bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basic polar and hydrophobic properties are the main characteristics that affect the binding of transcription factors to methylation sites
Authors: Shen Zijie , Zou Quan 
Published: May 2020

Abstract

Motivation
Methylation and transcription factors (TFs) are part of the mechanisms regulating gene expression. However, the numerous mechanisms regulating the interactions between methylation and TFs remain unknown. We employ machine-learning techniques to discover the characteristics of TFs that bind to methylation sites.

Results
The classical machine-learning analysis process focuses on improving the performance of the analysis method. Conversely, we focus on the functional properties of the TF sequences. We obtain the principal properties of TFs, namely, the basic polar and hydrophobic Ile amino acids affecting the interaction between TFs and methylated DNA. The recall of the positive instances is 0.878 when their basic polar value is &gt;0.1743. Both basic polar and hydrophobic Ile amino acids distinguish 74% of TFs bound to methylation sites. Therefore, we infer that basic polar amino acids affect the interactions of TFs with methylation sites. Based on our results, the role of the hydrophobic Ile residue is consistent with that described in previous studies, and the basic polar amino acids may also be a key factor modulating the interactions between TFs and methylation.

Supplementary information
Supplementary data are available at Bioinformatics online.
Revealing new therapeutic opportunities through drug target prediction: a class imbalance-tolerant machine learning approach
Authors: Liang Siqi , Yu Haiyuan 
Published: May 2020

Abstract

Motivation
In silico drug target prediction provides valuable information for drug repurposing, understanding of side effects as well as expansion of the druggable genome. In particular, discovery of actionable drug targets is critical to developing targeted therapies for diseases.

Results
Here, we develop a robust method for drug target prediction by leveraging a class imbalance-tolerant machine learning framework with a novel training scheme. We incorporate novel features, including drug–gene phenotype similarity and gene expression profile similarity that capture information orthogonal to other features. We show that our classifier achieves robust performance and is able to predict gene targets for new drugs as well as drugs that potentially target unexplored genes. By providing newly predicted drug–target associations, we uncover novel opportunities of drug repurposing that may benefit cancer treatment through action on either known drug targets or currently undrugged genes.

Supplementary information
Supplementary data are available at Bioinformatics online.
DNA-based species delimitation reveals cryptic and incipient species in synchronous flashing fireflies (Coleoptera: Lampyridae) of Southeast Asia
Authors: Jusoh Wan F A , Ballantyne Lesley , Chan Kin Onn 
Published: May 2020

AbstractSynchronous flashing fireflies of the genus Pteroptyx are ubiquitous throughout Southeast Asia, yet fundamental knowledge about their biodiversity is lacking. Recent studies have revealed notable population-level phylogeographical structure within the Pteroptyx tener and P. bearni groups in Malaysia, suggesting that cryptic species may exist. Additionally, morphological and genetic similarities between P. balingiana and P. malaccae have raised questions about the former’s validity as a distinct species. We collected samples from previously unsampled populations and assembled the most comprehensive genetic dataset for Pteroptyx to date, to characterize species boundaries within the P. tener, P. bearni and P. malaccae groups. Using a suite of species delimitation analyses, we show that P. tener along the west coast of Peninsular Malaysia (PM) is distinct from populations from the east coast and Borneo despite the absence of morphological differentiation. However, analyses could not conclusively differentiate P. bearni from Borneo and eastern PM, nor identify P. balingiana and P. malaccae as distinct species, indicating that these populations may be conspecific or represent incipient species. This study underlines the need to increase geographical, taxonomic and genetic sampling of Southeast Asian fireflies to provide a better understanding of their biodiversity.
ATN status in amnestic and non-amnestic Alzheimer’s disease and frontotemporal lobar degeneration
Authors: Cousins Katheryn A Q , Irwin David J , Wolk David A , Lee Edward B , Shaw Leslie M J , Trojanowski John Q , Da Re Fulvio , Gibbons Garrett S , Grossman Murray , Phillips Jeffrey S 
Published: May 2020

Abstract
Under the ATN framework, CSF analytes provide evidence of the presence or absence of Alzheimer’s disease pathological hallmarks: amyloid plaques (A), phosphorylated tau (T), and accompanying neurodegeneration (N). Still, differences in CSF levels across amnestic and non-amnestic variants or due to co-occurring pathologies might lead to misdiagnoses. We assess the diagnostic accuracy of CSF markers for amyloid, tau, and neurodegeneration in an autopsy cohort of 118 Alzheimer’s disease patients (98 amnestic; 20 non-amnestic) and 64 frontotemporal lobar degeneration patients (five amnestic; 59 non-amnestic). We calculated between-group differences in CSF concentrations of amyloid-β1–42 peptide, tau protein phosphorylated at threonine 181, total tau, and the ratio of phosphorylated tau to amyloid-β1–42. Results show that non-amnestic Alzheimer’s disease patients were less likely to be correctly classified under the ATN framework using independent, published biomarker cut-offs for positivity. Amyloid-β1–42 did not differ between amnestic and non-amnestic Alzheimer’s disease, and receiver operating characteristic curve analyses indicated that amyloid-β1–42 was equally effective in discriminating both groups from frontotemporal lobar degeneration. However, CSF concentrations of phosphorylated tau, total tau, and the ratio of phosphorylated tau to amyloid-β1–42 were significantly lower in non-amnestic compared to amnestic Alzheimer’s disease patients. Receiver operating characteristic curve analyses for these markers showed reduced area under the curve when discriminating non-amnestic Alzheimer’s disease from frontotemporal lobar degeneration, compared to discrimination of amnestic Alzheimer’s disease from frontotemporal lobar degeneration. In addition, the ATN framework was relatively insensitive to frontotemporal lobar degeneration, and these patients were likely to be classified as having normal biomarkers or biomarkers suggestive of primary Alzheimer’s disease pathology. We conclude that amyloid-β1–42 maintains high sensitivity to A status, although with lower specificity, and this single biomarker provides better sensitivity to non-amnestic Alzheimer’s disease than either the ATN framework or the phosphorylated-tau/amyloid-β1–42 ratio. In contrast, T and N status biomarkers differed between amnestic and non-amnestic Alzheimer’s disease; standard cut-offs for phosphorylated tau and total tau may thus result in misclassifications for non-amnestic Alzheimer’s disease patients. Consideration of clinical syndrome may help improve the accuracy of ATN designations for identifying true non-amnestic Alzheimer’s disease.
A Critical, Event-Related Appraisal of Denoising in Resting-State fMRI Studies
Authors: Power Jonathan D , Lynch Charles J , Adeyemo Babatunde , Petersen Steven E 
Published: May 2020

Abstract
This article advances two parallel lines of argument about resting-state functional magnetic resonance imaging (fMRI) signals, one empirical and one conceptual. The empirical line creates a four-part organization of the text: (1) head motion and respiration commonly cause distinct, major, unwanted influences (artifacts) in fMRI signals; (2) head motion and respiratory changes are, confoundingly, both related to psychological and clinical and biological variables of interest; (3) many fMRI denoising strategies fail to identify and remove one or the other kind of artifact; and (4) unremoved artifact, due to correlations of artifacts with variables of interest, renders studies susceptible to identifying variance of noninterest as variance of interest. Arising from these empirical observations is a conceptual argument: that an event-related approach to task-free scans, targeting common behaviors during scanning, enables fundamental distinctions among the kinds of signals present in the data, information which is vital to understanding the effects of denoising procedures. This event-related perspective permits statements like “Event X is associated with signals A, B, and C, each with particular spatial, temporal, and signal decay properties”. Denoising approaches can then be tailored, via performance in known events, to permit or suppress certain kinds of signals based on their desirability.
Coronaviruses and the Chemical Senses: Past, Present, and Future
Authors: Pellegrino Robert , Cooper Keiland W , Di Pizio Antonella , Joseph Paule V , Bhutani Surabhi , Parma Valentina 
Published: May 2020

AbstractA wealth of rapidly evolving reports suggests that olfaction and taste disturbances may be manifestations of the novel COVID-19 pandemic. While otolaryngological societies worldwide have started to consider chemosensory evaluation as a screening tool for COVID-19 infection, the true nature of the relationship between the changes in chemosensory ability and COVID-19 is unclear. Our goal with this review is to provide a brief overview of published and archived literature, as well as the anecdotal reports and social trends related to this topic up to April 29, 2020. We also aim to draw parallels between the clinical/chemosensory symptomology reported in association to past coronavirus pandemics (such as SARS and MERS) and the novel COVID-19. This review also highlights current evidence on persistent chemosensory disturbances after the infection has resolved. Overall, our analysis pinpoints the need for further studies: (1) to better quantify olfaction and taste disturbances associated with SARS-CoV-2 infection, compared to those of other viral and respiratory infections, (2) to understand the relation between smell, taste, and chemesthesis disturbances in COVID-19, and (3) to understand how persistent are these disturbances after the infection has resolved.
Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019
Authors: Rubin Sébastien , Orieux Arthur , Prevel Renaud , Garric Antoine , Bats Marie-Lise , Dabernat Sandrine , Camou Fabrice , Guisset Olivier , Issa Nahema , Mourissoux Gaelle , Dewitte Antoine , Joannes-Boyau Olivier , Fleureau Catherine , Rozé Hadrien , Carrié Cédric , Petit Laurent , Clouzeau Benjamin , Sazio Charline , Bui Hoang-Nam , Pillet Odile , Rigothier Claire , Vargas Frederic , Combe Christian , Gruson Didier , Boyer Alexandre 
Published: May 2020

Abstract

Background
Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported.

Methods
Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated.

Results
Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12–23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54–140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr &gt;200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively.

Conclusion
Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria.
Rapid Detection of SARS-CoV-2 by Low Volume Real-Time Single Tube Reverse Transcription Recombinase Polymerase Amplification Using an Exo Probe with an Internally Linked Quencher (Exo-IQ)
Authors: Behrmann Ole , Bachmann Iris , Spiegel Martin , Schramm Marina , Abd El Wahed Ahmed , Dobler Gerhard , Dame Gregory , Hufert Frank T 
Published: May 2020

Abstract

Background
The current outbreak of SARS-CoV-2 has spread to almost every country with more than 5 million confirmed cases and over 300,000 deaths as of May 26, 2020. Rapid first-line testing protocols are needed for outbreak control and surveillance.

Methods
We used computational and manual designs to generate a suitable set of reverse transcription recombinase polymerase amplification (RT-RPA) primer and exonuclease probe, internally quenched (exo-IQ), sequences targeting the SARS-CoV-2 N gene. RT-RPA sensitivity was determined by amplification of in vitro transcribed RNA standards. Assay selectivity was demonstrated with a selectivity panel of 32 nucleic acid samples derived from common respiratory viruses. To validate the assay against full-length SARS-CoV-2 RNA, total viral RNA derived from cell culture supernatant and 19 nasopharyngeal swab samples (8 positive and 11 negative for SARS-CoV-2) were screened. All results were compared to established RT-qPCR assays.

Results
The 95% detection probability of the RT-RPA assay was determined to be 7.74 (95% CI: 2.87–27.39) RNA copies per reaction. The assay showed no cross-reactivity to any other screened coronaviruses or respiratory viruses of clinical significance. The developed RT-RPA assay produced 100% diagnostic sensitivity and specificity when compared to RT-qPCR (n = 20).

Conclusions
With a run time of 15 to 20 minutes and first results being available in under 7 minutes for high RNA concentrations, the reported assay constitutes one of the fastest nucleic acid based detection methods for SARS-CoV-2 to date and may provide a simple-to-use alternative to RT-qPCR for first-line screening at the point of need.
Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance
Authors: Nambu Hideo , Takada Shingo , Maekawa Satoshi , Matsumoto Junichi , Kakutani Naoya , Furihata Takaaki , Shirakawa Ryosuke , Katayama Takashi , Nakajima Takayuki , Yamanashi Katsuma , Obata Yoshikuni , Nakano Ippei , Tsuda Masaya , Saito Akimichi , Fukushima Arata , Yokota Takashi , Nio-Kobayashi Junko , Yasui Hironobu , Higashikawa Kei , Kuge Yuji , Anzai Toshihisa , Sabe Hisataka , Kinugawa Shintaro 
Published: May 2020

Abstract

Aims
Exercise intolerance in patients with heart failure (HF) is partly attributed to skeletal muscle abnormalities. We have shown that reactive oxygen species (ROS) play a crucial role in skeletal muscle abnormalities, but the pathogenic mechanism remains unclear. Xanthine oxidase (XO) is reported to be an important mediator of ROS overproduction in ischaemic tissue. Here, we tested the hypothesis that skeletal muscle abnormalities in HF are initially caused by XO-derived ROS and are prevented by the inhibition of their production.

Methods and results
Myocardial infarction (MI) was induced in male C57BL/6J mice, which eventually led to HF, and a sham operation was performed in control mice. The time course of XO-derived ROS production in mouse skeletal muscle post-MI was first analysed. XO-derived ROS production was significantly increased in MI mice from Days 1 to 3 post-surgery (acute phase), whereas it did not differ between the MI and sham groups from 7 to 28 days (chronic phase). Second, mice were divided into three groups: sham + vehicle (Sham + Veh), MI + vehicle (MI + Veh), and MI + febuxostat (an XO inhibitor, 5 mg/kg body weight/day; MI + Feb). Febuxostat or vehicle was administered at 1 and 24 h before surgery, and once-daily on Days 1–7 post-surgery. On Day 28 post-surgery, exercise capacity and mitochondrial respiration in skeletal muscle fibres were significantly decreased in MI + Veh compared with Sham + Veh mice. An increase in damaged mitochondria in MI + Veh compared with Sham + Veh mice was also observed. The wet weight and cross-sectional area of slow muscle fibres (higher XO-derived ROS) was reduced via the down-regulation of protein synthesis-associated mTOR-p70S6K signalling in MI + Veh compared with Sham + Veh mice. These impairments were ameliorated in MI + Feb mice, in association with a reduction of XO-derived ROS production, without affecting cardiac function.

Conclusion
XO inhibition during the acute phase post-MI can prevent skeletal muscle abnormalities and exercise intolerance in mice with HF.
Applying machine learning to detect early stages of cardiac remodelling and dysfunction
Authors: Sabovčik František , Cauwenberghs Nicholas , Kouznetsov Dmitry , Haddad Francois , Alonso-Betanzos Amparo , Vens Celine , Kuznetsova Tatiana 
Published: May 2020

Abstract

Aims
Both left ventricular (LV) diastolic dysfunction (LVDD) and hypertrophy (LVH) as assessed by echocardiography are independent prognostic markers of future cardiovascular events in the community. However, selective screening strategies to identify individuals at risk who would benefit most from cardiac phenotyping are lacking. We, therefore, assessed the utility of several machine learning (ML) classifiers built on routinely measured clinical, biochemical, and electrocardiographic features for detecting subclinical LV abnormalities.

Methods and results
We included 1407 participants (mean age, 51 years, 51% women) randomly recruited from the general population. We used echocardiographic parameters reflecting LV diastolic function and structure to define LV abnormalities (LVDD, n = 252; LVH, n = 272). Next, four supervised ML algorithms (XGBoost, AdaBoost, Random Forest (RF), Support Vector Machines, and Logistic regression) were used to build classifiers based on clinical data (67 features) to categorize LVDD and LVH. We applied a nested 10-fold cross-validation set-up. XGBoost and RF classifiers exhibited a high area under the receiver operating characteristic curve with values between 86.2% and 88.1% for predicting LVDD and between 77.7% and 78.5% for predicting LVH. Age, body mass index, different components of blood pressure, history of hypertension, antihypertensive treatment, and various electrocardiographic variables were the top selected features for predicting LVDD and LVH.

Conclusion
XGBoost and RF classifiers combining routinely measured clinical, laboratory, and electrocardiographic data predicted LVDD and LVH with high accuracy. These ML classifiers might be useful to pre-select individuals in whom further echocardiographic examination, monitoring, and preventive measures are warranted.
Measuring and analysing social efficiency in the production of maternal health services in Mexico, 2008–15
Authors: Fene Fato , Serván-Mori Edson , Ángel Mendoza Miguel , Chivardi Carlos , Reyes-Morales Hortensia , Nigenda Gustavo 
Published: May 2020

Abstract
‘Social efficiency’ (SE) denotes the capacity of health systems to ensure equitable access to quality health services at no financial risk to users. Mexico and other low- and middle-income countries have rarely studied the performance of their health systems from an SE perspective. We propose a metric for assessing SE in the production of maternal health services in the public sector among populations without social security, analysing contextual correlates of the demand for these services. Analysis was based on administrative data collected from the 243 health jurisdictions (HJs) in Mexico for the period 2008–15. We defined production inputs as the availability of physical and human resources and social product as the unweighted sum of social sub-products, including an equitable distribution of maternal health resources, the provision of quality maternal health care and financial protection for users. We described the SE scores, the main contextual characteristics as well as those related to the demand for maternal health services. We then performed a variance decomposition analysis of the SE score by component and estimated the SE territorial concentration patterns. Finally, we identified the structural characteristics modelling SE by means of a spatial autoregressive panel data model with fixed effects by year. The SE score rose from 57.7% in 2008 to 71.9% in 2015 (P &lt; 0.01), with its quality component accounting for the largest proportion of variance (30%). SE peaked in HJs with low social marginalization and rurality, and with service demand characterized by low parity and older populations. Different SE levels demonstrated territorial concentration patterns. Analysing SE as a metric for health system performance offers elements that contribute to the achievement of UHC as well as to the design and implementation of effective maternal health interventions intended particularly for the most socially vulnerable sectors of the population.
Glucocerebrosidase deficiency promotes release of α-synuclein fibrils from cultured neurons
Authors: Gegg Matthew E , Verona Guglielmo , Schapira Anthony H V 
Published: May 2020

Abstract
Mutations in the GBA gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are the most important genetic risk factor for Parkinson disease (PD). GCase activity is also decreased in sporadic PD brains and with normal ageing. Loss of GCase activity impairs the autophagy lysosomal pathway resulting in increased α-synuclein (α-syn) levels. Furthermore, elevated α-syn results in decreased GCase activity. Although the role of α-syn in PD remains unclear, evidence indicates that aggregated α-syn fibrils are a pathogenic species in PD, passing between neurons and inducing endogenous native α-syn to aggregate; spreading pathology through the brain. We have investigated if preformed α-syn fibrils (PFFs) impair GCase activity in mouse cortical neurons and differentiated dopaminergic cells, and whether GCase deficiency in these models increased the transfer of α-syn pathology to naïve cells. Neurons treated with PFFs induced endogenous α-syn to become insoluble and phosphorylated at Ser129 to a greater extent than monomeric α-syn-treatment. PFFs, but not monomeric α-syn, inhibited lysosomal GCase activity in these cells and induced the unfolded protein response. Neurons in which GCase was inhibited by conduritol β-epoxide did not increase the amount of insoluble monomeric α-syn or its phosphorylation status. Instead the release of α-syn fibrils from GCase deficient cells was significantly increased. Co-culture studies showed that the transfer of α-syn pathology to naïve cells was greater from GCase deficient cells. This study suggests that GCase deficiency increases the spread of α-syn pathology and likely contributes to the earlier age of onset and increased cognitive decline associated with GBA-PD.