bluuebunny/crossref_metadata_2025_split 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

Abstract:
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.
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

Abstract::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.
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.
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

BackgroundEarly 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.ObjectiveThe 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.MethodsWe 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.ResultsOf 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.ConclusionseHealth 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.