bluuebunny/crossref_metadata_2025 huggingface dataset:
Journal rankings and publication strategy
Authors: Śpiewanowski Piotr , Talavera Oleksandr
Published: February 2021

We study the impact of journal ranking systems on publication outlet choice. We investigate the publication behavior of UK-based scholars registered on IDEAS/RePEc and analyze the publication outcomes of their academic work uploaded to the repository. Our estimates suggest that authors strategically choose outlets to maximize their publication scores. Our identification strategy is based on exploiting the change in the British ABS journal ranking in 2015. Working papers written before the 2015 ABS journal ranking change are significantly less likely to be published in ex-post downgraded journals. The effect cannot be attributed to the overall change in journal quality.
Specification testing in semi-parametric transformation models
Authors: Kloodt Nick , Neumeyer Natalie , Van Keilegom Ingrid
Published: February 2021

In transformation regression models, the response is transformed before fitting a regression model to covariates and transformed response. We assume such a model where the errors are independent from the covariates and the regression function is modeled nonparametrically. We suggest a test for goodness-of-fit of a parametric transformation class based on a distance between a nonparametric transformation estimator and the parametric class. We present asymptotic theory under the null hypothesis of validity of the semi-parametric model and under local alternatives. A bootstrap algorithm is suggested in order to apply the test. We also consider relevant hypotheses to distinguish between large and small distances of the parametric transformation class to the ‘true’ transformation.
Adsorption and Surface Diffusion of Metals on α-Al2O3 for Advanced Manufacturing Applications
Authors: Biaggne Austin , Noble Gregory , Li Lan
Published: February 2021

The adsorption and diffusion of Mo and Nb adatoms on the $$\alpha$$
α
-Al2O3 (0001) surface were explored using density functional theory-based methods. Adsorption energies of Mo and Nb adatoms at minima sites on the surface were determined. Mo and Nb adatoms prefer to adsorb to the same locations on the surface, and larger adsorption energies calculated for Nb compared to Mo indicate that Nb adatom-surface interactions are stronger than Mo. Using minima adsorption sites as initial and final locations for surface diffusion, energy barriers for diffusion were calculated using the nudged elastic band method. Overall, Mo and Nb follow roughly the same diffusion paths. The diffusion pre-factors for Mo and Nb are similar; however, Mo diffusion has a lower energy barrier and thus a larger diffusion coefficient compared with Nb. These results provide insight into the role of surface diffusion of Mo and Nb adatoms during advanced manufacturing processes.
Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept
Authors: González Astorga B. , Salvà Ballabrera F. , Aranda Aguilar E. , Élez Fernández E. , García-Alfonso P. , González Flores E. , Vera García R. , Fernández Montes A. , López Muñoz A. M. , Salud Salvia A.
Published: February 2021

Colorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.
Mindful attention awareness and cognitive defusion are indirectly associated with less PTSD-like symptoms via reduced maladaptive posttraumatic cognitions and avoidance coping
Authors: Ito Daisuke , Watanabe Asuka , Osawa Kaori
Published: February 2021

Recently, the effects of mindfulness-based interventions for posttraumatic stress disorder (PTSD) have been studied. However, we lack knowledge of the processes or mechanisms through which mindfulness influences resilience or promotes recovery following exposure to trauma. In this study, we examine the process by which mindfulness and cognitive-behavioral factors such as posttraumatic negative cognition and avoidance behaviors are associated with reduced PTSD-like symptoms. A questionnaire survey was conducted with 885 university students, using the Trauma Experience Questionnaire, Mindful Attention Awareness Scale, Cognitive Fusion Questionnaire, Post-Traumatic Stress Disorder Checklist, revised Ways of Coping Checklist, and a brief version of the Posttraumatic Cognitions Inventory. Data from 254 participants who experienced trauma with PTSD-like symptoms were analyzed. The final model using SEM indicated no direct association of mindful attention awareness on PTSD-like symptoms, a small direct association of cognitive defusion on PTSD-like symptoms, and a large indirect association mediated by posttraumatic negative cognitions and avoidance coping. Owing to the study’s cross-sectional design, strong conclusions cannot be drawn regarding the causal relationship of mindfulness and cognitive-behavioral factors or generalizations. However, our findings suggest that it would be worthwhile to continue to clarify the mechanism of mindfulness and to investigate its use in the treatment of PTSD. In the future, a highly accurate study design will hopefully be used to examine the mechanisms of several different factors associated with improvement in posttraumatic stress symptoms, preferably including them in the same model.
Feasibility of implementing a behavioral economics mobile health platform for individuals with behavioral health conditions
Authors: Granek Barry , Evans Aja , Petit Jorge , James Mary Crawford , Ma Yixuan (Matt) , Loper Matthew , Fuccillo Michael , Schmidt Rudy
Published: February 2021

Coordinated Behavioral Care’s (CBC) Pathway Home™ (PH) program partnered with Wellth, Inc., a mobile health platform grounded in behavioral economics theory, to help individuals with behavioral health conditions build and reinforce health habits by providing daily reminders to take medication, requiring tasks (photos demonstrating remembrance), and providing financial incentives tied to behaviors. CBC made Wellth, Inc. available to individuals enrolling in its PH program for the purpose of demonstrating the feasibility of implementing a novel mobile technology grounded in behavioral economic theory to increase habits of health activities, such as taking medication, among adults with behavioral health conditions.
The effect of non-uniformity in ground motions on the seismic response of arch dams
Authors: Pouya Mohammad Reza , Sohrabi-Gilani Morteza , Ghaemian Mohsen
Published: February 2021

Recorded ground accelerations at various locations of Karun III Dam during November 20, 2007, were recorded by an array of accelerometers located on the dam. In terms of amplitude and phase, these accelerations show non-uniformities in different elevations. In this paper, the effect of these non-uniform ground motions on the seismic response of the dam taking dam-reservoir-foundation interaction into account is investigated. The EACD-3D-2008 finite element program and ABAQUS Software are used for carrying out the seismic analyses. For this purpose, time histories of the earthquake accelerations are interpolated at nodal points located on the dam foundation interface. The analysis has been repeated, considering the common assumption of uniform ground motions. Comparing the results obtained from these two analyses reveals that the computed displacements in the crest due to the spatially varying excitations are in more conformity with the recorded information. Moreover, neglecting the non-uniform nature of ground motions in the model leads to underestimating the tensile stress values within the dam body.
Rhythm in Art, Psychology and New Materialism
Authors: Minissale Gregory
Published: February 2021

This book examines the psychology involved in handling, and responding to, materials in artistic practice, such as oils, charcoal, brushes, canvas, earth, and sand. Artists often work with intuitive, tactile sensations and rhythms that connect them to these materials. Rhythm connects the brain and body to the world, and the world of abstract art. The book features new readings of artworks by Matisse, Pollock, Dubuffet, Tápies, Benglis, Len Lye, Star Gossage, Shannon Novak, Simon Ingram, Lee Mingwei, L. N. Tallur and many others. Such art challenges centuries of philosophical and aesthetic order that has elevated the substance of mind over the substance of matter. This is a multidisciplinary study of different metastable patterns and rhythms: in art, the body, and the brain. This focus on the propagation of rhythm across domains represents a fresh art historical approach and provides important opportunities for art and science to cooperate.
The “Other” Relationship to Land: Property, Belonging, and Alternative Ontology
Authors: Carleton Alexandra
Published: February 2021

If land is divine and ought not be bought or sold,1 then bounded land, that which we term territory2 regardless of its form of being bounded, cannot be bought or sold without divine assent either. It may be defended, nurtured, utilised but not bought or sold. In defence of this is the human right to life and liberty. Were life and liberty to depend on access to land or territory then no hindrance would stand to merit. Theologically,3 the Divine created the land so the land belongs to the Divine.4 Similarly where humans labour (to work) and create (to make or build), such which is created is the property of the human, whether it is manufactured, built, sown. And from these personal properties flow the rights and privileges of personal property: alienation, transfer, purchase.5
On the Nature of Necessary Truths in Jurisprudence: Putting Wittgensteinian Hinges to Use
Authors: Tong Yi
Published: February 2021

Inquiring into the fundamental nature of law has been traditionally formulated as an attempt to answer the question, “What is Law?” Such an inquiry typically proceeds by identifying the necessary features of law. Joseph Raz, for example, writes:

A theory consists of necessary truths, for only necessary truths about the law reveal the nature of the law. We talk of ‘the nature of law’, or the nature of anything else, to refer to those of the law’s characteristics which are of the essence of law, which make law into what it is. That is those properties without which the law would not be law.1
Stochastic comparisons and ageing properties of an extended gamma process
Authors: Al Masry Zeina , Mercier Sophie , Verdier Ghislain
Published: February 2021

Extended gamma processes have been seen as a flexible extension of standard gamma processes in the recent reliability literature, for the purpose of cumulative deterioration modeling. The probabilistic properties of the standard gamma process have been well explored since the 1970s, whereas those of its extension remain largely unexplored. In particular, stochastic comparisons between degradation levels modeled by standard gamma processes and ageing properties for the corresponding level-crossing times are now well understood. The aim of this paper is to explore similar properties for extended gamma processes and see which ones can be broadened to this new context. As a by-product, new stochastic comparisons for convolutions of gamma random variables are also obtained.
Simple conditions for metastability of continuous Markov chains
Authors: Mangoubi Oren , Pillai Natesh , Smith Aaron
Published: February 2021

A family $\{Q_{\beta}\}_{\beta \geq 0}$ of Markov chains is said to exhibit metastable mixing with modes$S_{\beta}^{(1)},\ldots,S_{\beta}^{(k)}$ if its spectral gap (or some other mixing property) is very close to the worst conductance $\min\!\big(\Phi_{\beta}\big(S_{\beta}^{(1)}\big), \ldots, \Phi_{\beta}\big(S_{\beta}^{(k)}\big)\big)$ of its modes for all large values of $\beta$. We give simple sufficient conditions for a family of Markov chains to exhibit metastability in this sense, and verify that these conditions hold for a prototypical Metropolis–Hastings chain targeting a mixture distribution. The existing metastability literature is large, and our present work is aimed at filling the following small gap: finding sufficient conditions for metastability that are easy to verify for typical examples from statistics using well-studied methods, while at the same time giving an asymptotically exact formula for the spectral gap (rather than a bound that can be very far from sharp). Our bounds from this paper are used in a companion paper (O. Mangoubi, N. S. Pillai, and A. Smith, arXiv:1808.03230) to compare the mixing times of the Hamiltonian Monte Carlo algorithm and a random walk algorithm for multimodal target distributions.
Lyapunov-type conditions for non-strong ergodicity of Markov processes
Authors: Mao Yong-Hua , Wang Tao
Published: February 2021

We present Lyapunov-type conditions for non-strong ergodicity of Markov processes. Some concrete models are discussed, including diffusion processes on Riemannian manifolds and Ornstein–Uhlenbeck processes driven by symmetric $\alpha$-stable processes. In particular, we show that any process of d-dimensional Ornstein–Uhlenbeck type driven by $\alpha$-stable noise is not strongly ergodic for every $\alpha\in (0,2]$.
Tail asymptotics for the area under the excursion of a random walk with heavy-tailed increments
Authors: Denisov Denis , Perfilev Elena , Wachtel Vitali
Published: February 2021

We study the tail behaviour of the distribution of the area under the positive excursion of a random walk which has negative drift and heavy-tailed increments. We determine the asymptotics for tail probabilities for the area.
Double hypergeometric Lévy processes and self-similarity
Authors: Kyprianou Andreas E. , Pardo Juan Carlos , Vidmar Matija
Published: February 2021

Motivated by a recent paper (Budd (2018)), where a new family of positive self-similar Markov processes associated to stable processes appears, we introduce a new family of Lévy processes, called the double hypergeometric class, whose Wiener–Hopf factorisation is explicit, and as a result many functionals can be determined in closed form.
Business Model Innovation and Experimentation in Transforming Economies: ByteDance and TikTok
Authors: Ma Yulun , Hu Yue
Published: February 2021

Firms from transforming economies can leverage the characteristics of their location to develop innovative business models before internationalizing. This note showcases ByteDance's innovative business model for its TikTok app, which became one of the most downloaded apps globally. ByteDance used its large and increasingly demanding home market to experiment with creative combinations of business model elements to develop a unique business proposition that positions the TikTok app as a hybrid of social networking and video-sharing. In addition, TikTok benefitted from China's IT strength supported by national high-tech policy to an AI-based recommendation algorithm as a non-location bound resource. TikTok shows that firms from transforming economies can launch successful global products through business model innovation.
The Voice Gives It Away
Authors: Krahé Barbara , Uhlmann Andreas , Herzberg Meike
Published: February 2021

Abstract. Two experiments examined the impact of voice pitch on gender stereotyping. Participants listened to a text read by a female (Study 1; N = 171) or male (Study 2, N = 151) speaker, whose voice pitch was manipulated to be high or low. They rated the speaker on positive and negative facets of masculinity and femininity, competence, and likability. They also indicated their own gendered self-concept. High pitch was associated with the ascription of more feminine traits and greater likability. The high-pitch female speaker was rated as less competent, and the high-pitch male speaker was perceived as less masculine. Text content and participants’ gendered self-concept did not moderate the pitch effect. The findings underline the importance of voice pitch for impression formation.
Toward Constraining Mars' Thermal Evolution Using Machine Learning
Authors: Agarwal S. , Tosi N. , Kessel P. , Padovan S. , Breuer D. , Montavon G.
Published: February 2021

The thermal and convective evolution of terrestrial planets like Mars is governed by a number of initial conditions and parameters, which are poorly constrained. We use Mixture Density Networks (MDN) to invert various sets of synthetic present‐day observables and infer five parameters: reference viscosity, activation energy and activation volume of the diffusion creep rheology, an enrichment factor for radiogenic elements in the crust, and initial mantle temperature. The data set comes from 6,130 two‐dimensional simulations of the thermal evolution of Mars' interior. We quantify the possibility of constraining a parameter using the log‐likelihood value from the MDN. Reference viscosity can be constrained to within 32% of its entire range (1019 − 1022 Pa s), when all the observables are available: core‐mantle‐boundary heat flux, surface heat flux, radial contraction, melt produced, and duration of volcanism. Furthermore, crustal enrichment factor (1–50) can be constrained, at best, to within 15%, and the activation energy (105 − 5 × 105 J mol−1) to within 80%. Initial mantle temperature can be constrained to within 39% of its range (1,600–1,800 K). Using the full present‐day temperature profile or parts of it as an observable tightens the constraints further. The activation volume (4 × 10−6 − 10 × 10−6 m3 mol−1) cannot be constrained. We also tested different levels of uncertainty in the observables and found that constraints on different parameters loosen differently, with initial temperature being the most sensitive. Finally, we present how a joint probability model for all parameters can be obtained from the MDN.
Gypsum Deltas at the Holocene Dead Sea Linked to Grand Solar Minima
Authors: Weber N. , Lazar B. , Gavrieli I. , Yechieli Y. , Stein M.
Published: February 2021

Unique gypsum structures: large capes (termed “gypsum deltas”) and small pitted gypsum mounds are exposed along the western shores of the currently retreating Dead Sea, the hypersaline terminal lake in the Dead Sea Basin. The gypsum deltas were formed during time intervals of low lake stands (∼420 ± 10 m below mean sea level), when sulfate‐rich Ca chloride brines discharged from the coastal aquifer via saline springs, mixed with the Dead Sea brine and precipitated the gypsum (outsalting process). The ages of formation of the gypsum structures coincide with times of North Atlantic cooling events and grand solar minima suggesting a direct impact of the latter on the Dead Sea hydrology and high sensitivity of the regional hydrology (controlling lake level) to global solar‐related events. The temporal occurrence and numbers of the gypsum structures appear to follow the Hallstatt Cycle that approaches minima at ∼3,000–2,000 years before present.
Forecasting South China Sea Monsoon Onset Using Insight From Theory
Authors: Geen Ruth
Published: February 2021

Monsoon onset over the South China Sea occurs in April–May, marking the start of the wet season over East Asia. Skillful prediction of onset timing remains an open challenge. Recently, theoretical studies using idealized models have revealed feedbacks at work during the seasonal transitions of the Hadley cells and have shown that these are relevant to monsoon onset over Asia. Here, I hypothesize that monsoon onset occurs earlier in years when the atmosphere over the South China Sea is already in a state where these feedbacks are more easily triggered. I find that local anomalies in lower‐level moist static energy in the preceding January–March are well correlated with South China Sea Monsoon onset timing. This relationship remains relatively consistent on decadal timescales, while correlations with other teleconnections vary, and is used to develop a simple forecast model for onset timing that shows skill competitive with that of more complex models.
The Lithospheric Architecture of Australia From Seismic Receiver Functions
Authors: Birkey Andrew , Ford Heather A. , Dabney Page , Goldhagen Gillian
Published: February 2021

In the past decade, mounting evidence has pointed to complex, layered structure within and at the base of the mantle lithosphere of tectonically quiescent continental interiors. Sometimes referred to as negative velocity gradients or midlithospheric discontinuities (MLDs), the origin of intralithospheric layering has prompted considerable discussion, particularly as to how they may result from continent formation and/or evolution. Previous Sp receiver function analysis in Australia (Ford et al., 2010, https://doi.org/10.1016/j.epsl.2010.10.007) found evidence for complex lithospheric layering beneath permanent stations located within the North, South, and West Australian Cratons and characterized these as MLDs. This study provides an update to the original study by Ford et al. (2010, https://doi.org/10.1016/j.epsl.2010.10.007). Sp receiver function results are presented for 34 permanent, broadband stations. We observe the lithosphere–asthenosphere boundary (LAB) on the eastern margin of the continent, at depths of 75–85 km. The cratonic core of Australia has discontinuities within the lithosphere, with no observable LAB. On the western margin of the continent, we observe several stations with an ambiguous phase that may correspond to an MLD or the LAB. We also observe multiple negative phases at most stations, suggesting a complex and heterogeneous lithosphere. Australian MLDs are likely linked to the presence of hydrous minerals in the midlithosphere and may result from ancient processes such as subduction, plume interaction, or melt infiltration from the paleo‐LAB.
Publisher Correction: Implantation of Impella CP left ventricular assist device under the guidance of three-dimensional intracardiac echocardiography
Authors: Yastrebov Konstantin , Brunel Laurencie , Paterson Hugh S. , Williams Zoe A. , Wise Innes K. , Burrows Christopher S. , Bannon Paul G.
Published: February 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
In-field stereotactic body radiotherapy (SBRT) reirradiation for pulmonary malignancies as a multicentre analysis of the German Society of Radiation Oncology (DEGRO)
Authors: John Caroline , Dal Bello Riccardo , Andratschke Nicolaus , Guckenberger Matthias , Boda-Heggemann Judit , Gkika Eleni , Mantel Frederick , Specht Hanno M. , Stromberger Carmen , Zehentmayr Franz , Blanck Oliver , Balermpas Panagiotis
Published: February 2021

Data of thoracic in-field reirradiation with two courses of stereotactic body radiotherapy (SBRT) is scarce. Aim of this study is to investigate feasibility and safety of this approach. Patients with a second course of thoracic SBRT and planning target volume (PTV) overlap were analyzed in this retrospective, multicenter study. All plans and clinical data were centrally collected. 27 patients from 8 centers have been amenable for evaluation: 12 with non-small-cell lung cancer, 16 with metastases, treated from 2009 (oldest first course) to 2020 (latest second course). A median dose of 38.5 Gy to the 65%-isodose over a median of 5 fractions was prescribed in the first course and 40 Gy in 5 fractions for the second SBRT-course. Median PTV of the second SBRT was 29.5 cm3, median PTV overlap 22 cm3. With a median interval of 20.2 months between the two SBRT-courses, 1-year OS, and -LCR were 78.3% and 70.3% respectively. 3 patients developed grade 1 and one grade 2 pneumonitis. No grade > 2 toxicity was observed. Peripheral location and dose were the only factors correlating with tumor control. A second SBRT-course with PTV overlap appears safe and achieves reasonable local control.
Frame localisation optical projection tomography
Authors: Russell Craig T. , Vallejo Ramirez Pedro P. , Rees Eric
Published: February 2021

We present a tomographic reconstruction algorithm (flOPT), which is applied to Optical Projection Tomography (OPT) images, that is robust to mechanical jitter and systematic angular and spatial drift. OPT relies on precise mechanical rotation and is less mechanically stable than large-scale computer tomography (CT) scanning systems, leading to reconstruction artefacts. The algorithm uses multiple (5+) tracked fiducial beads to recover the sample pose and the image rays are then back-projected at each orientation. The quality of the image reconstruction using the proposed algorithm shows an improvement when compared to the Radon transform. Moreover, when adding a systematic spatial and angular mechanical drift, the reconstruction shows a significant improvement over the Radon transform.
Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
Authors: Starbuck John M. , Llambrich Sergi , Gonzàlez Rubèn , Albaigès Julia , Sarlé Anna , Wouters Jens , González Alejandro , Sevillano Xavier , Sharpe James , De La Torre Rafael , Dierssen Mara , Vande Velde Greetje , Martínez-Abadías Neus
Published: February 2021

Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.
Identification of distinct immune landscapes using an automated nine-color multiplex immunofluorescence staining panel and image analysis in paraffin tumor tissues
Authors: Parra Edwin R. , Zhai Jie , Tamegnon Auriole , Zhou Nicolas , Pandurengan Renganayaki Krishna , Barreto Carmelia , Jiang Mei , Rice David C. , Creasy Caitlin , Vaporciyan Ara A. , Hofstetter Wayne L. , Tsao Anne S. , Wistuba Ignacio I. , Sepesi Boris , Haymaker Cara
Published: February 2021

Immune profiling is becoming a vital tool for identifying predictive and prognostic markers for translational studies. The study of the tumor microenvironment (TME) in paraffin tumor tissues such as malignant pleural mesothelioma (MPM) could yield insights to actionable targets to improve patient outcome. Here, we optimized and tested a new immune-profiling method to characterize immune cell phenotypes in paraffin tissues and explore the co-localization and spatial distribution between the immune cells within the TME and the stromal or tumor compartments. Tonsil tissues and tissue microarray (TMA) were used to optimize an automated nine-color multiplex immunofluorescence (mIF) panel to study the TME using eight antibodies: PD-L1, PD-1, CD3, CD8, Foxp3, CD68, KI67, and pancytokeratin. To explore the potential role of the cells into the TME with this mIF panel we applied this panel in twelve MPM cases to assess the multiple cell phenotypes obtained from the image analysis and well as their spatial distribution in this cohort. We successful optimized and applied an automated nine-color mIF panel to explore a small set of MPM cases. Image analysis showed a high degree of cell phenotype diversity with immunosuppression patterns in the TME of the MPM cases. Mapping the geographic cell phenotype distribution in the TME, we were able to identify two distinct, complex immune landscapes characterized by specific patterns of cellular distribution as well as cell phenotype interactions with malignant cells. Successful we showed the optimization and reproducibility of our mIF panel and their incorporation for comprehensive TME immune profiling into translational studies that could refine our ability to correlate immunologic phenotypes with specific patterns of cells distribution and distance analysis. Overall, this will improve our ability to understand the behavior of cells within the TME and predict new treatment strategies to improve patient outcome.
A study of elastico-viscous fluid flow by a revolving disk with heat dissipation effects using HAM based package BVPh 2.0
Authors: Jafeer M. Burhan , Mustafa M.
Published: February 2021

Von Kármán problem of infinite disk is re-examined when fluid under consideration is elastico-viscous, satisfying the constitutive relations of Walters-B model. Main target here is to demonstrate how the presence of elasticity alters heat transfer phenomenon for the said problem especially when heat dissipation term is included in the analysis. We assume a self-similarity solution that results in a system of coupled non-linear equations. An easy to use package BVPh 2.0 based on the homotopy analysis method is used to present series solutions for values of elastico-viscous fluid parameter ($$K$$
K
) in the range $$0 \le K \le 1$$

0
≤
K
≤
1

. Residuals are evaluated numerically at various order of approximations which depict that obtained solutions converge to the exact solutions. Boundary layer is substantially suppressed due to the consideration of elastico-viscous fluid assumption. Furthermore, velocity of the entrained fluid is inversely proportional to the parameter $$K$$
K
. The results predict a substantial drop in heat transfer rate whenever elasticity effects are present. A considerable role of heat dissipation towards thickening of thermal boundary layer is apparent from the findings.
Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis
Authors: Müller-Deile Janina , Sarau George , Kotb Ahmed M. , Jaremenko Christian , Rolle-Kampczyk Ulrike E. , Daniel Christoph , Kalkhof Stefan , Christiansen Silke H. , Schiffer Mario
Published: February 2021

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, “the” actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient’s serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease.
Sex-dependent differences in the gut microbiota following chronic nasal inflammation in adult mice
Authors: Mishima Yuko , Osaki Takako , Shimada Atsuyoshi , Kamiya Shigeru , Hasegawa-Ishii Sanae
Published: February 2021

A growing body of evidence suggests a relationship between olfactory dysfunction and the pathogenesis of mental disorders. Our previous studies indicated that chronic nasal inflammation caused loss of olfactory sensory neurons and gross atrophy of the olfactory bulb, which may lead to olfactory dysfunction. Simultaneously, increasing numbers of reports have elucidated the importance of gut microbiota to maintain brain function and that dysbiosis may be associated with neuropsychiatric disorders. Here we examined whether chronic nasal inflammation perturbed gut microbiota and whether there were sex differences in this pattern. Eight-week-old C57BL/6 mice repeatedly received bilateral nasal administration of lipopolysaccharide (LPS) 3 times/week to cause chronic nasal inflammation or saline as a control. At 9 weeks, cecal feces were used for 16S metagenomic analysis and whole blood and fresh tissue of spleen were used for ELISA analyses. Microbiome analysis demonstrated a remarkable change of the gut microbiota in male mice with chronic nasal inflammation which was different from that in female mice. In both mice, systemic inflammation did not occur. This has shown for the first time that chronic nasal inflammation correlates with sex-dependent changes in the gut microbiota. The detailed mechanism and potential alteration to brain functions await further studies.
Association between parents’ smoking status and tobacco exposure in school-age children: assessment using major urine biomarkers
Authors: Jeong Sung Hoon , Jang Bich Na , Kang Soo Hyun , Joo Jae Hong , Park Eun-Cheol
Published: February 2021

Children are at risk of exposure to secondhand smoke. We aimed to evaluate the extent of their exposure to it in relation to their parents’ smoking status by using biomarkers relevant to smoking. We evaluated 847 school-age children (6–12 years) who lived with their parents, using data from the Korea National Health and Nutrition Examination Survey 2016–2018. Secondhand smoke exposure in children of non-smoking and smoking parents was assessed by measuring urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and cotinine concentrations. Overall, the parents of 482 (55.1%) children smoked and those of 392 (44.9%) children did not smoke. After adjusting for covariates, significantly higher concentrations of NNAL (β = 0.482, standard error [S.E.] = 0.065, P < 0.001) and cotinine (β = 0.472, S.E. = 0.06, P < 0.001) were found in children of smoking parents than in children of non-smoking parents. Children of parents who smoked a higher number of cigarettes showed higher NNAL and cotinine concentrations than children of non-smoking parents. Children with both parents who smoked showed the highest NNAL and cotinine concentrations. Children of smoking parents are at a higher risk of exposure to secondhand smoke. A smoke-free environment must be maintained to protect children from the harmful effects of secondhand smoke. Therefore, comprehensive national anti-smoking policies are required.
Sacrificial gold coating enhances transport of liquid metal in pressurized fountain pen lithography
Authors: Livshits Gideon I. , Bao Jiannan , Sakamoto Leo , Misaka Tomoki , Usami Yuki , Otsuka Yoichi , Matsumoto Takuya
Published: February 2021

Liquid metals have attracted attention as functional components for moldable electronics, such as soft flexible connectors, wires or conductive ink. The relatively high surface tension (> 400 mN m−1) and the fact that liquid metals do not readily wet ceramic or oxide surfaces have led to devising unique techniques to spread the liquid and mold its shape. These techniques include surface modification, electrowetting and vacuum filling of channels. This work presents an injection technique based on pressurized fountain pen lithography with glass nanopipettes developed to directly pattern liquid metal on flat hard substrates. The liquid metals were eutectic alloys of Gallium, including Gallium-Indium (EGaIn), Gallium-Indium-Zinc and Gallium-Indium-Tin. The nanopipettes were coated internally with gold, acting as a sacrificial layer and facilitating the wetting of the pipette down to its pore, with an inner diameter of ~ 100–300 nm. By applying hydrodynamic pressure to the connected end of the pipette, the metal was extruded through the pore, forming long continuous (> 3 mm) and narrow (~ 1–15 µm) metal lines on silicon oxide and gold surfaces at room temperature and ambient conditions. With this robust platform, it is possible to pattern liquid metals on a variety of substrates and geometries down to the micron range.
False-negative diagnosis of high anion gap in patients with end-stage kidney disease
Authors: Komatsuzaki You , Ikeda Masato , Shimizu Akihiro , Matsuo Nanae , Maruyama Yukio , Yokoo Takashi , Yamamoto Hiroyuki , Joki Nobuhiko , Ando Ryoichi , Inaguma Daijo , Yamaka Toshihiko , Nakayama Masaaki , Koiwa Fumihiko , Kawamoto Shinya , Negi Shigeo , Shigematsu Takashi
Published: February 2021

The traditional anion gap (AG) equation is widely used, but its misdiagnosis in end-stage kidney disease (ESKD) patients has not been investigated fully. Diagnostic accuracy to detect high AG was cross-sectionally evaluated using 3 AG equations in 1733 ESKD patients with an eGFR less than 15 mL/min/1.73 m2. The prevalence of high AG was 67.9%, 92.1% and 97.4% by the traditional, albumin-adjusted AG (aAG) and full AG equations, respectively. The sensitivity, specificity, accuracy and Kappa coefficient obtained with the traditional AG vs aAG equation were 0.70 vs 0.94, 0.98 vs 0.93, 0.7 vs 0.94, and 0.103 vs 0.44, respectively. Next, we created a subcohort comprising only patients with high full AG and investigated how the traditional AG equation leads to misdiagnoses. Multivariable-adjusted regression analysis in 1688 patients revealed that independent factors associated with a false-negative AG diagnosis were ARB use, eGFR, blood leukocyte count, serum chloride, bicarbonate, ionized calcium, potassium, albumin and phosphate. 93.2% of our subcohort prescribed any of RAAS inhibitors, Loop diuretics or Alkali which could increase either serum chloride or bicarbonate. Frequent use of these possible AG-reducing medications may conceal high AG state in patients with ESKD unless they have incidental inflammation which may increase AG value.
Comparison of the onset time between 0.375% ropivacaine and 0.25% levobupivacaine for ultrasound-guided infraclavicular brachial plexus block: a randomized-controlled trial
Authors: Kim Ha-Jung , Lee Sooho , Chin Ki Jinn , Kim Jin-Sun , Kim Hyungtae , Ro Young-Jin , Koh Won Uk
Published: February 2021

At centers with pressure on rapid operating room turnover, onset time is one of the important considerations for choosing a local anesthetic drug. To hasten the onset of the block, higher concentrations of local anesthetics are sometimes used. However, the use of diluted local anesthetics may be safer. Therefore, we aimed to compare the onset times of equipotential levobupivacaine and ropivacaine at low concentrations for infraclavicular brachial plexus block. Adult patients undergoing upper extremity surgery under ultrasound-guided infraclavicular brachial plexus block at our center were randomly allocated to the levobupivacaine and ropivacaine groups. Infraclavicular brachial plexus block was induced with 0.25% levobupivacaine or 0.375% ropivacaine depending on the assigned group. The degrees of sensory and motor blockade were assessed for 40 min after the administration of local anesthetics. A total of 46 patients were included in the analysis. Infraclavicular brachial plexus block with 0.25% levobupivacaine and 0.375% ropivacaine provided sufficient surgical anesthesia. The sensory onset time of 0.375% ropivacaine was shorter than that of 0.25% levobupivacaine (group R, 15 [15.0–22.5] min; group L, 30 [17.5–35.0] min, p = 0.001). There were no significant differences in other block characteristics and clinical outcomes between the two groups. Thus, when a quicker block onset is required, 0.375% ropivacaine is a better choice than 0.25% levobupivacaine.

Trial registration ClinicalTrials.gov (NCT03679897).
Tillage effects on soil properties and crop yield after land reclamation
Authors: Liu Zhe , Cao Shiliu , Sun Zenghui , Wang Huanyuan , Qu Shaodong , Lei Na , He Jing , Dong Qiguang
Published: February 2021

Tillage treatments have an important effect on soil microstructure characteristics, water thermal properties and nutrients, but little is known in the newly reclaimed cultivated land. For the reason, a long-term field study was to evaluate the tillage effects on soil physicochemical properties and crop yield in newly reclaimed cultivated land via the macroscopic and microscopic analysis. Three tillage treatments were tested: continuous conventional moldboard plow tillage (CT), sub-soiling/moldboard-tillage/sub-soiling tillage (ST) and no-tillage/sub-soiling/no-tillage (NT). Under CT, the microstructure was dominated by weakly separated plates structure and showed highest bulk density (BD) (1.49 g cm−3) and lowest soil organic matter (SOM) (3.68 g kg−1). In addition, CT reduced the capacity of soil moisture retention and temperature maintenance, resulting in aggregate structure deterioration and fragility. Unlike CT, the soil was characterized by moderately separated granular structure and highly separated aggregate structure under conservation tillage practice of ST and NT. NT was associated with the highest soil moisture content (20.42%), highest quantity of macroaggregates (> 0.25 mm) by wet-sieving (34.07%), and highest SOM (6.48 g kg−1) in the surface layer. Besides, NT was better able to regulate soil temperature and improved the values of geometric mean diameter. Under NT and ST, a stable soil structure with compound aggregates and pores was formed, and the maize yield was increased by 12.9% and 14.9% compared with CT, up to 8512.6 kg ha−1 and 8740.9 kg ha−1, respectively. These results demonstrated the positive effects of NT and ST on soil quality and crop yield in newly reclaimed cultivated land.
Modelling physiology of haemodynamic adaptation in short-term microgravity exposure and orthostatic stress on Earth
Authors: Mohammadyari Parvin , Gadda Giacomo , Taibi Angelo
Published: February 2021

Cardiovascular haemodynamics alters during posture changes and exposure to microgravity. Vascular auto-remodelling observed in subjects living in space environment causes them orthostatic intolerance when they return on Earth. In this study we modelled the human haemodynamics with focus on head and neck exposed to different hydrostatic pressures in supine, upright (head-up tilt), head-down tilt position, and microgravity environment by using a well-developed 1D-0D haemodynamic model. The model consists of two parts that simulates the arterial (1D) and brain-venous (0D) vascular tree. The cardiovascular system is built as a network of hydraulic resistances and capacitances to properly model physiological parameters like total peripheral resistance, and to calculate vascular pressure and the related flow rate at any branch of the tree. The model calculated 30.0 mmHg (30%), 7.1 mmHg (78%), 1.7 mmHg (38%) reduction in mean blood pressure, intracranial pressure and central venous pressure after posture change from supine to upright, respectively. The modelled brain drainage outflow percentage from internal jugular veins is 67% and 26% for supine and upright posture, while for head-down tilt and microgravity is 65% and 72%, respectively. The model confirmed the role of peripheral veins in regional blood redistribution during posture change from supine to upright and microgravity environment as hypothesized in literature. The model is able to reproduce the known haemodynamic effects of hydraulic pressure change and weightlessness. It also provides a virtual laboratory to examine the consequence of a wide range of orthostatic stresses on human haemodynamics.
Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells
Authors: Hsieh Kan-Yen , Tsai Ju-Ying , Lin Ya-Han , Chang Fang-Rong , Wang Hui-Chun , Wu Chin-Chung
Published: February 2021

Inflammation in the tumor microenvironment is positively correlated with cancer progression and metastasis as well as the risk of thromboembolism in lung cancer patients. Here we show, in human non-small cell lung cancer (NSCLC) cell lines, the master inflammatory cytokine tumor necrosis factor (TNF-α) induced tissue factor expression and procoagulant activity, and these effects were potently inhibited by 4β-hydroxywithanolide E (4HW), a natural compound isolated from Physalis peruviana. Furthermore, combination of 4HW and TNF-α caused synergistic cytotoxicity against NSCLC cells by inducing caspase-dependent apoptosis. The underlying mechanism by which 4HW reverses the procoagulant effect of TNF-α but enhances its cytotoxic effect appears to be due to inhibition of NF-κB, which is a key switch for both inflammation-induced coagulation and cell survival. Our results suggest that 4HW may have a potential application for treating inflammation-derived cancer progression and cancer-associated hypercoagulable state.