bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircaCompare: a method to estimate and statistically support differences in mesor, amplitude and phase, between circadian rhythms
Authors: Parsons Rex , Parsons Richard , Garner Nicholas , Oster Henrik , Rawashdeh Oliver 
Published: September 2019

Abstract

Motivation
A fundamental interest in chronobiology is to compare patterns between groups of rhythmic data. However, many existing methods are ill-equipped to derive statements concerning the statistical significance of differences between rhythms that may be visually apparent. This is attributed to both the form of data used (longitudinal versus cross-sectional) and the limitations of the statistical tests used to draw conclusions.

Results
To address this problem, we propose that a cosinusoidal curve with a particular parametrization be used to model and compare data of two sets of observations collected over a 24-h period. The novelty of our test is in the parametrization, which allows the explicit estimation of rhythmic parameters [mesor (the rhythm-adjusted mean level of a response variable around which a wave function oscillates), amplitude and phase], and simultaneously testing for statistical significance in all three parameters between two or more groups of datasets. A statistically significant difference between two groups, regarding each of these rhythmic parameters, is indicated by a P-value. The method is evaluated by applying the model to publicly available datasets, and is further exemplified by comparison to the currently recommended method, DODR. The results suggest that the method proposed may be highly sensitive to detect rhythmic differences between groups in phase, amplitude and mesor.

Availability and implementation
https://github.com/RWParsons/circacompare/
The CroCo cross-link converter: a user-centred tool to convert results from cross-linking mass spectrometry experiments
Authors: Bender Julian , Schmidt Carla 
Published: September 2019

Abstract

Motivation
A variety of search engines exists for the identification of peptide spectrum matches after cross-linking mass spectrometry experiments. The resulting diversity in output formats complicates data validation and visualization as well as exchange with collaborators, particularly from other research areas.

Results
Here, we present CroCo, a user-friendly standalone executable to convert cross-linking results to a comprehensive spreadsheet format. Using this format, CroCo can be employed to generate input files for a selection of the commonly utilized validation and visualization tools.

Availability and implementation
The source-code is freely available under a GNU general public license at https://github.com/cschmidtlab/croco. The standalone executable is available and documented at https://cschmidtlab.github.io/CroCo.

Supplementary information
Supplementary data are available at Bioinformatics online.
SubMito-XGBoost: predicting protein submitochondrial localization by fusing multiple feature information and eXtreme gradient boosting
Authors: Yu Bin , Qiu Wenying , Chen Cheng , Ma Anjun , Jiang Jing , Zhou Hongyan , Ma Qin 
Published: September 2019

Abstract

Motivation
Mitochondria are an essential organelle in most eukaryotes. They not only play an important role in energy metabolism but also take part in many critical cytopathological processes. Abnormal mitochondria can trigger a series of human diseases, such as Parkinson's disease, multifactor disorder and Type-II diabetes. Protein submitochondrial localization enables the understanding of protein function in studying disease pathogenesis and drug design.

Results
We proposed a new method, SubMito-XGBoost, for protein submitochondrial localization prediction. Three steps are included: (i) the g-gap dipeptide composition (g-gap DC), pseudo-amino acid composition (PseAAC), auto-correlation function (ACF) and Bi-gram position-specific scoring matrix (Bi-gram PSSM) are employed to extract protein sequence features, (ii) Synthetic Minority Oversampling Technique (SMOTE) is used to balance samples, and the ReliefF algorithm is applied for feature selection and (iii) the obtained feature vectors are fed into XGBoost to predict protein submitochondrial locations. SubMito-XGBoost has obtained satisfactory prediction results by the leave-one-out-cross-validation (LOOCV) compared with existing methods. The prediction accuracies of the SubMito-XGBoost method on the two training datasets M317 and M983 were 97.7% and 98.9%, which are 2.8–12.5% and 3.8–9.9% higher than other methods, respectively. The prediction accuracy of the independent test set M495 was 94.8%, which is significantly better than the existing studies. The proposed method also achieves satisfactory predictive performance on plant and non-plant protein submitochondrial datasets. SubMito-XGBoost also plays an important role in new drug design for the treatment of related diseases.

Availability and implementation
The source codes and data are publicly available at https://github.com/QUST-AIBBDRC/SubMito-XGBoost/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Identification of metabolites from tandem mass spectra with a machine learning approach utilizing structural features
Authors: Li Yuanyue , Kuhn Michael , Gavin Anne-Claude , Bork Peer 
Published: September 2019

Abstract

Motivation
Untargeted mass spectrometry (MS/MS) is a powerful method for detecting metabolites in biological samples. However, fast and accurate identification of the metabolites’ structures from MS/MS spectra is still a great challenge.

Results
We present a new analysis method, called SubFragment-Matching (SF-Matching) that is based on the hypothesis that molecules with similar structural features will exhibit similar fragmentation patterns. We combine information on fragmentation patterns of molecules with shared substructures and then use random forest models to predict whether a given structure can yield a certain fragmentation pattern. These models can then be used to score candidate molecules for a given mass spectrum. For rapid identification, we pre-compute such scores for common biological molecular structure databases. Using benchmarking datasets, we find that our method has similar performance to CSI: FingerID and those very high accuracies can be achieved by combining our method with CSI: FingerID. Rarefaction analysis of the training dataset shows that the performance of our method will increase as more experimental data become available.

Availability and implementation
SF-Matching is available from http://www.bork.embl.de/Docu/sf_matching.

Supplementary information
Supplementary data are available at Bioinformatics online.
Hexa-Longin domain scaffolds for inter-Rab signalling
Authors: Sanchez-Pulido Luis , Ponting Chris P 
Published: September 2019

Abstract

Summary
CPLANE is a protein complex required for assembly and maintenance of primary cilia. It contains several proteins, such as INTU, FUZ, WDPCP, JBTS17 and RSG1 (REM2- and RAB-like small GTPase 1), whose genes are mutated in ciliopathies. Using two contrasting evolutionary analyses, coevolution-based contact prediction and sequence conservation, we first identified the INTU/FUZ heterodimer as a novel member of homologous HerMon (Hermansky-Pudlak syndrome and MON1-CCZ1) complexes. Subsequently, we identified homologous Longin domains that are triplicated in each of these six proteins (MON1A, CCZ1, HPS1, HPS4, INTU and FUZ). HerMon complexes are known to be Rab effectors and Rab GEFs (Guanine nucleotide Exchange Factors) that regulate vesicular trafficking. Consequently, INTU/FUZ, their homologous complex, is likely to act as a GEF during activation of Rab GTPases involved in ciliogenesis.

Supplementary information
Supplementary data are available at Bioinformatics online.
Amino-terminal Pro-B-Type Natriuretic Peptide Among Patients Living With Both Human Immunodeficiency Virus and Heart Failure
Authors: Alvi Raza M , Zanni Markella V , Neilan Anne M , Hassan Malek Z O , Tariq Noor , Zhang Lili , Afshar Maryam , Banerji Dahlia , Mulligan Connor P , Rokicki Adam , Awadalla Magid , Januzzi James L , Neilan Tomas G 
Published: September 2019

AbstractBackgroundAmong persons living with human immunodeficiency virus (PHIV), incident heart failure (HF) rates are increased and outcomes are worse; however, the role of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among PHIV with HF has not been characterized.MethodsPatients were derived from a registry of those hospitalized with HF at an academic center in a calender year. We compared the NT-proBNP concentrations and the changes in NT-proBNP levels between PHIV with HF and uninfected controls with HF.ResultsAmong 2578 patients with HF, there were 434 PHIV; 90% were prescribed antiretroviral therapy and 62% were virally suppressed. As compared to controls, PHIV had higher admission (3822 [IQR, 2413–7784] pg/ml vs 5546 [IQR, 3257–8792] pg/ml, respectively; P &lt; .001), higher discharge (1922 [IQR, 1045–4652] pg/ml vs 3372 [IQR, 1553–5452] pg/ml, respectively; P &lt; .001), and lower admission-to-discharge changes in NT-proBNP levels (32 vs 48%, respectively; P = .007). Similar findings were noted after stratifying based on left ventricular ejection fraction (LVEF). In a multivariate analysis, cocaine use, a lower LVEF, a higher NYHA class, a higher viral load (VL), and a lower CD4 count were associated with higher NT-proBNP concentrations. In follow-up, among PHIV, a higher admission NT-proBNP concentration was associated with increased cardiovascular mortality (first tertile, 11.5; second tertile, 20; third tertile, 44%; P &lt; .001). Among PHIV, each doubling of NT-proBNP was associated with a 19% increased risk of death. However, among patients living without HIV, each doubling was associated with a 27% increased risk; this difference was attenuated among PHIV with lower VLs and higher CD4 counts.ConclusionsPHIV with HF had higher admission and discharge NT-proBNP levels, and less change in NT-proBNP concentrations. Among PHIV, VLs and CD4 counts were associated with NT-proBNP concentrations; in follow-up, higher NT-proBNP levels among PHIV were associated with cardiovascular mortality.
Relationship between serum phosphate levels and survival in chronic hemodialysis patients: interactions with age, malnutrition and inflammation
Authors: Ye Xiaoling , Kooman Jeroen P , van der Sande Frank M , Raimann Jochen G , Usvyat Len A , Wang Yuedong , Maddux Franklin W , Kotanko Peter 
Published: September 2019

Abstract

Background
Evidence indicates that the inverse relationships between phosphate levels and mortality maybe modified by age. Furthermore, malnutrition and inflammation could strengthen the risk associated with phosphate abnormalities. This study aimed to assess the associations between phosphate levels and mortality while accounting for the interactions with age and parameters associated with malnutrition and inflammation in hemodialysis (HD) patients.

Methods
Adult HD patients (n = 245 853) treated in Fresenius Medical Care North America clinics from January 2010 to October 2018 were enrolled. Baseline was defined as Months 4–6 on dialysis, with the subsequent 12 months as the follow-up period. Univariate and multivariate Cox proportional hazard models with spline terms were applied to study the nonlinear relationships between serum phosphate levels and mortality. The interactions of phosphate levels with albumin, creatinine, normalized protein catabolic rate (nPCR) and neutrophil–lymphocyte ratio (NLR) were assessed with smoothing spline analysis of variance Cox proportional hazard models.

Results
Older patients tended to have lower levels of serum phosphate, albumin, creatinine and nPCR. Additionally, both low (&lt;4.0 mg/dL) and high (&gt;5.5 mg/dL) phosphate levels were associated with higher risk of mortality across all age strata. The U-shaped relationships between phosphate levels and outcome persisted even for patients with low or high levels of serum albumin, creatinine, nPCR and NLR, respectively.

Conclusion
The consistent U-shaped relationships between serum phosphate and mortality across age strata and levels of inflammatory and nutritional status should prompt the search for underlying causes and potentially nutritional intervention in clinical practice.
Generation of Norovirus-Specific T Cells From Human Donors With Extensive Cross-Reactivity to Variant Sequences: Implications for Immunotherapy
Authors: Hanajiri Ryo , Sani Gelina M , Saunders Devin , Hanley Patrick J , Chopra Abha , Mallal Simon A , Sosnovtsev Stanislav V , Cohen Jeffrey I , Green Kim Y , Bollard Catherine M , Keller Michael D 
Published: September 2019

Abstract

Background
Chronic norovirus infection in immunocompromised patients can be severe, and presently there is no effective treatment. Adoptive transfer of virus-specific T cells has proven to be safe and effective for the treatment of many viral infections, and this could represent a novel treatment approach for chronic norovirus infection. Hence, we sought to generate human norovirus-specific T cells (NSTs) that can recognize different viral sequences.

Methods
Norovirus-specific T cells were generated from peripheral blood of healthy donors by stimulation with overlapping peptide libraries spanning the entire coding sequence of the norovirus genome.

Results
We successfully generated T cells targeting multiple norovirus antigens with a mean 4.2 ± 0.5-fold expansion after 10 days. Norovirus-specific T cells comprised both CD4+ and CD8+ T cells that expressed markers for central memory and effector memory phenotype with minimal expression of coinhibitory molecules, and they were polyfunctional based on cytokine production. We identified novel CD4- and CD8-restricted immunodominant epitopes within NS6 and VP1 antigens. Furthermore, NSTs showed a high degree of cross-reactivity to multiple variant epitopes from clinical isolates.

Conclusions
Our findings identify immunodominant human norovirus T-cell epitopes and demonstrate that it is feasible to generate potent NSTs from third-party donors for use in antiviral immunotherapy.
Long-term risk of hepatocellular carcinoma mortality in 23220 hospitalized patients treated with micafungin or other parenteral antifungals
Authors: Schneeweiss Sebastian , Carver Peggy L , Datta Kausik , Galar Alicia , Johnson Melissa D , Letourneau Alyssa R , Marty Francisco M , Nagel Jerod , Najdzinowicz Maryann , Saul Melissa , Schuster Mindy , Shoham Shmuel , Silveira Fernanda P , Varughese Christy , Wilck Marissa , Weatherby Lisa , Oene Joop van , Walker Alexander M 
Published: September 2019

Abstract

Background
Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin’s risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up.

Methods
We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs.

Results
A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04–2.24).

Conclusions
Both micafungin and comparator PAFs were associated with HCC mortality rates of &lt;0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.
Detection of exoplanet as a binary source of microlensing events in WFIRST survey
Authors: Bagheri Fatemeh , Sajadian Sedighe , Rahvar Sohrab 
Published: September 2019

ABSTRACT
We investigate the possibility of exoplanet detection orbiting source stars in microlensing events through WFIRST observations. We perform a Monte Carlo simulation on the detection rate of exoplanets via microlensing, assuming that each source star has at least one exoplanet. The exoplanet can reflect part of the light from the parent star or emit internal thermal radiation. In this new detection channel, we use microlensing as an amplifier to magnify the reflection light from the planet. In the literature, this mode of detecting exoplanets has been investigated much less than the usual mode in which the exoplanets are considered as one companion in binary-lens events. Assuming 72 d of observation per season with the cadence of 15 min, we find the probability of rocky planet detection with this method to be virtually zero. However, there is non-zero probability, for the detection of Jovian planets. We estimate the detection rates of the exoplanets by this method, using WFIRST observation to be $0.012{{\ \rm per\ cent}}$ in single-lens events and $0.9{{\ \rm per\ cent}}$ in the binary-lens events.
Gaussian mixture models for blended photometric redshifts
Authors: Jones Daniel M , Heavens Alan F 
Published: September 2019

ABSTRACTFuture cosmological galaxy surveys such as the Large Synoptic Survey Telescope (LSST) will photometrically observe very large numbers of galaxies. Without spectroscopy, the redshifts required for the analysis of these data will need to be inferred using photometric redshift techniques that are scalable to large sample sizes. The high number density of sources will also mean that around half are blended. We present a Bayesian photometric redshift method for blended sources that uses Gaussian mixture models to learn the joint flux–redshift distribution from a set of unblended training galaxies, and Bayesian model comparison to infer the number of galaxies comprising a blended source. The use of Gaussian mixture models renders both of these applications computationally efficient and therefore suitable for upcoming galaxy surveys.
A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor
Authors: Rodrigue Amélie , Margaillan Guillaume , Torres Gomes Thiago , Coulombe Yan , Montalban Gemma , da Costa e Silva Carvalho Simone , Milano Larissa , Ducy Mandy , De-Gregoriis Giuliana , Dellaire Graham , Araújo da Silva Jr Wilson , Monteiro Alvaro N , Carvalho Marcelo A , Simard Jacques , Masson Jean-Yves 
Published: September 2019

Abstract
While biallelic mutations in the PALB2 tumor suppressor cause Fanconi anemia subtype FA-N, monoallelic mutations predispose to breast and familial pancreatic cancer. Although hundreds of missense variants in PALB2 have been identified in patients to date, only a few have clear functional and clinical relevance. Herein, we investigate the effects of 44 PALB2 variants of uncertain significance found in breast cancer patients and provide detailed analysis by systematic functional assays. Our comprehensive functional analysis reveals two hotspots for potentially deleterious variations within PALB2, one at each terminus. PALB2 N-terminus variants p.P8L [c.23C>T], p.Y28C [c.83A>G], and p.R37H [c.110G>A] compromised PALB2-mediated homologous recombination. At the C-terminus, PALB2 variants p.L947F [c.2841G>T], p.L947S [c.2840T>C], and most strikingly p.T1030I [c.3089C>T] and p.W1140G [c.3418T>C], stood out with pronounced PARP inhibitor sensitivity and cytoplasmic accumulation in addition to marked defects in recruitment to DNA damage sites, interaction with BRCA2 and homologous recombination. Altogether, our findings show that a combination of functional assays is necessary to assess the impact of germline missense variants on PALB2 function, in order to guide proper classification of their deleteriousness.
22. Systemic onset juvenile idiopathic arthritis with multi-organ failure in a teenager
Authors: Law Hannah , Kelly Alison , Teoh Lisa 
Published: September 2019

Abstract

Introduction
Systemic onset juvenile idiopathic arthritis (JIA) is an often severe and potentially life-threatening subtype of chronic arthritis starting under the age of 16 years. It is characterised by fevers, rash and arthritis, although this may not be apparent until later in the disease course, which can add difficulty to making the diagnosis. We present a case of systemic onset JIA with multi-organ impairment to showcase its mimicry of other diseases and highlight importance of awareness

Case description
A 15-year-old girl presented with a 7 day history of fever, cough, sore neck, enlarged lymph nodes and widespread macular rash. She had been started on penicillin in the community for presumed scarlet fever, but was hospitalised due to worsening symptoms. Differential diagnoses discussed were lymphadenitis and EBV, due to ongoing fevers, high inflammatory markers, and raised liver function tests. She then developed an acute kidney injury and profound hypotension. She was treated with immunoglobulin for possible Kawasaki disease, broad spectrum antibiotics for possible toxic shock syndrome/sepsis, and transferred to the regional PICU for ongoing inotropic support and management of her multi-system illness.
She was found to have a non-dilated cardiomyopathy with poor left ventricular function, low complement and positive anti-streptolysin titres. No postive cultures or focus of infection were found. Antibody tests including dsDNA were negative. She required CPAP for respiratory support and was treated with pulsed methylprednisolone for systemic onset JIA. She then received a weaning course of prednisolone over several months and made an excellent recovery.

Discussion
This was an interesting case for those involved because the initial symptoms, evolving signs and investigation results didn’t easily tie together to give one suitable diagnosis. Several avenues of treatment were explored, including a range of antibiotics and immunoglobulin, before methylprednisolone. The patient also remained remarkably ‘well’ looking despite her multi-organ impairment.

Key learning points
This case highlighted the importance of awareness of systemic onset JIA and its complications, particularly in a non-typical age group, for the general paediatrician. Early discussion with and involvement of tertiary rheumatology services served to optimise management and outcome, and will hopefully also improve long-term prognosis.

Conflicts of interest
The authors have declared no conflicts of interest.