bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Transfer of Antarctic Circumpolar Waters to the Western South Atlantic Ocean
Authors: Olivé Abelló Anna , Pelegrí Josep L. , Machín Francisco J. , Vallès‐Casanova Ignasi 
Published: June 2021

AbstractSouthern Ocean waters enter the South Atlantic Ocean through the Scotia Sea along pathways constrained by the bathymetry of the northern Scotia Sea passages. We use the Argo profiling‐float data set to calculate the water transports in and out of the region, focusing on the water balances down to the deepest isoneutral sampled in all passages (γn = 28.0 kg m−3, located between about 500 and 2,000 m in the Drake Passage and even shallower in the Northern Passages). Down to this reference level, the water inflow through the Drake Passage is 140.8 ± 7.4 Sv and the water outflow through the deeper portions of the Northern Passages is 115.9 ± 8.3 Sv, implying a leakage of about 25 ± 11.1 Sv over topography shallower than 1,000 m. Below the reference isoneutral and down to 2,000 m, an additional 23.4 Sv enter through the Drake Passage; when added to reported inputs of about 20 Sv through the South Scotia Ridge, this accounts well for the observed 43.4 Sv outflow–from 28.0 kg m−3 to 2,000 m–through the Northern Passages. Relative to the 2,000 m reference level, the mean barotropic contribution always represents over half the total transports. We also observe substantial seasonal and moderate interannual variations in the water transports and composition (peak differences occur seasonally in the Drake Passage, with a range of 111–174 Sv), associated with changes in water exchange across the frontal systems. Two independent measures set the water mean‐residence time in the Scotia Sea at about 6–8 months.
Estimating mouthing exposure to chemicals in children’s products
Authors: Aurisano Nicolò , Fantke Peter , Huang Lei , Jolliet Olivier 
Published: June 2021

Abstract
Background
Existing models for estimating children’s exposure to chemicals through mouthing currently depends on the availability of chemical- and material-specific experimental migration rates, only covering a few dozen chemicals.

Objective
This study objective is hence to develop a mouthing exposure model to predict migration into saliva, mouthing exposure, and related health risk from a wide range of chemical-material combinations in children’s products.

Methods
We collected experimental data on chemical migration from different products into saliva for multiple substance groups and materials, identifying chemical concentration and diffusion coefficient as main properties of influence. To predict migration rates into saliva, we adapted a previously developed migration model for chemicals in food packaging materials. We also developed a regression model based on identified chemical and material properties.

Results
Our migration predictions correlate well with experimental data (R2 = 0.85) and vary widely from 8 × 10−7 to 32.7 µg/10 cm2/min, with plasticizers in PVC showing the highest values. Related mouthing exposure doses vary across chemicals and materials from a median of 0.005 to 253 µg/kgBW/d. Finally, we combined exposure estimates with toxicity information to yield hazard quotients and identify chemicals of concern for average and upper bound mouthing behavior scenarios.

Significance
The proposed model can be applied for predicting migration rates for hundreds of chemical-material combinations to support high-throughput screening.
Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia
Authors: Avram Mihai , Grothe Michel J. , Meinhold Lena , Leucht Claudia , Leucht Stefan , Borgwardt Stefan , Brandl Felix , Sorg Christian 
Published: June 2021

AbstractA potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decision-making. We hypothesized that BFCN structural integrity is altered in schizophrenia and associated with patients’ attentional deficits. We assessed gray matter (GM) integrity of cytoarchitectonically defined BFCN region-of-interest in 72 patients with schizophrenia and 73 healthy controls, matched for age and gender, from the COBRE open-source database, via structural magnetic resonance imaging (MRI)–based volumetry. MRI-derived measures of GM integrity (i.e., volumes) were linked with performance on a symbol coding task (SCT), a paper-pencil-based metric that assesses attention, by correlation and mediation analysis. To assess the replicability of findings, we repeated the analyses in an independent dataset comprising 26 patients with schizophrenia and 24 matched healthy controls. BFCN volumes were lower in patients (t(139)=2.51, p = 0.01) and significantly associated with impaired SCT performance (r = 0.31, p = 0.01). Furthermore, lower BFCN volumes mediated the group difference in SCT performance. When including global GM volumes, which were lower in patients, as covariates-of-no-interest, these findings disappeared, indicating that schizophrenia did not have a specific effect on BFCN relative to other regional volume changes. We replicated these findings in the independent cohort, e.g., BFCN volumes were lower in patients and mediated patients’ impaired SCT performance. Results demonstrate lower BFCN volumes in schizophrenia, which link with patients’ attentional deficits. Data suggest that a dysregulated cholinergic system might contribute to cognitive difficulties in schizophrenia via impaired BFCN.
The efficacy of anti-EGFR therapy in treating metastatic colorectal cancer differs between the middle/low rectum and the left-sided colon
Authors: Lee Kun-Han , Chen Wei-Shone , Jiang Jeng-Kai , Yang Shung-Haur , Wang Huann-Sheng , Chang Shih-Ching , Lan Yuan-Tzu , Lin Chun-Chi , Lin Hung-Hsin , Huang Sheng-Chieh , Cheng Hou-Hsuan , Chao Yee , Teng Hao-Wei 
Published: June 2021

Abstract
Background
Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers.

Methods
This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap.

Results
On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer.

Conclusions
Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.
Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis
Authors: Wu Hai-Yan , Zhou Yi-Min , Liao Zhu-Qin , Zhong Jia-Wen , Liu You-Bin , Zhao Hui , Liang Chi-Qian , Huang Rui-Jin , Park Kyu-Sang , Feng Shan-Shan , Zheng Li , Cai Dong-Qing , Qi Xu-Feng 
Published: June 2021

AbstractCardiovascular disease is the leading cause of death in the world due to losing regenerative capacity in the adult heart. Frogs possess remarkable capacities to regenerate multiple organs, including spinal cord, tail, and limb, but the response to heart injury and the underlying molecular mechanism remains largely unclear. Here we demonstrated that cardiomyocyte proliferation greatly contributes to heart regeneration in adult X. tropicalis upon apex resection. Using RNA-seq and qPCR, we found that the expression of Fos-like antigen 1 (Fosl1) was dramatically upregulated in early stage of heart injury. To study Fosl1 function in heart regeneration, its expression was modulated in vitro and in vivo. Overexpression of X. tropicalis Fosl1 significantly promoted the proliferation of cardiomyocyte cell line H9c2. Consistently, endogenous Fosl1 knockdown suppressed the proliferation of H9c2 cells and primary cardiomyocytes isolated from neonatal mice. Taking use of a cardiomyocyte-specific dominant-negative approach, we show that blocking Fosl1 function leads to defects in cardiomyocyte proliferation during X. tropicalis heart regeneration. We further show that knockdown of Fosl1 can suppress the capacity of heart regeneration in neonatal mice, but overexpression of Fosl1 can improve the cardiac function in adult mouse upon myocardium infarction. Co-immunoprecipitation, luciferase reporter, and ChIP analysis reveal that Fosl1 interacts with JunB and promotes the expression of Cyclin-T1 (Ccnt1) during heart regeneration. In conclusion, we demonstrated that Fosl1 plays an essential role in cardiomyocyte proliferation and heart regeneration in vertebrates, at least in part, through interaction with JunB, thereby promoting expression of cell cycle regulators including Ccnt1.
Investigating the utility of VR for spatial understanding in surgical planning: evaluation of head-mounted to desktop display
Authors: Hattab Georges , Hatzipanayioti Adamantini , Klimova Anna , Pfeiffer Micha , Klausing Peter , Breucha Michael , Bechtolsheim Felix von , Helmert Jens R. , Weitz Jürgen , Pannasch Sebastian , Speidel Stefanie 
Published: June 2021

AbstractRecent technological advances have made Virtual Reality (VR) attractive in both research and real world applications such as training, rehabilitation, and gaming. Although these other fields benefited from VR technology, it remains unclear whether VR contributes to better spatial understanding and training in the context of surgical planning. In this study, we evaluated the use of VR by comparing the recall of spatial information in two learning conditions: a head-mounted display (HMD) and a desktop screen (DT). Specifically, we explored (a) a scene understanding and then (b) a direction estimation task using two 3D models (i.e., a liver and a pyramid). In the scene understanding task, participants had to navigate the rendered the 3D models by means of rotation, zoom and transparency in order to substantially identify the spatial relationships among its internal objects. In the subsequent direction estimation task, participants had to point at a previously identified target object, i.e., internal sphere, on a materialized 3D-printed version of the model using a tracked pointing tool. Results showed that the learning condition (HMD or DT) did not influence participants’ memory and confidence ratings of the models. In contrast, the model type, that is, whether the model to be recalled was a liver or a pyramid significantly affected participants’ memory about the internal structure of the model. Furthermore, localizing the internal position of the target sphere was also unaffected by participants’ previous experience of the model via HMD or DT. Overall, results provide novel insights on the use of VR in a surgical planning scenario and have paramount implications in medical learning by shedding light on the mental model we make to recall spatial structures.
Radiation dosimetry effect evaluation of a carbon fiber couch on novel uRT-linac 506c accelerator
Authors: Jiang Dazhen , Cao Zhen , Wei Yongchang , Cao Tingting , Shen Jiuling , Xie Conghua , Zhou Yunfeng , Liu Hui , Zhang Jun 
Published: June 2021

AbstractRecently, a diagnostic helical CT is integrated into a linear accelerator, called uRT-linac 506c, whose CT scanning dataset can be directly used to do simulation. This novel structure provides a possibility for online adaptive radiotherapy. For adaptive radiotherapy, the carbon fiber couch is an essential external device for supporting and positioning patients. And the effect on dose attenuation and distribution caused by a couch is inevitable and vital for precise treatment. In this research, the couch equipped with uRT-linac 506c was evaluated on the radiation dosimetry effect. The treatment couch equipped on the uRT-linac 506c accelerator was evaluated, and its effect on the attenuation, surface dose and dose buildup were measured for different phantom positions (offset = 0 cm, offset =  + 10 cm and offset =  − 10 cm, respectively) and different gantry angles. Since uRT-linac 506c is exclusively capable to provide diagnostic CT scanning data with real relative electron density (RED), this CT scanning data of the couch can be used directly in uRT-TPS to design plans. This scanned couch dataset was designated as the model A. The model B was a dummy structure of a treatment couch inserted with artificially preset RED. The dose calculation accuracy of these two models was compared using PB, CC, and MC on uRT-TPS. With the effect of carbon fiber couch, the surface dose was increased at least 97.94% for 25 × 25 cm2 field and 188.83% for 10 × 10 cm2 field, compared with those without. At different phantom positions (offset = 0, + 10, − 10 cm), the attenuation for 6 MV photon beam at gantry angle 180° were 4.4%, 4.4%, and 4.3%, respectively, and varied with changes of gantry angle. There do exists dose deviation between measurement and TPS calculation with the involvement of treatment couch, among the three algorithms, MC presented the least deviation, and the model A made less and steadier deviation than the model B, showing promising superiority. The attenuation, surface dose, and buildup effects of the carbon fiber couch in this study were measured similarly to most counterparts. The dose deviation calculated based on the couch dataset scanned by the diagnostic helical CT was smaller than those based on a dummy couch. This result suggests that an accelerator equipped with a diagnostic CT, which can help reduce the dose deviation of the carbon fiber couch, is a promising platform for online adaptive radiotherapy.
Extended embryo culture is effective for patients of an advanced maternal age
Authors: Sainte-Rose R. , Petit C. , Dijols L. , Frapsauce C. , Guerif F. 
Published: June 2021

AbstractThe aim of this study was to determine the effectiveness of extended embryo culture in advanced maternal age (AMA) patients (37–43 years). In this retrospective analysis, 21,301 normally fertilized zygotes from 4952 couples were cultured until the blastocyst stage. Blastocyst development, including kinetics and morphology, transfer rate, implantation and live birth rates, were measured. In AMA patients, the blastocyst rate was significantly decreased as compared to that in younger women. On day 5, blastocysts underwent growth retardation in AMA patients, which was highlighted by a decreased rate of full/expanded blastocysts. Organization of the cells (trophectoderm and inner cell mass) was unaffected by age. However, in AMA patients, a ‘good’ morphology blastocyst had a decreased probability to implant compared with an ‘average’ morphology blastocyst in younger women. While the rates of blastocyst transfer and useful blastocysts were similar to younger patients, in AMA patients, both implantation and live birth rates were significantly reduced. Our results support the idea that extended embryo culture is not harmful for AMA patients. However, embryo selection allowed by such culture is not powerful enough to avoid chromosomal abnormalities in the developed blastocysts and therefore cannot compensate for the effect of a woman’s age.
NOD: a web server to predict New use of Old Drugs to facilitate drug repurposing
Authors: Narwani Tarun Jairaj , Srinivasan Narayanaswamy , Chakraborti Sohini 
Published: June 2021

AbstractComputational methods accelerate the drug repurposing pipelines that are a quicker and cost-effective alternative to discovering new molecules. However, there is a paucity of web servers to conduct fast, focussed, and customized investigations for identifying new uses of old drugs. We present the NOD web server, which has the mentioned characteristics. NOD uses a sensitive sequence-guided approach to identify close and distant homologs of a protein of interest. NOD then exploits this evolutionary information to suggest potential compounds from the DrugBank database that can be repurposed against the input protein. NOD also allows expansion of the chemical space of the potential candidates through similarity searches. We have validated the performance of NOD against available experimental and/or clinical reports. In 65.6% of the investigated cases in a control study, NOD is able to identify drugs more effectively than the searches made in DrugBank. NOD is freely-available at http://pauling.mbu.iisc.ac.in/NOD/NOD/.
A literature review and meta-analysis of safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus
Authors: Mukai Junichi , Kanno Shinya , Kubota Rie 
Published: June 2021

AbstractThe safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors may depend on races/ethnicities. We aimed to assess the safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies with no language restriction from their inception to August 2019. Trials were included in the analysis if they were randomized controlled trials (RCTs) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM > 18 years and reporting HbA1c and at least 1 adverse event. We calculated risk ratios with 95% CIs and used a random-effects model. Of the 22 RCTs included in our review, only 1 included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparison with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatment with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, such as patients with different types of DM, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.
Monitoring urinary collagen metabolite changes following collagen peptide ingestion and physical activity using ELISA with anti active collagen oligopeptide antibody
Authors: Osawa Yoshihiro , Nomura Kaho , Kimira Yoshifumi , Kushibe Seiji , Takeyama Ken-ichi , Nagao Masashi , Kataoka-Matsushita Aya , Koizumi Seiko , Mano Hiroshi 
Published: June 2021

AbstractActive collagen oligopeptides (ACOP) are bioactive collagen-derived peptides detected by a recently-established ELISA. To facilitate studies of the function and metabolism of these products, this study aims to determine which of these peptides is recognized by a novel anti-ACOP antibody used in this ELISA. We then investigate the effect of collagen peptide (CP) ingestion and exercise on urinary ACOP concentrations in a cohort of university student athletes using colorimetric, LC–MS/MS, and ELISA. We observed that the antibody showed strong cross-reactivity to Pro-Hyp and Gly-Pro-Hyp and weak cross-reactivity to commercial CP. CP ingestion increased the urinary level of ACOP over time, which correlated highly with urinary levels of peptide forms of Hyp and Pro-Hyp. Physical activity significantly decreased the urinary ACOP level. This study demonstrates changes in urinary ACOP following oral CP intake and physical activity using ELISA with the novel anti-ACOP antibody. Thus, ACOP may be useful as a new biomarker for collagen metabolism.
Bevacizumab improves tumor infiltration of mature dendritic cells and effector T-cells in triple-negative breast cancer patients
Authors: Boucher Yves , Kumar Ashwin S. , Posada Jessica M. , Gjini Evisa , Pfaff Kathleen , Lipschitz Mikel , Lako Ana , Duda Dan G. , Rodig Scott J. , Hodi F. Stephen , Jain Rakesh K. 
Published: June 2021

AbstractA single dose of bevacizumab reduced the density of angiopoietin-2-positive vessels while improving the infiltration of CD4+ T and CD8+ T cells, and mature dendritic cells in patients with primary triple-negative breast cancer. Our findings provide a rationale for including bevacizumab during neoadjuvant treatment to enhance the efficacy of immune checkpoint blockers in this disease.
A Bayesian semi-parametric model for thermal proteome profiling
Authors: Fang Siqi , Kirk Paul D. W. , Bantscheff Marcus , Lilley Kathryn S. , Crook Oliver M. 
Published: June 2021

AbstractThe thermal stability of proteins can be altered when they interact with small molecules, other biomolecules or are subject to post-translation modifications. Thus monitoring the thermal stability of proteins under various cellular perturbations can provide insights into protein function, as well as potentially determine drug targets and off-targets. Thermal proteome profiling is a highly multiplexed mass-spectrommetry method for monitoring the melting behaviour of thousands of proteins in a single experiment. In essence, thermal proteome profiling assumes that proteins denature upon heating and hence become insoluble. Thus, by tracking the relative solubility of proteins at sequentially increasing temperatures, one can report on the thermal stability of a protein. Standard thermodynamics predicts a sigmoidal relationship between temperature and relative solubility and this is the basis of current robust statistical procedures. However, current methods do not model deviations from this behaviour and they do not quantify uncertainty in the melting profiles. To overcome these challenges, we propose the application of Bayesian functional data analysis tools which allow complex temperature-solubility behaviours. Our methods have improved sensitivity over the state-of-the art, identify new drug-protein associations and have less restrictive assumptions than current approaches. Our methods allows for comprehensive analysis of proteins that deviate from the predicted sigmoid behaviour and we uncover potentially biphasic phenomena with a series of published datasets.
Insights into rumen microbial biosynthetic gene cluster diversity through genome-resolved metagenomics
Authors: Anderson Christopher L. , Fernando Samodha C. 
Published: June 2021

AbstractRuminants are critical to global food security as they transform lignocellulosic biomass into high-quality protein products. The rumen microbes ferment feed to provide necessary energy and nutrients for the ruminant host. However, we still lack insight into the metabolic processes encoded by most rumen microbial populations. In this study, we implemented metagenomic binning approaches to recover 2,809 microbial genomes from cattle, sheep, moose, deer, and bison. By clustering genomes based on average nucleotide identity, we demonstrate approximately one-third of the metagenome-assembled genomes (MAGs) to represent species not present in current reference databases and rumen microbial genome collections. Combining these MAGs with other rumen genomic datasets permitted a phylogenomic characterization of the biosynthetic gene clusters (BGCs) from 8,160 rumen microbial genomes, including the identification of 195 lanthipeptides and 5,346 diverse gene clusters for nonribosomal peptide biosynthesis. A subset of Prevotella and Selenomonas BGCs had higher expression in steers with lower feed efficiency. Moreover, the microdiversity of BGCs was fairly constant across types of BGCs and cattle breeds. The reconstructed genomes expand the genomic representation of rumen microbial lineages, improve the annotation of multi-omics data, and link microbial populations to the production of secondary metabolites that may constitute a source of natural products for manipulating rumen fermentation.