bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative Stress: Meeting Multiple Targets in Pathogenesis of Vascular
Endothelial Dysfunction
Authors: Gupta Vardan , Garg Anchal , Tomar Ritu , Arora Mandeep Kumar 
Published: March 2022

Abstract:
The vascular endothelium is the innermost lining of blood vessels, which maintains vaso-constriction and vasodilation. Loss of vascular tone is a hallmark for cardiovascular disorders. Nu-merous factors, such as over-activation of the renin-angiotensin-aldosterone system, kinases, growth factors, etc., play a crucial role in the induction and progression of vascular abrasion. Interestingly, dysregulation of these pathways either enhances the intensity of oxidative stress, or these pathways are affected by oxidative stress. Thus, oxidative stress has been considered a key culprit in the pro-gression of vascular endothelial dysfunction. Oxidative stress induced by reactive oxygen and nitro-gen species causes abnormal gene expression, alteration in signal transduction, and the activation of pathways, leading to induction and progression of vascular injury. In addition, numerous antioxidants have been noted to possess promising therapeutic potential in preventing the development of vascular endothelial dysfunction. Therefore, we have focused on current perspectives in oxidative stress sig-nalling to evaluate common biological processes whereby oxidative stress plays a crucial role in the progression of vascular endothelial dysfunction.
Overview on Thioredoxin-Interacting Protein (TXNIP): A Potential
Target for Diabetes Intervention
Authors: Basnet Rajesh , Basnet Til Bahadur , Basnet Buddha Bahadur , Khadka Sandhya 
Published: March 2022

Background:
Diabetes mellitus (DM) is a common metabolic disorder characterized by a persistent increment of blood glucose. Type 2 DM is characterized by insulin resistance and β-cell dysfunction. Thioredoxin-interacting protein (TXNIP) is among the factors that control the produc-tion and loss of pancreatic β-cells.

Objective:
Recent studies have shown that high glucose can significantly up-regulate the expression of the TXNIP. Overexpression of TXNIP in β-cells not only induced apoptosis but also decreased the production of insulin. At the same time, TXNIP deficiency protected the apoptosis of β-cells, leading to increased insulin production. Therefore, finding small molecules that can modulate TXNIP expression and downstream signalling pathways is essential. Thus, the inhibition of TXNIP has beneficial effects on the cardiovascular system and other tissues such as the heart and the kid-ney in DM. Therefore, DM treatment must target small TXNIP activity, inhibit expression, and promote endogenous cell mass and insulin production.

Conclusion:
This review briefly describes the effect mechanism, regulatory mechanism, and crystal structure of TXNIP. In addition, we highlight how TXNIP signalling networks contribute to diabe-tes and interact with drugs that inhibit the development often and its complexes. Finally, the current status and prospects of TXNIP targeted therapy are also discussed.
Current Status of In vitro Models of the Blood-brain Barrier
Authors: Dong Xiaowei , Shah Brijesh 
Published: March 2022

Abstract:Disorders of the brain constitute the most debilitating situation globally with increased mortality rates every year, while brain physiology and cumbersome drug development processes exacerbate this. Although blood-brain barrier (BBB) and its components are important for brain protection, their complexity creates major obstacles for brain drug delivery, and the BBB is the primary cause of treatment failure, leading to disease progression. Therefore, developing an ideal platform that can predict the behavior of a drug delivery system in the brain at the early development phase is extremely crucial. In this direction, in the last two decades, numerous in vitro BBB models have been developed and investigated by researchers to understand the barrier properties and how closely the in vitro models mimic in vivo BBB. In-vitro BBB models mainly involve the culture of endothelial cells or their coculture with other perivascular cells either in two or three-dimensional platforms. In this article, we have briefly summarized the fundamentals of BBB and outlined different types of in vitro BBB models with their pros and cons. Based on the available reports, no model seems to be robust that can truly mimic the entire properties of the in vivo BBB microvasculature. However, human stem cells, coculture and threedimensional models have been found to mimic the complexity of the barrier integrity not completely but more precisely than other in vitro models. More studies aiming towards combining these models together would be needed to develop an ideal in vitro model that can overcome the existing limitations and unravel the mysterious BBB vasculature.
Modifications of Ribonucleases in Order to Enhance Cytotoxicity in Anticancer Therapy
Authors: Nassiri Mohammadreza , Gopalan Vinod , Vakili-Azghandi Masoume 
Published: March 2022

Abstract:
Ribonucleases (RNases) are a superfamily of enzymes that have been extensively studied
since the 1960s. For a long time, this group of secretory enzymes was studied as an important model
for protein chemistry such as folding, stability, and enzymatic catalysis. Since it was discovered that
RNases displayed cytotoxic activity against several types of malignant cells, recent investigation has
focused mainly on the biological functions and medical applications of engineered RNases. In this review,
we describe the structures, functions, and mechanisms of antitumor activity of RNases. They
operate at the crossroads of transcription and translation, preferentially degrading tRNA. As a result,
this inhibits protein synthesis, induces apoptosis, and causes the death of cancer cells. This effect can
be enhanced thousands of times when RNases are conjugated with monoclonal antibodies. Such combinations,
called immunoRNases, have demonstrated selective antitumor activity against cancer cells
both in vitro and in animal models. This review summarizes the current status of engineered RNases
and immunoRNases as promising novel therapeutic agents for different types of cancer. Also, we describe
our experimental results from published or previously unpublished research and compare them
with other scientific information.
HDAC Inhibition as Neuroprotection in COVID-19 Infection
Authors: Sixto-López Yudibeth , Correa-Basurto José 
Published: March 2022

Abstract:
The SARS-CoV-2 virus is responsible for COVID-19 affecting millions of humans
around the world. COVID-19 shows various clinical symptoms (fever, cough, fatigue, diarrhea,
body aches, headaches, anosmia, and hyposmia). Approximately 30% of patients with COVID-19
showed neurological symptoms, from mild to severe manifestations including headache, dizziness,
impaired consciousness, encephalopathy, anosmia, hypogeusia, and hyposmia, among others. The
neurotropism of the SARS-CoV-2 virus explains its neuroinvasion provoking neurological damage
such as acute demyelination, neuroinflammation, etc. At the molecular level, the COVID-19 patients
had higher levels of cytokines and chemokines known as cytokines storms which disrupt the
blood-brain barrier allowing the entrance of monocytes and lymphocytes, causing neuroinflammation,
neurodegeneration, and demyelination. In addition, the proinflammatory cytokines have been
observed in ischemic, hemorrhagic strokes, seizures, and encephalopathy. In this sense, early neuroprotective
management should be adopted to avoid or decrease neurological damage due to
SARS-CoV-2 infection. Several approaches can be used; one of them includes using HDAC inhibitors
(HDACi) due to their neuroprotective effects. Also, the HDACi down-regulates the proinflammatory
cytokines (IL-6 and TNF decreasing the neurotoxicity. HDACi can also avoid and
prevent the entrance of the virus into the central nervous System (CNS) and decrease the virus replication
by downregulating the virus receptors. Here we review the mechanisms that could explain
how the SARS-CoV-2 virus could reach the CNS, induce neurological damage and symptoms, and
the possibility to use HDACi as neuroprotective therapy.
Accelerating Dynamic MRI Reconstruction Using Adaptive Sequentially
Truncated Higher-Order Singular Value Decomposition
Authors: Li Yang , Shen Qiannan , Jiang Mingfeng , Zhu Lingyan , Li Yongming , Wang Pin , Li Tie-Qiang 
Published: March 2022

Background:
Dynamic magnetic resonance imaging (dMRI) plays an important role in
cardiac perfusion and functional clinical exams. However, further applications are limited by the speed
of data acquisition.

Objective:
A low-rank plus sparse decomposition approach is often introduced for reconstructing dynamic
magnetic resonance imaging (dMRI) from highly under-sampling K-space data. In this paper,
the reconstruction problem of DMR is transformed into a low-rank tensor plus sparse tensor recovery
problem.

Methods:
A sequentially truncated higher-order singular value decomposition method is proposed to
quickly approximate the low-rank tensor space structure and learn sparse components by adding a tensor
kernel norm to the low-rank tensor and a l1 norm to the sparse tensor to constrain the two parts at
the same time. The optimization problem is solved by using the iterative soft-thresholding algorithm;
therefore, under the premise of ensuring the accuracy of the data, the amount of computation can be
effectively reduced.

Results:
Compared with the state-of-the-art methods, the experimental results show that the proposed
method can achieve better performance in terms of reconstruction speed and reconstruction quality on
3D and 4D dMRI datasets.

Conclusion:
The multidimensional MRI time series is represented by the tensor tool and decomposed
into low rank tensor terms and sparse tensor terms. The low rank spatial structure is captured by the
adaptive ST-HOSVD for fast approximation and the sparse component is constrained efficiently with a
sparsity transform and l1 norm. The optimization problem is solved by an iterative soft-thresholding
algorithm. Through extensive 3D and 4D dMRI experiments, it is demonstrated that our method can
achieve superior reconstruction performance and efficiency compared with the other three state-of-theart
methods reported in the literature.
Quinoline: Synthesis to Application
Authors: Purohit Priyank , Mittal Ravi Kumar , Aggarwal Meenu , Khatana Kavita 
Published: March 2022

Abstract:
This review aims to provide a comprehensive report on the quinoline ring with respect to
its synthesis, reactivity, and therapeutic values. The reactivity of quinoline for the metal, electrophile,
and other reactive counterparts defines the shape of the quinoline pharmacophore, which is an important
part of this report; moreover, its spectroscopic characteristics have been included herein with
suitable illustration. The quinoline and its derivatives have been presented as well as the general
synthetic approaches along with the new developments in the catalytic system; the relevant information
is also summarized under the various separate activity classes. The synthesis of heterocyclic
scaffolds has been a concern for scientists, so herein we have tried to include the synthetic parameters
of quinoline with regard to the important pharmacological aspects.
Deciphering the Significance of Plasma Chemokines as Prognostic
Biomarkers in Pegylated IFN-Α-2a /Ribavirin-Treated Chronic Hepatitis
C Genotype 4 Patients
Authors: Hamed M. Haroon , Pushparaj Peter Natesan , Rehman Shafiqur , Al-Karim Saleh , Bazarah Salem , Qadri Ishtiaq 
Published: March 2022

Background:
Hepatitis C viral (HCV) infection is a major clinical burden globally. Pegylated
IFN-α-2a (PEG-IFN-α-2a) with ribavirin (RIB) therapy induces an array of cellular antiviral responses,
including dsRNA kinases (PKR), chemokines, and cytokines to tackle the HCV infection.
However, many HCV patients develop resistance to PEG-IFN/RIB therapy rendering the therapy
ineffective.

Objectives:
Here, we assess the significance of chemokines in response to PEG-IFN-α-2a with ribavirin
(PEG-IFN/RIB) therapy.

Methods:
Twenty patients with HCV infection and ten healthy controls were enrolled in this study and
patients were categorized into two groups 1), HCV-Responder (HCV-R), and 2) HCV-non-responder
(HCV-NR). We analyzed IP-10, MIG, MCP-1, EOTAXIN, RANTES, IL-8, MIP-1a, and MIP-1b by a
magnetic bead-based multiplex immunoassay approach based on Luminex X-MAP multiplex technology,
using a MAGPIX instrument (Luminex Corporation, USA).

Results:
A significant elevation of ALT and AST enzymes was observed in HCV-NR. Besides, the
PEG-IFN/RIB therapy in both MIG and MCP-1 in HCV-NR patients was significantly induced. PEGIFN/
RIB therapy significantly increased the levels of chemokines, such as IL-8, IP-10, EOTAXIN,
MIG, RANTES, and MIP-1β, in HCV-R, indicating the chemokine response to PEG-IFN/RIB therapy.

Conclusions:
Hence, MCP-1 and MIG could be the potential biomarkers in HCV-NR and might be
associated with the development of liver fibrosis, liver failure, and hepatocellular carcinoma.

Limitations:
Our study has only twenty samples of PEG-IFN/RIB treated HCV patients. This might be
the reason for the lack of association between some of the inflammatory markers evaluated and the
SVR, therefore, the association found between the chemokine levels observed in the plasma of HCV-R
and HCV-NR and EVR cannot be extrapolated to patients infected with other HCV genotypes.
Neuroprotective Substances: Are they Able to Protect the Pancreatic Beta- Cells Too?
Authors: Ostrovskaya Rita U. , Ivanov Sergei V. 
Published: March 2022

Background:Growing pieces of evidence demonstrate a close relationship between type 2 diabetes (T2D) and neurodegenerative disorders such as Alzheimer’s disease. The similarity of physiological and pathological processes occurring in pancreatic β-cells and neurons over the course of these pathologies allows raising the question of the practicability of studying neuroprotective substances for their potential antidiabetic activity.Objective:This review analyzes studies of antidiabetic and cytoprotective action on pancreatic β-cells of the neuroprotective compounds that can attenuate the oxidative stress and enhance the expression of neurotrophins: low-molecular-weight NGF mimetic compound GK-2, selective anxiolytic afobazole, antidepressants lithium chloride, and lithium carbonate on the rat streptozotocin model of T2D.Results:It was found that all the above-listed neuroprotective substances have a pronounced antidiabetic activity. The decrease in the β-cells number, the average area of the pancreatic islets, as well as the violation of their morphological structure caused by the streptozotocin was significantly weakened by the therapy with the investigated neuroprotective substances. The extent of these morphological changes clearly correlates with the antihyperglycemic effect of these compounds.Conclusion:The presented data indicate that the neuroprotective substances attenuating the damaging effect of oxidative stress and neurotrophins deficit cannot only protect neurons but also exert their cytoprotective effect towards pancreatic β-cells. These data may provide a theoretical basis for the further study of neuroprotective drugs as potential therapeutic options for T2D prevention and treatment.
Use of Patent Information to Characterize Trends in the Therapeutic Applications of Extracellular Vesicles Derived from Mesenchymal Stem Cells (MSC-EVs)
Authors: Ponce-Polo Ángela , Hidalgo Alvaro Ritoré , Martínez Arturo Argüello , Guijarro Roke Iñaki Oruezabal 
Published: March 2022

Abstract:
Extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) are
gaining interest for medical purposes. The promising therapeutic effects exhibited in both
preclinical and clinical studies have suggested that they may become an alternative for certain
applications to cell-based therapies, which are subjected to stricter regulations. The
commercial exploitation of these candidates requires a proper patent strategy from both the
industry and public research organizations. Here, we performed a global patent literature
analysis to identify key players and therapeutic applications in the field. Our results
showed an increasing rate of patent publications since 2009, with Asia (specifically China)
leading the patenting activity. The therapeutic use of MSC-EVs within patent literature covers
a wide range of diseases, in which “Dermal and Wounds,” “Neurology” and “Cardiovascular”
are the main therapeutic areas. Moreover, most of these patents include “productby-
process” claims, since the therapeutic effects of MSC-EVs could be influenced by their
manufacturing process. Our results followed scientific and clinical literature trends.
The Impact of Metabolic Risk Factors, Diabetes, Medications, and
Comorbid Illness on Transit Time at Capsule Endoscopy: A Prospective
Cohort Study
Authors: Bassan Milan S. , Cheng Robert , Choi Nak-Jin , Vivekanandarajah Suhirdan , Abey Shehan , McDonald Jenny 
Published: March 2022

Background:
Video capsule endoscopy (VCE) is a safe and effective way of investigating obscure gastrointestinal bleeding. One of the main limitations of VCE is suboptimal visualisation due to prolonged gastric transit time (GTT) or rapid small intestinal transit time (SITT). The role of metabolic risk factors, diabetes, and medications on transit times remains unclear.

Aim:
The aim of this study was to assess the impact of diabetes, obesity, medications, and metabolic syndrome on transit times at VCE.

Method:
The study performed was a single centre, observational study.

Results:
Significant predictors of decreased GTT were increasing age and use of beta blocker medication. No predictive factors for increased GTT were identified. Significant predictors of decreased SITT on univariate analysis were increased GTT, serum glucose >5mmol/L, obesity, and diabetes. On multivariate analysis, increased GTT and glucose remained significant.

Conclusions:
Beta-blocker therapy reduces GTT. Hyperglycaemia at the time of VCE reduces SITT. These allow for possible therapeutic strategies to improve the diagnostic yield at VCE.
Motivations Toward Using Digital Health and Exploring the Possibility of Using Digital Health for Mental Health in Bangladesh University Students: Cross-sectional Questionnaire Study
Authors: Sifat Munjireen S , Saperstein Sandra L , Tasnim Naima , Green Kerry M 
Published: March 2022

Background
Digital health is efficacious for the management and prevention of mental health (MH) problems. It is particularly helpful for the young adult population, who appreciate the autonomy digital health provides, and in low-income countries, where the prevalence of MH problems is high but the supply of professionals trained in MH is low.

Objective
The objectives of this study are 2-fold: to determine whether university students in Bangladesh find using digital health for MH promotion acceptable and to examine motivational factors for using digital health for MH.

Methods
This study used a cross-sectional survey to examine the likelihood that university students in Bangladesh (n=311) would use different forms of digital health platforms for MH promotion and assessed drivers of intention to use and actual use of digital health generally and digital health for MH through the lens of the Technology Acceptance Model. The results provided evidence that the university student population in Bangladesh is likely to use digital health to promote their MH.

Results
Social influence (adjusted odds ratio [aOR] 1.68, 95% CI 1.40-2.01; P<.001), ease of use (aOR 1.85, 95% CI 1.35-2.53; P<.001), and perceived usefulness (aOR 4.12, 95% CI 1.79-9.51; P=.001) of digital health were found to be significant drivers of the intention to use general digital health, and having an intention to use digital health (aOR 2.10, 95% CI 1.17-3.78; P=.01) had the greatest influence on actual use of digital health. Social influence (aOR 1.71, 95% CI 1.43-2.04; P<.001), perceived usefulness (aOR 8.92, 95% CI 4.18-19.04; P<.001), and use of general digital health (aOR 2.16, 95% CI 1.18-3.97; P=.01) were associated with higher intention to use digital health for MH. The use of general digital health (aOR 4.19, 95% CI 2.37-7.41; P<.001) was associated with the actual use of digital health for MH, as were greater non–stigma-related barriers to using traditional clinical MH services (aOR 2.05, 95% CI 1.10-3.80; P=.02).

Conclusions
Overall, we see that the use of digital health for MH is acceptable in this population and can be helpful for students who perceive barriers to receiving traditional care. We also gain insight into how to promote the intention to use digital health, which in turn promotes the actual use of digital health.
Assessment of Preparedness for the COVID-19 Pandemic in Schools in Al-Rusafa District, Baghdad, Iraq, 2021
Authors: Kamoona Marha , Kumar Deepak , Yoos Alison , Abdul Latif Bashar , AL-Temeemy Ayad , Al Ghanimy Safaa 
Published: March 2022

Background
Following the international spread of the novel coronavirus (SARS-CoV-2) or COVID-19 pandemic, the Iraqi government took several steps to prevent community transmission, including the indefinite closure of schools as a measure to safeguard schoolchildren from COVID-19. The key rationale behind these decisions was the insufficient preparedness level within schools to prevent infection and the lack of appropriate vaccines for children.

Objective
Researchers assessed COVID-19 preparedness levels in schools in Al-Rusafa district, Baghdad, to prepare schools for reopening.

Methods
An observational study design was conducted to assess the schools. Stratified sampling was performed to make the sample more representative; we stratified the schools into 3 categories based on sex, level (primary or secondary), and administration (public or private). The study population comprised all students and teachers in the selected sample. The assessment was carried out retrospectively for 3 months, from May 31, 2021. Data were collected through face-to-face interviews and analyzed using Microsoft Excel. Tables and pie charts were used to display the results.

Results
The assessment was completed in 40 schools—20 (50%) primary schools, 10 (25%) high schools, 6 (15%) intermediate schools, and 4 (10%) secondary schools. Overall, the assessment covered 1162 teachers and 16,776 students. The highest infection rate, according to school category, was among primary school staff (6.14%). Moreover, 92% (n=39) of the schools did not have a contact number for a nearby ambulance, and early detection system was weak in 60% (n=24) of the schools, which reflected low levels of school participation in preparing against the COVID-19 pandemic. Referral system for any sick person to an appropriate health facility was not present or was disabled in 63% (n=25) of the schools.

Conclusions
The assessment concluded that none of the schools had a robust screening system to record students infected with COVID-19. The study discusses several actions and requirements that should be reviewed and addressed to prevent the spread of COVID-19 in the schools and the community.
Salve-te, Strela do mar: himnodia y mariología en las Cantigas de Santa María de Alfonso X el Sabio
Authors: Disalvo Santiago 
Published: March 2022

Además de los miracula marianos de tradición clerical latina, otro tipo de literatura está entretejido en los versos de las Cantigas de Santa María, de Alfonso X el Sabio. Si bien son producto de una novedosa creatividad poética en romance, estos textos dejan oír claramente las voces de un universo doctrinal teológico y mariológico y, especialmente, los ecos de la himnodia litúrgica. Como demostración de este fenómeno, se estudian la cantiga de loor 180 y la cantiga narrativa 288.