bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of one‐layer Utrecht pattern with two‐layer (simple continuous/Cushing) pattern for jejunojejunostomy in healthy horses in vivo
Authors: Roessner Holly A. , Hurcombe Samuel D. , Klein Chelsea E. , Hopster Klaus , Engiles Julie B. 
Published: July 2021

AbstractObjectiveTo compare end‐to‐end jejunal anastomoses with a one‐layer (Utrecht) and two‐layer (simple continuous/Cushing) patterns.Study DesignExperimental study.AnimalsEight healthy adult horses.MethodsJejunal end‐to‐end anastomoses were performed in randomly assigned one‐layer or two‐layer patterns. Horses were recovered from surgery and monitored for complications. At 14 days, the opposite pattern was performed (cross‐over design) prior to euthanasia. Duration of closures was compared between patterns. Serosal width was measured before harvesting anastomotic sites from the first procedure. Luminal diameter was measured, and sections were collected for histological evaluation of heating after routine and immunohistochemical staining.ResultsOne‐layer closure was faster (716 ± 86 s) than two‐layer closures (1136 ± 111 s). Postoperative complications were minimal. No difference was detected in lumen size between groups. The lumen was reduced by 18% after one‐layer and 15% after two‐layer closures (p = .34). Serosal adhesions to the mesentery without clinical evidence of obstruction were observed in two horses with two‐layer closure. Histopathological scores for inflammation, infection, and healing did not differ between groups.ConclusionJejunal anastomosis with one‐layer Utrecht technique was about 7 min faster and led to similar luminal reduction and histological healing scores as two‐layer jejunojejunostomies.Clinical SignificanceThe outcomes of one‐layer Utrecht jejunojejunostomies in healthy horses justify clinical evaluation of this technique.
Local recovery of cardiac calcium‐induced calcium release interrogated by ultra‐effective, two‐photon uncaging of calcium
Authors: Janicek Radoslav , Agarwal Hitesh , Gómez Ana M. , Egger Marcel , Ellis‐Davies Graham C. R. , Niggli Ernst 
Published: July 2021

Key points
In cardiac myocytes, subcellular local calcium release signals, calcium sparks, are recruited to form each cellular calcium transient and activate the contractile machinery.
Abnormal timing of recovery of sparks after their termination may contribute to arrhythmias.
We developed a method to interrogate recovery of calcium spark trigger probabilities and their amplitude over time using two‐photon photolysis of a new ultra‐effective caged calcium compound.
The findings confirm the utility of the technique to define an elevated sensitivity of the calcium release mechanism in situ and to follow hastened recovery of spark trigger probabilities in a mouse model of an inherited cardiac arrhythmia, which was used for validation.
Analogous methods are likely to be applicable to investigate other microscopic subcellular signalling systems in a variety of cell types.
AbstractIn cardiac myocytes Ca2+‐induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) governs activation of contraction. Ca2+ release occurs via subcellular Ca2+ signalling events, Ca2+ sparks. Local recovery of Ca2+ release depends on both SR refilling and restoration of Ca2+ sensitivity of the RyRs. We used two‐photon (2P) photolysis of the ultra‐effective caged Ca2+ compound BIST‐2EGTA and laser‐scanning confocal Ca2+ imaging to probe refractoriness of local Ca2+ release in control conditions and in the presence of cAMP or low‐dose caffeine (to stimulate CICR) or cyclopiazonic acid (CPA; to slow SR refilling). Permeabilized cardiomyocytes were loaded with BIST‐2EGTA and rhod‐2. Pairs of short 2P photolytic pulses (1 ms, 810 nm) were applied with different intervals to test Ca2+ release amplitude recovery and trigger probability for the second spark in a pair. Photolytic and biological events were distinguished by classification with a self‐learning support vector machine (SVM) algorithm. In permeabilized myocytes data recorded in the presence of CPA showed a lower probability of triggering a second spark compared to control or cAMP conditions. Cardiomyocytes from a mouse model harbouring the arrhythmogenic RyRR420Q mutation were used for further validation and revealed a higher Ca2+ sensitivity of CICR. This new 2P approach provides composite information of Ca2+ release amplitude and trigger probability recovery reflecting both SR refilling and restoration of CICR and RyR Ca2+ sensitivity. It can be used to measure the kinetics of local CICR recovery, alterations of which may be related to premature heart beats and arrhythmias.
Constraint Effect on Fracture Behavior of Underclad Crack in Reactor Pressure Vessel
Authors: Shimodaira Masaki , Tobita Tohru , Takamizawa Hisashi , Katsuyama Jinya , Hanawa Satoshi 
Published: July 2021

Abstract
According to JEAC4206-2016, in the structural integrity assessment of a reactor pressure vessel (RPV), the fracture toughness (KJc) should be higher than the stress intensity factor at the crack tip of a postulated underclad crack (UCC) near the inner surface of the RPV during a pressurized thermal shock event. Previous analytical studies show that the plastic constraint for UCC is lower than that for surface crack. Consequently, the apparent KJc for UCC is expected to be higher than that for surface crack. In this study, we performed three-point bending fracture toughness tests and finite element analyses (FEAs) for RPV steel containing a UCC or a surface crack to quantitatively investigate the effect of cladding on the plastic constraint and subsequent KJc evaluation. From the tests, we found that the apparent KJc for the UCC was considerably higher than that for the surface crack. Such a high KJc could be explained by the lower plastic constraint parameters, such as T-stress and Q-parameter, of the UCC compared with those for the surface crack. Additionally, local approach analysis showed that the KJc for the UCC was significantly higher than the master curve estimated from the fracture toughness tests using compact tension specimens.
Quantifying structural controls on submarine channel architecture and kinematics
Authors: Mitchell W. Hamish , Whittaker Alexander C. , Mayall Mike , Lonergan Lidia , Pizzi Marco 
Published: July 2021

Abstract
Over the past two decades, the increased availability of three-dimensional (3-D) seismic data and their integration with outcrop and numerical modeling studies have enabled the architectural evolution of submarine channels to be studied in detail. While tectonic activity is a recognized control on submarine channel morphology, the temporal and spatial complexity associated with these systems means submarine channel behavior over extended time periods, and the ways in which processes scale and translate into time-integrated sedimentary architecture, remain poorly understood. For example, tectonically driven changes in slope morphology may locally enhance or diminish a channel's ability to incise, aggrade, and migrate laterally, changing channel kinematics and the distribution of composite architectures. Here, we combined seismic techniques with the concept of stratigraphic mobility to quantify how gravity-driven deformation influenced the stratigraphic architecture of two submarine channels, from the fundamental architectural unit, a channel element, to channel complex scale, on the Niger Delta slope.
From a 3-D, time-migrated, seismic-reflection volume, we evaluated the evolution of widths, depths, sinuosities, curvatures, and stratigraphic mobilities at fixed intervals downslope as the channel complexes interacted with a range of gravity-driven structures. At channel element scale, sinuosity and bend amplitude were consistently elevated over structured reaches of the slope, displaying a nonlinear increase in length, perpendicular to flow direction. At channel complex scale, the same locations, updip of structure, correlated to an increase in channel complex width and aspect ratio. Normalized complex dimensions and complex-averaged stratigraphic mobilities showed lateral migration to be the dominant form of stratigraphic preservation in these locations. Our results explain the intricate relationship between the planform characteristics of channel elements and the cross-sectional dimensions of the channel complex. We show how channel element processes and kinematics translate to form higher-order stratigraphic bodies, and we demonstrate how tectonically driven changes in slope develop channel complexes with distinct cross-sectional and planform architectures.
Formation of the crater suevite sequence from the Chicxulub peak ring: A petrographic, geochemical, and sedimentological characterization
Authors: Kaskes Pim , de Graaff Sietze J. , Feignon Jean-Guillaume , Déhais Thomas , Goderis Steven , Ferrière Ludovic , Koeberl Christian , Smit Jan , Wittmann Axel , Gulick Sean P.S. , Debaille Vinciane , Mattielli Nadine , Claeys Philippe 
Published: July 2021

Abstract
This study presents a new classification of a ∼100-m-thick crater suevite sequence in the recent International Ocean Discovery Program (IODP)-International Continental Scientific Drilling Program (ICDP) Expedition 364 Hole M0077A drill core to better understand the formation of suevite on top of the Chicxulub peak ring. We provide an extensive data set for this succession that consists of whole-rock major and trace element compositional data (n = 212) and petrographic data supported by digital image analysis. The suevite sequence is subdivided into three units that are distinct in their petrography, geochemistry, and sedimentology, from base to top: the ∼5.6-m-thick non-graded suevite unit, the ∼89-m-thick graded suevite unit, and the ∼3.5-m-thick bedded suevite unit. All of these suevite units have isolated Cretaceous planktic foraminifera within their clastic groundmass, which suggests that marine processes were responsible for the deposition of the entire M0077A suevite sequence. The most likely scenario describes that the first ocean water that reached the northern peak ring region entered through a N-NE gap in the Chicxulub outer rim. We estimate that this ocean water arrived at Site M0077 within 30 minutes after the impact and was relatively poor in rock debris. This water caused intense quench fragmentation when it interacted with the underlying hot impact melt rock, and this resulted in the emplacement of the ∼5.6-m-thick hyaloclastite-like, non-graded suevite unit. In the following hours, the impact structure was flooded by an ocean resurge rich in rock debris, which caused the phreatomagmatic processes to stop and the ∼89-m-thick graded suevite unit to be deposited. We interpret that after the energy of the resurge slowly dissipated, oscillating seiche waves took over the sedimentary regime and formed the ∼3.5-m-thick bedded suevite unit. The final stages of the formation of the impactite sequence (estimated to be &lt;20 years after impact) were dominated by resuspension and slow atmospheric settling, including the final deposition of Chicxulub impactor debris. Cumulatively, the Site M0077 suevite sequence from the Chicxulub impact site preserved a high-resolution record that provides an unprecedented window for unravelling the dynamics and timing of proximal marine cratering processes in the direct aftermath of a large impact event.
Simulating the time projection chamber responses at the MPD detector using generative adversarial networks
Authors: Maevskiy A. , Ratnikov F. , Zinchenko A. , Riabov V. 
Published: July 2021

AbstractHigh energy physics experiments rely heavily on the detailed detector simulation models in many tasks. Running these detailed models typically requires a notable amount of the computing time available to the experiments. In this work, we demonstrate a new approach to speed up the simulation of the Time Projection Chamber tracker of the MPD experiment at the NICA accelerator complex. Our method is based on a Generative Adversarial Network – a deep learning technique allowing for implicit estimation of the population distribution for a given set of objects. This approach lets us learn and then sample from the distribution of raw detector responses, conditioned on the parameters of the charged particle tracks. To evaluate the quality of the proposed model, we integrate a prototype into the MPD software stack and demonstrate that it produces high-quality events similar to the detailed simulator, with a speed-up of at least an order of magnitude. The prototype is trained on the responses from the inner part of the detector and, once expanded to the full detector, should be ready for use in physics tasks.
Historical glass mosaic tesserae: a multi-analytical approach for their characterization
Authors: Marcucci Giulia , Scherillo Antonella , Cazzaniga Carlo , Lemasson Quentin , Lorenzi Roberto , Clemenza Massimiliano , Riccardi Maria Pia , Di Martino Daniela 
Published: July 2021

AbstractWe present a completely non-destructive approach to analyse a set of historical glass mosaic tesserae. Aim of the study is to obtain a qualitative and quantitative characterization of the glass matrix in terms of elements and mineralogical phases. Several non-destructive techniques have been applied like Particle-Induced X-ray Emission, Particle-Induced Gamma-ray Emission, micro-Raman spectroscopy, neutron resonance capture analysis and neutron activation analysis in order to combine different technique strengths and to explore the effect of different range sizes for the analysis. Yet, best practices require the use of combined analysis and different skills. The paradigm of a non-destructive multi-analytical approach is suggested for a comprehensive investigation in non-homogeneous real samples, like historical glass mosaic tesserae.
Single-Cell Analyses Reveal Diverse Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer
Authors: Kashima Yukie , Shibahara Daisuke , Suzuki Ayako , Muto Kyoko , Kobayashi Ikei S. , Plotnick David , Udagawa Hibiki , Izumi Hiroki , Shibata Yuji , Tanaka Kosuke , Fujii Masanori , Ohashi Akihiro , Seki Masahide , Goto Koichi , Tsuchihara Katsuya , Suzuki Yutaka , Kobayashi Susumu S. 
Published: July 2021

Abstract

Tumor heterogeneity underlies resistance to tyrosine kinase inhibitors (TKI) in lung cancers harboring EGFR mutations. Previous evidence suggested that subsets of preexisting resistant cells are selected by EGFR-TKI treatment, or alternatively, that diverse acquired resistance mechanisms emerge from drug-tolerant persister (DTP) cells. Many studies have used bulk tumor specimens or subcloned resistant cell lines to identify resistance mechanism. However, intratumoral heterogeneity can result in divergent responses to therapies, requiring additional approaches to reveal the complete spectrum of resistance mechanisms. Using EGFR-TKI-resistant cell models and clinical specimens, we performed single-cell RNA-seq and single-cell ATAC-seq analyses to define the transcriptional and epigenetic landscape of parental cells, DTPs, and tumor cells in a fully resistant state. In addition to AURKA, VIM, and AXL, which are all known to induce EGFR-TKI resistance, CD74 was identified as a novel gene that plays a critical role in the drug-tolerant state. In vitro and in vivo experiments demonstrated that CD74 upregulation confers resistance to the EGFR-TKI osimertinib and blocks apoptosis, enabling tumor regrowth. Overall, this study provides new insight into the mechanisms underlying resistance to EGFR-TKIs.

Significance:
Single-cell analyses identify diverse mechanisms of resistance as well as the state of tolerant cells that give rise to resistance to EGFR tyrosine kinase inhibitors.
Caregiver Health‐Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL
Authors: Gilotra Nisha A. , Pamboukian Salpy V. , Mountis Maria , Robinson Shawn W. , Kittleson Michelle , Shah Keyur B. , Forde‐McLean Rhondalyn C. , Haas Donald C. , Horstmanshof Douglas A. , Jorde Ulrich P. , Russell Stuart D. , Taddei‐Peters Wendy C. , Jeffries Neal , Khalatbari Shokoufeh , Spino Catherine A. , Richards Blair , Yosef Matheos , Mann Douglas L. , Stewart Garrick C. , Aaronson Keith D. , Grady Kathleen L. 
Published: July 2021

Background
Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health‐related quality of life (HRQOL) and burden in ambulatory advanced HF are limited.

Methods and Results

Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow‐up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow‐up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (
P
=0.007) and less burden by both time spent (
P
<0.0001) and difficulty (
P
=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (
P
=0.034) and being a married caregiver (
P
=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03–1.99;
P
=0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29–6.96;
P
=0.011).

Conclusions
Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient‐caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.
Activation of Glucagon‐Like Peptide‐1 Receptor Ameliorates Cognitive Decline in Type 2 Diabetes Mellitus Through a Metabolism‐Independent Pathway
Authors: Li Qiang , Jia Mengxiao , Yan Zhencheng , Li Qiang , Sun Fang , He Chengkang , Li Yingsha , Zhou Xunmei , Zhang Hexuan , Liu Xiaoli , Bu Xiaona , Gao Peng , He Hongbo , Zhao Zhigang , Zhu Zhiming 
Published: July 2021

Background
Patients with hypertension and diabetes mellitus are susceptible to dementia, but regular therapy fails to reduce the risk of dementia. Glucagon‐like peptide‐1 receptor agonists have neuroprotective effects in experimental studies. We aimed to assess the effect of liraglutide, a glucagon‐like peptide‐1 receptor agonist, on cognitive function and whether its effect was associated with metabolic changes in patients with type 2 diabetes mellitus.

Methods and Results

Fifty patients with type 2 diabetes mellitus were recruited in this prospective study. All patients underwent cognitive assessment and brain activation monitoring by functional near‐infrared spectroscopy. At 12 weeks, patients in the glucagon‐like peptide‐1 group acquired better scores in all cognitive tests and showed remarkable improvement in memory and attention (
P
=0.040) test compared with the control group after multivariable adjustment. Compared with the control group, liraglutide significantly increased activation of the dorsolateral prefrontal cortex and orbitofrontal cortex brain regions (
P
=0.0038). After liraglutide treatment, cognitive scores were significantly correlated with changes in these activating brain regions (
P
<0.05), but no correlation was observed between the changes in cognitive function and changes of body mass index, blood pressure, and glycemic levels.

Conclusions
We concluded that liraglutide improves cognitive decline in patients with type 2 diabetes mellitus. This beneficial effect is independent of its hypoglycemic effect and weight loss. The optimal intervention should be targeted to cognitive decline in the early stages of dementia.

Registration

URL:
https://www.ClinicalTrials.gov
; Unique identifier: NCT03707171.
Radical Tense-Indexical Historicality and the De Se
Authors: Humphries Carl 
Published: July 2021

Abstract
“Being is said in many ways,” claimed Aristotle, initiating a discussion about existential commitment that continues today. Might there not be reasons to say something similar about “having been,” or “having happened,” where these expressions denote something’s being located in the past? Moreover, if history – construed not only as an object of inquiry (actual events, etc.) but also as a way of casting light on certain matters – is primarily concerned with “things past,” then the question just posed also seems relevant to the question of what historical understanding amounts to. While the idea that ‘being’ may mean different things in different contexts has indisputable importance, the implications of other, past-temporal expressions are elusive. In what might any differences of substantive meaning encountered there consist? One starting point for responding – the one that provides the subject matter explored here – is furnished by the question of whether or not a certain way of addressing matters relating to the past permits or precludes forms of intelligibility that could be said to be ‘radically historical.’
After arguing that the existing options for addressing this issue remain unsatisfactory, I set out an alternative view of what it could mean to endorse or reject such an idea. This involves drawing distinctions and analogies connected with notions of temporal situatedness, human practicality and historicality, which are then linked to a further contrast between two ways of understanding the referential significance of what is involved when we self-ascribe a relation to a current situation in a manner construable as implying that we take ourselves to occupy a unique, yet circumstantially defined, perspective on that situation. As regards the latter, on one reading, the specific kind of indexically referring language we use – commonly labelled “de se” – is something whose rationale is exhausted by its practical utility as a communicative tool. On the other, it is viewed as capturing something of substantive importance about how we can be thought of as standing in relation to reality. I claim that this second reading, together with the line of thinking about self-identification and self-reference it helps foreground, can shed light on what it would mean to affirm or deny the possibility of radically historical forms of intelligibility – and thus also on what it could mean to ascribe a plurality of meanings to talk concerning things being ‘in the past.’
The Potential of Application of the ECHR in Climate Change Related Cases
Authors: Siwior Przemysław 
Published: July 2021

Abstract
The purpose of this article is to analyse the existing case-law of the European Court of Human Rights (ECtHR) in environmental cases in order to determine whether the European Convention on Human Rights (ECHR) ensures protection in cases related to climate change and its adverse impacts. Due to the fact that to date the ECtHR has not yet ruled on the issue of climate change, the article analyses environmental cases addressed by the ECtHR based on article 8 (right to respect for private and family life) and article 2 (right to life) of the ECHR taking into account potential application of their conclusions to climate change.