bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAD51 Expression as a Biomarker to Predict Efficacy of Preoperative Therapy and Survival for Esophageal Squamous Cell Carcinoma
Authors: Saeki Hiroshi , Jogo Tomoko , Kawazoe Tetsuro , Kamori Tomohiro , Nakaji Yu , Zaitsu Yoko , Fujiwara Minako , Baba Yoshifumi , Nakamura Tetsu , Iwata Naoki , Egashira Akinori , Nakanoko Tomonori , Morita Masaru , Tanaka Yoshihiro , Kimura Yasue , Shibata Tomotaka , Nakashima Yuichiro , Emi Yasunori , Makiyama Akitaka , Oki Eiji , Tokunaga Shoji , Shimokawa Mototsugu , Mori Masaki ,   Kyushu Study Group of Clinical Cancer (KSCC)
Published: June 2020

Objective:
The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC).

Background:
It is essential to improve the accuracy of preoperative molecular diagnostics to identify specific patients who will benefit from the treatment; thus, this issue should be resolved with a large-cohort, retrospective observational study.

Methods:
A total of 656 patients with ESCC who received surgery after preoperative CDDP + 5-FU therapy, docetaxel + CDDP + 5-FU therapy or chemoradiotherapy (CRT) were enrolled. Immunohistochemical analysis of TP53, CDKN1A, RAD51, MutT-homolog 1, and programmed death-ligand 1 was performed with biopsy samples obtained before preoperative therapy, and expression was measured by immunohistochemistry.

Results:
In all therapy groups, overall survival was statistically separated by pathological effect (grade 3 > grade 2 > grade 0, 1, P < 0.0001). There was no correlation between TP53, CDKN1A, MutT-homolog 1, programmed death-ligand 1 expression, and pathological effect, whereas the proportion of positive RAD51 expression (≥50%) in cases with grade 3 was lower than that with grade 0, 1, and 2 (P = 0.022). In the CRT group, the survival of patients with RAD51-positive tumor was significantly worse than RAD51-negative expressors (P = 0.0119). Subgroup analysis of overall survival with respect to positive RAD51 expression indicated preoperative chemotherapy (CDDP + 5-FU or docetaxel + CDDP + 5-FU) was superior to CRT.

Conclusions:
In ESCC, positive RAD51 expression was identified as a useful biomarker to predict resistance to preoperative therapy and poor prognosis in patients who received preoperative CRT. Administration of preoperative chemotherapy may be warranted for patients with positive RAD51 expression.
Expanded Demographic Norms for Version 3 of the Alzheimer Disease Centers’ Neuropsychological Test Battery in the Uniform Data Set
Authors: Sachs Bonnie C. , Steenland Kyle , Zhao Liping , Hughes Timothy M. , Weintraub Sandra , Dodge Hiroko H. , Barnes Lisa L. , Craft Suzanne , Parker Monica L. , Goldstein Felicia C. 
Published: June 2020

Background:
Norms for the Uniform Data Set Version 3 Neuropsychological Battery are available for cognitively normal individuals based on age, education, and sex; however, these norms do not include race. We provide expanded norms for African Americans and whites.

Methods:
Data from 32 Alzheimer’s Disease Centers (ADCs) and ADC affiliated cohorts with global Clinical Dementia Rating Scale (CDR) Dementia Staging Instrument scores of 0 were included. Descriptive statistics for each test were calculated by age, sex, race, and education. Multiple linear regressions were conducted to estimate the effect of each demographic variable; squared semipartial correlation coefficients measured the relative importance of variables.

Results:
There were 8313 participants (16% African American) with complete demographic information, ranging from 6600 to 7885 depending on the test. Lower scores were found for older and less educated groups, and African Americans versus whites. Education was the strongest predictor for most tests, followed in order by age, race, and sex. Quadratic terms were significant for age and education, indicating some nonlinearity, but did not substantially increase R
2.

Conclusions:
Although race-based norms represent incomplete proxies for other sociocultural variables, the appropriate application of these norms is important given the potential to improve diagnostic accuracy and to reduce misclassification bias in cognitive disorders of aging such as Alzheimer disease.
Brachial Flow-mediated Dilation and Risk of Dementia
Authors: Garg Parveen K. , Tan Annabel X. , Odden Michelle C. , Gardin Julius M. , Lopez Oscar L. , Newman Anne B. , Rawlings Andreea M. , Mukamal Kenneth J. 
Published: June 2020

Introduction:
Brachial flow-mediated dilation (FMD) is a physiologic measure of endothelial function. We determined the prospective association of brachial FMD with incident dementia among older adults.

Methods:
We included 2777 Cardiovascular Health Study participants who underwent brachial FMD measurement. Incident dementia was ascertained by medication use, International Classification of Diseases-9 codes, requirement for a proxy, and death certificates and calibrated to gold-standard assessments performed in a subset of the cohort.

Results:
Mean participant age at time of brachial FMD measurement was 77.9 years. We identified 1650 incident dementia cases (median follow-up=10.5 y). After adjusting for age, race, sex, education, clinic site, and baseline arterial diameter, risk of dementia for participants in the highest quartile of percent brachial FMD did not differ from those in lowest quartile (hazard ratio=0.89, 95% confidence interval: 0.77, 1.03).

Conclusions:
Brachial FMD, measured late in life, is not associated with an increased risk of incident dementia.
Assessing the ecological niche and invasion potential of the Asian giant hornet
Authors: Zhu Gengping , Illan Javier Gutierrez , Looney Chris , Crowder David W. 
Published: June 2020

AbstractThe Asian giant hornet (Vespa mandarinia) is the world’s largest hornet. It is native to East Asia, but was recently detected in British Columbia, Canada, and Washington State, USA.Vespa mandariniaare an invasion concern due to their potential to negatively affect honey bees and act as a human nuisance pest. Here, we assessed effects of bioclimatic variables onV. mandariniaand used ensemble forecasts to predict habitat suitability for this pest globally. We also simulated potential dispersal ofV. mandariniain western North America. We show thatV. mandariniaare most likely to invade areas with warm to cool annual mean temperature but high precipitation, and could be particularly problematic in regions with these conditions and high levels of human activity. We identified regions with suitable habitat on all six continents except Antarctica. The realized niche of introduced populations in the USA and Canada was small compared to native populations, implying high potential for invasive spread into new regions. Dispersal simulations showed that without containment,V. mandariniacould rapidly spread into southern Washington and Oregon, USA and northward through British Columbia, Canada. Given its potential negative impacts, and the capacity for spread within northwestern North America and worldwide, strong mitigation efforts are needed to prevent further spread ofV. mandarinia.
Risk factors of coronary microvascular obstruction
Authors: Li Yong , Lyu Shuzheng 
Published: June 2020

AbstractBackgroundCoronary microvascular obstruction /no-reflow(CMVO/NR) is a predictor of long-term mortality in survivors of ST elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PPCI).ObjectiveTo identify risk factors of CMVO/NR.MethodsTotally 2384 STEMI patients treated with PPCI were divided into two groups according to thrombolysis in myocardial infarction(TIMI) flow grade:CMVO/NR group(246cases, TIMI 0-2 grade) and control group(2138 cases, TIMI 3 grade). We used univariable and multivariable logistic regression to identify risk factors of CMVO/NR.ResultsA frequency of CMVO/NR was 10.3%(246/2384). Logistic regression analysis showed that the differences between the two groups in age(unadjusted odds ratios [OR] 1.032; 95% CI, 1.02 to 1.045; adjusted OR 1.032; 95% CI, 1.02 to 1.046; P <0.001), periprocedural bradycardia (unadjusted OR 2.357; 95% CI, 1.752 to 3.171; adjusted OR1.818; 95% CI, 1.338 to 2.471; P <0.001),using thrombus aspirationdevices during operation (unadjusted OR 2.489; 95% CI, 1.815 to 3.414; adjusted OR1.835; 95% CI, 1.291 to 2.606; P =0.001), neutrophil percentage (unadjusted OR 1.028; 95% CI, 1.014 to 1.042; adjusted OR1.022; 95% CI, 1.008 to 1.036; P =0.002), and completely block of culprit vessel (unadjusted OR 2.626; 95% CI, 1.85 to 3.728; adjusted-OR 1.656;95% CI, 1.119 to 2.45; P =0.012) were statistically significant (P <0. 05). The area under the receiver operating characteristic curve was 0.6896.ConclusionsAge, periprocedural bradycardia, using thrombus aspirationdevices during operation, neutrophil percentage, and completely block of culprit vessel may be independent risk factors for predicting CMVO/NR.We registered this study with WHO International Clinical Trials Registry Platform (ICTRP) (registration number: ChiCTR1900023213; registered date: 16 May 2019).http://www.chictr.org.cn/edit.aspx?pid=39057&htm=4.
Segmentation and Analysis of Anterior Lamina Cribrosa Surface using Non Local MRF and Metropolis Hasting Algorithm
Authors: Mano Abhisha 
Published: June 2020

AbstractThe segmentation of anterior Lamina Cribrosa surface from the OCT image is an essential task for analysis of glaucomatous damage. A Bayesian method is used to segment LC surface whereas prior knowledge about shape and position of LC layer is obtained by the non local Markov Random field and K-means segmentation. The Metropolis-Hastings (MH) algorithm provides autocorrelation graph and distribution of samples from a probability distribution. By using this technique acceptance probability is calculated. Finally, the LC layer is analysed whether it is normal or abnormal. This technique provides an accuracy of 96.7%
Synonymous sites in SARS-CoV-2 genes display trends affecting translational efficiency
Authors: Huang Qingsheng , Gao Huan , Zheng Lingling , Chen Xiujuan , Huang Shuai , Liang Huiying 
Published: June 2020

ABSTRACTA novel coronavirus, SARS-CoV-2, has caused a pandemic of COVID-19. The evolutionary trend of the virus genome may have implications for infection control policy but remains obscure. We introduce an estimation of fold change of translational efficiency based on synonymous variant sites to characterize the adaptation of the virus to hosts. The increased translational efficiency of the M and N genes suggests that the population of SARS-CoV-2 benefits from mutations toward favored codons, while the ORF1ab gene has slightly decreased the translational efficiency. In the coding region of the ORF1ab gene upstream of the −1 frameshift site, the decreasing of the translational efficiency has been weakening parallel to the growth of the epidemic, indicating inhibition of synthesis of RNA-dependent RNA polymerase and promotion of replication of the genome. Such an evolutionary trend suggests that multiple infections increased virulence in the absence of social distancing.
Sofosbuvir protects human brain organoids against SARS-CoV-2
Authors: Mesci Pinar , Macia Angela , Saleh Aurian , Martin-Sancho Laura , Yin Xin , Snethlage Cedric , Avansini Simoni , Chanda Sumit K. , Muotri Alysson 
Published: June 2020

AbstractCOVID-19 was rapidly declared a pandemic by the World Health Organization, only three months after the initial outbreak in Wuhan, China. Early clinical care mainly focused on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are also emerging. To determine whether SARS-CoV-2 could target the human brain, we infected iPSC-derived human brain organoids. Our findings show that SARS-CoV-2 was able to infect and kill neural cells, including cortical neurons. This phenotype was accompanied by impaired synaptogenesis. Finally, Sofosbuvir, an FDA-approved antiviral drug, was able to rescue these alterations. Given that there are currently no vaccine or antiviral treatments available, urgent therapies are needed. Our findings put Sofosbuvir forward as a potential treatment to alleviate COVID-19-related neurological symptoms.One Sentence SummarySARS-CoV-2 infection causes neuronal death and impaired synaptogenesis, both rescued by Sofosbuvir treatment.
The Bourque Distances for Mutation Trees of Cancers
Authors: Jahn Katharina , Beerenwinkel Niko , Zhang Louxin 
Published: June 2020

AbstractMutation trees are rooted trees of arbitrary node degree in which each node is labeled with a mutation set. These trees, also referred to as clonal trees, are used in computational oncology to represent the mutational history of tumours. Classical tree metrics such as the popular Robinson–Foulds distance are of limited use for the comparison of mutation trees. One reason is that mutation trees inferred with different methods or for different patients usually contain different sets of mutation labels. Here, we generalize the Robinson–Foulds distance into a set of distance metrics called Bourque distances for comparing mutation trees. A connection between the Robinson–Foulds distance and the nearest neighbor interchange distance is also presented.
A Mathematical Model to Simulate Intracranial Pressure and Unified Interpretation of Several Disease Entities
Authors: Wang Jingsheng , Lu Peng 
Published: June 2020

AbstractBACKGROUNDMany clinical phenomena related to cerebrospinal fluid(CSF) and intracranial pressure (ICP) are often contrary to common sense and difficult to explain by classical theory. Such as slit ventricle syndrome, normal intracranial pressure hydrocephalus / low pressure hydrocephalus, paradoxical herniation, and so on. Many authors have different theories about them but can’t have an unified explanation.OBJECTIVEWe try to simulate the above CSF disorders and ICP conduction with a mathematical method, and make theoretical interpretations to them.METHODSWe introduced a mathematical model based on several well-accepted hypothesesto simulate human CSF physiology and propose that ICP curve should be an U-shaped curve (especially, we introduce the hypothesis that CSF also play a role of decompression). Maple software was used to draw charts according to our formula. We use the theory and intuitive charts to explain those illnesses one by one.RESULTSThe formula: ICP =μ·MAP− δ · Vα·μ·MAP+ θ · Vβ·μ · MAP+C, and corresponding diagrams was conducted.CONCLUSIONThis mathematical model is a supplement to the classical Monro-Kellie’s theory, the curve and coordinate system can be used to analyze different pathophysiological states and give a reasonable unified explanation to them.
Aspiration-assisted Freeform Bioprinting of Tissue Spheroids in a Yield-stress Gel
Authors: Ayan Bugra , Zhang Zhifeng , Celik Nazmiye , Zhou Kui , Wu Yang , Costanzo Francesco , Ozbolat Ibrahim T 
Published: June 2020

AbstractBioprinting of cellular aggregates, such as tissue spheroids or organoids, in complex three-dimensional (3D) arrangements has been a major obstacle for scaffold-free fabrication of tissues and organs. In this research, we unveiled a new approach to the bioprinting of tissue spheroids in a yield stress granular gel, which exhibited unprecedented capabilities in freeform positioning of spheroids in 3D. Due to its Herschel-Bulkley and self-healing properties as well as its biological inertness, the granular gel supported both the positioning and self-assembly of tissue spheroids. We studied the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gel’s yield-stress during the transfer of spheroids from cell media to the gel. We demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.
GxEsum: a novel approach to estimate the phenotypic variance explained by genome-wide GxE interaction based on GWAS summary statistics for biobank-scale data
Authors: Shin Jisu , Lee S Hong 
Published: June 2020

AbstractGenetic variation in response to the environment is fundamental in the biology of complex traits and diseases, i.e. genotype-by-environment interaction (GxE). However, existing methods are computationally demanding and infeasible to handle biobank-scale data. Here we introduce GxEsum, a method for estimating the phenotypic variance explained by genome-wide GxE based on GWAS summary statistics. Through comprehensive simulations and analysis of UK Biobank with 288,837 individuals, we show that GxEsum can handle a large-scale biobank dataset with controlled type I error rates and unbiased GxE estimates, and its computational efficiency can be hundreds of times higher than existing GxE methods.
Curiosity, latent learning, and cognitive maps
Authors: Wang Maya Zhe , Hayden Benjamin Y. 
Published: June 2020

ABSTRACTCuriosity refers to a desire for information that is not driven by immediate strategic or instrumental concerns. Latent earning refers to a form of learning that is not directly driven by standard reinforcement learning processes. We propose that curiosity serves the purpose of motivating latent learning. Thus, while latent learning is often treated as an incidental or passive process, in practice it most often reflects a strong evolved pressure to consume large amounts of information. That large volume of information in turn allows curious decision makers to generate sophisticated representations of the structure of their environment, known as cognitive maps. Cognitive maps facilitate adaptive and flexible behavior while maintaining its adaptivity and flexibility via map updates based on new information. Here we describe data supporting the idea that orbitofrontal cortex (OFC) and dorsal anterior cingulate cortex (dACC) play complementary roles in curiosity-driven learning. Specifically, we propose that (1) OFC tracks the innate value of information and incorporates new information into a detailed cognitive map; and (2) dACC tracks the environmental demands and information availability to then use the cognitive map for guiding behavior.
Foraging analysis of Endangered Greater Adsjutant StorkLeptotilus dubiosGemlin in certain habitat of Assam, India
Authors: Barman Purnima Devi , Sharma D. K. 
Published: June 2020

AbstractThe endangered Greater Adjutant StokLeptotilus dubiusGemlin confined only in some pockets in Assam and Bihar in India and in certain areas of Laos and Cambodia has poorly understood in its foraging activities in its natural habitats. Attempt has been made to address the forage pattern in its natural habitat wetlands in the Kamup district and in a city garbage dump in Guwahati in Assam, India. The various forage methods like walking, visual tactile etc and their relation with the body metrices like beak length, tibia tarsus length and its mass were assessed in terms of foraging habits. Forage actvities were evaluated during the breeding (May to September) and non breeding (October to April) time of the study period of 2012-2017 at different water level of the wetland(s). The foraging range of this stork assessed at an confinement of aerial distance of 15 km from the nesting sites appears as resident non migratory birds by habits. Types of diet composition obtained from the regurgitated food at the ground of the nesting sites were mostly the fish group channa and cyprinids. Profitability index was determined at the captive stork showed in favour of these two groups within the size group of 5 to 15 cm. Larger food item showed lesser profitability index. PCA analysis showed negative foraging correlation with the Prey size greater than 8cm and 15 cm, while the captivity study was conducted Thus the present findings on the foraging assessment of Greater Adjutant might be the baseline information for conservation action plan.
Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene
Authors: Akerman Ildem , Maestro Miguel Angel , Grau Vane , García-Hurtado Javier , Mittler Gerhard , Ravassard Philippe , Piemonti Lorenzo , Ferrer Jorge 
Published: June 2020

ABSTRACTDespite the central role of chromosomal context in gene transcription, human noncoding DNA variants are generally studied outside of their endogenous genomic location. This poses major limitations to understand the true consequences of causal regulatory variants. We focused on a cis-regulatory mutation (c.-331C>G) in theINSgene promoter that is recurrently mutated in unrelated patients with recessive neonatal diabetes. We created mice in which a ~3.1 kb humanINSupstream region carrying −331C or −331G alleles replaced the orthologous mouseIns2region. This human sequence drove cell-specific transcription in mice. It also recapitulated poised chromatin during pancreas development and active chromatin in differentiated β-cells. The c.-331C>G mutation, however, blocked active chromatin formation in differentiated b-cells. We further show that another neonatal diabetes gene product, GLIS3, had a singular pioneer-like ability to activateINSchromatin in non-pancreatic cells, which was hampered by the c.-331C>G mutation. Thisin vivoanalysis of human regulatory defects, therefore, uncoveredcisandtranscomponents of a mechanism that is essential to activate the endogenousINSgene.
Nasal immunization with the C-terminal domain of BclA3 induced specific IgG production and attenuated disease symptoms in mice infected withClostridioides difficilespores
Authors: Maia Ana Raquel , Reyes-Ramírez Rodrigo , Pizarro-Guajardo Marjorie , Saggese Anella , Ricca Ezio , Baccigalupi Loredana , Paredes-Sabja Daniel 
Published: June 2020

AbstractClostridioides difficileis a Gram-positive, spore-forming bacterium that causes a severe intestinal infection. Spores of this pathogen enter in the human body through the oral route, interact with intestinal epithelial cells and persist in the gut. Once germinated, the vegetative cells colonize the intestine and produce toxins that enhance a strong immune response that perpetuate the disease. Therefore, spores are major players of the infection and ideal targets of new therapeutic treatments. In this context, spore surface proteins ofC. difficile, are potential antigens for the development of vaccines targetingC. difficilespores. Here we report that the C-terminal domain of the spore surface protein BclA3, BclA3CTD, was identified as an antigenic epitope, over-produced inEscherichia coliand tested as an immunogen in mice. To increase antigen stability and efficiency, BclA3CTDwas also exposed on the surface ofB. subtilisspores, a well-established mucosal vaccine delivery system. In the experimental conditions used in this study, free BclA3CTDinduced antibody production in mice and attenuated some CDI symptoms after a challenge with the pathogen, while the spore-displayed antigen resulted less effective. Although dose regimen and immunization route need to be optimized, our results suggest BclA3CTDas a potentially effective antigen to develop a new vaccination strategy targetingC. difficilespores.