bluuebunny/crossref_metadata_2025_split huggingface dataset:
The metabolome and lipidome of colorectal adenomas and cancers
Authors: Laczko Endre , Manser Christine , Marra Giancarlo 
Published: June 2021

AbstractIntroductionIn-depth knowledge of metabolic dysregulations in colorectal cancer (CRC) (and other cancers as well) is essential for developing treatments that specifically kill neoplastic cells. It may also allow us to pinpoint metabolites or lipids with potential for development as tumor biomarkers for use in body-fluid or breath assays. CRC onset is preceded by an interval of ∼10 years characterized by the presence of precancerous lesions, and our previous studies have revealed epigenomic, transcriptomic, and proteomic evidence in these lesions of certain metabolic changes typical of CRC. These findings prompted us to conduct untargeted metabolomic and lipidomic analyses of CRCs and colorectal adenomas (the most common precancerous lesions of the gut).MethodsWe analyzed 29 endoscopically collected tumor tissue samples (29 adenomas [ADNs], 10 CRCs, each with a colon segment-matched sample of normal mucosa [i.e., 29 NM-ADN, 10 NM-CRC]). The freshly collected samples were promptly frozen in liquid nitrogen and later processed to obtain metabolite and lipid extracts. Each of the 78 samples was analyzed with nano-flow LC-MS/MS (liquid chromatography with mass spectrometry) to characterize its metabolome (using HILIC, Hydrophilic Interaction Liquid Chromatography) and lipidome (using RP, Reversed Phase chromatography). The data acquired were processed using Progenesis QI. For statistical and multivariate analysis of the resulting peak tables, we used basic R packages and the R package made4.ResultsUnsupervised between-group analysis based on the full set of detected metabolites (n=1830) and lipids (n=2365) clearly discriminated ADNs and CRCs from their matched samples of normal mucosa at both the metabolome and lipidome levels. Compared with the NM-ADN, the ADNs contained significantly different levels of 14.6% of the metabolites and 10.8% of the lipids. Fewer compounds (9.1% of metabolites, 6.2% of lipids) displayed differential abundance in CRCs (vs. NM-CRC). The metabolome and lipidome of the NM-ADN also differed from those of the NM-CRC, probably reflecting the presence of a field cancerization effect exerted by the invasive tumors. A substantial number of metabolites (n=340) and lipids (n=201) also displayed abundance differentials across the sequential tumorigenic stages represented by the NM-ADN (considered more representative of NM from a lesion-free colon) → ADN → CRC. In most cases, the trend consisted of progressive increases or progressive decreases in abundance as the tumorigenesis advanced.ConclusionsOur findings provide a preliminary picture of the progressive metabolomic and lipidomic changes occurring during the adenomatous phase of colorectal tumorigenesis. Once definitively annotated, the numerous differentially abundant compounds detected in this study may well shed valuable light on the metabolic dysregulations occurring during this process and provide useful clues for the development of novel tools for the diagnosis and treatment of colorectal tumors.
Tracking-based rolling angles recovery method for holographic tomography of flowing cells
Authors: Pirone Daniele , Memmolo Pasquale , Merola Francesco , Miccio Lisa , Mugnano Martina , Capozzoli Amedeo , Curcio Claudio , Liseno Angelo , Ferraro Pietro 
Published: June 2021

AbstractHolographic Tomography (HT) is an emerging label-free technique for microscopic bioimaging applications, that allows reconstructing the three-dimensional (3D) refractive index (RI) distribution of biological specimens. Recently, an in-flow HT technique has been proposed in which multiple digital holograms are recorded at different viewing angles around the sample while it flows and rotates within a microfluidic channel. However, unlike conventional HT methods, there is no a priori information about cell 3D orientations, that are instead requested to perform any tomographic algorithm. Here we investigate a tracking-based rolling angles recovery method, showing robustness against the sample’s features. It is based on a phase images similarity metric recently demonstrated, that exploits the local contrast phase measurements to recognize a full cell rotation within the microfluidic channel. Hence, the orientations of the flowing cells are retrieved from their positions, which are in turn computed through the 3D holographic tracking. The performances of the rolling angles recovery method have been assessed both numerically, by simulating a 3D cell phantom, and experimentally, by reconstructing the 3D RI tomograms of two cancer cells. Both the numerical and the experimental analysis have been performed at different spatial resolutions. This rolling angles recovery method, not depending on the cell shapes, the RI contents, and the optical experimental conditions, could pave the way to the study of circulating tumor cells (CTCs) in the challenging tool of liquid biopsy.
Prepubertal ovariectomy alters dorsomedial striatum indirect pathway neuron excitability and explore/exploit balance in female mice
Authors: Delevich Kristen , Hall Christopher D. , Wilbrecht Linda 
Published: June 2021

AbstractDecision-making circuits are modulated across life stages (e.g. juvenile, adolescent, or adult)—as well as on the shorter timescale of reproductive cycles in females—to meet changing environmental and physiological demands. Ovarian hormonal modulation of relevant neural circuits is a potential mechanism by which behavioral flexibility is regulated in females. Here we examined the influence of prepubertal ovariectomy (pOVX) versus sham surgery on performance in an odor-based multiple choice reversal task. We observed that pOVX females made different types of errors during reversal learning compared to sham surgery controls. Using reinforcement learning models fit to trial-by-trial behavior, we found that pOVX females exhibited lower inverse temperature parameter (β) compared to sham females. These findings suggest that OVX females solve the reversal task using a more exploratory choice policy, whereas sham females use a more exploitative policy prioritizing estimated high value options. To seek a neural correlate of this behavioral difference, we performed whole-cell patch clamp recordings within the dorsomedial striatum (DMS), a region implicated in regulating action selection and explore/exploit choice policy. We found that the intrinsic excitability of dopamine receptor type 2 (D2R) expressing indirect pathway spiny projection neurons (iSPNs) was significantly higher in pOVX females compared to both unmanipulated and sham surgery females. Finally, to test whether mimicking this increase in iSPN excitability could recapitulate the pattern of reversal task behavior observed in pOVX females, we chemogenetically activated DMS D2R(+) neurons within intact female mice. We found that chemogenetic activation increased exploratory choice during reversal, similar to the pattern we observed in pOVX females. Together, these data suggest that pubertal status may influence explore/exploit balance in females via the modulation of iSPN intrinsic excitability within the DMS.
3-hydroxyanthranilic acid – a new metabolite for healthy lifespan extension
Authors: Dang Hope , Castro-Portuguez Raul , Espejo Luis , Backer Grant , Freitas Sam , Spence Erica , Meyers Jeremy , Shuck Karissa , Corban Caroline , Liu Teresa , Bean Shannon , Sheehan Susan , Korstanje Ron , Sutphin George L. 
Published: June 2021

SummaryThe metabolism of tryptophan to nicotinamide adenine dinucleotide (NAD+) through the kynurenine pathway is increasingly linked to aging and age-associated disease. Kynurenine pathway enzymes and metabolites influence a range of molecular processes critical to healthy aging, including regulation of inflammatory and immune responses, cellular redox homeostasis, and energy production. Aberrant kynurenine metabolism is observed during normal aging and has been implicated in a range of age-associated pathologies, including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. In previous work, we and others identified three genes—kynu-1, tdo-2, andacsd-1—encoding kynurenine pathway enzymes for which decreasing expression extends lifespan in invertebrate models. Here we report that knockdown ofhaao-1, a fourth kynurenine pathway gene encoding the enzyme 3-hydroxyanthranilic acid dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated decline in health inCaenorhabditis elegans. This lifespan extension is mediated by increased physiological levels of the HAAO substrate 3-hydroxyanthranilic acid (3HAA). 3HAA increases resistance to oxidative stress during aging by directly degrading hydrogen peroxide and activating the Nrf2/SKN-1 oxidative stress response. Aging mice fed a diet supplemented with 3HAA are similarly long-lived. Our results identify HAAO and 3HAA as novel therapeutic targets for age-associated disease. This works provides a foundation for more detailed examination of the molecular mechanisms underlying the benefits of 3HAA, and how these mechanisms interact with other interventions both within and beyond the kynurenine pathway. We anticipate that these findings will bolster growing interest in developing pharmacological strategies to target tryptophan metabolism to improve health aging.
XCVATR: Characterization of Variant Impact on the Embeddings of Single -Cell and Bulk RNA-Sequencing Samples
Authors: Harmanci Arif O , Harmanci Akdes Serin , Klisch Tiemo , Patel Akash J 
Published: June 2021

AbstractGene expression profiling via RNA-sequencing has become standard for measuring and analyzing the gene activity in bulk and at single cell level. Increasing sample sizes and cell counts provides substantial information about transcriptional architecture of samples. In addition to quantification of expression at cellular level, RNA-seq can be used for detecting of variants, including single nucleotide variants and small insertions/deletions and also large variants such as copy number variants. The joint analysis of variants with transcriptional state of cells or samples can provide insight about impact of mutations. To provide a comprehensive method to jointly analyze the genetic variants and cellular states, we introduce XCVATR, a method that can identify variants, detect local enrichment of expressed variants, within embedding of samples and cells. The embeddings provide information about cellular states among cells by defining a cell-cell distance metric. Unlike clustering algorithms, which depend on a cell-cell distance and use it to define clusters that explain cell clusters globally, XCVATR detects the local enrichment of expressed variants in the embedding space such that embedding can be computed using any type of measurement or method, for example by PCA or tSNE of the expression levels. XCVATR searches local patterns of association of each variant with the positions of cells in an embedding of the cells. XCVATR also visualizes the local clumps of small and large-scale variant calls in single cell and bulk RNA-sequencing datasets. We perform simulations and demonstrate that XCVATR can identify the enrichments of expressed variants. We also apply XCVATR on single cell and bulk RNA-seq datasets and demonstrate its utility.
A Unifying Mechanism Governing Inter-Brain Neural Relationship During Social Interactions
Authors: Zhang Wujie , Yartsev Michael M. 
Published: June 2021

AbstractA key goal of social neuroscience is to understand the relationship between the neural activity of socially interacting individuals. Decades of research have focused on a single aspect of that relationship: the similarity in neural activity across brains. Here we instead asked how neural activity differs between brains, and how that difference evolves alongside activity patterns shared between brains. Applying this framework to pairs of bats engaged in spontaneous social interactions revealed two complementary phenomena characterizing the inter-brain neural relationship: fast “inter-brain catch-up” unfolding in parallel with slow activity covariation across brains. A model reproduced these observations, generated multiple predictions that we confirmed using experimental data, and provided testable hypotheses for studying the inter-brain relationship in larger social groups. Together, the data and model suggest a parsimonious computational mechanism—opposite feedback to neural activity components reflecting inter-brain difference and similarity—that unifies diverse aspects of the inter-brain neural relationship.
Amyloid beta oligomers modulate neuronal autophagy through the primary cilium
Authors: Pampliega Olatz , Soria Federico N. , Pineda-Ramírez Narayana , Bezard Erwan 
Published: June 2021

ABSTRACTThe major neurodegenerative diseases, like Alzheimer’s disease (AD), accumulate neuropathogenic proteins that compromise autophagic function. In AD, autophagy contributes to intracellular APP processing and amyloid beta (Aβ) generation by mutant presenilin-1 (PS1). However, how extracellular soluble Aβ oligomers (Aβo) impact intracellular autophagy is not well understood. The primary cilium (PC), a signaling organelle on the surface of mature neurons and glia, is able to bind Aβ. Since PC signaling pathways knowingly modify autophagy in non-brain cells, we here investigated the role of neuronal PC in the modulation of autophagy during acute extracellular Aβo overload. Our results show that, in vivo, recombinant Aβo require the presence of neuronal PC to modulate early autophagy and to induce the accumulation of autophagic vacuoles in an age-dependent manner. We show that activated Akt mediates these effects in an age-dependent manner, and that ciliary p75NTR receptor is required to block autophagy by Aβo. These findings demonstrate that neuronal PC in the adult brain participates in the deleterious effects mediated by soluble Aβo. The PC should therefore be considered as a target organelle to modulate autophagy for the treatment of neurodegenerative diseases.HighlightsAβo requires the neuronal PC to impair learning in young and old mice.Autophagy in whole hippocampus differs from autophagy response in hippocampal neurons.Aβo induce autophagolysosome accumulation through primary cilia- and age-dependent Akt phosphorylation.
Robust adaptive preview control design for autonomous carrier landing of F/A-18 aircraft
Authors: Bhatia Ajeet Kumar , Ju Jiang , Ziyang Zhen , Ahmed Nigar , Rohra Avinash , Waqar Muhammad 
Published: June 2021

Purpose
The purpose of this paper is to design an innovative autonomous carrier landing system (ACLS) using novel robust adaptive preview control (RAPC) method, which can assure safe and successful autonomous carrier landing under the influence of airwake disturbance and irregular deck motion. To design a deck motion predictor based on an unscented Kalman filter (UKF), which predicts the touchdown point, very precisely.

Design/methodology/approach
An ACLS is comprising a UKF based deck motion predictor, a previewable glide path module and a control system. The previewable information is augmented with the system and then latitude and longitudinal controllers are designed based on the preview control scheme, in which the robust adaptive feedback and feedforward gain’s laws are obtained through Lyapunov stability theorem and linear matrix inequality approach, guarantying the closed-loop system’s asymptotic stability.

Findings
The autonomous carrier landing problem is solved by proposing robust ACLS, which is validated through numerical simulation in presence of sea disturbance and time-varying external disturbances.

Practical implications
The ACLS is designed considering the practical aspects of the application, presenting superior performance with extended robustness.

Originality/value
The novel RAPC, relative motion-based guidance system and deck motion compensation mechanism are developed and presented, never been implemented for autonomous carrier landing operations.
Mapping the urban environment using real-time physiological monitoring
Authors: Dritsa Dimitra , Biloria Nimish 
Published: June 2021

PurposeThis paper presents a critical review of studies which map the urban environment using continuous physiological data collection. A conceptual model is consequently presented for mitigating urban stress at the city and the user level.Design/methodology/approachThe study reviews relevant publications, examining the tools used for data collection and the methods used for data analysis and data fusion. The relationship between urban features and physiological responses is also examined.FindingsThe review showed that the continuous monitoring of physiological data in the urban environment can be used for location-aware stress detection and urban emotion mapping. The combination of physiological and contextual data helps researchers understand how the urban environment affects the human body. The review indicated a relationship between some urban features (green, land use, traffic, isovist parameters) and physiological responses, though more research is needed to solidify the existence of the identified links. The review also identified many theoretical, methodological and practical issues which hinder further research in this area.Originality/valueWhile there is large potential in this field, there has been no review of studies which map continuously physiological data in the urban environment. This study covers this gap and introduces a novel conceptual model for mitigating urban stress.
Project scheduling and performance prediction: a fuzzy-Bayesian network approach
Authors: Rezakhani Pejman 
Published: June 2021

PurposeDespite the extensive research in project risk management and availability of several techniques and tools, quantifying uncertainty in project schedules remains a challenge. Current risk analysis models suffer from several shortcomings that need to be addressed to provide more reliable and valid schedules. This paper aims to present a dynamic decision support system with the purpose of providing project managers with necessary tool for making real-time informed decisions.Design/methodology/approachThe proposed approach incorporates the widely accepted critical path method (CPM) calculations in a Bayesian network (BN). BN is employed to conduct inferencing and causal analysis and provide probabilistic results, which can improve the decision-making process. Time parameters of each activity in the CPM network is modeled by a set of simulation nodes in the BN. Prior probability distribution of activities duration is extracted from experts using a fuzzy analytical solution.FindingsThe model proposed in this paper is able to address some key outstanding issues of current project scheduling techniques through: (1) modeling the causality among different sources of schedule uncertainty, (2) minimizing uncertainty in experts' evaluations, (3) assessing effects of unknown risk factors and (4) using actual activity data for learning the behavior of project and predicting crew productivity.Originality/valueThe purposed methodology provides a framework for the new generation of project schedule analysis tools that are better informed by available knowledge and data, and hence, more reliable and useful.
Changes of base-year and Indian GDP growth: an agnostic look
Authors: Chakrabarty Manisha , Ray Partha 
Published: June 2021

PurposeWorld over, change of base year in the gross domestic product (GDP) is a standard practice of GDP estimation. However, unless a consistent series of GDP is released with respect to the new base for the earlier period, the existence of multiple growth rates creates problems for applied researchers, policymakers and the general public alike. Faced with such a menu of GDP series researchers often try to interpolate a consistent series of GDP. The main purpose of this paper is to analyses the nature of the data generating process of such multiple interpolated series of quarterly growth rates and tries to discern the consistency of such processes.Design/methodology/approachThe present paper tries to look into the statistical implications and complications of such interpolated quarterly GDP/growth series in India in terms of three series of GDP, namely, with 1999–2000, 2004–2005 and 2011–2012 as its bases.FindingsThe analysis reveals that as a result of a change of base year, the nature of the data generating process of the old and new GDP series could undergo changes and experience different breakpoints. While all these conclusions seem to be valid for GDP growth at quarterly intervals, taking the data at annual frequency is less problematic.Practical implicationsThe observation suggests that in most applied work, researchers may not have the luxury of only working with annual data and certain consistency checks will be necessary to check the veracity of the results based on quarterly data with those based on annual data. Second, moving forward it may be useful for the Authorities to make a transition to a chain-based linking method rather than fixed time-period-based bases as is currently done.Originality/valueThe analysis of Indian GDP in this paper is, perhaps, indicative of the fact that usage of quarterly GDP data is to be handled with caution and it is preferable that any serious empirical analysis uses annual GDP data whenever it is available/feasible. The comparison of GDP growth rates at different frequencies and examining the true nature of the process are quite unique in their contribution towards empirical macroeconomic research.
Which search queries are more powerful in tourism demand forecasting: searches via mobile device or PC?
Authors: Hu Mingming , Xiao Mengqing , Li Hengyun 
Published: June 2021

Purpose
While relevant research has considered aggregated data from mobile devices and personal computers (PCs), tourists’ search patterns on mobile devices and PCs differ significantly. This study aims to explore whether decomposing aggregated search queries based on the terminals from which these queries are generated can enhance tourism demand forecasting.

Design/methodology/approach
Mount Siguniang, a national geopark in China, is taken as a case study in this paper; another case, Kulangsu in China, is used as the robustness check. The authors decomposed the total Baidu search volume into searches from mobile devices and PCs. Weekly rolling forecasts were used to test the roles of decomposed and aggregated search queries in tourism demand forecasting.

Findings
Search queries generated from PCs can greatly improve forecasting performance compared to those from mobile devices and to aggregate search volumes from both terminals. Models incorporating search queries generated via multiple terminals did not necessarily outperform those incorporating search queries generated via a single type of terminal.

Practical implications
Major players in the tourism industry, including hotels, tourist attractions and airlines, can benefit from identifying effective search terminals to forecast tourism demand. Industry managers can also leverage search indices generated through effective terminals for more accurate demand forecasting, which can in turn inform strategic decision-making and operations management.

Originality/value
This study represents one of the earliest attempts to apply decomposed search query data generated via different terminals in tourism demand forecasting. It also enriches the literature on tourism demand forecasting using search engine data.