bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifactorial feature extraction and site prognosis model for protein methylation data
Authors: Khandelwal Monika , Kumar Rout Ranjeet , Umer Saiyed , Mallik Saurav , Li Aimin 
Published: October 2022

Abstract
Integrated studies (multi-omics studies) comprising genetic, proteomic and epigenetic data analyses have become an emerging topic in biomedical research. Protein methylation is a posttranslational modification that plays an essential role in various cellular activities. The prediction of methylation sites (arginine and lysine) is vital to understand the molecular processes of protein methylation. However, current experimental techniques used for methylation site predictions are tedious and expensive. Hence, computational techniques for predicting methylation sites in proteins are necessary. For predicting methylation sites, various computational methods have been proposed in recent years. Most existing methods require structural and evolutionary information for retrieving features, acquiring this information is not always convenient. Thus, we proposed a novel method, called multi-factorial feature extraction and site prognosis model (MufeSPM), for the prediction of protein methylation sites based on information theory features (Renyi, Shannon, Havrda–Charvat and Arimoto entropy), amino acid composition and physicochemical properties acquired from protein methylation data. A random forest algorithm was used to predict methylation sites in protein sequences. This paper also studied the impact of different features and classifiers on arginine and lysine methylation data sets. For the R methylation data set, MufeSPM yielded 82.45%($\pm $ 3.47) accuracy, and for the K methylation data set, it provided an average accuracy of 71.94%($\pm $ 2.12). Additionally, the area under the receiver operating characteristic curve for different classifiers in predicting methylation site was provided. The experimental results signify that MufeSPM performs better than the state-of-the-art predictors.
Towards future directions in data-integrative supervised prediction of human aging-related genes
Authors: Li Qi , Newaz Khalique , Milenković Tijana 
Published: October 2022

AbstractMotivationIdentification of human genes involved in the aging process is critical due to the incidence of many diseases with age. A state-of-the-art approach for this purpose infers a weighted dynamic aging-specific subnetwork by mapping gene expression (GE) levels at different ages onto the protein–protein interaction network (PPIN). Then, it analyzes this subnetwork in a supervised manner by training a predictive model to learn how network topologies of known aging- versus non-aging-related genes change across ages. Finally, it uses the trained model to predict novel aging-related gene candidates. However, the best current subnetwork resulting from this approach still yields suboptimal prediction accuracy. This could be because it was inferred using outdated GE and PPIN data. Here, we evaluate whether analyzing a weighted dynamic aging-specific subnetwork inferred from newer GE and PPIN data improves prediction accuracy upon analyzing the best current subnetwork inferred from outdated data.ResultsUnexpectedly, we find that not to be the case. To understand this, we perform aging-related pathway and Gene Ontology term enrichment analyses. We find that the suboptimal prediction accuracy, regardless of which GE or PPIN data is used, may be caused by the current knowledge about which genes are aging-related being incomplete, or by the current methods for inferring or analyzing an aging-specific subnetwork being unable to capture all of the aging-related knowledge. These findings can potentially guide future directions towards improving supervised prediction of aging-related genes via -omics data integration.Availability and implementationAll data and code are available at zenodo, DOI: 10.5281/zenodo.6995045.Supplementary informationSupplementary data are available at Bioinformatics Advances online.
GAVISUNK: genome assembly validation via inter-SUNK distances in Oxford Nanopore reads
Authors: Dishuck Philip C , Rozanski Allison N , Logsdon Glennis A , Porubsky David , Eichler Evan E 
Published: October 2022

Abstract

Motivation
Highly contiguous de novo phased diploid genome assemblies are now feasible for large numbers of species and individuals. Methods are needed to validate assembly accuracy and detect misassemblies with orthologous sequencing data to allow for confident downstream analyses.

Results
We developed GAVISUNK, an open-source pipeline that detects misassemblies and produces a set of reliable regions genome-wide by assessing concordance of distances between unique k-mers in Pacific Biosciences high-fidelity assemblies and raw Oxford Nanopore Technologies reads.

Availability and implementation
GAVISUNK is available at https://github.com/pdishuck/GAVISUNK.

Supplementary information
Supplementary data are available at Bioinformatics online.
Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal
Authors: Benatar Michael , Wuu Joanne , Turner Martin R 
Published: October 2022

Abstract
Interest in amyotrophic lateral sclerosis (ALS) biomarkers has grown exponentially over the course of the last 25 years, with great hope that they might serve as tools to facilitate the development of meaningful therapies for this otherwise inexorably progressive and invariably fatal disease. Effective use of biomarkers, however, requires an understanding of what it means for them to be ‘fit-for-purpose’ as well as an appreciation of the nuances of the clinical context(s) in which they will be applied.
Neurofilament light chain (NfL) has emerged as a leading candidate with enormous potential to aid ALS therapy development; it is, however, also profoundly misunderstood. Within the conceptual framework of the BEST (Biomarkers, EndpointS, and other Tools) Resource, developed by the National Institutes of Health and the Food and Drug Administration in the USA, we consider the evidence supporting the use of NfL for a variety of purposes in different clinical contexts.
We conclude that: (i) it may serve as a susceptibility/risk biomarker in populations at elevated risk for ALS; (ii) it has value as a prognostic biomarker when measured early in the course of established disease, empowering stratification or dynamic randomization to amplify the signal-to-noise ratio of promising therapeutics; and (iii) there is sufficient evidence to support the use of a reduction in NfL in response to an experimental therapeutic as a pharmacodynamic biomarker that may aid in phase 2 trial go/no-go decisions. Moreover, the basis for expecting that a reduction in NfL is a reasonably likely surrogate end-point (i.e. reasonably likely to predict clinical benefit—which may be more than simply survival) is nuanced, and depends on when in the course of disease the experimental therapeutic is administered.
The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands
Authors: Rocatcher Aude , Desquiret-Dumas Valérie , Charif Majida , Ferré Marc , Gohier Philippe , Mirebeau-Prunier Delphine , Verny Christophe , Milea Dan , Lenaers Guy ,   HON Collaborators Group, Vignal Catherine , Lamirel Cédric , Hage Rabih , Dollfus Hélène , Meunier Isabelle , Zanlonghi Xavier , Touitou Valérie , Lebranchu Pierre , Odent Sylvie , Tilikete Caroline Froment , Jeanjean Luc , Defoort-Dhellemmes Sabine , Drumare-Bouvet Isabelle , Smirnov Vasily , Vincent-Delorme Catherine , Biotti Damien , Varenne Fanny , Calvas Patrick , Chassaing Nicolas , Cohen Mickael , Orssaud Christophe , Mochel Fanny , Roubertie Agathe , Toutain Annick , Pollet-Villard Frédéric , Dupeyron Marie Noelle Bonnet , Boulicot Céline , Cochener Béatrice , Goldenberg Alice , Jacquemont Marie Line , Francannet Christine , Bonneau Dominique , Reynier Pascal , Amati-Bonneau Patrizia 
Published: October 2022

Abstract
Hereditary optic neuropathies are caused by the degeneration of retinal ganglion cells whose axons form the optic nerves, with a consistent genetic heterogeneity. As part of our diagnostic activity, we retrospectively evaluated the combination of Leber hereditary optic neuropathy mutations testing with the exon sequencing of 87 nuclear genes on 2186 patients referred for suspected hereditary optic neuropathies. The positive diagnosis rate in individuals referred for Leber hereditary optic neuropathy testing was 18% (199/1126 index cases), with 92% (184/199) carrying one of the three main pathogenic variants of mitochondrial DNA (m.11778G&gt;A, 66.5%; m.3460G&gt;A, 15% and m.14484T&gt;C, 11%). The positive diagnosis rate in individuals referred for autosomal dominant or recessive optic neuropathies was 27% (451/1680 index cases), with 10 genes accounting together for 96% of this cohort. This represents an overall positive diagnostic rate of 30%. The identified top 10 nuclear genes included OPA1, WFS1, ACO2, SPG7, MFN2, AFG3L2, RTN4IP1, TMEM126A, NR2F1 and FDXR. Eleven additional genes, each accounting for less than 1% of cases, were identified in 17 individuals. Our results show that 10 major genes account for more than 96% of the cases diagnosed with our nuclear gene panel.
Imbalance of NRG1-ERBB2/3 signalling underlies altered myelination in Charcot–Marie–Tooth disease 4H
Authors: El-Bazzal Lara , Ghata Adeline , Estève Clothilde , Gadacha Jihane , Quintana Patrice , Castro Christel , Roeckel-Trévisiol Nathalie , Lembo Frédérique , Lenfant Nicolas , Mégarbané André , Borg Jean-Paul , Lévy Nicolas , Bartoli Marc , Poitelon Yannick , Roubertoux Pierre L , Delague Valérie , Bernard-Marissal Nathalie 
Published: October 2022

AbstractCharcot–Marie–Tooth (CMT) disease is one of the most common inherited neurological disorders, affecting either axons from the motor and/or sensory neurons or Schwann cells of the peripheral nervous system (PNS) and caused by more than 100 genes. We previously identified mutations in FGD4 as responsible for CMT4H, an autosomal recessive demyelinating form of CMT disease. FGD4 encodes FRABIN, a GDP/GTP nucleotide exchange factor, particularly for the small GTPase Cdc42. Remarkably, nerves from patients with CMT4H display excessive redundant myelin figures called outfoldings that arise from focal hypermyelination, suggesting that FRABIN could play a role in the control of PNS myelination. To gain insights into the role of FGD4/FRABIN in Schwann cell myelination, we generated a knockout mouse model (Fgd4SC–/–), with conditional ablation of Fgd4 in Schwann cells. We show that the specific deletion of FRABIN in Schwann cells leads to aberrant myelination in vitro, in dorsal root ganglia neuron/Schwann cell co-cultures, as well as in vivo, in distal sciatic nerves from Fgd4SC–/– mice. We observed that those myelination defects are related to an upregulation of some interactors of the NRG1 type III/ERBB2/3 signalling pathway, which is known to ensure a proper level of myelination in the PNS. Based on a yeast two-hybrid screen, we identified SNX3 as a new partner of FRABIN, which is involved in the regulation of endocytic trafficking. Interestingly, we showed that the loss of FRABIN impairs endocytic trafficking, which may contribute to the defective NRG1 type III/ERBB2/3 signalling and myelination. Using RNA-Seq, in vitro, we identified new potential effectors of the deregulated pathways, such as ERBIN, RAB11FIP2 and MAF, thereby providing cues to understand how FRABIN contributes to proper ERBB2 trafficking or even myelin membrane addition through cholesterol synthesis. Finally, we showed that the re-establishment of proper levels of the NRG1 type III/ERBB2/3 pathway using niacin treatment reduces myelin outfoldings in nerves of CMT4H mice.Overall, our work reveals a new role of FRABIN in the regulation of NRG1 type III/ERBB2/3 NRG1signalling and myelination and opens future therapeutic strategies based on the modulation of the NRG1 type III/ERBB2/3 pathway to reduce CMT4H pathology and more generally other demyelinating types of CMT disease.
TCL1A acts as a tumour suppressor by modulating gastric cancer autophagy via miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop
Authors: Hao Jialing , Mei Haitao , Luo Qingshan , Weng Junyong , Lu Jing , Liu Mingmin , Wen Yugang 
Published: October 2022

Abstract
Gastric cancer is the third most commonly cause of tumour-related death worldwide and one of the most prevalent malignancies in China. TCL1A, TCL1 family Akt coactivator A, can active Akt/mTOR pathway and regulate the autophagy. However, the action of TCL1A in gastric cancer is not well understood. The present study is investigating the mechanism of action of TCL1A in gastric cancer. TCL1A was lowly expressed in gastric cancer tissues. Subsequent experiments demonstrated that miR-181a-5p can regulate c-MYC through the TCL1A-Akt/mTOR pathway and c-MYC can in turn affect the expression of miR-181a-5p, thus confirming the existence of the miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop. Flow cytometric apoptosis assay and mRFP-eGFP-LC3 autophagy assay demonstrated that both miR-181a-5p and TCL1A can affect autophagy and apoptosis of gastric cancer cells through the loop. In vivo experiments confirmed that TCL1A can affect the proliferation of gastric cancer. These results illustrate that TCL1A can exert tumour suppressive effects and affect gastric cancer autophagy and progression via the miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop, which could be a potential therapeutic target for gastric cancer.
Neurovascular decoupling measured with quantitative susceptibility mapping is associated with cognitive decline in patients with type 2 diabetes
Authors: Ni Min-Hua , Li Ze-Yang , Sun Qian , Yu Ying , Yang Yang , Hu Bo , Ma Teng , Xie Hao , Li Si-Ning , Tao Lan-Qiu , Yuan Ding-Xin , Zhu Jun-Ling , Yan Lin-Feng , Cui Guang-Bin 
Published: October 2022

Abstract
Disturbance of neurovascular coupling (NVC) is suggested to be one potential mechanism in type 2 diabetes mellitus (T2DM) associated mild cognitive impairment (MCI). However, NVC evidence derived from functional magnetic resonance imaging ignores the relationship of neuronal activity with vascular injury. Twenty-seven T2DM patients without MCI and thirty healthy controls were prospectively enrolled. Brain regions with changed susceptibility detected by quantitative susceptibility mapping (QSM) were used as seeds for functional connectivity (FC) analysis. NVC coefficients were estimated using combined degree centrality (DC) with susceptibility or cerebral blood flow (CBF). Partial correlations between neuroimaging indicators and cognitive decline were investigated. In T2DM group, higher susceptibility values in right hippocampal gyrus (R.PHG) were found and were negatively correlated with Naming Ability of Montreal Cognitive Assessment. FC increased remarkably between R.PHG and right middle temporal gyrus (R.MTG), right calcarine gyrus (R.CAL). Both NVC coefficients (DC-QSM and DC-CBF) reduced in R.PHG and increased in R.MTG and R.CAL. Both NVC coefficients in R.PHG and R.MTG increased with the improvement of cognitive ability, especially for executive function. These demonstrated that QSM and DC-QSM coefficients can be promising biomarkers for early evaluation of cognitive decline in T2DM patients and help to better understand the mechanism of NVC.
Structural neuroplasticity in computer programming beginners
Authors: Hongo Takeshi , Yakou Takao , Yoshinaga Kenji , Kano Toshiharu , Miyazaki Michiko , Hanakawa Takashi 
Published: October 2022

Abstract
We examined the structural neuroplastic changes associated with the learning of computer programming in university students with no previous programming experience. They participated in a 15-week course (26 lessons) on the “Processing” computer programming language. We have conducted a longitudinal analysis of gray matter volume (GMV) in the magnetic resonance images obtained before and after learning computer programming. Significant neuroplastic changes appeared in the following 8 sites: the left frontal pole; the right frontal pole; the right medial frontal gyrus; the left cuneus; the left lateral cerebellum (posterior lobule and tuber); the medial cerebellum (uvula and tonsil); the right pallidum; and the left pallidum. The amount of change in the GMV of the right frontal pole correlated positively with the final product score. Furthermore, the amount of change in the GMV of the right medial frontal gyrus and the bilateral pallidum correlated positively with the test scores. Thus, the right frontal pole was presumably associated with the function of persistent attempts to accomplish tasks (goal achievement-related function). The right medial frontal gyrus and the bilateral pallidum were presumably related to deduction and reward functions, respectively. Therefore, multiple brain regions appear to be involved in programming learning through different functions.
Employers’ Speech-Based First Impressions of Cochlear Implant Users
Authors: Freeman Valerie 
Published: October 2022

AbstractThis study is part of a series on speech-based first impressions of prelingually deaf cochlear implant (CI) users with differing speech intelligibility. Hiring managers with typical hearing (TH) rated CI users and TH young adults on various personality traits and suitability as job applicants after hearing recorded speech samples. Similar to prior peer listeners, managers rated TH speakers more positively than highly intelligible CI users (CI-Hi), with less-intelligible CI users rated even more negatively. Managers for white-collar or high-communication jobs rated CI-Hi lower than did managers of blue-collar or low-communication jobs. Positive attitudes and experience with deafness improved ratings of CI users. While underlining the importance of intelligibility, these patterns also highlight the impact of listeners’ underlying attitudes on their initial judgments of CI users, which could affect deaf employment opportunities. The study calls for workplace education about hearing loss and deaf communication to improve deaf inclusion and employment rates.
European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment
Authors: Lee G A , Aktaa S , Baker E , Gale C P , Yaseen Israa F , Gulati G , Asteggiano R , Szmit S , Cohen-Solal A , Abdin A , Jurczak W , Garrido Lopez P , Sverdlov A L , Tocchetti C G , Barac A , Parrini I , Zamorano P , Iakobishvili Z , Pudil R , Badimon L , Kirby A M , Blaes A H , Farmakis D , Curigliano G , Stephens R , Lyon A R , Lopez-Fernandez T 
Published: October 2022

Abstract

Aims
To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity.

Methods and results
We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy.

Conclusion
We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.
Women Leaving the Playpen: the Emancipating Role of Female Suffrage
Authors: Slotwinski Michaela , Stutzer Alois 
Published: October 2022

AbstractWe study how political empowerment affected women’s emancipation as reflected in their life choices. The staggered introduction of female suffrage in Swiss states allows us to exploit the variation in the age at which women were exposed to the right to vote to estimate the differences in life choices between women who were socialised in a world with politically empowered women and those who were socialised before. Our empirical findings document that early exposure to female suffrage increased female labour force participation, weakened marital bonds and motivated human capital investment.
General practitioners’ views and experiences of communicating with older people about cancer screening: a qualitative study
Authors: Smith Jenna , Dodd Rachael H , Wallis Katharine A , Naganathan Vasi , Cvejic Erin , Jansen Jesse , McCaffery Kirsten J 
Published: October 2022

Abstract

Background
Older adults should be supported to make informed decisions about cancer screening. However, it is unknown how general practitioners (GPs) in Australia communicate about cancer screening with older people.

Aim
To investigate GPs’ views and experiences of communicating about cancer screening (breast, cervical, prostate, and bowel) with older people (≥70 years).

Design and setting
Qualitative, semi-structured interviews, Australia.

Method
Interviews were conducted with GPs practising in Australia (n = 28), recruited through practice-based research networks, primary health networks, social media, and email invitation. Interviews were audio-recorded and analysed thematically using Framework Analysis.

Results
Findings across GPs were organized into 3 themes: (i) varied motivation to initiate cancer screening discussions; some GPs reported that they only initiated screening within recommended ages (&lt;75 years), others described initiating discussions beyond recommended ages, and some experienced older patient-initiated discussions; (ii) GPs described the role they played in providing screening information, whereby detailed discussions about the benefits/risks of prostate screening were more likely than other nationally funded screening types (breast, cervical, and bowel); however, some GPs had limited knowledge of recommendations and found it challenging to explain why screening recommendations have upper ages; (iii) GPs reported providing tailored advice and discussion based on personal patient preferences, overall health/function, risk of cancer, and previous screening.

Conclusions
Strategies to support conversations between GPs and older people about the potential benefits and harms of screening in older age and rationale for upper age limits to screening programmes may be helpful. Further research in this area is needed.