bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study and multi-trait analysis of opioid use disorder identifies novel associations in 639,709 individuals of European and African ancestry
Authors: Deak Joseph D. , Zhou Hang , Galimberti Marco , Levey Daniel , Wendt Frank R. , Sanchez-Roige Sandra , Hatoum Alexander , Johnson Emma C. , Nunez Yaira Z. , Demontis Ditte , Børglum Anders D. , Rajagopal Veera M. , Jennings Mariela V. , Kember Rachel L. , Justice Amy C. , Edenberg Howard J. , Agrawal Arpana , Polimanti Renato , Kranzler Henry R. , Gelernter Joel
Published: December 2021

Background

Despite the large toll of opioid use disorder (OUD), genome-wide association studies (GWAS) of OUD to date have yielded few susceptibility loci.

Methods

We performed a large-scale GWAS of OUD in individuals of European (EUR) and African (AFR) ancestry, optimizing genetic informativeness by performing MTAG (Multi-trait analysis of GWAS) with genetically correlated substance use disorders (SUDs). Meta-analysis included seven cohorts: the Million Veteran Program (MVP), Psychiatric Genomics Consortium (PGC), iPSYCH, FinnGen, Partners Biobank, BioVU, and Yale-Penn 3, resulting in a total N=639,709 (Ncases=20,858) across ancestries. OUD cases were defined as having lifetime OUD diagnosis, and controls as anyone not known to meet OUD criteria. We estimated SNP-heritability (h2SNP) and genetic correlations (rg). Based on genetic correlation, we performed MTAG on OUD, alcohol use disorder (AUD), and cannabis use disorder (CanUD).

Results

The EUR meta-analysis identified three genome-wide significant (GWS; p≤5×10−8) lead SNPs—one at FURIN (rs11372849; p=9.54×10−10) and two OPRM1 variants (rs1799971, p=4.92×10−09 ; rs79704991, p=1.37×10−08; r2=0.02). Rs1799971 (p=4.91×10−08) and another OPRM1 variant (rs9478500; p=1.95×10−8; r2=0.03) were identified in the cross-ancestry meta-analysis. Estimated h2SNP was 12.75%, with strong rg with CanUD (rg =0.82; p=1.14×10−47) and AUD (rg=0.77; p=6.36×10−78). The OUD-MTAG resulted in 18 GWS loci, some of which map to genes or gene regions that have previously been associated with psychiatric or addiction phenotypes.

Conclusions

We identified multiple OUD variant associations at OPRM1, single variant associations with FURIN, and 18 GWS associations in the OUD-MTAG. OUD is likely influenced by both OUD-specific loci and loci shared across SUDs.
In vivo NMDA receptor function in people with NMDA receptor antibody encephalitis
Authors: Galovic Marian , Al-Diwani Adam , Vivekananda Umesh , Torrealdea Francisco , Erlandsson Kjell , Fryer Tim D , Hong Young T , Thomas Benjamin A , McGinnity Colm J , Edmond Evan , Sander Kerstin , Årstad Erik , Jelcic Ilijas , Aigbirhio Franklin I , Groves Ashley M , Thielemans Kris , Hutton Brian , Hammers Alexander , Duncan John S , Coles Jonathan P , Barnes Anna , Stagg Charlotte J , Walker Matthew C , Irani Sarosh R , Koepp Matthias J ,   for the NEST investigators
Published: December 2021

In N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis, NMDAR-autoantibodies are hypothesised to cause prominent neuropsychiatric symptoms by internalizing NMDARs. However, supporting evidence comes chiefly from in vitro and rodent data with scant direct evidence from affected humans. Here, we used in vivo positron emission tomography (PET) with [18F]GE-179 to show a mean 30% reduction of the density of open, activated NMDARs in grey matter of persistently NMDAR-autoantibody seropositive patients following NMDAR-antibody encephalitis compared to healthy controls. The reduction was most prominent in the anterior temporal and superior parietal cortices. These patients had normal structural MRIs and mild residual symptoms. In contrast, one symptom-free patient who recovered from NMDAR-antibody encephalitis and was not NMDAR-autoantibody seropositive had normal density of active NMDARs. These findings reveal a functional deficit of open, activated NMDARs in humans with NMDAR-autoantibodies. Moreover, we observed a functional NMDAR deficit for up to 8 months following the disease peak, despite only mild residual symptoms, highlighting the considerable compensatory capacity of the human brain.

One Sentence Summary

Reductions of activated NMDA receptors detected in vivo in female patients following NMDA-receptor-antibody encephalitis.
A mixed-methods study of risk factors and experiences of healthcare workers tested for the novel coronavirus in Canada
Authors: Okpani Arnold Ikedichi , Barker Stephen , Lockhart Karen , Grant Jennifer , Delgado-Ron Jorge Andrés , Zungu Muzimkhulu , Naicker Nisha , Ehrlich Rodney , Yassi Annalee
Published: December 2021

Objectives

We aimed to investigate the contribution of occupational and non-work-related factors to the risk of novel coronavirus (SARS-CoV-2) infection among healthcare workers (HCWs) in Vancouver Coastal Health, British Columbia, Canada. We also aimed to examine how HCWs described their experiences.

Methods

We conducted a matched case-control study using data from online and phone questionnaires with optional open-ended questions completed by HCWs who sought SARS-CoV-2 testing between March 2020 and March 2021. Conditional logistic regression and thematic analysis were utilized.

Results

Data from 1340 HCWs were included. Free-text responses were provided by 257 respondents. Adjusting for age, gender, race, occupation, and number of weeks since pandemic was declared, community exposure to a known COVID-19 case (adjusted odds ratio -aOR: 2.45; 95% CI 1.67-3.59), and difficulty accessing personal protective equipment -PPE- (aOR: 1.84; 95% CI 1.07-3.17) were associated with higher infection odds. Care-aides/licensed practical nurses had substantially higher risk (aOR: 2.92; 95% CI 1.49-5.70) than medical staff who had the lowest risk. Direct COVID-19 patient care was not associated with elevated risk. HCWs’ experiences reflected the phase of the pandemic when they were tested. Suboptimal communication, mental stress, and situations perceived as unsafe were common sources of dissatisfaction.

Conclusions

Community exposures and occupation were important determinants of infection among HCWs in our study. The availability of PPE and clear communication enhanced a sense of safety. Varying levels of risk between occupational groups call for wider targeting of infection prevention measures. Strategies for mitigating community exposure and supporting HCW resilience are required.
S glycoprotein diversity of the Omicron variant
Authors: Sarkar Rakesh , Lo Mahadeb , Saha Ritubrita , Dutta Shanta , Chawla-Sarkar Mamta
Published: December 2021

On the backdrop of ongoing Delta variant infection and vaccine-induced immunity, the emergence of the new Variant of Concern, the Omicron, has again fuelled the fears of COVID-19 around the world. Currently, very little information is available about the S glycoprotein mutations, transmissibility, severity, and immune evasion behaviour of the Omicron variant. In the present study, we have performed a comprehensive analysis of the S glycoprotein mutations of 309 strains of the Omicron variant and also discussed the probable effects of observed mutations on several aspects of virus biology based on known available knowledge of mutational effects on S glycoprotein structure, function, and immune evasion characteristics.
Estimating area-level variation in SARS-CoV-2 infection fatality ratios
Authors: Ladau Joshua , Kuo Chaincy , Brodie Eoin L. , Falco Nicola , Bansal Ishan , Hoffman Elijah B. , Joachimiak Marcin P. , Mora Ana M. , Walker Angelica M. , Wainwright Haruko M. , Wu Yulun , Jacobson Daniel , Hess Matthias , Brown James B. , Abuabara Katrina
Published: December 2021

Background

During a pandemic, estimates of geographic variability in disease burden are important but limited by the availability and quality of data.

Methods

We propose a framework for estimating geographic variability in testing effort, total number of infections, and infection fatality ratio (IFR). Because symptomatic people are more likely to seek testing, we use a noncentral hypergeometric model that accounts for differential probability of positive tests. We apply this framework to the United States (U.S.) COVID-19 pandemic to estimate county-level SARS-CoV-2 IFRs from March 1, 2020 to October 31, 2020. Using data on population size, number of observed cases, number of reported deaths in each U.S. county and state, and number of tests in each U.S. state, we develop a series of estimators to identify the number of SARS-CoV-2 infections and IFRs at the county level. We then perform a simulation and compare the estimated values to simulated values to demonstrate the validity of our approach.

Findings

Applying the county-level estimators to the real, unsimulated COVID-19 data spanning March 1, 2020 to October 31, 2020 from across the U.S., we found that IFRs varied from 0 to 0.0273, with an interquartile range of 0.0022 and a median of 0.0018. The estimators for IFRs, number of infections, and number of tests showed high accuracy and precision; for instance, when applied to simulated validation data sets, across counties, Pearson correlation coefficients between estimator means and true values were 0.88, 0.95, and 0.74, respectively.

Interpretation

We propose an estimation framework that can be used to identify area-level variation in IFRs and performs well to estimate county-level IFRs in the U.S. COVID-19 pandemic.
Serum uric acid and total bilirubin as putative biomarkers of resistance in Prodromal Parkinson’s disease: Longitudinal data from the PPMI study
Authors: Koros Christos , Simitsi Athina-Maria , Bougea Anastasia , Papagiannakis Nikolaos , Prentakis Andreas , Papadimitriou Dimitra , Pachi Ioanna , Angelopoulou Efthalia , Beratis Ion , Efthymiopoulou Efthymia , Lourentzos Konstantinos , Bozi Maria , Papageorgiou Sokratis G. , Trapali Xenia Geronicola , Bonakis Anastasios , Stamelou Maria , Stefanis Leonidas
Published: December 2021

Background

The role of blood uric acid and more recently bilirubin as biomarkers in symptomatic motor PD has been increasingly established in the literature.

Objective

Our present study assessed the role of serum uric acid and total bilirubin as putative biomarkers in a prodromal PD cohort followed longitudinally.

Methods

Longitudinal 5-year serum uric acid and total bilirubin measurement data of 65 Prodromal PD patients (including REM Sleep Behavior disorder (RBD), N=39 and Hyposmia, N=26) with an abnormal DATSCAN imaging were downloaded from the Parkinson’s Progression Markers Initiative (PPMI) database. This cohort was compared with 423 de novo sporadic PD patients and 196 healthy controls enrolled in the same study.

Results

After adjusting for age, sex and Body Mass Index (BMI), baseline and 5-year longitudinal serum uric acid levels were higher in the Prodromal cohort and RBD subgroup as compared to the motor PD cohort. This was also true for longitudinal measurements in the Hyposmic subgroup. In contrast, baseline and longitudinal serum total bilirubin did not differ between each prodromal group and the PD cohort.

Conclusions

Our results are indicative of a role of serum uric acid (but probably not of total bilirubin) as a marker of neuroprotection, in a certain subgroup of premotor patients exhibiting exclusively non motor features (hyposmia or RBD). It is possible that an inherent antioxidant resistance of a subset of RBD or hyposmia patients with high serum uric acid level delayed or precluded the emergence of a motor PD phenotype as opposed to the PD cohort.
Characteristics of Patients Referred to a Cardiovascular Disease Clinic for Post-Acute Sequelae of SARS-CoV-2 Infection
Authors: Wang Stephen Y. , Adejumo Philip , See Claudia , Onuma Oyere K. , Miller Edward J. , Spatz Erica S.
Published: December 2021

There is limited literature on the cardiovascular manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC). We aimed to describe the characteristics, diagnostic evaluations, and cardiac diagnoses in patients referred to a cardiovascular disease clinic designed for patients with PASC from May 2020 to September 2021. Of 126 patients, average age was 46 years (range 19-81 years), 43 (34%) were male. Patients presented on average five months after COVID-19 diagnosis. 30 (24%) patients were hospitalized for acute COVID-19. Severity of acute COVID-19 was mild in 37%, moderate in 41%, severe in 11%, and critical in 9%. Patients were also followed for PASC by pulmonology (53%), neurology (33%), otolaryngology (11%), and rheumatology (7%). Forty-three patients (34%) did not have significant comorbidities. The most common symptoms were dyspnea (52%), chest pain/pressure (48%), palpitations (44%), and fatigue (42%), commonly associated with exertion or exercise intolerance. The following cardiovascular diagnoses were identified: nonischemic cardiomyopathy (5%); new ischemia (3%); coronary vasospasm (2%); new atrial fibrillation (2%), new supraventricular tachycardia (2%); myocardial involvement (15%) by cardiac MRI, characterized by late gadolinium enhancement (LGE; 60%) or inflammation (48%). The remaining 97 patients (77%) exhibited common symptoms of fatigue, dyspnea on exertion, tachycardia, or chest pain, which we termed “cardiovascular PASC syndrome.” Three of these people met criteria for postural orthostatic tachycardia syndrome. Lower severity of acute COVID-19 was a significant predictor of cardiovascular PASC syndrome. In this cohort of patients referred to cardiology for PASC, 23% had a new diagnosis, but most displayed a pattern of symptoms associated with exercise intolerance.
Increasing trends in mental health problems among Chinese young adolescents: results from repeated cross-sectional data in Changsha 2016-2020
Authors: Wu Zhipeng , Wang Biao , Zou Zhulin , Liu Zhening , Chen Xudong , Long Yicheng
Published: December 2021

This study performed a repeated cross-sectional analysis to explore possible trends in mental health problems among Chinese adolescents during 2016 to 2020. A total of 2837 seventh-grade students from Changsha city were surveyed in three waves in 2016, 2019 and 2020. The results showed that obsessive-compulsive tendencies, interpersonal sensitivity, depression, anxiety, academic stress and emotional disturbance problems were significantly increased in surveyed adolescents during 2016 to 2020. Moreover, positive rates of most of these problems were higher in females than males, and were significantly increased in only females. These results highlight the importance of focusing on mental health among Chinese adolescents, especially girls.
Duplication of NRAMP3 gene in poplars generated two homologous transporters with distinct functions
Authors: Pottier Mathieu , Le Thi Van Anh , Primard-Brisset Catherine , Marion Jessica , Bianchi Michele , Victor Cindy , Déjardin Annabelle , Pilate Gilles , Thomine Sébastien
Published: December 2021

Transition metals are essential for a wealth of metabolic reactions, but their concentrations need to be tightly controlled across cells and cell compartments, as metal excess or imbalance has deleterious effects. Metal homeostasis is achieved by a combination of metal transport across membranes and metal binding to a variety of molecules. Gene duplication is a key process in evolution, as emergence of advantageous mutations on one of the copies can confer a new function. Here, we report that the poplar genome contains two paralogues encoding NRAMP3 metal transporters localized in tandem. All Populus species analyzed had two copies of NRAMP3, whereas only one could be identified in Salix species indicating that duplication occurred when the two genera separated. Both copies are under purifying selection and encode functional transporters, as shown by expression in the yeast heterologous expression system. However, genetic complementation revealed that only one of the paralogues has retained the original function in release of metals stored in the vacuole previously characterized in A. thaliana. Confocal imaging showed that the other copy has acquired a distinct localization to the Trans Golgi Network (TGN). Expression in poplar suggested that the copy of NRAMP3 localized on the TGN has a novel function in the control of cell-to-cell transport of manganese. This work provides a clear case of neo-functionalization through change in the subcellular localization of a metal transporter as well as evidence for the involvement of the secretory pathway in cell-to-cell transport of manganese.
Dynamic interplay between RPL3- and RPL3L-containing ribosomes modulates mitochondrial activity in the mammalian heart
Authors: Milenkovic Ivan , Santos Vieira Helaine Graziele , Lucas Morghan C , Ruiz-Orera Jorge , Patone Giannino , Kesteven Scott , Wu Jianxin , Feneley Michael , Espadas Guadalupe , Sabidó Eduard , Hubner Norbert , van Heesch Sebastiaan , Voelkers Mirko , Novoa Eva Maria
Published: December 2021

The existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this heterogeneity leads to functionally diverse ‘specialized ribosomes’ is still a controversial topic. Here, we explore the biological function of RPL3L (uL3L), a ribosomal protein (RP) paralog of RPL3 (uL3) that is exclusively expressed in muscle and heart tissues, by generating a viable homozygousRpl3lknockout mouse strain. We identify a rescue mechanism in which, upon RPL3L depletion, RPL3 becomes upregulated, yielding RPL3-containing ribosomes instead of RPL3L-containing ribosomes that are typically found in cardiomyocytes. Using both ribosome profiling (Ribo-Seq) and a novel orthogonal approach consisting of ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), we find that RPL3L neither modulates translational efficiency nor ribosome affinity towards a specific subset of transcripts. By contrast, we show that depletion of RPL3L leads to increased ribosome-mitochondria interactions in cardiomyocytes, which is accompanied by a significant increase in ATP levels, potentially as a result of mitochondrial activity fine-tuning. Our results demonstrate that the existence of tissue-specific RP paralogs does not necessarily lead to enhanced translation of specific transcripts or modulation of translational output. Instead, we reveal a complex cellular scenario in which RPL3L modulates the expression of RPL3, which in turn affects ribosomal subcellular localization and, ultimately, mitochondrial activity.
Long-term labeling and imaging of synaptically-connected neuronal networksin vivousing double-deletion-mutant rabies viruses
Authors: Jin Lei , Sullivan Heather A. , Zhu Mulangma , Lavin Thomas K. , Matsuyama Makoto , Fu Xin , Lea Nicholas E. , Xu Ran , Hou YuanYuan , Rutigliani Luca , Pruner Maxwell , Babcock Kelsey R. , Ip Jacque Pak Kan , Hu Ming , Daigle Tanya L. , Zeng Hongkui , Sur Mriganka , Feng Guoping , Wickersham Ian R.
Published: December 2021

Monosynaptic tracing is a widely-used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Spread of the viruses requires expression of both deleted viral genesin transin postsynaptic source cells; suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imagingin vivoindicated that over 90% of both presynaptic and source cells survived for the full twelve-week course of imaging.Ex vivowhole-cell recordings at 5 weeks postinfection showed that the second-generation system perturbs input and source cells much less than does the first-generation system. Finally, two-photon calcium imaging of labeled networks of visual cortex neurons showed that their visual response properties appeared normal for 10 weeks, the longest we followed them.
Population genetics reveals divergent lineages and ongoing hybridization in a declining migratory fish species complex
Authors: Rougemont Quentin , Perrier Charles , Besnard Anne-Laure , Lebel Isabelle , Abdallah Yann , Feunteun Eric , Réveillac Elodie , Lasne Emilien , Acou Anthony , Nachón David José , Cobo Fernando , Evanno Guillaume , Baglinière Jean-Luc , Launey Sophie
Published: December 2021

Deciphering the effects of historical and recent demographic processes responsible for the spatial patterns of genetic diversity and structure is a key objective in evolutionary and conservation biology. Using population genetic analyses, we investigated the demographic history, the contemporary genetic diversity and structure, and the occurrence of hybridization and introgression of two species of anadromous fish with contrasting life history strategies and which have undergone recent demographic declines, the allis shad (Alosa alosa) and the twaite shad (Alosa fallax). We genotyped 706 individuals from 20 rivers and 5 sites at sea in Southern Europe at thirteen microsatellite markers. Genetic structure between populations was lower for the nearly semelparous species A. alosa, which disperses greater distances compared to the iteroparous species, A. fallax. Individuals caught at sea were assigned at the river level for A. fallax and at the region level for A. alosa. Using an approximate Bayesian computation framework, we inferred that the most likely long term historical divergence scenario between both species and lineages involved historical separation followed by secondary contact accompanied by strong population size decline. Accordingly, we found evidence for contemporary hybridization and bidirectional introgression due to gene flow between both species and lineages. Moreover, our results support the existence of at least one distinct species in the Mediterrannean sea: A. agone in Golfe du Lion area, and another divergent lineage in Corsica. Overall, our results shed light on the interplay between historical and recent demographic processes and life history strategies in shaping population genetic diversity and structure of closely related species. The recent demographic decline of these species’ populations and their hybridization should be carefully considered while implementing conservation programs.
PncA from bacteria improves diet-induced NAFLD by enabling the transition from NAM to NA in mice
Authors: Feng Shengyu , Guo Liuling , Liu Hailiang
Published: December 2021

Nicotinamide adenine dinucleotide (NAD+) is crucial for energy metabolism, oxidative stress, DNA damage repair, longevity regulation, and several signaling processes. To date, three NAD+ synthesis pathways have been found in microbiota and hosts, but the potential relationship between gut microbiota and their hosts in regulating NAD+ homeostasis remains unknown. Here, we show that an analog of the first-line tuberculosis drug pyrazinamide (a bacterial NAD+ synthesis inhibitor) affected NAD+ levels in the intestines and liver of mice and disrupted the intestinal microecological balance. Furthermore, using microbiota expressing the pyrazinamidase/nicotinamidase (PncA) gene, which is a target of pyrazinamide, hepatic NAD+ levels were greatly increased and significantly increased compared with other NAD+ precursors, and diet-induced non-alcoholic fatty liver disease (NAFLD) in mice was improved. Overall, the PncA gene in microbiota plays an important role in regulating NAD+ synthesis in the host, thereby providing a potential target for modulating the host’s NAD+ level.

Highlights

PncA inhibitors disrupt gut microbiome homeostasis and reduce host NAD+ levels but do not affect NAD+ levels in cultured cells

PncA gene in microbiota affects host liver NAD metabolism

PncA affects lipid metabolism-related genes and metabolites in mice with NAFLD

Diet-induced NAFLD is improved by PncA overexpression in the liver of mice

Graphical abstract
Spatially Resolved Phosphoproteomics Reveals Fibroblast Growth Factor Receptor Recycling-driven Regulation of Autophagy and Survival
Authors: Watson Joanne , Ferguson Harriet R. , Brady Rosie M. , Ferguson Jennifer , Fullwood Paul , Mo Hanyi , Bexley Katherine H. , Knight David , Schwartz Jean-Marc , Smith Michael P. , Francavilla Chiara
Published: December 2021

Receptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibroblast Growth Factor Receptor 2b (FGFR2b) recycling, we revealed FGFR signalling partners proximal to recycling endosomes (REs) by developing a Spatially Resolved Phosphoproteomics (SRP) approach based on APEX2-driven biotinylation followed by phosphopeptide enrichment. Combining this with traditional phosphoproteomics, bioinformatics, and targeted assays, we uncovered that FGFR2b stimulated by its recycling ligand FGF10 activates mTOR-dependent signalling and ULK1 at the REs, leading to autophagy suppression and cell survival. This adds to the growing importance of RTK recycling in orchestrating cell fate and suggests a therapeutically targetable vulnerability in ligand-responsive cancer cells. Integrating SRP with other systems biology approaches provides a powerful tool to spatially resolve celllar signalling.
The veterinary anti-parasitic selamectin is a novel inhibitor of the mycobacterial DprE1 enzyme
Authors: Ezquerra-Aznárez José Manuel , Degiacomi Giulia , Gašparovič Henrich , Stelitano Giovanni , Sammartino José Camilla , Korduláková Jana , Governa Paolo , Manetti Fabrizio , Pasca Maria Rosalia , Chiarelli Laurent Roberto , Ramón-García Santiago
Published: December 2021

Avermectins are macrocyclic lactones with anthelmintic activity. Recently, they were found to be effective against Mycobacterium tuberculosis, which accounts for one third of the worldwide deaths from antimicrobial resistance. However, their anti-mycobacterial mode of action remains to be elucidated. The activity of selamectin was determined against a panel of M. tuberculosis mutants. Two strains carrying mutations in DprE1, the decaprenylphosphoryl-β-D-ribose oxidase involved in the synthesis of mycobacterial arabinogalactan, were more susceptible to selamectin. Biochemical assays against the Mycobacterium smegmatis DprE1 protein confirmed this finding, and docking studies predicted a binding site in a loop that included Leu275. Sequence alignment revealed variants in this position among mycobacterial species, with the size and hydrophobicity of the residue correlating with their MIC values; M. smegmatis DprE1 variants carrying these point mutations validated the docking predictions. However, the correlation was not confirmed when M. smegmatis mutant strains were constructed and MIC phenotypic assays performed. Likewise, metabolic labeling of selamectin-treated M. smegmatis and M. tuberculosis cells with 14C-labeled acetate did not reveal the expected lipid profile associated with DprE1 inhibition. Together, our results confirm the in vitro interactions of selamectin and DprE1 but suggest that selamectin could be a multi-target anti-mycobacterial compound.
Does extracellular DNA mask microbial responses to a pulse disturbance?
Authors: Kittredge HA , Dougherty KM , Glanville K , Evans SE
Published: December 2021

A major goal in microbial ecology is to predict how microbial communities will respond to global change. However, DNA-based sequencing that is intended to characterize live microbial communities includes extracellular DNA (exDNA) from non-viable cells. This could obscure relevant microbial responses, particularly to pulse disturbances which kill bacteria and have disproportionate effects on ecosystems. Here, we characterize bacterial communities before and after a drying-rewetting pulse disturbance, using an improved method for exDNA exclusion. We find that exDNA removal is important for detecting subtle yet significant changes in microbial abundance, diversity, and community composition across the disturbance. However, inclusion of exDNA did not obscure results to a large extent, only sometimes altering statistical significance but rarely changing the direction of the response or general conclusions about bacterial disturbance dynamics. Although there may be instances where exDNA removal is essential for accurate representation of microbial communities, our study suggests these scenarios will be difficult to predict a priori. Overall, we found no evidence that certain time points across the distrubance were more affected by exDNA inclusion, nor did the size or composition of exDNA pools accurately predict when exDNA would alter significance levels. However, exDNA dynamics did vary strongly across the two soil types tested.
Unsupervised clustering of track-weighted dynamic functional connectivity reveals white matter substrates of functional connectivity dynamics
Authors: Basile Gianpaolo Antonio , Bertino Salvatore , Nozais Victor , Bramanti Alessia , Ciurleo Rosella , Anastasi Giuseppe Pio , Milardi Demetrio , Cacciola Alberto
Published: December 2021

The contribution of structural connectivity to functional connectivity dynamics is still far from being fully elucidated. Herein, we applied track-weighted dynamic functional connectivity (tw-dFC), a model integrating structural, functional, and dynamic connectivity, on high quality diffusion weighted imaging and resting-state fMRI data from two independent repositories. The tw-dFC maps were analyzed using independent component analysis, aiming at identifying spatially independent white matter components which support dynamic changes in functional connectivity. Each component consisted of a spatial map of white matter bundles that show consistent fluctuations in functional connectivity at their endpoints, and a time course representative of such functional activity. These components show high intra-subject, inter-subject, and inter-cohort reproducibility. We provided also converging evidence that functional information about white matter activity derived by this method can capture biologically meaningful features of brain connectivity organization, as well as predict higher-order cognitive performance.
Mental sequelae of the Covid-19 pandemic: Well-being one year into the crisis in children with and without complex medical histories and their parents
Authors: Ehrler Melanie , Hagmann Cornelia F. , Kretschmar Oliver , Landolt Markus A. , Latal Beatrice , Wehrle Flavia M.
Published: December 2021

Objectives

To understand the long-term mental sequelae for families over the course of the COVID-19 pandemic, the well-being of children with and without complex medical histories and their parents was investigated longitudinally.

Methods

Well-being of 200 school-aged children (73 typically-developing, 46 born very preterm, 73 with complex congenital heart disease) and 175 of their parents was assessed prior to and during the first (April–May 2020), second (October–November 2020), and third waves (April–May 2021) of the pandemic with standardized questionnaires. Social and COVID-19-specific determinants were investigated as predictors of impaired well-being.

Results

Child proxy-reported well-being was lower than before the pandemic during the first (P<0.001) and third waves (P=0.01) but not the second (P=0.13). Child self-reported well-being was not lower during the pandemic (all P>0.10). Parent well-being dropped during the first wave (P<0.001) and remained low during the first year (P<0.01). One year into the pandemic, 18/25% of children (self-/proxy-report) and 27% of parents scored below the normal range compared to 11%/10%, and 16%, respectively, before the pandemic. Parents of typically-developing children reported lower well-being than parents of children born very preterm (P=0.006) or with a complex congenital heart disease (P=0.03). Child and parent well-being was lower in families with sparse social support (P<0.001) and poor family functioning (P<0.01).

Conclusion

The pandemic continues to impact family well-being one year after its outbreak. Families with sparse social support and poor family functioning are particularly at risk for compromised well-being and support should be provided to them.
Comparison of different sequencing techniques with multiplex real-time PCR for detection to identify SARS-CoV-2 variants of concern
Authors: Ranasinghe Diyanath , Pramanayagam Jayadas Tibutius Thanesh , Jayathilaka Deshni , Jeewandara Chandima , Dissanayake Osanda , Guruge Dinuka , Ariyaratne Dinuka , Gunasinghe Dumni , Gomes Laksiri , Wijesinghe Ayesha , Wijayamuni Ruwan , Malavige Gathsaurie Neelika
Published: December 2021

As different SARS-CoV-2 variants emerge and with the continuous evolution of sub-lineages of the delta and other variants, it is crucial that all countries carry out sequencing of at least >1% of their infections, in order to detect emergence of variants with higher transmissibility and with ability to evade immunity. However, as many resource-poor countries are unable to sequence adequate number of viruses, we compared to usefulness of a commercially available multiplex real-time PCR assay to detect important single nucleotide polymorphisms (SNPs) associated with the variants and compared the sensitivity, accuracy and cost effectiveness of the Illumina sequencing platform and the Oxford Nanopore Technologies’ (ONT) platform. 138/143 (96.5%) identified as the alpha and 36/39 (92.3%) samples identified as the delta variants due to the presence of lineage defining SNPs by the multiplex real time PCR, were assigned to the same lineage by either of the two sequencing platforms. 34/37 of the samples sequenced by ONT had <5% ambiguous bases, while 21/37 samples sequenced using the Illumina generated <15% ambiguous bases. However, the mean PHRED scores averaged at 32.35 by Illumina reads but 10.78 in ONT. Sub-consensus single nucleotide variations (SNV) were highly correlated between both platforms (R2=0.79) while indels showed a weaker correlation (R2=0.13).

Although the ONT had a slightly higher error rate compared to the Illumina technology, it achieved higher coverage with a lower number of reads, generated less ambiguous bases and was significantly cheaper than Illumina sequencing technology.
Effect of environmental factors on electrochemical corrosion of galvanized steel wires for bridge cables
Authors: Li Rou , Miao Changqing , Wei Tinghua
Published: December 2021

Purpose

This paper aims to investigate the electrochemical corrosion rate of galvanized steel wires for bridge cables.

Design/methodology/approach

The electrochemical corrosion test and response surface analysis of galvanized steel wires were carried out, and the variety of polarization curves of galvanized steel wires under different corrosion parameters was discussed. The expression of corrosion rate of galvanized steel wires under the action of single and multi-factor coupling was established.

Findings

The polarization curves of galvanized steel wires under different Cl- concentrations, pH value and temperature were basically similar, but all show different degrees of deviation and some anodic polarization curves had inflection points. For example, when the Cl- concentration reached 3.5%, the corrosion rate of galvanized steel wire was four times that of pure water.

Originality/value

The influence relationship of single and multi-factor coupling on the corrosion rate of galvanized steel wires was as follows: RCl > RT * Cl > RT > RpH > RpH * T > RpH * Cl.
A new approach for task managing in the fog-based medical cyber-physical systems using a hybrid algorithm
Authors: Yu Jiuhong , Wang Mengfei , J.H. Yu , Arefzadeh Seyedeh Maryam
Published: December 2021

Purpose

This paper aims to offer a hybrid genetic algorithm and the ant colony optimization (GA-ACO) algorithm for task mapping and resource management. The paper aims to reduce the makespan and total response time in fog computing- medical cyber-physical system (FC-MCPS).

Design/methodology/approach

Swift progress in today’s medical technologies has resulted in a new kind of health-care tool and therapy techniques like the MCPS. The MCPS is a smart and reliable mechanism of entrenched clinical equipment applied to check and manage the patients’ physiological condition. However, the extensive-delay connections among cloud data centers and medical devices are so problematic. FC has been introduced to handle these problems. It includes a group of near-user edge tools named fog points that are collaborating until executing the processing tasks, such as running applications, reducing the utilization of a momentous bulk of data and distributing the messages. Task mapping is a challenging problem for managing fog-based MCPS. As mapping is an non-deterministic pol ynomial-time-hard optimization issue, this paper has proposed a procedure depending on the hybrid GA-ACO to solve this problem in FC-MCPS. ACO and GA, that is applied in their standard formulation and combined as hybrid meta-heuristics to solve the problem. As such ACO-GA is a hybrid meta-heuristic using ACO as the main approach and GA as the local search. GA-ACO is a memetic algorithm using GA as the main approach and ACO as local search.

Findings

MATLAB is used to simulate the proposed method and compare it to the ACO and MACO algorithms. The experimental results have validated the improvement in makespan, which makes the method a suitable one for use in medical and real-time systems.

Research limitations/implications

The proposed method can achieve task mapping in FC-MCPS by attaining high efficiency, which is very significant in practice.

Practical implications

The proposed approach can achieve the goal of task scheduling in FC-MCPS by attaining the highest total computational efficiency, which is very significant in practice.

Originality/value

This research proposes a GA-ACO algorithm to solve the task mapping in FC-MCPS. It is the most significant originality of the paper.
Dynamic linkages among international crude oil, exchange rate and Norwegian stock market: evidence from ARDL bound testing approach
Authors: Singhal Shelly , Choudhary Sangita , Biswal Pratap Chandra
Published: December 2021

Purpose

The purpose of this paper is to examine the long-run association and short-run causality among oil price, exchange rate and stock market in Norwegian context.

Design/methodology/approach

This work uses auto regressive distributed lag (ARDL) bound co-integration test to examine the long-run association among international crude oil, exchange rate and Norwegian stock market. Further to test the causality, Toda–Yamamoto Granger causality test is used. Daily data ranging from 1 January, 2011 to 31 December, 2018 is used in this study.

Findings

Findings of this study suggest the existence of long-run equilibrium relationship among oil price, exchange rate and Norwegian stock market when oil price is taken as dependent variable. Further, this study observes the bi-directional causality between Norwegian stock market and exchange rate and unidirectional causality between oil and Norwegian stock market (from oil to stock market).

Originality/value

To the best of the authors’ knowledge, this the first study in context of Norway to explore the long-run association and causal relationships among international crude oil price, exchange rate and stock market index. Particularly, association of exchange rate and stock market largely remains unexplored for Norwegian economy. Further, majority of studies conducted in Norwegian setup have considered the period up to year 2010 and association of these variables is found to be time varying. Finally, this study uses ARDL bound co-integration test and Toda–Yamamoto Granger causality test. These methodologies have been used in literature in context of other countries like India and Mexico but not yet applied to study the Norwegian case.
A pervasive health care device computing application for brain tumors with machine and deep learning techniques
Authors: D. Sreelakshmi , Inthiyaz Syed
Published: December 2021

Purpose

Pervasive health-care computing applications in medical field provide better diagnosis of various organs such as brain, spinal card, heart, lungs and so on. The purpose of this study is to find brain tumor diagnosis using Machine learning (ML) and Deep Learning(DL) techniques. The brain diagnosis process is an important task to medical research which is the most prominent step for providing the treatment to patient. Therefore, it is important to have high accuracy of diagnosis rate so that patients easily get treatment from medical consult. There are many earlier investigations on this research work to diagnose brain diseases. Moreover, it is necessary to improve the performance measures using deep and ML approaches.

Design/methodology/approach

In this paper, various brain disorders diagnosis applications are differentiated through following implemented techniques. These techniques are computed through segment and classify the brain magnetic resonance imaging or computerized tomography images clearly. The adaptive median, convolution neural network, gradient boosting machine learning (GBML) and improved support vector machine health-care applications are the advance methods used to extract the hidden features and providing the medical information for diagnosis. The proposed design is implemented on Python 3.7.8 software for simulation analysis.

Findings

This research is getting more help for investigators, diagnosis centers and doctors. In each and every model, performance measures are to be taken for estimating the application performance. The measures such as accuracy, sensitivity, recall, F1 score, peak-to-signal noise ratio and correlation coefficient have been estimated using proposed methodology. moreover these metrics are providing high improvement compared to earlier models.

Originality/value

The implemented deep and ML designs get outperformance the methodologies and proving good application successive score.
A web interface for WMN-PSODGA hybrid intelligent simulation system: performance evaluation for different mesh client distributions
Authors: Barolli Admir , Sakamoto Shinji
Published: December 2021

Purpose

The purpose of this paper is to implement a web interface for a hybrid intelligent system. By using the implemented web interface, one can find optimal assignments of mesh routers in wireless mesh networks (WMNs). This study evaluates the implemented system considering three distributions of mesh clients to solve the node placement problem in WMNs.

Design/methodology/approach

The node placement problem in WMNs is well known to be a computationally hard problem. Therefore, intelligent algorithms are used for solving this problem. The implemented system is a hybrid intelligent system based on meta-heuristics algorithms: particle swarm optimization (PSO) and distributed genetic algorithm (DGA). The proposed system is called WMN-PSODGA.

Findings

This study carried out simulations using the implemented simulation system. From the simulations results, it was found that the WMN-PSODGA system performs better for chi-square distribution of mesh clients compared with Weibull and exponential distributions.

Research limitations/implications

For simulations, three different distributions of mesh clients were considered. In the future, other mesh client distributions, number of mesh nodes and communication distance need to be considered.

Originality/value

This research work, different from other research works, implemented a hybrid intelligent simulation system for WMNs. This study also implemented a web interface for the proposed system, which make the simulation system user-friendly.
Footprints in the cloud: the hidden cost of IT infrastructure
Authors: Hirsch Peter Buell
Published: December 2021

Purpose

The purpose of this paper is to examine the hidden carbon footprint of corporate big data infrastructures and provide guidance for communicators responsible for corporate ESG and reputation.

Design/methodology/approach

It is based on a subjective view of the literature on this topic, selecting relevant examples.

Findings

The authors found that consciousness within corporations of the carbon footprint of their own information technology infrastructures is low and only a few companies have a strategy for identifying it.

Originality/value

To the best of the authors’ knowledge, this is the first treatment of this subject from the perspective of the corporate owner of ESG and reputation.
Research on the impact of online picture contents of agricultural products on consumers' willingness to click
Authors: Tian Wenhui , Li Yanjun , Li Linzhu
Published: December 2021

Purpose

The paper aims to clarify the influence of different picture contents on consumer's willingness to click pictures when shopping for agricultural products online and examine the intermediary mechanism and boundary conditions of the impact.

Design/methodology/approach

The paper opted for an empirical study based on the cue utilization theory and information processing theory, including three experiments to test the existence, intermediary mechanism and boundary conditions of the impact of online picture contents of agricultural products on consumers' clicking intention.

Findings

The paper provides empirical insights about the influence of picture contents on consumer's willingness to click when shopping for agricultural products online. The picture of product's production environment or grower on the search result page can effectively improve consumer's willingness to click the product under dual systemic information processing modes. Compared with product pictures, pictures displaying products and production environment can stimulate more cognitive system processing, and pictures displaying products and its growers can stimulate more emotional system processing, both resulting in higher click intention. However, the above effects only exist in the context of non-branded agricultural products.

Originality/value

The research results not only provide practical guidance for merchants, but also fill the gap in the research on the impact of picture contents on consumers in the field of agricultural products in online marketing.