bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unruh detectors and quantum chaos in JT gravity
Authors: Blommaert Andreas , Mertens Thomas G. , Verschelde Henri 
Published: March 2021

Abstract
We identify the spectral properties of Hawking-Unruh radiation in the eternal black hole at ultra low energies as a probe for the chaotic level statistics of quantum black holes. Level repulsion implies that there are barely Hawking particles with an energy smaller than the level separation. This effect is experimentally accessible by probing the Unruh heat bath with a linear detector. We provide evidence for this effect via explicit and exact calculations in JT gravity building on a radar definition of bulk observables in the model. Similar results are observed for the bath energy density. This universal feature of eternal Hawking radiation should resonate into the evaporating setup.
Quantum spin systems and supersymmetric gauge theories. Part I
Authors: Lee Norton , Nekrasov Nikita 
Published: March 2021

Abstract
The relation between supersymmetric gauge theories in four dimensions and quantum spin systems is exploited to find an explicit formula for the Jost function of the N site $$ \mathfrak{sl} $$
sl
2X X X spin chain (for infinite dimensional complex spin representations), as well as the SLN Gaudin system, which reduces, in a limiting case, to that of the N-particle periodic Toda chain. Using the non-perturbative Dyson-Schwinger equations of the supersymmetric gauge theory we establish relations between the spin chain commuting Hamiltonians with the twisted chiral ring of gauge theory. Along the way we explore the chamber dependence of the supersymmetric partition function, also the expectation value of the surface defects, giving new evidence for the AGT conjecture.
Effect of irradiation on the expression of E-cadherin and β-catenin in early and late radiation sequelae of the urinary bladder and its modulation by NF-κB inhibitor thalidomide
Authors: Krischak Alexander , Kowaliuk Jakob , Sarsarshahi Sina , Dörr Wolfgang , Kleiter Miriam 
Published: March 2021

Abstract
Purpose
In a previous study we have shown in a mouse model that administration of nuclear factor-kappa B (NF-κB) inhibitor thalidomide has promising therapeutic effects on early radiation cystitis (ERC) and late radiation sequelae (LRS) of the urinary bladder. The aim of this study was to evaluate in the same mice the effect of thalidomide on adherens junction (AJ) proteins in ERC and LRS.

Methods
Urothelial expressions of E‑cadherin and β‑catenin were assessed by immunohistochemistry in formalin-fixed paraffin-embedded (FFPE) bladder specimens over 360 days post single-dose irradiation on day 0. First, the effect of irradiation on AJ expression and then effects of thalidomide on irradiation-induced AJ alterations were assessed using three different treatment times.

Results
Irradiation provoked a biphasic upregulation of E‑cadherin and β‑catenin in the early phase. After a mild decrease of E‑cadherin and a pronounced decrease of β‑catenin at the end of the early phase, both increased again in the late phase. Early administration of thalidomide (day 1–15) resulted in a steeper rise in the first days, an extended and increased expression at the end of the early phase and a higher expression of β‑catenin alone at the beginning of the late phase.

Conclusion
Upregulation of AJ proteins is an attempt to compensate irradiation-induced impairment of urothelial barrier function. Early administration of thalidomide improves these compensatory mechanisms by inhibiting NF-κB signaling and its interfering effects.
Targeted LC-MS/MS platform for the comprehensive determination of peptides in the kallikrein-kinin system
Authors: Gangnus Tanja , Burckhardt Bjoern B. 
Published: March 2021

AbstractThe kallikrein-kinin system (KKS) is involved in many physiological and pathophysiological processes and is assumed to be connected to the development of clinical symptoms of angioedema or COVID-19, among other diseases. However, despite its diverse role in the regulation of physiological and pathophysiological functions, knowledge about the KKS in vivo remains limited. The short half-lives of kinins, their low abundance and structural similarities and the artificial generation of the kinin bradykinin greatly hinder reliable and accurate determination of kinin levels in plasma. To address these issues, a sensitive LC-MS/MS platform for the comprehensive and simultaneous determination of the four active kinins bradykinin, kallidin, des-Arg(9)-bradykinin and des-Arg(10)-kallidin and their major metabolites bradykinin 2-9, bradykinin 1-7 and bradykinin 1-5 was developed. This platform was validated according to the bioanalytical guideline of the US Food and Drug Administration regarding linearity, accuracy, precision, sensitivity, carry-over, recovery, parallelism, matrix effects and stability in plasma of healthy volunteers. The validated platform encompassed a broad calibration curve range from 2.0–15.3 pg/mL (depending on the kinin) up to 1000 pg/mL, covering the expected concentrations in disease states. No source-dependent matrix effects were identified, and suitable stability of the analytes in plasma was observed. The applicability of the developed platform was proven by the determination of endogenous levels in healthy volunteers, whose plasma kinin levels were successfully detected in the low pg/mL range. The established platform facilitates the investigation of kinin-mediated diseases (e.g. angioedema, COVID-19) and enables the assessment of the impact of altered enzyme activities on the formation or degradation of kinins.
Graphical abstract
Time dependent asymptotic analysis of the gene regulatory network of the AcrAB-TolC efflux pump system in gram-negative bacteria
Authors: Youlden George H. , Ricci Vito , Wang-Kan Xuan , Piddock Laura J. V. , Jabbari Sara , King John R. 
Published: March 2021

AbstractEfflux pumps are a mechanism of intrinsic and evolved resistance in bacteria. If an efflux pump can expel an antibiotic so that its concentration within the cell is below a killing threshold the bacteria are resistant to the antibiotic. Efflux pumps may be specific or they may pump various different substances. This is why many efflux pumps confer multi drug resistance (MDR). In particular over expression of the AcrAB−TolC efflux pump system confers MDR in bothSalmonellaandEscherichia coli. We consider the complex gene regulation network that controls expression of genes central to controlling the efflux associated genesacrABandacrEFinSalmonella. We present the first mathematical model of this gene regulatory network in the form of a system of ordinary differential equations. Using a time dependent asymptotic analysis, we examine in detail the behaviour of the efflux system on various different timescales. Asymptotic approximations of the steady states provide an analytical comparison of targets for efflux inhibition.
Feasibility and Safety of Office-Based Transnasal Balloon Dilation for Neopharyngeal and Proximal Esophageal Strictures in Patients with a History of Head and Neck Carcinoma
Authors: Schimberg Anouk S. , Wellenstein David J. , Schutte Henrieke W. , Honings J. , Marres Henri A. M. , Takes Robert P. , van den Broek Guido B. 
Published: March 2021

AbstractThe aim of this study was to assess feasibility and safety of office-based transnasal balloon dilation of neopharyngeal and proximal esophageal strictures in patients with a history of head and neck carcinoma. The secondary objective was to explore its effectiveness. This prospective case series included patients previously treated for head and neck carcinoma with neopharyngeal or proximal esophageal strictures who underwent transnasal balloon dilation under topical anesthesia. The target dilation diameter was 15 mm; if necessary dilation procedures were repeated every 2–4 weeks until this target was reached. Completion rates, adverse events, and patient experiences measured by VAS scores (0 = no complaints – 10 = unbearable complaints), dysphagia scores based on food consistency (0 = no dysphagia – 5 = unable to swallow liquids/saliva), and self-reported changes in swallowing symptoms were recorded. Follow-up was 2 months. Twenty-six procedures were performed in 12 patients, with a completion rate of 92%. One minor complication occurred, i.e. an infection of the dilation site. Tolerance of the procedure was good (median VAS = 2). The dysphagia score improved after a mean of 2.2 procedures per patient, however not significantly. Eight patients reported improvement in dysphagia, of whom 3 had recurrence of dysphagia within 1 month post-treatment. Office-based transnasal balloon dilation is a feasible and safe in-office procedure which is well-tolerated by patients. The dilations can improve dysphagia, although effects might be transient.
Stress Drop, Seismogenic Index and Fault Cohesion of Fluid-Induced Earthquakes
Authors: Shapiro Serge A. , Dinske Carsten 
Published: March 2021

AbstractSometimes, a rather high stress drop characterizes earthquakes induced by underground fluid injections or productions. In addition, long-term fluid operations in the underground can influence a seismogenic reaction of the rock per unit volume of the fluid involved. The seismogenic index is a quantitative characteristic of such a reaction. We derive a relationship between the seismogenic index and stress drop. This relationship shows that the seismogenic index increases with the average stress drop of induced seismicity. Further, we formulate a simple and rather general phenomenological model of stress drop of induced earthquakes. This model shows that both a decrease of fault cohesion during the earthquake rupture process and an enhanced level of effective stresses could lead to high stress drop. Using these two formulations, we propose the following mechanism of increasing induced seismicity rates observed, e.g., by long-term gas production at Groningen. Pore pressure depletion can lead to a systematic increase of the average stress drop (and thus, of magnitudes) due to gradually destabilizing cohesive faults and due to a general increase of effective stresses. Consequently, elevated average stress drop increases seismogenic index. This can lead to seismic risk increasing with the operation time of an underground reservoir.
Three-dimensional modeled environments versus 360 degree panoramas for mobile virtual reality training
Authors: Ritter K. A. , Chambers Terrence L. 
Published: March 2021

AbstractVirtual field trip is a way of providing users with some knowledge and exposure of a facility without requiring them to physically visit the location. Due to the high computational costs that are necessary to produce virtual environments (VEs), the potential for photorealism is sacrificed. Often these three-dimensional (3D) modeled applications use an unrealistic VE and, therefore, do not provide a full depiction of real-world environments. Panoramas can be used to showcase complex scenarios that are difficult to model and are computationally expensive to view in virtual reality (VR). Utilizing 360° panoramas can provide a low-cost and quick-to-capture alternative with photorealistic representations of the actual environment. The advantages of photorealism over 3D models for training and education are not clearly defined. This paper initially summarizes the development of a VR training application and initial pilot study. Quantitative and qualitative study then was conducted to compare the effectiveness of a 360° panorama VR training application and a 3D modeled one. Switching to a mobile VR headset saves money, increases mobility, decreases set-up and breakdown time, and has less spatial requirements. Testing results of the 3D modeled VE group had an average normalized gain of 0.03 and the 360° panorama group, 0.43. Although the 3D modeled group had slightly higher realism according to the presence questionnaire and had slightly higher averages in the comparative analysis questionnaire, the 360° panorama application has shown to be the most effective for training and the quickest to develop.
The New Normal: Coronavirus Pandemic Response Utilizing Microsoft SharePoint
Authors: Hiti Corey J. , Chang Jennifer , Gwal Kriti , Escobedo Eva , Rea Margaret , Bindra Jasjeet 
Published: March 2021

Abstract
On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus disease (COVID-19) a pandemic. Hospitals throughout the USA and the residency programs housed therein have drastically altered their standard operations to slow the spread of disease. Maintaining the educational mission of a residency program within the parameters of social distancing mandates is an unprecedented challenge to graduate medical education and will remain so for the near future. We evaluated resident perception of our efforts to transition educational activities within the residency to an online, remote format utilizing Microsoft SharePoint. Educational conferences were transitioned to a videoconferencing platform on March 13, 2020 in conjunction with the deployment of an intradepartmental Microsoft SharePoint site to provide educational resources, disseminate scheduling changes, and provide wellness resources in response to the COVID-19 pandemic. An 11-question survey available from 4 Jan 2020–4 Jun 2020 surveyed resident perceptions of the instituted changes. Twenty-six of 31 residents (83.8%) responded to the resident survey invitation. Twenty-four of 26 residents (92.3%) characterized the SharePoint as useful. Twenty of 26 residents (76.9%) desired attending guidance as to how to utilize the online resources for each resident rotation. A total of 92.3% (24/26) of residents felt that the program’s response utilizing SharePoint engendered a greater sense of belonging to their work community. Resident perception of the transition to online learning utilizing Microsoft SharePoint as a distribution platform was generally positive, helping to mitigate untoward educational consequences of the COVID-19 pandemic.
Supporting Virtual Dermatology Consultation in the Setting of COVID-19
Authors: Kutner Allison , Love Danielle , Markova Alina , Rossi Anthony , Lee Erica , Nehal Kishwer , Lacouture Mario , Rotemberg Veronica 
Published: March 2021

Abstract While telemedicine has been utilized with more frequency over the past two decades, there remained significant barriers to its broad implementation. The COVID-19 global pandemic served as a stimulus for rapid expansion and implementation of telemedicine services across medical institutions worldwide in order to maximize patient care delivery, minimize exposure risk among healthcare providers and patients alike, and avoid overcrowding of patient care facilities. In this experience report, we highlight the teledermatology initiatives executed by the Dermatology Service at Memorial Sloan Kettering Cancer Center in New York City, with particular emphasis on image ingestion and potential for future automation and improvement.
Conditional local recurrence risk: the effect of event-free years in different subtypes of breast cancer
Authors: Moossdorff M. , Vane Marissa L. G. , van Nijnatten T. J. A. , van Maaren M. C. , Goorts B. , Heuts E. M. , Strobbe L. J. A. , Smidt M. L. 
Published: March 2021

Abstract
Background
After breast cancer treatment, follow-up consists of physical examination and mammography for at least 5 years, to detect local and regional recurrence. The risk of recurrence may decrease after event-free time. This study aims to determine the risk of local recurrence (LR) as a first event until 5 years after diagnosis, conditional on being event-free for 1, 2, 3 and 4 years.

Methods
From the Netherlands Cancer Registry, all M0 breast cancers diagnosed between 2005 and 2008 were included. LR risk was calculated with Kaplan–Meier analysis, overall and for different subtypes. Conditional LR (assuming x event-free years) was determined by selecting event-free patients at x years, and calculating their LR risk within 5 years after diagnosis.

Results
Five-year follow-up was available for 34,453 patients. Overall, five-year LR as a first event occurred in 3.0%. This risk varied for different subtypes and was highest for triple negative (6.8%) and lowest for ER+PR+Her2− (2.2%) tumors. After 1, 2, 3 and 4 event-free years, the average risk of LR before 5 years after diagnosis decreased from 3.0 to 2.4, 1.6, 1.0, and 0.6%. The risk decreased in all subtypes, the effect was most pronounced in subtypes with the highest baseline risk (ER−Her2+ and triple negative breast cancer). After three event-free years, LR risk in the next 2 years was 1% or less in all subtypes except triple negative (1.6%).

Conclusion
The risk of 5-year LR as a first event was low and decreased with the number of event-free years. After three event-free years, the overall risk was 1%. This is reassuring to patients and also suggests that follow-up beyond 3 years may produce low yield of LR, both for individual patients and studies using LR as primary outcome. This can be used as a starting point to tailor follow-up to individual needs.
Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines
Authors: Yi Jae-Sung , Perla Sravan , Huang Yan , Mizuno Kana , Giordano Frank J. , Vinks Alexander A. , Bennett Anton M. 
Published: March 2021

Abstract
Purpose
Noonan syndrome with multiple lentigines (NSML) is an autosomal dominant disorder presenting with hypertrophic cardiomyopathy (HCM). Up to 85% of NSML cases are caused by mutations in the PTPN11 gene that encodes for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP2). We previously showed that low-dose dasatinib protects from the development of cardiac fibrosis in a mouse model of NSML harboring a Ptpn11Y279C mutation. This study is performed to determine the pharmacokinetic (PK) and pharmacodynamic (PD) properties of a low-dose of dasatinib in NSML mice and to determine its effectiveness in ameliorating the development of HCM.

Methods
Dasatinib was administered intraperitoneally into NSML mice with doses ranging from 0.05 to 0.5 mg/kg. PK parameters of dasatinib in NSML mice were determined. PD parameters were obtained for biochemical analyses from heart tissue. Dasatinib-treated NSML mice (0.1 mg/kg) were subjected to echocardiography and assessment of markers of HCM by qRT-PCR. Transcriptome analysis was performed from the heart tissue of low-dose dasatinib-treated mice.

Results
Low-dose dasatinib exhibited PK properties that were linear across doses in NSML mice. Dasatinib treatment of between 0.05 and 0.5 mg/kg in NSML mice yielded an exposure-dependent inhibition of c-Src and PZR tyrosyl phosphorylation and inhibited AKT phosphorylation. We found that doses as low as 0.1 mg/kg of dasatinib prevented HCM in NSML mice. Transcriptome analysis identified differentially expressed HCM-associated genes in the heart of NSML mice that were reverted to wild type levels by low-dose dasatinib administration.

Conclusion
These data demonstrate that low-dose dasatinib exhibits desirable therapeutic PK properties that is sufficient for effective target engagement to ameliorate HCM progression in NSML mice. These data demonstrate that low-dose dasatinib treatment may be an effective therapy against HCM in NSML patients.
Viscoelastic phase-field fracture using the framework of representative crack elements
Authors: Yin Bo , Storm Johannes , Kaliske Michael 
Published: March 2021

AbstractThe promising phase-field method has been intensively studied for crack approximation in brittle materials. The realistic representation of material degradation at a fully evolved crack is still one of the main challenges. Several energy split formulations have been postulated to describe the crack evolution physically. A recent approach based on the concept of representative crack elements (RCE) in Storm et al. (The concept of representative crack elements (RCE) for phase-field fracture: anisotropic elasticity and thermo-elasticity. Int J Numer Methods Eng 121:779–805, 2020) introduces a variational framework to derive the kinematically consistent material degradation. The realistic material degradation is further tested using the self-consistency condition, which is particularly compared to a discrete crack model. This work extends the brittle RCE phase-field modeling towards rate-dependent fracture evolution in a viscoelastic continuum. The novelty of this paper is taking internal variables due to viscoelasticity into account to determine the crack deformation state. Meanwhile, a transient extension from Storm et al. (The concept of representative crack elements (RCE) for phase-field fracture: anisotropic elasticity and thermo-elasticity. Int J Numer Methods Eng 121:779–805, 2020) is also considered. The model is derived thermodynamic-consistently and implemented into the FE framework. Several representative numerical examples are investigated, and consequently, the according findings and potential perspectives are discussed to close this paper.
Metaphor Comprehension in Individuals with Autism Spectrum Disorder: Core Language Skills Matter
Authors: Kalandadze Tamara , Braeken Johan , Brynskov Cecilia , Næss Kari-Anne Bottegaard 
Published: March 2021

AbstractPoor metaphor comprehension was considered a hallmark of autism spectrum disorder (ASD), but recent research has questioned the extent and the sources of these difficulties. In this cross-sectional study, we compared metaphor comprehension in individuals with ASD (N = 29) and individuals with typical development (TD; N = 31), and investigated the relationship between core language and metaphor comprehension. Individuals with ASD showed more difficulty but also a more variable performance in both metaphor and literal items of the task used than individuals with TD did. This indicates that core language ability accounts for metaphor comprehension and should be considered in future research and interventions aiming to improve metaphor comprehension in individuals with ASD.
Four propositions on integrated sustainability: toward a theoretical framework to understand the environment, peace, and sustainability nexus
Authors: Fisher Joshua , Arora Poonam , Chen Siqi , Rhee Sophia , Blaine Tempest , Simangan Dahlia 
Published: March 2021

AbstractThe sustainability agenda has evolved around a set of interconnected dilemmas regarding economic, social, and environmental goals. Progress has been made in establishing thresholds and targets that must be achieved to enable life to continue to thrive on the planet. However, much work remains to be done in articulating coherent theoretical frameworks that adequately describe the mechanisms through which sustainability outcomes are achieved. This paper reviews core concepts in the sustainability agenda to develop four propositions on integrated sustainability that collectively describe the underlying mechanisms of sustainable development. We then advance a framework for integrated sustainability and assess its viability through linear regression and principal components analysis of key selected indicators. The results provide preliminary evidence that countries with institutions that enable cooperation and regulate competition perform better in attaining integrated sustainability indicators. Our findings suggest that institutional design is important to sustainability outcomes and that further research into process-oriented mechanisms and institutional characteristics can yield substantial dividends in enabling effective sustainability policy.