bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Formulation Optimization of Methotrexate-loaded Human Serum Albumin Nanoparticles Modified by Mannose
Authors: Chen Zhenyu , Luo Zhongling , Lyu Jiayao , Wang Jianxin , Liu Zhongbing , Wei Jun , Lin Yan , Zhong Zhirong
Published: January 2021

Background:

Methotrexate (MTX) is the representative drug among the disease-
modifying anti-rheumatic drugs. However, the conventional treatment with MTX
showed many limitations and side effects.

Objective:

To strengthen the targeting ability and circulation time of MTX in the treatment
of rheumatoid arthritis, the present study focused on developing a novel drug delivery
system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified
by mannose, which are referred to as MTX-M-NPs.

Methods:

Firstly, mannose-derived carboxylic acid was synthesized and further modified
on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles
was optimized by the method of central composite design (CCD), with the drug lipid ratio,
oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The
average particle size and encapsulation efficiency were the response variables. The response
of different formulations was calculated, and the response surface diagram, contour
diagram, and mathematical equation were used to relate the dependent and independent
variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neutrophils
was studied through confocal laser detection. Further, MTX-M-NPs were subjected
to assessment of the pharmacokinetics profile after intravenous injection with
Sprague-Dawley rats.

Results:

This targeting drug delivery system was successfully developed. Results from
Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can
verify the successful preparation of this drug delivery system. Based on the optimized formula,
MTX-M-NPs were prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation
rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake
than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could prolong
the in vivo circulation time of MTX.

Conclusion:

This targeting drug delivery system laid a promising foundation for the treatment
of RA.
Murburn Precepts for Cytochrome P450 Mediated Drug/Xenobiotic Metabolism and Homeostasis
Authors: Parashar Abhinav , Manoj Kelath M.
Published: January 2021

Aims:

We aim to demonstrate why deeming diffusible reactive oxygen species (DROS) as toxic
wastes do not afford a comprehensive understanding of cytochrome P450 mediated microsomal xenobiotic
metabolism (mXM).

Background:

Current pharmacokinetic investigations consider reactive oxygen species formed in microsomal
reactions as toxic waste products, whereas our works (Manoj et al., 2016) showed that DROS are the reaction
mainstay in cytochrome P450 mediated metabolism and that they play significant roles in explaining several unexplained
physiologies.

Objective:

Herein, we strive to detail the thermodynamic and kinetic foundations of murburn precepts of cytochrome
P450 mediated drug metabolism.

Methodology:

Primarily, in silico approaches (using pdb crystal structure files), murburn reaction chemistry logic
and thermodynamic calculations to elucidate the new model of CYP-mediated drug metabolism. The theoretical
foundations are used to explain experimental observations.

Results:

We visually elucidate how murburn model better explains- (i) promiscuity of the unique P450-reductase;
(ii) prolific activity and inhibitions of CYP3A4; (iii) structure-function correlations of important key
CYP2 family isozymes- 2C9, 2D6 and 2E1; and (iv) mutation studies and mechanism-based inactivation of
CYPs. Several other miscellaneous aspects of CYP reaction chemistry are also addressed.

Conclusion:

In the light of our findings that DROS are crucial for explaining reaction outcomes in mXM, approaches
for understanding drug-drug interactions and methodologies for lead drug candidates' optimizations
should be revisited.
Antibiotics as Inhibitor of Glutathione S-transferase: Biological Evaluation and Molecular Structure Studies
Authors: Ayna Adnan , Khosnaw Luqman , Temel Yusuf , Ciftci Mehmet
Published: January 2021

Background:

The glutathione S-transferases (GSTs) are family of enzymes that are notable for their
role in phase II detoxification reactions. Antibiotics have been reported to have several adverse effects on the
activity of the enzymes in mammals.

Aim:

The aim of this study was the structural and biochemical characterization of rat erythrocyte GST and understanding
the effects of gentamicin, clindamycin, cefazolin, ampicillin and scopolamine butylbromide on the
activity of human erythrocyte GST using rat as a model.

Methods:

The enzyme was purified by GSH-agarose affinity chromatography. In vitro GST enzyme activity
was measured at 25°C using CDNB as a model substrate. IC50 of drugs was measured by activity % vs compound
concentration graphs. Lineweaver Burk graphs were drawn to determine the inhibition type and Ki constants
for the drugs. The structure of the enzyme was predicted via Protein Homology/analogy Recognition Engine.

Results:

In this study, GST was purified from rat erythrocyte with a specific activity of 6.3 EU/mg protein, 44
% yield and 115 fold. Gentamicin and clindamycin inhibited the enzymatic activity with IC50 of 1.69 and 6.9
mM and Ki of 1.70 and 2.36 mM, respectively. Ampicillin and scopolamine butylbromide were activators of
the enzyme, while the activity of the enzyme was insensitive to cefazolin. The enzyme was further characterized
by homology modeling and sequence alignment revealing similarities with human GST.

Conclusion:

Collectively, it could be concluded that gentamicin and clindamycin are the inhibitors of erythrocyte
GST.
Popularizing Recombinant Baculovirus-derived OneBac System for Laboratory Production of all Recombinant Adeno-associated Virus Vector Serotypes
Authors: Wu Yang , Han Zengpeng , Duan Mingzhu , Jiang Liangyu , Tian Tiantian , Jin Dingyu , Wang Qitian , Xu Fuqiang
Published: January 2021

Background:

On the basis of our previously established single recombinant baculovirus expression vector
(BEV)-derived OneBac system, we have optimized the process and expanded the rAAV production
range to the full range of serotypes rAAV1-13.

Objective:

Recombinant adeno-associated virus (rAAV) has been widely used as an efficient
transgenic vector in biomedical research, as well as gene therapy. Serotype-associated transduction
efficiency, tissue- or cell-type tropism and immunological profile are major considerations in
the various applications of rAAVs. There are increasing needs for different serotypes of rAAV, either
naturally isolated or artificially engineered. However, affordable and scalable production of a desired
serotype of rAAV remains very difficult, especially for researchers lacking relevant experience.

Methods:

Firstly, the AAV Cap gene was optimized to translate by ribosome leaky scanning and the
gene of interest (GOI) was cloned into the pFD/Cap-(ITR-GOI)-Rep2 shuttle plasmid. Following the
classical Bac-to-Bac method, sufficient BEV stock containing all rAAV packaging elements can be
quickly obtained. Finally, we can repeatedly scale up the production of rAAVs in one week by using a
single BEV to infect suspension-cultured Sf9 cells. The rAAV1-13 shows relatively high yields ranging
from 5×104 to 4×105 VG/cell. More than 1×1015 VG purified rAAVs can be easily obtained from 5
L suspension-cultured Sf9 cells.

Results:

As expected, rAAV serotypes 1-13 show different potencies for in vitro transduction and
cell-type tropisms.

Conclusion:

In summary, the single BEV-derived OneBac system should prove popular for laboratory
scaling-up production of any serotype of rAAV.
An Updated Review on Betacoronavirus Viral Entry Inhibitors: Learning from Past Discoveries to Advance COVID-19 Drug Discovery
Authors: Sabbah Dima A. , Hajjo Rima , Bardaweel Sanaa K. , Zhong Haizhen A.
Published: January 2021

Even after one year of its first outbreak reported in China, the coronavirus disease 2019
(COVID-19) pandemic is still sweeping the World, causing serious infections and claiming more
fatalities. COVID-19 is caused by the novel coronavirus SARS-CoV-2, which belongs to the genus
Betacoronavirus (β-CoVs), which is of greatest clinical importance since it contains many other viruses
that cause respiratory disease in humans, including OC43, HKU1, SARS-CoV, and MERS. The
spike (S) glycoprotein of β-CoVs is a key virulence factor in determining disease pathogenesis and
host tropism, and it also mediates virus binding to the host’s receptors to allow viral entry into host
cells, i.e., the first step in virus lifecycle. Viral entry inhibitors are considered promising putative
drugs for COVID-19. Herein, we mined the biomedical literature for viral entry inhibitors of other
coronaviruses, with special emphasis on β-CoVs entry inhibitors. We also outlined the structural features
of SARS-CoV-2 S protein and how it differs from other β-CoVs to better understand the structural
determinants of S protein binding to its human receptor (ACE2). This review highlighted several
promising viral entry inhibitors as potential treatments for COVID-19.
A Multi-target Drug Designing for BTK, MMP9, Proteasome and TAK1 for the Clinical Treatment of Mantle Cell Lymphoma
Authors: Qureshi Shahrukh , Khandelwal Ravina , Madhavi Maddala , Khurana Naveesha , Gupta Neha , Choudhary Saurav K. , Suresh Revathy A. , Hazarika Lima , Srija Chillamcherla D. , Sharma Khushboo , Hindala Mali R. , Hussain Tajamul , Nayarisseri Anuraj , Singh Sanjeev K.
Published: January 2021

Background:

Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma characterized
by the mutation and overexpression of the cyclin D1 protein by the reciprocal chromosomal
translocation t(11;14)(q13:q32).

Aim:

The present study aims to identify potential inhibition of MMP9, Proteasome, BTK, and TAK1
and determine the most suitable and effective protein target for the MCL.

Methodology:

Nine known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1
were screened. SB-3CT (PubChem ID: 9883002), oprozomib (PubChem ID: 25067547), zanubrutinib
(PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs
with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened
compounds were obtained after the similarity search with compound (PubChem ID:102173753),
PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound
SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual
screened compounds.

Results :

MMP9 inhibitors show commendable affinity and good interaction profile of compound holding
PubChem ID:102173753 over the most effective established inhibitor SB-3CT. The pharmacophore
study of the best virtual screened compound reveals its high efficacy based on various interactions.
The virtual screened compound's better affinity with the target MMP9 protein was deduced
using toxicity and integration profile studies.

Conclusion:

Based on the ADMET profile, the compound (PubChem ID: 102173753) could be a
potent drug for MCL treatment. Similar to the established SB-3CT, the compound was non-toxic with
LD50 values for both the compounds lying in the same range.
Multi-target Drug Discovery via PTML Modeling: Applications to the Design of Virtual Dual Inhibitors of CDK4 and HER2
Authors: Kleandrova Valeria V. , Scotti Marcus T. , Scotti Luciana , Speck-Planche Alejandro
Published: January 2021

Background:

Cyclin-dependent kinase 4 (CDK4) and the human epidermal growth factor
receptor 2 (HER2) are two of the most promising targets in oncology research. Thus, a series of computational
approaches have been applied to the search for more potent inhibitors of these cancerrelated
proteins. However, current approaches have focused on chemical analogs while predicting the
inhibitory activity against only one of these targets, but never against both.

Aims:

We report the first perturbation model combined with machine learning (PTML) to enable the
design and prediction of dual inhibitors of CDK4 and HER2.

Methods:

Inhibition data for CDK4 and HER2 were extracted from ChEMBL. The PTML model
relied on artificial neural networks to allow the classification/prediction of molecules as active or
inactive against CDK4 and/or HER2.

Results:

The PTML model displayed sensitivity and specificity higher than 80% in the training set.
The same statistical metrics had values above 75% in the test set. We extracted several molecular
fragments and estimated their quantitative contributions to the inhibitory activity against CDK4 and
HER2. Guided by the physicochemical and structural interpretations of the molecular descriptors in
the PTML model, we designed six molecules by assembling several fragments with positive contributions.
Three of these molecules were predicted as potent dual inhibitors of CDK4 and HER2, while
the other three were predicted as inhibitors of at least one of these proteins. All the molecules complied
with Lipinski’s rule of five and its variants.

Conclusion:

The present work represents an encouraging alternative for future anticancer chemotherapies.
5-Methoxy-1-methyl-2-{[4-(2-hydroxyphenyl)piperazin-1-yl]methyl}-1Hindole (KAD22) with Antioxidant Activity
Authors: Kaczor Agnieszka A. , Wojtunik-Kulesza Karolina , Wróbel Tomasz M. , Matosiuk Dariusz , Pitucha Monika
Published: January 2021

:

Compound KAD22 (5-methoxy-1-methyl-2-[4-(2-hydroxyphenyl)piperazin-1-yl]methyl-1H-indole) was designed as a potential dopamine D2 receptor agonist with antioxidant activity for possible treatment of Parkinson’s disease.
The compound was obtained from 5-methoxy-1-methyl-1H-indole-2-carbaldehyde and 2-(piperazin-1-yl)phenol. KAD22
showed no affinity to dopamine D2 receptor but it is a potent antioxidant. Experimental and computational structural studies
(conformational analysis, HOMO and LUMO orbitals, electrostatic potential map, non-covalent interaction plot, spectral
properties, ligand-receptor interactions) of KAD22 were performed to address its biological activity.
The Impact of Type 2 Diabetes on Women’s Health and Well-being During Their Reproductive Years: A Mixed-methods Systematic Review
Authors: Celik Aycan , Forde Rita , Racaru Simona , Forbes Angus , Sturt Jackie
Published: January 2021

Background:

The incidence of type 2 diabetes (T2DM) among younger women now accounts for 40% of females with T2DM. Women of reproductive age with T2DM have additional health considerations and their needs may differ from older populations.

Objectives:

To identify the health issues encountered by women aged 16-45 years living with T2DM; to determine the modifiable risk factors associated with living with diabetes; to specify ideas for interventions to meet age and genderspecific diabetes-related healthcare needs.

Methods:

A systematic search was performed in the following databases; MEDLINE, PsycINFO, EMBASE, CINAHL, Web of Science, and Maternity and Infant Care. Databases were searched without time and study design limits. The Mixed Methods Appraisal Tool was used to assess the methodological quality of included studies. Data were narratively synthesised due to the mixed methods evidence included.

Results:

A total of 32 papers were included in the review from which six domains were identified from the synthesis: (1) diabetes related modifiable risk factors: blood glucose, cardiovascular risk, neuropathy/nephropathy/retinopathy, diabetes self-management barriers (2) reproductive health: diabetes care before pregnancy, pre-pregnancy care barriers and expectations of women, contraceptive use (3) psychosocial wellbeing: depression symptoms and diabetes distress, perception of T2DM, emotional concerns about pregnancy (4) sexual function; (5) menopause; (6) sociocultural factors: social support, cultural norms.

Conclusion:

This review highlighted specific health issues affecting women of reproductive age with T2DM and which represent an important focus for health services research and health care delivery. Future research needs to address identified health domains to improve women’s health and well-being living with T2DM. Prospero Registration number: CRD42019146535.
Simultaneous Detection of Phillyrin and its Three Metabolites in Rat Bile, Excrement and Urine via HPLC-ESI-MS/MS Quantitative Method
Authors: Zhang Lantong , Liu Xizhe , Li Feigao
Published: January 2021

Introduction:

Phillyrin, the main pharmacological component of Forsythia suspensa,
exhibits a wide variability of therapeutic activities, such as anti-oxidative stress, free radicalclearing,
antibacterial activity, hepatic protection, restoration of endothelial glycocalyx damage,
prevention of bone loss, attenuation of inflammatory responses, and so on. Previous research has
found that phillyrin is not easily absorbed by the body and is rarely excreted into bile, excrement
and urine, suggesting that phillyrin circulates primarily in the form of metabolites.

Materials and Methods:

In the present study, HPLC-ESI-MS/MS method was used for the simultaneous
detection of phillyrin and its three metabolites in rat bile, excrement and urine samples.
Liquid-liquid extraction with ethyl acetate was carried out for the pretreatment of bile and urine
samples, while excrement samples were subjected to ultrasonic pretreatment with acetone. Chromatographic
separation was performed on a C18 column with gradient elution. A tandem mass
system coupled with a TurboIonSpray interface operating in simultaneous positive and negative
ion multiple reaction monitoring modes was employed for the simultaneous detection of
the analytes.

Results:

The proposed method demonstrated excellent accuracy and repeatability.

Conclusion:

This method was successfully applied for the pharmacokinetic evaluation of phillyrin
and its three metabolites simultaneously.
Spectrophotometric Determination of Vitamin B1 in Dosage forms Using Drugs Compounds as Reagents by Normal and Reverse Flow Injection Methods
Authors: Amir Rana , Hadi Hind
Published: January 2021

Background:

Thiamine hydrochloride (THY), also known as vitamin B1, is a water
soluble vitamin usually found in food, and considered as a dietary supplement and treatment in
case of vitamin deficiency for example in malabsorption and chronic diarrhea.

Objective:

Rapid, green, and sensitive methods for the assay of vitamin B1 (thiamine hydrochloride,
THY) in pharmaceutical forms, using normal and reverse flow injection manifolds and sulfonamide
drugs as green and safe reagents were reported. Sulfamethoxazole and sulfadimidine
drugs were used rather than toxic and expensive reagents.

Methods:

nFIA and rFIA manifolds were used for automated the reaction of THY with diazotized
sulfamethoxazole (DSMZ) and diazotized sulfadimidine (DSDM) in an alkaline medium, respectively.
The absorbance of the resultant red-orange azo dyes was monitored spectrophotometrically
at λmax494 and 496nm for both methods, respectively.

Results:

The linearity of the suggested methods was in the ranges 2–80 µg/mL (LOD 0.69
µg/mL, % RSD 0.32, n=6) for nFIA method and 0.5-70 µg/mL (LOD 0.29 µg/mL, %RSD 0.85,
n=6) for rFIA. Sampling frequency was 84 and 51 injections per hour for nFIA and rFIA
methods respectively. Chemical and physical variables for both methods were studied carefully.

Conclusion:

Both flow injection modes were effectively applied in assay of THY in its
pharmaceutical forms. The results were compared with those of standard pharmacopeia method
and the statistical analysis indicated insignificant differences in accuracy and precision between
the methods.
The Uses of Dimedone for the Synthesis of Thiophene, Thiazole and Annulated Derivatives with Antitumor, Pim-1 Kinase Inhibitions, PAINS Evaluations and Molecular Docking
Authors: Wardakhan Wagnat W. , Elmetwally Amira M. , Mohamed Abeer A. , Mohareb Rafat M.
Published: January 2021

Background:

Dimedone is considered as one of the most important classes of compounds belonging
to cyclohexan-1,3-dione. Such groups of compounds were considered as precursors for many pharmaceutically
active heterocyclic compounds.

Objective:

The target molecules in this work were synthesized from arylhydrazones of dimedone with different
substituents enhancing the study of their structure-activity relationship.

Methods:

Arylhydrazones of dimedones were subjected to a series of heterocyclization reactions affording annulated
compounds. The anti-proliferative activities of the synthesized molecules were evaluated against six
cancer cell lines. In addition, inhibitions toward tyrosine kinases, Pim-1 kinases and PAINS of the most active
compounds were also studied. c-Met enzymatic inhibitions and molecular docking studies were carried out for
three compounds.

Results:

Anti-cancer evaluations together with tyrosine and Pim-1 kinases of most of the synthesized compounds
were carried out through this work. The study revealed that changing of substituents had a strong impact
on the activity of the molecule.

Conclusion:

Many of the synthesized compounds exhibited high inhibitions towards the six cancer cell lines.
This will encourage further work through the synthesis of target molecules with the same ring systems. The
three compounds 7b, 8c and 12b that revealed excellent inhibitions were tested against c-Met kinase and their
molecular modelling was expressed.
ATP-sensitive Potassium Channel Subunits in Neuroinflammation: Novel
Drug Targets in Neurodegenerative Disorders
Authors: Maqoud Fatima , Scala Rosa , Hoxha Malvina , Zappacosta Bruno , Tricarico Domenico
Published: January 2021

:

Arachidonic acids and its metabolites modulate plenty of ligand-gated, voltage-dependent
ion channels, and metabolically regulated potassium channels including ATP-sensitive potassium
channels (KATP). KATP channels are hetero-multimeric complexes of sulfonylureas receptors
(SUR1, SUR2A or SUR2B) and the pore-forming subunits (Kir6.1 and Kir6.2) likewise expressed
in the pre-post synapsis of neurons and inflammatory cells, thereby affecting their proliferation and
activity. KATP channels are involved in amyloid-β (Aβ)-induced pathology, therefore emerging as
therapeutic targets against Alzheimer’s and related diseases. The modulation of these channels can
represent an innovative strategy for the treatment of neurodegenerative disorders; nevertheless, the
currently available drugs are not selective for brain KATP channels and show contrasting effects.
This phenomenon can be a consequence of the multiple physiological roles of the different varieties
of KATP channels. Openings of cardiac and muscular KATP channel subunits, are protective
against caspase-dependent atrophy in these tissues and some neurodegenerative disorders, whereas
in some neuroinflammatory diseases, benefits can be obtained through the inhibition of neuronal
KATP channel subunits. For example, glibenclamide exerts an anti-inflammatory effect in respiratory,
digestive, urological, and central nervous system (CNS) diseases, as well as in ischemia-reperfusion
injury associated with abnormal SUR1-Trpm4/TNF-α or SUR1-Trpm4/ Nos2/ROS signaling.
Despite this strategy being promising, glibenclamide may have limited clinical efficacy due to
its unselective blocking action of SUR2A/B subunits also expressed in cardiovascular apparatus
with pro-arrhythmic effects and SUR1 expressed in pancreatic beta cells with hypoglycemic risk.
Alternatively, neuronal selective dual modulators showing agonist/antagonist actions on KATP
channels can be an option.
An Investigation of Multilingual TDNN-BLSTM Acoustic Modeling for
Hindi Speech Recognition
Authors: Kumar Ankit , Aggarwal Rajesh Kumar
Published: January 2021

Background:

In India, thousands of languages or dialects are in use. Most Indian dialects are low asset dialects.
A well-performing Automatic Speech Recognition (ASR) system for Indian languages is unavailable due to a lack of
resources. Hindi is one of them as large vocabulary Hindi speech datasets are not freely available. We have only a few hours
of transcribed Hindi speech dataset. There is a lot of time and money involved in creating a well-transcribed speech dataset.
Thus, developing a real-time ASR system with a few hours of the training dataset is the most challenging task. The different
techniques like data augmentation, semi-supervised training, multilingual architecture, and transfer learning, have been
reported in the past to tackle the fewer speech data issues. In this paper, we examine the effect of multilingual acoustic
modeling in ASR systems for the Hindi language.

Objective:

This article’s objective is to develop a high accuracy Hindi ASR system with a reasonable computational load
and high accuracy using a few hours of training data.

Method:

To achieve this goal we used Multilingual training with Time Delay Neural Network- Bidirectional Long Short
Term Memory (TDNN-BLSTM) acoustic modeling. Multilingual acoustic modeling has significantly improved the ASR
system's performance for low and limited resource languages. The common practice is to train the acoustic model by
merging data from similar languages. In this work, we use three Indian languages, namely Hindi, Marathi, and Bengali.
Hindi with 2.5 hours of training data and Marathi with 5.5 hours of training data and Bengali with 28.5 hours of transcribed
data, was used in this work to train the proposed model.

Results:

The Kaldi toolkit was used to perform all the experiments. The paper is investigated over three main points. First,
we present the monolingual ASR system using various Neural Network (NN) based acoustic models. Second, we show that
Recurrent Neural Network (RNN) language modeling helps to improve the ASR performance further. Finally, we show that
a multilingual ASR system significantly reduces the Word Error Rate (WER) (absolute 2% WER reduction for Hindi and
3% for the Marathi language). In all the three languages, the proposed TDNN-BLSTM-A multilingual acoustic models help
to get the lowest WER.

Conclusion:

The multilingual hybrid TDNN-BLSTM-A architecture shows a 13.67% relative improvement over the
monolingual Hindi ASR system. The best WER of 8.65% was recorded for Hindi ASR. For Marathi and Bengali, the
proposed TDNN-BLSTM-A acoustic model reports the best WER of 30.40% and 10.85%.
History and Global Status of the New Coronavirus Covid-2019 and Aspects of Previous Infections of SARS-CoV and MERS-CoV: A Systematic Review
Authors: da Costa Amanda Pinato Alves , da Rocha Vinicius Lisboa , Ramos Rogério Rodrigo , Neto José Martins Pinto , da Silva Wagner Rafael , Pereira Luis Lenin Vicente , Ramos Kelys , Marques Tais Cristina Nascimento , Filho Idiberto José Zotarelli , Lozano André Wilian
Published: January 2021

Introduction:

Coronaviruses (CoV) is a diverse group of viruses that has been described
in the literature since 1960, SARS, MERS, and the most recent SARS-CoV-2. This new virus is
causing a worldwide pandemic outbreak in the first half of 2020, thousands of deaths, and a significant
economic crisis.

Objective:

Due to this new context, the present study aimed to conduct a systematic study review
of the new Coronavirus's global status (COVID-2019) and its aspects compared to the previous
SARS-CoV infections MERS-CoV.

Methods:

The study was conducted from January to September 2020, 89 clinical cases were submitted
to further analysis, and 77 studies were selected for systematic review under the PRISMA
guidelines.

Major findings and Conclusion:

In some countries, the SARS-CoV-2 pandemic appears to be out of control. In case of
suspicion, tests are essential to identify the early stages of infection. If necessary, patients need to
go into quarantine, and other public health measures should be taken following the World Health
Organization guidelines. Advanced support is needed to identify and isolate infected patients, especially
vaccines and medicines that help control the virus and the epidemiological situation in each
country. These measures are expected to reduce the rate of new cases of SARS-CoV-2.
A clivagem Estado-Igreja na Monarquia Liberal (1820-1910)
Authors: Leal Manuel M. Cardoso
Published: January 2021

After the serious conflict that opposed the Catholic Church to the liberal State in the 1820s and 1830s, in Portugal, the Church was deprived of its economic base and subject to the state control in the appointment of bishops and parish priests. But unlike other European countries, this cleavage did not, as has been tried, give rise to a relevant “catholic” party. To this end, the State (with the consent of the main parties) avoided any break in the country's Catholic identity, keeping the Catholic religion as an official religion and integrating the hierarchy and other clergy into political functions. At the end of the regime, republicanism grew inspired by a secular anti-clericalism
Photophysical characterization of 3-acyl-4-quinolones
Authors: Andrade Karine N. de , Costa Amanda R. P. , Teixeira Rodolfo I. , Moreira Micaeli L. da S. , Carneiro José Walkimar M. , Garden Nanci C. L. , Boechat Fernanda da C. S. , Souza Maria Cecília B. V. de , Batalha Pedro N. , Fiorot Rodolfo G.
Published: January 2021

4-quinolones derivatives can present fluorescent properties, depending on their substituents and on the chemical environment (e.g., acidic medium), allowing their application as ion sensors. We theoretically evaluated the photophysical properties of previously synthesized 3-acyl-4-quinolones to verify how different substituents (R1=H, NH2 and R2 = OEt, OH, NHPh) affect their absorption profiles and the emission profile of a reference compound, PB3. All DFT and TD-DFT calculations were performed at B3LYP-D3/6-311++G(d,p) level and continuum polarization model for simulated acetonitrile as solvent. For PB2 (R1 = H, R2 = OEt), we observed hypsochromic shift compared to PB3 due to the increase of the gap between HOMO/LUMO (absence of electron-donating group), in accordance with experimental data. For R1=NH2 and R2=OH, NHPh (PB6 and PB10, respectively), the gap between HOMO/LUMO increases, resulting in a soft bathochromic shift for the simulated absorption spectra. In addition, we evaluated the effect of acid addition on the absorption and emission profile of PB3 and the results were compared with experimental data. Our thermodynamic results suggest that protonation occurs on the endocyclic carbonyl of the quinolone moiety, probably due to an increased aromatic character, as suggested by our NICS calculations. Finally, we associate the increase of the fluorescence in the acidic medium to the establishment of an intramolecular hydrogen bond and, thus, increased rigidity.
Infrared intensities of imaginary frequencies: Gas-Phase SN2 Transition States
Authors: Duarte Leonardo José , Bruns Roy Edward
Published: January 2021

The gas phase SN2 reaction transition state structures for nine [XCZ_3 Y]^- systems, where X,Y=H,F,Cl and Z = H,F were optimized and their normal modes of vibrations were determined at the QCISD/aug-cc-pVTZ level of theory. Using Quantum Theory of Atoms in Molecules (QTAIM), the atomic charges and atomic dipoles were obtained and used to calculate the Charge – Charge Transfer – Dipolar Polarization (CCTDP) contributions to the imaginary normal mode intensity of transition states. The results show that the imaginary bands are strong, ranging from 1217 to 16086 〖km∙mol〗^(-1), much higher than occurs for most bands found in molecules. For all systems, the CT contribution is responsible for 80% of the total intensity on average. The Charge contributions are slightly higher for transitions states with Z = F. Dipolar polarization contributions are always small. The contributions from the Z atoms are negligible, thus only atoms aligned with the reaction axis X-C-Y contribute to total intensity. All charge transfers were evaluated taking the carbon atom as reference, implying that almost all infrared intensity is determined by electron transfers from the nucleophile and carbon and from carbon to the leaving group. The mechanism of charge transfer revealed by the CCTDP model is consistent with the reaction mechanism itself, which points towards the connection between the imaginary normal mode and the reaction coordinate.
The impact of Saudi lockdown to counter COVID-19
Authors:   Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia, Alyahya Khaleel I.
Published: January 2021

The study aimed to assess the impact of awareness of citizens and residents in Saudi Arabia toward the home isolation and social distancing during lockdown that might decrease the outbreak of COVID-19, to measure the importance of social behavior to maintain the constant decline of COVID-19 cases and to determine if there is a difference in the level of awareness and behavior between citizens and residents in Saudi Arabia toward the governmental measures during the pandemic. We have adopted a cross-sectional survey design to investigate the impact of Saudi lockdown on blockade COVID-19 by using an anonymous online questionnaire. The targeted population of the study was Saudi citizens and non-Saudi residents of different ages. The collected data were entered into Microsoft Excel (version 2011) and analyzed by using the Statistical Package for Social Sciences (SPSS), version 23. The Chi-square test with 95% confidence intervals (CI) was used to examine significant associations between the socio-demographic characteristic of participants, their awareness, and their behavior towards the COVOD-19 pandemic. AP value of <0.05 was considered statistically significant. The total number of the current study participants was 1168. The majority (70.50%) were married males with children (73.50%). Three-quarters of the participants were equally distributed between the age groups of 30-39, 40-49, and 50-59 years old. Almost all (90.90%) of the participants have received higher education, 73.60% living in the central region, and in large and crowded cities (75.30%). More than half (58.50%) of the Saudi respondents know about the coronavirus from media sources, while for the non-Saudis, 54.50% are well informed regarding the virus. The results of the current study revealed that the majority of the population in the country believe in home isolation and social distancing for the COVID-19 blockade. Additionally, they also consider non-compliance to these measures as one the main factor for the disease outbreak. Most of the participants were committed to home isolation, social distancing, and personal protective measures including wearing masks, gloves, and avoiding face contact.
Which Physiological Swallowing Parameters Change with Healthy Aging?
Authors: Mancopes Renata , Gandhi Pooja , Smaoui Sana , Steele Catriona M. ,   Swallowing Rehabilitation Research Laboratory, KITE Research Institute – Toronto Rehabilitation Institute – University Health Network , 550 University Avenue, 12th floor, Toronto, Ontario, Canada, M5G 2A2,   Rehabilitation Sciences Institute, Temerty Faculty of Medicine, University of Toronto, 500 University Avenue, Suite 160, Toronto, ON, Canada, M5G 1V7
Published: January 2021

Research suggests there are age-related changes in swallowing that do not constitute impairment (“presbyphagia”). The goal of this study was to explore the influence of age on quantitative measures of healthy swallowing by controlling for the effects of sex and sip volume in order to determine the specific characteristics of presbyphagia. Videofluoroscopy recordings of thin liquid swallows from 76 healthy adults (38 male), aged 21-82 were analysed. Blinded duplicate ratings of swallowing safety, efficiency, kinematics, and timing were made using the ASPEKT method. Hierarchical regression models were used to determine the effects of age, sex, and sip-volume on swallowing. There were no age-related changes in sip volume, number of swallows per bolus, frequency or severity of penetration-aspiration, duration of the hyoid-burst (HYB)-to-upper-esophageal-sphincter (UES) opening interval, time-to-laryngeal-vestibule-closure (LVC), peak hyoid position, hyoid speed, or pharyngeal residue. Significant changes seen with increasing age included: longer swallow reaction time, UES opening duration and LVC duration; larger pharyngeal area at rest and maximum constriction; and wider UES diameter. Male participants had larger sip volume and pharyngeal area at rest. Larger sip volumes were associated with multiple swallows per bolus and shorter hyoid-burst-to-UES opening intervals. These results help to define presbyphagic changes in swallowing that can be expected in healthy older adults up to 80 years of age, and distinguish them from changes that represent impairment. Certain parameters showed changes that were opposite in direction to changes that are usually considered to reflect impairment: longer UES opening, longer LVC duration and wider UES opening. These changes may reflect possible compensations for slower bolus transit. Further research is needed to determine the points along the age continuum where observed age-related changes in swallowing begin to emerge.
Use of Telehealth in Substance Use Disorder Services During and After COVID-19: Online Survey Study
Authors: Molfenter Todd , Roget Nancy , Chaple Michael , Behlman Stephanie , Cody Olivia , Hartzler Bryan , Johnson Edward , Nichols Maureen , Stilen Patricia , Becker Sara
Published: January 2021

Background

Social distancing guidelines for COVID-19 have caused a rapid transition to telephone and video technologies for delivering treatment for substance use disorders (SUDs).

Objective

This study examined the adoption of these technologies across the SUD service continuum, acceptance of these technologies among service providers, and intent of providers to use these technologies after the pandemic. Additional analysis using the validated technology acceptance model (TAM) was performed to test the potential applications of these technologies after the pandemic. The study objectives were as follows: (1) to assess the use of telehealth (telephone and video technologies) for different SUD services during COVID-19 in May-June 2020, (2) to assess the intended applications of telehealth for SUD services beyond COVID-19, (3) to evaluate the perceived ease of use and value of telehealth for delivering SUD services, and (4) to assess organizational readiness for the sustained use of telehealth services.

Methods

An online survey on the use of telephonic and video services was distributed between May and August 2020 to measure the current use of these services, perceived organizational readiness to use these services, and the intent to use these services after COVID-19. In total, 8 of 10 regional Addiction Technology Transfer Centers representing 43 states distributed the survey. Individual organizations were the unit of analysis.

Results

In total, 457 organizations responded to the survey. Overall, the technology was widely used; >70% (n>335) of organizations reported using telephone or video platforms for most services. The odds of the intent of organizations to use these technologies to deliver services post COVID-19 were significantly greater for all but two services (ie, telephonic residential counseling and buprenorphine therapy; mean odds ratio 3.79, range 1.87-6.98). Clinical users preferred video technologies to telephone technologies for virtually all services. Readiness to use telephone and video technologies was high across numerous factors, though telephonic services were considered more accessible. Consistent with the TAM, perceived usefulness and ease of use influenced the intent to use both telephone and video technologies.

Conclusions

The overall perceived ease of use and usefulness of telephonic and video services suggest promising post–COVID-19 applications of these services. Survey participants consistently preferred video services to telephonic services; however, the availability of telephonic services to those lacking easy access to video technology is an important characteristic of these services. Future studies should review the acceptance of telehealth services and their comparative impact on SUD care outcomes.
Psychological distress and sleep disturbance throughout thyroid nodule screening, diagnosis and treatment: a monoinstitutional prospective study (Preprint)
Authors: Lei Jianyong , Li Genpeng , Wang Yuting , Bao Ting , Lei Yali , Tian Liuyan , Tang Huairong , Li Zhihui , Zhu Jingqiang
Published: January 2021

BACKGROUND

Many controversies exist regarding the screening and treatment of thyroid cancer (TC), especially papillary thyroid microcarcinoma (PTMC). Numerous articles emphasize patients’ physical health, but few focus on psychological health.

OBJECTIVE

The aim of this study was to evaluate patients’ psychological distress and sleep disturbance throughout thyroid nodules (TNs) screening, diagnosis and treatment.

METHODS

Initially, 2905 eligible participants were enrolled, but some subjects were gradually excluded in different stages. Ultimately, 2834 participants (1153 participants with TNs) were enrolled during the screening phase, and 1105 individuals (87 individuals with TC) were enrolled during the diagnosis phase. Of the 87 TC patients, 66 patients underwent immediate operation (OP), and 21 patients with PTMC opted for active surveillance (AS). Four commonly used questionnaires were applied to quantify the outcome indicators at prescreening, postscreening, postdiagnosis and posttreatment.

RESULTS

Higher psychological distress and sleep disturbance were found postscreening than prescreening, except among those without nodules. Compared to postscreening, higher scores of psychological distress and sleep disturbance were identified in patients with suspicious TC (thyroid imaging reporting and data system ≥4) treated with fine needle aspiration (FNA) or AS , but no significant differences were found between the FNA group and AS group. Lower psychological distress and sleep disturbance were noted for benign nodule patients than for TC patients. OP for papillary thyroid cancer (PTC), especially PTMC, did not alleviate psychological distress or sleep disturbance compared with the same parameters in patients who underwent AS.

CONCLUSIONS

Based on the findings of impaired psychological health and sleep quality, screening for TNs in adults who show no symptoms should be performed with caution. Psychological distress and sleep disturbance should also be taken into consideration when FNA is performed for suspected TC or OP for PTC, especially PTMC.
Effects of an Animated Blood Clot Technology (Visual Clot) on the Decision-Making of Users Inexperienced in Viscoelastic Testing: Multicenter Trial (Preprint)
Authors: Said Sadiq , Roche Tadzio Raoul , Braun Julia , Ganter Micheal Thomas , Meybohm Patrick , Herrmann Johannes , Zacharowski Kai , Raimann Florian Jürgen , Piekarski Florian , Rivas Eva , López-Baamonde Manuel , Spahn Donat R , Nöthiger Christoph Beat , Tscholl David Werner
Published: January 2021

BACKGROUND

Viscoelastic test–guided coagulation management has become increasingly important in assessing hemostasis. We developed Visual Clot, an animated, 3D blood clot that illustrates raw rotational thromboelastometry (ROTEM) parameters in a user-centered and situation awareness–oriented method.

OBJECTIVE

This study aimed to evaluate the applicability of Visual Clot by examining its effects on users that are novices in viscoelastic-guided resuscitation.

METHODS

We conducted an investigator-initiated, international, multicenter study between September 16, 2020, and October 6, 2020, in 5 tertiary care hospitals in central Europe. We randomly recruited medical students and inexperienced resident physicians without significant prior exposure to viscoelastic testing. The 7 participants per center managed 9 different ROTEM outputs twice, once as standard ROTEM tracings and once as the corresponding Visual Clot. We randomly presented the 18 viscoelastic cases and asked the participants for their therapeutic decisions. We assessed the performance, diagnostic confidence, and perceived workload in managing the tasks using mixed statistical models and adjusted for possible confounding factors.

RESULTS

Analyzing a total of 630 results, we found that the participants solved more cases correctly (odds ratio [OR] 33.66, 95% CI 21.13-53.64; P<.001), exhibited more diagnostic confidence (OR 206.2, 95% CI 93.5-454.75; P<.001), and perceived less workload (coefficient –41.63; 95% CI –43.91 to –39.36; P<.001) using Visual Clot compared to using standard ROTEM tracings.

CONCLUSIONS

This study emphasizes the practical benefit of presenting viscoelastic test results in a user-centered way. Visual Clot may allow inexperienced users to be involved in the decision-making process to treat bleeding-associated coagulopathy. The increased diagnostic confidence, diagnostic certainty, reduced workload, and positive user feedback associated with this visualization may promote the further adoption of viscoelastic methods in diverse health care settings.
Understanding Health Empowerment From the Perspective of Information Processing: Questionnaire Study (Preprint)
Authors: Jiang Fei , Liu Yongmei , Hu Junhua , Chen Xiaohong
Published: January 2021

BACKGROUND

Massive, easily accessible online health information empowers users to cope with health problems better. Most patients search for relevant online health information before seeing a doctor to alleviate information asymmetry. However, the mechanism of how online health information affects health empowerment is still unclear.

OBJECTIVE

To study how online health information processing affects health empowerment.

METHODS

We conducted a cross-sectional questionnaire study that included 343 samples from participants who had searched online health information before the consultation. Respondents' perceptions of online information cues, benefits, health literacy, and health empowerment were assessed.

RESULTS

Perceived argument quality and perceived source credibility have significant and positive effects on perceived information benefits, but only perceived argument quality has a significant effect on perceived decision-making benefits. Two types of perceived benefits, in turn, affect health empowerment. The effects of perceived argument quality on perceived informational benefits and perceived decision-making benefits on health empowerment are significantly stronger for the high health literacy group than the low health literacy group (t269=7.156, P<.001; t269=23.240, P<.001). While, the effects of perceived source credibility on perceived informational benefits and perceived informational benefits on health empowerment are significantly weaker for the high health literacy group than the low health literacy group (t269=–10.497, P<.001; t269=–6.344, P<.001). The effect of perceived argument quality on perceived informational benefits shows no significant difference between high and low health literacy groups.

CONCLUSIONS

 In the context of online health information, perceived information benefits and perceived decision-making benefits are the antecedents of health empowerment, which in turn will be affected by perceived argument quality and perceived source credibility. Health literacy plays a moderating role in the relationship of some variables. To maximize health empowerment, online health information providers should strengthen information quality and provide differentiated information services based on users' health literacy.