bluuebunny/crossref_metadata_2025_split huggingface dataset:
MDeePred: novel multi-channel protein featurization for deep learning-based binding affinity prediction in drug discovery
Authors: Rifaioglu A S , Cetin Atalay R , Cansen Kahraman D , Doğan T , Martin M , Atalay V 
Published: October 2020

Abstract

Motivation
Identification of interactions between bioactive small molecules and target proteins is crucial for novel drug discovery, drug repurposing and uncovering off-target effects. Due to the tremendous size of the chemical space, experimental bioactivity screening efforts require the aid of computational approaches. Although deep learning models have been successful in predicting bioactive compounds, effective and comprehensive featurization of proteins, to be given as input to deep neural networks, remains a challenge.

Results
Here, we present a novel protein featurization approach to be used in deep learning-based compound–target protein binding affinity prediction. In the proposed method, multiple types of protein features such as sequence, structural, evolutionary and physicochemical properties are incorporated within multiple 2D vectors, which is then fed to state-of-the-art pairwise input hybrid deep neural networks to predict the real-valued compound–target protein interactions. The method adopts the proteochemometric approach, where both the compound and target protein features are used at the input level to model their interaction. The whole system is called MDeePred and it is a new method to be used for the purposes of computational drug discovery and repositioning. We evaluated MDeePred on well-known benchmark datasets and compared its performance with the state-of-the-art methods. We also performed in vitro comparative analysis of MDeePred predictions with selected kinase inhibitors’ action on cancer cells. MDeePred is a scalable method with sufficiently high predictive performance. The featurization approach proposed here can also be utilized for other protein-related predictive tasks.

Availability and implementation
The source code, datasets, additional information and user instructions of MDeePred are available at https://github.com/cansyl/MDeePred.

Supplementary information
Supplementary data are available at Bioinformatics online.
UNRES-Dock—protein–protein and peptide–protein docking by coarse-grained replica-exchange MD simulations
Authors: Krupa Paweł , Karczyńska Agnieszka S , Mozolewska Magdalena A , Liwo Adam , Czaplewski Cezary 
Published: October 2020

Abstract

Motivation
The majority of the proteins in living organisms occur as homo- or hetero-multimeric structures. Although there are many tools to predict the structures of single-chain proteins or protein complexes with small ligands, peptide–protein and protein–protein docking is more challenging. In this work, we utilized multiplexed replica-exchange molecular dynamics (MREMD) simulations with the physics-based heavily coarse-grained UNRES model, which provides more than a 1000-fold simulation speed-up compared with all-atom approaches to predict structures of protein complexes.

Results
We present a new protein–protein and peptide–protein docking functionality of the UNRES package, which includes a variable degree of conformational flexibility. UNRES-Dock protocol was tested on a set of 55 complexes with size from 43 to 587 amino-acid residues, showing that structures of the complexes can be predicted with good quality, if the sampling of the conformational space is sufficient, especially for flexible peptide–protein systems. The developed automatized protocol has been implemented in the standalone UNRES package and in the UNRES server.

Availability and implementation
UNRES server: http://unres-server.chem.ug.edu.pl; UNRES package and data used in testing of UNRES-Dock: http://unres.pl.

Supplementary information
Supplementary data are available at Bioinformatics online.
A pseudotemporal causality approach to identifying miRNA–mRNA interactions during biological processes
Authors: Cifuentes-Bernal Andres M , Pham Vu Vh , Li Xiaomei , Liu Lin , Li Jiuyong , Le Thuc Duy 
Published: October 2020

AbstractMotivationmicroRNAs (miRNAs) are important gene regulators and they are involved in many biological processes, including cancer progression. Therefore, correctly identifying miRNA–mRNA interactions is a crucial task. To this end, a huge number of computational methods has been developed, but they mainly use the data at one snapshot and ignore the dynamics of a biological process. The recent development of single cell data and the booming of the exploration of cell trajectories using ‘pseudotime’ concept have inspired us to develop a pseudotime-based method to infer the miRNA–mRNA relationships characterizing a biological process by taking into account the temporal aspect of the process.ResultsWe have developed a novel approach, called pseudotime causality, to find the causal relationships between miRNAs and mRNAs during a biological process. We have applied the proposed method to both single cell and bulk sequencing datasets for Epithelia to Mesenchymal Transition, a key process in cancer metastasis. The evaluation results show that our method significantly outperforms existing methods in finding miRNA–mRNA interactions in both single cell and bulk data. The results suggest that utilizing the pseudotemporal information from the data helps reveal the gene regulation in a biological process much better than using the static information.Availability and implementationR scripts and datasets can be found at https://github.com/AndresMCB/PTC.Supplementary informationSupplementary data are available at Bioinformatics online.
VirPreNet: a weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all eight segments
Authors: Yin Rui , Luo Zihan , Zhuang Pei , Lin Zhuoyi , Kwoh Chee Keong 
Published: October 2020

Abstract

Motivation
Influenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics.

Results
In this article, we propose a weighted ensemble convolutional neural network (CNN) for the virulence prediction of influenza A viruses named VirPreNet that uses all eight segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the eight-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble CNN is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNet’s main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza virulence.

Availability and implementation
Codes and data to generate the VirPreNet are publicly available at https://github.com/Rayin-saber/VirPreNet.

Supplementary information
Supplementary data are available at Bioinformatics online.
Therapeutic applications oftrans-splicing
Authors: Hong Elizabeth M , Ingemarsdotter Carin K , Lever Andrew M L 
Published: October 2020

AbstractBackgroundRNA trans-splicing joins exons from different pre-mRNA transcripts to generate a chimeric product. Trans-splicing can also occur at the protein level, with split inteins mediating the ligation of separate gene products to generate a mature protein.Sources of dataComprehensive literature search of published research papers and reviews using Pubmed.Areas of agreementTrans-splicing techniques have been used to target a wide range of diseases in both in vitro and in vivo models, resulting in RNA, protein and functional correction.Areas of controversyOff-target effects can lead to therapeutically undesirable consequences. In vivo efficacy is typically low, and delivery issues remain a challenge.Growing pointsTrans-splicing provides a promising avenue for developing novel therapeutic approaches. However, much more research needs to be done before developing towards preclinical studies.Areas timely for developing researchIncreasing trans-splicing efficacy and specificity by rational design, screening and competitive inhibition of endogenous cis-splicing.
Diet-dependent gut microbiota impacts on adult neurogenesis through mitochondrial stress modulation
Authors: Ribeiro Maria F , Santos André A , Afonso Marta B , Rodrigues Pedro M , Sá Santos Sónia , Castro Rui E , Rodrigues Cecília M P , Solá Susana 
Published: October 2020

Abstract
The influence of dietary factors on brain health and mental function is becoming increasingly recognized. Similarly, mounting evidence supports a role for gut microbiota in modulating central nervous system function and behaviour. Still, the molecular mechanisms responsible for the impact of diet and associated microbiome in adult neurodegeneration are still largely unclear. In this study, we aimed to investigate whether and how changes in diet-associated microbiome and its metabolites impact on adult neurogenesis. Mice were fed a high-fat, choline-deficient diet, developing obesity and several features of the metabolic syndrome, including non-alcoholic steatohepatitis. Strikingly, our results showed, for the first time, that animals fed with this specific diet display premature increased neurogenesis, possibly exhausting the available neural stem cell pool for long-term neurogenesis processes. The high-fat, choline-deficient diet further induced neuroinflammation, oxidative stress, synaptic loss and cell death in different regions of the brain. Notably, this diet-favoured gut dysbiosis in the small intestine and cecum, up-regulating metabolic pathways of short-chain fatty acids, such as propionate and butyrate and significantly increasing propionate levels in the liver. By dissecting the effect of these two specific short-chain fatty acids in vitro, we were able to show that propionate and butyrate enhance mitochondrial biogenesis and promote early neurogenic differentiation of neural stem cells through reactive oxygen species- and extracellular signal-regulated kinases 1/2-dependent mechanism. More importantly, neurogenic niches of high-fat, choline-deficient-fed mice showed increased expression of mitochondrial biogenesis markers, and decreased mitochondrial reactive oxygen species scavengers, corroborating the involvement of this mitochondrial stress-dependent pathway in mediating changes of adult neurogenesis by diet. Altogether, our results highlight a mitochondria-dependent pathway as a novel mediator of the gut microbiota–brain axis upon dietary influences.
The effect of differential force system and minimal surgical intervention on orthodontic tooth movement and root resorption
Authors: Nanda Anjali , Chen Po-Jung , Mehta Shivam , Kalajzic Zana , Dutra Eliane H , Allareddy Veerasathpurush , Nanda Ravindra , Yadav Sumit 
Published: October 2020

SummaryObjectiveThe primary objective of this study was to quantify the orthodontic tooth movement (OTM) and orthodontically induced root resorption (OIRR) with differential force system in conjunction with minimal surgical insult.Material and methods15-week-old, 48 male Wistar rats were used in the research and were randomly divided into six groups: 1. Group 1 (8 Wistar rats): OTM for 14 days with 8-g force; 2. Group 2 (8 Wistar rats): OTM for 14 days with 25-g force; 3. Group 3 (8 Wistar rats): OTM for 14 days with 100-g force; 4. Group 4 (8 Wistar rats): OTM for 14 days with 8-g force and alveolar decortications (ADs); 5. Group 5 (8 Wistar rats): OTM for 14 days with 25-g force and ADs; 6. Group 6 (8 Wistar rats): OTM for 14 days with 100-g force and ADs. A nickel–titanium spring was used to protract the molar mesially using maxillary incisors as an anchorage. ADs (minimal surgical insult) were done using a hand piece and a round bur, adjacent to the left first maxillary molar on the palatal alveolar bone. After 14 days of OTM, Wistar rats were killed and microfocus computed tomography and histological analysis were performed.ResultsThe 100-g group showed significant increase (P &lt; 0.05) in OTM. However, with ADs, the OTM was significantly higher (P &lt; 0.05) in 8 and 100 g. In addition, with ADs, there is significant increase (P &lt; 0.05) in OIRR and significant decrease (P &lt; 0.05) in bone volume fraction. Histological quantification of tartrate-resistant acid phosphatase indicated a significant increase (P &lt; 0.05) in the number of osteoclasts with ADs when compared without ADs.ConclusionsLight force in conjunction with ADs are optimal to accelerate the OTM. Additionally, ADs increases the OIRR.
High-sugar feeding and increasing cholesterol levels in infants
Authors: Zubin Maslov Petra , Hill Joseph A , Lüscher Thomas F , Narula Jagat 
Published: October 2020

Abstract
Hypercholesterolaemia is an important risk factor for cardiovascular disease. Both total and LDL cholesterol levels are three-fold higher at the end of the first year of life and about four-fold higher in adulthood compared with the neonatal period. In the USA, only 25% of infants are exclusively breastfed and simple carbohydrate-rich formulas are preferentially consumed. Spikes in fasting glucose and insulin have been reported in formula-fed infants and are associated with higher levels of proprotein convertase subtilisin/kexin type 9, suggesting a potential link between high simple sugar intake and consequent increase in LDL cholesterol in early childhood.
Genetic structuring in Atlantic haddock contrasts with current management regimes
Authors: Berg Paul R , Jorde Per E , Glover Kevin A , Dahle Geir , Taggart John B , Korsbrekke Knut , Dingsør Gjert E , Skjæraasen Jon E , Wright Peter J , Cadrin Steven X , Knutsen Halvor , Westgaard Jon-Ivar 
Published: October 2020

AbstractThe advent of novel genetic methods has made it possible to investigate population structure and connectivity in mobile marine fish species: knowledge of which is essential to ensure a sustainable fishery. Haddock (Melanogrammus aeglefinus) is a highly exploited marine teleost distributed along the coast and continental shelf on both sides of the North Atlantic Ocean. However, little is known about its population structure. Here, we present the first study using single-nucleotide polymorphism (SNP) markers to assess the genetic population structure of haddock at multiple geographic scales, from the trans-Atlantic to the local (fjord) level. Genotyping 138 SNP loci in 1329 individuals from 19 locations across the North Atlantic revealed three main genetic clusters, consisting of a Northwest Atlantic cluster, a Northeast Arctic cluster, and a Northeast Atlantic cluster. We also observed a genetically distinct fjord population and a pattern of isolation by distance in the Northeast Atlantic. Our results contrast with the current management regime for this species in the Northeast Atlantic, as we found structure within some management areas. The study adds to the growing recognition of population structuring in marine organisms in general, and fishes in particular, and is of clear relevance for the management of haddock in the Northeast Atlantic.
The missing whales: relevance of “struck and lost” rates for the impact assessment of historical whaling in the southwestern Atlantic Ocean
Authors: Vighi Morgana , Borrell Asunción , Jackson Jennifer A , Carroll Emma L , Pennino Maria Grazia , Aguilar Alex 
Published: October 2020

Abstract
The massive impact that open-boat historical whaling (18th to 20th centuries) had on whale populations has been traditionally estimated from records of oil and baleen plate production. However, an unknown proportion of hunted whales were struck, wounded, eventually killed, but lost, and not included in these records, suggesting that whaling impact may be critically underestimated. Whaling logbooks provide a key source for assessing past catches and losses. Here, we extract detailed records of 19875 days of activity in the southwestern Atlantic Ocean from 255 logbooks of offshore whaling voyages. During the period considered (1776–1923), whalers first targeted southern right whales (Eubalaena australis, 2497 sightings and 658 catches), gradually substituted by sperm whales (Physeter macrocephalus, 1157 sightings and 843 catches) after 1840. Loss rate factors, calculated to account for the number of “struck and lost” whales, decreased across time for both species, and were particularly high (ranging 1.09–1.6) for the southern right whale, whose population was drastically reduced by whaling, as compared to previous estimates based on rough catch records. Accurate accounting for these “lost” individuals is essential for reconstructing the impact of whaling on cetacean populations and for a proper assessment of their initial population size and demographic trends.
Trauma system accreditation and patient outcomes in British Columbia: an interrupted time series analysis
Authors: Batomen Brice , Moore Lynne , Strumpf Erin , Yanchar Natalie L , Thakore Jaimini , Nandi Arijit 
Published: October 2020

Abstract

Objective
We aim to assess the impact of several accreditation cycles of trauma centers on patient outcomes, specifically in-hospital mortality, complications and hospital length of stay.

Design
Interrupted time series.

Setting
British Columbia, Canada.

Participants
Trauma patients admitted to all level I and level II trauma centers between January 2008 and March 2018.

Exposure
Accreditation.

Main Outcomes and Measures
We first computed quarterly estimates of the proportions of in-hospital mortality, complications and survival to discharge standardized for change in patient case-mix using prognostic scores and the Aalen–Johansen estimator of the cumulative incidence function. Piecewise regressions were then used to estimate the change in levels and trends for patient outcomes following accreditation.

Results
For in-hospital mortality and major complications, the impact of accreditation seems to be associated with short- and long-term reductions after the first cycle and only short-term reductions for subsequent cycles. However, the 95% confidence intervals for these estimates were wide, and we lacked the precision to consistently conclude that accreditation is beneficial.

Conclusions
Applying a quasi-experimental design to time series accounting for changes in patient case-mix, our results suggest that accreditation might reduce in-hospital mortality and major complications. However, there was uncertainty around the estimates of accreditation. Further studies looking at clinical processes of care and other outcomes such as patient or health staff satisfaction are needed.
Phylogeny, Evolution, and Biogeography of the North American Trapdoor Spider Family Euctenizidae (Araneae: Mygalomorphae) and the Discovery of a New ‘Endangered Living Fossil’ Along California’s Central Coast
Authors: Bond Jason E , Hamilton Chris A , Godwin Rebecca L , Ledford Joel M , Starrett James 
Published: October 2020

Abstract
We report here the discovery of a remarkable new monotypic mygalomorph spider genus, known only from one geographical location along the central coast of California. The single relict species comprising Cryptocteniza kawtakn. gen. n. sp., is morphologically distinct and geographically isolated from other related genera, with its closest phylogenetic relatives found much further to the east in New Mexico and Arizona. Using a phylogenomic approach employing anchored hybrid enrichment, we reconstruct the evolutionary history of the family Euctenizidae Raven, 1985 to explore relationships among genera, affirmatively place previously undescribed taxa, explore rates of diversification, and reconstruct the group’s biogeography. A biogeographic analysis shows that extinction likely played a significant role in shaping the observed disjunct modern-day distribution of Cryptocteniza and its sister taxa. Our extinction hypothesis is further bolstered by a diversification rate analysis identifying considerably higher rates of speciation in other euctenizid lineages like AptostichusSimon, 1891. Consequently, changes in environmental conditions (or other related biotic and/or abiotic factors) may have spurred an adaptive radiation in related genera now widely distributed across the California Floristic Province biodiversity hotspot, with concomitant extinction in Cryptocteniza following the Miocene and establishment of a Mediterranean climate. Owing to its phylogenetic distinctiveness, incredibly narrow distribution and age, we show that Cryptocteniza meets all the criteria of an ‘Endangered Living Fossil’ and is consequently of grave conservation concern.
Examining the Gender Productivity Gap among Farm Households in Mali
Authors: Singbo A , Njuguna-Mungai E , Yila J O , Sissoko K , Tabo R 
Published: October 2020

Abstract
This paper decomposes the gender agricultural productivity gap and measures the factors that influence the gap between male and female agricultural plot managers in Mali. The Oaxaca–Blinder approach and the recentred influence function (RIF) decomposition methodology are applied to a nationally representative survey of Mali. The results show that the agricultural productivity of female plot managers is 20.18% lower than that of male plot managers. Additionally, while more than half (56%) of the agricultural productivity gap is influenced by female-specific structural disadvantages, 44% of the gap is due to an endowment effect. Socio-economic characteristics such as the educational level and age of the plot manager, environmental factors and agricultural production practices, i.e., the differential use of inputs (organic or inorganic fertiliser and improved seeds) and the use of hired female workers seem to affect the female-specific structural disadvantages. To reduce or close the gender productivity gap, the underlying causes of female-specific structural disadvantages must be addressed to enable female farmers to obtain the same returns as men. Traditional means of addressing the gender gap, such as providing education for women in rural areas and facilitating rural women’ access to extension services and improved seeds, can mitigate the endowment deficit. This paper highlights the need to develop a better understanding of the factors influencing the structural disadvantages faced by female farmers in Mali that could feed into the development of more effective policies to address the gender gap in agricultural productivity, improving productivity and gender equity and reducing poverty.