bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sample size requirement for achieving multisite harmonization using structural brain MRI features
Authors: Parekh Pravesh , Bhalerao Gaurav Vivek ,   the ADBS consortium, John John P , Venkatasubramanian G 
Published: March 2022

AbstractWhen data is pooled across multiple sites, the extracted features are confounded by site effects. Harmonization methods attempt to correct these site effects while preserving the biological variability within the features. However, little is known about the sample size requirement for effectively learning the harmonization parameters and their relationship with the increasing number of sites. In this study, we performed experiments to find the minimum sample size required to achieve multisite harmonization (using neuroHarmonize) using volumetric and surface features by leveraging the concept of learning curves. Our first two experiments show that site-effects are effectively removed in a univariate and multivariate manner; however, it is essential to regress the effect of covariates from the harmonized data additionally. Our following two experiments with actual and simulated data showed that the minimum sample size required for achieving harmonization grows with the increasing average Mahalanobis distances between the sites and their reference distribution. We conclude by positing a general framework to understand the site effects using the Mahalanobis distance. Further, we provide insights on the various factors in a cross-validation design to achieve optimal inter-site harmonization.
Effects of sub-chronic,in vivoadministration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats
Authors: Váczi Sándor , Barna Lilla , Laczi Krisztián , Tömösi Ferenc , Rákhely Gábor , Penke Botond , Fülöp Lívia , Janáky Tamás , Deli Mária A. , Mezei Zsófia 
Published: March 2022

AbstractDiabetes mellitus is a chronic metabolic disorder which induces endothelial dysfunction and platelet activation. Eicosanoids produced from arachidonic acid regulate cellular and vascular functions. Sigma-1 receptor expressed in platelets and endothelial cells can regulate intracellular signalization. Our aim was to examine the influence of sub-chronic,in vivoadministered sigma-1 receptor ligands (2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate, PRE-084; S-N-Benzyl-6,7-dimethoxy-1,2,3,4-tetrahydro-1-isoquinolineethanamine, a new compound (S)-L1; and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine monohydrochloride, NE-100) on theex vivoarachidonic acid metabolism of platelets and aorta in streptozotocin-induced diabetic rats. The serum level of sigma-1 receptor ligands was detected by liquid chromatography-mass spectrometry before theex vivoanalysis. Sigma-1 receptor and cyclooxygenase gene expression in platelets were determined by reverse transcription coupled quantitative polymerase chain reaction. The eicosanoid synthesis was examined by using of radiolabeled arachidonic acid substrate and enzyme-linked immunosorbent assay.In diabetic rats, the sub-chronic,in vivoadministration of the sigma-1 receptor ligands modified the transcript levels of sigma-1 receptor and cyclooxygenase-1, the concentration of cyclooxygenase in platelets and the eicosanoid synthesis in both platelets and aorta. Sigma-1 receptor ligands, by changing platelet and blood vessel eicosanoid synthesis, may play a role in modulating diabetic complications.
Mechanistic and thermodynamic characterization of antivirals targeting druggable pocket of SARS-CoV-2 nucleocapsid
Authors: Dhaka Preeti , Singh Ankur , Choudhary Shweta , Peddinti Rama Krishna , Kumar Pravindra , Sharma Gaurav Kumar , Tomar Shailly 
Published: March 2022

AbstractThe N-terminal (NTD) and the C-terminal (CTD) domains comprises the structure of the SARS-CoV-2 Nucleocapsid (N) protein. Crystal structure of the SARS-CoV-2 N protein determined by Kang et al, 2020, reveals the N-terminal RNA binding domain as a unique drug binding site. The present study targets this unique pocket with identified antivirals using structure-based drug repurposing approach. The high-affinity binding of potential molecules was characterised thermodynamically using Isothermal titration calorimetry. The selected molecules showed an inhibitory RNA binding potential between 8.8 μM and 15.7 μM IC50when evaluated with a fluorescent-based assay. Furthermore, in an in vitro cell-based antiviral assay, these ten antiviral molecules demonstrated high effectiveness in halting SARS-CoV-2 replication. Telmisartan and BMS-189453, the two highly potent antivirals, have ∼0.98μM and 1.02 μM EC50values with the selective index of >102, and >98, respectively. For the first time, this study presents drug molecules specifically targeting the NTD of SARS-CoV-2, offering essential insights for the development of therapeutic interventions against this virus, which is still a potential global threat to public health.
Impairments in fear extinction memory and basolateral amygdala plasticity in the TgF344-AD rat model of Alzheimer’s disease are distinct from non-pathological aging
Authors: Hernandez Caesar M. , Jackson Nateka L. , Hernandez Abbi R. , McMahon Lori L. 
Published: March 2022

AbstractFear-based disorders such as posttraumatic stress disorder (PTSD) steepen age-related cognitive decline and doubles the risk for developing Alzheimer’s disease. Due to the seemingly hyperactive properties of fear memories, PTSD symptoms can worsen with age. Perturbations in the synaptic circuitry supporting fear memory extinction are key neural substrates of PTSD. The basolateral amygdala (BLA) is a medial temporal lobe structure critical in the encoding, consolidation, and retrieval of fear memories. As little is known about fear extinction memory and BLA synaptic dysfunction within the context of aging and AD, the goal of this study was to investigate how fear extinction memory deficits and basal amygdaloid nucleus (BA) synaptic dysfunction differentially associate in non-pathological aging and AD in the TgF344AD (TgAD) rat model of AD. Young, middle-aged, and older-aged WT and TgAD rats were trained on a delay fear conditioning and extinction procedure prior to ex vivo extracellular field potential recording experiments in the BA. Relative to young WT rats, long-term extinction memory was impaired, and in general, associated with a hyperexcitable BA and impaired LTP in TgAD rats at all ages. In contrast, long-term extinction memory was impaired in aged WT rats and associated with impaired LTP but not BA hyperexcitability. Interestingly, the middle-aged TgAD rats showed intact short-term extinction and BA LTP, suggestive of a compensatory mechanism, whereas differential neural recruitment in older-aged WT rats may have facilitated short-term extinction. As such, associations between fear extinction memory and amygdala deficits in non-pathological aging and AD are dissociable.SignificanceAdults with fear-based disorders like post-traumatic stress disorder are at an increased risk for developing age-related cognitive decline and Alzheimer’s disease (AD). Moreover, negative emotional affect is an early marker of AD. The link between fear-based disorders and AD creates a disadvantage for achieving positive outcomes later in life. Central to the circuitry underlying fear disorders are medial temporal lobe structures like the basal amygdaloid nucleus (BA). However, the role of the BA in fear-based disorders exacerbated by aging and AD is not well understood. Using the TgF344AD rat model of AD, we investigated how fear extinction memory impairments and BA synaptic function are impacted by aging and AD and whether these processes differentially associate in non-pathological aging and AD.
Generative and interpretable machine learning for aptamer design and analysis of in vitro sequence selection
Authors: Di Gioacchino Andrea , Procyk Jonah , Molari Marco , Schreck John S. , Zhou Yu , Liu Yan , Monasson Rémi , Cocco Simona , Šulc Petr 
Published: March 2022

AbstractSelection protocols such as SELEX, where molecules are selected over multiple rounds for their ability to bind to a target molecule of interest, are popular methods for obtaining binders for diagnostic and therapeutic purposes. With the increasing amount of such high-throughput experimental data available, machine learning techniques have become increasingly popular for molecular datasets analysis. Here, we show that Restricted Boltzmann Machines (RBMs), a two-layer neural network architecture, can successfully be trained on sequence ensembles from SELEX experiments for thrombin aptamers, and used to estimate the fitness of the sequences obtained through the experimental protocol. As a direct consequence, we show that trained RBMs can be exploited to classify as well as generate novel molecules. To confirm our findings, we experimentally verify the generated sequences from RBM.
Landing manoeuvres predict roost-site preferences in bats
Authors: Chaverri Gloriana , Araya-Salas Marcelo , Barrantes Jose Pablo , Uribe-Etxebarria Tere , Peña-Acuña Marcela , Varela Angie Liz , Aihartza Joxerra 
Published: March 2022

ABSTRACTRoosts are vital for the survival of many species, and how individuals choose one site over another is affected by various ecological factors. Biomechanical constraints could also affect roost selection, particularly in volant taxa that require sites with easy access, thereby reducing costs (i.e., predation, accidents). To date, no studies have established an association between landing performance and roost-site selection, as predicted by biomechanical constraints associated with flight. We aim to determine roost-site selection in disc-winged bats (Thyroptera tricolor), a species known to roost within developing tubular leaves. This study is coupled with various experiments that measure how a conspicuous apex affects landing tactics and performance. We show that T. tricolor prefers leaves with a longer apex, the space typically used for landing. Bats also approach and enter these leaves more consistently, increasing task performance while reducing the risk of injuries.Summary statementSpix’s disc-winged bats prefer to roost in some types of leaves, which we show may be related to costly maneuvers during the approach and landing phases.
Invasiveness of Cancer Populations in a Two-dimensional Percolation cluster: a Stochastic Mathematical Approach
Authors: Yang Renlong , Shao Yuanzhi , Jiang Chongming 
Published: March 2022

AbstractA framework for the software Unstructured Reaction-Diffusion Master Equation (URDME) was developed. A mitogenic paracrine signaling pathway was introduced phenomenologically to show how cells cooperate with one another. We modeled the emerging Allee effect using low seeding density culture (LSDC) assays to fit the model parameters. Finite time scaling (FTS) was found to be a useful tool for quantifying invasiveness in cancer populations. Through simulation, we analyzed the growth-migration dynamics of BT474 cancer cell populations in-vitro in a 2D percolation cluster and calculated the SPR (successful penetration rate). By analyzing the temporal trajectories of the SPR, we could determine the critical exponents of the critical SPR scaling relation. Moreover, the SPR transition point defined according to the FTS theory,Pc, is negatively correlated with the invasiveness of cancer cell populations. ThePcof the three virtual cancer populations distinctly designated by varying the parameter set of the same model are 0.3408, 0.3675, and 0.4454, respectively. Therefore, the FTS algorithm may be useful in determining invasiveness. Through the simplistic phenomenological paracrine model, inter-cell cooperation and mutual mitogenic boosting are enabled, causing the Allee effect to occur. Such a method could be applied to other circumstances as an example of the quantitatively falsifiable emerging theory.
Comprehensive phylogenomics of Methylobacterium reveals four evolutionary distinct groups and underappreciated phyllosphere diversity
Authors: Leducq Jean-Baptiste , Sneddon David , Santos Malia , Condrain-Morel Domitille , Bourret Geneviève , Martinez-Gomez N. Cecilia , Lee Jessica A. , Foster James A. , Stolyar Sergey , Shapiro B. Jesse , Kembel Steven W. , Sullivan Jack M , Marx Christopher J. 
Published: March 2022

AbstractMethylobacterium is a group of methylotrophic microbes associated with soil, fresh water, and particularly the phyllosphere, the aerial part of plants that has been well-studied in terms of physiology but whose evolutionary history and taxonomy are unclear. Recent work has suggested that Methylobacterium is much more diverse than thought previously, questioning its status as an ecologically and phylogenetically coherent taxonomic genus. However, taxonomic and evolutionary studies of Methylobacterium have mostly been restricted to model species, often isolated from habitats other than the phyllosphere, and have yet to utilize comprehensive phylogenomic methods to examine gene trees, gene content, or synteny. By analyzing 189 Methylobacterium genomes from a wide range of habitats, including the phyllosphere, we inferred a robust phylogenetic tree while explicitly accounting for the impact of horizontal gene transfers. We showed that Methylobacterium contains four evolutionary distinct groups of bacteria (namely A, B, C, D), characterized by different genome size, GC content, gene content and genome architecture, revealing the dynamic nature of Methylobacterium genomes. In addition of recovering 59 described species, we identified 45 candidate species, mostly phyllosphere-associated, stressing the significance of plants as a reservoir of Methylobacterium diversity. We inferred an ancient transition from a free-living lifestyle to association with plant roots in Methylobacteriaceae ancestor, followed by phyllosphere association of three of the major groups (A, B, D), which early branching in Methylobacterium history was heavily obscured by HGT. Together, our work lays the foundations for a thorough redefinition of Methylobacterium taxonomy, beginning with the abandon of Methylorubrum.
Hyperuricemia triggers Renal Tubular Epithelial Pyroptosis by using ROS to activate the NLRP3 inflammasome
Authors: Wu Yansheng , Li Ruiling , Li Dongdong , Ou Jiaoying , Zhou Jiabao , Wang Chuanxu , Gao Jiandong 
Published: March 2022

ABSTRACTRenal injury resulting from hyperuricemia has gained a lot of interest. Pyroptosis refers to inflammatory cell death. The activated caspase-1 cleavage, and the pivotal protein - GSDMD could have an association with the hyperuricemic kidney lesion pathogenesis. ROS is a vital NLRP3 inflammasome antagonist in various cells. We investigated the mechanism through which ROS stimulates NLRP3 to modulate pyroptosis in renal tubular epithelial cells as well as hyperuricemic rat kidneys.MethodsIn vitrocultured renal tubular epithelial cells (NRK-52E cells) were incubated with a gradient concentration of uric acid for 24 hr to investigate the pyroptosis through flow cytometry. Next, we used the inhibitors of ROS, mitochondrial ROS, NLRP3 and Caspase-1 respectively to intervene in uric acid treated cells to analyse pyproptosis and activation of ROS- NLRP3 inflammasome signal pathway. Finally, we evaluated the mechanism of hyperuricemia triggering renal tubular epithelial pyroptosis in rat kidney tissues.ResultsThe levels of ROS and mitochondrial ROS, the mRNA and protein expression of pyroptosis-associated factors Caspase-1 (p45, p20/10), NLRP3, and GSDMD were upregulated in uric acid, the induced NRK-52E cells as well as hyperuricemic model kidneys. The inhibition of ROS, mitochondrial ROS, NLRP3, or caspase-1 in the uric acid-induced NRK-52E cells may help in controlling pyroptosis. The expression of mRNA and protein by the cytokines IL-18 and IL-1β also increased.ConclusionsGenerally, hyperuricemia triggered renal tubular epithelial pyroptosis via excessive ROS to modulate NLRP3 inflammasome activation in uric acid stimulated renal tubular epithelial cells as well as the oxonic acid potassium induced hyperuricemia.
Asexual stage synchronicity in symptomatic and asymptomatic falciparum malaria
Authors: Watson James A , White Nicholas J 
Published: March 2022

AbstractAndrade et al have reported that P. falciparum parasitised erythrocytes circulate for longer in persistent asymptomatic infections than in symptomatic malaria. This radical suggestion, attributed to in-vivo adaptation by the parasite population to reduced cytoadherence, is based largely on in-vivo transcriptomic data from 24 Malian children: 12 with acute falciparum malaria and 12 with asymptomatic parasitaemia. We show that the reported analysis generated erroneous results because of data formatting issues. We also show that the algorithm used to estimate the average asexual parasite developmental stage (hours post-invasion) from in-vivo transcriptomic data breaks down when applied to asynchronous infections. We argue that comparisons between asymptomatic and symptomatic malaria of asexual parasite developmental stage distributions are confounded by differences in synchronicity and gametocytaemia, and also by selection bias (because schizogony often precipitates clinical presentation). There is no convincing evidence of an adaptive delayed cytoadherence phenotype in chronic P. falciparum infections.
Experience of Adults with Upper-limb Difference and their Views on Sensory Feedback for Prostheses: A Mixed Methods Study
Authors: Jabban Leen , Metcalfe Benjamin W. , Raines Jonathan , Zhang Dingguo , Ainsworth Ben 
Published: March 2022

AbstractBackgroundUpper-limb prostheses are regularly abandoned, in part due to the mismatch between user needs and prostheses performance. Sensory feedback is among several technological advances that have been proposed to reduce device abandonment rates. While it has already been introduced in some high-end commercial prostheses, limited data is available about user expectations in relation to sensory feedback. The aim of this study is thus to use a mixed methods approach to provide a detailed insight of users’ perceptions and expectations of sensory feedback technology, to ensure the addition of sensory feedback is as acceptable, engaging and ultimately as useful as possible for users and, in turn, reduce the reliance on compensatory movements that lead to overuse syndrome.MethodsThe study involved an online survey (N=37) and video call interviews (N=15) where adults with upper-limb differences were asked about their experience with limb difference and prosthesis use (if applicable) and their expectations about sensory feedback to prostheses. The survey data were analysed quantitatively and descriptively to establish the range of sensory feedback needs and their variations across the different demographics. Reflexive thematic analysis was performed on the interview data, and data triangulation was used to understand key behavioural issues to generate actionable guiding principles for the development of sensory feedback systems.ResultsThe survey provided a list of practical examples and suggestions that did not vary with the different causes of limb difference or prosthesis use. The interviews showed that although sensory feedback is a desired feature, it must prove to have more benefits than drawbacks. The key benefit mentioned by participants was increasing trust, which requires a highly reliable system that provides input from several areas of the hand rather than just the fingertips. The feedback system should also complement existing implicit feedback sources without causing confusion or discomfort. Further, the effect sensory feedback has on the users’ psychological wellbeing was highlighted as an important consideration that varies between individuals and should therefore be discussed. The results obtained were used to develop guiding principles for the design and implementation of sensory feedback systems.ConclusionsThis study provides a mixed-methods research on the sensory feedback needs of adults with upper-limb differences, enabling a deeper understanding of their expectations and worries. Guiding principles were developed based on the results of a survey and interviews to inform the development and assessment of sensory feedback for upper-limb prostheses.
Quantitative Trend Analysis of SARS-CoV-2 RNA in Municipal Wastewater Exemplified with Sewershed-Specific COVID-19 Clinical Case Counts
Authors: Pileggi Vince , Shurgold Jayson , Sun Jianxian , Yang Minqing Ivy , Edwards Elizabeth , Peng Hui , Tehrani Amir , Gilbride Kimberley , Oswald Claire , Wijayasri Shinthuja , Al-Bargash Dana , Stuart Rebecca , Khansari Zeinab , Raby Melanie , Thomas Janis , Fletcher Tim , Simhon Albert 
Published: March 2022

AbstractWe present and demonstrate a quantitative statistical linear trend analysis (QTA) approach to analyze and interpret SARS-CoV-2 RNA wastewater surveillance results concurrently with clinical case data. This demonstration is based on the work completed under the Ontario (Canada) Wastewater Surveillance Initiative (WSI) by two laboratories in four large sewersheds within the Toronto Public Health (TPH) jurisdiction. The sewersheds were sampled over a 9-month period and data were uploaded to the Ontario Wastewater Surveillance Data and Visualization Hub (Ontario Dashboard) along with clinical case counts, both on a sewershed-specific basis. The data from the last 5-months, representing a range of high and low cases, was used for this demonstration. The QTA was conducted on a sewershed specific approach using the recommendations for public health interpretation and use of wastewater surveillance data by the United States Centers for Disease Control and Prevention (US CDC). The interpretation of the QTA results was based on the integration of both clinical and wastewater virus signals using an integration matrix in an interim draft guide by the Public Health Agency of Canada (PHAC). The key steps in the QTA consisted of (i) the calculation of Pepper Mild Mottle Virus (PMMoV), flow and flow-PMMoV-normalized virus loads; (ii) computation of the linear trends including interval estimation to identify the key inflection points using a segmented linear regression method and (iii) integrated interpretations based on consideration of both the cases and wastewater signals, as well as end user actionability. This approach is considered a complementary tool to commonly used qualitative analyses of SARS-CoV-2 RNA in wastewater and is intended to directly support public health decisions using a systematic quantitative approach.