bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis
Authors: Feng Jin , Wei Tianjiao , Cui Xiaona , Wei Rui , Hong Tianpei 
Published: September 2021

AbstractBackgroundThe global prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The pathogenesis of NAFLD is multifaceted, and the underlying mechanisms are elusive. We conducted data mining analysis to gain a better insight into the disease and to identify the hub genes associated with the progression of NAFLD.MethodsThe dataset GSE49541, containing the profile of 40 samples representing mild stages of NAFLD and 32 samples representing advanced stages of NAFLD, was acquired from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the R programming language. The Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database were used to perform the enrichment analysis and construct protein–protein interaction (PPI) networks, respectively. Subsequently, transcription factor networks and key modules were identified. The hub genes were validated in a mice model of high fat diet (HFD)‐induced NAFLD and in cultured HepG2 cells by real‐time quantitative PCR.ResultsBased on the GSE49541 dataset, 57 DEGs were selected and enriched in chemokine activity and cellular component, including the extracellular region. Twelve transcription factors associated with DEGs were indicated from PPI analysis. Upregulated expression of five hub genes (SOX9, CCL20, CXCL1, CD24, and CHST4), which were identified from the dataset, was also observed in the livers of HFD‐induced NAFLD mice and in HepG2 cells exposed to palmitic acid or advanced glycation end products.ConclusionThe hub genes SOX9, CCL20, CXCL1, CD24, and CHST4 are involved in the aggravation of NAFLD. Our results offer new insights into the underlying mechanism of NAFLD progression.
Occupational Health and Safety Measures in Healthcare Settings during COVID-19: Strategies for Protecting Staff, Patients and Visitors
Authors: Ahmad Isra Asma , Osei Ernest 
Published: September 2021

Abstract
The COVID-19 (SARS-CoV-2) pandemic has profoundly impacted almost every aspect of healthcare systems worldwide, placing the health and safety of frontline healthcare workers at risk, and it still continues to remain an important public health challenge. Several hospitals have put in place strategies to manage space, staff, and supplies in order to continue to deliver optimum care to patients while at the same time protecting the health and safety of staff and patients. However, the emergence of the second and third waves of the virus with the influx of new cases continue to add an additional level of complexity to the already challenging situation of containing the spread and lowering the rate of transmission, thus pushing healthcare systems to the limit. In this narrative review paper, we describe various strategies including administrative controls, environmental controls, and use of personal protective equipment, implemented by occupational health and safety departments for the protection of healthcare workers, patients, and visitors from SARS-CoV-2 virus infection. The protection and safeguard of the health and safety of healthcare workers and patients through the implementation of effective infection control measures, adequate management of possible outbreaks and minimization of the risk of nosocomial transmission is an important and effective strategy of SARS-CoV-2 pandemic management in any healthcare facility. High quality patient care hinges on ensuring that the care providers are well protected and supported so they can provide the best quality of care to their patients.
Hypertriglyceridemic waist phenotype and associated factors in individuals with arterial hypertension and/or diabetes mellitus
Authors: Borges Luiza Delazari , Comini Luma de Oliveira , Oliveira Laura Camargo de , Dias Heloísa Helena , Ferreira Emily de Souza , Batistelli Clara Regina Santos , da Costa Glauce Dias , Moreira Tiago Ricardo , da Silva Rodrigo Gomes , Cotta Rosângela Minardi Mitre 
Published: September 2021

Abstract
Cardiovascular diseases are among the main causes of death in Brazil and worldwide. The literature indicates the hypertriglyceridemic waist phenotype (HTWP) as an accessible alternative for the identification of cardiovascular and metabolic risk. The present study aimed to identify the prevalence and factors associated with HTWP in individuals diagnosed with arterial hypertension (AH) and/or diabetes mellitus type 2 (DM2). A cross-sectional study was conducted with individuals diagnosed with AH and/or DM2. The study data were collected through semi-structured interviews containing socio-demographic information, lifestyle, health care, in addition to anthropometric assessment, blood pressure measurement and biochemical blood tests. The prevalence of HTWP was estimated and bivariate and multivariate logistic regression was used to assess the factors associated with HTWP. Of the 788 individuals analysed, 21⋅5 % had the HTWP. In the adjusted model, the following variables remained associated with a greater chance of presenting HTWP: sex, age, body mass index (BMI) and very-low-density lipoprotein (VLDL). Being female increased the chance of HTWP by 7⋅7 times (OR 7⋅7; 95 % CI 3⋅9, 15⋅2). The one-year increase in age increased the chance of HTWP by 4 % (OR 1⋅04; 95 % CI 1⋅02, 1⋅06). The addition of 1 mg/dl of VLDL-c increased the chance of HTWP by 15 % (odds ratio (OR) 1⋅15; 95 % confidence interval (CI) 1⋅12, 1⋅18), as well as the increase of 1 kg/m2 in the BMI increased the chance of this condition by 20 % (OR 1⋅20; 95 % CI 1⋅15, 1⋅27). The prevalence of HTWP was associated with females, older age, higher BMI, higher VLDL-c and risk waist/height ratio.
Charged dust in the D-region incoherent scatter spectrum
Authors: Gunnarsdottir Tinna L. , Mann Ingrid 
Published: September 2021

We investigate the influence of charged dust on the incoherent scatter from the D-region ionosphere. Incoherent scatter is observed with high-power, large aperture radars and results from electromagnetic waves scattering at electrons that are coupled to other charged components through plasma oscillations. The influence of charged dust can hence be considered an effect of dusty plasma. The D-region contains meteoric smoke particles that are of nanometre size and form from incoming ablating meteors. Detection of such charged dust in the incoherent scatter spectrum from the D-region has previously been proposed and studied to some degree. We here present model calculations to investigate the influence of the charged dust component with a size distribution, instead of the one size dust components assumed in other works. The developed code to calculate the incoherent scatter spectrum from the D-region including dust particles with different sizes and different positive and negative charge states is made available (https://doi.org/10.18710/GHZIIY). We investigate how sizes, number density and charge state of the dust influence the spectrum during different ionospheric conditions. We consider the ionospheric parameters for the location of the EISCAT VHF radar during a year and find that conditions are most suitable for dust detection in winter below 80 km at times with increased electron densities. The prospects to derive dust parameters increase, when the incoherent scatter observations are combined with those of other instruments to provide independent information on electron density, neutral density and temperature.
Doctrines, modalities and comonads
Authors: Dagnino Francesco , Rosolini Giuseppe 
Published: September 2021

AbstractDoctrines are categorical structures very apt to study logics of different nature within a unified environment: the 2-categoryDtnof doctrines. Modal interior operators are characterised as particular adjoints in the 2-categoryDtn. We show that they can be constructed from comonads inDtnas well as from adjunctions in it, and we compare the two constructions. Finally we show the amount of information lost in the passage from a comonad, or from an adjunction, to the modal interior operator. The basis for the present work is provided by some seminal work of John Power.
Breastmilk or infant formula? Content analysis of infant feeding advice on breastmilk substitute manufacturer websites
Authors: Pomeranz Jennifer L , Chu Xiangying , Groza Oana , Cohodes Madeline , Harris Jennifer L 
Published: September 2021

AbstractObjective:To evaluate messages about infant feeding on breastmilk substitute (BMS) manufacturer websites directed at US caregivers and compare information and portrayals of breast-feeding/breastmilk with that of infant formula (IF) feeding.Design:We conducted a content analysis of US BMS companies’ websites. A codebook was created through an iterative process to identify messages and images about breast-feeding/breastmilk and IF feeding, including benefits or issues associated with each, and direct-to-consumer marketing practices that could discourage breast-feeding.Setting:Data were collected in 2019–2020 and analysed in 2020–2021 for US websites of five IF manufacturers.Participants:The websites of Similac, Enfamil and Gerber, which collectively represent approximately 98 % of the US IF market, and two US organic brands, Earth’s Best and Happy Baby.Results:Websites contained more messages about breast-feeding/breastmilk than IF but were significantly more likely to mention benefits to baby of IF (44 %) than breast-feeding/breastmilk (<26 %), including significantly more statements that IF provides brain, neural and gastrointestinal benefits; 40 % of breast-feeding/breastmilk content was dedicated to breast-feeding problems (e.g. sore nipples). Twice as many screenshots compared IF brands favourably to breastmilk than as superior to other brands. Certain companies displayed images indicating ease of IF feeding and difficulty of breast-feeding.Conclusions:Substantial messaging on BMS manufacturer websites encouraged IF feeding and discouraged breast-feeding. Health professionals should discourage their patients from visiting these websites and the US government should regulate misleading claims. Companies should refrain from providing breast-feeding advice and align their US marketing with the International Code of Marketing of Breast-milk Substitutes.
A 15-user quantum secure direct communication network
Authors: Qi Zhantong , Li Yuanhua , Huang Yiwen , Feng Juan , Zheng Yuanlin , Chen Xianfeng 
Published: September 2021

AbstractQuantum secure direct communication (QSDC) based on entanglement can directly transmit confidential information. However, the inability to simultaneously distinguish the four sets of encoded entangled states limits its practical application. Here, we explore a QSDC network based on time–energy entanglement and sum-frequency generation. In total,15 users are in a fully connected QSDC network, and the fidelity of the entangled state shared by any two users is >97%. The results show that when any two users are performing QSDC over 40 km of optical fiber, the fidelity of the entangled state shared by them is still >95%, and the rate of information transmission can be maintained above 1 Kbp/s. Our result demonstrates the feasibility of a proposed QSDC network and hence lays the foundation for the realization of satellite-based long-distance and global QSDC in the future.
Paternal weight prior to conception and infant birthweight: a prospective cohort study
Authors: Retnakaran Ravi , Wen Shi Wu , Tan Hongzhuan , Zhou Shujin , Ye Chang , Shen Minxue , Smith Graeme N. , Walker Mark C. 
Published: September 2021

Abstract
Background/Objective
Previous studies have consistently demonstrated that maternal weight status both before and during pregnancy is associated with infant birthweight. However, a fundamental limitation across this literature remains that previous studies have not evaluated the concomitant impact of paternal weight at conception, owing to the paucity of studies in which fathers were assessed prior to pregnancy. Thus, we established a cohort of preconception couples to prospectively evaluate the associations of maternal and paternal weight prior to pregnancy with infant birthweight at delivery.

Methods
In this prospective observational cohort study, 1292 newly-married women and their partners in Liuyang, China, were assessed at median of 23.3 weeks before a singleton pregnancy, thereby enabling concomitant assessment of preconception maternal and paternal body mass index (BMI) in relation to infant birthweight.

Results
Mean birthweight was 3294 ± 450 g with 147 neonates (11.4%) born large-for-gestational-age (LGA) and 94 (7.3%) small-for-gestational-age (SGA). After adjustment for maternal and paternal factors prior to conception (age, education, smoking, BMI, household income), length of gestation, total gestational weight gain, gestational diabetes, preeclampsia, and infant sex, it was noted that infant birthweight increased by 42.2 g (95% CI 29.5–54.8; p < 0.0001) per unit increase in maternal pregravid BMI and 10.7 g (95% CI 0.5–20.9; p = 0.04) per unit increase in paternal pregravid BMI. Maternal pregravid BMI explained 6.2% of the variance in birthweight whereas paternal BMI explained only 0.7%. Independent predictors of LGA delivery were maternal pregravid BMI (aOR = 1.91, 95% CI 1.50–2.44), maternal age (aOR = 1.48, 95% CI 1.09–2.00), and gestational weight gain (aOR = 1.80, 95% CI 1.40–2.30). Paternal pregravid BMI was not independently associated with LGA or SGA.

Conclusion
Paternal BMI prior to conception is associated with infant birthweight but only modestly so, in contrast to the dominant impact of maternal weight.
Therapeutic targeting of the inflammasome in myeloid malignancies
Authors: Chakraborty Samarpana , Shapiro Lauren C. , de Oliveira Sofia , Rivera-Pena Bianca , Verma Amit , Shastri Aditi 
Published: September 2021

AbstractEven though genetic perturbations and mutations are important for the development of myeloid malignancies, the effects of an inflammatory microenvironment are a critical modulator of carcinogenesis. Activation of the innate immune system through various ligands and signaling pathways is an important driver of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The DAMPs, or alarmins, which activate the inflammasome pathway via the TLR4/NLR signaling cascade causes the lytic cell death of hematopoietic stem and progenitor cells (HSPCs), ineffective hematopoiesis, and β-catenin-induced proliferation of cancer cells, leading to the development of MDS/AML phenotype. It is also associated with other myeloid malignancies and involved in the pathogenesis of associated cytopenias. Ongoing research suggests the interplay of inflammasome mediators with immune modulators and transcription factors to have a significant role in the development of myeloid diseases, and possibly therapy resistance. This review discusses the role and importance of inflammasomes and immune pathways in myeloid malignancies, particularly MDS/AML, to better understand the disease pathophysiology and decipher the scope of therapeutic interventions.
Chimeric antigen receptor T cells self-neutralizing IL6 storm in patients with hematologic malignancy
Authors: Xue Lei , Yi Yan , Xu Qianwen , Wang Li , Yang Xiaohui , Zhang Yongjing , Hua Xuefei , Chai Xiaoshan , Yang Junjie , Chen Yaxin , Tao Guangshi , Hu Biliang , Wang Xingbing 
Published: September 2021

AbstractIL6 is one of the most elevated cytokines during chimeric antigen receptor (CAR) T cell cytokine release syndrome (CRS), and IL6R blockade by Tocilizumab has successfully relieved the most life-threatening aspects of CRS in patients. In addition, latest studies demonstrated the essential role of IL1 in driving CART induced neurotoxicity in mouse models. Here we present a clinical investigation (ChiCTR2000032124; ChiCTR2000031868) of anti-CD19 and anti-BCMA CART (41BBζ) secreting an anti-IL6 scFv and IL1 receptor antagonist (IL1RA) in treating patients with hematologic malignancy. Our results revealed that IL6 and IL1B were maintained at low levels without significant elevation during CRS, rendering Tocilizumab dispensable. Moreover, treated patients did not show neurotoxicity during CRS and exhibited mild to moderate CRS. Notably, we observed high rate of complete response (CR) and significant CART expansion during treatment. In sum, we conclude that CART-secreting anti-IL6 scFv and IL1RA could self-neutralize IL6 storm and maintain low levels of IL1B during CART therapy to minimize IL6- and IL1-associated cytokine toxicity and neurotoxicity without impairing therapeutic efficacy.
Quantifying the unknown impact of segmentation uncertainty on image-based simulations
Authors: Krygier Michael C. , LaBonte Tyler , Martinez Carianne , Norris Chance , Sharma Krish , Collins Lincoln N. , Mukherjee Partha P. , Roberts Scott A. 
Published: September 2021

AbstractImage-based simulation, the use of 3D images to calculate physical quantities, relies on image segmentation for geometry creation. However, this process introduces image segmentation uncertainty because different segmentation tools (both manual and machine-learning-based) will each produce a unique and valid segmentation. First, we demonstrate that these variations propagate into the physics simulations, compromising the resulting physics quantities. Second, we propose a general framework for rapidly quantifying segmentation uncertainty. Through the creation and sampling of segmentation uncertainty probability maps, we systematically and objectively create uncertainty distributions of the physics quantities. We show that physics quantity uncertainty distributions can follow a Normal distribution, but, in more complicated physics simulations, the resulting uncertainty distribution can be surprisingly nontrivial. We establish that bounding segmentation uncertainty can fail in these nontrivial situations. While our work does not eliminate segmentation uncertainty, it improves simulation credibility by making visible the previously unrecognized segmentation uncertainty plaguing image-based simulation.
Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state
Authors: Cao Anne-Marinette , Quast Robert B. , Fatemi Fataneh , Rondard Philippe , Pin Jean-Philippe , Margeat Emmanuel 
Published: September 2021

AbstractMuch hope in drug development comes from the discovery of positive allosteric modulators (PAM) that display target subtype selectivity and act by increasing agonist potency and efficacy. How such compounds can allosterically influence agonist action remains unclear. Metabotropic glutamate receptors (mGlu) are G protein-coupled receptors that represent promising targets for brain diseases, and for which PAMs acting in the transmembrane domain have been developed. Here, we explore the effect of a PAM on the structural dynamics of mGlu2 in optimized detergent micelles using single molecule FRET at submillisecond timescales. We show that glutamate only partially stabilizes the extracellular domains in the active state. Full activation is only observed in the presence of a PAM or the Gi protein. Our results provide important insights on the role of allosteric modulators in mGlu activation, by stabilizing the active state of a receptor that is otherwise rapidly oscillating between active and inactive states.
Large scale enzyme based xenobiotic identification for exposomics
Authors: Liu Ken H. , Lee Choon M. , Singer Grant , Bais Preeti , Castellanos Francisco , Woodworth Michael H. , Ziegler Thomas R. , Kraft Colleen S. , Miller Gary W. , Li Shuzhao , Go Young-Mi , Morgan Edward T. , Jones Dean P. 
Published: September 2021

AbstractAdvances in genomics have revealed many of the genetic underpinnings of human disease, but exposomics methods are currently inadequate to obtain a similar level of understanding of environmental contributions to human disease. Exposomics methods are limited by low abundance of xenobiotic metabolites and lack of authentic standards, which precludes identification using solely mass spectrometry-based criteria. Here, we develop and validate a method for enzymatic generation of xenobiotic metabolites for use with high-resolution mass spectrometry (HRMS) for chemical identification. Generated xenobiotic metabolites were used to confirm identities of respective metabolites in mice and human samples based upon accurate mass, retention time and co-occurrence with related xenobiotic metabolites. The results establish a generally applicable enzyme-based identification (EBI) for mass spectrometry identification of xenobiotic metabolites and could complement existing criteria for chemical identification.
MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair
Authors: de Krijger Inge , Föhr Bastian , Pérez Santiago Hernández , Vincendeau Estelle , Serrat Judit , Thouin Alexander Marc , Susvirkar Vivek , Lescale Chloé , Paniagua Inés , Hoekman Liesbeth , Kaur Simranjeet , Altelaar Maarten , Deriano Ludovic , Faesen Alex C. , Jacobs Jacqueline J. L. 
Published: September 2021

AbstractMAD2L2 (REV7) plays an important role in DNA double-strand break repair. As a member of the shieldin complex, consisting of MAD2L2, SHLD1, SHLD2 and SHLD3, it controls DNA repair pathway choice by counteracting DNA end-resection. Here we investigated the requirements for shieldin complex assembly and activity. Besides a dimerization-surface, HORMA-domain protein MAD2L2 has the extraordinary ability to wrap its C-terminus around SHLD3, likely creating a very stable complex. We show that appropriate function of MAD2L2 within shieldin requires its dimerization, mediated by SHLD2 and accelerating MAD2L2-SHLD3 interaction. Dimerization-defective MAD2L2 impairs shieldin assembly and fails to promote NHEJ. Moreover, MAD2L2 dimerization, along with the presence of SHLD3, allows shieldin to interact with the TRIP13 ATPase, known to drive topological switches in HORMA-domain proteins. We find that appropriate levels of TRIP13 are important for proper shieldin (dis)assembly and activity in DNA repair. Together our data provide important insights in the dependencies for shieldin activity.
Real-time dynamics and structures of supported subnanometer catalysts via multiscale simulations
Authors: Wang Yifan , Kalscheur Jake , Su Ya-Qiong , Hensen Emiel J. M. , Vlachos Dionisios G. 
Published: September 2021

AbstractUnderstanding the performance of subnanometer catalysts and how catalyst treatment and exposure to spectroscopic probe molecules change the structure requires accurate structure determination under working conditions. Experiments lack simultaneous temporal and spatial resolution and could alter the structure, and similar challenges hinder first-principles calculations from answering these questions. Here, we introduce a multiscale modeling framework to follow the evolution of subnanometer clusters at experimentally relevant time scales. We demonstrate its feasibility on Pd adsorbed on CeO2(111) at various catalyst loadings, temperatures, and exposures to CO. We show that sintering occurs in seconds even at room temperature and is mainly driven by free energy reduction. It leads to a kinetically (far from equilibrium) frozen ensemble of quasi-two-dimensional structures that CO chemisorption and infrared experiments probe. CO adsorption makes structures flatter and smaller. High temperatures drive very rapid sintering toward larger, stable/metastable equilibrium structures, where CO induces secondary structure changes only.