bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Interactive Computational Pipeline to Investigate Ventricular Hemodynamics with Real‐Time Three‐Dimensional Echocardiography and Computational Fluid Dynamics
Authors: Thiel Jan‐Niklas , Verhülsdonk Daniel , Steinseifer Ulrich , Linden Katharina , Herberg Ulrike , Friehs Ingeborg , Diaz‐Gil Daniel , Neidlin Michael 
Published: November 2024

ABSTRACTBlood flow within the ventricle can provide important information on the performance of the heart. The determined blood flow structures are used to extract flow biomarkers to quantify cardiac function. Patient‐specific computational fluid dynamics (CFD) models that import segmented ventricular deformations from noninvasive imaging data for an individualized hemodynamical analysis are often used. However, tedious preprocessing of those geometries is often necessary and decisions on the modeling of the valve and the surrounding vessels have to be made on an individual level. This leads to a lack of reproducibility and usability of the existing computational models. In this work, we introduce IP‐HEART—an interactive and open‐source computational pipeline to perform geometry processing for CFD models of ventricular blood flow. We showcase its use on real‐time three‐dimensional echocardiography data of three patient datasets from two different clinical centers. We outline how different modeling assumptions of the mitral valve can be implemented and quantify their effect on CFD simulations. The results correspond well with clinical data on transvalvular Doppler ultrasound recordings and distinct flow features such as mitral jet and diastolic vortex formation can be observed. The pipeline is accompanied by an extensive video tutorial and freely available code for further use.
Epigenetic Modeling of Jumping Translocations of 1q Heterochromatin in Acute Myeloid Leukemia After 5'‐Azacytidine Treatment
Authors: Lema Fernandez Anair Graciela , Nardelli Carlotta , Pierini Valentina , Crescenzi Barbara , Pellanera Fabrizia , Matteucci Caterina , Crocioni Maria , Arniani Silvia , Di Battista Valeria , Quintini Martina , Mondanelli Giada , Orabona Ciriana , Gorello Paolo , Mecucci Cristina 
Published: November 2024

ABSTRACTJumping translocations (JT) are rare cytogenetic abnormalities associated with progression in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Typically, a tri–tetra‐somic 1q chromosome is translocated to two or more recipient chromosomes. In multiple myeloma JT were shown to originate after DNA demethylation and decondensation. Using epigenomics, we investigated sequential samples in an SRSF2‐mutated MDS and AML cohort with normal karyotype at diagnosis and 1qJT at disease evolution after 5′‐azacytidine (AZA). 1qJT breakpoints fell within repetitive DNA at both 1q12 and the translocation partners, namely acrocentrics n. 14, 15, 21, and 22, chromosome 16, and chromosome Y. The global methylome at diagnosis showed hypermethylation at 61% of the differentially methylated regions (DMRs), followed by hypomethylation at 80% of DMRs under AZA, mostly affecting pathways related to immune system, chromatin organization, chromosome condensation, telomere maintenance, rRNA, and DNA repair. At disease evolution, a shift toward hypermethylation, intronic enhancers enrichment and epigenetic involvement of the PI3K/AKT and MAPK signaling emerged. In particular, AKT1 phosphorylation behaved as a hallmark of the progression. Overall, we provided new insights on the characterization of 1qJT in SRSF2‐mutated myeloid neoplasms and first showed that epigenetics is a powerful tool to investigate the molecular landscape of repetitive DNA rearrangements.
LncRNA SNHG14 Facilitates Cisplatin Resistance Through Upregulating Notch2 via Binding to U2AF2 in Nasopharyngeal Carcinoma
Authors: Yan Sijia , Zhang Puhua , Tan Shuai , Mo Haiyun , Yang Yanlin 
Published: November 2024

ABSTRACTBackgroundCisplatin (DDP) is one of the commonly used chemotherapeutic drugs for nasopharyngeal carcinoma (NPC) patients, and the resistance of tumor cells to cisplatin is main obstacle for NPC treatment. This study explored effect and possible mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) on drug resistance of NPC cells to cisplatin.MethodsLevels of SNHG14 and Notch2 in NPC tissues and cells were confirmed using RT‐qPCR. Western blot detected Notch2 and ABCB1 expression in NPC cells. IC50 of cisplatin‐treated NPC cells was tested utilizing 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT). Cell proliferation and apoptosis were evaluated utilizing colony formation experiment and flow cytometry, respectively. RNA immunoprecipitation (RIP) assay was utilized to validate the target genes of U2AF2. Notch2 mRNA stability was tested using actinomycin D.ResultsSNHG14 level was increased in both cisplatin‐resistant NPC tissues and cell lines. SNHG14 silencing in HNE1/DDP cells resulted in inhibition of chemoresistance to cisplatin. Conversely, upregulation of SNHG14 in HNE1 cells enhanced their resistance to cisplatin. SNHG14 exhibited an interaction with U2AF2, leading to stabilization of Notch2 mRNA. Finally, Notch2 was involved in SNHG14‐mediated cisplatin resistance in NPC cells.ConclusionOur findings demonstrate SNHG14 plays a significant role in promoting chemoresistance of NPC cells to cisplatin through U2AF2/Notch2 axis. These results highlight potential therapeutic targets for NPC treatment.
Inflammatory pathways and anti‐inflammatory therapies in sickle cell disease
Authors: Tozatto‐Maio Karina , Rós Felipe A. , Weinlich Ricardo , Rocha Vanderson 
Published: November 2024

AbstractSickle cell disease (SCD) is a monogenic disease, resulting from a single‐point mutation, that presents a complex pathophysiology and high clinical heterogeneity. Inflammation stands as a prominent characteristic of SCD. Over the past few decades, the role of different cells and molecules in the regulation of the inflammatory process has been elucidated. In conjunction with the polymerization of hemoglobin S (HbS), intravascular hemolysis, which releases free heme, HbS, and hemoglobin‐related damage‐associated molecular patterns, initiates multiple inflammatory pathways that are not yet fully comprehended. These complex phenomena lead to a vicious cycle that perpetuates vaso‐occlusion, hemolysis, and inflammation. To date, few inflammatory biomarkers can predict disease complications; conversely, there is a plethora of therapies that reduce inflammation in SCD, although clinical outcomes vary widely. Importantly, whether the clinical heterogeneity and complications are related to the degree of inflammation is not known. This review aims to further our understanding of the roles of main immune cells, and other inflammatory factors, as potential prognostic biomarkers for predicting clinical outcomes or identifying novel treatments for SCD.
Disparities in childhood leukemia survival for Asian, Native Hawaiian, and Pacific Islanders in the United States
Authors: Hashibe Mia , Herget Kimberly A. , Schiffman Joshua D. , Chang Vivian Y. 
Published: November 2024

AbstractWhile some previous studies disaggregated the Asian, Native Hawaiian, and Pacific Islander (ANHPI) population to investigate survival for childhood leukemia, further studies are needed to understand the differences between subpopulations. The aim of our study was to estimate 5‐year relative survival for patients with childhood leukemia and to investigate disparities in prognostic factors with disaggregation of the ANHPI population. We used the Surveillance, Epidemiology, and End Results Program 17 database and included 1881 ANHPI patients with childhood leukemia and 8772 non‐Hispanic White (NHW) patients with childhood leukemia. The Cox proportional hazards model was used to estimate hazard ratios for the risk of death. We observed lower 5‐year relative survival rates for Southeast Asian and East Asian compared to NHW patients with childhood leukemia for acute lymphoid leukemia (ALL). The survival rates were higher for patients diagnosed at 1–9 years of age, more recent years of diagnosis, and patients residing in urban areas. The risk of death was 42% higher for East Asian patients and 50% higher for Southeast Asian patients compared to NHW patients for childhood ALL. For prognostic factors among East Asian patients with childhood leukemia, higher risks of death were observed for patients diagnosed at <12 months old and for acute myeloid leukemia compared to ALL. Further studies are needed to elucidate the reasons behind the disparities in survival rates for Southeast Asian and East Asian patients with childhood leukemia, including socioeconomic and genetic contributions to leukemia risk and clinical responses to different therapeutic modalities.
Does Algorithmic Trading Induce Herding?
Authors: Fu Servanna Mianjun , Alexakis Christos , Pappas Vasileios , Skarmeas Emmanouil , Verousis Thanos 
Published: November 2024

ABSTRACTAlgorithmic trading (AT) plays a major role in the trading activities of developed markets. This research breaks new ground by investigating how AT influences herding behaviour in stock markets. Utilising the implementation of the Markets in Financial Instruments Directive (MiFID II), we show that AT‐induced herding is quantitatively 14 times more pronounced compared to herding triggered by non‐AT elements. Algorithmic traders herd more when international volatility and market uncertainty are high, revealing a heightened sensitivity to global market signals. However, during periods of high local volatility, AT seems to disregard these fluctuations, indicating an ‘inattention effect’. AT‐induced anti‐herding is prominent in the volatile aggressive stocks, while no such behaviour is observed in the more stable defensive stocks. The findings carry critical implications for both regulators and market professionals, as we uncover dual behaviours of AT‐induced herding and anti‐herding in varying market conditions.
Texture Analysis of Fibrous Meningioma Using Label‐Free Multiphoton Microscopy
Authors: Fang Na , Shi Linjing , Su Xiaoli , Chen Rong , Hu Liwen , Li Lianhuang , Wang Xingfu , Wu Zanyi , Chen Jianxin 
Published: November 2024

ABSTRACTFibrous meningiomas, a common type of brain tumor, present surgical challenges due to their variable hardness, which is crucial for complete resection and patient prognosis. This study explores the use of label‐free multiphoton microscopy (MPM) for the objective assessment of the texture of fibrous meningiomas. Fresh tumor samples from 20 patients were analyzed using both multichannel and lambda mode MPM, with quantitative image analysis algorithms determining collagen content and multi‐peak spectral fitting providing additional optical collagen metrics. The study compared medium and hard fibrous meningiomas, utilizing receiver operating characteristic analysis to evaluate predictive performance. Microstructural features were clearly visualized, enabling accurate diagnosis. Collagen‐related parameters significantly differentiated between moderate and hard tumors (p < 0.05). High predictive values were observed for collagen content, collagen‐to‐NADH‐free ratio, and collagen‐to‐FAD ratio (AUC = 0.748–0.839). A multivariate logistic model combining these biomarkers significantly improved diagnostic accuracy (AUC = 0.907). The findings suggest that MPM, with its ability to visualize and quantify microstructures such as collagen and cells without the need for staining, holds strong potential for rapid, objective, and accurate assessment of tumor texture during neurosurgery. The integration of MPM with multiphoton endoscopy paves the way for potential in vivo applications in the future.
Molecular Mechanisms of Curdlan‐Induced Suppression of NFATc1 Expression in Osteoclasts
Authors: Koga Ayaka , Nagai‐Yoshioka Yoshie , Yamasaki Ryota , Adachi Yoshiyuki , Fujii Wataru , Ariyoshi Wataru 
Published: November 2024

ABSTRACTOsteoclasts derived from hematopoietic stem cells express immunoreceptors on their cell surface. Previously, we showed that the β‐glucan curdlan suppressed osteoclastogenesis via binding to dectin‐1, a pattern recognition receptor. Curdlan negatively regulates osteoclast differentiation and bone resorption capacity by suppressing the expression of nuclear factor of activated T cells 1 (NFATc1), a master factor for osteoclast differentiation, in a dectin‐1‐dependent manner; however, the mechanism involved in this process has not yet been fully elucidated. In this study, we aimed to elucidate the molecular mechanism involved in the suppression of RANKL‐induced osteoclast differentiation by curdlan. Real‐time RT‐qPCR results showed that curdlan suppressed the expression of NFATc1 in cells of the osteoclast progenitor cell line RAW264.7 overexpressing dectin‐1 (d‐RAW cells), without altering the expression of negative regulators. Therefore, we examined the effect of curdlan on the NF‐κB pathway, which is important for the induction of NFATc1 expression. Western blot analysis results showed that curdlan addition suppressed RANKL‐induced NF‐κB activation in the vector control line (c‐RAW) cells with low expression of dectin‐1, in d‐RAW cells, and the parental RAW264.7 (RAW) cells. The results of tartrate‐resistant alkaline phosphatase staining and real‐time RT‐qPCR showed that curdlan addition suppressed osteoclast differentiation in RAW cells, suggesting the presence of a dectin‐1‐independent modification system. Finally, we focused on the complement receptor 3 (CR3), which binds β‐glucan, and revealed that blocking the binding of β‐glucan to the CD11b molecule, a component of CR3, by neutralizing antibody, recovered the suppression of IκBα degradation by curdlan. These results suggest that the suppression of osteoclast differentiation by curdlan involves not only the dectin‐1‐dependent pathway but also the negative regulation of NFATc1 via modification of the NF‐κB pathway via CR3 recognition. The results of this study may aid to establish treatment methods for metabolic bone diseases and inflammatory bone destruction and to clarify their pathogenesis.
Tight Upper Bound on the Clique Size in the Square of 2‐Degenerate Graphs
Authors: Kim Seog‐Jin , Lian Xiaopan 
Published: November 2024

ABSTRACTThe square of a graph , denoted , has the same vertex set as and has an edge between two vertices if the distance between them in is at most 2. In general, for every graph . Charpentier (2014) asked whether if . But Hocquard, Kim, and Pierron (2019) answered his question negatively. For every even value of g, they constructed a 2‐degenerate graph such that . Note that if is a 2‐degenerate graph, then . Thus, we have that
So, it was naturally asked whether there exists a constant such that if is a 2‐degenerate graph with . Recently, Cranston and Yu (2024) showed that if is a 2‐degenerate graph, and if is a 2‐degenerate graph with . We show that there exists a constant such that if is a 2‐degenerate graph with . This upper bound on is tight by the construction in Hocquard, Kim, and Pierron.
Deep learning in fluorescence imaging and analysis
Authors: Mao Jian , He Hua 
Published: November 2024

AbstractFluorescence imaging (FI) has been instrumental in advancing biological research and enhancing biomedical diagnostics. Despite its widespread applications, FI faces challenges such as efficiently acquiring high signal‐to‐noise ratio (SNR) images, improving spatiotemporal resolution, and conducting precise quantitative analysis. Deep learning (DL), which emulates the neural network structure of the human brain, excels at learning from complex data patterns, extracting subtle features, and enhancing the SNR and spatiotemporal resolution of fluorescence images. These advancements significantly elevate the quality and usability of imaging data. Additionally, DL technology is adept at handling large datasets efficiently, which is crucial for improving the accuracy and efficiency of image analysis. This article reviews the latest advances in the application of DL to FI methodologies and their subsequent impact on biology and biomedicine. It also explores the future possibilities for DL in FI research, and providing insights and prospects could shape the field's trajectory.
Cause‐specific mortality and survival of northern bobwhite chicks
Authors: Kubečka Bradley W. , Terhune Theron M. 
Published: November 2024

AbstractSurvival of northern bobwhite (Colinus virginianus) chicks is an important parameter influencing population dynamics. We determined cause‐specific mortality and apparent daily survival of bobwhite chicks (n = 170) during 2018 and 2019 at Tall Timbers Research Station, Tallahassee, Florida, USA. We assigned cause‐specific mortality to 58 chicks and unknown fates to 45 chicks. Of those with assigned fates, avian predation comprised the majority (n = 21, 36%) followed by snakes (n = 17, 29%), mammals (n = 16, 28%), and research‐induced mortality (n = 4, 7%). Corn snakes (Pantherophis guttatus) were the primary snake species (13 of 17 snake predations) responsible for predation followed by northern cottonmouths (Agkistrodon piscivorus; n = 3) and 1 eastern diamondback rattlesnake (Crotalus adamanateus). We determined diel timing of mortalities during 2019. All corn snake predations during 2019 (n = 8) occurred during roosting (2100–0700 hrs), whereas the eastern diamondback mortality was a diurnal event; no cottonmouths depredated chicks during 2019. Nine of 11 mammalian events occurred during roosting. Two avian events occurred during 2019, both during daylight hours. Survival was best predicted by the model including the effects of chick age, hatch timing, year, and their interactions. Daily survival of chicks increased with age and reached an asymptote at approximately 70 days; late hatches (after 15 July) survived better than early hatches (βLateHatch×ChickAge = 0.059, 95% CI =−0.003–0.121) and survival for late hatches was marginally lower in 2019 (βLateHatch×ChickAge×Year19 = −0.058, 95% CI = −0.137–0.022). Management focused on increasing survival during the first 2 months of life and early nesting season may substantially benefit bobwhite population abundance. Additionally, roosting appeared to be a vulnerable period for bobwhite chicks.
β3‐Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta
Authors: Filippi Luca , Innocenti Francesca , Pascarella Francesca , Scaramuzzo Rosa Teresa , Morganti Riccardo , Bagnoli Paola , Cammalleri Maurizio , Dal Monte Massimo , Calvani Maura , Pini Alessandro 
Published: November 2024

ABSTRACTAt different stages of life, from embryonic to postnatal, varying oxygen concentrations modulate cellular gene expression by enhancing or repressing hypoxia‐inducible transcription factors. During embryonic/fetal life, these genes encode proteins involved in adapting to a low‐oxygen environment, including the induction of specific enzymes related to glycolytic metabolism, erythropoiesis, angiogenesis, and vasculogenesis. However, oxygen concentrations fluctuate during intrauterine life, enabling the induction of tissue‐specific differentiation processes. Fetal well‐being is thus closely linked to the physiological benefits of a dynamically hypoxic environment. Premature birth entails the precocious exposure of the immature fetus to a more oxygen‐rich environment compared to the womb. As a result, preterm newborns face a condition of relative hyperoxia, which alters the postnatal development of organs and contributes to prematurity‐related diseases. However, until recently, the molecular mechanism by which high oxygen tension alters normal fetal differentiation remained unclear. In this review, we discuss the research trajectory followed by our research group, which suggests that early exposure to a relatively hyperoxic environment may impair preterm neonates due to reduced expression of the β3‐adrenoceptor. Additionally, we explore how these impairments could be prevented through the pharmacological stimulation of the remaining β3‐adrenoceptors. Recent preclinical studies demonstrate that pharmacological stimulation of the β3‐adrenoceptor can decouple exposure to hyperoxia from its harmful effects, offering a glimpse of the possibility to recreating the conditions typical of intrauterine life, even after premature birth.
Multi‐collimator proton minibeam radiotherapy with joint dose and PVDR optimization
Authors: Zhang Weijie , Hong Xue , Wu Wei , Wang Chao , Johnson Daniel , Gan Gregory N. , Lin Yuting , Gao Hao 
Published: November 2024

AbstractBackgroundThe clinical translation of proton minibeam radiation therapy (pMBRT) presents significant challenges, particularly in developing an optimal treatment planning technique. A uniform target dose is crucial for maximizing anti‐tumor efficacy and facilitating the clinical acceptance of pMBRT. However, achieving a high peak‐to‐valley dose ratio (PVDR) in organs‐at‐risk (OAR) is essential for sparing normal tissue. This balance becomes particularly difficult when OARs are located distal to the beam entrance or require patient‐specific collimators.PurposeThis work proposes a novel pMBRT treatment planning method that can achieve high PVDR at OAR and uniform dose at target simultaneously, via multi‐collimator pMBRT (MC‐pMBRT) treatment planning method with joint dose and PVDR optimization (JDPO).MethodsMC‐pMBRT utilizes a set of generic and premade multi‐slit collimators with different center‐to‐center distances and does not need patient‐specific collimators. The collimator selection per field is OAR‐specific and tailored to maximize PVDR in OARs while preserving target dose uniformity. Then, the inverse optimization method JDPO is utilized to jointly optimize target dose uniformity, PVDR, and other dose‐volume‐histogram based dose objectives, which is solved by iterative convex relaxation optimization algorithm and alternating direction method of multipliers.ResultsThe need and efficacy of MC‐pMBRT is demonstrated by comparing the single‐collimator (SC) approach with the multi‐collimator (MC) approach. While SC degraded either PVDR for OAR or dose uniformity for the target, MC provided a good balance of PVDR and target dose uniformity. The proposed JDPO method is validated in comparison with the dose‐only optimization (DO) method for MC‐pMBRT, in reference to the conventional (CONV) proton RT (no pMBRT). Compared to CONV, MC‐pMBRT (DO and JDPO) preserved target dose uniformity and plan quality, while providing unique PVDR in OAR. Compared to DO, JDPO further improved PVDR via PVDR optimization during treatment planning.ConclusionA novel pMBRT treatment planning method called MC‐pMBRT is proposed that utilizes a set of generic and premade collimators with joint dose and PVDR optimization algorithm to optimize OAR‐specific PVDR and target dose uniformity simultaneously.