bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pak1 pathway hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer
Authors: Belli Stefania , Esposito Daniela , Allotta Alessandra , Servetto Alberto , Ciciola Paola , Pesapane Ada , Ascione Claudia M. , Napolitano Fabiana , Di Mauro Concetta , Vigliar Elena , Iaccarino Antonino , De Angelis Carmine , Bianco Roberto , Formisano Luigi 
Published: May 2023

AbstractCyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have been approved in combination with endocrine therapy (ET) to treat estrogen receptor-positive (ER+) metastatic breast cancer (BC). However, drug resistance represents the leading cause of breast cancer patients mortality. This study aimed to identify novel resistance mechanisms to ER antagonists in combination with CDK4/6 inhibitors. We generated two ER+ BC cell lines, T47D and MCF7, resistant to the combination of the ER antagonist fulvestrant and CDK4/6i abemaciclib, named T47D-FAR and MCF7-FAR. Transcriptomic analysis revealed common up-regulation of genes involved in MAPK and epithelial to mesenchymal transition (EMT) pathways in FAR cells, sustaining their hyper-invasive phenotype and increased anchorage-independent growth, compared to sensitive cells. FAR cells showed higher p21-activated kinase 1 (Pak1) expression and phosphorylation levels than parental cells. PAK1 knockdown by siRNAs hampered cell proliferation, reduced anchorage-independent growth and invasive properties of T47D-FAR and MCF7-FAR, re-sensitizing them to fulvestrant and abemaciclib. Conversely, over-expression of PAK1 in MCF7 and T47D cells increased tumor spheroids’ growth and invasion and reduced sensitivity to fulvestrant and abemaciclib, confirming its role in inducing drug resistance. Finally, treatment with Pak1 inhibitors, PF-3758309 (PF309) and NVS-PAK1-1, restored cell sensitivity to fulvestrant and abemaciclib of MCF7-FAR and T47D-FAR cells, both in vitro and in vivo. In conclusion, our data suggested a pivotal role for Pak1 in resistance to ET and CDK4/6i in ER+ breast cancers. These data might promote the rationale for the development of novel Pak1 inhibitors for treatment of patients with ER+ BC progressing on ET plus CDK4/6i.
An improved global vegetation health index dataset in detecting vegetation drought
Authors: Zeng Jingyu , Zhou Tao , Qu Yanping , Bento Virgílio A. , Qi Junyu , Xu Yixin , Li Ying , Wang Qianfeng 
Published: May 2023

AbstractDue to global warming, drought events have become more frequent, which resulted in aggravated crop failures, food shortage, larger and more energetic wildfires, and have seriously affected socio-economic development and agricultural production. In this study, a global long-term (1981–2021), high-resolution (4 km) improved vegetation health index (VHI) dataset integrating climate, vegetation and soil moisture was developed. Based on drought records from the Emergency Event Database, we compared the detection efficiency of the VHI before and after its improvement in the occurrence and scope of observed drought events. The global drought detection efficiency of the improved high-resolution VHI dataset reached values as high as 85%, which is 14% higher than the original VHI dataset. The improved VHI dataset was also more sensitive to mild droughts and more accurate regarding the extent of droughts. This improved dataset can play an important role in long-term drought monitoring but also has the potential to assess the impact of drought on the agricultural, forestry, ecological and environmental sectors.
A novel beam stopper-based approach for scatter correction in digital planar radiography
Authors: Sakaltras N. , Pena A. , Martinez C. , Desco M. , Abella M. 
Published: May 2023

AbstractX-ray scatter in planar radiography degrades the contrast resolution of the image, thus reducing its diagnostic utility. Antiscatter grids partially block scattered photons at the cost of increasing the dose delivered by two- to four-fold and posing geometrical restrictions that hinder their use for other acquisition settings, such as portable radiography. The few software-based approaches investigated for planar radiography mainly estimate the scatter map from a low-frequency version of the image. We present a novel method for scatter correction in planar imaging based on direct patient measurements. Samples from the shadowed regions of an additional partially obstructed projection acquired with a beam stopper placed between the X-ray source and the patient are used to estimate the scatter map. Evaluation with simulated and real data showed an increase in contrast resolution for both lung and spine and recovery of ground truth values superior to those of three recently proposed methods. Our method avoids the biases of post-processing methods and yields results similar to those for an antiscatter grid while removing geometrical restrictions at around half the radiation dose. It can be used in unconventional imaging techniques, such as portable radiography, where training datasets needed for deep-learning approaches would be very difficult to obtain.
Peripheral immune cell imbalance is associated with cortical beta-amyloid deposition and longitudinal cognitive decline
Authors: Mehta Neel H. , Zhou Liangdong , Li Yi , McIntire Laura Beth , Nordvig Anna , Butler Tracy , de Leon Mony , Chiang Gloria C. 
Published: May 2023

AbstractNeuroinflammation is believed to be a key process in Alzheimer’s disease (AD) pathogenesis. Recently, the neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratios (LMR) have been proposed to be useful peripheral markers of inflammation. However, it is unclear how these inflammatory ratios relate to AD pathology, such as β-amyloid (Aβ) plaques and tau tangles. Using 18F-florbetapir and 18F-flortaucipir positron emission tomography (PET), we sought to determine how the NLR and LMR are associated with AD pathology both cross-sectionally and longitudinally. We further evaluated associations between the NLR and LMR and longitudinal cognitive decline. Using data from the Alzheimer’s Disease Neuroimaging Initiative, we analyzed blood, PET, and cognitive data from 1544 subjects—405 cognitively normal, 838 with mild cognitive impairment (MCI), and 301 with AD. Associations between the NLR and LMR and Aβ and tau on PET were assessed using ordinary least-squares and mixed-effects regression models, while adjusting for age, sex, years of education, and apolipoprotein E ε2 or ε4 carrier status. Associations between the NLR and LMR and cognitive function, as measured by the AD Assessment Scale-Cognitive Subscale, 13-item version, were also assessed. MCI and AD subjects had higher NLR (p = 0.017, p < 0.001, respectively) and lower LMR (p = 0.013, p = 0.023). The NLR, but not the LMR, was significantly associated with Aβ (p = 0.028), suggesting that higher NLR was associated with greater Aβ deposition in the brain. Neither the NLR nor the LMR was associated with tau deposition (p > 0.05). A higher NLR was associated with greater longitudinal cognitive decline (p < 0.001). A higher ratio of peripheral neutrophils to lymphocytes, possibly reflecting an imbalance in innate versus adaptive immunity, is related to greater Aβ deposition and longitudinal cognitive decline. As the field moves toward blood-based biomarkers of AD, the altered balance of innate versus adaptive immunity could be a useful biomarker of underlying pathology and may also serve as a potential therapeutic target.
A sustainable approach for the degradation kinetics study and stability assay of the SARS-CoV-2 oral antiviral drug Molnupiravir
Authors: Edrees Fadwa H. , Draz Mohammed E. , Saad Ahmed S. , Hammad Sherif F. , Mohamed Heba M. 
Published: May 2023

AbstractMolnupiravir (MPV) is the first direct-acting oral antiviral drug that effectively decreases nasopharyngeal infections with SARS-CoV-2 virus. The stability of MPV was tested by subjecting the drug to various stress conditions. The drug is liable to oxidative, acidic, and alkaline degradation and showed significant stability against thermal degradation. Mass spectrometry identified the degradation products and guided suggestion of the degradation patterns. Interestingly, while inspecting the UV-absorption spectra, we observed no absorbance at 270 nm for the products of the three degradation pathways (c.f. intact MPV). Direct spectrophotometry seemed a solution that perfectly fit the purpose of the stability assay method in our case. It avoids sophisticated instrumentation and complex mathematical data manipulation. The method determined MPV accurately (100.32% ± 1.62) and selectively (99.49% ± 1.63) within the linear range of 1.50 × 10–5–4.0 × 10–4 M and down to a detection limit of 0.48 × 10–5 M. The proposed method is simple and does not require any preliminary separation or derivatization steps. The procedure proved its validity as per the ICH recommendations. The specificity was assessed in the presence of up to 90% degradation products. The study evaluated the greenness profile of the proposed analytical procedure using the National Environmental Methods Index (NEMI), the Analytical Eco-Scale, and the Green Analytical Procedure Index (GAPI). The three metrics unanimously agreed that the developed procedure results in a greener profile than the reported method. The method investigated the degradation reactions' kinetics and evaluated the reaction order, rate constant, and half-life time for each degradation process.
Dynamical analysis of an inverted pendulum with positive position feedback controller approximate uniform solution
Authors: Moatimid Galal M. , El-Sayed A. T. , Salman Hala F. 
Published: May 2023

AbstractThe inverted pendulum is controlled in this article by using the nonlinear control theory. From classical analytical mechanics, its substructure equation of motion is derived. Because of the inclusion of the restoring forces, the Taylor expansion is employed to facilitate the analysis. An estimated satisfactory periodic solution is obtained with the aid of the modified Homotopy perturbation method. A numerical technique based on the fourth-order Runge–Kutta method is employed to justify the previous solution. On the other hand, a positive position feedback control is developed to dampen the vibrations of an IP system subjected to multi-excitation forces. The multiple time scale perturbation technique of the second order is introduced as a mathematical method to solve a two-degree-of-freedom system that simulates the IP with the PPF at primary and 1:1 internal resonance. The stability of these solutions is checked with the aid of the Routh–Hurwitz criterion. A set of graphs, based on the frequency response equations resulting from the MSPT method, is incorporated. Additionally, a numerical simulation is set up with RK-4 to confirm the overall controlled performance of the studied model. The quality of the solution is confirmed by the match between the approximate solution and the numerical simulation. Numerous other nonlinear systems can be controlled using the provided control method. Illustrations are offered that pertain to implications in design and pedagogy. The linearized stability of IP near the fixed points as well as the phase portraits is depicted for the autonomous and non-autonomous cases. Because of the static stability of the IP, it is found that its instability can be suppressed by the increase of both the generalized force as well as the torsional constant stiffness of the spring. Additionally, the presence of the magnetic field enhances the stability of IP.
Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model
Authors: Rosmark Oskar , Kadefors Måns , Dellgren Göran , Karlsson Christofer , Ericsson Anders , Lindstedt Sandra , Malmström Johan , Hallgren Oskar , Larsson-Callerfelt Anna-Karin , Westergren-Thorsson Gunilla 
Published: May 2023

AbstractAlveolar epithelial cells (AEC) have been implicated in pathological remodelling. We examined the capacity of AEC to produce extracellular matrix (ECM) and thereby directly contribute towards remodelling in chronic lung diseases. Cryopreserved type 2 AEC (AEC2) from healthy lungs and chronic obstructive pulmonary disease (COPD) afflicted lungs were cultured in decellularized healthy human lung slices for 13 days. Healthy-derived AEC2 were treated with transforming growth factor ß1 (TGF-β1) to evaluate the plasticity of their ECM production. Evaluation of phenotypic markers and expression of matrisome genes and proteins were evaluated by RNA-sequencing, mass spectrometry and immunohistochemistry. The AEC2 displayed an AEC marker profile similar to freshly isolated AEC2 throughout the 13-day culture period. COPD-derived AECs proliferated as healthy AECs with few differences in gene and protein expression while retaining increased expression of disease marker HLA-A. The AEC2 expressed basement membrane components and a complex set of interstitial ECM proteins. TGF-β1 stimuli induced a significant change in interstitial ECM production from AEC2 without loss of specific AEC marker expression. This study reveals a previously unexplored potential of AEC to directly contribute to ECM turnover by producing interstitial ECM proteins, motivating a re-evaluation of the role of AEC2 in pathological lung remodelling.
Adaptive elevator kinematics optimization based dual response algorithm for determining proper levels in plaster milling process parameters
Authors: Luangpaiboon Pongchanun , Juttijudata Sirirat 
Published: May 2023

AbstractThis study proposes a novel hybrid approach, called Adaptive/Elevator Kinematics Optimization algorithm based on dual response algorithm (A/EKO-DRA), to enhance the robust parameters estimation and design of the plaster milling process. The A/EKO-DRA method reduces variability while maintaining the desired output target, thereby minimizing the impact of variance on the expected stucco combined water. The performance of the A/EKO-DRA is compared with conventional processes through numerical examples and simulations. The results show that the A/EKO-DRA method has the lowest mean absolute errors among other methods in terms of parameter estimation, and it achieves the response mean of 5.927 percent, which meets the target value of 5.9 percent for industrial enclosures, with much reduction in the response variance. Overall, the A/EKO-DRA method is a promising approach for optimizing the plaster milling process parameters.
Construction of an oxidative stress-related lncRNAs signature to predict prognosis and the immune response in gastric cancer
Authors: Zhang Hui , Feng Huawei , Yu Tiansong , Zhang Man , Liu Zhikui , Ma Lidan , Liu Hongsheng 
Published: May 2023

AbstractOxidative stress, as a characteristic of cellular aerobic metabolism, plays a crucial regulatory role in the development and metastasis of gastric cancer (GC). Long noncoding RNAs (lncRNAs) are important regulators in GC development. However, research on the prognostic patterns of oxidative stress-related lncRNAs (OSRLs) and their functions in the immune microenvironment is currently insufficient. We identified the OSRLs signature (DIP2A-IT1, DUXAP8, TP53TG1, SNHG5, AC091057.1, AL355001.1, ARRDC1-AS1, and COLCA1) from 185 oxidative stress-related genes in The Cancer Genome Atlas (TCGA) cohort via random survival forest and Cox analyses, and the results were subsequently validated in the Gene Expression Omnibus (GEO) dataset. The patients were divided into high- and low-risk groups by the risk score of the OSRLs signature. Longer overall survival was detected in the low-risk group than in the high-risk group in both the TCGA cohort (P < 0. 001, HR = 0.43, 95% CI 0.31–0.62) and the GEO cohort (P = 0.014, HR = 0.67, 95% CI 0.48–0.93). Next, multivariate Cox analysis identified that the risk model was an independent prognostic characteristic (HR > 1, P = 0.005), and time-dependent receiver operating characteristic (ROC) curve analysis and nomogram analysis were utilized to evaluate the predictive ability of the risk model. Next, gene set enrichment analysis revealed that the immune-related pathway, Wnt/$$\upbeta$$
β
-catenin signature, mammalian target of rapamycin complex 1 signature, and cytokine‒cytokine receptor interaction was enriched. High-risk patients were more responsive to CD200, TNFSF4, TNFSF9, and BTNL2 immune checkpoint blockade. The results of qRT‒PCR further proved the accuracy of our bioinformatic analysis. Overall, our study identified a novel OSRLs signature that can serve as a promising biomarker and prognostic indicator, which provides a personalized predictive approach for patient prognosis evaluation and treatment.
Improved measurement method for roadbed bearing capacity based on PFWD dynamic modulus control
Authors: Li Danfeng , Zhang Zhuojie , Zhang Guangming 
Published: May 2023

AbstractTo address current challenges of difficult standardisation of dynamic determination of roadbed bearing capacity and excessive deviations in deflection control, this paper proposes a improved measurement method for roadbed load-bearing capacity based on the dynamic modulus control using a portable falling weight deflectometer (PFWD). The detection range of PFWD is determined by theoretical analysis. Based on the range, a finite element numerical model was developed, the spatial distribution and attenuation of the dynamic stress of the roadbed soil in the depth and horizontal directions are determined. The variation of the vertical dynamic stress with depth is not characterized by a gradual decrease, as is commonly believed, but rather by an increase followed by a decrease. The underlying reasons for the difference between static and dynamic indicators are explored. Using the improved method, a prediction model with dynamic bending as the detection index and static rebound modulus as the control index was developed. The proposed model can improve precision accuracy as well as detection efficiency, verify the effectiveness of the improved method, which is important for accurate dynamic measurement and evaluation of highway roadbed bearing capacity.
Phase transitions in the classical simulability of open quantum systems
Authors: Azad F. , Hallam A. , Morley J. , Green A. G. 
Published: May 2023

AbstractWe introduce a Langevin unravelling of the density matrix evolution of an open quantum system over matrix product states, which we term the time-dependent variational principle-Langevin equation. This allows the study of entanglement dynamics as a function of both temperature and coupling to the environment. As the strength of coupling to and temperature of the environment is increased, we find a transition where the entanglement of the individual trajectories saturates, permitting a classical simulation of the system for all times. This is the Hamiltonian open system counterpart of the saturation in entanglement found in random circuits with projective or weak measurements. If a system is open, there is a limit to the advantage in simulating its behaviour on a quantum computer, even when that evolution harbours important quantum effects. Moreover, if a quantum simulator is in this phase, it cannot simulate with quantum advantage.
Bulk and single-cell transcriptome profiling reveal the metabolic heterogeneity in gastric cancer
Authors: Tao Guoqiang , Wen Xiangyu , Wang Xingxing , Zhou Qi 
Published: May 2023

AbstractMetabolic reprogramming has been defined as a key hall mark of human tumors. However, metabolic heterogeneity in gastric cancer has not been elucidated. Here we separated the TCGA-STAD dataset into two metabolic subtypes. The differences between subtypes were elaborated in terms of transcriptomics, genomics, tumor-infiltrating cells, and single-cell resolution. We found that metabolic subtype 1 is predominantly characterized by low metabolism, high immune cell infiltration. Subtype 2 is mainly characterized by high metabolism and low immune cell infiltration. From single-cell resolution, we found that the high metabolism of subtype 2 is dominated by epithelial cells. Not only epithelial cells, but also various immune cells and stromal cells showed high metabolism in subtype 2 and low metabolism in subtype 1. Our study established a classification of gastric cancer metabolic subtypes and explored the differences between subtypes from multiple dimensions, especially the single-cell resolution.
Engineering nanowires in bacteria to elucidate electron transport structural–functional relationships
Authors: Myers Ben , Catrambone Francesco , Allen Stephanie , Hill Phil J. , Kovacs Katalin , Rawson Frankie J. 
Published: May 2023

AbstractBacterial pilin nanowires are protein complexes, suggested to possess electroactive capabilities forming part of the cells’ bioenergetic programming. Their role is thought to be linked to facilitating electron transfer between cells and the external environment to permit metabolism and cell-to-cell communication. There is a significant debate, with varying hypotheses as to the nature of the proteins currently lying between type-IV pilin-based nanowires and polymerised cytochrome-based filaments. Importantly, to date, there is a very limited structure–function analysis of these structures within whole bacteria. In this work, we engineered Cupriavidus necator H16, a model autotrophic organism to express differing aromatic modifications of type-IV pilus proteins to establish structure–function relationships on conductivity and the effects this has on pili structure. This was achieved via a combination of high-resolution PeakForce tunnelling atomic force microscopy (PeakForce TUNA™) technology, alongside conventional electrochemical approaches enabling the elucidation of conductive nanowires emanating from whole bacterial cells. This work is the first example of functional type-IV pili protein nanowires produced under aerobic conditions using a Cupriavidus necator chassis. This work has far-reaching consequences in understanding the basis of bio-electrical communication between cells and with their external environment.
Termination of trastuzumab in HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression
Authors: Dogan Izzet , Aydin Esra , Khanmammadov Nijat , Paksoy Nail , Saip Pinar , Aydiner Adnan 
Published: May 2023

AbstractThe purpose of the study was to assess the prognosis of HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression and investigate the predictors of complete response. HER2-positive metastatic breast cancer patients who received long-term trastuzumab were included in the study. Predictors of complete response were analyzed with binary regression analysis. The prognosis of patients who had their trastuzumab-based treatment terminated was assessed. Eighty patients were involved in the study. The patients were received with trastuzumab for a median of 62 months (12–191). A complete response was observed in 60 (75%) patients. The median duration to development of complete response was found as 14.8 months (2.4–55). In logistic regression analysis: using endocrine therapy with trastuzumab (p = 0.04), menopausal status (p = 0.03), and the number of metastatic sites (p = 0.01) were found to be statistically significant factors for a complete response. Trastuzumab-based therapy of fifteen patients was terminated, six (40%) patients continued to receive an aromatase inhibitor, and nine (60%) patients were followed up without treatment. After termination of trastuzumab, at a median follow-up of 32 months (11–66), recurrence was detected in two (13.3%) patients. We detected that menopausal status, the number of metastatic sites, and using endocrine therapy with trastuzumab were predictors of complete response in HER2-positive metastatic breast cancer patients who received long-term trastuzumab-based therapy. We observed that HER2-positive metastatic breast cancer patients may be completely cured with trastuzumab-based therapy. There are no defined criteria for termination of trastuzumab treatment in this selected patient group. It is necessary to confirm our data with multicenter studies involving a large number of patients.