bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term safety of tiotropium/olodaterol in older patients with moderate-to-very-severe COPD in the TONADO® studies
Authors: Ferguson Gary T. , Maltais François , Karpel Jill , Bothner Ulrich , Kloer Isabel , Trampisch Matthias , Buhl Roland 
Published: December 2020

AbstractOlder patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of adverse events (AEs) due to decreased protective organ function and increased comorbidities. TONADO® 1 + 2 were replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials comparing the efficacy and safety of tiotropium/olodaterol (5/5 µg) versus the monocomponents via the Respimat® inhaler in patients with moderate-to-very-severe COPD. In this prespecified safety analysis, patients were grouped by age. Of 3100 patients, 1585 (51.1%) were aged <65 years, 1198 (38.7%) 65–<75 years, 309 (10.0%) 75–<85 years, and eight (0.3%) ≥85 years. At baseline, 23.4% had a pre-existing cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diagnosed diabetes. Overall, there was no increase in major adverse cardiac events, other AEs, or serious AEs with tiotropium/olodaterol versus the monocomponents in any age group, supporting the safety of tiotropium/olodaterol in older patients with COPD.
Experimental characterization of the energetics of quantum logic gates
Authors: Cimini V. , Gherardini S. , Barbieri M. , Gianani I. , Sbroscia M. , Buffoni L. , Paternostro M. , Caruso F. 
Published: December 2020

AbstractWe characterize the energetic footprint of a two-qubit quantum gate from the perspective of non-equilibrium quantum thermodynamics. We experimentally reconstruct the statistics of energy and entropy fluctuations following the implementation of a controlled-unitary gate, linking them to the performance of the gate itself and the phenomenology of Landauer’s principle at the single-quantum level. Our work thus addresses the energetic cost of operating quantum circuits, a problem that is crucial for the grounding of the upcoming quantum technologies.
Personalized estimates of morphometric similarity in bipolar disorder and schizophrenia
Authors: Doucet Gaelle E. , Lin Dongdong , Du Yuhui , Fu Zening , Glahn David C. , Calhoun Vincent D. , Turner Jessica , Frangou Sophia 
Published: December 2020

AbstractBipolar disorder and schizophrenia are associated with brain morphometry alterations. This study investigates inter-individual variability in brain structural profiles, both within diagnostic groups and between patients and healthy individuals. Brain morphometric measures from three independent samples of patients with schizophrenia (n = 168), bipolar disorder (n = 122), and healthy individuals (n = 180) were modeled as single vectors to generated individualized profiles of subcortical volumes and regional cortical thickness. These profiles were then used to compute a person-based similarity index (PBSI) for subcortical volumes and for regional cortical thickness, to quantify the within-group similarity of the morphometric profile of each individual to that of the other participants in the same diagnostic group. There was no effect of diagnosis on the PBSI for subcortical volumes. In contrast, compared to healthy individuals, the PBSI for cortical thickness was lower in patients with schizophrenia (effect size = 0.4, p ≤ 0.0002), but not in patients with bipolar disorder. The results were robust and reproducible across samples. We conclude that disease mechanisms for these disorders produce modest inter-individual variations in brain morphometry that should be considered in future studies attempting to cluster patients in subgroups.
Increased expression of LCN2 formed a positive feedback loop with activation of the ERK pathway in human kidney cells during kidney stone formation
Authors: Hui Zhang , Jiang Zhu , Qiao Du , Bo Zhao , Qiyuan Kang , Shaohua Bian , Wenbing Yuan , Wei Liu , Cheng Luo , Shuangning Liu , Zhengyi Li , Yingyi Li 
Published: December 2020

AbstractKidney stones are a common threat to the health of elderly patients with a high incidence of disease. However, the specific molecular mechanism of the formation of kidney stones has not been elucidated. Here, we combined signalling molecules with signalling pathways in a double positive circulation regulation model. In addition, we found that LCN2 plays a role in promoting kidney stones through regulation of the ERK signalling pathway and expression of other kidney stone-related genes. LCN2 expression was upregulated upon oxalate stimulation. P-ERK1/2 inhibition by U0126 in kidney epithelial cells resulted in decreased expression of LCN2. Furthermore, the upregulation of LCN2 not only depended on the activation of the ERK signalling pathway but also regulated the activation of the ERK signalling pathway. Importantly, upregulation of LCN2 not only caused kidney epithelial cell damage but also promoted the expression of other kidney stone-related genes. Our findings improved the understanding of LCN2 and might lead to the development of new therapeutic and prognostic markers for kidney stones.
Predicted climate change will increase the truffle cultivation potential in central Europe
Authors: Čejka Tomáš , Trnka Miroslav , Krusic Paul J. , Stobbe Ulrich , Oliach Daniel , Václavík Tomáš , Tegel Willy , Büntgen Ulf 
Published: December 2020

AbstractClimate change affects the distribution of many species, including Burgundy and Périgord truffles in central and southern Europe, respectively. The cultivation potential of these high-prized cash crops under future warming, however, remains highly uncertain. Here we perform a literature review to define the ecological requirements for the growth of both truffle species. This information is used to develop niche models, and to estimate their cultivation potential in the Czech Republic under current (2020) and future (2050) climate conditions. The Burgundy truffle is already highly suitable for cultivation on ~ 14% of agricultural land in the Czech Republic (8486 km2), whereas only ~ 8% of the warmest part of southern Moravia are currently characterised by a low suitability for Périgord truffles (6418 km2). Though rising temperatures under RCP8.5 will reduce the highly suitable cultivation areas by 7%, the 250 km2 (3%) expansion under low-emission scenarios will stimulate Burgundy truffles to benefit from future warming. Doubling the moderate and expanding the highly suitable land by 352 km2 in 2050, the overall cultivation potential for Périgord truffles will rise substantially. Our findings suggest that Burgundy and Périgord truffles could become important high-value crops for many regions in central Europe with alkaline soils. Although associated with uncertainty, long-term investments in truffle cultivation could generate a wide range of ecological and economic benefits.
Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture
Authors: Acevedo-Acevedo Suehelay , Millar Douglas C. , Simmons Aaron D. , Favreau Peter , Cobra Paulo F. , Skala Melissa , Palecek Sean P. 
Published: December 2020

AbstractBreast cancer metastasis occurs via blood and lymphatic vessels. Breast cancer cells ‘educate’ lymphatic endothelial cells (LECs) to support tumor vascularization and growth. However, despite known metabolic alterations in breast cancer, it remains unclear how lymphatic endothelial cell metabolism is altered in the tumor microenvironment and its effect in lymphangiogenic signaling in LECs. We analyzed metabolites inside LECs in co-culture with MCF-7, MDA-MB-231, and SK-BR-3 breast cancer cell lines using $$^1\hbox {H}$$

1

H

nuclear magnetic resonance (NMR) metabolomics, Seahorse, and the spatial distribution of metabolic co-enzymes using optical redox ratio imaging to describe breast cancer-LEC metabolic crosstalk. LECs co-cultured with breast cancer cells exhibited cell-line dependent altered metabolic profiles, including significant changes in lactate concentration in breast cancer co-culture. Cell metabolic phenotype analysis using Seahorse showed LECs in co-culture exhibited reduced mitochondrial respiration, increased reliance on glycolysis and reduced metabolic flexibility. Optical redox ratio measurements revealed reduced NAD(P)H levels in LECs potentially due to increased NAD(P)H utilization to maintain redox homeostasis. $$^{13}\hbox {C}$$

13

C

-labeled glucose experiments did not reveal lactate shuttling into LECs from breast cancer cells, yet showed other $$^{13}\hbox {C}$$

13

C

signals in LECs suggesting internalized metabolites and metabolic exchange between the two cell types. We also determined that breast cancer co-culture stimulated lymphangiogenic signaling in LECs, yet activation was not stimulated by lactate alone. Increased lymphangiogenic signaling suggests paracrine signaling between LECs and breast cancer cells which could have a pro-metastatic role.
Integrative genomic analysis implicates ERCC6 and its interaction with ERCC8 in susceptibility to breast cancer
Authors: Moslehi Roxana , Tsao Hui-Shien , Zeinomar Nur , Stagnar Cristy , Fitzpatrick Sean , Dzutsev Amiran 
Published: December 2020

AbstractUp to 30% of all breast cancer cases may be inherited and up to 85% of those may be due to segregation of susceptibility genes with low and moderate risk [odds ratios (OR) ≤ 3] for (mostly peri- and post-menopausal) breast cancer. The majority of low/moderate-risk genes, particularly those with minor allele frequencies (MAF) of < 30%, have not been identified and/or validated due to limitations of conventional association testing approaches, which include the agnostic nature of Genome Wide Association Studies (GWAS). To overcome these limitations, we used a hypothesis-driven integrative genomics approach to test the association of breast cancer with candidate genes by analyzing multi-omics data. Our candidate-gene association analyses of GWAS datasets suggested an increased risk of breast cancer with ERCC6 (main effect: 1.29 ≤ OR ≤ 2.91, 0.005 ≤ p ≤ 0.04, 11.8 ≤ MAF ≤ 40.9%), and implicated its interaction with ERCC8 (joint effect: 3.03 ≤ OR ≤ 5.31, 0.01 ≤ pinteraction ≤ 0.03). We found significant upregulation of ERCC6 (p = 7.95 × 10–6) and ERCC8 (p = 4.67 × 10–6) in breast cancer and similar frequencies of ERCC6 (1.8%) and ERCC8 (0.3%) mutations in breast tumors to known breast cancer susceptibility genes such as BLM (1.9%) and LSP1 (0.3%). Our integrative genomics approach suggests that ERCC6 may be a previously unreported low- to moderate-risk breast cancer susceptibility gene, which may also interact with ERCC8.
Management strategies in a SEIR-type model of COVID 19 community spread
Authors: Rǎdulescu Anca , Williams Cassandra , Cavanagh Kieran 
Published: December 2020

AbstractThe 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international focus. Significant gaps persist in our knowledge of COVID 19 epidemiology, transmission dynamics, investigation tools and management, despite (or possibly because of) the fact that the outbreak is an unprecedented global threat. On the positive side, enough is currently known about the epidemic process to permit the construction of mathematical predictive models. In our work, we adapt a traditional SEIR epidemic model to the specific dynamic compartments and epidemic parameters of COVID 19, as it spreads in an age-heterogeneous community. We analyze management strategies of the epidemic course (as they were implemented through lockdown and reopening procedures in many of the US states and countries worldwide); however, to more clearly illustrate ideas, we focus on the example of a small scale college town community, with the timeline of control measures introduced in the state of New York. We generate predictions, and assess the efficiency of these control measures (closures, mobility restrictions, social distancing), in a sustainability context.
Efficacy of low dose pirfenidone in idiopathic pulmonary fibrosis: real world experience from a tertiary university hospital
Authors: Song Myung Jin , Moon Sung Woo , Choi Ji Soo , Lee Sang Hoon , Lee Su Hwan , Chung Kyung Soo , Jung Ji Ye , Kang Young Ae , Park Moo Suk , Kim Young Sam , Chang Joon , Kim Song Yee 
Published: December 2020

AbstractPirfenidone is an antifibrotic agent that has been proven to slow down the progression of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the efficacy of low-dose pirfenidone (that is, less than 1200 mg/day). We retrospectively reviewed the medical records of patients with IPF. The patients were divided into the following three groups, those who were not treated with pirfenidone (control) and those who were treated with pirfenidone at doses < 1200 mg/day (low-dose group) and ≥ 1200 mg/day (high-dose group). The adjusted mean changes in forced vital capacity (FVC) in 1 year were − 200.7, − 88.4, and − 94.7 mL in the control, low-dose, and high-dose groups (p = 0.021). The FVC declined more significantly in the control group than in the low-dose and high-dose groups. No significant difference in FVC change was observed between the low-dose and high-dose groups. Dyspepsia, anorexia, and nausea were significantly more frequent in the low-dose than in the high-dose group, suggesting that dose reduction is attributed to gastrointestinal tract-related adverse events. Dose reduction may help patients to better control gastrointestinal tract-related adverse events; continuing taking the medication at low doses is also expected to be effective in reducing the FVC decline.
Stoichiometry of irreversible ligand binding to a one-dimensional lattice
Authors: Tsvetkov Philipp O. 
Published: December 2020

AbstractIn this paper we investigate the problem of irreversible binding of a ligand that covers several identical binding sites on a macromolecule with a one-dimensional lattice. Due to steric constraints, irreversible binding or binding with slow kinetics results in partial saturation of the binding sites thus impacting the stoichiometry of the interaction. Here we present a recursive formula to calculate the exact fraction of the occupied binding sites for a ligand and macromolecule of arbitrary lengths. We also provide an analytical result for the exact fraction of the occupied sites in case of an infinitely long lattice. We conclude with a simplified empirical formula for the exact fraction of the occupied sites in case of an infinitely long lattice.
Frequency spectrum recurrence analysis
Authors: Ladeira Guênia , Marwan Norbert , Destro-Filho João-Batista , Davi Ramos Camila , Lima Gabriela 
Published: December 2020

AbstractIn this paper, we present the new frequency spectrum recurrence analysis technique by means of electro-encephalon signals (EES) analyses. The technique is suitable for time series analysis with noise and disturbances. EES were collected, and alpha waves of the occipital region were analysed by comparing the signals from participants in two states, eyes open and eyes closed. Firstly, EES were characterized and analysed by means of techniques already known to compare with the results of the innovative technique that we present here. We verified that, standard recurrence quantification analysis by means of EES time series cannot statistically distinguish the two states. However, the new frequency spectrum recurrence quantification exhibit quantitatively whether the participants have their eyes open or closed. In sequence, new quantifiers are created for analysing the recurrence concentration on frequency bands. These analyses show that EES with similar frequency spectrum have different recurrence levels revealing different behaviours of the nervous system. The technique can be used to deepen the study on depression, stress, concentration level and other neurological issues and also can be used in any complex system.
Estimating the short-time rate of change in the trend of the Keeling curve
Authors: Nordebo Sven , Naeem Muhammad Farhan , Tans Pieter 
Published: December 2020

AbstractWhat exactly is the short-time rate of change (growth rate) in the trend of $$\text {CO}_2$$

CO
2

data such as the Keeling curve? The answer to this question will obviously depend very much on the duration in time over which the trend has been defined, as well as the smoothing technique that has been used. As an estimate of the short-time rate of change we propose to employ a very simple and robust definition of the trend based on a centered 1-year sliding data window for averaging and a corresponding centered 1-year difference (2-year data window) to estimate its rate of change. In this paper, we show that this simple strategy applied to weekly data of the Keeling curve (1974–2020) gives an estimated rate of change which is perfectly consistent with a more sophisticated regression analysis technique based on Taylor and Fourier series expansions. From a statistical analysis of the regression model and by using the Cramér–Rao lower bound, it is demonstrated that the relative error in the estimated rate of change is less than 5 $$\%$$
%
. As an illustration, the estimates are finally compared to some other publicly available data regarding anthropogenic $$\text {CO}_2$$

CO
2

emissions and natural phenomena such as the El Niño.
A diagnostic LAMP assay for the destructive grapevine insect pest, phylloxera (Daktulosphaira vitifoliae)
Authors: Agarwal Arati , Cunningham J. Paul , Valenzuela Isabel , Blacket Mark J. 
Published: December 2020

AbstractGrape phylloxera (Daktulosphaira vitifoliae) is a destructive insect pest of grapevines that is highly invasive worldwide, despite strict biosecurity containment measures in place at farm and regional levels. Current phylloxera identification by visual inspection and laboratory-based molecular methods is time-consuming and costly. More rapid and cost-effective methods for identification of this pest would benefit industry, growers, and biosecurity services. Loop mediated isothermal amplification (LAMP) is a new portable technology available for rapid and accurate in-field molecular diagnostics. This study outlines the development of a new LAMP assay to enable the identification of phylloxera specimens. New LAMP primers were developed to specifically amplify phylloxera mitochondrial DNA (5′-COI), which we have shown is effective as a DNA barcode for identification of phylloxera, using LAMP technology. Positive LAMP reactions, containing phylloxera DNA, amplified in less than twelve minutes with an anneal derivative temperature of approximately 79 °C to 80 °C compared to a newly designed synthetic DNA (gBlock) fragment which had an anneal derivative temperature of 82 °C. No LAMP amplification was detected in any of the non-target species tested, i.e. no false-positive identification resulted for these species. We also successfully optimised a non-destructive DNA extraction procedure, HotSHOT “HS6”, for use in the field on phylloxera adults, nymphs and eggs, to retain physical specimens. DNA extracted using this method was also suitable for species and genotype molecular identification methods, such as DNA barcoding, qPCR and microsatellite genotyping. The new LAMP assay provides a novel visual molecular tool for accurate diagnostics of phylloxera in the laboratory and field.
Voltage and pH difference across the membrane control the S4 voltage-sensor motion of the Hv1 proton channel
Authors: Schladt T. Moritz , Berger Thomas K. 
Published: December 2020

AbstractThe voltage-gated proton channel Hv1 is expressed in a variety of cells, including macrophages, sperm, and lung epithelial cells. Hv1 is gated by both the membrane potential and the difference between the intra- and extracellular pH (ΔpH). The coupling of voltage- and ∆pH-sensing is such that Hv1 opens only when the electrochemical proton gradient is outwardly directed. However, the molecular mechanism of this coupling is not known. Here, we investigate the coupling between voltage- and ΔpH-sensing of Ciona intestinalis proton channel (ciHv1) using patch-clamp fluorometry (PCF) and proton uncaging. We show that changes in ΔpH can induce conformational changes of the S4 voltage sensor. Our results are consistent with the idea that S4 can detect both voltage and ΔpH.
Transcriptome analysis reveals that exogenous ethylene activates immune and defense responses in a high late blight resistant potato genotype
Authors: Yang Xiaohui , Chen Li , Yang Yu , Guo Xiao , Chen Guangxia , Xiong Xingyao , Dong Daofeng , Li Guangcun 
Published: December 2020

AbstractEthylene (ET) is one of the many important signaling hormones that functions in regulating defense responses in plants. Gene expression profiling was conducted under exogenous ET application in the high late blight resistant potato genotype SD20 and the specific transcriptional responses to exogenous ET in SD20 were revealed. Analysis of differentially expressed genes (DEGs) generated a total of 1226 ET-specific DEGs, among which transcription factors, kinases, defense enzymes and disease resistance-related genes were significantly differentially expressed. GO enrichment and KEGG metabolic pathway analysis also revealed that numerous defense regulation-related genes and defense pathways were significantly enriched. These results were consistent with the interaction of SD20 and Phytophthora infestans in our previous study, indicating that exogenous ET stimulated the defense response and initiated a similar defense pathway compared to pathogen infection in SD20. Moreover, multiple signaling pathways including ET, salicylic acid, jasmonic acid, abscisic acid, auxin, cytokinin and gibberellin were involved in the response to exogenous ET, which indicates that many plant hormones work together to form a complex network to resist external stimuli in SD20. ET-induced gene expression profiling provides insights into the ET signaling transduction pathway and its potential mechanisms in disease defense systems in potato.
Bacterial diversity and functional analysis of severe early childhood caries and recurrence in India
Authors: Kalpana Balakrishnan , Prabhu Puniethaa , Bhat Ashaq Hussain , Senthilkumar Arunsaikiran , Arun Raj Pranap , Asokan Sharath , Gunthe Sachin S. , Verma Rama S. 
Published: December 2020

AbstractDental caries is the most prevalent oral disease affecting nearly 70% of children in India and elsewhere. Micro-ecological niche based acidification due to dysbiosis in oral microbiome are crucial for caries onset and progression. Here we report the tooth bacteriome diversity compared in Indian children with caries free (CF), severe early childhood caries (SC) and recurrent caries (RC). High quality V3–V4 amplicon sequencing revealed that SC exhibited high bacterial diversity with unique combination and interrelationship. Gracillibacteria_GN02 and TM7 were unique in CF and SC respectively, while Bacteroidetes, Fusobacteria were significantly high in RC. Interestingly, we found Streptococcus oralis subsp. tigurinus clade 071 in all groups with significant abundance in SC and RC. Positive correlation between low and high abundant bacteria as well as with TCS, PTS and ABC transporters were seen from co-occurrence network analysis. This could lead to persistence of SC niche resulting in RC. Comparative in vitro assessment of biofilm formation showed that the standard culture of S. oralis and its phylogenetically similar clinical isolates showed profound biofilm formation and augmented the growth and enhanced biofilm formation in S. mutans in both dual and multispecies cultures.