bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging the developmental science of psychosocial risk to strengthen youth psychotherapy
Authors: Vaughn-Coaxum Rachel A. , Weisz John R.
Published: March 2021

More than 50 years of randomized clinical trials for youth psychotherapies have resulted in moderate effect sizes for treatments targeting the most common mental health problems in children and adolescents (i.e., anxiety, depression, conduct problems, and attention disorders). Despite having psychotherapies that are effective for many children, there has been a dearth of progress in identifying the contextual factors that likely influence who will respond to a given psychotherapy, and under what conditions. The developmental psychopathology evidence base consistently demonstrates that psychosocial risk exposures (e.g., childhood adversities, interpersonal stressors, family dysfunction) significantly influence the onset and course of youth psychopathology. However, the developmental psychopathology framework remains to be well integrated into treatment development and psychotherapy research. We argue that advances in basic developmental psychopathology research carry promising implications for the design and content of youth psychotherapies. Research probing the effects of psychosocial risks on youth development can enrich efforts to identify contextual factors in psychotherapy effectiveness and to personalize treatment. In this article we review empirically supported and hypothesized influences of individual- and family-level risk factors on youth psychotherapy outcomes, and we propose a framework for leveraging developmental psychopathology to strengthen psychotherapies.
Coronary artery spasm in a 15-year-old male in diabetic ketoacidosis
Authors: Strah Danielle , Seckeler Michael , Mendelson Jenny
Published: March 2021

Coronary artery disease and myocardial infarction are known complications of long-standing diabetes mellitus in adults, but coronary artery spasm is far more rare and has not been reported in children. We present a 15-year-old male in diabetic ketoacidosis who developed diffuse ST segment elevations and elevated troponin with normal coronary arteries on coronary angiography and no signs of pericarditis that was due to coronary artery spasm.
Deserving of Social Support? Street-Level Bureaucrats’ Decisions on EU Migrants’ Benefit Claims in Germany
Authors: Ratzmann Nora
Published: March 2021

Migration raises the question of how street-level bureaucrats treat non-citizens when it comes to the distribution of limited welfare resources. Based on a German case study, this article reveals how local social administrators rationalise practices of inclusion in and exclusion from social assistance receipt and associated labour market integration services for mobile EU citizens, who are perceived first and foremost as ‘foreigners’. The findings from fifty-five qualitative interviews with job centre representatives show how politics of exclusion are justified by nationalistic and ethnic criteria of membership. Insofar as EU migrants are considered outsiders to the imagined welfare community of their host country, they are seen as less deserving than German-born claimants. However, mobile EU citizens can earn their legitimacy to access benefit receipt through sustained participation in the host society, demonstrating knowledge of the German language and societal norms so as to appear ‘German’. Such a cultural performance-based logic of deservingness tends to be intertwined with nationality-based and racialising stereotypes of welfare fraud to frame exclusionary practice.
István Hont, the Cosmopolitan Theory of Commercial Globalization, and Twenty-First-Century Capitalism
Authors: Cheney Paul
Published: March 2021

This critical essay explores the work of István Hont. Members of the Cambridge school eschewed the term “capitalism” as an anachronistic description of the contexts that informed early modern politico-economic thought, preferring instead the ostensibly more neutral “commercial society.” But Hont's understanding of the latter was nevertheless quite present-minded and politically charged. Hont drove nineteenth- and twentieth-century economic theory back into eighteenth-century models, and his view of the economy that gave rise to them was informed by concerns in the 1980s and 1990s over the competitiveness of advanced capitalist nations in the face of low-cost insurgents such as China. More deliberate choices of recent economic theory can produce more accurate alternatives to the supposedly neutral “commercial society” depicted by Hont. World systems and dependency theory may help us to better understand the economic thought produced in and about the specifically capitalist world economy of the early modern period.
Reading Heidegger against the Grain: Hans Jonas on Existentialism, Gnosticism, and Modern Science
Authors: Herskowitz Daniel M.
Published: March 2021

This article argues that the link Hans Jonas drew between Martin Heidegger's philosophy and Gnosticism cannot be properly understood without taking into consideration his philosophical interpretation of modern science. It claims that Jonas saw Heideggerian existentialism not as a modern instantiation of Gnosticism but as a specific experiential reaction to the new cosmological outlook that emerged from the seventeenth-century scientific revolution, which negated the conceptual world that made Gnosticism possible. Jonas's interpretation is “against the grain”: by claiming that Heidegger's thought is a product of the reduction of nature to measurable, manipulable, and calculable extension governing the modern scientific mind, Jonas attributed to Heidegger the very flaws Heidegger critiqued in others. It is further claimed that Jonas's original contribution to Heidegger's reception history is not in proposing the link to Gnosticism but in reading him as the philosophical outcome of the instrumental reasoning of modern science.
Should Strengthening Bonds Be a Public Health	Priority?
Authors: Wood Valerie M. , Stuart Heather
Published: March 2021

Abstract. Background: Previous research demonstrates the importance of close relationships on our physical health. However, to what extent the quality of our social relationships impacts our health, relative to other important health behaviors (e.g., smoking, drinking alcohol, and physical exercise), is less clear. Aims: Our goal was to use a nationally representative sample of Canadian adults to assess the relative importance of the quality of one’s social relationships (close emotional bonds and negative social interactions), relative to important health behaviors on physical health outcomes previously linked to social relationship quality. Method: Data ( N = 25,113) came from the Canadian Community Health Survey in 2012, a cross-sectional survey administered by Statistics Canada (2013) . The predictor variables were the presence of close emotional bonds, negative social relationships, type of smoker, type of drinker, and weekly hours of physical activity. The outcome variables were a current or previous diagnosis of high blood pressure, cancer, stroke, reports of current illness or injury, pain, and self-reported physical health. Results: Using regressions, we found that negative social interactions were more important than other health behaviors in relation to current injury/illness and pain. Physical activity was most strongly related to self-rated health, followed by negative social interactions and then close emotional bonds. Alcohol consumption was more related to the prevalence of stroke. Conclusions: Our findings suggest that negative social interactions may be more related to acute or minor physical health conditions, but social relationships may not be more strongly related to more chronic, life-threatening health conditions than other health behaviors.
Stable Carbon Isotopes Suggest Large Terrestrial Carbon Inputs to the Global Ocean
Authors: Kwon Eun Young , DeVries Tim , Galbraith Eric D. , Hwang Jeomshik , Kim Guebuem , Timmermann Axel
Published: March 2021

The transport of carbon from land to ocean, via rivers, groundwater, and aerosols, is an important component of the global carbon cycle that must be known to accurately assess anthropogenic CO2 storage on land and in the ocean. Current global carbon cycle budgets have adopted terrestrial carbon inputs to the ocean ranging from 0.5 GtC/yr to 0.9 GtC/yr, derived mainly from estimates of riverine fluxes. However, these budgets ignore the terrestrial carbon inputs from coastal ecosystems and through submarine groundwater discharge (collectively referred to as coastal margin inputs in this study) due to difficulties in making global assessments. Using a numerical model and globally distributed ocean observations of stable carbon isotopes, we estimate terrestrial carbon inputs to the ocean at 1.4 ± 0.5 GtC/yr, with 95% of the coastal margin inputs (0.8 ± 0.5 GtC/yr) occurring in the Pacific and Indian Oceans. This terrestrial carbon flux is largely balanced by an efflux to the atmosphere of 1.2 ± 0.5 GtC/yr, 40% of which occurs in poorly monitored coastal regions and may have been overlooked in previous observation‐based global estimates. Our results suggest more dynamic cycling of carbon in the land‐ocean transition zone than previously thought, and that rivers may not be the only important pathway for terrestrial carbon to the ocean.
Constraining Floating Ice Shelf Structures by Spectral Response of Teleseismic P‐Wave Coda: Ross Ice Shelf, Antarctica
Authors: Phạm Thanh‐Son , Tkalčić Hrvoje
Published: March 2021

The recent deployment of a broadband seismic array on the floating ice shelf in the Antarctica's Ross sea presents a great opportunity to study the shelf structure using broadband seismic data. In this study, we develop a further improvement of the P‐wave coda autocorrelation method, which proved capable of characterizing grounded ice‐cap structures. Ice shelves are floating ice sheets connected to a landmass, and in order to decipher their structures, a water layer has to be added to the problem. We construct the power spectrum stacks of P‐wave coda data, waveform records that immediately follow P arrivals, in the spectral domain, which are equivalent, via a Fourier transform, to widely used autocorrelograms in the time domain. At half of temporary seismic stations under consideration, we report prominent resonant peaks in the spectral autocorrelograms, associated with the ice‐water configuration of the ice shelf. The lack of clear resonant pattern for the rest of the stations is suspected due to a high noise level in the icy environment and significant lateral heterogeneity at the local scale. Subsequently, we develop a formalism to explain the observed resonance and devise a grid‐search scheme to estimate ice‐ and water‐thicknesses underneath the stations. Our water‐thickness estimates agree well with the previously documented measurements, but there is a discrepancy in the ice thickness results. Therefore, the method has a great potential to complement the existing ice‐shelf model, to be used in future monitoring applications of ice shelves, or near‐future space exploration to icy planets.
The Physics of Falling Raindrops in Diverse Planetary Atmospheres
Authors: Loftus Kaitlyn , Wordsworth Robin D.
Published: March 2021

The evolution of a single raindrop falling below a cloud is governed by fluid dynamics and thermodynamics fundamentally transferable to planetary atmospheres beyond modern Earth's. Here, we show how three properties that characterize falling raindrops—raindrop shape, terminal velocity, and evaporation rate—can be calculated as a function of raindrop size in any planetary atmosphere. We demonstrate that these simple, interrelated characteristics tightly bound the possible size range of raindrops in a given atmosphere, independently of poorly understood growth mechanisms. Starting from the equations governing raindrop falling and evaporation, we demonstrate that raindrop ability to vertically transport latent heat and condensible mass can be well captured by a new dimensionless number. Our results have implications for precipitation efficiency, convective storm dynamics, and rainfall rates, which are properties of interest for understanding planetary radiative balance and (in the case of terrestrial planets) rainfall‐driven surface erosion.
The Conductive Cooling of Planetesimals With Temperature‐Dependent Properties
Authors: Murphy Quinlan M. , Walker A. M. , Davies C. J. , Mound J. E. , Müller T. , Harvey J.
Published: March 2021

Modeling the planetary heat transport of small bodies in the early Solar System allows us to understand the geological context of meteorite samples. Conductive cooling in planetesimals is controlled by thermal conductivity, heat capacity, and density, which are functions of temperature (T). We investigate if the incorporation of the T‐dependence of thermal properties and the introduction of a nonlinear term to the heat equation could result in different interpretations of the origin of different classes of meteorites. We have developed a finite difference code to perform numerical models of a conductively cooling planetesimal with T‐dependent properties and find that including T‐dependence produces considerable differences in thermal history, and in turn the estimated timing and depth of meteorite genesis. We interrogate the effects of varying the input parameters to this model and explore the nonlinear T‐dependence of conductivity with simple linear functions. Then we apply non‐monotonic functions for conductivity, heat capacity, and density fitted to published experimental data. For a representative calculation of a 250 km radius pallasite parent body, T‐dependent properties delay the onset of core crystallization and dynamo activity by ∼40 Myr, approximately equivalent to increasing the planetary radius by 10%, and extend core crystallization by ∼3 Myr. This affects the range of planetesimal radii and core sizes for the pallasite parent body that are compatible with paleomagnetic evidence. This approach can also be used to model the T‐evolution of other differentiated minor planets and primitive meteorite parent bodies and constrain the formation of associated meteorite samples.
Phosphorus Inventory for the Conterminous United States (2002–2012)
Authors: Sabo Robert D. , Clark Christopher M. , Gibbs David A. , Metson Geneviève S. , Todd M. Jason , LeDuc Stephen D. , Greiner Diana , Fry Meridith M. , Polinsky Robyn , Yang Qichun , Tian Hanqin , Compton Jana E.
Published: March 2021

Published reports suggest efforts designed to prevent the occurrence of harmful algal blooms and hypoxia by reducing non‐point and point source phosphorus (P) pollution are not delivering water quality improvements in many areas. Part of the uncertainty in evaluating watershed responses to management practices is the lack of standardized estimates of phosphorus inputs and outputs. To assess P trends across the conterminous United States, we compiled an inventory using publicly available datasets of agricultural P fluxes, atmospheric P deposition, human P demand and waste, and point source discharges for 2002, 2007, and 2012 at the scale of the 8‐digit Hydrologic Unit Code subbasin (∼1,800 km2). Estimates of agricultural legacy P surplus accumulated from 1945 to 2001 were also developed. Fertilizer and manure inputs were found to exceed crop removal rates by up to 50% in many agricultural regions. This excess in inputs has led to the continued accumulation of legacy P in agricultural lands. Atmospheric P deposition increased throughout the Rockies, potentially contributing to reported increases in surface water P concentrations in undisturbed watersheds. In some urban areas, P fluxes associated with human waste and non‐farm fertilizer use has declined despite population growth, likely due, in part, to various sales bans on P‐containing detergents and fertilizers. Although regions and individual subbasins have different contemporary and legacy P sources, a standardized method of accounting for large and small fluxes and ready to use inventory numbers provide essential infromation to coordinate targeted interventions to reduce P concentrations in the nation's waters.
Evaporation Suppression From Small Reservoirs Using Floating Covers—Field Study and Modeling
Authors: Mady Bassem , Lehmann Peter , Or Dani
Published: March 2021

Evaporative losses from small seasonal water reservoirs in semiarid regions may significantly diminish storage and water availability to rural communities. Motivated by finding effective and economically feasible measures for suppressing evaporation, we study the efficacy of self‐assembling floating covers in suppressing evaporation under field conditions and potential ecological ramifications of the covers. We conducted a multi‐season study with eight identical small reservoirs (13.5 m2 area and 1.5 m deep) using ethylene‐vinyl acetate foam disks (200 mm in diameter, 15 mm thick) in white and black to cover six reservoirs (cover fraction of 91%), leaving two uncovered reservoirs for control. Physical attributes such as evaporative losses, radiative balance, temperature, and heat fluxes were measured and compared with modeling results. Evaporation suppression under field conditions ranged between 65% and 80% in the summer. Despite significant differences in energy partitioning, evaporation from white and black disks were relatively similar (∼20% for white and ∼30% evaporation for black disks compared to uncovered reservoir). Replacing black disks with water filled black polyethylene balls improved suppression efficiency and diminished seasonal variations (∼80% suppression irrespective of season). We developed a physically based model to describe and extend the experimental findings by exploring effects of reservoir management regimes on evaporation and to optimize cover and reservoir characteristics for different climatic conditions.
Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution
Authors: Lin Weimin , Li Qiwen , Zhang Danting , Zhang Xiaohan , Qi Xingying , Wang Qian , Chen Yaqian , Liu Caojie , Li Hanwen , Zhang Shiwen , Wang Yuan , Shao Bin , Zhang Li , Yuan Quan
Published: March 2021

Alveolar bone is the thickened ridge of jaw bone that supports teeth. It is subject to constant occlusal force and pathogens invasion, and is therefore under active bone remodeling and immunomodulation. Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern. However, a systematic explanation of alveolar bone at single-cell level is still lacking. Here, we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing (scRNA-seq). A more active immune microenvironment is identified in alveolar bone, with a higher proportion of mature immune cells than in long bone. Among all immune cell populations, the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells (MSCs) subpopulation. Alveolar bone monocytes/macrophages express a higher level of Oncostatin M (Osm) compared to long bone, which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs. In summary, our study reveals a unique immune microenvironment of alveolar bone, which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.
Correction to: The impact of COVID-19 on systemic anticancer treatment delivery in Scotland
Authors: Baxter Mark A. , Murphy John , Cameron David , Jordan Judith , Crearie Christine , Lilley Christina , Sadozye Azmat , Maclean Mary , Hall Peter , Phillips Angela , Greger Alex , Madeleine Jude , Petty Russell D.
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41416-021-01298-w
Investigation of circulating metabolites associated with breast cancer risk by untargeted metabolomics: a case–control study nested within the French E3N cohort
Authors: Jobard Elodie , Dossus Laure , Baglietto Laura , Fornili Marco , Lécuyer Lucie , Mancini Francesca Romana , Gunter Marc J. , Trédan Olivier , Boutron-Ruault Marie-Christine , Elena-Herrmann Bénédicte , Severi Gianluca , Rothwell Joseph A.
Published: March 2021

Background

Perturbations in circulating metabolites prior to a breast cancer diagnosis are not well characterised. We aimed to gain more detailed knowledge to help understand and prevent the disease.

Methods

Baseline plasma samples from 791 breast cancer cases and 791 matched controls from the E3N (EPIC-France) cohort were profiled by nuclear magnetic resonance (NMR)-based untargeted metabolomics. Partial least-squares discriminant analysis (PLS-DA) models were built from NMR profiles to predict disease outcome, and odds ratios and false discovery rate (FDR)-adjusted CIs were calculated for 43 identified metabolites by conditional logistic regression.

Results

Breast cancer onset was predicted in the premenopausal subgroup with modest accuracy (AUC 0.61, 95% CI: 0.49–0.73), and 10 metabolites associated with risk, particularly histidine (OR = 1.70 per SD increase, FDR-adjusted CI 1.19–2.41), N-acetyl glycoproteins (OR = 1.53, FDR-adjusted CI 1.18–1.97), glycerol (OR = 1.55, FDR-adjusted CI 1.11–2.18) and ethanol (OR = 1.44, FDR-adjusted CI 1.05–1.97). No predictive capacity or significant metabolites were found overall or for postmenopausal women.

Conclusions

Perturbed metabolism compared to controls was observed in premenopausal but not postmenopausal cases. Histidine and NAC have known involvement in inflammatory pathways, and the robust association of ethanol with risk suggests the involvement of alcohol intake.
A 10-gene prognostic signature points to LIMCH1 and HLA-DQB1 as important players in aggressive cervical cancer disease
Authors: Halle Mari K. , Sødal Marte , Forsse David , Engerud Hilde , Woie Kathrine , Lura Njål G. , Wagner-Larsen Kari S. , Trovik Jone , Bertelsen Bjørn I. , Haldorsen Ingfrid S. , Ojesina Akinyemi I. , Krakstad Camilla
Published: March 2021

Background

Advanced cervical cancer carries a particularly poor prognosis, and few treatment options exist. Identification of effective molecular markers is vital to improve the individualisation of treatment. We investigated transcriptional data from cervical carcinomas related to patient survival and recurrence to identify potential molecular drivers for aggressive disease.

Methods

Primary tumour RNA-sequencing profiles from 20 patients with recurrence and 53 patients with cured disease were compared. Protein levels and prognostic impact for selected markers were identified by immunohistochemistry in a population-based patient cohort.

Results

Comparison of tumours relative to recurrence status revealed 121 differentially expressed genes. From this gene set, a 10-gene signature with high prognostic significance (p = 0.001) was identified and validated in an independent patient cohort (p = 0.004). Protein levels of two signature genes, HLA-DQB1 (n = 389) and LIMCH1 (LIM and calponin homology domain 1) (n = 410), were independent predictors of survival (hazard ratio 2.50, p = 0.007 for HLA-DQB1 and 3.19, p = 0.007 for LIMCH1) when adjusting for established prognostic markers. HLA-DQB1 protein expression associated with programmed death ligand 1 positivity (p < 0.001). In gene set enrichment analyses, HLA-DQB1high tumours associated with immune activation and response to interferon-γ (IFN-γ).

Conclusions

This study revealed a 10-gene signature with high prognostic power in cervical cancer. HLA-DQB1 and LIMCH1 are potential biomarkers guiding cervical cancer treatment.
Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles
Authors: Ye Weiyu , Olsson-Brown Anna , Watson Robert A. , Cheung Vincent T. F. , Morgan Robert D. , Nassiri Isar , Cooper Rosalin , Taylor Chelsea A. , Akbani Umair , Brain Oliver , Matin Rubeta N. , Coupe Nicholas , Middleton Mark R. , Coles Mark , Sacco Joseph J. , Payne Miranda J. , Fairfax Benjamin P.
Published: March 2021

Background

Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.

Methods

Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.

Results

58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.

Conclusions

Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.
Correction to: The androgen receptor/filamin A complex as a target in prostate cancer microenvironment
Authors: Di Donato Marzia , Zamagni Alice , Galasso Giovanni , Di Zazzo Erika , Giovannelli Pia , Barone Maria Vittoria , Zanoni Michele , Gunelli Roberta , Costantini Matteo , Auricchio Ferdinando , Migliaccio Antimo , Tesei Anna , Castoria Gabriella
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03483-4
PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma via the PER1/RACK1/PI3K signaling complex
Authors: Gong Xiaobao , Tang Hong , Yang Kai
Published: March 2021

There is increasing evidence that the core clock gene Period 1 (PER1) plays important roles in the formation of various tumors. However, the biological functions and mechanism of PER1 in promoting tumor progression remain largely unknown. Here, we discovered that PER1 was markedly downregulated in oral squamous cell carcinoma (OSCC). Then, OSCC cell lines with stable overexpression, knockdown, and mutation of PER1 were established. We found that PER1 overexpression significantly inhibited glycolysis, glucose uptake, proliferation, and the PI3K/AKT pathway in OSCC cells. The opposite effects were observed in PER1-knockdown OSCC cells. After treatment of PER1-overexpressing OSCC cells with an AKT activator or treatment of PER1-knockdown OSCC cells with an AKT inhibitor, glycolysis, glucose uptake, and proliferation were markedly rescued. In addition, after treatment of PER1-knockdown OSCC cells with a glycolysis inhibitor, the increase in cell proliferation was significantly reversed. Further, coimmunoprecipitation (Co-IP) and cycloheximide (CHX) chase experiment demonstrated that PER1 can bind with RACK1 and PI3K to form the PER1/RACK1/PI3K complex in OSCC cells. In PER1-overexpressing OSCC cells, the abundance of the PER1/RACK1/PI3K complex was significantly increased, the half-life of PI3K was markedly decreased, and glycolysis, proliferation, and the PI3K/AKT pathway were significantly inhibited. However, these effects were markedly reversed in PER1-mutant OSCC cells. In vivo tumorigenicity assays confirmed that PER1 overexpression inhibited tumor growth while suppressing glycolysis, proliferation, and the PI3K/AKT pathway. Collectively, this study generated the novel findings that PER1 suppresses OSCC progression by inhibiting glycolysis-mediated cell proliferation via the formation of the PER1/RACK1/PI3K complex to regulate the stability of PI3K and the PI3K/AKT pathway-dependent manner and that PER1 could potentially be a valuable therapeutic target in OSCC.
NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin
Authors: Yue Rongchuan , Zheng Zaiyong , Luo Yu , Wang Xiaobo , Lv Mingming , Qin Dan , Tan Qingqing , Zhang Yulong , Wang Tao , Hu Houxiang
Published: March 2021

The exact mechanism of myocardial hypertrophy has not been completely elucidated. NOD-like receptor protein 3 (NLRP3) and the pyroptotic cascade play a critical role in cardiac hypertrophy and inflammation. The myokine irisin can inhibit NLRP3 activation, although its exact mechanism of action is unknown. In this study, we induced cardiac hypertrophy in a mouse model via aortic constriction (TAC) to further explore the pathological role of NLRP3 inflammasome-mediated pyroptosis and the potential therapeutic effects of irisin. Cardiac hypertrophy significantly increased the percentage of apoptotic cells and upregulated IL-1β, cleaved caspase-1, and GSDMD-N that lie downstream of the NLRP3 inflammasome. Subsequently, irisin was co-administered to the TAC mice or angiotensin II (Ang-II)-treated cardiomyocytes to observe whether it could attenuate pyroptosis and cardiac hypertrophy. We established a direct association between pyroptosis and cardiac hypertrophy and found that pharmacological or genetic inhibition of NLRP3 attenuated cardiac hypertrophy. Furthermore, ectopic overexpression of NLRP3 abrogated the cardioprotective effects of irisin. To summarize, pyroptosis is a pathological factor in cardiac hypertrophy, and irisin is a promising therapeutic agent that inhibits NLRP3-mediated pyroptosis of cardiomyocytes.
Dysregulation of miR-23b-5p promotes cell proliferation via targeting FOXM1 in hepatocellular carcinoma
Authors: Yang Xinchen , Yang Shikun , Song Jinhua , Yang Wenjie , Ji Yang , Zhang Feng , Rao Jianhua
Published: March 2021

Growing evidence demonstrates that MicroRNAs (miRNAs) play an essential role in contributing to tumor development and progression. However, the underlying role and mechanisms of miR-23b-5p in hepatocellular carcinoma (HCC) formation remain unclear. Our study showed that miR-23b-5p was downregulated in the HCC tissues and cell lines, and lower expression of miR-23b-5p was associated with more severe tumor size and poorer survival. Gain- or loss-of-function assays demonstrated that miR-23b-5p induced G0/G1 cell cycle arrest and inhibited cell proliferation both in vitro and in vivo. qRT-PCR, western blot and luciferase assays verified that Mammalian transcription factor Forkhead Box M1 (FOXM1), upregulated in HCC specimens, was negatively correlated with miR-23b-5p expression and acted as a direct downstream target of miR-23b-5p. In addition, miR-23b-5p could regulate cyclin D1 and c-MYC expression by directly targeting FOXM1. Further study revealed that restoration of FOXM1 neutralized the cell cycle arrest and cell proliferation inhibition caused by miR-23b-5p. Taken together, our findings suggest that miR-23b-5p acted as a tumor suppressor role in HCC progression by targeting FOXM1 and may serve as a potential novel biomarker for HCC diagnosis and prognosis.
Interactions between timing and transmissibility explain diverse flavivirus dynamics in Fiji
Authors: Henderson Alasdair D. , Kama Mike , Aubry Maite , Hue Stephane , Teissier Anita , Naivalu Taina , Bechu Vinaisi D. , Kailawadoko Jimaima , Rabukawaqa Isireli , Sahukhan Aalisha , Hibberd Martin L. , Nilles Eric J. , Funk Sebastian , Whitworth Jimmy , Watson Conall H. , Lau Colleen L. , Edmunds W. John , Cao-Lormeau Van-Mai , Kucharski Adam J.
Published: March 2021

Zika virus (ZIKV) has caused large, brief outbreaks in isolated populations, however ZIKV can also persist at low levels over multiple years. The reasons for these diverse transmission dynamics remain poorly understood. In Fiji, which has experienced multiple large single-season dengue epidemics, there was evidence of multi-year transmission of ZIKV between 2013 and 2017. To identify factors that could explain these differences in dynamics between closely related mosquito-borne flaviviruses, we jointly fit a transmission dynamic model to surveillance, serological and molecular data. We estimate that the observed dynamics of ZIKV were the result of two key factors: strong seasonal effects, which created an ecologically optimal time of year for outbreaks; and introduction of ZIKV after this optimal time, which allowed ZIKV transmission to persist over multiple seasons. The ability to jointly fit to multiple data sources could help identify a similar range of possible outbreak dynamics in other settings.
A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing
Authors: Zhang Jian , Zheng Yongjun , Lee Jimmy , Hua Jieyu , Li Shilong , Panchamukhi Ananth , Yue Jiping , Gou Xuewen , Xia Zhaofan , Zhu Linyong , Wu Xiaoyang
Published: March 2021

Effective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-β (TGFβ) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFβ signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFβ can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.
Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia
Authors: Eze Ugomma C. , Bhaduri Aparna , Haeussler Maximilian , Nowakowski Tomasz J. , Kriegstein Arnold R.
Published: March 2021

The human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.
Comparison of new implantation of cardiac implantable electronic device between tertiary and non-tertiary hospitals: a Korean nationwide study
Authors: Han Seungbong , Park Gyung-Min , Kim Yong-Giun , Hwang Ki Won , Kwon Chang Hee , Roh Jae-Hyung , Park Sangwoo , Won Ki-Bum , Ann Soe Hee , Kim Shin-Jae , Lee Sang-Gon
Published: March 2021

This study compared the characteristics and mortality of new implantation of cardiac implantable electronic device (CIED) between tertiary and non-tertiary hospitals. From national health insurance claims data in Korea, 17,655 patients, who underwent first and new implantation of CIED between 2013 and 2017, were enrolled. Patients were categorized into the tertiary hospital group (n = 11,560) and non-tertiary hospital group (n = 6095). Clinical outcomes including in-hospital death and all-cause death were compared between the two groups using propensity-score matched analysis. Patients in non-tertiary hospitals were older and had more comorbidities than those in tertiary hospitals. The study population had a mean follow-up of 2.1 ± 1.2 years. In the propensity-score matched permanent pacemaker group (n = 5076 pairs), the incidence of in-hospital death (odds ratio [OR]: 0.76, 95% confidence interval [CI]: 0.43–1.32, p = 0.33) and all-cause death (hazard ratio [HR]: 0.92, 95% CI 0.81–1.05, p = 0.24) were not significantly different between tertiary and non-tertiary hospitals. These findings were consistently observed in the propensity-score matched implantable cardioverter-defibrillator group (n = 992 pairs, OR for in-hospital death: 1.76, 95% CI 0.51–6.02, p = 0.37; HR for all-cause death: 0.95, 95% CI 0.72–1.24, p = 0.70). In patients undergoing first and new implantation of CIED in Korea, mortality was not different between tertiary and non-tertiary hospitals.
Pilot study of minimum occlusive force of vascular clamps on arterial vessels in rats
Authors: Sun Rui , Ren Lizhi , Zhang Zepeng , Wu Xiaofen , Wang Qianqian , Zhang Sui , Yang Xiaowen
Published: March 2021

Our aims were to determine the accuracy of an improved formula for determining the minimum occlusive force (MOF) of a vascular clamp on rats’ abdominal aortas, compare our findings with the calculated theoretical MOF, and provide reference data for clinical research and development of medical instruments that cause minimal damage. We created a vessel closure model and developed a formula for calculating the theoretical MOF of arterial vessels when they are occluded. This formula utilises the blood pressure in the blood vessel, its diameter, and the width of the vascular clamp. We then measured the actual MOF in 24 rat abdominal aortic segments with different diameters and different blood pressures and compared the theoretical and actual MOFs. Analysis of the experimental data showed a probability of 0.315, which means that, under the condition of normal distribution, the difference between the theoretical and actual MOF is not significant at the α = 0.05 level. Thus, the actual measured MOF tended to be consistent with the theoretical MOF calculated by the formula we developed. The improved formula will provide a reference for clinical research and development of medical instruments that cause minimal injury, thus contributing to the development of microsurgery.
Propensity score-matched analysis for comparing transpancreatic sphincterotomy and needle-knife precut in difficult biliary cannulation
Authors: Tabak Fatema , Wang Fei , Ji Guo-Zhong , Miao Lin
Published: March 2021

Transpancreatic sphincterotomy (TPS) can be an alternative approach of difficult biliary access in endoscopic retrograde cholangiopancreatography (ERCP). We aimed to evaluate the efficacy and safety of TPS compared to needle-knife precut (NKP), considering the early and late outcomes of both techniques. The prospectively collected clinical data, ERCP procedure findings, and outcomes of patients who underwent ERCP with difficult biliary access in our hospital from July 2016 to January 2018 were retrospectively analyzed. The patients were divided into two groups according to the applied secondary cannulation techniques. The propensity score matching (PSM) was applied to reduce the potential selection bias and unify the preventive measures of post-ERCP pancreatitis (PEP) in both groups. A total of 125 patients were enrolled in this study, with 54.4% male and a mean age of 63.29 ± 16.33 years. NKP group included 82 patients, and 43 patients received TPS. Prophylactic pancreatic stents were placed in all patients with TPS and 58.5% of patients with NKP. After applying PSM, the cohort was comprised to 86 patients with 43 patients in each TPS and NKP groups. Successful selective cannulation was achieved by 95.3% using TPS and by 93% using NKP. The mean procedure time was shorter in the TPS group without significant difference. Compared to NKP, using TPS did not affect the rate of PEP. Moreover, TPS was associated with less frequent post-ERCP bleeding and perforation, but without significant differences (all p > 0.05). Patients who received TPS or NKP had no symptoms related to papillary stenosis or chronic pancreatitis during the follow-up period. In conclusion, using TPS in difficult cannulation cases was useful to achieve success cannulation with an acceptable PEP rate and less frequent post-ERCP bleeding and perforation compared to NKP. There were no symptoms related to papillary stenosis or chronic pancreatitis during the follow-up period.
Acute and chronic effects of Titanium dioxide (TiO2) PM1 on honey bee gut microbiota under laboratory conditions
Authors: Papa G. , Di Prisco G. , Spini G. , Puglisi E. , Negri I.
Published: March 2021

Apis mellifera is an important provider of ecosystem services, and during flight and foraging behaviour is exposed to environmental pollutants including airborne particulate matter (PM). While exposure to insecticides, antibiotics, and herbicides may compromise bee health through alterations of the gut microbial community, no data are available on the impacts of PM on the bee microbiota. Here we tested the effects of ultrapure Titanium dioxide (TiO2) submicrometric PM (i.e., PM1, less than 1 µm in diameter) on the gut microbiota of adult bees. TiO2 PM1 is widely used as a filler and whitening agent in a range of manufactured objects, and ultrapure TiO2 PM1 is also a common food additive, even if it has been classified by the International Agency for Research on Cancer (IARC) as a possible human carcinogen in Group 2B. Due to its ubiquitous use, honey bees may be severely exposed to TiO2 ingestion through contaminated honey and pollen. Here, we demonstrated that acute and chronic oral administration of ultrapure TiO2 PM1 to adult bees alters the bee microbial community; therefore, airborne PM may represent a further risk factor for the honey bee health, promoting sublethal effects against the gut microbiota.
Impact of age, sex, and joint form on degenerative lesions of the sacroiliac joints on CT in the normal population
Authors: Ziegeler Katharina , Kreutzinger Virginie , Diekhoff Torsten , Roehle Robert , Poddubnyy Denis , Pumberger Matthias , Hamm Bernd , Hermann Kay Geert A.
Published: March 2021

Degeneration of the sacroiliac joints (SIJs) is a common finding, while its underlying cause and development remain incompletely understood. The aim of this investigation was to describe the spatial distribution of degenerative SIJ changes across age groups and to investigate for the first time their relationship to anatomical form and sex. For this IRB-approved investigation, demographic data of 818 patients without SIJ disease were retrieved from electronic patient records. High-resolution computed tomography (CT) datasets of all patients were analysed retrospectively for seven predefined age groups (ten-year increments, from < 25 to ≥ 75). A structured scoring system was applied to assess sclerosis, osteophytes, joint space alterations, and anatomical form. Chi-square tests were used to compare frequencies of degenerative lesions, and logistic regression analyses were performed to investigate associations between demographic data, anatomical form, and the presence of structural lesions. Sclerosis and osteophytes were common findings, with an overall prevalence of 45.7% and 46.8%, respectively. Female sex had an odds ratio (OR) of 0.15 (95% CI: 0.08–0.27) for the presence of ventral osteophytes and of 4.42 (95% CI: 2.77–7.04) for dorsal osteophytes. Atypical joint forms were significantly more prevalent in women with 62.1% vs. 14.1% in men (p < 0.001). Accessory joints increased the likelihood of dorsal sclerosis (OR 2.735; 95% CI 1.376–5.436) while a typical joint form decreased its likelihood (OR 0.174; 95% CI 0.104–0.293). Sex and anatomical joint form have a major impact on the development of degenerative lesions of the SIJs and their spatial distribution.
New insights into the standard method of assessing bacterial filtration efficiency of medical face masks
Authors: Pourchez Jérémie , Peyron Aurélien , Montigaud Yoann , Laurent Coralie , Audoux Estelle , Leclerc Lara , Verhoeven Paul O.
Published: March 2021

Based on the current knowledge of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission, wearing a mask has been recommended during the COVID-19 pandemic. Bacterial filtration efficiency (BFE) measurements enable designing and regulating medical masks to prevent bioaerosol dissemination; however, despite the simplicity of these measurements, several scientific questions remain unanswered regarding BFE tests. Here, we investigated (1) the impact of substituting 100-mm Petri dishes with 90-mm disposable Petri dishes, (2) the impact of colony-counting methods on the bioaerosol aerodynamic size, and (3) the impact of colony-counting methods on the total viable particle counts. We demonstrated that disposable 90-mm Petri dishes can be used to replace the 100-mm dishes. We also showed that an automatic high-resolution colony counter can be used to directly count viable particles on collection substrates and to measure the bioaerosol size parameters. Our results enable possible modernization of the outdated testing methods recommended in the US and European standards for BFE measurements. Specifically, use of a modernized colony counter should be clearly regulated and permitted to avoid the counting of positive holes. The median aerodynamic diameter appears to be the most relevant parameter for characterizing bioaerosol size.
Metabolic activity of extranodal NK/T cell lymphoma on 18F-FDG PET/CT according to immune subtyping
Authors: Lim Chae Hong , Yoon Sang Eun , Kim Seok Jin , Cho Junhun , Ko Young Hyeh , Lee Kyung-Han , Kim Won Seog
Published: March 2021

Disseminated extranodal NK/T cell lymphoma (ENKTL) is associated with dismal prognosis. Hence, distinct tumor immune microenvironment (TIME) subtypes were proposed to explain their influence on ENKTL progression and help predict treatment response. In this study, we investigated the capacity of FDG PET/CT to discern ENKTL TIME subtypes. A total of 108 pretreatment FDG PET/CT scans of 103 patients with newly diagnosed or relapsed ENKTL were retrospectively analyzed. TIME subtype was determined using three key immunohistochemical markers. SUVmax, MTV and TLG were measured, and metabolic features associated with TIME subtype were statistically extracted. TIME subtype was immune tolerance (IT) in 13.9%, immune evasion A (IE-A) in 56.5%, immune evasion B (IE-B) in 21.3%, and immune silenced (IS) in 8%. The IS group showed the highest SUVmax (15.9 ± 6.4, P = 0.037), followed by IE-A (14.1 ± 7.8), IE-B (10.9 ± 5.6), and IT groups (9.6 ± 5.1). Among 53 with only nasal FDG lesions, 52 had non-IS subtype. Among 55 with extra-nasal FDG lesions, those with IS subtype more often had adrenal (P = 0.001) or testis involvement (P = 0.043), greater MTV (P = 0.005), greater TLG (P = 0.005), and SUVmax located at extra-nasal sites. The presence of 0–2 and 3–4 of these four findings was associated with low probability (2/46) and high probability (6/9) of IS subtype, respectively. Furthermore, patients showing IS subtype-favoring PET/CT pattern had worse overall survival compared to their counterparts. These results demonstrate that FDG PET/CT can help predict immune subtype in ENKTL patients. The different patterns between glycolytic activity and involved site according to TIME subtype might be related to the interplay between tumor cells and immune cells in the tumor microenvironment.