bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complementary biological and computational approaches identify distinct mechanisms of chlorpyrifos versus chlorpyrifos oxon induced dopaminergic neurotoxicity
Authors: Sammi Shreesh Raj , Syeda Tauqeerunnisa , Conrow Kendra D. , Leung Maxwell C. K. , Cannon Jason R. 
Published: July 2022

AbstractOrganophosphate (OP) pesticides are widely used in agriculture. While acute cholinergic toxicity has been extensively studied, chronic effects on other neurons are less understood. Here, we demonstrated that the OP pesticide chlorpyrifos (CPF) and its oxon metabolite are dopaminergic neurotoxicants in Caenorhabditis elegans. CPF treatment led to inhibition of mitochondrial complex II, II + III, and V in rat liver mitochondria, while CPF oxon did not (complex II + III, and IV inhibition observed only at high doses). While the effect on C. elegans cholinergic behavior was mostly reversible with toxicant washout, dopamine-associated deficits persisted, suggesting dopaminergic neurotoxicity was irreversible. CPF reduced the mitochondrial content in a dose-dependent manner and the fat modulatory genes cyp-35A2 and cyp-35A3 were found to have a key role in CPF neurotoxicity. These findings were consistent with in vitro effects of CPF and CPF oxon on nuclear receptor signaling and fatty acid/steroid metabolism observed in ToxCast assays. Two-way hierarchical analysis revealed in vitro effects on estrogen receptor (ER,) pregnane X receptor (PXR), and peroxisome proliferator-activated receptor gamma (PPAR gamma) pathways as well as neurotoxicity of chlorpyrifos, malathion, and diazinon, while these effects were not detected in malaoxon and diazoxon. Taken together, our study suggests that mitochondrial toxicity and metabolic effects of CPF, but not CPF-oxon, have a key role of CPF neurotoxicity in the low-dose, chronic exposure. Further mechanistic studies are needed to examine mitochondria as a common target for all OP pesticide parent compounds, since this has important implications on cumulative pesticide risk assessment.
Quantifying Cell-type-specific Differences of Single-cell Datasets using UMAP and SHAP
Authors: Lim Hong Seo , Qiu Peng 
Published: July 2022

ABSTRACTWith the rapid advances in single-cell profiling technologies, larger-scale investigations that require comparisons of multiple single-cell datasets can lead to novel findings. Specifically, quantifying cell-type-specific responses to different conditions across single-cell datasets could be useful in understanding how the difference in conditions is induced at a cellular level. Here we present a computational pipeline that quantifies the cell-type-specific differences and identifies genes responsible for the differences. We quantify differences observed in a low-dimensional UMAP space as a proxy for the difference present in the high-dimensional space and use SHAP to quantify genes driving the differences. Here we applied our algorithm to the Iris flower dataset, scRNA-seq dataset, and mass cytometry dataset, and demonstrate that it can robustly quantify the cell-type-specific differences and it can also identify genes that are responsible for the differences.
Lower Risks of Incident Colorectal Cancer in SGLT2i Users Compared to DPP4i Users: A Propensity Score-matched Study with Competing Risk Analysis
Authors: Chiu Chan Raymond Ngai , Fung Chan Robert Ngai , In Chou Oscar Hou , Loy Lee Teddy Tai , Roever Leonardo , Li Guoliang , Wong Wing Tak , Chung Wai Abraham Ka , Liu Tong , Tse Gary , Lee Sharen 
Published: July 2022

AbstractBackgroundDiabetes mellitus is associated with the development of colorectal cancer (CRC). There have been a lack of study comparing the risk of colorectal cancer in sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i), both of which commonly prescribed second line agents for diabetes.MethodsWe conducted a territory wide retrospective cohort study on patients with type 2 diabetes who was prescribed either of the two agents. Baseline demographics, use of other medications, comorbidities and biochemical parameters were extracted. Propensity score matching was performed to reduce the impacts of cofounders. Cause specific Cox regression was used to evaluate the risk of incident colorectal cancer in SGLT2i users, as compared to DPP4i users. Subgroup analyses based on age, gender and estimated glomerular filtration rate were performed.ResultsAfter propensity score matching, we included 13029 subjects who were prescribed SGLT2i and DPP4i respectively. Incidence rate ratio of CRC was 0.566 (0.418-0.766) in SGLT2i users. Overall, use of SGLT2i was associated with a lower risk of incident CRC (HR: 0.526; 95% CI: 0.382-0.724; P <0.001). In subgroup analyses, use of SGLT2i was associated with lower risks of incident CRC only in men (HR: 0.461; 95% CI: 0.303-0.702; P <0.001), patients < 65 years old and patients (HR:0.294; 95% CI: 0.174-0.496; P<0.001) with eGFR ≥ 45 mL/min/ 1.73m2(HR: 0.560; 95% CI: 0.395-0.792; P =0.001).ConclusionUse of SGLT2i may reduce risk of incident CRC as compared to use of DPP4i, especially in younger male patients with fairly preserved renal function.
High-Resolution Spatiotemporal Analysis of Single Serotonergic Axons in an In Vitro System
Authors: Hingorani Melissa , Viviani Adele M.L. , Sanfilippo Jenna E. , Janušonis Skirmantas 
Published: July 2022

ABSTRACTVertebrate brains have a dual structure in that they are composed of (i) axons that can be well captured with graph-theoretical methods and (ii) axons that form a dense matrix in which neurons with precise connections operate. A core part of this matrix is formed by axons (fibers) that store and release 5-hydroxytryptamine (5-HT, serotonin), an ancient neurotransmitter that supports neuroplasticity and has profound implications for mental health. The self-organization of the serotonergic matrix is not well understood, despite recent advances in experimental and theoretical approaches. In particular, individual serotonergic axons produce highly stochastic trajectories, fundamental to the construction of regional fiber densities, but further advances in predictive computer simulations require more accurate experimental information. This study examined single serotonergic axons in culture systems (co-cultures and monolayers), by using a complementary set of high-resolution methods: confocal microscopy, holotomography (refractive index-based live imaging), and super-resolution (STED) microscopy. It shows that serotonergic axon walks in neural tissue may strongly reflect the stochastic geometry of this tissue and it also provides new insights into the morphology and branching properties of serotonergic axons. The proposed experimental platform can support next-generation analyses of the serotonergic matrix, including seamless integration with supercomputing approaches.
Dissecting the genetic basis of the heterosis of Y900, an elite super-hybrid rice
Authors: Sun Zhizhong , Peng Jianxiang , Lv Qiming , Ding Jia , Chen Siyang , Duan Meijuan , He Qiang , Wu Jun , Tian Yan , Yu Dong , Tan Yanning , Sheng Xiabing , Chen Jin , Sun Xuewu , Liu Ling , Peng Rui , Liu Hai , Zhou Tianshun , Xu Na , Yuan Longping , Wang Bingbing , Yuan Dingyang 
Published: July 2022

AbstractY900 is one of the top hybrid rice varieties with a yield exceeding 15 t/hm2. To dissect the mechanism of heterosis, the male parent line R900 and female parent line Y58S were sequenced using long-read and Hi-C technology. High-quality reference genomes of sizes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 SNPs and 299,149 Indels. No megabase level structural variations exist. >75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the Geng/japonica-type genetic components from different male parents showed an increasing trend from phase 2-4 super-hybrid rice; Transcriptome analysis revealed that additive and dominance effects are the main genetic effects that constitute the heterosis of Y900. Allele-specific expression patterns and expression regulation patterns are quite dynamic in different tissues. For young panicle tissues, cis-regulation is dominant, while trans-regulation is more popular in leaf issues. Overdominance is more likely regulated by the trans-regulation mechanism. The differential gene expression and regulation pattern are closely related to Geng/japonica introgression. Additionally, R900 contained several excellent japonica haplotypes, such as NAL1, OsSPL13, Ghd8, OsBRI1, and DTH2, which make a good complement to Y58S. The fine tune mechanism through dynamic expression or regulation pattern change, especially on some key functional genes, is the base for heterosis.
Exploring Differential Gene Expression Profiles OfDero (Allodero) HylaeIn Their Parasitic And Free-Living Forms
Authors: Bonham Claire , Roguski Ashley , Langford Gabriel , Macrander Jason 
Published: July 2022

ABSTRACTParasitism is ubiquitous in nature, yet little is known about the evolutionary mechanisms that lead to a parasitic lifestyle. Facultative parasites can switch between free-living and parasitic lifestyles, which may provide an opportunity to study the genetic mechanisms underlying a transition to parasitism. The oligochaeteDero (Allodero) hylaeis a facultative parasite commonly found within the ureter of various anuran species, such as the Cuban Tree Frog (Osteopilus septentrionalis).Dero hylaemakes passage through the frog’s cloaca, where it then infects the ureter. In the ureter, the worm loses free-living characteristics such as hair setae, dorsal setae, a digestive tract, and fossa with gills as it transitions to a parasitic lifestyle.Dero hylaemay be expelled from its host during urination, when this occurs the worm will reacquire free-living characteristics. The focus of this study is to compare the differential gene expression profiles observed when this rapid morphological change takes place. Specimens ofD. hylaewere collected from wild Cuban Tree Frogs and either flash-frozen for their parasitic stage RNA profile or cultured for two weeks to produce their free-living stage and then flash-frozen. Using the sequenced RNA, ade novotranscriptome was assembled and differential gene expression RNA Tag-Seq analysis between the free-living and parasitic life forms was analyzed. Based on these results, we have identified 213 genes differentially expressed transcripts between the two life forms, 190 of these being up-regulated in the free-living life form. While over half of the differential genes recovered did not recover any significant BLAST hits, many of these genes did provide insight into which molecular signals are potentially used byD. hylaeto lose and subsequently regrow their setae, digestive tract, and gills. This analysis provides significant insight into which differentially expressed genes are linked to drastic morphological changes observed in this rare oligochaete parasitism across the free-living and parasitic forms ofD. hylae.
Systematic comparison and rational design of theophylline riboswitches for efficient gene repression
Authors: Wang Xun , Fang Can , Wang Yifei , Shi Xinyu , Yu Fan , Xiong Jin , Chou Shan-Ho , He Jin 
Published: July 2022

ABSTRACTRiboswitches are promising regulatory tools in synthetic biology. To date, 25 theophylline riboswitches have been developed for gene expression regulation in bacteria. However, no one has systematically evaluated their regulatory effects. To facilitate rational selection of theophylline riboswitches, we examined 25 theophylline riboswitches in Escherichia coli and surprised to find that none of the five repressive riboswitches were more than 2-fold effective. To solve this problem, we rationally designed a transcriptional repressive riboswitch and demonstrated its effect not only in various bacterial strains but also in different growth media or different temperatures. By introducing two copies of theophylline riboswitches and a RepA protein degradation tag coding sequence at the 5’-end of a reporter gene, we successfully constructed a dual gene expression regulatory system with up to 150-fold potency, namely the R2-RepA system. R2-RepA system is only 218 bp in length, expression of any protein could be repressed efficiently by simply inserting this system upstream of the target protein-coding sequence. This study represented a crucial step toward harnessing theophylline riboswitches and expanding the synthetic biology toolbox.
Meta-analysis of fecal metagenomes reveals global viral signatures and its diagnostic potential for colorectal cancer and adenoma
Authors: Chen Fang , Li Shenghui , Guo Ruochun , Song Fanghua , Zhang Yue , Wang Xifan , Huo Xiaokui , Lv Qingbo , Ullah Hayan , Wang Guangyang , Ma Yufang , Yan Qiulong , Ma Xiaochi 
Published: July 2022

AbstractIntroductionGut microbiome plays an important role in maintaining human health. Although mounting evidence has revealed the critical function of the gut bacteriome in the progression of CRC, the contribution of gut viral community to CRC is rarely studied.ObjectivesThe present study aimed to reveal the gut virome signatures of colorectal adenoma patients and CRC patients and decipher the potential viral markers to build clinical predictive models for diagnosis.Methods1,282 available fecal metagenomes data from 9 published CRC studies were collected. A new virus database was constructed based on a reference-independent virome approach for further analysis. Viral markers were filtered by statistical methods and used to build machine learning models such as Random Forest and Least Absolute Shrinkage and Selection Operator (LASSO) to distinguish patients from controls. New fecal samples were collected to validate the generalization of predictive model.ResultsThe gut viral composition of CRC patients was drastically altered compared with healthy, as evidenced by changes in several Siphoviridae viruses and a reduction of Microviridae, whereas the virome variation in adenoma patients was relatively low. The viral markers contained the phages of Porphyromonas, Fusobacterium, Hungatella, and Ruminococcaceae. In 9 cohorts and independent validation cohorts, a random forest (RF) classifier and LASSO model got the optimal AUC 0.830 and 0.906, respectively. While the gut virome analysis of adenoma patients identified 88 differential viruses and achieved an optimal AUC of 0.772 for discriminating patients from controls.ConclusionOur findings demonstrate the distinctly different composition of gut virome between healthy controls and CRC patients, and highlight the potential of viral markers for clinical diagnosis.
Exploring Impacts to COVID-19 Herd Immunity Thresholds Under Demographic Heterogeneity that Lowers Vaccine Effectiveness
Authors: Paris Chloé Flore , Spencer Julie Allison , Castro Lauren A. , Del Valle Sara Y. 
Published: July 2022

AbstractThe COVID-19 pandemic has caused severe health, economic, and societal impacts across the globe. Although highly efficacious vaccines were developed at an unprecedented rate, the heterogeneity in vaccinated populations has reduced the ability to achieve herd immunity. Specifically, as of Spring 2022, the 0–4 year-old population is still unable to be vaccinated and vaccination rates across 5-11 year olds are low. Additionally, vaccine hesitancy for older populations has further stalled efforts to reach herd immunity thresholds. This heterogeneous vaccine landscape increases the challenge of anticipating disease spread in a population. We developed an age-structured Susceptible-Infectious-Recovered-type mathematical model to investigate the impacts of unvaccinated subpopulations on herd immunity. The model considers two types of undervaccination - age-related and behavior-related - by incorporating four age groups based on available FDA-approved vaccines. The model accounts for two different types of vaccines, mRNA (e.g., Pfizer, Moderna) and vector (e.g., Johnson and Johnson), as well as their effectiveness. Our goal is to analyze different scenarios to quantify which subpopulations and vaccine characteristics (e.g., rate or efficacy) most impact infection levels in the United States, using the state of New Mexico as an example.
Impacts of emotional regulation, adaptive selling and customer-oriented behavior on sales performance: the moderating role of job resourcefulness
Authors: Kuo Szu-Yu , Kao Ya-Ling , Tang Jia-Wei , Tsai Pei-Hsuan 
Published: July 2022

PurposeGiven the increasing intensity of highly competitive markets, this study aims to evaluate the effect of salespeople's emotional regulation, adaptive selling and customer-oriented behavior on sales performance.Design/methodology/approachA research model was tested by using a sample of 288 respondents from the logistics industry in Taiwan. Structural equation modeling was used to examine the relationships between emotional regulation, adaptive selling, job resourcefulness, customer-oriented behavior and sales performance.FindingsThe results indicate that emotional regulation, adaptive selling and job resourcefulness can improve customer-oriented behavior, and that customer-oriented behavior and job resourcefulness can enhance sales performance. By highlighting the role of job resourcefulness, the authors find a positive moderating effect among these four dimensions.Originality/valueThe findings can help salespeople integrate customer-oriented behaviors into strategic changes to regulate their own emotions and those of others to productively address and resolve difficult business conditions. The theoretical and managerial implications of this work's contributions to international logistics are also discussed.
Design of a voltage regulation device based on virtual air gap principle
Authors: Tiourguiouine Amar , Demian Cristian , Romary Raphael , Zmirli Mehdi , Bernard Philippe 
Published: July 2022

Purpose
This paper aims to present the principle of virtual air gap inductance and the design of a voltage regulation device based on this principle. The authors provide a comprehensive analysis of this specific application that consists of locally saturating the magnetic circuit of the voltage regulator to modify its global properties. This saturation is created by a direct current flowing in a small auxiliary coil inserted in the specific area of the magnetic circuit to saturate this zone.

Design/methodology/approach
Analytical calculation and finite elements simulations are used to optimize the device for a specific application tied to the supply of electrical ovens in metallurgic usage. Experimental results are presented at the end of the paper.

Findings
The experimental results presented in this paper are in concordance with the analytical calculation and with the finite element simulations for different operation points. The difficulty of the study of the virtual air gap comes mainly from the nonlinearity of the phenomena because the principle is based on a local and controllable saturation of the magnetic circuit.

Originality/value
The originality of the paper concerns the introduction of virtual air gap principle in a specific industrial application.
Effect of knowledge management and co-evolvement on green operations: the role of corporate environmental strategy
Authors: Das Chiranjit 
Published: July 2022

Purpose
This study aims to analyze the relationships between knowledge management and co-evolvement to green product and process design and green manufacturing and logistics. Besides, this study also analyses the direct and indirect effects of corporate environmental strategy, knowledge management and co-evolvement.

Design/methodology/approach
The data used in this study were collected by a survey of Indian manufacturing firms and analyzed by a variance-based structural equation modeling technique to test the hypotheses.

Findings
The results suggested that knowledge management and co-evolvement have significant positive relationships to green product and process design and green manufacturing and logistics. Likewise, corporate environmental strategy has positive effects on knowledge management and co-evolvement.

Practical implications
Manufacturing firms should invest and deploy corporate environmental strategies to develop knowledge management and co-evolvement capability that foster green product and process design and manufacturing and logistics.

Originality/value
This study investigates the role of knowledge management and co-evolvement to improve green product and process design and green manufacturing and logistics. The uniqueness of this study is that it investigates novel direct and indirect relationships between corporate environmental strategy and knowledge management and co-evolvement.
Revisiting the whole systems approach: designing supply chains in a turbulent world
Authors: Naim Mohamed M. , Gosling Jonathan 
Published: July 2022

PurposeThe systems approach is an exemplar of design science research (DSR), whereby specific designs yield generic knowledge. DSR is increasingly being adopted in logistics and operations management research, but many point to neglect of the human aspects of solutions developed. The authors argue that it is possible to look back at the history of the systems movement to seek precedent for ‘dealing’ with the social components, providing a methodologically pluralistic ‘research design’ framework. Thereby, systems approaches are foundational to providing a design-based ‘science’ to progressing the logistics and supply chain management field, dealing with contemporary topics such as resilience.Design/methodology/approachThe authors undertake a discursive assessment of relevant streams of engineering, social science and systems research, with a conceptual development of how the latter influences supply chain design approaches.FindingsBuilding on a phenomenological framework, the authors create a generic design science research design (DSRD) that enables researchers to choose and integrate the right tools and methods to address simple, complicated and complex problems, dealing with technological, process and social problems.Research limitations/implicationsThe DSRD provides a framework by which to exploit a range of methodological stances to problem solving, including quantitative modelling perspectives and ‘soft’ systems social science approaches. Four substantive gaps are identified for future research – establishing the root cause domain of the problem, how to deal with the hierarchy of systems within systems, establishing appropriate criteria for the solution design and how best to deal with chaotic and disordered systems.Originality/valueThe authors argue that the systems approaches offer methodological pluralism by which a generic DSRD may be applied to enhance supply chain design. The authors show the relevance of the DSRD to supply chain design problems including in reducing supply chain dynamics and enhance resilience. In doing so, the study points towards an integrated perspective and future research agenda for designing resilient supply chains.