bluuebunny/crossref_metadata_2025 huggingface dataset:
Tsunami risk management for crustal earthquakes and non-seismic sources in Italy
Authors: Selva J. , Amato A. , Armigliato A. , Basili R. , Bernardi F. , Brizuela B. , Cerminara M. , de’ Micheli Vitturi M. , Di Bucci D. , Di Manna P. , Esposti Ongaro T. , Lacanna G. , Lorito S. , Løvholt F. , Mangione D. , Panunzi E. , Piatanesi A. , Ricciardi A. , Ripepe M. , Romano F. , Santini M. , Scalzo A. , Tonini R. , Volpe M. , Zaniboni F.
Published: May 2021

Destructive tsunamis are most often generated by large earthquakes occurring at subduction interfaces, but also other “atypical” sources—defined as crustal earthquakes and non-seismic sources altogether—may cause significant tsunami threats. Tsunamis may indeed be generated by different sources, such as earthquakes, submarine or coastal landslides, volcano-related phenomena, and atmospheric perturbations. The consideration of atypical sources is important worldwide, but it is especially prominent in complex tectonic settings such as the Mediterranean, the Caribbean, or the Indonesian archipelago. The recent disasters in Indonesia in 2018, caused by the Palu-Sulawesi magnitude Mw 7.5 crustal earthquake and by the collapse of the Anak-Krakatau volcano, recall the importance of such sources. Dealing with atypical sources represents a scientific, technical, and computational challenge, which depends on the capability of quantifying and managing uncertainty efficiently and of reducing it with accurate physical modelling. Here, we first introduce the general framework in which tsunami threats are treated, and then we review the current status and the expected future development of tsunami hazard quantifications and of the tsunami warning systems in Italy, with a specific focus on the treatment of atypical sources. In Italy, where the memory of historical atypical events like the 1908 Messina earthquake or the relatively recent 2002 Stromboli tsunami is still vivid, specific attention has been indeed dedicated to the progressive development of innovative strategies to deal with such atypical sources. More specifically, we review the (national) hazard analyses and their application for coastal planning, as well as the two operating tsunami warning systems: the national warning system for seismically generated tsunamis (SiAM), whose upstream component—the CAT-INGV—is also a Tsunami Service Provider of the North-eastern Atlantic, the Mediterranean and connected seas Tsunami Warning System (NEAMTWS) coordinated by the Intergovernmental Coordination Group established by the Intergovernmental Oceanographic Commission (IOC) of UNESCO, and the local warning system for tsunamis generated by volcanic slides along the Sciara del Fuoco of Stromboli volcano. Finally, we review the state of knowledge about other potential tsunami sources that may generate significant tsunamis for the Italian coasts, but that are not presently considered in existing tsunami warning systems. This may be considered the first step towards their inclusion in the national tsunami hazard and warning programs.
Young’s Social Connection Model and Corporate Responsibility
Authors: Phillips Robert , Schrempf-Stirling Judith
Published: May 2021

Recent structural innovations in global commerce present difficult challenges for legacy understandings of responsibility. The rise of outsourcing, sub-contracting, and mobile app-based platforms have dramatically restructured relationships between and among economic actors. Though not entirely new, the remarkable rise in the prevalence of these “not-quite-arm’s-length” relationships present difficulties for conceptions of responsibility based on interrogating the past for specifiable actions by blameworthy actors. Iris Marion Young invites investigation of a “social connection model of responsibility” (SCMR) that is, in many ways, better suited to this new commercial reality. Scholars working to understand corporate responsibility have invoked Young’s model to some good effect, though often superficially and uncritically. In this paper, we look closely at Young’s social connection model and its potential for helping us understand corporate responsibility in a radically networked world.
Morality and Tribalism
Authors: Corradetti Claudio
Published: May 2021

This contribution has two main goals which might be labelled for convenience as apars construensandpars denstruensreversing the usual order of these terms. The first aim is to offer an overview of the main tenets of the book, while the second aim is to raise some critical concerns while remaining sympathetic to the author’s overall project. With regard to the first point, I present the context of intellectual debate where Buchanan’s contribution fits comfortably: Darwin’s evolutionary theory, anthropology, psychology, moral analysis etc. The target here is to show the internal complexity and different layers of analysis of the book. These initial reconstructions are, next, used to formulate some thoughts on what I consider possible problematic points in need of clarification. In particular, first, I hold that Buchanan presents too narrow oppositional views between intergroup relations whereupon the notion of “tribalism” is constructed. Such strong identitarian conception does not seem to depict adequately the sociological dynamics of intergroup relations. Second, I consider the terms in which it can be addressed the notion of the rise of the moral mind in evolutionary terms. The suggestion is to consider in a milder form the author’s key concept of a “Great Uncoupling” for the moral reason.
Sustainability over sets and the business cycle
Authors: Hao Lixiao , Manousiouthakis Vasilios I.
Published: May 2021

Many rigorous works have examined the behavior of Kaldor business cycle models. In this paper, utilizing the sustainability over sets (SOS) concept, a general theorem is proven establishing necessary and sufficient conditions for the existence and identification of rectangular sustainable sets for a general Kaldor model. These conditions can be readily verified, either in the two-dimensional space of lower and upper bounds on income, or in the one-dimensional space of upper bound on income, thus enabling identification of the region of economic sustainability for the considered Kaldor model. The Theorem’s power is illustrated with a case study of a particular Kaldor business cycle model from the literature that can exhibit rich dynamic behavior, and can give rise to economic sustainability regions that encompass multiple stable equilibrium points. Furthermore, a methodology is also presented that identifies non-rectangular sustainable sets, when the imposition of tight lower and upper bounds on one of the economic system variables (e.g., income) prevents the existence of a sustainable rectangular set.
Surgical outcomes of combined modified Blumgart pancreaticojejunostomy and long internal pancreatic duct stent for pancreaticoduodenectomy
Authors: Wongta Kitti , Tangsirapat Vorapatu
Published: May 2021

ABSTRACT

Background:

Postoperative pancreatic fistula (POPF) is the most serious complication in patients who underwent pancreaticoduodenectomy (PD). The Blumgart anastomosis and its modifications are the favorable techniques of pancreaticojejunostomy anastomosis (PJ) performed worldwide. This report proposed the surgical outcomes of combined the new technique of modified Blumgart anastomosis with the long internal pancreatic duct stent for the (PJ).

Study design:

We evaluated the surgical outcomes of a consecutive series of the patients at Panyananthaphikkhu Chonprathan Medical Center who underwent PD from June 2017 to June 2020. PJ was conducted in all cases using the transpancreatic mattress suture modified from the original Blumgart's technique and the long pancreatic duct stent was placed across the anastomosis. The primary endpoints were clinically relevant postoperative pancreatic fistula (CR-POPF) and 30-day mortality rate. The secondary endpoints were the early postoperative complications.

Results:

Twelve patients underwent PD using the proposed technique. Overall mortality was 8.3%. The rate of CR-POPF was 33.3%, two patients had a prolonged period of the intraabdominal drain, and one patient underwent the percutaneous drainage of the intraabdominal collection. The only patient with Grade C-POPF died after re-exploration due to severe septicemia. The median postoperative length of stay (LOS) was 12 days.

Conclusions:

The combination of the new technique of modified Blumgart PJ with the long internal pancreatic duct stent is an alternative technique that may prevent the pancreatic fistula. The CR-POPF rate and the overall survival are comparable to prior literature. However, further study is needed to clarify the definite outcomes.

Highlights
Using Shiny to Teach Econometric Models
Authors: Metzger Shawna K.
Published: May 2021

This Element discusses how shiny, an R package, can help instructors teach quantitative methods more effectively by way of interactive web apps. The interactivity increases instructors' effectiveness by making students more active participants in the learning process, allowing them to engage with otherwise complex material in an accessible, dynamic way. The Element offers four detailed apps that cover two fundamental linear regression topics: estimation methods (least squares, maximum likelihood) and the classic linear regression assumptions. It includes a summary of what the apps can be used to demonstrate, detailed descriptions of the apps' full capabilities, vignettes from actual class use, and example activities. Two other apps pertain to a more advanced topic (LASSO), with similar supporting material. For instructors interested in modifying the apps, the Element also documents the main apps' general code structure, highlights some of the more likely modifications, and goes through what functions need to be amended.
Dynamics of hyperbolic correspondences
Authors: SIQUEIRA CARLOS
Published: May 2021

This paper establishes the geometric rigidity of certain holomorphic correspondences in the family
$(w-c)^q=z^p$
, whose post-critical set is finite in any bounded domain of
$\mathbb {C}$
. In spite of being rigid on the sphere, such correspondences are J-stable by means of holomorphic motions when viewed as maps of
$\mathbb {C}^2$
. The key idea is the association of a conformal iterated function system to the return branches near the critical point, giving a global description of the post-critical set and proving the hyperbolicity of these correspondences.
Recent Approaches on Classification and Feature Extraction of EEG Signal: A Review
Authors: Pooja  , Pahuja SK , Veer Karan
Published: May 2021

Objective:

Electroencephalography (EEG) has an influential role in neuroscience and commercial applications. Most of the tools available for EEG signal analysis use machine learning to extract the required information. So, the study of robust techniques for feature extraction and classification is an important thing to understand the practical use of EEG. The paper aims that if there is any special tool for a particular task. Which feature domain or classifier has a significant role in EEG signal analysis?

Approach:

It presents a detailed report of the current trend for bio-electrical signals classification focusing on various classifiers’ advantages and disadvantages. This study includes literature from 2000 to 2021 with a brief description of EEG signal origin and advancement in classification techniques.

Results:

Randomly used classifiers for EEG signal can be categorized into five classes, namely Linear Classifiers, Nearest Neighbor Classifiers, Nonlinear Bayesian Classifiers, Neural Networks, and Combinations of Classifiers. Approximately 40% of studies use Support Vector Machine, Nearest Neighbor, and their combination with others. For specific tasks, particular classifiers are recommended in the survey. Features can be defined into four categories, namely TDFs, FDFs, TFDFs, and statistical features, where 39% of studies used TFDFs. Multi-domains features are preferred when the required information cannot be obtained from one domain.

Significance:

The paper summarizes the recent approaches for feature extraction and classification of EEG signals. It describes the brain waves with their classification, related behavior, and task with the physiological correlation. The comparative analysis of different classifiers, toolbox, the channel used, accuracy, and the number of subjects from various studies can help the practitioners choose a suitable classifier. Furthermore, future directions can cope up with the relevant problems and can lead to accurate classification.
Development of nonmotorized mechanisms for lower limb rehabilitation
Authors: Gonçalves Rogério S. , Rodrigues Lucas A. O.
Published: May 2021

This paper concerns with the development of three nonmotorized individual lower limb joints rehabilitation mechanisms based on a four-bar linkage, and mechanical movement transmission from the motion of the patient’s upper limb. Initially, mathematical and computational models are built based on the desired angular motions for the hip, knee, and ankle. A prototype for the knee mechanism was constructed for initial experimental tests. The first test with wooden mannequin show that this prototype is lightweight, has an output movement compatible with the amplitudes, is easy to build and operate, being thus ready for clinical tests with healthy and impaired subjects.
DATING THROUGH THE FILTERS
Authors: Nader Karim
Published: May 2021

In this essay, I explore ethical considerations that might arise from the use of collaborative filtering algorithms on dating apps. Collaborative filtering algorithms can predict the preferences of a target user by looking at the past behavior of similar users. By recommending products through this process, they can influence the news we read, the movies we watch, and more. They are extremely powerful and effective on platforms like Amazon and Google. Recommender systems on dating apps are likely to group people by race, since they exhibit similar patterns of behavior: users on dating platforms seem to segregate themselves based on race, exclude certain races from romantic and sexual consideration (except their own), and generally show a preference for white men and women. As collaborative filtering algorithms learn from these patterns to predict preferences and build recommendations, they can homogenize the behavior of dating app users and exacerbate biased sexual and romantic behavior.
Radio navigation systems: definitions and classifications
Authors: Specht Cezary
Published: May 2021

Radio navigation systems (RNSs) are commonly applied in air, land and marine navigation. They are most often used for position determination. However, when comparing the definitions of this concept provided by global organisations, such as the International Association of Marine Aids to Navigation and Lighthouse Authorities (IALA), International Civil Aviation Organization (ICAO), International Maritime Organization (IMO) or International Telecommunication Union (ITU), it should be noted that the definitions presented differ significantly. Due to the ambiguity and numerous contradictions, the RNS classification varies depending on the definition of the term ‘radio navigation’ adopted, which poses serious interpretation problems. This article analyses the concept of radio navigation based on the most important global documents and legal acts on this issue. It points to fundamental differences in the understanding of the term and proposes the adoption of a new, uniform definition for air, land and marine navigation. Based on this definition, the current paper proposes a uniform RNS classification. The proposed definition of the concept of radio navigation and the resulting RNS classification are essential for the understanding of this term to achieve global uniformity and fundamental to the harmonious development of the scientific discipline of navigation. The current proposal should initiate a discussion on the meaning of the concept of radio navigation and the RNS classification.
An Evaluation of Suicide Prevention Education for People Working With Refugees and Asylum Seekers
Authors: Procter Nicholas , Posselt Miriam , Ferguson Monika , McIntyre Heather , Kenny Mary-Anne , Curtis Rachel , Loughhead Mark , Clement Noel , Mau Vicki
Published: May 2021

Abstract. Background: There are concerning rates of suicidality among asylum seekers and refugees in Australia, and tailored suicide prevention initiatives are needed. Aims: We aimed to evaluate the impact of a tailored suicide prevention education program for people working with asylum seekers and refugees. Method: Attendees of the education program completed self-report questionnaires at pretraining, posttraining, and 4–6 months follow-up. Results: Over 400 workers, volunteers, and students across Australia took part in the education program. A series of linear mixed-effects models revealed significant improvements in outcome measures from pretraining ( n = 247) to posttraining ( n = 231). Improvements were maintained at follow-up ( n = 75). Limitations: Limitations of this research were the lack of a control group and a low follow-up response rate. Conclusion: Findings suggest that a 2 days tailored suicide prevention education program contributes to significant improvements in workers’ attitudes toward suicide prevention, and their confidence and competence in assessing and responding to suicidal distress.
An Investigation Into Biases in Instantaneous Aerosol Radiative Effects Calculated by Shortwave Parameterizations in Two Earth System Models
Authors: Freidenreich S. , Paynter D. , Lin P. , Ramaswamy V. , Jones A. L. , Feldman D. , Collins W. D.
Published: May 2021

Because the forcings to which Coupled Model Intercomparison Project ‐ Phase 5 (CMIP5) models were subjected were poorly quantified, recent efforts from the Radiative Forcing Model Intercomparison Project (RFMIP) have focused on developing and testing models with exacting benchmarks. Here, we focus on aerosol forcing to understand if for a given distribution of aerosols, participating models are producing a radiometrically‐accurate forcing. We apply the RFMIP experimental protocol for assessing flux biases in aerosol instantaneous radiative effect (IRE) on two participating models, GFDL AM4 and CESM 1.2.2. The latter model contains the RRTMG radiation code which is widely used among CMIP6 GCM's. We conduct a series of calculations that test different potential sources of error in these models relative to line‐by‐line benchmarks. We find two primary sources of error: two‐stream solution methods and the techniques to resolve spectral dependencies of absorption and scattering across the solar spectrum. The former is the dominant source of error for both models but the latter is more significant as a contributing factor for CESM 1.2.2. Either source of error can be addressed in future model development, and these results both demonstrate how the RFMIP protocol can help determine the origins of parameterized errors relative to their equivalent benchmark calculations for participating models, as well as highlight a viable path towards a more rigorous quantification and control of forcings for future CMIP exercises.
Oceanic Pathways of an Active Pacific Meridional Overturning Circulation (PMOC)
Authors: Thomas M. D. , Fedorov A. V. , Burls N. J. , Liu W.
Published: May 2021

In contrast to the modern‐day climate, North Pacific deep water formation and a Pacific meridional overturning circulation (PMOC) may have been active during past climate conditions, in particular during the Pliocene epoch (some 3–5 million years ago). Here, we use a climate model simulation with a robust PMOC cell to investigate the pathways of the North Pacific deep water from subduction to upwelling, as revealed by Lagrangian particle trajectories. We find that similar to the present‐day Atlantic Meridional Overturning Circulation (AMOC), most subducted North Pacific deep water upwells in the Southern Ocean. However, roughly 15% upwells in the tropical Indo‐Pacific Oceans instead—a key feature distinguishing the PMOC from the AMOC. The connection to the Indian Ocean is relatively fast, at about 250 years. The connection to the tropical Pacific is slower (∼800 years) as water first travels to the subtropical South Pacific then gradually upwells through the thermocline.
Characterizing Uncertainties in Ground “Truth” of Precipitation Over Complex Terrain Through High‐Resolution Numerical Modeling
Authors: Ouyang Lin , Lu Hui , Yang Kun , Leung L. Ruby , Wang Yan , Zhao Long , Zhou Xu , Lazhu  , Chen Yingying , Jiang Yaozhi , Yao Xiangnan
Published: May 2021

Ground observation of precipitation over complex terrain is subject to large uncertainties due to inadequate sampling. This study explores a method that combines limited gauge data and a high‐resolution numerical simulation to quantify the precipitation uncertainties in central Himalaya. Specifically, the Coefficient of spatial Variability (CV) of precipitation and the minimum Number of Required Stations (NRS) to obtain areal‐mean precipitation ground truth values within a 0.25° area are investigated using fine‐scale meteorological simulation at 1.5 km grid spacing. Evaluation over a densely‐gauged area demonstrates comparable CV and NRS values between station observations and simulations. The simulated CV and NRS values in a larger area show a strong and positive dependence on each other and an expected positive (negative) correlation with topographic complexity (temporal scale). The proposed method sheds lights on evaluating precipitation products and holds promise for informing the layout of rain gauge networks in complex terrain.
A Regime‐State Framework for Morphodynamic Modeling of Seabed Roughness
Authors: DuVal Carter B. , Trembanis Arthur C. , Miller Douglas C.
Published: May 2021

Seabed roughness in the dynamic near‐shore environment is continuously modified by the interplay of physical and biological processes including bedform morphodynamics and bioturbation. We introduce a novel regime‐state framework to determine the dominant modifier of seabed roughness based on observed or estimated physical forcing, which are classified by critical Shields parameter or wave mobility thresholds. The regime‐state framework is applied to a set of field observations containing time‐lapse sonar imagery of ripple growth, decay, and bioturbation. The rate of ripple decay varies in both physical and biological processes. The decay rate is sensitive to oscillatory forcing magnitude and direction relative to relict ripple orientation and time‐evolving ripple height. We found two distinct episodes of ripples decayed by 20%–30% within 4–5 days. Ripple decay models and observations did not agree in rate of decay up to and following the same time period. By varying decay rate using a time‐dependent diffusion coefficient determined by the dominant decay mechanism, the regime‐state framework resulted in better agreement to field observations. Benthic megafauna are also shown to create seabed roughness, excavating dense fields (>1 pit/m2) of pits (≤84 cm in diameter) that introduce acoustic roughness comparable to 8–12 cm high ripples. The spatiotemporal variability of megafaunal pit formation suggests diffusion‐based bioturbation models are not adequate and megafaunal pits require additional parameterization to mechanistically model. The regime‐state framework presented in this study serves as a framework for future investigations and modeling of ripple morphodynamics, bioturbation, and roughness.
Morphology, Morphometry and Distribution of Isolated Landforms in Southern Chryse Planitia, Mars
Authors: McNeil Joseph D. , Fawdon Peter , Balme Matthew R. , Coe Angela L.
Published: May 2021

The margin of Chryse Planitia, Mars, contains >105kilometer‐scale mesas, buttes, and plateaus (“mounds”), many of which are found in and around Oxia Planum, the ExoMars 2022 Rover landing site. Despite this, their origins and evolution are unknown. We have analyzed the morphologies and morphometries of 14,386 individual mounds to: (1) classify them based on their geomorphology; (2) constrain when they formed based on their stratigraphic and spatial relationships; and (3) develop hypotheses for their geological history. The mounds are classified as compound mounds, mesas, clustered mounds, and hills. Mound heights show that their elevations above the plains tend to a maximum height of 500 m. We interpret this as the thickness of a previously continuous layer that extended several hundred kilometers from the southern highlands into Chryse Planitia. Stratigraphy constrains the deposition of this layer to the Early‐Middle Noachian, correlatable to the phyllosilicate‐bearing strata of Mawrth Vallis, with similar layering also observable in some mounds, suggesting a genetic relationship. The mounds sometimes occur in circular arrangements, interpreted as an association with buried impact structures. We propose that the mounds formed through differential erosion after the premound layer was indurated by mineralization from groundwater in areas superposing underlying crustal weaknesses, for example, at buried crater margins. The subsequent differential erosion of this layer preferentially removed areas unaffected by this induration in the Late Noachian‐Early Hesperian leaving the mound population seen at present. These features present accessible three‐dimensional exposures of ancient layered rocks, and so are exciting targets for future study.
Cloud-to-Ground Lightning May Have Struck a Key Ingredient for Life
Authors: Rocheleau Jackie
Published: May 2021

On early Earth, rock created by lightning strikes to the ground likely held a form of phosphorus necessary for prebiotic chemistry.
Risk factors for non-communicable diseases related to obesity among first- and second-generation Bangladeshi migrants living in north-east or south-east England
Authors: Akhter N. , Begum K. , Nahar P. , Cooper G. , Vallis D. , Kasim A. , Bentley G. R.
Published: May 2021

Background

Obesity is a global burden, which significantly increases the risk of non-communicable diseases (NCDs). More than a quarter of adults in the United Kingdom are obese, but prevalence varies by ethnicity, and South Asians have the largest burden of NCDs. This paper assesses how sex, generation, and region interplay to vary the predisposition to obesity-related (OR) NCDs among UK Bangladeshis.

Methods

We used National Institute for Health and Care Excellence suggested grading for combining body mass index and waist circumference to define populations at risk of OR-NCDs. Data from 517 adults of Bangladeshi origin from a cross-sectional study (March 2013 to April 2015) were analysed. Male and female participants from London and north-east England were equally sampled including: (1) adult migrants, who came to the UK aged >16 years; (2) child migrants, who came to the UK aged ≤16 years; and (3) second-generation Bangladeshis (who were born and brought up in the UK). A generalised estimating equation using a binomial distribution and a logit link was used to explore the relationship between the binary outcome of being ‘at risk of OR-NCDs’ and associated factors.

Results

Females, married individuals, those living in London, the second-generation, and those of lower self-assessed financial status, with low acculturation status, or who did not walk daily for at least 20 min were more likely to develop OR-NCDs. A striking sex difference was found with more females prone to OR-NCD risk in the north-east than in London.

Conclusions

Our study observed important inter- and intra-regional inequality in OR-NCD risk which worsens the health of ethnic minorities and widens inequality.
Hairy cell leukemia and COVID-19 adaptation of treatment guidelines
Authors: Grever Michael , Andritsos Leslie , Banerji Versha , Barrientos Jacqueline C. , Bhat Seema , Blachly James S. , Call Timothy , Cross Matthew , Dearden Claire , Demeter Judit , Dietrich Sasha , Falini Brunangelo , Forconi Francesco , Gladstone Douglas E. , Gozzetti Alessandro , Iyengar Sunil , Johnston James B. , Juliusson Gunnar , Kraut Eric , Kreitman Robert J. , Lauria Francesco , Lozanski Gerard , Parikh Sameer A. , Park Jae , Polliack Aaron , Ravandi Farhad , Robak Tadeusz , Rogers Kerry A. , Saven Alan , Seymour John F. , Tadmor Tamar , Tallman Martin S. , Tam Constantine S. , Tiacci Enrico , Troussard Xavier , Zent Clive , Zenz Thorsten , Zinzani Pier Luigi , Wörmann Bernhard
Published: May 2021

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.
The noncoding MIR100HG RNA enhances the autocrine function of transforming growth factor β signaling
Authors: Papoutsoglou Panagiotis , Rodrigues-Junior Dorival Mendes , Morén Anita , Bergman Andrew , Pontén Fredrik , Coulouarn Cédric , Caja Laia , Heldin Carl-Henrik , Moustakas Aristidis
Published: May 2021

Activation of the transforming growth factor β (TGFβ) pathway modulates the expression of genes involved in cell growth arrest, motility, and embryogenesis. An expression screen for long noncoding RNAs indicated that TGFβ induced mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) expression in diverse cancer types, thus confirming an earlier demonstration of TGFβ-mediated transcriptional induction of MIR100HG in pancreatic adenocarcinoma. MIR100HG depletion attenuated TGFβ signaling, expression of TGFβ-target genes, and TGFβ-mediated cell cycle arrest. Moreover, MIR100HG silencing inhibited both normal and cancer cell motility and enhanced the cytotoxicity of cytostatic drugs. MIR100HG overexpression had an inverse impact on TGFβ signaling responses. Screening for downstream effectors of MIR100HG identified the ligand TGFβ1. MIR100HG and TGFB1 mRNA formed ribonucleoprotein complexes with the RNA-binding protein HuR, promoting TGFβ1 cytokine secretion. In addition, TGFβ regulated let-7a-2–3p, miR-125b-5p, and miR-125b-1–3p expression, all encoded by MIR100HG intron-3. Certain intron-3 miRNAs may be involved in TGFβ/SMAD-mediated responses (let-7a-2–3p) and others (miR-100, miR-125b) in resistance to cytotoxic drugs mediated by MIR100HG. In support of a model whereby TGFβ induces MIR100HG, which then enhances TGFβ1 secretion, analysis of human carcinomas showed that MIR100HG expression correlated with expression of TGFB1 and its downstream extracellular target TGFBI. Thus, MIR100HG controls the magnitude of TGFβ signaling via TGFβ1 autoinduction and secretion in carcinomas.
The impact of alloying on defect-free nanoparticles exhibiting softer but tougher behavior
Authors: Bisht Anuj , Koju Raj Kiran , Qi Yuanshen , Hickman James , Mishin Yuri , Rabkin Eugen
Published: May 2021

The classic paradigm of physical metallurgy is that the addition of alloying elements to metals increases their strength. It is less known if the solution-hardening can occur in nano-scale objects, and it is totally unknown how alloying can impact the strength of defect-free faceted nanoparticles. Purely metallic defect-free nanoparticles exhibit an ultra-high strength approaching the theoretical limit. Tested in compression, they deform elastically until the nucleation of the first dislocation, after which they collapse into a pancake shape. Here, we show by experiments and atomistic simulations that the alloying of Ni nanoparticles with Co reduces their ultimate strength. This counter-intuitive solution-softening effect is explained by solute-induced local spatial variations of the resolved shear stress, causing premature dislocation nucleation. The subsequent particle deformation requires more work, making it tougher. The emerging compromise between strength and toughness makes alloy nanoparticles promising candidates for applications.
Visualizing delocalized correlated electronic states in twisted double bilayer graphene
Authors: Zhang Canxun , Zhu Tiancong , Kahn Salman , Li Shaowei , Yang Birui , Herbig Charlotte , Wu Xuehao , Li Hongyuan , Watanabe Kenji , Taniguchi Takashi , Cabrini Stefano , Zettl Alex , Zaletel Michael P. , Wang Feng , Crommie Michael F.
Published: May 2021

The discovery of interaction-driven insulating and superconducting phases in moiré van der Waals heterostructures has sparked considerable interest in understanding the novel correlated physics of these systems. While a significant number of studies have focused on twisted bilayer graphene, correlated insulating states and a superconductivity-like transition up to 12 K have been reported in recent transport measurements of twisted double bilayer graphene. Here we present a scanning tunneling microscopy and spectroscopy study of gate-tunable twisted double bilayer graphene devices. We observe splitting of the van Hove singularity peak by ~20 meV at half-filling of the conduction flat band, with a corresponding reduction of the local density of states at the Fermi level. By mapping the tunneling differential conductance we show that this correlated system exhibits energetically split states that are spatially delocalized throughout the different regions in the moiré unit cell, inconsistent with order originating solely from onsite Coulomb repulsion within strongly-localized orbitals. We have performed self-consistent Hartree-Fock calculations that suggest exchange-driven spontaneous symmetry breaking in the degenerate conduction flat band is the origin of the observed correlated state. Our results provide new insight into the nature of electron-electron interactions in twisted double bilayer graphene and related moiré systems.
A hypothalamic-thalamostriatal circuit that controls approach-avoidance conflict in rats
Authors: Engelke D. S. , Zhang X. O. , O’Malley J. J. , Fernandez-Leon J. A. , Li S. , Kirouac G. J. , Beierlein M. , Do-Monte F. H.
Published: May 2021

Survival depends on a balance between seeking rewards and avoiding potential threats, but the neural circuits that regulate this motivational conflict remain largely unknown. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited during conflict. Inactivation of aPVTCRF neurons during conflict biases animal’s response toward food, whereas activation of these cells recapitulates the food-seeking suppression observed during conflict. aPVTCRF neurons project densely to the nucleus accumbens (NAc), and activity in this pathway reduces food seeking and increases avoidance. In addition, we identified the ventromedial hypothalamus (VMH) as a critical input to aPVTCRF neurons, and demonstrated that VMH-aPVT neurons mediate defensive behaviors exclusively during conflict. Together, our findings describe a hypothalamic-thalamostriatal circuit that suppresses reward-seeking behavior under the competing demands of avoiding threats.
Heterologous protection against malaria by a simple chemoattenuated PfSPZ vaccine regimen in a randomized trial
Authors: Sulyok Zita , Fendel Rolf , Eder Bianca , Lorenz Freia-Raphaella , KC Natasha , Karnahl Matthias , Lalremruata Albert , Nguyen The T. , Held Jana , Adjadi Folashade Almeine Cyntiche , Klockenbring Torsten , Flügge Judith , Woldearegai Tamirat Gebru , Lamsfus Calle Carlos , Ibáñez Javier , Rodi Miriam , Egger-Adam Diane , Kreidenweiss Andrea , Köhler Carsten , Esen Meral , Sulyok Mihály , Manoj Anita , Richie Thomas L. , Sim B. Kim Lee , Hoffman Stephen L. , Mordmüller Benjamin , Kremsner Peter G.
Published: May 2021

Immunization with Plasmodium falciparum (Pf) sporozoites under chemoprophylaxis (PfSPZ-CVac) is the most efficacious approach to malaria vaccination. Implementation is hampered by a complex chemoprophylaxis regimen and missing evidence for efficacy against heterologous infection. We report the results of a double-blinded, randomized, placebo-controlled trial of a simplified, condensed immunization regimen in malaria-naive volunteers (EudraCT-Nr: 2018-004523-36). Participants are immunized by direct venous inoculation of 1.1 × 105 aseptic, purified, cryopreserved PfSPZ (PfSPZ Challenge) of the PfNF54 strain or normal saline (placebo) on days 1, 6 and 29, with simultaneous oral administration of 10 mg/kg chloroquine base. Primary endpoints are vaccine efficacy tested by controlled human malaria infection (CHMI) using the highly divergent, heterologous strain Pf7G8 and safety. Twelve weeks following immunization, 10/13 participants in the vaccine group are sterilely protected against heterologous CHMI, while (5/5) participants receiving placebo develop parasitemia (risk difference: 77%, p = 0.004, Boschloo’s test). Immunization is well tolerated with self-limiting grade 1–2 headaches, pyrexia and fatigue that diminish with each vaccination. Immunization induces 18-fold higher anti-Pf circumsporozoite protein (PfCSP) antibody levels in protected than in unprotected vaccinees (p = 0.028). In addition anti-PfMSP2 antibodies are strongly protection-associated by protein microarray assessment. This PfSPZ-CVac regimen is highly efficacious, simple, safe, well tolerated and highly immunogenic.
MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells
Authors: Wei Qiaozhi , Pinho Sandra , Dong Shuxian , Pierce Halley , Li Huihui , Nakahara Fumio , Xu Jianing , Xu Chunliang , Boulais Philip E. , Zhang Dachuan , Maryanovich Maria , Cuervo Ana Maria , Frenette Paul S.
Published: May 2021

Haematopoietic stem cells (HSCs) tightly regulate their quiescence, proliferation, and differentiation to generate blood cells during the entire lifetime. The mechanisms by which these critical activities are balanced are still unclear. Here, we report that Macrophage-Erythroblast Attacher (MAEA, also known as EMP), a receptor thus far only identified in erythroblastic island, is a membrane-associated E3 ubiquitin ligase subunit essential for HSC maintenance and lymphoid potential. Maea is highly expressed in HSCs and its deletion in mice severely impairs HSC quiescence and leads to a lethal myeloproliferative syndrome. Mechanistically, we have found that the surface expression of several haematopoietic cytokine receptors (e.g. MPL, FLT3) is stabilised in the absence of Maea, thereby prolonging their intracellular signalling. This is associated with impaired autophagy flux in HSCs but not in mature haematopoietic cells. Administration of receptor kinase inhibitor or autophagy-inducing compounds rescues the functional defects of Maea-deficient HSCs. Our results suggest that MAEA provides E3 ubiquitin ligase activity, guarding HSC function by restricting cytokine receptor signalling via autophagy.
Knowledge, attitudes and practices of patients and healthcare professionals regarding oral health and COPD in São Paulo, Brazil: a qualitative study
Authors: Riley Matthew , Swann Amber , Morris Alexander J. , Martins Sonia M. , Adams Rachel , Jordan Rachel E.
Published: May 2021

Poor oral health is associated with worse clinical outcomes in Chronic Obstructive Pulmonary Disease (COPD). This qualitative study aimed to investigate the knowledge, attitudes and practices of COPD patients and primary health care professionals (HCPs) in Brazil - where there are high rates of COPD and periodontal disease. Semi-structured interviews with COPD patients (n = 9) and three semi-structured focus groups with HCPs (n = 25) were conducted in São Paulo. Interviews were thematically analysed using The Framework Method. Despite a high prevalence of edentulism, patients viewed tooth loss and decay as a norm and neglected preventative oral health practices. HCPs blamed patients for avoiding preventative opportunities, whilst patients discussed significant barriers to oral healthcare. Knowledge of the relationship between oral health and COPD was lacking among HCPs and patients, but all participants were receptive to oral health education. Practitioners identified the need for a COPD primary care pathway that integrates oral health protocols. This study indicates that Brazil must incorporate preventative oral health into COPD management and expand public dental services to increase uptake.
Systematic review on effects of bioenergy from edible versus inedible feedstocks on food security
Authors: Ahmed Selena , Warne Teresa , Smith Erin , Goemann Hannah , Linse Greta , Greenwood Mark , Kedziora Jeremy , Sapp Meghan , Kraner Debra , Roemer Kelli , Haggerty Julia H. , Jarchow Meghann , Swanson David , Poulter Benjamin , Stoy Paul C.
Published: May 2021

Achieving food security is a critical challenge of the Anthropocene that may conflict with environmental and societal goals such as increased energy access. The “fuel versus food” debate coupled with climate mitigation efforts has given rise to next-generation biofuels. Findings of this systematic review indicate just over half of the studies (56% of 224 publications) reported a negative impact of bioenergy production on food security. However, no relationship was found between bioenergy feedstocks that are edible versus inedible and food security (P value = 0.15). A strong relationship was found between bioenergy and type of food security parameter (P value < 0.001), sociodemographic index of study location (P value = 0.001), spatial scale (P value < 0.001), and temporal scale (P value = 0.017). Programs and policies focused on bioenergy and climate mitigation should monitor multiple food security parameters at various scales over the long term toward achieving diverse sustainability goals.
Social exclusion increases the executive function of attention networks
Authors: Zhang Huoyin , Zhang Shiyunmeng , Lu Jiachen , Lei Yi , Li Hong
Published: May 2021

Previous studies in humans have shown that brain regions activating social exclusion overlap with those related to attention. However, in the context of social exclusion, how does behavioral monitoring affect individual behavior? In this study, we used the Cyberball game to induce the social exclusion effect in a group of participants. To explore the influence of social exclusion on the attention network, we administered the Attention Network Test (ANT) and compared results for the three subsystems of the attention network (orienting, alerting, and executive control) between exclusion (N = 60) and inclusion (N = 60) groups. Compared with the inclusion group, the exclusion group showed shorter overall response time and better executive control performance, but no significant differences in orienting or alerting. The excluded individuals showed a stronger ability to detect and control conflicts. It appears that social exclusion does not always exert a negative influence on individuals. In future research, attention to network can be used as indicators of social exclusion. This may further reveal how social exclusion affects individuals' psychosomatic mechanisms.
Machine learning based models for prediction of subtype diagnosis of primary aldosteronism using blood test
Authors: Kaneko Hiroki , Umakoshi Hironobu , Ogata Masatoshi , Wada Norio , Iwahashi Norifusa , Fukumoto Tazuru , Yokomoto-Umakoshi Maki , Nakano Yui , Matsuda Yayoi , Miyazawa Takashi , Sakamoto Ryuichi , Ogawa Yoshihiro
Published: May 2021

Primary aldosteronism (PA) is associated with an increased risk of cardiometabolic diseases, especially in unilateral subtype. Despite its high prevalence, the case detection rate of PA is limited, partly because of no clinical models available in general practice to identify patients highly suspicious of unilateral subtype of PA, who should be referred to specialized centers. The aim of this retrospective cross-sectional study was to develop a predictive model for subtype diagnosis of PA based on machine learning methods using clinical data available in general practice. Overall, 91 patients with unilateral and 138 patients with bilateral PA were randomly assigned to the training and test cohorts. Four supervised machine learning classifiers; logistic regression, support vector machines, random forests (RF), and gradient boosting decision trees, were used to develop predictive models from 21 clinical variables. The accuracy and the area under the receiver operating characteristic curve (AUC) for predicting of subtype diagnosis of PA in the test cohort were compared among the optimized classifiers. Of the four classifiers, the accuracy and AUC were highest in RF, with 95.7% and 0.990, respectively. Serum potassium, plasma aldosterone, and serum sodium levels were highlighted as important variables in this model. For feature-selected RF with the three variables, the accuracy and AUC were 89.1% and 0.950, respectively. With an independent external PA cohort, we confirmed a similar accuracy for feature-selected RF (accuracy: 85.1%). Machine learning models developed using blood test can help predict subtype diagnosis of PA in general practice.
Introducing a new pleosporalean family Sublophiostomataceae fam. nov. to accommodate Sublophiostoma gen. nov.
Authors: Hongsanan Sinang , Phookamsak Rungtiwa , Goonasekara Ishani D. , Thambugala Kasun M. , Hyde Kevin D. , Bhat Jayarama D. , Suwannarach Nakarin , Cheewangkoon Ratchadawan
Published: May 2021

Collections of microfungi on bamboo and grasses in Thailand revealed an interesting species morphologically resembling Lophiostoma, but which can be distinguished from the latter based on multi-locus phylogeny. In this paper, a new genus, Sublophiostoma is introduced to accommodate the taxon, S. thailandica sp. nov. Phylogenetic analyses using combined ITS, LSU, RPB2, SSU, and TEF sequences demonstrate that six strains of the new species form a distinct clade within Pleosporales, but cannot be assigned to any existing family. Therefore, a new family Sublophiostomataceae (Pleosporales) is introduced to accommodate the new genus. The sexual morph of Sublophiostomataceae is characterized by subglobose to hemisphaerical, ostiolate ascomata, with crest-like openings, a peridium with cells of textura angularis to textura epidermoidea, cylindric-clavate asci with a bulbous or foot-like narrow pedicel and a well-developed ocular chamber, and hyaline, fusiform, 1-septate ascospores surrounded by a large mucilaginous sheath. The asexual morph (coelomycetous) of the species are observed on culture media.
Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males
Authors: Liu Hui , Yu Hongling , Sun Lisi , Qiao Jingtao , Wan Sainan , Li Shuang , Li Jiaqi , Tan Huiwen , Yu Yerong
Published: May 2021

Insulin aspart (IAsp) is one of the main therapies used to control blood glucose after a meal. This study aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 rapid-acting IAsp products: a new IAsp biosimilar (RD10046) and NovoRapid. In a single-center, randomized, single-dose, 2-period, crossover, euglycemic clamp study (registry number: CTR20180517, registration date: 2018-05-30), healthy Chinese males were randomized to receive 0.2 U/kg of the IAsp biosimilar RD10046 and NovoRapid under fasted conditions on two separate occasions. PK and PD were assessed for up to 10 h. Of the 30 randomized subjects, all 30 completed both treatment periods. The PK (area under the curve [AUC] of total IAsp; maximum observed IAsp concentration [Cmax]) and PD (maximum glucose infusion rate [GIRmax]; total glucose infusion during the clamp [AUCGIR,0–10h]) were similar between the new IAsp biosimilar RD10046 and NovoRapid. In all cases, the 90% CIs for the ratios of the geometric means were completely contained in the prespecified acceptance limits of 0.80–1.25. No hypoglycemic events, allergic reactions, or local injection adverse reactions occurred in this trial. We concluded that the studied IAsp biosimilar (RD10046) was bioequivalent to NovoRapid.