bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drugmonizome and Drugmonizome-ML: integration and abstraction of small molecule attributes for drug enrichment analysis and machine learning
Authors: Kropiwnicki Eryk , Evangelista John E , Stein Daniel J , Clarke Daniel J B , Lachmann Alexander , Kuleshov Maxim V , Jeon Minji , Jagodnik Kathleen M , Ma’ayan Avi 
Published: March 2021

AbstractUnderstanding the underlying molecular and structural similarities between seemingly heterogeneous sets of drugs can aid in identifying drug repurposing opportunities and assist in the discovery of novel properties of preclinical small molecules. A wealth of information about drug and small molecule structure, targets, indications and side effects; induced gene expression signatures; and other attributes are publicly available through web-based tools, databases and repositories. By processing, abstracting and aggregating information from these resources into drug set libraries, knowledge about novel properties of drugs and small molecules can be systematically imputed with machine learning. In addition, drug set libraries can be used as the underlying database for drug set enrichment analysis. Here, we present Drugmonizome, a database with a search engine for querying annotated sets of drugs and small molecules for performing drug set enrichment analysis. Utilizing the data within Drugmonizome, we also developed Drugmonizome-ML. Drugmonizome-ML enables users to construct customized machine learning pipelines using the drug set libraries from Drugmonizome. To demonstrate the utility of Drugmonizome, drug sets from 12 independent SARS-CoV-2 in vitro screens were subjected to consensus enrichment analysis. Despite the low overlap among these 12 independent in vitro screens, we identified common biological processes critical for blocking viral replication. To demonstrate Drugmonizome-ML, we constructed a machine learning pipeline to predict whether approved and preclinical drugs may induce peripheral neuropathy as a potential side effect. Overall, the Drugmonizome and Drugmonizome-ML resources provide rich and diverse knowledge about drugs and small molecules for direct systems pharmacology applications.Database URL: https://maayanlab.cloud/drugmonizome/.
CA125 but not NT-proBNP predicts the presence of a congestive intrarenal venous flow in patients with acute heart failure
Authors: Núñez-Marín Gonzalo , de la Espriella Rafael , Santas Enrique , Lorenzo Miguel , Miñana Gema , Núñez Eduardo , Bodí Vicent , González Miguel , Górriz José Luis , Bonanad Clara , Sanchis Juan , Bayés-Genís Antoni , Núñez Julio 
Published: March 2021

Abstract

Background
Intrarenal venous flow (IRVF) measured by Doppler ultrasound has gained interest as a potential surrogate marker of renal congestion and adverse outcomes in heart failure. In this work, we aimed to determine if antigen carbohydrate 125 (CA125) and plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with congestive IRVF patterns (i.e., biphasic and monophasic) in acute heart failure (AHF).

Methods and results
We prospectively enrolled a consecutive cohort of 70 patients hospitalized for AHF. Renal Doppler ultrasound was assessed within the first 24-h of hospital admission. The mean age of the sample was 73.5 ± 12.3 years; 47.1% were female, and 42.9% exhibited heart failure with preserved ejection fraction. The median (interquartile range) for NT-proBNP and CA125 were 6149 (3604–12 330) pg/mL and 64 (37–122) U/mL, respectively. The diagnostic performance of both exposures for identifying congestive IRVF patterns was tested using the receiving operating curve (ROC). The cut-off for CA125 of 63.5 U/mL showed a sensibility and specificity of 67% and 74% and an area under the ROC curve of 0.71. After multivariate adjustment, CA125 remained non-linearly and positively associated with congestive IRVF (P-value = 0.008) and emerged as the most important covariate explaining the variability of the model (R2: 47.5%). Under the same multivariate setting, NT-proBNP did not show to be associated with congestive IRVF patterns (P-value = 0.847).

Conclusions
CA125 and not NT-proBNP is a useful marker for identifying patients with AHF and congestive IRVF patterns.
Machine learning phenotyping of scarred myocardium from cine in hypertrophic cardiomyopathy
Authors: Mancio Jennifer , Pashakhanloo Farhad , El-Rewaidy Hossam , Jang Jihye , Joshi Gargi , Csecs Ibolya , Ngo Long , Rowin Ethan , Manning Warren , Maron Martin , Nezafat Reza 
Published: March 2021

Abstract

Aims
Cardiovascular magnetic resonance (CMR) with late-gadolinium enhancement (LGE) is increasingly being used in hypertrophic cardiomyopathy (HCM) for diagnosis, risk stratification, and monitoring. However, recent data demonstrating brain gadolinium deposits have raised safety concerns. We developed and validated a machine-learning (ML) method that incorporates features extracted from cine to identify HCM patients without fibrosis in whom gadolinium can be avoided.

Methods and results
An XGBoost ML model was developed using regional wall thickness and thickening, and radiomic features of myocardial signal intensity, texture, size, and shape from cine. A CMR dataset containing 1099 HCM patients collected using 1.5T CMR scanners from different vendors and centres was used for model development (n=882) and validation (n=217). Among the 2613 radiomic features, we identified 7 features that provided best discrimination between +LGE and −LGE using 10-fold stratified cross-validation in the development cohort. Subsequently, an XGBoost model was developed using these radiomic features, regional wall thickness and thickening. In the independent validation cohort, the ML model yielded an area under the curve of 0.83 (95% CI: 0.77–0.89), sensitivity of 91%, specificity of 62%, F1-score of 77%, true negatives rate (TNR) of 34%, and negative predictive value (NPV) of 89%. Optimization for sensitivity provided sensitivity of 96%, F2-score of 83%, TNR of 19% and NPV of 91%; false negatives halved from 4% to 2%.

Conclusion
An ML model incorporating novel radiomic markers of myocardium from cine can rule-out myocardial fibrosis in one-third of HCM patients referred for CMR reducing unnecessary gadolinium administration.
A chromosome-level genome of the spider Trichonephila antipodiana reveals the genetic basis of its polyphagy and evidence of an ancient whole-genome duplication event
Authors: Fan Zheng , Yuan Tao , Liu Piao , Wang Lu-Yu , Jin Jian-Feng , Zhang Feng , Zhang Zhi-Sheng 
Published: March 2021

Abstract

Background
The spider Trichonephila antipodiana (Araneidae), commonly known as the batik golden web spider, preys on arthropods with body sizes ranging from ∼2 mm in length to insects larger than itself (&gt;20‒50 mm), indicating its polyphagy and strong dietary detoxification abilities. Although it has been reported that an ancient whole-genome duplication event occurred in spiders, lack of a high-quality genome has limited characterization of this event.

Results
We present a chromosome-level T. antipodiana genome constructed on the basis of PacBio and Hi-C sequencing. The assembled genome is 2.29 Gb in size with a scaffold N50 of 172.89 Mb. Hi-C scaffolding assigned 98.5% of the bases to 13 pseudo-chromosomes, and BUSCO completeness analysis revealed that the assembly included 94.8% of the complete arthropod universal single-copy orthologs (n = 1,066). Repetitive elements account for 59.21% of the genome. We predicted 19,001 protein-coding genes, of which 96.78% were supported by transcriptome-based evidence and 96.32% matched protein records in the UniProt database. The genome also shows substantial expansions in several detoxification-associated gene families, including cytochrome P450 mono-oxygenases, carboxyl/cholinesterases, glutathione-S-transferases, and ATP-binding cassette transporters, reflecting the possible genomic basis of polyphagy. Further analysis of the T. antipodiana genome architecture reveals an ancient whole-genome duplication event, based on 2 lines of evidence: (i) large-scale duplications from inter-chromosome synteny analysis and (ii) duplicated clusters of Hox genes.

Conclusions
The high-quality T. antipodiana genome represents a valuable resource for spider research and provides insights into this species’ adaptation to the environment.
Rapid development of cloud-native intelligent data pipelines for scientific data streams using the HASTE Toolkit
Authors: Blamey Ben , Toor Salman , Dahlö Martin , Wieslander Håkan , Harrison Philip J , Sintorn Ida-Maria , Sabirsh Alan , Wählby Carolina , Spjuth Ola , Hellander Andreas 
Published: March 2021

Abstract

Background
Large streamed datasets, characteristic of life science applications, are often resource-intensive to process, transport and store. We propose a pipeline model, a design pattern for scientific pipelines, where an incoming stream of scientific data is organized into a tiered or ordered “data hierarchy". We introduce the HASTE Toolkit, a proof-of-concept cloud-native software toolkit based on this pipeline model, to partition and prioritize data streams to optimize use of limited computing resources.

Findings
In our pipeline model, an “interestingness function” assigns an interestingness score to data objects in the stream, inducing a data hierarchy. From this score, a “policy” guides decisions on how to prioritize computational resource use for a given object. The HASTE Toolkit is a collection of tools to adopt this approach. We evaluate with 2 microscopy imaging case studies. The first is a high content screening experiment, where images are analyzed in an on-premise container cloud to prioritize storage and subsequent computation. The second considers edge processing of images for upload into the public cloud for real-time control of a transmission electron microscope.

Conclusions
Through our evaluation, we created smart data pipelines capable of effective use of storage, compute, and network resources, enabling more efficient data-intensive experiments. We note a beneficial separation between scientific concerns of data priority, and the implementation of this behaviour for different resources in different deployment contexts. The toolkit allows intelligent prioritization to be `bolted on' to new and existing systems – and is intended for use with a range of technologies in different deployment scenarios.
Runs of homozygosity are associated with staging of periodontitis in isolated populations
Authors: Mezzavilla Massimo , Navarra Chiara Ottavia , Di Lenarda Roberto , Gasparini Paolo , Bevilacqua Lorenzo , Robino Antonietta 
Published: March 2021

AbstractPeriodontitis is a common inflammatory disease characterized by a complex etiology, which is the result of a combination of genetic and environmental factors. Genetic variants linked to the periodontitis disease were already investigated, however, little was known regarding the severity of this disease. Recently, long runs of homozygosity (ROH) were associated with several multifactorial diseases. Therefore, in our work, we tried to assess the role of ROH and periodontitis status. We found an association between the excess of homozygosity owing to ROH and staging of periodontitis. More in detail, the total amount of homozygosity owing to ROH is positively associated with an increased severity of periodontitis (P = 0.0001). Regression tree analysis showed the impact of ROH burden in discriminating individuals with mild periodontitis stages I and II and periodontitis stages III and IV (P &lt; 0.001). Furthermore, ROH mapping highlights several regions associated with a severe status of periodontitis (odds ratio &gt; 1). Among them, we found a total of 33 genes. Interestingly, some of these genes were previously associated with granulocyte or platelet measures, both linked to the onset and the progression of periodontal disease. Our results suggest the not only single variants association test could help to risk assessment but even individual genomic features; furthermore, our ROH mapping highlighted the possible role of multiple genes in periodontal development.
Learning by doing: collaborative conceptual modelling as a path forward in ecosystem-based management
Authors: DePiper Geret , Gaichas Sarah , Muffley Brandon , Ardini Greg , Brust Jeffrey , Coakley Jessica , Dancy Kiley , Elliott G Warren , Leaning Dustin C , Lipton Douglas , McNamee Jason , Perretti Charles , Rootes-Murdy Kirby , Wilberg Michael J 
Published: March 2021

AbstractManagers, stakeholders, and scientists recognize the need for collaborative, transparent, integrated approaches to complex resource management issues, and frameworks to address these complex issues are developing. Through the course of 2019, the Mid-Atlantic Fishery Management Council developed a conceptual model of ecosystem linkages and risks for summer flounder, a species of recreational and commercial fisheries importance. The proximal aim of the model was to develop a list of integrated management questions that could be refined and addressed through a future quantitative management strategy evaluation. As such, this conceptual model served as a scoping tool. However, the true value of the conceptual model lays elsewhere: familiarizing resource managers historically focused on single-species management with the potential utility of an ecosystem approach to management. This paper details the goals and development of the conceptual model and situates this process in the broader context of best practices for collaborative open science and scientific reproducibility. Further, it highlights a successful path by which the shift towards ecosystem-based management can be actuated.
Pricing formulas for perpetual American options with general payoffs
Authors: Rodrigo Marianito R 
Published: March 2021

Abstract
An American option gives the holder the right, but not the obligation, to buy/sell an underlying asset from/to the writer at an agreed strike price at any time on or before the expiry date. Options are mainly used for speculation and hedging. The pricing of options is a fundamental problem in mathematical finance. One of the attractions of options is that they can be used to construct a wide range of trading strategies characterized by different payoff functions. As a preliminary step in the valuation of American options for a variety of trading strategies, in this article the pricing of perpetual American options with general payoffs is considered, where the perpetual American call and put are special cases. Four broad classes of payoff functions are identified for which analytical pricing formulas can be derived by utilizing a Mellin transform technique and an optimization procedure. Depending on the class of payoff functions considered, free boundary problems with one or two boundaries are obtained. Illustrative examples are provided and benchmarked numerically with the binomial method. The characterization of different payoffs for perpetual American options considered in this article will be instrumental in the identification and pricing of new free boundary problems for (non-perpetual) American-style financial derivatives.
Integrating oscillator-based circadian clocks with crop growth simulations
Authors: Lochocki Edward B , McGrath Justin M 
Published: March 2021

Abstract
Circadian rhythms play critical roles in plant physiology, growth, development and survival, and their inclusion in crop growth models is essential for high-fidelity results, especially when considering climate change. Commonly used circadian clock models are often inflexible or result in complex outputs, limiting their use in general simulations. Here we present a new circadian clock model based on mathematical oscillators that easily adapts to different environmental conditions and produces intuitive outputs. We then demonstrate its utility as an input to Glycine max development models. This oscillator clock model has the power to simplify the inclusion of circadian cycles and photoperiodic effects in crop growth models and to unify experimental data from field and controlled environment observations.
Discovery of New Genera Challenges the Subtribal Classification of Tok-Tok Beetles (Coleoptera: Tenebrionidae: Sepidiini)
Authors: Gearner Olivia M , Kamiński Marcin J , Kanda Kojun , Swichtenberg Kali , Smith Aaron D 
Published: March 2021

Abstract
Sepidiini is a speciose tribe of desert-inhabiting darkling beetles, which contains a number of poorly defined taxonomic groups and is in need of revision at all taxonomic levels. In this study, two previously unrecognized lineages were discovered, based on morphological traits, among the extremely speciose genera Psammodes Kirby, 1819 (164 species and subspecies) and Ocnodes Fåhraeus, 1870 (144 species and subspecies), namely the Psammodes spinosus species-group and Ocnodes humeralis species-group. In order to test their phylogenetic placement, a phylogeny of the tribe was reconstructed based on analyses of DNA sequences from six nonoverlapping genetic loci (CAD, wg, COI JP, COI BC, COII, and 28S) using Bayesian and maximum likelihood inference methods. The aforementioned, morphologically defined, species-groups were recovered as distinct and well-supported lineages within Molurina + Phanerotomeina and are interpreted as independent genera, respectively, Tibiocnodes Gearner & Kamiński gen. nov. and Tuberocnodes Gearner & Kamiński gen. nov. A new species, Tuberocnodes synhimboides Gearner & Kamiński sp. nov., is also described. Furthermore, as the recovered phylogenetic placement of Tibiocnodes and Tuberocnodes undermines the monophyly of Molurina and Phanerotomeina, an analysis of the available diagnostic characters for those subtribes is also performed. As a consequence, Phanerotomeina is considered as a synonym of the newly redefined Molurina sens. nov. Finally, spectrograms of vibrations produced by substrate tapping of two Molurina species, Toktokkus vialis (Burchell, 1822) and T. synhimboides, are presented.
Novel photochromic inhibitor for mitotic kinesin Eg5 which forms multiple isomerization states
Authors: Alrazi Islam Md , Sadakane Kei , Maruta Shinsaku 
Published: March 2021

Abstract
The mitotic kinesin Eg5 is a plus-end directed homotetrameric molecular motor essential for the formation of bipolar spindles during cell division. Kinesin Eg5 is overexpressed in cancer cells and hence considered as a target for cancer therapy; the inhibitors specific for Eg5 have been developed as anticancer drugs. In this study, we synthesized a novel functional photoresponsive inhibitor composed of spiropyran and azobenzene derivatives to control Eg5 function with multistage inhibitory activity accompanied by the formation of different isomerization states. The photochromic inhibitor spiropyran-sulfo-azobenzene (SPSAB) exhibited three isomerization states: spiro (SP)-trans, merocyanine (MC)-cis and MC-trans, upon exposure to visible light, ultraviolet and in the dark, respectively. SPSAB-induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with photoisomerization among the three states. Among the three isomerization states of SPSAB, the SP-trans isomer showed potent inhibitory activity at an IC50 value of 30 µM in the basal ATPase assay. MC-trans and MC-cis exhibited less inhibitory activity at IC50 values of 38 and 86 µM, respectively. The results demonstrated that the novel photochromic inhibitor enabled precise control of Eg5 function at three different levels using light irradiation.
The 2019 International Society of Hip Preservation (ISHA) physiotherapy agreement on assessment and treatment of femoroacetabular impingement syndrome (FAIS): an international consensus statement
Authors: Takla Amir , O'Donnell John , Voight Michael , Byrd Thomas , Dienst Michael , Martin Rob Roy , Philippon Marc J , Enseki Keelan , Andrade Tony , Safran Marc , Christoforetti John Joseph , Martin Hal , Grant Louise , Campbell Ashley , Ryan Mark , Tyler Tim , McGovern Ryan P , Bizzini Mario , Kohlrieser David 
Published: March 2021

Abstract
The 2019 International Society of Hip Preservation (ISHA) physiotherapy agreement on femoroacetabular impingement syndrome (FAIS) was intended to build an international physiotherapy consensus on the assessment, non-surgical physiotherapy treatment, pre-/post-operative management, and return to sport decisions for those patients with FAIS. The panel consisted of 11 physiotherapists and 8 orthopaedic surgeons. There is limited evidence regarding the use of physiotherapy in the overall management of those with FAIS. Therefore, a group of ISHA member physiotherapists, who treat large numbers of FAIS patients and have extensive experience in this area, constructed a consensus statement to guide physiotherapy-related decisions in the overall management of those with FAIS. The consensus was conducted using a modified Delphi technique. Six major topics were the focus of the consensus statement: (i) hip assessment, (ii) non-surgical physiotherapy management, (iii) pre-habilitation prior to hip arthroscopy, (iv) post-operative physiotherapy rehabilitation, (v) stages of post-operative rehabilitation and (vi) return to sports criteria/guidelines after surgery.
Barriers and Facilitators to Adolescent and Young Adult Cancer Trial Enrollment: NCORP Site Perspectives
Authors: Siembida Elizabeth J , Loomans-Kropp Holli A , Tami-Maury Irene , Freyer David R , Sung Lillian , Crosswell Howland E , Pollock Brad H , Roth Michael E 
Published: March 2021

Abstract

Background
Although it is well documented that adolescents and young adults (AYAs) with cancer have low participation in cancer clinical trials (CCTs), the underlying reasons are not well understood. We used the National Cancer Institute Community Oncology Research Program (NCORP) network to identify barriers and facilitators to AYA CCT enrollment, and strategies to improve enrollment at community-based and minority and/or underserved sites.

Methods
We performed one-on-one semistructured qualitative interviews with stakeholders (NCORP site principle investigators, NCORP administrators, physicians involved in enrollment, lead clinical research associates or clinical research nurses, nurse navigators, regulatory research associates, patient advocates) in the AYA CCT enrollment process. NCORP sites that included high and low AYA–enrolling affiliate sites and were diverse in geography and department representation (eg, pediatrics, medical oncology) were invited to participate. All interviews were recorded and transcribed. Themes related to barriers and facilitators and strategies to improve enrollment were identified.

Results
We conducted 43 interviews across 10 NCORP sites. Eleven barriers and 13 facilitators to AYA enrollment were identified. Main barriers included perceived limited trial availability and eligibility, physician gatekeeping, lack of provider and research staff time, and financial constraints. Main facilitators and strategies to improve AYA enrollment included having a patient screening process, physician endorsement of trials, an “AYA champion” on site, and strong communication between medical and pediatric oncology.

Conclusions
Stakeholders identified several opportunities to address barriers contributing to low AYA CCT enrollment at community-based and minority and/or underserved sites. Results of this study will inform development and implementation of targeted interventions to increase AYA CCT enrollment.
Vibration of rotating circular cylindrical shells with distributed springs
Authors: Yang Fuchun , Jiang Xiaofeng , Du Fuxin 
Published: March 2021

Abstract
Free vibrations of rotating cylindrical shells with distributed springs were studied. Based on the Flügge shell theory, the governing equations of rotating cylindrical shells with distributed springs were derived under typical boundary conditions. Multicomponent modal functions were used to satisfy the distributed springs around the circumference. The natural responses were analyzed using the Galerkin method. The effects of parameters, rotation speed, stiffness, and ratios of thickness/radius and length/radius, on natural response were also examined.