bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheumatoid Arthritis–Specific Autoimmunity in the Lung Before and at the Onset of Disease
Authors: Joshua Vijay , Loberg Haarhaus Malena , Hensvold Aase , Wähämaa Heidi , Gerstner Christina , Hansson Monika , Israelsson Lena , Stålesen Ragnhild , Sköld Magnus , Grunewald Johan , Klareskog Lars , Grönwall Caroline , Réthi Bence , Catrina Anca , Malmström Vivianne 
Published: May 2023

ObjectiveThe lung is implicated as a site for breach of tolerance prior to onset of seropositive rheumatoid arthritis (RA). To substantiate this, we investigated lung‐resident B cells in bronchoalveolar lavage (BAL) samples from untreated early RA patients and anti–citrullinated protein antibody (ACPA)–positive individuals at risk for developing RA.MethodsSingle B cells (n = 7,680) were phenotyped and isolated from BAL samples from individuals at risk of RA (n = 3) and at RA diagnosis (n = 9). The immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n = 141). Monoclonal ACPAs were tested for reactivity patterns and binding to neutrophils.ResultsUsing our single‐cell approach, we found significantly increased proportions of B lymphocytes in ACPA+ compared to ACPA– individuals. Memory and double‐negative B cells were prominent in all subgroups. Upon antibody re‐expression, 7 highly mutated citrulline‐autoreactive clones originating from different memory B cell subsets were identified, both in individuals at risk of RA and early RA patients. Lung IgG variable gene transcripts from ACPA+ individuals carried frequent mutation‐induced N‐linked Fab glycosylation sites (P < 0.001), often in the framework 3 of the variable region. Two of the lung ACPAs bound to activated neutrophils, 1 from an individual at risk of RA and 1 from an early RA patient.ConclusionT cell–driven B cell differentiation resulting in local class switching and somatic hypermutation are evident in lungs before as well as in early stages of ACPA+ RA. Our findings add to the notion of lung mucosa being a site for initiation of citrulline autoimmunity preceding seropositive RA.image
Dynamische Zug‐Brücken‐Kompatibilität: Das Referenzverfahren als neue Nachweisform
Authors: Grunert Günther , Behnke Ronny , Liu Xiaohan 
Published: May 2023

AbstractNeu entwickelte Schienenfahrzeuge sind vor ihrem Einsatz auf dem Schienennetz der DB Netz AG hinsichtlich dynamischer Brückenkompatibilität zu untersuchen. Hierbei wird die dynamische Einwirkung auf Brücken aus Zugüberfahrt (Zug‐Brücken‐Interaktion) anhand von dynamischen Berechnungsergebnissen im Grenzzustand der Tragfähigkeit (GZT) und im Grenzzustand der Gebrauchstauglichkeit (GZG) bewertet und mit rechnerischen (bisher statischen) Mindestkapazitäten der Infrastruktur (Widerstand) verglichen. In diesem Beitrag wird eine neue Nachweisform vorgestellt, welche ermöglicht, die vorhandenen statischen Kapazitäten der Brücken um vorhandene dynamische Kapazitäten zu erweitern. Diese erlauben i. d. R. höhere zulässige Fahrzeuggeschwindigkeiten im Netz. Hierfür wird auf rechnerische Ergebnisse und datenbankgestütztes Expertenwissen (Fusion) aus Kurz‐ und Langzeitüberwachungen von Bestandsfahrzeugen und deren Einwirkung auf die Infrastruktur zurückgegriffen, um den Brückenbestand für diese Bestandsfahrzeuge als betriebserprobt zu erklären. Auf dieser Basis ist eine ansetzbare dynamische Kapazität für Neufahrzeuge formulierbar. Das Vorgehen wird exemplarisch für den ICE 3 (Bestandsfahrzeug) und die Neuentwicklung der Baureihe (BR) 408 (ICE 3neo) gezeigt.
Digitalisierung im Verkehrswasserbau – von der Bestandspflege zur Neubauidee
Authors: Akkermann Jan , Müller Stephan 
Published: May 2023

AbstractNeubau‐, Sanierungs‐, Erweiterungs‐ und Instandsetzungsplanungen von Verkehrswasserbauwerken setzen sich nahezu immer mit zum Teil sehr alter Bauwerkssubstanz auseinander. Im Kontext von Digitalisierung und infraBIM sind Bestandsmodelle ein wichtiger Startpunkt. Ein Bauwerksinformationsmodell, welches oftmals in ganzheitlicher Abschnittsbetrachtung von Wasserstraßen mit Teilmodellen zu sehen ist, dient als Basis der weiteren Instandhaltungs‐ und Neubauplanung. Die im Verkehrswasserbau im Vergleich zum Hoch‐ und Brückenbau noch relativ unerprobte BIM‐Planung steht vor der Herausforderung überwiegend unikaler Bauwerke. Darüber hinaus stellen die Schnittstellen zwischen Bauingenieurkonstruktionen und integriertem Maschinenbau wichtige Bereiche der integralen Planung dar. Der Beitrag gibt anhand von Praxisbeispielen einen Überblick über die verschiedenen Digitalisierungsansätze im Konstruktiven Verkehrswasserbau und legt hierbei den Fokus auf Besonderheiten und Best Practice.
Geotechnik beim Bau des neuen Schiffshebewerks Niederfinow
Authors: Puscher Christian , Heeling Anne , Bäumker Jan , Cudmani Roberto , Schwab Christian 
Published: May 2023

AbstractDas neue Schiffshebewerk Niederfinow an der Havel‐Oder‐Wasserstraße überbrückt einen Geländesprung von 36 m und verbindet eine Hochebene mit überwiegend bindigen Böden mit dem Oderbruch, wo unterhalb von bindigen und organischen Schichten v. a. nichtbindige Sedimente anstehen. Der Baugrund besteht überwiegend aus eiszeitlichen Böden (Geschiebemergel, Schmelzwasser‐ und Beckensedimente). Untergeordnet treten in den tieferen Bereichen tertiäre Schichten (tertiäre Sande, Tone und Schluffe sowie kohlige Bildungen) und oberflächennah nacheiszeitliche Böden (holozäne Sande und Schluffe sowie Mudde und Torf) auf. Der Bau des Hebewerks erfolgt in einer 13 m, in Teilbereichen bis zu 16 m tiefen Baugrube mit nur einer Verankerungslage aus Verpressankern, einer kombinierten Wand sowie einer mit GEWI‐Pfählen rückverankerten Unterwasserbetonsohle im Bereich der gut tragfähigen nichtbindigen Sedimente. Da die Hebewerksmechanik gegenüber einer Schleuse nur ein vergleichsweise geringes Maß an Schrägstellung erfahren darf, wurde besonderes Augenmerk auf das Setzungsverhalten gerichtet. Hierzu wurden vor Baubeginn und baubegleitend vom Technischen Büro der Bilfinger Berger Ingenieurbau GmbH umfangreiche numerische Betrachtungen ausgeführt, um diese mit den während des Baus gemessenen Verformungen abzugleichen. Zusätzlich waren umfangreiche Erdarbeiten an hohen und steilen Dammböschungen mit entsprechenden Einbauanforderungen und Verdichtungsprüfungen auszuführen. Hier wurden auch entsprechende geohydraulische Untersuchungen ausgeführt.
Comprehensive mRNA‐sequencing‐based characterization of three HEK‐293 cell lines during an rAAV production process for gene therapy applications
Authors: Pistek Martina , Kahlig Carolin‐Isabel , Hackl Matthias , Unterthurner Sabine , Kraus Barbara , Grabherr Reingard , Grillari Johannes , Hernandez Bort Juan A. 
Published: May 2023

AbstractHuman embryonal kidney cells (HEK‐293) are the most common host cells used for transient recombinant adeno‐associated virus (rAAV) production in pharmaceutical industry. To better cover the expected gene therapy product demands in the future, different traditional strategies such as cell line sub‐cloning and/or addition of chemical substances to the fermentation media have been used to maximize titers and improve product quality. A more effective and advanced approach to boost yield can be envisaged by characterizing the transcriptome of different HEK‐293 cell line pedigrees with distinct rAAV productivity patterns to subsequently identify potential gene targets for cell engineering. In this work, the mRNA expression profile of three HEK‐293 cell lines, resulting in various yields during a fermentation batch process for rAAV production, was investigated to gain basic insight into cell variability and eventually to identify genes that correlate with productivity. Mock runs using only transfection reagents were performed in parallel as a control. It finds significant differences in gene regulatory behaviors between the three cell lines at different growth and production stages. The evaluation of these transcriptomics profiles combined with collected in‐process control parameters and titers shed some light on potential cell engineering targets to maximize transient production of rAAV in HEK‐293 cells.
Determination of binding affinities between nuclear localization signal peptides of irradiated EGFR and KPNA using single‐molecule pull‐down assay and development of assay system for inhibitor screening
Authors: Oh Jiwon , Park Namwuk , Ham Seung Wook 
Published: May 2023

AbstractEpidermal growth factor receptor (EGFR) is transported into the nucleus during irradiation therapy and can cause the radiation resistance. It has been shown that irradiation activates EGFR transport to the nuclear by karyopherin alpha (KPNA) in the classical pathway, whereas ligand‐activated EGFR binds with karyopherin subunit beta 1 (KPNB1). Phosphorylation of T654 located within the nuclear localization signal (NLS) of EGFR is known to activate radiation‐induced nuclear EGFR transport. Therefore, we investigated the binding affinities between the NLS peptides of EGFR (645RRRHIVRKRXLRR657) and KPNA using a single‐molecule pull‐down assay in this study. We also showed the possible assay system for developing small molecules to modulate nuclear EGFR transport by high throughput screening, which potentially reduces the resistance during radiation therapy.
The value of vestibular graviceptive pathway evaluation in the diagnosis of unilateral peripheral vestibular dysfunction
Authors: Zhao Tong‐tong , Zhang Meng‐lu , Feng Yu‐fei , Wang Qian‐qian , Song Ning , Yang Xu , Ba Xiao‐hong 
Published: May 2023

AbstractBackgroundEvaluation of vestibular graviceptive pathway (VGP) in patients with unilateral peripheral vestibular dysfunction (UPVD) has received increasing attention from researchers. The study aimed to investigate the value of VGP evaluation in the diagnosis of UPVD.MethodsNinety‐five UPVD patients were divided into attack and remission phase groups. VGP evaluation‐related indicators, including subjective visual vertical (SVV), subjective visual horizontal (SVH), head tilt, ocular torsion (OT), and skew deviation (SD), were measured, and their correlations with cochleovestibular function test results were analyzed. The possible etiologies of contralesional VGP (c‐VGP) were analyzed.ResultsPositive rates of SVV, SVH, OT, and SD were significantly higher, and the degrees of SVV, SVH, and OT were significantly greater in the attack phase group than the remission phase group. The sides with abnormal VGP evaluation results were correlated with the sides with hearing loss, abnormal caloric, and video head impulse test (vHIT) results. A total of 14 patients showed c‐VGP, and possible etiologies included contralateral benign paroxysmal positional vertigo (n = 4), bilateral hearing loss (n = 8), bilateral vHIT gain reduction (n = 1), autoimmune diseases (n = 6), vascular risk factors (n = 6), lacunar infarction (n = 3), and endolymphatic hydrops (n = 3).ConclusionsAlterations in SVV, SVH, OT, and SD were noted in UPVD patients in different phases, which are presumed to be related to dynamic vestibular compensation; correlations between VGP evaluation results and cochleovestibular function test results indicate that VGP evaluation may be helpful for the diagnosis of the side affected in UPVD; the presence of c‐VGP may be related to bilateral labyrinth lesions or endolymphatic hydrops on the affected side; and the involvement of autoimmune mechanisms also deserves attention.
Altered brain activity in patients with end‐stage renal disease: A meta‐analysis of resting‐state functional imaging
Authors: Song Wenjuan , Zhao Liuyan , Li Xuekun , Wu Baolin 
Published: May 2023

AbstractIntroduction: Previous studies have revealed abnormal resting‐state brain activity in patients with end‐stage renal disease (ESRD); however, the results are inconsistent. Thus, we conducted a coordinate‐based meta‐analysis of whole‐brain resting‐state functional neuroimaging studies in ESRD to identify the most consistent neural activity alterations in ESRD patients and explore their relation to serological indicators.Methods: A comprehensive literature search strategy was applied to select pertinent studies up to December 2022 in PubMed, Web of Science, and Embase databases. Voxel‐wise meta‐analysis was conducted via the latest meta‐analytic algorithm, seed‐based d mapping with permutation of subject images software. Meta‐regression analyses were also conducted to explore the potential effect of clinical variables on resting‐state neural activity.Results: Eleven studies comprising 304 patients with ESRD and 296 healthy controls (HCs) were included. Compared with HCs, ESRD patients showed decreased brain activity in the default mode network (DMN) regions, including the bilateral anterior cingulate cortex/medial prefrontal cortex, bilateral midcingulate cortex/posterior cingulate cortex, bilateral precuneus, and right angular gyrus. The neural activities in the bilateral midcingulate cortex, bilateral midcingulate cortex/posterior cingulate cortex, and right angular gyrus were significantly associated with serological indexes including hemoglobin, urea, and creatinine levels.Conclusion: The present study provides a quantitative overview of brain activity alterations in patients with ESRD, and the results confirm the essential role of the DMN in ESRD patients, which may be the potential neural basis of their cognitive deficits. Additionally, some serological indicators may be used as predictive markers for progressive impairment of brain function.
Youth involvement in alcohol and drug prevention: A systematic review
Authors: Aresi Giovanni , Ferrari Valentina , Marta Elena , Simões Francisco 
Published: May 2023

AbstractTo review and analyse how youth involvement was conceptualised and applied in published alcohol and drug preventive interventions. A systematic review of the scientific literature on alcohol and drug prevention where young people (18–29 years old) participated at any stage of the intervention was conducted. We searched relevant bibliographic databases and online repositories for peer‐reviewed studies published between 2001 and 2021. Twenty‐seven articles reporting on studies in different countries and settings and using a variety of intervention strategies were eligible for inclusion. The analysis of the stages of youth involvement and the dimension of power sharing in decision‐making showed that only a minority of studies could be considered genuinely youth‐led whereas many involved young people merely as implementers of highly controlled research‐led interventions. However, the few studies that promoted sustained youth involvement struggled with translating results into rigorously evaluated interventions, thus demonstrating a tension between adoption of effective interventions and support to genuinely participatory processes. Knowledge gaps and implications for practice and research are discussed from a participatory research perspective. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.
Improvements to Stochastic Approaches for Simulating Agglomeration in Particle‐Laden Flows
Authors: Rupp David A. , Mortimer Lee F. , Fairweather Michael 
Published: May 2023

AbstractDirect numerical simulation, facilitated by the spectral element method, has been used to study collisions and agglomeration in particle‐laden fluid flows through a channel at shear Reynolds number. The particulate phase is simulated by deterministic Lagrangian particle tracking alongside a stochastic technique to resolve collisions. Interestingly, the implementation of agglomeration in the deterministic approach caused a major reduction in the particle collision rate. To determine the cause of this effect, analysis of the collision rate and location across the channel for different particle properties was performed. For systems without agglomeration, collisions between particles tend to be located on consistent streamlines, occurring between single pairs of particles. A numerical analysis of this effect confirmed the result, where inter‐particle collisions across the channel mostly took place between consistent particle pairs in close proximity. Repeat collisions are shown to be almost eliminated with the addition of the agglomeration mechanism. The impact and implications of this effect on the accuracy of the stochastic technique is discussed, and modifications are suggested to offer improvements while accounting for the repeat collisions.
Rationale and design of the optimal antithrombotic treatment for acute coronary syndrome patients with concomitant atrial fibrillation and implanted with new‐generation drug‐eluting stent: OPtimal management of anTIthroMbotic Agents (OPTIMA)‐4 trial
Authors: Gong Xiaoxuan , Hua Rui , Bai Jianling , Wu Tianyu , Wang Qin , Zhang Jinhua , Zhang Wenhao , Ying Lianghong , Ke Yongsheng , Wang Xiaoyan , Zhang Xiwen , Liu Kun , Chen Yan , Zhang Boqing , Dong Peng , Xiao Jianqiang , Li Changling , Zhu Li , Li Chunjian 
Published: May 2023

AbstractBackgroundAbout 5%–15% of acute coronary syndrome (ACS) patients undergoing stent implantation have concomitant atrial fibrillation and need both antiplatelet and anticoagulant therapies. The optimal antithrombotic regimen remains uncertain in this scenario.HypothesisA multicenter randomized controlled trial (OPtimal management of anTIthroMbotic Agents [OPTIMA]‐4) is designed to test the hypothesis that, for ACS patients with concomitant nonvalvular atrial fibrillation (NVAF) and having low‐to‐moderate risk of bleeding, clopidogrel is comparable in efficacy but superior in safety compared to ticagrelor while being used in combination with dabigatran after new‐generation drug‐eluting stent (DES) implantation.MethodsACS patients who have low‐to‐moderate risk of bleeding (e.g., HAS‐BLED score ≤ 2) and require anticoagulation therapy (CHA2DS2‐VASc score ≥ 2) will be recruited after implantation of new‐generation DES. A total of 1472 eligible patients will be randomly assigned to receive a 12‐month dual antithrombotic treatment of either clopidogrel 75 mg daily or ticagrelor 90 mg twice daily in combination with dabigatran 110 mg twice daily. Participants will be followed up for 12 months after randomization. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, unplanned revascularization, ischemic stroke, and systemic thromboembolism. The primary safety endpoint is set as major bleeding or clinically relevant nonmajor bleeding defined by the International Society of Thrombosis and Hemostasis. The enrollment and follow‐up have been launched.ResultsThe first enrollment occurred on March 12, 2018. The recruitment is anticipated to be completed before December 31, 2024.ConclusionsThe OPTIMA‐4 trial offers an opportunity to assess the optimal dual antithrombotic regimen in ACS patients with concomitant NVAF after the implantation of new‐generation DES.
Typical cathode materials for lithium‐ion and sodium‐ion batteries: From structural design to performance optimization
Authors: Ren Jincan , Zhu He , Fang Yongjin , Li Weibao , Lan Si , Wei Shaochong , Yin Zijia , Tang Yu , Ren Yang , Liu Qi 
Published: May 2023

AbstractRechargeable lithium‐ion and sodium‐ion batteries (SIB) have dominated the energy storage fields such as electric vehicles and portable electronics due to their high energy density, long cycle life, and environmental friendliness. However, the critical bottleneck hindering the further improvement of their electrochemical performance is the unsatisfactory cathode materials, typically exhibiting inherent drawbacks such as low reversible capacity, initial capacity loss, fast capacity decay, and poor rate performance. These issues are mainly attributed to changes in the internal structure of cathode materials, such as irreversible transformation of particle morphology, evolution of crystal structure, and undesired physicochemical interfacial reactions during the electrochemical process. To address above obstacles, abundant research efforts have been devoted to stabilizing the structural evolution of cathode materials and enhancing their electrochemical performance. Herein, we reviewed the research progress on the cathode materials for lithium‐ion and SIBs. The typical cathodes and their structural characteristics, electrochemical behaviors, reaction mechanisms, and strategies for electrochemical performance optimization were summarized. This review aims to promote the understanding of the structure‐performance relationship in the cathode materials and provide some guidance for the design of advanced cathode materials for lithium‐ion and SIBs from the perspective of crystal structure.
5‐Nitrofuryl‐Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity
Authors: Rodríguez‐Arce Esteban , Gavrilov Eric , Alvite Ximena , Nayeem Nazia , León Ignacio E. , Neary Michelle C. , Otero Lucía , Gambino Dinorah , Olea Azar Claudio , Contel María 
Published: May 2023

AbstractThis work describes the synthesis of four gold(I) [AuClL] compounds containing chloro and biologically active protonated thiosemicarbazones based on 5‐nitrofuryl (L=HSTC). The stability of the compounds in dichloromethane, DMSO, and DMSO/culture media solutions was investigated by spectroscopy, cyclic voltammetry, and conductimetry, indicating the formation overtime of cationic monometallic [Au(HTSC)(DMSO)]± or [Au(HTSC)2]±, and/or dimeric species. Neutral [{Au(TSC)}2] species were obtained from one of the compounds in dichlomethane/n‐hexane solution and characterized by X‐ray crystallography revealing a Au−Au bond, and deprotonated thiosemicarbazone (TSC). The cytotoxicity of the gold compounds and thiosemicarbazone ligands was evaluated against selected cancer cell lines and compared to that of Auranofin. Studies of the most stable, cytotoxic, and selective compound on a renal cancer cell line (Caki‐1) demonstrated its relevant antimigratory and anti‐angiogenic properties, and preferential accumulation in the cell nuclei. Its mode of action seems to involve interaction with DNA, and subsequent cell death via apoptosis.
Quantifying biodiversity using eDNA from water bodies: General principles and recommendations for sampling designs
Authors: Altermatt Florian , Carraro Luca , Antonetti Manuel , Albouy Camille , Zhang Yan , Lyet Arnaud , Zhang Xiaowei , Pellissier Loïc 
Published: May 2023

AbstractReliable and comparable estimates of biodiversity are the foundation for understanding ecological systems and informing policy and decision‐making, especially in an era of massive anthropogenic impacts on biodiversity. Environmental DNA (eDNA) metabarcoding is at the forefront of technological advances in biodiversity monitoring, and the last few years have seen major progress and solutions to technical challenges from the laboratory to bioinformatics. Water eDNA has been shown to allow the fast and efficient recovery of biodiversity signals, but the rapid pace of technological development has meant that some important principles regarding sampling design, which are well established in traditional biodiversity inventories, have been neglected. Using a spatially explicit river flow model, we illustrate how sampling must be adjusted to the size of the watercourse to increase the quality of the biodiversity signal recovered. We additionally investigate the effect of sampling parameters (volume, number of sites, sequencing depth) on detection probability in an empirical data set. Based on traditional sampling principles, we propose that aquatic eDNA sampling replication and volume must be scaled to match the organisms' and ecosystems' properties to provide reliable biodiversity estimates. We present a generalizable conceptual equation describing sampling features as a function of the size of the ecosystem monitored, the abundance of target organisms, and the properties of the sequencing procedure. The aim of this formalization is to enhance the standardization of critical steps in the design of biodiversity inventory studies using eDNA. More robust sampling standards will generate more comparable biodiversity data from eDNA, which is necessary for the method's long‐term plausibility and comparability.