bluuebunny/crossref_metadata_2025 huggingface dataset:
A Network Pharmacology‐Based Identification Study on the Mechanism of Xiao‐Xu‐Ming Decoction for Cerebral Ischemic Stroke
Authors: Li De-Hui , Su Yi-Fan , Sun Chun-Xia , Fan Huan-Fang , Gao Wei-Juan
Published: October 2020

Objective. We used the network pharmacological analysis method to explore the mechanism of multicomponent, multitarget, and multiway actions of Xiao‐Xu‐Ming decoction (XXMD) for cerebral ischemic stroke (CIS), which provided a basis on the research of innovative drugs. Method. We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) to retrieve the active ingredients and targets of 12 herbs of XXMD; we used the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information (NCBI) to screen for differentially expressed genes in CIS to obtain the disease targets of CIS and to intersect it with the action targets of XXMD, and then the target drug efficacy is obtained. We used Cytoscape 3.6 software to construct the drug‐active ingredient‐action target interaction network of XXMD to treat CIS and conduct protein‐protein interaction (PPI) network and topology analysis. The action target Gene Ontology (GO) biological processes and metabolic pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) of XXMD to treat CIS were enrichment analyzed with R software. Result. We screened out 226 active ingredients and 3646 action targets for XXMD. Among them, XXMD to treat CIS has 144 active ingredients, 12 targets, and proteins in the core network of PPI having STAT3, HIF1A, etc. Pathway enrichment analysis was based on the GO and KEGG biological processes involved in active oxygen metabolism, smooth muscle cell proliferation, cytokine production, angiogenesis, redox coenzyme metabolism, and oxidative stress. The main action processes are significantly associated with CIS signal pathways involved in microRNAs, ovarian steroid hormones, NF‐кB signaling pathway, Th17 cell differentiation pathway, HIF‐1 signaling pathway, folic acid synthesis pathway, galactose metabolism, and fructose and mannose metabolism. Conclusion. This study initially clarified the main targets and pathways of XXMD in the treatment of CIS, which can lay the foundation for further research on its pharmacological effects.
Mechanistic Insight on the Interaction between OPN and Integrin ανβ3 in Osteoarthritis
Authors: Yuan Yuhao , Liu Qing , Wu Ziyi , Luo Wei
Published: October 2020

Osteoarthritis (OA) is a joint disease characterized by cartilage degeneration. Osteopontin (OPN) is involved in the initiation, repair, and maintenance of metabolic homeostasis in normal articular cartilage. This study investigated the role of OPN and its interaction with the integrin ανβ3 receptor in the expression of hyaluronic acid (HA) in OA chondrocytes. Overexpression of OPN significantly increased the expression of integrin ανβ3 and hyaluronic acid synthases (HAS) and synthesis of HA. Depleting OPN in OA chondrocytes showed the opposite trend for integrin alpha;νβ3, HAS, and HA. Nonspecifically and specifically blocking integrin receptor using GRGDSP and integrin ανβ3 antibody downregulated HAS and HA; both were inhibited to similar extents. The expression of HAS and HA was predominantly regulated by the interaction between OPN and integrin ανβ3. Taken together, we have delineated the importance of the OPN/integrin ανβ3/HAS/HA axis in OA and identified OPN as a promising candidate for molecular therapy for use in patients with OA.
ATP‐Sensitive Potassium Channels Mediate the Cardioprotective Effect of Panax notoginseng Saponins against Myocardial Ischaemia–Reperfusion Injury and Inflammatory Reaction
Authors: Ning Ke , Jiang Li , Hu Ting , Wang Xingyu , Liu Aihua , Bao Yimin
Published: October 2020

Inflammatory response during myocardial ischemia reperfusion injury (MIRI) is essential for cardiac healing, while excessive inflammation extends the infarction and promotes adverse cardiac remodeling. Understanding the mechanism of these uncontrolled inflammatory processes has a significant impact during the MIRI therapy. Here, we found a critical role of ATP‐sensitive potassium channels (KATP) in the inflammatory response of MIRI and its potential mechanism and explored the effects of Panax Notoginseng Saponins (PNS) during this possess. Rats underwent 40 min ischemia by occlusion of the left anterior descending (LAD) coronary artery and 60 min of reperfusion. PNS was treated at the corresponding time point before operation; 5‐hydroxydecanoate (5‐HD) and glybenclamide (Gly) (or Nicorandil (Nic)) were used as pharmacological blocker (or nonselective opener) of KATP. Cardiac function and pathomorphology were evaluated and a set of molecular signaling experiments was tested. KATP current density was measured by patch‐clamp. Results revealed that in MIRI, PNS pretreatment restored cardiac function, reduced infarct size, and ameliorated inflammation through KATP. However, inhibiting KATP by 5‐HD and Gly significantly reversed the effects, including NLRP3 inflammasome and inflammatory mediators IL‐6, MPO, TNF‐α, and MCP‐1. Moreover, PNS inhibited the phosphorylation and nuclear translocation of NF‐κB in I/R myocardium when the KATP was activated. Importantly, PNS promoted the expression of subunits and activation of KATP. The study uncovered KATP served as a new potential mechanism during PNS modulating MIRI‐induced inflammation and promoting injured heart recovery. The manipulation of KATP could be a potential therapeutic approach for MIRI and other inflammatory diseases.
Mesenteric Lymph Duct Drainage Attenuates Lung Inflammatory Injury and Inhibits Endothelial Cell Apoptosis in Septic Rats
Authors: Liu Yongjun , Chen Chuanxi , Sun Qing , Sun Huadong , Liu Ning , Liu Qier , Ma Jie , Wang Pingping , Hu Chunlin , Wu Jianfeng , Ouyang Bin , Chen Juan , Chen Minying , Guan Xiangdong
Published: October 2020

The present study was to investigate the effect of mesenteric lymph duct drainage on lung inflammatory response, histological alteration, and endothelial cell apoptosis in septic rats. Animals were randomly assigned into four groups: control, sham surgery, sepsis, and sepsis plus mesenteric lymph drainage. We used the colon ascendens stent peritonitis (CASP) procedure to induce the septic model in rats, and mesenteric lymph drainage was performed with a polyethylene (PE) catheter inserted into mesenteric lymphatic. The animals were sacrificed at the end of CASP in 6 h. The mRNA expression levels of inflammatory mediators were measured by qPCR, and the histologic damage were evaluated by the pathological score method. It was found that mesenteric lymph drainage significantly reduced the expression of TNF‐α, IL‐1β, and IL‐6 mRNA in the lung. Pulmonary interstitial edema and infiltration of inflammatory cells were alleviated by mesenteric lymph drainage. Moreover, increased mRNA levels of TNF‐α, IL‐1β, IL‐6 mRNA, and apoptotic rate were observed in PMVECs treated with septic lymph. These results indicate that mesenteric lymph duct drainage significantly attenuated lung inflammatory injury by decreasing the expression of pivotal inflammatory mediators and inhibiting endothelial apoptosis to preserve the pulmonary barrier function in septic rats.
Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking
Authors: Yin Bei , Bi Yi-Ming , Fan Guan-Jie , Xia Ya-Qing
Published: October 2020

Background. Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Methods. Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. Results. There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Conclusion. Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.
Silver, Gold, and Silver-Gold Bimetallic Nanoparticle-Decorated Dextran: Facile Synthesis and Versatile Tunability on the Antimicrobial Activity
Authors: Diem Phan Nu Ha , Phuong Ton Nu My , Hien Nguyen Quoc , Quang Duong Tuan , Hoa Tran Thai , Cuong Nguyen Duc
Published: October 2020

The noble metal-based nanoparticles (NPs) have been considered as potential antimicrobial agents because of their good antibacterial and antifungal activities as well as biocompatible nature. In this study, we have introduced a simple and fast route to synthesize silver, gold, and silver-gold bimetallic NP-decorated dextran. The as-synthesized noble metal-based NPs with spherical geometry showed high dispersity in dextran. The antibacterial and antifungal of obtained nanomaterials were tested with Xanthomonas oryzae pv. oryzae (Xoo) bacteria and Magnaporthe grisea (M. grisea) fungi. The silver NPs and bimetallic NPs with high silver content in dextran exhibited excellent activity to inhibited the growth of the bacteria and fungi, whereas the gold/dextran has weak antimicrobial effects. The antibacterial and antifungal properties of silver-gold bimetallic NPs in dextran biopolymer can be tuned according to the content of silver in the bimetallic NPs. The obtained nanomaterials could open an entry to a new class of antibiotics.
Identification of Differential Intestinal Mucosa Transcriptomic Biomarkers for Ulcerative Colitis by Bioinformatics Analysis
Authors: Cheng Fang , Li Qiang , Wang Jinglin , Zeng Fang , Wang Kaiping , Zhang Yu
Published: October 2020

Background. Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affect mucosal homeostasis and triggers inappropriate immune response. The purpose of the study was to identify significant biomarkers with potential therapeutic targets and the underlying mechanisms. Methods. The gene expression profiles of GSE48958, GSE73661, and GSE59071 are from the GEO database. Differentially expressed genes (DEGs) were screened by the GEO2R tool. Next, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then, protein-protein interaction (PPI) was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Results. There were a total of 128 common DEGs genes, including 86 upregulated genes enriched in extracellular space, regulation of inflammatory response, chemokine-mediated signaling pathway, response to lipopolysaccharide, and cell proliferation, while 42 downregulated genes enriched in the integral component of the membrane, the integral component of the plasma membrane, apical plasma membrane, symporter activity, and chloride channel activity. The KEGG pathway analysis results demonstrated that DEGs were particularly enriched in cytokine-cytokine receptor interaction, TNF signaling pathway, chemokine signaling pathway, pertussis, and rheumatoid arthritis. 18 central modules of the PPI networks were selected with Cytotype MCODE. Furthermore, 18 genes were found to significantly enrich in the extracellular space, inflammatory response, chemokine-mediated signaling pathway, TNF signaling pathway, regulation of cell proliferation, and immune response via reanalysis of DAVID. Conclusion. The study identified DEGs, key target genes, functional pathways, and pathway analysis of UC, which may provide potential molecular targets and diagnostic biomarkers for UC.
How Does Endothelial Permeability Affect the Development of Juvenile Idiopathic Arthritis? Vascular Endothelial Cadherin as a Promising New Tool Helpful in the Diagnostic Process
Authors: Orczyk Krzysztof , Smolewska Elzbieta
Published: October 2020

Introduction. Vascular endothelial cadherin (VE-cadherin) is a calcium-dependent protein essential for stabilization of the adherens junctions of the endothelial cells. Through vasculogenic mimicry, VE-cadherin may influence angiogenesis in synovial fibroblast-like cells. The soluble extracellular domain of VE-cadherin may be considered an indicator of endothelial dysfunction. Its potential as a diagnostic biomarker in rheumatic diseases, including juvenile idiopathic arthritis (JIA), needs to be investigated. Materials and Methods. The study group included 80 patients diagnosed with JIA. In 53 individuals, blood samples were obtained twice with an average interval of

102.4
±
4.6

days. Results from the study group were compared to 29 age- and sex-matched healthy children. Results. Serum levels of VE-cadherin were significantly higher in JIA patients than in healthy controls. In such comparison, VE-cadherin had 87.5% sensitivity and 69.0% specificity for the cutoff level 4.36 ng/ml (Youden index 0.56, area under the curve 0.724). VE-cadherin concentrations negatively correlated with the disease activity score. However, such finding may be a false result because of the downregulation of VE-cadherin induced by glucocorticosteroids. Conclusions. VE-cadherin may become a promising diagnostic biomarker of early stages of JIA. Its predictive significance may be decreased by utilization of glucocorticosteroids. A multicentre study including patients with other arthritides is recommended for further evaluation of this protein.
Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction
Authors: Packer Milton , Anker Stefan D. , Butler Javed , Filippatos Gerasimos , Ferreira João Pedro , Pocock Stuart J. , Carson Peter , Anand Inder , Doehner Wolfram , Haass Markus , Komajda Michel , Miller Alan , Pehrson Steen , Teerlink John R. , Brueckmann Martina , Jamal Waheed , Zeller Cordula , Schnaidt Sven , Zannad Faiez ,   For the EMPEROR-Reduced Trial Committees and Investigators
Published: October 2020

Background:

Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure.

Methods:

We randomly assigned 3730 patients with class II to IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite end points.

Results:

Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 versus 519 patients; empagliflozin versus placebo, respectively; hazard ratio [HR], 0.76; 95% CI, 0.67–0.87;
P
<0.0001). This benefit reached statistical significance at 12 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (HR, 0.67; 95% CI, 0.50–0.90;
P
=0.008) and that required a vasopressor or positive inotropic drug or mechanical or surgical intervention (HR, 0.64; 95% CI, 0.47–0.87;
P
=0.005). As compared with placebo, fewer patients in the empagliflozin group reported intensification of diuretics (297 versus 414 [HR, 0.67; 95% CI, 0.56–0.78;
P
<0.0001]). Additionally, patients assigned to empagliflozin were 20% to 40% more likely to experience an improvement in New York Heart Association functional class and were 20% to 40% less likely to experience worsening of New York Heart Association functional class, with statistically significant effects that were apparent 28 days after randomization and maintained during long-term follow-up. The risk of any inpatient or outpatient worsening heart failure event in the placebo group was high (48.1 per 100 patient-years of follow-up), and it was reduced by empagliflozin (HR, 0.70; 95% CI, 0.63–0.78;
P
<0.0001).

Conclusions:

In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03057977.
A Model of Online Temporal-Spatial Integration for Immediacy and Overrule in Discourse Comprehension
Authors: Uchida Takahisa , Lair Nicolas , Ishiguro Hiroshi , Dominey Peter Ford
Published: October 2020

During discourse comprehension, information from prior processing is integrated and appears to be immediately accessible. This was remarkably demonstrated by an N400 for “salted” and not “in love” in response to “The peanut was salted/in love.” Discourse overrule was induced by prior discourse featuring the peanut as an animate agent. Immediate discourse overrule requires a model that integrates information at two timescales. One is over the lifetime and includes event knowledge and word semantics. The second is over the discourse in an event context. We propose a model where both are accounted for by temporal-to-spatial integration of experience into distributed spatial representations, providing immediate access to experience accumulated over different timescales. For lexical semantics, this is modeled by a word embedding system trained by sequential exposure to the entire Wikipedia corpus. For discourse, this is modeled by a recurrent reservoir network trained to generate a discourse vector for input sequences of words. The N400 is modeled as the difference between the instantaneous discourse vector and the target word. We predict this model can account for semantic immediacy and discourse overrule. The model simulates lexical priming and discourse overrule in the “Peanut in love” discourse, and it demonstrates that an unexpected word elicits reduced N400 if it is generally related to the event described in prior discourse, and that this effect disappears when the discourse context is removed. This neurocomputational model is the first to simulate immediacy and overrule in discourse-modulated N400, and contributes to characterization of online integration processes in discourse.
At the Nexus of Refugee and Labour Migration: US Refugee Policy Formulation after the Second World War
Authors: Wasem Ruth Ellen
Published: October 2020

After the Second World War, liberal reformers in the US Congress pushed refugee legislation and included refugee provisions in their immigration reform bills. Presidents Harry Truman and Dwight Eisenhower were among those who urged Congress to enact refugee legislation. Without a statutory pathway for persons entering as refugees or asylees to become lawful permanent residents (lprs), refugee admissions were reactive. Some presidents would draw on other executive authorities to bring refugees into the United States, relying on Congress to subsequently enact laws providing lpr status. In other instances, Congress would enact refugee legislation aimed at specific populations and limited numbers. As a result, refugee policy was handled in a piecemeal and incremental fashion during this period. It is within this context that this article explores the nexus of refugee and labour migration policies and the role the nativist right-wing political leaders played in shaping US policy in this period.
1. In the beginning...
Authors: Robertson Stephen
Published: October 2020

This chapter discusses what is meant by both technology and information, and goes on to discuss briefly the origins of language and of writing. The meat of the chapter is about the development of the alphabet as a system of writing, and the build-up to this development, indicating why it is such a special and important, though not obvious, invention. Then, the author moves on to the Arabic numbers, which is a roughly equivalent system of writing numbers, equally unobvious and equally important.
Two Different Tracts and Origin of Pyriform Sinus Fistula
Authors: Sakakura Koichi , Yasuoka Yoshihito , Shino Masato , Toyoda Minoru , Obi Kisho , Chikamatsu Kazuaki
Published: October 2020

Objective:

Suppurative acute thyroiditis is caused by pyriform sinus fistula (PSF), and PSF frequently elicits deep neck abscess. However, complete fistulectomy is the ideal management of PSF, and studies on surgical findings of PSF are exceedingly rare. This study aimed to reveal the origins of PSF, each route, and clinical presentation.

Methods:

This is a multicenter study. We have conducted 19 complete fistulectomies of PSF in Japan, analyzed routes of the fistulas, estimated the origins, and investigated their histological and clinical findings.

Results:

No recurrence was observed in all cases. Five of 12 cases showed thymic and/or parathyroid tissues around the fistulas, passing inside the inferior horn of thyroid cartilage, were regarded as having 3rd pouch origin, and tended to have low frequency of severe deep neck abscess. The remaining 7 cases originated from the 4th pouch running outside of the horn and showed frequent severe infection.

Conclusion:

PSF have 2 different routes depending on their generation and may present different clinical manifestations.
Understanding social adversity and stress and mood symptoms: The Bayesian network approach
Authors: Ding Cody
Published: October 2020

Social adversity events commonly occur in our daily lives. However, an individual’s perception of social adversity experienced may be more important than actual events in impacting an individual’s psychological functioning and reactions. In the current study, we examined how individuals’ perception of social adversity events they experienced is associated with their traumatic stress symptoms as well as mood and anxiety symptoms using the Bayesian network model. The findings indicated that individuals with a perception of social adversity events as traumatic and frequent showed an increase in the probability of displaying a high level of posttraumatic stress symptoms.
Citizen Contacting in Response to Crisis: Voicing Grievances to the Consumer Financial Protection Bureau
Authors: Gimpel James G.
Published: October 2020

The Consumer Financial Protection Bureau (CFPB) came into being in response to the housing and debt crisis that accompanied the Great Recession. Created as a means for aggrieved consumers to bring problems to the attention of federal regulators empowered to fine banking and finance companies, the inflow of complaints began late in 2010 and has steadily risen in the years since. This research examines the variable emergence of complaints across 5 years, asking what types of constituencies are most likely to register grievances with the CFPB. The filing of complaints is mostly responsive to the presence of middle and upper income populations with mortgages, though contacts are also high from African American neighborhoods. Government contacting among lower income populations is facilitated by the presence of counseling and consultative services at the grassroots. Notably, legal aid services often present in lower and moderate income neighborhoods are associated with higher complaint frequency for several financial products. Through street-level consultative organizations, the gap in government service provision separating the affluent, who complain on their own, and less privileged, who do not know where to express their grievances, can be reduced.
A Prospective Multicenter Clinical Performance Evaluation of the C-CGM System
Authors: Rebec Mihailo , Cai Kevin , Dutt-Ballerstadt Ralph , Anderson Ellen
Published: October 2020

Background:

Continuous glucose monitors (CGMs) have had a significant impact on the management of diabetes mellitus. We present the results of a multinational evaluation of the Cascade CGM (“C-CGM”) over 14 days of in-clinic and home use.

Method:

Each of the 57 enrolled type 1 diabetes mellitus and type 2 diabetes mellitus subjects wore 2 C-CGMs on the abdomen for 14 days. One part of the evaluation was the performance versus reference glucose values generated for 12 -hour in-clinic sessions on days 1, 4, 7, 10, and 14. Glucose blood samples were drawn every 15 minutes and analyzed with the Yellow Spring Instruments (YSI) 2300 glucose analyzer. The performance assessment on in-clinic days was based on paired YSI/CGM data points and on home-use days was based on paired fingerstick BGM (blood glucose monitoring)/CGM data points.

Results:

A total of 17 823 CGM/YSI data points during in-clinic use was analyzed. The mean absolute relative difference for glucose values between 100 and 400 mg/dL (MARD) and mean absolute difference for values between 40 and 100 mg/dL (MAD) were 11.5% and 15.1 mg/dL, respectively. The system accuracy during home use was 12.7% and 15 mg/dL for MARD and MAD, respectively. There were no serious adverse events or infectious complications reported. A modified algorithm “Hybrid Algorithm” was used in a prospective analysis of the in-clinic data, resulting in a MARD of 9.9% and MAD of 14.5 mg/dL.

Conclusions:

The performance of the C-CGM device over 14 days meets the safety and efficacy standards of CGM systems for managing blood glucose levels in people with diabetes. This was further confirmed when the C-CGM system was given approval for CE Mark in October 2019.
Techno-solutionism and the standard human in the making of the COVID-19 pandemic
Authors: Milan Stefania
Published: October 2020

Quantification is particularly seductive in times of global uncertainty. Not surprisingly, numbers, indicators, categorizations, and comparisons are central to governmental and popular response to the COVID-19 pandemic. This essay draws insights from critical data studies, sociology of quantification and decolonial thinking, with occasional excursion into the biomedical domain, to investigate the role and social consequences of counting broadly defined as a way of knowing about the virus. It takes a critical look at two domains of human activity that play a central role in the fight against the virus outbreak, namely medical sciences and technological innovation. It analyzes their efforts to craft solutions for their user base and explores the unwanted social costs of these operations. The essay argues that the over-reliance of biomedical research on “whiteness” for lab testing and the techno-solutionism of the consumer infrastructure devised to curb the social costs of the pandemic are rooted in a distorted idea of a “standard human” based on a partial and exclusive vision of society and its components, which tends to overlook alterity and inequality. It contends that to design our way out of the pandemic, we ought to make space for distinct ways of being and knowing, acknowledging plurality and thinking in terms of social relations, alterity, and interdependence.
Associations Between Fear of Missing Out, Problematic Smartphone Use, and Social Networking Services Fatigue Among Young Adults
Authors: Tugtekin Ufuk , Barut Tugtekin Esra , Kurt Adile Aşkım , Demir Kadir
Published: October 2020

In this study, we aimed to adapt the Information and communication technology (ICT) Overload and social networking service (SNS) Fatigue Scale to measure the overload and SNSs fatigue experienced by individuals while using ICTs in the Turkish language and analyze the adapted scale based on various variables. The scale adaptation procedure was conducted by surveying 225 undergraduate-level university students. In addition to discriminant and convergent reliability, the general fitness index parameters were compared with confirmatory factor analysis (CFA), and the model results were found in accordance with the acceptable fitness index criteria, with clarification as a complete model in all sub-dimensions. The relationships between fear of missing out (FoMO), problematic smartphone use (PSU), and SNSs Fatigue levels of the participants were also investigated. The adapted scale was then applied to 469 participants. The findings demonstrated that there was a significant difference between PSU and SNS Fatigue levels of participants based on gender, favoring females. It was also revealed that the variables of interest FoMO and SNS Fatigue together predicted the PSU.
Doxorubicin and subsequent risk of cardiovascular diseases among survivors of diffuse large B-cell lymphoma in Hong Kong
Authors: Lee Shing Fung , Luque-Fernandez Miguel Angel , Chen Yu Hui , Catalano Paul J. , Chiang Chi Leung , Wan Eric Yuk-Fai , Wong Ian Chi-Kei , Chen Ming Hui , Ng Andrea K.
Published: October 2020

Evidence regarding the dose-related impact of doxorubicin on subsequent cardiovascular diseases (CVDs) in Asian patients with diffuse large B-cell lymphoma (DLBCL) without preexisting CVDs is lacking. From a territory-wide electronic database in Hong Kong, we identified adults who were diagnosed with DLBCL and treated with chemotherapy between 2000 and 2018. We evaluated the patients for incident CVDs (including ischemic heart disease, heart failure, and cardiomyopathy). We evaluated the cause-specific cumulative incidence (csCI) of CVD with levels of doxorubicin exposure by using flexible parametric competing risk analysis and adjusting for demographics, comorbidities, therapeutic exposure, cardiovascular risk factors, and lifestyle factors. Controls were age- and sex-matched to DLBCL patients. We analyzed 2600 patients and 13 000 controls. The adjusted cause-specific hazard ratio (HR) for CVD in patients treated with >500 mg doxorubicin compared with non-doxorubicin regimens was 2.65 (95% confidence interval [CI], 1.23-5.74; P = .013). The 5-, 10-, and 15-year csCIs were 8.2%, 11.3%, and 12.8% in patients vs 3.1%, 4.4%, and 5.2% in controls, respectively. Hypertension (HR, 6.20; 95% CI, 0.79-48.44; P = .082) and use of aspirin/angiotensin-converting enzyme inhibitor/beta-blocker at baseline (HR, 2.13-4.63; P < .001 to .002) might confer a higher risk of subsequent CVDs. In this Hong Kong population-based study, doxorubicin exposure (absolute dose >500 mg), together with hypertension or baseline use of medication for cardiovascular risk factors, was found to be associated with an increase in csCIs of CVDs. Tailoring therapeutic strategies to underlying CVD risk factors and risk-adapted monitoring and follow-up of susceptible DLBCL patients are advisable.
DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma
Authors: Menzies-Gow Andrew , Ponnarambil Sandhia , Downie John , Bowen Karin , Hellqvist Åsa , Colice Gene
Published: October 2020

Background

Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies.

Methods

DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated.

Discussion

DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma.

Trial registration

NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.
Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study
Authors: Sonnweber Thomas , Boehm Anna , Sahanic Sabina , Pizzini Alex , Aichner Magdalena , Sonnweber Bettina , Kurz Katharina , Koppelstätter Sabine , Haschka David , Petzer Verena , Hilbe Richard , Theurl Markus , Lehner Daniela , Nairz Manfred , Puchner Bernhard , Luger Anna , Schwabl Christoph , Bellmann-Weiler Rosa , Wöll Ewald , Widmann Gerlig , Tancevski Ivan , Judith-Löffler-Ragg  , Weiss Günter
Published: October 2020

Background

Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology.

Methods

We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing.

Results

We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia.

Discussion

Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19.

Trial registration

ClinicalTrials.gov number: NCT04416100.
Distinct genomic subclasses of high-grade/progressive meningiomas: NF2-associated, NF2-exclusive, and NF2-agnostic
Authors: Williams Erik A. , Santagata Sandro , Wakimoto Hiroaki , Shankar Ganesh M. , Barker Fred G. , Sharaf Radwa , Reddy Abhinav , Spear Phoebe , Alexander Brian M. , Ross Jeffrey S. , Brastianos Priscilla K. , Cahill Daniel P. , Ramkissoon Shakti H. , Juratli Tareq A.
Published: October 2020

Background

Genomic studies of high-grade/progressive meningiomas have reported a heterogeneous mutation spectrum, identifying few recurrently mutated genes. Most studies have been underpowered to detect genomic subclasses of aggressive meningiomas due to relatively small number of available samples. Here, we present a genomic survey of one of the largest multi-institutional cohorts of high-grade/progressive meningiomas to date.

Methods

850 high-grade/progressive meningiomas, including 441 WHO grade 2 and 176 WHO grade 3 meningiomas and 220 progressive WHO grade 1 meningiomas, were tested as part of a clinical testing program by hybridization capture of 406 cancer-related genes to detect base substitutions, indels, amplifications, deletions, and rearrangements. Information from pathology reports, histopathology review, and patient clinical data was assessed.

Results

Genomic analyses converged to identify at least three distinct patterns of biologically-aggressive meningiomas. The first and most common contained NF2-mutant tumors (n = 426, 50%), was associated with male sex (64.4% %, p = 0.0001) and often harbored additional mutations in CDKN2A/B (24%), and the chromatin regulators ARID1A (9%), and KDM6A (6%). A second group (NF2-agnostic) featured TERT promoter (TERTp; n = 56) or TP53 mutations (n = 25) and were either NF2-mutant or wild-type, and displayed no association with either sex (p = 0.39). The remaining group generally lacked NF2 mutations, and accounted for 40% of the cases—with three subgroups. One consistent primarily of grade 3 lesions harboring alterations in chromatin regulators BAP1 (n = 22) or PBRM1 (n = 16). A second subgroup contained AKT1 (n = 26), PIK3CA (n = 14) and SMO (n = 7) mutant skull-based meningiomas, and a third mixed subgroup included 237 meningiomas with a heterogeneous spectrum of low frequency and non-recurrent alterations.

Conclusions

Our findings indicate that the patterns of genomic alterations in high-grade/progressive meningiomas commonly group into three different categories. The most common NF2-associated canonical group frequently harbored CDKN2A/B alterations, which is potentially amenable to targeted therapies. An NF2-agnostic group harbored frequent TERTp and TP53 mutations. The final subclass, distinct from the canonical NF2 mutant associated pathway, was partly characterized by BAP1/PBRM1 alterations (rhabdoid/papillary histology) or skull-base disease. Overall, these data increase our understanding of the pathobiology of high-grade/progressive meningiomas and can guide the design of clinical trials.

IRB approval status

Reviewed and approved by Western IRB; Protocol No. 20152817.
Altered interoception in patients with borderline personality disorder: a study using heartbeat-evoked potentials
Authors: Flasbeck Vera , Popkirov Stoyan , Ebert Andreas , Brüne Martin
Published: October 2020

Background

Patients with borderline personality disorder (BPD) experience difficulties in emotional awareness (alexithymia), and often develop dissociative symptoms, which may reflect broader deficits in interoceptive awareness. Whether this is associated with alterations in cortical processing of interoception is currently unknown.

Methods

We utilized an electrophysiological marker of interoception, i.e. heartbeat-evoked potentials (HEP), and examined its relationship with electrocardiographic correlates of autonomic nervous system (ANS) functioning (heart rate variability), and with self-report measures of alexithymia, dissociation and borderline symptom severity in patients with BPD.

Results

Individuals with BPD had higher HEP amplitudes over frontal electrodes compared to healthy controls. Sympathetic ANS activity was greater in BPD patients than in controls. Across groups, HEP amplitudes were associated with parasympathetic activity over central electrodes and correlated with alexithymia over frontal electrodes.

Conclusions

These findings support the idea that difficulties in emotional awareness in BPD are reflected in altered frontal electrophysiological markers of interception. Therefore, emotional awareness can be understood as failures of modulation between interoceptive and exteroceptive attention. Future research may aim to investigate whether altered interoception and its electrophysiological correlates are malleable by therapeutic intervention.
Characterization of polyvinyl alcohol-borax/agarose (PVA-B/AG) double network hydrogel utilized for the cleaning of works of art
Authors: Al-Emam Ehab , Soenen Hilde , Caen Joost , Janssens Koen
Published: October 2020

Since cleaning of artworks may cause undesirable physicochemical alterations and is a nonreversible procedure, it is mandatory to adopt the proper cleaning procedure. Such a procedure should remove undesired materials whilst preserving the original surface. In this regard, numerous gels have been developed and exploited for the cleaning of various artwork surfaces. Lately, agarose (AG) and polyvinyl alcohol-borax (PVA-B) hydrogels have been widely employed as cleaning tools by conservators. Both hydrogels show some limitations in specific cleaning practices. In this work, we investigated the influence of including increased levels of agarose into PVA-B systems. For this reason, we performed a detailed characterization on the double network (DN) hydrogel including the chemical structure, the liquid phase retention, the rheological behavior, and the self-healing behavior of various PVA-B/AG double network hydrogels. These new hydrogels revealed better properties than PVA-B hydrogels and obviated their limitations. The inclusion of AG into PVA-B systems enhanced the liquid retention capacity, shape-stability, and mechanical strength of the blend. Furthermore, AG minimized the expelling/syneresis issue that occurs when loading PVA-B systems with low polarity solvents or chelating agents. The resultant double network hydrogel exhibits relevant self-healing properties. The PVA-B/AG double network is a new and useful cleaning tool that can be added to the conservators’ tool-kit. It is ideal for cleaning procedures dealing with porous and complex structured surfaces, vertical surfaces and for long time applications.
Association of meal timing with dietary quality in a Serbian population sample
Authors: Djuric Zora , Nikolic Marina , Zekovic Milica , Plegue Melissa , Glibetic Marija
Published: October 2020

Background

The world-wide adoption of Western lifestyles and eating patterns is associated with adverse effects on nutrient intakes. Here we evaluated the relationships between timing of meals and diet quality in Serbia, a Balkan country with a traditional eating pattern that includes the largest meal of the day as a late lunch.

Methods

A dietary survey was done in the Republic of Serbia using a nationally-representative sample of 74 children and 260 non-pregnant adults. Nutrient intakes were calculated from two 24-h recalls. A Dietary Quality Score (DQS) enumerated how many European Union (EU) Science Hub recommendations were met for fruit and vegetables, fiber, saturated fat, sodium, and sugar. We evaluated whether the timing of dietary intakes is associated with DQS and body mass index.

Results

The dietary intakes of children ages 10–17 and adults were similar and were high in total fat intake, with an average of 40% of energy from fat. Mean fruit and vegetable intakes of 473 g/day in adults exceeded the minimal EU recommendation. The most worrisome aspects of the Serbian diet were high intakes of saturated fat, sugar and sodium. Lunch was the meal with the highest mean content of energy, followed by breakfast and dinner, and the average time for lunch was 15:15. Consumption of a higher percentage of calories before 16:00 in adults was associated with higher fruit and vegetable intakes and with higher DQS. The subgroup of adults consuming their largest meal after 20:00 had a lower mean age, more men, and a larger percentage was employed outside of the home. There were no associations of meal timing with BMI, but the prevalence of obesity in this population sample was only 13%.

Conclusions

These results indicate that an earlier meal pattern, and especially consuming the largest meal of the day earlier in the day, was associated with better quality diets. Public health efforts are needed to preserve nutrient intakes as the population shifts away from the traditional Serbian eating pattern. Long-term, deterioration of nutrient intakes could contribute to the increasing rates of obesity that have been observed in Serbia and world-wide.