bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computable conditions for order-2 CP symmetry in NHDM potentials
Authors: Plantey R. , Solberg M. Aa. 
Published: May 2024

Abstract
We derive necessary and sufficient conditions for order-2 CP (CP2) symmetry in N-Higgs-doublet potentials for N > 2. The conditions, which are formulated as relations between vectors that transform under the adjoint representation of SU(N) under a change of doublet basis, are representation theoretical in nature. Making use of Lie algebra and representation theory we devise an efficient, computable algorithm which may be applied to decide whether or not a given numerical potential is CP2 invariant.
Complexity growth and the Krylov-Wigner function
Authors: Basu Ritam , Ganguly Anirban , Nath Souparna , Parrikar Onkar 
Published: May 2024

Abstract
For any state in a D-dimensional Hilbert space with a choice of basis, one can define a discrete version of the Wigner function — a quasi-probability distribution which represents the state on a discrete phase space. The Wigner function can, in general, take on negative values, and the amount of negativity in the Wigner function has an operational meaning as a resource for quantum computation. In this note, we study the growth of Wigner negativity for a generic initial state under time evolution with chaotic Hamiltonians. We introduce the Krylov-Wigner function, i.e., the Wigner function defined with respect to the Krylov basis (with appropriate phases), and show that this choice of basis minimizes the early time growth of Wigner negativity in the large D limit. We take this as evidence that the Krylov basis (with appropriate phases) is ideally suited for a dual, semi-classical description of chaotic quantum dynamics at large D. We also numerically study the time evolution of the Krylov-Wigner function and its negativity in random matrix theory for an initial pure state. We observe that the negativity broadly shows three phases: it rises gradually for a time of $$ O\left(\sqrt{D}\right) $$
O

D

, then hits a sharp ramp and finally saturates close to its upper bound of $$ \sqrt{D} $$

D

.
Transverse compression of a thin elastic disc
Authors: Alzaidi Ahmed S. M. , Kaplunov Julius , Nikonov Anatolij , Zupančič Barbara 
Published: May 2024

AbstractThe mathematical formulations for transverse compression of a thin elastic disc are considered, including various boundary conditions along the faces of the disc. The mixed boundary conditions corresponding to the loading by normal stresses in absence of sliding are studied in detail. These conditions support an explicit solution in a Fourier series for the boundary layers localised near the edge of the disc and also do not assume making use of the Saint-Venant principle underlying the traditional asymptotic theory for thin elastic structures. As an example, an axisymmetric problem is studied. Along with the leading order solution for a plane boundary layer, a two-term outer expansion is derived. The latter is expressed through the derivatives of the prescribed stresses. Generalisations of the developed approach are addressed.
Differential Calculi on Quantum Principal Bundles Over Projective Bases
Authors: Aschieri P. , Fioresi R. , Latini E. , Weber T. 
Published: May 2024

AbstractWe propose a sheaf-theoretic approach to the theory of differential calculi on quantum principal bundles over non-affine bases. After recalling the affine case we define differential calculi on sheaves of comodule algebras as sheaves of covariant bimodules together with a morphism of sheaves -the differential- such that the Leibniz rule and surjectivity hold locally. The main class of examples is given by covariant calculi over quantum flag manifolds, which we provide via an explicit Ore extension construction. In a second step we introduce principal covariant calculi by requiring a local compatibility of the calculi on the total sheaf, base sheaf and the structure Hopf algebra in terms of exact sequences. In this case Hopf–Galois extensions of algebras lift to Hopf–Galois extensions of exterior algebras with compatible differentials. In particular, the examples of principal (covariant) calculi on the quantum principal bundles $$\mathcal {O}_q(\textrm{SL}_2(\mathbb {C}))$$

O
q

(

SL
2

(
C
)

)

and $$\mathcal {O}_q(\textrm{GL}_2(\mathbb {C}))$$

O
q

(

GL
2

(
C
)

)

over the projective space $$\textrm{P}^1(\mathbb {C})$$

P
1

(
C
)

are discussed in detail.
Physiologically-based pharmacokinetic models versus allometric scaling for prediction of tyrosine-kinase inhibitor exposure from adults to children
Authors: Centanni Maddalena , Zaher Omar , Elhad David , Karlsson Mats O. , Friberg Lena E. 
Published: May 2024

Abstract
Purpose
Model-based methods can predict pediatric exposure and support initial dose selection. The aim of this study was to evaluate the performance of allometric scaling of population pharmacokinetic (popPK) versus physiologically based pharmacokinetic (PBPK) models in predicting the exposure of tyrosine kinase inhibitors (TKIs) for pediatric patients (≥ 2 years), based on adult data. The drugs imatinib, sunitinib and pazopanib were selected as case studies due to their complex PK profiles including high inter-patient variability, active metabolites, time-varying clearances and non-linear absorption.

Methods
Pediatric concentration measurements and adult popPK models were derived from the literature. Adult PBPK models were generated in PK-Sim® using available physicochemical properties, calibrated to adult data when needed. PBPK and popPK models for the pediatric populations were translated from the models for adults and were used to simulate concentration-time profiles that were compared to the observed values.

Results
Ten pediatric datasets were collected from the literature. While both types of models captured the concentration-time profiles of imatinib, its active metabolite, sunitinib and pazopanib, the PBPK models underestimated sunitinib metabolite concentrations. In contrast, allometrically scaled popPK simulations accurately predicted all concentration-time profiles. Trough concentration (Ctrough) predictions from the popPK model fell within a 2-fold range for all compounds, while 3 out of 5 PBPK predictions exceeded this range for the imatinib and sunitinib metabolite concentrations.

Conclusion
Based on the identified case studies it appears that allometric scaling of popPK models is better suited to predict exposure of TKIs in pediatric patients ≥ 2 years. This advantage may be attributed to the stable enzyme expression patterns from 2 years old onwards, which can be easily related to adult levels through allometric scaling. In some instances, both methods performed comparably. Understanding where discrepancies between the model methods arise, can further inform model development and ultimately support pediatric dose selection.
Performance of an ultra-fast deep-learning accelerated MRI screening protocol for prostate cancer compared to a standard multiparametric protocol
Authors: Oerther B. , Engel H. , Nedelcu A. , Strecker R. , Benkert T. , Nickel D. , Weiland E. , Mayrhofer T. , Bamberg F. , Benndorf M. , Weiß J. , Wilpert C. 
Published: May 2024

Abstract
Objectives
To establish and evaluate an ultra-fast MRI screening protocol for prostate cancer (PCa) in comparison to the standard multiparametric (mp) protocol, reducing scan time and maintaining adequate diagnostic performance.

Materials and methods
This prospective single-center study included consecutive biopsy-naïve patients with suspected PCa between December 2022 and March 2023. A PI-RADSv2.1 conform mpMRI protocol was acquired in a 3 T scanner (scan time: 25 min 45 sec). In addition, two deep-learning (DL) accelerated sequences (T2- and diffusion-weighted) were acquired, serving as a screening protocol (scan time: 3 min 28 sec). Two readers evaluated image quality and the probability of PCa regarding PI-RADSv2.1 scores in two sessions. The diagnostic performance of the screening protocol with mpMRI serving as the reference standard was derived. Inter- and intra-reader agreements were evaluated using weighted kappa statistics.

Results
We included 77 patients with 97 lesions (mean age: 66 years; SD: 7.7). Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100%/100% and 89%/98% (cut-off ≥ PI-RADS 4) for reader 1 (R1) and reader 2 (R2), respectively. Mean image quality was 3.96 (R1) and 4.35 (R2) for the standard protocol vs. 4.74 and 4.57 for the screening protocol (p < 0.05). Inter-reader agreement was moderate (κ: 0.55) for the screening protocol and substantial (κ: 0.61) for the multiparametric protocol.

Conclusion
The ultra-fast screening protocol showed similar diagnostic performance and better imaging quality compared to the mpMRI in under 15% of scan time, improving efficacy and enabling the implementation of screening protocols in clinical routine.

Clinical relevance statement
The ultra-fast protocol enables examinations without contrast administration, drastically reducing scan time to 3.5 min with similar diagnostic performance and better imaging quality. This facilitates patient-friendly, efficient examinations and addresses the conflict of increasing demand for examinations at currently exhausted capacities.

Key Points

Time-consuming MRI protocols are in conflict with an expected increase in examinations required for prostate cancer screening.

An ultra-fast MRI protocol shows similar performance and better image quality compared to the standard protocol.

Deep-learning acceleration facilitates efficient and patient-friendly examinations, thus improving prostate cancer screening capacity.

Graphical Abstract
Recognizing $$\mathbf {W_2}$$ Graphs
Authors: Levit Vadim E. , Tankus David 
Published: May 2024

AbstractLet G be a graph. A set $$S \subseteq V(G)$$

S
⊆
V
(
G
)

is independent if its elements are pairwise nonadjacent. A vertex $$v \in V(G)$$

v
∈
V
(
G
)

is shedding if for every independent set $$S \subseteq V(G) {\setminus } N[v]$$

S
⊆
V
(
G
)
\
N
[
v
]

there exists $$u \in N(v)$$

u
∈
N
(
v
)

such that $$S \cup \{u\}$$

S
∪
{
u
}

is independent. An independent set S is maximal if it is not contained in another independent set. An independent set S is maximum if the size of every independent set of G is not bigger than |S|. The size of a maximum independent set of G is denoted $$\alpha (G)$$

α
(
G
)

. A graph G is well-covered if all its maximal independent sets are maximum, i.e. the size of every maximal independent set is $$\alpha (G)$$

α
(
G
)

. The graph G belongs to class $$\mathbf {W_2}$$

W
2

if every two disjoint independent sets in G are included in two disjoint maximum independent sets. If a graph belongs to the class $$\mathbf {W_2}$$

W
2

, then it is well-covered. Finding a maximum independent set in an input graph is a well-known NP-hard problem. Recognizing well-covered graphs is co-NP-complete. Recently, it was proved that deciding whether an input graph belongs to the class $$\mathbf {W_2}$$

W
2

is co-NP-complete. However, when the input is restricted to well-covered graphs, the complexity status of recognizing graphs in $$\mathbf {W_2}$$

W
2

is still not known. In this article, we investigate the connection between shedding vertices and $$\mathbf {W_2}$$

W
2

graphs. On the one hand, we prove that recognizing shedding vertices is co-NP-complete. On the other hand, we find polynomial solutions for restricted cases of the problem. We also supply polynomial characterizations of several families of $$\mathbf {W_2}$$

W
2

graphs.
Ventriculoperitoneal shunt failures at Red Cross War Memorial Children’s Hospital
Authors: Lazarus J. S. , Ohonba E. , Li Y. J. , Rohlwink U. K. , Figaji A. A. , Enslin J. M. N. 
Published: May 2024

Abstract
Introduction
Ventriculoperitoneal shunt (VP shunt) insertion is one of the mainstays of treatment of hydrocephalus and although very effective, a high rate of shunt failure persists globally. The purpose of the study was to quantify the ventriculoperitoneal shunt failure rate at Red Cross War Memorial Children’s Hospital (RCWMCH) and assess potential factors contributing to shunt failures.

Methods
A retrospective review of VP shunts done at RCWMCH between August 2015 through December 2019 was performed. Operative notes, discharge summaries and patient folders were reviewed to collect information about patient age, aetiology of hydrocephalus, index vs revision shunt, shunt system and other noticeable variables. Overall shunt failure was recorded. Univariate and multivariate models were used to determine causal relationship.

Results
Four hundred and ninety-four VP shunt operations were performed on 340 patients with 48.8% being index shunts and 51.2% revision shunts. The average patient age was 3.4 months. The total VP shunt failure rate over the study period was 31.2%, with a 7.3% infection rate, 13.6% blockage and 3.6% disconnection rate. The most common aetiologies were post-infectious hydrocephalus 29.4%, myelomeningocele 19.7% and premature intraventricular haemorrhage 14.1%. Orbis-sigma II (OSVII), distal slit valves and antibiotic-impregnated catheters were used most frequently. Failure rates were highest in the revision group, 34.7% compared to 27.3% in index shunts. Sixty-five percent (65%) of the head circumferences measured were above the + 3 Z score (> 90th centile).

Conclusion
VP shunt failure occurs most commonly in revision surgery, and care should be taken at the index operation to reduce failure risk. Surgeon level, duration of surgery, aetiology of hydrocephalus and shunt system used did not influence overall failure rates. A closer look at larger head circumferences, their effect on shunt systems and the socio-economic factors behind late presentations should be investigated further in the future.
Efficacy and safety of intravenous tenecteplase compared to alteplase before mechanical thrombectomy in acute ischemic stroke: a meta-analysis
Authors: Wu Nihong , Doeppner Thorsten R. , Hermann Dirk M. , Gronewold Janine 
Published: May 2024

Abstract
Background
The benefits and risks of tenecteplase (TNK) versus alteplase (ALT) have recently been assessed in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT) with diverse results. Due to its high fibrin specificity and lack of excitotoxicity, TNK may have a higher efficacy and safety profile. This study aimed to evaluate the benefits and risks of TNK compared to ALT in AIS patients prior to thrombectomy.

Methods
We systematically searched four key databases, PubMed, Embase, Web of Science and Cochrane Library until January 27, 2024 for clinical studies evaluating the effects of TNK versus ALT in patients with large vessel occlusion undergoing MT. A random-effect meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results
Ten studies involving 3722 patients receiving TNK (1266 patients) or ALT (2456 patients) were included (age: 69.05 ± 14.95 years; 55.64% male). Compared to ALT-treated patients, TNK-treated patients demonstrated significantly higher rates of early recanalization (odds ratio 2.02, 95%-confidence interval 1.20–3.38, p = 0.008) without increased risk of symptomatic intracerebral hemorrhage (1.06, 0.64–1.76, p = 0.82) or intracerebral hemorrhage (1.21, 0.66–2.25, p = 0.54). TNK-treated patients showed similar rates of functional independence at 90 days (1.13, 0.87–1.46, p = 0.37) as ALT-treated patients, but lower rates of mortality within 90 days (0.65, 0.44–0.96, p = 0.03).

Conclusion
TNK is superior to ALT in achieving early recanalization and is associated with lower mortality within 90 days in AIS patients undergoing MT. Compared with ALT, TNK does not significantly alter functional independence at 90 days, symptomatic intracerebral hemorrhage or intracerebral hemorrhage.
The efficacy and safety of ketamine in the treatment of super-refractory status epilepticus: a systematic review
Authors: Yan Mingyuan , Sun Tianye , Liu Jinmin , Chang Qing 
Published: May 2024

Abstract
Background
Ketamine, as an anesthetic, has been considered for terminating status epilepticus (SE); however, due to the urgency and severity of the condition, there are currently no randomized controlled trials internationally assessing the efficacy of ketamine for treating super-refractory status epilepticus. Similarly, there appears to be a lack of systematic reviews addressing this topic in the literature. Therefore, this systematic review aims to explore the effectiveness and safety of ketamine for terminating super-refractory status epilepticus.

Methods
We conducted a systematic search on PubMed, EMBASE, and Web of Science databases. Manuscripts unrelated to the research on super-refractory status epilepticus were excluded, as were manuscripts published in non-English languages. The quality assessment and risk of bias were evaluated using the MINORS criteria. Data extraction was limited to qualitative synthesis due to the unsuitability of the data for meta-analysis.

Results
Out of 782 studies retrieved from electronic databases, 11 met the inclusion criteria. Among them, 10 studies were retrospective, and 1 study was prospective. Patient data for inclusion were sourced from the case registries of the researchers' respective hospitals. Across all included studies, the administration of ketamine significantly reduced the duration of status epilepticus and demonstrated higher safety compared to patients not receiving ketamine treatment for super-refractory status epilepticus. Additionally, early administration of ketamine correlated with improved treatment outcomes. The risk of bias across all studies was deemed low.

Conclusion
This systematic review suggests that ketamine may be a feasible treatment option for super-refractory status epilepticus. However, given the critical nature of super-refractory status epilepticus, clinicians should prioritize its termination over evaluating the efficacy of specific medications, ensuring patient safety remains paramount. If feasible in real-world medical settings, future research should focus on designing randomized controlled trials to observe the specific efficacy and mechanisms of ketamine. Careful validation is necessary before considering ketamine as a first-line treatment for super-refractory status epilepticus.
Validating multiple variants of an automotive light system with Alloy 6
Authors: Cunha Alcino , Macedo Nuno , Liu Chong 
Published: May 2024

AbstractThis paper reports on the development and validation of a formal model for an automotive adaptive exterior lights system (ELS) with multiple variants in 6, which is the most recent version of the lightweight formal specification language that supports mutable relations and temporal logic. We explore different strategies to address variability, one in pure and another through an annotative language extension. We then show how and its can be used to validate systems of this nature, namely by checking that the reference scenarios are admissible, and to automatically verify whether the established requirements hold. A prototype was developed to translate the provided validation sequences into and back to further automate the validation process. The resulting ELS model was validated against the provided validation sequences and verified for most of requirements for all variants.
Evaluation of CHROMagar™ B. cepacia agar for the detection of Burkholderia cepacia complex species from sputum samples of patients with cystic fibrosis
Authors: Maruri-Aransolo Ainhize , de Dios Caballero Juan , Michelena Malkoa , Medina-Pascual María José , Carrasco Gema , Asensio Oscar , Cols Maria , Cantón Rafael ,   the GEIFQ group
Published: May 2024

Abstract
Introduction
Burkholderia cepacia complex (BCC) are non-fermenting Gram-negative bacteria that can chronically colonize the lungs of people with cystic fibrosis (pwCF), causing a severe and progressive respiratory failure, post-transplant complications and epidemic outbreaks. Therefore, rapid and accurate identification of these bacteria is relevant for pwCF, in order to facilitate early eradication and prevent chronic colonization. However, BCCs are often quite difficult to detect on culture media as they have a slow growth rate and can be hidden by other fast-growing microorganisms, including Pseudomonas aeruginosa and filamentous fungi.

Material and methods
We evaluated the sensitivity of CHROMagar™ B. cepacia agar using 11 isolates from a well-characterized BCC collection, using BCA agar (Oxoid, UK) as a gold standard. We also studied 180 clinical sputum samples to calculate positive (PPV) and negative (NPV) predictive values. Furthermore, we used three of the well-characterized BCC isolates to determine the limit of detection (LOD).

Results
Eleven isolates grew on CHROMagar™ B. cepacia at 37ºC after 48 h. The NPV and PPV of CHROMagar™ B. cepacia were 100% and 87.5%, respectively. The LOD of CHROMagar™ B. cepacia was around 1 × 103 CFU/ml, requiring a ten-fold dilution lower bacterial load than BCA for BCC detection.

Conclusion
CHROMagar™ B. cepacia agar proved to have a very good sensitivity and specificity for the detection of clinical BCCs. Moreover, the chromogenic nature of the medium allowed us to clearly differentiate BCC from other Gram-negative species, filamentous fungi and yeasts, thereby facilitating the identification of contaminants.
YAP inhibition overcomes adaptive resistance in HER2-positive gastric cancer treated with trastuzumab via the AKT/mTOR and ERK/mTOR axis
Authors: Qiao Jiao , Feng Mei , Zhou Wenyuan , Tan Yuan , Yang Shuo , Liu Qi , Wang Qingchen , Feng Weimin , Pan Yisheng , Cui Liyan 
Published: May 2024

Abstract
Background
Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) is a heterogeneous GC subtype characterized by the overexpression of HER2. To date, few specific targeted therapies have demonstrated durable efficacy in HER2-positive GC patients, with resistance to trastuzumab typically emerging within 1 year. However, the mechanisms of resistance to trastuzumab remain incompletely understood, presenting a significant challenge to clinical practice.

Methods
In this study, we integrated genetic screening and bulk transcriptome and epigenomic profiling to define the mechanisms mediating adaptive resistance to HER2 inhibitors and identify potential effective therapeutic strategies for treating HER2-positive GCs.

Results
We revealed a potential association between adaptive resistance to trastuzumab in HER2-positive GC and the expression of YES-associated protein (YAP). Notably, our investigation revealed that long-term administration of trastuzumab triggers extensive chromatin remodeling and initiates YAP gene transcription in HER2-positive cells characterized by the initial inhibition and subsequent reactivation. Furthermore, treatment of HER2-positive GC cells and cell line-derived xenografts (CDX) models with YAP inhibitors in combination with trastuzumab was found to induce synergistic effects through the AKT/mTOR and ERK/mTOR pathways.

Conclusion
These findings underscore the pivotal role of reactivated YAP and mTOR signaling pathways in the development of adaptive resistance to trastuzumab and may serve as a promising joint target to overcome resistance to trastuzumab.