bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 Challenge: A Quest for Effective Vaccine Strategies Against Circulating
and Emerging SARS-CoV-2 Variants
Authors: Yogesh Ruchika , Srivastava Noopur , Abbas Bukhari Syed Nasir 
Published: July 2022

Introduction:
SARS-CoV-2 belongs to the coronavirus family, a large family of viruses infecting avian and mammalian hosts. Accumulated mutations over time in the genome of SARS-CoV-2 have given rise to different variants differing in type and sequence. Variants that did not affect transmissibility, infectivity, and severity have gone unnoticed, and mutations that made the virus unfit for survival were deleted eventually from the gene pool. An emerging variant in the host population needs to be monitored closely for its infection consequences. In addition, the variants of concern (VOC) need to be focused on developing effective disease-fighting regimes. As viral epidemics are better fought using effective vaccines, several vaccines have been developed and used since December 2020. The central point of the present study is the continuous variation in the genome of SARS-CoV-2, instigating the researchers to refine their modus operandi to fight against COVID-19.

Methods:
Prominent medical and literature databases were searched using relevant keywords to gather study results, reports, and other data helpful in writing this traditional, narrative review.

Results:
This article successfully collates information about the structure and life cycle of SARS-CoV-2, followed by types and nomenclature of mutations in SARS-CoV-2. Variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron) are current VOCs due to their widespread transmission capability and probable immune evasion. Furthermore, this review article presents information about the major vaccines available and those under development. Based on the original and new strains of SARS-CoV-2, 19 vaccines have been granted emergency use or conditional marketing approvals, 141 are under clinical development, and 194 in preclinical development stages worldwide.

Conclusion:
Continuous variation in the genome of SARS-CoV-2, presenting new VOCs frequently, has posed a compelling need to amend and evolve current and future vaccine development strategies to overpower the ever-evolving virus.
Machine Learning Assisted Discovery of Novel p38α Inhibitors from Natural Products
Authors: Shen Tianze , Tao Yongxing , Liu Biaoqi , Kong Deliang , Zhang Ruihan , Xiao Weilie 
Published: July 2022

Background:P38α, emerging as a hot spot for drug discovery, is a member of the mitogen- activated protein kinase (MAPK) family and plays a crucial role in regulating the production of inflammatory mediators. However, despite a massive number of highly potent molecules being reported and several under clinical trials, no p38α inhibitor has been approved yet. There is still demand to discover novel p38α to deal with the safety issue induced by off-target effects.Objective:In this study, we performed a machine learning-based virtual screening to identify p38α inhibitors from a natural products library, expecting to find novel drug lead scaffolds.Method:Firstly, the training dataset was processed with similarity screening to fit the chemical space of the natural products library. Then, six classifiers were constructed by combing two sets of molecular features with three different machine learning algorithms. After model evaluation, the three best classifiers were used for virtual screening.Results:Among the 15 compounds selected for experimental validation, picrasidine S was identified as a p38α inhibitor with the IC50 as 34.14 μM. Molecular docking was performed to predict the interaction mode of picrasidine S and p38α, indicating a specific hydrogen bond with Met109.Conclusion:This work provides a protocol and example for machine learning-assisted discovery of p38α inhibitor from natural products, as well as a novel lead scaffold represented by picrasidine S for further optimization and investigation.
Pharmacokinetics and Metabolism of Traditional Chinese Medicine in the Treatment
of COVID-19
Authors: Xu Xiaofang , Shen Qian , Wang Hui , Zeng Zian , Liu Meng , Wu Guang , Zhou Yusheng , Li Rong 
Published: July 2022

Background:
The outbreak of coronavirus disease 19 (COVID-19) has caused great concern to public
health. Convincing clinical experiences showed that traditional Chinese medicine (TCM) has exhibited remarkable
efficacy in the prevention, treatment and rehabilitation of COVID-19. The research on the treatment of COVID-19
disease with TCM mainly focused on the pharmacological effects and mechanistic analysis. However, the TCM’s
pharmacokinetics and potential herb-drug interaction in the treatment of COVID-19 are currently unclear.

Method:
This review summarizes the pharmacokinetics and characteristics of cytochrome P450 enzyme (CYP450)
metabolism of TCM recommended in the Guidelines for diagnosis and treatment of coronavirus disease 2019 (trial
version eighth), and meanwhile analyzes the potential interactions between TCM and western medicine.

Results:
The pharmacokinetics of TCM mainly focused on preclinical pharmacokinetics, and fewer clinical pharmacokinetics
research was reported. When TCM and western are both metabolized by CYP450 and coadministered,
a potential herb-drug interaction might occur.

Conclusion:
Knowledge of the pharmacokinetics and metabolism of TCM is key to understanding rational TCM
use of COVID-19 and developing antiviral TCM.
The Role of Aquatic Plants in Natural Products and Drug Discovery
Authors: Verma Surjeet , Nakin Motebang D.V. , Makhosayafana Zesipho , Lall Namrita 
Published: July 2022

Background:Phytochemicals and their derivatives/analogues represent over 50% of the current medicines worldwide in clinical use. Despite a significant contribution to the total bioactive natural plant products, aquatic plants are underestimated, and several species are extinct and in the endangered list.Objective:The aim of this review article is to draw the attention of common people and scientists toward a few important contributions of the aquatic plants to natural product chemistry and drug discovery by highlighting the chemical and pharmaceutical aspects of the same.Methods:The presented data were collected and selected from the literature obtained by an online search for the ethnomedicinal properties, biological activities and bioactive chemical constituents of aquatic plants using Google Scholar, PubMed and Scifinder chemical abstract service.Results:The selected literature data revealed that the extract and compounds isolated from several aquatic plants possess significant biological/pharmaceutical properties. For example, the α-asarone (24) and asiatic acid (33) isolated from Acorus calamus and Centella asiatica, respectively, exhibited significant neuroprotective effects in vitro and in vivo. The cripowellin A (59), cripowellin C (60), cripowellin B (61) and cripowellin D (62), isolated from Crinum erubescens, exhibited potent antiplasmodial and antiproliferative activities with half maximal inhibitory concentration (IC50) in nanomolar range (11-260 nM). Several other alkaloids from different Crinum species have also shown anticancer properties against different cancer cell lines with IC50 value <5 μM. Alkaloids and resin glycosides, isolated from different Ipomoea species, have displayed significant psychotropic, psychotomimetic, anticancer, and antibacterial activities with IC50 value <5 μM.Conclusion:The aquatic plants play a significant role in the discovery of bioactive natural products. Although several biological activities and bioactive compounds have been reported from these plants, further assessment and scientific validation of most of their traditional usages still need to be done. There are several other similar species that are underestimated and not much explored. Many aquatic plants, such as Ipomoea carnea Jacq., Juncus lomatophyllus Spreng., Commelina benghalensis Linn, Gunnera perpensa L., Scirpus maritimus L. and Mentha longifolia (L.) L., may be considered for further evaluation. In addition to these, one should not undermine the potential of Crinum macowanii for COVID-19 pathogenesis, as its chemical constituent lycorine has shown significant SARS-CoV-2 inhibitory potential (EC50, 0.3 μM; SI >129). Furthermore, most rural communities are still using the wetland resources for their cultural, medicinal, economic, domestic, and agricultural needs. Hence, the conservation of aquatic plants and wetlands is an issue of great concern.
Effects of p-Hydroxybenzaldehyde, Vanillin, and Syringaldehyde on
Protein Tyrosine Phosphatase 1B Activity
Authors: Mohammed Aminu , Peter Joy Atule , Olatunde Ahmed , Aminu Suleiman , Umar Ismaila Alhaji 
Published: July 2022

Background:
The PTP 1B is a negative regulator of insulin signal transduction and hence, serves as a therapeutic target in the treatment of diabetes.

Objective:
The present study investigated the inhibitory effects of p-hydroxybenzaldehyde, vanillin, and syringaldehyde on the activity of protein tyrosine phosphatases phosphatase 1B (PTP 1B) in vitro.

Method:
The PTP 1B inhibitory assay and mode of inhibition of the three compounds were determined using p-nitrophenyl phosphate (p-NPP) in a 96 well microplate. Molecular docking was used to predict the binding affinities of the compounds with the PTP 1B.

Results:
The results showed that syringaldehyde exhibited significantly (p< 0.05) higher PTP 1B inhibitory activity (IC50: 12.75 µM) compared to p-hydroxybenzaldehyde (IC50: 33.79 µM) and vanillin (IC50: 42.82 µM) as well as the standards suramin (IC50: 28.35 µM) and ursolic acid (IC50: 19.45 µM). Syringaldehyde and vanillin showed uncompetitive inhibition whereas, p-hydroxybenzaldehyde showed a mixed inhibition type. The molecular docking simulation predicted negative binding energies of -5.0 kcal/mol, -5.5 kcal/mol, and -5.5 kcal/mol for p-hydroxybenzaldehyde, vanillin, and syringaldehyde respectively.

Conclusion:
Syringaldehyde showed higher inhibition of PTP 1B compared to other phenolic aldehydes and could be the mechanism of its antidiabetic activity. Hence, further studies are warranted to confirm the efficacy and toxicity of the compound
Flexible Graphene Sheet Loaded Curved Patch Applicator for Superficial
Hyperthermia Treatment Planning Utilizing Ripple Effect of Armchair
and Zigzag Bending
Authors: Singla Alka , Marwaha Anupma , Marwaha Sanjay , Rani Surekha 
Published: July 2022

Background:
Non-invasive microwave hyperthermia approaches suffer from several limitations,
such as maximum energy localization in the target tissue, reduced unwanted hotspots, less
penetration time at specific penetration depth, and maximum directivity of applicators. For conformal
body structures, curved patch applicators avoid mismatch losses and provide circular polarization
to achieve maximum power deposition at the target tissue. At microwave frequencies, graphene
also exhibits good absorption properties and utilizing graphene strips on both sides of a curved patch
offers potential benefits of enhancement of gain, directional radiation pattern, and suppressed sidelobes.

Objective:
Designing a flexible graphene sheet-loaded curved patch for a non-invasive microwave
hyperthermia applicator resonating at 2.45 GHz is the prime objective of current work. The proposed
work is based on utilizing the absorbing properties of graphene sheets with hybrid hexagonal boron
nitride (hBN) under various bending conditions on both sides of a curved patch.

Methods:
Graphene-loaded curved design offers structural flexibility due to the presence of ripples
on the surface and their alignment in armchair configuration (ARC) and zigzag configuration (ZGC).
The bending flexibility along the two configurations alters the electronic properties and opens the
band gap. Thus, the FEM model has been developed for coupling bio-electromagnetic problems of
human body phantom with graphene-loaded curved patch applicator by bending it in two different
configurations.

Results:
For both ARC and ZGC antenna design, parameters, such as return loss and realized gain,
have been investigated. The proposed design achieved a maximum return loss value of -30 dB and
gain of 7.1 dBi for ARC configuration since it provides the maximum difference in valance band and
conduction band in band gap structure, while these values are relatively less in the case of ZGC. The
implementation of the design on cylindrical body phantom is realized for ARC with a maximum Efield
value of 80.2 V/m at a maximum penetration depth of 40 mm. Further simulations are performed
for evaluation of penetration time and fractional tissue damage due to necrosis, and it has
been observed that 10 W of input power is sufficient to achieve maximum temperature range and
tissue necrosis in a duration of 15 minutes.

Conclusion:
The results show that a curved graphene patch applicator provides a potential solution
for targeted heating in hyperthermia applications.
Facile Synthesis and Enhanced Photocatalytic Properties of La2O3/SrSn(OH)6 Nanorods
Authors: Pei Lizhai , Zhang Yong , Zhuang Lihong , Tao Feihu , Xue Zeyang 
Published: July 2022

Background:
The efficient removal of the environmental organic pollutants using the photocatalytic technology catalyzed by the semiconductors has attracted great research interest in recent years. La2O3/SrSn(OH)6 nanorods show enhanced photo-catalytic activity towards crystal violet (CV).

Objective:
The aim is to obtain La2O3/SrSn(OH)6 nanorods by a simple hydrothermal route using lanthanum acetate and SrSn(OH)6 nanorods, and research the photo-catalytic properties for the CV degradation.

Methods:
La2O3/SrSn(OH)6 nanorods were obtained by a hydrothermal route using lanthanum acetate and SrSn(OH)6 nanorods and characterized by X-ray diffraction (XRD), transmission electron microscopy, X-ray photoelectron spectroscopy (XPS), diffuse reflectance spectroscopy (DRS), photoluminescence (PL) and photo-catalytic experiments.

Results:
The composite nanorods are comprised of hexagonal SrSn(OH)6 and cubic La2O3 phases. Some nanoscale particles attach to the surface of the nanorods with the diameter and length of about 100 nm and longer than 1 μm, respectively. La2O3/SrSn(OH)6 nanorods show lower band gap value than that of the SrSn(OH)6 nanorods. The photocatalytic reaction rate constant for the CV degradation using 15wt.%-La2O3/SrSn(OH)6 nanorods is 3 times higher than that of the pure nanorods.

Conclusion:
La2O3/SrSn(OH)6 nanorods possess good reusability and stability for the CV removal. The photo-catalytic activity for the CV removal of the SrSn(OH)6 nanorods can be greatly enhanced by the La2O3.
Patient-Reported Outcomes for the Assessment of Sexual Health Among
Patients Affected by Inflammatory Bowel Disease
Authors: Pugliese Daniela , Parisio Laura , Schepis Tommaso , Privitera Giuseppe , Calvez Valentin , Gasbarrini Antonio , Armuzzi Alessandro 
Published: July 2022

Abstract:
Patients affected by inflammatory bowel disease (IBD) frequently report impaired quality of sexual life and complain of sexual dysfunctions. Both disease-specific features and psy-chological factors can be held responsible for these conditions. However, sexuality and all matters relating to sexual health are often wrongfully considered unrelated to IBD and, therefore, over-looked during medical visits. To overcome these difficulties and to best assess patients’ percep-tions about their sexual health status, the use of patient-reported outcomes (PROs) could represent a valid strategy. In real-world studies, several non-IBD specific questionnaires, exploring differ-ent domains of sexuality, have been applied and validated for the IBD population.
This review summarizes the available evidence on sexual health among IBD patients and the data supporting the application of PROs to screen the quality of sexual life, as well as the rate and types of sexual dysfunctions, among IBD patients.
Improved Neural Differentiation of Human-induced Pluripotent Stem Cell
[hiPSCs] on a Novel Polyurethane-based Scaffold Containing Iron
Oxide Nanoparticles [Fe2O3 NPs]
Authors: Hoseinian Monireh Sadat , Poormoghadam Delaram , Kheirollahzadeh Fatemeh , Mojtahedi Arya , Salimi Ali , Halabian Raheleh 
Published: July 2022

Background:
Repair of the nervous system in humans has always been complicated and faced
difficulties. Cell transplantation approaches using biocompatible scaffolds might be an attractive therapeutic
strategy for neuronal regeneration.

Objective:
We designed a cell delivery platform based on polyurethane [PU] and modified it with iron
oxide nanoparticles [Fe2O3 NPs] for neural induction of human-induced pluripotent stem cells [hiPSC].
Forskolin, IBMX, and different ratios of FBS were employed to induce neurogenesis of hiPSCs. Neural
differentiations were assessed at the level of genes and proteins.

Methods:
As was shown by MTT colorimetric assay, the proliferation and viability of SNL 76/7 on PU/
Fe2O3 were superior in comparison with pure PU and Fe2O3. hiPSCs cultured with PU/Fe2O3 exhibited
an elevated expression of β3-tubulin, MAP2, NSE, OLIG2, as compared to controls. Furthermore, Acridine
Orange staining assured the survival and viability of hiPSCs after 14 days of differentiation.

Result:
All in all, our findings pointed out the biocompatibility and positive regulatory effect of
PU/Fe2O3 on neural markers.

Conclusion:
We believe this scaffold could be a potential candidate for future nerve differentiation applications.
In silico and In vitro Determination of Antiproliferative Activity of Series N-Pyrrolyl
Hydrazide-Hydrazones and Evaluation of their Effects on Isolated Rat Mycrosomes
and Hepatocytes
Authors: Georgieva Maya , Tzankova Diana , Mateev Emilio , Angelov Borislav , Kondeva-Burdina Magdalena , Momekov Georgi , Tzankova Virginia , Zlatkov Alexander 
Published: July 2022

Background:
The significant increase of patients suffering from different types of cancer, guides scientists to take prompt measures in the development of novel and effective antiproliferative agents, where the intercalation of heterocyclic fragment in the designed molecules has proven to be a useful practice.

Objective:
The newly synthesized compounds were obtained from the corresponding 1,4-dicarbonyl derivative through multicomponent reactions to produce biologically active target molecules and assessed by in silico and in vitro assays for their possible antitumor activity.

Methods:
The pharmacological bioassay was conducted in the panel of human tumor cell lines (i) SKW-3 (ACC 53) – human T-cell leukemia and (ii) HL-60 (ACC 3) - human acute myeloid leukemia (AML). The statistical processing of MTT data included the paired Student’s t-test with p ≤ 0.05 set as significance level.

Results:
All evaluated structures displayed higher cytotoxic effect against the acute myeloid leukemia HL-60 with 11o and 11p as the most active compared to the activity against SKW-3 cell line. Throughout the cytotoxicity screening two molecules, 11l and 12o, displayed comparable chemosensitivity on both cell lines. The corresponding hepatotoxicity on isolated rat hepatocytes and microsomes was also established, identifying 11, 12 and 12a as the least toxic and 11x, 11d, 12x and 12d as the most toxic derivatives.

Conclusion:
As most promising compound is underlined ethyl 1-(2-(2-((1-acetyl-1H-indol-3-yl)methylene)hydrazinyl)-2-oxoethyl)-5-(4-bromophenyl)-2-methyl-1H-pyrrole-3-carboxylate (11l) demonstrating highest activity on both evaluated tumor cell lines, decreased hepatotoxicity on all evaluated parameters and docking score of -7.517 kcal/mol.
Psychiatric Manifestations of COVID-19: A Literature Review
Authors: Khatun A. , Tamilanban T. , Chitra V. 
Published: July 2022

Background:
COVID19 (coronavirus disease of 2019) occurs due to the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It uses angiotensin-converting enzyme-2 (ACE-2) as its primary receptor to enter the host cell. Recent reports suggest that this pathogen also has a large impact on the CNS alongside other organs. Various inflammatory mediators such as cytokines, chemokines, and numerous metabolites are poorly regulated during infection as well as in several psychiatric diseases, which leads to conditions of hypoxia and cytokine storm. The persistence of COVID-19 infection may also result in aggravation of the already present neuro-psychiatric symptoms in patients.

Methods:
We systematically searched various sources of journals and assessed the varied neurological routes of propagation and pathogenesis of SARS-CoV-2 neurotoxicity like ACE2-mediated neuro-invasion induced hypoxia, and the cytokine storm syndrome. Several case studies were also referred to obtain a better idea of the current mental health scenario as a consequence of infection and inflammation due to SARS-CoV-2.

Conclusion:
Several risk factors for the causation of mental health issues during as well as after the infection include female gender, presence of necrosis, and pain in avascular regions. Most of the psychiatric disorders are directly associated with the socioeconomic and psychosocial changes that occurred as a consequence of the pandemic. These psychiatric manifestations have only started to unravel, which calls for the development of faster means of diagnosis and integrated pharmacological and epidemiological studies to curb the growing rate of neuronal complications as well as mortality.
Emerging Promise of Phytochemicals in Ameliorating Neurological Disorders
Authors: Jayaraman Megala , Dutta Parijat , Krishnan Sabari , Arora Khyati , Sivakumar Diveyaa , Raghavendran Hanumanth Rao Balaji 
Published: July 2022

Background:The field of medicine and synthetic drug development have advanced rapidly over the past few decades. However, research on alternative medicine, such as phytochemicals cannot be ignored. The main reason for prominent curiosity about phytochemicals stems from the belief that the usage of natural compounds are safer and have lesser detrimental side effects.Objective:The aim of the present review was to discuss in detail several phytochemicals that have been studied or are being studied in the context of various neurological disorders, including depression, Alzheimer’s disease, Huntington’s disease and even neuroinflammatory disorders, such as encephalitis.Methods:The potential roles of phytochemicals in treating or managing symptoms associated with neurological disorders have been included in this article. All data included in this paper have been pooled from various databases, including Google Scholar, PubMed, Science Direct, Springer, and Wiley Online Library.Results:Phytochemicals have been widely studied for their therapeutic properties associated with neurological disorders. Using various experimental techniques for both in vivo and in vitro experiments, studies have shown that phytochemicals do have antioxidant, anti-inflammatory and neuroprotective activities, which play major roles in the treatment of neurological diseases.Conclusion:Even though there has been compelling evidence of the therapeutic role of phytochemicals, further research is still required to evaluate the safety and efficacy of these medicines. Using previously published papers as the foundation for additional research, such as preclinical studies and clinical trials, phytochemicals can become a safer alternative to synthetic drugs for treating a spectrum of neurological diseases.