bluuebunny/crossref_metadata_2025_split huggingface dataset:
A European proposal for quality control and quality assurance of tandem mass spectral libraries
Authors: Oberacher Herbert , Sasse Michael , Antignac Jean-Philippe , Guitton Yann , Debrauwer Laurent , Jamin Emilien L. , Schulze Tobias , Krauss Martin , Covaci Adrian , Caballero-Casero Noelia , Rousseau Kathleen , Damont Annelaure , Fenaille François , Lamoree Marja , Schymanski Emma L. 
Published: March 2020

Abstract
Background
High resolution mass spectrometry (HRMS) is being used increasingly in the context of suspect and non-targeted screening for the identification of bioorganic molecules. There is correspondingly increasing awareness that higher confidence identification will require a systematic, group effort to increase the fraction of compounds with tandem mass spectra available in central, publicly available resources. While typical suspect screening efforts will only result in tentative annotations with a moderate level of confidence, library spectral matches will yield higher confidence or even full confirmation of the identity if the reference standards are available.

Results
This article first explores representative percent coverage of measured tandem mass spectra in selected major environmental suspect databases of interest in the context of human biomonitoring, demonstrating the current extensive gap between the number of potential substances of interest (up to hundreds of thousands) and measured spectra (0.57–3.6% of the total chemicals have spectral information available). Furthermore, certain datasets are benchmarked, based on previous efforts, to show the extent to which acquired experimental data were comparable between laboratories, even with HRMS instruments based on different technologies (i.e., quadrupole–quadrupole-time of flight versus ion trap/quadrupole-Orbitrap). Instruments and settings that are less comparable are also revealed, primarily linear ion trap instruments, which show distinctly lower comparability.

Conclusions
Based on these efforts, harmonization guidelines for the acquisition and processing of tandem mass spectrometry data are proposed to enable European (and ideally worldwide) laboratories to contribute to common resources, without requiring extensive changes to their current in house methods.
Prediction of tumor location in prostate cancer tissue using a machine learning system on gene expression data
Authors: Hamzeh Osama , Alkhateeb Abedalrhman , Zheng Julia , Kandalam Srinath , Rueda Luis 
Published: March 2020

Abstract
Background
Finding the tumor location in the prostate is an essential pathological step for prostate cancer diagnosis and treatment. The location of the tumor – the laterality – can be unilateral (the tumor is affecting one side of the prostate), or bilateral on both sides. Nevertheless, the tumor can be overestimated or underestimated by standard screening methods. In this work, a combination of efficient machine learning methods for feature selection and classification are proposed to analyze gene activity and select them as relevant biomarkers for different laterality samples.

Results
A data set that consists of 450 samples was used in this study. The samples were divided into three laterality classes (left, right, bilateral). The aim of this work is to understand the genomic activity in each class and find relevant genes as indicators for each class with nearly 99% accuracy. The system identified groups of differentially expressed genes (RTN1, HLA-DMB, MRI1) that are able to differentiate samples among the three classes.

Conclusion
The proposed method was able to detect sets of genes that can identify different laterality classes. The resulting genes are found to be strongly correlated with disease progression. HLA-DMB and EIF4G2, which are detected in the set of genes can detect the left laterality, were reported earlier to be in the same pathway called Allograft rejection SuperPath.
visGReMLIN: graph mining-based detection and visualization of conserved motifs at 3D protein-ligand interface at the atomic level
Authors: Ribeiro Vagner S. , Santana Charles A. , Fassio Alexandre V. , Cerqueira Fabio R. , da Silveira Carlos H. , Romanelli João P. R. , Patarroyo-Vargas Adriana , Oliveira Maria G. A. , Gonçalves-Almeida Valdete , Izidoro Sandro C. , de Melo-Minardi Raquel C. , Silveira Sabrina de A. 
Published: March 2020

Abstract
Background
Interactions between proteins and non-proteic small molecule ligands play important roles in the biological processes of living systems. Thus, the development of computational methods to support our understanding of the ligand-receptor recognition process is of fundamental importance since these methods are a major step towards ligand prediction, target identification, lead discovery, and more. This article presents visGReMLIN, a web server that couples a graph mining-based strategy to detect motifs at the protein-ligand interface with an interactive platform to visually explore and interpret these motifs in the context of protein-ligand interfaces.

Results
To illustrate the potential of visGReMLIN, we conducted two cases in which our strategy was compared with previous experimentally and computationally determined results. visGReMLIN allowed us to detect patterns previously documented in the literature in a totally visual manner. In addition, we found some motifs that we believe are relevant to protein-ligand interactions in the analyzed datasets.

Conclusions
We aimed to build a visual analytics-oriented web server to detect and visualize common motifs at the protein-ligand interface. visGReMLIN motifs can support users in gaining insights on the key atoms/residues responsible for protein-ligand interactions in a dataset of complexes.
BLAMM: BLAS-based algorithm for finding position weight matrix occurrences in DNA sequences on CPUs and GPUs
Authors: Fostier Jan 
Published: March 2020

Abstract
Background
The identification of all matches of a large set of position weight matrices (PWMs) in long DNA sequences requires significant computational resources for which a number of efficient yet complex algorithms have been proposed.

Results
We propose BLAMM, a simple and efficient tool inspired by high performance computing techniques. The workload is expressed in terms of matrix-matrix products that are evaluated with high efficiency using optimized BLAS library implementations. The algorithm is easy to parallelize and implement on CPUs and GPUs and has a runtime that is independent of the selected p-value. In terms of single-core performance, it is competitive with state-of-the-art software for PWM matching while being much more efficient when using multithreading. Additionally, BLAMM requires negligible memory. For example, both strands of the entire human genome can be scanned for 1404 PWMs in the JASPAR database in 13 min with a p-value of 10−4 using a 36-core machine. On a dual GPU system, the same task can be performed in under 5 min.

Conclusions
BLAMM is an efficient tool for identifying PWM matches in large DNA sequences. Its C++ source code is available under the GNU General Public License Version 3 at https://github.com/biointec/blamm.
Mortality prediction by SOFA score in ICU-patients after cardiac surgery; comparison with traditional prognostic–models
Authors: Schoe Abraham , Bakhshi-Raiez Ferishta , de Keizer Nicolette , van Dissel Jaap T. , de Jonge Evert 
Published: March 2020

Abstract
Background
There are many prognostic models and scoring systems in use to predict mortality in ICU patients. The only general ICU scoring system developed and validated for patients after cardiac surgery is the APACHE-IV model. This is, however, a labor-intensive scoring system requiring a lot of data and could therefore be prone to error. The SOFA score on the other hand is a simpler system, has been widely used in ICUs and could be a good alternative.
The goal of the study was to compare the SOFA score with the APACHE-IV and other ICU prediction models.

Methods
We investigated, in a large cohort of cardiac surgery patients admitted to Dutch ICUs, how well the SOFA score from the first 24 h after admission, predict hospital and ICU mortality in comparison with other recalibrated general ICU scoring systems. Measures of discrimination, accuracy, and calibration (area under the receiver operating characteristic curve (AUC), Brier score, R2, and Ĉ-statistic) were calculated using bootstrapping. The cohort consisted of 36,632 Patients from the Dutch National Intensive Care Evaluation (NICE) registry having had a cardiac surgery procedure for which ICU admission was necessary between January 1st, 2006 and June 31st, 2018.

Results
Discrimination of the SOFA-, APACHE-IV-, APACHE-II-, SAPS-II-, MPM24-II - models to predict hospital mortality was good with an AUC of respectively: 0.809, 0.851, 0.830, 0.850, 0.801. Discrimination of the SOFA-, APACHE-IV-, APACHE-II-, SAPS-II-, MPM24-II - models to predict ICU mortality was slightly better with AUCs of respectively: 0.809, 0.906, 0.892, 0.919, 0.862. Calibration of the models was generally poor.

Conclusion
Although the SOFA score had a good discriminatory power for hospital- and ICU mortality the discriminatory power of the APACHE-IV and SAPS-II was better. The SOFA score should not be preferred as mortality prediction model above traditional prognostic ICU-models.
Effects of Pidotimod on recurrent respiratory infections in children with Down syndrome: a retrospective Italian study
Authors: Valentini Diletta , Di Camillo Chiara , Mirante Nadia , Marcellini Valentina , Carsetti Rita , Villani Alberto 
Published: March 2020

Abstract
Background
Children with Down syndrome (DS) show a high susceptibility to recurrent infections (RI), caused by immune defects and abnormalities of the airways. Our goal was to investigate the effects of Pidotimod on RI prevention in children with DS, comparing immune and clinical parameters before (T0) and after (T1) the treatment with Pidotimod.

Methods
The study was conducted at the Down syndrome outpatient Center of Bambino Gesù Children’s Hospital, in Rome. We reviewed the medical records of all children with a positive history for RI and who received oral prophylaxis of Pidotimod from September 2016 to February 2017.

Results
Thirty-three children met the inclusion criteria (males: 51.5%; average age: 6 years ±SD: 3). We found a significant decrease in the number of children with upper respiratory infections (82% at T0 vs 24% at T1; p = 0,0001) and with lower respiratory infections (36% at T0 vs 9% at T1; p = 0.003) after treatment with Pidotimod. We also demonstrated a significant decrease in the number of children hospitalized for respiratory infections (18% at T0 vs 3% at T1; p = 0.03). We measured T and B cells in the peripheral blood and B cell function in vitro at T0 and T1. We found that the response to CpG improved at T1. A significant increase of B cell frequency (p = 0.0009), B cell proliferation (p = 0.0278) and IgM secretion (p = 0.0478) were observed in children with DS after treatment.

Conclusions
Our results provided evidence that Pidotimod may be able to prevent RI in children with Down syndrome.
Diffuse optical spectroscopic imaging reveals distinct early breast tumor hemodynamic responses to metronomic and maximum tolerated dose regimens
Authors: Tank Anup , Peterson Hannah M. , Pera Vivian , Tabassum Syeda , Leproux Anais , O’Sullivan Thomas , Jones Eric , Cabral Howard , Ko Naomi , Mehta Rita S. , Tromberg Bruce J. , Roblyer Darren 
Published: March 2020

Abstract
Background
Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedback about treatment response at the earliest stages of therapy to identify patients likely to benefit from changing treatment. Diffuse optical spectroscopic imaging (DOSI) has emerged as a promising functional imaging technique for NAC monitoring. DOSI uses non-ionizing near-infrared light to provide non-invasive measures of absolute concentrations of tissue chromophores such as oxyhemoglobin. In 2011, we reported a new DOSI prognostic marker, oxyhemoglobin flare: a transient increase in oxyhemoglobin capable of discriminating NAC responders within the first day of treatment. In this follow-up study, DOSI was used to confirm the presence of the flare as well as to investigate whether DOSI markers of NAC response are regimen dependent.

Methods
This dual-center study examined 54 breast tumors receiving NAC measured with DOSI before therapy and the first week following chemotherapy administration. Patients were treated with either a standard of care maximum tolerated dose (MTD) regimen or an investigational metronomic (MET) regimen. Changes in tumor chromophores were tracked throughout the first week and compared to pathologic response and treatment regimen at specific days utilizing generalized estimating equations (GEE).

Results
Within patients receiving MTD therapy, the oxyhemoglobin flare was confirmed as a prognostic DOSI marker for response appearing as soon as day 1 with post hoc GEE analysis demonstrating a difference of 48.77% between responders and non-responders (p < 0.0001). Flare was not observed in patients receiving MET therapy. Within all responding patients, the specific treatment was a significant predictor of day 1 changes in oxyhemoglobin, showing a difference of 39.45% (p = 0.0010) between patients receiving MTD and MET regimens.

Conclusions
DOSI optical biomarkers are differentially sensitive to MTD and MET regimens at early timepoints suggesting the specific treatment regimen should be considered in future DOSI studies. Additionally, DOSI may help to identify regimen-specific responses in a more personalized manner, potentially providing critical feedback necessary to implement adaptive changes to the treatment strategy.
Enzymatic production of 4-O-methyl d-glucaric acid from hardwood xylan
Authors: Vuong Thu V. , Master Emma R. 
Published: March 2020

Abstract
Background
Dicarboxylic acids offer several applications in detergent builder and biopolymer fields. One of these acids, 4-O-methyl d-glucaric acid, could potentially be produced from glucuronoxylans, which are a comparatively underused fraction of wood and agricultural biorefineries.

Results
Accordingly, an enzymatic pathway was developed that combines AxyAgu115A, a GH115 α-glucuronidase from Amphibacillus xylanus, and GOOX, an AA7 gluco-oligosaccharide oxidase from Sarocladium strictum, to produce this bio-based chemical from glucuronoxylan. AxyAgu115A was able to release almost all 4-O-methyl d-glucuronic acid from glucuronoxylan while a GOOX variant, GOOX-Y300A, could convert 4-O-methyl d-glucuronic acid to the corresponding glucaric acid at a yield of 62%. Both enzymes worked effectively at alkaline conditions that increase xylan solubility. Given the sensitivity of AxyAgu115A to hydrogen peroxide and optimal performance of GOOX-Y300A at substrate concentrations above 20 mM, the two-step enzyme pathway was demonstrated as a sequential, one-pot reaction. Additionally, the resulting xylan was easily recovered from the one-pot reaction, and it was enzymatically hydrolysable.

Conclusions
The pathway in this study requires only two enzymes while avoiding a supplementation of costly cofactors. This cell-free approach provides a new strategy to make use of the underutilized hemicellulose stream from wood and agricultural biorefineries.
Murine hepatoblast-derived liver tumors resembling human combined hepatocellular-cholangiocarcinoma with stem cell features
Authors: Cai Xiong , Li Heli , Kaplan David E. 
Published: March 2020

Abstract
Background
Combined hepatocellular-cholangiocarcinoma (CHC) is a primary hepatic malignancy with heterogeneously combined histological features of putative hepatic progenitor cells (HPC) origin. We describe a mouse model that exhibits the heterogenous histological and phenotypic finding similar to human CHC.

Methods
We injected hepatoblasts isolated from p53−/− C57BL/6 mice into syngeneic wild-type pre-conditioned C57BL/6 mice. We confirmed that p53−/− murine hepatoblasts act as tumor-initiating cells (TICs) that generate CHC both in situ and within metastases. For comparative pathological study, 8 human cases of CHC with stem cell features were recruited by immunohistochemistry and multicolor fluorescence immunostaining.

Results
We identified corresponding areas in murine tumors matching each WHO criteria-described subtype of human CHC. In both murine and human tumors, HPC-like cells in tumor nests and associated stem cell features/traits are suggested histologically to be the progenitor origin of the cancer

Conclusions
The pathological characteristics of murine tumors recapitulate human CHC with stem cell features. These data provide additional comparative pathological evidence that CHC with stem cell features originate from HPCs and validate a model to study this cancer type in vivo.
Colorimetric detection of Cr3+ based on gold nanoparticles functionalized with 4-mercaptobenzoic acid
Authors: Zhang Zhikun , Ye Xiaojie , Liu Qingqing , Liu Yumin , Liu Runjing 
Published: March 2020

AbstractHerein, we report the construction of a colorimetric probe used to detecting Cr3+ ions in aqueous solution based on functionalized gold nanoparticles. We investigated 4-mercaptobenzoic acid, 4-nitrobenzenethiol, and a mixture of 4-mercaptobenzoic acid and 4-nitrobenzenethiol as ligands for Cr3+ ions to functionalize the gold nanoparticles, respectively. The results showed that the three probes were all aggregated in the presence of Cr3+ ions, which induces a color change from ruby to violet. Moreover, gold nanoparticles modified with 4-mercaptobenzoic acid exhibit a higher response toward Cr3+ than the two other probes, which can be detected by the naked eye and UV-vis absorption spectroscopy. The detection time was rapid (within 25 min). A linear relationship was obtained from 20 to 25 μM between the ratio of the absorbance observed at 635 nm and 520 nm (A635 nm/A520 nm) with the limit of detection was 5 × 10−6 M. This method exhibited excellent selectivity for Cr3+ ions over other tested heavy metal ions, anions, and organic molecules in the absence of another shielding reagent of metal ion. The system was successfully utilized to detect Cr3+ ions in simulated samples.
Nonprostatic diseases on PSMA PET imaging: a spectrum of benign and malignant findings
Authors: de Galiza Barbosa Felipe , Queiroz Marcelo Araujo , Nunes Rafael Fernandes , Costa Larissa Bastos , Zaniboni Elaine Caroline , Marin José Flavio Gomes , Cerri Giovanni Guido , Buchpiguel Carlos Alberto 
Published: March 2020

AbstractPSMA PET imaging was originally used to assess biochemical recurrence of prostate cancer (PCa), but its clinical use was promptly extended to detection, staging and therapy response assessment. The expanding use of PSMA PET worldwide has also revealed PSMA ligand uptake in diverse nonprostatic diseases, which raised questions about the specificity of this imaging modality. Although not very common initially, a growing number of pathologies presenting PSMA uptake on PET have been reported in the last few years, and a proper interpretation of PSMA PET imaging findings suddenly became challenging and, to some extent, confusing. Compared to cytoplasmic PSMA expression in nonprostatic cells, the molecular features of apical PSMA expression in PCa cells can help to distinguish these various conditions. Correlations of imaging findings to patient history, to the expected pattern of disease spread and mainly to computed tomography (CT) and/or magnetic resonance imaging (MRI) characteristics will reinforce the distinction of lesions that are more likely related to PCa from those that could lead to an incorrect diagnosis. The overall benefits of endothelial PSMA expression, which is associated with the neovasculature of malignant neoplasms, will be highlighted, stating the potential use of PSMA ligand uptake as a theranostic tool. This review aims to cover the collection of nonprostatic diseases, including benign and malignant tumors, in a didactic approach according to disease etiology, with discussion of bone-related conditions and inflammatory and infectious processes.
In vitro assessment of the cytotoxic effects of secondary metabolites from Spirulina platensis on hepatocellular carcinoma
Authors: Akbarizare Mahboobeh , Ofoghi Hamideh , Hadizadeh Mahnaz , Moazami Nasrin 
Published: March 2020

Abstract
Background
Spirulina platensis, an edible cyanobacterium, is considered as a valuable and natural resource of novel anticancer agents. This study aimed to investigate the anticancer potential of major bioactive metabolites from Spirulina platensis on hepatocellular carcinoma cells. The total phenolic and alkaloid content of S. platensis were determined using spectrophotometric procedures and thin-layer chromatography. ‍‍Cellular viability of HepG2 cancer cells and normal fibroblasts was evaluated using MTT assay after 24 h treatment with 0.02–2 mg/ml of alkaloids, phenolic compounds, aqueous, and methanol extracts from Spirulina platensis.

Results
Total phenolic and total alkaloid compounds were 150.5 ± 1.18 mg gallic acid equivalents/mg extract and 11.4 ± 0.05 mg atropine equivalents/mg extract, respectively. All tested extracts and compounds demonstrated the inhibitory effect on the viability of HepG2 cells in a dose-dependent manner without cytotoxicity on normal cells. The most potent anticancer activity was induced by alkaloids (2 ± 0.001 mg/ml) with 80% reduction in cell viability and an IC50 of 0.53 ± 0.08 mg/ml. IC50 values of the aqueous extract, the methanolic extract, and phenolic compounds were 1.7 ± 0.14, 1.28 ± 0.22, and 0.86 ± 0.14 mg/ml, respectively.

Conclusions
This is the first report to demonstrate anticancer effects of alkaloids and phenolic compounds of Spirulina platensis in relation to liver cancer.
Sex differences in cognitive functioning of patients at-risk for psychosis and healthy controls: Results from the European Gene–Environment Interactions study
Authors: Menghini-Müller Stephanie , Studerus Erich , Ittig Sarah , Valmaggia Lucia R. , Kempton Matthew J. , van der Gaag Mark , de Haan Lieuwe , Nelson Barnaby , Bressan Rodrigo A. , Barrantes-Vidal Neus , Jantac Célia , Nordentoft Merete , Ruhrmann Stephan , Sachs Garbiele , Rutten Bart P. , van Os Jim , Riecher-Rössler Anita ,   the EU-GEI High Risk Study Group
Published: March 2020

Abstract

Background.
Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.

Methods.
The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).

Results.
Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.

Conclusions.
Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.