bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting EGFR Mutation Status by a Deep Learning Approach in Patients with Non-Small Cell Lung Cancer Brain Metastases
Authors: Haim Oz , Abramov Shani , Shofty Ben , Fanizzi Claudia , DiMeco Francesco , Avisdris Netanell , Ram Zvi , Artzi Moran , Grossman Rachel 
Published: November 2021

Abstract
PURPOSE: Non-small cell lung cancer (NSCLC), the most prevalent subtype of lung cancer, tends to metastasize to the brain. Between 10-60% of NSCLCs harbor an activating mutation in the epidermal growth factor receptor (EGFR), which may be targeted with selective EGFR inhibitors. However, due to a high discordance rate between the molecular profile of the primary tumor and the brain metastases (BMs), identifying an individual patient’s EGFR status of the BMs necessitates tissue diagnosis via an invasive surgical procedure. We employed a deep learning (DL) method with the aim of noninvasive detection of the EGFR mutation status in NSCLC BM. METHODS: We retrospectively collected clinical, radiological, and pathological-molecular data of all the NSCLC patients who had been diagnosed with BMs and underwent resection of their BM during 2006-2019. The study population was then divided into 2 groups based upon EGFR mutational status. We further employed a DL technique to classify the 2 groups according to their preoperative magnetic resonance imaging features. Finally, we established the accuracy of our model in predicting EGFR mutation status of BM of NSCLC. RESULTS: Fifty-nine patients were included in the study, 16 patients harbored EGFR mutations. Our model predicted mutational status with mean accuracy of 89.8%, sensitivity of 68.7%, specificity of 97.7%, and a receiver operating characteristic curve )ROC( value of 0.91 across the 5 validation datasets.CONCLUSION: DL based noninvasive molecular characterization is feasible, has high accuracy and should be further validated in large prospective cohorts.
When Left Does Not Seem Right: Epigenetic and Bioelectric Differences Between Left- and Right-Sided Breast Cancer
Authors: Masuelli Sofia , Real Sebastián , Campoy Emanuel , Branham Maria Teresita , Matías Marzese Diego , Salomon Matthew , De Blas Gerardo , Arias Rodolfo , Levin Michael , Moreno Maria Roqué 
Published: November 2021

Abstract
Background: During embryogenesis, lateral symmetry is broken giving rise to Left/Right (L/R) breast tissues with distinct identity. L/R-sided breast tumors exhibit consistently-biased incidence, gene expression, and DNA methylation. We postulate that a differential L/R tumor-microenvironment crosstalk generates different tumorigenesis mechanisms. Methods: We performed in-silico analyses on breast tumors of public datasets, developed xenografted tumors, and conditioned MDA-MB-231 cells with L/R mammary extracts. Results: We found L/R differential DNA methylation involved in embryogenic and neuron-like functions. Focusing on ion-channels, we discovered significant L/R epigenetic and bioelectric differences. Specifically, L-sided cells presented increased methylation of hyperpolarizing ion channel genes and increased Ca2+ concentration and depolarized membrane potential, compared to R-ones. Functional consequences were associated with increased proliferation in left tumors, assessed by KI67 expression and mitotic count. Conclusions: Our findings reveal considerable L/R asymmetry in cancer processes, and suggest specific L/R epigenetic and bioelectric differences as future targets for cancer therapeutic approaches in the breast and many other paired organs.
Evaluation of Biochemical Markers of Cardiac Risk in ART-Treated HIV-Infected Adults in Rwanda
Authors: Bushaku Marcus , Nyamwange Caleb , Kwena Arthur , Twagirumukiza Marc , Utumatwishima Jean Nepo , Mugeni Regine , Davila-Roman Victor , Reeds Dominic , Schectman Kenneth , Nishimwe Aurore , Cade William Todd , Mutimura Eugene 
Published: November 2021

Abstract
Background
Life expectancy of people living with HIV infection has improved due to access to antiretroviral therapy (ART) in Rwanda like other African countries. However, both HIV infection and use of ART are associated with cardiovascular disease (CVD) risks, due to adverse changes in some biochemical markers, causing dyslipidemia and other metabolic imbalances. The CVD risk associated with metabolic biomarkers that may affect cardiac function with use of the ART, has not been well characterized in Rwanda. We evaluated the association between the use and duration of ART and abnormal changes in biochemical markers of CVD risk among HIV infected adults in Rwanda.
Methods
Participants were enrolled from HIV Clinics Public Health Centers in a cross-sectional study in Kigali. A total of 150 participants between 18-45 years included 30 HIV-Uninfected (HIV-) and 120 HIV-infected (HIV+) adults. Among the HIV+ adults, 40 participants were ART-naïve. Data were collected on health-related behaviors and biochemical markers of CVD risk. We compared changes in CVD-related biochemical markers between HIV-, HIV+ ART-naïve and HIV+ on ART treatment groups.
Results
Majority of participants were women (60%), and HIV- were younger (35±6 vs. 31±6 years). We observed differences in levels of cholesterol and triglycerides in HIV+ ART-treated and HIV+ ART-naïve groups. Total cholesterol and triglycerides were associated with use of ART. Serum triglycerides were lower in HIV+ ART-naïve compared to HIV+ on ART treatment (61.20±18.30 mg/dl vs. 85.00±38.30 mg/dl; p< 0.01). While total cholesterol was higher in HIV+ on ART than HIV+ ART-naïve (136.00±45.00 mg/dl vs. 119.00±36.00 mg/dl; p<0.04), HDL-C was associated with longer exposure to ART (68.70±30.00 mg/dl vs. 54.90±25.70 mg/dl; p=0.02) among HIV+ on ART for 0-6 months and 7-12 months respectively.
Conclusion
Changes in serum total cholesterol and triglycerides were associated with use of ART. Although these changes were within the upper limits of normal ranges, our findings suggest early increases in both biochemical biomarkers of cardiac risk associated. These findings underscore the need for early evaluation of lipid profiles as biomarkers of cardiovascular disease risk, to effectively monitor how ART may contribute to cardiovascular disease and deter treatment programs in African countries.
Research on Tribological Properties of H13 Steel of Shield Machine Hob by Laser Shot Peening
Authors: Zhang Yifeng , Yang XueFeng , Wang Shouren , Li Wanyang , Wu Qiang , Zhao Wangliang , Gao Yang , Wang Kai 
Published: November 2021

Abstract
In this paper, the laser shot peening technology of H13 steel is studied to improve the friction and wear performance of shield machine hob. And to utilize the laser shot peening (LSP) experiment and simulation analysis, the influence of LSP parameters on the friction and wear performance of H13 steel after strengthening is studied. The results show that the residual stress and the depth of stress layer are increased after LSP, which is beneficial to reduce the friction and wear of material surface. In addition, the surface has a paint absorption layer which can absorb laser energy to avoid surface annealing. The maximum residual stress of H13 steel is 911 MPa and the hardness is 650.7 HV, when there are three-times of black paint absorption and LSP. Compared with the raw material, the residual stress is increased by 125% and the hardness is increased by 18%. And its friction coefficients and wear volume were relatively lower than other schemes. The average friction coefficient and wear volume were reduced by 10.8% and 57.2% respectively.
The Brain Activation of Anxiety Disorders During Emotional Stimulations: A Coordinate-Based Activation Likelihood Estimation Meta-Analysis
Authors: Liu Xia , Wang Xiuzhen , Li Yongchao , Ji Shanling , Zhang Yu , Zhang Yinghui , Hu Bin 
Published: November 2021

Abstract
Many studies have been analyzed the state of brain activation about anxiety under neuroimaging experiments with emotional stimuli. However, there is no meta-analysis to assess the commonality and specificity activation of different anxiety subtypes. Here, we used the activation likelihood estimation (ALE) to define the common and different activation between different subtypes of anxiety. A total of 29 functional magnetic resonance imaging (fMRI) studies revealed significantly increased bilateral amygdala, anterior cingulate gyrus, and parahippocampal gyrus activation in anxiety during emotional stimuli. Moreover, we observed the decreased activations in the posterior cingulate, lingual gyrus, and precuneus. In subanalyses of anxiety disorders, the increased activation of generalized anxiety and specific phobias are present in the left hippocampus and thalamus, respectively. Social anxiety and panic disorders showed increased activation in the parahippocampal gyrus, amygdala, thalamus, and insula. Social anxiety, generalized anxiety, and panic disorders displayed decreased activations in the fusiform gyrus, posterior cingulate, and specific phobias exhibited in the medial frontal gyrus. Although different anxiety showed dissimilar activations, the principal activations were observed in the limbic lobe, which might indicate the limbic circuit was a neural reflection of anxiety symptoms.
Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson disease: A post-mortem observational study
Authors: Isonaka Risa , Sullivan Patti , Goldstein David S 
Published: November 2021

Abstract
Background: Parkinson disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker; however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples. Methods: We assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innervation) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control (CTRL) subjects who did not have a neurodegenerative disease. Results: PD patients had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times CTRL, p<0.0001), SMG (35 times CTRL, p=0.0011), and myocardium (11 times CTRL, p=0.0011). Myocardial TH in the PD group was decreased from CTRL by 65% (p=0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group (p<0.0001), but the groups did not differ in NE in either scalp skin or SMG. Conclusions: PD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.
Graphene Oxide-Lignin/Silk Fibroin/ZnO Nanobiocomposite: A Novel Bioactive Scaffold With Antibacterial Activity
Authors: Eivazzadeh-Keihan Reza , Zare-Bakheir Ensiye , Aliabadi Hooman Aghamirza Moghim , Gorab Mostafa Ghafori , Ghafuri Hossein , Maleki Ali , Madanchi Hamid , mahdavi Mohammad 
Published: November 2021

Abstract
In this study, a novel nanobiocomposite was synthesized using graphene oxide, lignin, silk fibroin and ZnO and used in biological fields. To synthesize this structure, after preparing graphene oxide by the Hummer method, lignin, silk fibroin, and ZnO nanoparticles (NPs) were added to it, respectively. Also, ZnO NPs with a particle size of about 18 nm to 33 nm was synthesized via Camellia sinensis extract by green methodology. The synthesized structure was examined as anti-biofilm agent and it was observed that the Graphene oxide-lignin/silk fibroin/ZnO nanobiocomposite has a significant ability to prevent the formation of P. aeruginosa biofilm. In addition, due to the importance of the possibility of using this structure in biological environments, its toxicity and blood compatibility were also evaluated. According to the obtained results from MTT assay, the viability percentages of Hu02 cells treated with Graphene oxide-lignin/silk fibroin/ZnO nanobiocomposite after 24, 48, and 72 h of incubation were 89.96%, 89.32%, and 91.28%. On the other hand, the hemolysis percentage of the synthesized structure after 24 h and 72 h of extraction was 9.5% and 11.76% respectively. As a result, the synthesized structure is hemocompatible and had no toxic effects on Hu02 cells.
The Clinical Characteristics and Outcomes of Incidentally Discovered Glioblastoma
Authors: Kawauchi Daisuke , Ohno Makoto , Honda-Kitahara Mai , Miyakita Yasuji , Takahashi Masamichi , Yanagisawa Shunsuke , Tamura Yukie , Kikuchi Miyu , Ichimura Koichi , Narita Yoshitaka 
Published: November 2021

Abstract
Objective
With an increase in the number of imaging examinations and the development of imaging technology, a small number of glioblastomas (GBMs) are identified by incidental radiological images. These incidentally discovered glioblastomas (iGBMs) are rare, and their clinical features are not well understood. Here, we investigated the clinical characteristics and outcomes of iGBM.
Methods
Data of newly diagnosed iGBM patients who were treated at our institution between August 2005 and October 2019 were reviewed. An iGBM was defined as a GBM without a focal sign, discovered on radiological images obtained for reasons unrelated to the tumor. Kaplan-Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS).
Results
Of 234 patients with newly diagnosed GBM, four (1.7%) were classified as having iGBM. Health screening was the most common reason for tumor discovery (75.0%). The preoperative Karnofsky performance status score was 100 in three patients. Tumors were found on the right side in three cases. The mean volume of preoperative enhanced tumor lesion was 16.8 cm3. The median duration from confirmation of an enhanced lesion to surgery was 13.5 days. In all cases, either total (100%) or subtotal (95–99%) resections were achieved. The median PFS and OS were 11.5 and 20.0 months, respectively.
Conclusions
The iGBMs were often small and in the right non-eloquent area, and the patients had good performance status. We found that timely therapeutic intervention provided iGBM patients with favorable outcomes. This report suggests that early detection of GBM may lead to a better prognosis.
Nutrient resorption tightens plant nitrogen and phosphorus coupling and decreases with sulfur deposition as mediated by interannual precipitation in a meadow
Authors: Feng Xue , Wang Ruzhen , Li Tianpeng , Cai Jiangping , Liu Heyong , Wang Bin , Lü Xiaotao , Jiang Yong 
Published: November 2021

Abstract
Purpose

Sulfur (S) deposition as a global change issue causes worldwide soil acidification, nutrient mobilization and marked changes in plant nutrition. Here, we investigated how S deposition would affect leaf nutrient resorption and how this effect varies with yearly fluctuations in precipitation.
Methods

In a semiarid meadow exposed to S addition, we measured nitrogen (N), phosphorus (P) and S concentrations in green and senescent leaves of a grass and a sedge and calculated nutrient resorption efficiencies (NuRE) across two years with contrasting precipitation (13% higher and 27% lower than long-term mean annual precipitation).
Results

Concentrations of N, P, and S in green and senescent leaves generally increased with S addition across the two years, with the exception of N and P concentrations in green leaves of the grass that showed no response or even decreased with S addition. The coupling relationships between N and P concentrations showed interannual variations and tightened by nutrient resorption, as evidenced by stronger N and P correlations in senescent leaves than in green leaves in the wet year. Leaf NuRE convergently decreased with S addition across the two years congruent with soil acidification and increased soil N, P and S availability, while NuRE was higher in the wet year due to lower soil nutrient availability herein.
Conclusions

This study provides new evidence on the role of nutrient resorption in tightening stoichiometric N:P relationships, and a three-dimensional feedback framework that plant nutrient resorption was favored by higher precipitation to sharpen its tradeoff with soil nutrient availability.
HOXA7 Promotes Metastasis in KRAS Mutant Colorectal Cancer by Regulating Myeloid-derived Suppressor Cells
Authors: Dang Yunzhi , Yu Jiao , Zhao Shuhong , Cao Ximing , Wang Qing 
Published: November 2021

Abstract
Background: KRAS mutation accounts for 30-50% of human colorectal cancer (CRC). Due to paucity of effective treatment options, KRAS mutant CRC is difficult to treat in clinic. Metastasis is still the major reason for the high mortality of KRAS mutant CRC, but the exact mechanism remains unclear. Here, we report a novel role of Homeobox 7 (HOXA7) in promoting KRAS mutant CRC metastasis and probed therapy strategies for these subpopulation patients.Methods: The expression of HOXA7 was detected in human CRC cohort by immunohistochemistry. The function of HOXA7 in KRAS mutant CRC metastasis was analyzed by cecum orthotopic model. Results: The elevated expression of HOXA7 was positively correlated with lymph node metastasis, distant metastasis, poorer tumor differentiation, higher TNM stage, and poor prognosis in CRC patients. Furthermore, HOXA7 is an independent prognostic marker of KRAS mutant CRC patients (P<0.001), while not for KRAS wild-type CRC patients (P=0.575). HOXA7 overexpression increased the metastasis ability of KRAS mutant CT26 cell, and promoted the infiltration of MDSCs at the same time. When MDSCs infiltration was depleted by CXCR2 inhibitor, it can markedly suppress the metastasis rate in CT26 cell. The combination of CXCR2 inhibitor SB265610 and anti-programmed death-ligand 1 (anti-PD-L1) can largely inhibit metastasis in KRAS mutant CRC. Conclusions: HOXA7 overexpression upregulated CXCL1, which promoted MDSCs infiltration. Interruption of this loop might provide a promising treatment strategy for HOXA7-mediated KRAS mutant CRC metastasis.
Lignocellulose degradation in Protaetia brevitarsis larvae digestive tract: refining on a tightly designed microbial fermentation production line
Authors: Wang Kui , Gao Peiwen , Geng Lili , Liu Chunqin , Zhang Jie , Shu Changlong 
Published: November 2021

Abstract
Background

The Scarabaeidae insect Protaetia brevitarsis (PB) has recently gained increasing research interest as resource insects, because its larvae can effectively use various organic matter ranging from decaying plant residues to humus and livestock waste and convert those compounds to nonphytotoxic and high humic acid content frass fertilizer, as well as healthy nutritional insect protein sources. Lignocellulose is the main component of PB larvae (PBLs) food sources. PBLs show high lignin and polysaccharide degradation efficiency; however, genome annotation shows that PBLs’ carbohydrate-active enzymes (CAZymes) are not able to complete the lignocellulose degradation process. Therefore, the mechanism by which PBLs efficiently degrade lignocellulose is a worthy issue for further study.
Results

Here, we used a combined host genomic and gut metagenomic datasets to investigate the lignocellulose degradation activity of PBLs. First, a comprehensive gut gene catalog comprising gut microbial genes and host gut transcriptomic genes was established. The data showed that PBLs selectively enriched lignocellulose-degrading microbial species mainly from Firmicutes and Bacteroidetes, which are capable of producing a broad array of cellulases and hemicellulases, thus playing a major role in lignocellulosic biomass degradation. Gene annotation revealed PBLs gut microbiome encoded a full spectrum of CAZymes involving in the hydrolysis of lignocellulose (including 39,969 CAZymes), while the host only expressed 33 lignocellulose degradation-related CAZymes in the guts. The PBL hosts provide lignin pretreatment processes via their evolved strong mouthparts as well as a strong alkaline environment in the midgut, which thus complements the lack of laccases in the PBL holobiont. In addition, most of the lignocellulose degradation-related gene sequences in the PBL microbiome were novel, and most of the recovered high-quality genome bins with independent (hemi)cellulose degradation capability from the PBL gut microbiome were novel species.
Conclusions

This work shows that there is a unique teamwork between PBLs and their gut bacterial flora for efficient lignocellulose degradation. PBLs are a promising model to study lignocellulose degradation, which can provide highly abundant novel enzymes and relevant lignocellulose-degrading bacterial strains for biotechnological biomass conversion industries.
Ultra-high speed reconfigurable microwave and radio frequency photonic intensity differentiators using Kerr frequency optical microcombs
Authors: Moss David 
Published: November 2021

Abstract
We propose and experimentally demonstrate a microwave photonic intensity differentiator based on a Kerr optical comb generated by a compact integrated micro-ring resonator (MRR). The on-chip Kerr optical comb, containing a large number of comb lines, serves as a high-performance multi-wavelength source for the transversal filter, which will greatly reduce the cost, size, and complexity of the system. Moreover, owing to the compactness of the integrated MRR, up to 200-GHz frequency spacing of the Kerr optical comb can be achieved, enabling a potential operation bandwidth of over 100 GHz. By programming and shaping individual comb lines according to the calculated tap weights, a reconfigurable intensity differentiator with variable differentiation orders can be realized. The operation principle is theoretically analyzed, and experimental demonstrations of first-order, second-order, and third-order differentiation functions based on the principle are presented. The radio frequency (RF) amplitude and phase responses of multi-order intensity differentiations are characterized, and system demonstrations of real-time differentiations for Gaussian input signal are also performed. The experimental results show good agreement with theory, confirming the effectiveness of our approach.