bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell Type Assignments for Spatial Transcriptomics Data
Authors: Teng Haotian , Yuan Ye , Bar-Joseph Ziv 
Published: February 2021

ABSTRACTMotivationRecent advancements in fluorescencein situhybridization (FISH) techniques enable them to concurrently obtain information on the location and gene expression of single cells. A key question in the initial analysis of such spatial transcriptomics data is the assignment of cell types. To date, most studies used methods that only rely on the expression levels of the genes in each cell for such assignments. To fully utilize the data and to improve the ability to identify novel sub-types we developed a new method, FICT, which combines both expression and neighborhood information when assigning cell types.ResultsFICT optimizes a probabilistic function that we formalize and for which we provide learning and inference algorithms. We used FICT to analyze both simulated and several real spatial transcriptomics data. As we show, FICT can accurately identify cell types and sub-types improving on expression only methods and other methods proposed for clustering spatial transcriptomics data. Some of the spatial sub-types identified by FICT provide novel hypotheses about the new functions for excitatory and inhibitory neurons.AvailabilityFICT is available at:https://github.com/haotianteng/FICTContactzivbj@andrew.cmu.edu
Nothing in evolution makes sense except in the light of parasitism: evolution of complex replication strategies
Authors: Hickinbotham Simon J. , Stepney Susan , Hogeweg Paulien 
Published: February 2021

AbstractParasitism emerges readily in models and laboratory experiments of RNA world and would lead to extinction unless prevented by compartmentalisation or spatial patterning. Modelling replication as an active computational process opens up many degrees of freedom that are exploited to meet environmental challenges, and to modify the evolutionary process itself. Here we use automata chemistry models and spatial RNA world models to study the emergence of parasitism and the complexity that evolves in response. The system is initialised with a hand-designed replicator that copies other replicators with a small chance of point mutation. Almost immediately, short parasites arise; these are copied more quickly, and so have an evolutionary advantage. The replicators also become shorter, and so are replicated faster; they evolve a mechanism to slow down replication, which reduces the difference of replication rate of replicators and parasites. They also evolve explicit mechanisms to discriminate copies of self from parasites; these mechanisms become increasingly complex. New parasite species continually arise from mutated replicators, rather than from evolving parasite lineages. Evolution itself evolves, eg by effectively increasing point mutation rates, and by generating novel emergent mutational operators. Thus, parasitism drives the evolution of complex replicators and complex ecosystems.
Pax3 repairs a neural circuit through a program of directed axon outgrowth
Authors: Jara J. Sebastian , Avci Hasan X. , Kouremenou Ioanna , Doulazmi Mohamed , Bakouche Joelle , Dubacq Caroline , Goyenvalle Catherine , Mariani Jean , Lohof Ann M. , Sherrard Rachel M. 
Published: February 2021

ABSTRACTRepairing damaged or dysfunctional human brain circuits remains an ongoing challenge for biomedical science. While surviving neuronal networks can be reorganised after lesion, for example by neurotrophins, these new connections are disorganised and rarely produce clinical improvement. Here we investigate how to promote axonal growth while retaining correct cellular targeting. We show that, in response to brain-derived neurotrophic factor (BDNF) in target-tissue, potential reinnervating neurons upregulate Pax3. Pax3 in turn increases polysialic acid-neural cell adhesion molecule (PSA-NCAM) on their axon terminals, facilitating their outgrowth and pathfinding, and resulting in correctly-targeted neural circuit repair in the mature nervous system. This is a novel role for Pax3, which we confirmed by showing its expression in afferent neurons is essential for spontaneous and BDNF-induced reinnervation in the developing and mature brains, respectively. Together these results suggest that Pax3 contributes to a repair program, in which axon growth is promotedanddirection signaling maintained. These data advance our understanding for accurately rebuilding neural circuits: restricting growth-promotion to potential afferent neurons, as opposed to stimulating the whole circuit, allows axon growth without impairing its guidance.
Different historical generation intervals in human populations inferred from Neanderthal fragment lengths and patterns of mutation accumulation
Authors: Coll Macià Moisès , Skov Laurits , Peter Benjamin Marco , Schierup Mikkel Heide 
Published: February 2021

AbstractAfter the main out-of-Africa event, humans interbred with Neanderthals leaving 1-2% of Neanderthal DNA scattered in small fragments in all non-African genomes today1,2. Here we investigate the size distribution of these fragments in non-African genomes3. We find consistent differences in fragment length distributions across Eurasia with 11% longer fragments in East Asians than in West Eurasians. By comparing extant populations and ancient samples, we show that these differences are due to a different rate of decay in length by recombination since the Neanderthal admixture. In line with this, we observe a strong correlation between the average fragment length and the accumulation of derived mutations, similar to what is expected by changing the ages at reproduction as estimated from trio studies4. Altogether, our results suggest consistent differences in the generation interval across Eurasia, by up to 20% (e.g. 25 versus 30 years), over the past 40,000 years. We use sex-specific accumulations of derived alleles to infer how these changes in generation intervals between geographical regions could have been mainly driven by shifts in either male or female age of reproduction, or both. We also find that previously reported variation in the mutational spectrum5may be largely explained by changes to the generation interval and not by changes to the underlying mutational mechanism. We conclude that Neanderthal fragment lengths provide unique insight into differences of a key demographic parameter among human populations over the recent history.
Regulation of plasmodesmata at specific cell-cell interfaces
Authors: Li Zhongpeng , Aung Kyaw 
Published: February 2021

AbstractPrecise exchange of information and resources among cells is essential for multicellular organisms. Intercellular communication among diverse cell types requires differential mechanisms to achieve the specific regulation. Despite the significance of intercellular communication, it is largely unknown how the communication between different cells is regulated. Here, we report that two members of plasmodesmata-located proteins modulate plasmodesmata at two distinct cell-cell interfaces.
The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma
Authors: Pan Min , Wright William C. , Chapple Rich , Zubair Asif , Sandhu Manbir , Batchelder Jake , Low Jonathan , Blankenship Kaley B , Wang Yingzhe , Gordon Brittney , Archer Payton , Brady Samuel W. , Natarajan Sivaraman , Posgai Matthew J. , Schuetz John , Miller Darcie , Kalathur Ravi , Chen Siquan , Connelly Jon Patrick , Madan Babu M. , Dyer Michael A. , Pruett-Miller Shondra M. , Freeman Burgess B. , Chen Taosheng , Godley Lucy A. , Blanchard Scott , Stewart Elizabeth , Easton John , Geeleher Paul 
Published: February 2021

ABSTRACTSurvival in high-risk pediatric neuroblastoma has remained around 50% for the last 20 years, with immunotherapies and targeted therapies having had minimal impact. Here, we identify the small molecule CX-5461 as selectively cytotoxic to high-risk neuroblastoma and synergistic with low picomolar concentrations of topoisomerase I inhibitors improving survivalin vivoin orthotopic patient-derived xenograft neuroblastoma mouse models. CX-5461 recently progressed through phase I clinical trial as a first-in-human inhibitor of RNA-POL I. However, we also use a comprehensive panel ofin vitroandin vivoassays to demonstrate that CX-5461 has been mischaracterized and that its primary target at pharmacologically relevant concentrations, is in fact topoisomerase II beta (TOP2B), not RNA-POL I. These findings are important because existing clinically approved chemotherapeutics have well-documented off-target interactions with TOP2B, which have previously been shown to cause both therapy-induced leukemia and cardiotoxicity—often-fatal adverse events, which can emerge several years after treatment. Thus, while we show that combination therapies involving CX-5461 have promising anti-tumor activityin vivoin neuroblastoma, our identification of TOP2B as the primary target of CX-5461 indicates unexpected safety concerns that should be examined in ongoing phase II clinical trials in adult patients before pursuing clinical studies in children.
A Mixed-Modeling Framework for Whole-Brain Dynamic Network Analysis
Authors: Bahrami Mohsen , Laurienti Paul J. , Shappell Heather M. , Simpson Sean L. 
Published: February 2021

AbstractThe emerging area of dynamic brain network analysis has gained considerable attraction in recent years. While current tools have proven useful in providing insight into dynamic patterns of brain networks, development of multivariate statistical frameworks that allow for examining the associations between phenotypic traits and dynamic patterns of system-level properties of the brain, and drawing statistical inference about such associations, has largely lagged behind. To address this need we developed a mixed-modeling framework that allows for assessing the relationship between any desired phenotype and dynamic patterns of whole-brain connectivity and topology. Unlike current tools which largely use data-driven methods, our model-based method enables aligning neuroscientific hypotheses with the analytic approach. We demonstrate the utility of this model in identifying the relationship between fluid intelligence and dynamic brain networks using resting-state fMRI (rfMRI) data from 200 subjects in the Human Connectome Project (HCP) study. To our knowledge, this approach provides the first model-based statistical method for examining dynamic patterns of system-level properties of the brain and their relationships to phenotypic traits.
Negative DNA supercoiling makes protein-mediated looping deterministic and ergodic within the bacterial doubling time
Authors: Yan Yan , Xu Wenxuan , Kumar Sandip , Zhang Alexander , Leng Fenfei , Dunlap David , Finzi Laura 
Published: February 2021

AbstractProtein-mediated DNA looping is fundamental to gene regulation and such loops occur stochastically in purified systems. Additional proteins increase the probability of looping, but these probabilities maintain a broad distribution. For example, the probability of lac repressor-mediated looping in individual molecules ranged 0-100%, and individual molecules exhibited representative behavior only in observations lasting an hour or more. Titrating with HU protein progressively compacted the DNA without narrowing the 0-100% distribution. Increased negative supercoiling produced an ensemble of molecules in which all individual molecules more closely resembled the average. Furthermore, in only twelve minutes of observation, well within the doubling time of the bacterium, most molecules exhibited the looping probability of the ensemble. DNA supercoiling, an inherent feature of all genomes, appears to impose time-constrained, emergent behavior on otherwise random molecular activity.
AIM-CICs: automatic identification method for Cell-in-cell structures based on convolutional neural network
Authors: Tang Meng , Su Yan , Zhao Wei , Niu Zubiao , Ruan Banzhan , Li Qinqin , Zheng You , Wang Chenxi , Zhou Yong , Zhang Bo , Zhou Fuxiang , Huang Hongyan , Shi Hanping , Sun Qiang 
Published: February 2021

AbstractWhereas biochemical markers are available for most types of cell death, current studies on non-autonomous cell death by entosis relays strictly on the identification of cell-in-cell structure (CICs), a unique morphological readout that can only be quantified manually at present. Moreover, the manual CICs quantification is generally over-simplified as CICs counts, which represents a major hurdle against profound mechanistic investigations. In this study, we take advantage of artificial intelligence (AI) technology to develop an automatic identification method for CICs (AIM-CICs), which performs comprehensive CICs analysis in an automated and efficient way. The AIM-CICs, developed on the algorithm of convolutional neural network (CNN), can not only differentiate between CICs and non-CICs (AUC > 0.99), but also accurately categorize CICs into five subclasses based on CICs stages and cell number involved (AUC > 0.97 for all subclasses). The application of AIM-CICs would systemically fuel researches on CICs-mediated cell death such as high-throughput screening.
Dynamic arrest and aging of biomolecular condensates are regulated by low-complexity domains, RNA and biochemical activity
Authors: Linsenmeier Miriam , Hondele Maria , Grigolato Fulvio , Secchi Eleonora , Weis Karsten , Arosio Paolo 
Published: February 2021

AbstractBiomolecular condensates require suitable material properties to properly carry out their function. Yet, modulators that affect the material properties of condensates have remained largely unexplored.Here we apply Differential Dynamic Microscopy (DDM) to probe the material properties of anin vitromodel of processing bodies (P-bodies) consisting of condensates formed by the DEAD-box ATPase Dhh1 in the presence of ATP and RNA. DDM allows us to measure the viscosity of liquid droplets and to distinguish between liquid-like and gel- or glass-like condensates. By applying this single-droplet technique we show that condensates within the same population exhibit a distribution of material properties, which can be drastically affected by several modulators such as the low-complexity domains (LCDs) of the protein, the protein/RNA ratio, the type of RNA as well as the enzymatic activity.In particular, we show that structured RNA leads to a large fraction of dynamically arrested condensates with respect to unstructured polyuridylic acid (polyU), emphasizing the role of RNA structure in condensate dynamics. We further demonstrate that the ageing of the condensates and the formation of gel or glass-like structures is reduced by promoting the enzymatic ATPase activity of Dhh1 and the rate of droplet formation and dissolution.Our study shows that not only the reversible formation and dissolution of condensates but also their material properties are regulated on several levels, and that biochemical activity and material turnover can be important to maintain fluid-like properties over time.
A supply chain risk management maturity model and a multi-criteria classification approach
Authors: Cavalcante de Souza Feitosa Ingrid Saiala , Ribeiro Carpinetti Luiz Cesar , de Almeida-Filho Adiel Teixeira 
Published: February 2021

PurposeThe purpose of this paper is to propose a supply chain risk management (SCRM) maturity model combined with a fuzzy TOPSIS classification method to evaluate and sort an organization into a pre-defined maturity level.Design/methodology/approachAn axiomatic and prescriptive research method guided this study. Therefore, it proposes a prescriptive approach of maturity classification based on a theoretical SCRM maturity model combined with a multi-criteria decision technique.FindingsThe results of a pilot application indicated a consistent classification and the value of the model for diagnosing flaws and pointing directions for improving operational and disruption risk management. Its comprehensiveness allows applying it to supply chains of several industry sectors.Research limitations/implicationsThe proposed model does not include all possible risks and could be revised in further developments. Also, adjustment of the maturity profiles of the multi-criteria decision-making (MCDM) model requires a learning process from practical applications.Practical implicationsThe adoption of the risk management maturity grid by practitioners may bring the benefit of a more objective and comprehensive evaluation of risk management processes in the supply chain context.Social implicationsAn immediate social implication derives from the improvement actions that may result from the diagnosis of risk management vulnerabilities identified in the pilot application. In general, the proposed model has the potential to reduce risks, improve results and contribute to economic sustainability.Originality/valueThe maturity grid and decision model integrate overall aspects of risk management, bringing together managerial concepts to deal with a variety of supply chain operational risks. The combined multi-criteria classification procedure to sort the maturity level of an organization is also a novelty.
Reconsidering religious gender normativity in graphic novel adaptations: a quantitative and qualitative case study
Authors: Hurwich Talia 
Published: February 2021

Purpose
This paper aims to illustrate how graphic novel adaptations can engage adolescents in conversations about gender and society, particularly when adaptations are weighed against messaging found in a student’s everyday life such as religiously motivated gender normativity.

Design/methodology/approach
This paper is based on quantitative and qualitative analyzes of the interview, think-aloud and survey data collected from 15 adolescents who self-identified as Modern Orthodox Jewish women. Texts used for think-aloud were three graphic novel adaptations that critically adapted potentially misogynistic readings and interpretations of religious Jewish texts such as the Bible.

Findings
Epistemic network analysis and constructivist grounded theory show that visual elements found in each adaptation can spark deeply personal reflections on topics that are often explicitly or implicitly suppressed by social norms such as gender normativity in Jewish texts and practices.

Originality/value
This paper is timely and contributes to understanding the apparent cultural clash between religious conservativism and movements for social change, using the graphic novel to mediate between them.
Remaining useful life prediction of lithium-ion battery based on auto-regression and particle filter
Authors: Lin Jie , Wei Minghua 
Published: February 2021

PurposeWith the rapid development and stable operated application of lithium-ion batteries used in uninterruptible power supply (UPS), the prediction of remaining useful life (RUL) for lithium-ion battery played an important role. More and more researchers paid more attentions on the reliability and safety for lithium-ion batteries based on prediction of RUL. The purpose of this paper is to predict the life of lithium-ion battery based on auto regression and particle filter method.Design/methodology/approachIn this paper, a simple and effective RUL prediction method based on the combination method of auto-regression (AR) time-series model and particle filter (PF) was proposed for lithium-ion battery. The proposed method deformed the double-exponential empirical degradation model and reduced the number of parameters for such model to improve the efficiency of training. By using the PF algorithm to track the process of lithium-ion battery capacity decline and modified observations of the state space equations, the proposed PF + AR model fully considered the declined process of batteries to meet more accurate prediction of RUL.FindingsExperiments on CALCE dataset have fully compared the conventional PF algorithm and the AR + PF algorithm both on original exponential empirical degradation model and the deformed double-exponential one. Experimental results have shown that the proposed PF + AR method improved the prediction accuracy, decreases the error rate and reduces the uncertainty ranges of RUL, which was more suitable for the deformed double-exponential empirical degradation model.Originality/valueIn the running of UPS device based on lithium-ion battery, the proposed AR + PF combination algorithm will quickly, accurately and robustly predict the RUL of lithium-ion batteries, which had a strong application value in the stable operation of laboratory and other application scenarios.
Can protection motivation theory explain the perception of international tourists' on medical tourism?
Authors: Seow Ai Na , Choong Chee Keong , Chen I-Chi , Choong Yuen Onn 
Published: February 2021

PurposeMedical tourism has grown to become a formidable multinational industry to generate revenue. This phenomenon has also increased impact on the healthcare sector as well as strategies development opportunities. The present study emphases on the international tourists' behavioural intention for medical tourism in Malaysia. A research framework is derived from the exceptional component of fear appeal in protection motivation theory (PMT).Design/methodology/approachData were collected with a sample of 501 respondents and analysed via structural equation modelling approach. Both measurement model and structural model were assessed to generate the result.FindingsThe outcomes have shown a good backing on the use of adapted PMT theoretical model. There is a higher predictive power on health coping than health threats. Coping alternatives can be served as the linkage between the PMT appraisals and behavioural intention.Research limitations/implicationsThe study confirmed the effectiveness of using a theoretical framework in predicting international tourists' behavioural intention for medical tourism. It is suggesting that risk adaptive behaviour does offer a valuable proposition in contributing to the reception of medical tourism.Practical implicationsThe present study argues the need for greater clarity in understanding the emergent implications for health policy and healthcare delivery for future medical tourism development.Originality/valueThe fundamental theories and current literature do not incorporate the component of fear appeal in explaining decision making. The study findings demonstrate that protection motivation theory has provide another promising theoretical model in explaining international tourists' behaviour intention for medical tourism.
HIV/AIDS and child malnutrition in eastern and southern Africa
Authors: Adika Gameli 
Published: February 2021

AbstractHIV/AIDS and child malnutrition are pervasive in eastern and southern Africa. This paper employs cross‐country panel data on 20 countries from 1991 to 2017 to explore the macro‐level relationship between HIV/AIDS and child malnutrition. Using instrumental variables (IV) regression, we find that HIV/AIDS is a robust predictor of long‐term and chronic malnutrition. Conditional on various controls, the results demonstrate a positive empirical association between HIV/AIDS and stunting. Moreover, increased access to improved water, female education, and food availability are critical for reducing stunting. These findings underscore the need for an integrated national policy on nutrition and HIV/AIDS and intersectoral collaboration between government agencies responsible for managing nutrition and HIV/AIDS programs.