bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic overlap and causal associations between smoking behaviours and mental health
Authors: Barkhuizen Wikus , Dudbridge Frank , Ronald Angelica 
Published: July 2021

AbstractCigarette smoking is a modifiable behaviour associated with mental health. We investigated the degree of genetic overlap between smoking behaviours and psychiatric traits and disorders, and whether genetic associations exist beyond genetic influences shared with confounding variables (cannabis and alcohol use, risk-taking and insomnia). Second, we investigated the presence of causal associations between smoking initiation and psychiatric traits and disorders. We found significant genetic correlations between smoking and psychiatric disorders and adult psychotic experiences. When genetic influences on known covariates were controlled for, genetic associations between most smoking behaviours and schizophrenia and depression endured (but not with bipolar disorder or most psychotic experiences). Mendelian randomization results supported a causal role of smoking initiation on psychiatric disorders and adolescent cognitive and negative psychotic experiences, although not consistently across all sensitivity analyses. In conclusion, smoking and psychiatric disorders share genetic influences that cannot be attributed to covariates such as risk-taking, insomnia or other substance use. As such, there may be some common genetic pathways underlying smoking and psychiatric disorders. In addition, smoking may play a causal role in vulnerability for mental illness.
A precision medicine approach to sex-based differences in ideal cardiovascular health
Authors: Leopold Jane A. , Antman Elliott M. 
Published: July 2021

AbstractCardiovascular disease risk factor profiles and health behaviors are known to differ between women and men. Sex-based differences in ideal cardiovascular health were examined in the My Research Legacy study, which collected cardiovascular health and lifestyle data via Life’s Simple 7 survey and digital health devices. As the study overenrolled women (n = 1251) compared to men (n = 310), we hypothesized that heterogeneity among women would affect comparisons of ideal cardiovascular health. We identified 2 phenogroups of women in our study cohort by cluster analysis. The phenogroups differed significantly across all 7 cardiovascular health and behavior domains (all p < 0.01) with women in phenogroup 1 having a lower Life’s Simple 7 Health Score than those in phenogroup 2 (5.9 ± 1.3 vs. 7.6 ± 1.3, p < 0.01). Compared to men, women in phenogroup 1 had a higher burden of cardiovascular disease risk factors, exercised less, and had lower ideal cardiovascular health scores (p < 0.01). In contrast, women in phenogroup 2 had fewer cardiovascular risk factors but similar exercise habits and higher ideal cardiovascular health scores than men (p < 0.01). These findings suggest that heterogeneity among study participants should be examined when evaluating sex-based differences in ideal cardiovascular health.
SHH-N non-canonically sustains androgen receptor activity in androgen-independent prostate cancer cells
Authors: Trnski Diana , Sabol Maja , Tomić Sanja , Štefanac Ivan , Mrčela Milanka , Musani Vesna , Rinčić Nikolina , Kurtović Matea , Petrić Tina , Levanat Sonja , Ozretić Petar 
Published: July 2021

AbstractProstate cancer is the second most frequent cancer diagnosed in men worldwide. Localized disease can be successfully treated, but advanced cases are more problematic. After initial effectiveness of androgen deprivation therapy, resistance quickly occurs. Therefore, we aimed to investigate the role of Hedgehog-GLI (HH-GLI) signaling in sustaining androgen-independent growth of prostate cancer cells. We found various modes of HH-GLI signaling activation in prostate cancer cells depending on androgen availability. When androgen was not deprived, we found evidence of non-canonical SMO signaling through the SRC kinase. After short-term androgen deprivation canonical HH-GLI signaling was activated, but we found little evidence of canonical HH-GLI signaling activity in androgen-independent prostate cancer cells. We show that in androgen-independent cells the pathway ligand, SHH-N, non-canonically binds to the androgen receptor through its cholesterol modification. Inhibition of this interaction leads to androgen receptor signaling downregulation. This implies that SHH-N activates the androgen receptor and sustains androgen-independence. Targeting this interaction might prove to be a valuable strategy for advanced prostate cancer treatment. Also, other non-canonical aspects of this signaling pathway should be investigated in more detail and considered when developing potential therapies.
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

AbstractImage 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

AbstractThe 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

AbstractAbsorption 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

AbstractAn 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

AbstractLipid 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

AbstractInterleukin-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

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractC57BL/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

AbstractWe 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.