treated tumor-derived exosomes on the expression pattern of Twist and Bcl-2 oncogenic genes in fibroblast cells. MCF-7 breast cancer cell line and fibroblast cells were purchased and cultured in a complete culture medium. After the appropriate number of cells was reached, they were treated with the appropriate concentration of tamoxifen. Cellular supernatant was then gathered in flasks, and exosomes were extracted from them. After extracting RNA from exosomes and cDNA synthesis, the expression level of miR-206, Twist-1, and Bcl-2 genes were evaluated using the Real-Time PCR method. The electronic microscope results confirmed the correctness of the exosomes isolated from the tumor cell culture medium. It has also been shown that tamoxifen treatment increases the expression of miR-206 in exosomes derived from breast tumor cells. The control group which has been kept untreated induced the expression level of Twist-1 and Bcl-2 genes time-dependently. However, when tamoxifen-treated tumor-derived exosomes treated the target cells, the expression level of oncogenic miRs Twist-1 and Bcl-2 were declined over time. Overall, this study showed that tamoxifen treatment on breast cancer cells could apply its antioncogenic effects on tumor stromal cells, such as fibroblasts, by altering the expression levels of exosomal microRNAs in tumor cells.
Size variation of morphological traits in Bosmina freyi and its relation with environmental variables in a tropical eutrophic reservoir
Authors: López-Cardona Yury Catalina , Parra-García Edison , Palacio-Baena Jaime , Villabona-González Silvia Lucía
Published: May 2021

We assessed the size variation of morphological traits in Bosmina freyi regarding changes in environmental variables, the biomass of invertebrate predators, and algal food availability in two depths of the photic zone, the riverine zone, and near the dam zone (lacustrine zone) in The Riogrande II reservoir. In 200 individuals of B. freyi, using the software TpsDig2 we measured the body size, mucron and antennule lengths, and the antennule aperture percentage. Using the Mann-Whitney U test, we assessed the differences between these traits considering the zones and the photic depths; however, we used a canonical discriminant analysis with morphologic traits and environmental variables. Measured morphological traits showed a heterogeneous distribution between sampled zones and depths (p < 0.05). The highest values mucron and antennule lengths and the smallest antennule aperture angle were observed on small body size individuals, associated with physical, chemical, and biological characteristics in the riverine zone and the subsurface. Size structure distribution in B. freyi was related to changes in water temperature, trophic state, depredation, availability, and quality of food, of which implications related to the zooplankton community structure, predator-prey relations, and energy flow in the reservoir.
A Spatio-temporal distribution analysis of vesicular stomatitis outbreak in Ecuador, 2018
Authors: Salinas María Teresa , De La Torre Euclides José , Moreno Paola Katerine , Vaca Andrés Alejandro , Maldonado Rubén Alexander
Published: May 2021

Vesicular stomatitis (VS) is a viral disease primarily affecting cattle, swine, and equine causing economic losses. It is of particular interest because its outward signs are similar to those of foot-and-mouth disease. Outbreaks of VS occurred in several herds in Ecuador in 2018, affecting principally bovines. In this sense, the present study was conducted to characterize the temporal and spatial dynamics of Vesicular stomatitis occurrence between January and December 2018. During the study period, 583 animals with symptoms of VS were reported. In this way, tissue samples were collected, VS was diagnosed, and outbreaks were defined as herds with a confirmed positive test for the disease.
Outbreaks were georeferenced, and Space-time clusters were used to determine zones where the number of reported outbreaks was more significant than expected. A space-time permutation scan statistic (STPSS) was used to identify hot spots of space-time interaction within patterns of the cases reported. Standard Monte Carlo Critical Value was used to test for the cluster's significance. A total of 399 outbreaks were presented in 18 provinces. Spatial scan statistics allowed the detection of four significant space-time clusters of VS outbreaks. The highest incidence was reported around week 35 and week 44, which were observed outbreaks increase in the country's north region. In this sense, clusters coincided with the areas with the highest incidence of outbreaks. Besides, maps showed places where the disease is not shared. The information showed in the present study may contribute to prevents VS spread into regions of Ecuador that is only sporadically affected by the disease. Monitoring in affected zones may lead to quick responses to possible outbreaks issuing alerts when there is a greater than typical risk of spreading the disease
Protective potential of Cynara scolymus extract in thioacetamide model of hepatic injury in rats
Authors: El-Deberky Deena , Rizk Manar , Elsayd Faten , Amin Aziza , El-Mahmoudy Abubakr
Published: May 2021

Hepatic injury is a worldwide health problem. This study aimed to evaluate the possible hepatoprotective potential of Artichoke (Cynara scolymus) extract (CSE) in albino rats using the thioacetamide (TAA) a model of liver injury. Acclimatized 42 rats were divided randomly into seven groups, each consists of six rats, and subjected to different treatments. Hepatic injury model was induced by administration of TAA at a dose of 100 mg per kg, intraperitoneally, twice weekly for 8 weeks (+ve control); test groups rats received CSE at doses of 100 or 200 mg/kg BW, orally, daily for 8 weeks adjunct with TAA; standard group rats received Silymarin at a dose of 100 mg per kg, orally, daily for 8 weeks adjunct with TAA; other 2 groups of rats received only CSE at the same dose levels; while -ve control rats received only the vehicles. Blood and liver tissue samples were collected at the end of the experimental course for different assessments. Results revealed that CSE exhibited dose-dependent hepatoprotection indicated by nearly normalized parameters, including enzymatic liver function parameters (AST, ALT, GGT & ALP with potential % of 94.06, 86.96, 85.93, 64.85, respectively, after large dose when standardized by Silymarin); non-enzymatic parameters (total protein, albumin, globulins, total bilirubin, conjugated bilirubin, unconjugated bilirubin, TAGs, Cholesterol, HDL, LDL & VLDL with potential % of 83.42, 85.9, 83.44, 98.1, 77.41, 91.5, 97.51, 97.46, 81.41, 88.52 & 89.4, respectively, after large dose when standardized by Silymarin). The underlying mechanism of the observed hepatoprotection of CSE was attributed to impeding the oxidative stress-mediated by TAA, indicated by reduced hepatocyte lipid peroxidation product MDA (95.96 % of Silymarin), and improved antioxidative enzymes in liver homogenate, namely, GPx, Catalase & SOD with potentials of 95.44, 87.02 & 81.48 % of Silymarin, respectively. Macroscopic and microscopic pathological pictures were supportive to the biochemical findings, where the pathological lesions caused by TAA as congestion and dilatation of central and portal veins with perivascular fibrous connective tissue proliferation admixed with few mononuclear leukocytes plus necrotic hepatocytes and hyperplastic biliary epithelium, were ameliorated dose-dependently when CSE was administered together with TAA. The present study's data may suggest CSE as a natural source for promising hepatoprotective and antioxidant drug preparations.
Fermentation study of Cassava bagasse starch hydrolyzed's using INIAP 650 and INIAP 651 varieties and a strain of Lactobacillus leichmannii for the lactic acid production
Authors: Inguillay Shirley , Jadán Felipe , Maldonado-Alvarado Pedro
Published: May 2021

Ecuador is an agricultural country, which has an actual production of starch obtained from cassava. Tuber processing residues do not have an economic impact; for example, the cassava bagasse, only used for plant fertilization and animal feeding. This project aimed to study the influence of the fermentation variables (pH and agitation), on the lactic acid production. Enzymatic hydrolysis of cassava bagasse starch for the varieties INIAP 650 and INIAP 651 was performed using α-amylase and glucoamylase. Then, glucose was fermented by Lactobacillus leichmannii ATCC 7830 strains, varying conditions such as agitation (150 rpm and absence) and pH (4.5, 5.0, and 5.5). Finally, the determination of lactic acid was performed by potentiometric and FTIR analysis. Conversions of cassava bagasse to reduced sugars were 71.66 and 85.05 % for INIAP 650 and INIAP 651 varieties. The best lactic acid concentrations were 27.62 and 33.48 g/L, obtained at pH 5.5 and agitation, for INIAP 650 and INIAP 651 varieties. Qualitative analysis conducted by FTIR spectrophotometry confirmed the presence of lactic acid in the reacted products. Lactic acid production from cassava bagasse starch could contribute to the Manabí and Esmeraldas provinces of Ecuador's economic development.
The behavior of Mean Platelet Volume in Sepsis in critical patients with and without sepsis
Authors: Vélez Pablo Andrés , Baldeón R Lucy , Vélez-Paez Jorge Luis
Published: May 2021

The mean platelet volume is an anatomical biomarker that has shown its usefulness in various cardiovascular and metabolic pathologies; in sepsis, it has been positioning itself as an indicator of mortality, easily accessible and immediately applicable when reported in the routine blood count. This study demonstrates the mean platelet volume's biological behavior in critical patients with sepsis compared with non-septic patients. An observational, longitudinal, prospective, monocentric cohort study was conducted in 250 patients treated at the intensive care unit of the Pablo Arturo Suárez Hospital, Quito- Ecuador, from January 2019 January 2020. A group of patients with sepsis (n = 125) and without infectious pathologies (n = 125) were studied. The inclusion criteria were patients over 18 years of age of both genders, diagnosed with sepsis or septic shock using SEPSIS 3 criteria, and patients without septic pathology. The mean platelet volume (MPV) of days 1, 2, and 3 were studied. Septic patients had a mean APACHE (18.74 SD 9.52) higher than the non-septic ones (11.93 SD 7.01) (p = < 0.000). The MPV was consistently higher in patients with sepsis than non-septic patients, but it reached statistical significance on day 3 (9.13 SD 1.55 vs. 8.66 SD 1.34, p=0.042). The MPV on day 3 presented a significant area under the curve (AUC =0.580) (CI. 0.500-0.661), where the cut-off point according to Youden's index was positive for sepsis if MPV≥ 9.85 femtoliter (fL) with OR=3.30 and p-value= 0.005. Likewise, lactate on admission showed an AUC of 0.625 (CI. 0.555-0.694), with a cut-off point ≥of 1.15 mmol / L, OR=2.51, and p=0.007. Age and hypertension did not show a multivariate relationship with the presence of sepsis. It was shown that MPV is higher in patients with sepsis compared to non-septic ones. This observation reaches significance on day 3. Additionally, elevated lactate at admission was also associated with a septic state. On the other hand, platelet count did not show the expected behavior.
Efficiency, Usability, and Outcomes of Proctored Next-Level Exams for Proficiency Testing in Primary Care Education: Observational Study
Authors: Schoenmakers Birgitte , Wens Johan
Published: May 2021

Background

The COVID-19 pandemic has affected education and assessment programs and has resulted in complex planning. Therefore, we organized the proficiency test for admission to the Family Medicine program as a proctored exam. To prevent fraud, we developed a web-based supervisor app for tracking and tracing candidates’ behaviors.

Objective

We aimed to assess the efficiency and usability of the proctored exam procedure and to analyze the procedure’s impact on exam scores.

Methods

The application operated on the following three levels to register events: the recording of actions, analyses of behavior, and live supervision. Each suspicious event was given a score. To assess efficiency, we logged the technical issues and the interventions. To test usability, we counted the number of suspicious students and behaviors. To analyze the impact that the supervisor app had on students’ exam outcomes, we compared the scores of the proctored group and those of the on-campus group. Candidates were free to register for off-campus participation or on-campus participation.

Results

Of the 593 candidates who subscribed to the exam, 472 (79.6%) used the supervisor app and 121 (20.4%) were on campus. The test results of both groups were comparable. We registered 15 technical issues that occurred off campus. Further, 2 candidates experienced a negative impact on their exams due to technical issues. The application detected 22 candidates with a suspicion rating of >1. Suspicion ratings mainly increased due to background noise. All events occurred without fraudulent intent.

Conclusions

This pilot observational study demonstrated that a supervisor app that records and registers behavior was able to detect suspicious events without having an impact on exams. Background noise was the most critical event. There was no fraud detected. A supervisor app that registers and records behavior to prevent fraud during exams was efficient and did not affect exam outcomes. In future research, a controlled study design should be used to compare the cost-benefit balance between the complex interventions of the supervisor app and candidates’ awareness of being monitored via a safe browser plug-in for exams.
Feasibility, Efficacy, and Efficiency of eHealth-Supported Pediatric Asthma Care: Six-Month Quasi-Experimental Single-Arm Pretest-Posttest Study
Authors: van der Kamp Mattienne , Reimering Hartgerink Pamela , Driessen Jean , Thio Bernard , Hermens Hermie , Tabak Monique
Published: May 2021

Background

Early detection of loss of asthma control can effectively reduce the burden of the disease. However, broad implementation in clinical practice has not been accomplished so far. We are in need of research investigating the operationalization of eHealth pediatric asthma care in practice, which can provide the most potential benefits in terms of adoption, efficiency, and effectiveness.

Objective

The aim of this study was to investigate the technical and clinical feasibility, including an exploration of the efficacy and cost-efficiency, of an eHealth program implemented in daily clinical pediatric asthma practice.

Methods

We designed an eHealth-supported pediatric asthma program facilitating early detection of loss of asthma control while increasing symptom awareness and self-management. In the 6-month program, asthma control was monitored by 4 health care professionals (HCPs) by using objective home measurements and the web-based Puffer app to allow timely medical anticipation and prevent treatment delay. Technical feasibility was assessed by technology use, system usability, and technology acceptance. Clinical feasibility was assessed by participation and patient-reported health and care outcomes and via a focus group with HCPs regarding their experiences of implementing eHealth in daily practice. The efficacy and cost-efficiency were explored by comparing pretest-posttest program differences in asthma outcomes (asthma control, lung function, and therapy adherence) and medical consumption.

Results

Of 41 children, 35 children with moderate-to-severe asthma volunteered for participation. With regard to technical feasibility, the Puffer app scored a good usability score of 78 on the System Usability Scale and a score of 70 for technology acceptance on a scale of 1 to 100. Approximately 75% (18/24) of the children indicated that eHealth helped them to control their asthma during the program. HCPs indicated that home measurements and real time communication enabled them to make safe and substantiated medical decisions during symptom manifestations. With an average time commitment of 15 minutes by patients, eHealth care led to a 80% gross reduction (from €71,784 to €14,018, US $1=€0.85) in health care utilization, 8.6% increase (from 18.6 to 20.2, P=.40) in asthma control, 25.0% increase (from 2.8 to 3.5, P=.04) in the self-management level, and 20.4% improved (from 71.2 to 76.8, P=.02) therapy adherence.

Conclusions

eHealth asthma care seems to be technically and clinically feasible, enables safe remote care, and seems to be beneficial for pediatric asthma care in terms of health outcomes and health care utilization. Follow-up research should focus on targeted effectiveness studies with the lessons learned, while also enabling individualization of eHealth for personalized health care.
Transforming Health and Resiliency Through Integration of Values-based Experiences: Implementation of an Electronic Evidence-based Whole Health Clinical Program
Authors: Haun Jolie N , Paykel Jacquelyn , Melillo Christine
Published: May 2021

Background

Complementary and integrative health (CIH) is the foundation of the Department of Veterans Affairs (VA) Whole Health System program (WH), including Transforming Health and Resiliency through Integration of Values-based Experiences (THRIVE). The global COVID-19 pandemic prompted an urgent need to provide services such as THRIVE while following guidelines for social distancing.

Objective

The objective of this paper was to describe the systematic implementation of THRIVE using an electronic delivery model.

Methods

The study involved an observational clinical program implementation project using the RE-AIM framework to contextualize the implementation strategies and results, and then the implementation of an electronically delivered CIH group medical appointment program (eTHRIVE).

Results

Clinical staff transitioned to 100% electronic delivery of the THRIVE curriculum using the new eTHRIVE delivery model. The current electronic delivery model, eTHRIVE, has effectively enrolled 10-12 veterans per cohort, with 8 cohorts, totaling 87 veterans to date. eTHRIVE attrition has been 6% (5/87) since initiation.

Conclusions

The current climate of the VA WH programmatic initiative combined with the public health needs during a global pandemic prompted the move of THRIVE program into an electronic format to broaden scalability and reach.