bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractPatients 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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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.

Abstract
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

AbstractLeishmania 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

AbstractPill 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

Abstract
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

AbstractSunshine 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

Abstract
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

Abstract
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

Abstract
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.