bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reprogramming of stromal fibroblasts by chemotherapy-induced secretion of IFNβ1 drives re-growth of breast cancer cells after treatment
Authors: Maia Ana , Gu Zuguang , Koch André , Will Rainer , Schlesner Matthias , Wiemann Stefan 
Published: August 2020

AbstractChemotherapy is still the standard of care for a large number of aggressive tumours including breast cancer. In breast cancer, chemotherapeutic regimens are administered in intervaled cycles of the maximum tolerated dose, allowing cancer cells to re-grow or adapt during the resting periods between cycles. However, how stromal fibroblasts impact the fate of cancer cells after chemotherapy treatment remains poorly understood. We show that cancer cells utilize paracrine signalling with stromal fibroblasts to drive their recovery after treatment withdrawal. Secretion of IFNβ1 by cancer cells after treatment with high doses of chemotherapy instigates the acquisition of an anti-viral state in stromal fibroblasts associated with the expression of several interferon stimulated genes (ISGs), including numerous pro-inflammatory cytokines. This crosstalk is an important driver of the expansion of breast cancer cells after chemotherapy and blocking of IFNβ1 in tumour cells abrogated their increased recovery potential. Analysis of human breast carcinomas supports the proposed role of IFNβ1 since its expression is inversely correlated with recurrence free survival (RFS). Moreover, expression of the interferon signature identified in stromal fibroblasts is equally associated with higher recurrence rates and a worse outcome in breast cancer patients. Our study unravels a novel paracrine communication between cancer cells and fibroblasts that ultimately results in the escape of malignant cells to treatment. Targeting of this axis could potentially improve the outcome of breast cancer patients to chemotherapy treatment.
Explaining decisions of Graph Convolutional Neural Networks: patient-specific molecular subnetworks responsible for metastasis prediction in breast cancer
Authors: Chereda Hryhorii , Bleckmann Annalen , Menck Kerstin , Perera-Bel Júlia , Stegmaier Philip , Auer Florian , Kramer Frank , Leha Andreas , Beißbarth Tim 
Published: August 2020

AbstractMotivationContemporary deep learning approaches show cutting-edge performance in a variety of complex prediction tasks. Nonetheless, the application of deep learning in healthcare remains limited since deep learning methods are often considered as non-interpretable black-box models. Layer-wise Relevance Propagation (LRP) is a technique to explain decisions of deep learning methods. It is widely used to interpret Convolutional Neural Networks (CNNs) applied on image data. Recently, CNNs started to extend towards non-euclidean domains like graphs. Molecular networks are commonly represented as graphs detailing interactions between molecules. Gene expression data can be assigned to the vertices of these graphs. In other words, gene expression data can be structured by utilizing molecular network information as prior knowledge. Graph-CNNs can be applied to structured gene expression data, for example, to predict metastatic events in breast cancer. Therefore, there is a need for explanations showing which part of a molecular network is relevant for predicting an event, e.g. distant metastasis in cancer, for each individual patient.ResultsWe extended the procedure of LRP to make it available for Graph-CNN and tested its applicability on a large breast cancer dataset. We present Graph Layer-wise Relevance Propagation (GLRP) as a new method to explain the decisions made by Graph-CNNs. We demonstrate a sanity check of the developed GLRP on a hand-written digits dataset, and then applied the method on gene expression data. We show that GLRP provides patient-specific molecular subnetworks that largely agree with clinical knowledge and identify common as well as novel, and potentially druggable, drivers of tumor progression. As a result this method could be potentially highly useful on interpreting classification results on the individual patient level, as for example in precision medicine approaches or a molecular tumor board.Availabilityhttps://gitlab.gwdg.de/UKEBpublic/graph-lrphttps://frankkramer-lab.github.io/MetaRelSubNetVis/Contacttim.beissbarth@bioinf.med.uni-goettingen.de
Kinetics of Plasma cfDNA Predicts Clinical Response in Non-Small Cell Lung Cancer Patients
Authors: Zhou Xiaorong , Li Chenchen , Zhang Zhao , Li Daniel Y. , Du Jinwei , Li Ronglei , Ho Effie , Zhang Aiguo , Okunieff Paul , Lu Jianwei , Sha Michael Y. 
Published: August 2020

AbstractBackgroundTyrosine Kinases Inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs, bevacizumab) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancer including non-small-cell lung cancer (NSCLC). Cell-free DNA (cfDNA) has been adapted as a convenient liquid biopsy that reflects characteristics of the status of both the primary and metastatic tumors, assisting in personalized medicine. This study aims to evaluate the utility of cfDNA as a prognostic biomarker and efficacy predictor of chemotherapy with or without these precision therapies in NSCLC patients.MethodsPeripheral cfDNA levels were quantified in 154 patients with NSCLC before (baseline) and after (post-chemotherapy) the first target cycle of chemotherapy. These patients were divided into four subgroups receiving chemotherapy only, chemotherapy plus TKIs, chemotherapy plus VEGFIs, and chemotherapy plus immune checkpoint inhibitors (ICIs), respectively. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS), objective response ratio (ORR), and therapy regimens were analyzed.ResultsBaseline cfDNA, but not post-chemotherapy, positively correlates with tumor burden. cfDNA Ratio (post-chemotherapy/baseline) well distinguished responsive individuals (CR/PR) from non-responsive patients (PD/SD). Additionally, cfDNA Ratio was found to be negatively correlated with PFS in lung adenocarcinoma (LUAD), but not in lung squamous-cell carcinoma (LUSC). LUAD patients with low cfDNA Ratio benefit significantly including prolonged PFS and improved ORR, compared with those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs.ConclusionThe kinetics of plasma cfDNA during the chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.
Occurrence of Drosophilids in the Pernambuco’s coastal region (years 2000-2001) and the Frequency of chromosomal inversions found inDrosophila malerkotliana
Authors: Félix Pierre Teodósio , dos Santos José Ferreira 
Published: August 2020

AbstractDrosophilids were collected in thecampusof UFPE (Recife), Rio Doce (Olinda), Vila Velha (Itamaracá), Parque de dois Irmãos (Recife) and Charles Darwin Ecological Refuge (Igarassu), in the years 2000 and 2001, seeking to establish the frequency of occurrence of the various species of the genus Drosophila. In these collections,D. malerkotlianaoccurred in an average frequency of 64%, followed byD. melanogaster, with an average frequency of 23%. The frequency ofD. malerkotlianawas higher than that ofD. melanogasterin localities with high and medium degree of urbanization. Despite the great distance from the distribution center of the species (Africa),D. malerkotlianapresented high polymorphism of chromosomal inversions. In the locality of Rio Doce, inversions In(IIL)24B-39A and In(IIL)21-25, occurred with frequencies of 18.5% and 100%, respectively, while inversion In(IIIR)84-88B occurred with a frequency of 100%. In the population ofcampusUFPE (Recife), also with high urbanization, two inversions were found, In(IIIR)93C-94A and In(IIIL)64A-72A with frequencies of 37.1 and 60%, respectively. In the population of The Parque de Dois Irmãos (Recife), with medium urbanization, four inversions were visualized: In(IIIL)70C-73B (66%); In(IIIR)93C-94A (52%); In(IIL)24B-39A (33%); and In(IIR)50B-51A (33%). In the population of the Charles Darwin Ecological Refuge (Igarassu), of low urbanization, only the inversion In(IIIR)100A-98B(?) was found. −88(?), with 100% frequency. These data suggest that the polymorphism of inversions is higher in localities with greater urbanization, possibly due to the longer colonization time, which allowed the accumulation of genetic variations.
Continuous psychophysics shows millisecond-scale visual processing delays are faithfully preserved in movement dynamics
Authors: Burge Johannes , Cormack Lawrence K. 
Published: August 2020

AbstractImage differences between the eyes can cause interocular discrepancies in the speed of visual processing. Millisecond-scale differences in visual processing speed can cause dramatic misperceptions of the depth and 3D direction of moving objects. Here, we develop a monocular and binocular continuous target-tracking psychophysics paradigm that can quantify such tiny differences in visual processing speed. Human observers continuously tracked a target undergoing Brownian motion with a range of luminance levels in each eye. Suitable analyses recover the time-course of the visuomotor response in each condition, the dependence of visual processing speed on luminance level, and the temporal evolution of processing differences between the eyes. Importantly, using a direct within-observer comparison, we show that continuous target-tracking and traditional forced-choice psychophysical methods provide estimates of interocular delays that agree on average to within a fraction of a millisecond. Thus, visual processing delays are preserved in the movement dynamics of the hand. Finally, we show analytically, and partially confirm experimentally, that differences between the temporal impulse response functions in the two eyes predicts how lateral target motion causes misperceptions of motion-in-depth and associated tracking responses. Because continuous target-tracking can accurately recover millisecond-scale differences in visual processing speed and has multiple advantages over traditional psychophysics, it should facilitate the study of temporal processing in the future.
Songbirds can learn flexible contextual control over syllable sequencing
Authors: Veit Lena , Tian Lucas Y , Hernandez Christian J Monroy , Brainard Michael S 
Published: August 2020

AbstractThe flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (syllables or words). Songbirds are phylogenetically distant from humans but share both the capacity for vocal learning and neural circuitry for vocal control that includes direct pallial-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment by-moment control over vocalizations. Here, we demonstrate that Bengalese finches (Lonchura striata domestica), which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. ‘ab-c’ versus ‘ab-d’) in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists without external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels human cognitive control over syllable sequencing in speech.
Dietary diversity and its correlates among pregnant adolescent girls in Ghana
Authors: Gyimah Linda A. , Annan Reginald A. , Apprey Charles , Edusei Anthony K. , Aduku Linda Esi , Asamoah-Boakye Odeafo , Azanu Wisdom , Lutterodt Herman 
Published: August 2020

AbstractBackgroundDietary diversity, a qualitative measure of dietary intake, which reflects the variety of foods consumed has been recommended to assuage nutritional problems related to insufficient micronutrients and food insecurity. To better understand the underlying factors for poor birth outcomes in Ghana, we assessed factors associated with dietary diversity among rural and urban pregnant adolescents in the Ashanti Region of Ghana.MethodsAs part of a larger longitudinal cohort of 416 pregnant adolescents, the FAO women’s dietary diversity index was used to determine dietary diversity score (DDS) of the participants from a 3-day repeated 24-hour dietary recall data. The household hunger scale (HHS) and lived poverty index (LPI) were used to determine hunger and socioeconomic status. Eating behavior and socio-demographic data were gathered using interviewer-administered questionnaires.ResultsThe mean DDS for participants was 4.3 but 59.7% of participants were below the minimum DD. More rural (67.1%) than urban dwellers (53.9%) had inadequate DDS (p=0.008). Urban dwelling adolescents recorded higher odds for adequate DD (OR=1.8 CI =1.0-2.8, p=0.034) compared to the rural respondents. Other factors associated with higher odds for adequate DD are income (OR=12.1, p = 0.043, 95%CI= 1.1-136.8), moderate (OR=2.1, p = 0.019, 95%CI=1.1-3.8) and high LPI (OR=2.2, p=0.007, 95%CI=1.2-3.9), practicing food aversion (OR=1.6, p = 0.046, 95%CI= 1.0-2.4), and pica (OR 1.6, p =0.043, 95%CI= 1.0-2.5).ConclusionsLow DD is common among pregnant adolescents in this study and associated with poverty, food insecurity, rural living, pica practice, and food aversions. Livelihood support for pregnant teenagers and nutrition education are recommended interventions to improve dietary quality and limit the consequences of poor dietary diversity.
Children’s Anxiety and Physical Activity during COVID-19 in Relation to Prenatal Exposure to Gestational Diabetes
Authors: Alves Jasmin M. , Yunker Alexandra G. , DeFendis Alexis , Xiang Anny H. , Page Kathleen A. 
Published: August 2020

AbstractResearch goalAssess the relationships between anxiety levels, physical activity and in utero exposure to Gestational Diabetes mellitus (GDM) in children age 9 to 15, during the coronavirus disease 2019 (COVID-19) pandemic.MethodsDuring the COVID-19 pandemic, participants completed phone call or video calls with study personnel where they were asked to report on their physical activity and anxiety levels using the 24-hour physical activity recall and the State-Trait Anxiety Inventory for Children. GDM-exposure was assessed using electronic medical records.ResultsChildren who reported higher levels of moderate to vigorous physical activity or vigorous physical activity, reported lower anxiety symptoms. Children exposed to GDM in utero reported higher anxiety scores and lower engagement in vigorous physical activity compared to unexposed children. Moreover, the pathway through which children exposed to GDM in utero, reported higher anxiety was partially explained by reduced engagement in vigorous physical activity (75%, p=0.05).ConclusionsEngaging in physical activity during the COVID-19 pandemic may be beneficial for reducing anxiety, particularly among children exposed to GDM in utero, who are at increased risk for adverse psychological outcomes.
Automated measurement of the foveal avascular zone in healthy eyes on Heidelberg Spectralis Optical Coherence Tomography Angiography
Authors: Gutierrez-Benitez Laura , Palomino Yolanda , Casas Noe , Asaad Mouafk 
Published: August 2020

ABSTRACTPurposeTo develop and evaluate an automated method to measure the foveal avascular zone (FAZ) area in healthy eyes on Heidelberg Spectralis Optical Coherence Tomography Angiography (HS-OCTA). This method is referred to as the modified Kanno-Saitama macro (mKSM) and it is an evolution of the original Kanno-Saitama macro (KSM) approach.MethodsThis cross-sectional study included 29 eyes of 25 healthy volunteers who underwent HS-OCTA at the macular area twice at the same time. Regardless of the quality of the images, all of them were included. Macular data on the superficial vascular plexus, intermediate capillary plexus and deep capillary plexus were processed by mKSM. The FAZ area was measured twice automatically using the mKSM and KSM and twice manually by two independent examiners.ResultsFrom 174 images, KSM could not measure correctly 31% while mKSM could successfully measure all of them. Intrascan intraclass coefficient ranged from 0,948 to 0,993 for manual measurements and was 1 for mKSM method, which means that mKSM FAZ area value is always the same for the same OCTA image. Despite that the difference between human examiners is smaller than between human examiners and mKSM according to Bland-Altman plots, the scatterplots show a strong correlation between human and automatic measurements. The best results are obtained in intermediate capillary plexus.ConclusionsWith mKSM, the automated determination of the FAZ area in HS-OCTA is feasible and less human-dependent. It solves the inability of KSM to measure the FAZ area in suboptimal quality images which are frequent in daily clinical practice. Therefore, the mKSM processing could contribute to our understanding of the three vascular plexuses.
Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19
Authors: Ying Kejun , Zhai Ranran , Pyrkov Timothy V. , Mariotti Marco , Fedichev Peter O. , Shen Xia , Gladyshev Vadim N. 
Published: August 2020

AbstractEpidemiological studies have revealed that the elderly and those with co-morbidities are most susceptible to COVID-19. To understand the genetic link between aging and the risk of COVID-19, we conducted a multi-instrument Mendelian randomization analysis and found that the genetic variation that leads to a longer lifespan is significantly associated with a lower risk of COVID-19 infection. The odds ratio is 0.32 (95% CI: 0.18 to 0.57; P = 1.3 × 10-4) per additional 10 years of life, and 0.62 (95% CI: 0.51 to 0.77; P = 7.2 × 10-6) per unit higher log odds of surviving to the 90th percentile age. On the other hand, there was no association between COVID-19 susceptibility and healthspan (the lifespan free of the top seven age-related morbidities). To examine the relationship at the phenotypic level, we applied various biological aging clock models and detected an association between the biological age acceleration and future incidence and severity of COVID-19 infection for all subjects as well as for the individuals free of chronic disease. Biological age acceleration was also significantly associated with the risk of death in COVID-19 patients. Our findings suggest a causal relationship between aging and COVID-19, defined by genetic variance, the rate of aging, and the burden of chronic diseases.
Predation impacts late but not early community assembly in model marine biofilms
Authors: Tobias-Hünefeldt Sven P. , Wenley Jess , Baltar Federico , Morales Sergio E. 
Published: August 2020

AbstractBottom-up selection plays an important role in microbial community assembly but is unable to account for all observed variance. Other processes like top-down selection (e.g. predation) may be partially responsible for the unexplained variance. However, top-down processes often remain unexplored, especially in interaction with bottom-up selective pressures. We utilised anin situmarine biofilm model system to test the effects of bottom-up (i.e. substrate properties) and top-down (i.e. predator exclusion via 100 µm mesh) selective pressures on community assembly over time (56 days). Community compositions were monitored using 16S and 18S rRNA amplicon sequencing. Wooden substrates promoted heterotrophic growth, while the inert substrates’ (i.e., plastic, glass, tile) lack of degradable material selected for autotrophs. Early wood communities contained 9-50% more mixotrophs and heterotrophs (e.g. Proteobacteria and Euglenozoa) compared to inert substrates. Inert substrates instead showed twice the autotrophic (e.g. Cyanobacteria and Ochrophyta) abundance. Late communities differed mainly due to exclusion status, as large predators preferably pruned heterotrophs. This resulted in the autotrophic domination of native communities, while high heterotrophic abundance characterised exclusive conditions. Top-down control through exclusion increased explainable variance by 18-53%, depending on community age, leading to increased understanding of the underlying ecological framework that guides microbial community assembly.
Molecular markers characterization determining cell fate specification in an adult neurogenesis model ofAlzheimer’s disease
Authors: Blanco-Luquin Idoia , Cabello Juan , Urdánoz-Casado Amaya , Acha Blanca , Gómez-Orte Eva Ma , Roldan Miren , Pérez-Rodríguez Diego R. , Mendioroz Maite 
Published: August 2020

ABSTRACTAdult hippocampal neurogenesis (AHN) study is still a challenge. In addition to methodological difficulties is the controversy of results derived of human or animal system approaches. In view of the proven link between AHN and learning and memory impairment, we generated a straightforwardin vitromodel to recapitulate adult neurogenesis in the context of Alzheimer’s disease (AD).Neural progenitor cells (NPCs) monolayer culture was differentiated for a period of 29 days and Aβ peptide 1-42 was administered once a week. mRNA expression ofNEUROD1, NCAM1, TUBB3, RBFOX3, CALB1andGFAPgenes was determined by RT-qPCR.Phenotypic changes were observed during directed differentiation. Except forGFAPandCALB1, these changes correlated with altered expression profile of all genes since 9 days. OnlyTUBB3expression remained constant whileNEUROD1, NCAM1andRBFOX3expression increased over time. Moreover, Aβ treated NPCs showed transient decreases of mRNA expression forNCAM1, TUBB3andRBFOX3genes at 9 or 19 days.Ourin vitrohuman NPCs model is framed within the multistep process of AHN in the SGZ of the DG. Remarkably, its transcriptional assessment might reflect alterations detected in AD human patients, deepening our understanding of the disorder and possibly of its pathogenesis.SUMMARY STATEMENTTranscriptional profile of a number of genes recapitulating particular stages of Adult hippocampal neurogenesis in the context of Alzheimer’s disease
Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer
Authors: Iqbal Mohammad Askandar , Siddiqui Shumaila , Ur Rehman Asad , Siddiqui Farid Ahmad , Singh Prithvi , Kumar Bhupender , Saluja Daman 
Published: August 2020

AbstractStriking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1 (cPRC1), play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients (N>3000 combined), we performed pathway-based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we provide evidence for the role of mTORC1 signaling in mediating contrary effects of CBX2 and CBX7 on breast cancer metabolism. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up- and down-regulated isoforms, respectively, in breast tumors compared to normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor subtype aggressiveness and the proliferation markers. Consistently, genomic data also showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, disease-specific survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to FDA-approved clinical drugs. In summary, this work identifies novel cross-talk between CBX2/7 and breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer.