bluuebunny/crossref_metadata_2025 huggingface dataset:
RHINOORBITAL CEREBRAL MYCOSIS: A CASE SERIES OF NON-MUCORALES IN COVID PATIENTS
Authors: Patil Rajashri , Ajagunde Jyoti , KHAN SAMEENA , KANNURI SRIRAM , Gandham Nageswari , Mukhida Sahjid
Published: February 2023

Introduction

Rhinocerebral mycoses are not only caused by Aspergillus spp. and Zygomycetes group but also can be associated with other rare species like Neurospora, Cladosporium, and Fusarium spp. post-COVID mucormycosis is caused by geriatric age group patients who have comorbidities like Diabetes Mellitus and/or Hypertension too. Clinical symptoms of COVID and Mucormycosis are a critical and relentless situation without a saving grace even with treatment.

Case series

We are reporting 3 patients with COVID-19 infection, who during the course of the treatment, developed rhino-orbital-cerebral mycosis including oral cavity involvement. Rhinocerebral mycosis along with Oral cavity involvement was diagnosed by radiological investigations and preliminary screening for fungal infection (KOH mount) in all three cases. Empirical treatment was started but patients were not responding to treatment. All patients succumbed even after debridement and Maxillectomy type crucial surgical procedures. Onculture, rare species of fungi were isolated in all cases which were identified with the help of a reference laboratory. Neurospora is considered nonpathogenic to humans. Cladosporium is a dematiaceous fungus found in soil in all climates, associated with disseminated or cerebral infections; and Fusarium though considered a saprophytic colonizer of skin and respiratory mucosa along with other bacteria and common cause of mycotic keratitis worldwide.

Conclusion

Immune system modifications due to COVID-19 with/without other risk factors result in fungal co-infections proving to be fatal for the patients. It is vital to be aware that COVID-19 patients, particularly those who are critically ill, may acquire secondary fungal infections and early detection is critical.
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new genetic hits
Authors: Alemany Silvia , Soler Artigas María , Cabana Judit , Fakhreddine Dana Salim , Llonga Natalia , Vilar-Ribó Laura , Rodríguez-Urrutia Amanda , Palacio Judit , González-Castro Ana María , Lobo Beatriz , Alonso-Cotoner Carmen , Simrén Magnus , Santos Javier , Ramos-Quiroga Josep Antoni , Ribasés Marta
Published: February 2023

Background

Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them.

Methods

We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date.

Results

IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant hits for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety.

Conclusions

These findings provide evidence of the polygenic architecture of IBS, identify novel hits for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.
MUC17 mutations and methylation are associated with poor prognosis in adult-type diffuse glioma patients
Authors: Machado Gabriel Cardoso , Ferrer Valéria Pereira
Published: February 2023

Diffuse gliomas are tumors that arise from glial or glial progenitor cells. They are currently classified as astrocytoma isocitrate dehydrogenase (IDH)-mutant or oligodendroglioma IDH-mutant, and 1p/19q-codeleted, both slower-growing tumors, or glioblastoma (GBM), a more aggressive tumor. Despite advances in the diagnosis and treatment of gliomas, the median survival time after diagnosis of GBM remains low, approximately 15 months, with a 5-year overall survival rate of only 6.8%. Therefore, new biomarkers that could support the earlier diagnosis and prognosis of these tumors would be of great value. MUC17, a membrane-bound mucin, has been identified as a potential biomarker for several tumors. However, the role of this mucin in adult gliomas has not yet been explored. Here, we show for the first time, in a retrospective study and byin silicoanalysis that MUC17 is one of the relevant mutant genes in adult gliomas. Moreover, that an increase in MUC17 methylation correlates with an increase in glioma malignancy grade. Patients with MUC17 mutations had a poorer prognosis than their wild-type counterparts in both GBM and non-GBM glioma cohorts. We also analyzed mutational profiles that correlated strongly with poor survival. Therefore, in this study, we present a new potential biomarker for further investigation, especially for the prognosis of adult diffuse gliomas.
MNRR1 activation by nitazoxanide abrogates lipopolysaccharide-induced preterm birth in mice
Authors: Purandare Neeraja , Gomez-Lopez Nardhy , Arenas-Hernandez Marcia , Galaz Jose , Romero Roberto , Xi Yue , Fribley Andrew , Grossman Lawrence I. , Aras Siddhesh
Published: February 2023

Intra-amniotic inflammation leading to preterm birth is one of the leading causes of neonatal morbidity and mortality. We recently found that the mitochondrial levels of MNRR1 (Mitochondrial Nuclear Retrograde, Regulator 1; also called CHCHD2, AAG10, or PARK22), an important bi-organellar regulator of cellular function, are reduced in the context of inflammation and that both genetic and pharmacological increase in MNRR1 levels can counter the inflammatory profile. We show here that nitazoxanide, a clinically-approved drug, is an activator of MNRR1 and prevents preterm birth in a well-characterized murine model caused by intra-amniotic lipopolysaccharide (LPS) injection.

Highlights

Nitazoxanide exerts anti-inflammatory functions via activation of MNRR1.

Oral administration of nitazoxanide prevents preterm birth in mouse model of intra-intraamniotic LPS-induced inflammation.
The omnitig framework can improve genome assembly contiguity in practice
Authors: Schmidt Sebastian , Toivonen Santeri , Medvedev Paul , Tomescu Alexandru I.
Published: February 2023

Despite the long history of genome assembly research, there remains a large gap between the theoretical and practical work. There is practical software with little theoretical underpinning of accuracy on one hand and theoretical algorithms which have not been adopted in practice on the other. In this paper we attempt to bridge the gap between theory and practice by showing how the theoretical safe-and-complete framework can be integrated into existing assemblers in order to improve contiguity. The optimal algorithm in this framework, called the omnitig algorithm, has not been used in practice due to its complexity and its lack of robustness to real data. Instead, we pursue a simplified notion of omnitigs, giving an efficient algorithm to compute them and demonstrating their safety under certain conditions. We modify two assemblers (wtdbg2 and Flye) by replacing their unitig algorithm with the simple omnitig algorithm. We test our modifications using real HiFi data from the Drosophilia melanogaster and the Caenorhabditis elegans genome. Our modified algorithms lead to a substantial improvement in alignment-based contiguity, with negligible computational costs and either no or a small increase in the number of misassemblies.
Skin microbiome attributes associate with biophysical skin aging
Authors: Zhou Wei , Fleming Elizabeth , Legendre Guylaine , Roux Lauriane , Latreille Julie , Gendronneau Gaëlle , Forestier Sandra , Oh Julia
Published: February 2023

Two major arms of skin aging are changes in the skin’s biophysical conditions and alterations in the skin microbiome. This work partitioned both arms to study their interaction in detail. Leveraging the resolution provided by shotgun metagenomics, we explored how skin microbial species, strains, and gene content interact with the biophysical traits of the skin during aging. With a dataset well-controlled for confounding factors, we found that skin biophysical traits, especially the collagen diffusion coefficient, are associated with the composition and the functional potential of the skin microbiome, including the abundance of bacterial strains found in nosocomial infections and the abundance of antibiotic resistance genes. Our findings reveal important associations between skin biophysical features and aging-related changes in the skin microbiome and generate testable hypotheses for the mechanisms of such associations.
Plasma and Liver Lipids are Differentially Regulated After Cannabinoid Treatments in Male and Female Mice
Authors: Johnson Clare T , Bosquez-Berger Taryn , Bentz Hannah R , de Abreu Gabriel H Dias , Mackie Ken , Lu Hui-Chen , Bradshaw Heather B
Published: February 2023

Cannabinoids (CBs) have sex-dependent behavioral and physiological effects and modulate lipids across the body. To understand how some of these sex differences may be due to differences how both phyto- and endocannabinoids are regulated in the liver and plasma, male and female CD1 mice were administered 10 mg/kgi.p. of cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), or THC+CBD then core blood and liver tissue were collected after 2 hours. Lipids were extracted from both liver and plasma, and samples were screened via HPLC/MS/MS for Δ9-tetrahydrocannabinol (THC), metabolites 11-OH-THC and 11-COOH-THC, cannabidiol (CBD), metabolites 7-OH-CBD and 7-COOH-CBD, ~70 endolipids including the endocannabinoids,N-arachidonoyl ethanolamine (Anandamide; AEA) and 2-sn-arachidonoyl glycerol (2-AG). Structural analogs to AEA (e.g. lipoamino acids, lipoamines) and 2-acyl glycerols) as well as free fatty acids and prostaglandins were also evaluated. Results show that at 2 hours post injection levels of CBs demonstrate key differences between males and females in both plasma and liver, and that these differences vary when co-administered as opposed to administered alone. Illustrating a link between liver and plasma, directionality of CB differences are similar between the two tissue types as a function of both sex and CB treatment. By contrast, endolipids had very different profiles as a function of sex, CB administration, and tissue type. Importantly, there are baseline differences between male and female mice in endocannabinoids and related lipids, which likely impact how CB administration modulates these endolipids. These data illustrate the complexity of outcomes of CB treatment between males and females on circulating CBs and endolipids and highlight the need to consider these factors when evaluating efficacy of CB drug treatments or usage.
Characterizing transcriptomic responses to sediment stress across location and morphology in reef-building corals
Authors: Ashey Jill , McKelvie Hailey , Freeman John D. , Shpilker Polina , Zane Lauren H. , Becker-Polinski Danielle M. , Cowen Lenore , Richmond Robert H. , Paul Valérie , Seneca Francois , Putnam Hollie M.
Published: February 2023

Anthropogenic activities increase sediment suspended in the water column and deposition on reefs can be largely dependent on colony morphology. Massive and plating corals have a high capacity to trap sediments, and active removal mechanisms can be energetically costly. Branching corals trap less sediment, but are more susceptible to light limitation caused by suspended sediment. Despite deleterious effects of sediments on corals, few studies have examined the molecular response of corals with different morphological characteristics to sediment stress. To address this knowledge gap, this study assessed the transcriptomic responses of branching and massive corals in Florida and Hawai□i to varying levels of sediment exposure. Gene expression analysis revealed a molecular responsiveness to sediments across species and sites. Differentially Gene Expression (DEG) followed by Gene Ontology (GO) enrichment analysis identified that branching corals had the largest transcriptomic response to sediments, in developmental processes and metabolism, while significantly enriched GO terms were highly variable between massive corals, despite similar morphologies. Comparison of DEGs within orthogroups revealed that while all corals had DEGs in response to sediment, there was not a concerted gene set response by morphology or location. These findings illuminate the species specificity and genetic basis underlying coral susceptibility to sediments.
BZINB model-based pathway analysis and module identification facilitates integration of microbiome and metabolome data
Authors: Lin Bridget , Cho Hunyong , Liu Chuwen , Roach Jeff , Ribeiro Apoena Aguiar , Divaris Kimon , Wu Di
Published: February 2023

Integration of multi-omics data is a challenging but necessary step to advance our understanding of the biology underlying human health and disease processes. To date, investigations seeking to integrate multi-omics (e.g., microbiome and metabolome) employ simple correlation-based network analyses; however, these methods are not always well-suited for microbiome analyses because they do not accommodate the excess zeros typically present in these data. In this paper, we introduce a bivariate zero-inflated negative binomial (BZINB) model-based network and module analysis method that addresses this limitation and improves microbiome-metabolome correlation-based model fitting by accommodating excess zeros. We use real and simulated data based on a multi-omics study of childhood oral health (ZOE 2.0; investigating early childhood dental disease, ECC) and find that the accuracy of the BZINB model-based correlation method is superior compared to Spearman’s rank and Pearson correlations in terms of approximating the underlying relationships between microbial taxa and metabolites. The new method, BZINB-iMMPath facilitates the construction of metabolite-species and species-species correlation networks using BZINB and identifies modules of (i.e., correlated) species by combining BZINB and similarity-based clustering. Perturbations in correlation networks and modules can be efficiently tested between groups (i.e., healthy and diseased study participants). Upon application of the new method in the ZOE 2.0 study microbiome-metabolome data, we identify that several biologically-relevant correlations of ECC-associated microbial taxa with carbohydrate metabolites differ between healthy and dental caries-affected participants. In sum, we find that the BZINB model is a useful alternative to Spearman or Pearson correlations for estimating the underlying correlation of zero-inflated bivariate count data and thus is suitable for integrative analyses of multi-omics data such as those encountered in microbiome and metabolome studies.
BIRDMAn: A Bayesian differential abundance framework that enables robust inference of host-microbe associations
Authors: Rahman Gibraan , Morton James T. , Martino Cameron , Sepich-Poore Gregory D. , Allaband Celeste , Guccione Caitlin , Chen Yang , Hakim Daniel , Estaki Mehrbod , Knight Rob
Published: February 2023

Quantifying the differential abundance (DA) of specific taxa among experimental groups in microbiome studies is challenging due to data characteristics (e.g., compositionality, sparsity) and specific study designs (e.g., repeated measures, meta-analysis, cross-over). Here we present BIRDMAn (BayesianInferentialRegression forDifferentialMicrobiomeAnalysis), a flexible DA method that can account for microbiome data characteristics and diverse experimental designs. Simulations show that BIRDMAn models are robust to uneven sequencing depth and provide a >20-fold improvement in statistical power over existing methods. We then use BIRDMAn to identify antibiotic-mediated perturbations undetected by other DA methods due to subject-level heterogeneity. Finally, we demonstrate how BIRDMAn can construct state-of-the-art cancer-type classifiers using The Cancer Genome Atlas (TCGA) dataset, with substantial accuracy improvements over random forests and existing DA tools across multiple sequencing centers. Collectively, BIRDMAn extracts more informative biological signals while accounting for study-specific experimental conditions than existing approaches.
Effects of IL2/anti-IL2 antibody complex on chikungunya virus-induced arthritis in a mouse model
Authors: Tritsch Sarah R. , Porzucek Abigail J. , Schwartz Arnold M. , Proctor Abigale M. , Amdur Richard , Latham Patricia S. , Simon Gary L. , Mores Christopher N. , Chang Aileen Y.
Published: February 2023

Chikungunya virus (CHIKV) is characterized by disabling joint pain that can cause persistent arthritis in approximately one-fourth of patients. Currently, no standard treatments are available for chronic CHIKV arthritis. Our preliminary data suggest that decreases in interleukin-2 (IL2) levels and regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Low-dose IL2-based therapies for autoimmune diseases have been shown to up-regulate Tregs, and complexing IL2 with anti-IL2 antibodies can prolong the half-life of IL2. A mouse model for post-CHIKV arthritis was used to test the effects of IL-2, an anti-IL2 monoclonal antibody (mAb), and the complex on tarsal joint inflammation, peripheral IL2 levels, Tregs, effector (Teff) T cells, and histological disease scoring. The complex treatment resulted in the highest levels of IL2 and Tregs, but also increased Teffs, and therefore did not significantly reduce inflammation or disease scores. However, the antibody group, which had moderately increased levels of IL2 and activated Tregs, resulted in a decreased average disease score. These results suggest the IL2/anti-IL2 complex stimulates both Tregs and Teffs in post-CHIKV arthritis, while the anti-IL2 mAb increases IL2 availability enough to shift the immune environment towards a tolerogenic one.
Organism-Wide Analysis of Sepsis Reveals Mechanisms of Systemic Inflammation
Authors: Takahama Michihiro , Patil Ashwini , Johnson Katherine , Cipurko Denis , Miki Yoshimi , Taketomi Yoshitaka , Carbonetto Peter , Plaster Madison , Richey Gabriella , Pandey Surya , Cheronis Katerina , Ueda Tatsuki , Gruenbaum Adam , Dudek Steven M. , Stephens Matthew , Murakami Makoto , Chevrier Nicolas
Published: February 2023

Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the impact of sepsis across organs of the body is rudimentary. Here, using mouse models of sepsis, we generate a dynamic, organism-wide map of the pathogenesis of the disease, revealing the spatiotemporal patterns of the effects of sepsis across tissues. These data revealed two interorgan mechanisms key in sepsis. First, we discover a simplifying principle in the systemic behavior of the cytokine network during sepsis, whereby a hierarchical cytokine circuit arising from the pairwise effects of TNF plus IL-18, IFN-γ, or IL-1β explains half of all the cellular effects of sepsis on 195 cell types across 9 organs. Second, we find that the secreted phospholipase PLA2G5 mediates hemolysis in blood, contributing to organ failure during sepsis. These results provide fundamental insights to help build a unifying mechanistic framework for the pathophysiological effects of sepsis on the body.
Ecological and life-history traits and their relationship with West Nile virus and Saint Louis Encephalitis virus exposure risk
Authors: Giayetto O. , Mansilla A.P. , Nazar F.N. , Diaz A.
Published: February 2023

Host life-history traits can influence host-vector encounter rates, and so differentially determine the exposure risk of bird species. This modulation of host-virus encounters’ dynamics is especially important when facing “generalist” arboviruses like West Nile virus (WNV) and Saint Louis Encephalitis virus (SLEV). Using prevalence data collected by our laboratory since 2004, we tested several hypothesis that included birds’ ecological and life-history traits to determine which traits were better predictors of birds’ exposure risk to these arboviruses. By means of information-theoretic procedures and generalized mixed linear models, we observed that body mass was an important trait when predicting birds’ exposure risk to WNV and SLEV and migratory status significantly influenced birds’ exposure risk only to WNV. Our study highlights important traits to consider when studying the transmission system of these arboviruses, being useful to focus resources when characterizing viral transmission networks and discuss the repercussions of these traits over birds’ immune function throughout the pace of life syndrome and trade-offs theory.
Premature Aging and Reduced Cancer Incidence Associated with Near-Complete Body-WideMycInactivation
Authors: Wang Huabo , Lu Jie , Stevens Taylor , Roberts Alexander , Mandel Jordan , Avula Raghunandan , Ma Bingwei , Wu Yijen , Wang Jinglin , Van’t Land Clinton , Finkel Toren , Vockley Jerry E. , Airik Merlin , Airik Rannar , Muzumdar Radhika , Gong Zhenwei , Torbenson Michel S. , Prochownik Edward V.
Published: February 2023

MYCproto-oncogene dysregulation alters metabolism, translation and other functions in ways that support tumor induction and maintenance. AlthoughMyc+/-mice are healthier and longer-lived than control mice, the long-term ramifications of more completeMycloss remain unknown. We now describe the chronic consequences of body-wideMycinactivation initiated postnatally. “MycKO” mice acquire numerous features of premature aging including altered body composition and habitus, metabolic dysfunction, hepatic steatosis and the dysregulation of numerous gene sets involved in functions that normally deteriorate with aging. Yet,MycKO mice have extended life spans that correlate with a 3-4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also down-regulate Myc and gradually deregulate many of the same Myc target gene sets that are dysregulated inMycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc and its target genes and can be genetically separated.
MicroRNA-221/222-expression in HSC and MPP safeguards their quiescence and multipotency by downregulating stress-independent and dependent expression of IEG and of several myelo/granulopoiesis-enhancing target genes
Authors: Jani Peter K. , Petkau Georg , Kawano Yohei , Klemm Uwe , Guerra Gabriela Maria , Heinz Gitta Anne , Heinrich Frederik , Durek Pawel , Mashreghi Mir-Farzin , Melchers Fritz
Published: February 2023

The microRNA cluster-221/222 is expressed in hematopoietic stem cells (HSC) and multipotent progenitors (MPP). To study its function in hematopoiesis, we generated mice, in which this cluster is selectively deleted by Vav-cre in HSC and, thus, in all hematopoietic cells. Fluorescence-activated cell sorting analyses of the lineage-negative HSC and MPP compartments in bone marrow at unperturbed, steady state hematopoiesis detect strong activation of HSC to MPP, as well as increased granulocytes in the periphery, induced by miR-221/222-deficiency. Short-term social stress on mice also activates HSC to MPP, but the time of stress is too short to detect further increases in granulocyte numbers. Single cell deep mRNA sequencing identifies Fos as direct, and Jun as well as six other immediate early genes (IEG) as indirect targets of miR-221/222 at unperturbed hematopoiesis. Three of these IEG - Klf6, Nr4a1 and Zfp36 - have previously been found to influence myelo/granulopoiesis. Short stress induces higher levels of the same, and an even larger number of IEGs, now also in MPP, indicating, that stress and miR-221/222 both activate HSC to MPP by IEG upregulation in perturbed hematopoiesis. Furthermore, combined stress and miR-221/222-deficiency rapidly increase numbers of myelo/granulocyte progenitors (MEP, GMP) in bone marrow. Additional indirect miR-221/222-targets become detectable in MPP, of which H3f3b has previously been found to influence myelopoiesis. In serial transplantations, miR-221/222-deficient HSC retain their capacity to home to, and become resident in bone marrow, but they loose their lymphopoietic capacities, thus their multipotency. Our results suggest, that miR-221/222-expression in HSC and MPP safeguards their quiescence and multipotency by downregulating the expression of IEG and of myelo/granulopoiesis-enhancing target genes. Since miR-221/222 is also expressed in human HSC and MPP, its expression should improve clinical settings of human bone marrow transplantations.
HLAin isolated REM sleep behavior disorder and Lewy body dementia
Authors: Yu Eric , Krohn Lynne , Ruskey Jennifer A. , Asayesh Farnaz , Spiegelman Dan , Shah Zalak , Chia Ruth , Arnulf Isabelle , Hu Michele T.M. , Montplaisir Jacques Y. , Gagnon Jean-François , Desautels Alex , Dauvilliers Yves , Gigli Gian Luigi , Valente Mariarosaria , Janes Francesco , Bernardini Andrea , Högl Birgit , Stefani Ambra , Ibrahim Abubaker , Heidbreder Anna , Sonka Karel , Dusek Petr , Kemlink David , Oertel Wolfgang , Janzen Annette , Plazzi Giuseppe , Antelmi Elena , Figorilli Michela , Puligheddu Monica , Mollenhauer Brit , Trenkwalder Claudia , Sixel-Döring Friederike , Cochen De Cock Valérie , Ferini-Strambi Luigi , Dijkstra Femke , Viaene Mineke , Abril Beatriz , Boeve Bradley F. , Rouleau Guy A. , Postuma Ronald B. , Scholz Sonja W. ,   the International LBD Genomics Consortium, Gan-Or Ziv
Published: February 2023

Background and Objectives

Isolated/idiopathic REM sleep behavior disorder (iRBD) and Lewy body dementia (LBD) are synucleinopathies that have partial genetic overlap with Parkinson’s disease (PD). Previous studies have shown that neuroinflammation plays a substantial role in these disorders. In PD, specific residues of the human leukocyte antigen (HLA) were suggested to be associated with a protective effect. This study examined whether theHLAlocus plays a similar role in iRBD, LBD and PD.

Methods

We performed HLA imputation on iRBD genotyping data (1,072 patients and 9,505 controls) and LBD whole-genome sequencing (2,604 patients and 4,032 controls) using the multi-ethnic HLA reference panel v2 from the Michigan Imputation Server. Using logistic regression, we tested the association of HLA alleles, amino acids and haplotypes with disease susceptibility. We included age, sex and the top 10 principal components as covariates. We also performed an omnibus test to examine which HLA residue positions explain the most variance.

Results

In iRBD,HLA-DRB1*11:01 was the only allele passing FDR correction (OR=1.57, 95% CI=1.27-1.93,p=2.70e-05). We also discovered associations between iRBD andHLA-DRB170D (OR=1.26, 95%CI=1.12-1.41,p=8.76e-05), 70Q (OR=0.81, 95% CI=0.72-0.91,p=3.65e-04) and 71R (OR=1.21, 95% CI=1.08-1.35,p=1.35e-03). InHLA-DRB1, position 71 (pomnibus=0.00102) and 70 (pomnibus=0.00125) were associated with iRBD. We found no association in LBD.

Discussion

This study identified an association betweenHLA-DRB111:01 and iRBD, distinct from the previously reported association in PD. Therefore, theHLAlocus may play different roles across synucleinopathies. Additional studies are required better to understand HLA’s role in iRBD and LBD.
Road networks to explore COVID-19 infection
Authors: Uddin Shahadat , Khan Arif , Lu Haohui , Zhou Fangyu , Karim Shakir , Hajati Farshid , Moni Mohammad Ali
Published: February 2023

COVID-19 pandemic triggered an unprecedented level of restrictive measures globally. Most countries resorted to lockdowns at some point to buy the much-needed time for flattening the curve and scaling up vaccination and treatment capacity. Although lockdowns, social distancing and business closures generally slowed down the case growth, there is a growing concern about the social, economic and psychological impact of these restrictions, especially on the disadvantaged and poorer part of society. While we are all in this together, these segments are often taking the heavier toll of the pandemic and facing harsher restrictions or getting blamed for community transmission. This study tries to explore this perspective using quantitative analysis and network theory. The research is set in the context of the latest delta and omicron outbreaks in the Greater Sydney area, Australia, during late 2021. We first try to model how the local road networks between the neighbouring suburbs (i.e., neighbourhood measure) and current infection count affect the case growth and how they differ between delta and omicron variants. We use a geographic information system, population and infection data to measure - road connections, mobility and transmission probability across the suburbs. We then looked at three socio-demographic variables – age, education and income and explored how they moderate independent and dependent variables (infection rates and neighbourhood measures). The result shows strong model performance to predict infection rate based on neighbourhood road connection. However, apart from age in the delta variant’s context, the other two variables – income and education level do not seem to moderate the relation between infection rate and neighbourhood measure. The results indicate that suburbs with a more socio- economically disadvantaged population do not necessarily contribute to more community transmission. The study findings could be potentially helpful for stakeholders in tailoring any health decision for future pandemics.
Standardization of a High-Fidelity Postpartum Hemorrhage Simulation Scenario Across Two Geographically Separated Campuses
Authors: Khalepai Miriam S. , Sturgeon Shannon , Done Andrea , Yates Tyler , Wardle Mark , Zapata Isain , Carter Susan
Published: February 2023

Introduction

The utilization of high fidelity simulations across medical school campuses has grown in recent years as simulation is a useful tool in allowing students to practice real life scenarios in a safe space, as well as providing exposure to rarer cases in medicine. This study evaluated second and third-year medical students’ recognition and management of a postpartum hemorrhage (PPH) due to a retained placenta in SimMom®. The objective was to describe the methods and procedures used in PPH simulation to educate these students across two geographically separated medical school campuses. It became apparent that there is a need to standardize medical simulation to maintain the quality of medical education.

Methods

A case-scenario simulation with retained tissue had a run-time of 10 minutes. Times were marked when students identified the retained placental tissue was the cause of hemorrhage and when students extracted the fragment. A debrief with faculty followed the scenario regarding performance and education about the “4 T’s”of post-partum hemorrhage differential diagnosis (Tone, Trauma, Tissue, Thrombin), and the students’ feelings towards the simulation were evaluated with a post simulation survey.

Results

Despite efforts to maintain consistent simulations between the two campuses, there was a significant difference of timing between the two campuses to successful completion of the simulation, as well as in the number of students that did not successfully complete the goals of the simulation. However, the post-simulation survey did show that students on both campuses found value in participating in the simulation.

Discussion

The performance across the two campuses was statistically different, which illustrates a need to standardize simulation education experiences across medical school campuses. However, this protocol was an effective way to educate students and allow students to have hands-on experience in diagnosing and treating a rare but deadly complication of childbirth. This initial study may facilitate expansion on this particular, topic, as well as suggest more simulation education delivery within the medical school curriculum.
Selective pressure by rifampicin modulates mutation rates and evolutionary trajectories of mycobacterial genomes
Authors: Cebrián-Sastre E. , Chiner-Oms A. , Torres-Pérez R. , Comas I. , Oliveros J.C. , Blázquez J. , Castañeda-García A.
Published: February 2023

Resistance to the frontline antibiotic rifampicin constitutes a challenge to the treatment and control of tuberculosis. Here, we analyzed the mutational landscape ofMycobacterium smegmatisduring long-term evolution with increasing concentrations of rifampicin, using a mutation accumulation assay combined with whole genome sequencing. Antibiotic treatment enhanced the acquisition of mutations, doubling the genome-wide mutation rate of the wild type cells. While antibiotic exposure led to extinction of almost all wild type lines, the hypermutable phenotype of the ΔnucSstrain (noncanonical mismatch repair deficient) provided an efficient response to the antibiotic, leading to high rates of survival. This adaptative advantage resulted in the emergence of higher levels of rifampicin resistance, an accelerated acquisition of drug resistance mutations inrpoB(β RNA polymerase) and a wider diversity of evolutionary pathways that led to drug resistance. Lastly, this approach revealed a subset of adaptive genes under positive selection with rifampicin that were able to drive novel rifampicin resistance mechanisms.
Genetic profiling ofPlasmodium ovale wallikerirelapses with microsatellite markers and whole-genome sequencing
Authors: Joste Valentin , Colard-Itté Emma , Guillochon Émilie , Ariey Frédéric , Coppée Romain , Clain Jérôme , Houzé Sandrine
Published: February 2023

LikePlasmodium vivax, bothPlasmodium ovale curtisiandPlasmodium ovale wallikerihave the ability to cause relapse in humans, defined as recurring asexual parasitaemia originating from liver dormant forms subsequent to a primary infection. Here, we investigated relapse patterns inP. ovale wallikeriinfections from a cohort of travelers who were exposed to the parasite in Sub-Saharan Africa and then experienced relapses after their return to France. Using a novel set of eight highly polymorphic microsatellite markers, we genotyped 15P. ovale wallikerirelapses. For most relapses, the paired primary and relapse infections were highly genetically related (with 12 being homologous), an observation that was confirmed by whole-genome sequencing for the four relapses we further studied. This is, to our knowledge, the first genetic evidence of relapses inP. ovalespp.
Multi-input drug-controlled switches of mammalian gene expression based on engineered nuclear hormone receptors
Authors: Kretschmer Simon , Perry Nicholas , Zhang Yang , Kortemme Tanja
Published: February 2023

Protein-based switches that respond to different inputs to regulate cellular outputs, such as gene expression, are central to synthetic biology. For increased controllability, multi-input switches that integrate several cooperating and competing signals for the regulation of a shared output are of particular interest. The nuclear hormone receptor (NHR) superfamily offers promising starting points for engineering multi-input-controlled responses to clinically approved drugs. Starting from the VgEcR/RXR pair, we demonstrate that novel (multi-)drug regulation can be achieved by exchange of the ecdysone receptor (EcR) ligand binding domain (LBD) for other human NHR-derived LBDs. For responses activated to saturation by an agonist for the first LBD, we show that outputs can be boosted by an agonist targeting the second LBD. In combination with an antagonist, output levels are tunable by up to three simultaneously present small-molecule drugs. Such high-level control validates NHRs as a versatile, engineerable platform for programming multi-drug-controlled responses.
Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses
Authors: Zvornicanin Sarah N. , Shaqra Ala M. , Huang Qiu Yu J. , Ornelas Elizabeth , Moghe Mallika , Knapp Mark , Moquin Stephanie , Dovala Dustin , Schiffer Celia A. , Yilmaz Nese Kurt
Published: February 2023

With the spread of SARS-CoV-2 throughout the globe to cause the COVID-19 pandemic, the threat of zoonotic transmissions of coronaviruses (CoV) has become even more evident. As human infections have been caused by alpha- and beta-CoVs, structural characterization and inhibitor design mostly focused on these two genera. However, viruses from the delta and gamma genera also infect mammals and pose potential zoonotic transmission threat. Here, we determined the inhibitor-bound crystal structures of the main protease (Mpro) from the delta-CoV porcine HKU15 and gamma-CoV SW1 from beluga whale. Comparison with the apo structure of SW1 Mpro, which we also present here, enabled identifying structural arrangements upon inhibitor binding at the active site. The binding modes and interactions of two covalent inhibitors, PF-00835231 (lufotrelvir) bound to HKU15 and GC376 bound to SW1 Mpro, reveal features that may be leveraged to target diverse coronaviruses and toward structure-based design of pan-CoV inhibitors.
Revisiting “Cool Japan” in country-of-origin research: a commentary and future research directions
Authors: Miyamoto Junji , Shimizu Akira , Hayashi Junya , Cheah Isaac
Published: February 2023

Purpose

This commentary and conceptual paper is aimed at investigating marketing perceptions of the country-of-origin (COO) perspectives, and emphasis is placed on the “Cool Japan” concept.

Design/methodology/approach

A review of research on COO and the concept of “Cool Japan” was conducted, including commentary of previous relevant theoretical frameworks.

Findings

The evidence has shown that the brand images of various COOs is dependent on their cultural exports. In the case of Japan, the “Cool Japan” initiative, which initiated the creation and dissemination of Japanese cultural contents such as anime, games and art, has led to tremendous and sustainable economic growth in Japan till date.

Research limitations/implications

As previous studies on COO are wide-ranging, they are not exhaustively presented in this paper. However, the importance of considering not only animosity, which has traditionally been taken into account, but also the coolness aspect is suggested.

Practical implications

This paper shows that “coolness” is an important concept when nations or regions consider their branding strategies and an integrated approach is needed.

Originality/value

This paper extends previous COO research and adds coolness to the traditional animosity. It also considers these in comparison across countries and goes as far as the need to propose a new scale. Conceptual findings from this paper would therefore provide future directions for advancing COO research Cool Japan.
The effect of visibility of country of origin labelling on consumers' fresh meat preferences
Authors: Holdershaw Judith , Konopka Roman
Published: February 2023

Purpose

The intent of displaying country of origin (COO) detail on food packaging is to inform consumers' purchase decisions. Of interest is whether how the COO information is displayed is important to consumers. This study examines the importance of attributes associated with the visibility of COO labelling in the context of packaged fresh meat.

Design/methodology/approach

Best–worst Scaling (BWS) is used to investigate consumers' preferences for label attributes. Treatments involved two countries (New Zealand and Australia), four font sizes and two placement positionings of COO information on the packaging.

Findings

First, the study indicated consumers' preference for domestic than imported meat. This finding supports the intent of COO labelling, which is to inform product selection. Second, the authors ascertained that how COO information is displayed in terms of visibility is important also. Consumers indicated a preference for larger than smaller font size. However, where the COO detail is located on the packaging is of less importance.

Originality/value

While regulations increasingly apply to provision of COO labelling of fresh foods, surprisingly little research has considered consumers' preferences for labelling practice. The study’s findings have implications for public policy decisions and contribute guidelines for retail practice.
Hotel branding and COVID-19 managed isolation and quarantine (MIQ) facilities: consequences and lessons learnt
Authors: Wisker Zazli Lily , Morgan Zoe
Published: February 2023

Purpose

This study aims to understand the consequences of the decision by some hotels during the COVID-19 pandemic to contract their accommodation to be used as managed isolation and quarantine (MIQ) facilities. Specifically, this study aims to understand the impact of this decision in terms of corporate brand image, brand loyalty, negative word of mouth (NWOM) and purchase intention.

Design/methodology/approach

Data were collected through a quasi-experimental research design and was analysed through a t-test.

Findings

This study hypothesises that the use of a hotel brand as a COVID-19 MIQ facility will be detrimental to its corporate brand image because of the expectation disconfirmation theory and attribution theory, thus reducing brand loyalty and increasing NWOM. The result supports the hypotheses.

Research limitations/implications

This study does not factor in a time period for the observed effects. While the results indicate that hotels used for MIQ purposes have reduced corporate brand image, brand loyalty and purchase intention, this study does not establish the duration of the damage.

Originality/value

This study provides insight into consumers' perceptions of hotel brands that served as COVID-19 MIQ facilities. The originality lies in the discovery that the decision by hoteliers to opt to use their facilities for COVID-19 MIQ facilities was detrimental to corporate brand image and brand loyalty.
A system modeling approach to simulate post-COVID-19 student intention to use online learning platforms
Authors: Vatsa Ruchika , Bhatnagar Purnima
Published: February 2023

Purpose

The purpose of this paper is to apply systems modeling to explore the usability of the online learning platform in the future compared to its usefulness during the pandemic era.

Design/methodology/approach

The applied systems research methodology has been used to develop a stock-flow model encompassing enablers and constraints for learning platform usage from the primary data collected through a survey of 163 respondents.

Findings

The model simulation observed promising trends over one year for online learning platforms provided the challenges are reduced in seven to eight months. Challenges linked to the Internet and interaction need must be removed for future usage.

Research limitations/implications

The results of the survey and model simulation suggest actions for product planning and development of online learning platforms based on customer insights. Product customization and feature enhancement will be required for the continued usability of online learning products. Actions for Internet service providers are to capture the online learner market by removing issues of Internet access bandwidth, and quality of content. Also, there should be sufficient teacher–student interaction in the online learning mode.

Originality/value

This is an original study using systems modeling to evaluate factors contributing to students' intention to use online learning conducted at Dayalbagh Educational Institute (Deemed to be University) Dayalbagh Agra, UP, India, 282005.
Defect reduction using DMAIC and Lean Six Sigma: a case study in a manufacturing car parts supplier
Authors: Condé Giovanni Cláudio Pinto , Oprime Pedro Carlos , Pimenta Marcio Lopes , Sordan Juliano Endrigo , Bueno Carlos Renato
Published: February 2023

Purpose

Competitive pressures force companies to seek solutions to eliminate wastes while improving product quality. Lean Six Sigma (LSS) has been considered one of the most effective approaches for business transformation. This article aims to present an empirical case study where LSS and Define, Measure–Analyze–Improve–Control (DMAIC) methodologies are applied to reduce defects in a car parts manufacturer.

Design/methodology/approach

The study follows the DMAIC methodology. Design of experiments and hypothesis testing were applied in a single case study.

Findings

The main defects and the main factors that cause defective parts were indicated for die-casting and machining processes. Solutions implemented reduced the defect incidence from a chronically high level to an acceptable one. The sigma level rose from 3.4 s to 4 s sustainably.

Research limitations/implications

The study is limited to a single case study, without intention of generalizing the results to other types of industries.

Practical implications

This paper can be a useful guide of how to use DMAIC Six Sigma approach to defect reduction and can be applied in many sectors.

Social implications

This study offers the knowledge on how to apply the Six Sigma DMAIC methodology, reducing the dependence on specialization courses.

Originality/value

This study describes in detail the process used in a structured improvement exercise including sigma-level calculation, factorial experiments and hypothesis tests – a set of techniques still poorly combined in the literature.
Self-regulation versus government oversight: audit fees research
Authors: Agana Joseph Akadeagre , Alon Anna , Zamore Stephen
Published: February 2023

Purpose

With Sarbanes–Oxley Act of 2002 (SOX), the self-regulation of the auditing profession was replaced with standard setting and oversight by the government. The authors focus on the audit fees literature to examine how this change impacted research trends over time and shaped different aspects of audits.

Design/methodology/approach

The authors utilized bibliometric and content analysis to identify research themes pre- and post-SOX.

Findings

The change in regulation contributed to an increased focus on clients and continued interest in engagement characteristics as added requirements emphasized the client's governance structure, the auditor's tenure and the type of services provided.

Originality/value

The prominent issue that emerged is how deficiencies in the audit processes and in the client's internal controls are translated into audit fees. The authors discuss regulatory initiatives pursued in other jurisdictions, including mandatory rotation of firms, joint audits and further limitations on non-audit services, as intended and unintended consequences of these requirements warrant further examination.