bluuebunny/crossref_metadata_2025 huggingface dataset:
Child Avoidance of Anxiety-Provoking Situations in the Classroom and Teacher Accommodation
Authors: Ginsburg Golda S. , Pella Jeffrey E. , DeVito Anneliese , Chan Grace
Published: December 2021

This study examined: (1) school-based avoidance among students with problematic anxiety, (2) teachers’ levels of accommodation of avoidant behaviour, and (3) the relation between teacher accommodation and student avoidance and anxiety. Participants included 31 elementary school students with problematic anxiety (mean age = 7.7 years; range 5–11; 58% female; 71% White) and their teachers (mean age = 41.1 years; 100% female; 100% White). Children completed interviews about their anxiety, and teachers reported on students’ avoided situations and completed a questionnaire about their own use of accommodation. Results indicated that the most commonly avoided situations involved individual and group academic performance (e.g., reading aloud in front of class). All teachers engaged in some form of accommodating behaviour more than one day a week (e.g., assisted a student in avoiding things that might make him/her more anxious), and teachers who reported engaging in more accommodating behaviours had students with higher avoidance and anxiety. Findings suggest that additional training and research on teachers’ behaviours that maintain and/or reduce anxiety via reducing accommodating behaviours appears warranted.
Attributions About Self-Harm: A Comparison Between Young People’s Self-Report and the Functions Ascribed by Preservice Teachers and School Counsellors
Authors: Dawson Kristy , Deane Frank P. , Miller Leonie
Published: December 2021

Globally, adolescent self-harm rates remain high, while help-seeking behaviour remains low. School staff are in a position to facilitate access to appropriate care for young people who self-harm (YPS-H), but little is known about gatekeepers’ attributions of self-harm or whether these attributions influence the support they provide. This study investigates the perceived functions of self-harm reported by potential gatekeepers and examines how these compare to the self-reported functions of self-harm in young people; 386 students from postgraduate teaching (n = 111), school counselling (n = 37), and undergraduate psychology (n = 238) programs completed a survey regarding their beliefs about YPS-H, which included the Inventory of Statements about Self-Harm. Responses were compared to those of 281 young people attending treatment at a suicide prevention program who completed the same measure. Preservice teachers, school counsellors and psychology students endorsed all functions of self-harm at a higher rate than treatment-seeking young people themselves. In particular, they endorsed interpersonal functions to a greater extent than the clinical reference group. The potential effect of greater endorsement of interpersonal influence as a function of self-harm gatekeeper’s responding to YPS-H is discussed.
FINITE SUM OF COMPOSITION OPERATORS ON FOCK SPACE
Authors: HAI PHAM VIET
Published: December 2021

We investigate unbounded, linear operators arising from a finite sum of composition operators on Fock space. Real symmetry and complex symmetry of these operators are characterised.
Parish Politics and Godly Agitation in Late Interregnum Scotland
Authors: Langley Chris R.
Published: December 2021

Following the English invasion of Scotland in July 1650, ministers and laymen in the Church of Scotland splintered between Protester and Resolutioner factions: The Protesters argued that the Church of Scotland required further moral reformation in order to appease a vengeful God, and the Resolutioners were more content to accept the reintegration of former royalists into places of trust following the civil wars. This article explores the profound ways in which this split fundamentally altered relationships in the unusually well-documented parish of Crichton in Midlothian. Unlike other studies that have emphasized the ways in which the Protesters moved toward a position of separation from the rest of the kirk, this article explores a group of Protesters who sought to actively reform the kirk from within. Godly agitation in parish affairs was characterized by three traits: it was coordinated, remarkably litigious, and disseminated in manuscript libels and petitions rather than print. Ultimately, while this godly elite was adept at agitating for further reformation at the parish level, it did so without seceding from the structures of the national church altogether.
Gordon Keith Chalmers and the Politics of Advanced Placement
Authors: ABRAMS ANN
Published: December 2021

This article investigates the role of mid-century conservatism in shaping the College Board's Advanced Placement program. Kenyon president Gordon Keith Chalmers and superintendent of New Trier public schools William Cornog, who led the committee that directly gave rise to the AP Program, understood themselves as classically liberal but socially conservative, and their proposed program was rooted in principles associated with that movement. In keeping with other mid-century conservative thinkers, they promoted humanistic inquiry that introduced all American students, regardless of backgrounds, to the notion of individual freedom, in spaces set apart from economic activity. This article explains that Chalmers and Cornog agreed that schools should focus on reinforcing and transmitting a distinctly American heritage of constitutionalism, individualism, and universal morality by way of the liberal arts. The article ends by establishing how this ideological framing contradicts the Advanced Placement program's current shape.
Disability and Employment Policy in Canada: National Policy Variation for Working Age Individuals
Authors: DINAN SHANNON , BOUCHER NORMAND
Published: December 2021

This article analyses and compares disability policies for working-age individuals in Canada with a focus on the mode of policy provision and type of measure to determine the degree to which direct funding is used in this country. To consider policy diversity in this federal system, policies are compared using a mixed-methods approach. Using quantitative methods, federal, provincial and territorial policies are first compared using hierarchical cluster analysis. This provides evidence of three distinct clusters in Canada according to policy provision and measure type. In a second, qualitative analysis, the disability strategies of four provinces’ (British Columbia, Ontario, Newfoundland and Labrador and Quebec) are compared, to determine over arching policy orientations. Findings indicate that policy provision in Canada largely favours money over services. Furthermore, most provinces emphasize either health or integration measures over substantive measures. Despite these commonalities, significant variation persists across Canada. This extends to poverty and disability reduction strategies with two of the four provinces having a broader orientation while the other two provinces focus specifically on employment as a means of social inclusion. The article concludes with a discussion on the state of employment policies for individuals with a disability in Canada.
Recrafting ontology
Authors: Trownsell Tamara
Published: December 2021

A pluriversal encounter that includes interlocutors from other ways of knowing and being requires recrafting how we commonly approach ontology in IR. Our shared ontological register only acknowledges separation as the fundamental existential assumption, and not all lifeways depart from this assumption. The article prods us to move beyond considering ontology as the study of being, a more substantialist reading, to include other fundamental existential commitments so that we can address how distinct presuppositions shape and are shaped by how we perceive and engage existence. With this reorientation, the article first establishes how even relational approaches in the discipline, including variations of constructivism, poststructuralism, and new materialism privilege separation as the primordial condition of existence to the exclusion of any other option. A conceptual toolset is then elaborated to examine how a singular commitment to separation constitutes an ontological parochialism that enforces reductionism, exclusion, and domination towards lifeways that embrace the interconnection as fundamental existential commitment. Even though more effective engagement across pluriversal worlds would be crucial for developing more complex tools for confronting the current planetary crisis, the discipline's reductionist concept of ontology itself keeps us quite far from effectively being able to engage in such an exchange.
Sympathetic nervous system functioning during the face-to-face still-face paradigm in the first year of life
Authors: Klein Louis , Doyle Frances L. , Northam Jaimie C. , Eapen Valsamma , Frick Paul J. , Kimonis Eva R. , Hawes David J. , Moul Caroline , Richmond Jenny L. , Mehta Divya , Mendoza Diaz Antonio , Dadds Mark R.
Published: December 2021

Contemporary theories of early development and emerging child psychopathology all posit a major, if not central role for physiological responsiveness. To understand infants’ potential risk for emergent psychopathology, consideration is needed to both autonomic reactivity and environmental contexts (e.g., parent–child interactions). The current study maps infants’ arousal during the face-to-face still-face paradigm using skin conductance (n = 255 ethnically-diverse mother–infant dyads; 52.5% girls, mean infant age = 7.4 months; SD = 0.9 months). A novel statistical approach was designed to model the potential build-up of nonlinear counter electromotive force over the course of the task. Results showed a significant increase in infants’ skin conductance between the Baseline Free-play and the Still-Face phase, and a significant decrease in skin conductance during the Reunion Play when compared to the Still-Face phase. Skin conductance during the Reunion Play phase remained significantly higher than during the Baseline Play phase; indicating that infants had not fully recovered from the mild social stressor. These results further our understanding of infant arousal during dyadic interactions, and the role of caregivers in the development of emotion regulation during infancy.
“Half-uncovered technique” to secure larger stents for postoperative pulmonary vein stenosis
Authors: Kise Hiroaki , Fujii Takanari , Tomita Hideshi
Published: December 2021

Although larger stent placement could be effective for pulmonary vein stenosis, stents extrusion tends to occur due to caliber narrowing, small landing area, and the slippery nature. We placed stents with diameter ≧8 mm for four stenotic lesions using the “half-uncovered technique”. All stents were precisely placed and successfully resolved the stenosis. This technique allows us to avoid extrusion and to perform safe and effective dilatation when placing larger stents for pulmonary vein stenosis.
“I Will Bless Those Who Bless You”: Evangelicalism and Support for Israel in Latin America
Authors: Ziv Tom
Published: December 2021

The relations of the Evangelical movement and Israel have drawn the attention of many scholars of religion, public opinion, and political science in the last two decades. This study examines the influence of Evangelicals on their country's policy toward Israel. I conduct the first quantitative, cross-national research, investigating the links between the size of the Evangelical population of a country and its support for Israel. Analyzing 198 UN General Assembly votes of 18 Latin American countries from 2009 to 2019, my results show that as the Evangelical population in a country grows, so does its support for Israel. Unpredictably, I also find that a state of armed conflict between Israel and the Palestinians does not decrease the support for Israel.
Self-Efficacy, Self-Regulation and Mathematics Performance of Competitive Junior Rowers vs. Regular Students
Authors: Vent Larissa , Schiemann Stephan , Freund Philipp Alexander
Published: December 2021

Abstract. Young athletes face mental challenges both in competitive sports and in school. High self-efficacy and self-regulation competence contribute to an individual’s ability to successfully master these challenges. The present study links the domains of competitive sports and academic education by investigating the relationships of self-efficacy and self-regulation to performance in mathematics lessons. Here, we compare competitive rowers ( n = 239) and “regular” students ( n = 171; total N = 410). The competitive rowers showed a higher subjective expectation of self-efficacy, which in both groups had a positive effect on mathematics grades. While self-regulation had a mediating effect on the competitive rowers in this context, we observed no significant effect for the regular students. The study provides evidence that competitive athletes are apt to use psychosocial resources fostered by professional sports training across domains.
Influence of the Fundamental Attribution Error on Perceptions of Blame and Negligence
Authors: Flick Cassandra , Schweitzer Kimberly
Published: December 2021

Abstract. Automobile accidents are a frequent occurrence in the United States and commonly result in legal ramifications. Through a fundamental attribution error (FAE) framework ( Ross, 1977 ), the current research examined how individuals perceive blame and negligence in these cases. In Study 1 ( N = 360), we manipulated the driver (you vs. stranger) of a hypothetical accident scenario and the situational circumstances surrounding the accident (favorable vs. unfavorable). Supporting the FAE, individuals' situational blame attributions only varied as a function of situational circumstances when they themselves were hypothetically driving. However, neither the driver nor the situation significantly predicted dispositional blame attributions. Yet, Study 1 provided initial support for the importance of an individual's trait tendency to neglect situational constraints when making dispositional blame attributions. In Study 2 ( N = 212), we again manipulated situational circumstances surrounding the hypothetical accident, but within the context of a mock civil trial. Results provided additional support for the importance of this trait tendency and expanded our findings of dispositional blame attributions to perceptions of negligence. Implications include the importance of considering trait individual differences in the likelihood to ignore situational demands when individuals are making legally relevant judgments about automobile accidents.
Wildfires May Alter the Nitrogen Cycle—and Air Pollution
Authors: Vasquez Krystal
Published: December 2021

Research indicates that wildfires could be bolstering soil emissions of air pollutants that contribute to smog and climate change.
Methane Plume Emissions Associated With Puget Sound Faults in the Cascadia Forearc
Authors: Johnson H. Paul , Merle Susan G. , Bjorklund Tor A. , Hautala Susan L. , Baumberger Tamara , Walker Sharon L. , Liu Junzhe , Ward Nicholas D. , Wang Chenyu
Published: December 2021

Methane gas plumes have been discovered to issue from the seafloor in the Puget Sound estuary. These gas emission sites are co‐located over traces of three major fault zones that fracture the entire forearc crust of the Cascadia Subduction Zone. Multibeam and single‐beam sonar data from cruises conducted in years 2011, 2018, 2019, 2020, and 2021 identified the acoustic signature of 349 individual bubble plumes. Dissolved CH4 gas from the plumes combines to elevate seawater methane concentrations of the entire Puget Sound estuary. Fluid samples from adjacent terrestrial hot springs and deep‐water wells surrounding the estuary contain a helium‐3 isotope signature, suggesting a deep fluid source located near the underlying Cascadia Subduction Zone plate interface. However, limited data from this pilot study suggest that Puget Sound seawater emission sites lack both similar chemical isotope signatures and elevated thermal anomalies that would be expected from association with a deep plate‐interface reservoir. A shallow reservoir within the Holocene sediments that cover the older Puget Sound basement with horizontal transfer to the thinly covered Alki Point and Kingston Arch anticlines is also a possibility, as has been suggested for other methane seep areas. The existence of vigorous marine methane plumes arising from areas of thin sediment cover associated with deeply penetrating forearc fault zones but presenting no thermal or chemical anomalies found in other similar forearc environments, remains an unresolved paradox.
Summer Surface CO2 Dynamics on the Bering Sea and Eastern Chukchi Sea Shelves From 1989 to 2019
Authors: Wang Hongjie , Lin Peigen , Pickart Robert S. , Cross Jessica N.
Published: December 2021

By compiling boreal summer (June to October) CO2 measurements from 1989 to 2019 on the Bering and eastern Chukchi Sea shelves, we find that the study areas act as a CO2 sink except when impacted by river runoff and wind‐driven upwelling. The CO2 system in this area is seasonally dominated by the biological pump especially in the northern Bering Sea and near Hanna Shoal, while wind‐driven upwelling of CO2‐rich bottom water can cause episodic outgassing. Seasonal surface ΔfCO2 (oceanic fCO2 – air fCO2) is dominantly driven by temperature only during periods of weak CO2 outgassing in shallow nearshore areas. However, after comparing the mean summer ΔfCO2 during the periods of 1989–2013 and 2014–2019, we suggest that temperature does drive long‐term, multi‐decadal patterns in ΔfCO2. In the northern Chukchi Sea, rapid warming concurrent with reduced seasonal sea‐ice persistence caused the regional summer CO2 sink to decrease. By contrast, increasing primary productivity caused the regional summer CO2 sink on the Bering Sea shelf to increase over time. While additional time series are needed to confirm the seasonal and annual trajectory of CO2 changes and ocean acidification in these dynamic and spatially complex ecosystems, this study provides a meaningful mechanistic analysis of recent changes in inorganic carbonate chemistry. As high‐resolution time series of inorganic carbonate parameters lengthen and short‐term variations are better constrained in the coming decades, we will have stronger confidence in assessing the mechanisms contributing to long‐term changes in the source/sink status of regional sub‐Arctic seas.
A Method for Assessment of Sub‐Daily Flow Alterations Using Wavelet Analysis for Regulated Rivers
Authors: Ashraf Faisal Bin , Haghighi Ali Torabi , Riml Joakim , Mathias Kondolf G. , Kløve Bjørn , Marttila Hannu
Published: December 2021

New tools are needed to evaluate the impacts of short‐term hydropower regulation practices on downstream river systems and to progress towards sustainable river‐flow management. As hydropower is increasingly being used to balance the energy load deficit caused by other less flexible sources, sub‐daily flow conditions across many regulated river (RR) systems are changing. To address this, we used wavelet analyses to quantify the discharge variability in RRs and categorized the level of variability based on the conditions in natural free‐flowing rivers. The presented framework used the definition of fluvial connectivity (Grill et al., 2019) to identify free‐flowing rivers used in the study. We tested the developed framework in 12 different RRs in Finland and found higher overall averaged subdaily variations, with up to 20 times larger variability than natural conditions. A large, highly regulated Finnish river system was found to have the highest sub‐daily variations in winter, while smaller RRs with lower levels of regulation the highest variations in summer. The proposed framework offers a novel tool for sustainable river management and can be easily applied to various rivers and regions globally. It had flexibility to analyze sub‐daily variations in desired seasonal or other ecologically sensitive periods.
An overview of kinase downregulators and recent advances in discovery approaches
Authors: Wang Beilei , Wu Hong , Hu Chen , Wang Haizhen , Liu Jing , Wang Wenchao , Liu Qingsong
Published: December 2021

Since the clinical approval of imatinib, the discovery of protein kinase downregulators entered a prosperous age. However, challenges still exist in the discovery of kinase downregulator drugs, such as the high failure rate during development, side effects, and drug-resistance problems. With the progress made through multidisciplinary efforts, an increasing number of new approaches have been applied to solve the above problems during the discovery process of kinase downregulators. In terms of in vitro and in vivo drug evaluation, progress was also made in cellular and animal model platforms for better and more clinically relevant drug assessment. Here, we review the advances in drug design strategies, drug property evaluation technologies, and efficacy evaluation models and technologies. Finally, we discuss the challenges and perspectives in the development of kinase downregulator drugs.
Differential brain ADRA2A and ADRA2C gene expression and epigenetic regulation in schizophrenia. Effect of antipsychotic drug treatment
Authors: Brocos-Mosquera Iria , Miranda-Azpiazu Patricia , Muguruza Carolina , Corzo-Monje Virginia , Morentin Benito , Meana J. Javier , Callado Luis F. , Rivero Guadalupe
Published: December 2021

Postsynaptic α2A-adrenoceptor density is enhanced in the dorsolateral prefrontal cortex (DLPFC) of antipsychotic-treated schizophrenia subjects. This alteration might be due to transcriptional activation, and could be regulated by epigenetic mechanisms such as histone posttranslational modifications (PTMs). The aim of this study was to evaluate ADRA2A and ADRA2C gene expression (codifying for α2-adrenoceptor subtypes), and permissive and repressive histone PTMs at gene promoter regions in the DLPFC of subjects with schizophrenia and matched controls (n = 24 pairs). We studied the effect of antipsychotic (AP) treatment in AP-free (n = 12) and AP-treated (n = 12) subgroups of schizophrenia subjects and in rats acutely and chronically treated with typical and atypical antipsychotics. ADRA2A mRNA expression was selectively upregulated in AP-treated schizophrenia subjects (+93%) whereas ADRA2C mRNA expression was upregulated in all schizophrenia subjects (+53%) regardless of antipsychotic treatment. Acute and chronic clozapine treatment in rats did not alter brain cortex Adra2a mRNA expression but increased Adra2c mRNA expression. Both ADRA2A and ADRA2C promoter regions showed epigenetic modification by histone methylation and acetylation in human DLPFC. The upregulation of ADRA2A expression in AP-treated schizophrenia subjects might be related to observed bivalent chromatin at ADRA2A promoter region in schizophrenia (depicted by increased permissive H3K4me3 and repressive H3K27me3) and could be triggered by the enhanced H4K16ac at ADRA2A promoter. In conclusion, epigenetic predisposition differentially modulated ADRA2A and ADRA2C mRNA expression in DLPFC of schizophrenia subjects.
Dental Policy Lab 3: towards oral and dental health through partnership
Authors: Pitts Nigel B. , Newton J. Tim , Pow Ross , Miller Nicholas , Mayne Catherine
Published: December 2021

The third and last of the successful Alliance for a Cavity-Free Future (ACFF)/King's College London Dental Policy Lab series, held in 2019, focused on outlining how dental and oral health industries could benefit from enabling positive behaviour change in patients and the public, allowing progress towards caries reduction. During a two-day event, experts from across public health, dentists, global multi-national corporations and dental industry start-ups discussed the issue, collaboratively developing ideas around policy, technology, messaging and engagement for change. An analysis of the current trends in oral health laid out how the implications for industry and corporate social responsibility were identified as crucial. The report and accompanying infographic explored in this paper have been well received and acted as a catalyst for future developments in the area.
NLPR3 inflammasome inhibition alleviates hypoxic endothelial cell death in vitro and protects blood–brain barrier integrity in murine stroke
Authors: Bellut Maximilian , Papp Lena , Bieber Michael , Kraft Peter , Stoll Guido , Schuhmann Michael K.
Published: December 2021

In ischemic stroke (IS) impairment of the blood–brain barrier (BBB) has an important role in the secondary deterioration of neurological function. BBB disruption is associated with ischemia-induced inflammation, brain edema formation, and hemorrhagic infarct transformation, but the underlying mechanisms are incompletely understood. Dysfunction of endothelial cells (EC) may play a central role in this process. Although neuronal NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome upregulation is an established trigger of inflammation in IS, the contribution of its expression in EC is unclear. We here used brain EC, exposed them to oxygen and glucose deprivation (OGD) in vitro, and analyzed their survival depending on inflammasome inhibition with the NLRP3-specific drug MCC950. During OGD, EC death could significantly be reduced when targeting NLRP3, concomitant with diminished endothelial NLRP3 expression. Furthermore, MCC950 led to reduced levels of Caspase 1 (p20) and activated Gasdermin D as markers for pyroptosis. Moreover, inflammasome inhibition reduced the secretion of pro-inflammatory chemokines, cytokines, and matrix metalloproteinase-9 (MMP9) in EC. In a translational approach, IS was induced in C57Bl/6 mice by 60 mins transient middle cerebral artery occlusion and 23 hours of reperfusion. Stroke volume, functional outcome, the BBB integrity, and—in good agreement with the in vitro results—MMP9 secretion as well as EC survival improved significantly in MCC950-treated mice. In conclusion, our results establish the NLRP3 inflammasome as a critical pathogenic effector of stroke-induced BBB disruption by activating inflammatory signaling cascades and pyroptosis in brain EC.
USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3/COL6A5 stabilisation
Authors: Wu Xiaosheng , Wang Hao , Zhu Danping , Chai Yixia , Wang Jing , Dai Weiyu , Xiao Yizhi , Tang Weimei , Li Jiaying , Hong Linjie , Pei Miaomiao , Zhang Jieming , Lin Zhizhao , Wang Jide , Li Aimin , Liu Side
Published: December 2021

As an important regulator of intracellular protein degradation, the mechanism of the deubiquitinating enzyme family in tumour metastasis has received increasing attention. Our previous study revealed that USP3 promotes tumour progression and is highly expressed in gastric cancer (GC). Herein, we report two critical targets, COL9A3 and COL6A5, downstream of USP3, via the isobaric tags for relative and absolute quantification technique. Mechanistically, we observed that USP3 interacted with and stabilised COL9A3 and COL6A5 via deubiquitination in GC. Importantly, we found that COL9A3 and COL6A5 were essential mediators of USP3-modulated oncogenic activity in vitro and in vivo. Examination of clinical samples confirmed that elevated expression of USP3, concomitant with increased COL9A3 and COL6A5 abundance, correlates with human GC progression. These data suggest that USP3 promotes GC progression and metastasis by deubiquitinating COL9A3 and COL6A5. These findings identify a mechanism of GC metastasis regarding USP3-mediated deubiquitinating enzyme activity and suggest potential therapeutic targets for GC management.
CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition
Authors: Li Dandan , Zhang Jiawei , Yang Jing , Wang Jie , Zhang Runling , Li Jinming , Zhang Rui
Published: December 2021

CircRNA mitochondrial tRNA translation optimization 1 (circMTO1) functions as a tumor suppressor usually and is related to the progression of many tumors, including hepatocellular carcinoma (HCC). CircMTO1 is downregulated in HCC as compared to adjacent nontumor tissue, which may suppress the HCC progression by certain signal pathways. However, the underlying signal pathway remains largely unknown. The interactions between circMTO1 and miR-541-5p were predicted through bioinformatics analysis and verified using pull-down and dual-luciferase reporter assays. CCK-8, transwell, and apoptosis assays were performed to determine the effect of miR-541-5p on HCC progression. Using bioinformatic analysis, dual-luciferase reporter assay, RT-qPCR, and western blot, ZIC1 was found to be the downstream target gene of miR-541-5p. The regulatory mechanisms of circMTO1, miR-541-5p, and ZIC1 were investigated using in vitro and in vivo rescue experiments. The results depicted that silencing circMTO1 or upregulating miR-541-5p expression facilitated HCC cell proliferation, migration, and invasion and inhibited apoptosis. CircMTO1 silencing upregulated the expression of downstream ZIC1 regulators of the Wnt/β-catenin pathway markers, β-catenin, cyclin D1, c-myc, and the mesenchymal markers N-cadherin, Vimentin, and MMP2, while the epithelial marker E-cadherin was downregulated. MiR-541-5p knockdown had the opposite effect and reversed the effect of circMTO1 silencing on the regulation of downstream ZIC1 regulators. Intratumoral injection of miR-541-5p inhibitor suppressed tumor growth and reversed the effect of circMTO1 silencing on the promotion of tumor growth in HCC. These findings indicated that circMTO1 suppressed HCC progression via the circMTO1/ miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling and epithelial-to-mesenchymal transition, making it a novel therapeutic target.
UBQLN4 is activated by C/EBPβ and exerts oncogenic effects on colorectal cancer via the Wnt/β-catenin signaling pathway
Authors: Tang Xiaolong , Liang Yahang , Sun Guorui , He Qingsi , Qu Hui , Gao Peng
Published: December 2021

Ubiquilin 4 (UBQLN4) is an important member of the ubiquitin-like protein family. An increasing number of studies have shown that UBQLN4 is an important regulator of tumorigenesis. Nevertheless, the biological function and detailed mechanisms of UBQLN4 in colorectal cancer (CRC) development and progression remain unclear. Here, we identified UBQLN4 upregulation in CRC tissues and it is positively associated with CRC size, TNM stage, and lymphatic metastasis. Patients with high UBQLN4 expression had a poor prognosis. Functionally, overexpression of UBQLN4 significantly promoted CRC cell proliferation, migration, and invasion, while UBQLN4 silencing elicited the opposite effect. This result was consistent with the conclusion that UBQLN4 expression correlated positively with the CRC size and lymphatic metastasis. In vivo, UBQLN4 silencing also inhibited tumor growth. Mechanistically, using gene set enrichment analysis (GSEA) and western blot experiments, we identified that UBQLN4 activated the Wnt/β-catenin signaling pathway to upregulate β-catenin and c-Myc expression, thereby promoting CRC proliferation, migration and invasion. A rescue experiment further verified this conclusion. Dual luciferase reporter, real-time quantitative PCR (RT-qPCR), western blot and chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor CCAAT/enhancer-binding protein beta (C/EBPβ) directly bound to the UBQLN4 core promoter region and activated its transcription, upregulating β-catenin and c-Myc expression to promote CRC progression. Thus, our findings suggest that UBQLN4 is a key oncogene in CRC and may be a promising target for the diagnosis and treatment of patients with CRC.
Common microscopic origin of the phase transitions in Ta2NiS5 and the excitonic insulator candidate Ta2NiSe5
Authors: Windgätter Lukas , Rösner Malte , Mazza Giacomo , Hübener Hannes , Georges Antoine , Millis Andrew J. , Latini Simone , Rubio Angel
Published: December 2021

The structural phase transition in Ta2NiSe5 has been envisioned as driven by the formation of an excitonic insulating phase. However, the role of structural and electronic instabilities on crystal symmetry breaking has yet to be disentangled. Meanwhile, the phase transition in its complementary material Ta2NiS5 does not show any experimental hints of an excitonic insulating phase. We present a microscopic investigation of the electronic and phononic effects involved in the structural phase transition in Ta2NiSe5 and Ta2NiS5 using extensive first-principles calculations. In both materials the crystal symmetries are broken by phonon instabilities, which in turn lead to changes in the electronic bandstructure also observed in the experiment. A total energy landscape analysis shows no tendency towards a purely electronic instability and we find that a sizeable lattice distortion is needed to open a bandgap. We conclude that an excitonic instability is not needed to explain the phase transition in both Ta2NiSe5 and Ta2NiS5.
Importance of charge self-consistency in first-principles description of strongly correlated systems
Authors: Acharya Swagata , Pashov Dimitar , Rudenko Alexander N. , Rösner Malte , van Schilfgaarde Mark , Katsnelson Mikhail I.
Published: December 2021

First-principles approaches have been successful in solving many-body Hamiltonians for real materials to an extent when correlations are weak or moderate. As the electronic correlations become stronger often embedding methods based on first-principles approaches are used to better treat the correlations by solving a suitably chosen many-body Hamiltonian with a higher level theory. The success of such embedding theories, often referred to as second-principles, is commonly measured by the quality of self-energy Σ which is either a function of energy or momentum or both. However, Σ should, in principle, also modify the electronic eigenfunctions and thus change the real space charge distribution. While such practices are not prevalent, some works that use embedding techniques do take into account these effects. In such cases, choice of partitioning, of the parameters defining the correlated Hamiltonian, of double-counting corrections, and the adequacy of low-level Hamiltonian hosting the correlated subspace hinder a systematic and unambiguous understanding of such effects. Further, for a large variety of correlated systems, strong correlations are largely confined to the charge sector. Then an adequate nonlocal low-order theory is important, and the high-order local correlations embedding contributes become redundant. Here we study the impact of charge self-consistency within two example cases, TiSe2 and CrBr3, and show how real space charge re-distribution due to correlation effects taken into account within a first-principles Green’s function-based many-body perturbative approach is key in driving qualitative changes to the final electronic structure of these materials.
Development of multi-angle fiber array for accurate measurement of flexion and rotation in human joints
Authors: Jeong Sang-Mi , Son Minkyun , Kang Youngsoo , Yang Jonguk , Lim Taekyung , Ju Sanghyun
Published: December 2021

Herein, we have proposed a method that uses a highly stretchable and conductive fiber-based multi-angle fiber array, which precisely measures human joint motion in various degrees of freedom (flexion and rotation) at the shoulders, knees, and wrists in real time. By embedding conductive carbon nanotubes (CNTs) within spandex fibers of high elasticity and shape recovery ratio, we monitored joint motion stably without degrading the fiber’s conductivity even during repeated stretching and contraction of different lengths. The strain occurring in a specific direction was monitored using mapping images generated due to the change in resistance that occurred when 12 CNT-embedded spandex fibers arranged in radial lines at intervals of 15° were stretched or contracted by an external force. The proposed high-precision joint-monitoring technology measures human motion accurately and is applicable for use in wearable healthcare devices that require precise measurements.
Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson’s disease
Authors: Vacchi Elena , Senese Camilla , Chiaro Giacomo , Disanto Giulio , Pinton Sandra , Morandi Sara , Bertaina Ilaria , Bianco Giovanni , Staedler Claudio , Galati Salvatore , Gobbi Claudio , Kaelin-Lang Alain , Melli Giorgia
Published: December 2021

The proximity ligation assay (PLA) is a specific and sensitive technique for the detection of αSyn oligomers (αSyn-PLA), early and toxic species implicated in the pathogenesis of PD. We aimed to evaluate by skin biopsy the diagnostic and prognostic capacity of αSyn-PLA and small nerve fiber reduction in PD in a longitudinal study. αSyn-PLA was performed in the ankle and cervical skin biopsies of PD (n = 30), atypical parkinsonisms (AP, n = 23) including multiple system atrophy (MSA, n = 12) and tauopathies (AP-Tau, n = 11), and healthy controls (HC, n = 22). Skin biopsy was also analyzed for phosphorylated αSyn (P-αSyn) and 5G4 (αSyn-5G4), a conformation-specific antibody to aggregated αSyn. Intraepidermal nerve fiber density (IENFD) was assessed as a measure of small fiber neuropathy. αSyn-PLA signal was more expressed in PD and MSA compared to controls and AP-Tau. αSyn-PLA showed the highest diagnostic accuracy (PD vs. HC sensitivity 80%, specificity 77%; PD vs. AP-Tau sensitivity 80%, specificity 82%), however, P-αSyn and 5G4, possible markers of later phases, performed better when considering the ankle site alone. A small fiber neuropathy was detected in PD and MSA. A progression of denervation not of pathological αSyn was detected at follow-up and a lower IENFD at baseline was associated with a greater cognitive and motor decline in PD. A skin biopsy-derived compound marker, resulting from a linear discrimination analysis model of αSyn-PLA, P-αSyn, αSyn-5G4, and IENFD, stratified patients with accuracy (77.8%), including the discrimination between PD and MSA (84.6%). In conclusion, the choice of pathological αSyn marker and anatomical site influences the diagnostic performance of skin biopsy and can help in understanding the temporal dynamics of αSyn spreading in the peripheral nervous system during the disease. Skin denervation, not pathological αSyn is a potential progression marker for PD.
Magnetic particles and strings in iron langasite
Authors: Barts Evgenii , Mostovoy Maxim
Published: December 2021

Magnetic topological defects can store and carry information. Replacement of extended defects, such as domain walls and Skyrmion tubes, by compact magnetic particles that can propagate in all three spatial directions may open an extra dimension in the design of magnetic memory and data processing devices. We show that such objects can be found in iron langasite, which exhibits a hierarchy of non-collinear antiferromagnetic spin structures at very different length scales. We derive an effective model describing long-distance magnetic modulations in this chiral magnet and find unusual two- and three-dimensional topological defects. The order parameter space of our model is similar to that of superfluid 3He-A, and the particle-like magnetic defect is closely related to the Shankar monopole and hedgehog soliton in the Skyrme model of baryons. Mobile magnetic particles stabilized in non-collinear antiferromagnets can play an important role in antiferromagnetic spintronics.
Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2
Authors: Lassaunière Ria , Polacek Charlotta , Gram Gregers J. , Frische Anders , Tingstedt Jeanette Linnea , Krüger Maren , Dorner Brigitte G. , Cook Anthony , Brown Renita , Orekov Tatyana , Putmon-Taylor Tammy , Campbell Tracey-Ann , Greenhouse Jack , Pessaint Laurent , Andersen Hanne , Lewis Mark G. , Fomsgaard Anders
Published: December 2021

New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.
Mobile BCI dataset of scalp- and ear-EEGs with ERP and SSVEP paradigms while standing, walking, and running
Authors: Lee Young-Eun , Shin Gi-Hwan , Lee Minji , Lee Seong-Whan
Published: December 2021

We present a mobile dataset obtained from electroencephalography (EEG) of the scalp and around the ear as well as from locomotion sensors by 24 participants moving at four different speeds while performing two brain-computer interface (BCI) tasks. The data were collected from 32-channel scalp-EEG, 14-channel ear-EEG, 4-channel electrooculography, and 9-channel inertial measurement units placed at the forehead, left ankle, and right ankle. The recording conditions were as follows: standing, slow walking, fast walking, and slight running at speeds of 0, 0.8, 1.6, and 2.0 m/s, respectively. For each speed, two different BCI paradigms, event-related potential and steady-state visual evoked potential, were recorded. To evaluate the signal quality, scalp- and ear-EEG data were qualitatively and quantitatively validated during each speed. We believe that the dataset will facilitate BCIs in diverse mobile environments to analyze brain activities and evaluate the performance quantitatively for expanding the use of practical BCIs.
Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome
Authors: Cheng Lan , Fu Qianyu , Zhou Longhua , Fan Yuqin , Liu Fenfen , Fan Yuanyuan , Zhang Xin , Lin Weiqing , Wu Xiaohe
Published: December 2021

The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People’s Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.
Long-term macrolide treatment for non-cystic fibrosis bronchiectasis in children: a meta-analysis
Authors: Lee Eun , Sol In Suk , Kim Jong Deok , Yang Hyeon-Jong , Min Taek Ki , Jang Gwang Cheon , Hwang Yoon Ha , Cho Hyun-Ju , Suh Dong In , Kim Kyunghoon , Kim Hwan Soo , Kim Yoon Hee , Woo Sung Il , Lee Yong Ju , Jung Sungsu , Jeon You Hoon
Published: December 2021

Recurrent bacterial infection causes frequent bronchiectasis (BE) exacerbations. The effectiveness and safety of long-term administration of macrolides in BE remain controversial, especially in children who require minimal treatment to prevent exacerbation. We conducted this meta-analysis to determine the usefulness of long-term macrolide use in pediatric BE. We searched PubMed, Cochrane Library databases, Embase, KoreaMed, Igaku Chuo Zasshi, and Chinese National Knowledge Infrastructure databases. We identified randomized controlled trials (RCTs) which elucidated long-term macrolide treatment (≥ 4 weeks) in non-cystic fibrosis BE in children aged < 18 years. The primary outcome was frequency of acute exacerbation; secondary outcomes included changes in pulmonary function, sputum scores, and adverse events including bacterial resistance. We included four RCTs. Long-term macrolide treatment showed a significant decrease in the frequency of exacerbation (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.10–0.87), mean number of exacerbations per patient (mean difference, − 1.40; 95% CI, − 2.26 to − 0.54), and sputum purulence score (mean difference, − 0.78; 95% CI, − 1.32 to − 0.24). However, long-term macrolide treatment was accompanied by an increased carriage of azithromycin-resistant bacteria (OR, 7.13). Long-term macrolide administration prevents exacerbation of BE in children; however, there are risks of increasing antibiotic resistance. Benefits and risks should be weighed and determined on a patient-by-patient basis.
Insulin signalling in tanycytes gates hypothalamic insulin uptake and regulation of AgRP neuron activity
Authors: Porniece Kumar Marta , Cremer Anna Lena , Klemm Paul , Steuernagel Lukas , Sundaram Sivaraj , Jais Alexander , Hausen A. Christine , Tao Jenkang , Secher Anna , Pedersen Thomas Åskov , Schwaninger Markus , Wunderlich F. Thomas , Lowell Bradford B. , Backes Heiko , Brüning Jens C.
Published: December 2021

Insulin acts on neurons and glial cells to regulate systemic glucose metabolism and feeding. However, the mechanisms of insulin access in discrete brain regions are incompletely defined. Here we show that insulin receptors in tanycytes, but not in brain endothelial cells, are required to regulate insulin access to the hypothalamic arcuate nucleus. Mice lacking insulin receptors in tanycytes (IR∆Tan mice) exhibit systemic insulin resistance, while displaying normal food intake and energy expenditure. Tanycytic insulin receptors are also necessary for the orexigenic effects of ghrelin, but not for the anorexic effects of leptin. IR∆Tan mice exhibit increased agouti-related peptide (AgRP) neuronal activity, while displaying blunted AgRP neuronal adaptations to feeding-related stimuli. Lastly, a highly palatable food decreases tanycytic and arcuate nucleus insulin signalling to levels comparable to those seen in IR∆Tan mice. These changes are rooted in modifications of cellular stress responses and of mitochondrial protein quality control in tanycytes. Conclusively, we reveal a critical role of tanycyte insulin receptors in gating feeding-state-dependent regulation of AgRP neurons and systemic insulin sensitivity, and show that insulin resistance in tanycytes contributes to the pleiotropic manifestations of obesity-associated insulin resistance.
Creation of stable water-free antibody based protein liquids
Authors: Slocik Joseph M. , Dennis Patrick B. , Kuang Zhifeng , Pelton Anthony , Naik Rajesh R.
Published: December 2021

Antibodies represent highly specific and high binding affinity biomolecular recognition elements for diagnostic assays, biosensors, and therapeutics, but are sensitive to denaturation and degradation. Consequently, the combination of existing in a hydrated state with a large and complex biomolecular structure results in loss of antibody-antigen binding, limited shelf-life, and decreased sensor response over time and under non-optimal conditions. The development and use of water-free protein liquids has led to stabilization of labile biomolecules, solvents for biotransformation reactions, and formation of new bio-composites with incompatible materials. Here, we exploit the polycationic nature of modified antibodies and their ability to form ion pairs for the conversion of primary Immunoglobulin G antibodies into stable protein liquids that retained more than 60% binding activity after repeated heating up to 125 °C, and demonstrate compatibility with thermoplastics.