bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of active CDK4-cyclin D and mechanistic basis for abemaciclib efficacy
Authors: Gharbi Severine Isabelle , Pelletier Laura A. , Espada Alfonso , Gutiérrez Jesus , Sanfeliciano Sonia Maria Gutiérrez , Rauch Charles T. , Ganado Maria Patricia , Baquero Carmen , Zapatero Elisabet , Zhang Aiping , Benach Jordi , Russell Anna-Maria , Cano Leticia , Gomez Sandra , Broughton Howard , Pulliam Nicholas , Perez Carmen Maria , Torres Raquel , Debets Marjoke F. , de Dios Alfonso , Puig Oscar , Hilgers Mark T. , Lallena Maria Jose 
Published: November 2022

AbstractDespite the biological and therapeutic relevance of CDK4/6 for the treatment of HR+, HER2- advanced breast cancer, the detailed mode of action of CDK4/6 inhibitors is not completely understood. Of particular interest, phosphorylation of CDK4 at T172 (pT172) is critical for generating the active conformation, yet no such crystal structure has been reported to date. We describe here the x-ray structure of active CDK4-cyclin D3 bound to the CDK4/6 inhibitor abemaciclib and discuss the key aspects of the catalytically-competent complex. Furthermore, the effect of CDK4/6 inhibitors on CDK4 T172 phosphorylation has not been explored, despite its role as a potential biomarker of CDK4/6 inhibitor response. We show mechanistically that CDK4/6i stabilize primed (pT172) CDK4-cyclin D complex and selectively displace p21 in responsive tumor cells. Stabilization of active CDK4-cyclin D1 complex can lead to pathway reactivation following alternate dosing regimen. Consequently, sustained binding of abemaciclib to CDK4 leads to potent cell cycle inhibition in breast cancer cell lines and prevents rebound activation of downstream signaling. Overall, our study provides key insights demonstrating that prolonged treatment with CDK4/6 inhibitors and composition of the CDK4/6-cyclin D complex are both critical determinants of abemaciclib efficacy, with implications for this class of anticancer therapy.
Analytical and numerical modeling of optical second harmonic generation in anisotropic crystals using ♯SHAARP package
Authors: Zu Rui , Wang Bo , He Jingyang , Wang Jian-Jun , Weber Lincoln , Chen Long-Qing , Gopalan Venkatraman 
Published: November 2022

AbstractElectric-dipole optical second harmonic generation (SHG) is a second-order nonlinear process that is widely used as a sensitive probe to detect broken inversion symmetry and local polar order. Analytical modeling of the SHG polarimetry of a nonlinear optical material is essential to extract its point group symmetry and the absolute nonlinear susceptibilities. Current literature on SHG analysis involves numerous approximations and a wide range of (in)accuracies. We have developed an open-source package called the Second Harmonic Analysis of Anisotropic Rotational Polarimetry (♯SHAARP.si) which derives analytical and numerical solutions of reflection SHG polarimetry from a single interface (.si) for bulk homogeneous crystals with arbitrary symmetry group, arbitrary crystal orientation, complex and anisotropic linear dielectric tensor with frequency dispersion, a general SHG tensor and arbitrary light polarization. ♯SHAARP.si enables accurate modeling of polarimetry measurements in reflection geometry from highly absorbing crystals or wedge-shaped transparent crystals. The package is extendable to multiple interfaces.
Effects of non-Newtonian viscosity on arterial and venous flow and transport
Authors: Lynch Sabrina , Nama Nitesh , Figueroa C. Alberto 
Published: November 2022

AbstractIt is well known that blood exhibits non-Newtonian viscosity, but it is generally modeled as a Newtonian fluid. However, in situations of low shear rate, the validity of the Newtonian assumption is questionable. In this study, we investigated differences between Newtonian and non-Newtonian hemodynamic metrics such as velocity, vorticity, and wall shear stress. In addition, we investigated cardiovascular transport using two different approaches, Eulerian mass transport and Lagrangian particle tracking. Non-Newtonian solutions revealed important differences in both hemodynamic and transport metrics relative to the Newtonian model. Most notably for the hemodynamic metrics, in-plane velocity and vorticity were consistently larger in the Newtonian approximation for both arterial and venous flows. Conversely, wall shear stresses were larger for the non-Newtonian case for both the arterial and venous models. Our results also indicate that for the Lagrangian metrics, the history of accumulated shear was consistently larger for both arterial and venous flows in the Newtonian approximation. Lastly, our results also suggest that the Newtonian model produces larger near wall and luminal mass transport values compared to the non-Newtonian model, likely due to the increased vorticity and recirculation. These findings demonstrate the importance of accounting for non-Newtonian behavior in cardiovascular flows exhibiting significant regions of low shear rate and recirculation.
Evaluation of input geological parameters and tunnel strain for strain-softening rock mass based on GSI
Authors: Cui Lan , Sheng Qian , Zhang Jun , Dong You-kou , Guo Zhen-shan 
Published: November 2022

AbstractThe regression analysis method is being widely adopted to analyse the tunnel strain, most of which ignore the strain-softening effect of the rock mass and fail to consider the influence of support pressure, initial stress state, and rock mass strength classification in one fitting equation. This study aims to overcome these deficiencies with a regression model used to estimate the tunnel strain. A group of geological strength indexes (GSI) are configured to quantify the input strength parameters and deformation moduli for the rock mass with a quality ranging from poor to excellent. A specific semi-analytical procedure is developed to calculate the tunnel strain around a circular opening, which is validated by comparison with those using existing methods. A nonlinear regression model is then established to analyse the obtained tunnel strain, combining twelve fitting equations to relate the tunnel strain and the factors including the support pressure, GSI, initial stress state, and critical softening parameter. Particularly, three equations are for the estimation of the critical tunnel strain, critical support pressure, and tunnel strain under elastic behaviour, respectively; and the other nine equations are for the tunnel strain with different strain-softening behaviours. The relative significance between the GSI, the initial stress and the support pressure on the tunnel strain is assessed.
Recent and rapid ecogeographical rule reversals in Northern Treeshrews
Authors: Juman Maya M. , Millien Virginie , Olson Link E. , Sargis Eric J. 
Published: November 2022

AbstractTwo of the most-studied ecogeographical rules describe patterns of body size variation within species. Bergmann’s rule predicts that individuals have larger body sizes in colder climates (typically at higher latitudes), and the island rule predicts that island populations of small-bodied species average larger in size than their mainland counterparts (insular gigantism). These rules are rarely tested in conjunction or assessed across space and time simultaneously. We investigated these patterns in the Northern Treeshrew (Tupaia belangeri) using museum specimens collected across a wide spatial and temporal range. Contrary to Bergmann’s rule, size increases with temperature in T. belangeri, a signal that is highly consistent across space and time. We also show that these rules are intertwined: Bergmann’s rule is reversed on the mainland but holds on islands, and therefore the island rule is upheld at higher, but not lower, latitudes. Moreover, we demonstrate a rapid reversal of both rules over time. The mechanism behind these inversions remains unclear, though temperature and precipitation are significant predictors of body size. Ecogeographical rules rely on the assumption of a constant relationship between size and the factors driving its variation. Our results highlight the need to question this assumption and reevaluate these rules in the context of accelerating and uneven climate change.
Incidence and challenges in management of hemodialysis catheter-related infections
Authors: Hajji Meriam , Neji Manel , Agrebi Sahar , Nessira Saoussen Ben , Hamida Fethi Ben , Barbouch Samia , Harzallah Amel , Abderrahim Ezzedine 
Published: November 2022

AbstractCatheter-related infections (CRI) are a major cause of morbidity and mortality in chronic hemodialysis (HD) patients. In this paper, we share our experience with CRI in HD patients. We recorded 49 cases of CRI among 167 patients during a period of 40 months (January 2018–April 2021). The incidence of CRI was 3.7 per 1000 catheter-days. The revealing symptoms were dominated by fever or chills (90%). Inflammatory signs were observed in 74% of cases with respectively concurrent exit-site (51%) and tunnel infection (6%). The biological inflammatory syndrome was found in 74% of patients (average CRP level = 198.9 mg/l). Blood cultures were performed in all cases and were positive in 65% of cases. Thirteen patients have been diagnosed with Infection complications, which were respectively infective endocarditis in 7 cases, septic arthritis in 3 cases, infective myositis in one case, cerebral thrombophlebitis in 1 case and mediastinitis in 1 case. The death occurred in eleven patients, it was due to septic shock in 9 cases, pulmonary embolism in one case and neurologic alterations related to cerebral thrombophlebitis. The mean seniority in HD was 16.5 months in the group with CRI and 3.7 months in the group without CRI (p < 0.04). We did not notice significant difference in mortality between tunnelled and non-tunnelled catheters. CRI does not seem to be more severe in patients with diabetes. Duration of use of the HD catheter (p < 0.007) and ferritin level (p < 0.0001) were independent factors that predispose to CRI in our population.
Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
Authors: Hall Andrew R. , Karwi Qutuba G. , Kumar Sanjeev , Dongworth Rachel , Aksentijević Dunja , Altamimi Tariq R. , Fridianto Kevin Timothy , Chinda Kroekkiat , Hernandez-Resendiz Sauri , Mahmood Mohammad U. , Michelakis Evangelos , Ramachandra Chrishan J. , Ching Jianhong , Vicencio Jose M. , Shattock Michael J. , Kovalik Jean-Paul , Yellon Derek M. , Lopaschuk Gary , Hausenloy Derek J. 
Published: November 2022

AbstractFasting increases susceptibility to acute myocardial ischaemia/reperfusion injury (IRI) but the mechanisms are unknown. Here, we investigate the role of the mitochondrial NAD+-dependent deacetylase, Sirtuin-3 (SIRT3), which has been shown to influence fatty acid oxidation and cardiac outcomes, as a potential mediator of this effect. Fasting was shown to shift metabolism from glucose towards fatty acid oxidation. This change in metabolic fuel substrate utilisation increased myocardial infarct size in wild-type (WT), but not SIRT3 heterozygous knock-out (KO) mice. Further analysis revealed SIRT3 KO mice were better adapted to starvation through an improved cardiac efficiency, thus protecting them from acute myocardial IRI. Mitochondria from SIRT3 KO mice were hyperacetylated compared to WT mice which may regulate key metabolic processes controlling glucose and fatty acid utilisation in the heart. Fasting and the associated metabolic switch to fatty acid respiration worsens outcomes in WT hearts, whilst hearts from SIRT3 KO mice are better adapted to oxidising fatty acids, thereby protecting them from acute myocardial IRI.
Fully automated condyle segmentation using 3D convolutional neural networks
Authors: Jha Nayansi , Kim Taehun , Ham Sungwon , Baek Seung-Hak , Sung Sang-Jin , Kim Yoon-Ji , Kim Namkug 
Published: November 2022

AbstractThe aim of this study was to develop an auto-segmentation algorithm for mandibular condyle using the 3D U-Net and perform a stress test to determine the optimal dataset size for achieving clinically acceptable accuracy. 234 cone-beam computed tomography images of mandibular condyles were acquired from 117 subjects from two institutions, which were manually segmented to generate the ground truth. Semantic segmentation was performed using basic 3D U-Net and a cascaded 3D U-Net. A stress test was performed using different sets of condylar images as the training, validation, and test datasets. Relative accuracy was evaluated using dice similarity coefficients (DSCs) and Hausdorff distance (HD). In the five stages, the DSC ranged 0.886–0.922 and 0.912–0.932 for basic 3D U-Net and cascaded 3D U-Net, respectively; the HD ranged 2.557–3.099 and 2.452–2.600 for basic 3D U-Net and cascaded 3D U-Net, respectively. Stage V (largest data from two institutions) exhibited the highest DSC of 0.922 ± 0.021 and 0.932 ± 0.023 for basic 3D U-Net and cascaded 3D U-Net, respectively. Stage IV (200 samples from two institutions) had a lower performance than stage III (162 samples from one institution). Our results show that fully automated segmentation of mandibular condyles is possible using 3D U-Net algorithms, and the segmentation accuracy increases as training data increases.
Disease-related compound identification based on deeping learning method
Authors: Yang Bin , Bao Wenzheng , Wang Jinglong , Chen Baitong , Iwamori Naoki , Chen Jiazi , Chen Yuehui 
Published: November 2022

AbstractAcute lung injury (ALI) is a serious respiratory disease, which can lead to acute respiratory failure or death. It is closely related to the pathogenesis of New Coronavirus pneumonia (COVID-19). Many researches showed that traditional Chinese medicine (TCM) had a good effect on its intervention, and network pharmacology could play a very important role. In order to construct "disease-gene-target-drug" interaction network more accurately, deep learning algorithm is utilized in this paper. Two ALI-related target genes (REAL and SATA3) are considered, and the active and inactive compounds of the two corresponding target genes are collected as training data, respectively. Molecular descriptors and molecular fingerprints are utilized to characterize each compound. Forest graph embedded deep feed forward network (forgeNet) is proposed to train. The experimental results show that forgeNet performs better than support vector machines (SVM), random forest (RF), logical regression (LR), Naive Bayes (NB), XGBoost, LightGBM and gcForest. forgeNet could identify 19 compounds in Erhuang decoction (EhD) and Dexamethasone (DXMS) more accurately.
Incorporating social determinants of health into the mathematical modeling of HIV/AIDS
Authors: de Oliveira Robson Bruniera , Rubio Felipe Alves , Anderle Rodrigo , Sanchez Mauro , de Souza Luis Eugenio , Macinko James , Dourado Ines , Rasella Davide 
Published: November 2022

AbstractCurrently, it is estimated that 37.6 million people are living with the HIV/AIDS virus worldwide, placing HIV/AIDS among the ten leading causes of death, mostly among low- and lower-middle-income countries. Despite the effective intervention in the prevention and treatment, this reduction did not occur equally among populations, subpopulations and geographic regions. This difference in the occurrence of the disease is associated with the social determinants of health (SDH), which could affect the transmission and maintenance of HIV. With the recognition of the importance of SDH in HIV transmission, the development of mathematical models that incorporate these determinants could increase the accuracy and robustness of the modeling. This article aims to propose a theoretical and conceptual way of including SDH in the mathematical modeling of HIV/AIDS. The theoretical mathematical model with the Social Determinants of Health has been developed in stages. For the selection of SDH that were incorporated into the model, a narrative literature review was conducted. Secondly, we proposed an extended model in which the population (N) is divided into Susceptible (S), HIV-positive (I), Individual with AIDS (A) and individual under treatment (T). Each SDH had a different approach to embedding in the model. We performed a calibration and validation of the model. A total of 31 SDH were obtained in the review, divided into four groups: Individual Factors, Socioeconomic Factors, Social Participation, and Health Services. In the end, four determinants were selected for incorporation into the model: Education, Poverty, Use of Drugs and Alcohol abuse, and Condoms Use. the section “Numerical simulation” to simulate the influence of the poverty rate on the AIDS incidence and mortality rates. We used a Brazilian dataset of new AIDS cases and deaths, which is publicly available. We calibrated the model using a multiobjective genetic algorithm for the years 2003 to 2019. To forecast from 2020 to 2035, we assumed two lines of poverty rate representing (i) a scenario of increasing and (ii) a scenario of decreasing. To avoid overfitting, we fixed some parameters and estimated the remaining. The equations presented with the chosen SDH exemplify some approaches that we can adopt when thinking about modeling social effects on the occurrence of HIV. The model was able to capture the influence of the employment/poverty on the HIV/AIDS incidence and mortality rates, evidencing the importance of SDOH in the occurrence of diseases. The recognition of the importance of including the SDH in the modeling and studies on HIV/AIDS is evident, due to its complexity and multicausality. Models that do not take into account in their structure, will probably miss a great part of the real trends, especially in periods, as the current on, of economic crisis and strong socioeconomic changes.
Spatial and temporal changes in moth assemblages along an altitudinal gradient, Jeju-do island
Authors: Choi Sei-Woong , An Jeong-Seop , Lee Jae-Young , Koo Kyung Ah 
Published: November 2022

AbstractMontane species on islands attract attention due to their small and isolated populations and limited dispersal potential, making them vulnerable to extinction. We investigated the diversity pattern of moth assemblages over the 12-years-period (2009–2020) at 11 study plots on an island mountain (Mount Hallasan, Jeju-do Island, South Korea) to assess the changes in the moth assemblages in terms of species composition, richness, and abundances. We expected to find a decline in the number of species at these sites, given the reported decline in similar taxa in other temperate regions, such as Europe and North America. In contrast, we found that the numbers of species and individuals of moth populations on the island mountain have not significantly changed, except at the high-elevation sites, where the number of species has increased. Our results also show that the numbers of species and individuals are closely related to energy availability, actual evapotranspiration. Moreover, we found that the species composition during the study period has not been greatly changed, except at the lowermost and uppermost elevations. The mechanism driving this high dissimilarity of moth assemblages differed: the low-elevation site experienced high temporal turnover, and the high elevation sites also experienced high temporal turnover and nestedness resulting from active species replacement due to a recent forest fire and vegetation changes and the geographic and ecological constraints of the high elevations. To date, the moth species diversity of the temperate forests of the island mountain is not showing a drastic change. However, we observed that the moth assemblages had changed the number of species and individuals at low and high elevations. Given the biological and ecological limitations of moths (ectothermic organisms with limited habitat range) and considering the results of our study, we infer that climate change has impacted the diversity and species composition of moths on the island mountain.
Effect of a temperature gradient on the behaviour of an endangered Mexican topminnow and an invasive freshwater fish
Authors: Gomez-Maldonado Sebastian , Camacho-Cervantes Morelia 
Published: November 2022

AbstractClimate change and biological invasions are two of the major threats to biodiversity. They could act synergistically to the detriment of natives as non-native species may be more plastic and resilient when facing changing environments. The twoline skiffia (Skiffia bilineata) is an endangered Mexican topminnow that cohabits with invasive guppies (Poecilia reticulata) in some areas in central Mexico. Guppies have been found to take advantage from associating with the twoline skiffia and are considered partially responsible for the decline of its populations. Refuge use and exploratory behaviours are trade-offs between being safe from the unknown and the opportunity to explore novel areas in search for better resources or to disperse. The aim of this study is to investigate how a change in temperature affects the refuge use and exploratory behaviours for both species. We found that temperature affects the refuge use of twoline skiffias, and the swimming activity of both species. Skiffias explored the rock more than guppies regardless of the temperature scenario. Also, smaller fish spent more time performing exploratory behaviours than bigger ones. Our study is the first to test the effect of temperature on the refuge use and exploratory behaviour of a goodeid species, and our results contribute to the idea that some natives could be more affected by climate change than some invaders.
Innovative multi-material tool use in the pant-hoot display of a chimpanzee
Authors: Watson Stuart K. , Lambeth Susan P. , Schapiro Steven J. 
Published: November 2022

Abstract‘Pant-hoot displays’ are a species-typical, multi-modal communicative behaviour in chimpanzees in which pant-hoot vocalisations are combined with varied behavioural displays. In both captivity and the wild, individuals commonly incorporate striking or throwing elements of their environment into these displays. In this case study, we present five videos of an unenculturated, captive, adult male chimpanzee combining a large rubber feeding tub with excelsior (wood wool) in a multi-step process, which was then integrated into the subject’s pant-hoot displays as a percussive tool or ‘instrument’. During the construction process, the subject demonstrated an understanding of the relevant properties of these materials, ‘repairing’ the tub to be a more functional drum when necessary. We supplement these videos with a survey of care staff from the study site for additional detail and context. Although care must be taken in generalising data from a single individual, the behaviour reported here hints at three intriguing features of chimpanzee communicative cognition: (1) it suggests a degree of voluntary control over vocal production, (2) it is a so-far unique example of compound tool innovation and use in communicative behaviour and (3) it may represent an example of forward planning in communicative behaviour. Each of these would represent hitherto undocumented dimensions of flexibility in chimpanzee communication, mapping fertile ground for future research.