bluuebunny/crossref_metadata_2025 huggingface dataset:
Tree Based Co-Clustering Identifies Variation in Chromatin Accessibility Across Hematopoietic Cell Types
Authors: George Thomas B. , Strawn Nathaniel K. , Leviyang Sivan
Published: May 2021

Chromatin accessibility, as measured by ATACseq, varies between hematopoietic cell types in different branches of the hematopoietic differentiation tree, e.g. T cells vs B cells, but methods that relate variation in chromatin accessibility to the placement of a cell type on the differentiation tree are lacking. Using an ATACseq dataset recently published by the ImmGen consortium, we construct associations between chromatin accessibility and hematopoietic cell types using a novel co-clustering approach that accounts for the structure of the hematopoietic, differentiation tree. Under a model in which all loci and cell types within a co-cluster have a shared accessibility state, we show that roughly 80% of cell type associated accessibility variation can be captured through 12 cell type clusters and 20 genomic locus clusters. Using publicly available ChIPseq datasets, we show that our clustering reflects transcription factor binding patterns with implications for regulation across cell types. Our results provide a framework for analysis of chromatin state variation across cell types related by a tree or network.
Molecular basis of selective cytokine signaling inhibition by antibodies targeting a shared receptor
Authors: Fields James K. , Kihn Kyle , Birkedal Gabriel S. , Klontz Erik H. , Sjöström Kjell , Günther Sebastian , Beadenkopf Robert , Forsberg Göran , Liberg David , Snyder Greg A. , Deredge Daniel , Sundberg Eric J.
Published: May 2021

Interleukin-1 (IL-1) family cytokines are potent mediators of inflammation, acting to coordinate local and systemic immune responses to a wide range of stimuli. Aberrant signaling by IL-1 family cytokine members, however, is linked to myriad inflammatory syndromes, autoimmune conditions and cancers. As such, blocking the inflammatory signals inherent to IL-1 family signaling is an established and expanding therapeutic strategy. While several FDA-approved IL-1 inhibitors exists, including an Fc fusion protein, a neutralizing antibody, and an antagonist cytokine, none specifically targets the co-receptor IL-1 receptor accessory protein (IL-1RAcP). Most IL-1 family cytokines form productive signaling complexes by binding first to their cognate receptors – IL-1RI for IL-1α and IL-1β; ST2 for IL-33; and IL-36R for IL-36α, IL-36β and IL-36γ – after which they recruit the shared secondary receptor IL-1RAcP to form a ternary cytokine/receptor/co-receptor complex. Recently, IL-1RAcP was identified as a biomarker for both AML and CML. IL-1RAcP has also been implicated in tumor progression in solid tumors and an anti-IL1RAP antibody (nadunolimab, CAN04) is in phase II clinical studies in pancreatic cancer and non-small cell lung cancer (NCT03267316). As IL-1RAcP is common to all of the abovementioned IL-1 family cytokines, targeting this co-receptor raises the possibility of selective signaling inhibition for different IL-1 family cytokines. Indeed, previous studies of IL-1β and IL-33 signaling complexes have revealed that these cytokines employ distinct mechanisms of IL-1RAcP recruitment even though their overall cytokine/receptor/co-receptor complexes are structurally similar. Here, using functional, biophysical, and structural analyses, we show that antibodies specific for IL-1RAcP can differentially block signaling by IL-1 family cytokines depending on the distinct IL-1RAcP epitopes that they engage. Our results indicate that targeting a shared cytokine receptor is a viable therapeutic strategy for selective cytokine signaling inhibition.
Harnessing genetic diversity in the USDA pea (Pisum sativumL.) germplasm collection through genomic prediction
Authors: Al Bari Md. Abdullah , Zheng Ping , Viera Indalecio , Worral Hannah , Szwiec Stephen , Ma Yu , Main Dorrie , Coyne Clarice J. , McGee Rebecca , Bandillo Nonoy
Published: May 2021

Phenotypic evaluation and efficient utilization of germplasm collections can be time-intensive, laborious, and expensive. However, with the plummeting costs of next-generation sequencing and the addition of genomic selection to the plant breeder’s toolbox, we now can more efficiently tap the genetic diversity within large germplasm collections. In this study, we applied and evaluated genomic selection’s potential to a set of 482 pea accessions – genotyped with 30,600 single nucleotide polymorphic (SNP) markers and phenotyped for seed yield and yield-related components – for enhancing selection of accessions from the USDA Pea Germplasm Collection. Genomic prediction models and several factors affecting predictive ability were evaluated in a series of cross-validation schemes across complex traits. Different genomic prediction models gave similar results, with predictive ability across traits ranging from 0.23 to 0.60, with no model working best across all traits. Increasing the training population size improved the predictive ability of most traits, including seed yield. Predictive abilities increased and reached a plateau with increasing number of markers presumably due to extensive linkage disequilibrium in the pea genome. Accounting for population structure effects did not significantly boost predictive ability, but we observed a slight improvement in seed yield. By applying the best genomic prediction model (e.g., RR-BLUP), we then examined the distribution of genotyped but nonphenotyped accessions and the reliability of genomic estimated breeding values (GEBV). The distribution of GEBV suggested that none of the nonphenotyped accessions were expected to perform outside the range of the phenotyped accessions. Desirable breeding values with higher reliability can be used to identify and screen favorable germplasm accessions. Expanding the training set and incorporating additional orthogonal information (e.g., transcriptomics, proteomics, metabolomics, physiological traits, etc.) into the genomic prediction framework could enhance prediction accuracy.
Mutation-specific reporter for the optimization and enrichment of prime editing
Authors: Schene I.F. , Joore I.P. , Baijens J.H.L. , Shehata S. , Ilcken E.F. , Bolhuis D.P. , van Rees R.C.M. , Spelier S.A. , van der Doef P.J. , Beekman J.M. , Nieuwenhuis E.E.S. , Fuchs S.A.
Published: May 2021

We present a fluorescent prime editing and enrichment reporter (fluoPEER), which can be tailored to any genomic target site. This system rapidly and faithfully ranks the efficiency of prime edit guide RNAs (pegRNAs) and any prime editor protein, including novel variants with flexible PAM recognition. Successful reporter editing enriches for genomic editing. FluoPEER can be employed for efficient correction of patient cells and to elucidate cellular mechanisms needed for successful prime editing.
Foldamers Reveal and Validate Novel Therapeutic Targets Associated with Toxic α-Synuclein Self-Assembly
Authors: Ahmed Jemil , Fitch Tessa C. , Donnelly Courtney M. , Joseph Johnson A. , Bassil Mikaela M. , Son Ahyun , Zhang Chen , Ledreux Aurélie , Horowitz Scott , Qin Yan , Paredes Daniel , Kumar Sunil
Published: May 2021

Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based novel targets that are essential for aggregation and will have significant therapeutic implications. An extensive array ofin vitro, ex vivo, andin vivoassays was utilized to validate αS sequences and their structural characteristics that are essential for aggregation and propagation of PD phenotypes. The study aids in developing significant mechanistic and therapeutic insights into various facets of αS aggregation, which will pave the way for novel and effective treatments for PD.
Metabolic Complementation between Glucose and Amino Acid Drives HepaticDe NovoLipogenesis and Steatosis
Authors: Liao Yilie , Liu Lei , Li Honghao , Bai Xiaojie , Sun Fangfang , Xiao Xia , Fu Suneng
Published: May 2021

Increasedde novolipogenesis (DNL) is a hallmark of nonalcoholic fatty liver disease (NAFLD) in obesity, but the macronutrient source for >80% carbon backbone for fatty acid synthesis has not been determined. Here we take an integrated approach to dissect nutrient metabolism, bothex vivoandin vivo. We discover a castling effect of glucose and glutamine metabolism throughex vivoisotope tracing studies that limits the entrance of glucose carbon into the glutamine-dominated tricarboxylic acid cycle (TCA) and DNL pathways.In vivotracing studies with a high carbohydrate drink (glucose/amino acid, 3:1,w/w) confirm dietary amino acids are twice more efficient than glucose in labeling the hepatic acetyl-CoA and fatty acid pool, and together they account for over 70% of hepatic DNL substrate. Both glucose and glutamine carbon flux into DNL pathways are increased in obese hepatocytes, and metabolic rerouting of substrate carbon toward glycogen synthesis and energy production through GYS2 and GLUD1 overexpression improves hepatic steatosis. Together, these data reveal the quantitative contribution of glucose and amino acid carbon toward hepatic DNL and the development of hepatic steatosis in obesity.
An Enhanced Sampling Approach to the Induced Fit Docking Problem in Protein-Ligand Binding: the case of mono-ADP-ribosylation hydrolases inhibitors
Authors: Zhao Qianqian , Capelli Riccardo , Carloni Paolo , Lüscher Bernhard , Li Jinyu , Rossetti Giulia
Published: May 2021

A variety of enhanced sampling methods can predict free energy landscapes associated with protein/ligand binding events, characterizing in a precise way the intermolecular interactions involved. Unfortunately, these approaches are challenged by not uncommon induced fit mecchanisms. Here, we present a variant of the recently reported volume-based metadynamics (MetaD) method which describes ligand binding even when it affects protein structure. The validity of the approach is established by applying it to a substrate/enzyme complexes of pharmacological relevance: this is the mono-ADP-ribose (ADPr) in complex with mono-ADP-ribosylation hydrolases (MacroD1 and MacroD2), where induced-fit phenomena are known to be operative. The calculated binding free energies are consistent with experiments, with an absolute error less than 0.5 kcal/mol. Our simulations reveal that in all circumstances the active loops, delimiting the boundaries of the binding site, rearrange from an open to a closed conformation upon ligand binding. The calculations further provide, for the first time, the molecular basis of the experimentally observed affinity changes in ADPr binding on passing from MacroD1 to MacroD2 and all its mutants. Our study paves the way to investigate in a completely general manner ligand binding to proteins and receptors.
Design, immunogenicity and efficacy of a Pan-SARS-CoV-2 synthetic DNA vaccine
Authors: Reed Charles C. , Schultheis Katherine , Andrade Viviane M. , Kalia Richa , Tur Jared , Schouest Blake , Elwood Dustin , Walters Jewell N. , Maricic Igor , Doan Arthur , Vazquez Miguel , Eblimit Zeena , Pezzoli Patrick , Amante Dinah , Porto Maciel , Narvaez Brandon , Lok Megan , Spence Brittany , Bradette Heath , Horn Heather , Yang Maria , Fader Joseph , Ferrer Roi , Weiner David B. , Kar Swagata , Kim J. Joseph , Humeau Laurent M. , Ramos Stephanie J. , Smith Trevor R.F. , Broderick Kate E.
Published: May 2021

Here we have employed SynCon® design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants of concern (VOC). Compared to WT and VOC-matched vaccines which showed reduced cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster challenge model demonstrated that INO-4802 conferred superior protection following intranasal B.1.351 challenge. Protection against weight loss associated with WT, B.1.1.7, P.1 and B.1.617.2 challenge was also demonstrated. Vaccinated hamsters showed enhanced humoral responses against VOC in a heterologous WT vaccine prime and INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOC as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT-matched vaccines.
Structure determination of organic compounds by a fit to the pair distribution function from scratch without prior indexing
Authors: Schlesinger Carina , Habermehl Stefan , Prill Dragica
Published: May 2021

A method for the ab initio crystal structure determination of organic compounds by a fit to the pair distribution function (PDF), without prior knowledge of lattice parameters and space group, has been developed. The method is called `PDF-Global-Fit' and is implemented by extension of the program FIDEL (fit with deviating lattice parameters). The structure solution is based on a global optimization approach starting from random structural models in selected space groups. No prior indexing of the powder data is needed. The new method requires only the molecular geometry and a carefully determined PDF. The generated random structures are compared with the experimental PDF and ranked by a similarity measure based on cross-correlation functions. The most promising structure candidates are fitted to the experimental PDF data using a restricted simulated annealing structure solution approach within the program TOPAS, followed by a structure refinement against the PDF to identify the correct crystal structure. With the PDF-Global-Fit it is possible to determine the local structure of crystalline and disordered organic materials, as well as to determine the local structure of unindexable powder patterns, such as nanocrystalline samples, by a fit to the PDF. The success of the method is demonstrated using barbituric acid as an example. The crystal structure of barbituric acid form IV solved and refined by the PDF-Global-Fit is in excellent agreement with the published crystal structure data.
On the use of the scattering amplitude in coherent X-ray Bragg diffraction imaging
Authors: Godard Pierre
Published: May 2021

Lens-less imaging of crystals with coherent X-ray diffraction offers some unique possibilities for strain-field characterization. It relies on numerically retrieving the phase of the scattering amplitude from a crystal illuminated with coherent X-rays. In practice, the algorithms encode this amplitude as a discrete Fourier transform of an effective or Bragg electron density. This short article suggests a detailed route from the classical expression of the (continuous) scattering amplitude to this discrete function. The case of a heterogeneous incident field is specifically detailed. Six assumptions are listed and quantitatively discussed when no such analysis was found in the literature. Details are provided for two of them: the fact that the structure factor varies in the vicinity of the probed reciprocal lattice vector, and the polarization factor, which is heterogeneous along the measured diffraction patterns. With progress in X-ray sources, data acquisition and analysis, it is believed that some approximations will prove inappropriate in the near future.
A combined approach to characterize ligand-induced solid–solid phase transitions in biomacromolecular crystals
Authors: Ramakrishnan Saminathan , Stagno Jason R. , Magidson Valentin , Heinz William F. , Wang Yun-Xing
Published: May 2021

Solid–solid phase transitions (SSPTs) are widespread naturally occurring phenomena. Understanding the molecular mechanisms and kinetics of SSPTs in various crystalline materials, however, has been challenging due to technical limitations. In particular, SSPTs in biomacromolecular crystals, which may involve large-scale changes and particularly complex sets of interactions, are largely unexplored, yet may have important implications for time-resolved crystallography and for developing synthetic biomaterials. The adenine riboswitch (riboA) is an RNA control element that uses ligand-induced conformational changes to regulate gene expression. Crystals of riboA, upon the addition of a ligand, undergo an SSPT from monoclinic to triclinic to orthorhombic. Here, solution atomic force microscopy (AFM) and polarized video microscopy (PVM) are used to characterize the multiple transition states throughout the SSPT in both the forward and the reverse directions. This contribution describes detailed protocols for growing crystals directly on mica or glass surfaces for AFM and PVM characterization, respectively, as well as methods for image processing and phase-transition kinetics analysis.
Robust surface structure analysis with reliable uncertainty estimation using the exchange Monte Carlo method. Corrigendum
Authors: Nagai Kazuki , Anada Masato , Nakanishi-Ohno Yoshinori , Okada Masato , Wakabayashi Yusuke
Published: May 2021

An error in the article by Nagai, Anada, Nakanishi-Ohno, Okada & Wakabayashi [J. Appl. Cryst. (2020), 53, 387–392] is corrected.
8-Hydroxy-6-methoxy-7-(3-methylbut-2-enyloxy)coumarin (capensine)
Authors: Mamadrakhimov Azimjon , Mutalliyev Luqmonjon , Abdullaev Sirojiddin , Khodjaniyazov Khamid , Izotova Lidiya , Aisa Haji Akber
Published: May 2021

The title coumarin derivative, C15H16O5, was isolated from the roots ofSophora japonica. The coumarin (2H-chromen-2-one) fragment is almost planar, with an r.m.s. deviation of 0.0356 Å. The carbon atom of the methoxy substituent is coplanar with the benzopyran oxa-heterocycle. The 3-methylbut-2-enyloxy group is disordered over two sets of sites with occupation factors of 0.920 (3) and 0.080 (3). In the crystal, molecules are linked by O—H...O and C—H...O hydrogen bonds into chains propagating along the [101] direction.
Risk categorization in Portuguese organizations in times of the COVID-19 pandemic – an exploratory statistical analysis
Authors: Tavares Fernando , Santos Eulália , Tavares Vasco
Published: May 2021

Purpose

This work aims to characterize the risks companies deal with in the context of a pandemic, and to ascertain which risk type is most present in Portuguese organizations. It is also intended to verify whether there are differences in the various risk types between companies that had or did not have a plan or strategy to act in a pandemic, such as the one caused by COVID-19.

Design/methodology/approach

A quantitative methodology was used, based on the application of a questionnaire survey targeting the Portuguese companies. The sample is composed of 1,647 Portuguese companies, which were queried through a questionnaire survey that analyses different risk types. Then, the software R was used to treat the results.

Findings

The results show that companies are exposed and vulnerable to uncertain events, and five risk types were formed: legal, image, financial, strategic and operational. There is a bigger concern about the management of financial risks.

Practical implications

Academics and companies can become more aware and master the concept of risk and its different branches, which consequently favours the adoption of strategies to better manage and plan risk.

Originality/value

The literature on international businesses and their risks assumes that all crises are the same. However, the COVID-19 pandemic, besides causing a recession, obliges people and companies to adapt to a new scenario. Risks become more important to companies, in a way that had not been academically studied.
“I had a big bias”: disrupting children's biases, stereotypes through studying cultures
Authors: Torres Heidi J.
Published: May 2021

Purpose

This article describes a study examining the influence of a curricular intervention on 25 third-graders' stereotypes and biases related to world cultures and the people who embody them.

Design/methodology/approach

The qualitative study focused on privileging student voice through an inductive analytical approach. Triangulated data sources include focus group and paired interviews, recorded lessons, student and teacher curricular documents, as well as field notes.

Findings

Results—primarily reported through the children's own thoughts and voices—describe students' initial ideas about world cultures and people prior to experiencing the curriculum, and afterward, documenting shifts in stereotypical beliefs and biased attitudes. Findings indicate many students made positive changes, altering incorrect assumptions about other cultures and people. In addition, some children became able to recognize stereotypes and biases, generalize what they learned to other situations beyond those addressed in the curriculum and identify their own bias.

Originality/value

This study provides insight into an understudied topic and population in social studies education. It presents evidence that young children are capable of successfully engaging with the complex topics of bias and stereotypes in meaningful ways, thus providing a rationale for addressing stereotypes and bias concerning world cultures in elementary classrooms.
Association between metabolic syndrome and Behçet's disease: A nationwide population‐based study
Authors: Lee JiHyun , Yoo SeungAh , Han Kyung Do , Han Ju Hee , Bang Chul Hwan , Park YoungMin , Lee Jun Young , Park Yong‐Gyu , Lee YoungBok
Published: May 2021

Metabolic syndrome (MetS) is characterized by insulin resistance, high blood pressure/sugar, dyslipidemia, and obesity. Whether MetS and its components affect the development of Behçet's disease (BD) remains unclear. This study was performed to investigate the associations between metabolic syndrome and risk of BD using nationwide population data. We conducted a retrospective cohort study of 10 505 818 Korean subjects who received health checkups in 2009–2012. Patients were classified into a MetS and its components group and were followed‐up until 2016 for new‐onset BD. A Cox proportional hazards model was used to assess the independent or synergistic effects of MetS and its components on the risk of incident BD. Compared to subjects without MetS components, the hazard ratio (HR) for development of BD in patients with MetS was 0.874 (95% confidence interval [CI]: 0.819–0.933) and this association was more prominent when all components of MetS were present (HR = 0.675, 95% CI = 0.571–0.798). Subjects with low high density lipoprotein (HDL) has a significantly increased risk of the development of BD (HR = 1.51, 95% CI = 1.4–1.594) compared to controls. This study showed that the incidence of Behçet's disease was reduced in subjects with MetS. Moreover, the presence of MetS components, with the exception of HDL, was negatively related to the development of BD.
An increase in normetanephrine in hair follicles of acne lesions through the sympatho‐adrenal medullary system in acne patients with anxiety
Authors: Mizuno Koji , Sakaue Hiroaki , Kohsaka Keita , Takeda Hidetomo , Hayashi Nobukazu , Sato Takashi
Published: May 2021

Acne vulgaris, a chronic inflammatory skin disease, has been associated with not only sebaceous gland dysfunction but also various endogenous and exogenous stresses. Since sebaceous glands are under neuroendocrine control, including the hypothalamic–pituitary–adrenal axis and neuro‐autocrine mechanisms, it remains unclear how psychological stress relates to the pathogenesis of acne. In this study, we investigated the relationship between psychological stress and catecholamine in acne lesions from 18 patients with mild or moderate acne. The State‐Trait Anxiety Inventory (STAI) revealed that all patients were anxious, with six having low anxiety and 12 high anxiety. Salivary α‐amylase activity (sAA), which is regulated by the sympatho‐adrenal medullary (SAM) system, positively correlated with the STAI State Anxiety scores (STAI‐S) and was significantly detectable in acne patients with high rather than low anxiety. In addition, the level of normetanephrine, but not metanephrine, both of which are catecholamine metabolites, in hair follicles of acne lesions also positively correlated with the STAI‐S. Furthermore, the normetanephrine level was higher in patients with high rather than low anxiety, whereas there was no change in metanephrine in the hair follicles of the acne lesions. Moreover, neither the sAA nor metanephrine and normetanephrine in the acne lesions was related to acne severity in the patients. Thus, these results provide novel evidence that a SAM system‐associated increase of normetanephrine level in hair follicles is involved in the acne pathology of patients with anxiety.
Occupational therapy for people with mask anxiety undergoing radiotherapy
Authors: Effeney Lauren C. , Nixon Jodie L. , Pigott Amanda E.
Published: May 2021

Introduction

Up to one third of people with head and neck cancer undergoing radiation therapy experience mask anxiety. However, there is limited literature guiding the role of health professionals, including occupational therapists, in managing mask anxiety. This study aimed to explore the content of occupational therapy interactions with people who have identified mask anxiety.

Methods

A cohort of 20 participants with identified mask anxiety engaged in semi‐structured interviews with occupational therapists. Theoretical thematic analysis and the framework provided by the Canadian Model of Occupational Performance and Engagement (CMOP‐E) were employed to explore the content of occupational therapy interactions with people experiencing mask anxiety.

Results

Theoretical thematic analysis identified 13 relevant themes with 49 codes relating to the interaction between participants and occupational therapists. Analysis of these interactions identified the occupational therapy role to be holistic and multifaceted. The cognitive, affective, and institutional components of the CMOP‐E were dominantly explored by the occupational therapists with participants. Occupation, spirituality, and the cultural environment were either not addressed or minimally discussed with participants.

Conclusion

The management of mask anxiety during radiation therapy is a novel area of practice for occupational therapists. The results of this study suggest that the occupational therapy profession explores a range of factors with the person undergoing radiation therapy with mask anxiety, and that the CMOP‐E model can be used to guide these interactions. Future research is required to further define this role and its efficacy in managing mask anxiety.
Estuarine microbial diversity and nitrogen cycling increase along sand–mud gradients independent of salinity and distance
Authors: Boey Jian Sheng , Mortimer Redmond , Couturier Agathe , Worrallo Katie , Handley Kim M.
Published: May 2021

Estuaries are depositional environments prone to terrigenous mud sedimentation. While macrofaunal diversity and nitrogen retention are greatly affected by changes in sedimentary mud content, its impact on prokaryotic diversity and nitrogen cycling activity remains understudied. We characterized the composition of estuarine tidal flat prokaryotic communities spanning a habitat range from sandy to muddy sediments, while controlling for salinity and distance. We also determined the diversity, abundance and expression of ammonia oxidizers and N2O‐reducers within these communities by amoA and clade I nosZ gene and transcript analysis. Results show that prokaryotic communities and nitrogen cycling fractions were sensitive to changes in sedimentary mud content, and that changes in the overall community were driven by a small number of phyla. Significant changes occurred in prokaryotic communities and N2O‐reducing fractions with only a 3% increase in mud, while thresholds for ammonia oxidizers were less distinct, suggesting other factors are also important for structuring these guilds. Expression of nitrogen cycling genes was substantially higher in muddier sediments, and results indicate that the potential for coupled nitrification–denitrification became increasingly prevalent as mud content increased. Altogether, results demonstrate that mud content is a strong environmental driver of diversity and N‐cycling dynamics in estuarine microbial communities.
Fake News, Epistemic Coverage and Trust
Authors: Ryan Shane
Published: May 2021

This article makes the case that a deficit or absence of trust in media sources to report on newsworthy items facilitates acceptance of fake news. The article begins by identifying the sort of fake news that is of interest for the purposes of this article. Epistemic coverage is then explained—in particular, how an individual's expectations about their epistemic environment can lead them to accepting or rejecting claims. The article explains that when an individual believes that mainstream media report on what is deemed newsworthy, it follows that an individual will have grounds to dismiss a newsworthy claim that has not been reported upon—such as a claim made by fake news. Trust—which has both a believed competence requirement and a believed goodwill requirement—is then discussed as part of this explanation. The article concludes with a discussion of the implications of the argument for regulating mainstream media.
Comparing the value of community benefit and Tax‐Exemption in non‐profit hospitals
Authors: Zare Hossein , Eisenberg Matthew D. , Anderson Gerard
Published: May 2021

Objective

We examined the characteristics of non‐profit hospitals providing more community benefits and charity care than value of their tax exemptions and how this relationship changed between 2011 and 2018.

Data sources

Primary dataset was schedule H Form IRS 990 data. This data was merged with the American Hospital Association, Medicare Hospital Cost Report, and the America Community Survey.

Study design

We measured six categories of tax benefits and 17 types of community benefits. Subtracting the average value of community benefits provided by for‐profit hospitals, we computed incremental community benefit and charity care provided by each non‐profit hospital.

Extraction methods

A nationally representative sample was created of 11 776 non‐profit hospital‐year observations from 1472 unique hospitals over the 2011 to 2018 period was created. Descriptive analyses and random effect logistic regression were used to show associations between hospital characteristics and difference between incremental net community benefits and the value of tax‐exemption.

Principal findings

After adjusting for community benefits provided by for‐profits hospitals, on average, non‐profit hospitals spent 5.9% (CI: 5.8%‐6.0%) of their total expenses on community benefits; 1.3% (CI: 1.2%‐1.3%) on charity care; and received 4.3% (CI: 4.2%‐4.4%) of total expenses in tax exemptions. A total of 38.5% of non‐profit hospitals did not provide more community benefit and 86% did not provide more charity care than the value of their tax exemption. Hospitals with fewer beds, providing residency education and located in high poverty communities were more likely to provide more incremental community benefits and charity care than the value of their tax exemption, while system affiliation had a negative association.

Conclusion

The amount of community benefits and charity care provided by non‐profits varied substantially across non‐profit hospitals. Establishing minimum requirements for non‐profit hospitals or publicly ranking hospitals based on their community benefit or charity care contributions, could encourage greater community benefits and charity care.
Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients
Authors: Kanai Hidetoshi , Nangaku Masaomi , Nagai Reiko , Okuda Nobuhiko , Kurata Kyo , Nagakubo Takashi , Endo Yukihiro , Cobitz Alexander
Published: May 2021

Daprodustat is a hypoxia‐inducible factor‐prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease. This phase 3 study evaluated the efficacy and safety of daprodustat in an uncontrolled cohort of 56 Japanese peritoneal dialysis patients with anemia over 52 weeks. Subjects received daprodustat 4 mg orally once daily for 4 weeks and the dose was subsequently adjusted every 4 weeks. Mean baseline hemoglobin was 10.9 g/dL (95% CI 10.59, 11.12). Mean hemoglobin reached the target range (11.0–13.0 g/dL) at week 12 and was maintained until week 52. Mean hemoglobin during weeks 40–52 was 12.1 g/dL (95% CI 12.0, 12.2). The most frequent adverse events included nasopharyngitis (29%), catheter‐site infection (18%), peritonitis (16%), diarrhea (14%), and nausea (11%). No deaths were reported. Once‐daily oral daprodustat treatment was generally well tolerated and mean hemoglobin was achieved and maintained within the target range in Japanese peritoneal dialysis participants.
Fatty acid composition, oxidative stability, and sensory evaluation of the sausages produced from the meat of pigs fed a diet enriched with 8% of fish oil
Authors: Komprda Tomas , Jůzl Miroslav , Matejovičová Milena , Piechowiczová Markéta , Popelková Vendula , Vymazalová Pavla , Nedomová Šárka , Levá Lenka
Published: May 2021

The objective of the present study was to increase by dietary means the long‐chain polyunsaturated fatty acid (LC‐PUFA) n‐3 content in selected meat products. Fatty acid (FA) composition, texture, sensory characteristics, and oxidative stability were determined in the Vienna sausages (V‐sausages) and Bologna‐type salami (B‐salami) produced from the meat of six pigs fed a standard feed (control, C) and six pigs fed a standard feed enriched with 8% of fish oil (F), respectively. The saturated FA content in the unheated FV and FB products was decreased (p < 0.05) by 24% and 39%, PUFA n‐6/n‐3 ratio improved (p < 0.001) from 13.9 to 2.8 and from 13.5 to 2.6, respectively. LC‐PUFA n‐3 content in the VF and BF products was 360 and 214 mg/100 g, which corresponds to 80% and 48% of the recommended daily intake. Interestingly, dietary fish oil decreased (p < 0.01) instrumentally the measured core hardness of the V‐sausages, but increased (p < 0.001) this texture characteristic in the B‐salami. Malondialdehyde content in the VF and BF products increased (p < 0.05) on average by 23% and the flavor of the heated FV sausages scored lower (p < 0.05) in comparison with the C‐counterparts.
Microbiome and osteoarthritis: New insights from animal and human studies
Authors: Tan Tze Chin , Chong Timothy Kit Yeong , Low Andrea Hsiu Ling , Leung Ying Ying
Published: May 2021

Osteoarthritis (OA) is a common cause of disability, especially among the elderly. With an ageing and increasingly obese population, OA will become more prevalent. Obesity and metabolic syndrome are risk factors for OA and have been implicated in its pathogenesis. The gut microbiome may shed light on this possible common pathogenesis. Recent animal and human studies have gained important insights into the relationship between OA, obesity, and the gut microbiome. Animal studies have demonstrated links between obesity and increased severity of OA and altered gut microbial DNA profile. Use of prebiotics and probiotics in animal trials provides proof‐of‐concept that interventional options to the gut microbiome can modulate the progression of OA favorably. Current evidence in human studies is limited. Shifts in gut microbial profile and reduced gut microbial diversity have been associated with people with OA, as well as blood and synovial fluid lipopolysaccharide endotoxemia. Linkages between microbiome dysbiosis and host responses may help in the understanding of OA pathogenesis and the discovery of therapeutic targets. This narrative review provides a summary of up‐to‐date animal and human studies on the gut microbiome and its link with OA.
Perioperative management of children with neuromuscular disorders based on a common protocol: A prospective, national study in Italy
Authors: Racca Fabrizio , Longhitano Yaroslava , Wolfler Andrea , Carfagna Fabio , Grattarola Claudia , Serio Paola , Sbaraglia Fabio , Amigoni Angela , Savron Fabio , Caramelli Fabio , Montagnini Luigi , Astuto Marinella , Gallo Elisa , Zanza Christian , Vaschetto Rosanna , Conti Giorgio
Published: May 2021

Background

Children with neuromuscular diseases (NMDs) often display respiratory muscle weakness which increases the risk of postoperative pulmonary complications (PPCs) after general anaesthesia. Non‐invasive ventilation (NIV) associated with mechanical insufflation–exsufflation (MI‐E) can reduce the incidence and severity of PPCs. The aim of this study was to report our experience with a shared perioperative protocol that consists in using NIV combined with MI‐E to improve the postoperative outcome of NMD children (IT‐NEUMA‐Ped).

Method

We conducted a multicentre, observational study on 167 consecutive paediatric patients with NMDs undergoing anaesthesia from December 2015 to December 2018 in a network of 13 Italian hospitals.

Results

We found that 89% of the 167 children (mean age 8 years old) were at high risk of PPCs, due to the presence of at least one respiratory risk factor. In particular, 51% of them had preoperative ventilatory support dependence. Only 14 (8%) patients developed PPCs, and only two patients needed tracheostomy. Average hospital length of stay (LOS) was 6 (2‐14) days. The study population was stratified according to preoperative respiratory devices dependency and invasiveness of the procedure. Patients with preoperative ventilatory support dependence showed significantly higher intensive care unit (ICU) admission rate and longer hospital LOS.

Conclusion

Disease severity seems to be more related to the outcome of this population than invasiveness of procedures. NIV combined with MI‐E can help in preventing and resolve PPCs.
Microglial MT1 activation inhibits LPS‐induced neuroinflammation via regulation of metabolic reprogramming
Authors: Gu Chao , Wang Fen , Zhang Yu‐Ting , Wei Shi‐Zhuang , Liu Jun‐Yi , Sun Hong‐Yang , Wang Guang‐Hui , Liu Chun‐Feng
Published: May 2021

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Although its pathogenesis remains unclear, a number of studies indicate that microglia‐mediated neuroinflammation makes a great contribution to the pathogenesis of PD. Melatonin receptor 1 (MT1) is widely expressed in glia cells and neurons in substantia nigra (SN). Neuronal MT1 is a neuroprotective factor, but it remains largely unknown whether dysfunction of microglial MT1 is involved in the PD pathogenesis. Here, we found that MT1 was reduced in microglia of SN in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced PD mouse model. Microglial MT1 activation dramatically inhibited lipopolysaccharide (LPS)‐induced neuroinflammation, whereas loss of microglial MT1 aggravated it. Metabolic reprogramming of microglia was found to contribute to the anti‐inflammatory effects of MT1 activation. LPS‐induced excessive aerobic glycolysis and impaired oxidative phosphorylation (OXPHOS) could be reversed by microglial MT1 activation. MT1 positively regulated pyruvate dehydrogenase alpha 1 (PDHA1) expression to enhance OXPHOS and suppress aerobic glycolysis. Furthermore, in LPS‐treated microglia, MT1 activation decreased the toxicity of conditioned media to the dopaminergic (DA) cell line MES23.5. Most importantly, the anti‐inflammatory effects of MT1 activation were observed in LPS‐stimulated mouse model. In general, our study demonstrates that MT1 activation inhibits LPS‐induced microglial activation through regulating its metabolic reprogramming, which provides a mechanistic insight for microglial MT1 in anti‐inflammation.
Accuracy of Consumer‐marketed smartphone‐paired alcohol breath testing devices: A laboratory validation study
Authors: Delgado Mucio Kit , Shofer Frances , Wetherill Reagan , Curtis Brenda , Hemmons Jessica , Spencer Evan , Branas Charles , Wiebe Douglas J. , Kranzler Henry R.
Published: May 2021

Background

Although alcohol breath testing devices that pair with smartphones are promoted for the prevention of alcohol‐impaired driving, their accuracy has not been established.

Methods

In a within‐subjects laboratory study, we administered weight‐based doses of ethanol to two groups of 10 healthy, moderate drinkers aiming to achieve a target peak blood alcohol concentration (BAC) of 0.10%. We obtained a peak phlebotomy BAC and measured breath alcohol concentration (BrAC) with a police‐grade device (Intoxilyzer 240) and two randomly ordered series of 3 consumer smartphone‐paired devices (6 total devices) with measurements every 20 min until the BrAC reached <0.02% on the police device. Ten participants tested the first 3 devices, and the other 10 participants tested the other 3 devices. We measured mean paired differences in BrAC with 95% confidence intervals between the police‐grade device and consumer devices.

Results

The enrolled sample (N = 20) included 11 females; 15 white, 3 Asian, and 2 Black participants; with a mean age of 27 and mean BMI of 24.6. Peak BACs ranged from 0.06–0.14%. All 7 devices underestimated BAC by >0.01%, though the BACtrack Mobile Pro and police‐grade device were consistently more accurate than the Drinkmate and Evoc. Compared with the police‐grade device measurements, the BACtrack Mobile Pro readings were consistently higher, the BACtrack Vio and Alcohoot measurements similar, and the Floome, Drinkmake, and Evoc consistently lower. The BACtrack Mobile Pro and Alcohoot were most sensitive in detecting BAC driving limit thresholds, while the Drinkmate and Evoc devices failed to detect BAC limit thresholds more than 50% of the time relative to the police‐grade device.

Conclusions

The accuracy of smartphone‐paired devices varied widely in this laboratory study of healthy participants. Although some devices are suitable for clinical and research purposes, others underestimated BAC, creating the potential to mislead intoxicated users into thinking that they are fit to drive.
Megafire causes persistent loss of an old‐forest species
Authors: Jones G. M. , Kramer H. A. , Berigan W. J. , Whitmore S. A. , Gutiérrez R. J. , Peery M. Z.
Published: May 2021

Climate change and a long legacy of fire suppression are leading to an increased prevalence of ‘mega‐disturbances’ such as drought and wildfire in terrestrial ecosystems. Evidence for the immediate effects of these novel disturbances on wildlife is accumulating, but little information exists on longer term impacts to species and ecosystems. We studied the occurrence dynamics of an iconic old‐forest species, the spotted owl (Strix occidentalis), on a long‐term study area in the Sierra Nevada, CA, USA from 1989 to 2020 to evaluate their multi‐scale population response following a 2014 megafire (the ‘King’ Fire) that affected a portion of our study area. We found that extensive severe fire within spotted owl sites resulted in both immediate site abandonment and prolonged lack of re‐colonization by owls six years post‐fire. Sites that experienced high pyrodiversity – a mosaic of burn severities – were more likely to persist after the fire, but this effect was only apparent at finer spatial scales. A potentially confounding factor, post‐fire salvage logging, did not explain variability in the probability of either owls persisting at sites or sites becoming re‐colonized; effects could be attributed only to severe fire extent and pyrodiversity. Our study demonstrates the prolonged effects of severe fire on the occupancy of this forest‐dependent species, suggesting that forest restoration that reduces megafires could benefit spotted owls. Our work emphasizes that long‐term monitoring can offer surprising learning opportunities and provide unparalleled value for understanding and addressing emerging environmental concerns.
Mutation spectrum of hereditary myopathies in Turkish patients and novel variants
Authors: Saat Hanife , Sahin Ibrahim
Published: May 2021

Hereditary myopathies are a heterogeneous disorder known to be associated with more than 100 genes. Although hereditary myopathy subgroups can be partially described with traditional methods such as muscle biopsy, next‐generation sequencing (NGS) is essential to reveal the disease's underlying genetic etiology and molecular mechanisms. In this study, we performed clinical exome sequencing or whole‐exome sequencing (CES/WES) in 20 unrelated Turkish patients. Thirteen pathogenic or likely pathogenic variants, including five novel variantswere detected in the 16 known hereditary myopathy genes. We achieved a high rate of diagnosis (65%) compared to previous studies. The most common condition noticed was limb‐girdle muscular dystrophy (LGMD), which should not be ignored in patients diagnosed with myopathy. CES or WES provides a certain molecular diagnosis from a broad perspective to demonstrate underlying genetic causes in heterogeneous disorders. Therefore, exome sequencing offers a higher and more complete diagnosis than the gene panel.
Bilateral diffuse uveal melanocytic proliferation with multifocal diffuse integumentary melanocytic proliferation paraneoplastic syndrome: A case report
Authors: Navarrete‐Dechent Cristián , Monnier Jilliana , Marghoob Nadeem G , Liopyris Konstantinos , Busam Klaus J , Francis Jasmine H , Marghoob Ashfaq A
Published: May 2021

Bilateral diffuse uveal melanocytic proliferation (B‐DUMP) is a rare paraneoplastic syndrome typically presenting with bilateral visual loss. B‐DUMP is associated with extraocular systemic malignancies with the most common being lung cancer in males and uro‐gynaecological cancer in females (mainly ovarian cancer). Cutaneous and/or mucosal involvement in patients with B‐DUMP has been reported but it is not well characterised. Herein, we present a female in her 70s with diagnosis of stage IV vaginal clear‐cell carcinoma and metastatic melanoma of unknown primary that developed progressive bilateral loss of visual acuity compatible with ‘B‐DUMP’. Simultaneously, she developed multifocal bilateral bluish‐greyish patches on the skin that were shown to have a proliferation of dermal melanocytes. We propose that the clinical and histopathologic cutaneous findings seen in patients with B‐DUMP be termed ‘diffuse integumentary melanocytic proliferation (DIMP)’.