bluuebunny/crossref_metadata_2025 huggingface dataset:
CT-derived 3D-diaphragm motion in emphysema and IPF compared to normal subjects
Authors: Kang Ji Hee , Choi Jiwoong , Chae Kum Ju , Shin Kyung Min , Lee Chang-Hoon , Guo Junfeng , Lin Ching-Long , Hoffman Eric A. , Lee Changhyun
Published: July 2021

Image registration-based local displacement analysis enables evaluation of respiratory motion between two computed tomography-captured lung volumes. The objective of this study was to compare diaphragm movement among emphysema, idiopathic pulmonary fibrosis (IPF) and normal subjects. 29 normal, 50 emphysema, and 51 IPF subjects were included. A mass preserving image registration technique was used to compute displacement vectors of local lung regions at an acinar scale. Movement of the diaphragm was assumed to be equivalent to movement of the basal lung within 5 mm from the diaphragm. Magnitudes and directions of displacement vectors were compared between the groups. Three-dimensional (3D) and apico-basal displacements were smaller in emphysema than normal subjects (P = 0.003, P = 0.002). Low lung attenuation area on expiration scan showed significant correlations with decreased 3D and apico-basal displacements (r = − 0.546, P < 0.0001; r = − 0.521, P < 0.0001) in emphysema patients. Dorsal–ventral displacement was smaller in IPF than normal subjects (P < 0.0001). The standard deviation of the displacement angle was greater in both emphysema and IPF patients than normal subjects (P < 0.0001). In conclusion, apico-basal movement of the diaphragm is reduced in emphysema while dorsal–ventral movement is reduced in IPF. Image registration technique to multi-volume CT scans provides insight into the pathophysiology of limited diaphragmatic motion in emphysema and IPF.
Characterizing intra-tumor regions on quantitative ultrasound parametric images to predict breast cancer response to chemotherapy at pre-treatment
Authors: Taleghamar Hamidreza , Moghadas-Dastjerdi Hadi , Czarnota Gregory J. , Sadeghi-Naini Ali
Published: July 2021

The efficacy of quantitative ultrasound (QUS) multi-parametric imaging in conjunction with unsupervised classification algorithms was investigated for the first time in characterizing intra-tumor regions to predict breast tumor response to chemotherapy before the start of treatment. QUS multi-parametric images of breast tumors were generated using the ultrasound radiofrequency data acquired from 181 patients diagnosed with locally advanced breast cancer and planned for neo-adjuvant chemotherapy followed by surgery. A hidden Markov random field (HMRF) expectation maximization (EM) algorithm was applied to identify distinct intra-tumor regions on QUS multi-parametric images. Several features were extracted from the segmented intra-tumor regions and tumor margin on different parametric images. A multi-step feature selection procedure was applied to construct a QUS biomarker consisting of four features for response prediction. Evaluation results on an independent test set indicated that the developed biomarker coupled with a decision tree model with adaptive boosting (AdaBoost) as the classifier could predict the treatment response of patient at pre-treatment with an accuracy of 85.4% and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.89. In comparison, the biomarkers consisted of the features derived from the entire tumor core (without consideration of the intra-tumor regions), and the entire tumor core and the tumor margin could predict the treatment response of patients with an accuracy of 74.5% and 76.4%, and an AUC of 0.79 and 0.76, respectively. Standard clinical features could predict the therapy response with an accuracy of 69.1% and an AUC of 0.6. Long-term survival analyses indicated that the patients predicted by the developed model as responders had a significantly better survival compared to the non-responders. Similar findings were observed for the two response cohorts identified at post-treatment based on standard clinical and pathological criteria. The results obtained in this study demonstrated the potential of QUS multi-parametric imaging integrated with unsupervised learning methods in identifying distinct intra-tumor regions in breast cancer to characterize its responsiveness to chemotherapy prior to the start of treatment.
Enhancing sensitivity in absorption spectroscopy using a scattering cavity
Authors: Oh Jeonghun , Lee KyeoReh , Park YongKeun
Published: July 2021

Absorption spectroscopy is widely used to detect samples with spectral specificity. Here, we propose and demonstrate a method for enhancing the sensitivity of absorption spectroscopy. Exploiting multiple light scattering generated by a boron nitride (h-BN) scattering cavity, the optical path lengths of light inside a diffusive reflective cavity are significantly increased, resulting in more than ten times enhancement of sensitivity in absorption spectroscopy. We demonstrate highly sensitive spectral measurements of low concentrations of malachite green and crystal violet aqueous solutions. Because this method only requires the addition of a scattering cavity to existing absorption spectroscopy, it is expected to enable immediate and widespread applications in various fields, from analytical chemistry to environmental sciences.
Electromagnetic wave transparency of X mode in strongly magnetized plasma
Authors: Mandal Devshree , Vashistha Ayushi , Das Amita
Published: July 2021

An electromagnetic (EM) pulse falling on a plasma medium from vacuum can either reflect, get absorbed or propagate inside the plasma depending on whether it is overdense or underdense. In a magnetized plasma, however, there are usually several pass and stop bands for the EM wave depending on the orientation of the magnetic field with respect to the propagation direction. The EM wave while propagating in a plasma can also excite electrostatic disturbances in the plasma. In this work Particle-In-Cell simulations have been carried out to illustrate the complete transparency of the EM wave propagation inside a strongly magnetized plasma. The external magnetic field is chosen to be perpendicular to both the wave propagation direction and the electric field of the EM wave, which is the X mode configuration. Despite the presence of charged electron and ion species the plasma medium behaves like a vacuum. The observation is understood with the help of particle drifts. It is shown that though the two particle species move under the influence of EM fields their motion does not lead to any charge or current source to alter the dispersion relation of the EM wave propagating in the medium. Furthermore, it is also shown that the stop band for EM wave in this regime shrinks to a zero width as both the resonance and cut-off points approach each other. Thus, transparency to the EM radiation in such a strongly magnetized case appears to be a norm.
Glycosphingolipid GM3 is localized in both exoplasmic and cytoplasmic leaflets of Plasmodium falciparum malaria parasite plasma membrane
Authors: Koudatsu Shiomi , Masatani Tatsunori , Konishi Rikako , Asada Masahito , Hakimi Hassan , Kurokawa Yuna , Tomioku Kanna , Kaneko Osamu , Fujita Akikazu
Published: July 2021

Lipid rafts, sterol-rich and sphingolipid-rich microdomains on the plasma membrane are important in processes like cell signaling, adhesion, and protein and lipid transport. The virulence of many eukaryotic parasites is related to raft microdomains on the cell membrane. In the malaria parasitePlasmodium falciparum, glycosylphosphatidylinositol-anchored proteins, which are important for invasion and are possible targets for vaccine development, are localized in the raft. However, rafts are poorly understood. We used quick-freezing and freeze-fracture immuno-electron microscopy to examine the localization of monosialotetrahexosylganglioside (GM1) and monosialodihexosylganglioside (GM3), putative raft microdomain components inP. falciparumand infected erythrocytes. This method immobilizes molecules in situ, minimizing artifacts. GM3 was localized in the exoplasmic (EF) and cytoplasmic leaflets (PF) of the parasite and the parasitophorous vacuole (PV) membranes, but solely in the EF of the infected erythrocyte membrane, as in the case for uninfected erythrocytes. Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) was localized solely in the PF of erythrocyte, parasite, and PV membranes. This is the first time that GM3, the major component of raft microdomains, was found in the PF of a biological membrane. The unique localization of raft microdomains may be due toP. falciparumlipid metabolism and its unique biological processes, like protein transport from the parasite to infected erythrocytes.
Interleukin-27 promotes autophagy in human serum-induced primary macrophages via an mTOR- and LC3-independent pathway
Authors: Laverdure Sylvain , Wang Ziqiu , Yang Jun , Yamamoto Takuya , Thomas Tima , Sato Toyotaka , Nagashima Kunio , Imamichi Tomozumi
Published: July 2021

Interleukin-27 (IL-27) is a cytokine that suppresses human immunodeficiency virus (HIV)-1 infection in macrophages and is considered as an immunotherapeutic reagent for infectious diseases. It is reported that IL-27 suppresses autophagy in Mycobacterium tuberculosis-infected macrophages; however, a role for IL-27 on autophagy induction has been less studied. In this study, we investigated the impact of IL-27 in both autophagy induction and HIV-1 infection in macrophages. Primary human monocytes were differentiated into macrophages using human AB serum (huAB) alone, macrophage-colony stimulating factor (M-CSF) alone, or a combination of IL-27 with huAB or M-CSF. Electron microscopy and immunofluorescence staining demonstrated that a 20-fold increase in autophagosome formation was only detected in IL-27 + huAB-induced macrophages. Western blot analysis indicated that the autophagosome induction was not linked to either dephosphorylation of the mammalian target of rapamycin (mTOR) or lipidation of microtubule-associated protein 1A/1B-light chain 3 (LC3), an autophagosomal marker, implying that IL-27 can induce autophagy through a novel non-canonical pathway. Here we show for the first time that IL-27 induces autophagy during monocyte-to-macrophage differentiation in a subtype-dependent manner.
Gα15 in early onset of pancreatic ductal adenocarcinoma
Authors: Innamorati Giulio , Wilkie Thomas M. , Malpeli Giorgio , Paiella Salvatore , Grasso Silvia , Rusev Borislav , Leone Biagio Eugenio , Valenti Maria Teresa , Carbonare Luca dalle , Cheri Samuele , Giacomazzi Alice , Zanotto Marco , Guardini Vanessa , Deiana Michela , Zipeto Donato , Serena Michela , Parenti Marco , Guzzi Francesca , Lawlor Rita Teresa , Malerba Giovanni , Mori Antonio , Malleo Giuseppe , Giacomello Luca , Salvia Roberto , Bassi Claudio
Published: July 2021

The GNA15 gene is ectopically expressed in human pancreatic ductal adenocarcinoma cancer cells. The encoded Gα15 protein can promiscuously redirect GPCR signaling toward pathways with oncogenic potential. We sought to describe the distribution of GNA15 in adenocarcinoma from human pancreatic specimens and to analyze the mechanism driving abnormal expression and the consequences on signaling and clinical follow-up. We detected GNA15 expression in pre-neoplastic pancreatic lesions and throughout progression. The analysis of biological data sets, primary and xenografted human tumor samples, and clinical follow-up shows that elevated expression is associated with poor prognosis for GNA15, but not any other GNA gene. Demethylation of the 5′ GNA15 promoter region was associated with ectopic expression of Gα15 in pancreatic neoplastic cells, but not in adjacent dysplastic or non-transformed tissue. Down-modulation of Gα15 by shRNA or CRISPR/Cas9 affected oncogenic signaling, and reduced adenocarcimoma cell motility and invasiveness. We conclude that de novo expression of wild-type GNA15 characterizes transformed pancreatic cells. The methylation pattern of GNA15 changes in preneoplastic lesions coincident with the release a transcriptional blockade that allows ectopic expression to persist throughout PDAC progression. Elevated GNA15 mRNA correlates with poor prognosis. In addition, ectopic Gα15 signaling provides an unprecedented mechanism in the early steps of pancreas carcinogenesis distinct from classical G protein oncogenic mutations described previously in GNAS and GNAQ/GNA11.
Removal behavior and chemical speciation distributions of heavy metals in sewage sludge during bioleaching and combined bioleaching/Fenton-like processes
Authors: Qiu Chunsheng , Xie Shangyu , Liu Nannan , Meng Kequan , Wang Chenchen , Wang Dong , Wang Shaopo
Published: July 2021

The removal and chemical speciation changes of heavy metals in the sewage sludge during the single bioleaching and combined bioleaching/Fenton-like processes were compared in this study. The improvement in the dewaterability of the treated sludge was also investigated. The single bioleaching led to a removal of Zn, Cu, Cd, Cr, Mn, Ni, As and Pb of 67.28%, 50.78%, 64.86%, 6.32%, 56.15%, 49.83%, 20.78% and 10.52% in 10 days, respectively. The chemical speciation analysis showed that the solubilization of heavy metals in mobile forms (exchangeable/acid soluble and reducible forms) and oxidizable form was the main reason for their removal. Subsequent Fenton-like treatment was carried out at different bioleaching stages when the bioleached sludge dropped to certain pH values (4.5, 4.0 and 3.0), by adding H2O2 at different dosages. The highest removal ratio of Zn, Cu, Cd, Cr, Mn and Ni could reach 75.53%, 52.17%, 71.91%, 11.63%, 66.29% and 65.19% after combined bioleaching/Fenton-like process, respectively, with appropriate pH and H2O2 dosages in less than 6 days. The solubilization efficiencies of these heavy metals in mobile forms were further improved by Fenton-like treatment. The removal efficiencies of As and Pb decreased due to their transformation into insoluble forms (mostly residual fraction) after Fenton treatment. The capillary suction times (CST) of the raw sludge (98.7 s) decreased by 79.43% after bioleaching and 87.44% after combined process, respectively.
Genetic association studies of alterations in protein function expose recessive effects on cancer predisposition
Authors: Brandes Nadav , Linial Nathan , Linial Michal
Published: July 2021

The characterization of germline genetic variation affecting cancer risk, known as cancer predisposition, is fundamental to preventive and personalized medicine. Studies of genetic cancer predisposition typically identify significant genomic regions based on family-based cohorts or genome-wide association studies (GWAS). However, the results of such studies rarely provide biological insight or functional interpretation. In this study, we conducted a comprehensive analysis of cancer predisposition in the UK Biobank cohort using a new gene-based method for detecting protein-coding genes that are functionally interpretable. Specifically, we conducted proteome-wide association studies (PWAS) to identify genetic associations mediated by alterations to protein function. With PWAS, we identified 110 significant gene-cancer associations in 70 unique genomic regions across nine cancer types and pan-cancer. In 48 of the 110 PWAS associations (44%), estimated gene damage is associated with reduced rather than elevated cancer risk, suggesting a protective effect. Together with standard GWAS, we implicated 145 unique genomic loci with cancer risk. While most of these genomic regions are supported by external evidence, our results also highlight many novel loci. Based on the capacity of PWAS to detect non-additive genetic effects, we found that 46% of the PWAS-significant cancer regions exhibited exclusive recessive inheritance. These results highlight the importance of recessive genetic effects, without relying on familial studies. Finally, we show that many of the detected genes exert substantial cancer risk in the studied cohort determined by a quantitative functional description, suggesting their relevance for diagnosis and genetic consulting.
A phosphate and calcium-enriched diet promotes progression of 5/6-nephrectomy-induced chronic kidney disease in C57BL/6 mice
Authors: Radloff J. , Latic N. , Pfeiffenberger U. , Schüler C. , Tangermann S. , Kenner L. , Erben R. G.
Published: July 2021

C57BL/6 mice are known to be rather resistant to the induction of experimental chronic kidney disease (CKD) by 5/6-nephrectomy (5/6-Nx). Here, we sought to characterize the development of CKD and its cardiac and skeletal sequelae during the first three months after 5/6-Nx in C57BL/6 mice fed a calcium- and phosphate enriched diet (CPD) with a balanced calcium/phosphate ratio. 5/6-NX mice on CPD showed increased renal fibrosis and a more pronounced decrease in glomerular filtration rate when compared to 5/6-Nx mice on normal diet (ND). Interestingly, despite comparable levels of serum calcium, phosphate, and parathyroid hormone (PTH), circulating intact fibroblast growth factor-23 (FGF23) was 5 times higher in 5/6-Nx mice on CPD, relative to 5/6-Nx mice on ND. A time course experiment revealed that 5/6-Nx mice on CPD developed progressive renal functional decline, renal fibrosis, cortical bone loss, impaired bone mineralization as well as hypertension, but not left ventricular hypertrophy. Collectively, our data show that the resistance of C57BL/6 mice to 5/6-Nx can be partially overcome by feeding the CPD, and that the CPD induces a profound, PTH-independent increase in FGF23 in 5/6-Nx mice, making it an interesting tool to assess the pathophysiological significance of FGF23 in CKD.
A multi-hazard map-based flooding, gully erosion, forest fires, and earthquakes in Iran
Authors: Pouyan Soheila , Pourghasemi Hamid Reza , Bordbar Mojgan , Rahmanian Soroor , Clague John J.
Published: July 2021

We used three state-of-the-art machine learning techniques (boosted regression tree, random forest, and support vector machine) to produce a multi-hazard (MHR) map illustrating areas susceptible to flooding, gully erosion, forest fires, and earthquakes in Kohgiluyeh and Boyer-Ahmad Province, Iran. The earthquake hazard map was derived from a probabilistic seismic hazard analysis. The mean decrease Gini (MDG) method was implemented to determine the relative importance of effective factors on the spatial occurrence of each of the four hazards. Area under the curve (AUC) plots, based on a validation dataset, were created for the maps generated using the three algorithms to compare the results. The random forest model had the highest predictive accuracy, with AUC values of 0.994, 0.982, and 0.885 for gully erosion, flooding, and forest fires, respectively. Approximately 41%, 40%, 28%, and 3% of the study area are at risk of forest fires, earthquakes, floods, and gully erosion, respectively.
Selective activation of pro-anti-IL-1β antibody enhances specificity for autoinflammatory disorder therapy
Authors: Lin Wen-Wei , Lu Yun-Chi , Huang Bo-Cheng , Chuang Chih-Hung , Cheng Yi-An , Chen I.-Ju , Liu Hui-Ju , Ho Kai-Wen , Liao Tzu-Yi , Liu En-Shuo , Wu Ting-Yi , Chang Long-Sen , Hong Shih-Ting , Cheng Tian-Lu
Published: July 2021

Canakinumab is a fully human monoclonal antibody that specifically neutralizes human interleukin (IL)-1β and has been approved by the US Food and Drug Administration for treating different types of autoinflammatory disorders such as cryopyrin-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome and systemic juvenile idiopathic arthritis. However, long-term systemic neutralization of IL-1β by Canakinumab may cause severe adverse events such as serious upper respiratory tract infections and inflammation, thereby decreasing the quality of life of patients. Here, we used an IgG1 hinge as an Ab lock to cover the IL-1β-binding site of Canakinumab by linking with matrix metalloprotease 9 (MMP-9) substrate to generate pro-Canakinumab that can be specifically activated in the inflamed regions in autoinflammatory diseases to enhance the selectivity and safety of treatment. The Ab lock significantly inhibited the IL-1β-binding by 68-fold compared with Canakinumab, and MMP-9 completely restored the IL-1β neutralizing ability of pro-Canakinumab within 60 min and blocked IL-1β-downstream signaling and IL-1β-regulated genes (i.e., IL-6). It is expected that MMP-9 cleavable and efficient Ab lock will be able to significantly enhance the selective reaction of Canakinumab at the disease site and reduce the on-target toxicities of Canakinumab during systemic circulation, thereby showing potential for development to improve the safety and quality of life of patients with autoinflammatory disorders in the future.
Characterization and visualization of murine coagulation factor VIII-producing cells in vivo
Authors: Hayakawa Morisada , Sakata Asuka , Hayakawa Hiroko , Matsumoto Hikari , Hiramoto Takafumi , Kashiwakura Yuji , Baatartsogt Nemekhbayar , Fukushima Noriyoshi , Sakata Yoichi , Suzuki-Inoue Katsue , Ohmori Tsukasa
Published: July 2021

Coagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31high, CD146high, and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1)+. EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin− and C-type lectin-like receptor-2 (CLEC-2)+. In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31high, CD146high, Lyve1+, CLEC-2+, and podoplanin− in liver sinusoidal endothelial cells.
The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma
Authors: Patarat Rathasapa , Riku Shoji , Kunadirek Pattapon , Chuaypen Natthaya , Tangkijvanich Pisit , Mutirangura Apiwat , Puttipanyalears Charoenchai
Published: July 2021

Early detection improves survival and increases curative probability in hepatocellular carcinoma (HCC). Peripheral blood mononuclear cells (PBMCs) can provide an inexpensive, less-invasive and highly accurate method. The objective of this study is to find the potential marker for HCC screening, utilizing gene expression of the PBMCs. Data from the NCBI GEO database of gene expression in HCC patients and healthy donor's PBMCs was collected. As a result, GSE 49515 and GSE 58208 were found. Using both, a statistical significance test was conducted in each gene expression of each data set which resulted in 187 genes. We randomized three selected genes (FLNA, CAP1, and CLU) from the significant p-value group (p-values < 0.001). Then, a total of 76 healthy donors, 153 HCC, 20 hepatic fibrosis, 20 non-alcoholic fatty liver were collected. Quantitative RT-PCR (qRT-PCR) was performed in cDNA from all blood samples from the qRT-PCR, The Cycle threshold (Ct) value of FLNA, CLU, CAP1 of HCC group (28.47 ± 4.43, 28.01 ± 3.75, 29.64 ± 3.90) were lower than healthy group (34.23 ± 3.54, 32.90 ± 4.15, 32.18 ± 5.02) (p-values < 0.0001). The accuracy, sensitivity and specificity of these genes as a screening tool were: FLNA (80.8%, 88.0%, 65.8%), CLU (63.4%, 93.3%, 31.3%), CAP1 (67.2%, 83.3%, 39.1%). The tests were performed in two and three gene combinations. Results demonstrated high accuracy of 86.2%, sensitivity of 85% and specificity of 88.4% in the FLNA and CLU combination. Furthermore, after analyzed using hepatic fibrosis and non-alcoholic fatty liver as a control, the FLNA and CLU combination is shown to have accuracy of 76.9%, sensitivity of 77.6% and specificity of 75%. Also, we founded that our gene combination performs better than the current gold standard for HCC screening. We concluded that FLNA and CLU combination have high potential for being HCC novel markers. Combined with current tumor markers, further research of the gene’s expression might help identify more potential markers and improve diagnosis methods.
Psychopathic traits mediate guilt-related anterior midcingulate activity under authority pressure
Authors: Cheng Yawei , Chou Judith , Martínez Róger Marcelo , Fan Yang-Teng , Chen Chenyi
Published: July 2021

Coercive power has different effects on individuals, and which were unable to be fully addressed in Milgram’s famous studies on obedience to authority. While some individuals exhibited high levels of guilt-related anxiety and refused orders to harm, others followed coercive orders throughout the whole event. The lack of guilt is a well-known characteristic of psychopathy, and recent evidence portrays psychopathic personalities on a continuum of clustered traits, while being pervasive in a significant proportion in the population. To investigate whether psychopathic traits better explain discrepancies in antisocial behavior under coercion, we applied a virtual obedience paradigm, in which an experimenter ordered subjects to press a handheld button to initiate successive actions that carry different moral consequences, during fMRI scanning. Psychopathic traits modulated the association between harming actions and guilt feelings on both behavioral and brain levels. This study sheds light on the individual variability in response to coercive power.
Ultrasensitive and label free electrochemical immunosensor for detection of ROR1 as an oncofetal biomarker using gold nanoparticles assisted LDH/rGO nanocomposite
Authors: Abolhasan Rozita , Khalilzadeh Balal , Yousefi Hadi , Samemaleki Sahar , Chakari-Khiavi Forough , Ghorbani Farzaneh , Pourakbari Ramin , Kamrani Amin , Khataee Alireza , Rad Tannaz Sadeghi , Rashidi Mohammad Reza , Yousefi Mehdi , AghebatiMaleki Leili
Published: July 2021

In the present article, we developed a highly sensitive label-free electrochemical immunosensor based on NiFe-layered double hydroxides (LDH)/reduced graphene oxide (rGO)/gold nanoparticles modified glassy carbon electrode for the determination of receptor tyrosine kinase-like orphan receptor (ROR)-1. In this electrochemical immunoassay platform, NiFe-LDH/rGO was used due to great electron mobility, high specific surface area and flexible structures, while Au nanoparticles were prepared and coated on the modified electrodes to improve the detection sensitivity and ROR1 antibody immobilizing (ROR1Ab). The modification procedure was approved by using cyclic voltammetry and differential pulse voltammetry based on the response of peak current to the step by step modifications. Under optimum conditions, the experimental results showed that the immunosensor revealed a sensitive response to ROR1 in the range of 0.01–1 pg mL−1, and with a lower limit of quantification of 10 attogram/mL (10 ag mL−1). Furthermore, the designed immunosensor was applied for the analysis of ROR1 in several serum samples of chronic lymphocytic leukemia suffering patients with acceptable results, and it also exhibited good selectivity, reproducibility and stability.
Prevalence and predictors of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan
Authors: Abdel-Razeq Hikmat , Abujamous Lama , Abunasser Mahmoud , Edaily Sara , Bater Rayan
Published: July 2021

BRCA1 and BRCA2 mutations are not uncommon in breast cancer patients. Western studies show that such mutations are more prevalent among younger patients. This study evaluates the prevalence of germline mutations in BRCA1 and BRCA2 among breast cancer patients diagnosed at age 40 or younger in Jordan. Blood samples of patients with breast cancer diagnosed at age 40 years or younger were obtained for DNA extraction and BRCA sequencing. Mutations were classified as benign/likely benign (non-carrier), pathogenic/likely pathogenic variant (carrier) and variant of uncertain significance (VUS). Genetic testing and counseling were completed on 616 eligible patients. Among the whole group, 75 (12.2%) had pathogenic or likely pathogenic variants; two of the BRCA2 mutations were novel. In multivariate analysis, triple-negative disease (Odd Ratio [OR]: 5.37; 95% CI 2.88–10.02, P < 0.0001), breast cancer in ≥ 2 family members (OR: 4.44; 95% CI 2.52–7.84, P < 0.0001), and a personal history ≥ 2 primary breast cancers (OR: 3.43; 95% CI 1.62–7.24, P = 0.001) were associated with higher mutation rates. In conclusion, among young Jordanian patients with breast cancer, mutation rates are significantly higher in patients with triple-negative disease, personal history of breast cancer and those with two or more close relatives with breast cancer.
Synthesis, physico-mechanical and microstructural characterization of Al6063/SiC/PKSA hybrid reinforced composites
Authors: Ikubanni P. P. , Oki M. , Adeleke A. A. , Omoniyi P. O.
Published: July 2021

The utilization of agro-residues ash as complementary reinforcing materials continues to gain prominence for metal matrix composite (MMCs) development. A rarely investigated but largely available ash among these agro-residues is the palm kernel shell ash (PKSA). Thus, the present study investigates the influence of PKSA particulates hybridized with SiC on the physico-mechanical properties and microstructure of Al6063 metal composites. The composites are synthesized using the double stir-casting technique with SiC held constant at 2 wt.%, while the PKSA contents are varied from 0 to 8 wt.%. The phases present and morphology of the composites are investigated using X-ray diffractometer (XRD) and scanning electron microscopy (SEM), respectively. The density, porosity, hardness, tensile and fracture toughness tests are carried out on the hybrid composites. X-ray diffractometer revealed that for Al 6063, only Al cubic crystal system was identifiable within the matrix. However, for the reinforced composites, major phases identified are Al, Fe3Si, SiC, MgO, and SiO2. The SEM images show that the particulates reinforcements (SiC and PKSA) were uniformly dispersed in the matrix. The percentage porosity for the composites ranged from 2.06 to 2.39%. In addition, hardness, yield strength and ultimate tensile strength of the composites are about 10.3%, 18.5% and 10.4%, respectively better than for Al 6063. However, the percent elongation and fracture toughness are lower for the hybrid composites than for Al 6063 and SiC reinforced composite with values decreasing with increase in ash content. Hence, the MMCs produced will be applicable for light-weight engineering applications.
The initial effects of microclimate and invertebrate exclusion on multi-site variation in the mass loss of temperate pine and oak deadwoods
Authors: Kim Seongjun , Han Seung Hyun , Li Guanlin , Roh Yujin , Kim Hyun-Jun , Son Yowhan
Published: July 2021

Quantifying deadwood decomposition is prioritized by forest ecologists; nonetheless, uncertainties remain for its regional variation. This study tracked variations in deadwood decomposition of Korean red pine and sawtooth oak in three environmentally different regions of the Republic of Korea, namely western, eastern, and southern regions. After 24 months, dead pine and oak woods lost 47.3 ± 2.8% and 23.5 ± 1.6% in the southern region, 13.3 ± 2.6% and 20.2 ± 2.8% in the western region, and 11.9 ± 7.9% and 13.9 ± 2.3% in the eastern region, respectively. The regional variation in the decomposition rate was significant only for dead pine woods (P < 0.05). Invertebrate exclusion treatment reduced the decomposition rate in all region, and had the greatest effect in the southern region where warmer climate and concentrated termite colonization occurred. The strongest influential factor for the decomposition of dead pine woods was invertebrate exclusion (path coefficient: 0.63). Contrastingly, the decomposition of dead oak woods was highly controlled by air temperature (path coefficient: 0.88), without significant effect of invertebrate exclusion. These findings reflect the divergence in regional variation of deadwood decomposition between pine and oak, which might result from the different sensitivity to microclimate and decomposer invertebrates.
Development of edible Thai rice film fortified with ginger extract using microwave-assisted extraction for oral antimicrobial properties
Authors: Utama-ang Niramon , Sida Sirinapa , Wanachantararak Phenphichar , Kawee-ai Arthitaya
Published: July 2021

This study aimed to investigate microwave-assisted extraction (MAE) of dried ginger and to develop a rice-based edible film incorporating ginger extract. The optimal MAE conditions of 400 W microwave power and an extraction time of 1 min were determined using a 32full factorial design. The optimized extract showed total phenolic compounds (TPC, 198.2 ± 0.7 mg gallic acid equivalent/g), antioxidant activity measured by DPPH (91.4 ± 0.6% inhibition), ABTS (106.4 ± 3.1 mg Trolox/g), and FRAP (304.6 ± 5.5 mg Trolox/g), and bioactive compounds including 6-gingerol (71.5 ± 3.6 mg/g), 6-shogaol (12.5 ± 1.0 mg/g), paradol (23.1 ± 1.1 mg/g), and zingerone (5.0 ± 0.3 mg/g). Crude extract of dried ginger showed antimicrobial activity againstStreptococcus mutansDMST 18777, with a minimum inhibitory concentration and minimum bactericidal concentration of 0.5 and 31.2 mg/mL, respectively. The rice-based edible film incorporating 3.2% (w/v) ginger extract tested againstS. mutansDMST 18777 had a mean zone of inhibition of 12.7 ± 0.1 mm. Four main phenolic compounds, 6-gingerol, 6-shogaol, paradol, and zingerone, and six volatile compounds, α-curcumene, α-zingiberene, γ-muurolene, α-farnesene, β-bisabolene, and β-sesquiphellandrene, were found in rice film fortified with crude ginger extract.
Development of rapid and cost-effective top-loading device for the detection of anti-SARS-CoV-2 IgG/IgM antibodies
Authors: Ibrahim Essam H. , Ghramh Hamed A. , Kilany Mona
Published: July 2021

Infection with SARS-CoV-2, the Betacoronavirus, caused a pandemic that affected the globe negatively. The gold method, RT-PCR, can detect SARS-CoV-2 but it is time-consuming and needs sophisticated equipment and professional personnel. On the other hand, rapid tests offer fast results and can detect anti-SARS-CoV-2 antibodies (Abs). The aim of this study is to develop a new rapid and cost-effective method for the detection of anti-SARS-CoV-2 IgG/IgM Abs. A new top-loading detection device was developed and composed of a small piece of plastic (25 × 25 × 0.5 mm) with an opening in the center, a piece of nitrocellulose (NC) membrane enough to block the opening from one side and adhesive tape to affix the NC to the plastic piece. The NC is blotted with anti-human IgG/IgM and rabbit serum. The device was evaluated against a commercially available IgG/IgM ELISA detection kit using normal, Covid-19-positive, HCV, HBV, and Cytomegalovirus-positive sera. Outcomes demonstrated simplicity, reproducibility, and accuracy of the new device and results can be obtained in less than 5 min. We anticipate our developed assay method to be used widely in point of care before deciding on the use of expensive nucleic acid assays.
Outside testing of wearable robots for gait assistance shows a higher metabolic benefit than testing on treadmills
Authors: Haufe Florian Leander , Duroyon Eléonore Gascou , Wolf Peter , Riener Robert , Xiloyannis Michele
Published: July 2021

Most wearable robots that assist the gait of workers, soldiers, athletes, and hobbyists are developed towards a vision of outdoor, overground walking. However, so far, these devices have predominantly been tested indoors on laboratory treadmills. It is unclear whether treadmill-based laboratory tests are an accurate representation of overground ambulation outdoors with respect to essential outcomes such as the metabolic benefits of robotic assistance. In this study, we investigated the metabolic benefits of the Myosuit, a wearable robot that assists hip and knee extension during the stance phase of gait, for eight unimpaired participants during uphill walking trials in three settings: outside, on a self-paced treadmill with a virtual reality display, and on a standard treadmill at a fixed gait speed. The relative metabolic reduction with Myosuit assistance was most pronounced in the outside setting at − 10.6% and significantly larger than in the two treadmill settings (− 6.9%, p = 0.015 and − 6.2%, p = 0.008). This indicates that treadmill tests likely result in systematically low estimate for the true metabolic benefits of wearable robots during outside, overground walking. Hence, wearable robots should preferably be tested in an outdoor environment to obtain more representative—and ultimately more favorable—results with respect to the metabolic benefit of robotic gait assistance.
A parametric neutron Bragg edge imaging study of additively manufactured samples treated by laser shock peening
Authors: Busi Matteo , Kalentics Nikola , Morgano Manuel , Griffiths Seth , Tremsin Anton S. , Shinohara Takenao , Logé Roland , Leinenbach Christian , Strobl Markus
Published: July 2021

Laser powder bed fusion is an additive manufacturing technique extensively used for the production of metallic components. Despite this process has reached a status at which parts are produced with mechanical properties comparable to those from conventional production, it is still prone to introduce detrimental tensile residual stresses towards the surfaces along the building direction, implying negative consequences on fatigue life and resistance to crack formations. Laser shock peening (LSP) is a promising method adopted to compensate tensile residual stresses and to introduce beneficial compressive residual stress on the treated surfaces. Using neutron Bragg edge imaging, we perform a parametric study of LSP applied to 316L steel samples produced by laser powder bed fusion additive manufacturing. We include in the study the novel 3D-LSP technique, where samples are LSP treated also during the building process, at intermediate build layers. The LSP energy and spot overlap were set to either 1.0 or 1.5 J and 40$$\%$$
%
or 80$$\%$$
%
respectively. The results support the use of 3D-LSP treatment with the higher LSP laser energy and overlap applied, which showed a relative increase of surface compressive residual stress (CRS) and CRS depth by 54$$\%$$
%
and 104$$\%$$
%
respectively, compared to the conventional LSP treatment.
Roles for B[a]P and FICZ in subchondral bone metabolism and experimental temporomandibular joint osteoarthritis via the AhR/Cyp1a1 signaling axis
Authors: Yoshikawa Yuri , Izawa Takashi , Hamada Yusaku , Takenaga Hiroko , Wang Ziyi , Ishimaru Naozumi , Kamioka Hiroshi
Published: July 2021

Bone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) and its ligands contributes to both bone homeostasis and inflammatory diseases. It remains unclear whether the same AhR signaling axis affects the temporomandibular joint (TMJ). The aim of this study was to investigate possible mechanisms which mediate bone loss in the TMJ due to smoking. In particular, whether benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke, induces expression of the AhR target gene, Cyp1a1, in mandibular condyles. Possible functions of an endogenous ligand of FICZ, were also investigated in a TMJ-osteoarthritis (OA) mouse model. B[a]P was administered orally to wild-type and AhR−/− mice and bone metabolism was subsequently examined. TMJ-OA was induced in wild-type mice with forceful opening of the mouth. Therapeutic functions of FICZ were detected with μCT and histology. Exposure to B[a]P accelerated bone loss in the mandibular subchondral bone. This bone loss manifested with osteoclastic bone resorption and upregulated expression of Cyp1a1 in an AhR-dependent manner. In a mouse model of TMJ-OA, FICZ exhibited a dose-dependent rescue of mandibular subchondral bone loss by repressing osteoclast activity. Meanwhile, in vitro, pre-treatment with FICZ reduced RANKL-mediated osteoclastogenesis. B[a]P regulates mandibular subchondral bone metabolism via the Cyp1a1. The AhR ligand, FICZ, can prevent TMJ-OA by regulating osteoclast differentiation.
Depressive symptoms and 5-year incident metabolic syndrome among older adults
Authors: Wu Qian , Hua Yi-Ying , Ma Qing-Hua , Xu Yong , Chen Xing , Pan Chen-Wei
Published: July 2021

Little is known regarding the association between depressive symptoms and metabolic syndrome (MetS) among older Chinese adults. This study aimed to examine the association of depressive symptoms with MetS and its components among Chinese elderly. Based on whether they showed depressive symptoms at baseline, 262 age-gender-matched participants from a community-based cohort study were included. The presence of depressive symptoms was measured using the nine-item Patient Health Questionnaire (PHQ-9). MetS was defined according to the Adult Treatment Panel III of the National Cholesterol Education Program. Linear regression and logistic regression analyses were performed to assess associations of depressive symptoms with MetS and its components. The incidence of MetS among the participants with depressive symptoms at baseline was 15.27% (20/131). The association of the presence of depressive symptoms with MetS was significant (odds ratio [OR] = 2.53, 95% confidence intervals [CI] = 1.07, 5.95). There was a negative association between depressive symptoms and hypertension (OR = 0.04, 95% CI = 0.002, 0.98). The change in mean arterial pressure varies approximately 1.03 mmHg with a 1-point change in PHQ-9 score. In this study, baseline depressive symptoms were associated with subsequent MetS. The presence of depressive symptoms was negatively associated with elevated mean arterial pressure.
Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma
Authors: Caso Raul , Connolly James G. , Zhou Jian , Tan Kay See , Choi James J. , Jones Gregory D. , Mastrogiacomo Brooke , Sanchez-Vega Francisco , Nguyen Bastien , Rocco Gaetano , Molena Daniela , Sihag Smita , Adusumilli Prasad S. , Bott Matthew J. , Jones David R.
Published: July 2021

While next-generation sequencing (NGS) is used to guide therapy in patients with metastatic lung adenocarcinoma (LUAD), use of NGS to determine pathologic LN metastasis prior to surgery has not been assessed. To bridge this knowledge gap, we performed NGS using MSK-IMPACT in 426 treatment-naive patients with clinical N2-negative LUAD. A multivariable logistic regression model that considered preoperative clinical and genomic variables was constructed. Most patients had cN0 disease (85%) with pN0, pN1, and pN2 rates of 80%, 11%, and 9%, respectively. Genes altered at higher rates in pN-positive than in pN-negative tumors were STK11 (p = 0.024), SMARCA4 (p = 0.006), and SMAD4 (p = 0.011). Fraction of genome altered (p = 0.037), copy number amplifications (p = 0.001), and whole-genome doubling (p = 0.028) were higher in pN-positive tumors. Multivariable analysis revealed solid tumor morphology, tumor SUVmax, clinical stage, SMARCA4 and SMAD4 alterations were independently associated with pathologic LN metastasis. Incorporation of clinical and tumor genomic features can identify patients at risk of pathologic LN metastasis; this may guide therapy decisions before surgical resection.
Temperature dependent moiré trapping of interlayer excitons in MoSe2-WSe2 heterostructures
Authors: Mahdikhanysarvejahany Fateme , Shanks Daniel N. , Muccianti Christine , Badada Bekele H. , Idi Ithwun , Alfrey Adam , Raglow Sean , Koehler Michael R. , Mandrus David G. , Taniguchi Takashi , Watanabe Kenji , Monti Oliver L. A. , Yu Hongyi , LeRoy Brian J. , Schaibley John R.
Published: July 2021

MoSe2–WSe2 heterostructures host strongly bound interlayer excitons (IXs), which exhibit bright photoluminescence (PL) when the twist angle is near 0° or 60°. Over the past several years, there have been numerous reports on the optical response of these heterostructures but no unifying model to understand the dynamics of IXs and their temperature dependence. Here we perform a comprehensive study of the temperature, excitation power, and time-dependent PL of IXs. We observe a significant decrease in PL intensity above a transition temperature that we attribute to a transition from localized to delocalized IXs. Astoundingly, we find a simple inverse relationship between the IX PL energy and the transition temperature, which exhibits opposite power-dependent behaviors for near 0° and 60° samples. We conclude that this temperature dependence is a result of IX–IX exchange interactions, whose effect is suppressed by the moiré potential trapping IXs at low temperature.
Structure-function analysis of purified proanthocyanidins reveals a role for polymer size in suppressing inflammatory responses
Authors: Andersen-Civil Audrey Inge Schytz , Leppä Milla Marleena , Thamsborg Stig M. , Salminen Juha-Pekka , Williams Andrew R.
Published: July 2021

Proanthocyanidins (PAC) are dietary compounds that have been extensively studied for beneficial health effects due to their anti-inflammatory properties. However, the structure-function relationships of PAC and their mode-of-action remain obscure. Here, we isolated a wide range of diverse PAC polymer mixtures of high purity from plant material. Polymer size was a key factor in determining the ability of PAC to regulate inflammatory cytokine responses in murine macrophages. PAC polymers with a medium (9.1) mean degree of polymerization (mDP) induced substantial transcriptomic changes, whereas PAC with either low (2.6) or high (12.3) mDP were significantly less active. Short-term oral treatment of mice with PAC modulated gene pathways connected to nutrient metabolism and inflammation in ileal tissue in a polymerization-dependent manner. Mechanistically, the bioactive PAC polymers modulated autophagic flux and inhibited lipopolysaccharide-induced autophagy in macrophages. Collectively, our results highlight the importance of defined structural features in the health-promoting effects of PAC-rich foods.
Assessing teachers’ knowledge: incorporating context-based learning in chemistry
Authors: Tal Marina , Herscovitz Orit , Dori Yehudit Judy
Published: July 2021

Content knowledge (CK), pedagogical content knowledge (PCK) and, assessment knowledge (AK) are fundamental types of teachers’ knowledge. Second-career, pre-service chemistry teachers leave the industry and return to the Technion to study in theViewsprogram to obtain a high school teaching certificate. Their background can potentially contribute to higher quality of science teaching and learning in general and of chemistry teaching in particular. We investigated how pre-service chemistry teachers’ knowledge develops as they are exposed to chemistry context-based learning, and what differences are there between pre- and in-service teachers’ knowledge types and their self-efficacy. The participants were 25 second-career pre-service teachers and 29 in-service chemistry teachers who served as a comparison group. The teachers’ professional growth was examined by assessing their CK, PCK, AK, and self-efficacy by using three questionnaires that included adapted scientific articles on energy, acid-base, and oxidation-reduction in the context of sustainability. Five expert chemistry teachers validated the questionnaires. We found that all three knowledge types of the pre-service teachers improved during the course and they became more aware of sustainable chemistry issues than the in-service teachers. The study contributes to chemistry education by narrowing the gap that exists in the literature between chemistry teachers’ PCK and AK on the one hand and self-efficacy on the other hand. We offer an assessment tool for identifying and quantifying teachers’ knowledge. We offer recommendations for science educators about the needs, strengths, and weaknesses of pre- and in-service teachers related to teaching sustainable chemistry.