bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractNon-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

AbstractTinnitus 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

AbstractThere 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

AbstractChinese 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

AbstractGastric 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

AbstractInterneurons 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

AbstractThis 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

AbstractFor 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

AbstractCharacterizing 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

AbstractVisceral 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

AbstractSporadic 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

AbstractIn 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.
Pathways for the formation of ice polymorphs from water predicted by a metadynamics method
Authors: Nada Hiroki 
Published: March 2020

AbstractThe mechanism of how ice crystal form has been extensively studied by many researchers but remains an open question. Molecular dynamics (MD) simulations are a useful tool for investigating the molecular-scale mechanism of crystal formation. However, the timescale of phenomena that can be analyzed by MD simulations is typically restricted to microseconds or less, which is far too short to explore ice crystal formation that occurs in real systems. In this study, a metadynamics (MTD) method was adopted to overcome this timescale limitation of MD simulations. An MD simulation combined with the MTD method, in which two discrete oxygen–oxygen radial distribution functions represented by Gaussian window functions were used as collective variables, successfully reproduced the formation of several different ice crystals when the Gaussian window functions were set at appropriate oxygen–oxygen distances: cubic ice, stacking disordered ice consisting of cubic ice and hexagonal ice, high-pressure ice VII, layered ice with an ice VII structure, and layered ice with an unknown structure. The free-energy landscape generated by the MTD method suggests that the formation of each ice crystal occurred via high-density water with a similar structure to the formed ice crystal. The present method can be used not only to study the mechanism of crystal formation but also to search for new crystals in real systems.
Sjögren syndrome/scleroderma autoantigen 1 is a direct Tankyrase binding partner in cancer cells
Authors: Perdreau-Dahl Harmonie , Progida Cinzia , Barfeld Stefan J. , Guldsten Hanne , Thiede Bernd , Arntzen Magnus , Bakke Oddmund , Mills Ian G. , Krauss Stefan , Morth J. Preben 
Published: March 2020

AbstractSjögren syndrome/scleroderma autoantigen 1 (SSSCA1) was first described as an auto-antigen over-expressed in Sjögren’s syndrome and in scleroderma patients. SSSCA1 has been linked to mitosis and centromere association and as a potential marker candidate in diverse solid cancers. Here we characterize SSSCA1 for the first time, to our knowledge, at the molecular, structural and subcellular level. We have determined the crystal structure of a zinc finger fold, a zinc ribbon domain type 2 (ZNRD2), at 2.3 Å resolution. We show that the C-terminal domain serves a dual function as it both behaves as the interaction site to Tankyrase 1 (TNKS1) and as a nuclear export signal. We identify TNKS1 as a direct binding partner of SSSCA1, map the binding site to TNKS1 ankyrin repeat cluster 2 (ARC2) and thus define a new binding sequence. We experimentally verify and map a new nuclear export signal sequence in SSSCA1.