bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioelectrical impedance analysis for perioperative water management in adult cardiovascular valve disease surgery
Authors: Watanabe Tatsuya , Ishida Naomasa , Takaoka Munenori , Tsujimoto Kotone , Kondo Kensuke , Isoda Ryutaro , Yukawa Takuro , Tokunaga Noriyuki , Ishida Atsuhisa , Fukazawa Takuya , Morita Ichiro , Yoshida Hideo , Kuinose Masahiko , Yamatsuji Tomoki
Published: December 2020

Purpose

Bioelectrical impedance analysis (BIA) has been used recently to measure the body water of patients with acute heart failure. We used BIA in this study to better understand, and possibly identify a predictive marker for, perioperative water behavior in cardiac surgery patients.

Methods

We measured body water and studied its behavior in 44 patients undergoing surgery for cardiac valvular disease at our hospital. Measurements included the levels of extracellular water (ECW), intracellular water (ICW), and total body water, the edema index (EI), and the ratio of ECW to total body water. The first measured EI was defined as the “preoperative EI” and the maximum as the “peak EI”.

Results

A negative correlation was found between the preoperative EI and the preoperative estimated glomerular filtration rate (eGFR) (R = 0.644, p < 0.001). Positive correlations were found between the peak EI and the ICU stay (R = 0.625, p < 0.001), the peak EI and the ventilation time (R = 0.366, p < 0.01), and the preoperative EI and the ICU stay (R = 0.464, p = 0.026).

Conclusion

The EI is possibly a predictive marker for perioperative water management in cardiac surgery.
Libra Project: Regulators Act on Global Stablecoins
Authors: Read Oliver , Schäfer Stefan
Published: December 2020

Governments, regulatory authorities and standard-setting bodies started acting on global stablecoins triggered by the Libra announcement. Among the concerns expressed by the G7 and the G20 are risks to the stability of the financial system. The Financial Stability Board and the Financial Action Task Force have worked on regulatory issues and anti-money laundering ahead of the G20 summit in November 2020. Overall the Libra project has raised many questions on the regulatory front. Facebook had to revise the concept as Libra 2.0 and resubmit it for approval in April 2020. The European Commission announced a new regulation on Markets in Crypto-assets (MiCA) including stablecoins in September 2020 as part of a new Digital Finance Package. This opens the next chapter in a regulatory cat and mouse game.
Relationships between pathological factors and long-term outcomes in patients enrolled in two prospective randomized controlled trials comparing the efficacy of oral tegafur–uracil with CMF (N·SAS-BC 01 trial and CUBC trial)
Authors: Ohno Shinji , Saji Shigehira , Masuda Norikazu , Tsuda Hitoshi , Akiyama Futoshi , Kurosumi Masafumi , Shimomura Akihiko , Sato Nobuaki , Takao Shintaro , Ohsumi Shozo , Tokuda Yutaka , Inaji Hideo , Watanabe Toru , Ohashi Yasuo
Published: December 2020

Purpose

To evaluate the efficacies of cyclophosphamide, methotrexate, and fluorouracil (CMF) and tegafur–uracil (UFT) as adjuvant therapy in patients with resected stage I–IIIA breast cancer by immunohistochemistry (IHC)-based subtype and to determine the relationships between clinicopathological factors and long-term outcomes.

Methods

A pooled analysis of the randomized controlled N·SAS-BC 01 and CUBC studies was conducted. Expression of hormone receptors (HRs; estrogen and progesterone receptors), human epidermal growth factor receptor 2 (HER2), and Ki67were assessed by IHC. Tumor-infiltrating lymphocytes (TILs) and nuclear/histological grades were determined by hematoxylin and eosin staining. Relapse-free survival (RFS) and overall survival (OS) were estimated by Kaplan–Meier analysis and hazard ratios were determined by Cox model adjusted for baseline tumor size and nodal status.

Results

A total of 689 patients (342 CMF and 347 UFT) were included in the analyses with a median follow-up of 11.1 years. There was no significant difference in RFS or OS between the two cohorts (RFS: 0.96 [95% confidence interval: 0.71–1.30], log-rank test p = 0.80; OS: 0.93 [0.64–1.35], p = 0.70). There was no difference in RFS or OS between the two cohorts for HR+/HER2− and HR+/HER2+ subtypes. RFS was significantly longer in patients treated with UFT compared with CMF in patients with HR−/HER2+ subtype (0.30 [0.10–0.88], p = 0.03). A high TILs level was associated with a better OS compared with low TILs level (p = 0.02).

Conclusions

This long-term follow-up study showed that RFS and OS were similar in patients with luminal-type breast cancer treated with CMF and UFT.
Diagnostic reasoning in internal medicine: a practical reappraisal
Authors: Corazza Gino Roberto , Lenti Marco Vincenzo , Howdle Peter David
Published: December 2020

The practice of clinical medicine needs to be a very flexible discipline which can adapt promptly to continuously changing surrounding events. Despite the huge advances and progress made in recent decades, clinical reasoning to achieve an accurate diagnosis still seems to be the most appropriate and distinctive feature of clinical medicine. This is particularly evident in internal medicine where diagnostic boundaries are often blurred. Making a diagnosis is a multi-stage process which requires proper data collection, the formulation of an illness script and testing of the diagnostic hypothesis. To make sense of a number of variables, physicians may follow an analytical or an intuitive approach to clinical reasoning, depending on their personal experience and level of professionalism. Intuitive thinking is more typical of experienced physicians, but is not devoid of shortcomings. Particularly, the high risk of biases must be counteracted by de-biasing techniques, which require constant critical thinking. In this review, we discuss critically the current knowledge regarding diagnostic reasoning from an internal medicine perspective.
“For me democracy is …” meanings of democracy from a phenomenological perspective
Authors: Frankenberger Rolf , Buhr Daniel
Published: December 2020

Meanings of democracy are far more complex than results of standardized survey research imply. They are diverse and intertwined with other individual concepts and subjective experiences. In terms of phenomenological adequacy, they are important first order constructions that can be used for building second order typologies and explanations for political action. Survey-based quantitative research has clear limits in terms of gathering such first order constructions, even if one wants to integrate them. Drawing from a phenomenological perspective of methodology and experience from 389 qualitative interviews conducted in the state of Baden-Württemberg, Germany, we argue that research on meanings of democracy might rather use open, qualitative assessments and consider four methodological aspects. First, we need to have a theoretical and methodological basis for analyzing “everyday philosophies” and root our concepts in these first order constructions. Phenomenology and the concept of lifeworld offer such a guideline. Second, we should not oversimplify analysis. People differ greatly in how they define democracy, and this should be reflected in research. Third, we advocate a qualitative multi-dimensional analysis that separates democracy, politics and actual use of democracy. This can be used to develop a typology of individual, but collectively shared, political lifeworlds. Finally, we argue that insights from this kind of research could be used to compliment standard survey instruments and contribute to developing and frequently testing a comprehensive instrument to assess the meanings of democracy in a more holistic way and to control our scientific second-order constructions of democracy.
Incorporating stakeholders’ preferences into a multi-criteria framework for planning large-scale Nature-Based Solutions
Authors: Ruangpan Laddaporn , Vojinovic Zoran , Plavšić Jasna , Doong Dong-Jiing , Bahlmann Tobias , Alves Alida , Tseng Leng-Hsuan , Randelović Anja , Todorović Andrijana , Kocic Zvonimir , Beljinac Vladimir , Wu Meng-Hsuan , Lo Wei-Cheng , Perez-Lapeña Blanca , Franca Mário J.
Published: December 2020

Hydro-meteorological risks are a growing issue for societies, economies and environments around the world. An effective, sustainable response to such risks and their future uncertainty requires a paradigm shift in our research and practical efforts. In this respect, Nature-Based Solutions (NBSs) offer the potential to achieve a more effective and flexible response to hydro-meteorological risks while also enhancing human well-being and biodiversity. The present paper describes a new methodology that incorporates stakeholders’ preferences into a multi-criteria analysis framework, as part of a tool for selecting risk mitigation measures. The methodology has been applied to Tamnava river basin in Serbia and Nangang river basin in Taiwan within the EC-funded RECONECT project. The results highlight the importance of involving stakeholders in the early stages of projects in order to achieve successful implementation of NBSs. The methodology can assist decision-makers in formulating desirable benefits and co-benefits and can enable a systematic and transparent NBSs planning process.
Influence of laminate direction and glue area on in-plane shear modulus of cross-laminated timber
Authors: Turesson Jonas , Sharifi Zahra , Berg Sven , Ekevad Mats
Published: December 2020

The use of cross-laminated timber (CLT) in constructing tall buildings has increased. So, it has become crucial to get a higher in-plane stiffness in CLT panels. One way of increasing the shear modulus, G, for CLT panels can be by alternating the layers to other angles than the traditional 0° and 90°. The diagonal compression test can be used to measure the shear stiffness from which G is calculated. A general equation for calculating the G value for the CLT panels tested in the diagonal compression test was established and verified by tests, finite element simulations and external data. The equation was created from finite element simulations of full-scale CLT walls. By this equation, the influence on the G value was a factor of 2.8 and 2.0 by alternating the main laminate direction of the mid layer from the traditional 90° to 45° and 30°, respectively. From practical tests, these increases were measured to 2.9 and 1.8, respectively. Another influence on the G value was studied by the reduction of the glue area between the layers. It was shown that the pattern of the contact area was more important than the size of the contact area.
“Advise and Rule” or “Rule by Advising”: The Changing Nature of the Advisory Jurisdiction of the Constitutional Court of Kosovo
Authors: Korenica Fisnik
Published: December 2020

Constitutional courts play an essential role in authoritatively interpreting constitutions. Oftentimes they go beyond the constitutional text by inventing so-called judge-made law. Their authority to interpret the text covers not only substantive parts but also the clause authorizing their jurisdiction. Such power, namely the power to interpret the limits of their jurisdiction, is often used to intervene in the interpretation of the constitution more vigorously than explicitly authorized. One example is the invention, designation, and development of the advisory jurisdiction by the Constitutional Court of the Republic of Kosovo. On that basis, the Court has, for almost ten years of its existence, pronounced on numerous fundamental issues relating to the governing system, power maps, and entitlements on political authority. The Court developed its advisory jurisdiction in a rather unpredictable and impulsive fashion; however, it steadily revealed its willingness to engage with interpretations that sought to resolve high-stakes issues. Such braveness also had a credibility cost for the Court. The year 2018 marked a major shift in the Court’s interpretation of its own jurisdiction to “advise.” In the Central Election Commission case, it abandoned its previous precedent and commenced a passive, restrained attitude in engaging with the constitutional interpretation on the basis of case or controversy. This Article analyzes the Court’s path and change of course in this cycle.
Fourier transform infrared spectroscopy of milk samples as a tool to estimate energy balance, energy- and dry matter intake in lactating dairy cows
Authors: Rachah Amira , Reksen Olav , Afseth Nils Kristian , Tafintseva Valeria , Ferneborg Sabine , Martin Adam Dunstan , Kohler Achim , Prestløkken Egil
Published: December 2020

The objective of the study was to evaluate the potential of Fourier transform infrared spectroscopy (FTIR) analysis of milk samples to predict body energy status and related traits (energy balance (EB), dry matter intake (DMI) and efficient energy intake (EEI)) in lactating dairy cows. The data included 2371 milk samples from 63 Norwegian Red dairy cows collected during the first 105 days in milk (DIM). To predict the body energy status traits, calibration models were developed using Partial Least Squares Regression (PLSR). Calibration models were established using split-sample (leave-one cow-out) cross-validation approach and validated using an external test set. The PLSR method was implemented using just the FTIR spectra or using the FTIR together with milk yield (MY) or concentrate intake (CONCTR) as predictors of traits. Analyses were conducted for the entire first 105 DIM and separately for the two lactation periods: 5 ≤ DIM ≤ 55 and 55 < DIM ≤ 105. To test the models, an external validation using an independent test set was performed. Predictions depending on the parity (1st, 2nd and 3rd-to 6th parities) in early lactation were also investigated. Accuracy of prediction (r) for both cross-validation and external test set was defined as the correlation between the predicted and observed values for body energy status traits. Analyzing FTIR in combination with MY by PLSR, resulted in relatively high r-values to estimate EB (r = 0.63), DMI (r = 0.83), EEI (r = 0.84) using an external validation. Only moderate correlations between FTIR spectra and traits like EB, EEI and dry matter intake (DMI) have so far been published. Our hypothesis was that improvements in the FTIR predictions of EB, EEI and DMI can be obtained by (1) stratification into different stages of lactations and different parities, or (2) by adding additional information on milking and feeding traits. Stratification of the lactation stages improved predictions compared with the analyses including all data 5 ≤ DIM ≤105. The accuracy was improved if additional data (MY or CONCTR) were included in the prediction model. Furthermore, stratification into parity groups, improved the predictions of body energy status. Our results show that FTIR spectral data combined with MY or CONCTR can be used to obtain improved estimation of body energy status compared to only using the FTIR spectra in Norwegian Red dairy cattle. The best prediction results were achieved using FTIR spectra together with MY for early lactation. The results obtained in the study suggest that the modeling approach used in this paper can be considered as a viable method for predicting an individual cow's energy status.
From Compliance, to Acceptance, to Teaching: On Relocating Rule Consequentialism's Stipulations
Authors: Miller Timothy D.
Published: December 2020

Several recent formulations of Rule Consequentialism (RC) have broken with the consensus that RC should be formulated in terms of codeacceptance, claiming instead that RC should focus on the consequences of codes' beingtaught. I begin this article with an examination of the standard case for acceptance formulations. In addition to depending on the mistaken assumption thatcomplianceandacceptanceformulations are the only options, the standard case claims advantages for acceptance formulations that, upon closer examination, favor teaching formulations. In the remainder of the article, I defend this new teaching-centered approach against some recent criticisms. I argue that preoccupation with the somewhat technical problem of identifying the best criterion for making choices under conditions of uncertainty has distracted rule consequentialists from paying more careful attention to the advantages and disadvantages that result from decisions concerning where they locate RC's stipulated assumptions within the theory.
A New Measure for the Assessment of Student–Teacher	Connectedness in Adolescence
Authors: García-Moya Irene , Brooks Fiona , Moreno Carmen
Published: December 2020

Abstract. Student–teacher relationships have received a lot of attention in the social sciences. It is well-known that relationships with teachers tend to become more distant during adolescence, but most adolescents single out specific teachers they feel connected to. To better capture this latter phenomenon, the aim of this paper is to propose and evaluate the psychometric properties of a new measure for the assessment of student–teacher connectedness in adolescent samples from two countries. Samples consisted of 2,323 adolescents from England and 8,000 adolescents from Spain, who had answered a specific package of questions for the assessment of student–teacher connectedness included in the 17/18 edition of the WHO-collaborative survey Health Behaviour in School-aged Children (HBSC) in the aforementioned two countries. After analyses of item performance and factorial structure, we obtained a 12-item scale with high internal consistency and a factorial structure consistent with the definition of student–teacher connectedness used for scale development in both datasets. Some evidence of validity was also obtained (the scale correlated positively with teacher support, school satisfaction and life satisfaction and negatively with school-related stress). Finally, invariance analysis (configural, metric, and scalar invariance) supported an equivalent functioning of the scale in England and Spain.
Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway
Authors: Ng Benjamin , Cook Stuart A. , Schafer Sebastian
Published: December 2020

Interleukin (IL)-11 evolved as part of the innate immune response. In the human lung, IL-11 upregulation has been associated with viral infections and a range of fibroinflammatory diseases, including idiopathic pulmonary fibrosis. Transforming growth factor-beta (TGFβ) and other disease factors can initiate an autocrine loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely ERK-dependent manner, triggers the translation of profibrotic proteins. Lung epithelial cells also express the IL-11 receptor and transition into a mesenchymal-like state in response to IL-11 exposure. In mice, therapeutic targeting of IL-11 with antibodies can arrest and reverse bleomycin-induced pulmonary fibrosis and inflammation. Intriguingly, fibroblast-specific blockade of IL-11 signaling has anti-inflammatory effects, which suggests that lung inflammation is sustained, in part, through IL-11 activity in the stroma. Proinflammatory fibroblasts and their interaction with the damaged epithelium may represent an important but overlooked driver of lung disease. Initially thought of as a protective cytokine, IL-11 is now increasingly recognized as an important determinant of lung fibrosis, inflammation, and epithelial dysfunction.
Superchiral near fields detect virus structure
Authors: Kakkar Tarun , Keijzer Chantal , Rodier Marion , Bukharova Tatyana , Taliansky Michael , Love Andrew J. , Milner Joel J. , Karimullah Affar S. , Barron Laurence D. , Gadegaard Nikolaj , Lapthorn Adrian J. , Kadodwala Malcolm
Published: December 2020

Optical spectroscopy can be used to quickly characterise the structural properties of individual molecules. However, it cannot be applied to biological assemblies because light is generally blind to the spatial distribution of the component molecules. This insensitivity arises from the mismatch in length scales between the assemblies (a few tens of nm) and the wavelength of light required to excite chromophores (≥150 nm). Consequently, with conventional spectroscopy, ordered assemblies, such as the icosahedral capsids of viruses, appear to be indistinguishable isotropic spherical objects. This limits potential routes to rapid high-throughput portable detection appropriate for point-of-care diagnostics. Here, we demonstrate that chiral electromagnetic (EM) near fields, which have both enhanced chiral asymmetry (referred to as superchirality) and subwavelength spatial localisation (∼10 nm), can detect the icosahedral structure of virus capsids. Thus, they can detect both the presence and relative orientation of a bound virus capsid. To illustrate the potential uses of the exquisite structural sensitivity of subwavelength superchiral fields, we have used them to successfully detect virus particles in the complex milieu of blood serum.
FOXO3a-driven miRNA signatures suppresses VEGF-A/NRP1 signaling and breast cancer metastasis
Authors: Song Ying , Zeng Shanshan , Zheng Guopei , Chen Danyang , Li Pan , Yang Mingqiang , Luo Kai , Yin Jiang , Gu Yixue , Zhang Zhijie , Jia Xiaoting , Qiu Ni , He Zhimin , Li Hongsheng , Liu Hao
Published: December 2020

Metastasis remains the major obstacle to improved survival for breast cancer patients. Downregulation of FOXO3a transcription factor in breast cancer is causally associated with the development of metastasis through poorly understood mechanisms. Here, we report that FOXO3a is functionally related to the inhibition of VEGF-A/NRP1 signaling and to the consequent suppression of breast cancer metastasis. We show that FOXO3a directly induces miR-29b-2 and miR-338 expression. Ectopic expression of miR-29b-2/miR-338 significantly suppresses EMT, migration/invasion, and in vivo metastasis of breast cancer. Moreover, we demonstrate that miR-29b-2 directly targets VEGF-A while miR-338 directly targets NRP1, and show that regulation of miR-29b-2 and miR-338 mediates the ability of FOXO3a to suppress VEGF-A/NRP1 signaling and breast cancer metastasis. Clinically, our results show that the FOXO3a-miR-29b-2/miR-338-VEGF-A/NRP1 axis is dysregulated and plays a critical role in disease progression in breast cancer. Collectively, our findings propose that FOXO3a functions as a metastasis suppressor, and define a novel signaling axis of FOXO3a-miRNA-VEGF-A/NRP1 in breast cancer, which might be potential therapeutic targets for breast cancer.
Putting Warburg to work: how imaging of tumour acidosis could help predict metastatic potential in breast cancer
Authors: Rolver Michala Gylling , Pedersen Stine Falsig
Published: December 2020

Solid tumours are often highly acidic compared to normal tissue, and tumour extracellular acidosis contributes to multiple aspects of cancer progression. Now, Anemone et al. in this issue of the British Journal of Cancer provide in vivo evidence that the degree to which various breast cancer cell lines acidify their environment correlates with their ability to metastasise to the lungs. This indicates that measurements of tumour extracellular acidosis have the potential to become a clinical tool for assessing the risk of metastasis.
Postoperative, but not preoperative, inflammation-based prognostic markers are prognostic factors in stage III colorectal cancer patients
Authors: Yasui Kohei , Shida Dai , Nakamura Yuya , Ahiko Yuka , Tsukamoto Shunsuke , Kanemitsu Yukihide
Published: December 2020

Background

Recent evidence suggests that both preoperative and postoperative inflammation-based prognostic markers are useful for predicting the survival of colorectal cancer (CRC) patients. However, associations between longitudinal changes in inflammation-based prognostic markers and prognosis are controversial.

Methods

The subjects of this study were 568 patients with stage III CRC between 2008 and 2014. Preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR) and lymphocyte-to-C-reactive protein ratio (LCR) were calculated to assess the inflammatory state of subjects. Subjects were stratified into three groups for each marker: preoperatively low inflammatory state (normal group), preoperatively high but postoperatively low inflammatory state (normalised group) and persistently high inflammatory state (elevated group). Multivariable analyses for overall survival (OS) and recurrence-free survival (RFS) were performed to adjust for well-established clinicopathologic factors.

Results

For all assessed markers, the normalised group had a significantly better prognosis than the elevated group and a similar prognosis as the normal group for both OS and RFS.

Conclusions

Postoperative, but not preoperative, inflammation-based prognostic markers more accurately predict OS and RFS in patients with stage III CRC.
Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection
Authors: Yao Hangping , Sun Yao , Deng Yong-Qiang , Wang Nan , Tan Yongcong , Zhang Na-Na , Li Xiao-Feng , Kong Chao , Xu Yan-Peng , Chen Qi , Cao Tian-Shu , Zhao Hui , Yan Xintian , Cao Lei , Lv Zhe , Zhu Dandan , Feng Rui , Wu Nanping , Zhang Wenhai , Hu Yuhao , Chen Keda , Zhang Rong-Rong , Lv Qingyu , Sun Shihui , Zhou Yunhua , Yan Run , Yang Guan , Sun Xinglu , Liu Chanjuan , Lu Xiangyun , Cheng Linfang , Qiu Hongying , Huang Xing-Yao , Weng Tianhao , Shi Danrong , Jiang Weidong , Shao Junbin , Wang Lei , Zhang Jie , Jiang Tao , Lang Guojun , Qin Cheng-Feng , Li Lanjuan , Wang Xiangxi
Published: December 2020

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
Identification of key gene networks controlling organic acid and sugar metabolism during watermelon fruit development by integrating metabolic phenotypes and gene expression profiles
Authors: Umer Muhammad Jawad , Bin Safdar Luqman , Gebremeskel Haileslassie , Zhao Shengjie , Yuan Pingli , Zhu Hongju , Kaseb M. O. , Anees Muhammad , Lu Xuqiang , He Nan , Gong Chengsheng , Liu Wenge
Published: December 2020

The organoleptic qualities of watermelon fruit are defined by the sugar and organic acid contents, which undergo considerable variations during development and maturation. The molecular mechanisms underlying these variations remain unclear. In this study, we used transcriptome profiles to investigate the coexpression patterns of gene networks associated with sugar and organic acid metabolism. We identified 3 gene networks/modules containing 2443 genes highly correlated with sugars and organic acids. Within these modules, based on intramodular significance and Reverse Transcription Quantitative polymerase chain reaction (RT-qPCR), we identified 7 genes involved in the metabolism of sugars and organic acids. Among these genes,Cla97C01G000640,Cla97C05G087120andCla97C01G018840(r2= 0.83 with glucose content) were identified as sugar transporters (SWEET,EDR6andSTP) andCla97C03G064990(r2=0.92 with sucrose content) was identified as a sucrose synthase from information available for other crops. Similarly,Cla97C07G128420,Cla97C03G068240andCla97C01G008870, having strong correlations with malic (r2= 0.75) and citric acid (r2= 0.85), were annotated as malate and citrate transporters (ALMT7,CS, andICDH). The expression profiles of these 7 genes in diverse watermelon genotypes revealed consistent patterns of expression variation in various types of watermelon. These findings add significantly to our existing knowledge of sugar and organic acid metabolism in watermelon.
A CCAAT-binding factor, SlNFYA10, negatively regulates ascorbate accumulation by modulating the d-mannose/l-galactose pathway in tomato
Authors: Chen Weifang , Hu Tixu , Ye Jie , Wang Bing , Liu Genzhong , Wang Ying , Yuan Lei , Li Jiaming , Li Fangman , Ye Zhibiao , Zhang Yuyang
Published: December 2020

Ascorbic acid (AsA), an important antioxidant and growth regulator, and it is essential for plant development and human health. Specifically, humans have to acquire AsA from dietary sources due to their inability to synthesize it. The AsA biosynthesis pathway in plants has been elucidated, but its regulatory mechanism remains largely unknown. In this report, we biochemically identified a CCAAT-box transcription factor (SlNFYA10) that can bind to the promoter of SlGME1, which encodes GDP-Man-3’,5’-epimerase, a pivotal enzyme in the d-mannose/l-galactose pathway. Importantly, SlNFYA10 simultaneously binds to the promoter of SlGGP1, a downstream gene of SlGME1 in the d-mannose/l-galactose pathway. Binding assays in yeast and functional analyses in plants have confirmed that SlNFYA10 exerts a negative effect on the expression of both SlGME1 and SlGGP1. Transgenic tomato lines overexpressing SlNFYA10 show decreased levels of SlGME1 and SlGGP1 abundance and AsA concentration in their leaves and fruits, accompanied by enhanced sensitivity to oxidative stress. Overall, SlNFYA10 is the first CCAAT-binding factor identified to date to negatively regulate the AsA biosynthetic pathway at multiple sites and modulate plant responses to oxidative stress.
Melon short internode (CmSi) encodes an ERECTA-like receptor kinase regulating stem elongation through auxin signaling
Authors: Yang Sen , Zhang Kaige , Zhu Huayu , Zhang Xiaojing , Yan Wenkai , Xu Nana , Liu Dongming , Hu Jianbin , Wu Yufeng , Weng Yiqun , Yang Luming
Published: December 2020

Plant height is one of the most important agronomic traits that directly determines plant architecture, and compact or dwarf plants can allow for increased planting density and land utilization as well as increased lodging resistance and economic yield. At least four dwarf/semidwarf genes have been identified in different melon varieties, but none of them have been cloned, and little is known about the molecular mechanisms underlying internode elongation in melon. Here, we report map-based cloning and functional characterization of the first semidwarf gene short internode (Cmsi) in melon, which encodes an ERECTA-like receptor kinase regulating internode elongation. Spatial-temporal expression analyses revealed that CmSI exhibited high expression in the vascular bundle of the main stem during internode elongation. The expression level of CmSI was positively correlated with stem length in the different melon varieties examined. Ectopic expression of CmSI in Arabidopsis and cucumber suggested CmSI as a positive regulator of internode elongation in both species. Phytohormone quantitation and transcriptome analysis showed that the auxin content and the expression levels of a number of genes involved in the auxin signaling pathway were altered in the semidwarf mutant, including several well-known auxin transporters, such as members of the ABCB family and PIN-FORMED genes. A melon polar auxin transport protein CmPIN2 was identified by protein–protein interaction assay as physically interacting with CmSI to modulate auxin signaling. Thus, CmSI functions in an auxin-dependent regulatory pathway to control internode elongation in melon. Our findings revealed that the ERECTA family gene CmSI regulates stem elongation in melon through auxin signaling, which can directly affect polar auxin transport.
Online sonification improves cycling performance through kinematic and muscular reorganisations
Authors: O’Brien Benjamin , Hardouin Romain , Rao Guillaume , Bertin Denis , Bourdin Christophe
Published: December 2020

Based on a previous study that demonstrated the beneficial effects of sonification on cycling performance, this study investigated which kinematic and muscular activities were changed to pedal effectively. An online error-based sonification strategy was developed, such that, when negative torque was applied to the pedal, a squeak sound was produced in real-time in the corresponding headphone. Participants completed four 6-min cycling trials with resistance values associated with their first ventilatory threshold. Different auditory display conditions were used for each trial (Silent, Right, Left, Stereo), where sonification was only presented for 20 s at the start of minutes 1, 2, 3, and 4. Joint kinematics and right leg muscular activities of 10 muscles were simultaneously recorded. Our results showed participants were more effective at pedalling when presented sonification, which was consistent with previously reported findings. In comparison to the Silent condition, sonification significantly limited ankle and knee joint ranges of motion and reduced muscular activations. These findings suggest performance-based sonification significantly affected participants to reduce the complexity of the task by altering the coordination of the degrees of freedom. By making these significant changes to their patterns, participants improved their cycling performance despite lowering joint ranges of motion and muscular activations.
Author Correction: Bromodomain protein Brd3 promotes Ifnb1 transcription via enhancing IRF3/p300 complex formation and recruitment to Ifnb1 promoter in macrophages
Authors: Ren Wenhui , Wang Chunmei , Wang Qinlan , Zhao Dezhi , Zhao Kai , Sun Donghao , Liu Xingguang , Han Chaofeng , Hou Jin , Li Xia , Zhang Qian , Cao Xuetao , Li Nan
Published: December 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Analyzing the effects of memory biases and mood disorders on social performance
Authors: Sreenivas Nanda Kishore , Rao Shrisha
Published: December 2020

Realistic models of decision-making and social interactions, considering the nature of memory and biases, continue to be an area of immense interest. Emotion and mood are a couple of key factors that play a major role in decisions, nature of social interactions, size of the social network, and the level of engagement. Most of the prior work in this direction focused on a single trait, behavior, or bias. However, this work builds an integrated model that considers multiple traits such as loneliness, the drive to interact, the memory, and mood biases in an agent. The agent system comprises of rational, manic, depressed, and bipolar agents. The system is modeled with an interconnected network, and the size of the personal network of each agent is based on its nature. We consider a game of iterated interactions where an agent cooperates based on its past experiences with the other agent. Through simulation, the effects of various biases and comparative performances of agent types is analyzed. Taking the performance of rational agents as the baseline, manic agents do much better, and depressed agents do much worse. The payoffs also exhibit an almost-linear relationship with the extent of mania. It is also observed that agents with stronger memory perform better than those with weaker memory. For rational agents, there is no significant difference between agents with a positive bias and those with a negative bias. Positive bias is linked with higher payoffs in manic and bipolar agents. In depressed agents, negative bias is linked with higher payoffs. In manic agents, an intermediate value of mood dependence offers the highest payoff. But the opposite is seen in depressed agents. In bipolar agents, agents with weak mood dependence perform the best.
Control of response interference: caudate nucleus contributes to selective inhibition
Authors: Schmidt Claudia C. , Timpert David C. , Arend Isabel , Vossel Simone , Fink Gereon R. , Henik Avishai , Weiss Peter H.
Published: December 2020

While the role of cortical regions in cognitive control processes is well accepted, the contribution of subcortical structures (e.g., the striatum), especially to the control of response interference, remains controversial. Therefore, the present study aimed to investigate the cortical and particularly subcortical neural mechanisms of response interference control (including selective inhibition). Thirteen healthy young participants underwent event-related functional magnetic resonance imaging while performing a unimanual version of the Simon task. In this task, successful performance required the resolution of stimulus–response conflicts in incongruent trials by selectively inhibiting interfering response tendencies. The behavioral results show an asymmetrical Simon effect that was more pronounced in the contralateral hemifield. Contrasting incongruent trials with congruent trials (i.e., the overall Simon effect) significantly activated clusters in the right anterior cingulate cortex, the right posterior insula, and the caudate nucleus bilaterally. Furthermore, a region of interest analysis based on previous patient studies revealed that activation in the bilateral caudate nucleus significantly co-varied with a parameter of selective inhibition derived from distributional analyses of response times. Our results corroborate the notion that the cognitive control of response interference is supported by a fronto-striatal circuitry, with a functional contribution of the caudate nucleus to the selective inhibition of interfering response tendencies.
Longitudinal time-lapse in vivo micro-CT reveals differential patterns of peri-implant bone changes after subclinical bacterial infection in a rat model
Authors: Stadelmann Vincent A. , Thompson Keith , Zeiter Stephan , Camenisch Karin , Styger Ursula , Patrick Sheila , McDowell Andrew , Nehrbass Dirk , Richards R. Geoff , Moriarty T. Fintan
Published: December 2020

Subclinical infection associated with orthopedic devices can be challenging to diagnose. The goal of this study was to evaluate longitudinal, microcomputed tomography (microCT) imaging in a rat model of subclinical orthopedic device-related infection caused byStaphylococcus epidermidisand four differentCutibacterium(previouslyPropionibacterium)acnesstrains, and compare outcomes with non-inoculated and historicalS. aureus-inoculated controls. Sterile screws or screws colonized with bacteria were placed in the tibia of 38 adult Wistar rats [n = 6 sterile screws; n = 6S. epidermidis-colonized screws; n = 26C. acnes-colonized screws (covering all three main subspecies)]. Regular microCT scans were taken over 28 days and processed for quantitative time-lapse imaging with dynamic histomorphometry. At euthanasia, tissues were processed for semiquantitative histopathology or quantitative bacteriology. All rats receiving sterile screws were culture-negative at euthanasia and displayed progressive bony encapsulation of the screw. All rats inoculated withS. epidermidis-colonized screws were culture-positive and displayed minor changes in peri-implant bone, characteristic of subclinical infection. Five of the 17 rats in theC. acnesinoculated group were culture positive at euthanasia and displayed bone changes at the interface of the screw and bone, but not deeper in the peri-implant bone. Dynamic histomorphometry revealed significant differences in osseointegration, bone remodeling and periosteal reactions between groups that were not measurable by visual observation of still microCT images. Our study illustrates the added value of merging 3D microCT data from subsequent timepoints and producing inherently richer 4D data for the detection and characterization of subclinical orthopedic infections, whilst also reducing animal use.
Dynamic constitutive model of frozen soil that considers the evolution of volume fraction of ice
Authors: Xie Qijun , Su Lijun , Zhu Zhiwu
Published: December 2020

A new constitutive model for frozen soils under high strain rate is developed. By taking the frozen soil as a composite material and considering the adiabatic temperature rise and interfacial debonding damage, the nonlinear dynamic response (NDR) of the frozen soil is predicted. At the same time, the relationship between instantaneous temperature and unfrozen water content is given, and an evolution rule of the volume fraction of ice particles is obtained. This relationship shows good agreement with experimental data. Using this new constitutive model, the stress–strain relationship of frozen soil under impact loading at temperatures of − 3 °C, − 8 °C, − 18 °C, and − 28 °C is calculated. There is good agreements between the results based on this new constitutive model and the data of dynamic impact.
Atmospheric pressure air microplasma current time series for true random bit generation
Authors: Allagui Anis , Majzoub Sohaib , Elwakil Ahmed S. , Rojas Andrea Espinel , Alawadhi Hussain
Published: December 2020

Generating true random bits of high quality at high data rates is usually viewed as a challenging task. To do so, physical sources of entropy with wide bandwidth are required which are able to provide truly random bits and not pseudorandom bits, as it is the case with deterministic algorithms and chaotic systems. In this work we demonstrate a reliable high-speed true random bit generator (TRBG) device based on the unpredictable electrical current time series of atmospheric pressure air microplasma (APAMP). After binarization of the sampled current time series, no further post-processing was needed in order for the bitstreams to pass all 15 tests of the NIST SP 800-22 statistical test suite. Several configurations of the system have been successfully tested at different sampling rates up to 100 MS/s, and with different inter-electrode distances giving visible/non-visible optical emissions. The cost-effectiveness, simplicity and ease of implementation of the proposed APAMP system compared to others makes it a very promising solution for portable TRBGs.
High rate of major drug–drug interactions of lopinavir–ritonavir for COVID-19 treatment
Authors: Macías Juan , Pinilla Ana , Lao-Dominguez Francisco A. , Corma Anaïs , Contreras-Macias Enrique , González-Serna Alejandro , Gutierrez-Pizarraya Antonio , Fernández-Fuertes Marta , Morillo-Verdugo Ramón , Trigo Marta , Real Luis M. , Pineda Juan A.
Published: December 2020

The impact of drug–drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69–85%) patients, and in 33 (26%, 95% CI 19–35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10–731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04–0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.
A systematic review of corticosteroid treatment for noncritically ill patients with COVID-19
Authors: Shuto Hisayuki , Komiya Kosaku , Yamasue Mari , Uchida Sonoe , Ogura Takashi , Mukae Hiroshi , Tateda Kazuhiro , Hiramatsu Kazufumi , Kadota Jun-ichi
Published: December 2020

The World Health Organization (WHO) has published guidance recommending systemic corticosteroids for the treatment of patients with severe or critical COVID-19 and no corticosteroids for those with nonsevere COVID-19. Although their recommendations for critical cases were based on the results from seven randomized controlled trials (RCTs), those for noncritical cases were based on the results from only one RCT, the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial. In search of additional evidence of corticosteroids’ effect on COVID-19, we systematically reviewed controlled observational studies, besides RCTs, that assessed the impact of corticosteroid treatment on any type of mortality and/or other outcomes in noncritical patients. Of the 4037 titles and abstracts screened, we ultimately included the RECOVERY trial and five controlled observational studies using propensity score matching, (accessed on September 8, 2020). Two of the controlled observational studies assessed the association between corticosteroid treatment and in-hospital mortality, without finding statistical significance. Four of the controlled observational studies assessed corticosteroids’ effect on other outcomes, demonstrating that they were associated with reduced risk of intubation in patients requiring oxygen and with longer hospitalization and viral shedding in mild or moderate cases. These results support the WHO recommendations not to use corticosteroids for nonsevere COVID-19.
Understanding the biogeochemical mechanisms of metal removal from acid mine drainage with a subsurface limestone bed at the Motokura Mine, Japan
Authors: Fuchida Shigeshi , Suzuki Kohei , Kato Tatsuya , Kadokura Masakazu , Tokoro Chiharu
Published: December 2020

Subsurface limestone beds (SLBs) are used as a passive treatment technique to remove toxic metals from acid mine drainage (AMD). In this study, we investigated the mechanisms and thermodynamics of metal (manganese, copper, zinc, cadmium, and lead) precipitation in the SLB installed at the Motokura Mine. Field surveys in 2017 and 2018 showed that the pH of the SLB influent (initially 5–6) increased to approximately 8 in the drain between 24 and 45 m from the inlet. This increase was caused by limestone dissolution and resulted in the precipitation of hydroxides and/or carbonates of copper, zinc, and lead, as expected from theoretical calculations. Manganese and cadmium were removed within a pH range of approximately 7–8, which was lower than the pH at which they normally precipitate as hydroxides (pH 9–10). X-ray absorption near-edge structure analysis of the sediment indicated that δ-MnO2, which has a high cation-exchange capacity, was the predominant tetravalent manganese compound in the SLB rather than trivalent compound (MnOOH). Biological analysis indicates that microorganism activity of the manganese-oxidizing bacteria in the SLB provided an opportunity for δ-MnO2 formation, after which cadmium was removed by surface complexation with MnO2 (≡ MnOH0 + Cd2+  ⇄  ≡ MnOCd+  +  H+). These findings show that biological agents contributed to the precipitation of manganese and cadmium in the SLB, and suggest that their utilization could enhance the removal performance of the SLB.