bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts
Authors: Martin Miguel , Ramos-Medina Rocio , Bernat Rebeca , García-Saenz Jose Angel , del Monte-Millan Maria , Alvarez Enrique , Cebollero Maria , Moreno Fernando , Gonzalez-Haba Eva , Bueno Oscar , Romero Paula , Massarrah Tatiana , Echavarria Isabel , Jerez Yolanda , Herrero Blanca , Gonzalez del Val Ricardo , Lobato Nerea , Rincon Patricia , Palomero Maria Isabel , Marquez-Rodas Ivan , Lizarraga Santiago , Asensio Fernando , Lopez-Tarruella Sara 
Published: March 2021

AbstractTriple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate information on the individual contribution of each of these agents to the global activity of the combinations, and the use of combinations of up to four of these drugs is associated with relevant toxicity. Identifying single-drug activity in the clinical neoadjuvant setting is challenging. We developed patient-derived xenografts (PDXs) from several chemotherapy-naïve TNBC samples to assess the antitumor activity of single drugs and combinations of drugs. PDXs were established from chemotherapy-naïve TNBC samples. Nine TNBC PDX models (all of which corresponded to a basal-like phenotype according to the PAM50 classifier) were treated with carboplatin, docetaxel, and doxorubicin and the combination of docetaxel and carboplatin. Only one of nine PDX models showed sensitivity to doxorubicin, while eight of nine PDX models showed sensitivity to docetaxel and carboplatin as single agents. The 3 PDX models derived from patients with gBRCA-1 or gPALB2 mutations were very sensitive to carboplatin single agent. All 6 PDX models from patients without hereditary germ-line mutations showed increased sensitivity to the combination of docetaxel and carboplatin. In the present study, docetaxel and carboplatin single agents were active drugs against basal-like TNBC, while doxorubicin monotherapy showed low activity. The combination of docetaxel and carboplatin was more effective than the drugs used as single agents, except in the PDX from patients with gBRCA1/PALB2 mutations.
Comprehensive transcriptomic analysis of COVID-19 blood, lung, and airway
Authors: Daamen Andrea R. , Bachali Prathyusha , Owen Katherine A. , Kingsmore Kathryn M. , Hubbard Erika L. , Labonte Adam C. , Robl Robert , Shrotri Sneha , Grammer Amrie C. , Lipsky Peter E. 
Published: March 2021

AbstractSARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients.
Insight into the direct interaction of Na+ with NhaA and mechanistic implications
Authors: Quick Matthias , Dwivedi Manish , Padan Etana 
Published: March 2021

AbstractNa+/H+ antiporters comprise a family of membrane proteins evolutionarily conserved in all kingdoms of life that are essential in cellular ion homeostasis. While several human homologues have long been drug targets, NhaA of Escherichia coli has become the paradigm for this class of secondary active transporters as NhaA crystals provided insight in the structure of this molecular machine. However, structural data revealing the composition of the binding site for Na+ (or its surrogate Li+) is missing, representing a bottleneck in our understanding of the correlation between the structure and function of NhaA. Here, by adapting the scintillation proximity assay (SPA) for direct determination of Na+ binding to NhaA, we revealed that (i) NhaA is well adapted as the main antiporter for Na+ homeostasis in Escherichia coli and possibly in other bacteria as the cytoplasmic Na+ concentration is similar to the Na+ binding affinity of NhaA, (ii) experimental conditions affect NhaA-mediated cation binding, (iii) in addition to Na+ and Li+, the halide Tl+ interacts with NhaA, (iv) whereas acidic pH inhibits maximum binding of Na+ to NhaA, partial Na+ binding by NhaA is independent of the pH, an important novel insight into the effect of pH on NhaA cation binding.
Screening of osteoarthritis diagnostic markers based on immune-related genes and immune infiltration
Authors: Yuan Wen-Hua , Xie Qi-Qi , Wang Ke-Ping , Shen Wei , Feng Xiao-Fei , Liu Zheng , Shi Jin-Tao , Zhang Xiao-Bo , Zhang Kai , Deng Ya-Jun , Zhou Hai-Yu 
Published: March 2021

AbstractOsteoarthritis (OA) is a chronic degenerative disease of the bone and joints. Immune-related genes and immune cell infiltration are important in OA development. We analyzed immune-related genes and immune infiltrates to identify OA diagnostic markers. The datasets GSE51588, GSE55235, GSE55457, GSE82107, and GSE114007 were downloaded from the Gene Expression Omnibus database. First, R software was used to identify differentially expressed genes (DEGs) and differentially expressed immune-related genes (DEIRGs), and functional correlation analysis was conducted. Second, CIBERSORT was used to evaluate infiltration of immune cells in OA tissue. Finally, the least absolute shrinkage and selection operator logistic regression algorithm and support vector machine-recurrent feature elimination algorithm were used to screen and verify diagnostic markers of OA. A total of 711 DEGs and 270 DEIRGs were identified in this study. Functional enrichment analysis showed that the DEGs and DEIRGs are closely related to cellular calcium ion homeostasis, ion channel complexes, chemokine signaling pathways, and JAK-STAT signaling pathways. Differential analysis of immune cell infiltration showed that M1 macrophage infiltration was increased but that mast cell and neutrophil infiltration were decreased in OA samples. The machine learning algorithm cross-identified 15 biomarkers (BTC, PSMD8, TLR3, IL7, APOD, CIITA, IFIH1, CDC42, FGF9, TNFAIP3, CX3CR1, ERAP2, SEMA3D, MPO, and plasma cells). According to pass validation, all 15 biomarkers had high diagnostic efficacy (AUC > 0.7), and the diagnostic efficiency was higher when the 15 biomarkers were fitted into one variable (AUC = 0.758). We developed 15 biomarkers for OA diagnosis. The findings provide a new understanding of the molecular mechanism of OA from the perspective of immunology.
Integrating buccal and occlusal dental microwear with isotope analyses for a complete paleodietary reconstruction of Holocene populations from Hungary
Authors: Hernando Raquel , Gamarra Beatriz , McCall Ashley , Cheronet Olivia , Fernandes Daniel , Sirak Kendra , Schmidt Ryan , Lozano Marina , Szeniczey Tamás , Hajdu Tamás , Bárány Annamária , Kalli András , Tutkovics Eszter K. , Köhler Kitti , Kiss Krisztián , Koós Judit , Csengeri Piroska , Király Ágnes , Horváth Antónia , Hajdu Melinda L. , Tóth Krisztián , Patay Róbert , Feeney Robin N. M. , Pinhasi Ron 
Published: March 2021

AbstractDietary reconstruction is used to make inferences about the subsistence strategies of ancient human populations, but it may also serve as a proxy to characterise their diverse cultural and technological manifestations. Dental microwear and stable isotope analyses have been shown to be successful techniques for paleodietary reconstruction of ancient populations but, despite yielding complementary dietary information, these techniques have rarely been combined within the same study. Here we present for the first time a comprehensive approach to interpreting ancient lifeways through the results of buccal and occlusal microwear, and δ13C and δ15N isotope analyses applied to the same individuals of prehistoric populations of Hungary from the Middle Neolithic to the Late Bronze Age periods. This study aimed to (a) assess if the combination of techniques yields a more precise assessment of past dietary and subsistence practices, and (b) contribute to our understanding of the dietary patterns of the prehistoric Hungarian populations. Overall, no correlations between microwear and δ13C and δ15N isotope variables were observed, except for a relationship between nitrogen and the vertical and horizontal index. However, we found that diachronic differences are influenced by the variation within the period. Particularly, we found differences in microwear and isotope variables between Middle Neolithic sites, indicating that there were different dietary practices among those populations. Additionally, microwear results suggest no changes in the abrasiveness of the diet, neither food processing methods, despite higher C4plant resource consumption shown by carbon isotopic signal. Thus, we demonstrate that the integration of dental microwear and carbon and nitrogen stable isotope methodologies can provide complementary information for making inferences about paleodietary habits.
Perceptual judgments of duration of parabolic motions
Authors: Jörges Björn , La Scaleia Barbara , López-Moliner Joan , Lacquaniti Francesco , Zago Myrka 
Published: March 2021

AbstractIn a 2-alternative forced-choice protocol, observers judged the duration of ball motions shown on an immersive virtual-reality display as approaching in the sagittal plane along parabolic trajectories compatible with Earth gravity effects. In different trials, the ball shifted along the parabolas with one of three different laws of motion: constant tangential velocity, constant vertical velocity, or gravitational acceleration. Only the latter motion was fully consistent with Newton’s laws in the Earth gravitational field, whereas the motions with constant velocity profiles obeyed the spatio-temporal constraint of parabolic paths dictated by gravity but violated the kinematic constraints. We found that the discrimination of duration was accurate and precise for all types of motions, but the discrimination for the trajectories at constant tangential velocity was slightly but significantly more precise than that for the trajectories at gravitational acceleration or constant vertical velocity. The results are compatible with a heuristic internal representation of gravity effects that can be engaged when viewing projectiles shifting along parabolic paths compatible with Earth gravity, irrespective of the specific kinematics. Opportunistic use of a moving frame attached to the target may favour visual tracking of targets with constant tangential velocity, accounting for the slightly superior duration discrimination.
Bayes Factors show evidence against systematic relationships between the anchoring effect and the Big Five personality traits
Authors: Schindler Sebastian , Querengässer Jan , Bruchmann Maximilian , Bögemann Nele Johanna , Moeck Robert , Straube Thomas 
Published: March 2021

AbstractExamining personality traits as predictors of human behaviour is of high interest. There are several but inconclusive reported relationships of personality and the susceptibility to the “anchoring effect”, a tendency to adjust estimates towards a given anchor. To provide an answer to variably reported links between personality traits and the anchoring effect, we collected data from 1000 participants in the lab and validated typical anchoring effects and representative personality scores of the sample. Using Bayesian statistical data analyses, we found evidence for the absence of a relationship between anchoring effects and personality scores. We, therefore, conclude that there are no specific personality traits that relate to a higher susceptibility to the anchoring effect. The lack of a relationship between personality and the susceptibility to the anchoring effect might be due to the specific anchoring design, be limited to specific cognitive domains, or the susceptibility to anchors might reflect no reliable individual cognitive phenomena. In the next step, studies should examine the reliability of anchoring effects on the individual level, and testing relationships of individual traits and anchoring effects for other types of anchors, anchoring designs, or cognitive domains.
Inferring ecosystem networks as information flows
Authors: Li Jie , Convertino Matteo 
Published: March 2021

AbstractThe detection of causal interactions is of great importance when inferring complex ecosystem functional and structural networks for basic and applied research. Convergent cross mapping (CCM) based on nonlinear state-space reconstruction made substantial progress about network inference by measuring how well historical values of one variable can reliably estimate states of other variables. Here we investigate the ability of a developed optimal information flow (OIF) ecosystem model to infer bidirectional causality and compare that to CCM. Results from synthetic datasets generated by a simple predator-prey model, data of a real-world sardine-anchovy-temperature system and of a multispecies fish ecosystem highlight that the proposed OIF performs better than CCM to predict population and community patterns. Specifically, OIF provides a larger gradient of inferred interactions, higher point-value accuracy and smaller fluctuations of interactions and $$\alpha$$
α
-diversity including their characteristic time delays. We propose an optimal threshold on inferred interactions that maximize accuracy in predicting fluctuations of effective $$\alpha$$
α
-diversity, defined as the count of model-inferred interacting species. Overall OIF outperforms all other models in assessing predictive causality (also in terms of computational complexity) due to the explicit consideration of synchronization, divergence and diversity of events that define model sensitivity, uncertainty and complexity. Thus, OIF offers a broad ecological information by extracting predictive causal networks of complex ecosystems from time-series data in the space-time continuum. The accurate inference of species interactions at any biological scale of organization is highly valuable because it allows to predict biodiversity changes, for instance as a function of climate and other anthropogenic stressors. This has practical implications for defining optimal ecosystem management and design, such as fish stock prioritization and delineation of marine protected areas based on derived collective multispecies assembly. OIF can be applied to any complex system and used for model evaluation and design where causality should be considered as non-linear predictability of diverse events of populations or communities.
Bevacizumab plus capecitabine as later-line treatment for patients with metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines
Authors: Bang Yeong Hak , Kim Jeong Eun , Lee Ji Sung , Kim Sun Young , Kim Kyu-Pyo , Kim Tae Won , Hong Yong Sang 
Published: March 2021

AbstractThere is an unmet medical need for later-line treatment options for patients with metastatic colorectal cancer (mCRC). Considering that, beyond progression, co-treatment with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate, we aimed to evaluate the efficacy of capecitabine and bevacizumab. This single-center retrospective study included 157 patients between May 2011 and February 2018, who received bevacizumab plus capecitabine as later-line chemotherapy after progressing with irinotecan, oxaliplatin, and fluoropyrimidines. The study treatment consisted of bevacizumab 7.5 mg/kg on day 1 and capecitabine 1,250 mg/m2 orally (PO) twice daily on day 1 to 14, repeated every 3 weeks. The primary endpoint was progression-free survival (PFS). The median PFS was 4.6 months (95% confidence interval [CI] 3.9–5.3). The median overall survival (OS) was 9.7 months (95% CI 8.3–11.1). The overall response rate was 14% (22/157). Patients who had not received prior targeted agents showed better survival outcomes in the multivariable analysis of OS (hazard ratio [HR] = 0.59, 95% CI 0.43–0.82, P = 0.002) and PFS (HR = 0.61, 95% CI 0.43–0.85, P = 0.004). Bevacizumab plus capecitabine could be a considerably efficacious option for patients with mCRC refractory to prior standard treatments.
Associations between second to fourth digit ratio, cortisol, vitamin D, and body composition among Polish children
Authors: Pruszkowska-Przybylska Paulina , Sitek Aneta , Rosset Iwona , Sobalska-Kwapis Marta , Słomka Marcin , Strapagiel Dominik , Żądzińska Elżbieta , Morling Niels 
Published: March 2021

AbstractAssociations between body characteristics (body composition: fat mass, muscle mass, cell, and water mass as well as body proportion—BMI), the 2D:4D digit ratio, and the concentrations of cortisol and vitamin (25-OH)D among Polish children have not been studied before. A total of 133 (73 girls and 60 boys) healthy Polish children aged 7–11 years were examined. The investigation was divided into three parts: measuring (the length of the second and fourth fingers in both hands, body composition, and body height and mass), questionnaires (socioeconomic status), and laboratory investigations (25-OH vitamin D and cortisol concentrations in saliva measured with ELISA methods). Boys with digit ratios below 1 had lower vitamin D concentration than those with digit ratios equal to or higher than 1 (Z = − 2.33; p = 0.019). Only boys with the male-typical pattern of 2D:4D digit ratio tended to have a lower 25-OH vitamin D concentration in saliva. Thus, it might indicate an effect of prenatal programming on the concentrations of steroid hormones in later life. Neither vitamin D, 2D:4D digit ratio nor the cortisol level was associated with the body components or proportions. More studies are needed to evaluate the molecular and genetic background of this phenomenon.
The deep and slow breathing characterizing rest favors brain respiratory-drive
Authors: Girin Baptiste , Juventin Maxime , Garcia Samuel , Lefèvre Laura , Amat Corine , Fourcaud-Trocmé Nicolas , Buonviso Nathalie 
Published: March 2021

AbstractA respiration-locked activity in the olfactory brain, mainly originating in the mechano-sensitivity of olfactory sensory neurons to air pressure, propagates from the olfactory bulb to the rest of the brain. Interestingly, changes in nasal airflow rate result in reorganization of olfactory bulb response. By leveraging spontaneous variations of respiratory dynamics during natural conditions, we investigated whether respiratory drive also varies with nasal airflow movements. We analyzed local field potential activity relative to respiratory signal in various brain regions during waking and sleep states. We found that respiration regime was state-specific, and that quiet waking was the only vigilance state during which all the recorded structures can be respiration-driven whatever the respiratory frequency. Using CO2-enriched air to alter respiratory regime associated to each state and a respiratory cycle based analysis, we evidenced that the large and strong brain drive observed during quiet waking was related to an optimal trade-off between depth and duration of inspiration in the respiratory pattern, characterizing this specific state. These results show for the first time that changes in respiration regime affect cortical dynamics and that the respiratory regime associated with rest is optimal for respiration to drive the brain.
Reducing the foot trajectory variabilities during walking through vibratory stimulation of the plantar surface of the foot
Authors: Yamashita Shun , Igarashi Kotaro , Ogihara Naomichi 
Published: March 2021

AbstractVariabilities or fluctuations in foot clearance are considered as a risk factor for falls during walking in older adults. The present study aimed to investigate whether the foot trajectory variability can be reduced by applying vibratory stimulation to the foot's plantar surface during walking. Ten healthy adults were asked to walk on a treadmill with vibratory shoes, and body kinematics were measured. Changes in the mean absolute deviations of the foot trajectory and joint and trunk angles were compared between the periods of applied or absent vibratory stimulus. Our results demonstrated that toe trajectory variability in the swing phase was significantly smaller when a vibratory stimulus was applied. Applying vibratory stimulus to the soles of the forefoot could potentially be used to reduce foot trajectory variability, which could reduce the risk of trips and associated falls during walking in older adults.
Amyloid related cerebral microbleed and plasma Aβ40 are associated with cognitive decline in Parkinson’s disease
Authors: Tsai Hsin-Hsi , Tsai Li-Kai , Lo Yen-Ling , Lin Chin-Hsien 
Published: March 2021

AbstractCerebral microbleeds (MBs) have been found in patients with cognitive decline. We aimed to examine whether MBs are associated with motor or cognitive decline in patients with Parkinson’s disease (PD). We enrolled 135 PD patients and 34 healthy controls. All participants underwent brain MRI and plasma biomarker assays, including tau, Aβ42, Aβ40, and α-synuclein. PD with dementia (PDD) was operationally defined as Mini-Mental State Examination (MMSE) score < 26 and advanced motor stage was defined as Hoehn-Yahr stage ≥ 3 during “on” status. The association between MBs and disease severity was examined using multivariate logistic regression models. More lobar MBs were observed in PD patients than controls (20.7% vs. 3.3%, p = 0.031). PDD patients had more lobar MBs (33.3% vs. 15.6%, p = 0.034), more white matter hyperintensity (p = 0.021) and reduced hippocampal volume (p = 0.001) than PD with normal cognition. The presence of lobar MB (odds ratio = 2.83 [95% confidence interval 1.04–7.70], p = 0.042) and severe white matter hyperintensity (3.29 [1.21–8.96], p = 0.020) was independently associated with PDD after adjusting for vascular risk factors and other confounders. Furthermore, plasma Aβ40 levels were associated the MMSE score (p = 0.004) after adjusting for age and sex. Our findings demonstrated that lobar MBs, reduced hippocampal volume, and elevated plasma Aβ40 levels are associated with PDD.