bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Significance of COL11A1 and Its Effect on Immune Infiltration in Colorectal Cancer
Authors: Wu Yibin , Cai Yuankun , Chen Wenjie , Ye Tao , Xu Ye , Wang Huipeng 
Published: February 2021

Abstract
Background

Collagen type XI alpha 1 chain (COL11A1) is an extracellular matrix (ECM) protein and plays a crucial role in tumors. However, the correlations of COL11A1 to prognosis and tumor-infiltrating lymphocytes in colorectal cancer (CRC) remain unclear.
Methods

Here, we used bioinformatics methods with experimental exploration to evaluate the prognostic value of COL11A1 in CRC, while the alteration of the gene and its function in CRC was explored by using cBioPortal and DAVID. Furthermore, the correlations between COL11A1 expression and cancer immune infiltrates, gene marker sets of immune infiltrates were analyzed by TIMER, GEPIA and human samples.
Results

Increased COL11A1 expression was found in CRC and positive correlated with tumor stage, node metastasis and histological type. Patients with higher COL11A1 expression had shorter survival data. Function network revealed that COL11A1 mainly regulated pathways involving in focal adhesion, PI3K-AKT signaling pathways and ECM-receptor interaction. Furthermore, COL11A1 expression was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and dendritic cells (DCs) in colon adenocarcinoma (COAD). COL11A1 expression showed strong correlations with diverse immune marker sets in COAD. In addition, COL11A1 expression potentially contributes to regulation of tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in COAD.
Conclusions

Our data identify COL11A1 as a novel prognostic biomarker for determining prognosis and immune infiltration in COAD, which might optimize therapeutic strategies for CRC patients.
Using Historical Data to Facilitate Clinical Prevention Trials in Alzheimer Disease?
Authors: Berres Manfred , Monsch Andreas U. , Spiegel René 
Published: February 2021

Abstract
BackgroundThe Placebo Group Simulation Approach (PGSA) aims at partially replacing Randomized Placebo-Controlled Trials (RPCTs) using data from historical control groups in order to decrease the needed number of study participants exposed to lengthy placebo treatment. PGSA algorithms were originally derived from Mild Cognitive Impairment (MCI) data of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. To produce more generalizable algorithms, we aimed to compile five different MCI databases in an heuristic manner to create a ‘standard control algorithm’ for use in future clinical trials.MethodsWe compared data from two North American cohort studies (n= 395 and 4,328, respectively) one international clinical drug trial (n= 831) and two convenience patient samples, one from Germany (n=726), and one from Switzerland (n=1,558).ResultsDespite differences between the five MCI samples regarding inclusion and exclusion criteria, their baseline demographic and cognitive performance data varied less than expected. However, the five samples differed markedly with regard to their subsequent cognitive performance and clinical development: (1) MCI patients from the drug trial did not deteriorate on verbal fluency over 3 years, whereas patients in the other samples did; (2) relatively few patients from the drug trial progressed from MCI to dementia (about 10% after 4 years), in contrast to the other four samples with progression rates over 30 percent.ConclusionConventional MCI criteria were insufficient to allow for the creation of well-defined and internationally comparable samples of MCI patients. More recently published MCI criteria are unlikely to remedy this situation. The Alzheimer scientific community needs to agree on a standard set of neuropsychological tests including appropriate selection criteria to make MCI a scientifically more useful concept. Patient data from different sources would then be comparable and the scientific merits of algorithm-based study designs such as the PGSA could be properly assessed.
HP1 oligomerization compensates for low-affinity H3K9me recognition and provides a tunable mechanism for heterochromatin-specific localization
Authors: Biswas Saikat , Karslake Joshua , Chen Ziyuan , Farhat Ali , Freddolino Peter , Biteen Julie , Ragunathan Kaushik 
Published: February 2021

Abstract
HP1 proteins bind with low affinity but high specificity to histone H3 lysine 9 methylation (H3K9me), forming transcriptionally inactive genomic compartments referred to as heterochromatin. How HP1 proteins traverse a complex and crowded chromatin landscape on the millisecond timescale to bind H3K9me chromatin remains paradoxical. Here, we apply single-molecule imaging to visualize an HP1 homolog, the fission yeast Swi6, in its native chromatin environment. By analyzing Swi6 motions, we identify individual mobility states that map to discrete biochemical intermediates. Using mutants that perturb Swi6 H3K9me recognition, oligomerization, or nucleic acid binding, we mechanistically parse how each biochemical property affects protein dynamics. While nucleic acid binding titrates Swi6 away from heterochromatin, as few as four tandem chromodomains are sufficient to restore H3K9me-dependent localization. Our studies propose a new paradigm where HP1 oligomerization stabilizes higher-order complexes to outcompete inhibitory nucleic acid and non-specific chromatin interactions, enabling high specificity H3K9me recognition in cells.
Hopping conduction mechanism and impedance spectroscopy analyses of La0.70Sr0.25Na0.05Mn0.70Ti0.30O3 ceramic
Authors: raddaoui zeineb , safwen elkossi , Trukhanov alex , Kozlovskiy alex , Zdorovets M , dhahri jemai 
Published: February 2021

Abstract
The perovskite sample La0.7Sr0.25Na0.05Mn0.7Ti0.3O3 (LSNM0.70T0.30) was produced via a solid-state route process. Impedance spectra of LSNM0.70T0.30 in the frequency interval [40Hz -1MHz] were studied at several temperatures [80K to 440 K]. The ac conductivity (σac) established that according to the Jonscher law. σac is described by Non-overlapping Small Polaron Tunneling model at low temperatures and Correlated Barrier Hopping model at high temperatures. From dc conductance analysis, conduction seems to be thermally activated, suggesting the existence of semiconductor process. Detailed investigation of impedance data revealed the non-Debye nature of the relaxation processes in the sample. In addition, Dielectric constant curves were applied to examine the relaxation dynamics of charge carriers. In fact, the Debye-like relaxation was performed on the basis of the polarization of spatial charges following Maxwell-Wagner model and Koop’s phenomenological theory.
Estimating High Mobility Group Box Protein 1 (HMGB1) Single Nucleotide Polymorphisms Among Hepatitis B Virus Infected Patients of Pakistan Origin
Authors: Tabassum Sobia , Khalid Zanib , Piracha Zahra Zahid , Saeed Umar , Ashraf Muhammad , Aziz Hafsa 
Published: February 2021

Abstract
HMGB1 is nuclear non-histone protein and unique member of cytokines. In viral hepatitis infection HMGB1 serum level increases and translocates towards cytoplasm and extracellular spaces where it activates single stimulating hepatic stellate cell proliferation which inducesfibrogenic protein expression and causes hepatocellular carcinoma. In this study, total 150 subjects were recruited to assess the association between HMGB1 SNPs and HBV. Three types of genotypes were found visible in rs3742305 of HMGB1; wild type homozygous GG with 65%, homozygous minor type CC with 6% and heterozygous minor type GC with 26% frequency distribution. High prevalence of GG genotype in the selected population presenting that GG genotype may have higher risk for susceptibility to HBV infection. Our resultsshowedsignificant correlationof HMGB1 polymorphism with HBV infection in the selected Pakistani population.
Gastrointestinal and Genitourinary Toxicity Profiles of Metformin Versus Placebo in Men With Prostate Cancer Receiving Pelvic Radiotherapy: Interim Toxicity Results of a Double-blinded, Multicenter, Phase II Randomized Controlled Trial
Authors: Usmani Nawaid , McDonald Megan O. , Ong Aldrich , Koul Rashmi , Dubey Arbind , Hunter William , Ahmed Shahida , Quon Harvey , Yee Don , Parliament Matthew , Sivananthan Gokulan , Danielson Brita , Rowe Lindsay , Ghosh Sunita , Kim Julian O. 
Published: February 2021

Abstract
Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18-36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p=0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p=0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p=0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.
Genomic and phenotypic description of Streptococcus resistens sp. nov., Streptococcus buccae sp. nov. and Streptococcus mediterraneus sp. nov., three new members of the Streptococcus genus isolated from the human oral cavity
Authors: Naud Sabrina , Hasni Issam , Bellali Sara , Kieu Hoang Thong , Lo Cheikh Ibrahima , Anani Hussein , Bonnet Marion , Armstrong Nicholas , Richez Magali , Robinne Simon , Raoult Didier , Lagier Jean-Christophe , Alou Maryam Tidjani 
Published: February 2021

Abstract
Phenotypic, phylogenetic and genomic studies were carried out on three unidentified Gram-stain positive, facultative anaerobic, and cocci-shaped bacteria isolated from the human oral cavity. The 16S rRNA gene of strains Marseille-P5794 T , Marseille-P6264 T and Marseille-P7376 T exhibited a sequence identity of 99,41%, 99.67% and 97.88%, respectively with Streptococcus cristatus, their closest phylogenetic relative with standing in nomenclature. Moreover, the rpoB gene sequence of strains Marseille-P5794 T and Marseille-P6264 T shared a similarity level with 96.1%, and 95.9% with Streptococcus cristatus whereas strain Marseille-P7376 T shared a 93.98% identity with Streptococcus sanguinis. Whole genome comparison of strains Marseille-P5794 T , Marseille-P6264 T and Marseille-P7376 T with their phylogenetic neighbours were under the threshold values set to define new species using digital DNA-DNA hybridization and Orthologous Average Nucleotide Identity. The taxonogenomics analysis thus allowed the classification of these strains as new species within the Streptococcus genus named Streptoccocus resistens sp. nov. Strain Marseille-P5794 T (=CSUR P5794 = CECT9902), Streptococcus buccae sp. nov. Strain Marseille-P6264 T (=CSUR P6264 = CECT9910) and Streptococcus mediterraneus sp. nov. Strain Marseille-P7376 (=CSUR P7376 = CECT30035).
Follower Link Prediction using the XGBoostClassification Model with Multiple Graph Features
Authors: Behera Dayal Kumar , Dash Madhabananda , Swetanisha Subhra , Nayak Janmenjoy , Vimal S , Naik Bighnaraj 
Published: February 2021

Abstract
The Follower Link Prediction is an emerging application preferred by social networking sites to increase their user network. It helps in finding potential unseen individual and can be used for identifying relationship between nodes in social network. With the rapid growth of many users in social media, which users to follow leads to information overload problems. Previous works on link prediction problem are generally based on local and global features of a graph and limited to a smaller dataset. The number of users in social media is increasing in an extraordinary rate. Generating features for supervised learning from a large user network is challenging. In this paper, a supervised learning model (LPXGB) using XGBoost is proposed to consider the link prediction problem as a binary classification problem. Many hybrid graph feature techniques are used to represent the dataset suitable for machine learning. The efficiency of the LPXGB model is tested with three real world datasets Karate, Polblogs and Facebook. The proposed model is compared with various machine learning classifiers and also with traditional link prediction models. Experimental results are evident that the proposed model achieves higher classification accuracy and AUC value.
Controlling COVID-19 via test-trace-quarantine
Authors: Kerr Cliff , Mistry Dina , Stuart Robyn , Rosenfeld Katherine , Hart Gregory , Núñez Rafael , Cohen Jamie , Selvaraj Prashanth , Abeysuriya Romesh , Jastrzębski Michał , George Lauren , Hagedorn Brittany , Panovska-Griffiths Jasmina , Fagalde Meaghan , Duchin Jeffrey , Famulare Mike , Klein Daniel 
Published: February 2021

Abstract
Initial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures. However, these interventions have had enormous societal and economic costs. Here we demonstrate the feasibility of an alternative control strategy, test-trace-quarantine: routine testing of primarily symptomatic individuals, tracing and testing their known contacts, and placing their contacts in quarantine. We performed this analysis using Covasim, an open-source agent-based model, which was calibrated to detailed demographic, mobility, and epidemiological data for the Seattle region from January through June 2020. With current levels of mask use and schools remaining closed, we found that high but achievable levels of testing and tracing are sufficient to maintain epidemic control even under a return to full workplace and community mobility and with low vaccine coverage. The easing of mobility restrictions in June 2020 and subsequent scale-up of testing and tracing programs through September provided real-world validation of our predictions. Although we show that test-trace-quarantine can control the epidemic in both theory and practice, its success is contingent on high testing and tracing rates, high quarantine compliance, relatively short testing and tracing delays, and moderate to high mask use. Thus, in order for test-trace-quarantine to control transmission with a return to high mobility, strong performance in all aspects of the program is required.
Plasticity in thermal hardening of the invasive Asian house gecko
Authors: Lapwong Yingyod , Dejtaradol Ariya , Webb Jonathan K. 
Published: February 2021

Abstract
The Asian house gecko (Hemidactylus frenatus) is a tropical invasive species that has established and spread throughout several temperate regions around the world. In some invasive species, rapid thermal acclimation (thermal hardening) may contribute to their success in occupying a wide range of climates. In this study, we investigated whether invasive house geckos from southeastern Australia show differing thermal hardening responses than individuals from the native range in Thailand. In the laboratory, we measured the basal heat tolerance (CTmax) of the geckos and their heat hardening response after being subjected to the second thermal stress after 1, 3, 5, 7, 9, or 11 hours. When geckos had recovered, we measured their basal cold tolerance (CTmin) and cold hardening response over the same time intervals. We then explored whether hardening responses differed between populations or among time intervals. We found that basal heat tolerances did not differ between populations, but geckos from Australia had lower cold tolerance than geckos from Thailand. The magnitude of the heat hardening was similar between populations, but the introduced geckos had a higher magnitude of cold hardening. The native geckos could maximize their cold tolerance capacity for only 0.6 °C, comparing to 0.9 °C of the introduced geckos. Also, geckos from Australia exhibited faster responses to thermal stress than did geckos from Thailand. Maximum thermal tolerances as a result of hardening responses peaked within three hours after thermal stress in Australian geckos (adjusted means = 44.0 °C for CTmax and 9.9 °C for CTmin) and at five hours after thermal stress in Thai geckos (adjusted means = 44.2 °C and 10.2 °C, respectively). The plasticity in the thermal hardening of the invasive gecko should enable it to survive rapid temperature fluctuations, especially cold snap, that occasionally occur in temperate regions.
Rapid sequence evolution driven by transposable elements at a virulence locus in a fungal wheat pathogen
Authors: Singh Nikhil Kumar , Badet Thomas , Abraham Leen , Croll Daniel 
Published: February 2021

Abstract
Background: Plant pathogens cause substantial crop losses in agriculture production and threaten food security. Plants evolved the ability to recognize virulence factors and pathogens have repeatedly escaped recognition due rapid evolutionary change at pathogen virulence loci (i.e. effector genes). The presence of transposable elements (TEs) in close physical proximity of effector genes can have important consequences for gene regulation and sequence evolution. Species-wide investigations of effector gene loci remain rare hindering our ability to predict pathogen evolvability.Results: Here, we performed genome-wide association studies (GWAS) on a highly polymorphic mapping population of 120 isolates of Zymoseptoria tritici, the most damaging pathogen of wheat in Europe. We identified a major locus underlying significant variation in reproductive success of the pathogen and damage caused on the wheat cultivar Claro. The most strongly associated locus is intergenic and flanked by genes encoding a predicted effector and a serine type protease, respectively. The center of the locus contained a highly dynamic region consisting of multiple families of TEs. Based on a large global collection of assembled genomes, we show that the virulence locus has undergone substantial recent sequence evolution. Large insertion and deletion events generated length variation between the flanking genes by a factor of seven (5–35 kb). The locus showed also strong signatures of genomic defenses against TEs (i.e. RIP) contributing to the rapid diversification of the locus.Conclusions: In conjunction, our work highlights the power of combining GWAS and population-scale genome analyses to investigate major effect loci in pathogens.
Generalized Mixed Modeling in Massive Electronic Health Record Databases: What is a Healthy Serum Potassium?
Authors: Bologa Cristian G. , Pankratz Vernon Shane , Unruh Mark L , Roumelioti Maria Eleni , Shah Vallabh , Shaffi Saeed Kamran , Arzhan Soraya , Cook John , Argyropoulos Christos 
Published: February 2021

Abstract
Background: Converting electronic health record (EHR) entries to useful clinical inferences requires one to address the poor scalability of existing implementations of Generalized Linear Mixed Models (GLMM) for repeated measures. The major computational bottleneck concerns the numerical evaluation of multivariable integrals, which even for the simplest EHR analyses may involve millions of dimensions (one for each patient). The hierarchical likelihood (h-lik) approach to GLMMs is a methodologically rigorous framework for the estimation of GLMMs that is based on the Laplace Approximation (LA), which replaces integration with numerical optimization, and thus scales very well with dimensionality. Methods: We present a high-performance implementation of the h-lik for GLMMs in the R package TMB. Using this approach, we examined the relation of repeated serum potassium measurements and survival in the Cerner Real World Data (CRWD) EHR database. Analyzing this data requires the evaluation of an integral in over 3 million dimensions, putting this problem beyond the reach of conventional approaches. We also assessed the scalability and accuracy of LA in smaller samples of 1 and 10% size of the full dataset that were analyzed via the a) original, interconnected Generalized Linear Models (iGLM), approach to h-lik, b) Adaptive Gaussian Hermite (AGH) and c) the gold standard of Markov Chain Monte Carlo (MCMC) for multivariate integration. Results: Random effects estimates generated by the LA were within 10% of the values obtained by the iGLMs, AGH and MCMC techniques. The H-lik approach was 4-30 times faster than AGH and nearly 800 times faster than MCMC. The major clinical inferences in this problem are the establishment of the non-linear relationship between the potassium level and the risk of mortality, as well as estimates of the individual and health care facility sources of variations for mortality risk in CRWD. Conclusions: We found that the combination of the LA and AD offers a computationally efficient, numerically accurate approach for the analysis of extremely large, real world repeated measures data via the h-lik approach to GLMMs. The clinical inference from our analysis may guide choices of threatment thresholds for treating potassium disorders in the clinic.
Investigating mechanical properties of 3D printed parts manufactured in different orientations on Multijet printer
Authors: Chand Ramesh , Sharma Vishal S , Rajeev Trehan 
Published: February 2021

Abstract
Polymer material based products in the engineering field are most widely produced by the multi jet printing (MJP). These products impart inherent benefits in manufacturing intricate contours and shapes at less additional expenses. This emphasizes the importance of studying the mechanical behavior of the manufactured parts, using polymeric materials in different orientations. In this investigation density, tensile behavior & hardness were studied for 3D-printed parts produced in four different orientations (A, B, C and D). It is found that for the best mechanical properties part should be fabricated using orientation ‘A’. Furthermore, for density and tensile strength part should not be fabricated using orientation ‘C’. Also in case of hardness part should not be fabricated in orientation ‘B’.