bluuebunny/crossref_metadata_2025 huggingface dataset:
How vague is vague? How informative is informative? Reference analysis for Bayesian meta‐analysis
Authors: Ott Manuela , Plummer Martyn , Roos Małgorzata
Published: May 2021

Meta‐analysis provides important insights for evidence‐based medicine by synthesizing evidence from multiple studies which address the same research question. Within the Bayesian framework, meta‐analysis is frequently expressed by a Bayesian normal‐normal hierarchical model (NNHM). Recently, several publications have discussed the choice of the prior distribution for the between‐study heterogeneity in the Bayesian NNHM and used several “vague” priors. However, no approach exists to quantify the informativeness of such priors, and thus, we develop a principled reference analysis framework for the Bayesian NNHM acting at the posterior level. The posterior reference analysis (post‐RA) is based on two posterior benchmarks: one induced by the improper reference prior, which is minimally informative for the data, and the other induced by a highly anticonservative proper prior. This approach applies the Hellinger distance to quantify the informativeness of a heterogeneity prior of interest by comparing the corresponding marginal posteriors with both posterior benchmarks. The post‐RA is implemented in the freely accessible R package ra4bayesmeta and is applied to two medical case studies. Our findings show that anticonservative heterogeneity priors produce platykurtic posteriors compared with the reference posterior, and they produce shorter 95% credible intervals (CrI) and optimistic inference compared with the reference prior. Conservative heterogeneity priors produce leptokurtic posteriors, longer 95% CrI and cautious inference. The novel post‐RA framework could support numerous Bayesian meta‐analyses in many research fields, as it determines how informative a heterogeneity prior is for the actual data as compared with the minimally informative reference prior.
Inspired by Vitamin a for Anti-Ageing: Searching for Plant-Derived Functional Retinoid Analogues
Authors: Sadgrove N. J. , Oblong J. E. , Simmonds M. S. J.
Published: May 2021

Background

Cosmetic treatments that inspire one's appearance to resemble their younger portrait often utilize ingredients that confer acute effects, particularly hydration by creating hydrophobic barriers or transient elevation of barrier water content. But superior therapies successfully promote morphogenesis of the dermal-epidermal junction, inspiring extracellular matrix (ECM) formation. This can be achieved by agonism of the very well-known retinoid nuclear receptors using the endogenous ligand all-trans retinoic acid (tRA), tRA precursors or plant-based functional analogues, with reduced side effects.

Aims, Materials and Methods

While there are already many promising cosmetic ingredients available from the world's flora, higher potency is favoured, so increasing known candidates is a worth undertaking. Functional analogues of retinoic acid can be identified by culturing fibroblasts with lipophilic candidates from the plant kingdom and assessing gene-arrays. Modern approaches to validating these findings include the coculturing of fibroblasts with keratinocytes as a measure to predict the potential effects of crosstalk.

Results and Discussion

In this regard, the most promising plant-derived candidates are of terpene or meroterpene origin, including derivatives of squalene and phytol. Surprisingly pimaric or abietic acids and labdane diterpenes are also noteworthy agonists of the retinoic acid receptor, stimulating collagen expression in dermal fibroblasts.

Conclusion

There are numerous derivatives of these terpenes available from the world's flora and research conducted thus far encourages further screening of these chemical candidates.
Preparation of All‐Cellulose Composites Based on Controlled Dissolution Procedure
Authors: Zhang Qian , Wang Zhaoqi , Hao Sufen , Huang Jintian
Published: May 2021

In this study, all‐cellulose composite materials are prepared through the dissolution and regeneration process using waste kraft papers as raw material in the sodium hydroxide/thiourea/urea solvent system. The degree of conversion is controlled by adjusting the microenvironment of the cellulose solvents, and the composite membrane is prepared by mixing the regenerated cellulose with the insoluble cellulose, which aims at adjusting the morphology and mechanical properties of the composite material. The shape of the regenerated cellulose after the dissolution and regeneration change from the original fiber into a sphere as shown by SEM images. The composite films show different phenomena, the insoluble part, and the matrix phase form a dense and strong network structure. The presence of this insoluble part increases the strength of the matrix phase and fundamentally changes the brittleness of the regenerated cellulose. This work provides a green and promising method to prepare high‐performance, environmentally friendly all‐cellulose composite materials.
Progress in the sustainable recycling of spent lithium‐ion batteries
Authors: Fan Min , Chang Xin , Meng Qinghai , Wan Li‐Jun , Guo Yu‐Guo
Published: May 2021

Lithium‐ion batteries (LIBs) are booming in multiple fields due to a rapid development in the last decade. However, limited by operational lifespans, a growing number of spent LIBs reaching the end of their lives are consequently faced with serious accumulation and descended to hazardous waste. Without proper disposal, the spent LIBs will inevitably cause negative influence on the ecology and undermine the sustainable manufacture of LIBs. The initial research of recycling strategies mainly focused on the optimization of metallurgical processes. Recently, the sustainability of the recycling process has attracted much more attention and become an important factor. Here, we summarize the recent progress of the spent LIBs recycling from a sustainable perspective, especially discussing the green innovations in recycling strategies for spent LIBs. Through this article, we expect to reveal the challenges and developing tendency of the recycling strategies and provide a guideline for future researches on processing spent LIBs and beyond, like the recycling of the solid‐state lithium metal batteries.
Displaced new physics at colliders and the early universe before its first second
Authors: Calibbi Lorenzo , D’Eramo Francesco , Junius Sam , Lopez-Honorez Laura , Mariotti Alberto
Published: May 2021

Abstract

Displaced vertices at colliders, arising from the production and decay of long-lived particles, probe dark matter candidates produced via freeze-in. If one assumes a standard cosmological history, these decays happen inside the detector only if the dark matter is very light because of the relic density constraint. Here, we argue how displaced events could very well point to freeze-in within a non-standard early universe history. Focusing on the cosmology of inflationary reheating, we explore the interplay between the reheating temperature and collider signatures for minimal freeze-in scenarios. Observing displaced events at the LHC would allow to set an upper bound on the reheating temperature and, in general, to gather indirect information on the early history of the universe.
Remarks on holographic models of the Kerr-AdS5 geometry
Authors: Amado Julián Barragán , da Cunha Bruno Carneiro , Pallante Elisabetta
Published: May 2021

Abstract

We study the low-temperature limit of scalar perturbations of the Kerr-AdS5black-hole for generic rotational parameters. We motivate the study by considering real-time holography of small black hole backgrounds. Using the isomonodromic technique, we show that corrections to the extremal limit can be encoded in the monodromy parameters of the Painlevé V transcendent, whose expansion is given in terms of irregular chiral conformal blocks. After discussing the contribution of the intermediate states to the quasinormal modes, we perform a numerical analysis of the low-lying frequencies. We find that the fundamental mode is perturbatively stable at low temperatures for small black holes and that excited perturbations are superradiant, as expected from thermodynamical considerations. We close by considering the holographic interpretation of the unstable modes and the decaying process.
A model-driven approach for engineering customizable MES with the application to the food and beverage industry
Authors: Chen Xinyu , Nophut Christoph , Voigt Tobias
Published: May 2021

The Manufacturing Execution System (MES) is a process-oriented IT solution collecting and managing information from the shop floor manufacturing processes. Because of the programming and customization effort required for specific production processes, the MES implementation is not widespread in the food and beverage industry, as most food and beverage manufacturers are small- and medium-sized enterprises with limited resources to invest in MES. For engineering the MES that should be customized according to the target production processes, a model-driven approach has been presented in this paper with six phases covering the entire lifecycle of the MES engineering process. By using this approach, MES can be automatically generated and sustainably improved, which has the potential to reduce the complexity of implementation as well as the resources required for the engineering of customizable MES. Based on two use cases in the processing and packaging areas in the food and beverage industry, the feasibility and practicality of the presented approach have been proven.
Bayesian graphical models for modern biological applications
Authors: Ni Yang , Baladandayuthapani Veerabhadran , Vannucci Marina , Stingo Francesco C.
Published: May 2021

Graphical models are powerful tools that are regularly used to investigate complex dependence structures in high-throughput biomedical datasets. They allow for holistic, systems-level view of the various biological processes, for intuitive and rigorous understanding and interpretations. In the context of large networks, Bayesian approaches are particularly suitable because it encourages sparsity of the graphs, incorporate prior information, and most importantly account for uncertainty in the graph structure. These features are particularly important in applications with limited sample size, including genomics and imaging studies. In this paper, we review several recently developed techniques for the analysis of large networks under non-standard settings, including but not limited to, multiple graphs for data observed from multiple related subgroups, graphical regression approaches used for the analysis of networks that change with covariates, and other complex sampling and structural settings. We also illustrate the practical utility of some of these methods using examples in cancer genomics and neuroimaging.
Implicit incentives for fund managers with partial information
Authors: Angelini Flavio , Colaneri Katia , Herzel Stefano , Nicolosi Marco
Published: May 2021

We study the optimal asset allocation problem for a fund manager whose compensation depends on the performance of her portfolio with respect to a benchmark. The objective of the manager is to maximise the expected utility of her final wealth. The manager observes the prices but not the values of the market price of risk that drives the expected returns. Estimates of the market price of risk get more precise as more observations are available. We formulate the problem as an optimization under partial information. The particular structure of the incentives makes the objective function not concave. Therefore, we solve the problem by combining the martingale method and a concavification procedure and we obtain the optimal wealth and the investment strategy. A numerical example shows the effect of learning on the optimal strategy.
Comparing methods for determining landslide early warning thresholds: potential use of non-triggering rainfall for locations with scarce landslide data availability
Authors: Peres David J. , Cancelliere Antonino
Published: May 2021

Rainfall intensity-duration landslide-triggering thresholds have become widespread for the development of landslide early warning systems. Thresholds can be in principle determined using rainfall event datasets of three types: (a) rainfall events associated with landslides (triggering rainfall) only, (b) rainfall events not associated with landslides (non-triggering rainfall) only, (c) both triggering and non-triggering rainfall. In this paper, through Monte Carlo simulation, we compare these three possible approaches based on the following statistical properties: robustness, sampling variation, and performance. It is found that methods based only on triggering rainfall can be the worst with respect to those three investigated properties. Methods based on both triggering and non-triggering rainfall perform the best, as they could be built to provide the best trade-off between correct and wrong predictions; they are also robust, but still require a quite large sample to sufficiently limit the sampling variation of the threshold parameters. On the other side, methods based on non-triggering rainfall only, which are mostly overlooked in the literature, imply good robustness and low sampling variation, and performances that can often be acceptable and better than thresholds derived from only triggering events. To use solely triggering rainfall—which is the most common practice in the literature—yields to thresholds with the worse statistical properties, except when there is a clear separation between triggering and non-triggering events. Based on these results, it can be stated that methods based only on non-triggering rainfall deserve wider attention. Methods for threshold identification based on only non-triggering rainfall may have the practical advantage that can be in principle used where limited information on landslide occurrence is available (newly instrumented areas). The fact that relatively large samples (about 200 landslides events) are needed for a sufficiently precise estimation of threshold parameters when using triggering rainfall suggests that threshold determination in future applications may start from identifying thresholds from non-triggering events only, and then move to methods considering also the triggering events as landslide information starts to become more available.
“It Happens, But I’m Not There”: On the Phenomenology of Childbirth
Authors: Trigg Dylan
Published: May 2021

Phenomenologically grounded research on pregnancy is a thriving area of activity in feminist studies and related disciplines. But what has been largely omitted in this area of research is the experience of childbirth itself. This paper proposes a phenomenological analysis of childbirth inspired by the work of Merleau-Ponty. The paper proceeds from the conviction that the concept of anonymity can play a critical role in explicating the affective structure of childbirth. This is evident in at least two respects. First, the concept of anonymity gives structural specificity to the different levels of bodily existence at work in childbirth. Second, the concept of anonymity can play a powerful explanatory role in accounting for the sense of strangeness accompanying childbirth. To flesh these ideas out, I focus on two attributes of birth, sourced from first-person narratives of childbirth. The first aspect concerns the sense of leaving one’s body behind during childbirth while the second aspect concerns the sense of strangeness accompanying the first encounter with the baby upon successful delivery. I take both of these aspects of childbirth seriously, treating them as being instructive not only of the uniqueness of childbirth but also revealing something important about bodily life more generally. Accordingly, the paper unfolds in three stages. First, I will critically explore the concept of anonymity in Merleau-Ponty; second, I will apply this concept to childbirth; finally, I will provide an outline of how childbirth sheds light on the broader nature of bodily life.
Metabolomics: towards acceleration of antibacterial plant-based leads discovery
Authors: Sieniawska Elwira , Georgiev Milen I.
Published: May 2021

The wide and not yet fully uncovered potential of plant secondary metabolites make plants a rich source of drug leads. Metabolomics enables the study of the metabolic perturbations taking place in bacterial cells under the influence of plant-based bioactive molecules. It reveals the changes in metabolic pathways within bacteria, reflecting the reprogramming of the biochemical networks. From this point of view, metabolomics is valuable in understanding the alteration of cell functions when bacteria are subjected to metabolic stress caused by treatment with secondary metabolites, that inhibit their growth. In this review the application of metabolomics in revealing bacteria response to plant-derived secondary metabolites is presented. Metabolomics may be a way to select antibacterial plant-based bioactive secondary metabolites and to understand their mode of action. Therefore, herein the usefulness of metabolomic approach in screening for antimicrobials from plants, as well as in exploring the target points in bacteria metabolism and in uncovering the mechanisms of bacteria adaptation and resistance to natural antimicrobials are discussed. Basic chemometrics and molecular networking are successfully applied for the identification of antimicrobial molecules in complex plant mixtures. Determination of antibacterial modes of action is done through classification strategy, pathway analysis and integration of transcriptomics, genomics and metabolomics, whereas, comparative metabolomics and integrative approach is useful in revealing the bacterial mechanisms of resistance.
Economics of autonomous equipment for arable farms
Authors: Lowenberg-DeBoer James , Franklin Kit , Behrendt Karl , Godwin Richard
Published: May 2021

By collecting more data at a higher resolution and by creating the capacity to implement detailed crop management, autonomous crop equipment has the potential to revolutionise precision agriculture (PA), but unless farmers find autonomous equipment profitable it is unlikely to be widely adopted. The objective of this study was to identify the potential economic implications of autonomous crop equipment for arable agriculture using a grain-oilseed farm in the United Kingdom as an example. The study is possible because the Hands Free Hectare (HFH) demonstration project at Harper Adams University has produced grain with autonomous equipment since 2017. That practical experience showed the technical feasibility of autonomous grain production and provides parameters for farm-level linear programming (LP) to estimate farm management opportunities when autonomous equipment is available. The study shows that arable crop production with autonomous equipment is technically and economically feasible, allowing medium size farms to approach minimum per unit production cost levels. The ability to achieve minimum production costs at relatively modest farm size means that the pressure to “get big or get out” will diminish. Costs of production that are internationally competitive will mean reduced need for government subsidies and greater independence for farmers. The ability of autonomous equipment to achieve minimum production costs even on small, irregularly shaped fields will improve environmental performance of crop agriculture by reducing pressure to remove hedges, fell infield trees and enlarge fields.
Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation
Authors: Yuan Shuai , Bruzelius Maria , Larsson Susanna C.
Published: May 2021

Whether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.
Predicting COVID-19 cases using bidirectional LSTM on multivariate time series
Authors: Said Ahmed Ben , Erradi Abdelkarim , Aly Hussein Ahmed , Mohamed Abdelmonem
Published: May 2021

To assist policymakers in making adequate decisions to stop the spread of the COVID-19 pandemic, accurate forecasting of the disease propagation is of paramount importance. This paper presents a deep learning approach to forecast the cumulative number of COVID-19 cases using bidirectional Long Short-Term Memory (Bi-LSTM) network applied to multivariate time series. Unlike other forecasting techniques, our proposed approach first groups the countries having similar demographic and socioeconomic aspects and health sector indicators using K-means clustering algorithm. The cumulative case data of the clustered countries enriched with data related to the lockdown measures are fed to the bidirectional LSTM to train the forecasting model. We validate the effectiveness of the proposed approach by studying the disease outbreak in Qatar and the proposed model prediction from December 1st until December 31st, 2020. The quantitative evaluation shows that the proposed technique outperforms state-of-art forecasting approaches.
Shortening the Frommelt Attitude Toward the Care Of the Dying Scale (FATCOD-B): a Brief 9-Item Version for Medical Education and Practice
Authors: Molinengo Giorgia , Loera Barbara , Miniotti Marco , Leombruni Paolo
Published: May 2021

End-of-life care training has gaps in helping students to develop attitudes toward caring for the dying. Valid and reliable assessment tools are essential in building effective educational programmes. The Frommelt Attitude Toward the Care Of the Dying scale (FATCOD-B) is widely used to measure the level of comfort/discomfort in caring for the dying and to test the effectiveness of end-of-life care training. However, its psychometric properties have been questioned and different proposals for refinement and shortening have been put forward. The aim of this study is to get to a definitive reduction of the FATCOD-B through a valid and parsimonious synthesis of the previous attempts at scale revision. Data were gathered from a sample of 220 medical students. The item response theory approach was used in this study. Of the 14 items selected from two previous proposals for scale revision, 3 had a weak correlation with the whole scale and were deleted. The resulting 11-item version had good fit indices and withstood a more general and parsimonious specification (rating scale model). This solution was further shortened to 9 items by deleting 2 of 3 items at the same level of difficulty. The final 9-item version was invariant for gender, level of religiosity and amount of experience with dying persons, free from redundant items and able to scale and discriminate the respondents.
Fujita decomposition on families of abelian varieties
Authors: Pirola Gian Pietro
Published: May 2021

Let $$F:{\mathcal {V}}\rightarrow B$$

F
:
V
→
B

be a smooth non-isotrivial $$1-$$

1
-

dimensional family of complex polarized abelian varieties and $$V_b=F^{-1}(b)$$

V
b

=

F

-
1

(
b
)

be the general fiber. Let $${\mathcal {F}}^1\subset R^1F_*{\mathbb {C}}$$

F

1

⊂

R
1

F

∗

C

be the associated Hodge bundle filtration, $${\mathcal {F}}^1_b=H^{1.0}(V_b).$$

F

b
1

=

H

1.0

(

V
b

)

.

Under the assumption that the Fujita decomposition for $${\mathcal {F}}^1$$

F

1

is non trivial, that is there is a non trivial flat sub-bundle $$0\ne {\mathbb {U}}\subset {\mathcal {F}}^1,$$

0
≠
U
⊂

F

1

,

we show that $$V_b$$

V
b

has non-trivial endomorphism: $$End(V_b)\ne {\mathbb {Z}}.$$

E
n
d
(

V
b

)
≠
Z
.
Who suffers and how much from corruption? Evidence from firm-level data
Authors: Cieślik Andrzej , Goczek Łukasz
Published: May 2021

In this article, we study firm-level determinants of corruption using a sample of 164,000 companies from 144 countries for the 2005–2020 period. We analyze two variables related to corruption: the perception of corruption as an obstacle to doing business using an ordinal logit model and actual bribe tax payments using a fractional logit model. Controlling for other factors, both sets of our empirical results show that the extent of corruption is related to the time spent dealing with regulations and inspections. We argue that firms which spend more time dealing with administrative procedures have a greater perception of corruption and are forced to make significantly higher bribe payments. Therefore, in a successful fight against corruption, it is essential to simplify administrative procedures by reducing their number and eliminating direct contacts between firms and officials.
Fighting Against Plant Saline Stress: Development of a Novel Bioactive Composite Based on Bentonite and L-Proline
Authors: Merino Danila , Iglesias María J. , Mansilla Andrea Y , Casalongué Claudia A. , Alvarez Vera A.
Published: May 2021

Soil salinity is one of the most critical environmental stresses that affects crop productivity. In a context in which world demand for food is growing continuously, this problem requires urgent attention. Actions that go beyond traditional agricultural practices are needed. The objective of the current study was to develop a bioactive, economic, and sustainable compound that can increase the tolerance of cultivated plants in saline-stress situations by combining the hosting capacity of natural bentonite nanoclay (Bent) with a phytoactive osmoprotective compound, L-Proline (Pro). The Bent-Pro nanocomposite synthesis method, its final chemical structure, and in vitro bioactivity were addressed here. The results indicated that Bent can retain a maximum of 14.4% (w/w) of Pro. The (001) X-ray diffraction (XRD) peak of Bent shifted to smaller angles in the pattern of Bent-Pro, indicating that Pro has a monolayer arrangement between the Bent layers. The results of transmission electron microscopy (TEM) also supported this result. Pro was also retained on the edges or external surfaces of Bent, as indicated by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). In addition, Pro functional groups identified by Fourier-transform infrared (FTIR) spectroscopy indicated that it was present in its zwitterionic form. The role of Bent-Pro as a protector against plant saline stress was assayed using Arabidopsis thaliana (A. thaliana) as a model, demonstrating that it mitigates the detrimental effects of NaCl-mediated salt stress on seed germination and the leaf chlorophyll level, thus highlighting the relevance of this contribution and the versatility and broad applicability of clays.
Effects of equal channel angular pressing and heat treatments on the microstructures and mechanical properties of selective laser melted and cast AlSi10Mg alloys
Authors: Snopiński Przemysław , Król Mariusz , Pagáč Marek , Petrů Jana , Hajnyš Jiří , Mikuszewski Tomasz , Tański Tomasz
Published: May 2021

This study investigated the impact of the equal channel angular pressing (ECAP) combined with heat treatments on the microstructure and mechanical properties of AlSi10Mg alloys fabricated via selective laser melting (SLM) and gravity casting. Special attention was directed towards determining the effect of post-fabrication heat treatments on the microstructural evolution of AlSi10Mg alloy fabricated using two different routes. Three initial alloy conditions were considered prior to ECAP deformation: (1) as-cast in solution treated (T4) condition, (2) SLM in T4 condition, (3) SLM subjected to low-temperature annealing. Light microscopy, transmission electron microscopy, X-ray diffraction line broadening analysis, and electron backscattered diffraction analysis were used to characterize the microstructures before and after ECAP. The results indicated that SLM followed by low-temperature annealing led to superior mechanical properties, relative to the two other conditions. Microscopic analyses revealed that the partial-cellular structure contributed to strong work hardening. This behavior enhanced the material’s strength because of the enhanced accumulation of geometrically necessary dislocations during ECAP deformation.
Equipartition principle for Wigner matrices
Authors: Bao Zhigang , Erdős László , Schnelli Kevin
Published: May 2021

We prove that the energy of any eigenvector of a sum of several independent large Wigner matrices is equally distributed among these matrices with very high precision. This shows a particularly strong microcanonical form of the equipartition principle for quantum systems whose components are modelled by Wigner matrices.
Eddy Induced Trapping and Homogenization of Freshwater in the Bay of Bengal
Authors: Paul Nihar , Sukhatme Jai , Sengupta Debasis , Gayen Bishakhdatta
Published: May 2021

Freshwater from rivers influences Indian summer monsoon rainfall and tropical cyclones by stratifying the upper layer and warming the subsurface ocean in the Bay of Bengal (BoB). Here, we use in situ and satellite data with reanalysis to showcase how river water experiences a significant increase in salinity on sub‐seasonal timescales. This involves the trapping and homogenization of freshwater by a cyclonic eddy in the Bay. Using a specific example from 2015, river water is shown to enter an eddy along its attracting manifolds within a period of 2 weeks. This leads to the formation of a highly stratified subsurface layer within the eddy. When freshest, the eddy has the largest sea‐level anomaly, spins fastest, and supports strong lateral gradients in salinity. Subsequently, observations reveal a progressive increase in salinity inside the eddy within a month. In particular, salty water spirals in, and freshwater is pulled out across the eddy boundary. Lagrangian experiments elucidate this process, whereby horizontal chaotic mixing provides a mechanism for the rapid increase in surface salinity. A salinity budget also suggests that horizontal advection explains much of the change in mixed layer salinity. Further, the adjustment of this freshwater eddy triggers submesoscale dynamics which appear to be an integral part of the process of salinity homogenization. This pathway is distinct from vertical diffusive mixing and is likely to be important for the evolution of salinity in the BoB.
Chromosomal copy number heterogeneity predicts survival rates across cancers
Authors: van Dijk Erik , van den Bosch Tom , Lenos Kristiaan J. , El Makrini Khalid , Nijman Lisanne E. , van Essen Hendrik F. B. , Lansu Nico , Boekhout Michiel , Hageman Joris H. , Fitzgerald Rebecca C. , Punt Cornelis J. A. , Tuynman Jurriaan B. , Snippert Hugo J. G. , Kops Geert J. P. L. , Medema Jan Paul , Ylstra Bauke , Vermeulen Louis , Miedema Daniël M.
Published: May 2021

Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.
Exploring protein hotspots by optimized fragment pharmacophores
Authors: Bajusz Dávid , Wade Warren S. , Satała Grzegorz , Bojarski Andrzej J. , Ilaš Janez , Ebner Jessica , Grebien Florian , Papp Henrietta , Jakab Ferenc , Douangamath Alice , Fearon Daren , von Delft Frank , Schuller Marion , Ahel Ivan , Wakefield Amanda , Vajda Sándor , Gerencsér János , Pallai Péter , Keserű György M.
Published: May 2021

Fragment-based drug design has introduced a bottom-up process for drug development, with improved sampling of chemical space and increased effectiveness in early drug discovery. Here, we combine the use of pharmacophores, the most general concept of representing drug-target interactions with the theory of protein hotspots, to develop a design protocol for fragment libraries. The SpotXplorer approach compiles small fragment libraries that maximize the coverage of experimentally confirmed binding pharmacophores at the most preferred hotspots. The efficiency of this approach is demonstrated with a pilot library of 96 fragment-sized compounds (SpotXplorer0) that is validated on popular target classes and emerging drug targets. Biochemical screening against a set of GPCRs and proteases retrieves compounds containing an average of 70% of known pharmacophores for these targets. More importantly, SpotXplorer0 screening identifies confirmed hits against recently established challenging targets such as the histone methyltransferase SETD2, the main protease (3CLPro) and the NSP3 macrodomain of SARS-CoV-2.
Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
Authors: Gharbharan Arvind , Jordans Carlijn C. E. , GeurtsvanKessel Corine , den Hollander Jan G. , Karim Faiz , Mollema Femke P. N. , Stalenhoef – Schukken Janneke E. , Dofferhoff Anthonius , Ludwig Inge , Koster Adrianus , Hassing Robert-Jan , Bos Jeannet C. , van Pottelberge Geert R. , Vlasveld Imro N. , Ammerlaan Heidi S. M. , van Leeuwen – Segarceanu Elena M. , Miedema Jelle , van der Eerden Menno , Schrama Thijs J. , Papageorgiou Grigorios , te Boekhorst Peter , Swaneveld Francis H. , Mueller Yvonne M. , Schreurs Marco W. J. , van Kampen Jeroen J. A. , Rockx Barry , Okba Nisreen M. A. , Katsikis Peter D. , Koopmans Marion P. G. , Haagmans Bart L. , Rokx Casper , Rijnders Bart J. A.
Published: May 2021

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.
A long term global daily soil moisture dataset derived from AMSR-E and AMSR2 (2002–2019)
Authors: Yao Panpan , Lu Hui , Shi Jiancheng , Zhao Tianjie , Yang Kun , Cosh Michael H. , Gianotti Daniel J. Short , Entekhabi Dara
Published: May 2021

Long term surface soil moisture (SSM) data with stable and consistent quality are critical for global environment and climate change monitoring. L band radiometers onboard the recently launched Soil Moisture Active Passive (SMAP) Mission can provide the state-of-the-art accuracy SSM, while Advanced Microwave Scanning Radiometer for EOS (AMSR-E) and AMSR2 series provide long term observational records of multi-frequency radiometers (C, X, and K bands). This study transfers the merits of SMAP to AMSR-E/2, and develops a global daily SSM dataset (named as NNsm) with stable and consistent quality at a 36 km resolution (2002–2019). The NNsm can reproduce the SMAP SSM accurately, with a global Root Mean Square Error (RMSE) of 0.029 m3/m3. NNsm also compares well with in situ SSM observations, and outperforms AMSR-E/2 standard SSM products from JAXA and LPRM. This global observation-driven dataset spans nearly two decades at present, and is extendable through the ongoing AMSR2 and upcoming AMSR3 missions for long-term studies of climate extremes, trends, and decadal variability.
3-D thermal regime and dehydration processes around the regions of slow earthquakes along the Ryukyu Trench
Authors: Suenaga Nobuaki , Yoshioka Shoichi , Ji Yingfeng
Published: May 2021

Several interplate seismic events, such as short-term slow slip events (S-SSEs) and low-frequency earthquakes (LFEs), have been identified in the Ryukyu Trench, southwestern Japan. As one of the specific characteristics of this seismicity, the depths at which S-SSEs occur at the plate interface beneath Okinawa Island are approximately 5–10 km shallower than those beneath the Yaeyama Islands. To elucidate the cause of this difference in depth, we constructed a three-dimensional, Cartesian thermomechanical subduction model and applied the subduction history of the Philippine Sea (PHS) plate in the model region. As a result, the interplate temperatures at which S-SSEs take place were estimated to range from 350 to 450 °C beneath Okinawa Island and from 500 to 600 °C beneath the Yaeyama Islands. The former temperature range is consistent with previous thermal modelling studies for the occurrence of slow earthquakes, but the latter temperature range is by approximately 150 °C higher than the former. Therefore, explaining how the depth difference in S-SSEs could be caused from the aspect of only the thermal regime is difficult. Using phase diagrams for hydrous minerals in the oceanic crust and mantle wedge, we also estimated the water content distribution on and above the plate interface of the PHS plate. Near the S-SSE fault planes, almost the same amount of dehydration associated with phase transformations of hydrous minerals from blueschist to amphibolite and from amphibolite to amphibole eclogite within the oceanic crust were inferred along Okinawa Island and the Yaeyama Islands, respectively. On the other hand, the phase transformations within the mantle wedge were inferred only beneath the Yaeyama Islands, whereas no specific phase transformation was inferred beneath Okinawa Island around the S-SSE occurrence region. Therefore, we conclude that dehydrated fluid derived from the oceanic crust at the plate interface would play a key role in the occurrence of S-SSEs.
Growth performance of five different strains of Nile tilapia (Oreochromis niloticus) introduced to Tanzania reared in fresh and brackish waters
Authors: Moses Mbiru , Chauka Leonard J. , de Koning Dirk Jan , Palaiokostas Christos , Mtolera Matern S. P.
Published: May 2021

Five introduced strains of Nile tilapia (Oreochromis niloticus) were tested for growth performance both in fresh- and brackish-water (2 salinity units) environments for 56 days. The BIG NIN, GIFT, Chitralada, “Ruvu Farm” and Silver YY strains with initial mean average weight (± standard error) of 96.4 ± 6.90 g, 104.1 ± 7.19 g, 137.2 ± 7.21 g, 53.2 ± 6.98 g and 95.3 ± 7.11 g, respectively were used. Individuals were tagged and pooled in hapas (12 m × 8.5 m × 2 m each), aligned into different ponds (20 m × 20 m each). Stocking density of 5 fish/m2 and 350 g/kg crude protein diet were used. Overall, the average weight gain for GIFT strain was 7.5%, 32%, 45% and 86.5% higher than BIG NIN, Chitralada, “Ruvu Farm” and Silver YY strains, respectively, across both environments. All strains performed significantly better (p < 0.05) when reared in brackish-water than their respective counterparts in freshwater, except for the BIG NIN strain. The morphometric correlations for all strains in both environments ranged from moderate (0.50) to strong positive (0.92). The GIFT strain demonstrated superior growth and genotype by environment interaction was weak and not important to be prioritized in breeding programs.
A localization method for wireless capsule endoscopy using side wall cameras and IMU sensor
Authors: Vedaei Seyed Shahim , Wahid Khan A.
Published: May 2021

Localizing the endoscopy capsule inside gastrointestinal (GI) system provides key information which leads to GI abnormality tracking and precision medical delivery. In this paper, we have proposed a new method to localize the capsule inside human GI track. We propose to equip the capsule with four side wall cameras and an Inertial Measurement Unit (IMU), that consists of 9 Degree-Of-Freedom (DOF) including a gyroscope, an accelerometer and a magnetometer to monitor the capsule’s orientation and direction of travel. The low resolution mono-chromatic cameras, installed along the wide wall, are responsible to measure the actual capsule movement, not the involuntary motion of the small intestine. Finally, a fusion algorithm is used to combine all data to derive the traveled path and plot the trajectory. Compared to other methods, the presented system is resistive to surrounding conditions, such as GI nonhomogeneous structure and involuntary small bowel movements. In addition, it does not require external antenna or arrays. Therefore, GI tracking can be achieved without disturbing patients’ daily activities.
A hybrid modeling approach for assessing mechanistic models of small molecule partitioning in vivo using a machine learning-integrated modeling platform
Authors: Antontsev Victor , Jagarapu Aditya , Bundey Yogesh , Hou Hypatia , Khotimchenko Maksim , Walsh Jason , Varshney Jyotika
Published: May 2021

Prediction of the first-in-human dosing regimens is a critical step in drug development and requires accurate quantitation of drug distribution. Traditional in vivo studies used to characterize clinical candidate’s volume of distribution are error-prone, time- and cost-intensive and lack reproducibility in clinical settings. The paper demonstrates how a computational platform integrating machine learning optimization with mechanistic modeling can be used to simulate compound plasma concentration profile and predict tissue-plasma partition coefficients with high accuracy by varying the lipophilicity descriptor logP. The approach applied to chemically diverse small molecules resulted in comparable geometric mean fold-errors of 1.50 and 1.63 in pharmacokinetic outputs for direct tissue:plasma partition and hybrid logP optimization, with the latter enabling prediction of tissue permeation that can be used to guide toxicity and efficacy dosing in human subjects. The optimization simulations required to achieve these results were parallelized on the AWS cloud and generated outputs in under 5 h. Accuracy, speed, and scalability of the framework indicate that it can be used to assess the relevance of other mechanistic relationships implicated in pharmacokinetic-pharmacodynamic phenomena with a lower risk of overfitting datasets and generate large database of physiologically-relevant drug disposition for further integration with machine learning models.
Age-adjusted cut-off values of lipid accumulation product (LAP) for predicting hypertension
Authors: Kaneva Anastasiya M. , Bojko Evgeny R.
Published: May 2021

Among the many factors considered relevant to hypertension, obesity and metabolic disturbances play an important role in the development of this pathology. Therefore, lipid accumulation product (LAP), an index of visceral adiposity, is a simple and effective indicator of hypertension risk. To date, the reference and cut-off values for LAP have not been defined. The aim of the study was to determine the age-adjusted optimal cut-off values of LAP for the prediction of hypertension risk. This cross-sectional case–control study comprised 1960 subjects ranging from 20 to 64 years of age. The participants underwent anthropometric tests, blood pressure measurements, questionnaire surveys and laboratory examinations. The cut-off values of LAP were determined using receiver operating characteristic (ROC) curve analysis. According to our study results, LAP values in healthy subjects increased with age, whereas there was no effect of age on LAP values in patients with hypertension. These two findings determine the presence of age-adjusted cut-off values of LAP for diagnosing hypertension. Increasing age is associated with an increase in the cut-off values of LAP to detect hypertension. In conclusion, hypertension risk should be estimated using the age-adjusted cut-off values of LAP; otherwise, the risk of hypertension might be overestimated or underestimated.
Life long follow up and management strategies of patients living with native livers after Kasai portoenterostomy
Authors: Chung Patrick Ho Yu , Chan Edwin Kin Wai , Yeung Fanny , Chan Albert Chi Yan , Mou Jennifer Wai Cheung , Lee Kim Hung , Hung Judy Wing Suet , Leung Michael Wai Yip , Tam Paul Kwong Hang , Wong Kenneth Kak Yuen
Published: May 2021

We present a 37 years’ experience in the management of biliary atresia (BA) and discuss long-term complications after Kasai portoenterostomy (KPE). A retrospective territory-wide study from 1980 to 2017 on 231 patients with open KPE from three tertiary paediatric surgical centres was performed. Outcome parameters were clearance of jaundice (COJ), native liver survival (NLS) and long-term complications. Factors affecting the operative outcomes were analyzed. The median duration of follow up was 17.5 (IQR: 13.5–22) years. Over 66% of patients became jaundice-freed at 1 year after KPE. Seventy patients (30.3%) received liver transplant (LT) at a median age of 6.2 (IQR: 4.3–8.4) years. The NLS rates at 10 and 20 years were 70.7% and 61.5% respectively with no significant change over the study period. The median age at KPE was 59 (IQR: 49–67) days. KPE performed before 70 days was associated with higher odd ratios for successful drainage but the age of KPE did not have an impact on the long-term NLS. Among all native liver survivors (n = 153), the median bilirubin level was 24 (IQR: 16–36) µmol/L. Portal hypertension (PHT) and recurrent cholangitis were found in 51.6% and 27.5% of them respectively. With a vigilant follow up program, more than 60% of BA patients could remain stable with the disease and achieve long-term survival without LT. Although cholestasis, portal hypertension and recurrent cholangitis are common in long-term NLS, with a comprehensive follow management strategy, they do not always necessitate LT. Our study serves as an example for countries where deceased donor organs are scarce due to very low donation rate.
Scar tissue removal-activated endogenous neural stem cells aid Taxol-modified collagen scaffolds in repairing chronic long-distance transected spinal cord injury
Authors: Yin Wen , Xue Weiwei , Zhu Hecheng , Shen He , Xiao Zhifeng , Wu Shuyu , Zhao Yannan , Cao Yudong , Tan Jun , Li Juan , Liu Weidong , Wang Lei , Meng Li , Chen Bing , Zhao Ming , Jiang Xingjun , Li Xing , Ren Caiping , Dai Jianwu
Published: May 2021

Only the first scar tissue removal is a key time point for chronic complete SCI repair. Endogenous NSCs could be intensively activated after the first scar tissue removal and contribute to the chronic SCI repair after bio-scaffold implantation.