bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficiency of thrombospondin‐2 alleviates intimal hyperplasia in mice by modulating vascular smooth muscle cell proliferation and migration
Authors: Li Xu , Ding Yong , Zhou Min , Zhou Zhenyu , Xie Tianchen , Wang Yonggang , Liu Zhenjie , Si Yi , Shi Zhenyu 
Published: January 2023

AbstractThrombospondin‐2 (Tsp2), a glycoprotein in the extracellular matrix, plays a critical role in the maintenance of vascular homeostasis. However, its role in the pathogenesis of cardiovascular disorders such as intimal hyperplasia is not fully elucidated. This study, therefore, aims to explore the effect of Tsp2 on intimal hyperplasia and its associated underlying mechanisms. Intimal hyperplasia (IH) was established using a modified wire‐mediated femoral artery injury model. Immunofluorescence and qPCR identified upregulated Tsp2 expression in the injured femoral artery compared with the uninjured femoral artery. Similarly, TSP2 expression was also increased in human samples from the atherosclerotic femoral artery and colocalized with vascular smooth muscle cells (VSMCs). Compared with the wild‐type littermates, Tsp2 knockout mice displayed a mitigated IH in the injured femoral artery, as demonstrated by a decreased neointimal area and intimal/median ratio. Primary mouse VSMCs were cultured to explore the mechanism by which Tsp2 influenced IH in vitro. PDGF‐stimulated VSMCs presented an elevated Tsp2 expression and enhanced migration and proliferation. However, Tsp2 knockdown by siRNA blocked the increased migration and proliferation of VSMCs. Further analysis identified an association between Notch3 and IH when the intracellular domain of Notch3 (Nicd3) was upregulated in PDGF‐stimulated VSMCs and femoral arteries with IH in human tissues. Along with the overexpression and downregulation of Tsp2, the Nicd3 expression was also up and downregulated accordingly. Tsp2 was associated with IH and may serve as a therapeutic target for IH. Downregulation of Tsp2 could mitigate the progression of IH by modulating the proliferation and migration of VSMCs.
Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach
Authors: Piscitelli Joseph , Nikanjam Mina , Capparelli Edmund V. , Blaquera Chelsea L. , Penzak Scott R. , Nolin Thomas D. , Paine Mary F. , Ma Joseph D. 
Published: January 2023

Background:
Fexofenadine is a recommended in vivo probe drug for phenotyping P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3 transporter activities. This study evaluated a limited sampling strategy using a population pharmacokinetic approach to estimate plasma fexofenadine exposure as an index of P-gp and OATP activities.

Methods:
In a previous study, a single oral dose of fexofenadine (120 mg) was administered alone or in combination with grapefruit juice, Panax ginseng, or Echinacea purpurea to healthy adult participants. Serial plasma samples were collected up to 72 hours after administration and fexofenadine concentrations were measured. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling. Limited sampling models (LSMs) using single and 2-timepoint fexofenadine concentrations were compared with full profiles from intense sampling using empirical Bayesian post hoc estimations of systemic exposure derived from the population pharmacokinetic model. Predefined criteria for LSM selection and validation included a coefficient of determination (R2) ≥ 0.90, relative percent mean prediction error ≥ −5 to ≤5%, relative percent mean absolute error ≤ 10%, and relative percent root mean square error ≤ 15%.

Results:
Fexofenadine concentrations (n = 1520) were well described using a 2-compartment model. Grapefruit juice decreased the relative oral bioavailability of fexofenadine by 25%, whereas P. ginseng and E. purpurea had no effect. All the evaluated single timepoint fexofenadine LSMs showed unacceptable percent mean prediction error, percent mean absolute error, and/or percent root mean square error. Although adding a second time point improved precision, the predefined criteria were not met.

Conclusions:
Identifying novel fexofenadine LSMs to estimate P-gp and OATP1B1/3 activities in healthy adults for future transporter-mediated drug–drug interaction studies remains elusive.
5S rRNA pseudogene transcripts are associated with interferon production and inflammatory responses in alcohol-associated hepatitis
Authors: Wu Jianguo , Kim Adam , Wu Xiaoqin , Ray Semanti , Allende Daniela S. , Welch Nicole , Bellar Annette , Dasarathy Jaividhya , Dasarathy Srinivasan , Nagy Laura E. 
Published: January 2023

Background and Aims:
Interferon (IFN) signaling is critical to the pathogenesis of alcohol-associated hepatitis (AH), yet the mechanisms for activation of this system are elusive. We hypothesize that host-derived 5S rRNA pseudogene (RNA5SP) transcripts regulate IFN production and modify immunity in AH.

Approach and Results:
Mining of transcriptomic datasets revealed that in patients with severe alcohol-associated hepatitis (sAH), hepatic expression of genes regulated by IFNs was perturbed and gene sets involved in IFN production were enriched. RNA5SP transcripts were also increased and correlated with expression of type I IFNs. Interestingly, inflammatory mediators upregulated in sAH, but not in other liver diseases, were positively correlated with certain RNA5SP transcripts. Real-time quantitative PCR demonstrated that RNA5SP transcripts were upregulated in peripheral blood mononuclear cells (PBMCs) from patients with sAH. In sAH livers, increased 5S rRNA and reduced nuclear MAF1 (MAF1 homolog, negative regulator of RNA polymerase III) protein suggested a higher activity of RNA polymerase III (Pol III); inhibition of Pol III reduced RNA5SP expression in monocytic THP-1 cells. Expression of several RNA5SP transcript-interacting proteins was downregulated in sAH, potentially unmasking transcripts to immunosensors. Indeed, siRNA knockdown of interacting proteins potentiated the immunostimulatory activity of RNA5SP transcripts. Molecular interaction and cell viability assays demonstrated that RNA5SP transcripts adopted Z-conformation and contributed to ZBP1-mediated caspase-independent cell death.

Conclusions:
Increased expression and binding availability of RNA5SP transcripts was associated with hepatic IFN production and inflammation in sAH. These data identify RNA5SP transcripts as a potential target to mitigate inflammation and hepatocellular injury in AH.
Structural plasticity of axon initial segment in spinal cord neurons underlies inflammatory pain
Authors: Caspi Yaki , Mazar Michael , Kushnir Yishai , Mazor Yoav , Katz Ben , Lev Shaya , Binshtok Alexander M. 
Published: January 2023

Abstract
Physiological or pathology-mediated changes in neuronal activity trigger structural plasticity of the action potential generation site—the axon initial segment (AIS). These changes affect intrinsic neuronal excitability, thus tuning neuronal and overall network output. Using behavioral, immunohistochemical, electrophysiological, and computational approaches, we characterized inflammation-related AIS plasticity in rat's superficial (lamina II) spinal cord dorsal horn (SDH) neurons and established how AIS plasticity regulates the activity of SDH neurons, thus contributing to pain hypersensitivity. We show that in naive conditions, AIS in SDH inhibitory neurons is located closer to the soma than in excitatory neurons. Shortly after inducing inflammation, when the inflammatory hyperalgesia is at its peak, AIS in inhibitory neurons is shifted distally away from the soma. The shift in AIS location is accompanied by the decrease in excitability of SDH inhibitory neurons. These AIS location and excitability changes are selective for inhibitory neurons and reversible. We show that AIS shift back close to the soma, and SDH inhibitory neurons' excitability increases to baseline levels following recovery from inflammatory hyperalgesia. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of inflammatory pain-mediated AIS plasticity in the central nervous system, which differentially affects the excitability of inhibitory SDH neurons and contributes to inflammatory hyperalgesia.
A dyadic analysis of parent and child pain catastrophizing and health-related quality of life in pediatric sickle cell disease
Authors: Shih Sharon , Donati Matthew R. , Cohen Lindsey L. , Shneider Caitlin , Sil Soumitri 
Published: January 2023

Abstract
The purpose of this study was to examine the dyadic and individual level effects of parent and child pain catastrophizing on child health-related quality of life (HRQOL) in pediatric sickle cell disease. Questionnaires assessing child pain frequency, child and parent pain catastrophizing, and child HRQOL were completed by youth and their primary caregiver. A Common Fate Model was estimated to test the dyadic level relationship between parent and child pain catastrophizing and child HRQOL. An Actor-Partner-Common Fate Model hybrid was estimated to test the relationship between child HRQOL and individual-level child pain catastrophizing and parent pain catastrophizing, respectively. In each model, child HRQOL was modelled as a dyadic variable by factoring parent and child ratings. Patients (N = 100, Mage = 13.5 years, 61% female) and their caregivers (Mage = 41.8 years, 86% mothers) participated. Dyad-level pain catastrophizing was negatively associated with child HRQOL, demonstrating a large effect (β = −0.809). Individual-level parent and child pain catastrophizing were each uniquely negatively associated with child HRQOL, demonstrating small to medium effects (β = −0.309, β = −0.270). Individual level effects were net of same-rater bias, which was significant for both parents and children. Both the unique and the overlapping aspects of parent and child pain catastrophizing are significant contributors to associations with child HRQOL, such that higher levels of pain catastrophizing are associated with worse child HRQOL. Findings suggest the need for multipronged intervention targeting factors common to parent–child dyads and factors unique to parents and children, respectively.
TRAUMATIC BRAIN INJURY–INDUCED INFLAMMATION AND GASTROINTESTINAL MOTILITY DYSFUNCTION
Authors: Cannon Abigail R. , Anderson Lillian J. , Galicia Kevin , Murray Mary Grace , Kamran Aadil S. , Li Xiaoling , Gonzalez Richard P. , Choudhry Mashkoor A. 
Published: January 2023

ABSTRACT

Background: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States, with an annual cost of 60 billion dollars. There is evidence suggesting that in the post-TBI period, the gastrointestinal tract plays a central role in driving organ and immune dysfunction and may be the source of increased circulating proinflammatory mediators. In this study, we examined systemic inflammation and bacterial dysbiosis in patients who sustained a TBI with or without polytrauma. Using a mouse model of TBI, we further show how neuroinflammation after TBI is potentially linked to disruptions in gut homeostasis such as intestinal transit and inflammation. Methods: During a study of trauma patients performed from September 1, 2018, to September 1, 2019, at a single, level 1 trauma center, TBI patients aged 21 to 95 years were enrolled. Patients were categorized as TBI based on evidence of acute abnormal findings on head computed tomographic scan, which was a combination of isolated TBI and TBI with polytrauma. Blood and stool samples were collected between 24 h and 3 days after admission. Twelve plasma samples and 10 fecal samples were used for this study. Healthy control samples were obtained from a healthy control biobank. We examined systemic inflammation and bacterial changes in patients who sustained a TBI. In addition, TBI was induced in 9- to 10-week-old male mice; we assessed neuroinflammation, and intestine transit (motility) and bacterial changes 24 h after TBI. Results: When compared with healthy controls, TBI patients had increased systemic inflammation as evidenced by increased levels of IFN-γ and MCP-1 and a trend toward an increase of IL-6 and IL-8 (P = 0.0551 and P = 0.0549), respectively. The anti-inflammatory cytokine, IL-4, was also decreased in TBI patients. Although there was a trend of an increase in copy number of Enterobacteriaceae and a decrease in copy number of Lactobacillus in both patients and mice after TBI, these trends were not found to be significantly different. However, TBI significantly increased the copy number of another potential pathogenic bacteria Bilophila wadsworthia in TBI patients compared with healthy controls. After a moderate TBI, mice had increased expression of TNF-α, IL-6 and IL-1β, CXCL1, s100a9, and Ly6G and decreased IL-10 in the brain lesion after TBI. This accompanied decreased transit and increased TNF-α in the small intestine of mice after TBI. Conclusions: Our findings suggest that TBI increases systemic inflammation, intestinal dysfunction, and neuroinflammation. More studies are needed to confirm whether changes in intestinal motility play a role in post-TBI neuroinflammation and cognitive deficit.
BRCA1 expression, its correlation with clinicopathological features and response to neoadjuvant chemotherapy in high grade serous ovarian cancer from an Indian centre
Authors: Patil Akkamahadevi , Patil Sharada , Anupama CE , Rajarajan Savitha , Nimbalkar Vidya Prasad , Amirtham Usha , Champaka G , Suma MN , Patil Geetha V , Nargund Ashwini , Pallavi VR , Jacob Linu , Premalatha CS , Prabhu Jyothi S 
Published: January 2023

AbstractIn high grade serous ovarian cancers (HG-SOC), BRCA1/2 mutations have been reported as the most predominant mutations by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We aimed to evaluate BRCA1 inactivation by estimating its expression along with its repressor in primary and neoadjuvant chemotherapy (NACT) treated HG-SOC tumors with known therapeutic response.The expression pattern of BRCA1 protein was evaluated by immunohistochemistry (IHC) in 119 cases of HG-SOC from a hospital cohort consisting of primary (N= 69) and NACT treated (N=50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs) and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4 was estimated by qPCR. Association of BRCA1 protein and mRNA with clinicopathological features was studied. Relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS.BRCA1 protein expression was observed in 12% of primary and 19% of NACT treated HG-SOC tumors. Moderate concordance was observed between BRCA1 protein and mRNA expression (AUC-0.677). High BRCA1 mRNA expression was significantly associated with more frequent SET pattern (p=0.024), higher sTILs density (p=0.042), increased mitosis (p=0.028). BRCA1 negative tumors showed higher expression of ID4 though not statistically significant. Higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p=0.042) and NACT treated tumors (p=0.040). Our findings show the utility of BRCA1/ID4 ratio to predict neoadjuvant therapy response, which needs further evaluation in larger cohort with long term outcomes.
Construction of Model Animals to Explore Intestinal Microbiome for Detection of Breast Cancer
Authors: Ji Xia , Li Ruipeng , Hu Xiaoyu , Tian Yufang , Liu Liqiong , Zhang Chenyu , Xu Liangxiong , Chen Yongzhi , Xie Haiwei , Mao Lutian , Cai Tianshu , Li Weiwei 
Published: January 2023

AbstractBreast cancer ranks first among female cancers and has become a major public health problem in the current society. More studies indicated that these cancers are related to the change in the gut microbiome that can cause metabolic and immune system disorders in the body. However, there are few studies on the changes in gut microbiome caused by the onset of breast cancer, and the relationship between breast cancer and gut microbiome needs to be further clarified. In this study, we inoculated 4T1 breast cancer cells to induce breast cancer tumorigenesis in mice and collected their feces samples at different stages during this process. These intestinal florae were analyzed using 16S rRNA gene amplicon sequencing, and the results showed that at the phylum level, the ratio ofFirmicutes/Bacteroidetesdecreased with the development of the tumor; at the family level, the intestinal microbiome had obvious variations ofLachnospiraceae, Bacteroidaceae, Erysipelotrichaceae, etc. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated that decreased abundance of cancer related signaling pathways. This study elucidated the relationship between breast cancer and intestinal microbiome, and the research results can be used as an important biomarker for the diagnosis of breast cancer.
A novel method for identifying corrosion types and transitions based on Adaboost and electrochemical noise
Authors: Ren Zexing , Li Qiushi , Yang Xiaorui , Wang Jihui 
Published: January 2023

PurposeThe purpose of this paper is to identify corrosion types and corrosion transitions by a novel electrochemical noise analysis method based on Adaboost.Design/methodology/approachThe corrosion behavior of Q235 steel was investigated in typical passivation, uniform corrosion and pitting solution by electrochemical noise. Nine feature parameters were extracted from the electrochemical noise data based on statistical analysis and shot noise theory. The feature parameters were analysis by Adaboost to train model and identify corrosion types. The trained Adaboost model was used to identify corrosion type transitions.FindingsAdaboost algorithm can accurately identify the corrosion type, and the accuracy rate is 99.25%. The identification results of Adaboost for the corrosion type are consistent with corroded morphology analysis. Compared with other machine learning, Adaboost can identify corrosion types more accurately. For corrosion type transition, Adaboost can effectively identify the transition from passivation to uniform corrosion and from passivation to pitting corrosion consistent with corroded morphology analysis.Originality/valueAdaboost is a suitable method for prediction of corrosion type and transitions. Adaboost can establish the classification model of metal corrosion, which can more conveniently and accurately explore the corrosion types. Adaboost provides important reference for corrosion prediction and protection.
Personal prestige through travel? Developing and testing the personal prestige inventory in a tourism context
Authors: Kuhn Friedericke , Kock Florian , Lohmann Martin 
Published: January 2023

Purpose
Leisure travel has long been seen as a means of conspicuous consumption in pursuance of personal prestige; yet, there is no empirical evidence that travel affects personal prestige of tourists. The aims of this study are to develop a scale measuring personal prestige and to experimentally test prestige evaluations based on amount of leisure information, tourism participation and different types of leisure.

Design/methodology/approach
In an experimental online survey, 477 respondents were presented with a manipulated social media profile and asked to evaluate personal prestige of the person on the profile.

Findings
Results present evidence that representation of travel experience has a positive effect on personal prestige evaluations of tourists. The authors found significant differences in personal prestige depending on experimental variations.

Originality/value
This study advances methodological approaches towards the study of tourists’ prestige by providing a reliable, multidimensional measurement scale for personal prestige. The findings yielded by subsequent application of the scale in an experimental setting provide empirical evidence that sharing travel experiences has measurable and experimentally testable personal prestige benefits for tourists.
Policy traps and policy placebos: assessing drug policy network responses to drug related deaths
Authors: McPhee Iain , Sheridan Barry 
Published: January 2023

Purpose
This study focuses on emergency and strategic responses to drug-related deaths. This paper uses policy network theory and policy analysis frameworks to subject programme development and financial decision-making processes to critical scrutiny.

Design/methodology/approach
A qualitative, case-based design focuses on Scottish Government responses to rising drug-related deaths, using publicly available data to produce interpretive critical analysis.

Findings
Analysis indicates that established drug policy communities influence emergency and strategic policy and programme development in relation to drug deaths. Results reveal that policy communities aid government to develop placebo policies and avoid policy traps associated with social determinants of drug-related deaths. This study documents a lack of transparency and accountability in financial decision-making by a third party operating on behalf of Scottish Government. To improve accountability necessitates that drug policy decisions acknowledge existing legislative duties to address socio-economic inequality in this policy area.

Research limitations/implications
In seeking convergence and corroboration publicly available data sources were identified that focus on emergency and strategic responses to drug-related deaths in Scotland. The authors recognise the potential for bias in qualitative and interpretive analysis of this data (Bowen, 2009).

Practical implications
This study provides robust critical analysis on how policy networks exert influence on spending decisions related to drug policy in Scotland. This is useful for researchers and drug policy advisors.

Originality/value
While much has been written on drug deaths in Scotland, using policy network and policy success frameworks to examine policy and programme development, provides originality of analysis in this under-researched aspect of drug policy.
Measuring financial resilience with consumer sentiment data from India
Authors: Yadav Priti , Shaikh Imlak 
Published: January 2023

PurposeCovid-19 sparked new interest in consumer financial resilience (CFR) amongst regulatory authorities, financial institutions, policymakers and the academia. No financial and health crisis has been worse than Covid-19, erasing the growth momentum of nations at all development stages. This study measures consumers' current financial resilience and future expectations within India's emerging market and its likely response to policy measures.Design/methodology/approachCFR is investigated using individual household data on economic state, employment, income and savings from the Reserve Bank of India's consumer confidence survey. The empirical approach is based on the temporal time-series data with mixed frequency regression. Consumers' current and future expectation indices appear as the regressand, whereas credit-deposit ratio, credit outstanding, number of bank accounts and digital transactions act as main regressors.FindingsThe response of consumers' current situation is 3.50 times higher than that of their future expectations. This implies that a rise in the credit-deposit ratio and credit line positively affects CFR. In contrast, a higher number of bank accounts, a proxy for financial inclusion, adversely affect consumer's well-being possibly owing to the government's failure to provide financial support through banking networks. Digital payments (value) positively affect consumers' current situation and future expectations.Practical implicationsThe results of this study inform policy formulation for enhancing financial resilience. Consumer sentiment index acts as a proxy for CFR.Originality/valueFinancial resilience is a concern for policymakers. This study is one of the first studies linking CFR with financial inclusion, credit creation and digital financial capability.