bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of poor prognostic factors in extensive-stage small cell lung cancer under etoposide- platinum-atezolizumab treatment
Authors: Lim Jeong Uk , Kang Hye Seon , Shin Ah Young , Yeo Chang Dong , Kim Sung Kyoung , Kim Jin Woo , Kim Seung Joon , Lee Sang Haak 
Published: July 2022

Abstract
The phase III trial IMpower133 showed that platinum and etoposide plus atezolizumab was associated with improved overall survival (OS) and progression free-survival (PFS) when compared to the placebo group in treatment-naïve extensive-stage (ES)-small cell lung cancer (SCLC). Due to superiority in clinical outcomes, combination immunotherapy plus chemotherapy became mainstay treatment modalities as first line treatment in ES-SCLC. Nevertheless, real-world data are still lacking and search for potential biomarkers is necessary. This study aims to evaluate potential predictive biomarkers applicable in ES-SCLC under the combination therapy. Patients with ES-SCLC who are under etoposide-platinum-atezolizumab enrolled from 7 university hospitals affiliated to the Catholic University of Korea were evaluated. Pretreatment clinical parameters were evaluated for association with OS and PFS. Adverse events (AEs) during induction and maintenance phases were also evaluated. P-value below 0.05 was counted as statistically significant. Total of 41 patients were evaluated. Six-month survival was 68.6%. As best response to treatment, 26 (63.4%) showed partial response, 9 (22.0%) showed stable disease, and 4 (9.8%) showed progressive disease. During induction phase, grade I-II AEs occurred in 22 (53.7%) patients, and grade III-IV AEs occurred in 26 (63.4%) patients. During maintenance phase, 9 out of 25 (36.0%) patients experienced any grade AEs. In multivariate analysis for OS, lactate dehydrogenase (LDH), c-reactive protein (CRP), and forced vital capacity (%) were significant factors. In multivariate analysis for PFS, sex, and LDH were significant. In ES-SCLC under etoposide-platinum-atezolizumab, pretreatment CRP, LDH and FVC (%) were independent prognostic factors.
How does Apolipoprotein E genotype influence the relationship between physical activity and Alzheimer’s disease risk? A novel integrative model
Authors: Lucas Jaisalmer Frutos , Sewell Kelsey , García-Colomo Alejandra , Markovic Shaun , Erickson Kirk I. , Brown Belinda M. 
Published: July 2022

Abstract
Background: Wide evidence suggests that physical activity (PA) confers protection against Alzheimer’s disease (AD). On the other hand, the Apolipoprotein E gene (APOE) ε4 allele represents the greatest genetic risk factor for developing AD. Extensive research has been conducted to determine whether frequent PA can mitigate the increased AD risk associated with APOE ε4. However, thus far these attempts have produced inconclusive results. In this context, one possible explanation could be that the influence of the combined effect of PA and APOE ε4 carriage might be dependent on the specific outcome measure utilized.Main body: In order to bridge these discrepancies, the aim of this theoretical article is to propose a novel model on the interactive effects of PA and APOE ε4 carriage on well-established mechanisms underlying AD. Available literature was searched to investigate how PA and APOE ε4 carriage, independently and in combination, may alter several molecular pathways involved in AD pathogenesis. The reviewed mechanisms include amyloid beta (Aβ) and tau deposition and clearance, neuronal resilience and neurogenesis, lipid function and cerebrovascular alterations, brain immune response and glucose metabolism. Finally, combining all this information we have built an integrative model, which includes evidence-based and theoretical synergistic interactions across mechanisms. Moreover, we have identified key knowledge gaps in the literature, providing a list of testable hypotheses that future studies need to address. Conclusions: We conclude that PA influences a wide array of molecular targets involved in AD neuropathology. A deeper understanding of where, when and, most importantly, how PA decreases AD risk even in the presence of the APOE ε4 allele will enable the creation of new protocols using exercise along pharmaceuticals in combined therapeutic approaches.
An Alternative Modeling and Control Approach for Fixed Boundary Motion Requirement in Industrial Automation and Robotics Using Constraint Following Method
Authors: Zhang Xinrong , Zhao Ruiying , Chen Ye-Hwa , Zhang Xiaoyan 
Published: July 2022

Abstract
In industrial automation and robotics, the motion control of the automatic equipment (e.g., mobile robots, assembling manipulators, machine tools, etc.) is an important task for intelligent and flexible manufacturing. Because of the limited space on the factory floor and limited operating conditions, most tasks require work in confined spaces and subject to regulatory requirements. This confined motion control objective is considered as the constraints in the paper (hence, it belongs to the constraint following control field). There are two categories of constraints for the motion control: equality and inequality which are corresponding to the two motion requirements. The problem of motion requirement with fixed boundary has not been solved systematically using constraint following method. The equation of motion for a constrained mechanical system which addresses both constraints is presented. This can be considered a generalization of the Udwadia-Kalaba (U-K) equation. The advantages of the equation include that it does not require additional pseudo variables and the solution is analytical. This exhibits profound applications. As a demonstration, a pan/tilt device mounted under the firefighting unmanned aerial vehicles (UAVs) is manipulated. The water-jet nozzle need motion requirements of swaying horizontally and not overshooting limits in vertical. Simulation and experimental results are presented to validate the effectiveness of the proposed approach.
Inventory System with Generalized Triangular Neutrosophic Cost Pattern incorporating Maximum Lifetime based Deterioration and Novel Demand through PSO
Authors: Bhavani G. Durga , Mahapatra G S 
Published: July 2022

Abstract
At the manufacturing plant or while the products are being transferred from one supply layer to another, there is a considerable possibility of receiving damaged or faulty items mixed in with non-defective commodities.
This research focuses on the non-defective and defective products that are shipped to retailers by their suppliers. The retailer reworks faulty items to make them non-defective, and the retailer receives a discount on the cost of purchasing defective items.
The presented inventory system addresses the uncertainty in inventory costs and also considers the deterioration of items with prioritized maximum product life. In this study, our aim is to minimize the total inventory cost when demand rate as a function of quality and power pattern of time under crisp and generalized triangular neutrosophic environments.
Based on the payment deal, interest charges are imposed only when the payment delay has passed a particular allowable time limit.
The neutrosophic number, which provides three different types of membership functions representing truth, hesitation, and falseness, is used in the inventory model to handle the cost pattern's uncertainty. A particle swarm optimization approach is used to analyze the proposed inventory model, and the results are validated using a numerical example and sensitivity analysis for various parameters.
Improving awareness of kidney function through electronic urine output monitoring: a comparative study
Authors: Murad Omar , Cruz Daniel F Orjuela , Goldman Aliza , Stern Tal , Heerden Peter Vernon van 
Published: July 2022

Abstract
Background: The current classification for acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria integrates both serum creatinine (SCr) and UO. Most reports on AKI claim to use KDIGO guidelines but fail to include the UO criterion. It has been shown that patients who had intensive UO monitoring, with or without AKI, had significantly less cumulative fluid volume and fluid overload, reduced vasopressor use, and improved 30-day mortality. We examined whether real-time monitoring of this simple, sensitive, and easy-to-use biomarker in the ICU led to more appropriate intervention by healthcare providers and better outcomes. Methods: RenalSense Clarity RMS Consoles were installed in the General ICU at the Hadassah Medical Center, Israel, from Dec 2019 to Nov 2020. Using its Sensor Kit, the system continuously monitors UO in real-time. 100 patients were randomly selected from this period as the study group (UOreal-time) and compared to a matched control group (UOmanual) from the same period two years earlier. To test whether there was an association between oliguric hours and fluid treatment in each group, the correlation was calculated and analyzed for each of the different UO monitoring methods. Results: Therapeutic intervention: The correlation of the sum of all oliguric hours on Day 1 and 2 with the sum of any therapeutic intervention (fluid bolus or furosemide) showed a significant correlation for the study group UOreal-time (P = 0.017). The matched control group UOmanual showed no such correlation (P = 0.932). Length of Stay (LOS): Median LOS [IQR] in the ICU of UOreal-time versus UOmanual was 69.46 [44.7, 125.9] hours and 116.5 [62.46, 281.3] hours, respectively (P = 0.0002). Conclusions: The results of our study strongly suggest that ICU patients had more meaningful and better medical intervention, and improved outcomes, with electronic UO monitoring than with manual monitoring.
Validation of SIMIND Monte Carlo for 99mTc and 177Lu
Authors: Domenico Giovanni Di , Biaso Simona Di , Longo Lorenzo , Turra Alessandro , Tonini Eugenia , Longo MariaConcetta , Uccelli Licia , Bartolomei Mirco 
Published: July 2022

Abstract
Purpose : Monte Carlo (MC) simulation in Nuclear Medicine is a powerful tool for modelling many physical phenomena which are difficult to track or to measure directly. MC simulation in SPECT/CT imaging is particularly suitable for optimizing the quantification of activity in a patient, and, consequently, the absorbed dose to each organ. To do so, it is mandatory validate MC results with real data acquired with gamma camera. The aim of this study was the validation of SIMIND Monte Carlo code for modelling a Siemens Symbia Intevo Excel SPECT-CT gamma camera both for 99m Tc and 177 Lu. Methods : Phantom experiments using 99m Tc and 177 Lu have been performed with the purpose to measure spatial resolution, sensitivity and evaluate the calibration factor (CF) and recovery coefficients (RC) from acquired data. The geometries used for 2D planar imaging were (1) Petri dish and (2) capillary source while for 3D volumetric imaging were (3) a uniform filled cylinder phantom and (4) a Jaszczack phantom with spheres with different volumes. The experimental results have been compared with the results obtained from Monte Carlo simulations performed in the same geometries. Results : Comparison shows good accordance between simulated and experimental data. The measured planar spatial resolution was 8.3±0.8mm for 99m Tc and 12.2±0.7mm for 177 Lu. The corresponding data obtained by SIMIND for 99mTc was 7.4±0.1 mm, while for 177Lu was 11.7±0.1 mm. The CF was 110.1±5.5 cps/MBq for Technetium and 18.3±1.0 cps/MBq for Lutetium. The corresponding CF obtained by SIMIND for 99mTc was 100.1±0.3 cps/MBq, while for 177 Lu 20.4±0.7 cps/MBq. Moreover, a complete curve RCs vs Volume (ml) both for Technetium and Lutetium was determined to correct the PVE for all volumes of clinical interest. In none of the cases a RC factor equal to 100 was found. Conclusions : The results of validation process show that SIMIND can be used for simulating both gamma camera planar and SPECT images of Siemens Symbia Intevo using 99mTc and 177Lu radionuclides for different medical purposes and treatments.
Activation of the NF-κB pathway by the Human Cytomegalovirus Envelope Protein gpUL132 in human trophoblast cells
Authors: Huang Ying , Wang Min 
Published: July 2022

Abstract
Human Cytomegalovirus (HCMV) is a widespread double-stranded DNA virus, which can cause serious complications in fetuses and neonates after infection by pregnant women. HCMV can synthesize a variety of glycoproteins, among which gpUL132,a 270-amino-acid type I envelope glycoprotein has attracted more and more attention because it was found to be involved in the formation of viral assembly compartment in recent years. Human placental trophoblast cells, as the first layer of placental barrier cells, can play an antiviral role after pathogen invasion. However, whether gpUL132 is involved in HCMV infection of human placental trophoblast cells and its specific mechanism is still unclear. In this study, we found gpUL132 protein of HCMV could activate the nuclear factor-kappa B (NF-κB) pathway induced by polyinosinic-polycytidylic acid [poly(I:C)], a synthetic analog of double-stranded RNA. Poly(I:C) treatment induced a higher level of P65 phosphorylation in HPT-8 cells expressing gpUL132 as compared to control cells. Additionally, HCMV gpUL132 activated NF-κB P65 via the toll-interleukin 1 receptor homology-domain-containing adapter-inducing interferon-β (TRIF)-dependent TLR3 pathway. Finally, gpUL132 protein could increase the TRIF level by extending its half-life.
Association of MARCH7 with tumor progression and T-cell infiltration in esophageal cancer
Authors: Singh Shivam , Bano Arjumand , Saraya Anoop , Das Prasenjit , Sharma Rinu 
Published: July 2022

Abstract
MARCH7 is an E3 ubiquitin ligase known to regulate neuronal development, T-cell proliferation, and cell and tissue differentiation. But, the altered expression of MARCH7 has been observed in various malignancies. Herein, the cellular localization and role of MARCH7have been elucidated in esophageal squamous cell carcinoma (ESCC), the information regarding which is currently limited. To check the expression of MARCH7 and its correlation with immune cells infiltration in ESCC, immunohistochemical analysis was performed. RNAi approach was used to investigate the role of MARCH7 in esophagealcancer cells. Interestingly, we found a significantly higher expression of MARCH7 protein in 84% of ESCC tissues than in distant matched non-malignant tissues (p ≤ 0.001). In addition to this, immunohistochemistry results have shown a negative correlation between MARCH7 protein expression and tumor-infiltrating immune cells such as CD8 + T cells (r=-0.667, p = 0.035) and PD1 + T cells (r=-0.509, p = 0.133). Furthermore, MARCH7 silencing inhibited the ESCC cell growth and reduced the clonogenic and invasion/migration potential of ESCC cells. MARCH7 silencing also significantly increased E-cadherin protein levels in ESCC cells relative to those in negative control cells (p < 0.05). Thus, MARCH7 is oncogenic and might have a possible role in esophageal carcinogenesis. Moreover, E-cadherin may be a downstream target of MARCH7 in ESCC.
Integrated transcriptomic and metabolomic analyses reveal key genes controlling flavonoid biosynthesis in Citrus grandis ‘Tomentosa’ fruits
Authors: Fan Ruiyi , Zhu Congyi , Qiu Diyang , Mao Genlin , Mueller-Roeber Bernd , Zeng Jiwu 
Published: July 2022

Abstract
Background
As a well-recognized Traditional Chinese medicine (TCM), immature fruits of Citrus grandis ‘Tomentosa’ serve to cure chronic cough in humans, to which flavonoids may contribute. Knowledge about the molecular mechanisms underlying flavonoid biosynthesis in ‘Tomentosa’ fruits would, therefore, favor the breeding of varieties with improved health supporting properties.
Results
To this end, we determined the transcriptomes, using RNA-seq, and metabolic profiles of two contrasting C. grandis varieties, namely ‘Tomentosa’ (‘ZM’) used for TCM production, and a locally cultivated pomelo (‘GQ’), at four fruit development stages. A total of 39 flavonoids, including 14 flavanone/flavone, five isoflavonoids, 12 flavonols, and six anthocyanins, were identified and 16 of them were quantitatively determined in fruits of the two varieties. We found that ‘ZM’ fruits contain more flavonoids than ‘GQ’, whereby rhoifolin accumulated to significantly higher levels in ‘ZM’. Transcriptome sequencing of ‘ZM’ and ‘GQ’ allowed the annotation of 31,510 genes, including 1,387 previously unknown ones. A total of 646 genes were found to be differentially expressed between ‘ZM’ and ‘GQ’ throughout all four fruit developmental stages, indicating them as robust expression markers in future breeding programs. Weighted gene co-expression network analysis (WGCNA) identified 18 modules.
Conclusions
Combined transcriptional and metabolic analysis revealed 25 flavonoid biosynthesis structural genes and 16 transcriptional regulators (MYBs, bHLHs, WD40) to be likely involved in the biosynthesis of flavonoids in C. grandis ‘Tomentosa’ fruits.
Temporal expression of myogenic regulatory genes in different chicken breeds during embryonic development
Authors: Gu Shuang , Wen Chaoliang , Li Junying , Liu Honghong , Huang Qiang , Zheng Jiangxia , Sun Congjiao , Yang Ning 
Published: July 2022

Abstract
Background
The basic units of skeletal muscle in all vertebrates are multinucleate myofibers, which are formed from the fusion of mononuclear myoblasts during the embryonic period. Understanding the regulation of embryonic skeletal muscle development is important to improve animal production efficiency and meat quality. The processes of myofiber formation and maturation are controlled by multiple regulatory factors. Therefore, we selected four chicken breeds, namely, Cornish, White Plymouth Rock, White Leghorn and Beijing-You Chicken, for evaluation of their temporal expression patterns of known key regulatory genes (Myomaker, MYOD and MSTN) during pectoral and thigh muscle development to characterize the embryonic muscle development of different chicken breeds.
Results
The highest expression level of Myomaker, a vital gene for controlling myoblast fusion, was occurred from E13 to E15 for all breeds, while its expression level was close to zero at D1, indicating that E13 to E15 was the crucial stage of myoblast fusion in chickens. Interestingly, the gene expression level of Myomaker in both pectoral and thigh muscle of Cornish chickens, which are fast-growing, was the highest during the crucial stage. The expression of the MYOD gene in muscles at D1 was much higher than that in the embryonic development period, implying that MYOD might have an important role in chicken growth after hatching. In addition, a significant difference was found in the expression level of MYOD among the four chicken breeds at D1. Hematoxylin and eosin staining of both pectoral and thigh muscles suggested that the formation of myofibers was largely complete at E17 in chicken embryos, and myofiber hypertrophy subsequently began, which was speculated to have occurred because of the increase in MSTN gene expression and the decrease in Myomaker gene expression at E17.
Conclusion
These findings revealed the same temporal expression patterns of the key regulatory genes among different breeds, but they also showed some variation across different breeds within the long-term selection for growth. Our research contributes to lay a foundation for the study of myofiber development during the embryonic period in different chicken breeds.
Identification of potential inhibitors of PDE5 based on structure-based virtual screening approaches
Authors: Xu Lei , Sun Lilei , Su Peng , Ma Teng , Yu Yingcong , Liu Haibin , Huang Xianfeng 
Published: July 2022

Abstract
Cyclic adenosine monophosphate (cAMP) and cyclic guanidine monophosphate (cGMP) are the basis for understanding a large variety of physiological functions. Phosphodiesterase type 5 (PDE5), exclusively specific for cGMP, is mainly located in heart, lungs, smooth muscle cells and central nervous system, which can regulate intracellular levels of cGMP. Therefore, PDE5 is a potential target for the therapy of various diseases, and PDE5 inhibitors could be used as treatment for erectile dysfunction (ED) or chronic pulmonary hypertension. Herein, an integrated computer-aided virtual screening technique against the natural products in the ZINC database was used to discover PDE5 inhibitors. Pharmacophore, molecular docking and ADMET (Absorption, distribution, metabolism, excretion and toxicity) properties filtration were carried out to select the PDE5 inhibitors with best binding affinities and drug-like properties. The binding modes of PDE5-inhibitors were investigated and the stabilities of these complexes were explored by molecular dynamic simulations and MM/GBSA free energy calculations. The MM/GBSA free energy decomposition analysis quantitatively analyzed the importance of hydrophobic interaction in PDE5-ligands binding. As a result, two natural compounds were identified and may be used as critical starting point for development of novel PDE5 inhibitors. These results may promote the de novo design of new compounds against PDE5.
Meta-Analysis of Transcriptomic Datasets Quantifies Differential Gene Expression, Affected Pathways, and Predicted Drugs from Hantavirus-Infected Human Material
Authors: Krapohl John , Pickett Brett E. 
Published: July 2022

Abstract
Background
We performed a meta-analysis that consisted of re-analyzing publicly available RNA-sequencing datasets across representative species within Orthohantavirus and across host cell types to identify differentially expressed genes associated with hantavirus infection. In addition, we determined signaling pathways that were significantly perturbed in human tissue, as well as predicted existing drugs that could be repurposed to potentially reduce the effects of acute hantavirus infection.
Methods
NCBI-GEO and ENA databases were searched to find datasets for this analysis, then processed using the Automated Reproducible MOdular Workflow for Preprocessing and Differential Analysis of RNA-seq Data (ARMOR) to identify differentially expressed genes (DEGs). The results from this analysis were then processed using signaling pathway impact analysis (SPIA) to identify enriched signaling pathways. Finally, that data was processed using the Pathways2Targets program to identify existing therapeutics that target the impacted cellular pathways.
Results
Our results include affirming the roles of the previously identified interferon pathway and the MYBL1 and CCR7 genes, as well as newly identified genes, including SLC27A3, TSEN34 and neuron associated NOG and AMIGO1. We predicted dinaciclib, alvodicib, and ruxolitinib, among many other drugs, that could be useful as potential HFRS and HCPS treatments.
Conclusion
These data can be used in the design of future wet lab experiments to better characterize the human transcriptional response to infection, as well as to improve host-based diagnostics and/or therapeutics to reduce the severity of hantavirus infection.