bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the potential of transcutaneous auricular vagus nerve stimulation to reduce visually induced motion sickness
Authors: Molefi Emmanuel , McLoughlin Ian , Palaniappan Ramaswamy 
Published: September 2022

Abstract
Transcutaneous auricular vagus nerve stimulation (taVNS) is a potent therapeutic tool for a broad spectrum of diseases and disorders. Here, we investigated the effects of taVNS on autonomic function during visually induced motion sickness, through the analysis of spectral and time-frequency heart rate variability. To determine the efficacy of taVNS, we compared sham and taVNS condition in a randomized, within-subjects, cross-over design in 14 healthy participants. We found that taVNS reduced motion sickness symptoms by significantly increasing normalized high-frequency (HF) power and decreasing both normalized low-frequency (LF) power and the power ratio of LF and HF components (sympathovagal balance). Furthermore, behavioral data recorded using the motion sickness assessment questionnaire (MSAQ) showed significant differences in decreased symptoms during taVNS compared to sham condition for the total MSAQ scores and, central and sopite categories of the MSAQ. Our findings suggest that by administering taVNS, parasympathetic modulation is increased, and autonomic imbalance induced by motion sickness is restored. This study provides first evidence that taVNS has potential as a non-pharmacological neuromodulation tool to keep motion sickness at bay. Thus, this sheds new light towards protecting people from becoming motion sick and possible accelerated recovery from the malady.
A genome-wide CRISPR-Cas9 knockout screen reveals FSP1 as warfarin-resistant vitamin K reductase
Authors: Jin Da-Yun , Chen Xuejie , Liu Yizhou , Williams Craig M. , Pedersen Lars C. , Stafford Darrel W. , Tie Jian-Ke 
Published: September 2022

Abstract

Vitamin K is a vital micronutrient implicated in a variety of human diseases1. Warfarin, a vitamin K antagonist, is the most commonly prescribed oral anticoagulant2. Warfarin exerts its effect by inhibiting vitamin K epoxide reductase (VKOR) leading to the depletion of reduced vitamin K, a cofactor of gamma-glutamyl carboxylase (GGCX) required for the post-translational modification of proteins with diverse functions. Patients overdosed on warfarin can be rescued by administering high doses of vitamin K because of the existence of a warfarin-resistant vitamin K reductase (VKR)3,4. Despite the functional discovery of VKR over eight decades ago, the identity of VKR remained elusive. Here, we report the identification of warfarin-resistant VKR using a genome-wide CRISPR-Cas9 knockout screening with a novel vitamin K-dependent (VKD) apoptotic reporter cell line. We found that ferroptosis suppressor protein 1 (FSP1) is responsible for vitamin K reduction in a warfarin-resistant manner. Knocking out FSP1 in HEK293 cells dramatically decreased VKR activity, while HEK293 cells overexpressing FSP1 exhibited robust VKR activity that is resistant to warfarin inhibition. Inhibitor of FSP1 that inhibited ubiquinone reduction and thus triggering cancer cell ferroptosis, displayed strong inhibition of VKD carboxylation. Intriguingly, dihydroorotate dehydrogenase (DHODH), another ubiquinone-associated ferroptosis suppressor protein parallel to the function of FSP15, does not support VKD carboxylation and its inhibitors have no effect on carboxylation. These findings provide new insights into selectively controlling the physiological and pathological processes involving electron transfers mediated by vitamin K and ubiquinone.
Perfluorinated Compounds (PFCs) in river waters of central Italy: monthly variation and Ecological Risk Assessment (ERA)
Authors: Castellani Federica , Galletti Mara , Charavgis Fedra , Cingolani Alessandra , Renzi Sonia , Nucci Mirko , Protano Carmela , Vitali Matteo 
Published: September 2022

Abstract

Perfluorinated compounds (PFCs) are a wide class of emerging pollutants still under study. In this work, we developed and validate a sensitive analytical method based on HPLC-MS/MS for the determination of 21 PFCs. This method was then used to investigate the presence of the target PFCs in six rivers in central Italy during a 4-months long monitoring campaign. 73% of the analytical determinations resulted higher than the limit of detection (LOD). The ∑21PFCs ranged from 4.3 to 68.5 ng L− 1 with the highest concentrations measured in June month, due to a minor river streamflow occurring in the warm periods. Between the individual congeners, PFBA and PFPeA, followed by PFHxA and PFOA were the predominant congeners detected. The evidence that short and medium chain PFCs (C4-C9) prevail over the long chain PFCs (C10-C18) could be attributed to the increased use and higher solubility of short chain PFCs compared to long chain PFCs. The ecological risk assessment, conducted by using risk quotient (RQ) method, highlighted that for PFBA, PFPeA, PFBS, PFHxA and PFOA the risk for aquatic environments was low or negligible. Only for PFOA there was a medium risk in 2 rivers in June month. As regard PFOS, 54% of the river water samples were classified as “high risk” for the aquatic environment. The remaining 46% of the samples were classified as “medium risk”.
Relationships between Indices of Arm Anthropometry, Bioimpedance, and Laboratory in Maintenance Hemodialysis Patients
Authors: Wang Jenn-Yeu , Chen Shu-Chin , Lin Yuh-Feng , Hwang Betau 
Published: September 2022

Abstract
Background: Maintenance hemodialysis patients often experience protein- calorie malnutrition. Our aim is to evaluate the independent prediction accuracy of bioelectrical impedance analysis derived variables by the measurements of upper arm anthropometry and clinical laboratory indexes for evaluation of nutritional status of hemodialysis patients. Furthermore, the relationship between measurements of upper arm anthropometry and clinical laboratory indexes and cross –sectional evaluation of the prevalence of malnutrition with the use of the norms and thresholds were done.
Methods: In a retrospectively cross- sectional survey of 32 stable hemodialysis patients (aged 28 to 82 years) in hemodialysis unit of Taipei Municipal Zhongxiao Hospital, we evaluated measurements of upper arm anthropometry with measurements of single frequency bioelectrical impedance analysis and clinical laboratory indexes.
Results: The comparisons between measurements of upper arm anthropometry with measurements of single frequency bioelectrical impedance analysis and some of clinical laboratory indexes were statistically significant. This study further found that both mid-arm fat area and triceps skin-fold thickness were independent contributors to percent fat mass after adjustment for body mass index and gender in the hierarchical multiple regression models. This study also demonstrated that mid-arm muscle circumference, or mid-arm muscle area, or corrected mid-arm muscle area independently predicted height normalized indices of fat-free mass, respectively, after adjustment for body mass index and gender in the hierarchical multiple regression models. Prediction equations for height normalized indices of lean body mass and percent fat mass were showed. The prevalence of protein wasting measured by mid-arm muscle circumference (50%) appears to be equivalent to that measured by serum albumin concentration (50%).
Conclusions: Mid-arm muscle and fat variables by upper arm anthropometry correlated with nutritional variables of single frequency bioelectrical impedance analysis and clinical laboratory indexes. Mid-arm muscle and fat variables by upper arm anthropometry were independent predictors of body composition regarding height-normalized indices of fat-free mass and percent fat mass of hemodialysis patients even after adjustment of gender and body mass index.
Recent Advances in Chitosan-Based Composite Materials in Organic Transformations
- A Review
Authors: Rao Kummari Subba Venkata Krishna , Nagaraja Kasula , Adilakshmi Boddu , Lakshmidevi Jangam , Reddy Guddety Viswanatha , Han Sung Soo , Rao Kummara Madhusudana 
Published: September 2022

Abstract:
Chitosan (CS) is a crustacean-derived bio-macromolecular base. Physico-chemical properties of CS resemble cellulose, and the chemical structure constitutes β-(1-4)-linked D-glucosamine and N-acetyl-D-glucosamine units. It has tunable characteristics such as molecular weight, degree of acetylation, and acetyl distribution. It is proven to be a very good support in making catalysts and functional materials. This article comprises the recently published articles using CS-based composites as heterogeneous catalysts in numerous chemical transformations of industrial relevance. In this connection, the CS-based composite materials have been successfully used as heterogeneous catalysts in a wide range of organic transformations including cycloaddition, trimethylsilylation, cyanation, Suzuki-Miyaura, Heck, Beckmann rearrangement, O-carboxymethylation, nitroarenes reduction, nucleophilic acylation (phenyl acetates from acid chlorides), Knoevenagel condensation, biomass valorization, P–O bond formation, imination, dipolar addition, and multicomponent reactions. The CS has also been used to prepare magnetic nanocomposite-based catalysts that showed easy separation and high reusability. This article is highly helpful in designing further chemical transformations where the role of the bio-polymeric base, CS may be critical.
The Genus Ageratina (Asteraceae) in America: An Insight into its Chemistry
and Pharmacological Potential
Authors: Rivero-Cruz Isabel , Gutiérrez-González José Alberto , Pérez-Vásquez Araceli , Villaseñor José Luis , Mata Rachel 
Published: September 2022

Background:
Ageratina is an American genus of the tribe Eupatorieae (Asteraceae),
comprising about 320 species. In Mexico, some species of this genus are highly valued for their
medicinal properties, particularly A. pichinchensis, A. petiolaris, and A. grandifolia. Furthermore,
herbal preparations of A. pichinchensis are available for treating several mycoses.

Aim and Objective:
The present review is aimed to summarize the chemical and pharmacological
properties of 37 species of the Ageratina genus up to April, 2022.

Methods:
Data were recorded using online scientific databases, including Scopus, PubMed,
Google Scholar, Taylor and Francis Imprints, National Center for Biotechnology Information, Science
Direct, JSTOR, and SciFinder. The information was gathered from research articles, relevant
books on herbal medicinal plants and the history of medicinal plants from Mexico, theses, reports,
and web pages.

Results:
The specialized metabolites present in the Ageratina genus belong to different chemical
classes, including flavonoids, benzyl benzoates, benzofurans, chromenes, and terpenoids. The
chromenes, benzofurans, and benzyl benzoates are the metabolites most widespread in the genus.
So far, the species more thoroughly investigated is A. adenophora. Ageratina has received little attention
from the pharmacological point of view. The studies are limited to 10 species. Biological
studies have been conducted on extracts and/or compounds isolated from plants collected mainly
from China and Mexico. The results revealed that the extracts and metabolites possess several biological
activities, including antiviral, antioxidant, antimicrobial, anti-inflammatory, antinociceptive,
antifeedant, larvicidal, acaricidal, antidiabetic, antiprotozoal, and wound-healing properties. In
the case of A. pichinchensis, A. petiolaris, and A. grandifolia, the pharmacological studies provided
evidence for their use for treating gastrointestinal complaints and diabetes. Furthermore, herbal
preparations of A. pichinchensis are now widely used for alleviating onychomycosis. A. adenophora,
is the most investigated species, chemically and biologically; however, some hepatotoxicity effect
has been recorded.

Conclusion:
This review recapitulates information on the Ageratina genus, highlighting the phytochemistry
and biological activities of the species investigated. It is important to point out that the
pharmacological potential of this large genus remains largely unexplored.
A Perspective on EGFR and Proteasome-based Targeted Therapy for
Cancer
Authors: Patel Asha , Panjwani Drishti , Mishra Deepak , Patel Shruti , Patel Viral , Dharamsi Abhay 
Published: September 2022

Background:
Cancer is known to be the most leading cause of death worldwide. It is understood that the sources causing cancer are mainly the activity of endogenous oncogenes, non-viral compounds and the fundamental portion of these oncogenes; the tyrosine kinase activity and proteasome activity as the main biomarkers responsible for cell proliferation. These biomarkers can be used as main targets and are believed to be the ‘prime switches’ for the signal communication activity to regulate cell death and cell cycle. Thus, signal transduction inhibitors (ligand receptor tyrosine kinase inhibitors) and proteosome inhibitors can be used as therapeutic modality to block the action of signaling between the cells as well as protein breakdown in order to induce cell apoptosis.

Aim:
This article highlights the key points and overview of the recent patents on EGFR and proteosome based inhibitors as a therapeutic efficacy. This review focuses on the patents related to therapeutic agent, process preparation and product patent.

Objective:
The main objective of this study is to facilitate the advancement and current perspectives in the treatment of cancer.

Conclusion:
There are numerous strategies that are discussed in these patents to improve the pharmacokinetics and pharmacodynamics of EGFR and proteosome inhibitors. Further, resistance of targeted therapy after long term treatment can be overcome by using various excipients that can be used as a strategy to carry drug in order to overcome resistance. However, there is a need and scope for improving targeted therapeutics for cancer treatment with better fundamentals and characteristics.
The widespread research over cancer therapy can create the path for future advancements in therapy with more prominent outcomes.
Cyclophilin D Regulates Oxidative Stress and Apoptosis via
Mitochondrial Permeability Transition Pore in Acute Acalculous
Cholecystitis
Authors: Hong Kunqiao , Yang Qian , Liu Gen , Qiu Hu , Yu Baoping 
Published: September 2022

Objective:
Acute acalculous cholecystitis (AAC) is characterized by acute
onset, rapid progression, high mortality, and various complications. Cyclophilin D
(CypD) regulates the mitochondrial permeability transition pore (MPTP) and is involved
in the occurrence of ischemia-reperfusion injury and inflammation; however, the role of
CypD in AAC remains unclear.

Methods:
Guinea pigs of 300–350 g were randomly divided into three groups, namely
the sham group, the common bile duct ligation-24h group (CBDL-24h group), and the
CBDL-48h group. Western blot and qRT-PCR were applied to analyze the differential
expression of CypD in each group, and transmission electron microscopy was employed
to detect changes in mitochondrial structure. Inhibiting the activity of CypD by Cyclosporine
A (CsA), we evaluated the difference of mitochondrial utilizing mitochondrial
swelling, reactive oxygen species (ROS) detection and mitochondrial membrane potential.

Results:
Compared with the sham group, the prolongation of obstruction aggravated
gallbladder inflammation and upregulated CypD expression in the CBDL-24h and
CBDL-48h groups. The degree of mitochondrial swelling was increased, and the opening
of MPTP was prolonged in the CBDL-24h and 48h groups. Decreasing the expression
of CypD could repress the opening of MPTP, prevent manipulation of the
mitochondrial membrane potential, and ultimately diminish the levels of intracellular
ROS and apoptosis.

Conclusion:
CypD plays a proinflammatory role in the development of AAC by regulating
the opening of MPTP. Inhibiting the activity of CypD could reduce the levels of
ROS and apoptosis, rescue the function of mitochondria and finally alleviate AAC.
Therefore, CypD might serve as a potential therapeutic target for ACC.
Insights of Valacyclovir in Treatment of Alzheimer’s Disease: Computational Docking Studies and Scopolamine Rat Model
Authors: Shah Jigna , Patel Parmi , Faldu Khushboo , Borisa Ankit , Bhatt Hardik 
Published: September 2022

Background:Alzheimer’s disease (AD) impairs memory and cognitive functions in the geriatric population and is characterized by intracellular deposition of neurofibrillary tangles, extracellular deposition of amyloid plaques, and neuronal degeneration. Literature suggests that latent viral infections in the brain act as prions and promote neurodegeneration. Memantine possesses both anti-viral and N-methyl-D-aspartate (NMDA) receptor antagonistic activity.Objectives:This research was designed to evaluate the efficacy of antiviral agents, especially valacyclovir, a prodrug of acyclovir in ameliorating the pathology of AD based on the presumption that anti-viral agents targeting the Herpes simplex virus (HSV) can have a protective effect on neurodegenerative diseases like Alzheimer’s disease.Methods:Thus, we evaluated acyclovir’s potential activity by in-silico computational docking studies against acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase 1 (BACE-1). These findings were further evaluated by in-vivo scopolamine-induced cognitive impairment in rats. Two doses of valacyclovir, a prodrug of acyclovir (100 mg/kg and 150 mg/kg orally) were tested.Results:Genetic Optimisation for Ligand Docking scores and fitness scores of acyclovir were comparable to donepezil. Valacyclovir improved neurobehavioral markers. It inhibited AChE and BuChE (p<0.001) enzymes. It also possessed disease-modifying efficacy as it decreased the levels of BACE-1 (p<0.001), amyloid beta 1-42 (p<0.001), amyloid beta 1-40 (p<0.001), phosphorylated-tau (p<0.001), neprilysin (p<0.01), and insulin-degrading enzyme. It ameliorated neuroinflammation through decreased levels of tumour necrosis factor α (p<0.001), nuclear factor-kappa B (p<0.001), interleukin 6 (p<0.001), interleukin 1 beta (p<0.001), and interferon-gamma (p<0.001). It also maintained synaptic plasticity and consolidated memory. Histopathology showed that valacyclovir could restore cellular density and also preserve the dentate gyrus.Conclusion:Valacyclovir showed comparable activity to donepezil and thus can be further researched for the treatment of Alzheimer’s disease.
Cytokine Storm and Neuropathological Alterations in Patients with Neurological Manifestations of COVID-19
Authors: Tsagkaris Christos , Bilal Muhammad , Aktar Irem , Aboufandi Youssef , Tas Ahmet , Aborode Abdullahi Tunde , Suvvari Tarun Kumar , Ahmad Shoaib , Shkodina Anastasiia , Phadke Rachana , Emhamed Marwa S. , Baig Atif Amin , Alexiou Athanasios , Ashraf Ghulam Md. , Kamal Mohammad Amjad 
Published: September 2022

Abstract:The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), a respiratory pathogen with neuroinvasive potential. Neurological COVID-19 manifestations include loss of smell and taste, headache, dizziness, stroke, and potentially fatal encephalitis. Several studies found elevated proinflammatory cytokines, such as TNF-α, IFN-γ, IL-6 IL-8, IL- 10 IL-16, IL-17A, and IL-18 in severely and critically ill COVID-19 patients may persist even after apparent recovery from infection. Biomarker studies on CSF and plasma and serum from COVID-19 patients have also shown a high level of IL-6, intrathecal IgG, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and tau protein. Emerging evidence on the matter has established the concept of COVID-19-associated neuroinflammation, in the context of COVID-19-associated cytokine storm. While the short-term implications of this condition are extensively documented, its longterm implications are yet to be understood. The association of the aforementioned cytokines with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, may increase COVID-19 patients' risk of developing neurodegenerative diseases. Analysis of proinflammatory cytokines and CSF biomarkers in patients with COVID-19 can contribute to the early detection of the disease's exacerbation, monitoring the neurological implications of the disease and devising risk scales, and identifying treatment targets.
AHNAK2 Promotes the Progression of Differentiated Thyroid Cancer through PI3K/AKT Signaling Pathway
Authors: Xu Min , Wen Jialiang , Xu Qiding , Li Huihui , Lin Bangyi , Bhandari Adheesh , Qu Jinmiao 
Published: September 2022

Aims:
AHNAK2 may be used as a candidate marker for TC diagnosis and treatment.

Background:
Thyroid cancer [TC] is the most frequent malignancy in endocrine carcinoma, and the
incidence has been increasing for decades.

Objective:
To understand the molecular mechanism of DTC, we performed next-generation sequencing
[NGS] on 79 paired DTC tissues and normal thyroid tissues. The RNA-sequencing [RNA-seq] data
analysis results indicated that AHNAK nucleoprotein 2 [AHNAK2] was significantly upregulated in the
thyroid cancer patient’s tissue.

Methods:
We also analyzed AHNAK2 mRNA levels of DTC tissues and normal tissues from The Cancer
Genome Atlas [TCGA]. The association between the expression level of AHNAK2 and clinicopathological
features was evaluated in the TCGA cohort. Furthermore, AHNAK2 gene expression was
analyzed by quantitative real-time polymerase chain reaction [qRT-PCR] in 40 paired DTC tissues and
adjacent normal thyroid tissues. The receiver operating characteristic [ROC] curve was performed to
evaluate the diagnostic value of AHNAK2. For cell experiments in vitro, AHNAK2 was knocked down
using small interfering RNA [siRNA], and the biological function of AHNAK2 in TC cell lines was investigated.
The expression of AHNAK2 was significantly upregulated in both the TCGA cohort and the
local cohort.

Results:
The analysis results of the TCGA cohort indicated that the upregulation of AHNAK2 was associated
with tumor size [P<0.001], lymph node metastasis [P<0.001], and disease stage [P<0.001]. The
area under the curve [AUC, TCGA: P<0.0001; local validated cohort: P<0.0001.] in the ROC curve
revealed that AHNAK2 might be considered a diagnostic biomarker for TC. The knockdown of
AHNAK2 reduced TC cell proliferation, colony formation, migration, invasion, cell cycle, and induced
cell apoptosis

Conclusion:
Furthermore, the protein levels of phospho-PI3 Kinase p85 and phospho-AKT were downregulated
in the transfected TC cell. Our study results indicate that AHNAK2 may promote metastasis
and proliferation of thyroid cancer through PI3K/AKT signaling pathway. Thus, AHNAK2 may be used
as a candidate marker for TC diagnosis and treatment.