bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional activity mediated by β-CATENIN and TCF/LEF family members is completely dispensable for survival of multiple human colorectal cancer cell lines
Authors: Fröhlich Janna , Rose Katja , Hecht Andreas 
Published: December 2022

AbstractUnrestrained transcriptional activity of β-CATENIN and its binding partner TCF7L2 frequently underlies colorectal tumor initiation and is considered an obligatory oncogenic driver throughout intestinal carcinogenesis. Yet, theTCF7L2gene carries inactivating mutations in about 10 % of colorectal tumors and is non-essential in colorectal cancer (CRC) cell lines. To determine whether CRC cells acquire TCF7L2-independence through cancer-specific compensation by other T-cell factor (TCF)/lymphoid enhancer-binding factor (LEF) family members, or rather lose addiction to β-CATENIN/TCF7L2-driven gene expression altogether, we generated multiple CRC cell lines entirely negative for TCF/LEF or β-CATENIN expression. Viability of these cells demonstrates complete β-CATENIN- and TCF/LEF-independence, albeit one β-CATENIN-deficient cell line eventually became senescent. Absence of TCF/LEF proteins and β-CATENIN consistently impaired CRC cell proliferation, reminiscent of mitogenic effects of WNT/β-CATENIN signaling in the healthy intestine. Despite this common phenotype, β-CATENIN-deficient cells exhibited highly cell-line-specific gene expression changes with little overlap between β-CATENIN- and TCF7L2-dependent transcriptomes. Apparently, β-CATENIN and TCF7L2 control sizeable fractions of their target genes independently from each other. The observed divergence of β-CATENIN and TCF7L2 transcriptional programs, and the finding that neither β-CATENIN nor TCF/LEF activity is strictly required for CRC cell survival has important implications when evaluating these factors as potential drug targets.
Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane
Authors: Shi Wei , Cai Yongfei , Zhu Haisun , Peng Hanqin , Voyer Jewel , Rits-Volloch Sophia , Cao Hong , Mayer Megan L. , Song Kangkang , Xu Chen , Lu Jianming , Zhang Jun , Chen Bing 
Published: December 2022

AbstractEntry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells depends on refolding of the virus-encoded spike protein from a prefusion conformation, metastable after cleavage, to a lower energy, stable postfusion conformation. This transition overcomes kinetic barriers for fusion of viral and target cell membranes. We report here a cryo-EM structure of the intact postfusion spike in a lipid bilayer that represents single-membrane product of the fusion reaction. The structure provides structural definition of the functionally critical membraneinteracting segments, including the fusion peptide and transmembrane anchor. The internal fusion peptide forms a hairpin-like wedge that spans almost the entire lipid bilayer and the transmembrane segment wraps around the fusion peptide at the last stage of membrane fusion. These results advance our understanding of the spike protein in a membrane environment and may guide development of intervention strategies.
Neuro-immune modulation of cholinergic signaling in an addiction vulnerability trait
Authors: Carmon Hanna , Haley Evan C. , Parikh Vinay , Tronson Natalie C. , Sarter Martin 
Published: December 2022

AbstractSign-tracking (ST) describes the propensity to approach and contact a Pavlovian reward cue. By contrast, goal-trackers (GTs) respond to such a cue by retrieving the reward. These behaviors index the presence of opponent cognitive-motivational traits, with STs exhibiting attentional control deficits, behavior dominated by incentive motivational processes, and vulnerability for addictive drug taking. Attentional control deficits in STs were previously attributed to attenuated cholinergic signaling, resulting from deficient translocation of intracellular choline transporters (CHTs) into synaptosomal plasma membrane. Here we investigated a post-translational modification of CHTs – poly-ubiquitination - and tested the hypothesis that elevated cytokine signaling in STs contributes to CHT modification. We demonstrated that intracellular CHTs, but not plasma membrane CHTs, are highly ubiquitinated in male and female sign-tracking rats when compared with GTs. Moreover, levels of cytokines measured in cortex and striatum, but not spleen, were higher in STs than in GTs. Activation of the innate immune system by systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) elevated ubiquitinated CHT levels in cortex and striatum of GTs only, suggesting ceiling effects in STs. In spleen, LPS increased levels of most cytokines in both phenotypes. In cortex, LPS particularly robustly increased levels of the chemokines CCL2 and CXCL10. Phenotype-specific increases were restricted to GTs, again suggesting ceiling effects in STs. These results indicate that interactions between elevated brain immune modulator signaling and CHT regulation are essential components of the neuronal underpinnings of the addiction vulnerability trait indexed by sign-tracking.Significance StatementSign-tracking rats (STs) have emerged as a fruitful animal model for determining the neuro-behavioral foundations, including the cholinergic-attentional control deficits, which heighten the risk for the manifestation of addictive behaviors. The results from the present experiments suggest that, in STs, elevated levels of neuro-immune signaling interact with a post-translational modification of choline transporters that yields a relatively low transporter capacity. Furthermore, the effects of activation of the innate immune system, by administrating the endotoxin lipopolysaccharide, mechanistically supported such an interaction. The results extend research on the neuronal vulnerabilities for addictive behaviors to the role of neuro-immune signaling and suggests a new role of neuro-immune modulators in influencing complex cognitive-motivational traits.
The 3D chromatin landscape of rhabdomyosarcoma
Authors: Wang Meng , Sreenivas Prethish , Sunkel Benjamin D. , Wang Long , Ignatius Myron , Stanton Benjamin Z. 
Published: December 2022

ABSTRACTRhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with a lack of precision therapy option for patients. We hypothesized that with a general paucity of known mutations in RMS, chromatin structural driving mechanisms are essential for tumor proliferation. Thus, we carried out high-depthin situHi-C in representative cell lines and patient-derived xenografts to understand chromatin architecture in each major RMS subtype. We report a comprehensive 3D chromatin structural analysis and characterization of fusion-positive (FP-RMS) and fusion-negative rhabdomyosarcoma (FN-RMS). We have generated spike-inin situHi-C chromatin interaction maps for the most common FP-RMS and FN-RMS cell lines, and compared our data with patient derived xenograft (PDX) models. In our studies we uncover common and distinct structural elements in large Mb-scale chromatin compartments, tumor-essential genes within variable topologically associating domains, and unique patterns of structural variation. Our comprehensive analysis provides high-depth chromatin interactivity maps for contextualizing gene regulation events identification of functionally critical chromatin domains in RMS.HIGHLIGHTSPAX3-FOXO1 and MYOD localize in both A- and B-compartmentsConserved mechanisms dictate CTCF orientation at TAD boundaries in RMSDifferential TADs in each RMS subtype encompass tumor-specific genesNeo-TADs are formed from SV events in each subtype of RMSBoth major RMS subtypes have structural variation that is identifiable from Hi-CDistinct mechanisms can produce the major fusion alleles in rhabdomyosarcomaPAX3-FOXO1 and MYOD genomic binding is more enriched at regions with CNV
Characterization of a strain-specific CD-1 reference genome reveals potential inter- and intra-strain functional variability
Authors: Jung Yoon-Hee , Wang Hsiao-Lin , Ali Samir , Corces Victor G. , Kremsky Isaac 
Published: December 2022

AbstractBackgroundCD-1 is an outbred mouse stock that is frequently used in toxicology, pharmacology, and fundamental biomedical research. Although inbred strains are typically better suited for such studies due to minimal genetic variability, outbred stocks confer practical advantages over inbred strains, such as improved breeding performance and low cost. Knowledge of the full genetic variability of CD-1 would make it more useful in toxicology, pharmacology, and fundamental biomedical research.ResultsWe performed deep genomic DNA sequencing of CD-1 mice and used the data to identify genome-wide SNPs, indels, and germline transposable elements relative to the mm10 reference genome. We used multiple genome-wide sequencing data types and previously published CD-1 SNPs to validate our called variants. We used the called variants to construct a strain-specific CD-1 reference genome, which we show can improve mappability and reduce experimental biases from genome-wide sequencing data derived from CD-1 mice. Based on previously published ChIP-seq and ATAC-seq data, we find evidence that genetic variation between CD-1 individuals can lead to alterations in transcription factor binding. We also identified a number of variants in the coding region of genes which could have effects on splicing and translation of genes.ConclusionsWe have identified millions of previously unidentified CD-1 variants with the potential to confound studies involving CD-1. We used the identified variants to construct a CD-1-specific reference genome, which can improve accuracy and reduce bias when aligning genomics data derived from CD-1 individuals.
Electrogenetic signaling and information propagation for controlling microbial consortia via programmed lysis
Authors: VanArsdale Eric , Navid Ali , Chu Monica J. , Halvorsen Tiffany M. , Payne Gregory F. , Jiao Yongqin , Bentley William E. , Yung Mimi C. 
Published: December 2022

AbstractTo probe signal propagation and genetic actuation in microbial consortia, we have coopted the components of both redox and quorum sensing (QS) signaling into a communication network for guiding composition by “programming” cell lysis. Here, we use an electrode to generate hydrogen peroxide as a redox cue that determines consortia composition. The oxidative stress regulon ofEscherichia coli, OxyR, is employed to receive and transform this signal into a QS signal that coordinates the lysis of a subpopulation of cells. We examine a suite of information transfer modalities including “monoculture” and “transmitter-receiver” models, as well as a series of genetic circuits that introduce time-delays for altering information relay, thereby expanding design space. A simple mathematical model aids in developing communication schemes that accommodate the transient nature of redox signals and the “collective” attributes of QS signals. We suggest this platform methodology will be useful in understanding and controlling synthetic microbial consortia for a variety of applications, including biomanufacturing and biocontainment.
Modified bronchoscopy masks mitigate aerosols during gastroscopies
Authors: Phillips Frank , Crowley Jane , Warburton Samantha , Gordon George S.D. , Parra-Blanco Adolfo 
Published: December 2022

AbstractDigestive endoscopy has been proven to produce aerosols (1–3). This represents a risk of infection by COVID-19 and other airborne viruses. A number of protective barriers have been proposed to minimise that risk. Continuous suction of the oral cavity (1), shielding barriers (4,5), masks (6,7), and increasing the distance between patient and endoscopist (8) have been proposed as methods to reduce the exposure of endoscopists and endoscopy staff to aerosols. Here, we present a study that uses modified bronchoscopy masks (Explorer endoscopy facemask, Intersurgical Ltd., United Kingdom) to attenuate aerosol production at the patient’s mouth (bare mask shown in Fig. 1a and in use during an upper GI endoscopy in Fig. 1b). We find that this approach offers 47% (p=0.01) reduction in particle count for particles <5μm in diameter (i.e. aerosols), which are known to spread SARS-CoV-2.
Quality and safety for the public through domiciliary nursing in Italy: a multicentre cross-sectional descriptive observational study (The AIDOMUS-IT Protocol)
Authors: Bagnasco Annamaria , Alvaro Rosaria , Lancia Loreto , Manara Duilio Fiorenzo , Rasero Laura , Rocco Gennaro , Maurizio Zega , Mazzoleni Beatrice , Sasso Loredana 
Published: December 2022

ABSTRACTIntroductionThe development of this study protocol occurred in conjunction with the new Regulation defining models and standards for the development of community care in the National Health Service (Ministerial Decree n. 77-2022) with the redefinition of care in the community. Considered the increase in the elderly population, in the complexity of care and the workload for home care, it is important and urgent to describe the work environment and the Italian community care reality. The main objective of this study is to evaluate the characteristics of nursing care and the quality of home care in the community in Italy.MethodsThis is a cross-sectional descriptive observational study using the survey method. The study protocol uses quantitative data from three sources: 1) primary data on organizational characteristics, professional satisfaction, intention to leave home care services, and burnout; 2) secondary data on the experience of patients and their informal carers; 3) data on improper access to the emergency department, readmission to hospital, comorbidities, services offered, and user level of autonomy, and main and secondary diagnoses. Data will be analyzed using descriptive and inferential statistics.ConclusionsThe systematic analysis of the different national community care contexts will enable to increase the knowledge and awareness of the need for community health care. The availability of specific data will promote and support the role of the family and community nurse in district health care contexts, to increase the quality of care perceived by patients and their families.
Strategies and interventions to strengthen pharmacovigilance systems in low- and middle-income countries: a scoping review
Authors: Menang Olga , de Soyres-Kuemmerle Andrea , Maigetter Karen , Burri Christian 
Published: December 2022

ABSTRACTIntroductionIn the past decades, numerous strategies have been proposed to strengthen pharmacovigilance (PV) systems in low-and-middle-income countries (LMIC). Though there has been progress, many PV systems in LMIC are still not performing adequately. The objectives of this scoping review are to describe strategies to strengthen PV in LMIC and to propose recommendations for future investments in capacity building.MethodsThe review was conducted following the Joanna Briggs Institute (JBI) guidelines on conducting scoping reviews. Literature searches were performed in MEDLINE, EMBASE, Web of Science, PDQ-evidence, CINAHL and relevant websites from 1990 to January 2021. Publications included were primary studies, articles, and policy and guideline papers, describing interventions to strengthen PV in LMIC. Two reviewers independently screened titles, abstracts and full-texts, and one reviewer performed data extraction and carried out a descriptive data analysis.Results10,903 unique titles were screened and 152 were eligible for full text review. Of these, 57 and an additional 13 reports from grey literature fulfilled eligibility criteria for inclusion in the review. Forty-five papers (64%) described interventions aimed at increasing PV knowledge and reporting of adverse drug reactions (ADR), primarily education of healthcare professionals (HCP), alone or in combination with other interventions such as mobile and electronic reporting, enhanced passive and active surveillance. Twenty-five papers (36%) discussed interventions or strategies implemented at the national targeting different components of the national PV system, such as legal basis and guidelines for PV, PV organisation and infrastructure and PV procedures.ConclusionsResults of this review suggest that educating HCP on ADR reporting is the most common approach to build PV capacity in LMIC. Though important, education alone is insufficient and should ideally be organised within the holistic framework of strengthening national PV systems, with a focus on building capacity for advanced activities such as signal detection.Key messageThere are numerous strategies and recommendations to strengthen PV systems in LMIC. However, the effective implementation of these strategies has not been extensively described in literature. This scoping review describes different interventions and strategies that have been implemented to build and improve PV capacity in systems in LMIC. An overview of current PV strengthening strategies and interventions, and when available, their outcome and impact, is useful to guide decision making for future investments in PV development in developing countries.Trial registrationOpen Science Framework (https://osf.io/ge56p)
The seasonality of varicella in the tropical climates of Colombia: A statistical and mathematical modeling study
Authors: Barrero Guevara Laura Andrea , Goult Elizabeth , Rodriguez Dayanne , Hernandez Luis Jorge , Kaufer Benedikt , Kurth Tobias , Domenech de Cellès Matthieu 
Published: December 2022

AbstractBackgroundVaricella remains a major burden in many tropical regions, where low- to middle-income countries report the highest mortality rates. Understanding when and where varicella incidence increases could help us understand viral transmission and optimize the allocation of resources. Due to the lack of surveillance data, the epidemiology of varicella in the tropics has not been well characterized. Here, we assessed varicella seasonality and analyzed its correlation with climatic variables across Colombia.MethodsWe compiled an extensive dataset of weekly varicella reports in children up to the age of ten in 25 municipalities across Colombia. We used generalized additive models to describe the seasonality of varicella in each municipality. Using clustering methods and matrix correlation tests, we then compared the spatial variability in varicella seasonality with that in five meteorological variables across the municipalities. Finally, we developed a mathematical model to examine whether the influence of the climate on transmission rates could result in the observed seasonal patterns of varicella in Colombia and other Central American countries.FindingsVaricella seasonality was markedly bimodal, with a more pronounced peak early in the year in northern municipalities (≈week 15), while later in the year (≈week 40) in southern municipalities, including Bogotá. This spatial gradient was strongly correlated with humidity (Mantel statistic = 0·412, p-value = 0·001) but not temperature (Mantel statistic = 0·077 and p-value = 0·225). Furthermore, a mathematical model that included a small, negative association between humidity and transmission was able to reproduce the observed spatial patterns in Colombia and México. This model also predicted a latitudinal gradient in other tropical countries of Central America, where the seasonality of varicella has not yet been characterized.InterpretationThese results demonstrate a large variability in varicella seasonality across the tropical climates of Colombia. They further suggest that seasonal fluctuations of humidity explain the varicella epidemics calendar in Colombia and other Central American countries. More generally, our results highlight the need to carefully consider the subnational heterogeneity of climates when studying the seasonal epidemiology of varicella and assessing the impact of control measures.FundingCore funding from the Max Planck Institute for Infection Biology of the Max Planck Society, Berlin, Germany.
FeIII in the high-spin state in dimethylammonium bis[3-ethoxysalicylaldehyde thiosemicarbazonato(2–)-κ3
O
2,N
1,S]ferrate(III)
Authors: Powell Robyn E. , Lees Martin R. , Tizzard Graham J. , Coles Simon J. , Yuan Qingchun , Koningsbruggen Petra J. van 
Published: December 2022

The synthesis and crystal structure (100 K) of the title compound, [(CH3)2NH2][Fe(C10H11O2N3S)2], are reported. The asymmetric unit consists of an octahedral [FeIII(L)2]− fragment, where L
2− is 3-ethoxysalicylaldehyde thiosemicarbazonate(2−), and a dimethylammonium cation. Each L
2− ligand binds with the thiolate S, the imine N and the phenolate O atoms as donors, resulting in an FeIIIS2N2O2 chromophore. The ligands are orientated in two perpendicular planes, with the O and S atoms in cis positions, and mutually trans N atoms. The FeIII ion is in the high-spin state at 100 K. The variable-temperature magnetic susceptibility measurements (5–320 K) are consistent with the presence of a high-spin FeIII ion with D = 0.83 (1) cm−1 and g = 2.
A comparative study of frequentist vs Bayesian A/B testing in the detection of E-commerce fraud
Authors: Westland James Christopher 
Published: December 2022

PurposeThis paper tests whether Bayesian A/B testing yields better decisions that traditional Neyman-Pearson hypothesis testing. It proposes a model and tests it using a large, multiyear Google Analytics (GA) dataset.Design/methodology/approachThis paper is an empirical study. Competing A/B testing models were used to analyze a large, multiyear dataset of GA dataset for a firm that relies entirely on their website and online transactions for customer engagement and sales.FindingsBayesian A/B tests of the data not only yielded a clear delineation of the timing and impact of the intellectual property fraud, but calculated the loss of sales dollars, traffic and time on the firm’s website, with precise confidence limits. Frequentist A/B testing identified fraud in bounce rate at 5% significance, and bounces at 10% significance, but was unable to ascertain fraud at the standard significance cutoffs for scientific studies.Research limitations/implicationsNone within the scope of the research plan.Practical implicationsBayesian A/B tests of the data not only yielded a clear delineation of the timing and impact of the IP fraud, but calculated the loss of sales dollars, traffic and time on the firm’s website, with precise confidence limits.Social implicationsBayesian A/B testing can derive economically meaningful statistics, whereas frequentist A/B testing only providep-value’s whose meaning may be hard to grasp, and where misuse is widespread and has been a major topic in metascience. While misuse ofp-values in scholarly articles may simply be grist for academic debate, the uncertainty surrounding the meaning ofp-values in business analytics actually can cost firms money.Originality/valueThere is very little empirical research in e-commerce that uses Bayesian A/B testing. Almost all corporate testing is done via frequentist Neyman-Pearson methods.