bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling the Coupled Atmosphere‐Ocean‐Ice Interactions Driving Arctic Sea Ice Response to CO2 Increases
Authors: Garuba Oluwayemi A. , Singh Hansi A. , Hunke Elizabeth , Rasch Philip J. 
Published: November 2020

AbstractA novel decomposition of the ocean heat energy that contributes to sea ice melt and growth (ocean‐ice and frazil heat) into components that are driven by surface heat flux and ocean circulation changes is used to isolate the evolving roles of the atmosphere and ocean in the Arctic sea ice loss from CO2 increases. A sea ice volume budget analysis is used to separate the impacts of the anomalous frazil/ocean‐ice heat from those of atmosphere‐ice heat on the evolving Arctic sea ice volume. The role of atmosphere‐ocean coupling in augmenting or curtailing the atmosphere‐ and ocean‐driven sea ice losses is further isolated by comparing the ice volume budget and the anomalous frazil/ocean‐ice heat components in partially and fully coupled experiments. Atmosphere‐ice heat fluxes drive most of Arctic sea ice loss in the first decade following CO2 increase by increasing the sea ice top face melt in summer, while ocean circulation changes drive the loss over the longer term through the anomalous increase of heat transport into the Arctic, which drive decreases in frazil ice growth and sea ice extent in winter. Atmosphere‐ocean coupling in the subpolar Atlantic further supports a negative feedback that attenuates the ocean‐driven sea ice losses over time; by accelerating the weakening of the Atlantic meridional overturning circulation, it causes a large cooling of the subpolar Atlantic and attenuation of the anomalous heat transport into the Arctic in winter, allowing for a seasonal Arctic sea ice in the fully coupled experiment, while the Arctic completely becomes ice free in the partially coupled experiment.
Supermoon Drives Beach Morphological Changes in the Swash Zone
Authors: Banno Masayuki , Kuriyama Yoshiaki 
Published: November 2020

AbstractThe effect of the supermoon, which appears much larger than a normal full moon, on the morphological changes of a sandy beach was investigated by analyzing a 25‐year daily observation data set of beach morphology in the swash zone. The beach morphology fluctuated in two cycles related to the supermoon: the semisynodic month cycle (from full moon to new moon, and vice versa) and the anomalistic month cycle (from perigee to perigee). The supermoon makes the erosion of the upper swash zone more likely by generating a larger tidal range. The high‐water‐level contour positions observed during supermoons retreated significantly, although there were no trends in the change for all the observations. Erosion due to high waves coincident with a supermoon can be expected to be more severe in the upper swash zone; including the supermoon effect in beach morphodynamic models can improve coastal management.
Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice
Authors: Sportoletti Paolo , Sorcini Daniele , Guzman Anna G. , Reyes Jaime M. , Stella Arianna , Marra Andrea , Sartori Sara , Brunetti Lorenzo , Rossi Roberta , Papa Beatrice Del , Adamo Francesco Maria , Pianigiani Giulia , Betti Camilla , Scialdone Annarita , Guarente Valerio , Spinozzi Giulio , Tini Valentina , Martelli Maria Paola , Goodell Margaret A. , Falini Brunangelo 
Published: November 2020

AbstractRecurrent loss-of-function mutations ofBCL6 co-repressor(BCOR)gene are found in about 4% of AML patients with normal karyotype and are associated withDNMT3amutations and poor prognosis. Therefore, new anti-leukemia treatments and mouse models are needed for this combinatorial AML genotype. For this purpose, we first generated aBcor−/−knockout mouse model characterized by impaired erythroid development (macrocytosis and anemia) and enhanced thrombopoiesis, which are both features of myelodysplasia/myeloproliferative neoplasms. We then created and characterized doubleBcor−/−/Dnmt3a−/−knockout mice. Interestingly, these animals developed a fully penetrant acute erythroid leukemia (AEL) characterized by leukocytosis secondary to the expansion of blasts expressing c-Kit+ and the erythroid marker Ter119, macrocytic anemia and progressive reduction of the thrombocytosis associated with loss ofBcoralone. Transcriptomic analysis of double knockout bone marrow progenitors revealed that aberrant erythroid skewing was induced by epigenetic changes affecting specific transcriptional factors (GATA1-2) and cell-cycle regulators (Mdm2, Tp53). These findings prompted us to investigate the efficacy of demethylating agents in AEL, with significant impact on progressive leukemic burden and mice overall survival. Information gained from our model expands the knowledge on the biology of AEL and may help designing new rational treatments for patients suffering from this high-risk leukemia.
Fractionating autism based on neuroanatomical normative modeling
Authors: Zabihi Mariam , Floris Dorothea L. , Kia Seyed Mostafa , Wolfers Thomas , Tillmann Julian , Arenas Alberto Llera , Moessnang Carolin , Banaschewski Tobias , Holt Rosemary , Baron-Cohen Simon , Loth Eva , Charman Tony , Bourgeron Thomas , Murphy Declan , Ecker Christine , Buitelaar Jan K. , Beckmann Christian F. , Marquand Andre ,   The EU-AIMS LEAP Group
Published: November 2020

AbstractAutism is a complex neurodevelopmental condition with substantial phenotypic, biological, and etiologic heterogeneity. It remains a challenge to identify biomarkers to stratify autism into replicable cognitive or biological subtypes. Here, we aim to introduce a novel methodological framework for parsing neuroanatomical subtypes within a large cohort of individuals with autism. We used cortical thickness (CT) in a large and well-characterized sample of 316 participants with autism (88 female, age mean: 17.2 ± 5.7) and 206 with neurotypical development (79 female, age mean: 17.5 ± 6.1) aged 6–31 years across six sites from the EU-AIMS multi-center Longitudinal European Autism Project. Five biologically based putative subtypes were derived using normative modeling of CT and spectral clustering. Three of these clusters showed relatively widespread decreased CT and two showed relatively increased CT. These subtypes showed morphometric differences from one another, providing a potential explanation for inconsistent case–control findings in autism, and loaded differentially and more strongly onto symptoms and polygenic risk, indicating a dilution of clinical effects across heterogeneous cohorts. Our results provide an important step towards parsing the heterogeneous neurobiology of autism.
Oxytocin treatment attenuates amygdala activity in autism: a treatment-mechanism study with long-term follow-up
Authors: Bernaerts Sylvie , Boets Bart , Steyaert Jean , Wenderoth Nicole , Alaerts Kaat 
Published: November 2020

AbstractIntranasal administration of the neuropeptide oxytocin (IN-OT) is increasingly considered as a potential treatment for targeting the core symptoms of autism spectrum disorder (ASD), but the effects of continual use on neural substrates are fairly unexplored and long-term effects are unknown. In this double-blind, randomized, placebo-controlled study, we investigated the effects of single-dose and multiple-dose IN-OT treatment (4 weeks of daily (24 IU) administrations) on brain activity related to processing emotional states. Thirty-eight adult men with ASD (aged between 18 and 35 years) underwent functional magnetic resonance imaging of the posterior superior temporal gyrus (pSTS) and amygdala regions while processing emotional states from point-light biological motion. In line with prior research, a single dose of IN-OT induced a reliable increase in pSTS brain activity during the processing of point-light biological motion, but no consistent long-term changes in pSTS activity were induced after the multiple-dose treatment. In terms of bilateral amygdala, the multiple-dose treatment induced a consistent attenuation in brain activity, which outlasted the period of actual administrations until four weeks and one year post-treatment. Critically, participants with stronger attenuations in amygdala-activity showed greater behavioral improvements, particularly in terms of self-reported feelings of avoidant attachment and social functioning. Together, these observations provide initial insights into the long-lasting neural consequences of chronic IN-OT use on amygdala functioning and provide first indications that the acute versus chronic effects of IN-OT administration may be qualitatively different. Larger studies are however warranted to further elucidate the long-term impact of IN-OT treatment on human neural substrates and its behavioral consequences.
FOLFIRI plus cetuximab or bevacizumab for advanced colorectal cancer: final survival and per-protocol analysis of FIRE-3, a randomised clinical trial
Authors: Heinemann Volker , von Weikersthal Ludwig Fischer , Decker Thomas , Kiani Alexander , Kaiser Florian , Al-Batran Salah-Edin , Heintges Tobias , Lerchenmüller Christoph , Kahl Christoph , Seipelt Gernot , Kullmann Frank , Moehler Markus , Scheithauer Werner , Held Swantje , Miller-Phillips Lisa , Modest Dominik Paul , Jung Andreas , Kirchner Thomas , Stintzing Sebastian 
Published: November 2020

Abstract
Background
Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.

Methods
The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated.

Results
Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours.

Conclusions
FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases.

ClinicalTrials.gov identifier
NCT00433927.
Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19
Authors: Liu Yuying , Lv Jiadi , Liu Jiangning , Li Man , Xie Jing , Lv Qi , Deng Wei , Zhou Nannan , Zhou Yabo , Song Jiangping , Wang Peng , Qin Chuan , Tong Wei-Min , Huang Bo 
Published: November 2020

AbstractSilent hypoxia has emerged as a unique feature of coronavirus disease 2019 (COVID-19). In this study, we show that mucins are accumulated in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients and are upregulated in the lungs of severe respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected mice and macaques. We find that induction of either interferon (IFN)-β or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity. These findings potentially explain the silent hypoxia formation in COVID-19 patients, and suggest a possible intervention strategy by targeting the AhR pathway.
The R2 non-neuroinvasive HSV-1 vaccine affords protection from genital HSV-2 infections in a guinea pig model
Authors: Bernstein David I. , Cardin Rhonda D. , Smith Gregory A. , Pickard Gary E. , Sollars Patricia J. , Dixon David A. , Pasula Rajamouli , Bravo Fernando J. 
Published: November 2020

AbstractHerpes simplex virus (HSV) infections are common and can cause severe illness but no vaccine is currently available. The recent failure of subunit HSV vaccines has highlighted the need for vaccines that present a diverse array of antigens, including the development of next-generation live-attenuated vaccines. However, most attenuated HSV strains propagate poorly, limiting their ability to elicit protective immune responses. A live-attenuated vaccine that replicates in non-neural tissue but is ablated for transmission into the nervous system may elicit protective immune responses without evoking neurologic complications or establishing life-long infections. Initial studies of R2, a live-attenuated vaccine that is engineered to be unable to invade the nervous system, used the guinea pig genital HSV model to evaluate the ability of R2 to replicate at the site of inoculation, cause disease and infect neural tissues. R2 was then evaluated as a vaccine using three routes of inoculation: intramuscular (IM), intradermal (ID) and intravaginal (IVag) and compared to IM administered gD2+MPL/Alum vaccine in the same model. R2 replicated in the genital tract but did not produce acute or recurrent disease and did not infect the neural tissue. The R2 vaccine-induced neutralizing antibody and decreased the severity of acute and recurrent HSV-2 disease as well as recurrent shedding. The ID route was the most effective. ID administered R2 was more effective than gD2+MPL/Alum at inducing neutralizing antibody, suppressing acute disease, and acute vaginal virus replication. R2 was especially more effective at reducing recurrent virus shedding, the most common source of HSV transmission. The live-attenuated prophylactic HSV vaccine, R2, was effective in the guinea pig model of genital HSV-2 especially when administered by the ID route. The use of live-attenuated HSV vaccines that robustly replicate in mucosal tissues but are ablated for neuroinvasion offers a promising approach for HSV vaccines.
Study on mechanism of differential concentration corrosion
Authors: Liu Bin , Liu Yingwei 
Published: November 2020

AbstractThe pipeline easily gets corroded in a seawater environment. The oxygen in the seawater is one of major parameters causing the corrosion. In practice, the corrosion due to the oxygen concentration difference, i.e. differential concentration corrosion (DCC), cannot be avoided. However, a one-dimensional DCC model cannot satisfactorily predict the corrosion because the oxygen distribution near the pipe wall is two-dimensional. In this regard, a two-dimensional DCC model was proposed in this study to numerically investigate the distribution of corrosion potential and current in the ionic conductive layer near the pipe wall as well as the overall corrosion current. The results show that DCC plays a significant role in determining the corrosion potential and current. Without considering DCC, a large corrosion potential and current exist at the location with high oxygen concentration near the pipe wall, whereas the occurrence of the low corrosion potential and current corresponds to the location with low oxygen concentration. However, as DCC is considered, at the location with high corrosion potential, cathodic polarization was produced and the corrosion rate decreases; at the location with low corrosion potential, anodic polarization was produced and the corrosion rate increases. In general, the corrosion potential can be homogenized in terms of DCC.
Molecular identification and geographic origin of a post-Medieval elephant finding from southwestern Portugal using high-throughput sequencing
Authors: Psonis Nikolaos , de Carvalho Carlos Neto , Figueiredo Silvério , Tabakaki Eugenia , Vassou Despoina , Poulakakis Nikos , Kafetzopoulos Dimitris 
Published: November 2020

AbstractMolecular species identification plays a crucial role in archaeology and palaeontology, especially when diagnostic morphological characters are unavailable. Molecular markers have been used in forensic science to trace the geographic origin of wildlife products, such as ivory. So far, only a few studies have applied genetic methods to both identify the species and circumscribe the provenance of historic wildlife trade material. Here, by combining ancient DNA methods and genome skimming on a historical elephantid tooth found in southwestern Portugal, we aimed to identify its species, infer its placement in the elephantid phylogenetic tree, and triangulate its geographic origin. According to our results the specimen dates back to the eighteenth century CE and belongs to a female African forest elephant (non-hybrid Loxodonta cyclotis individual) geographically originated from west—west-central Africa, from areas where one of the four major mitochondrial clades of L. cyclotis is distributed. Historical evidence supports our inference, pointing out that the tooth should be considered as post-Medieval raw ivory trade material between West Africa and Portugal. Our study provides a comprehensive approach to study historical products and artefacts using archaeogenetics and contributes towards enlightening cultural and biological historical aspects of ivory trade in western Europe.
Electrophysiological differences in older and younger adults’ anaphoric but not cataphoric pronoun processing in the absence of age-related behavioural slowdown
Authors: Arslan Seçkin , Palasis Katerina , Meunier Fanny 
Published: November 2020

AbstractThis study reports on an event-related potentials experiment to uncover whether per-millisecond electrophysiological brain activity and analogous behavioural responses are age-sensitive when comprehending anaphoric (referent-first) and cataphoric (pronoun-first) pronouns. Two groups of French speakers were recruited (young n = 18; aged 19–35 and older adults n = 15; aged 57–88) to read sentences where the anaphoric/cataphoric pronouns and their potential referents either matched or mismatched in gender. Our findings indicate that (1) the older adults were not less accurate or slower in their behavioural responses to the mismatches than the younger adults, (2) both anaphoric and cataphoric conditions evoked a central/parietally distributed P600 component with similar timing and amplitude in both the groups. Importantly, mean amplitudes of the P600 effect were modulated by verbal short-term memory span in the older adults but not in the younger adults, (3) nevertheless, the older but not the younger adults displayed an additional anterior negativity emerging on the frontal regions in response to the anaphoric mismatches. These results suggest that pronoun processing is resilient in healthy ageing individuals, but that functional recruitment of additional brain regions, evidenced with the anterior negativity, compensates for increased processing demands in the older adults’ anaphora processing.
Optimization technique combined with deep learning method for teeth recognition in dental panoramic radiographs
Authors: Mahdi Fahad Parvez , Motoki Kota , Kobashi Syoji 
Published: November 2020

AbstractComputer-assisted analysis of dental radiograph in dentistry is getting increasing attention from the researchers in recent years. This is mainly because it can successfully reduce human-made error due to stress, fatigue or lack of experience. Furthermore, it reduces diagnosis time and thus, improves overall efficiency and accuracy of dental care system. An automatic teeth recognition model is proposed here using residual network-based faster R-CNN technique. The detection result obtained from faster R-CNN is further refined by using a candidate optimization technique that evaluates both positional relationship and confidence score of the candidates. It achieves 0.974 and 0.981 mAPs for ResNet-50 and ResNet-101, respectively with faster R-CNN technique. The optimization technique further improves the results i.e. F1 score improves from 0.978 to 0.982 for ResNet-101. These results verify the proposed method’s ability to recognize teeth with high degree of accuracy. To test the feasibility and robustness of the model, a tenfold cross validation (CV) is presented in this paper. The result of tenfold CV effectively verifies the robustness of the model as the average F1 score obtained is more than 0.970. Thus, the proposed model can be used as a useful and reliable tool to assist dental care professionals in dentistry.
Better understanding and prediction of antiviral peptides through primary and secondary structure feature importance
Authors: Chowdhury Abu Sayed , Reehl Sarah M. , Kehn-Hall Kylene , Bishop Barney , Webb-Robertson Bobbie-Jo M. 
Published: November 2020

AbstractThe emergence of viral epidemics throughout the world is of concern due to the scarcity of available effective antiviral therapeutics. The discovery of new antiviral therapies is imperative to address this challenge, and antiviral peptides (AVPs) represent a valuable resource for the development of novel therapies to combat viral infection. We present a new machine learning model to distinguish AVPs from non-AVPs using the most informative features derived from the physicochemical and structural properties of their amino acid sequences. To focus on those features that are most likely to contribute to antiviral performance, we filter potential features based on their importance for classification. These feature selection analyses suggest that secondary structure is the most important peptide sequence feature for predicting AVPs. Our Feature-Informed Reduced Machine Learning for Antiviral Peptide Prediction (FIRM-AVP) approach achieves a higher accuracy than either the model with all features or current state-of-the-art single classifiers. Understanding the features that are associated with AVP activity is a core need to identify and design new AVPs in novel systems. The FIRM-AVP code and standalone software package are available at https://github.com/pmartR/FIRM-AVP with an accompanying web application at https://msc-viz.emsl.pnnl.gov/AVPR.