bluuebunny/crossref_metadata_2025 huggingface dataset:
Empirical estimation of rock mass deformation modulus of rocks: comparison of intact rock properties and rock mass classifications as inputs
Authors: Aladejare Adeyemi Emman , Malachi Ozoji Toochukwu , Adebayo Idris Musa , Lawal Abiodun Ismail , Onifade Moshood
Published: May 2022

Deformation modulus of rock mass (Em) is an important parameter for the analysis and design of mining engineering projects. However, field tests for measuring deformation modulus of rock mass are difficult, time-consuming, and capital intensive. This has led to the development of numerous empirical models for estimating rock mass deformation modulus, which are in different forms and scattered in the literature. The numerous models available in the literature use different types of inputs. Therefore, this study provides a comprehensive compilation of different empirical models for estimating the deformation modulus of rock masses. The compiled models are grouped based on their type of input parameter(s) into three categories such as those using intact rock properties, rock mass classification indices, and combination of intact rock properties and rock mass classification indices. Then, a comparative analysis was performed using absolute average relative error percentage (AAREP) and variance accounted for (VAF) to assess the reliability of using different types of inputs for estimation of deformation modulus of rock masses using data from two sites. The results of the analyses show that rock mass classification indices are the most reliable indices for estimating the deformation modulus of rock masses among the categories considered for analyses. For AAREP analyses in the two illustrative examples considered in this study, models (7 out of 10) using rock mass classification indices in the estimation of Em have the best performances with AAREP values ranging from 24.07 to 55.15%. For VAF analyses in the two examples, models (8 out of 10) using rock mass classification indices in the estimation of Em have the best performances with values ranging from 59.81 to 88.11%. The lowest errors and highest deviation similarities from models using rock mass classification indices indicate that they produce the most reliable estimations of Em. It is important to note that the reliability of deformation modulus estimated from empirical models depends on the quality of input data as the models performed differently across the sites used in this study. This study therefore provides a compilation of available models for estimating deformation modulus, performance evaluation of available models for estimating deformation modulus, and guidelines for selecting appropriate model for estimating deformation modulus of rock mass.
Making it abstract, making it contestable: politicization at the intersection of political and cognitive science
Authors: Mazzuca Claudia , Santarelli Matteo
Published: May 2022

The notion of politicization has been often assimilated to that of partisanship, especially in political and social sciences. However, these accounts underestimate more fine-grained, and yet pivotal, aspects at stake in processes of politicization. In addition, they overlook cognitive mechanisms underlying politicizing practices. Here, we propose an integrated approach to politicization relying on recent insights from both social and political sciences, as well as cognitive science. We outline two key facets of politicization, that we call partial indetermination and contestability, and we show how these can be accounted for by appealing to recent literature in cognitive science concerned with abstract conceptual knowledge. We suggest that politicizing a concept often implies making its more abstract components more salient, hence legitimating its contestable character. Finally, we provide preliminary suggestions to test our proposal, using the concept of gender as case study.
A review on enhanced biofuel production from coffee by-products using different enhancement techniques
Authors: Sugebo Berhanu
Published: May 2022

Coffee by-products are a renewable, plentiful, cost-effective, and mostly untapped resource that could be used as a biofuel feedstock. However, the energy efficiency and biofuel yields are mostly determined by the biofuel production technologies. Pretreatment procedure, hydrolysis methods, fermentation methods, oil to biodiesel conversion techniques, binders employed, applying pressure and temperature are the main factors to improve the biofuel yields from coffee by-products. This paper examines state-of-the-art methods for increasing biogas, bio-ethanol, biodiesel, briquettes, and pellets outputs from coffee by-products. Pretreatment and co-digestion of coffee by-products with other low carbon to nitrogen ratio animal manure boost the biogas yield of coffee by-products, which is also discussed. A yield of bio-ethanol from coffee by-products was also improved using advanced pretreatment procedures, production processes, and the use of genetically modified yeast strains that ferment the majority of sugar monomers. Additionally, oil extraction methods from spent coffee grounds were reviewed, as well as optimizing biodiesel yield from spent coffe grounds oil. The process of making briquettes and pellets, as well as the types of binders utilized, are discussed. The main novelty of this review is on improving biofuel yields such as biogas, bio-ethanol, biodiesel, briquettes, and pellets from the entire dry cherry coffee beans processing residues, wet coffee (coffee pulp or peeled) beans processing residues, and optimizing oil and biodiesel yield from spent coffee grounds.
Contrast-enhanced ultrasound (CEUS) in patients with metastasis-like hepatic alveolar echinococcosis: a cohort study
Authors: Schweizer Melissa , Schmidberger Julian , Schlingeloff Patrycja , Kratzer Wolfgang
Published: May 2022

Purpose

Hepatic alveolar echinococcosis (HAE) of the metastasis-like pattern, according to the Echinococcus Ulm classification, is usually discovered as an incidental finding, and the diagnostic differentiation from “true metastases” is difficult. The aim of this study was to investigate whether lesions of the “metastasis-like pattern” in HAE show a typical contrast behavior that can be used for differentiation from metastasis in malignancies.

Methods

This prospective clinical study included 11 patients with histologically confirmed HAE of the metastasis-like pattern (7 female and 4 male; mean age, 57.1 years; mean disease duration, 59.5 months), who had been examined by B-scan sonography and CEUS, from the National Echinococcosis Registry Germany.

Results

On contrast-enhanced sonography, 11/11 reference lesions showed annular rim enhancement in the arterial and portal venous phases. Throughout the entire 4-min study period, none of the reference lesions showed central contrast enhancement—i.e., all exhibited a complete “black hole sign”. A small central scar was seen in 81.8% of cases.

Conclusion

In clinically unremarkable patients with incidentally detected metastasis-like lesions of the liver, contrast-enhanced sonographic detection of rim enhancement without central contrast uptake (black hole sign) should be considered evidence supporting a diagnosis of hepatic alveolar echinococcosis with a rare metastasis-like pattern. This can help to differentiate HAE from metastases, especially in high-endemic areas.
An overview of functional biolubricants
Authors: Yang Lumin , Zhao Xiaoduo , Ma Zhengfeng , Ma Shuanhong , Zhou Feng
Published: May 2022

At present, more and more diseases are associated with the lubrication dysfunction, which requires a systematic study of the complex lubrication behavior of tissues and organs in human body. Natural biomacromolecular lubricants are essential for maintaining ultra-low coefficients of friction between sliding biological interfaces. However, when the surface lubrication performance of tissues or organs destroys heavily, it will bring friction/shear damage for sliding contact interfaces. Therefore, the application of exogenous biological lubricating materials to improve the lubrication situation of damaged tissue or organ interfaces has attracted extensive attention of researchers. In this review, based on a simple summary of lubrication mechanism at sliding biological interface, we systematically introduce the research progress of several kinds of representatively biolubrication materials, including eye drops, tissue anti-adhesion agents, joint lubricants, and medical device lubricants. Meanwhile, the lubrication mechanism and individual advantage and shortcoming for each of these synthetic exogenous lubricated materials are clarified. Correspondingly, the important lubrication application functionality of these biolubricant materials in typically medical surgery scenes, such as dry eye syndrome, tissue adhesion, arthritis, and interventional medical devices, is discussed. Finally, we look forward to the future development direction of artificial biolubricant materials.
Critical review and functional safety of a battery management system for large-scale lithium-ion battery pack technologies
Authors: See K. W. , Wang Guofa , Zhang Yong , Wang Yunpeng , Meng Lingyu , Gu Xinyu , Zhang Neng , Lim K. C. , Zhao L. , Xie Bin
Published: May 2022

The battery management system (BMS) is the main safeguard of a battery system for electric propulsion and machine electrification. It is tasked to ensure reliable and safe operation of battery cells connected to provide high currents at high voltage levels. In addition to effectively monitoring all the electrical parameters of a battery pack system, such as the voltage, current, and temperature, the BMS is also used to improve the battery performance with proper safety measures within the system. With growing acceptance of lithium-ion batteries, major industry sectors such as the automotive, renewable energy, manufacturing, construction, and even some in the mining industry have brought forward the mass transition from fossil fuel dependency to electric powered machinery and redefined the world of energy storage. Hence, the functional safety considerations, which are those relating to automatic protection, in battery management for battery pack technologies are particularly important to ensure that the overall electrical system, regardless of whether it is for electric transportation or stationary energy storage, is in accordance with high standards of safety, reliability, and quality. If the system or product fails to meet functional and other safety requirements on account of faulty design or a sequence of failure events, then the environment, people, and property could be endangered. This paper analyzed the details of BMS for electric transportation and large-scale energy storage systems, particularly in areas concerned with hazardous environment. The analysis covers the aspect of functional safety that applies to BMS and is in accordance with the relevant industrial standards. A comprehensive evaluation of the components, architecture, risk reduction techniques, and failure mode analysis applicable to BMS operation was also presented. The article further provided recommendations on safety design and performance optimization in relation to the overall BMS integration.
Are Bankers “Crying Wolf”? Type I, Type II Errors and Deterrence in Anti-Money Laundering: The Italian Case
Authors: dalla Pellegrina Lucia , Di Maio Giorgio , Masciandaro Donato , Saraceno Margherita
Published: May 2022

Excessive and useless reporting, called the “crying wolf effect,” is a crucial shortcoming that any anti-money laundering (AML) design aims to address. For this reason, in recent years, AML policies in both the US and Europe have switched from a rule-based to a risk-based approach. This study theoretically and empirically investigates whether the risk-based approach delivers the expected results. The theoretical model shows that a trade-off can emerge between accuracy (fewer type-I and type-II errors) and deterrence. The empirical analysis, conducted after the risk-based approach was introduced in Italy, confirms this trade-off. More specifically, deterrence seems a priority, whereas accuracy is sacrificed. In this respect, the data suggest that Italian bankers are likely to “cry wolf.”
Like Visiting an Old Friend: Fischer Glycosylation in the Twenty-First Century: Modern Methods and Techniques
Authors: Haese Matteo , Winterhalter Kai , Jung Jessica , Schmidt Magnus S.
Published: May 2022

Fischer glycosylation is typically the chemical reaction of a monosaccharide and an alcohol in presence of an acidic catalyst to afford glycosides in pyranosidic and furanosidic forms. This reaction is still applied today for the synthesis of specialized glycosides, and optimization and modification of the method have continued since its discovery by Emil Fischer in the 1890s. This review presents advancements in Fischer glycosylation described in literature of the past 15 years and its implementation in modern chemical methods.
Environmental performance of insect protein: a case of LCA results for fish feed produced in Norway
Authors: Modahl Ingunn Saur , Brekke Andreas
Published: May 2022

In this article, life cycle assessments for six insect protein production cases are examined, and their life cycle inventories are systematically combined to create consistent data and results for the environmental performance of insect protein. The LCAs are on mealworms farmed in the Netherlands or France, fed on cereals or vegetable waste food and brewery side stream (four cases); and black soldier fly larvae farmed in Germany, fed on brewery side stream or brewery side stream with vegetable waste (two cases). The focus is on those insect proteins which can be utilised as fish feed with use in Norway as an example. Special attention is paid to obtain consistent system boundaries, method choices, background data, and indicators. The results show that the insect diet is crucial for all the analysed environmental indicators for insects fed a diet of high economic value vegetables. Emissions from the utilisation of insect manure for biogas, fertilisers or similar, and direct insect greenhouse gas emissions, seem to have little importance. The article further shows results compared with the greenhouse gas emissions for the most important salmon protein feed ingredients in Norway. Insect protein based on vegetables with low economic value has the potential to compete in environmental performance with existing protein sources for fish feed and can also cover 10 to 15% of the volumes of crude protein currently imported to the EU.
Design and Development of a Cold-Flow Test-Bench for Study of Advanced Nozzles in Subsonic Counter-Flows
Authors: Scarlatella Giuseppe , Sieder-Katzmann Jan , Roßberg Florian , Weber Felix , Mancera Carlos T. , Bianchi Daniele , Tajmar Martin , Bach Christian
Published: May 2022

As advanced nozzles may offer alternative solutions to conventional nozzles for the future class of reusable launch vehicles, a critical aspect is to tailor these novel technologies to current recovery strategies, more specifically to vertical landing sustained by retro-propulsion. Researchers at Technische Universität Dresden have developed a dedicated test-bench for the vacuum wind tunnel facility, where Advanced Nozzle Concepts (ANCs), such as aerospike and dual-bell nozzles, are tested in cold-gas configuration while invested by subsonic counter-flows. The main objective of the test campaign is to evaluate the performance and altitude–compensation characteristics of such ANCs by simulating a vertical landing manoeuvre through the variation of ambient pressure experienced during the landing burn. A detailed description of design and development of the test-bench, together with preliminary results from the commissioning activities, are here offered to the reader. The force measurements, together with pressure and temperature data, contribute to evaluate thrust levels and coefficients, as well as the monitoring of the interaction between the nozzle cold-flow and the opposing free-stream. A background-oriented schlieren system allows to visualise the external flow-field. In conclusion, an outline of the upcoming test campaign and a description of the expected results is offered.
Analysis of Space Launch Vehicle Failures and Post-Mission Disposal Statistics
Authors: Fernández Lucía Ayala , Wiedemann Carsten , Braun Vitali
Published: May 2022

In a time in which a significant number of launch vehicles are being developed, boosted by numerous new space actors demanding cheaper access to space, the need to ensure the reliability of launch vehicles and the performance of a successful Post-Mission Disposal (PMD) is undeniable. The first step to ensure the reliability of new launch vehicles is to analyse previous launch failures, learning from past mistakes. In this paper, the launch failures that occurred over the past 16 years are analysed. These failures are classified as a function of the subsystems involved in the failure, as well as the phase of the mission in which the failure occurred. As a result, the most critical subsystems are identified for every mission phase. Subsequently, the most critical subsystem is further investigated, and its most critical components are identified. Furthermore, aiming to improve the present PMD practices, an understanding of the current status is necessary. This paper provides an overview of the evolution in terms of mean orbital lifetime of the rocket bodies launched since the year 2000. Moreover, the number of manoeuvres performed and the orbital lifetime saved by these manoeuvres is analysed between 2016 and 2020, further classifying the statistics by launcher family and country.
A closure result for differential forms in the context of superdensity, approximation of measurable functions by density-degree functions
Authors: Delladio Silvano
Published: May 2022

Some properties ofm-density points and density-degree functions are studied. Moreover, the following main results are provided:

Let$$\lambda$$λbe a continuous differential form of degreehin$${\mathbb {R}}^n$$Rn(with$$h\ge 0$$h≥0) having the following property: there exists a continuous differential form$$\Delta$$Δof degree$$h+1$$h+1in$${\mathbb {R}}^n$$Rnsuch that$$\begin{aligned} \int _{{\mathbb {R}}^n}\Delta \wedge \omega =\int _{{\mathbb {R}}^n}\lambda \wedge \mathrm{{d}}\omega , \end{aligned}$$∫RnΔ∧ω=∫Rnλ∧dω,for every$$C^\infty _c$$Cc∞differential form$$\omega$$ωof degree$$n-h-1$$n-h-1in$${\mathbb {R}}^n$$Rn. Moreover let$$\mu$$μbe a$$C^1$$C1differential form of degree$$h+1$$h+1in$${\mathbb {R}}^n$$Rnand set$$E:=\{y\in {\mathbb {R}}^n\,\vert \, \Delta (y)=\mu (y)\}$$E:={y∈Rn|Δ(y)=μ(y)}. Then$$\mathrm{{d}}\mu (x) = 0$$dμ(x)=0wheneverxis a$$(n+1)$$(n+1)-density point ofE.

Let$$f:{\mathbb {R}}^n\rightarrow {\overline{{\mathbb {R}}}}$$f:Rn→R¯be a measurable function such that$$f(x)\in \{0\}\cup [n,+\infty ]$$f(x)∈{0}∪[n,+∞]for a.e.$$x\in {\mathbb {R}}^n$$x∈Rn. Then there exists a countable family$$\{F_k\}_{k=1}^\infty$${Fk}k=1∞of closed subsets of$${\mathbb {R}}^n$$Rnsuch that the corresponding sequence of density-degree functions$$\{d_{F_k}\}_{k=1}^\infty$${dFk}k=1∞converges almost everywhere tof.
Charting Paths to New Knowledge
Authors: Goss Heather
Published: May 2022

In our June issue of Eos, we home in on the unique ways researchers are using maps to better understand Earth and beyond.
Snow Albedo Feedbacks Enhance Snow Impurity‐Induced Radiative Forcing in the Sierra Nevada
Authors: Huang Huilin , Qian Yun , He Cenlin , Bair Edward H. , Rittger Karl
Published: May 2022

This study employs a fully coupled meteorology‐chemistry‐snow model to investigate the impacts of light‐absorbing particles (LAPs) on snow darkening in the Sierra Nevada. After comprehensive evaluation with spatially and temporally complete satellite retrievals, the model shows that LAPs in snow reduce snow albedo by 0.013 (0–0.045) in the Sierra Nevada during the ablation season (April‐July), producing a midday mean radiative forcing of 4.5 W m−2 which increases to 15–22 W m−2 in July. LAPs in snow accelerate snow aging processes and reduce snow cover fraction, which doubles the albedo change and radiative forcing caused by LAPs. The impurity‐induced snow darkening effects decrease snow water equivalent and snow depth by 20 and 70 mm in June in the Sierra Nevada bighorn sheep habitat. The earlier snowmelt reduces root‐zone soil water content by 20%, deteriorating the forage productivity and playing a negative role in the survival of bighorn sheep.
Hot Plasma Effects on Electron Resonant Scattering by Electromagnetic Ion Cyclotron Waves
Authors: Bashir M. Fraz , Artemyev Anton , Zhang Xiao‐Jia , Angelopoulos Vassilis
Published: May 2022

Resonant scattering by electromagnetic ion cyclotron (EMIC) waves is one of the most effective mechanisms of relativistic electron losses in Earth’s inner magnetosphere. Low‐altitude spacecraft measurements, however, often show that the energy range of precipitating electrons is wider than theoretical predictions based on the cold plasma dispersion of EMIC waves. To explain this discrepancy, we examine the diffusion rates of EMIC waves by including hot plasma effects in their dispersion relation. Using the observed ion distribution functions, we investigate the hot plasma effects on the EMIC wave dispersion for a wide frequency range. We develop analytical equations for hot plasma effects on EMIC dispersion, and apply this model to diffusion rate evaluations. We show that hot ion effects tend to increase the minimum resonant energy for the frequency range around wave intensity maxima, but can decrease the minimum resonant energy for the higher‐frequency part of wave spectra.
Inability to phosphorylate Y88 of p27Kip1 enforces reduced p27 protein levels and accelerates leukemia progression
Authors: Jäkel Heidelinde , Taschler Martin , Jung Karin , Weinl Christina , Pegka Fragka , Kullmann Michael Keith , Podmirseg Silvio Roland , Dutta Sayantanee , Moser Markus , Hengst Ludger
Published: May 2022

The cyclin-dependent kinase (CDK) inhibitor p27Kip1 regulates cell proliferation. Phosphorylation of tyrosine residue 88 (Y88) converts the inhibitor into an assembly factor and activator of CDKs, since Y88-phosphorylation restores activity to cyclin E,A/CDK2 and enables assembly of active cyclin D/CDK4,6. To investigate the physiological significance of p27 tyrosine phosphorylation, we have generated a knock-in mouse model where Y88 was replaced by phenylalanine (p27-Y88F). Young p27-Y88F mice developed a moderately reduced body weight, indicative for robust CDK inhibition by p27-Y88F. When transformed with v-ABL or BCR::ABL1p190, primary p27-Y88F cells are refractory to initial transformation as evidenced by a diminished outgrowth of progenitor B-cell colonies. This indicates that p27-Y88 phosphorylation contributes to v-ABL and BCR::ABL1p190 induced transformation. Surprisingly, p27-Y88F mice succumbed to premature v-ABL induced leukemia/lymphoma compared to p27 wild type animals. This was accompanied by a robust reduction of p27-Y88F levels in v-ABL transformed cells. Reduced p27-Y88F levels seem to be required for efficient cell proliferation and may subsequently support accelerated leukemia progression. The potent downregulation p27-Y88F levels in all leukemia-derived cells could uncover a novel mechanism in human oncogenesis, where reduced p27 levels are frequently observed.
Noncoding RNA actions through IGFs and IGF binding proteins in cancer
Authors: Kerr Aidan , Baxter Robert C.
Published: May 2022

The insulin-like growth factors (IGFs) and their regulatory proteins—IGF receptors and binding proteins—are strongly implicated in cancer progression and modulate cell survival and proliferation, migration, angiogenesis and metastasis. By regulating the bioavailability of the type-1 IGF receptor (IGF1R) ligands, IGF-1 and IGF-2, the IGF binding proteins (IGFBP-1 to -6) play essential roles in cancer progression. IGFBPs also influence cell communications through pathways that are independent of IGF1R activation. Noncoding RNAs (ncRNAs), which encompass a variety of RNA types including microRNAs (miRNAs) and long-noncoding RNAs (lncRNAs), have roles in multiple oncogenic pathways, but their many points of intersection with IGF axis functions remain to be fully explored. This review examines the functional interactions of miRNAs and lncRNAs with IGFs and their binding proteins in cancer, and reveals how the IGF axis may mediate ncRNA actions that promote or suppress cancer. A better understanding of the links between ncRNA and IGF pathways may suggest new avenues for prognosis and therapeutic intervention in cancer. Further, by exploring examples of intersecting ncRNA-IGF pathways in non-cancer conditions, it is proposed that new opportunities for future discovery in cancer control may be generated.
The contribution of imprinted genes to neurodevelopmental and neuropsychiatric disorders
Authors: Isles Anthony R.
Published: May 2022

Imprinted genes are a subset of mammalian genes that are subject to germline parent-specific epigenetic modifications leading monoallelic expression. Imprinted gene expression is particularly prevalent in the brain and it is unsurprising that mutations affecting their expression can lead to neurodevelopmental and/or neuropsychiatric disorders in humans. Here I review the evidence for this, detailing key neurodevelopmental disorders linked to imprinted gene clusters on human chromosomes 15q11-q13 and 14q32, highlighting genes and possible regulatory links between these different syndromes. Similarly, rare copy number variant mutations at imprinted clusters also provide strong links between abnormal imprinted gene expression and the predisposition to severe psychiatric illness. In addition to direct links between brain-expressed imprinted genes and neurodevelopmental and/or neuropsychiatric disorders, I outline how imprinted genes that are expressed in another tissue hotspot, the placenta, contribute indirectly to abnormal brain and behaviour. Specifically, altered nutrient provisioning or endocrine signalling by the placenta caused by abnormal expression of imprinted genes may lead to increased prevalence of neurodevelopmental and/or neuropsychiatric problems in both the offspring and the mother.
Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker
Authors: Schmid Felicitas , Dahlmann Mathias , Röhrich Hanna , Kobelt Dennis , Hoffmann Jens , Burock Susen , Walther Wolfgang , Stein Ulrike
Published: May 2022

Background

The metastasis inducing gene MACC1 is a prognostic and predictive biomarker for metastasis in several cancers. Its mechanism of inducing metastasis includes the transcriptional control of other cancer-related target genes. Here, we investigate the interplay with the metastasis driver S100P in CRC progression.

Methods

MACC1-dependent S100P expression was analysed by qRT-PCR. The binding of MACC1 to the S100P promoter was determined by ChIP. Alterations in cell proliferation and motility were determined by functional in vitro assays. In vivo metastasis after intrasplenic transplantation was assessed by bioluminescence imaging and evaluation of tumour growth and liver metastasis. The prognostic value of S100P was determined in CRC patients by ROC-based Kaplan–Meier analyses.

Results

Expression of S100P and MACC1 correlated positively in CRC cells and colorectal tumours. MACC1 was found binding to the S100P promoter and induces its expression. The overexpression of S100P increased proliferation, migration and invasion in vitro and significantly induced liver metastasis in vivo. S100P expression was significantly elevated in metachronously metastasising CRC and was associated with shorter metastasis-free survival.

Conclusions

We identified S100P as a transcriptional target gene of MACC1. Expression of S100P increases the metastatic potential of CRC cells in vitro and in vivo, and serves as a prognostic biomarker for metastasis-free survival of CRC patients, emphasising novel therapeutic interventions targeting S100P.
Regulatory T cells induce a suppressive immune milieu and promote lymph node metastasis in intrahepatic cholangiocarcinoma
Authors: Konishi Daisuke , Umeda Yuzo , Yoshida Kazuhiro , Shigeyasu Kunitoshi , Yano Shuya , Toji Tomohiro , Takeda Sho , Yoshida Ryuichi , Yasui Kazuya , Fuji Tomokazu , Matsumoto Kazuyuki , Kishimoto Hiroyuki , Michiue Hiroyuki , Teraishi Fuminori , Kato Hironari , Tazawa Hiroshi , Yanai Hiroyuki , Yagi Takahito , Goel Ajay , Fujiwara Toshiyoshi
Published: May 2022

Background

Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma (ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC.

Methods

Highly immunogenic ICCs identified in the public dataset and the Cancer Immunome Atlas (TCIA) were assessed to determine the prognostic impact of immunogenicity in ICC and key components after curative resection. We also investigated the clinical relevance of the immune milieu in ICC.

Results

Using the Gene Expression Omnibus dataset 89749 and TCIA, we identified CD8+/forkhead box P3 (FoxP3)+ tumour-infiltrating lymphocytes (TILs), T-cell immunoglobulin and mucin domain 3 (TIM-3) and human leukocyte antigen-A (HLA-A) in highly immunogenic ICCs. Immunohistochemical analysis of the in-house cohort showed that intratumoral FoxP3+ TILs correlated with CD8+ TILs (P = 0.045, Fisher’s exact test) and that high FoxP3+/CD8+ ratio (FCR) was an important marker for poor survival (P < 0.001, log-rank test). Furthermore, the FCR was higher in tumour-free lymph nodes in ICCs with lymph node metastases than in those without lymph node metastases (P = 0.003, Mann–Whitney U test).

Conclusions

FCR should be considered an important biomarker that represents the immune environment of ICC based on its potentially important role in tumour progression, especially lymph node metastasis.
Dedifferentiation-mediated stem cell niche maintenance in early-stage ductal carcinoma in situ progression: insights from a multiscale modeling study
Authors: Butner Joseph D. , Dogra Prashant , Chung Caroline , Ruiz-Ramírez Javier , Nizzero Sara , Plodinec Marija , Li Xiaoxian , Pan Ping-Ying , Chen Shu-hsia , Cristini Vittorio , Ozpolat Bulent , Calin George A. , Wang Zhihui
Published: May 2022

We present a multiscale agent-based model of ductal carcinoma in situ (DCIS) to study how key phenotypic and signaling pathways are involved in the early stages of disease progression. The model includes a phenotypic hierarchy, and key endocrine and paracrine signaling pathways, and simulates cancer ductal growth in a 3D lattice-free domain. In particular, by considering stochastic cell dedifferentiation plasticity, the model allows for study of how dedifferentiation to a more stem-like phenotype plays key roles in the maintenance of cancer stem cell populations and disease progression. Through extensive parameter perturbation studies, we have quantified and ranked how DCIS is sensitive to perturbations in several key mechanisms that are instrumental to early disease development. Our studies reveal that long-term maintenance of multipotent stem-like cell niches within the tumor are dependent on cell dedifferentiation plasticity, and that disease progression will become arrested due to dilution of the multipotent stem-like population in the absence of dedifferentiation. We have identified dedifferentiation rates necessary to maintain biologically relevant multipotent cell populations, and also explored quantitative relationships between dedifferentiation rates and disease progression rates, which may potentially help to optimize the efficacy of emerging anti-cancer stem cell therapeutics.
Antibiotic pretreatment attenuates liver ischemia–reperfusion injury by Farnesoid X receptor activation
Authors: Liu Hanyi , Wang Jinglin , Ding Yitao , Shi Xiaolei , Ren Haozhen
Published: May 2022

Prophylactic antibiotics (Abx) are used before liver surgery, and the influence of antibiotic pretreatment on hepatic ischemia–reperfusion injury (IRI) remains unclear. Hence, we explored the impact of Abx pretreatment on hepatic IRI in the present work. The gut microbiota has an essential role in hepatic bile acid (BA) metabolism, and we assumed that depletion of the gut microbiota could affect the composition of hepatic BAs and affect liver IRI. The IRI model demonstrated that Abx pretreatment attenuated liver IRI by alleviating cell apoptosis, reducing the inflammatory response, and decreasing the recruitment of CCR2+ monocytes. Mechanistically, Abx pretreatment reshaped the gut microbiota, especially decreasing the relative abundance of Firmicutes and increasing the relative abundance of Clostridium, which were related to the transformation of BAs and were consistent with the altered bile acid species (unconjugated BAs, especially UDCA). These altered BAs are known FXR agonists and lead to the activation of the farnesoid X receptor (FXR), which can directly bind to the FXR response element (FXRE) harbored in the TLR4 promoter and further suppress downstream mitogen-activated protein kinase (MAPK) and nuclear kappa B (NF-κB) pathways. Meanwhile, the CCL2–CCR2 axis was also involved in the process of FXR activation, as we confirmed both in vivo and in vitro. Importantly, we proved the importance of FXR in mice and clinical occlusion samples, which were inversely correlated with liver injury. Taken together, our study identified that Abx pretreatment before liver resection was a beneficial event by activating FXR, which might become a potential therapeutic target in treating liver injury.
A novel spiral infinity reactor for continuous hydrothermal synthesis of nanoparticles
Authors: Pukkella Arjun Kumar , Nadimpalli Naga Ravikumar Varma , Runkana Venkataramana , Subramanian Sivakumar
Published: May 2022

Hydrothermal synthesis is an attractive route to make nanoparticles utilizing inexpensive precursors under moderate process conditions. Though it provides flexibility and robustness in controlling particle characteristics, process scale-up for continuous production is a major challenge. A novel ‘infinity-’ shaped spiral continuous flow reactor is proposed here, to exploit the large density difference between the precursor solution and supercritical water to provide rapid mixing, leading to uniform conditions for reaction kinetics and particle growth. Hydrothermal synthesis is simulated by coupling computational fluid dynamics with population balance modeling and appropriate reaction kinetics. Simulations indicate three distinct regimes of declining, recovering, and stable flow fields. These regimes are strongly dependent on the flow ratio between the precursor solution and supercritical water. The infinity reactor provides two distinct reaction environments: initial turns of the spiral which serve as a mixed flow reactor facilitating rapid mixing and uniform reaction, followed by a plug flow reactor stabilizing the particle growth. It produces particles with a relatively small mean diameter and a narrow size distribution in comparison to the conventional batch stirred tank reactor and the T-mixer.
Patterns of alcohol consumption in Brazilian adults
Authors: Plens Juliana A. , Valente Juliana Y. , Mari Jair J. , Ferrari Gerson , Sanchez Zila M. , Rezende Leandro F. M.
Published: May 2022

In this study, we aimed to describe the patterns of alcohol consumption in Brazilian adults by sociodemographic characteristics and states according to sex. Cross-sectional study including 87,555 adults from the 2019 Brazilian National Health Survey who responded to a questionnaire on alcohol consumption and were classified as non-drinkers (0 g/day), light (1–12.5 g/day), moderate (12.6–49.9 g/day), and heavy drinkers (≥ 50 g/day). Of the Brazilian adults, 73.5% were non-drinkers. Among the drinkers, 14.8% were light drinkers. 82.6% of heavy drinkers were men. White participants drank more than non-white participants, except black women who were 38% more likely to be moderate drinkers than white women (ROR 1.38, 95% CI 1.09 to 1.76). Unmarried were more likely to be drinkers. Women over 55 and men over 65 years old were less likely to be drinkers. Compared to participants with none or incomplete primary education, both men and women with higher educational attainment were more likely to be light and moderate drinkers. The largest consumption of alcohol was found in Sergipe and Mato Grosso for men, and Mato Grosso do Sul and Bahia for women. Our findings may be useful to inform policies for reducing alcohol consumption in Brazil.
Cross-sectional metabolic subgroups and 10-year follow-up of cardiometabolic multimorbidity in the UK Biobank
Authors: Mulugeta Anwar , Hyppönen Elina , Ala-Korpela Mika , Mäkinen Ville-Petteri
Published: May 2022

We assigned 329,908 UK Biobank participants into six subgroups based on a self-organizing map of 51 biochemical measures (blinded for clinical outcomes). The subgroup with the most favorable metabolic traits was chosen as the reference. Hazard ratios (HR) for incident disease were modeled by Cox regression. Enrichment ratios (ER) of incident multi-morbidity versus randomly expected co-occurrence were evaluated by permutation tests; ER is like HR but captures co-occurrence rather than event frequency. The subgroup with high urinary excretion without kidney stress (HR = 1.24) and the subgroup with the highest apolipoprotein B and blood pressure (HR = 1.52) were associated with ischemic heart disease (IHD). The subgroup with kidney stress, high adiposity and inflammation was associated with IHD (HR = 2.11), cancer (HR = 1.29), dementia (HR = 1.70) and mortality (HR = 2.12). The subgroup with high liver enzymes and triglycerides was at risk of diabetes (HR = 15.6). Multimorbidity was enriched in metabolically favorable subgroups (3.4 ≤ ER ≤ 4.0) despite lower disease burden overall; the relative risk of co-occurring disease was higher in the absence of obvious metabolic dysfunction. These results provide synergistic insight into metabolic health and its associations with cardiovascular disease in a large population sample.
Quantum blockchain based on asymmetric quantum encryption and a stake vote consensus algorithm
Authors: Wang Wusheng , Yu Yang , Du Lingjie
Published: May 2022

As emerging next-generation information technologies, blockchains have unique advantages in information transparency and transaction security. They have attracted great attentions in social and financial fields. However, the rapid development of quantum computation and the impending realization of quantum supremacy have had significant impacts on the advantages of traditional blockchain based on traditional cryptography. Here, we propose a blockchain algorithm based on asymmetric quantum encryption and a stake vote consensus algorithm. The algorithm combines a consensus algorithm based on the delegated proof of stake with node behaviour and Borda count (DPoSB) and quantum digital signature technology based on quantum state computational distinguishability with a fully flipped permutation ($${\text{QSC}}{\text{D}}_{\text{ff}}$$

QSCD
ff

) problem. DPoSB is used to generate blocks by voting, while the quantum signature applies quantum one-way functions to guarantee the security of transactions. The analysis shows that this combination offers better protection than other existing quantum-resistant blockchains. The combination can effectively resist the threat of quantum computation on blockchain technology and provide a new platform to ensure the security of blockchain.
Refractive astigmatism in phaco-canaloplasty vs phaco-non-penetrating deep sclerectomy
Authors: Byszewska Anna , Rudowicz Jacek , Lewczuk Katarzyna , Jabłońska Joanna , Rękas Marek
Published: May 2022

This study aimed to assess refractive astigmatism, in phaco-canaloplasty (PC) vs phaco-non-penetrating deep sclerectomy (PDS) in a randomized, prospective study within 24 months. Patients were randomized pre-operatively, 37 underwent PC and 38 PDS. The following data was collected: BCVA, IOP, number of antiglaucoma medications, refraction with autokeratorefractometry. The assessment of astigmatism was simple arithmetic and vector analysis (calculations included cylinder with axis in form of centroids) and included double angle plots and cumulative refractive astigmatism graphs. Pre-operative mean BCVA in PC was 0.40 ± 0.43 and was comparable to BCVA in PDS 0.30 ± 0.32logMAR (P = 0.314). In the sixth month follow-up, mean BCVA showed no difference (P = 0.708) and was 0.07 ± 0.13 and 0.05 ± 0.11, respectively. However, 2 years after the intervention mean BCVA was better in PC 0.05 ± 0.12 than in PDS 0.12 ± 0.23 and it was statistically significant (P = 0.039). Mean astigmatism in PC at baseline was 1.13 ± 0.73Dcyl, at 6 months it was 1.09 ± 0.61 and at 2 years 1.17 ± 0.51. In PDS at baseline 1.35 ± 0.91 at 6 months 1.24 ± 0.86 and at 2 years 1.24 ± 0.82. There were no differences between the groups in mean astigmatism throughout the study. Centroids (mean of a cylinder with axis) in PC were pre-operatively 0.79D@172˚ ± 1.10Dcyl, at 6 months 0.75D@166˚ ± 1.01 and at 24-months 0.64D@164˚ ± 1.11 and in PDS pre-operatively 0.28D@10˚ ± 1.63D at 6 months 0.26D@11˚ ± 1.5 and at 24-months 0.47D@20˚ ± 1.43. The direction of mean astigmatism was against the rule in all analyzed time points. The mean baseline IOP in PC was 19.4 ± 5.8 mmHg and 19.7 ± 5.4 mmHg in PDS(P = 0.639). From the 6-month IOP was lower in PC, at 24-months it was 13.8 ± 3.3 mmHg in PC and 15.1 ± 2.9 mmHg in PDS(P = 0.048). In both groups preoperatively patients used median(Me) of three antiglaucoma medications(P = 0.197), at 24-months in PC mean 0.5 ± 0.9 Me = 0.0 and 1.1 ± 1.2 Me = 1.0 in PDS(P = 0.058). Both surgeries in mid-term observation are safe and effective. They do not generate vision-threatening astigmatism and do not even change the preoperative direction of mean astigmatism. Refractive astigmatism is stable throughout the observation.
Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells
Authors: Rivet-Noor Courtney R. , Merchak Andrea R. , Li Sihan , Beiter Rebecca M. , Lee Sangwoo , Thomas Jalon Aaron , Fernández-Castañeda Anthony , Shin Jung-Bum , Gaultier Alban
Published: May 2022

Current treatments for major depressive disorder are limited to neuropharmacological approaches and are ineffective for large numbers of patients. Recently, alternative means have been explored to understand the etiology of depression. Specifically, changes in the microbiome and immune system have been observed in both clinical settings and in mouse models. As such, microbial supplements and probiotics have become a target for potential therapeutics. A current hypothesis for the mechanism of action of these supplements is via the aryl hydrocarbon receptor’s (Ahr) modulation of the T helper 17 cell (Th17) and T regulatory cell axis. As inflammatory RORγt + CD4 + Th17 T cells and their primary cytokine IL-17 have been implicated in the development of stress-induced depression, the connection between stress, the Ahr, Th17s and depression remains critical to understanding mood disorders. Here, we utilize genetic knockouts to examine the role of the microbial sensor Ahr in the development of stressinduced despair behavior. We observe an Ahr-independent increase in gut-associated Th17s in stressed mice, indicating that the Ahr is not responsible for this communication. Further, we utilized a CD4-specific RAR Related Orphan Receptor C (Rorc) knockout line to disrupt the production of Th17s. Mice lacking Rorc-produced IL-17 did not show any differences in behavior before or after stress when compared to controls. Finally, we utilize an unsupervised machine learning system to examine minute differences in behavior that could not be observed by traditional behavioral assays. Our data demonstrate that neither CD4 specific Ahr nor Rorc are necessary for the development of stress-induced anxiety- or depressive-like behaviors. These data suggest that research approaches should focus on other sources or sites of IL-17 production in stress-induced depression.
Comparative analysis of mesenchymal stem cells cultivated in serum free media
Authors: Lee Joo Youn , Kang Min Hee , Jang Ji Eun , Lee Jeong Eon , Yang Yuyeong , Choi Ji Yong , Kang Hong Seok , Lee Uiil , Choung Ji Woong , Jung Hyeryeon , Yoon Young-Chan , Jung Kyung Hee , Hong Soon–Sun , Yi Eugene C. , Park Sang Gyu
Published: May 2022

Stem cells are attractive candidates for the regeneration of tissue and organ. Mesenchymal stem cells (MSCs) have been extensively investigated for their potential applications in regenerative medicine and cell therapy. For developing effective stem cell therapy, the mass production of consistent quality cells is required. The cell culture medium is the most critical aspect of the mass production of qualified stem cells. Classically, fetal bovine serum (FBS) has been used as a culture supplement for MSCs. Due to the undefined and heterologous composition of animal origin components in FBS, efforts to replace animal-derived components with non-animal-derived substances led to safe serum free media (SFM). Adipose derived mesenchymal stem cells (ADSCs) cultivated in SFM provided a more stable population doubling time (PDT) to later passage and more cells in a shorter time compared to FBS containing media. ADSCs cultivated in SFM had lower cellular senescence, lower immunogenicity, and higher genetic stability than ADSCs cultivated in FBS containing media. Differential expression analysis of mRNAs and proteins showed that the expression of genes related with apoptosis, immune response, and inflammatory response were significantly up-regulated in ADSCs cultivated in FBS containing media. ADSCs cultivated in SFM showed similar therapeutic efficacy in an acute pancreatitis mouse model to ADSCs cultivated in FBS containing media. Consideration of clinical trials, not only pre-clinical trial, suggests that cultivation of MSCs using SFM might offer more safe cell therapeutics as well as repeated administration due to low immunogenicity.
A longitudinal study of the impact of university student return to campus on the SARS-CoV-2 seroprevalence among the community members
Authors: Arnold Callum R. K. , Srinivasan Sreenidhi , Rodriguez Sophie , Rydzak Natalie , Herzog Catherine M. , Gontu Abhinay , Bharti Nita , Small Meg , Rogers Connie J. , Schade Margeaux M. , Kuchipudi Suresh V. , Kapur Vivek , Read Andrew F. , Ferrari Matthew J.
Published: May 2022

Returning university students represent large-scale, transient demographic shifts and a potential source of transmission to adjacent communities during the COVID-19 pandemic. In this prospective longitudinal cohort study, we tested for IgG antibodies against SARS-CoV-2 in a non-random cohort of residents living in Centre County prior to the Fall 2020 term at the Pennsylvania State University and following the conclusion of the Fall 2020 term. We also report the seroprevalence in a non-random cohort of students collected at the end of the Fall 2020 term. Of 1313 community participants, 42 (3.2%) were positive for SARS-CoV-2 IgG antibodies at their first visit between 07 August and 02 October 2020. Of 684 student participants who returned to campus for fall instruction, 208 (30.4%) were positive for SARS-CoV-2 antibodies between 26 October and 21 December. 96 (7.3%) community participants returned a positive IgG antibody result by 19 February. Only contact with known SARS-CoV-2-positive individuals and attendance at small gatherings (20–50 individuals) were significant predictors of detecting IgG antibodies among returning students (aOR, 95% CI 3.1, 2.07–4.64; 1.52, 1.03–2.24; respectively). Despite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents was low and stable from before student arrival for the Fall 2020 term to after student departure. The study implies that heterogeneity in SARS-CoV-2 transmission can occur in geographically coincident populations.