bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medication Overuse Headache, Chronic Migraine and Monoclonal Antibodies Anti-CGRP: A Real-World Study
Authors: Krymchantowski Abouch , Jevoux Carla , Krymchantowski Ana Gabriela , Silva-Néto Raimundo Pereira 
Published: June 2023

Objective
Medication overuse headache (MOH) in chronic migraineurs may be a cause or consequence of the overuse of symptomatic medications for headache attacks. It is highly prevalent in tertiary centers. We compared the efficacy of 3 anti-CGRP monoclonal antibodies with traditional pharmacological agents in patients with chronic migraine (CM) and MOH.

Methods
A randomized, cross-sectional, prospective, and open trial with real-world comparison groups was carried out. The sample consisted of 100 consecutive patients having CM and MOH.

Results
Eighty-eight patients (65 women and 23 men) were included in the study and divided into 4 groups: those having used erenumab (19.3%), galcanezumab (29.6%), fremanezumab (25%) and conventional medications, and the control group (26.1%). Ages ranged from 18 to 78 years (mean, 44.1 ± 13.6 years). In the 6 months of follow-up, there was a significant reduction in the number of headache days in the 3 groups when compared with the control (P < 0.0001).

Conclusions
The small number of patients included in each group and the open design do not allow definitive conclusions, but the use of anti-CGRP monoclonal antibodies in patients with CM and MOH may result in lessening the number of headache days when compared with conventional treatment with drugs.
Thermodynamics 2.0: Bridging the natural and social sciences
Authors: Poudel Ram , McGowan Jon , Georgiev Georgi Y. , Haven Emmanuel , Gunes Umit , Zhang Hongkun 
Published: June 2023

Thermodynamics is a universal science. The language of thermodynamics is energy and its derivatives such as entropy and power. The physical theory of thermodynamics reigns across a full spectrum of non-living objects as well as living beings. In the traditions of the past, the dichotomy between matter and life resulted in the natural sciences studying matter while the social sciences focused on living beings. As the state of human knowledge continues to evolve, anticipating the sciences of matter (natural science) and of life (social science) becoming unified under a single overarching theory is not unnatural.
This article is part of the theme issue ‘Thermodynamics 2.0: Bridging the natural and social sciences (Part 1)’.
Clinical prediction models for the management of blunt chest trauma in the Emergency Department: a systematic review
Authors: Battle Ceri , Cole Elaine , Carter Kym , Baker Edward 
Published: June 2023

ABSTRACTIntroductionThe aim of this systematic review was to investigate how clinical prediction models compare in terms of their methodological development, validation, and predictive capabilities, for patients with blunt chest trauma presenting to the Emergency Department.MethodsA systematic review was conducted across databases from Jan 2000 until March 2023. Studies were categorised into three types of multivariable prediction research and data extracted regarding methodological issues and the predictive capabilities of each model. Risk of bias and applicability were assessed.Results39 studies were included that discussed 22 different models. The most commonly observed study design was a single-centre, retrospective, chart review. The most widely externally validated clinical prediction models with moderate to good discrimination were the Thoracic Trauma Severity Score and the STUMBL Score.DiscussionThis review demonstrates that the predictive ability of some of the existing clinical prediction models is acceptable, but high risk of bias and lack of subsequent external validation limits the extensive application of the models. The Thoracic Trauma Severity Score and STUMBL Score demonstrate better predictive accuracy in both development and external validation studies than the other models, but require recalibration and / or update and evaluation of their clinical and cost effectiveness.
Acceleration of Large-Scale Single Cell Differential Gene Expression Analysis with FastDE
Authors: Connolly Erin , Aluru Maneesha , Chockalingam Sriram , Dhere Vishal , Gibson Greg , Pan Tony 
Published: June 2023

ABSTRACTThe major bottleneck in single cell transcriptomic processing is identification of marker genes for individual cell clusters. We introduce FastDE, an implementation of the standard Wilcoxon Rank Sum test in C++ that results in 50X speed-up of the standard Seurat pipeline on a dataset of 1.2 million cells. Proof of methodology is demonstrated by replicating age and gender effects on immune cell differentiation in two large PBMC atlases.
SULFATED POLYSACCHARIDE FROM BROWN ALGAEDICTYOTA CARIBAEASTIMULATES MACROPHAGES TO AN ANTITUMORAL PHENOTYPE
Authors: Assef Alexia Nathália Brígido , Teles Felipe Barros , Cinelli Leonardo Paes , Wilke Diego Veras 
Published: June 2023

AbstractFucoidans are sulfated polysaccharides capable of exerting biological activities such as antitumor and immunomodulatory effects. Previous studies demonstrated the antitumor activity of non-cytotoxic fucoidan from the seaweedDictyota caribaea(Dc-SP)in vivo. Macrophages (Mφ) are innate immune cells capable of promoting or inhibiting tumor growth depending on the stimulus. This study aimed to evaluate the immunostimulant activity of Dc-SP on murine Mφ (RAW264.7)in vitro. Dc-SP was assessed for its ability to modify cell viability and stimulate the production of antitumor markers on RAW264.7 cells. Dc-SP induced an increase (p<0.05) in the production of NO and cytokines TNF-α, IL-1β, and IL-10. The exposure of Mφ to Dc-SP also increased (p<0.05) the expression of M1 macrophage markers such as iNOS, CD86, and MHC II. The antiproliferative activity of RAW264.7 cells stimulated with DC-SP on melanoma cells (B16-F10)in vitro. Dc-SP did not exhibit direct cytotoxicity on B16-F10, however, the conditioned medium (CM) of RAW264.7 previously stimulated with Dc-SP (CM-Dc-SP) showed antiproliferative activity on tumor cells. B16-F10 incubated with CM-Dc-SP showed a cytostatic profile, tumor cells did not alter membrane integrity, however, suffered morphological changes such as cell shrinkage and high granularity. In conclusion, Dc-SP stimulated Mφ to an antitumor phenotype.
A high-sensitivity ELISA for detection of human FGF18 in culture supernatants from tumor cell lines
Authors: Tsuchiya Yuichi , Komazawa-Sakon Sachiko , Tanaka Masato , Kanakogi Takumi , Moriwaki Kenta , Akiba Hisaya , Yagita Hideo , Okumura Ko , Entzminger Kevin C , Okumura CJ , Maruyama Toshiaki , Nakano Hiroyasu 
Published: June 2023

AbstractFibroblast growth factor 18 (FGF18) is elevated in several human cancers, such as gastrointestinal and ovarian cancers, and stimulates the proliferation of tumor cells. This suggests that FGF18 may be a promising candidate biomarker in cancer patients. However, the lack of a high-sensitivity enzyme-linked immunosorbent assay (ELISA) does not permit testing of this possibility. In this study, we generated monoclonal antibodies against human FGF18 and developed a high-sensitivity ELISA to measure human FGF18 at concentrations as low as 10 pg/mL. Of the eight tumor cell lines investigated, we detected human FGF18 in culture supernatants from four tumor cell lines, including HeLa, OVCAR-3, BxPC-3, and SW620 cells, albeit the production levels were relatively low in the latter two cell lines. Moreover, the in-house ELISA could detect murine FGF18 in sera from mice overexpressing murineFgf18in hepatocytes, although the sensitivity in detecting murine FGF18 was relatively low. This FGF18 ELISA could be a valuable tool to validate FGF18 as a potential biomarker for cancer patients and to test the contribution of FGF18 for various disease models in vivo and in vitro.
Salivary corticosterone reflects plasmatic levels in a wild seabird
Authors: Carbillet Jeffrey , Saks Lauri , Sepp Tuul 
Published: June 2023

AbstractWild animals have been increasingly exposed to a wide range of stressors, mainly due to the intensification of human activities and habitat modifications. Consequently, new tools in order to assess the physiological and health status of wild animals have been developed. In particular, glucocorticoids have received a special attention. Primarily metabolic hormones, they are also used to evaluate the stress level of organisms. While historically measured in blood samples, new less-invasive methods have been recently developed to measure glucocorticoids in matrices such as faeces, hairs/feathers, or saliva. To date, measurements in saliva are still in their infancy despite the numerous advantages of the matrix: non-invasive, reflects the biologically active portion of glucocorticoids, allows to measure both baseline and stress-induced levels. In addition, most studies using saliva have been performed on domestic and captive animals, and recent development in wild animals have focused on mammals. Here, we show, for the first time that saliva could also be reliably used in free-ranging birds, as glucocorticoid levels in saliva strongly correlated with plasma levels. This promising result opens new avenues for a non-invasive sampling method to assess health status of wild birds in conservation biology and ecology.
The T766M-EGFR lung cancer mutation promotes tumor growth by exploiting newfound mechanisms assembling ligand-free EGFR oligomer structures
Authors: Iyer R. Sumanth , Needham Sarah R. , Galdadas Ioannis , Davis Benjamin M. , Roberts Selene K. , Man Rico C.H. , Zanetti-Domingues Laura C. , Clarke David T. , Fruhwirth Gilbert O. , Parker Peter J. , Rolfe Daniel J. , Gervasio Francesco L. , Martin-Fernandez Marisa L. 
Published: June 2023

SummaryEpidermal growth factor receptor (EGFR) is central to cell growth in physiology and pathophysiologies, including non-small cell lung cancer (NSCLC). EGFR has been successfully targeted with tyrosine kinase inhibitor generations, but the missense secondary T766M mutation is a common cause of resistance. Overcoming this therapeutic challenge has been hindered by poor understanding of how T766M dysregulates EGFR function leading to tumor progression. Here we show that T766M amplifies tumor growthin vivoby exploiting newly discovered oligomer assembly mechanisms employed by wild type (WT)-EGFR to maintain ligand-independent basal phosphorylation. These mechanisms, also shared by drug-resistant exon 20 EGFR insertions, reveal tumor growth promoting functions for hitherto orphan transmembrane and kinase interfaces and for the ectodomain tethered conformation of EGFR. Placing our findings into the context of a ligand-free oligomer structure model, we provide a framework for future drug discovery directed at tackling EGFR mutations in cancer by disabling oligomer-assembling interactions.
DNA binding analysis of rare variants in homeodomains reveals novel homeodomain specificity-determining residues
Authors: Kock Kian Hong , Kimes Patrick K. , Gisselbrecht Stephen S. , Inukai Sachi , Phanor Sabrina K. , Anderson James T. , Ramakrishnan Gayatri , Lipper Colin H. , Song Dongyuan , Kurland Jesse V. , Rogers Julia M. , Jeong Raehoon , Blacklow Stephen C. , Irizarry Rafael A. , Bulyk Martha L. 
Published: June 2023

SummaryHomeodomains (HDs) are the second largest class of DNA binding domains (DBDs) among eukaryotic sequence-specific transcription factors (TFs) and play important roles in regulating development, body patterning, and cellular differentiation. Here, we analyzed 92 human HD mutants, including disease-associated variants and variants of unknown significance (VUSs), for their effects on DNA binding activity. Many of the variants altered DNA binding affinity and/or specificity. Biochemical analysis and structural modeling identified 14 novel specificity-determining positions, 5 of which do not contact DNA. The same missense substitution at analogous positions within different HDs often exhibited different effects on DNA binding. Variant effect prediction tools perform moderately well in distinguishing variants with altered binding affinity, but poorly in identifying those with altered specificity. Our results highlight the need for biochemical assays of TF coding variants and prioritize dozens of variants for further investigations into their pathogenicity and development of clinical diagnostics and precision therapies.
A functional single nucleotide polymorphism upstream of the collagen type III gene may contribute to catastrophic fracture risk in Thoroughbred horses
Authors: Lago Esther Palomino , Baird Arabella , Blott Sarah C. , McPhail Rhona E. , Ross Amy C. , Durward-Akhurst Sian A. , Guest Deborah J. 
Published: June 2023

AbstractFractures caused by bone overloading are a leading cause of euthanasia in Thoroughbred racehorses. The risk of fatal fracture has been shown to be influenced by both environmental and genetic factors but, to date, no specific genetic mechanisms underpinning fracture have been identified. The aim of this study was to utilise a genome-wide polygenic risk score to establish anin vitrocell system to study bone gene regulation in horses at high and low genetic risk of fracture. Candidate gene expression analysis revealed differential expression ofCOL3A1andSTAT1genes in osteoblasts derived from high and low risk horses. Whole genome sequencing of fracture case and control horses revealed a single nucleotide polymorphism (SNP) upstream ofCOL3A1that was confirmed in a larger cohort to be significantly associated with fracture. Bioinformatics tools predicted that this SNP may impact the binding of the transcription factor SOX11. Gene modulation demonstrated SOX11 is upstream ofCOL3A1and the region binds to nuclear proteins. Furthermore, luciferase assays demonstrated that the region containing the SNP has promoter activity. However, the specific effect of the SNP depends on the broader genetic background of the cells and suggest other factors may also be involved in regulatingCOL3A1expression. In conclusion, this approach provides a powerful means to identify novel DNA variants and understand their mechanism of action to enable the development of new ways to identify and treat horses at high risk of a catastrophic fracture.
Serine ubiquitination of p62 regulates Nrf2 dependent redox homeostasis
Authors: Mukherjee Rukmini , Hoffmann Marina , Gonzalez Alexis , Bhattacharya Anshu , Kuncha Santosh Kumar , Rathore Rajeshwari , Shin Donghyuk , Colby Thomas , Matic Ivan , Misra Mohit , Dikic Ivan 
Published: June 2023

AbstractThe KEAP1–Nrf2 axis is essential for the cellular response against metabolic and oxidative stress. KEAP1 is an adaptor protein of Cullin-3 ubiquitin ligase that controls the cellular levels of Nrf2, a critical transcription factor of several cytoprotective genes. Oxidative stress, defective autophagy and pathogenic infections activate Nrf2 signaling through phosphorylation of the adaptor protein p62, which competes with Nrf2 for binding to KEAP1. Here we show that phosphoribosyl-linked serine ubiquitination of p62 catalyzed by SidE effectors ofLegionella pneumophilacontrols Nrf2 signaling and cell metabolism uponLegionellainfection. Serine ubiquitination of p62 sterically blocks its binding to KEAP1, resulting in Nrf2 ubiquitination and degradation. This reduces Nrf2-dependent antioxidant synthesis in the early phase of infection. Levels of serine ubiquitinated p62 diminish in the later stage of infection allowing the expression of Nrf2-target genes; resulting in a differential regulation of the host metabolome and proteome in a Nrf2 dependent manner.
Synergistic genomic mechanisms of adaptation to ocean acidification in a coral holobiont
Authors: Leiva Carlos , Pérez-Portela Rocío , Lemer Sarah 
Published: June 2023

AbstractOcean acidification, caused by anthropogenic CO2emissions, is predicted to have major consequences for reef-building corals, jeopardizing the scaffolding of the most biodiverse marine habitats. However, whether corals can adapt to ocean acidification and how remains unclear. We addressed these questions by re-examining transcriptome and genome data ofAcropora milleporacoral holobionts from volcanic CO2seeps with end-of-century pH levels. We show that adaptation to ocean acidification is a wholistic process involving the three main compartments of the coral holobiont. We identified 441 coral host candidate adaptive genes involved in calcification, response to acidification, and symbiosis; population genetic differentiation in dinoflagellate photosymbionts; and consistent transcriptional microbiome activity despite microbial community shifts. Coral holobionts from natural analogues to future ocean conditions harbor beneficial genetic variants with far-reaching rapid adaptation potential. In the face of climate change, these populations require immediate conservation strategies as they could become key to coral reef survival.
Non-cognate immunity proteins provide broader defenses against interbacterial effectors in microbial communities
Authors: Knecht Abigail , Sirias Denise , Utter Daniel R. , Gibbs Karine A. 
Published: June 2023

AbstractDense microbial communities, like the gut and soil microbiomes, are dynamic societies. Bacteria can navigate these environments by deploying proteins that alter foreign cells’ behavior, such as interbacterial effectors. Current models suggest that adjacent sibling cells are protected by an immunity protein, as compared to toxin-antitoxin systems that act only within the effector-producing cell. A prevailing hypothesis is that immunity proteins binding to specific (cognate) protein partners is sufficient to disrupt effector function. Further, there is little-to-no crosstalk with other non-cognate effectors. In this research, we build on sporadic reports challenging these hypotheses. We show that immunity proteins from a newly defined protein family can bind and protect against non-cognate PD-(D/E)XK-containing effectors from diverse phyla. We describe the domains essential for binding and function and show that binding alone is insufficient for protective activity. Moreover, we found that these effector and immunity genes co-occur in individual human microbiomes. These results expand the growing repertoire of bacterial protection mechanisms and the models on how non-cognate interactions impact community structure within complex ecosystems.
Literate programming for iterative design-build-test-learn cycles in bioengineering
Authors: Petersen Søren , Levassor Lucas , Pedersen Christine M. , Madsen Jan , Hansen Lea G. , Zhang Jie , Haidar Ahmad K. , Frandsen Rasmus , Keasling Jay D. , Weber Tilmann , Sonnenschein Nikolaus , Jensen Michael K. 
Published: June 2023

AbstractSynthetic biology dictates the data-driven engineering of biocatalysis, cellular functions, and organism behavior. Integral to synthetic biology is the aspiration to efficiently find, access, interoperate, and reuse high-quality data on genotype-phenotype relationships of native and engineered biosystems under FAIR principles, and from this facilitate forward-engineering strategies. However, biology is complex at the regulatory level, and noisy at the operational level, thus necessitating systematic and diligent data handling at all levels of the design, build, and test phases in order to maximize learning in the iterative design-build-test-learn engineering cycle. To enable user-friendly simulation, organization, and guidance for the engineering of complex biosystems, we have developed an open-source python-based computer-aided design and analysis platform operating under a literate programming user-interface hosted on Github. The platform is called teemi and is fully compliant with FAIR principles. In this study we apply teemi for i) designing and simulating bioengineering, ii) integrating and analyzing multivariate datasets, and iii) machine-learning for predictive engineering of a metabolic pathway designs for production of a key precursor to medicinal alkaloids. The teemi platform is publicly available atPyPiandGitHub.
The effect of social support on teleworker environment and work engagement: a multimethod analysis
Authors: Kakkar Shiva , Kuril Samvet , Saha Surajit , Gupta Parul , Singh Swati 
Published: June 2023

PurposeEmploying the “Job demands-resources (JD-R)” framework, this study examines the impact of co-occurring social supports (supervisor, coworker, and family support) on the telework environment and employee engagement.Design/methodology/approachThe study uses a multimethod approach. Data from 294 employees belonging to Indian technology organizations were collected and analyzed using the partial least squares (PLS)-based structure equation modeling software SmartPLS4. Following this, necessary condition analysis (NCA) was carried out using the NCA package for R.FindingsTelework environment was found to mediate the relationship between social support and work engagement. Supervisor support and instrumental family support were identified as predictors as well as necessary conditions for telework environment. Coworker support was identified both as a predictor and necessary condition for telework environment. Although emotional family support was found to be a predictor of telework environment, it was not identified as a necessary condition.Practical implicationsThe findings indicate that coworker support and family instrumental support are as important for telework success as supervisor support. Moreover, our findings suggest that varying levels of telework environments (low, moderate, and high) may necessitate distinct social support configurations. Consequently, organizations should match their social support configuration to match their overall teleworking strategy.Originality/valueA basic premise of the JD-R framework is that resources exist in caravans (bundles). However, previous research (in telework) has concentrated on only one or two kinds of social support, that too in varying situational contexts, limiting generalizability of the findings. This has also produced inconsistent conclusions concerning the role of support providers such as coworkers and family. Recent developments in JD-R also suggest that the role of resources may vary in terms of their importance (necessity) for work engagement. By augmenting standard regression-based techniques with NCA, the authors explore these issues to provide a more thorough understanding of the influence of social supports on work engagement in telework situations.
To disclose or not disclose, is no longer the question – effect of AI-disclosed brand voice on brand authenticity and attitude
Authors: Kirkby Alexandra , Baumgarth Carsten , Henseler Jörg 
Published: June 2023

PurposeThis paper aims to explore consumer perception of “brand voice” authenticity, brand authenticity and brand attitude when the source of text is disclosed as either artificial intelligence (AI)-generated or human-written.Design/methodology/approachA 3 × 3 experimental design using Adidas marketing texts disclosed as either “AI” or “human”, or not disclosed was applied to data gathered online from 624 English-speaking students.FindingsText disclosed as AI-generated is not perceived as less authentic than that disclosed as human-written. No negative effect on brand voice authenticity and brand attitude results if an AI-source is disclosed.Practical implicationsFindings offer brand managers the potential for cost and time savings but emphasise the strong effect of AI technology on perceived brand authenticity and brand attitude.Originality/valueResults show that brands can afford to be transparent in disclosing the use of AI to support brand voice as communicated in product description or specification or in chatbot text.