bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-135-5p alleviates bone cancer pain by regulating astrocyte-mediated neuroinflammation in spinal cord through JAK2/STAT3 signaling pathway
Authors: Liu Ming , Cheng Xuefeng , Yan Hong , Chen Jingli , Liu Caihua , Chen Zhonghui 
Published: May 2021

AbstractBone cancer pain (BCP) was associated with microRNA dysregulation. In this study, we intended to clarify the potential role of miR-135-5p in a BCP mouse model, which was established by tumor cell implantation (TCI) in the medullary cavity of the mouse femur. The BCP related behaviors were tested, including the paw withdrawal mechanical threshold (PWMT) and number of spontaneous flinches (NSF). The miRNA expression profiles in astrocytes of the sham and tumor groups were compared, and miRNA microarray and quantitative real-time PCR (qRT-PCR) assays confirmed that the amount of expression of miR-135-5p was significantly decreased in astrocytes of the tumor group. Gain- and loss-of-function studies showed that miR-135-5p could inhibit astrocytes activation and inflammation cytokines (TNF-α and IL-1β) expression. The relation between miR-135-5p and JAK2 was detected by bioinformatic analysis and dual luciferase reporter gene assay. By conducting in vitro experiments, it was shown that the miR-135-5P mimics lowered the level of JAK2/STAT3 proteins and inflammatory factors in astrocytes. Moreover, in vivo analysis on BCP mice model indicated that the miR-135-5p agonist could sufficiently increase PWMT and decrease NSF. Meanwhile, reduced activation of astrocytes in the spinal cord, as well as decreased expression of JAK2/STAT3 and inflammatory mediators, were found after miR-135-5p agonist treatment. Collectively, the results showed that miR-135-5p could potentially reduce BCP in mice through inhibiting astrocyte-mediated neuroinflammation and blocking of the JAK2/STAT3 signaling pathway, indicating that the upregulation of miR-135-5P could be a therapeutic focus in BCP treatment.
Inference of tissue relative proportions of the breast epithelial cell types luminal progenitor, basal, and luminal mature
Authors: Bartlett Thomas E. , Jia Peiwen , Chandna Swati , Roy Sandipan 
Published: May 2021

AbstractSingle-Cell Analysis has revolutionised genomic science in recent years. However, due to cost and other practical considerations, single-cell analyses are impossible for studies based on medium or large patient cohorts. For example, a single-cell analysis usually costs thousands of euros for one tissue sample from one volunteer, meaning that typical studies using single-cell analyses are based on very few individuals. While single-cell genomic data can be used to examine the phenotype of individual cells, cell-type deconvolution methods are required to track the quantities of these cells in bulk-tissue genomic data. Hormone receptor negative breast cancers are highly aggressive, and are thought to originate from a subtype of epithelial cells called the luminal progenitor. In this paper, we show how to quantify the number of luminal progenitor cells as well as other epithelial subtypes in breast tissue samples using DNA and RNA based measurements. We find elevated levels of cells which resemble these hormone receptor negative luminal progenitor cells in breast tumour biopsies of hormone receptor negative cancers, as well as in healthy breast tissue samples from BRCA1 (FANCS) mutation carriers. We also find that breast tumours from carriers of heterozygous mutations in non-BRCA Fanconi Anaemia pathway genes are much more likely to be hormone receptor negative. These findings have implications for understanding hormone receptor negative breast cancers, and for breast cancer screening in carriers of heterozygous mutations of Fanconi Anaemia pathway genes.
Metabolic Reprogramming from Glycolysis to Fatty Acid Uptake and beta-Oxidation in Platinum-Resistant Cancer Cells
Authors: Li Junjie , Tan Yuying , Zhao Guangyuan , Huang Kai-Chih , Cardenas Horacio , Matei Daniela , Cheng Ji-Xin 
Published: May 2021

ABSTRACTIncreased aerobic glycolysis is widely considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during development of therapeutic resistance is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we found that cisplatin-resistant cells exhibit increased uptake of exogenous fatty acids, accompanied with decreased glucose uptake and de novo lipogenesis, indicating a reprogramming from glucose and glycolysis dependent to fatty acid uptake and beta-oxidation dependent anabolic and energy metabolism. A metabolic index incorporating measurements of glucose derived anabolism and fatty acid uptake correlates linearly to the level of resistance to cisplatin in ovarian cancer cell lines and in primary cells isolated from ovarian cancer patients. Mechanistically, the increased fatty acid uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing energy production through beta-oxidation. Consequently, blocking fatty acid beta-oxidation by a small molecule inhibitor in combination with cisplatin or carboplatin synergistically suppressed ovarian cancer proliferation in vitro and growth of patient-derived xenograft in vivo. Collectively, these findings support a new way for rapid detection of cisplatin-resistance at single cell level and a new strategy for treatment of cisplatin-resistant tumors.
Effect of Covid-19 on inequalities in premature mortality in England: an analysis of excess mortality by deprivation and ethnicity
Authors: Barnard Sharmani , Fryers Paul , Fitzpatrick Justine , Fox Sebastian , Baker Allan , Burton Paul , Newton John , Doyle Yvonne , Goldblatt Peter 
Published: May 2021

AbstractObjectivesTo examine the impact of the Covid-19 pandemic on inequalities in premature mortality in England by deprivation and ethnicity.DesignA statistical model to estimate increased mortality in population sub-groups during the Covid-19 pandemic by comparing observed with expected mortality in each group based on trends over the previous five years.SettingInformation on deaths registered in England since 2015 was used, including age, sex, area of residence, and cause of death. Ethnicity was obtained from Hospital Episode Statistics (HES) records linked to death registration data.ParticipantsPopulation study of England, including all 569,824 deaths from all causes registered between 21 March 2020 and 26 February 2021.Main outcome measuresExcess mortality in each sub-group over and above the number expected based on trends in mortality in that group over the previous five years.ResultsThe gradient in excess mortality by deprivation was greater in the under 75s (most deprived had 1.25 times as many deaths as expected, least deprived 1.14) than in all ages (most deprived had 1.24 times as many deaths as expected, least deprived 1.20). Among the Black and Asian groups, all deprivation quintiles had significantly larger excesses than the most deprived White group and there were no clear gradients across quintiles. Among the White group, only the most deprived had more excess deaths than deaths directly involving Covid-19. Among the Black group all deprivation quintiles experienced more excess deaths than deaths directly involving Covid-19.ConclusionThe Covid-19 pandemic has widened inequalities in premature mortality by deprivation. Among those under 75, the direct and indirect effects of the pandemic on deaths have disproportionately impacted ethnic minority groups irrespective of deprivation, and the most deprived White group. Statistics limited to deaths directly involving Covid-19 understate the pandemic’s impact on inequalities by deprivation and ethnic group at younger ages.Key MessagesWhat is already known on this topicEstimates of excess mortality for all ages combined for the period March 2020 to February 2021 show a small difference in the relative impact of Covid-19 on excess mortality between the most deprived and the least deprivedThroughout the pandemic estimates of excess mortality have been greater for ethnic minority groups compared with the white group.What this study addsAmong the under 75s the gradient of excess mortality across the deprivation spectrum indicates a stark increase in already established inequalities in premature mortalityIndependent of deprivation, excess mortality in Black and Asian ethnic groups is much higher than that of the white group, indicating that ethnicity is a determinant of excess mortality, regardless of level of area-based deprivation.
Preserved metacognition despite impaired perception of intentionality cues in schizophrenia
Authors: Muthesius Ana , Grothey Farina , Cunningham Carter , Hölzer Susanne , Vogeley Kai , Schultz Johannes 
Published: May 2021

AbstractSocial cognition and metacognition are frequently impaired in schizophrenia, and these impairments complicate recovery. Recent work suggests that different aspects of metacognition may not be impaired to the same degree. Furthermore, metacognition and the cognitive capacity being monitored need not be similarly impaired. Here, we assessed performance in detecting cues of intentional behaviour as well as metacognition about detecting those cues in schizophrenia. Thirty patients and controls categorized animations of moving dots into those displaying a dyadic interaction demonstrating a chase or no chase and indicated their confidence in these judgments. Perception and metacognition were assessed using signal detection theoretic measures, which were analysed using frequentist and Bayesian statistics. Patients showed a deficit compared to controls in detecting intentionality cues, but showed preserved metacognitive performance into this task. Our study reveals a selective deficit in the perception of intentionality cues, but preserved metacognitive insight into the validity of this perception. It thus appears that impairment of metacognition in schizophrenia varies across cognitive domains - metacognition should not be considered a monolithic stone that is either impaired or unimpaired.Highlights-Impaired detection of chasing between two moving objects in schizophrenia-No impairment in metacognition during this task in schizophrenia-Preserved metacognition into social perception despite impaired social perception
Glycine-Rich RNA-Binding Protein 7 interacts with and potentiates effector-induced immunity by Gpa2 and Rx1 based on an intact RNA Recognition Motif
Authors: Sukarta Octavina C. A. , Zheng Qi , Slootweg Erik J. , Mekken Mark , Mendel Melanie , Putker Vera , Overmars Hein , Pomp Rikus , Roosien Jan , Boeren Sjef , Smant Geert , Goverse Aska 
Published: May 2021

SUMMARYThe activity of intracellular plant Nucleotide-Binding Leucine-Rich Repeat (NB-LRR) immune receptors is fine-tuned by interactions between the receptors and their partners. Identifying NB-LRR interacting proteins is, therefore, crucial to advance our understanding of how these receptors function.A Co-Immunoprecipitation/Mass-Spectrometry screening was performed inNicotiana benthamianato identify host proteins associated with the Gpa2 CC-NB-LRR, which confers resistance against the potato cyst nematodeGlobodera pallida. A combination of biochemical, cellular, and functional assays was used to assess the role of a candidate interactor in defence.AN. benthamianahomolog of the Glycine-Rich RNA-Binding Protein 7 (NbGRP7) protein was prioritized as a novel Gpa2-interacting protein for further investigations.NbGRP7 also associatesin plantawith the homologous Rx1 receptor, which confers immunity to Potato Virus X. We show thatNbGRP7 positively regulates extreme resistance by Rx1 and cell death by Gpa2. Mutating theNbGRP7 RNA recognition motif compromises its role in Rx1-mediated defence. Strikingly, ectopicNbGRP7 expression impacts the steady-state levels of Rx1, which relies on an intact RNA recognition motif.Combined, our findings illustrate thatNbGRP7 is a novel pro-immune component in effector-triggered immunity by regulating Gpa2/Rx1 functioning at a post-transcriptional level.
Rieske head domain dynamics and indazole-derivative inhibition of Candida albicans complex III
Authors: Di Trani Justin M. , Liu Zhongle , Whitesell Luke , Brzezinski Peter , Cowen Leah E. , Rubinstein John L. 
Published: May 2021

ABSTRACTDuring cellular respiration, electron transfer between the integral membrane protein complexes of the electron transport chain is coupled to proton translocation across the inner mitochondrial membrane, which in turn powers synthesis of ATP and transmembrane transport processes. The homodimeric electron transport chain Complex III (CIII2) oxidizes ubiquinol (UQH2) to ubiquinone (UQ), transferring electrons to cytochrome c, and translocating protons through a mechanism known as the Q cycle. The Q cycle involves UQH2 oxidation and UQ reduction at two different sites within each CIII monomer, as well as movement of the head domain of the Rieske subunit. We used cryoEM to determine the structure of CIII2 from Candida albicans, revealing density for endogenous UQ in the structure and allowing us to directly visualize the continuum of conformations of the Rieske head domain. Analysis of these conformations does not indicate cooperativity in the position of the Rieske head domains or binding of ligands in the two CIIIs of the CIII2 dimer. CryoEM with the indazole derivative Inz-5, which inhibits fungal CIII2 and is fungicidal when administered with fungistatic azole drugs, showed that inhibition by Inz-5 alters the equilibrium of the Rieske head domain positions.
The COVID-19 pandemic and sovereign credit risk
Authors: Pan Wei-Fong , Wang Xinjie , Wu Ge , Xu Weike 
Published: May 2021

PurposeThe purpose of this study is to examine the effects of the coronavirus disease 2019 (COVID-19) pandemic on sovereign credit default swap (CDS) spreads using a large sample of countries.Design/methodology/approachIn this paper, the authors use a wide set of the sovereign CDS data of 78 countries. To measure the magnitude of the COVID-19 pandemic, the authors use the daily change of confirmed cases collected from Our World in Data. They use panel regressions to estimate the impact of the COVID-19 pandemic on sovereign credit risk.FindingsThe authors show how sovereign CDS spreads have widened significantly in response to the COVID-19 pandemic. Based on the most conservative estimate, a 1% increase in COVID-19 infections leads to a 0.17% increase in sovereign CDS spreads. Furthermore, this effect is stronger for developing countries and countries with worse healthcare systems. Government policies partially offset the impact of the COVID-19 pandemic, although these same policies also lead to widening sovereign CDS spreads. Sovereign CDS spreads narrow dramatically several months after the outbreak of the COVID-19 pandemic. Overall, the results suggest that the ongoing COVID-19 pandemic has been a massive shock to the global financial stability.Originality/valueThis paper provides new evidence that COVID-19 widens sovereign CDS spreads. The authors further show that this widening effect is felt most strongly in developing economies.
The use of fitness centre apps and its relation to customer satisfaction: a UTAUT2 perspective
Authors: Ferreira Barbosa Helena , García-Fernández Jerónimo , Pedragosa Vera , Cepeda-Carrion Gabriel 
Published: May 2021

PurposeThe purpose of this paper is to analyse the intention of using fitness app made available by the fitness centre to its members and their relationship with overall customer satisfaction.Design/methodology/approachThe present study uses the extended unified theory of acceptance and use of technology (UTAUT2) as the base model. All the hypothesised relationships were tested through partial least square structural equation modelling (PLS-SEM), in a quantitative study with data from 1,676 fitness consumers from Portugal.FindingsThe results support the ability of UTAUT2 in predicting the customer´s intention to use the fitness app. Performance expectancy, effort expectancy, social influence, facilitating conditions, hedonic motivation and habit have a positive impact on behavioural intentions to use the fitness app. Performance expectancy and habit have the strongest relationships. Behavioural intentions are positively related both to the usage behaviour of the fitness app and to overall customer satisfaction.Practical implicationsThe results of this study present a strong contribution for fitness centre managers, since it highlights the importance of using these apps as a way to increase customer satisfaction, increasing retention levels.Originality/valueThis study is paramount as regards to examine the behavioural intention to use the fitness apps that the fitness centres make available to their members using UTAUT2 model.
Diminishing traditional methods and inaccessible modern healthcare: the dilemma of tribal health in India
Authors: Negi Dandub Palzor , Abdul Azeez E.P. 
Published: May 2021

PurposeThis paper critically examines the state of tribal health in India by analyzing the accessibility and availability of traditional medicine and modern healthcare.Design/methodology/approachThis essay is the product of an extensive review of the literature and authors' personal experience in working with the tribal communities.FindingsThe traditional medicinal practices once very prevalent among the tribal communities are diminishing due to various socio-economic, environmental and political factors. Modern healthcare in India's tribal region is characterized by a lack of availability, accessibility and affordability. As a result of the diminishing traditional practices and inaccessible modern healthcare provisions, tribal communities depend on quacks and magico-religious practices.Originality/valueThis essay advocates for urgent policy interventions to integrate traditional medicine and modern healthcare practices to address critical tribal health issues. Preservation of traditional medicinal knowledge-base and improving research in the field have the potential to address the health of tribal communities and of others. The accessibility and availability of modern healthcare facilities in tribal regions should be improved to ensure better health outcomes.
Optimal pricing model for non-instantaneous deterioration items with price and freshness sensitive demand under the e-commerce environment in China
Authors: Xu Weihua , Zhou Shujun , Zhao Ketong , Shi Yixuan , Bingzhen Sun 
Published: May 2021

Purpose
The purpose of this paper is to focus on determining the optimal sales price for non-instantaneous deterioration items according to consideration of freshness and demand.

Design/methodology/approach
In this model, the authors have described the demand function which is dependent on price as well time. The products that the deterioration is considered as non-instantaneous have a determinate shelf life, and their demand rate will decrease over time after the beginning of the selling period. This paper depicts that the total profit of non-instantaneous deterioration items using the dynamic pricing strategy is higher than that using fixed pricing strategy.

Findings
Finally, to illustrate and validate the model, the authors have used some numerical examples. A new freshness function and the model to study pricing policy are developed as well applied to solve managerial decision problems.

Originality/value
This paper complements the lack of the existing theoretical research of pricing for non-instantaneous deterioration items under an e-commerce environment. A new freshness function and the model to study pricing policy are developed as well applied to solve managerial decision problems.
Cross-border and sedentary workers' job satisfaction
Authors: Wodociag Sophie , Dolce Valentina , Molino Monica 
Published: May 2021

PurposeThis study aims to explore cross-border and sedentary workers' job satisfaction, analyzing the role played by employability dimensions (occupational expertise, anticipation/optimization and personal flexibility), a job resource (autonomy) and job demands (job insecurity and toxic leadership), using the job demands–resources (JD-R) model as a theoretical framework. Moreover, this study tried to detect possible discrepancies between the two subsamples.Design/methodology/approachThe study involved a sample of 250 employees, 40% of whom were frontier workers. Data were collected with a self-report questionnaire and analyzed with SPSS 25. A hierarchical regression analysis andt-test for independent samples were performed.FindingsThe findings evidenced differences between the two subsamples concerning the job satisfaction predictors. Specifically, for cross-border workers, optimization/anticipation appeared significantly positively related to job satisfaction. For sedentary workers, toxic leadership and job insecurity were significantly negatively related to job satisfaction. Autonomy was positively related to the outcome for both samples. Furthermore, cross-border workers reported a higher level of optimization/anticipation, personal flexibility and job satisfaction than sedentary workers.Originality/valueThis paper contributed to fill a gap currently present in the literature on the cross-border population, with a specific focus on job satisfaction. This study confirmed the existence of peculiar working dynamics for cross-border workers.
Sarcoid‐like reaction of the extrathoracic lymph node in a patient with lung adenocarcinoma treated with pembrolizumab
Authors: Takamori Shinkichi , Furubayashi Nobuki , Taguchi Kenichi , Matsubara Taichi , Fujishita Takatoshi , Ito Kensaku , Yamaguchi Masafumi , Toyozawa Ryo , Seto Takashi , Negishi Takahito , Nakamura Motonobu , Okamoto Tatsuro 
Published: May 2021

AbstractImmune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of non‐small cell lung cancer (NSCLC). With the increasing use of ICIs, clinicians should be familiar with their immune‐related adverse events, including sarcoid‐like reactions, which have been associated with the use of ICIs in patients with cancer. Sarcoid‐like reactions are caused by uncontrolled T helper 1‐mediated immune responses resulting from ICIs, but their pathophysiology is not fully understood. Sarcoid‐like reactions are often clinically important because they mimic metastases from treated cancer. According to previous reports, sarcoid‐like reactions are typically observed in intrathoracic locations (lung and/or mediastinal lymph nodes) and the skin. In this study, we report an extremely rare case of extrathoracic sarcoid‐like reaction in the right external iliac lymph node following two cycles of pembrolizumab therapy in a patient with lung adenocarcinoma. The laboratory data and computed tomography images suggested that infectious and autoimmune diseases were not considered to be the causative agents. Residual bone metastasis might have caused T helper 1‐mediated immune responses by pembrolizumab, and contributed to sarcoid‐like reactions in the right external iliac lymph node. Sarcoid‐like reactions should be considered in the differential diagnosis of patients with lung cancer treated with ICIs who exhibit worsening extrathoracic lymph node swelling. Clinicians should be cautious not to mistake extrathoracic sarcoid‐like reactions of the lymph nodes for progression of the treated disease.