bluuebunny/crossref_metadata_2025_split huggingface dataset:
REVISED CHRONOLOGY AND SETTLEMENT HISTORY OF TULA AND THE TULA REGION
Authors: Healan Dan M. , Cobean Robert H. , Bowsher Robert T. 
Published: May 2021

AbstractThis article offers a revision of the chronology and settlement history of Tula, Hidalgo, synthesizing information obtained from numerous investigations and 68 radiocarbon and seven archaeomagnetic dates. Tula Chico's earliest settlement appeared while the region was under the control of Teotihuacan as one of many hilltop Coyotlatelco settlements in the region. The monumental center at Tula Grande did not appear until after Tula grew to power, presumably with the consolidation of the other Coyotlatelco polities. Extensive exposure of residential structures in numerous localities have revealed a widespread pattern of barrios containing households exhibiting a wide range of social status that enjoyed access to a wide variety of luxury items including the first reported objects of gold. Tula Grande and the Tollan phase city appear to have already been abandoned and in ruins prior to the arrival of Aztec II peoples. The Late Aztec period occupation shows a preoccupation with Tula's ruins that parallels similar evidence from the Templo Mayor excavations suggesting it was indeed the place the Aztecs called Tollan.
Formalising nominal C-unification generalised with protected variables
Authors: Ayala-Rincón Mauricio , de Carvalho-Segundo Washington , Fernández Maribel , Silva Gabriel Ferreira , Nantes-Sobrinho Daniele 
Published: May 2021

AbstractThis work extends a rule-based specification of nominal C-unification formalised in Coq to include ‘protected variables’ that cannot be instantiated during the unification process. By introducing protected variables, we are able to reuse the C-unification simplification rules to solve nominal C-matching (as well as equality check) problems. From the algorithmic point of view, this extension is sufficient to obtain a generalised C-unification procedure; however, it cannot be formally checked by simple reuse of the original formalisation. This paper describes the additional effort necessary in order to adapt the specification of the inference rules and reuse previous formalisations. We also generalise a functional recursive nominal C-unification algorithm specified in PVS with protected variables, effectively adapting this algorithm to the tasks of nominal C-matching and nominal equality check. The PVS formalisation is applied to test the correctness of a Python manual implementation of the algorithm.
New Evidence for the Psychometric Properties of the Spanish Version of the Gain in Alzheimer Care Instrument
Authors: García-Castro F. Javier , Holgado-Tello F. Pablo , Blanca María J. 
Published: May 2021

Abstract
The aim was to analyze the psychometric properties of the Spanish version of the Gain in Alzheimer Care Instrument (GAIN), providing validity evidence based on its internal structure, reliability, item analysis, and relationships with other variables. A sample of 113 informal caregivers of people with dementia completed the GAIN, along with questionnaires assessing burden, general mental health, stress, anxiety, depression, and life satisfaction. Confirmatory factor analysis showed a single-factor structure with adequate fit indices. Reliability of GAIN scores was satisfactory, with McDonald’s omega equal to .91. Items yielded adequate homogeneity indices. Validity evidence based on relationships with other variables was provided by positive correlations between GAIN scores and life satisfaction, and negative correlations with burden, general mental health problems, stress, anxiety, and depression. All these correlations were statistically significant, and most of them were of moderate magnitude. The Spanish version of the GAIN has a single-factor structure and satisfactory psychometric properties. It is quick and easy to apply and given the association between GAIN scores and other variables, it may be used to provide information about a caregiver’s psychological health status.
Response of Surface Erosion to Crustal Shortening and its Influence on Tectonic Evolution in Fold‐and‐Thrust Belts: Implications From Sandbox Modeling on Tectonic Geomorphology
Authors: Mao Yuqiong , Li Yiquan , Yan Bing , Wang Xianyan , Jia Dong , Chen Yingying 
Published: May 2021

AbstractStructural deformation affects surface processes and the consequent distribution of tectonic stress and structural deformation patterns via crustal isostasy. The associated processes and mechanisms are widely concerned topics in tectonic geomorphology. In this study, we discuss the interaction between tectonic deformation and surface processes in fold‐and‐thrust belts by sandbox experimental modeling. The tectonic deformation patterns under different conditions are studied, including the occurrence of detachment and the different crustal shortening rates. Furthermore, we discussed the influence of surface erosion and sedimentation on the spatial distribution, morphology, amplitude, and process of tectonic deformation. The results show that the occurrence of plastic detachment links the interaction of surface erosion and tectonics such as deformation patterns. Thin‐skinned structures develop when plastic detachment occurs, thus amplifying surface processes. In turn, the erosion and deposition affect the position and morphology of new structures as well as the lateral propagation and connection of isolated structures. Different shortening rates lead to different propagation distances and structure arrangements. These different tectonic conditions result in diverse drainage evolution and the specific processes of surface erosion and deposition. In general, structural development is controlled by both endogenic forces and surface erosion and deposition processes. The physical properties of detachments and crustal shortening rates play an important role in linking deep tectonic activity and surface processes. These results are comparable to natural examples, such as the fold‐and‐thrust belts along the Tianshan Mountains, thus providing new clues for understanding the mechanism of the interaction between endogenic tectonic activity and surface processes.
Non-cell-autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse
Authors: Vincent Clémentine , Gilabert-Juan Javier , Gibel-Russo Rachel , Alvarez-Fischer Daniel , Krebs Marie-Odile , Le Pen Gwenaëlle , Prochiantz Alain , Di Nardo Ariel A. 
Published: May 2021

AbstractThe OTX2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, which projects to limbic structures controlling complex behaviors. OTX2 is also produced in choroid plexus epithelium, from which it is secreted into cerebrospinal fluid and transferred to limbic structure parvalbumin interneurons. Previously, adult male mice subjected to early-life stress were found susceptible to anxiety-like behaviors, with accompanying OTX2 expression changes in ventral tegmental area or choroid plexus. Here, we investigated the consequences of reduced OTX2 levels in Otx2 heterozygote mice, as well as in Otx2+/AA and scFvOtx2tg/0 mouse models for decreasing OTX2 transfer from choroid plexus to parvalbumin interneurons. Both male and female adult mice show anxiolysis-like phenotypes in all three models. In Otx2 heterozygote mice, we observed no changes in dopaminergic neuron numbers and morphology in ventral tegmental area, nor in their metabolic output and projections to target structures. However, we found reduced expression of parvalbumin in medial prefrontal cortex, which could be rescued in part by adult overexpression of Otx2 specifically in choroid plexus, resulting in increased anxiety-like behavior. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of anxiety-related phenotypes in the mouse.
PLK1/vimentin signaling facilitates immune escape by recruiting Smad2/3 to PD-L1 promoter in metastatic lung adenocarcinoma
Authors: Jang Hay-Ran , Shin Sol-Bi , Kim Chang-Hyeon , Won Jae-Yeon , Xu Rong , Kim Da-Eun , Yim Hyungshin 
Published: May 2021

AbstractThe prerequisite function of vimentin for the epithelial–mesenchymal transition (EMT) is not clearly elucidated yet. Here, we show that vimentin phosphorylated by PLK1, triggers TGF-β-signaling, which consequently leads to metastasis and PD-L1 expression for immune suppression in lung adenocarcinoma. The clinical correlation between expression of both vimentin and PLK1, and overall survival rates of patients was significant in lung adenocarcinoma but not in squamous cell carcinoma. The phosphorylation of vimentin was accompanied by the activation of PLK1 during TGF-β-induced EMT in lung adenocarcinoma. Among the several phosphorylation sites determined by phospho-proteomic analysis and the site-specific mutagenesis, the phosphorylation at S339 displayed the most effective metastasis and tumourigenesis with the highest expression of PD-L1, compared with that of wild-type and other versions in both 3D cell culture and tail-vein injection metastasis models. Phosphomimetic vimentin at S339 interacted with p-Smad2 for its nuclear localization, leading to the expression of PD-L1. Clinical relevance revealed the inverse correlation between the survival rates of patients and the expressions of VIM, PLK1, and CD274 in primary and metastatic lung adenocarcinoma. Thus, PLK1-mediated phosphorylation of vimentin activates TGF-β signaling pathway, leading to the metastasis and immune escape through the expression of PD-L1, functioning as a shuttling protein in lung adenocarcinoma.
Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment
Authors: Terrisse Safae , Derosa Lisa , Iebba Valerio , Ghiringhelli François , Vaz-Luis Ines , Kroemer Guido , Fidelle Marine , Christodoulidis Stergios , Segata Nicola , Thomas Andrew Maltez , Martin Anne-Laure , Sirven Aude , Everhard Sibille , Aprahamian Fanny , Nirmalathasan Nitharsshini , Aarnoutse Romy , Smidt Marjolein , Ziemons Janine , Caldas Carlos , Loibl Sibylle , Denkert Carsten , Durand Sylvere , Iglesias Claudia , Pietrantonio Filippo , Routy Bertrand , André Fabrice , Pasolli Edoardo , Delaloge Suzette , Zitvogel Laurence 
Published: May 2021

AbstractThe prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.
Whole genome sequencing reveals high differentiation, low levels of genetic diversity and short runs of homozygosity among Swedish wels catfish
Authors: Jensen Axel , Lillie Mette , Bergström Kristofer , Larsson Per , Höglund Jacob 
Published: May 2021

AbstractThe use of genetic markers in the context of conservation is largely being outcompeted by whole-genome data. Comparative studies between the two are sparse, and the knowledge about potential effects of this methodology shift is limited. Here, we used whole-genome sequencing data to assess the genetic status of peripheral populations of the wels catfish (Silurus glanis), and discuss the results in light of a recent microsatellite study of the same populations. The Swedish populations of the wels catfish have suffered from severe declines during the last centuries and persists in only a few isolated water systems. Fragmented populations generally are at greater risk of extinction, for example due to loss of genetic diversity, and may thus require conservation actions. We sequenced individuals from the three remaining native populations (Båven, Emån, and Möckeln) and one reintroduced population of admixed origin (Helge å), and found that genetic diversity was highest in Emån but low overall, with strong differentiation among the populations. No signature of recent inbreeding was found, but a considerable number of short runs of homozygosity were present in all populations, likely linked to historically small population sizes and bottleneck events. Genetic substructure within any of the native populations was at best weak. Individuals from the admixed population Helge å shared most genetic ancestry with the Båven population (72%). Our results are largely in agreement with the microsatellite study, and stresses the need to protect these isolated populations at the northern edge of the distribution of the species.
The influence of different intraocular pressure on lamina cribrosa parameters in glaucoma and the relation clinical implication
Authors: Wu Jian , Du Yifan , Li Jiaying , Fan Xiaowei , Lin Caixia , Wang Ningli 
Published: May 2021

AbstractElevated intraocular pressure (IOP) is one of the main risk factors for glaucoma, and pathological changes in the lamina cribrosa (LC) may play a leading role. This study aimed to explore the influence of different IOP on LC parameters and the correlation between parameters and glaucoma severity. A total of 91 eyes were examined by swept-source OCT and divided into IOP ≥ 30 mmHg (group A), 21 mmHg ≤ IOP < 30 mmHg (group B), and normal IOP (control, group C). Clinical parameters and all LC parameters such as cup depth (CD), lamina cribrosa depth (LCD), prelaminar tissue thickness (PTT) and LC curvature index (LCCI) were used for statistical analysis. The bulk of parameters were greater in group A than in the other groups (group B, P < 0.05; group C, P < 0.001). PTT and Bruch’s membrane opening minimum rim width (BMO-MRW) were thinner in group A than in group C (P < 0.01). In univariate and multivariable linear regression analysis, visual field (VF), mean retinal nerve fiber layer (RNFL) thickness, CD, LCD, PLCSD, PTT, LCCI, aLCCI, and BMO-MRW were significantly correlated with IOP changes (P < 0.05). Pearson test showed that LCD and LCCI were correlated with mean retinal nerve fiber layer (RNFL) thickness (LCD, r = − 0.420, P = 0.002; LCCI, r = − 0.449, P < 0.001) and BMO-MRW (LCD, r = − 0.245, P = 0.019; LCCI, r = − 0.345, P < 0.001). Therefore, different levels of IOP have a remarkable effect on clinical symptoms (VF, BCVA) and LC parameters, between which there may be a linear relationship. LCCI may exhibit a more significant correlation with RNFL thickness and BMO-MRW, which may further suggest that LCCI shows a better correlation with clinical symptoms under the influence of long-term high IOP.
Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461
Authors: Masud Tehmina , Soong Charles , Xu Hong , Biele Justina , Bjornson Saelin , McKinney Steven , Aparicio Samuel 
Published: May 2021

AbstractCX-5461 is a G-quadruplex (G4) ligand currently in trials with initial indications of clinical activity in cancers with defects in homologous recombination repair. To identify more genetic defects that could sensitize tumors to CX-5461, we tested synthetic lethality for 480 DNA repair and genome maintenance genes to CX-5461, pyridostatin (PDS), a structurally unrelated G4-specific stabilizer, and BMH-21, which binds GC-rich DNA but not G4 structures. We identified multiple members of HRD, Fanconi Anemia pathways, and POLQ, a polymerase with a helicase domain important for G4 structure resolution. Significant synthetic lethality was observed with UBE2N and RNF168, key members of the DNA damage response associated ubiquitin signaling pathway. Loss-of-function of RNF168 and UBE2N resulted in significantly lower cell survival in the presence of CX-5461 and PDS but not BMH-21. RNF168 recruitment and histone ubiquitination increased with CX-5461 treatment, and nuclear ubiquitination response frequently co-localized with G4 structures. Pharmacological inhibition of UBE2N acted synergistically with CX-5461. In conclusion, we have uncovered novel genetic vulnerabilities to CX-5461 with potential significance for patient selection in future clinical trials.
Mucosal IFNγ production and potential role in protection in Escherichia coli O157:H7 vaccinated and challenged cattle
Authors: Schaut Robert G. , Palmer Mitchell V. , Boggiatto Paola M. , Kudva Indira T. , Loving Crystal L. , Sharma Vijay K. 
Published: May 2021

AbstractShiga-toxin producingEscherichia coliO157:H7 (O157)-based vaccines can provide a potential intervention strategy to limit foodborne zoonotic transmission of O157. While the peripheral antibody response to O157 vaccination has been characterized, O157-specific cellular immunity at the rectoanal junction (RAJ), a preferred site for O157 colonization, remains poorly described. Vaccine induced mucosal O157-specific antibodies likely provide some protection, cellular immune responses at the RAJ may also play a role in protection. Distinct lymphoid follicles were increased in the RAJ of vaccinated/challenged animals. Additionally, increased numbers of interferon (IFN)γ-producing cells and γδ + T cells were detected in the follicular region of the RAJ of vaccinated/challenged animals. Likewise, adjuvanted-vaccine formulation is critical in immunogenicity of the O157 parenteral vaccine. Local T cell produced IFNγ may impact epithelial cells, subsequently limiting O157 adherence, which was demonstrated using in vitro attachment assays with bovine epithelial cells. Thus, distinct immune changes induced at the mucosa of vaccinated and challenged animals provide insight of mechanisms associated with limiting O157 fecal shedding. Enhancing mucosal immunity may be critical in the further development of efficacious vaccines for controlling O157 in ruminants and thus limiting O157 transmission to humans.
Comparison of radiomic feature aggregation methods for patients with multiple tumors
Authors: Chang Enoch , Joel Marina Z. , Chang Hannah Y. , Du Justin , Khanna Omaditya , Omuro Antonio , Chiang Veronica , Aneja Sanjay 
Published: May 2021

AbstractRadiomic feature analysis has been shown to be effective at analyzing diagnostic images to model cancer outcomes. It has not yet been established how to best combine radiomic features in cancer patients with multifocal tumors. As the number of patients with multifocal metastatic cancer continues to rise, there is a need for improving personalized patient-level prognosis to better inform treatment. We compared six mathematical methods of combining radiomic features of 3,596 tumors in 831 patients with multiple brain metastases and evaluated the performance of these aggregation methods using three survival models: a standard Cox proportional hazards model, a Cox proportional hazards model with LASSO regression, and a random survival forest. Across all three survival models, the weighted average of the largest three metastases had the highest concordance index (95% confidence interval) of 0.627 (0.595–0.661) for the Cox proportional hazards model, 0.628 (0.591–0.666) for the Cox proportional hazards model with LASSO regression, and 0.652 (0.565–0.727) for the random survival forest model. This finding was consistent when evaluating patients with different numbers of brain metastases and different tumor volumes. Radiomic features can be effectively combined to estimate patient-level outcomes in patients with multifocal brain metastases. Future studies are needed to confirm that the volume-weighted average of the largest three tumors is an effective method for combining radiomic features across other imaging modalities and tumor types.
Incorporating false negative tests in epidemiological models for SARS-CoV-2 transmission and reconciling with seroprevalence estimates
Authors: Bhattacharyya Rupam , Kundu Ritoban , Bhaduri Ritwik , Ray Debashree , Beesley Lauren J. , Salvatore Maxwell , Mukherjee Bhramar 
Published: May 2021

AbstractSusceptible-Exposed-Infected-Removed (SEIR)-type epidemiologic models, modeling unascertained infections latently, can predict unreported cases and deaths assuming perfect testing. We apply a method we developed to account for the high false negative rates of diagnostic RT-PCR tests for detecting an active SARS-CoV-2 infection in a classic SEIR model. The number of unascertained cases and false negatives being unobservable in a real study, population-based serosurveys can help validate model projections. Applying our method to training data from Delhi, India, during March 15–June 30, 2020, we estimate the underreporting factor for cases at 34–53 (deaths: 8–13) on July 10, 2020, largely consistent with the findings of the first round of serosurveys for Delhi (done during June 27–July 10, 2020) with an estimated 22.86% IgG antibody prevalence, yielding estimated underreporting factors of 30–42 for cases. Together, these imply approximately 96–98% cases in Delhi remained unreported (July 10, 2020). Updated calculations using training data during March 15-December 31, 2020 yield estimated underreporting factor for cases at 13–22 (deaths: 3–7) on January 23, 2021, which are again consistent with the latest (fifth) round of serosurveys for Delhi (done during January 15–23, 2021) with an estimated 56.13% IgG antibody prevalence, yielding an estimated range for the underreporting factor for cases at 17–21. Together, these updated estimates imply approximately 92–96% cases in Delhi remained unreported (January 23, 2021). Such model-based estimates, updated with latest data, provide a viable alternative to repeated resource-intensive serosurveys for tracking unreported cases and deaths and gauging the true extent of the pandemic.
Multiple social network influences can generate unexpected environmental outcomes
Authors: Yletyinen J. , Perry G. L. W. , Stahlmann-Brown P. , Pech R. , Tylianakis J. M. 
Published: May 2021

AbstractUnderstanding the function of social networks can make a critical contribution to achieving desirable environmental outcomes. Social-ecological systems are complex, adaptive systems in which environmental decision makers adapt to a changing social and ecological context. However, it remains unclear how multiple social influences interact with environmental feedbacks to generate environmental outcomes. Based on national-scale survey data and a social-ecological agent-based model in the context of voluntary private land conservation, our results suggest that social influences can operate synergistically or antagonistically, thereby enabling behaviors to spread by two or more mechanisms that amplify each other’s effects. Furthermore, information through social networks may indirectly affect and respond to isolated individuals through environmental change. The interplay of social influences can, therefore, explain the success or failure of conservation outcomes emerging from collective behavior. To understand the capacity of social influence to generate environmental outcomes, social networks must not be seen as ‘closed systems’; rather, the outcomes of environmental interventions depend on feedbacks between the environment and different components of the social system.