bluuebunny/crossref_metadata_2025 huggingface dataset:
Using extreme value theory to evaluate the leading pedestrian interval road safety intervention
Authors: Hewett Nicola , Fawcett Lee , Golightly Andrew , Thorpe Neil
Published: April 2024

Improving road safety is hugely important with the number of deaths on the world's roads remaining unacceptably high; an estimated 1.3 million people die each year as a result of road traffic collisions. Current practice for treating collision hotspots is almost always reactive: once a threshold level of collisions has been overtopped during some pre‐determined observation period, treatment is applied (e.g., road safety cameras). Traffic collisions are rare, so prolonged observation periods are necessary. However, traffic conflicts are more frequent and are a margin of the social cost; hence, traffic conflict before/after studies can be conducted over shorter time periods. We investigate the effect of implementing the leading pedestrian interval treatment at signalised intersections as a safety intervention in a city in north America. Pedestrian‐vehicle traffic conflict data were collected from treatment and control sites during the before and after periods. We implement a before/after study on post‐encroachment times (PETs) where small PET values denote ‘near‐misses’. Hence, extreme value theory is employed to model extremes of our PET processes, with adjustments to the usual modelling framework to account for temporal dependence and treatment effects.
Numerical investigation of corroded reinforced concrete exterior beam‐column joints under quasi‐static reverse cyclic loading
Authors: Dangwal Shubham , Singh Heaven
Published: April 2024

The performance of corroded exterior beam‐column joints (BCJs) at varying levels of corrosion‐induced damage has been investigated in the current research study using numerical simulation. Two reinforcement detailing regimes, that is, non‐seismic traditional detailing in accordance with IS 456:2000 and seismically detailed as per IS 13920:2016, were adopted. A three‐dimensional (3D) nonlinear finite‐element (FE) model has been proposed using the ABAQUS software. The accuracy of the numerical model was verified by the results reported in the experimental study available in the published literature. The numerical results reported a significant reduction of approximately 54.24% and 43.9% in the peak load‐carrying capacity of maximum corroded non‐seismically and seismically detailed BCJs, respectively, when compared with that of uncorroded specimens. The corrosion level influences the damage progression. The present FE model was observed to correctly capture the ultimate failure mode of the tested specimens, indicating a good correlation with the experimental results.
RETRACTED: Leptin receptor Gln223Arg and Lys109Arg polymorphisms may be associated with HBV‐related hepatocellular carcinoma risk: A system review and meta‐analysis
Authors: Dong Xiaofeng , Zou Mengjie , Li Chunxing , Luo Honglin , Zhu Shaoliang , Gong Zheng
Published: April 2024

Increasing evidence has suggested a strong association of hepatocellular carcinoma (HCC) susceptibility and Gln223Arg (rs1137101) and Lys109Arg (rs1137100) polymorphisms in leptin receptor (LEPR) genes. To provide a quantitative assessment for such correlation, we reviewed all related systems and conducted meta‐analysis for case and control researches. A literature search of Web of Science, EMBASE, PubMed, Scopus as well as China National Knowledge Infrastructure databases was collected. 95% confidence intervals (95% CIs) together with odds ratios (ORs) were calculated. Five case–control researches consisting of 1323 cases and 1919 control cases were incorporated into meta‐analysis. Researches indicated A‐allelic and AA genotype of rs1137101 were substantially related to boosted susceptibility of hepatitis B virus (HBV)‐related HCC (mutant model, OR = 1.81, 95% CI = 1.36–2.41, p < .001; allelic model, OR = 1.55, 95% CI = 1.32–1.83, p < .001). On the contrary, we observed GG genotype of rs1137101 substantially related to reduced risk of HBV‐related HCC (wild model, OR 0.59, 95%CI = 0.46–0.75, p < .001). We observed AA genotype of rs1137100 relevant to boosted HCC risk (mutant model, OR = 1.51, 95%CI = 1.14–2.01, p = .005) as well as in those with HBV‐related HCCs (homozygous model, OR = 2.12, 95%CI = 1.49–3.02, p < .001; mutant model, OR = 1.67, 95%CI = 1.23–2.26, p = .001). G‐allele and AA genotype of rs1137101 might be in connection with boosted HBV‐related HCC susceptibility, and wild‐type GG genotype might prevent diseases. AA genotype of rs1137100 might also improve HBV‐related HCC susceptibility. Such conclusions ought to be validated by larger and better‐designed researches.
Africa's overlooked top predator: Towards a better understanding of martial eagle feeding ecology in the Maasai Mara, Kenya
Authors: Hatfield Richard Stratton , Davis Allison G. , Buij Ralph , Cox John J. , Kapila Shiv , Parmuntoro Lemein , Thomsett Simon , Virani Munir Z. , Njoroge Peter , van Langevelde Frank
Published: April 2024

Raptors exert top‐down influences on ecosystems via their effects on prey population dynamics and community composition. Most raptors are sympatric with other predators, thus complicating our understanding of their relative influence in these systems. Estimates of kill rates and prey biomass recycling have been used as predation metrics that allow quantitative comparison among species and assessment of the relative role of single species within complex food webs. Few studies have produced findings of kill rates or prey biomass recycling for raptors. We used a supervised machine learning algorithm to behaviourally classify high resolution accelerometer informed GPS locations of tagged adult non‐breeding martial eagles Polemaetus bellicosus in the Maasai Mara region of Kenya to estimate kill rates and prey biomass recycling. Eagle locations classified as feeding were clustered using distance and time thresholds to identify kills and calculate kill rates. Identified kill sites were quickly ground‐truthed to confirm kills and identify prey species. We estimated kill rates for martial eagles at 0.59 kills day‐1 for males and 0.38 kills day‐1 for females, and we estimated biomass recycling per ground‐truthed kill at 1796 g for males and 3860 g for females. From our sample of identified ground‐truthed kills, ‘gamebirds' was the most frequently recorded prey category for male eagles and ‘small ungulates' was the most frequently recorded prey category for female eagles. These results position martial eagles close to sympatric mammalian top predators in trophic pyramids and provide evidence for their classification as a top predator.
Introduction
Authors: Münster Sander , Apollonio Fabrizio Ivan , Bluemel Ina , Fallavollita Federico , Foschi Riccardo , Grellert Marc , Ioannides Marinos , Jahn Peter Heinrich , Kurdiovsky Richard , Kuroczyński Piotr , Lutteroth Jan-Eric , Messemer Heike , Schelbert Georg
Published: April 2024

This chapter provides a brief overview of the history of digital 3D reconstruction. It shows in which contexts the first research projects were undertaken and how the resulting 3D models were presented to the public. It sheds light on the institutionalization of 3D reconstruction in research at universities, presentations at conferences, and specialization of architectural companies.
Infrastructure
Authors: Münster Sander , Apollonio Fabrizio Ivan , Bluemel Ina , Fallavollita Federico , Foschi Riccardo , Grellert Marc , Ioannides Marinos , Jahn Peter Heinrich , Kurdiovsky Richard , Kuroczyński Piotr , Lutteroth Jan-Eric , Messemer Heike , Schelbert Georg
Published: April 2024

Currently, a large variety of infrastructures are targeting 3D models. Recently, several overview reports on extant platforms and repositories [1–5] and 3D visualization frameworks and formats [6] were compiled. Infrastructures differ from services by including tools or services and facilities for operation. Particularly for 3D models, there is a main difference between such as repositories and aggregators for storing, collecting, and preserving 3D data as well as 3D viewers or virtual research environments that allow access to 3D models and research activities with them.
Towards an Intensional Notion of Harmony
Authors: Tranchini Luca
Published: April 2024

In this chapter we discuss how the intensional account of harmony sketched in the first chapter can be developed in a systematic way for a class of connectives whose rules are obtained in a uniform way using an inversion principle. To handle disjunction and disjunction-like connectives, the formulation of the expansions requires particular care. We discuss and compare two different ways of formulating the inversion principle and finally we investigate the prospects of developing an account of harmony for connectives whose rules do not obey inversion, pointing at the weakness of the approaches proposed in the literature so far.
Validity, Sense and Denotation in the Face of Paradoxes
Authors: Tranchini Luca
Published: April 2024

Which modifications does the account of PTS developed in the second chapter need to undergo for it to be applicable to languages containing paradoxical expressions? We argue that one of the basic tenets of Prawitz-Dummett PTS—namely, the definition of the correctness of an inference as validity preservation—must be given up. As a result, the proposed account of PTS is enriched by introducing a notion of sense alongside the one of denotation. Paradoxical derivations are shown to act as the proof-theoretic analog of singular terms endowed with sense but lacking a denotation. The question of which class of derivations should be regarded as having a denotation is reconsidered, and we show the consequences of the choice of different criteria of identity of proofs for the analysis of languages containing paradoxical expressions.
Two Kinds of Difficulties
Authors: Tranchini Luca
Published: April 2024

Two distinct kinds of cases, going back to Crabbé and Ekman, show that the Tennant-Prawitz criterion for paradoxicality overgenerates, that is, there are derivations which are intuitively non-paradoxical but which fail to normalize. We argue that a solution to “Ekman’s paradox” consists in restricting the set of admissible reduction procedures to those that do not yield a trivial notion of identity of proofs. We then discuss a different kind of solution, due to von Plato, and recently advocated by Tennant, consisting in reformulating natural deduction elimination rules in general (or parallelized) form. Developing intuitions of Ekman we show that the adoption of general rules has the consequence of hiding redundancies within derivations. Once reductions to get rid of the hidden redundancies are devised, it is clear that the adoption of general elimination rules offers no remedy to the overgeneration of the Prawitz-Tennant analysis. In this way, we indirectly provide further support for our own solution to Ekman’s paradox.
Clusters
Authors: Barrientos Armando
Published: April 2024

The chapter studies differences and similarities in social protection institutions across countries in the region with the aim of identifying country groupings or clusters. The methodological approach implemented was borrowed from the literature in social policy regimes. The grouping of countries is based on the causal outcomes of social protection institutions—employment, protection, and incorporation—and repeated for the periods associated with institutional development. The results largely confirm the findings in the social policy regime literature. There are three main clusters of countries: Southern cone countries plus Costa Rica, Mexico, and Panama; Andean countries including Paraguay; and Central American countries. Repeating the cluster analysis for different periods characterised by social protection reforms provides additional insights. The temporal analysis suggests a measure of continuity in the country groupings over time, but it also shows disruption in the membership of the clusters during the neoliberal period. Cluster memberships loosen up during this period, especially for countries like Chile and Mexico. Paying attention to measures of the distribution of transfers introduces fluidity in the membership sets of Andean and Central American countries.
Mixed boundary conditions and double-trace like deformations in Celestial holography and Wedge-like holography
Authors: Fukada Machiko , Miyata Akihiro
Published: April 2024

Abstract

According to the AdS/CFT dictionary, adding a relevant double-trace deformation f ∫ O2 to a holographic CFT action is dual to imposing mixed Neumann/Dirichlet boundary conditions for the field dual to O in AdS. We observed similar behaviour in codimension-two flat space holographies. We consider deformations of boundary conditions in flat spacetimes under flat space codimension-two holographies, Celestial holography and Wedge-like holography. In the former Celestial-holographic approach, we imposed boundary conditions on initial and final bulk states in the scattering. We find that these non-trivial boundary conditions in the bulk induce “double deformations” on the Celestial CFT side, which can be understood as an analogy of double trace deformations in the usual AdS/CFT. We compute two-point bulk scattering amplitudes under the non-trivial deformed boundary conditions. In the latter Wedge-like holography approach, we consider mixed Neumann/Dirichlet boundary conditions on the null infinity of the light-cone. We find that this mixing induces a renormalization flow in the dual Wedge CFT side under the Wedge holography, as in the usual AdS/CFT. We argue that the discrepancy between the Wedge two-point function and the Celestial two-point function originates from a sensitivity of bulk massless fields to a regularization parameter to use the usual AdS/CFT techniques.
Vascular mimicry as a facilitator of melanoma brain metastasis
Authors: Provance Olivia K. , Oria Victor O. , Tran Thuy T. , Caulfield Jasmine I. , Zito Christopher R. , Aguirre-Ducler Adam , Schalper Kurt A. , Kluger Harriet M. , Jilaveanu Lucia B.
Published: April 2024

Melanoma has the highest propensity among solid tumors to metastasize to the brain. Melanoma brain metastases (MBM) are a leading cause of death in melanoma and affect 40–60% of patients with late-stage disease. Therefore, uncovering the molecular mechanisms behind MBM is necessary to enhance therapeutic interventions. Vascular mimicry (VM) is a form of neovascularization linked to invasion, increased risk of metastasis, and poor prognosis in many tumor types, but its significance in MBM remains poorly understood. We found that VM density is elevated in MBM compared to paired extracranial specimens and is associated with tumor volume and CNS edema. In addition, our studies indicate a relevant role of YAP and TAZ, two transcriptional co-factors scarcely studied in melanoma, in tumor cell-vasculogenesis and in brain metastasis. We recently demonstrated activation of the Hippo tumor suppressor pathway and increased degradation of its downstream targets YAP and TAZ in a metastasis impaired cell line model. In the current study we establish the utility of anti-YAP/TAZ therapy in mouse models of metastatic melanoma whereby treatment effectively inhibits VM and prolongs survival of mice with MBM. The data presented herein suggest that VM may be an important and targetable mechanism in melanoma and that VM inhibition might be useful for treating MBM, an area of high unmet clinical need, thus having important implications for future treatment regimens for these patients.
Impacts of demand and supply-side interventions on South Korea’s housing markets: a dynamic housing-CGE analysis
Authors: Kim Euijune , Kim Ayoung , Nam Kyung-Min
Published: April 2024

This paper examines the impacts of housing market policies in Korea by developing a dynamic computable general equilibrium model integrating regional housing markets and multiregional mobility. We compare simulation outcomes of demand- and/or supply-side approaches in housing market interventions and address how these various policy instruments affect housing prices, demand, and household welfare. Policy simulation results suggest that supply-based interventions would be more effective than housing tax policies for cooling down overheated housing markets without decreasing consumer welfare. Tax-based demand-side approaches result in a 1.8–2.2% housing price drop and a 1.1–1.2% welfare decline annually between 2021 and 2024. In the supply-side policy, investing in housing construction leads to 3.4–4.1% lower housing prices and 1.5–1.8% enhanced welfare.
Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation
Authors: Lee Chien-Ying , Wu Sheng-Wen , Yang Jiann-Jou , Chen Wen-Ying , Chen Chun-Jung , Chen Hsin-Hung , Lee Yi-Chia , Su Chun-Hung , Kuan Yu-Hsiang
Published: April 2024

3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNFα and IL-6, were induced by 3-BrFlu through phosphorylation of NF-κB p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.
Interconnected Codons: Unravelling the Epigenetic Significance of Flanking Sequences in CpG Dyads
Authors: Creasey Leo Douglas , Tauber Eran
Published: April 2024

Hypothesizing that CpG codon dyads, formed by consecutive codons containing a cytosine-guanine pair (NNC-GNN), may play a crucial role in gene function, we conducted an extensive analysis to investigate their distribution and conservation within mammalian genes. Our findings reveal that genes characterized by a high density of CpG codon dyads are notably associated with homeobox domains and RNA polymerase II transcription factors. Conversely, genes exhibiting low CpG codon dyad density have links to DNA damage repair and mitosis. Importantly, our study identifies a re-markable increase in expressed genes that harbor CpG during embryonic development, suggesting their potential involvement in gene regulation at these developmental stages. These results under-score the functional significance of CpG codon dyads in DNA methylation and gene expression, fur-ther demonstrating the coevolution of consecutive codons and their contribution to codon usage bias.
Comparison of Different Suture Techniques on Nasal Soft Tissue Envelope to Prevent Supratip Deformity: A Histologic Study
Authors: Şibar Serhat , Erdal Ayhan Işık , Şibar Duygu , Özkoçer Süheyla Esra
Published: April 2024

Background

Studies have described various surgical maneuvers in rhinoplasty to limit thickening from excessive scarring in the supratip region. This study aimed to compare the effectiveness of three maneuvers—a simple suture, a U suture, and bolster dressing—used to avoid supratip deformity in a rabbit model.

Methods

Thirty-two male New Zealand white rabbits were included. The animals were divided into four groups, and dissection was performed in the supra-perichondrial plane up to the supratip region through an open rhinoplasty incision. After dissection, the following approaches were applied to the supratip region: Group 1, simple approximation suture; Group 2, U suture; Group 3, bolster dressing; and Group 4 (control group), no suture. All animals were sacrificed after 12 weeks. Histological analysis was performed.

Results

In Group 4, scar thickness was significantly greater than in the other groups (p < 0.05). Group 3 had greater scar thickness than Group 2 (p < 0.05). The ratio of scar thickness to skin thickness was higher in Group 4 compared with the other groups (p < 0.05). Finally, there was no difference in the ratio of scar thickness to skin thickness between Groups 1, 2, and 3 (p > 0.05).

Conclusions

In this study, it was concluded that surgical methods using sutures in the supratip region reduced scar thickness in a rabbit model, and these surgical methods had similar levels of effectiveness.

No Level Assigned

This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
COVID-19 severity in patients with chronic lymphocytic leukemia treated with venetoclax: a single-center observational cohort study
Authors: Thau Sophie , Poulsen Christian Bjørn , Brieghel Christian , Larsen Morten Kranker , Wiese Lothar , Nielsen Xiaohui Chen , Pedersen Lars Møller
Published: April 2024

Patients with chronic lymphocytic leukemia (CLL) are at high risk of developing severe COVID-19. The present study was undertaken to elucidate COVID-19 related morbidity and mortality in CLL patients treated with venetoclax. We present a single-center study of 108 patients with small lymphocytic lymphoma or CLL treated with venetoclax. Primary outcome was 30-day COVID-19 mortality. Secondary outcomes included COVID-19 severity and hospitalization rate. Forty-eight (44%) patients had PCR-verified SARS-COV-2 between March 2020 and January 2023. Thirty-six patients (75%) presented with asymptomatic/mild COVID-19 and 12 (25%) with severe/critical disease. The hospitalization rate was 46% with a 30-day mortality rate of only 4% and severe comorbidities as the primary cause of death. COVID-19 severity and mortality were similar before and during the Omicron era. High CIRS-scores (P < 0.02) and thrombocytopenia (P < 0.01) were more frequent in patients with severe/critical disease. In real-world data, most venetoclax treated patients presented with mild COVID-19. Hospitalization and mortality rates were low compared to data of general CLL populations. Our data indicate that venetoclax was a safe treatment option for CLL patients during the pandemic.
Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review
Authors: Brandel Michael G. , Plonsker Jillian H. , Rennert Robert C. , Produturi Gautam , Saripella Megana , Wali Arvin R. , McCann Carson , Ravindra Vijay M. , Santiago-Dieppa David R. , Pannell J. Scott , Steinberg Jeffrey A. , Khalessi Alexander A. , Levy Michael L.
Published: April 2024

Introduction

Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes.

Methods

We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected.

Results

Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0–2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively.

Conclusions

Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.
Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and PD-L1 Yields
Authors: Khoury Lara M. , Sheehan Kristin N. , Mariencheck William I. , Gershner Katherine A. , Maslonka Matthew , Niehaus Angela G. , Isom Scott , Bellinger Christina R.
Published: April 2024

Purpose

Immunotherapy is a leading approach for treating advanced non-small cell lung cancer (NSCLC) by targeting the PD-1/PD-L1 checkpoint signaling pathway, particularly in tumors expressing high levels of PD-L1 (Jug et al. in J Am Soc Cytopathol 9:485–493, 2020; Perrotta et al. in Chest 158: 1230–1239, 2020). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method to obtain tissue for molecular studies, including PD-L1 analysis, in unresectable tumors (Genova et al. in Front Immunol 12: 799455, 2021; Wang et al. in Ann Oncol 29: 1417–1422, 2018). This study aimed to assess the adequacy of PD-L1 assessment in EBUS-TBNA cytology specimens.

Methods

Data was collected retrospectively from patients who underwent EBUS-TBNA between 2017 and 2021 for suspected lung cancer biopsy. Samples positive for NSCLC were examined for PD-L1 expression. EBUS was performed by experienced practitioners, following institutional guidelines of a minimum of five aspirations from positively identified lesions. Sample adequacy for molecular testing was determined by the pathology department.

Results

The analysis involved 387 NSCLC cases (149 squamous cell, 191 adenocarcinoma, 47 unspecified). Of the 263 EBUS-TBNA specimens tested for PD-L1, 237 (90.1%) were deemed adequate. While 84% adhered to the protocol, adherence did not yield better results. Significantly higher PD-L1 adequacy was observed in squamous cell carcinomas (93.2%) compared to adenocarcinoma (87.6%). The number of aspirations and sedation type did not correlate with PD-L1 adequacy in either cancer type, but lesion size and location had a significant impact in adenocarcinomas. Adenocarcinoma exhibited higher PD-L1 expression (68%) compared to squamous cell carcinoma (48%).

Conclusion

EBUS-TBNA offers high yields for assessing immunotherapy markers like PD-L1, with satisfactory adequacy regardless of NSCLC subtype, lesion size, or location.
How ceramides affect the development of colon cancer: from normal colon to carcinoma
Authors: Merz Nadine , Hartel Jennifer Christina , Grösch Sabine
Published: April 2024

The integrity of the colon and the development of colon cancer depend on the sphingolipid balance in colon epithelial cells. In this review, we summarize the current knowledge on how ceramides and their complex derivatives influence normal colon development and colon cancer development. Ceramides, glucosylceramides and sphingomyelin are essential membrane components and, due to their biophysical properties, can influence the activation of membrane proteins, affecting protein–protein interactions and downstream signalling pathways. Here, we review the cellular mechanisms known to be affected by ceramides and their effects on colon development. We also describe which ceramides are deregulated during colorectal carcinogenesis, the molecular mechanisms involved in ceramide deregulation and how this affects carcinogenesis. Finally, we review new methods that are now state of the art for studying lipid-protein interactions in the physiological environment.
KAR1-induced dormancy release in Avena fatua caryopses involves reduction of caryopsis sensitivity to ABA and ABA/GAs ratio in coleorhiza and radicle
Authors: Kępczyński Jan , Dziurka Michal , Wójcik Agata
Published: April 2024

Main conclusion

The dormancy release by KAR1 is associated with a reduction of coleorhiza and radicle sensitivity to ABA as well as with reduction the ABA/GAs ratio in the coleorhiza, by a decrease content of ABA, and in the radicle, by a decrease the ABA and an increase of the GAs contents.

Both, karrikin 1 (KAR1) and gibberellin A3 (GA3), release dormancy in Avena fatua caryopses, resulting in the emergence of coleorhiza (CE) and radicle (RE). Moreover, KAR1 and GA3 stimulate CE and RE in the presence of abscisic acid (ABA), the stimulation being more effective in CE. The stimulatory effects of KAR1 and GA3 involve also the CE and RE rates. A similar effect was observed at KAR1 concentrations much lower than those of GA3. KAR1 increased the levels of bioactive GA5 and GA6 in embryos and the levels of GA1, GA5, GA3, GA6 and GA4 in radicles. The stimulatory effect of KAR1 on germination, associated with increased levels of gibberellins (GAs) and reduced levels of ABA in embryos, was counteracted by paclobutrazol (PAC), commonly regarded as a GAs biosynthesis inhibitor. Consequently, KAR1 decreased the ABA/GAs ratio, whereas PAC, used alone or in combination with KAR1, increased it. The ABA/GAs ratio was reduced by KAR1 in both coleorhiza and radicle, the effect being stronger in the latter. We present the first evidence that KAR1-induced dormancy release requires a decreased ABA/GAs ratio in coleorhiza and radicle. It is concluded that the dormancy-releasing effect of KAR1 in A. fatua caryopses includes (i) a reduction of the coleorhiza and radicle sensitivity to ABA, and (2) a reduction of the ABA/GAs ratio (i) in the coleorhiza, by decreasing the ABA content, and (ii) in the radicle, by decreasing the ABA and increasing the content GAs, particularly GA1. The results may suggest different mechanisms of dormancy release by KAR1 in monocot and dicot seeds.
Piperine, quercetin, and curcumin identified as promising natural products for topical treatment of cutaneous leishmaniasis
Authors: Clemente Camila M. , Murillo Javier , Garro Ariel G. , Arbeláez Natalia , Pineda Tatiana , Robledo Sara M. , Ravetti Soledad
Published: April 2024

Leishmania braziliensis(L. braziliensis) causes cutaneous leishmaniasis (CL) in the New World. The costs and the side effects of current treatments render imperative the development of new therapies that are affordable and easy to administer. Topical treatment would be the ideal option for the treatment of CL. This underscores the urgent need for affordable and effective treatments, with natural compounds being explored as potential solutions. The alkaloid piperine (PIP), the polyphenol curcumin (CUR), and the flavonoid quercetin (QUE), known for their diverse biological properties, are promising candidates to address these parasitic diseases. Initially, the in vitro cytotoxicity activity of the compounds was evaluated using U-937 cells, followed by the assessment of the leishmanicidal activity of these compounds against amastigotes ofL. braziliensis. Subsequently, a golden hamster model with stationary-phaseL. braziliensispromastigote infections was employed. Once the ulcer appeared, hamsters were treated with QUE, PIP, or CUR formulations and compared to the control group treated with meglumine antimoniate administered intralesionally. We observed that the three organic compounds showed high in vitro leishmanicidal activity with effective concentrations of less than 50 mM, with PIP having the highest activity at a concentration of 8 mM. None of the compounds showed cytotoxic activity for U937 macrophages with values between 500 and 700 mM. In vivo, topical treatment with QUE daily for 15 days produced cured in 100% of hamsters while the effectiveness of CUR and PIP was 83% and 67%, respectively. No failures were observed with QUE. Collectively, our data suggest that topical formulations mainly for QUE but also for CUR and PIP could be a promising topical treatment for CL. Not only the ease of obtaining or synthesizing the organic compounds evaluated in this work but also their commercial availability eliminates one of the most important barriers or bottlenecks in drug development, thus facilitating the roadmap for the development of a topical drug for the management of CL caused byL. braziliensis.
The Psychological Impacts of Pill Dysphagia: A Mixed Methods Study
Authors: Adams Rowan , Crisp Dimity A , Thomas Jackson
Published: April 2024

Pill dysphagia is a common problem amongst older adults, with significant health consequences. Previous research has found that dysphagia can negatively affect an individuals mental health and wellbeing. However, this research has not been extended to pill-specific dysphagia, which presents distinct differences from the challenges posed by swallowing food and liquids. These differences extend to causes, demographics, and physical health ramifications. This study aimed to address this gap in the literature by investigating the effects of pill dysphagia on the wellbeing of older adults. A community sample of 132 Australians aged 65–97 years completed a survey about their wellbeing and difficulty swallowing pills. Thirty-one participants who met the criteria for pill dysphagia completed further open-ended questions detailing the effects of pill dysphagia and how they manage it. Analyses of the quantitative data indicated that difficulty swallowing pills was unrelated to negative affect but negatively related to positive affect, life satisfaction, and eudemonic wellbeing. Supplementary analyses controlling for health-related variables found no significant relationships between difficulty swallowing pills and wellbeing. Responses to the open-ended questions revealed a range of physical, psychological, and practical impacts of pill dysphagia, and successful and unsuccessful methods used to assist in swallowing pills. The findings partially support the hypothesised effects of pill dysphagia on wellbeing. However, further research is required to establish if more severe pill dysphagia predicts wellbeing over and above self-rated health. Future interventions should incorporate wellbeing promotion strategies for older adults with pill dysphagia.
Effect of radiotherapy on the surface roughness and microhardness of contemporary bioactive restorative materials
Authors: Atalay Cansu , Yazici A. Ruya
Published: April 2024

Objective

The aim of this in vitro study was to evaluate the effect of radiotherapy on the surface microhardness and roughness of different bioactive restorative materials.

Materials and methods

A total of 60-disc specimens (5 mm × 2 mm) were performed in four groups (n = 15 each) from Equia Forte HT, Cention N, Activa Bioactive Restorative, and Beautifil II. Following the polishing procedure (600, 1000, 1200 grit silicon carbide papers), all specimens were irradiated at 2 Gy per fraction, five times a week for a total dose of 70 Gy in 30 fractions over 7 weeks. Before and after the irradiation, the specimens were analyzed regarding the surface roughness and microhardness. Surface morphology was also analyzed by scanning electron microscopy. Kruskal–Wallis test, Wilcoxon test, and paired sample t-test were used for statistical analysis.

Results

Significant differences were found after radiation with increased mean roughness of both Cention N (p = 0.001) and Beautifil II (p < 0.001) groups. In terms of microhardness, only the Beautifil II group showed significant differences with decreased values after radiation. There were statistically significant differences among the groups’ roughness and microhardness data before and after radiotherapy (p < 0.05).

Conclusion

The effect of radiotherapy might differ according to the type of the restorative material. Although results may differ for other tested materials, giomer tends to exhibit worse behaviour in terms of both surface roughness and microhardness.

Clinical relevance

In patients undergoing head and neck radiotherapy, it should be taken into consideration that the treatment process may also have negative effects on the surface properties of anti-caries restorative materials.
Estimation of monthly sunshine duration using satellite derived cloud data
Authors: Kaba Kazım , Erdi Erdem , Avcı Mutlu , Kandırmaz H. Mustafa
Published: April 2024

Sunshine duration (SD) is one of the critical meteorological parameters used in different fields of application such as climate, renewable energy and agriculture. In this respect, determination and/or estimation of the temporal and spatial variability of SD is critical. Meteorological satellite data/products can be used for estimating SD and in constructing their maps due to their frequent observation of large areas at once. In this study, a multilayer perceptron type artificial neural network model was built to estimate the monthly mean SD for Türkiye using the EUMETSAT CM SAF (Satellite Application Facility on Climate Monitoring) CFC (Cloud Fractional Coverage) and CTY (Cloud Type) data, GMTED2010 (Global Multi-resolution Terrain Elevation Data) data, month number and daylength. The datasets of 45 stations, spanning nine years (2005–2013), were used for training the model and 12 stations for testing and validating the simulated values. We have compared the results of our model with the ground-measured values for the whole period under consideration and the root mean square error (RMSE), mean absolute error (MAE), mean bias error (MBE) and the coefficient of determination (R2) were found as 0.7803 h, 0.6206 h, 0.1751 h and 0.9387, respectively. It has been shown that using the new generation cloud products such as CFC and CTY, elevation data such as GMTED2010 and daylength, it is possible to predict the SD for regions under the coverage of the satellite, in case no measurement is possible or may be unreliable, without needing any measured meteorological data.
Optimising patient outcomes: temporal trends in remission rates of rheumatoid arthritis patients in the Australian OPAL dataset between 2009 and 2022
Authors: Littlejohn Geoffrey , Anbumurali Nithila , O’Sullivan Catherine , Smith Tegan , Tymms Kathleen , Bird Paul , Nicholls David , Griffiths Hedley
Published: April 2024

Objective

To describe the trends in remission rates among RA patients in the OPAL dataset, spanning from 2009 to 2022, and provide insights into the effectiveness of evolving RA management approaches in real-world clinical settings.

Methods

Patients with a physician diagnosis of RA and at least 3 visits between 1 January 2009 and December 2022 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 117 Australian rheumatologists. Demographics, disease history, prescribed medications and proportions of patients in Disease Activity Score 28-joint count C-reactive protein (DAS28CRP)) categories (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)) were described.

Results

A large population (n = 48,388) of eligible patients with RA were identified in the OPAL dataset. A consistent and substantial improvement in DAS28CRP remission rates were found in (i) all patients, (ii) patients managed on conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and (iii) patients treated with biological or targeted synthetic (b/ts)DMARD therapy, increasing from approximately 50% in 2009 to over 70% by 2022. The increase in DAS28CRP remission was accompanied by reduced proportions of patients in MDA and HDA states.

Conclusion

This study highlights a consistent improvement in disease activity and rising remission rates among Australian RA patients within the OPAL dataset, offering the potential for enhanced patient outcomes and reduced disease burden.

Key Points• The treat-to-target (T2T) approach, with the treatment goal of remission or, as an alternative, a state of LDA, has been widely adopted for the management of RA in Australia.• This study demonstrates an encouraging trend of improved disease activity over time, with remission rates of Australian patients with RA steadily increasing year on year.
An update-and-stabilize framework for the minimum-norm-point problem
Authors: Fujishige Satoru , Kitahara Tomonari , Végh László A.
Published: April 2024

We consider the minimum-norm-point (MNP) problem over polyhedra, a well-studied problem that encompasses linear programming. We present a general algorithmic framework that combines two fundamental approaches for this problem: active set methods and first order methods. Our algorithm performs first order update steps, followed by iterations that aim to ‘stabilize’ the current iterate with additional projections, i.e., find a locally optimal solution whilst keeping the current tight inequalities. Such steps have been previously used in active set methods for the nonnegative least squares (NNLS) problem. We bound on the number of iterations polynomially in the dimension and in the associated circuit imbalance measure. In particular, the algorithm is strongly polynomial for network flow instances. Classical NNLS algorithms such as the Lawson–Hanson algorithm are special instantiations of our framework; as a consequence, we obtain convergence bounds for these algorithms. Our preliminary computational experiments show promising practical performance.
Molecular profiling of Greek native germplasm collection of Rosa canina L. for enhanced fruit extract production: a comprehensive approach utilizing neutral, gene, and exon-based markers
Authors: Boutsika Anastasia , Mellidou Ifigeneia , Grigoriadou Katerina , Papapanastasi Katerina , Krigas Nikos , Maloupa Eleni , Ganopoulos Ioannis , Xanthopoulou Aliki
Published: April 2024

The genus Rosa L. is globally distributed and Rosa canina L. is a distinguished member of multifaceted interest. Apart from the traditional uses of R. canina in folk medicine, food and cosmetic industries, or its ornamental applications, its rose hips are renowned for their functional bioactive components. Thus, identifying the genetic diversity within this species is crucial for any plant breeding project. This study employed three molecular markers namely inter simple sequence repeats; (ISSRs), start codon-targeted (SCoTs), and exon-based amplified polymorphisms; (EBAPs) to conduct the first comprehensive genetic analysis of 12 R. canina genotypes. DNA extraction, marker selection, and sequences’ amplification were performed following established protocols. The resulting genetic data were analyzed for polymorphism, diversity indices, and population structure using various statistical methods including principal component analysis (PCA), unweighted pair group method with arithmetic mean (UPGMA) clustering, and STRUCTURE analysis. The ISSR analysis revealed a high level of polymorphism (81.82%) and identified two major clusters in the UPGMA dendrogram. SCoT and EBAP markers also exhibited substantial polymorphism (74.56% and 82.11%, respectively) and formed three distinct clusters. PCA indicated a consistent pattern across markers suggesting reliable genetic grouping. STRUCTURE analysis supported the presence of three genetically uniform subpopulations (K = 3) within the studied R. canina germplasm collection. This study provided a comprehensive genetic characterization of the Greek native R. canina genebank collection. The observed genetic diversity and population structure offered valuable insights for future breeding programs targeting specific R. canina genetic clusters.
Arginine ingestion inhibits phagocyte invasion in eccentrically contracted rat fast-twitch muscle
Authors: Kanzaki Keita , Wada Masanobu
Published: April 2024

Eccentric contraction (ECC) has been shown to induce leukocyte invasion into skeletal muscle, resulting in muscle inflammation. This study aimed to investigate whether prior ingestion of L-arginine (ARG), a nitric oxide precursor, inhibits ECC-induced macrophage invasion. Male Wistar rats received ARG in water for 7 days, beginning 3 days prior to ECC. ECCs were induced in the anterior crural muscles for 200 cycles. Three days later, the tibialis anterior and extensor digitorum longus muscles were excised for biochemical analysis and force measurement, respectively. ARG ingestion increased nitrite and nitrate levels in plasma and muscle, inhibiting force depression and reducing CD68 content in muscles subjected to ECC. ARG ingestion also ameliorated an ECC-induced increase in protein nitration, although neither ARG ingestion nor ECC induction affected protein carbonyl levels. The present results suggest that ingestion of ARG or ARG-rich foods may alleviate inflammation by attenuating phagocyte invasion in eccentrically contracted skeletal muscles.
Determinants of bank efficiency in developed (G7) and developing (E7) countries: role of regulatory and economic environment
Authors: Nasim Asma , Nasir Muhammad Ali , Downing Gareth
Published: April 2024

Efficiency is one of the key factors promoting the long-term performance and sustainability of the banking industry. In this context, this paper investigates the implications of the regulatory environment, macroeconomic factors, monetary conditions, and uncertainty for the banking sectors’ operating as well as investment efficiencies. Using data from G7 and E7 countries from 2001 to 2020, we employ a set of empirical techniques, including Fixed Effects, Random Effects, Panel Fully Modified Least Squares, Panel Dynamic Least Squares and Generalized Method of Moments. Our key findings show that leverage, capital adequacy, monetary conditions, economic growth, price stability as well as exchange rate stability and uncertainty have substantial effects on bank efficiency, with notable differences between impact on operational and investment efficiencies and developed (G7) and developing (E7) economies.