bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell-in-the-loop pattern formation with optogenetically emulated cell-to-cell signaling
Authors: Perkins Melinda Liu , Benzinger Dirk , Arcak Murat , Khammash Mustafa
Published: March 2020

Designing and implementing synthetic biological pattern formation remains challenging due to underlying theoretical complexity as well as the difficulty of engineering multicellular networks biochemically. Here, we introduce a cell-in-the-loop approach where living cells interact through in silico signaling, establishing a new testbed to interrogate theoretical principles when internal cell dynamics are incorporated rather than modeled. We present an easy-to-use theoretical test to predict the emergence of contrasting patterns in gene expression among laterally inhibiting cells. Guided by the theory, we experimentally demonstrate spontaneous checkerboard patterning in an optogenetic setup, where cell-to-cell signaling is emulated with light inputs calculated in silico from real-time gene expression measurements. The scheme successfully produces spontaneous, persistent checkerboard patterns for systems of sixteen patches, in quantitative agreement with theoretical predictions. Our research highlights how tools from dynamical systems theory may inform our understanding of patterning, and illustrates the potential of cell-in-the-loop for engineering synthetic multicellular systems.
Pretreatment tumor-related leukocytosis misleads positron emission tomography-computed tomography during lymph node staging in gynecological malignancies
Authors: Mabuchi Seiji , Komura Naoko , Sasano Tomoyuki , Shimura Kotaro , Yokoi Eriko , Kozasa Katsumi , Kuroda Hiromasa , Takahashi Ryoko , Kawano Mahiru , Matsumoto Yuri , Kato Hiroki , Hatazawa Jun , Kimura Tadashi
Published: March 2020

The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) can be influenced by the increased glycolytic activity of inflammatory lesions. Here, using clinical data obtained from gynecological cancer patients, tumor samples and animal models, we investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. We demonstrate that pretreatment TRL misleads 18F-FDG-PET/CT during lymph node staging in gynecological malignancies. In the mechanistic investigations, we show that the false-positive 18F-FDG-PET/CT result for detecting nodal metastasis can be reproduced in animal models of TRL-positive cancer bearing G-CSF expressing cervical cancer cells. We also show that increased 18F-FDG uptake in non-metastatic nodes can be explained by the MDSC-mediated premetastatic niche formation in which proinflammatory factors, such as S100A8 or S100A9, are abundantly expressed. Together, our results suggest that the MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis.
Cell lineage-specific transcriptome analysis for interpreting cell fate specification of proembryos
Authors: Zhou Xuemei , Liu Zhenzhen , Shen Kun , Zhao Peng , Sun Meng-Xiang
Published: March 2020

In Arabidopsis, a zygote undergoes asymmetrical cell division that establishes the first two distinct cell types of early proembryos, apical and basal cells. However, the genome-wide transcriptional activities that guide divergence of apical and basal cell development remain unknown. Here, we present a comprehensive transcriptome analysis of apical and basal cell lineages, uncovering distinct molecular pathways during cell lineage specification. Selective deletion of inherited transcripts and specific de novo transcription contribute to the establishment of cell lineage-specific pathways for cell fate specification. Embryo-related pathways have been specifically activated in apical cell lineage since 1-cell embryo stage, but quick transcriptome remodeling toward suspensor-specific pathways are found in basal cell lineage. Furthermore, long noncoding RNAs and alternative splicing isoforms may be involved in cell lineage specification. This work also provides a valuable lineage-specific transcriptome resource to elucidate the molecular pathways for divergence of apical and basal cell lineages at genome-wide scale.
Temporospatial shifts in the human gut microbiome and metabolome after gastric bypass surgery
Authors: Ilhan Zehra Esra , DiBaise John K. , Dautel Sydney E. , Isern Nancy G. , Kim Young-Mo , Hoyt David W. , Schepmoes Athena A. , Brewer Heather M. , Weitz Karl K. , Metz Thomas O. , Crowell Michael D. , Kang Dae-Wook , Rittmann Bruce E. , Krajmalnik-Brown Rosa
Published: March 2020

Although the etiology of obesity is not well-understood, genetic, environmental, and microbiome elements are recognized as contributors to this rising pandemic. It is well documented that Roux-en-Y gastric bypass (RYGB) surgery drastically alters the fecal microbiome, but data are sparse on temporal and spatial microbiome and metabolome changes, especially in human populations. We characterized the structure and function (through metabolites) of the microbial communities in the gut lumen and structure of microbial communities on mucosal surfaces in nine morbidly obese individuals before, 6 months, and 12 months after RYGB surgery. Moreover, using a comprehensive multi-omic approach, we compared this longitudinal cohort to a previously studied cross-sectional cohort (n = 24). In addition to the expected weight reduction and improvement in obesity-related comorbidities after RYGB surgery, we observed that the impact of surgery was much greater on fecal communities in comparison to mucosal ones. The changes in the fecal microbiome were linked to increased concentrations of branched-chain fatty acids and an overall decrease in secondary bile acid concentrations. The microbiome and metabolome data sets for this longitudinal cohort strengthen our understanding of the persistent impact of RYGB on the gut microbiome and its metabolism. Our findings highlight the importance of changes in mucosal and fecal microbiomes after RYGB surgery. The spatial modifications in the microbiome after RYGB surgery corresponded to persistent changes in fecal fermentation and bile acid metabolism, both of which are associated with improved metabolic outcomes.
Risk factors of meconium-related ileus in very low birth weight infants: patients-control study
Authors: Byun Jeik , Han Ji-Won , Youn Joong Kee , Yang Hee-Beom , Shin Seung Han , Kim Ee-Kyung , Kim Hyun-Young , Jung Sung-Eun
Published: March 2020

Very low birth weight (VLBW) neonates experience various problems, including meconium-related ileus (MRI). This study investigated the risk factors of MRI and surgical MRI in VLBW infants. VLBW neonates admitted to the Neonatal Intensive Care Unit of Seoul National University Children’s Hospital from October 2002 to September 2016 were included in the study. The diagnostic criteria for MRI were a decreased frequency of defecation with intolerable feeding, vomiting, and increased gastric residue (>50%); meconium-filled bowel dilatation in an imaging study; and no evidence of necrotizing enteritis or spontaneous intestinal perforation. Medical MRIs and surgical MRIs were managed through conventional treatment and surgical intervention. Of 1543 neonates, 69 and 1474 were in the patient and control groups, respectively. The risk factors for MRI include low birth weight (BW), cesarean section delivery, fetal distress, maternal diabetes, maternal hypertension, and maternal steroid use. Low BW and fetal distress were independent risk factors for MRI. Compared to the medical MRI group (n = 44), the risk factors for surgical MRI (n = 25) included males, younger gestational age, low BW, and meconium located at the small bowel. Male gender and low BW were independent risk factors for surgical MRI. Low BW and fetal distress were independent risk factors for MRI and male gender and low BW were independent risk factors for surgical MRI. In VLBW neonates, careful attention to the risk factors for MRI could minimize or avoid surgical interventions.
Snow Mountain Virus recovery by synthetic human histo-blood group antigens is heavily influenced by matrix effects
Authors: Kirby Amy E. , Kienast Yvonne , Aldeco Milagros , Steele Molly , Dhawane Abasaheb N. , Liu Dandan , Cui Xikai , Das Amrita , Iyer Suri , Moe Christine L.
Published: March 2020

Noroviruses are known to bind to histo-blood group antigens (HBGAs) and the specific binding patterns depend on the virus genotype. However, the development of point-of-care diagnostic assays based on this binding has been challenging due to low assay sensitivity. This study utilized a well-defined stool collection from a GII.2 Snow Mountain Virus (SMV) human challenge study to investigate virus recovery from stool and emesis samples using HBGA-coated beads. SMV was recovered from H type III-coated beads for 13 stool specimens out of 27 SMV-positive specimens tested. After adjusting for non-specific binding to PEG-coated beads, the mean percent recovery by H type III-coated beads was 308.11% +/− 861.61. Recovery by H type III ligands was subject-specific and weakly correlated with stool consistency. Input virus titer was not correlated with SMV recovery. The results suggest that the generally low virus recovery we observed may be due to bead saturation or hindrance by existing glycans in the matrix that precluded the virus from being captured by the synthetic glycans. These results indicate a strong role for subject-specific and matrix effects in HBGA binding by SMV. Further investigation of the nature of this interference is needed to facilitate development of high sensitivity diagnostic assays.
Input attributes optimization using the feasibility of genetic nature inspired algorithm: Application of river flow forecasting
Authors: Afan Haitham Abdulmohsin , Allawi Mohammed Falah , El-Shafie Amr , Yaseen Zaher Mundher , Ahmed Ali Najah , Malek Marlinda Abdul , Koting Suhana Binti , Salih Sinan Q. , Mohtar Wan Hanna Melini Wan , Lai Sai Hin , Sefelnasr Ahmed , Sherif Mohsen , El-Shafie Ahmed
Published: March 2020

In nature, streamflow pattern is characterized with high non-linearity and non-stationarity. Developing an accurate forecasting model for a streamflow is highly essential for several applications in the field of water resources engineering. One of the main contributors for the modeling reliability is the optimization of the input variables to achieve an accurate forecasting model. The main step of modeling is the selection of the proper input combinations. Hence, developing an algorithm that can determine the optimal input combinations is crucial. This study introduces the Genetic algorithm (GA) for better input combination selection. Radial basis function neural network (RBFNN) is used for monthly streamflow time series forecasting due to its simplicity and effectiveness of integration with the selection algorithm. In this paper, the RBFNN was integrated with the Genetic algorithm (GA) for streamflow forecasting. The RBFNN-GA was applied to forecast streamflow at the High Aswan Dam on the Nile River. The results showed that the proposed model provided high accuracy. The GA algorithm can successfully determine effective input parameters in streamflow time series forecasting.
From antagonism to synergism: Extreme differences in stressor interactions in one species
Authors: Straub Lars , Minnameyer Angela , Strobl Verena , Kolari Eleonora , Friedli Andrea , Kalbermatten Isabelle , Merkelbach Antoine Joseph Willem Marie , Victor Yañez Orlando , Neumann Peter
Published: March 2020

Interactions between stressors are involved in the decline of wild species and losses of managed ones. Those interactions are often assumed to be synergistic, and per se of the same nature, even though susceptibility can vary within a single species. However, empirical measures of interaction effects across levels of susceptibility remain scarce. Here, we show clear evidence for extreme differences in stressor interactions ranging from antagonism to synergism within honeybees, Apis mellifera. While female honeybee workers exposed to both malnutrition and the pathogen Nosema ceranae showed synergistic interactions and increased stress, male drones showed antagonistic interactions and decreased stress. Most likely sex and division of labour in the social insects underlie these findings. It appears inevitable to empirically test the actual nature of stressor interactions across a range of susceptibility factors within a single species, before drawing general conclusions.
Temperature-related body size change of marine benthic macroinvertebrates across the Early Toarcian Anoxic Event
Authors: Piazza Veronica , Ullmann Clemens V. , Aberhan Martin
Published: March 2020

The Toarcian Oceanic Anoxic Event (TOAE, Early Jurassic, ~182 Ma ago) was characterised by severe environmental perturbations which led to habitat degradation and extinction of marine species. Warming-induced anoxia is usually identified as main driver, but because marine life was also affected in oxygenated environments the role of raised temperature and its effects on marine life need to be addressed. Body size is a fundamental characteristic of organisms and is expected to decrease as a response to heat stress. We present quantitative size data of bivalves and brachiopods across the TOAE from oxygenated habitats in the Iberian Basin, integrated with geochemical proxy data (δ13C and δ18O), to investigate the relationship between changes in temperature and body size. We find a strong negative correlation between the mean shell size of bivalve communities and isotope-derived temperature estimates, suggesting heat stress as a main cause of body size reduction. While within-species size changes were minor, we identify changes in the abundance of differently sized species as the dominant mechanism of reduced community shell size during the TOAE. Brachiopods experienced a wholesale turnover across the early warming phase and were replaced by a virtually monotypic assemblage of a smaller-sized, opportunistic species.
Emergence of Visual Center-Periphery Spatial Organization in Deep Convolutional Neural Networks
Authors: Mohsenzadeh Yalda , Mullin Caitlin , Lahner Benjamin , Oliva Aude
Published: March 2020

Research at the intersection of computer vision and neuroscience has revealed hierarchical correspondence between layers of deep convolutional neural networks (DCNNs) and cascade of regions along human ventral visual cortex. Recently, studies have uncovered emergence of human interpretable concepts within DCNNs layers trained to identify visual objects and scenes. Here, we asked whether an artificial neural network (with convolutional structure) trained for visual categorization would demonstrate spatial correspondences with human brain regions showing central/peripheral biases. Using representational similarity analysis, we compared activations of convolutional layers of a DCNN trained for object and scene categorization with neural representations in human brain visual regions. Results reveal a brain-like topographical organization in the layers of the DCNN, such that activations of layer-units with central-bias were associated with brain regions with foveal tendencies (e.g. fusiform gyrus), and activations of layer-units with selectivity for image backgrounds were associated with cortical regions showing peripheral preference (e.g. parahippocampal cortex). The emergence of a categorical topographical correspondence between DCNNs and brain regions suggests these models are a good approximation of the perceptual representation generated by biological neural networks.
Streptococcus gallolyticus abrogates anti-carcinogenic properties of tannic acid on low-passage colorectal carcinomas
Authors: Oehmcke-Hecht Sonja , Mandl Vanessa , Naatz Lukas Tim , Dühring Lara , Köhler Juliane , Kreikemeyer Bernd , Maletzki Claudia
Published: March 2020

The tannase-producing Gram-positive bacterial species Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathogen of the human gut and strongly associated with colorectal cancer (CRC). A unique feature of Sgg is its ability to degrade tannic acids (TA). TA constitute an important part of the human diet with known anti-tumorigenic properties. Here, we examined whether Sgg is able to protect tumor cells from the toxic effect of TA and thus drive tumorigenesis indirectly. Human CRC cell lines (n = 8) were treated with increasing concentrations of TA. We confirmed the cytotoxic activity of TA in a dose-dependent manner. In virtually all cell lines, viability decreased significantly (>60% inhibition). Moreover, pyrogallol, the degradation product of TA, had no effect on the tested cell lines. This suggests a specific effect of TA. Cytotoxicity was due to necrosis and induction of senescence in residual cells. Finally, when TA was degraded by Sgg, the cytotoxic effect could be abolished. Tumor cells even responded with boosted cell proliferation, highlighting the impact of Sgg on CRC progression. We here provide another piece of evidence for the active interplay between Sgg and cancer preventive components. These data will help to move forward in designing concepts for therapeutic and eventually also prophylactic approaches to combat gastrointestinal malignancies.
Circulating CD34+ cells and active arterial wall thickening among elderly men: A prospective study
Authors: Shimizu Yuji , Kawashiri Shin-Ya , Kiyoura Kairi , Koyamatsu Jun , Fukui Shoichi , Tamai Mami , Nobusue Kenichi , Yamanashi Hirotomo , Nagata Yasuhiro , Maeda Takahiro
Published: March 2020

Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60–69 years who participated in a general health check-up at least twice from 2014–2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. This study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects.
Improving understanding of carbon stock characteristics of Eucalyptus and Acacia trees in southern China through litter layer and woody debris
Authors: Zhang Hui , Jiang Yinhua , Song Mingwei , He Jiajun , Guan Dongsheng
Published: March 2020

Surveying the quality and quantity of carbon stock in litter layer and woody debris of Eucalyptus and Acacia plantations is critical in understanding their carbon pools. Here, the focus of the present study was on a number of Eucalyptus and Acacia plantations of different stand aged in the Pearl River Delta region of southern China. The plantation type proved to be a crucial driver of the carbon concentration in litter layer and woody debris, with Acacia exhibiting a superior ability to Eucalyptus to accumulate carbon with stand age in both these materials. The relative contribution of the litter layer and woody debris to the carbon stock of the ecosystem was also significantly higher under mature Acacia (8% and 7%, respectively) than that under mature Eucalyptus (4% and 1%, respectively). Most of the carbon stock within the litter layer was present in the leaf debris. The carbon stock in woody debris was mainly contained in the components within the 10–20 cm diameter class during the primary decay stage, represented as snags in middle-aged and mature Acacia, and as logs for mature Eucalyptus, respectively. The results indicate that both plantation type and stand age influence the characteristics of carbon stored in litter layer and woody debris significantly.
Tead transcription factors differentially regulate cortical development
Authors: Mukhtar Tanzila , Breda Jeremie , Grison Alice , Karimaddini Zahra , Grobecker Pascal , Iber Dagmar , Beisel Christian , van Nimwegen Erik , Taylor Verdon
Published: March 2020

Neural stem cells (NSCs) generate neurons of the cerebral cortex with distinct morphologies and functions. How specific neuron production, differentiation and migration are orchestrated is unclear. Hippo signaling regulates gene expression through Tead transcription factors (TFs). We show that Hippo transcriptional coactivators Yap1/Taz and the Teads have distinct functions during cortical development. Yap1/Taz promote NSC maintenance and Satb2+ neuron production at the expense of Tbr1+ neuron generation. However, Teads have moderate effects on NSC maintenance and do not affect Satb2+ neuron differentiation. Conversely, whereas Tead2 blocks Tbr1+ neuron formation, Tead1 and Tead3 promote this early fate. In addition, we found that Hippo effectors regulate neuronal migration to the cortical plate (CP) in a reciprocal fashion, that ApoE, Dab2 and Cyr61 are Tead targets, and these contribute to neuronal fate determination and migration. Our results indicate that multifaceted Hippo signaling is pivotal in different aspects of cortical development.
Accelerated identification of serine racemase inhibitor from Centella asiatica
Authors: Rani Komal , Tyagi Mitali , Mazumder Mohit , Singh Akanksha , Shanmugam Annaian , Dalal Krishna , Pillai Manoj , Samudrala Gourinath , Kumar Saroj , Srinivasan Alagiri
Published: March 2020

Serine racemase (SR) converts the free form of L-serine into D-serine (DS) in the mammalian brain. The DS functions as a co-agonist of N-methyl D-aspartate (NMDA) receptor. The over- activation of NMDA receptor leads to many neurological disorders like stroke, amyotrophic lateral sclerosis, Alzheimer’s disease and an effective inhibitor of SR could be a corrective method for the receptor over-activation. We report for the first time here a rapid way of purifying and identifying an inhibitor from medicinal plants known to have the neuro-protective effect. We have purified SR inhibitor from the methanolic extract ofCentella asiaticaby affinity method. High resolution mass spectrometry and infrared spectroscopy were used to identify the ligand to be madecassoside. We have shown the madecassoside bindingin silicoand its inhibition of recombinant human serine racemasein vitroandex vivo.
Circulating leptin levels are associated with adiposity in survivors of childhood brain tumors
Authors: Sims E. Danielle , Jennings William J. , Empringham Brianna , Fleming Adam , Portwine Carol , Johnston Donna L. , Zelcer Shayna M. , Rassekh Shahrad Rod , Burrow Sarah , Thabane Lehana , Samaan M. Constantine
Published: March 2020

Survivors of Childhood Brain Tumors (SCBT) are at a higher risk of developing cardiovascular disease and type 2 diabetes compared to the general population. Adiposity is an important risk factor for the development of these outcomes, and identifying biomarkers of adiposity may help the stratification of survivors based on their cardiovascular risk or allow for early screening and interventions to improve cardiometabolic outcomes. Leptin is an adipokine that positively correlates with the adipose mass in the general population and is a predictor of adverse cardiometabolic outcomes, yet its association with adiposity in SCBT has not been studied. The aim of this study was to determine if leptin levels are associated with the adipose mass in SCBT, and to define its predictors. This cross-sectional study included 74 SCBT (n = 32 females) with 126 non-cancer controls (n = 59 females). Total adiposity was measured using Bioelectrical Impendence Analysis (BIA) and central adiposity was measured using waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). We used multivariable linear regression analysis to determine if leptin predicts adiposity in SCBT and adjusted for age, sex, puberty, and cancer status. Leptin correlated strongly with total (p < 0.001) and central (WHR p = 0.001; WHtR p < 0.001) adiposity in SCBT and non-cancer controls. In conclusion, leptin is a potential biomarker for adiposity in SCBT, and further investigation is needed to clarify if leptin is a predictor of future cardiometabolic risk in SCBT.
Unraveling the Origin of Social Bursts in Collective Attention
Authors: De Domenico Manlio , Altmann Eduardo G.
Published: March 2020

In the era of social media, every day billions of individuals produce content in socio-technical systems resulting in a deluge of information. However, human attention is a limited resource and it is increasingly challenging to consume the most suitable content for one’s interests. In fact, the complex interplay between individual and social activities in social systems overwhelmed by information results in bursty activity of collective attention which are still poorly understood. Here, we tackle this challenge by analyzing the online activity of millions of users in a popular microblogging platform during exceptional events, from NBA Finals to the elections of Pope Francis and the discovery of gravitational waves. We observe extreme fluctuations in collective attention that we are able to characterize and explain by considering the co-occurrence of two fundamental factors: the heterogeneity of social interactions and the preferential attention towards influential users. Our findings demonstrate how combining simple mechanisms provides a route towards understanding complex social phenomena.
Chiral supramolecular architecture of stable transmembrane pores formed by an α-helical antibiotic peptide in the presence of lyso-lipids
Authors: Strandberg Erik , Bentz David , Wadhwani Parvesh , Ulrich Anne S.
Published: March 2020

The amphipathic α-helical antimicrobial peptide MSI-103 (aka KIA21) can form stable transmembrane pores when the bilayer takes on a positive spontaneous curvature, e.g. by the addition of lyso-lipids. Solid-state 31P- and 15N-NMR demonstrated an enrichment of lyso-lipids in these toroidal wormholes. Anionic lyso-lipids provided additional stabilization by electrostatic interactions with the cationic peptides. The remaining lipid matrix did not affect the nature of the pore, as peptides maintained the same orientation independent of lipid charge, and a change in membrane thickness did not considerably affect their tilt angle. Under optimized conditions (i.e. in the presence of lyso-lipids and appropriate bilayer thickness), stable and well-aligned pores could be obtained for solid-state 2H-NMR analysis. These data revealed for the first time the complete 3D alignment of this representative amphiphilic peptide in fluid membranes, which is compatible with either monomeric helices as constituents, or left-handed supercoiled dimers as building blocks from which the overall toroidal wormhole is assembled.
Overall survival prediction of non-small cell lung cancer by integrating microarray and clinical data with deep learning
Authors: Lai Yu-Heng , Chen Wei-Ning , Hsu Te-Cheng , Lin Che , Tsao Yu , Wu Semon
Published: March 2020

Non-small cell lung cancer (NSCLC) is one of the most common lung cancers worldwide. Accurate prognostic stratification of NSCLC can become an important clinical reference when designing therapeutic strategies for cancer patients. With this clinical application in mind, we developed a deep neural network (DNN) combining heterogeneous data sources of gene expression and clinical data to accurately predict the overall survival of NSCLC patients. Based on microarray data from a cohort set (614 patients), seven well-known NSCLC biomarkers were used to group patients into biomarker- and biomarker+ subgroups. Then, by using a systems biology approach, prognosis relevance values (PRV) were then calculated to select eight additional novel prognostic gene biomarkers. Finally, the combined 15 biomarkers along with clinical data were then used to develop an integrative DNN via bimodal learning to predict the 5-year survival status of NSCLC patients with tremendously high accuracy (AUC: 0.8163, accuracy: 75.44%). Using the capability of deep learning, we believe that our prediction can be a promising index that helps oncologists and physicians develop personalized therapy and build the foundation of precision medicine in the future.
Development and internal validation of a depression severity prediction model for tinnitus patients based on questionnaire responses and socio-demographics
Authors: Niemann Uli , Brueggemann Petra , Boecking Benjamin , Mazurek Birgit , Spiliopoulou Myra
Published: March 2020

Tinnitus is a complex condition that is associated with major psychological and economic impairments – partly through various comorbidities such as depression. Understanding the interaction between tinnitus and depression may thus improve either symptom cluster’s prevention, diagnosis and treatment. In this study, we developed and validated a machine learning model to predict depression severityafteroutpatient therapy (T1) based on variables obtainedbeforetherapy (T0). 1,490 patients with chronic tinnitus (comorbid major depressive disorder: 52.2%) who completed a 7-day multimodal treatment encompassing tinnitus-specific components, cognitive behavioural therapy, physiotherapy and informational counselling were included. 185 variables were extracted from self-report questionnaires and socio-demographic data acquired at T0. We used 11 classification methods to train models that reliably separate between subclinical and clinical depression at T1 as measured by the general depression questionnaire. To ensure highly predictive and robust classifiers, we tuned algorithm hyperparameters in a 10-fold cross-validation scheme. To reduce model complexity and improve interpretability, we wrapped model training around an incremental feature selection mechanism that retained features that contributed to model prediction. We identified a LASSO model that included all 185 features to yield highest predictive performance (AUC = 0.87 ± 0.04). Through our feature selection wrapper, we identified a LASSO model with good trade-off between predictive performance and interpretability that used only 6 features (AUC = 0.85 ± 0.05). Thus, predictive machine learning models can lead to a better understanding of depression in tinnitus patients, and contribute to the selection of suitable therapeutic strategies and concise and valid questionnaire design for patients with chronic tinnitus with or without comorbid major depressive disorder.
Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors
Authors: Abdellatif Ahmed A. H. , Ibrahim Mohamed A. , Amin Mohammed A. , Maswadeh Hamzah , Alwehaibi Muhammed N. , Al-Harbi Sultan N. , Alharbi Zayed A. , Mohammed Hamdoon A. , Mehany Ahmed B. M. , Saleem Imran
Published: March 2020

There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through GIT.
Genome survey of Chinese fir (Cunninghamia lanceolata): Identification of genomic SSRs and demonstration of their utility in genetic diversity analysis
Authors: Lin Erpei , Zhuang Hebi , Yu Jinjian , Liu Xueyu , Huang Huahong , Zhu Muyuan , Tong Zaikang
Published: March 2020

Chinese fir (Cunninghamia lanceolata) is an important coniferous species that accounts for 20–30% of the total commercial timber production in China. Though traditional breeding of Chinese fir has achieved remarkable success, molecular-assisted breeding has made little progress due to limited availability of genomic information. In this study, a survey of Chinese fir genome was performed using the Illumina HiSeq Xten sequencing platform. K-mer analysis indicated that Chinese fir has a large genome of approximately 11.6 Gb with 74.89% repetitive elements and is highly heterozygous. Meanwhile, its genome size was estimated to be 13.2 Gb using flow cytometry. A total of 778.02 Gb clean reads were assembled into 10,982,272 scaffolds with an N50 of 1.57 kb. In total, 362,193 SSR loci were detected with a frequency of 13.18 kb. Dinucleotide repeats were the most abundant (up to 73.6% of the total SSRs), followed by trinucleotide and tetranucleotide repeats. Forty-six polymorphic pairs were developed, and 298 alleles were successfully amplified from 199 Chinese fir clones. The average PIC value was 0.53, indicating that the identified genomic SSR (gSSR) markers have a high degree of polymorphism. In addition, these breeding resources were divided into three groups, and a limited gene flow existed among these inferred groups.
MicroRNA hsa-mir-3923 serves as a diagnostic and prognostic biomarker for gastric carcinoma
Authors: Yang Xiaohui , Zhang Ze , Zhang Lichao , Zhou Li
Published: March 2020

Gastric carcinoma (GC) refers to a common digestive system disease that exhibits a very high incidence. MicroRNA hsa-mir-3923 belongs to a type of miRNA, of which the function has been merely investigated in breast, pancreatic cancers and pre-neoplasic stages of gastric cancer. It has not been studied or reported in gastric carcinoma, so the relationship between gastric hsa-mir-3923 expression and the clinics feature and pathology of GC cases was examined. This study employed data mining for analyzing gastric carcinoma data in The Cancer Genome Atlas database. A Chi squared test was performed for assessing the relations of hsa-mir-3923 expression with clinics-related and pathology-regulated variables. This study conducted the assessment of the role of hsa-mir-3923 in prognostic process using Kaplan–Meier curves, Receiver operating characteristic (ROC) analysis and proportional hazards model (Cox) study. With the use of Gene Expression Omnibus, this study carried out gene set enrichment analysis (GSEA). In the meantime, the common miRNA database was compared to predict potential target genes; as revealed by co-expression analysis, a regulatory network probably existed, containing hsa-mir-3923. For the analysis of the most tightly associated cytological behavior and pathway in GC, this study adopted the databases for Annotation, Visualization and Integrated Discovery (David) and KO-Based Annotation System (KOBAS). Cytoscape, R and STRING were employed for mapping probable regulatory networks displaying relations to hsa-mir-3923. Lastly, we obtained 69 genes most tightly associated with hsa-mir-3923 and described their relationship with Circos plot. As revealed from the results, hsa-mir-3923 displayed up-regulation in gastric carcinoma, and it displayed associations with vital status, N stage and histologic grade when being expressed. The predicted results of miRNA target genes suggested that there may be a close relationship between 66 genes and hsa-mir-3923 in gastric cancer. As indicated from co-expression data, a small regulating network of 4 genes probably existed. Our results elucidated that hsa-mir-3923 high-expression reveals poor prognosis of GC patients.
Computational Investigation of Contributions from Different Subtypes of Interneurons in Prefrontal Cortex for Information Maintenance
Authors: Zhang Qian , Zeng Yi , Yang Taoyi
Published: March 2020

Interneurons play crucial roles in neocortex associated with high-level cognitive functions; however, the specific division of labor is still under investigation. Interneurons are exceptionally diverse in their morphological appearance and functional properties. In this study, we modify a prefrontal multicolumn circuit in which five subtypes of inhibitory interneurons play distinct roles in the maintenance of transient information. These interneurons are classified according to the extending range of axonal projections. Our work simplifies the division of labor between different types of interneurons for the maintenance of information and the principle of functional redundancy of the brain from the perspective of computational modeling. This model presents a framework to understand the cooperation between different interneurons in a recurrent cortical circuit.
Occurrence, partition and environmental risk assessment of per- and polyfluoroalkyl substances in water and sediment from the Baiyangdian Lake, China
Authors: Guo Rui , Liu Xiaolei , Liu Jie , Liu Yan , Qiao Xiaocui , Ma Mengyu , Zheng Binghui , Zhao Xingru
Published: March 2020

This work examined the contamination of poly- and perfluorinated compounds (PFASs) in the water and sediment of the Baiyangdian Lake. The total concentration of PFASs in the surface water varied from 140.5 to 1828.5 ng/L, and the highest concentration of PFASs were observed near the entrance of Fuhe river. The topmost contaminant was sodium perfluorohexanesulfonate (PFHxS) and perfluorooctanoic acid (PFOA) in the north and south of the Baiyangdian Lake respectively, which indicated different contamination sources. The total concentration of PFASs in the sediment varied from 0.48 to 30 ng/g, and the distribution of PFASs in the sediment was similar with that in the surface water. The concentrations of polyfluoroalkyl phosphoric diesters (diPAPs) were three to four orders of magnitude lower than those of perfluorocarboxylates (PFCAs) and PFSAs. Although the pore water and the surface water had similar ΣPFASs, the concentration of perfluorodecanoic acid (PFDA) in pore water was 1.4 to 4.4 times higher than that in surface water, and the concentration of perfluoropentanoic acid (PFPeA) in pore water was 20–70% that in surface water. The results of ecological risk assessment showed that the PFASs were currently of no immediate risk to the aquatic life.
A Supersensitive, Multidimensional Flexible Strain Gauge Sensor Based on Ag/PDMS for Human Activities Monitoring
Authors: Li Hui , Zhang Jinjie , Chen Jing , Luo Zebang , Zhang Jinyong , Alhandarish Yousef , Liu Qiuhua , Tang Wei , Wang Lei
Published: March 2020

For more comprehensive monitoring human state of motion, it is necessary to sense multidimensional stimulus information. In this paper, we reported a supersensitive flexible sensor based on Ag/PDMS composites with sensing abilities of strain and force. The fabrication method is simple and rapid, which only need physically grinding the silver particles and mixing with liquid PDMS. The flexible sensor has excellent performances in multidimensional detection. The strain gauge factor can reach as high as 939 when it was stretched to 36%, and the minimum resolution for force detection is 0.02 N. The sensing characteristic of the sensors with different filling fraction and thickness were analyzed from the microscopic point of view. Multidimensional sensing abilities of flexible sensor have greatly expands its applications. We experimentally verified the Ag/PDMS based sensor in human body dynamic monitoring and sound detecting in real-time, which has shown great potential in motion recognition, haptic perception and soft robotics.
Short and long period growth markers of enamel formation distinguish European Pleistocene hominins
Authors: Modesto-Mata Mario , Dean M. Christopher , Lacruz Rodrigo S. , Bromage Timothy G. , García-Campos Cecilia , Martínez de Pinillos Marina , Martín-Francés Laura , Martinón-Torres María , Carbonell Eudald , Arsuaga Juan Luis , Bermúdez de Castro José María
Published: March 2020

Characterizing dental development in fossil hominins is important for distinguishing between them and for establishing where and when the slow overall growth and development of modern humans appeared. Dental development of australopiths and earlyHomowas faster than modern humans. The Atapuerca fossils (Spain) fill a barely known gap in human evolution, spanning ~1.2 to ~0.4 million years (Ma), during whichH. sapiensand Neandertal dental growth characteristics may have developed. We report here perikymata counts, perikymata distributions and periodicities of all teeth belonging to the TE9 level of Sima del Elefante, level TD6.2 of Gran Dolina (H. antecessor) and Sima de los Huesos. We found some components of dental growth in the Atapuerca fossils resembled more recentH. sapiens. Mosaic evolution of perikymata counts and distribution generate three distinct clusters:H. antecessor, Sima de los Huesos andH. sapiens.
Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening
Authors: Ong Han Boon , Clare Simon , Roberts Adam Jonathan , Wilson Mary Edythe , Wright Gavin James
Published: March 2020

Visceral leishmaniasis is an infectious parasitic disease caused by the protozoan parasitesLeishmania donovaniandLeishmania infantum. The drugs currently used to treat visceral leishmaniasis suffer from toxicity and the emergence of parasite resistance, and so a better solution would be the development of an effective subunit vaccine; however, no approved vaccine currently exists. The comparative testing of a large number of vaccine candidates requires a quantitative and reproducible experimental murine infection model, but the parameters that influence infection pathology have not been systematically determined. To address this, we have established an infection model using a transgenic luciferase-expressingL. donovaniparasite and longitudinally quantified the infections usingin vivobioluminescent imaging within individual mice. We examined the effects of varying the infection route, the site of adjuvant formulation administration, and standardised the parasite preparation and dose. We observed that the increase in parasite load within the liver during the first few weeks of infection was directly proportional to the parasite number in the initial inoculum. Finally, we show that immunity can be induced in pre-exposed animals that have resolved an initial infection. This murine infection model provides a platform for systematic subunit vaccine testing against visceral leishmaniasis.
Prognostic implications of EGFR protein expression in sporadic colorectal tumors: Correlation with copy number status, mRNA levels and miRNA regulation
Authors: del Carmen Sofía , Corchete Luís Antonio , Gervas Ruth , Rodriguez Alba , Garcia María , Álcazar José Antonio , García Jacinto , Bengoechea Oscar , Muñoz-Bellvis Luis , Sayagués José María , Abad Mar
Published: March 2020

Sporadic colorectal cancer (sCRC) is the third most frequent cancer worldwide and the second most common cause of cancer-related deaths (mainly due metastatic dissemination). We investigated the immunohistochemical expression of frequently altered proteins in primary tumors from 51 patients (25 liver metastatic and 26 non-metastatic cases) with a median 103 months follow-up (103 months). We evaluated EGFR copy number (using SNP arrays and FISH) and its expression and regulation (by mRNA and miRNA arrays). We found differences between metastatic and non-metastatic sCRCs for MLH1 (p = 0.05), PMS2 (p = 0.02), CEA (p < 0.001) and EGFR (p < 0.001) expression. EGFR expression was associated with lymph node metastases (p = 0.001), liver metastases at diagnosis (p < 0.001), and advanced stage (p < 0.001). There were associations between EGFR expression-, EGFR gene copy number- and EGFR mRNA levels. We found potential interactions of two miRNAs targeting EGFR expression, (miR-134 and miR-4328, in non-metastatic and metastatic tumors, respectively). EGFR expression was associated with a worse outcome (p = 0.005). Multivariate analysis of prognostic factors for overall survival identified that, the expression of EGFR expression (p = 0.047) and pTNM stage (p < 0.001) predicted an adverse outcome. EGFR expression could be regulated by amplification or polysomies (in metastatic tumors), or miRNAs (miRNA-134, in non-metastatic tumors). EGFR expression in sCRC appears to be related to metastases and poor outcome.
Lumbar spinal stenosis and disc alterations affect the upper lumbar spine in adults with achondroplasia
Authors: Huet Thomas , Cohen-Solal Martine , Laredo Jean-Denis , Collet Corinne , Baujat Geneviève , Cormier-Daire Valérie , Yelnik Alain , Orcel Philippe , Beaudreuil Johann
Published: March 2020

In achondroplasia, lumbar spinal stenosis arises from congenital dysplasia and acquired degenerative changes. We here aimed to describe the changes of the lumbar spinal canal and intervertebral disc in adults. We included 18 adults (age ≥ 18 years) with achondroplasia and lumbar spinal stenosis. Radiographs were used to analyze spinal-pelvic angles. Antero-posterior diameter of the spinal canal and the grade of disc degeneration were measured by MRI. Antero-posterior diameters of the spinal canal differed by spinal level (P < 0.05), with lower values observed at T12-L1, L1-2 and L2-3. Degrees of disc degeneration differed by intervertebral level, with higher degrees observed at L1-2, L2-3 and L3-4. A significant correlation was found between disc degeneration and thoraco-lumbar kyphosis at L2-3, between antero-posterior diameter of the spinal canal and lumbar lordosis at T12-L1 and L2-3, and between antero-posterior diameter of the spinal canal and thoraco-lumbar kyphosis at L1-2. Unlike the general population, spinal stenosis and disc degeneration involve the upper part of the lumbar spine in adults with achondroplasia, associated with thoraco-lumbar kyphosis and loss of lumbar lordosis.