bluuebunny/crossref_metadata_2025_split huggingface dataset:
TIMEOR: a web-based tool to uncover temporal regulatory mechanisms from multi-omics data
Authors: Conard Ashley Mae , Goodman Nathaniel , Hu Yanhui , Perrimon Norbert , Singh Ritambhara , Lawrence Charles , Larschan Erica 
Published: April 2021

Abstract
Uncovering how transcription factors regulate their targets at DNA, RNA and protein levels over time is critical to define gene regulatory networks (GRNs) and assign mechanisms in normal and diseased states. RNA-seq is a standard method measuring gene regulation using an established set of analysis stages. However, none of the currently available pipeline methods for interpreting ordered genomic data (in time or space) use time-series models to assign cause and effect relationships within GRNs, are adaptive to diverse experimental designs, or enable user interpretation through a web-based platform. Furthermore, methods integrating ordered RNA-seq data with protein–DNA binding data to distinguish direct from indirect interactions are urgently needed. We present TIMEOR (Trajectory Inference and Mechanism Exploration with Omics data in R), the first web-based and adaptive time-series multi-omics pipeline method which infers the relationship between gene regulatory events across time. TIMEOR addresses the critical need for methods to determine causal regulatory mechanism networks by leveraging time-series RNA-seq, motif analysis, protein–DNA binding data, and protein-protein interaction networks. TIMEOR’s user-catered approach helps non-coders generate new hypotheses and validate known mechanisms. We used TIMEOR to identify a novel link between insulin stimulation and the circadian rhythm cycle. TIMEOR is available at https://github.com/ashleymaeconard/TIMEOR.git and http://timeor.brown.edu.
Aviator: a web service for monitoring the availability of web services
Authors: Fehlmann Tobias , Kern Fabian , Hirsch Pascal , Steinhaus Robin , Seelow Dominik , Keller Andreas 
Published: April 2021

Abstract
With Aviator, we present a web service and repository that facilitates surveillance of online tools. Aviator consists of a user-friendly website and two modules, a literature-mining based general and a manually curated module. The general module currently checks 9417 websites twice a day with respect to their availability and stores many features (frontend and backend response time, required RAM and size of the web page, security certificates, analytic tools and trackers embedded in the webpage and others) in a data warehouse. Aviator is also equipped with an analysis functionality, for example authors can check and evaluate the availability of their own tools or those of their peers. Likewise, users can check the availability of a certain tool they intend to use in research or teaching to avoid including unstable tools. The curated section of Aviator offers additional services. We provide API snippets for common programming languages (Perl, PHP, Python, JavaScript) as well as an OpenAPI documentation for embedding in the backend of own web services for an automatic test of their function. We query the respective APIs twice a day and send automated notifications in case of an unexpected result. Naturally, the same analysis functionality as for the literature-based module is available for the curated section. Aviator can freely be used at https://www.ccb.uni-saarland.de/aviator.
Sensory Effects of Nicotine and Tobacco
Authors: Carstens Earl , Carstens M Iodi 
Published: April 2021

Abstract

Introduction
Ingestion of nicotine by smoking, vaping, or other means elicits various effects including reward, antinociception, and aversion due to irritation, bitter taste, and unpleasant side effects such as nausea and dizziness.

Aims and Methods
Here we review the sensory effects of nicotine and the underlying neurobiological processes.

Results and Conclusions
Nicotine elicits oral irritation and pain via the activation of neuronal nicotinic acetylcholine receptors (nAChRs) expressed by trigeminal nociceptors. These nociceptors excite neurons in the trigeminal subnucleus caudalis (Vc) and other brainstem regions in a manner that is significantly reduced by the nAChR antagonist mecamylamine. Vc neurons are excited by lingual application of nicotine and exhibit a progressive decline in firing to subsequent applications, consistent with desensitization of peripheral sensory neurons and progressively declining ratings of oral irritation in human psychophysical experiments. Nicotine also elicits a nAChR-mediated bitter taste via excitation of gustatory afferents. Nicotine solutions are avoided even when sweeteners are added. Studies employing oral self-administration have yielded mixed results: Some studies show avoidance of nicotine while others report increased nicotine intake over time, particularly in adolescents and females. Nicotine is consistently reported to increase human pain threshold and tolerance levels. In animal studies, nicotine is antinociceptive when delivered by inhalation of tobacco smoke or systemic infusion, intrathecally, and by intracranial microinjection in the pedunculopontine tegmentum, ventrolateral periaqueductal gray, and rostral ventromedial medulla. The antinociception is thought to be mediated by descending inhibition of spinal nociceptive transmission. Menthol cross-desensitizes nicotine-evoked oral irritation, reducing harshness that may account for its popularity as a flavor additive to tobacco products.

Implications
Nicotine activates brain systems underlying reward and antinociception, but at the same time elicits aversive sensory effects including oral irritation and pain, bitter taste, and other unpleasant side effects mediated largely by nicotinic acetylcholine receptors (nAChRs). This review discusses the competing aversive and antinociceptive effects of nicotine and exposure to tobacco smoke, and the underlying neurobiology. An improved understanding of the interacting effects of nicotine will hopefully inform novel approaches to mitigate nicotine and tobacco use.
DOTFL1 affects the floral transition in orchid Dendrobium Chao Praya Smile
Authors: Li Yan , Zhang Bin , Wang Yanwen , Gong Ximing , Yu Hao 
Published: April 2021

Abstract
A major obstacle for orchid (Orchidaceae) breeding and production is a long juvenile phase before orchid reproductive development. The molecular basis for prolonged vegetative growth in orchids remains largely unclear despite many efforts to clarify the relevant mechanisms. In this study, we report functional characterization of Dendrobium Orchid TERMINAL FLOWER1 (DOTFL1), an ortholog of TFL1 in Arabidopsis (Arabidopsis thaliana), from the orchid Dendrobium Chao Praya Smile. DOTFL1 is highly expressed in pseudobulbs and the shoot apical meristem (SAM) before and during the floral transition, but is downregulated in inflorescence apices and open flowers. Ectopic expression of DOTFL1 rescues the early-flowering and terminal-flower phenotypes of tfl1-20 in Arabidopsis. Overexpression of DOTFL1 in Dendrobium orchids delays flowering and produces defective inflorescence meristems and flowers with vegetative traits, whereas knockdown of DOTFL1 accelerates flowering and perturbs the maintenance of the inflorescence meristem. Notably, DOTFL1 suppresses orchid flowering and associated pseudobulb formation during the floral transition. We further reveal that two orchid MADS-box transcription factors, Dendrobium Orchid SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (DOSOC1) and AGAMOUS-LIKE 24 (DOAGL24), could interact with each other and bind to the CArG-box motif at DOTFL1, implying a regulatory hierarchy similar to their counterparts in Arabidopsis. Taken together, our findings suggest that DOTFL1 promotes vegetative growth, modulates successive developmental events required for reproductive success in Dendrobium orchids, and may have evolved with a previously unknown role in controlling pseudobulb formation in the Orchidaceae family.
Entiers Ultrafriables En Progressions Arithmétiques
Authors: Dartyge Cécile , Feutrie David , Tenenbaum Gérald 
Published: April 2021

Abstract
A natural integer is called y-ultrafriable if none of the prime powers occurring in its canonical decomposition exceed y. We investigate the distribution of y-ultrafriable integers not exceeding x among arithmetic progressions to the modulus q. Given a sufficiently small, positive constant ɛ, we obtain uniform estimates valid for $q\leqslant y^{c/\log_2y}$ whenever $\log y\leqslant (\log x)^\varepsilon$, and for $q\leqslant \sqrt{y}$ if $(\log x)^{2+\varepsilon}\leqslant y\leqslant x$.
The role of PD-1/PD-Ls in the pathogenesis of IgG4-related disease
Authors: Zhang Xia , Lu Hui , Peng Linyi , Zhou Jiaxin , Wang Mu , Li Jieqiong , Liu Zheng , Zhang Wen , Zhao Yan , Zeng Xiaofeng , Lu Liwei 
Published: April 2021

AbstractObjectiveTo investigate the role of programmed cell death protein 1 (PD-1) and its two ligands, PD-L1 and PD-L2, in the pathogenesis of IgG4-related disease (IgG4-RD).MethodsPatients with IgG4-RD (n = 43) and healthy controls (n = 34) were recruited. Expression levels of PD-1, PD-L1 and PD-L2 in plasma, submandibular gland and T cell subsets were determined by ELISA, immunohistochemistry and flow cytometry. Naïve T cells were stimulated with or without PD-L1/PD-L2 or anti-PD-L1/anti-PD-L2 for 7 days and the proportion of CD4+CD25+ Treg cells was detected by flow cytometry.ResultsThe expression of PD-1, PD-L1 and PD-L2 in the plasma, submandibular gland and on the surface of Treg cells was increased in IgG4-RD patients. Plasma soluble (s)PD-1 was positively correlated with serum IgG, IgG1, IgG3, IgG4, IgG4-RD responder index and numbers of organs involved, and negatively correlated with serum IgM, IgA, C3 and C4. Plasma sPD-L2 was positively correlated with serum IgG1, and plasma sPD-L1 was positively correlated with sPD-L2 and negatively correlated with C3. Stimulation of PD-L1 but not PD-L2 promoted the differentiation of naïve T cells from IgG4-RD patients into CD4+CD25+ Treg cells.ConclusionPlasma concentrations of sPD-1, sPD-L1 and sPD-L2 were significantly increased in patients with IgG4-RD, and the expression of PD-1 and PD-L2 on Treg cells was upregulated. PD-1–PD-L1 can promote the differentiation of naïve T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.
Relationship Between White Matter Microstructure and Hallucination Severity in the Early Stages of Psychosis: A Diffusion Tensor Imaging Study
Authors: Sato Yutaro , Sakuma Atsushi , Ohmuro Noriyuki , Katsura Masahiro , Abe Koichi , Tomimoto Kazuho , Iizuka Kunio , Ito Fumiaki , Tomita Hiroaki , Matsumoto Kazunori 
Published: April 2021

Abstract

Background
Diffusion tensor imaging (DTI) studies have investigated the relationship between hallucinations in schizophrenia and white matter (WM) microstructure. However, only a few studies have focused on hallucination severity in the early stages of psychosis, and the involvement of the WM microstructure in the development of hallucinations remains unclear. This study aimed to examine the WM microstructure related to hallucination severity in the early stages of psychosis.

Methods
DTI analysis using tract-based spatial statistics (TBSS) was applied to 138 participants, consisting of 105 individuals with early stages of psychosis (56 individuals with clinical high risk for psychosis [CHR] and 49 individuals with first-episode psychosis [FEP]) and 33 healthy controls (HCs). Group comparisons of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were performed. We examined the association of FA, MD, RD, and AD with hallucination severity in the early stages of psychosis.

Results
Lower FA and higher MD and RD in multiple WM tracts were observed in the early stages of psychosis compared to HCs. We found an association between hallucination severity and increased MD in the WM tract, consisting mainly of the left superior longitudinal fasciculus (SLF) and inferior fronto-occipital fasciculus (IFOF).

Conclusions
Our findings indicate that dysconnectivity in brain networks associated with language processing is related to the development of hallucinations. Further studies of the early stages of psychosis are needed to elucidate the mechanism of hallucinations.
Worksite Temperature Screening for COVID-19
Authors: Stave Gregg M. , Smith Sharon E. , Hymel Pamela A. , Heron Richard J.L. 
Published: April 2021

Objective:
To determine whether temperature screening is useful in detecting and reducing workplace transmission of SARS-CoV-2.

Methods:
A survey was conducted to determine whether temperature screening successfully identified workers with coronavirus disease 2019 (COVID-19) among a convenience sample of medical directors of multinational corporations in a wide range of industries.

Results:
More than 15 million screenings were performed by 14 companies. Fewer than 700 episodes of fever were identified. Of these, only about 53 cases of COVID-19 were detected. By contrast about 2000 workers with diagnosed COVID-19 were in the workplace and not detected by screening.

Conclusions:
One case of COVID-19 was identified by screening for approximately every 40 cases that were missed. Worksite temperature screening was ineffective for detecting workers with COVID-19 and is not recommended.
High proportion of post-acute sequelae of SARS-CoV-2 infection in individuals 1-6 months after illness and association with disease severity in an outpatient telemedicine population
Authors: O’Keefe James B. , Minton H. Caroline , Johnson Colin , Moore Miranda A. , O’Keefe Ghazala A. D. , Benameur Karima , Higdon Jason , Fairley Jessica K. 
Published: April 2021

AbstractBackgroundIndividuals with coronavirus disease 2019 (COVID-19) may have persistent symptoms following their acute illness. The prevalence and predictors of these symptoms, termed post-acute sequelae of SARS-CoV-2 (PASC), are not fully described.MethodsParticipants discharged from an outpatient telemedicine program for COVID-19 were emailed a survey (1-6 months after discharge) about ongoing symptoms, acute illness severity, and quality of life. Standardized telemedicine notes from acute illness were used for covariates (comorbidities and provider-assessed symptom severity). Bivariate and multivariable analyses were performed to assess predictors of persistent symptoms.ResultsTwo hundred and ninety patients completed the survey, of whom 115 (39.7%) reported persistent symptoms including fatigue (n= 59, 20.3%), dyspnea on exertion (n=41, 14.1%), and mental fog (n=39, 13.5%) among others. Proportion of persistent symptoms did not differ based on duration since illness (<90 days: n=32, 37.2% versus>90 days: n=80, 40.4%, p = 0.61). Predictors of persistent symptoms included provider-assessed moderate-severe illness (aOR 3.24, 95% CI 1.75, 6.02), female sex (aOR 1.99 95% 0.98, 4.04; >90 days out: aOR 2.24 95% CI 1.01, 4.95), and middle age (aOR 2.08 95% CI 1.07, 4.03). Common symptoms associated with reports of worse physical health included weakness, fatigue, myalgias, and mental fog.ConclusionsSymptoms following acute COVID-19 are common and may be predicted by factors during the acute phase of illness. Fatigue and neuropsychiatric symptoms figured prominently. Select symptoms seem to be particularly associated with perceptions of physical health following COVID-19 and warrant specific attention on future studies of PASC.
Association of single nucleotide polymorphisms in XRCC1 and ATM with recurrence in patients with cervical cancer
Authors: Cho Soo Youn , Kim Kidong , Ryu Sang Young , Kim Moon-Hong , Kim Beob-Jong 
Published: April 2021

AbstractObjectiveThe primary objective of this study was to determine the association of the genotype of X-ray repair complementing defective repair in Chinese hamster cell 1 (XRCC1) 580C>T with recurrence-free survival (RFS) in patients with cervical cancer who underwent radical surgery followed by adjuvant concurrent chemoradiation (CRT). Secondary objectives were to assess 1) the association of single nucleotide polymorphisms (SNPs) in XRCC1 and ataxia telangiectasia mutated (ATM) gene with RFS, overall survival (OS) and completion of CRT, 2) the association of haplotypes of XRCC1 and ATM with RFS, OS and completion of CRT, 3) concordance rate between genotypes from cancer tissue and that from normal tissue and 4) the association of clinicopathologic variables with RFS and OS.Materials and MethodsClinicopathologic variables were extracted from medical records of 159 patients who underwent radical hysterectomy followed by adjuvant CRT in a cancer center between 1999 and 2004. After exclusion of six patients without paraffin blocks, 153 patients were included in this study. DNA was extracted from a formalin-fixed, paraffin embedded tissue block containing tumor tissue and another block containing uninvolved lymph node. Genotyping for XRCC1 580C>T (rs 1799782), XRCC1 1196A>G (rs 25487), ATM 3078-77C>T (rs 664677), ATM 5557G>A (rs 1801516) and ATM 6807+238G>C (rs609429) was performed using pyrosequencing. Haplotype estimation was performed using haplo.stats in R version 2.15.0. The association of genotype or haplotype of SNPs with RFS, OS and completion of CRT was evaluated via Cox regression analysis, chi-square or Fisher’s exact test. The concordance rate between genotype from cancer tissue and that from normal tissue was examined according to SNP. The association of clinicopathologic variables with RFS and OS was estimated via Cox regression analysis.ResultsNone of SNPs was associated with RFS, OS and completion of CRT. Concordance rate between genotype from cancer tissue and that from normal tissue for XRCC1 580C>T, XRCC1 1196A>G, ATM 3078-77C>T, ATM 5557G>A and ATM 6807+238G>C were 72%, 88%, 73%, 100% and 54%, respectively. Age, stage, histologic type, LVSI and parametrial invasion were associated with RFS, and clinical tumor size, resection margin, lymph node involvement and completion of CRT were associated with OS.ConclusionGenotype of XRCC1 580C>T was not associated with RFS in patients with cervical cancer who underwent radical surgery followed by adjuvant CRT. Low concordance rate between cancer and germline genotype was identified in cervical cancer.
Reopening California : Seeking Robust, Non-Dominated COVID-19 Exit Strategies
Authors: de Lima Pedro Nascimento , Lempert Robert , Vardavas Raffaele , Baker Lawrence , Ringel Jeanne , Rutter Carolyn M. , Ozik Jonathan , Collier Nicholson 
Published: April 2021

AbstractAmid global scarcity of COVID-19 vaccines and the threat of new variant strains, California and other jurisdictions face the question of when and how to implement and relax COVID-19 Nonpharmaceutical Interventions (NPIs). While policymakers have attempted to balance the health and economic impacts of the pandemic, decentralized decision-making, deep uncertainty, and the lack of widespread use of comprehensive decision support methods can lead to the choice of fragile or inefficient strategies. This paper uses simulation models and the Robust Decision Making (RDM) approach to stress-test California’s reopening strategy and other alternatives over a wide range of futures. We find that plans which respond aggressively to initial outbreaks are required to robustly control the pandemic. Further, the best plans adapt to changing circumstances, lowering their stringent requirements to reopen over time or as more constituents are vaccinated. While we use California as an example, our results are particularly relevant for jurisdictions where vaccination roll-out has been slower.
COVID-19 vaccine willingness and cannabis use histories
Authors: Spechler Philip A. , Stewart Jennifer L. , Kuplicki Rayus ,   the Tulsa 1000 Investigators, Paulus Martin P. 
Published: April 2021

AbstractBackgroundCannabis use is associated with problematic health-behaviors such as excessive alcohol and tobacco use, and sedentary behavior. Here, we examined the association between cannabis use history and an especially topical health-behavior, willingness to receive a COVID-19 vaccine.MethodsCOVID-19 vaccine willingness was surveyed in a subset of participants from the Tulsa 1000 Study, which is a longitudinal study of psychiatric treatment-seeking and healthy control participants. We identified 45 participants who completed a COVID-19 vaccine questionnaire and reported more than 10 lifetime cannabis uses. Those participants were compared to a group of 45 individuals with very light (<10) cannabis use histories who were propensity score-matched on age, sex, income, and race. Two-group t-tests and Bayes factor analysis on vaccine willingness were conducted between groups. Exploratory correlation analyses were conducted on vaccine willingness and lifetime cannabis use levels within the cannabis group only.ResultsVaccine willingness did not differ between the two groups (t88=0.33, p=.74; BF01=4.3). However, a negative correlation was identified within the cannabis group, such that higher lifetime cannabis use histories correlated with less willingness to receive a vaccine (rho43= -.33, p=.03).ConclusionsAlthough vaccine willingness did not differ between the two matched groups, preliminary evidence suggests that heavy lifetime cannabis use might indicate a reluctance to engage in health-promoting behaviors like receiving a COVID-19 vaccine.
Local density determines nuclear movements during syncytial blastoderm formation in a cricket
Authors: Donoughe Seth , Hoffmann Jordan , Nakamura Taro , Rycroft Chris H. , Extavour Cassandra G. 
Published: April 2021

AbstractAnimal embryos pass through an early stage called the blastoderm, in which cells are arranged in a continuous layer at the periphery of the embryo. Despite the broad evolutionary conservation of this embryonic stage, the cellular behaviours that lead to blastoderm formation vary across animals, and the mechanisms that regulate these behaviours are poorly understood. In most insects, pre-blastoderm development begins as a syncytium: that is, many nuclei divide and move throughout the single shared cytoplasm of the embryo. Then these syncytial nuclei must move from their scattered positions within the cytoplasm to form a single layer at the cortex. Recent work showed that in the fruit flyDrosophila melanogaster, some of these early nuclear movements are caused by pulses of cytoplasmic flows that are coupled to synchronous divisions. Here, we show that the cricketGryllus bimaculatushas an altogether different solution to the problem. We quantified nuclear dynamics during the period of syncytial cleavages and movements that lead to blastoderm formation inG. bimaculatusembryos with transgenically labeled nuclei. We found that: (1) cytoplasmic flows were unimportant for nuclear movement, and (2) division cycles, nuclear speeds, and the directions of nuclear movement were not synchronized across the embryo as inD. melanogaster, but instead were heterogeneous in space and time. Moreover, several aspects of nuclear divisions and movements were correlated with local nuclear density. We show that previously proposed models for the movement ofD. melanogastersyncytial nuclei cannot explain the behaviours ofG. bimaculatussyncytial nuclei. We introduce a novel geometric model based on asymmetric local pulling forces on nuclei, which recapitulates the density-dependent nuclear speeds and orientations of unperturbedG. bimaculatusembryos, without invoking the common paradigms of localized polarity cues or cell lineage as determinants of nuclear activity. Our model also accurately predicts nuclear behavior in embryos physically manipulated to contain regions of atypical nuclear densities. We show that this model can be used to generate falsifiable predictions about the dynamics of blastoderm formation in other insect species.