bluuebunny/crossref_metadata_2025_split huggingface dataset:
Storm‐Scale and Fine‐Scale Boundary Layer Structures of Tropical Cyclones Simulated With the WRF‐LES Framework
Authors: Liu Qingyuan , Wu Liguang , Qin Nannan , Li Yubin 
Published: October 2021

AbstractPrevious studies demonstrated that the tropical cyclone (TC) boundary layer (TCBL) contains small‐scale coherent structures, such as roll vortices and tornado‐scale vortices (TSVs), and they play important roles in energy transport and intensity changes in TCs. However, little is known about how horizontal resolutions can affect storm‐scale and fine‐scale structures in the TCBL with the grid spacing decreasing from the turbulent gray zone (100 m–1 km) to the large‐eddy scale (<100 m). In this study, numerical experiments with the large eddy simulation technique are used to investigate the effect of the model horizontal resolution on the simulated TC‐scale and fine‐scale structures in the TCBL. The simulated TC tends to have a shallower BL, a lower BL jet associated with stronger near‐surface vertical wind shear in the TCBL when the grid spacing decreases from 333 to 111 m or 37 m. When the grid spacing decreases to 111 m or 37 m, the fine‐scale coherent structures and near‐surface wind streaks associated with roll vortices and TSVs can be simulated, and the characteristics of the simulated turbulent kinetic energy in the TCBL are in good agreement with observational studies. With the grid spacing of 111 and 37 m, no significant differences in TC intensity are found in terms of instantaneous maximum and azimuthal‐mean maximum wind speeds. This study suggests that simulations with the horizontal grid spacing of 100 m or less can simulate the small coherent structures in the TCBL and their effect on TC intensity.
Field‐Based Estimation of Net Primary Productivity and Its Above‐ and Belowground Partitioning in Global Grasslands
Authors: Sun Yuanfeng , Feng Yuhao , Wang Yupin , Zhao Xia , Yang Yuanhe , Tang Zhiyao , Wang Shaopeng , Su Haojie , Zhu Jiangling , Chang Jinfeng , Fang Jingyun 
Published: October 2021

AbstractNet primary productivity (NPP) in global grasslands is a critical component of terrestrial carbon cycling and the primary source of food for herbivores. However, the size and spatial distribution of NPP across global grasslands remain unclear, especially for belowground NPP (BNPP), which limits our understanding of above‐ and belowground carbon cycling and the assessments of herbivore food security. Here, we compiled a comprehensive grassland NPP database with 1,467 field measurements to estimate the spatial distributions of aboveground NPP (ANPP), BNPP, total NPP (TNPP), and the fraction of BNPP (fBNPP) using the random forest (RF) model. The global mean grassland ANPP, BNPP, TNPP, and fBNPP were 433 ± 31 g m−2 yr−1, 593 ± 47 g m−2 yr−1, 979 ± 78 g m−2 yr−1, and 0.54 ± 0.02, respectively. The total ANPP, BNPP, and TNPP over global grasslands were 6.84 ± 0.49, 9.36 ± 0.74, and 15.46 ± 1.23 Pg C yr−1, respectively. ANPP, BNPP, and TNPP exhibited decreasing trends from low latitudes toward the poles. The spatial pattern of fBNPP was almost opposite to that of ANPP. Climate was a major determinant in shaping the spatial distribution of ANPP and TNPP, while soil and vegetation had significant impacts on that of BNPP and fBNPP. Our findings suggest that field data‐driven estimation of NPP using the RF model could be a useful approach for obtaining spatially explicit NPP of grasslands, particularly BNPP products, and that more attention should be paid on belowground and non‐climatic factors to better assess the carbon cycle in global grasslands.
Lnc-DC promotes estrogen independent growth and tamoxifen resistance in breast cancer
Authors: Peng Wan-Xin , Koirala Pratirodh , Zhou Huaixiang , Jiang Jiahong , Zhang Ziqiang , Yang Liu , Mo Yin-Yuan 
Published: October 2021

Abstract
Selective estrogen receptor modulators (SERMs) such as tamoxifen have proven to be effective in the treatment of estrogen receptor (ER) positive breast cancer. However, a major obstacle for such endocrine therapy is estrogen independent growth, leading to resistance, and the underlying mechanism is not fully understood. The purpose of this study was to determine whether long non-coding RNAs (lncRNAs) are involved in regulation of estrogen independent growth and tamoxifen resistance in ER positive breast cancer. Using a CRISPR/Cas9-based SAM (synergistic activation mediator) library against a focus group of lncRNAs, we identify Lnc-DC as a candidate lncRNA. Further analysis suggests that Lnc-DC is able to reduce tamoxifen-induced apoptosis by upregulation of anti-apoptotic genes such as Bcl2 and Bcl-xL. Furthermore, Lnc-DC activates STAT3 by phosphorylation (pSTAT3Y705), and the activated STAT3 subsequently induces expression of cytokines which in turn activate STAT3, forming an autocrine loop. Clinically, upregulation of Lnc-DC is associated with poor prognosis. In particular, analysis of a tamoxifen-treated patient cohort indicates that Lnc-DC expression can predict the response to tamoxifen. Together, this study demonstrates a previously uncharacterized function of Lnc-DC/STAT3/cytokine axis in estrogen independent growth and tamoxifen resistance, and Lnc-DC may serve as a potential predictor for tamoxifen response.
p62/SQSTM1-induced caspase-8 aggresomes are essential for ionizing radiation-mediated apoptosis
Authors: Lee Su Hyun , Cho Won Jin , Najy Abdo J. , Saliganan Allen-Dexter , Pham Tri , Rakowski Joseph , Loughery Brian , Ji Chang Hoon , Sakr Wael , Kim Seongho , Kato Ikuko , Chung Weon Kuu , Kim Harold E. , Kwon Yong Tae , Kim Hyeong-Reh C. 
Published: October 2021

AbstractThe autophagy–lysosome pathway and apoptosis constitute vital determinants of cell fate and engage in a complex interplay in both physiological and pathological conditions. Central to this interplay is the archetypal autophagic cargo adaptor p62/SQSTM1/Sequestosome-1 which mediates both cell survival and endoplasmic reticulum stress-induced apoptosis via aggregation of ubiquitinated caspase-8. Here, we investigated the role of p62-mediated apoptosis in head and neck squamous cell carcinoma (HNSCC), which can be divided into two groups based on human papillomavirus (HPV) infection status. We show that increased autophagic flux and defective apoptosis are associated with radioresistance in HPV(-) HNSCC, whereas HPV(+) HNSCC fail to induce autophagic flux and readily undergo apoptotic cell death upon radiation treatments. The degree of radioresistance and tumor progression of HPV(-) HNSCC respectively correlated with autophagic activity and cytosolic levels of p62. Pharmacological activation of the p62-ZZ domain using small molecule ligands sensitized radioresistant HPV(-) HNSCC cells to ionizing radiation by facilitating p62 self-polymerization and sequestration of cargoes leading to apoptosis. The self-polymerizing activity of p62 was identified as the essential mechanism by which ubiquitinated caspase-8 is sequestered into aggresome-like structures, without which irradiation fails to induce apoptosis in HNSCC. Our results suggest that harnessing p62-dependent sequestration of ubiquitinated caspase-8 provides a novel therapeutic avenue in patients with radioresistant tumors.
Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus
Authors: Payne Jennifer A. E. , Tailhades Julien , Ellett Felix , Kostoulias Xenia , Fulcher Alex J. , Fu Ting , Leung Ryan , Louch Stephanie , Tran Amy , Weber Severin A. , Schittenhelm Ralf B. , Lieschke Graham J. , Qin Chengxue Helena , Irima Daniel , Peleg Anton Y. , Cryle Max J. 
Published: October 2021

AbstractThe pathogenStaphylococcus aureuscan readily develop antibiotic resistance and evade the human immune system, which is associated with reduced levels of neutrophil recruitment. Here, we present a class of antibacterial peptides with potential to act both as antibiotics and as neutrophil chemoattractants. The compounds, which we term ‘antibiotic-chemoattractants’, consist of a formylated peptide (known to act as chemoattractant for neutrophil recruitment) that is covalently linked to the antibiotic vancomycin (known to bind to the bacterial cell wall). We use a combination of in vitro assays, cellular assays, infection-on-a-chip and in vivo mouse models to show that the compounds improve the recruitment, engulfment and killing ofS. aureusby neutrophils. Furthermore, optimizing the formyl peptide sequence can enhance neutrophil activity through differential activation of formyl peptide receptors. Thus, we propose antibiotic-chemoattractants as an alternate approach for antibiotic development.
Pparg signaling controls bladder cancer subtype and immune exclusion
Authors: Tate Tiffany , Xiang Tina , Wobker Sarah E. , Zhou Mi , Chen Xiao , Kim Hyunwoo , Batourina Ekatherina , Lin Chyuan-Sheng , Kim William Y. , Lu Chao , Mckiernan James M. , Mendelsohn Cathy Lee 
Published: October 2021

AbstractPparg, a nuclear receptor, is downregulated in basal subtype bladder cancers that tend to be muscle invasive and amplified in luminal subtype bladder cancers that tend to be non-muscle invasive. Bladder cancers derive from the urothelium, one of the most quiescent epithelia in the body, which is composed of basal, intermediate, and superficial cells. We find that expression of an activated form of Pparg (VP16;Pparg) in basal progenitors induces formation of superficial cells in situ, that exit the cell cycle, and do not form tumors. Expression in basal progenitors that have been activated by mild injury however, results in luminal tumor formation. We find that these tumors are immune deserted, which may be linked to down-regulation of Nf-kb, a Pparg target. Interestingly, some luminal tumors begin to shift to basal subtype tumors with time, down-regulating Pparg and other luminal markers. Our findings have important implications for treatment and diagnosis of bladder cancer.
Competitive and cooperative electronic states in Ba(Fe1−xTx)2As2 with T = Co, Ni, Cr
Authors: Zou Qiang , Fu Mingming , Wu Zhiming , Li Li , Parker David S. , Sefat Athena S. , Gai Zheng 
Published: October 2021

AbstractThe electronic inhomogeneities in Co, Ni, and Cr doped BaFe2As2 single crystals are compared within three bulk property regions: a pure superconducting (SC) dome region, a coexisting SC and antiferromagnetic (AFM) region, and a non-SC region. Machine learning is utilized to categorize the inhomogeneous electronic states: in-gap, L-shape, and S-shape states. Although the relative percentages of the states vary in the three samples, the total volume fraction of the three electronic states is quite similar. This is coincident with the number of electrons (Ni0.04 and Co0.08) and holes (Cr0.04) doped into the compounds. The in-gap state is confirmed as a magnetic impurity state from the Co or Ni dopants, the L-shape state is identified as a spin density wave which competes with the SC phase, and the S-shape state is found to be another form of magnetic order which constructively cooperates with the SC phase, rather than competing with it.
Treatment for COVID-19—a cohort study from Northern Italy
Authors: Guglielmetti Lorenzo , Aschieri Daniela , Kontsevaya Irina , Calabrese Francesco , Donisi Alessandra , Faggi Alberto , Ferrante Patrizia , Fronti Elisa , Gerna Laura , Leoni Maria Cristina , Paolillo Franco , Ratti Giovanna , Ruggieri Alessandro , Sacchini Daria , Scotti Marta , Valdatta Caterina , Stabile Marco , Taliani Gloria , Codeluppi Mauro 
Published: October 2021

AbstractMulticentre, retrospective cohort study with multivariable Cox proportional-hazards modelling and survival-time inverse-probability-weighting, evaluating the impact of different treatments on survival of proven COVID-19 patients admitted to two Hospitals in the province of Piacenza, Italy. Use of tocilizumab and of high doses of low molecular weight heparin, but not of antivirals (either alone or in combination), azithromycin, and any corticosteroid, was independently associated with lower mortality. Our results support further clinical evaluation of high doses of low molecular weight heparin and tocilizumab as COVID-19 therapeutics.
Optimization of RNA extraction methods from human metabolic tissue samples of the COMET biobank
Authors: Nouvel Agathe , Laget Jonas , Duranton Flore , Leroy Jérémy , Desmetz Caroline , Servais Marie-Dominique , de Préville Nathalie , Galtier Florence , Nocca David , Builles Nicolas , Rebuffat Sandra , Lajoix Anne-Dominique 
Published: October 2021

AbstractConstitution of biobank of human tissues requires careful handling and storage of biological material, to guarantee the quality of samples. Tissue preparation is also critical for further applications such as transcriptomic profiling. In this study, our aim was to evaluate the impact of different disruption techniques (FastPrep-24 instrument, GentleMACS dissociator, and syringe/needle) and homogenizing buffers (RLT versus QIAzol) on RNA purity and quality of metabolic tissues (adipose tissues, liver and skeletal muscle) present in the COMET Biobank. For all homogenization methods used and tissue types, the A260/280 ratios reached values ≥ 1.8, which are in the range of what is found in human tissues and cell lines, while the A260/230 ratios were however ≤ 1.8, with the lowest value obtained with GentleMACS Dissociator. In addition, GentleMACS Dissociator combined with QIAzol reagent gave the highest RIN value and 28S/18S ratio for all tissues tested, except for muscle. Performing RT-qPCR, Ct values for different housekeeping genes can be influenced by extraction methods and RNA quality of samples. In conclusion, we have demonstrated that different disruption techniques and homogenizing buffers impact the purity and some quality markers of RNA, and can also impact quantification of mRNAs by RT-qPCR in human metabolic tissues.
Artificial selection optimizes clonality in chaya (Cnidoscolus aconitifolius)
Authors: Munguía-Rosas Miguel A. 
Published: October 2021

AbstractThe clonal propagation of crops offers several advantages to growers, such as skipping the juvenile phase, faster growth, and reduced mortality. However, it is not known if the wild ancestors of most clonal crops have a similar ability to reproduce clonally. Therefore, it is unclear whether clonality was an ancestral condition, or if it evolved during domestication in the majority of these crops. Here, I assessed some traits that are relevant to clonal propagation using stem cuttings from chaya (Cnidoscolus aconitifolius) and compared these traits to those of its wild ancestor. Chaya is highly relevant crop to food security in its domestication center (Yucatan Peninsula) and is now cultivated in several countries. Chaya is also an excellent model for assessing the effect of domestication on clonality because wild relatives and selection targets are known. Specifically, I compared resistance to desiccation, water and resource storage, as well as the production of new organs (shoots and leaves) by the stems of wild and domesticated plants. I also compared their performance in root development and clone survival. I found that, relative to their wild ancestors, the stem cuttings of domesticated chaya had 1.1 times greater storage capacity for water and starch. Additionally, the stems of domesticated plants produced 1.25 times more roots, 2.69 times more shoots and 1.94 more leaves, and their clones lived 1.87 times longer than their wild relatives. In conclusion, the results suggest that artificial selection has optimized water and starch storage by stems in chaya. Because these traits also confer greater fitness (i.e. increased fecundity and survival of clones), they can be considered adaptations to clonal propagation in the agroecosystems where this crop is cultivated.
Oxytocin increases physiological linkage during group therapy for methamphetamine use disorder: a randomized clinical trial
Authors: Thorson Katherine R. , McKernan Scott M. , West Tessa V. , Woolley Joshua D. , Mendes Wendy Berry , Stauffer Christopher S. 
Published: October 2021

AbstractPatients and psychotherapists often exhibit behavioral, psychological, and physiological similarity. Here, we test whether oxytocin—a neuropeptide that can enhance expressivity and social perception—influences time-lagged “linkage” of autonomic nervous system responses among participants and facilitators during group therapy. Physiological linkage estimates (n = 949) were created from ten cohorts, each with two facilitators (n = 5) and four to six participants (n = 48), over six weekly sessions of group therapy for methamphetamine use disorder. All participants of a cohort received oxytocin or placebo intranasally in a randomized double-blind procedure before each session. Cardiac interbeat intervals (IBI) were measured continuously during sessions to estimate physiological linkage, operationalized as one cohort-mate’s IBI reactivity during one minute predicting another cohort-mate’s IBI reactivity during the following minute. In oxytocin cohorts, participants and facilitators experienced significant physiological linkage to their cohort-mates (i.e., their physiological responses were predicted by the prior responses of their cohort-mates) and significantly more linkage than people in placebo cohorts. Both effects occurred during the first and second sessions but not later sessions. Results suggest that oxytocin may enhance psychosocial processes often associated with linkage—such as social engagement—in groups and highlight oxytocin’s potential to improve group cohesion during group therapy.Clinical Trials Registration: NCT02881177, First published on 26/08/2016.
Eine Trendanalyse zur zeitlichen Entwicklung von
Qualitätsunterschieden zweier Versorgungsformen auf Basis von
Sekundärdaten
Authors: Karimova Kateryna , Klaaßen-Mielke Renate , Sawicki Olga A. , Glushan Anastasiya , Müller Angelina , Beyer Martin 
Published: October 2021

Zusammenfassung
Ziel der Studie Die Evaluation komplexer Interventionen wie
Versorgungsformen ist methodisch herausfordernd. Ziel dieser Analyse ist anhand
generalisierter Schätzungsgleichungen (GEE) zu prüfen, wie sich
die Qualitätsunterschiede zwischen der Hausarztzentrierten Versorgung
(HZV) und der Regelversorgung über die Zeit entwickeln.
Methoden Auf der Basis von Routinedaten der AOK Baden-Württemberg
wurde eine längsschnittliche Sekundärdatenanalyse der Jahre 2011
bis 2018 durchgeführt. Versicherte mit passenden Einschlusskriterien
wurden im Sinne einer dynamischen Kohorte zu Beginn des jeweiligen
Beobachtungsjahres in die Analyse eingeschlossen, sodass der Umfang und die
Zusammensetzung der Kohorte von Jahr zu Jahr variierten. Mithilfe von GEE wurden
Qualitätsunterschiede in dichotomen Indikatoren zwischen der HZV und der
Regelversorgung untersucht, wobei für Mehrfachmessungen eine
autoregressive Kovarianzstruktur (AR1) zugrunde gelegt wurde. An Variablen
wurden berücksichtigt: Eine Gruppenvariable für die
Versorgungsformen, eine Variable für das betrachtete Jahr sowie eine
Wechselwirkung zwischen den beiden Variablen. Die aus der Modellierung
resultierenden Schätzer lieferten Auskunft darüber, wie das
Verhältnis der beiden Gruppen zu Beginn der Beobachtungsstudie war und
wie sich die Gruppentrends sowohl individuell als auch im Verhältnis
zueinander über die Zeit entwickelten.
Ergebnisse GEE wird beispielhaft auf den Qualitätsindikator
Verordnung von potenziell inadäquater Medikation (PIM) bei
älteren Versicherten angewandt. Die Chance einer PIM-Verordnung bei
über 65-jährigen (Jahr 2018; N=628 523) war zu
Beginn der Beobachtungszeit innerhalb der HZV signifikant niedriger als in der
Regelversorgungsgruppe (Odds Ratio 0,978; 95%-Konfidenzintervall:
0,968–0,987). In beiden Gruppen nahm die Chance einer PIM-Verordnung in
den betrachteten 7 Beobachtungsjahren ab, in der HZV-Gruppe stärker als
in der Regelversorgungsgruppe.
Schlussfolgerung Eine Trendanalyse mit GEE basierend auf
Sekundärdaten, die die Qualitätsunterschiede zwischen
Vergleichsgruppen abbildet, bietet großes Potenzial zur Evaluation neuer
und bestehender Versorgungsformen über die Zeit.
Nutzung von Sekundärdaten für die
pharmakoepidemiologische Forschung – machen wir das Beste
draus!
Authors: Pigeot Iris , Kollhorst Bianca , Didelez Vanessa 
Published: October 2021

ZusammenfassungIn Studien mit Sekundärdaten wie Abrechnungsdaten von Krankenkassen wird
man häufig vor methodische Herausforderungen gestellt, die v. a.
durch die Zeitabhängigkeit, aber auch durch ungemessenes Confounding
entstehen. In diesem Paper stellen wir Strategien vor, um verschiedene
Biasquellen zu vermeiden und um den durch ungemessenes Confounding entstehenden
Bias abzuschätzen. Wir illustrieren das Prinzip der Targets Trials,
marginale Strukturmodelle und instrumentelle Variablen anhand von Studien mit
der GePaRD Datenbank. Abschließend werden die Chancen und Limitationen
von Record Linkage diskutiert, um fehlende Information in den Daten zu
ergänzen.
Important Regulatory Roles of Erythrocytes in Platelet Adhesion to the von Willebrand Factor on the Wall under Blood Flow Conditions
Authors: Tamura Noriko , Shimizu Kazuya , Shiozaki Seiji , Sugiyama Kazuyasu , Nakayama Masamitsu , Goto Shinichi , Takagi Shu , Goto Shinya 
Published: October 2021

AbstractThe role of erythrocytes in platelet adhesion to von Willebrand factor (VWF) on the vessel wall through their membrane glycoprotein (GP)Ibα under blood flow conditions has not yet been elucidated. Blood specimens containing fluorescent-labeled platelets and native, biochemically fixed, or artificial erythrocytes at various hematocrits were perfused on the surface of VWF immobilized on the wall at a shear rate of 1,500 s−1. The rates of platelet adhesion were measured under each condition. The computer simulation of platelet adhesion to the VWF on the wall at the same shear rate was conducted by solving the governing equations with a finite-difference method on a K computer. The rates of platelet adhesion were calculated at various hematocrit conditions in the computational domain of 100 µm (x-axis) × 400 µm (y-axis) × 100 µm (z-axis). Biological experiments demonstrated a positive correlation between the rates of platelet adhesion and hematocrit values in native, fixed, and artificial erythrocytes. (r = 0.992, 0.934, and 0.825 respectively, p < 0.05 for all). The computer simulation results supported the hematocrit-dependent increase in platelet adhesion rates on VWF (94.3/second at 10%, 185.2/second at 20%, and 327.9/second at 30%). These results suggest that erythrocytes play an important role in platelet adhesion to VWF. The augmented z-axis fluctuation of flowing platelets caused by the physical presence of erythrocytes is speculated to be the cause of the hematocrit-dependent increase in platelet adhesion.