bluuebunny/crossref_metadata_2025_split huggingface dataset:
Affinity maturation of cross-reactive CR3022 antibody against the receptor binding domain of SARS-CoV-2 via in silico site-directed mutagenesis
Authors: Saini Samvedna , Agarwal Manusmriti , Pradhan Amartya , Pareek Savitha , Singh Ashish K , Dhawan Gagan , Kumar Yatender 
Published: April 2021

Abstract
Introduction: Computational antibody engineering, affinity maturation, and screening greatly aid in vaccine and therapeutic antibody development by increasing the speed and accuracy of predictions. This study presents a protocol for designing affinity enhancing mutants of antibodies through in silico mutagenesis. A SARS-CoV-2 cross-reactive neutralizing antibody, CR3022, is considered as a case study.Methods: Our study aimed at generating antibody candidates from the human antibody CR3022 (derived from convalescent SARS patient) against the RBD of SARS-CoV-2 via in silico affinity maturation using site-directed mutagenesis in mutation hotspots. We optimized the paratope of the CR3022 antibody towards the RBD of SARS-CoV-2 for better binding affinity and stability, employing molecular modeling, docking, dynamics simulations, and molecular mechanics energies combined with generalized Born and surface area (MM-GBSA). Results: Nine antibody candidates were generated post in silico site-directed mutagenesis followed by preliminary screening. Molecular dynamics simulation of 100 nanoseconds and MM-GBSA analysis confirmed L-K45S as a lead antibody with the highest binding affinity against the RBD compared to wild-type and mutant counterparts. Three out of the remaining mutants were also found to have distinct epitopes and binding, possessing a potential to be developed against emerging SARS-CoV-2 variants of concern. Conclusion: The study demonstrates the use of an integrative antibody engineering protocol for enhancing affinity and neutralization potential through mutagenesis using robust open-source computational tools and predictors. This study highlights unique scoring and ranking methods for evaluating docking efficiency. It also underscores the importance of framework mutations for developing broadly neutralizing antibodies.
Uzupełnienie braku upoważnienia do asystowania przy zawieraniu małżeństwa wyrazem ochrony dobra wspólnego
Authors: Góralski Wojciech 
Published: April 2021

Even though marriage arises from the consent of parties (can. 1057 § 1 of the Code of Canon Law), it is necessary to preserve the canonical form (ordinary or extraordinary) for the validity of this relationship.
Assuming that the form of marriage was established in order to eliminate secret marriages, canon 144 § 1 of the current Code of Canon Law states that in the event of factual or legal common error and in positive and probable doubt of law or of fact, the Church supplies executive power of governance for both the external and internal forum.
Canon 144 § of the same Code, on the other hand, declares that the same provision applies to the powers referred to, e.g. in canon 1111 § 1 of the Code of Canon Law. This canon regulates that a local ordinary can delegate (to priests and deacons) of assisting at celebrating marriages.
After discussing the role of a marriage witness and the character of his/her delegation as well as the development of legal form of supplying this delegation, the author takes up the issue of supplying this delegation in an event of common error or positive and probable doubt of law or fact in historical context, and then provides examples of supplying the delegation to assist in marriage in sentences of the Tribunal of the Roman Rota (from years 1992 -2006), including a precedent-setting sentence in the case of Stankiewicz of 15 December 1992.
In conclusion, attention was paid to the ratio legis of the legal norm on supplying the delegation, which is bonum commune.
Advances in Ethnobotany, Synthetic Phytochemistry and Pharmacology of
Endangered Herb Picrorhiza kurroa (Kutki): A Comprehensive Review
(2010-2020)
Authors: Mehta Sharuti , Sharma Anil Kumar , Singh Rajesh K. 
Published: April 2021

:
Picrorhiza kurroa Royle ex Benth. (Family: Plantaginaceae) is a well-recognized Ayurvedic
herb. It is commonly called “Kutki” or “Kurro” and ‘Indian gentian’. Iridoid glycosides are the
plant’s bioactive constituents accountable for the bitter taste and medicinal properties of the plant. The
iridoid glycosides such as picrosides and other active metabolites of the plant exhibit many pharmacological
activities like hepatoprotective, antioxidant, anti-inflammatory, anticancer, immunomodulator,
anti-ulcerative colitis, antimicrobial, etc. This review aims to provide updated information on the ethnobotany,
synthetic phytochemistry, pharmacological potential, safety and toxicology of P. kurroa
and its active metabolites. Indiscriminate exploitation, ecological destruction of natural habitats, slower
plant growth and unawareness regarding cultivation and uprooting of plants have brought kutki an
endangered status. Therefore, various techniques used for the conservation and production of bioactive
metabolites from P. kurroa have also been reported. Information on the plant has been collected
from Science Direct, Google Scholar, PubMed, Scopus using ‘Picrorhiza kurroa’, ‘Picroside-‘,
‘Picroside-II’, ‘Picroliv’, ‘Immunomodulator’ keywords. All studies on ethnobotany, phytochemistry
and pharmacology of plant from 2010- 2020 were comprised in this review article. The possible directions
for future research have also been outlined briefly in this review article.
Antioxidant Activity of 1,2,4-Triazole and its Derivatives: A Mini-Review
Authors: Pachuta-Stec Anna 
Published: April 2021

Abstract:
The information about the presence of free radicals in biological materials was given for the first time about 70 years ago. Since then, numerous scientific studies have been conducted and the science of free radicals was introduced. Today we know that free radicals are by-products of enzymatic reactions occurring in the organism. They are produced during endogenous processes such as cell respiration, phagocytosis, biosynthesis, catalysis, and biotransformation. They can also be produced by exogenous processes (radiation, sunlight, heavy metals, bacteria, fungi, protozoa, and viruses). The overproduction of free radicals affects the aging processes, Oxidative Stress (OS) and takes part in the pathogenesis of various diseases. Among them are cancer, rheumatoid arthritis, neurodegenerative diseases: Alzheimer and Parkinson, pulmonary diseases, atherosclerosis, and DNA damage. Compounds with antioxidant activity are very important nowadays because they allow organisms to keep a balance between the production of free radicals and the speed of their neutralization in the body. Next to the natural antioxidants (flavonoids, carotenoids, vitamins, etc.), synthetic ones are also of great importance. Among synthetic compounds with antioxidant activity are 1,2,4-triazoles and their derivatives. 1,2,4-Triazoles are heterocyclic compounds with three nitrogen atoms. Due to a broad spectrum of biological activities, these derivatives have been of interest to scientists for many years. Some of them are also used as drugs. The finding of new synthetic compounds with antioxidant features in the triazole group has become an important problem of medicinal chemistry.
Antioxidant, Anti-Inflammatory and Anticancer Activities of the Methanolic Extract of Thottea siliquosa: An In Vitro and In Silico Study
Authors: Koottasseri Amrutha , Babu Amal , Augustin Anna , Job Joice Tom , Narayanankutty Arunaksharan 
Published: April 2021

Background:
Oxidative stress and inflammation are the predominant cause of chronic
diseases, including multiple forms of cancers. Prevention of oxidative stress and inflammation is
considered to be a target for preventing these disorders due to their significant roles in various degenerative
diseases. Various natural products and plant extracts prevent the process of free radical-
induced damages.

Objectives:
The present study evaluated the biological properties of Thottea siliquosa, belonging to
the family Aristolochiaceae, which is a traditionally used Ayurvedic plant.

Methods:
Antioxidant assays carried out were DPPH, FRAP, hydrogen peroxide scavenging, and
hemolysis inhibition assay; nitric oxide and lipoxygenase inhibition assays were used for anti-inflammatory
studies. Anticancer activity was evaluated using human endometrial and breast cancer
cells by MTT assay. Bioactive compounds present in T. siliquosa were identified by LCMS and
each was docked with various cancer targets, including EGFR, VEGFR, GST, COX2, and Lipooxygenase.

Results:
The results of the present study showed antioxidant properties of the methanolic crude extract
of T. siliquosa as DPPH radical scavenging (110.40 ± 4.5 μg/mL), FRAP capacity (41.1 ±
6.2), and peroxide scavenging (233.4 ± 14.2 μg/mL). Besides, anti-inflammatory properties were also
evident in terms of nitric oxide radical scavenging (28.76± 3.9 μg/mL) and lipoxygenase inhibition
(39.2 ± 3.2 μg/mL) assays. In silico analysis confirmed the inhibitory potential of the bioactive
compounds of T. siliquosa against cancer drug targets such as EGFR, VEGFR, and inflammatory
enzymes cyclooxygenase as well as lipooxygenase. Further, the anticancer activity of the extract
has been identified against human endometrial and breast cancer cells. The possible mechanism of
anticancer action of the extract is mediated through the apoptosis induction mechanism acting
through increased caspase and APAF-1 expressions.

Conclusion:
The study thus concludes that T. siliquosa showed significant antioxidant, anti-inflammatory
and anticancer properties. Further studies together with a bioassay-guided fractionation
may identify possible bioactive compounds.
Effect of Various Sequence Descriptors in Predicting Human Proteinprotein Interactions Using ANN-based Prediction Models
Authors: Dholaniya Pankaj Singh , Rizvi Samreen 
Published: April 2021

Aims:
A number of sequence-based descriptors for proteins have been proposed by
many researchers. This study aims to evaluate the performance of these descriptors in predicting
protein-protein interactions on the benchmark dataset.

Background:
The behavior of a protein inside or outside the cell is defined by its interaction with
the elements present in the surrounding environment, which include small metabolites to the macromolecules
such as RNA, DNA, or proteins. Of these, understanding protein-protein interactions
(PPIs) is one of the important aspects to investigate the biological role of a protein. The interactions
of a protein are determined by how it folds in 3-dimensional space, and this threedimensional
folding of a protein largely depends on the linear sequence of amino acids. This information
makes it possible to exploit the sequences for proteins to computationally determine the
possible interactions among them.

Objective:
This study aims at studying the efficacy of various sequence-based descriptors in predicting
protein-protein interactions.

Methods:
In this study, we have used the benchmark dataset of interacting and non-interacting
protein pairs provided by Pan et al. to build the PPI prediction models using artificial neural networks.
We have compared the efficacy of different descriptors on two types of datasets, one with
all the protein pairs and the second with proteins having less than 25% identity.

Results:
The results show that conjoint-triad descriptors performed better than other descriptors in
predicting PPIs. The feature selection on the conjoint triad was performed and the effect on the
prediction model with reduced features versus all feature sets was studied.

Conclusion:
The classification model with conjoint-triad descriptors obtained the highest accuracy.
The feature ranking for the conjoint triad descriptor was utilized and the model performance
was compared with all and selected features. The model with reduced features shows less overfitting.
Zanthoxylum bungeanum Seed Oil Elicits Autophagy and Apoptosis in Human Laryngeal Tumor Cells via PI3K/AKT/mTOR Signaling Pathway
Authors: Bai Yun’e , Hou Jing , Zhang Xiao T. , Gao Jian P. , Zhou Jiang T. 
Published: April 2021

Background:
Zanthoxylum bungeanum seed oil (ZBSO) is the main extract of the edible drug
Zanthoxylum bungeanum seeds. Recent reports have proved that it has a significant cytotoxic effect on various
cancer cells. However, systematic investigation on the role of ZBSO in laryngeal carcinoma (LC) is rare.

Objective:
The aim of the study was to reveal the function of ZBSO on human laryngeal squamous carcinoma
cells (Hep-2) and to elucidate its underlying mechanism.

Methods:
In this study, the chemical composition analysis of ZBSO was done using Ultra Performance Liquid
Chromatography (UPLC), and the anti-tumor effect of ZBSO on Hep-2 cells was evaluated by cell proliferation,
apoptosis and cell cycle experiments. qRT-PCR, immunohistochemistry (IHC) and Western blotting were used
for mechanistic investigation at the molecular level.

Results:
The main compound of ZBSO was identified as polyunsaturated fatty acids. Furthermore, as compared
to normal cells, significant inhibitory activities of ZBSO were observed on Hep-2 cells with dose- and timedependency,
which induced apoptosis, blocked cell cycle at the S phase, and inhibited cell proliferation. In
addition, IHC results showed a difference in the level of protein expression of ZBSO-induced autophagy-related
markers. At last, Western blotting results indicated that ZBSO could inhibit the expression and phosphorylation
levels of PI3K/AKT/mTOR protein.

Conclusions:
The anti-LC effect of ZBSO might be intimately associated with the induction of autophagy and the
inhibition of the PI3K/AKT/mTOR signaling pathway. ZBSO may be a potential anti-laryngocarcinoma agent.
SphK1 Promotes Cancer Progression through Activating JAK/STAT Pathway and
Up-Regulating S1PR1 Expression in Colon Cancer Cells
Authors: Long Jianting , Yao Zhijia , Sui Yi , Fang Shi 
Published: April 2021

Background:
SphK1 is a conserved lipid kinase, which can catalyze the formation of tumorpromoting
factor sphingosine phosphate-1 (S1P).

Objective:
This study aimed to investigate the effect of SphK1 on the proliferation/migration of colon cancer
cells and associated mechanisms.

Methods:
Transcription of the SphK1 gene in colon cancer cells was detected. Gene transcription of SphK1 was
inhibited by transfecting with the si-SphK1 gene in colon cancer cells. Effects of SphK1 inhibition (si-SphK1) on
cell migration/proliferation were detected using the transwell system and MTS. Gene transcription of SIP,
S1PR1, S1PR2, S1PR3, and activation of JAK/STAT3 pathway were examined using RT-PCR and western blot
assay. S1PR1 over-expressing plasmid was constructed and transfected into cells. Effects of S1PR1 overexpression
on migration/proliferation of si-SphK1 transfected colon cancer cells and activation of JAK/STAT3
pathway were determined using RT-PCR and western blotting.

Results:
Gene transcription of SphK1 in SW480 and HT-29 colon cancer cells was significantly inhibited by
transfection of the si-SphK1 gene. Transwell migration and MTS findings showed that si-SphK1 transfection (si-
SphK1 group) could reduce migration quantity and cell viability of colon cancer cells compared to the negative
control (NC) (p<0.0001). SphK1 inhibition (si-SphK1 group) significantly down-regulated S1PR1 and S1PR3
gene transcription in SW480 and HT-29 cells (p<0.0001) and decreased activation level of JAKSTAT3 signaling
pathway compared to NC group (p<0.05). Over-expression of S1PR1 reversed inhibitory effects of si-SphK1 on
migration/proliferation of SW480 and activation of JAK/Stat3.

Conclusion:
SphK1 promoted proliferation and migration of colon cancer cells through promoting JAK/STAT
activation and up-regulating S1PR1 expression.
Prevention of Vancomycin-Induced Nephrotoxicity; An Updated Review
of Clinical and Preclinical Studies
Authors: Rahmani Hamid , Khalili Hossein 
Published: April 2021

Purpose:
Clinical and preclinical evidences regarding new strategies for prevention of vancomycin-induced nephrotoxicity are reviewed.

Methods:
Evidence from 2014 to end of 2019 was included. Finally, twelve animal studies and one clinical trial were evaluated.

Results:
Although incidence of vancomycin-induced nephrotoxicity was not reduced significantly in the clinical trial, antioxidants reduced incidence of vancomycin-induced nephrotoxicity in preclinical studies.

Conclusions:
Antioxidants including vitamin C, vitamin E, cilastatin, melatonin, zingerone, rutin, naringenin, saffron, silymarin and dexmedetomidine were nephroprotective against vancomycin-induced nephrotoxicity in preclinical studies. The nephroprotective effects of these antioxidants must be confirmed before routine use in the clinical practice.
Infectious and Non-infectious Factors Affecting Somatic Cell Count and New Diagnostic Approaches of Intramammary Infections in Dairy Goats: A Review
Authors: Margatho Gisele , Quintas Hélder , Rodríguez-Estévez Vicente , Simóes João 
Published: April 2021

Background:
Intramammary infections constitute major animal health and economic
problem in commercial dairy goat farms, being responsible for decreases in milk yield, alter milk
composition, and lower milk quality.

Objectives:
This paper reviews the published literature during the last three decades, highlighting
the multiplicity of non-infectious and infectious factors that influence somatic cell count (SCC).
Besides that, it intends to contribute to understanding the conventional diagnostic methods and their
limitations, and supports the implementation of new technologies for efficient mastitis control, including
the use of infrared thermography and ultrasonography.

Methods:
A search on Medline, ScienceDirect, and University Institutional Repositories databases
was performed using “goats, AND mastitis OR intramammary infections OR somatic cells count”
for publications from 1990 to present (2020).

Results:
A total of 144 publications were selected. The SCC is the most important criteria to evaluate
the inflammatory status of the mammary glands in goats, but several non-infectious factors (e.g.,
phenotypic, reproductive, lactational factors) should be taken into consideration for its interpretation.
Bacteria and fungi as well as lentivirus are commonly responsive for intramammary infections.
Intermittent secretion or environmental contamination of milk pathogens, costs, and time delay poses
challenges using conventional diagnostic methods. Ultrasonographic and thermographic techniques
applied to the udder seem to be of diagnostic value in acute and chronic mastitis.

Conclusions:
Unlike other ruminants species, non-infectious factors have a major impact on SCC
which should be taken in account for mastitis diagnosis, and according to milk pathogens detection.
Further research in imagological techniques is needed to accurately contribute to implant new mastitis
control strategies.
Top-down and Bottom-up Approaches Revealed New Categories of Peptides
from the Venom of Moroccan Scorpion Androctonus mauretanicus
Authors: Daoudi Khadija , Malosse Christian , Darkaoui Bouchra , Chakir Salma , Chgoury Fatima , Cadi Rachida , Sabatier Jean-Marc , Chamot-Rooke Julia , Oukkache Naoual 
Published: April 2021

Background:
Androctonus mauretanicus (Am ) is one of the most hazardous scorpions
in Morocco and has a highly toxic venom responsible for severe cases of envenomation. However,
few studies have focused on deciphering its proteic composition.

Objectives:
Herein, we aim to map out the complete proteome of the Am venom filtrate to highlight
its complexity and the polymorphism of its toxic content. This, in turn, will lead to a deeper understanding
of the toxins’ mechanism of action and will help uncover those with therapeutic potential.

Methods:
Top-down and bottom-up proteomic approaches were used complementarily to decipher
the proteome of the Am venom. These approaches were carried out on nano-high liquid chromatography
coupled to nano-electrospray tandem mass spectrometry (Nano-LC-ESI-MS/MS).

Results:
Am venom encloses a complex mixture of 269 different compounds with molecular
weights ranging from 1618.74 to 14 214.84 Da. The most abundant ones showed masses from
6185.92 to 7899.53 Da (53.89%) followed by those ranging from 2079.25 to 5969.63 Da (37.81%).
Interestingly, the combination of the results of both approaches allowed the screening of a total of
112 peptides. The highest percentage was represented by neuropeptides (87%), including NaTxs,
KTxs, ClTxs, venom proteins, venom neuropeptides, and myotropic neuropeptides. Moreover,
other peptides were identified, such as antimicrobial peptides, amphipathic peptides, cysteine-rich
venom peptides, enzymes, kunitz-type inhibitors and orphan peptides.

Conclusion:
The Am venom appears to contain a great number of diverse peptides, some of which
could prospectively be exploited for their pharmaceutical potential.
Andragogical Approach and Distance Learning Quality in PAUD Qolbun Salim Jatiendah Village, Cilengkrang District Bandung district
Authors: Suwarni Reni , Akhyadi Ade Sadikin , Saripah Iip 
Published: April 2021

Abstract This study aims to describe the implementation, constraints, resistance, and factors that must be considered in Distance Learning through the andragogical approach in the 2019/2020 Academic Year at PAUD Qolbun Salim, Jatiendah Village, Cilengkrang District, Bandung Regency. The research subjects were 26 parents (mothers) during the Covid-19 pandemic. This research is exploratory with descriptive analysis. The results showed that the implementation of Distance Learning in PAUD Qolbun Salim through an andragogical approach was 92% followed, only 8% of parents (mothers) could not follow it. Of the 8% who cannot participate in PJJ, 4% are due to busy doing business online, and 4% are inadequate / decent cellphones. Constraints and resistance in implementing Distance Learning are related to infrastructure, parents' abilities and environmental conditions. Therefore the need for readiness from the institutions and parents, especially the availability of adequate learning facilities, infrastructure and the importance of an andragogical approach in the learning process.Key Words: Andragogical Approach, and Quality of Distance Learning.
PANDEMI COVID-19, PEMBERDAYAAN KELUARGA MELALUI PEMBUATAN PRODUK HOME INDUSTRY HAND SANITIZER ALAMI LIDAH BUAYA & DAUN SIRIH
Authors: Pratiwi Ane Lia 
Published: April 2021

Penelitian ini dilaksanakan dalam rangka memberdayakan masyarakat agar tetap produktif dimasa pandemi Corona Virus Desease -19 (COVID-19) dengan meningkatkan keberdayaan masyarakat dalam menciptakan produk yang dapat membantu mengurangi angka penyebaran virus corona 19. Bencana non alam yang terjadi saat ini mengubah tatanan kehidupan. Kebutuhan akan pentingnya menjaga diri sendiri agar tidak terpapar virus menjadi sebuah keharusan. Kebutuhan alat pelindung diri yang praktis membuat tingginya permintaan handsanitizer dipasaran. Handsanitizer menjadi upaya dalam pencegahan virus corona. Dalam melengkapi kebutuhan terhadap handsanitizer tersebut dilakukanlah pemberdayaan ibu-ibu rumah tangga dalam mengembangkan produk handsanitizer home industry. Hal ini dilakukan dengan tujuan meningkatkan produktifitas Masyarakat dan memutus rantai penyebaran Virus Covid-19. Penelitian ini menggunakan metode kualitatif yang dengan pendekatan studi kasus. Subjek penelitian ini adalah ibu-ibu rumah tangga di Puri Angreek. Hasil dari peneltiian ini adalah meningkatknya pengetahuan dan keterampilan ibu –ibu di bukit mekarwangi dalam memanfaatkan peluang untuk dapat memenuhi kebutuhan public terhadap handsanitizer dan mengembangkan kapasitas diri agar tetap produktif dimasa pandemi.Kata Kunci : Pemberdayaan Masyarakat, Hand Sanitizer, Covid-19.