bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nimbin analog N2 alleviates high testosterone induced oxidative stress in CHO cells and alters the expression of Tox3 and Dennd1a signal transduction pathway involved in the PCOS zebrafish
Authors: Sudhakaran Gokul , Rajesh Ravi , Murugan Raghul , Velayutham Manikandan , Guru Ajay , Boopathi Seenivasan , Muthupandian Saravanan , Gopinath Pushparathinam , Arockiaraj Jesu 
Published: December 2022

AbstractPolycystic ovarian syndrome (PCOS) is a hormonal disorder that causes enlargement of ovaries and follicular maturation arrest, which lacks efficient treatment. N2, a semi‐natural triterpenoid from the neem family, was already reported to have antioxidant and antiinflammatory properties in our previous report. This study investigated the anti‐androgenic property of N2 on testosterone‐induced oxidative stress in Chinese Hamster Ovarian cells (CHO) and PCOS zebrafish model. The testosterone exposure disrupted the antioxidant enzymes and ROS level and enhanced the apoptosis in both CHO cells and PCOS zebrafish. However, N2 significantly protected the CHO cells from ROS and apoptosis. N2 improved the Gonado somatic index (GSI) and upregulated the expression of the SOD enzyme in zebrafish ovaries. Moreover, the testosterone‐induced follicular maturation arrest was normalized by N2 treatment in histopathology studies. In addition, the gene expression studies of Tox3 and Denndla in zebrafish demonstrated that N2 could impair PCOS condition. Furthermore, to confirm the N2 activity, the in‐silico studies were performed against PCOS susceptible genes Tox3 and Dennd1a using molecular docking and molecular dynamic simulations. The results suggested that N2 alleviated the oxidative stress and apoptosis in‐vitro and in‐vivo and altered the expression of PCOS key genes.
A misuse of the EWMA‐type statistic in acceptance sampling applications
Authors: Haq Abdul , Woodall William H. 
Published: December 2022

AbstractWe study a widely recommended acceptance sampling approach based on the use of an exponentially weighted moving average statistic. A correct mathematical assessment of the resulting sampling plans shows that the required statistical performance cannot be maintained over time. For this reason, these plans are flawed and thus should not be used.
H∞ performance of multi‐agent consensus with output feedback and saturated input
Authors: Aggarwal Shubham , Goyal Jitendra Kumar , Ghosh Sandip , Kamal Shyam 
Published: December 2022

AbstractThis article addresses the distributed consensus problem for linear multi‐agent systems (MASs) with undirected connected communication topology and saturation limits on the controller input. The networked system has been modeled using a multigraph consisting of directed self‐loops. We first represent the saturated control scheme using a polytopic formulation, for appropriate consideration of the control input. Subsequently, we derive sufficient conditions for design of a robust static output feedback controller to achieve consensus of the MAS. The synthesis problem is formulated in the form of linear matrix inequalities for controller design. Next, the leader‐follower topology is considered, with a single leader, for which it is shown that the same controller design technique applies, under a multigraph with single self‐loop. Finally, we validate the theoretical results using numerical examples and further simulate the designed control method on a network of spring‐mass systems.
DLGAP5 knockdown inactivates the Wnt/β‐catenin signal to repress endometrial cancer cell malignant activities
Authors: Chen Ruipu , Liu Jing , Hu Jun , Li Chunxia , Liu Yanhua , Pan Weiwei 
Published: December 2022

AbstractHuman discs large‐associated protein 5 (DLGAP5), a microtubule‐associated protein, has been reported to be upregulated in several tumors. However, the role of DLGAP5 in endometrial cancer (EC) progression and the related underlying mechanism were still unknown. A bioinformatics analysis was performed to analyze the expression and prognostic significance of DLGAP5 in EC tissues using TCGA, CPTAC, Human Protein Atlas, and GSE63678 databases, UALCAN web tool, and the Kaplan–Meier plotter. Effects of DLGAP on EC cell malignant properties were evaluated by CCK‐8, flow cytometry analysis, TUNEL assay, caspase‐3 activity assay, and Transwell invasion assay. The expression of DLGAP5, Wnt3, c‐Myc, Ki67, and cleaved caspase‐3 was detected by western blot analysis. DLGAP5 was highly expressed and correlated with poor prognosis in EC patients. DLGAP5 knockdown inhibited proliferation and invasion, triggered apoptosis, and increased caspase‐3 activity in EC cells. Additionally, DLGAP5 knockdown inactivated the Wnt/β‐catenin signaling pathway in EC cells. Moreover, β‐catenin overexpression abolished the effects of DLGAP5 knockdown on the malignant phenotypes of EC cells. DLGAP5 silencing suppressed the malignant properties in EC cells by inactivating the Wnt/β‐catenin pathway.
Linguistic Rights in Greece: Crossing Through Territorial and Non-Territorial Arrangements
Authors: Tsitselikis Konstantinos 
Published: December 2022

AbstractSince 1913, when Greece significantly increased her territory, minority protection has come under the spotlight of international consideration and guarantees. During the past 110 years, language rights, among other minority rights, were either reluctantly granted or ignored. Although minority languages have been treated asymmetrically and incoherently, a particular pattern seems to have emerged: minority languages spoken by Christians (Vlach, Slavic languages, Arvanitika) are subject to assimilation dynamics, whereas minority languages spoken by non-Christians (Muslims, Jews) are governed by protection norms, with or without territorial criteria. This trend was shaped by international political influences and legal regulations through a very narrow perspective, which actually screened out any attempt at establishing non-territorial arrangements. Today, only one minority language enjoys special rights (mostly in the field of education), namely Turkish spoken by the Muslims of Thrace. Despite this, migratory flows after 1990, primarily from Albania, the former USSR and the Middle East, once again brought up the question of multiculturalism, language contact and language management. However, subsequent Greek governments have been reluctant to introduce special language rights for immigrants and refugees. Since Greece refrains from adhering to the main European legal instruments that safeguard language rights, such as the European Charter for Regional of Minority Languages or the Framework Convention for the Protection of National Minorities, the single protective mechanism granting linguistic rights remains the Treaty of Lausanne, which is limited to a specific minority language within a specific region. The legal protection of linguistic otherness in Greece was and still is fragmented and ambivalent, ranging from non-territorial autonomy invisibility to strict institutional territoriality.
Communication Features Facilitating Appreciation of Cultural Heritage Values for IDN
Authors: Goud Srushti , Lombardo Vincenzo 
Published: December 2022

AbstractCultural heritage values are defined as a set of characteristics perceived in heritage by certain individuals or groups. Cultural heritage values highlight the motivations for the conservation of heritage properties by national and international organizations. These include value associations selected by experts and communities. Heritage values of communities are passed down over generations and help in conservation. Historic and traditional (pre-digital) narratives communicated values but not all sources were credible. Current efforts using digital technologies for the communication of cultural heritage disproportionately focuses on engagement and spectacularization. This has had a negative effect on research towards the sharing of cultural heritage values through Interactive Digital Narratives (IDN). We believe that a number of communication features can be beneficial to value appreciation especially when using IDN. In this paper, we discuss values included by the designer(s) and also appreciated by the user(s) of IDN in the communication of cultural heritage. We address four types of features that are suggested as being influential for the communication of cultural heritage values, namely 1) narrative significance, 2) multiperspectivity, 3) dialogue facilitation, 4) contextualization. We go through six case studies and show how to exploit these IDN features to effectively communicate the associated values of cultural heritage to a larger audience.
Case Study on Verification-Witness Validators: Where We Are and Where We Go
Authors: Beyer Dirk , Strejček Jan 
Published: December 2022

AbstractSoftware-verification tools sometimes produce incorrect answers, which can be a false alarm or a wrong claim of correctness. To increase the reliability of verification results, many verifiers now accompany their answers by witnesses in an interoperable standard format. There exist witness validators that can examine the witnesses and potentially confirm the verification results. This case study analyzes the quality of existing witness validators for C programs using the witnesses produced by a wide variety of 40 verification tools that participated in SV-COMP 2022. In particular, we show that many witness validators sometimes confirm witnesses that are invalid. To remedy this situation, we suggest some advances in witness validation, including a regular comparative evaluation of validators. Our suggestions were recently adopted by the SV-COMP community for the next edition of the competition.
Flat JT gravity and the BMS-Schwarzian
Authors: Afshar Hamid , Oblak Blagoje 
Published: December 2022

Abstract
We consider Minkowskian Jackiw-Teitelboim (JT) gravity in Bondi gauge at finite temperature, with non-zero vacuum energy. Its asymptotic symmetries span an extension of the warped Virasoro group, dubbed ‘BMS2’, which we investigate in detail. In particular, we show that this extension has a single coadjoint orbit when central charges are real and non-zero. The ensuing BMS-Schwarzian action has no saddle points, and only coincides with the boundary action functional of flat JT gravity up to a crucial dilatonic zero-mode that ensures the existence of a well-defined bulk variational principle. We evaluate the corresponding gravitational partition function, which turns out to be one-loop exact precisely thanks to the presence of such a zero-mode.
Multi-objective robust optimization using adaptive surrogate models for problems with mixed continuous-categorical parameters
Authors: Moustapha Maliki , Galimshina Alina , Habert Guillaume , Sudret Bruno 
Published: December 2022

AbstractExplicitly accounting for uncertainties is paramount to the safety of engineering structures. Optimization which is often carried out at the early stage of the structural design offers an ideal framework for this task. When the uncertainties are mainly affecting the objective function, robust design optimization is traditionally considered. This work further assumes the existence of multiple and competing objective functions that need to be dealt with simultaneously. The optimization problem is formulated by considering quantiles of the objective functions which allows for the combination of both optimality and robustness in a single metric. By introducing the concept of common random numbers, the resulting nested optimization problem may be solved using a general-purpose solver, herein the non-dominated sorting genetic algorithm (NSGA-II). The computational cost of such an approach is however a serious hurdle to its application in real-world problems. We therefore propose a surrogate-assisted approach using Kriging as an inexpensive approximation of the associated computational model. The proposed approach consists of sequentially carrying out NSGA-II while using an adaptively built Kriging model to estimate the quantiles. Finally, the methodology is adapted to account for mixed categorical-continuous parameters as the applications involve the selection of qualitative design parameters as well. The methodology is first applied to two analytical examples showing its efficiency. The third application relates to the selection of optimal renovation scenarios of a building considering both its life cycle cost and environmental impact. It shows that when it comes to renovation, the heating system replacement should be the priority.
Witten deformation on non-compact manifolds: heat kernel expansion and local index theorem
Authors: Dai Xianzhe , Yan Junrong 
Published: December 2022

AbstractAsymptotic expansions of heat kernels and heat traces of Schrödinger operators on non-compact spaces are rarely explored, and even for cases as simple as $${\mathbb {C}}^n$$

C

n

with (quasi-homogeneous) polynomials potentials, it’s already very complicated. Motivated by path integral formulation of the heat kernel, we introduced a parabolic distance, which also appeared in Li–Yau’s famous work on parabolic Harnack estimate. With the help of the parabolic distance, we derive a pointwise asymptotic expansion of the heat kernel for the Witten Laplacian with strong remainder estimate. When the deformation parameter of Witten deformation and time parameter are coupled, we derive an asymptotic expansion of trace of heat kernel for small-time t, and obtain a local index theorem. This is the second of our papers in understanding Landau–Ginzburg B-models on nontrivial spaces, and in subsequent work, we will develop the Ray–Singer torsion for Witten deformation in the non-compact setting.
Evaluation of the clinical molecule anti-human-PD-L1/IL-15 KD033 in the human-PD-1/PD-L1-expressing murine model demonstrates PD-L1 targeting of IL-15 in vivo
Authors: Martomo Stella A. , Patel Jeegar 
Published: December 2022

AbstractKD033 is a clinical-stage immunocytokine composed of a high-affinity anti-human-PD-L1 antibody and the human IL-15/ IL-15 receptor sushi-domain complex. We have previously shown that KD033-surrogate, the anti-mouse-PD-L1/IL-15 immunocytokine, was efficacious in several syngeneic murine tumor models including those that were refractory to anti-PD-1/PD-L1 checkpoint blockers. KD033-surrogate showed better efficacy than the combination treatment of its component, anti-PD-L1 antibody with the non-targeting IL-15. KD033-surrogate was also efficacious in both low and high PD-L1-expressing tumors. In this study, we have utilized double knock-in mice expressing functional human PD-1/PD-L1 to show that the clinical molecule, KD033, reproduced the anti-tumor efficacy observed with KD033-surrogate in the syngeneic models. KD033 was equally efficacious in reducing the growth of human-PD-L1 positive (hPDL1+) and negative (hPDL1-) MC38 murine tumors. We observed similar peripheral pharmacodynamics changes in KD033-treated mice bearing either hPDL1+ or hPDL1- MC38 tumors. However, different transcriptomic profiles were observed between KD033-treated hPDL1+ and hPDL1- MC38 tumors with marked changes involving mostly downregulated genes in hPDL1- tumors in addition to the immune-related genes changes observed in both hPDL1+ and hPDL1- MC38 tumors. Cytotoxic and myeloid cell signatures were upregulated in both tumors with relatively greater increases observed in hPDL1- MC38 tumors. These effects of KD033 treatment in PD-L1 positive and negative tumors demonstrate the role of PD-L1 in targeting of IL-15 cytokine in vivo.
Diagnostic performance of serum pentraxin-3 in pediatric acute appendicitis: a prospective diagnostic validation study
Authors: Arredondo Montero Javier , Antona Giuseppa , Bronte Anaut Mónica , Bardají Pascual Carlos , Ros Briones Raquel , Fernández-Celis Amaya , Rivero Marcotegui Adriana , López-Andrés Natalia , Martín-Calvo Nerea 
Published: December 2022

Abstract
Introduction
Pediatric acute appendicitis (PAA) is a pathology with a high rate of diagnostic error. The search for new diagnostic tools is justified by the high morbidity and healthcare costs associated with diagnostic error.

Methods
We designed a prospective study to validate serum pentraxin-3 (PTX3) as a diagnostic tool in PAA. Participants were divided into three groups: (1) patients with no underlying pathology (2) patients with non-surgical abdominal pain and (3) patients with a confirmed diagnosis of PAA. For further analyses, patients in group 3 were divided into complicated or uncomplicated PAA. Quantitative variables were expressed as medians and interquartile ranges and categorical variables as percentages. Quantitative variables were compared using the Kruskal–Wallis test and the Mann–Whitney U test. Diagnostic performance was evaluated with ROC curves.

Results
This study included 215 patients divided into group 1 (n = 63), group 2 (n = 53) and group 3 (n = 99). Median serum PTX3 values were 2.54 (1.70–2.95) ng/mL, 3.29 (2.19–7.64) ng/mL and 8.94 (6.16–14.05) in groups 1, 2 and 3, respectively (p = 0.001). Patients with complicated PAA showed significantly higher values than patients with uncomplicated PAA (p = 0.04). The AUC (group 2 vs. 3) was 0.77 (95% CI 0.69–0.85) and the best cut-off point was at 7.28 ng/mL, with a sensitivity of 61.3% and a specificity of 73.1%. The AUC (complicated vs. uncomplicated PAA) was 0.65 (95% CI 0.54–0.77) and the best cut-off point was 12.33 ng/mL, with a sensitivity of 51.72% and a specificity of 72.73%.

Conclusions
The diagnostic ability of serum PTX3 in PAA is only moderate and therefore it cannot be considered a definitive diagnostic test. The discriminatory ability of PTX3 between complicated and uncomplicated PAA is poor. These findings, which contrast with those reported to date, should be validated with future properly designed prospective studies.
Hepatic artery intervention combined with immune-targeted therapy is superior to sequential therapy in BCLC-C hepatocellular carcinoma
Authors: Dong Hanzhi , Jian Yan , Wang Meijian , Liu Fangfang , Zhang Qi , Peng Zhiqiang , Cheng Na , Zhang Wenfeng 
Published: December 2022

Abstract
Background
Hepatic artery intervention combined with immunotarget therapy exerts excellent disease control and prolongs survival. However, the arrangement of hepatic artery intervention and systemic therapy confuses clinical decisions.

Methods
A two-center, retrospective clinical study was approved by the Institutional Ethics Committee. From December 2018 to February 2022, patients with Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) who received targeted therapy plus PD-1 inhibitors with or without hepatic artery intervention were included. According to the treatment mode, the patients were assigned to three groups: initial hepatic artery intervention combined with immunotarget therapy, immunotarget therapy sequential hepatic artery interventional therapy, and immunotarget therapy only. The survival, response, and adverse events were compared among the three groups. Subgroup analysis and univariate and multivariate prognostic analyses were also evaluated.

Results
The median follow-up time was 18.3 months (95% CI 16.7 to 20.0 months). A total of 163 patients with BCLC-C stage HCC were assigned to three groups: initial hepatic artery intervention plus PD-1 inhibitors plus targeted therapy (HPT, n = 66), PD-1 inhibitors plus targeted therapy followed by hepatic artery intervention (PTH, n = 56) and PD-1 inhibitors plus targeted therapy (PT, n = 41). The median progression-free survival was 8.37 months (95% CI 6.35–10.39) with HPT versus 5.3 months (95% CI 3.48–7.12) with PTH versus 6.33 months (95% CI 3.75–8.92) with PT. The progression-free survival of the HPT group was better than that of the PTH group (HR 0.66, 95% CI 0.45–0.97, p = 0.027) and PT group (HR 0.60, 95% CI 0.39–0.92, p = 0.01). The median overall survival was 14.6 months (95% CI 10.6–18.7) with HPT, 10.0 months (95% CI 8.2–11.8) with PTH and 11.3 months (95% CI 8.3–14.3) with PT. The 1-year overall survival (OS) rates in the HPT, PTH and PT groups were 50%, 33.9%, and 34.1%, respectively. Overall survival was significantly longer in the HTP group than in the PT group (HR 0.60, 95% CI 0.361–0.996, p = 0.032). Compared with the PTH group, the overall survival of the HTP group had a prolonged survival trend (HR 0.66, 95% CI 0.416–1.032, p = 0.059). All treatment modalities were deemed equally safe. Multivariate analysis suggested that the mode of treatment, albumin level, Child‒Pugh grade and hepatectomy history were independent prognostic factors for BCLC-C HCC patients.

Conclusions
Initial hepatic artery intervention combined with immunotarget therapy gained survival benefits with tolerable side effects compared with immunotarget sequential hepatic artery intervention and immunotarget therapy alone. Multivariate analysis suggested that liver reserve function was closely correlated with prognosis.
Assessment of pyloric sphincter physiology after Ivor-Lewis esophagectomy using an endoluminal functional lumen imaging probe
Authors: Brunner Stefanie , Lorenz Florian , Dratsch Thomas , Schröder Lorenz , Toex Ulrich , Babic Benjamin , Fuchs Hans Friedrich , Schmidt Thomas , Bruns Christiane Josephine , Goeser Tobias , Chon Seung-Hun 
Published: December 2022

Abstract
Objective of the study
The most common functional complication after Ivor-Lewis esophagectomy is the delayed emptying of the gastric conduit (DGCE) for which several diagnostic tools are available, e.g. chest X-ray, upper esophagogastroduodenoscopy (EGD) and water-soluble contrast radiogram. However, none of these diagnostic tools evaluate the pylorus itself. Our study demonstrates the successful measurement of pyloric distensibility in patients with DGCE after esophagectomy and in those without it.

Methods and procedures
Between May 2021 and October 2021, we performed a retrospective single-centre study of all patients who had an oncological Ivor-Lewis esophagectomy and underwent our post-surgery follow-up programme with surveillance endoscopies and computed tomography scans. EndoFlip™ was used to perform measurements of the pylorus under endoscopic control, and distensibility was measured at 40 ml, 45 ml and 50 ml balloon filling.

Results
We included 70 patients, and EndoFlip™ measurement was feasible in all patients. Successful application of EndoFlip™ was achieved in all interventions (n = 70, 100%). 51 patients showed a normal postoperative course, whereas 19 patients suffered from DGCE. Distensibility proved to be smaller in patients with symptoms of DGCE compared to asymptomatic patients. For 40 ml, 45 ml and 50 ml, the mean distensibility was 6.4 vs 10.1, 5.7 vs 7.9 and 4.5 vs 6.3 mm2/mmHg. The differences were significant for all three balloon fillings. No severe EndoFlip™ treatment-related adverse events occurred.

Conclusion
Measurement with EndoFlip™ is a safe and technically feasible endoscopic option for measuring the distensibility of the pylorus. Our study shows that the distensibility in asymptomatic patients after esophagectomy is significantly higher than that in patients suffering from DGCE. However, more studies need to be conducted to demonstrate the general use of EndoFlip™ measurement of the pylorus after esophagectomy.