bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trustworthiness of Systematic Review Automation An interview at Coventry University
Authors: Jiang Xiaorui 
Published: December 2023

AbstractTo reduce both time and labour for systematic review, much effort has been made on developing automated tools using artificial intelligence and machine learning in nearly two decades. Unfortunately, systematic review automation tools still face a serious problem of social acceptance. Previous studies identified lack of trust as one important adoption barrier for systematic review automation. However, further discussion about building trust was limited to building trusted evidence base by benchmarked large-scale evaluation. This study extended the previous discussions of the trustworthiness of systematic review automation. Through semi-structure interviews with regular systematic reviewers, we tried to not only get answers for to what extent human reviewers trust automated tools and why, but also reveal more measures of building trust from human reviewers’ points of view and the impact of such measures on the trust in and adoption of systematic review automation tools. We believe that the results of this study may also shed light on some new directions of systematic review automation research.
Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast
Authors: Chalivendra Subbaiah , Shi Shasha , Li Xueni , Kuang Zhiling , Giovinazzo Joseph , Zhang Lingdi , Rossi John , Saviola Anthony J. , Wang Jingxin , Welty Robb , Liu Shiheng , Vaeth Katherine , Zhou Z. Hong , Hansen Kirk C. , Taliaferro J. Matthew , Zhao Rui 
Published: December 2023

AbstractThe recognition of 5’ splice site (5’ ss) is one of the earliest steps of pre-mRNA splicing. To better understand the mechanism and regulation of 5’ ss recognition, we selectively humanized components of the yeast U1 snRNP to reveal the function of these components in 5’ ss recognition and splicing. We targeted U1C and Luc7, two proteins that interact with and stabilize the yeast U1 (yU1) snRNA and the 5’ ss RNA duplex. We replaced the Zinc-Finger (ZnF) domain of yU1C with its human counterpart, which resulted in cold-sensitive growth phenotype and moderate splicing defects. Next, we added an auxin-inducible degron to yLuc7 protein and found that Luc7-depleted yU1 snRNP resulted in the concomitant loss of PRP40 and Snu71 (two other essential yeast U1 snRNP proteins), and further biochemical analyses suggest a model of how these three proteins interact with each other in the U1 snRNP. The loss of these proteins resulted in a significant growth retardation accompanied by a global suppression of pre-mRNA splicing. The splicing suppression led to mitochondrial dysfunction as revealed by a release of Fe2+into the growth medium and an induction of mitochondrial reactive oxygen species. Together, these observations indicate that the human U1C ZnF can substitute that of yeast, Luc7 is essential for the incorporation of the Luc7-Prp40-Snu71 trimer into yeast U1 snRNP, and splicing plays a major role in the regulation of mitochondria function in yeast.
A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy
Authors: Wiche Salinas Tomas Raul , Zhang Yuwei , Gosselin Annie , Do Rosario Natalia Fonseca , El-Far Mohamed , Filali-Mouhim Ali , Routy Jean-Pierre , Chartrand-Lefebvre Carl , Landay Alan L. , Durand Madeleine , Tremblay Cécile L. , Ancuta Petronela ,   the Canadian HIV and Aging Cohort Study (CHACS)
Published: December 2023

ABSTRACTCardiovascular disease (CVD) remains an important co-morbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed on the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) >5%), revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by Computed tomography angiography scan (CTAScan) as total (TPV) and low attenuated plaque volume (LAPV) in ART-treated PLWH (HIV+)versusuninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4+T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells, were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1 and triglyceride levels, lower Th17/Treg ratios, and classical monocyte expansion. Among HIV+, TPV+versusTPV−exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9lowHLADRhighmonocyte, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhighmonocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.
Pseudoreplication and inappropriate statistical tests in the analysis of preference index data from the T-maze group assay forDrosophila behaviour
Authors: Winklhofer Michael 
Published: December 2023

AbstractThe binary choice chamber (T-maze) assay has been used as a standard behavioural screen in Drosophila research to test mutants in terms of sensory discrimination skills and synaptic plasticity during memory consolidation and decay. Typically, ca. 100 individuals are tested as a group at the same time and the behavioural readout consists in counting the number of individuals in the testing tube exposed to a stimulus versus the number of flies in the control tube, with the normalized difference in fly count being defined as the batch preference index (PI). Unfortunately, the batch PI has widely been taken as a precise metric of group behaviour, to the point where ANOVA/t-tests have been considered the most powerful statistical tests for analyzing samples in terms of batch PI values, which has led to a hyperinflation of apparently very highly significant effects for small differences in PI values (e.g. -0.1 vs 0.1), leading to problems with replicability. Here it is shown on the basis of a well-established statistical model for binary decisions that application of the t-test to PI data implicitly assumes that each fly in a batch is an independent biological replicate in the extremely strict sense that the decision of each individual was interrogated independently of the other flies. Therefore, t-test analysis of PI data obtained with the intrinsically pseudoreplicative group assay is the cause of extremely optimistic P-values, as suggested recently by Bassetto et al. (2023) on the basis of effect size considerations for proportions. Thus, rather than using inferential statistics, PI data should be assessed on the basis of effect size. A more fundamental problem with the batch PI value is the uncertainty in whether it measures the mean individual preference and if so, with what precision, given the simple readout? This aspect is illustrated here by modelling distributions of flies in the T-maze, which suggest that the effective precision of the PI value is clearly worse than the nominal precision of +/- 0.01 for 100 flies, so that the batch PI can only serve as a rough indicator of group tendencies.
Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice
Authors: Poudel Sher Bahadur , Ruff Ryan R , Yildirim Gozde , Miller Richard A , Harrison David E , Strong Randy , Kirsch Thorsten , Yakar Shoshana 
Published: December 2023

AbstractThis study investigated the prevalence and progression of primary osteoarthritis (OA) in aged UM-HET3 mice. Using the Osteoarthritis Research Society International (OARSI) scoring system, we assessed articular cartilage (AC) integrity in 182 knee joints of 22-25 months old mice.Aged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13 (MMP-13), inducible nitric oxide synthase (iNOS), and the NLR family pyrin domain containing-3 (NLRP3) inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and β-galactosidase, also correlated with AC scores. Using micro-CT, we examined the correlations between subchondral bone (SCB) morphology traits and AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density.Finally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging. Notably, MB and MitoQ treatments influenced the disease’s progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance.In conclusion, our study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.
Motor mirror neurons may not be a predictor of learning but reflect the effect of motor learning
Authors: Ekaterina Pomelova , Matteo Feurra , Alena Popyvanova , Vadim Nikulin , Roman Solodkov , Tamara Banjevich , Evgeny Blagovechtchenski 
Published: December 2023

AbstractThe mirror neurons system (MNS) fires during both the performance of an action and observation of the same action being performed by another. On the level of motor output, activation of the MNS is thought to be represented in the phenomenon of motor resonance, which manifests in a muscle-specific increase in corticospinal excitability during action observation. This study focused on how and to what extent sensorimotor learning alters the initial mirror response and whether the rate of sensorimotor learning is associated with pretraining or post-training levels of mirror response. The study involved 23 healthy adults aged 22.7 years. The experiment consisted of six sessions. On the first and last days, a transcranial magnetic stimulation session was held to assess the putative activity of mirror neurons, as reflected in the level of motor-evoked potential facilitation during action observation in different conditions. From the second to the fifth sessions (four sessions in total), the sensorimotor learning part was performed, as represented in the form of a serial reaction time (SRT) task. We observed a statistically significant decrease of reaction time in the process of learning in the SRT task and motor facilitation during action observation, thus reflecting the process of putative mirror neurons’ activity. However, our data demonstrate that the sensorimotor learning rate was not associated with either pretraining or post-training estimates of motor facilitation during action observation and that sensorimotor learning does not affect the pattern of motor resonance.
Imaging the master regulator of the antioxidant response in non-small cell lung cancer with positron emission tomography
Authors: Greenwood Hannah E. , Edwards Richard S. , Tyrrell Will E. , Barber Abigail R. , Baark Friedrich , Tanc Muhammet , Khalil Eman , Falzone Aimee , Ward Nathan P. , DeBlasi Janine M. , Torrente Laura , Pearce David R. , Firth George , Smith Lydia M. , Timmermand Oskar Vilhelmsson , Huebner Ariana , George Madeleine E. , Swanton Charles , Hynds Robert E. , DeNicola Gina M. , Witney Timothy H. 
Published: December 2023

AbstractMutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. The cystine/glutamate antiporter, system xc−, is one of the >200 cytoprotective proteins controlled by NRF2, which can be non-invasively imaged by (S)-4-(3-18F-fluoropropyl)-ʟ-glutamate ([18F]FSPG) positron emission tomography (PET). Through genetic and pharmacologic manipulation, we show that [18F]FSPG provides a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC. We validate imaging readouts with metabolomic measurements of system xc−activity and their coupling to intracellular glutathione concentration. A redox gene signature was measured in patients from the TRACERx 421 cohort, suggesting an opportunity for patient stratification prior to imaging. Furthermore, we reveal that system xc−is a metabolic vulnerability that can be therapeutically targeted for sustained tumour growth suppression in aggressive NSCLC. Our results establish [18F]FSPG as predictive marker of therapy resistance in NSCLC and provide the basis for the clinical evaluation of both imaging and therapeutic agents that target this important antioxidant pathway.
Assessing Immune Factors in Maternal Milk and Paired Infant Plasma Antibody Binding to Human Rhinoviruses
Authors: Vera Jessica M. , McIlwain Sean J. , Fye Samantha , Palmenberg Ann , Bochkov Yury , Li Hanying , Pinapati Richard , Tan John , Gern James E. , Seroogy Christine , Ong Irene M. 
Published: December 2023

AbstractBefore they can produce their own antibodies, newborns are protected from infections by transplacental transfer of maternal IgG antibodies and after birth through breast milk IgA antibodies. Rhinovirus (RV) infections are extremely common in early childhood, and while RV infections often result in only mild upper respiratory illnesses, they can also cause severe lower respiratory illnesses such as bronchiolitis and pneumonia. We used high-density peptide arrays to profile infant and maternal antibody reactivity to capsid and full proteome sequences of three human RVs - A16, B52, and C11. Numerous plasma IgG and breast milk IgA RV epitopes were identified that localized to regions of the RV capsid surface and interior, and also to several non-structural proteins. While most epitopes were bound by both IgG and IgA, there were several instances where isotype-specific and RV-specific binding were observed. We also profiled 62 unique RV-C dominant protein loop sequences characteristic of this species’ capsid VP1 protein. Many of these RV-C sites were highly bound by IgG from one-year-old infants, indicating recent or ongoing active infections, or alternatively, a level of cross-reactivity among homologous RV-C sites.
Aerosol deposition increases conductance to water in immobilized stomata closed with abscisic acid or opened with fusicoccin
Authors: Grantz David A. , Chi Chia-JuEllen , Burkhardt Juergen 
Published: December 2023

SummaryHypothesized effects of aerosol deposition on plant water balance have been difficult to establish. This is due to variability between species, stomatal response to the treatment itself, and to environmental effects. Here we attempt a quantitative evaluation with a defined aerosol application, a paired leaf experimental design, and immobilized stomata.Attached leaves of poplar were treated with ammonium nitrate aerosol. After 17 or 20 days for deliquescence to develop an aqueous film, leaves were excised and stomata held closed with abscisic acid or open with fusicoccin. Transpiration and stomatal conductance were measured in a greenhouse with a porometer and leaf health was assessed by fluorescence.Median stomatal conductance was increased significantly, by 60 and 65%, following aerosol loading of 31.3 μg cm-2in ABA- and FC-treated leaves, respectively.Aerosol induced transpiration, probably associated with a liquid film that lines the stomatal pore and not effectively regulated by stomatal closure, may be significant in magnitude. As aerosol deposition is ubiquitous, and its chemical nature may be changing, this factor should be considered in models of transpiration from leaf to canopy scale.
Estradiol regulates local synthesis of synaptic proteome via sex-specific mechanisms
Authors: Raval Pooja , Rae Hannah , Duarte Rodrigo R. R. , Watson Iain A. , Sellers Katherine J. , Pachon Kathryn M. C. , Sichlinger Laura , Powell Timothy R. , Yasvoina Marina V. , Mukherjee Jayanta , Moss Stephen J. , Brandon Nicholas J. , Srivastava Deepak P. 
Published: December 2023

AbstractEstrogens, specifically 17β-estradiol (estradiol), can modulate synaptic function by regulating the expression and localisation of synaptic proteins. However, the mechanisms underlying estradiol’s regulation of synaptic protein expression, and whether if they occur in a sex specific manner, is not well understood. In this study, using sex-specific hippocampal slice cultures and mixed-sex primary hippocampal neurons, we investigated whether local protein synthesis is required for estradiol- induced synaptic protein expression. Estradiol rapidly increased the rate of protein synthesis and the number of actively translating ribosomes along dendrites and near synapses in both male and female hippocampal neurons. Importantly, these effects occurred independently of gene transcription. Moreover, estradiol also increased the abundance of nascent proteins localised to synapses, independently of gene transcription. Specifically, estradiol increased the synaptic expression of GluN2B- containingN-methyl-D-aspartate receptors and PSD-95 in male and female hippocampus. Mechanistically, mTOR signalling was required for estradiol-induced increases in overall local protein synthesis only in male but not female hippocampus. Consistent with this, mTOR signalling mediated estradiol increases in GluN2B in male, but not female, hippocampus. Conversely, mTOR inhibition, blocked estradiol-induced increased PSD-95 expression in both male and female hippocampus. Collectively, these data suggest that the rapid modulation of local protein synthesis by estradiol is required for changes in the synaptic proteome in male and female hippocampus, and that the requirement of the mTOR signalling pathway in these effects occur in both a sex-specific and protein-dependent manner, with this signalling pathway have a greater role in male compared to female hippocampus.
Identifying patterns to uncover the importance of biological pathways on known drug repurposing scenarios
Authors: Otero-Carrasco Belén , Ugarte Carro Esther , Prieto Santamaría Lucía , Diaz Uzquiano Marina , Caraça-Valente Hernández Juan Pedro , Rodríguez-González Alejandro 
Published: December 2023

AbstractBackgroundDrug repurposing plays a significant role in bringing effective treatments for certain diseases faster and more cost-effectively. Successful repurposing cases are mostly supported by a classical paradigm that stems from de novo drug development. This paradigm is based on the “one-drug-one-target-one-disease” idea. It consists of designing drugs specifically for a single disease and its drug’s gene target. In this article, we investigated the use of biological pathways as potential elements to achieve effective drug repurposing.MethodsConsidering a total of 4.214 successful cases of drug repurposing, we identified cases in which biological pathways serve as the underlying basis for successful repurposing, referred to as DREBIOP. Once the repurposing cases based on pathways were identified, we studied the inherent patterns within them by considering the different biological elements associated with this dataset, as well as the pathways involved in these cases. Furthermore, we obtained gene-disease association values to demonstrate the diminished significance of the drug’s gene target in these repurposing cases. To achieve this, we compared the values obtained for the DREBIOP set with the overall association values found in DISNET, as well as with the drug’s target gene (DREGE) based repurposing cases using the Mann-Whitney U Test.ResultsA collection of drug repurposing cases, known as DREBIOP, was identified as a result. DREBIOP cases exhibit distinct characteristics when compared to DREGE cases. Notably, DREBIOP cases are associated with a higher number of biological pathways, with Vitamin D Metabolism and ACE inhibitor being the most prominent pathways involved. Additionally, it was observed that the association values of GDAs in DREBIOP cases are significantly lower than those in DREGE cases (p-value < 0.05).ConclusionsBiological pathways assume a pivotal role in drug repurposing cases. This investigation successfully revealed patterns that distinguish drug repurposing instances associated with biological pathways. These identified patterns can be applied to any known repurposing case, enabling the detection of pathway-based repurposing scenarios or the classical paradigm.
An ovine model for investigation of the microenvironment of the male mammary gland
Authors: Davies Benjamin P. , Crew Rachael C. , Cochrane Anna L. K. , Davies Katie , Baptista Andre Figueiredo , Jeckel Sonja , McCrone Ian , Niu Youguo , Strugnell Benjamin W. , Waine Katie , Fowden Abigail L. , Bryant Clare E. , Wills John W. , Giussani Dino A. , Hughes Katherine 
Published: December 2023

AbstractThe specific biology of the male breast remains relatively unexplored in spite of the increasing global prevalence of male breast cancer. Delineation of the microenvironment of the male breast is restricted by the low availability of human samples and a lack of characterisation of appropriate animal models. Unlike the mouse, the male ovine gland persists postnatally. We suggest that the male ovine mammary gland constitutes a promising adjunctive model for the male human breast. In this study we evaluate the male ovine mammary gland microenvironment, comparing intact and neutered males. Assessment of the glandular histo-anatomy highlights the resemblance of the male gland to that of the neonatal female sheep and confirms the presence of rudimentary terminal duct lobular units. Irrespective of neutered status, cell proliferation in epithelial and stromal compartments is low in males, and cell proliferation in epithelial cells and in the intralobular stroma is significantly lower than in pubertal female sheep. Between 42% and 72% of the luminal mammary epithelial cells in the male gland express the androgen receptor, and expression is significantly reduced by neutering. Luminal epithelial cells within the intact and neutered male gland also express oestrogen receptor alpha, but minimal progesterone receptor expression is observed. The distrubution of mammary leukocytes within the ducts and stroma is similar in the female mammary gland of sheep and other species. Both macrophages and T lymphocytes are intercalated in the epithelial bilayer and are more abundant in the intralobular stroma than the interlobular stroma, suggesting that they may have a protective immunological function within the vestigial glandular tissue of the male sheep. Mast cells are also observed within the stroma. These cells cluster nearer the glandular tissue and are frequently located adjacent to blood vessels. The abundance of mast cells is significantly higher in intact males compared to neutered males, suggesting that hormone signalling may impact mast cell recruitment. In this study, we demonstrate the utility of the male ovine mammary gland as a model for furthering our knowledge of postnatal male mammary biology.