bluuebunny/crossref_metadata_2025_split huggingface dataset:
An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip
Authors: Subedi Nikita , Van Eyndhoven Laura C. , Hokke Ayla M. , Houben Lars , Van Turnhout Mark C. , Bouten Carlijn V. C. , Eyer Klaus , Tel Jurjen 
Published: August 2021

AbstractCytotoxicity is a vital effector mechanism used by immune cells to combat pathogens and cancer cells. While conventional cytotoxicity assays rely on averaged end-point measures, crucial insights on the dynamics and heterogeneity of effector and target cell interactions cannot be extracted, emphasizing the need for dynamic single-cell analysis. Here, we present a fully automated droplet-based microfluidic platform that allowed the real-time monitoring of effector-target cell interactions and killing, allowing the screening of over 60,000 droplets identifying 2000 individual cellular interactions monitored over 10 h. During the course of incubation, we observed that the dynamics of cytotoxicity within the Natural Killer (NK) cell population varies significantly over the time. Around 20% of the total NK cells in droplets showed positive cytotoxicity against paired K562 cells, most of which was exhibited within first 4 h of cellular interaction. Using our single cell analysis platform, we demonstrated that the population of NK cells is composed of individual cells with different strength in their effector functions, a behavior masked in conventional studies. Moreover, the versatility of our platform will allow the dynamic and resolved study of interactions between immune cell types and the finding and characterization of functional sub-populations, opening novel ways towards both fundamental and translational research.
Accessing depth-resolved high spatial frequency content from the optical coherence tomography signal
Authors: Alexandrov Sergey , Arangath Anand , Zhou Yi , Murphy Mary , Duffy Niamh , Neuhaus Kai , Shaw Georgina , McAuley Ryan , Leahy Martin 
Published: August 2021

AbstractOptical coherence tomography (OCT) is a rapidly evolving technology with a broad range of applications, including biomedical imaging and diagnosis. Conventional intensity-based OCT provides depth-resolved imaging with a typical resolution and sensitivity to structural alterations of about 5–10 microns. It would be desirable for functional biological imaging to detect smaller features in tissues due to the nature of pathological processes. In this article, we perform the analysis of the spatial frequency content of the OCT signal based on scattering theory. We demonstrate that the OCT signal, even at limited spectral bandwidth, contains information about high spatial frequencies present in the object which relates to the small, sub-wavelength size structures. Experimental single frame imaging of phantoms with well-known sub-micron internal structures confirms the theory. Examples of visualization of the nanoscale structural changes within mesenchymal stem cells (MSC), which are invisible using conventional OCT, are also shown. Presented results provide a theoretical and experimental basis for the extraction of high spatial frequency information to substantially improve the sensitivity of OCT to structural alterations at clinically relevant depths.
Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling
Authors: Kwon Yumi , Park Seong-Jun , Nguyen Binh Thanh , Kim Mi Jeong , Oh Sejin , Lee Hwanho , Park Narae , Kim Hyun Seok , Kang Min-Jung , Min Byung Soh , Lee Jin-Won , Yang Eun Gyeong , Lee Cheolju 
Published: August 2021

AbstractThe role of matrix metalloproteinase-2 (MMP-2) in tumor cell migration has been widely studied, however, the characteristics and effects of MMP-2 in clinical sample of metastatic colorectal cancer (CRC) remain poorly understood. Here, in order to unveil the perturbed proteomic signal during MMP-2 induced cancer progression, we analyzed plasma proteome of CRC patients according to disease progression, HCT116 cancer secretome upon MMP-2 knockdown, and publicly available CRC tissue proteome data. Collectively, the integrative analysis of multi-layered proteomes revealed that a protein cluster containing EMT (Epithelial-to-Mesenchymal Transition)-associated proteins such as CD9-integrin as well as MMP-2. The proteins of the cluster were regulated by MMP-2 perturbation and exhibited significantly increased expressions in tissue and plasma as disease progressed from TNM (Tumor, Node, and Metastasis) stage I to II. Furthermore, we also identified a plausible association between MMP-2 up-regulation and activation of focal adhesion kinase signaling in the proteogenomic analysis of CRC patient tissues. Based on these comparative and integrative analyses, we suggest that the high invasiveness in the metastatic CRC resulted from increased secretion of MMP-2 and CD9-integrin complex mediated by FAK signaling activation.
Oxidative stress and radioiodine treatment of differentiated thyroid cancer
Authors: Buczyńska Angelika , Sidorkiewicz Iwona , Rogucki Mariusz , Siewko Katarzyna , Adamska Agnieszka , Kościuszko Maria , Maliszewska Katarzyna , Kozłowska Gabryela , Szumowski Piotr , Myśliwiec Janusz , Dzięcioł Janusz , Krętowski Adam , Popławska-Kita Anna 
Published: August 2021

AbstractIt is hypothesized that the oxidative stress level in thyroid cancer patients is additionally upregulated by radioactive iodine (RAI) treatment, that may exert an important impact on future health concerns. In our study, we evaluated the oxidative stress level changes using the measurement of malondialdehyde (MDA) concentration in patients with differentiated thyroid cancer (DTC) undergoing RAI treatment. Considering the results obtained in the study group, the serum levels of MDA in DTC patients were significantly higher compared to the healthy subjects (p < 0.05). The MDA concentration was significantly higher on the third day after RAI (p < 0.001) and significantly lower one year after RAI (p < 0.05) in DTC patients compared to the baseline concentration. Moreover, the redox stabilization after RAI treatment in patients with DTC during a year-long observation was demonstrated. Accordingly, an increased oxidative stress impact on the related biochemical parameters reflecting the health conditions of the DTC patients was determined. Our study showed that increased oxidative stress reflected by MDA measurements in DTC patients is further enhanced by RAI, but this effect is no longer observed one year after the therapy.
Development and validation of LAMP primer sets for rapid identification of Aspergillus fumigatus carrying the cyp51A TR46 azole resistance gene
Authors: Trabasso Plinio , Matsuzawa Tetsuhiro , Arai Teppei , Hagiwara Daisuke , Mikami Yuzuru , Moretti Maria Luiza , Watanabe Akira 
Published: August 2021

AbstractInfections due to triazole-resistant Aspergillus fumigatus are increasingly reported worldwide and are associated with treatment failure and mortality. The principal class of azole-resistant isolates is characterized by tandem repeats of 34 bp or 46 bp within the promoter region of the cyp51A gene. Loop-mediated isothermal amplification (LAMP) is a widely used nucleic acid amplification system that is fast and specific. Here we describe a LAMP assay method to detect the 46 bp tandem repeat insertion in the cyp51A gene promoter region based on novel LAMP primer sets. It also differentiated strains with TR46 tandem repeats from those with TR34 tandem repeats. These results showed this TR46-LAMP method is specific, rapid, and provides crucial insights to develop novel antifungal therapeutic strategies against severe fungal infections due to A. fumigatus with TR46 tandem repeats.
Future hydrology and hydrological extremes under climate change in Asian river basins
Authors: Shrestha Sangam , Bae Deg-Hyo , Hok Panha , Ghimire Suwas , Pokhrel Yadu 
Published: August 2021

AbstractThe diverse impacts of anthropogenic climate change in the spatiotemporal distribution of global freshwater are generally addressed through global scale studies, which suffer from uncertainties arising from coarse spatial resolution. Multi-catchment, regional studies provide fine-grained details of these impacts but remain less explored. Here, we present a comprehensive analysis of climate change impacts on the hydrology of 19 river basins from different geographical and climatic conditions in South and Southeast Asia. We find that these two regions will get warmer (1.5 to 7.8 °C) and wetter (− 3.4 to 46.2%) with the expected increment in river flow (− 18.5 to 109%) at the end of the twenty-first century under climate change. An increase in seasonal hydro-climatic extremes in South Asia and the rising intensity of hydro-climatic extremes during only one season in Southeast Asia illustrates high spatiotemporal variability in the impact of climate change and augments the importance of similar studies on a larger scale for broader understanding.
A new family of boat-shaped Ln8 clusters exhibiting the magnetocaloric effect and slow magnetic relaxation
Authors: Li Jia-Nian , Li Ning-Fang , Wang Ji-Lei , Liu Xiao-Mei , Ping Qing-Dong , Zang Ting-Ting , Mei Hua , Xu Yan 
Published: August 2021

Three novel boat-shaped Ln8 clusters have been successfully synthesized. Magnetic measurements reveal that 1-Gd exhibits larger MCE, while 2-Dy displays slow magnetization relaxation. Besides, the luminescence properties of 3-Eu were investigated.
Copper-catalyzed redox neutral ketoalkylation of Csp2–H bonds via C–C bond cleavage
Authors: Chen He , Guo Li-Na , Sun Qing-Xin , Chen Lei , Tao Jing-Qi , Gao Pin 
Published: August 2021

An efficient copper-catalyzed ketoalkylation of Csp2–H bonds with cycloalkyl silyl peroxides under mild conditions is presented. A series of Csp2–H bonds in quinoxalin-2(1H)-ones, heteroaromatic N-oxides and quinones were amenable to this protocol.
Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis
Authors: Rayego-Mateos Sandra , Campillo Sofia , Rodrigues-Diez Raúl R. , Tejera-Muñoz Antonio , Marquez-Exposito Laura , Goldschmeding Roel , Rodríguez-Puyol Diego , Calleros Laura , Ruiz-Ortega Marta 
Published: August 2021

AbstractChronic kidney disease (CKD) is characterized by pathological accumulation of extracellular matrix (ECM) proteins in renal structures. Tubulointerstitial fibrosis is observed in glomerular diseases as well as in the regeneration failure of acute kidney injury (AKI). Therefore, finding antifibrotic therapies comprises an intensive research field in Nephrology. Nowadays, ECM is not only considered as a cellular scaffold, but also exerts important cellular functions. In this review, we describe the cellular and molecular mechanisms involved in kidney fibrosis, paying particular attention to ECM components, profibrotic factors and cell–matrix interactions. In response to kidney damage, activation of glomerular and/or tubular cells may induce aberrant phenotypes characterized by overproduction of proinflammatory and profibrotic factors, and thus contribute to CKD progression. Among ECM components, matricellular proteins can regulate cell–ECM interactions, as well as cellular phenotype changes. Regarding kidney fibrosis, one of the most studied matricellular proteins is cellular communication network-2 (CCN2), also called connective tissue growth factor (CTGF), currently considered as a fibrotic marker and a potential therapeutic target. Integrins connect the ECM proteins to the actin cytoskeleton and several downstream signaling pathways that enable cells to respond to external stimuli in a coordinated manner and maintain optimal tissue stiffness. In kidney fibrosis, there is an increase in ECM deposition, lower ECM degradation and ECM proteins cross-linking, leading to an alteration in the tissue mechanical properties and their responses to injurious stimuli. A better understanding of these complex cellular and molecular events could help us to improve the antifibrotic therapies for CKD.
The science of science: Clinical Science launches a new translational meta-research collection
Authors: Weissgerber Tracey L. 
Published: August 2021

Abstract
Clinical Science is proud to launch a new translational meta-research collection. Meta-research, or the science of science, applies the scientific method to study science itself. Meta-research is a powerful tool for identifying common problems in scientific papers, assessing their impact, and testing solutions to improve the transparency, rigor, trustworthiness, and usefulness of biomedical research. The collection welcomes science of science studies that link basic science to disease mechanisms, as well as meta-research articles highlighting opportunities to improve transparency, rigor, and reproducibility among the types of papers published in Clinical Science. Submissions might include science of science studies that explore factors linked to successful translation, or meta-research on experimental methods or study designs that are often used in translational research. We hope that this collection will encourage scientists to think critically about current practices and take advantage of opportunities to make their own research more transparent, rigorous, and reproducible.
Characterizing Swallows From People With Neurodegenerative Diseases Using High-Resolution Cervical Auscultation Signals and Temporal and Spatial Swallow Kinematic Measurements
Authors: Donohue Cara , Khalifa Yassin , Mao Shitong , Perera Subashan , Sejdić Ervin , Coyle James L. 
Published: August 2021

Purpose
The prevalence of dysphagia in patients with neurodegenerative diseases (ND) is alarmingly high and frequently results in morbidity and accelerated mortality due to subsequent adverse events (e.g., aspiration pneumonia). Swallowing in patients with ND should be continuously monitored due to the progressive disease nature. Access to instrumental swallow evaluations can be challenging, and limited studies have quantified changes in temporal/spatial swallow kinematic measures in patients with ND. High-resolution cervical auscultation (HRCA), a dysphagia screening method, has accurately differentiated between safe and unsafe swallows, identified swallow kinematic events (e.g., laryngeal vestibule closure [LVC]), and classified swallows between healthy adults and patients with ND. This study aimed to (a) compare temporal/spatial swallow kinematic measures between patients with ND and healthy adults and (b) investigate HRCA's ability to annotate swallow kinematic events in patients with ND. We hypothesized there would be significant differences in temporal/spatial swallow measurements between groups and that HRCA would accurately annotate swallow kinematic events in patients with ND.

Method

Participants underwent videofluoroscopic swallowing studies with concurrent HRCA. We used linear mixed models to compare temporal/spatial swallow measurements (
n
= 170 ND patient swallows,
n
= 171 healthy adult swallows) and deep learning machine-learning algorithms to annotate specific temporal and spatial kinematic events in swallows from patients with ND.

Results

Differences (
p
< .05) were found between groups for several temporal and spatial swallow kinematic measures. HRCA signal features were used as input to machine-learning algorithms and annotated upper esophageal sphincter (UES) opening, UES closure, LVC, laryngeal vestibule reopening, and hyoid bone displacement with 66.25%, 85%, 68.18%, 70.45%, and 44.6% accuracy, respectively, compared to human judges' measurements.

Conclusion
This study demonstrates HRCA's potential in characterizing swallow function in patients with ND and other patient populations.
Fault‐tolerant strategies for open‐circuit switch failures in open‐end winding PMSM drives
Authors: Zhu Bin , Priestley Matthew , Fletcher John Edward 
Published: August 2021

AbstractMany safety‐critical drive systems require post‐fault operation after an open‐circuit switch failure occurs in the inverter. The open‐end winding inverter topology facilitates the injection of zero‐sequence current such that a faulty switch leg can still be used to generate sufficient voltage states to continue operation. Therefore, only a minimal increase in the post‐fault torque ripple is experienced. However, the injection of this zero‐sequence current results in an increase in the copper loss which de‐rates the maximum post‐fault torque of the machine. Existing post‐fault techniques that inject zero‐sequence current, during an open‐circuit switch fault, do not minimize the copper loss resulting in sub‐optimal post‐fault torque per ampere. A method for reducing copper loss by optimizing the zero‐sequence current waveform to achieve the maximum post‐fault torque per ampere is proposed here. The proposed strategy has been experimentally assessed for both three‐phase and five‐phase drive systems. The experimental results demonstrate the continuous post‐fault operation of the drive system with a more balanced thermal load distribution between phases. A 2.8% and 5.6% improvement in post‐fault torque per ampere for three‐phase and five‐phase systems are demonstrated.
Magnetic accretion disk-outflow model for the state transition in X-ray binaries
Authors: Cao Xinwu , You Bei , Yan Zhen 
Published: August 2021

Context. The hard-to-soft state transition of the outbursts in X-ray binaries (XRBs) is triggered by the rising of the mass accretion rate as a result of the disk instability. The hard X-ray transition luminosity is found to be tightly correlated to the soft X-ray peak luminosity in the soft state, the physical origin of which is still a mystery.
Aims. In order to explain the observed correlation between the hard X-ray transition luminosity and the soft X-ray peak luminosity in the soft state, we construct a magnetic disk-outflow model for the state transition in XRBs.
Methods. We assumed that the large-scale magnetic field in the outer thin disk is formed through an inverse cascade of the field generated by the small-scale dynamo, which is then advected by the inner advection-dominated accretion flow (ADAF). The advected field accelerates a fraction of the gas in the ADAF into the outflows. We calculated the transition luminosity of an ADAF that is driven by these magnetic outflows, which vary with the mass accretion rate of the outer disk.
Results. During the outbursts, the heating front moves inward, and the field strength at the heating front of the outer disk is proportional to the accretion rate of the disk. Much angular angular momentum of the inner ADAF is carried away by the outflows for a stronger magnetic field, which leads to a high radial velocity of the ADAF. This increases the critical mass accretion rate of the ADAF with the field strength, and it therefore leads to a correlation between transition luminosity and the peak luminosity in the thermal state. We found that the values of the viscosity parameter α of the neutron star XRBs are systematically higher for those of the black hole (BH) XRBs (α ∼ 0.05−0.15 for BHs, and α ∼ 0.15−0.4 for neutron stars). Our model predicts that the transition luminosity may be higher than the peak luminosity provided α is sufficiently high, which is able to explain a substantial fraction of outbursts in BHXRBs that do not reach the thermally dominant accretion state.
Cinq types de travail scientifique « interdisciplinaire »
Authors: Li Vigni Fabrizio 
Published: August 2021

La littérature sur l’« interdisciplinarité » est imposante. Toutefois, peu de travaux fournissent des taxonomies descriptives des différentes figures du travail scientifique au croisement entre savoirs différents. Ceux qui le font adoptent soit un point de vue normatif et internaliste relativement à une discipline donnée, soit le point de vue de la sociologie de l’identité. En outre, le concept de « zone de transaction » est si utilisé en sciences sociales et au-delà qu’il semble pouvoir recouvrir la plupart des échanges « interdisciplinaires », mais se révèle en fait insuffisant. À partir d’un terrain auprès d’équipes de recherche en sciences de la complexité, cet article se propose de fournir une taxonomie descriptive du travail scientifique « interdisciplinaire » selon cinq types (transfrontaliers, ambassadeurs, polyglottes, binationaux et traducteurs) illustrés par des extraits d’entretiens et d’archives.
Processing and decisions relating to water resources data: The case of Morocco
Authors: Hicham Jamil , Elhassan Jamal , Bouabid El Mansouri , Aniss Moumen , Jamal Chao 
Published: August 2021

The national water strategy has been an essential vector of government strategy for a long time. The management of water resources is an integral part of the economic development of Morocco. Nevertheless, the definition of the strategic axes of this component and the adequate decision-making depends directly on the collection and use of all the data relating to water resources.
If big data technologies present a suitable solution to ensure optimal and rapid use of its data, the success of functional and technical designs can only be provided after total control of the processing and decision-making processes relating to the water domain.
In this paper, we will try to identify the aspects relating to the processes of data collection, processing, consolidation, and decision-making through the use of the results of field surveys and interviews with business managers.
Digital Signature for data and documents using operating PKI certificates
Authors: El Mane Adil , Chihab Younes , Korchiyne Redouan 
Published: August 2021

This report represents my researching work for a six-month internship in Lex Persona Enterprise. "The implementation of applications that sign data and files electronically using operating digital certificates" is the central theme of this research. This project brings together many applications related to compliance with well-specified programming constraints to sign files electronically.
The research has the goal of signing PDF documents digitally using the hash-and-sign method. The SHA-256 function as the hash function and RSA as encryption algorithm, accompanied with PKI certificates type X.509. The link between the applications and the certificates is the cryptographic API PKCS #11. This humbled work got dedicated to smartphones and computers. The use of WebView in all applications provides a taste of consistency. This article presents several processes carried out to accomplish this work.
Aktuelles zur medikamentösen Therapie des rezidivierten/metastasierten Nierenzellkarzinom (mNCC)
Authors: Virchow Isabel , Grünwald Viktor 
Published: August 2021

ZusammenfassungDas Nierenzellkarzinom gehört zu den häufigen malignen Tumoren bei weiterhin steigender Inzidenz über die letzten 10 Jahre. Bei zunehmend verbesserter Operationstechniken, Nierenerhalt und minimal invasiven Eingriffen in der Lokaltherapie primär resektabler, nicht metastasierter Stadien, bleiben adjuvante Behandlungskonzepte bislang nicht indiziert und die medikamentöse Therapie den fortgeschritten metastasierten oder rezidivierten Tumoren vorbehalten. Nachdem zu Beginn des Jahrtausends durch den Einsatz von Zytokinen, als erstem Immuntherapeutischen Ansatz, das Gesamtüberleben von Patienten mit Nierenzellkarzinom im median 13 Monate betrug, dominierte über die letzte Dekade die zielgerichtete Therapie mit Angiogeneseinhibitoren in Form von Antikörpern oder Tyrosinkinase-Inhibitoren (TKI), sowie der Therapieoption der mTOR-Inhibition. Demzufolge prägte die Wahl der therapeutischen Sequenztherapie die Diskussionen. Mittlerweile stellt die kombinierte Therapie mit Immun-Checkpoint-Inhibitoren (ICI) in der Erstlinientherapie des metastasierten Nierenzellkarzinoms einen neuen Standard dar und konnte das mediane Gesamtüberleben auf >40 Monate anheben. Tyrosinkinase-Inhibitoren haben als Kombinationspartner und in einzelnen Fällen auch als Monotherapie weiter ihren Stellenwert behalten. Derzeit sind in der Erstlinientherapie des Nierenzellkarzinoms in Deutschland eine rein immunonkologische Kombination und 3 Kombinationen aus jeweils einem Immun-Checkpoint-Inhibitor und einem TKI zugelassen.