bluuebunny/crossref_metadata_2025_split huggingface dataset:
Target space entanglement in a matrix model for the bubbling geometry
Authors: Tsuchiya Asato , Yamashiro Kazushi 
Published: April 2022

Abstract
We study the target space entanglement entropy in a complex matrix model that describes the chiral primary sector in $$ \mathcal{N} $$
N
= 4 super Yang-Mills theory, which is associated with the bubbling AdS geometry. The target space for the matrix model is a two-dimensional plane where the eigenvalues of the complex matrix distribute. The eigenvalues are viewed as the position coordinates of fermions, and the eigenvalue distribution corresponds to a droplet formed by the fermions. The droplet is identified with one that specifies a boundary condition in the bubbling geometry. We consider states in the matrix model that correspond to AdS5× S5, an AdS giant graviton and a giant graviton in the bubbling geometry. We calculate the target space entanglement entropy of a subregion for each of the states in the matrix model as well as the area of the boundary of the subregion in the bubbling geometry, and find a qualitative agreement between them.
On the Stokes-Type Resolvent Problem Associated with Time-Periodic Flow Around a Rotating Obstacle
Authors: Eiter Thomas 
Published: April 2022

AbstractConsider the resolvent problem associated with the linearized viscous flow around a rotating body. Within a setting of classical Sobolev spaces, this problem is not well posed on the whole imaginary axis. Therefore, a framework of homogeneous Sobolev spaces is introduced where existence of a unique solution can be guaranteed for every purely imaginary resolvent parameter. For this purpose, the problem is reduced to an auxiliary problem, which is studied by means of Fourier analytic tools in a group setting. In the end, uniform resolvent estimates can be derived, which lead to the existence of solutions to the associated time-periodic linear problem.
Extending the viability of human precision-cut intestinal slice model for drug metabolism studies
Authors: Biel C. , Martinec O. , Sibering B. , van Summeren K. , Wessels A. M. A. , Touw D. J. , de Jong K. P. , de Meijer V. E. , Faber K. N. , Klooster J. P. ten , de Graaf I. A. M. , Olinga P. 
Published: April 2022

AbstractHuman Precision-cut intestinal slices (hPCIS) are used to study intestinal physiology, pathophysiology, drug efficacy, toxicology, kinetics, and metabolism. However, the use of this ex vivo model is restricted to approximately a 24 h timeframe because of declining viability of the hPCIS during traditional culture. We hypothesized that we could extend the hPCIS viability by using organoid medium. Therefore, we cultured hPCIS for up to 72 h in organoid media [expansion medium (Emed) and differentiation medium (Dmed)]. After incubation, we assessed culture-induced changes on viability markers, specific cell type markers and we assessed the metabolic activity of enterocytes by measuring midazolam metabolite formation. We show that the adenosine triphosphate (ATP)/protein ratio of Emed-cultured hPCIS and morphology of both Emed- and Dmed-cultured hPCIS was improved compared to WME-cultured hPCIS. Emed-cultured hPCIS showed an increased expression of proliferation and stem cell markers, whereas Dmed-cultured hPCIS showed an increased expression of proliferation and enterocyte markers, along with increased midazolam metabolism. Using the Emed, the viability of hPCIS could be extended for up to 72 h, and proliferating stem cells remained preserved. Using Dmed, hPCS also remained viable for up to 72 h, and specifically rescued the metabolizing enterocytes during culture. In conclusion, by using two different organoid culture media, we could extend the hPCIS viability for up to 72 h of incubation and specifically steer stem cells or enterocytes towards their original function, metabolism, and proliferation, potentially allowing pharmacokinetic and toxicology studies beyond the 24 h timeframe.
Rotations with Constant $$\mathbf {{\text {curl }}}$$ are Constant
Authors: Ginster Janusz , Acharya Amit 
Published: April 2022

AbstractWe address a problem that extends a fundamental classical result of continuum mechanics from the time of its inception, as well as answers a fundamental question in the recent, modern nonlinear elastic theory of dislocations. Interestingly, the implication of our result in the latter case is qualitatively different from its well-established analog in the linear elastic theory of dislocations. It is a classical result that if $$u\in C^2({\mathbb {R}}^n;{\mathbb {R}}^n)$$

u
∈

C
2

(

R

n

;

R

n

)

and $$\nabla u \in SO(n)$$

∇
u
∈
S
O
(
n
)

, it follows that u is rigid. In this article this result is generalized to matrix fields with non-vanishing $${\text {curl }}$$

curl

. It is shown that every matrix field $$R\in C^2(\varOmega ;SO(3))$$

R
∈

C
2

(
Ω
;
S
O

(
3
)

)

such that $${\text {curl }}R = constant$$

curl

R
=
c
o
n
s
t
a
n
t

is necessarily constant. Moreover, it is proved in arbitrary dimensions that a measurable rotation field is as regular as its distributional $${\text {curl }}$$

curl

allows. In particular, a measurable matrix field $$R: \varOmega \rightarrow SO(n)$$

R
:
Ω
→
S
O
(
n
)

, whose $${\text {curl }}$$

curl

in the sense of distributions is smooth, is also smooth.
Convergence Rate to the Tracy–Widom Laws for the Largest Eigenvalue of Wigner Matrices
Authors: Schnelli Kevin , Xu Yuanyuan 
Published: April 2022

AbstractWe show that the fluctuations of the largest eigenvalue of a real symmetric or complex Hermitian Wigner matrix of size N converge to the Tracy–Widom laws at a rate $$O(N^{-1/3+\omega })$$

O
(

N

-
1
/
3
+
ω

)

, as N tends to infinity. For Wigner matrices this improves the previous rate $$O(N^{-2/9+\omega })$$

O
(

N

-
2
/
9
+
ω

)

obtained by Bourgade (J Eur Math Soc, 2021) for generalized Wigner matrices. Our result follows from a Green function comparison theorem, originally introduced by Erdős et al. (Adv Math 229(3):1435–1515, 2012) to prove edge universality, on a finer spectral parameter scale with improved error estimates. The proof relies on the continuous Green function flow induced by a matrix-valued Ornstein–Uhlenbeck process. Precise estimates on leading contributions from the third and fourth order moments of the matrix entries are obtained using iterative cumulant expansions and recursive comparisons for correlation functions, along with uniform convergence estimates for correlation kernels of the Gaussian invariant ensembles.
The soluble form of CD160 acts as a tumor mediator of immune escape in melanoma
Authors: Gauci Marie-Léa , Giustiniani Jérôme , Lepelletier Clémence , Garbar Christian , Thonnart Nicolas , Dumaz Nicolas , Foussat Arnaud , Lebbé Céleste , Bensussan Armand , Marie-Cardine Anne 
Published: April 2022

AbstractMelanoma is responsible for 90% of skin cancer-related deaths. Major therapeutic advances have led to a considerable improvement in the prognosis of patients, with the development of targeted therapies (BRAF or MEK inhibitors) and immunotherapy (anti-CTLA-4 or -PD-1 antibodies). However, the tumor constitutes an immunosuppressive microenvironment that prevents the therapeutic efficacy and/or promotes the development of secondary resistances. CD160 is an activating NK-cell receptor initially described as delineating the NK and CD8+T-cell cytotoxic populations. Three forms of CD160 have been described: (1) the GPI isoform, constitutively expressed and involved in the initiation of NK-cells' cytotoxic activity, (2) the transmembrane isoform, neo-synthesized upon cell activation, allowing the amplification of NK cells' cytotoxic functions and (3) the soluble form, generated after cleavage of the GPI isoform, which presents an immuno-suppressive activity. By performing immunohistochemistry analyses, we observed a strong expression of CD160 at the primary cutaneous tumor site of melanoma patients. We further demonstrated that melanoma cells express CD160-GPI isoform and constitutively release the soluble form (sCD160) into the tumor environment. sCD160 was shown to inhibit the cytotoxic activity of NK-cells towards their target cells. In addition, it was found in the serum of melanoma patients and associated with increased tumor dissemination. Altogether these results support a role for sCD160 in the mechanisms leading to the inhibition of anti-tumor response and immune surveillance in melanoma.
Comparison and Trends of Endovascular, Surgical and Hybrid Revascularizations and the Influence of Comorbidity in 1 Million Hospitalizations Due to Peripheral Artery Disease in Germany Between 2009 and 2018
Authors: Decker Josua A. , Helmer Magnus , Bette Stefanie , Schwarz Florian , Kroencke Thomas J. , Scheurig-Muenkler Christian 
Published: April 2022

Abstract
Objective
To analyze trends and differences of endovascular, surgical and hybrid revascularization approaches and the impact of comorbidity on characteristics, costs, and outcome of in-patients with peripheral artery disease (PAD) of the lower extremity.

Methods
Analyzing data provided by the Research Data Center of the German Federal Statistical Office, we included all hospitalizations due to PAD Fontaine IIb (Rutherford 2–3) or higher in Germany between 2009–2011 and 2016–2018. According to the individually performed procedures encoded by the Operation and Procedure Classification System, we divided hospitalizations by revascularization procedures into sole endovascular, sole surgical, hybrid, two-step and no revascularization. Patient’s comorbidity was assessed using the linear van Walraven comorbidity score (vWs).

Results
1,067,671 hospitalizations (mean age 71.3 ± 11.1 years; 60.1% male) were analyzed. Between 2009–2011 and 2016–2018, reimbursement costs rose by 28.0% from €2.72 billion (€5,350/case) to €3.49 billion (€6,238/case). The share of hospitalizations with any revascularization increased by 8.9% (67.7–73.7%) driven by an increase in two-step (+ 63.3%), hybrid (+ 58.2%) and sole endovascular revascularizations (+ 32.6%), while sole surgical approaches declined (− 18.2%). Hospitalizations of more comorbid patients (vWs ≥ 20) rose by 46.8% (21,444–31,478 cases), showed an overproportionate increase in costs of 124.6% (+ €1,750/case) and were associated with more individual procedures (+ 90.6%).

Conclusions
In-patient treatment of PAD patients shows increasing numbers of hybrid and sole endovascular revascularizations and more patients with higher comorbidity, while sole surgical interventions and in-hospital mortality decrease. Consequently, associated costs are surging especially in more comorbid patients due to an increasing number of performed procedures and escalation of therapy.
Assessment of cytochrome P450 3A4-mediated drug–drug interactions for ipatasertib using a fit-for-purpose physiologically based pharmacokinetic model
Authors: Jing Jing , Chen Yuan , Musib Luna , Jin Jin Y. , Cheung Kit Wun Kathy , Yoshida Kenta , Sane Rucha 
Published: April 2022

Abstract
Purpose
Ipatasertib, a potent and highly selective small-molecule inhibitor of AKT, is currently under investigation for treatment of cancer. Ipatasertib is a substrate and a time-dependent inhibitor of CYP3A4. It exhibits non-linear pharmacokinetics at subclinical doses in the clinical dose escalation study. To assess the DDI risk of ipatasertib at the intended clinical dose of 400 mg with CYP3A4 inhibitors, inducers, and substrates, a fit-for-purpose physiologically based pharmacokinetic (PBPK) model of ipatasertib was developed.

Methods
The PBPK model was constructed in Simcyp using in silico, in vitro, and clinical data and was optimized and verified using clinical data.

Results
The PBPK model described non-linear pharmacokinetics of ipatasertib and captured the magnitude of the observed clinical DDIs. Following repeated doses of 400 mg ipatasertib once daily (QD), the PBPK model predicted a 3.3-fold increase of ipatasertib exposure with itraconazole; a 2–2.5-fold increase with moderate CYP3A4 inhibitors, erythromycin and diltiazem; and no change with a weak CYP3A4 inhibitor, fluvoxamine. Additionally, in the presence of strong or moderate CYP3A4 inducers, rifampicin and efavirenz, ipatasertib exposures were predicted to decrease by 86% and 74%, respectively. As a perpetrator, the model predicted that ipatasertib (400 mg) caused a 1.7-fold increase in midazolam exposure.

Conclusion
This study demonstrates the value of using a fit-for-purpose PBPK model to assess the clinical DDIs for ipatasertib and to provide dosing strategies for the concurrent use of other CYP3A4 perpetrators or victims.
The impact of body mass index on prognosis in patients with colon carcinoma
Authors: Fuchs Julian , Schellerer Vera S , Brunner Maximilian , Geppert Carol I , Grützmann Robert , Weber Klaus , Merkel Susanne 
Published: April 2022

Abstract
Background
The impact of body mass index (BMI) on prognosis in patients with curatively resected stage I–III colon carcinoma was analyzed.

Methods
The prospectively collected data of 694 patients who underwent complete mesocolic excision between 2003 and 2014 were analyzed. BMI was classified into four categories: underweight (BMI < 18.5 kg/m2; n = 13), normal weight (BMI 18.5 to 24.9 kg/m2; n = 221), overweight (BMI 25.0 to 29.9 kg/m2; n = 309), and obese (BMI ≥ 30.0 kg/m2; n = 151). Univariate and multivariate analyses for comparison of prognosis were performed.

Results
The 5-year rate of locoregional recurrence in all 694 patients was 2.1%, and no differences were found with respect to BMI (p = 0.759). For distant metastasis, the 5-year rate for all patients was 13.4%, and BMI did not have a significant impact (p = 0.593). The 5-year rate of disease-free survival for all 694 patients was 72.4%. The differences with respect to BMI were not found to be significant in univariate analysis (p = 0.222). In multivariate Cox regression analysis, disease-free survival was significantly better in obese patients (HR 0.7; p = 0.034). Regarding overall survival, the 5-year rate for all patients was 78.1%. In univariate analyses, no significant differences were found for BMI (p = 0.094). In the Cox regression analysis, overweight and obese patients had significantly better survival (overweight: HR 0.7; p = 0.027; obese: HR 0.6; p = 0.019).

Conclusion
The better survival of overweight and obese patients in multivariate analyses must be interpreted with caution. It is influenced by several factors and seems to correspond to the phenomenon of the obesity paradox.
On a virtual element formulation for trusses and beams
Authors: Wriggers P.  
Published: April 2022

AbstractThe virtual element method (VEM) was developed not too long ago, starting with the paper [2] related to elasticity in solid mechanics. The virtual element method allows to revisit the construction of different elements; however, it has so far not applied to one-dimensional structures like trusses and beams. Here we study several VEM elements suitable for trusses and beams and show that the virtual element methodology produces elements that are equivalent to well-known finite elements but also elements that are different, especially for higher-order ansatz functions. It will be shown that these elements can be easily incorporated in classical finite element codes since they have the same number of unknowns as finite beam elements. Furthermore, the formulation allows to compute nonlinear structural problems undergoing large deflections and rotations.
Nuclear survivin is a prognosticator in gastroenteropancreatic neuroendocrine neoplasms: a meta-analysis
Authors: Krieg Sarah , Roderburg Christoph , Fung Stephen , Luedde Tom , Knoefel Wolfram Trudo , Krieg Andreas 
Published: April 2022

Abstract
Purpose
Gastroenteropancreatic neuroendocrine neosplasms (GEP-NEN) are biologically heterogenous tumors with an increasing incidence over the past decades. Although efforts have been made in the treatment of these tumors, survival rates in metastasized tumor stages remain frustrating. Thus, there is an urgent need to identify novel targets as alternative treatment options. In this regard, the inhibitor of apoptosis protein (IAP) family member survivin could be such an attractive target. Therefore, aim of our meta-analysis was to assess the role of survivin as a biomarker and predictor in GEP-NEN.

Methods
Medline, Web of Science and Scopus were screened for studies that fulfilled our selection criteria. Quality assessement of the studies was based on design, methodology, generalizability and results analysis. Meta-analyses were conducted using a random-effects model and effect size measures were expressed as pooled Hazard Ratio (HR) or Odds Ratio (OR) with 95% Confidence Interval (CI).

Results
Six eligible studies with 649 patients (range 77–132) assessed survivin expression in GEP-NEN by immunohistochemistry. High expression levels of nuclear survivin in GEP-NEN correlated with a shorter overall survival (HR 3.10; 95% CI 2.15–4.47; p < 0.0001). In contrast to cytoplasmic survivin (OR 1.24; CI 0.59–2.57; p = 0.57), nuclear survivin was also associated (OR 15.23; CI 3.61–64.23; p = 0.0002) with G3/poorly differentiated GEP-NEN.

Conclusion
Nuclear Survivin is highly expressed in more aggressive G3 GEP-NEN and correlates with a poor outcome. Survivin is therefore an interesting molecule for a targeted therapy, especially for patients with highly proliferative G3 GEP-NENs.
Addressing symptoms that affect patients’ eating according to the Head and Neck Patient Symptom Checklist©
Authors: Granström Brith , Holmlund Thorbjörn , Laurell Göran , Fransson Per , Tiblom Ehrsson Ylva 
Published: April 2022

AbstractPurposeThe purpose of this prospective study was to assess which nutritional impact symptoms (NIS) interfere with oral intake in patients with head and neck cancer (HNC) and how the symptoms interfere with body weight loss, up to 1 year after treatment.MethodsThis was a prospective study of 197 patients with HNC planned for treatment with curative intention. Body weight was measured before the start of treatment, at 7 weeks after the start of treatment, and at 6 and 12 months after completion of treatment. NIS and NIS interfering with oral intake at each follow-up were examined with the Head and Neck Patient Symptom Checklist©(HNSC©).ResultsAt 7 weeks of follow-up, patients experienced the greatest symptom and interference burden, and 12 months after treatment the NIS scorings had not returned to baseline. One year after treatment, the highest scored NIS to interfere with oral intake was swallowing problems, chewing difficulties, and loss of appetite. At all 3 follow-ups, the total cumulative NIS and NIS interfering with oral intake were associated with body weight loss. Factors increasing the risk for a body weight loss of ≥ 10% at 12 months after treatment were pain, loss of appetite, feeling full, sore mouth, difficulty swallowing, taste changes, and dry mouth. Women scored higher than men in NIS and NIS interfering with oral intake. Furthermore, during the study period about half of the population had a body weight loss > 5%.ConclusionBecause both nutritional and clinical factors may affect body weight, this study highlights the importance of a holistic approach when addressing the patients’ nutritional issues.Trial registrationClinicalTrials.gov NCT03343236, date of registration: November 17, 2017.
Scoping review on trauma and recovery in youth after natural disasters: what Europe can learn from natural disasters around the world
Authors: Witt Andreas , Sachser Cedric , Fegert Jörg M. 
Published: April 2022

AbstractIn the last decade, Europe has seen a rise in natural disasters. Due to climate change, an increase of such events is predicted for the future. While natural disasters have been a rare phenomenon in Europe so far, other regions of the world, such as Central and North America or Southeast Asia, have regularly been affected by Hurricanes and Tsunamis. The aim of the current study is to synthesize the literature on child development in immediate stress, prolonged reactions, trauma, and recovery after natural disasters with a special focus on trajectories of (mal-)adaptation. In a literature search using PubMed, Psychinfo and EBSCOhost, 15 studies reporting about 11 independent samples, including 11,519 participants aged 3–18 years, were identified. All studies identified resilience, recovery, and chronic trajectories. There was also evidence for delayed or relapsing trajectories. The proportions of participants within each trajectory varied across studies, but the more favorable trajectories such as resilient or recovering trajectory were the most prevalent. The results suggested a more dynamic development within the first 12 months post-disaster. Female gender, a higher trauma exposure, more life events, less social support, and negative coping emerged as risk factors. Based on the results, a stepped care approach seems useful for the treatment of victims of natural disasters. This may support victims in their recovery and strengthen their resilience. As mental health responses to disasters vary, a coordinated screening process is necessary, to plan interventions and to detect delayed or chronic trauma responses and initiate effective interventions.
Schlaganfallpfad Tirol
Authors: Boehme Christian , Krebs Stefan , Geley Theresa , Rinner Heinrich , Maurer Andreas , Runge Julia , Schoech Johannes , Willeit Johann , Kiechl Stefan , Knoflach Michael 
Published: April 2022

Zusammenfassung
Hintergrund
In der Behandlung des Schlaganfalls gibt es Fortschritte auf vielen Ebenen. Dies führt zu besseren Heilungschancen und einer Minderung körperlicher Beeinträchtigung. Akuttherapiemaßnahmen sind auf ein kurzes Zeitfenster nach Auftreten limitiert, deshalb ist das Notfallmanagement besonders kritisch. Das Projekt Schlaganfallpfad Tirol wurde realisiert, um die Versorgungskette beim Krankheitsbild Schlaganfall von der prähospitalen Phase bis zum Abschluss der Rehabilitation zu optimieren.

Ziel der Arbeit
Beschreibung des Tiroler Schlaganfallpfads als Beispiel für die Optimierung der Schlaganfallversorgung in einer mitteleuropäischen alpinen Region mit Schwerpunkt auf die prähospitale Versorgung.

Material und Methoden
In vier Teilprojekten von der Prähospitalphase bis zur Nachbehandlung wurden Versorgungsprozesse und Schnittstellen optimiert und mit Qualitätssicherungsmaßnahmen evaluiert.

Ergebnisse
Nach Implementierung hat sich die Thrombolyserate fast verdoppelt und die Rate an gutem funktionellem Outcome nach 3 Monaten verbessert. Komplikationen wie eine Aspirationspneumonie haben deutlich abgenommen. Der Zugang zu rehabilitativen Maßnahmen hat sich verbessert, insbesondere auch wegen des Aufbaus einer qualitätskontrollierten und finanzierten ambulanten Rehabilitation.

Schlussfolgerung
Ein ganzheitliches Versorgungsprojekt kann gut in die Praxis umgesetzt werden und verbessert die Versorgungsqualität beim ischämischen Schlaganfall. Der europäische Aktionsplan Schlaganfall 2018–2030 empfiehlt die Etablierung umfassender Schlaganfallpfade in allen Regionen und Ländern Europas.