bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Knowledge and Insights on the Mechanisms of Immediate Hypersensitivity
and Anaphylaxis: IgE/FcεRI- and Non-IgE/FcεRI-Dependent Anaphylaxis
Authors: Ebo Didier G. , Beyens Michiel , Heremans Kevin , van der Poorten Marie-Line M. , Van Gasse Athina L. , Mertens Christel , Houdt Michel Van , Sabato Vito , Elst Jessy 
Published: October 2022

Abstract:
Immediate hypersensitivity reactions can pose a clinical and diagnostic challenge, mainly because of
the multifarious clinical presentation and distinct underlying – frequently uncertain – mechanisms. Anaphylaxis
encompasses all rapidly developing and life-threatening signs and may cause death. Evidence has accumulated
that immediate hypersensitivity and anaphylaxis do not necessarily involve an allergen-specific immune response with cross-linking of specific IgE (sIgE) antibodies bound to their high-affinity IgE receptor (FcεRI) on
the surface of mast cells (MCs) and basophils. Immediate hypersensitive and anaphylaxis can also result from
alternative specific and nonspecific MC and basophils activation and degranulation, such as complementderived anaphylatoxins and off-target occupancy of MC and/or basophil surface receptors such as the Masrelated G protein-coupled receptor X2 (MRGPRX2). Degranulation of MCs and basophils results in the release
of inflammatory mediators, which can be, depending on the underlying trigger, in a different spatiotemporal
manner. In addition, hypersensitivity and anaphylaxis can occur entirely independently of MC and basophil
degranulation, as observed in hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) that divert
normal arachidonic acid metabolism by inhibiting the cyclooxygenase (COX)-1 isoenzyme. Finally, one should
remember that anaphylaxis might be part of the phenotype of particular - sometimes poorly recognizable - conditions such as clonal MC diseases (e.g. mastocytosis) and MC activation syndrome (MCAS). This review provides a status update on the molecular mechanisms involved in both sIgE/FcεRI- and non-sIgE/FcεRIdependent immediate hypersensitivity and anaphylaxis. In conclusion, there is increasing evidence for alternative pathophysiological hypersensitivity and anaphylaxis endotypes that are phenotypically and biologically indistinguishable, which are frequently difficult to diagnose, mainly because of uncertainties associated with diagnostic tests that might not enable to unveil the underlying mechanism.
Protective Effect of Chrysin Against Chlorpyrifos-induced Hepatotoxicity
in Rats: Biochemical and Histopathological Approaches in a Sub-chronic
Study
Authors: Samarghandian Saeed , Roshanravan Babak , Farkhondeh Tahereh , Darroudi Majid 
Published: October 2022

Background:
Chrysin (CH) is one of the important natural flavonoids with antioxidant
and anti-inflammatory activity. The aim of this study was to assess the protective effects of CH on
biochemical indexes and histopathological changes in the liver of male Wistar rats exposed to chlorpyrifos
(CPF).

Methods:
We induced sub-chronic toxicity in rats using CPF (10 mg/kg/day, orally) and administrated
CH at 12.5, 25, and 50 mg/kg/day for 45 days.

Results:
In this study, CPF increased liver enzyme activities compared with the control group (p <
0.05), and co-treated CH with CPF reduced them compared with the non-treated CPF group (p <
0.05). A significant reduction in the liver GSH concentration along with a significant elevation in the
concentrations of MDA and NO in the CPF group was observed compared with the control group (p
< 0.001). However, CH at a dose of 50 mg could reverse them nearly to the control group (p <
0.001). In the CPF, CPF + CH1, and CPF + CH2 groups, a marked (p < 0.05) increase was found in
the serum concentration of IL-6 compared with the control animals. No significant changes were
found in the IL-6 concentration of the CPF + CH3 compared with the controls. Moreover, the coadministration
of CH plus CPF induced histopathological alterations in liver.

Conclusion:
These results suggest that CH attenuates hepatic enzymes and histopathological alterations
induced by CPF via modulating oxidative stress and inflammatory indices in rats.
COVID-19 Induces Cytokine Storm and Dysfunctional Hemostasis
Authors: Ploplis Victoria A. , Charles Jermilia 
Published: October 2022

Background:
Infection with SARS-CoV-2 leads to COVID-19 which can manifest in various ways from asymptomatic or mild disease to acute respiratory distress syndrome. The occur-rence of dysregulated inflammatory responses in the form of a cytokine storm has been reported in patients with severe COVID-19. Infection can also lead to dysfunctional hemostasis reflected in el-evated circulating D-dimer and fibrin degradation products. Components of hemostasis and the im-mune system during infection can result in a procoagulation and/or proinflammatory state. The in-terplay between coagulation and inflammation has been elucidated in a number of diseases.

Objective:
In this article, we discuss the occurrence of cytokine storms and dysfunctional hemosta-sis induced in COVID-19.

Methods:
This review was written using literature from the past two to three years investigating co-agulation and inflammation in COVID-19. Additional literature, both clinical and basic research, related to pathogen infection and host responses were also considered in this review.

Results/Conclusions:
Infection with SARS-CoV-2 can lead to dysregulated inflammatory respons-es that may be detrimental to the host. The increased expression of various inflammatory factors can ultimately create an environment that promotes thrombosis.
Role of Mitophagy in Cigarette Smoke-induced Lung Epithelial
Cell Injury In Vitro
Authors: Wang Suwen , Song Xiaomin , Wei Liangyu , Liu Qi , Li Chenfei , Wang Jiong 
Published: October 2022

Background:
Mitochondria are important in mediating airway inflammatory responses to cigarette smoke (CS). Removal of damaged or defective mitochondrial (mitophagy) may prevent the detrimental impact of CS extract (CSE) on airway and lung epithelial cells.

Methods::
We studied the effect of a mitophagy activator (Urolithin A, UA) and a mitophagy inhibitor (Liensinine diperchlorate, Ld) on CSE-exposed alveolar (A549) and airway (BEAS-2B) epithelial cell proliferation, intracellular and mitochondrial ROS, inflammatory response, mitochondrial membrane potential (DYm), mitochondrial morphology, mitochondrial complex activities, and protein levels of mitochondrial fission (DRP1, MFF) and mitophagy (SQSTM1/p62, LC3B). In both cell types, CSE exposure led to increased intracellular and mitochondrial oxidative stress, decreased DYm and resulted in structural disruption of the mitochondrial network. CSE increased the expression of DRP1, MFF and SQSTM1/p62, while decreasing the ratio of LC3B-II/I protein expression. CSE also increased inflammatory (IL-1β, IL-6, IL-18, CXCL1, CXCL8) and necroptosis factors (RIPK1, RIPK3, MLKL) mRNA expression.

Results::
Pre-treatment with UA attenuated CSE-induced oxidative stress, inflammatory and necroptosis gene expression and restored mitochondrial structure and function. UA also prevented CSE-evoked increases in DRP1, MFF and SQSTM1/p62 protein expression and increased LC3B-II/I ratio.

Conclusion::
Conversely, pre-treatment with Ld aggravated CSE-induced cellular and mitochondrial responses. In conclusion, mitophagy mediates CSE-induced damage and inflammation to lung epithelial cells and may represent a therapeutic target in CS-driven diseases.
Extracellular Matrix Remodeling Biomarkers in Coronary Artery Disease
Authors: Theofilis Panagiotis , Sagris Marios , Oikonomou Evangelos , Antonopoulos Alexios S , Lazaros George , Theofilis Anastasios , Papastamos Charalambos , Papaioannou Spyridon , Siasos Gerasimos , Tsioufis Kostas , Tousoulis Dimitris 
Published: October 2022

Abstract:
Atherosclerosis and one of its most serious consequences, coronary artery disease, are important sources of morbidity and mortality globally, necessitating early detection and treatment. Considering their complex pathophysiology, including several harmful processes, a comprehensive approach to diagnosis, prognosis, and therapy is very desirable. Extracellular matrix remodeling is a major component of this dangerous cascade, including the cleavage of constituents (collagen, elas-tin, proteoglycans) and the propagation or exacerbation of the inflammatory response. Several ex-tracellular matrix degradation indicators have been hypothesized to correlate with the existence, se-verity, and prognosis of coronary artery disease. The potency of matrix metalloproteinases, notably collagenases and gelatinases, has been the most thoroughly investigated in clinical studies. Strome-lysins, matrilysins, transmembrane matrix metalloproteinases, collagen and laminin turnover indica-tors, as well as fibronectin, have also been studied to a lesser level. Among the most well-studied markers, MMP-1, MMP-2, MMP-8, and MMP-9 have been found increased in patients with cardio-vascular risk factors such as metabolic syndrome, its components (obesity, dyslipidemia, diabetes mellitus), and smoking. Increasing concentrations are detected in acute coronary syndromes com-pared to stable angina pectoris and healthy control groups. It should also be stressed that those ex-tracellular matrix biomarkers may also be detected in high concentrations in other vascular patholo-gies such as peripheral artery disease, carotid artery disease, aortic aneurysms, and dissections. De-spite the advances gained, future research should focus on their importance and, more crucially, their added utility as biomarkers in identifying persons at risk of developing overt coronary artery disease. At the same time, determining the prognosis of coronary artery disease patients using such biomarkers may be important for their adequate care.
The Tetrahydroisoquinoline Scaffold in ABC Transporter Inhibitors that
Act as Multidrug Resistance (MDR) Reversers
Authors: Teodori Elisabetta , Braconi Laura , Manetti Dina , Romanelli Maria Novella , Dei Silvia 
Published: October 2022

Background:
The failure of anticancer chemotherapy is often due to the development of resistance to a variety of anticancer drugs. This phenomenon is called multidrug resistance (MDR) and is related to the overexpression of ABC transporters, such as P-glycoprotein, multidrug re-sistance-associated protein 1 and breast cancer resistance protein. Over the past few decades, sever-al ABC protein modulators have been discovered and studied as a possible approach to evade MDR and increase the success of anticancer chemotherapy. Nevertheless, the co-administration of pump inhibitors with cytotoxic drugs, which are substrates of the transporters, does not appear to be asso-ciated with an improvement in the therapeutic efficacy of antitumor agents. However, more recently discovered MDR reversing agents, such as the two tetrahydroisoquinoline derivatives tariquidar and elacridar, are characterized by high affinity towards the ABC proteins and by reduced negative properties. Consequently, many analogs of these two derivatives have been synthesized, with the aim of optimizing their MDR reversal properties.

Objective:
This review aims to describe the MDR modulators carrying the tetraidroisoquinoline scaffold reported in the literature in the period 2009-2021, highlighting the structural characteristics that confer potency and/or selectivity towards the three ABC transport proteins.

Results and Conclusions:
Many compounds have been synthesized in the last twelve years showing interesting properties, both in terms of potency and selectivity. Although clear structure-activity re-lationships can be drawn only by considering strictly related compounds, some of the compounds reviewed could be promising starting points for the design of new ABC protein inhibitors.
Hand, Foot, and Mouth Disease: A Narrative Review
Authors: Leung Alexander K. C. , Lam Joseph M. , Barankin Benjamin , Leong Kin Fon , Hon Kam Lun 
Published: October 2022

Background:Hand, foot, and mouth disease is a common viral disease in childhood. Because the disease has the potential to reach epidemic levels and the mortality is high in some countries, early recognition of this disease is of paramount importance.Objective:This purpose of this article is to familiarize pediatricians with the clinical manifestations and management of hand, foot, and mouth disease.Methods:A search was conducted in February 2022 in PubMed Clinical Queries using the key term " hand, foot, and mouth disease". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review.Results:Hand, foot, and mouth disease is characterized by a painful oral enanthem and asymptomatic exanthem on the palms and soles. Children younger than 5 years are most commonly affected. Hand, foot, and mouth disease caused by enterovirus A71 is more severe and has a higher rate of complications than that attributed to other viruses such as coxsackievirus A16. Circulatory failure secondary to myocardial impairment and neurogenic pulmonary edema secondary to brainstem damage are the main causes of death. Fortunately, the disease is usually benign and resolves in 7 to10 days without sequelae. Given the self-limited nature of most cases, treatment is mainly symptomatic and supportive. Intravenous immunoglobulin should be considered for the treatment of severe/complicated hand, foot, and mouth disease and has been recommended by several national and international guideline committees. Currently, there are no specific antiviral agents approved for the treatment of the disease. Drugs such as ribavirin, suramin, mulberroside C, aminothiazole analogs, and sertraline have emerged as potential candidates for treatment of hand, foot, and mouth disease. Vaccination of susceptible individuals in high-risk areas and good personal hygiene are important preventative measures to combat the disease.Conclusion:Familiarity of the disease including its atypical manifestations is crucial so that a correct diagnosis can be made, and appropriate treatment initiated. A timely diagnosis can help avoid contact with the affected individual and decrease the risk of an outbreak.
Computational Studies of Allylpyrocatechol from Piper betle L. as Inhibitor Against Superoxide Dismutase, Catalase, and Glutathione peroxidase as Antioxidant Enzyme
Authors: Tumilaar Sefren Geiner , Hutabarat Geofanny Sarah , Hardianto Ari , Kurnia Dikdik 
Published: October 2022

Background:The most significant antioxidant enzymes are glutathione peroxidase (GSHPx), catalase (CAT), and superoxide dismutase (SOD) have a significant role in the scavenging of free radicals, but overexpressing of these enzymes can have deleterious effects. Therefore, compounds outside the body must suppress this enzyme's growth rate. Several previous studies have stated that Piper betle L. has high antioxidants and inhibits enzyme activity, including allypyrocatechol.Objectives:The current study aimed to evaluate the molecular mechanism of allylpyrocatecachol with SOD, CAT, and GSHPx and determine the lead compounds' potential against some antioxidant enzymes by an in silico approach.Methods:Allylpyrocatechol was docked to SOD, CAT, and GSHPx enzyme using Autodock4 tools. An evaluation of receptor-ligand interactions was conducted based on comparing binding affinity, the accuracy of involved amino acid residues, and gallic acid as a positive control ligand.Results:By in silico analysis showed that the binding affinity between the ligand and the three receptors were -4.3, -6.8, and -4.5 kcal/mol for the SOD, CAT, and GHSPx receptors, respectively.Conclusion:This finding indicates that Allylpyrocatechol has a promising candidate as a compound to inhibit antioxidant enzyme activity. It can be seen from the accuracy of the amino acids residue involved and the value of the binding affinity compared to the positive control ligand.
Mini-Review on Analytical Methods Applied for Analysis and Characterization
of Sericin
Authors: Kanoujia Jovita , Dubey Rudrakshi , Debgharia Sumana , Sisodia Priyanjali , Mohanalakshmi Sabapathi , Bhatt Shvetank , Parashar Poonam , Kishore Ankita 
Published: October 2022

Abstract:
Sericin is a serine-rich polydispersed glycoprotein found in Bombyx mori's cocoons. Sericin is
extracted from cocoons as a protein, composed of amino acids like aspartic acid, glycine, tyrosine, serine,
and glutamic acid with carboxyl, hydroxyl, and an amino group. Sericin has been explored for various
pharmacological activities, such as antioxidant, anti-inflammatory, antiapoptotic, antiproliferative, antibacterial,
anti-hypercholesteremia, and wound healing activity. Moreover, sericin has also been explored
as a biopolymer for the preparation of nanoparticles, scaffolds, hydrogels, films, etc. This mini-review
illustrates the reported methods for the characterization of extracted sericin and quantification in pharmaceutical
formulations. The review covers analytical methods like UV-Visible Spectroscopy, Fouriertransform
infrared spectroscopy, amino acid analysis, mass spectroscopy, and high-performance liquid
chromatography with a brief explanation of every analytical method.
Cost-effectiveness of Internet Interventions Compared With Treatment as Usual for People With Mental Disorders: Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Rohrbach Pieter J , Dingemans Alexandra E , Evers Catharine , Van Furth Eric F , Spinhoven Philip , Aardoom Jiska J , Lähde Irene , Clemens Fleur C , Van den Akker-Van Marle M Elske 
Published: October 2022

Background
The economic costs of mental disorders for society are huge. Internet-based interventions are often coined as cost-effective alternatives to usual care, but the evidence is mixed.

Objective
The aim was to review the literature on the cost-effectiveness of internet interventions for mental disorders compared with usual care and to provide an estimate of the monetary benefits of such interventions compared with usual care.

Methods
A systematic review and meta-analysis of randomized controlled trials was conducted, which included participants with symptoms of mental disorders; investigated a telephone- or internet-based intervention; included a control condition in the form of treatment as usual, psychological placebo, waiting list control, or bibliotherapy; reported outcomes on both quality of life and costs; and included articles published in English. Electronic databases such as PubMed (including MEDLINE), Embase, Emcare, PsycINFO, Web of Science, and the Cochrane Library were used. Data on risk of bias, quality of the economic evaluation, quality-adjusted life years, and costs were extracted from the included studies, and the incremental net benefit was calculated and pooled.

Results
The search yielded 6226 abstracts, and 37 studies with 14,946 participants were included. The quality of economic evaluations of the included studies was rated as moderate, and the risk of bias was high. A random-effects approach was maintained. Analyses suggested internet interventions were slightly more effective than usual care in terms of quality-adjusted life years gain (Hedges g=0.052, 95% CI 0.010-0.094; P=.02) and equally expensive (Hedges g=0.002, 95% CI −0.080 to 0.84; P=.96). The pooled incremental net benefit was US $255 (95% CI US $91 to US $419; P=.002), favoring internet interventions over usual care. The perspective of the economic evaluation and targeted mental disorder moderated the results.

Conclusions
The findings indicate that the cost-effectiveness of internet interventions for mental disorders compared with a care-as-usual approach is likely, but generalizability to new studies is poor given the substantial heterogeneity. This is the first study in the field of mental health to pool cost-effectiveness outcomes in an aggregate data meta-analysis.

Trial Registration
PROSPERO CRD42019141659; https://tinyurl.com/3cu99b34
Young People’s Trust in Cocreated Web-Based Resources to Promote Mental Health Literacy: Focus Group Study
Authors: Ito-Jaeger Sachiyo , Perez Vallejos Elvira , Logathasan Saruka , Curran Thomas , Crawford Paul 
Published: October 2022

Background
There is a pressing need to create resources to promote mental health literacy among young people. Digital media is one of the methods that can be used to successfully promote mental health literacy. Although digital mental health resources are generally favorably perceived by young people, one of the essential factors in whether they choose to use these interventions is trust.

Objective
The objective of this study was to explore young people’s trust-related concerns about and recommendations for the cocreated mental health website “What’s Up With Everyone” by using TrustScapes. Our aim was to use the findings to improve the trustworthiness of the website and to inform future creators of web-based mental health resources.

Methods
In total, 30 young people (mean age 19, SD 1.509; range 17-21 years) participated in TrustScapes focus groups. Thematic analysis was carried out to analyze both the TrustScapes worksheets and audio transcripts.

Results
Qualitative analysis revealed that the mental health website contains elements perceived to be both trustworthy and untrustworthy by young people. The relatable and high-quality design, which was achieved by cocreating the website with a team of design professionals and young people, was considered to increase trust. Creators’ credibility also positively affected trust, but the logos and other information about the creators were recommended to be more salient for users. Suggestions were made to update the privacy policy and cookie settings and include communication functions on the platform to improve the trustworthiness of the website.

Conclusions
Factors perceived to be trustworthy included the website's relatable, high-quality design and creators’ credibility, whereas those perceived to be untrustworthy included the privacy policy and cookie settings. The findings highlighted the significance of collaborating with end users and industrial partners and the importance of making the trust-enabling factors salient for users. We hope that these findings will inform future creators of web-based mental health resources to make these resources as trustworthy and effective as possible.