bluuebunny/crossref_metadata_2025_split huggingface dataset:
iCysMod: an integrative database for protein cysteine modifications in eukaryotes
Authors: Wang Panqin , Zhang Qingfeng , Li Shihua , Cheng Ben , Xue Han , Wei Zhen , Shao Tian , Liu Ze-Xian , Cheng Han , Wang Zhenlong 
Published: December 2020

Abstract
As important post-translational modifications, protein cysteine modifications (PCMs) occurring at cysteine thiol group play critical roles in the regulation of various biological processes in eukaryotes. Due to the rapid advancement of high-throughput proteomics technologies, a large number of PCM events have been identified but remain to be curated. Thus, an integrated resource of eukaryotic PCMs will be useful for the research community. In this work, we developed an integrative database for protein cysteine modifications in eukaryotes (iCysMod), which curated and hosted 108 030 PCM events for 85 747 experimentally identified sites on 31 483 proteins from 48 eukaryotes for 8 types of PCMs, including oxidation, S-nitrosylation (-SNO), S-glutathionylation (-SSG), disulfide formation (-SSR), S-sulfhydration (-SSH), S-sulfenylation (-SOH), S-sulfinylation (-SO2H) and S-palmitoylation (-S-palm). Then, browse and search options were provided for accessing the dataset, while various detailed information about the PCM events was well organized for visualization. With human dataset in iCysMod, the sequence features around the cysteine modification sites for each PCM type were analyzed, and the results indicated that various types of PCMs presented distinct sequence recognition preferences. Moreover, different PCMs can crosstalk with each other to synergistically orchestrate specific biological processes, and 37 841 PCM events involved in 119 types of PCM co-occurrences at the same cysteine residues were finally obtained. Taken together, we anticipate that the database of iCysMod would provide a useful resource for eukaryotic PCMs to facilitate related researches, while the online service is freely available at http://icysmod.omicsbio.info.
CorGAT: a tool for the functional annotation of SARS-CoV-2 genomes
Authors: Chiara Matteo , Zambelli Federico , Tangaro Marco Antonio , Mandreoli Pietro , Horner David S , Pesole Graziano 
Published: December 2020

Abstract

Summary
While over 200 000 genomic sequences are currently available through dedicated repositories, ad hoc methods for the functional annotation of SARS-CoV-2 genomes do not harness all currently available resources for the annotation of functionally relevant genomic sites. Here, we present CorGAT, a novel tool for the functional annotation of SARS-CoV-2 genomic variants. By comparisons with other state of the art methods we demonstrate that, by providing a more comprehensive and rich annotation, our method can facilitate the identification of evolutionary patterns in the genome of SARS-CoV-2.

Availabilityand implementation
Galaxy

http://corgat.cloud.ba.infn.it/galaxy; software: https://github.com/matteo14c/CorGAT/tree/Revision_V1; docker: https://hub.docker.com/r/laniakeacloud/galaxy_corgat.

Supplementary information
Supplementary data are available at Bioinformatics online.
IDDkin: network-based influence deep diffusion model for enhancing prediction of kinase inhibitors
Authors: Shen Cong , Luo Jiawei , Ouyang Wenjue , Ding Pingjian , Chen Xiangtao 
Published: December 2020

Abstract

Motivation
Protein kinases have been the focus of drug discovery research for many years because they play a causal role in many human diseases. Understanding the binding profile of kinase inhibitors is a prerequisite for drug discovery, and traditional methods of predicting kinase inhibitors are time-consuming and inefficient. Calculation-based predictive methods provide a relatively low-cost and high-efficiency approach to the rapid development and effective understanding of the binding profile of kinase inhibitors. Particularly, the continuous improvement of network pharmacology methods provides unprecedented opportunities for drug discovery, network-based computational methods could be employed to aggregate the effective information from heterogeneous sources, which have become a new way for predicting the binding profile of kinase inhibitors.

Results
In this study, we proposed a network-based influence deep diffusion model, named IDDkin, for enhancing the prediction of kinase inhibitors. IDDkin uses deep graph convolutional networks, graph attention networks and adaptive weighting methods to diffuse the effective information of heterogeneous networks. The updated kinase and compound representations are used to predict potential compound-kinase pairs. The experimental results show that the performance of IDDkin is superior to the comparison methods, including the state-of-the-art kinase inhibitor prediction method and the classic model widely used in relationship prediction. In experiments conducted to verify its generalizability and in case studies, the IDDkin model also shows excellent performance. All of these results demonstrate the powerful predictive ability of the IDDkin model in the field of kinase inhibitors.

Availability and implementation
Source code and data can be downloaded from https://github.com/CS-BIO/IDDkin.

Supplementary information
Supplementary data are available at Bioinformatics online.
Not out of the woods yet: genetic insights related to the recovery of the pine marten (Martes martes) in Ireland
Authors: O’Reilly Catherine , Turner Peter , O’Mahony Declan T , Twining Joshua P , Tosh David G , Smal Christopher , McAney Kate , Powell Ciara , Power John , O’Meara Denise B 
Published: December 2020

AbstractIn this study, the history of the pine marten (Martes martes) in Ireland is reviewed, revealing that the population has undergone several retractions and expansions over the last few hundred years. Here, we consider the genetic legacy of this flux in fortunes and its likely impacts upon the conservation and future recovery of the species. Using nuclear DNA markers (microsatellites), we found that the genetic diversity present in Ireland today is like that of other Irish carnivores, but there is evidence of a genetic bottleneck and low effective population size that might result in further reductions of diversity in the future. There is a lack of genetic structure, showing that the population has not been fragmented genetically, despite the low percentage of woodland in Ireland. We also reviewed the mitochondrial DNA diversity present in the Irish population and showed that there is only one contemporary and one extinct haplotype present; a reduced diversity relative to other Irish carnivores. The Irish haplotypes, both extant and extinct, are shared or are genetically similar to haplotypes commonly present in southern Europe today. We discuss the possibility of reinforcing the Irish population with animals from these sources to help supplement and maintain genetic diversity for future generations.
Surrogate post-coital testing for contraceptive efficacy against human sperm activity in the ovine vaginal model†
Authors: Zhu Yong , Saada Jamal , Bhawana Shrestha , Lai Sam , Villarreal Paula , Pyles Richard , Motamedi Massoud , Vargas Gracie , Moench Tom , Vincent Kathleen L 
Published: December 2020

Abstract
High unintended pregnancy rates are partially due to lack of effective nonhormonal contraceptives; development of safe, effective topical vaginal methods will address this need. Preclinical product safety and efficacy assessment requires in vivo testing in appropriate models. The sheep is a good model for the evaluation of vaginally delivered products due to its close similarities to humans. The study objective was to develop an ovine model for efficacy testing of female nonhormonal contraceptives that target human sperm. Fresh human semen was pooled from male volunteers. Nonpregnant female Merino sheep were treated with control or vaginal contraceptive product (IgG antibody with action against sperm or nonoxynol-9 [N9]). Pooled semen was added to the sheep vagina and mixed with product and vaginal secretions. Microscopic assessment of samples was performed immediately and progressive motility (PM) of sperm was compared between treatments. Cytokines CXCL8 and IL1B were assessed in vaginal fluid after instillation of human semen. No adverse reactions or elevations in proinflammatory cytokines occurred in response to human semen. N9 produced signs of acute cellular toxicity while there were no cellular changes after IgG treatment. N9 and IgG had dose-related effects with the highest dose achieving complete sperm immobilization (no sperm with PM). Surrogate post-coital testing of vaginally administered contraceptives that target human semen was developed in an ovine model established for vaginal product preclinical testing. This expanded model can aid the development of much needed nonhormonal topical vaginal contraceptives, providing opportunities for rapid iterative drug development prior to costly, time-intensive human testing.
A New Approach for Researching Victims: The ‘Strength-Growth-Resilience’ Framework
Authors: Green Simon , Calverley Adam , O’Leary Nicola 
Published: December 2020

AbstractThis paper proposes a new framework for researching victims that blends appreciative inquiry methods used by prison researchers with narrative interview methods used by desistance researchers to investigate victim ‘strength-growth-resilience’. Alongside established victimological concerns with the extent, distribution and treatment of crime victims, this framework offers an alternative lens that focuses on victim agency, identity and transformation. Building on the emancipatory project of feminist victimology, narrative and cultural criminology and an emerging narrative victimology the framework aims to provide a new conceptual reference point for victimological research. The article’s objectives are to demonstrate that this framework delivers a theoretically, empirically and ethically robust approach for exploring the mechanisms by which victims become resilient, and can even flourish, in the aftermath of criminal harm.
SNAIL regulates gastric carcinogenesis through CCN3 and NEFL
Authors: Chen Ru , Masuo Kenji , Yogo Akitada , Yokoyama Shoko , Sugiyama Aiko , Seno Hiroshi , Yoshizawa Akihiko , Takaishi Shigeo 
Published: December 2020

Abstract
Among cancer cells, there are specific cell populations of whose activities are comparable to those of stem cells in normal tissues, and for whom the levels of cell dedifferentiation are reported to correlate with poor prognosis. Information concerning the mechanisms that modulate the stemness like traits of cancer cells is limited. Therefore, we examined five gastric cancer cell lines and isolated gastric oncospheres from three gastric cancer cell lines. The gastric cancer cells that expanded in the spheres expressed relatively elevated proportion of CD44, which is a marker of gastric cancer stem cells (CSCs), and displayed many properties of CSCs, for example: chemoresistance, tumorigenicity and epithelial–mesenchymal transition (EMT) acquisition. SNAIL, which is a key factor in EMT, was highly expressed in the gastric spheres. Microarray analysis in gastric cancer cell line HGC27 showed that CCN3 and NEFL displayed the greatest differential expression by knocking down of SNAIL; the former was upregulated and the latter downregulated, respectively. Downregulation of CCN3 and upregulation of NEFL gene expression impaired the SNAIL-dependent EMT activity: high tumorigenicity, and chemoresistance in gastric cancer cells. Thus, approach that disrupts SNAIL/CCN3/NEFL axis may be credible in inhibiting gastric cancer development.
Three-Year Reliability of MEG Visual and Somatosensory Responses
Authors: McCusker Marie C , Lew Brandon J , Wilson Tony W 
Published: December 2020

AbstractA major goal of many translational neuroimaging studies is the identification of biomarkers of disease. However, a prerequisite for any such biomarker is robust reliability, which for magnetoencephalography (MEG) and many other imaging modalities has not been established. In this study, we examined the reliability of visual (Experiment 1) and somatosensory gating (Experiment 2) responses in 19 healthy adults who repeated these experiments for three visits spaced 18 months apart. Visual oscillatory and somatosensory oscillatory and evoked responses were imaged, and intraclass correlation coefficients (ICC) were computed to examine the long-term reliability of these responses. In Experiment 1, ICCs showed good reliability for visual theta and alpha responses in occipital cortices, but poor reliability for gamma responses. In Experiment 2, the time series of somatosensory gamma and evoked responses in the contralateral somatosensory cortex showed good reliability. Finally, analyses of spontaneous baseline activity indicated excellent reliability for occipital alpha, moderate reliability for occipital theta, and poor reliability for visual/somatosensory gamma activity. Overall, MEG responses to visual and somatosensory stimuli show a high degree of reliability across 3 years and therefore may be stable indicators of sensory processing long term and thereby of potential interest as biomarkers of disease.
PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain
Authors: Smart Kelly , Naganawa Mika , Baldassarri Stephen R , Nabulsi Nabeel , Ropchan Jim , Najafzadeh Soheila , Gao Hong , Navarro Antonio , Barth Vanessa , Esterlis Irina , Cosgrove Kelly P , Huang Yiyun , Carson Richard E , Hillmer Ansel T 
Published: December 2020

Abstract
Acetylcholine (ACh) has distinct functional roles in striatum compared with cortex, and imbalance between these systems may contribute to neuropsychiatric disease. Preclinical studies indicate markedly higher ACh concentrations in the striatum. The goal of this work was to leverage positron emission tomography (PET) imaging estimates of drug occupancy at cholinergic receptors to explore ACh variation across the human brain, because these measures can be influenced by competition with endogenous neurotransmitter. PET scans were analyzed from healthy human volunteers (n = 4) and nonhuman primates (n = 2) scanned with the M1-selective radiotracer [11C]LSN3172176 in the presence of muscarinic antagonist scopolamine, and human volunteers (n = 10) scanned with the α4β2* nicotinic ligand (−)-[18F]flubatine during nicotine challenge. In all cases, occupancy estimates within striatal regions were consistently lower (M1/scopolamine human scans, 31 ± 3.4% occupancy in striatum, 43 ± 2.9% in extrastriatal regions, p = 0.0094; nonhuman primate scans, 42 ± 26% vs. 69 ± 28%, p &lt; 0.0001; α4β2*/nicotine scans, 67 ± 15% vs. 74 ± 16%, p = 0.0065), indicating higher striatal ACh concentration. Subject-level measures of these concentration differences were estimated, and whole-brain images of regional ACh concentration gradients were generated. These results constitute the first in vivo estimates of regional variation in ACh concentration in the living brain and offer a novel experimental method to assess potential ACh imbalances in clinical populations.
Simple and Rapid LC–MS/MS Methods for Quantifying Catabolites of Antibody-Drug Conjugates with SMCC Linker
Authors: Li Li , Wang Chanrui , Wu Yijue , Dong Lihou , Chen Fang , Dong Kelly , Song Haifeng 
Published: December 2020

Abstract
The stability and exposure of toxin-related catabolites in system circulation contributes to the evaluation of the stability, targeted delivery and off-target toxicity for antibody–drug conjugates (ADC) at different stages during drug development. In this study, simple and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods for determination catabolites of Mertansine (DM1), MCC-DM1 and Lys-MCC-DM1 in cynomolgus serum have been developed. The serum samples are processed by protein precipitation. The LC–MS/MS methods are applied on a Phenomenex C8 column (50 × 2.0 mm, 5 μm) with gradient elution with water–formic acid 0.1% (A) and acetonitrile-formic acid 0.1% (B) at a flow rate of 0.5 mL/min. The analytical run time is only 4.0 min and the calibration ranges of the standard curve are 0.500–200 ng/mL for DM1, 1.00–500 ng/mL for MCC-DM1 and 2.00–1000 ng/mL for Lys-MCC-DM1. Intra- and inter-day precision of low, middle and high quality controls was &lt;15%, and accuracy was 99.2–110.9%. The methods were successfully applied to evaluate three catabolites of novel ADCs with N-succinimidyl-4-(N-maleimidomethyl)-cyclohexane-1-carboxylate linker in vitro and in vivo studies.
Validation of VIRSTA and Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT) Scores to Determine the Priority of Echocardiography in Patients With Staphylococcus aureus Bacteremia
Authors: Peinado-Acevedo Juan Sebastián , Hurtado-Guerra Juan José , Hincapié Carolina , Mesa-Abad Juanita , Uribe-Delgado José Roberto , Giraldo-Ramírez Santiago , Lengerke-Diaz Paula A , Jaimes Fabián 
Published: December 2020

Abstract

Background
Infective endocarditis (IE) secondary to Staphylococcus aureus bacteremia (SAB) has high morbidity and mortality. The systematic use of echocardiography in SAB is controversial. We aimed to validate VIRSTA and Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT) scores for predicting the risk of IE in Colombian patients with SAB and, consequently, to determine the need for echocardiography.

Methods
Cohort of patients hospitalized with SAB in 2 high complexity institutions in Medellin, Colombia, between 2012 and 2018. The diagnosis of IE was established based on the modified Duke criteria. The VIRSTA and PREDICT scores were calculated from the clinical records, and their operational performance was calculated.

Results
The final analysis included 922 patients, 62 (6.7%) of whom were diagnosed with IE. The frequency of IE in patients with a negative VIRSTA scale was 0.44% (2/454). The frequency of IE in patients with a negative PREDICT scale on day 5 was 4.8% (30/622). The sensitivity and negative predictive value (NPV) of the VIRSTA scale was 96.7% and 99.5%, respectively. For the PREDICT scale on day 5, the sensitivity and NPV were 51.6% and 95.1%, respectively. The discrimination, given by the area under the receiver operating characteristic curve, was 0.86 for VIRSTA and 0.64 for PREDICT.

Conclusions
In patients with negative VIRSTA, screening echocardiography may be unnecessary because of the low frequency of IE. In PREDICT-negative patients, despite the low frequency of IE, it is not safe to omit echocardiography.
Understanding Drivers of Coronavirus Disease 2019 (COVID-19) Racial Disparities: A Population-Level Analysis of COVID-19 Testing Among Black and White Populations
Authors: Mody Aaloke , Pfeifauf Kristin , Bradley Cory , Fox Branson , Hlatshwayo Matifadza G , Ross Will , Sanders-Thompson Vetta , Joynt Maddox Karen , Reidhead Mat , Schootman Mario , Powderly William G , Geng Elvin H 
Published: December 2020

Abstract

Background
Disparities in coronavirus disease 2019 (COVID-19) testing—the pandemic’s most critical but limited resource—may be an important but modifiable driver of COVID-19 inequities.

Methods
We analyzed data from the Missouri State Department of Health and Senior Services on all COVID-19 tests conducted in the St Louis and Kansas City regions. We adapted a well-established tool for measuring inequity—the Lorenz curve—to compare COVID-19 testing rates per diagnosed case among Black and White populations.

Results
Between 14/3/2020 and 15/9/2020, 606 725 and 328 204 COVID-19 tests were conducted in the St Louis and Kansas City regions, respectively. Over time, Black individuals consistently had approximately half the rate of testing per case than White individuals. In the early period (14/3/2020 to 15/6/2020), zip codes in the lowest quartile of testing rates accounted for only 12.1% and 8.8% of all tests in the St Louis and Kansas City regions, respectively, even though they accounted for 25% of all cases in each region. These zip codes had higher proportions of residents who were Black, without insurance, and with lower median incomes. These disparities were reduced but still persisted during later phases of the pandemic (16/6/2020 to 15/9/2020). Last, even within the same zip code, Black residents had lower rates of tests per case than White residents.

Conclusions
Black populations had consistently lower COVID-19 testing rates per diagnosed case than White populations in 2 Missouri regions. Public health strategies should proactively focus on addressing equity gaps in COVID-19 testing to improve equity of the overall response.
Stress in Parents of School-Age Children and Adolescents With Cochlear Implants
Authors: Wiseman Kathryn B , Warner-Czyz Andrea D , Nelson Jackie A 
Published: December 2020

Abstract
Parents of children with cochlear implants (CIs) face unique challenges in caring for their child, potentially fostering parental stress. Most studies of stress in parents of CI users do not examine stress specific to having a deaf and hard-of-hearing (DHH) child. This study compares general and condition-specific stress (via the Family Stress Scale) in 31 parents of CI users (8–16 years) to previously published samples of DHH children, and it examines child- and CI-related factors associated with parental stress. Parents of modern-day CI users reported significantly lower stress than parents of children using older-generation CI technology and similar levels of overall stress to parents of young children preimplantation. However, significant item-level differences emerged (e.g., communication, device management) pre- versus postimplant. Child temperament significantly predicted parental stress after controlling for other variables. Intervention strategies for children with CIs should engage a family systems approach to reduce parental stress and better support the child.
Food Additive Emulsifiers and Their Impact on Gut Microbiome, Permeability, and Inflammation: Mechanistic Insights in Inflammatory Bowel Disease
Authors: Bancil Aaron S , Sandall Alicia M , Rossi Megan , Chassaing Benoit , Lindsay James O , Whelan Kevin 
Published: December 2020

Abstract
The global burden of inflammatory bowel disease [IBD] has increased over the 21st century. Despite multiple studies investigating the pathogenesis of IBD, the causative mechanisms pertaining to its increased prevalence remain unclear. There is growing evidence that aspects of a ‘Western diet’ increase the risk of developing IBD. More recently, evidence implicating dietary emulsifiers has accumulated, with ecological studies showing a positive correlation between inflammatory bowel disease and emulsifier consumption. Further to these, cell and animal studies have demonstrated plausible mechanisms by which dietary emulsifiers may contribute to IBD pathogenesis through mechanisms including: promotion of pro-inflammatory intestinal microbiota; disruption of mucus architecture; increased intestinal permeability; activation of inflammatory pathways; and disruption of the cell cycle. This review critically analyses the current evidence for these mechanisms that may be of pathological relevance to IBD, evaluates recent dietary trials, acknowledges the challenges of dietary intervention studies, and gives an overview of ongoing and future clinical trials in this important area.