bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroinflammation, Depressive Affect, and Amyloid Burden in Alzheimer’s Disease: Insights from the Kynurenine Pathway
Authors: Willette Auriel A. , Pappas Colleen , Hoth Nathan , Wang Qian , Klinedinst Brandon , Willette Sara A. , Larsen Brittany , Pollpeter Amy , Li Tianqi , Le Scott , Mochel Jonathan P. , Allenspach Karin , Dantzer Robert ,   and for the Alzheimer’s disease Neuroimaging Initiative
Published: August 2020

Background

Depressive symptoms in Alzheimer’s disease (AD) predict worse cognitive and functional outcomes. Both AD and major depression are characterized by shunted tryptophan metabolism away from serotonin (5-HT) and toward the neuroinflammatory kynurenine (Kyn) pathway. The present study assessed the role of Kyn across the AD continuum in behavioral, neuroanatomical, neuropathological, and physiological outcomes.

Methods

In 746 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI1) cohort, serum markers of 5-HT, tryptophan, and Kyn were measured and their relationships investigated with immunologic markers, affect and functional outcomes, CSF markers of beta-amyloid (Aβ) and tau, and regional gray matter.

Results

A higher Kyn/Tryptophan ratio was linked to many inflammatory markers, as well as lower functional independence and memory scores. A higher Kyn/5-HT ratio showed similar associations, but also strong relationships with depressive affect and neuropsychiatric disturbance, executive dysfunction, and global cognitive decline. Further, gray matter atrophy was seen in hippocampus, anterior cingulate, and prefrontal cortices, as wel as greater amyloid and total tau deposition. Finally, using moderated-mediation, several pro-inflammatory factors partially mediated Kyn/5-HT and depressive affect scores in participants with subclinical Aβ (i.e., Aβ-), whereas such associations were fully mediated by Complement 3 in Aβ+ participants.

Conclusions

These findings suggest that neuroinflammatory signaling cascades may occur during AD, resulting in increased Kyn metabolism that influences the pathogenesis of depressive symptoms. Aβ and the complement system may be critical contributing factors in this process.
Quantitative analysis of SARS-CoV-2 RNA from wastewater solids in communities with low COVID-19 incidence and prevalence
Authors: D’Aoust Patrick M. , Mercier Élisabeth , Montpetit Danika , Jia Jian-Jun , Alexandrov Ilya , Neault Nafisa , Baig Aiman Tariq , Mayne Janice , Zhang Xu , Alain Tommy , Servos Mark R. , MacKenzie Malcolm , Figeys Daniel , MacKenzie Alex E. , Graber Tyson E. , Delatolla Robert
Published: August 2020

In the absence of an effective vaccine to prevent COVID-19 it is important to be able to track community infections to inform public health interventions aimed at reducing the spread and therefore reduce pressures on health-care units, improve health outcomes and reduce economic uncertainty. Wastewater surveillance has rapidly emerged as a potential tool to effectively monitor community infections for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through measuring trends of viral RNA signal in wastewater systems. In this study SARS-CoV-2 viral RNA N1 and N2 genes are quantified in solids collected from influent post grit solids (PGS) and primary clarified sludge (PCS) in two water resource recovery facilities (WRRF) serving Canada’s national capital region, i.e., the City of Ottawa, ON (pop. ≈ 1.1M) and the City of Gatineau, QC (pop. ≈ 280K). PCS samples show signal inhibition using RT-ddPCR compared to RT-qPCR, with PGS samples showing similar quantifiable concentrations of RNA using both assays. RT-qPCR shows higher frequency of detection of N1 and N2 genes in PCS (92.7, 90.6%) as compared to PGS samples (79.2, 82.3%). Sampling of PCS may therefore be an effective approach for SARS-CoV-2 viral quantification, especially during periods of declining and low COVID-19 incidence in the community. The pepper mild mottle virus (PMMV) is determined to have a less variable RNA signal in PCS over a three month period for two WRRFs, regardless of environmental conditions, compared to Bacteroides 16S rRNA or human eukaryotic 18S rRNA, making PMMV a potentially useful biomarker for normalization of SARS-CoV-2 signal. PMMV-normalized PCS RNA signal from WRRFs of two cities correlated with the regional public health epidemiological metrics, identifying PCS normalized to a fecal indicator (PMMV) as a potentially effective tool for monitoring trends during decreasing and low-incidence of infection of SARS-Cov-2 in communities.
Development and Validation of a Simple Risk Score for Diagnosing COVID-19 in the Emergency Room
Authors: Sung Joowhan , Choudry Naveed , Bachour Rima
Published: August 2020

As the COVID-19 pandemic continues to escalate and place pressure on hospital system resources, a proper screening and risk stratification score is essential. We aimed to develop a risk score to identify patients with increased risk of COVID-19, allowing proper identification and allocation of limited resources. A retrospective study was conducted of 338 patients who were admitted to the hospital from the emergency room and tested for COVID-19 at an acute care hospital in the Metropolitan Washington D.C. area. The dataset was split into development and validation sets with a ratio of 6:4. Demographics, presenting symptoms, sick contact, triage vital signs, initial laboratory and chest X-ray results were analyzed to develop a prediction model for COVID-19 diagnosis. Multivariable logistic regression was performed in a stepwise fashion to develop a prediction model, and a scoring system was created based on the coefficients of the final model. Among 338 patients admitted to the hospital from the emergency room, 136 (40.2%) patients tested positive for COVID-19 and 202 (59.8%) patients tested negative. Nursing facility residence (2 points), sick contact (2 points), constitutional symptom (1 point), respiratory symptom (1 point), gastrointestinal symptom (1 point), obesity (1 point), hypoxia at triage (1 point), and leukocytosis (−1 point) were included in the prediction score. A risk score for COVID-19 diagnosis achieved AUROC of 0.87 (95% CI 0.83-0.92) in the development dataset and 0.83 (95% CI 0.76-0.90) in the validation dataset. A risk prediction score for COVID-19 can be used as a supplemental tool to assist clinical decision to triage, test, and quarantine patients admitted to the hospital from the emergency room.
Displaying emergency patient estimated wait times: a multi-centre, qualitative study of patient, community, paramedic and health administrator perspectives
Authors: Walker Katie , Stephenson Melanie , Hutton Jennie , Loupis Anne , Joe Keith , Ben-Meir Michael , Martini Ella , Stephenson Michael , Lowthian Judy , Yip Beatrice , Wu Elena , Ho James , Blecher Gabriel , Hansen Kim , Buntine Paul
Published: August 2020

Background

Emergency Departments have the potential ability to predict patient wait times and to display this to patients and other stakeholders. Little is known about whether consumers and stakeholders would want this information and how wait time predictions might be used. The aim of this study was to gain perspectives from consumer, referrer and health services personnel regarding the concept of emergency wait time visibility.

Methods

In 2019, 103 semi-structured interviews and one focus group were conducted with emergency medicine patients/families, paramedics, well community members and hospital/paramedic administrators. Nine emergency departments and multiple organisations in Victoria, Australia, contributed data. Transcripts were coded and themes are presented.

Results

Consumers and paramedics face physical and psychological difficulties when wait times aren’t visible. Consumers believe about a 2-hour wait is tolerable, beyond this most begin to consider alternative strategies for seeking care. Consumers want to see triage to doctor times; paramedics want door to off-stretcher times (for all possible transport destinations); with 47/50 consumers and 30/31 paramedics potentially using this information. Twenty-eight of 50 consumers would use times to inform facility or provider choice, 19/50 want information once in the waiting room. During prolonged waits, 1/52 consumers would consider not seeking care. Visibility of approximate waits would better inform decision-making, improve load-spreading, allow planning and access to basic needs and might reduce anxiety.

Conclusions

Consumers and paramedics want wait time information visibility. They would use the information in a variety of ways, both pre-hospital and whilst waiting for care.
Extensive Genetic Diversity and Host Range of Rodent-borne Coronaviruses
Authors: Wang Wen , Lin Xian-Dan , Zhang Hai-Lin , Wang Miao-Ruo , Guan Xiao-Qing , Holmes Edward C. , Zhang Yong-Zhen
Published: August 2020

To better understand the genetic diversity, host association and evolution of coronaviruses (CoVs) in China we analyzed a total of 696 rodents encompassing 16 different species sampled from Zhejiang and Yunnan provinces. Based on the reverse transcriptase PCR-based CoV screening CoVs of fecal samples and subsequent sequence analysis of the RdRp gene, we identified CoVs in diverse rodent species, comprisingApodemus agrarius, Apodemus latronum, Bandicota indica, Eothenomys miletus, E. eleusis, Rattus andamanesis, Rattus norvegicus, andR. tanezumi. Apodemus chevrieriwas a particularly rich host, harboring 25 rodent CoVs. Genetic and phylogenetic analysis revealed the presence of three groups of CoVs carried by a range of rodents that were closely related to the Lucheng Rn rat coronavirus (LRNV), China Rattus coronavirus HKU24 (ChRCoV_HKU24) and Longquan Rl rat coronavirus (LRLV) identified previously. One newly identifiedA. chevrieri-associated virus closely related to LRNV lacked an NS2 gene. This virus had a similar genetic organization to AcCoV-JC34, recently discovered in the same rodent species in Yunnan, suggesting that it represents a new viral subtype. Notably, additional variants of LRNV were identified that contained putative nonstructural NS2b genes located downstream of the NS2 gene that were likely derived from the host genome. Recombination events were also identified in the ORF1a gene of Lijiang-71. In sum, these data reveal the substantial genetic diversity and genomic complexity of rodent-borne CoVs, and greatly extend our knowledge of these major wildlife virus reservoirs.
Obesity, old age and frailty are the true risk factors for COVID-19 mortality and not chronic disease or ethnicity in Croydon
Authors: Philipose Zinu , Smati Nadia , Wong Chun Shing Jefferson , Aspey Karen , Mendall Michael
Published: August 2020

Background

Coronavirus-19 (COVID-19) mortality in hospitalised patients is strongly associated with old age, nursing home residence, male sex and obesity, with a more controversial association with ethnicity and chronic diseases, in particular diabetes mellitus. Further complicating the evaluation of the independent impacts of these risk factors is the failure to control for frailty in the published studies thus far.

Aim

To determine the true risk factors for mortality in patients confirmed to have COVID-19 in Croydon needing hospital admission and to evaluate the independence of these risk factors in this group after adjusting for body mass index (BMI) and frailty.

Methods

This observational study retrospectively reviewed hospital electronic medical records of 466 consecutive patients who were admitted to Croydon University Hospital confirmed positive by rapid PCR test from 11th March 2020 to 9th April 2020. Statistical analysis was performed by multiple unconditional and univariate logistic regression.

Results

After multivariate analysis, male sex [OR 1.44 (CI 0.92-2.40)], age (per year) [OR 1.07 (CI 1.05-1.09)], morbid obesity (BMI > 40 kg/m2 vs reference BMI 18.5-24.9 kg/m2) [OR 14.8 (CI 5.25-41.8)], and nursing home residence (OR 3.01 (CI 1.56-5.79) were independently associated with COVID-19 mortality with no statistically significant association found with chronic diseases or ethnicity. In the non-nursing home population, after adjusting for age and sex, the odds ratio for type 2 diabetes mellitus (T2DM) as a risk factor was 1.64 (CI 1.03-2.61, p = 0.03) and was and was attenuated to 1.30 (CI 0.78-2.18)) after controlling for BMI; the association of mortality with male sex was strengthened [OR 1.66 (CI 0.96-2.87)] and that for ethnic minority patients was weakened [South Asians [from OR 1.30 (CI 0.67-2.53)) to OR 1.21 (CI 0.60-2.46)]; African Caribbeans [from OR 1.24 (CI 0.65-2.34) to OR 1.16 (CI 0.58-2.30)]. There was a borderline but potentially large protective effect (p= 0.09) in patients who were on anticoagulation drugs prior to admission [OR 0.56 (CI 0.28-1.11)].

Conclusion

Our study found no significant effect of ethnicity and chronic diseases as independent risk factors on COVID-19 mortality in Croydon population whereas male sex, high BMI, old age and frailty were found to be independent risk factors. Routine prophylactic treatment with anticoagulant drugs in the high-risk COVID-19 population warrants further prompt investigation.
Place and underlying cause of death during the COVID19 pandemic: retrospective cohort study of 3.5 million deaths in England and Wales, 2014 to 2020
Authors: Wu Jianhua , Malfam Marion , Mamas Mamas , Rashid Muhammad , Kontopantelis Evangelos , Deanfield John E , de Belder Mark A , Gale Chris P
Published: August 2020

Background

The COVID-19 pandemic has resulted in a high death toll. We aimed to describe the place and cause of death during the COVID-19 pandemic.

Methods

This national death registry included all adult (aged ≥18 years) deaths in England and Wales between 1st January 2014 and 30th June 2020. Analyses were based upon ICD-10 codes corresponding to the underlying cause of death as stated on the Medical Certificate of Cause of Death. Daily deaths during COVID-19 pandemic were compared against the expected daily deaths estimated using Farrington surveillance algorithm for daily historical data between 2014 and 2020, by place and cause of death.

Findings

Between 2nd March and 30th June 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (86.2%) were COVID-19 related. Almost half the excess deaths occurred in care homes (25,611 deaths) where deaths were 55% higher than expected. One fifth of the excess deaths occurred in hospital (15,938 deaths; a proportional increase of 21%) with the remainder occurring at home (16,190 deaths; a proportional increase of 39%). At home, only 14% of 16,190 excess deaths were related to COVID-19, with 5,963 deaths due to cancer and 2,485 deaths due to cardiac disease, very few of which involved COVID-19. In care homes or hospices, 61% of the 25,611 excess deaths were related to COVID-19, 5,539 of which were due to respiratory disease and most of these (4,315 deaths) involved COVID-19. In hospital, there were 16,174 fewer deaths than expected which did not involve COVID-19, and there were 4,088 fewer deaths due to cancer and 1,398 fewer deaths due to cardiac disease than expected.

Interpretation

The COVID-19 pandemic has resulted in a substantial increase in the absolute numbers of deaths occurring at home and care homes. There was a huge burden of excess deaths occurring in care homes, which were poorly characterised, and were likely to be, at least in part, the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, which suggests avoidance of hospital care for non-COVID-19 conditions.

Funding

The study is unfunded.
Immediate Effects of COVID-19 Outbreak on Psychiatric Outpatients: Posttraumatic Stress and Influencing Factors
Authors: Poyraz Burç Çağrı , Poyraz Cana Aksoy , Turan Şenol , Demirel Ömer Faruk , Kavla Yasin , Bulu Ersel , Hacısalihoğlu İrem , Ersungur Elif Burcu
Published: August 2020

We aimed to investigate the effects of COVID-19 outbreak and public health measures on the psychological well-being of patients with psychiatric disorders. This cross-sectional study assessed 436 outpatients recruited from a tertiary psychiatry clinic in Istanbul, Turkey, nearly one month after the government introduced strict measures of lockdown against the ongoing outbreak. Respondents completed a web-based survey on sociodemographic data, subjective sleep quality, and a range of psychiatric symptoms using the Impact of Events Scale-Revised (IES-R), and Hospital Anxiety and Depression Scale (HADS). Respondents reported high frequencies of clinically significant posttraumatic stress disorder (PTSD) (32.6%, IES-R score ≥ 33), anxiety (36.4%, HADS anxiety score > 10), and depression (51%, HADS depression score > 10). 20.5% of respondents described that their psychological status worsened during the COVID-19 outbreak, and 12.1% of respondents described poor or very poor sleep in the prior month. Positive predictors of increased PTSD symptoms included the chronic medical diseases, knowing someone in the social vicinity diagnosed with the COVID-19 infection, job loss or being on temporary leave after the outbreak, and increased exposure time to TV or social media. In contrast, male gender, older age, higher educational attainment, and the psychiatric diagnoses of schizophrenia and (to a lesser degree) bipolar disorder were the negative predictors. Our results suggest that patients with psychiatric disorders are prone to substantial psychological distress during the COVID-19 outbreak, and various individual, behavioral, and social factors mediate this effect.
Strengthening Policy Coding Methodologies to Improve COVID-19 Disease Modeling and Policy Responses: A Proposed Coding Framework and Recommendations
Authors: Lane Jeff , Garrison Michelle M. , Kelley James , Sarma Priya , Katz Aaron
Published: August 2020

In recent months, multiple efforts have sought to characterize COVID-19 social distancing policy responses. These efforts have used various coding frameworks, but most have relied on binary coding that may not adequately describe the gradient in social distancing policies as states “re-open.” We developed a COVID-19 social distancing intensity framework that is sufficiently specific and sensitive to capture this gradient. Based on a review of policies from a 12-state sample, we developed a social distancing intensity framework consisting of 16 domains and intensity scales of 0-5 for each domain. We found that the states with the highest average daily intensity from our sample were Pennsylvania, Washington, Colorado, California, and New Jersey, with Georgia, Florida, Massachusetts, and Texas having the lowest. While some domains (such as restaurants and movie theaters) showed bimodal policy intensity distributions compatible with binary (yes/no) coding, others (such as childcare and religious gatherings) showed broader variability that would be missed without more granular coding. We also present a range of methodological recommendations to strengthen COVID-19 comparative policy coding efforts.
Comparative Evaluation of SARS-CoV-2 IgG Assays in India
Authors:   DBT India Consortium for Covid-19 Research, Shinjini Bhatnagar
Published: August 2020

IgG immunoassays have been developed and used widely for clinical samples and serosurveys for SARS-CoV-2. We compared the performance of three immunoassays, an in-house RBD assay, and two commercial assays, the Diasorin LIAISON SARS-CoV-2 IgG CLIA which detects antibodies against S1/S2 domains of the Spike protein and the Zydus Kavach assay based on inactivated virus using a well-characterized sera-panel. 379 sera/plasma samples from RT-PCR positive individuals >20 days of illness in symptomatic or RT-PCR positivity in asymptomatic individuals and 184 pre-pandemic samples were used. The sensitivity of the assays were 84.7, 82.6 and 75.7 respectively for RBD, LIAISON and Kavach. Kavach and the in-house RBD ELISA showed a specificity of 99.5% and 100%, respectively. The RBD and LIAISON (S1/S2) assays showed high agreement (94.7%;95%CI:92.0,96.6) and were able to correctly identify more positives than Kavach. All three assays are suitable for serosurveillance studies, but in low prevalence sites, estimation of exposure may require adjustment based on our findings.
The genetic variation landscape of African swine fever virus reveals frequent positive selection and adaptive flexibility
Authors: Bao Yun-Juan , Qiu Junhui , Luo Yuzi , Rodríguez Fernando , Qiu Hua-Ji
Published: August 2020

African swine fever virus (ASFV) is a lethal disease agent that causes high mortality in swine population and devastating loss in swine industries. The development of efficacious vaccines has been hindered by the gap in knowledge concerning genetic variation of ASFV and the genetic factors involved in host adaptation and virus-host interactions. In this study, we performed a meta-genetic study of ASFV aiming to profile the variation landscape and identify genetic factors with signatures of positive selection and relevance to host adaptation. Our data reveals a high level of genetic variability of ASFV shaped by both diversifying selection and selective sweep. The selection signatures are widely distributed across the genome with the diversifying selection falling within 29 genes and selection sweep within 25 genes, highlighting strong signals of adaptive evolution of ASFV. Further examination of the sequence properties reveals the link of the selection signatures with virus-host interactions and adaptive flexibility. Specifically, we discovered a site at 157th of the key antigen protein EP402R under diversifying selection, which is located in the cytotoxic T-cell epitope related with the low level of cross-reaction in T-cell response. Importantly, two multigene families MGF360 and MGF505, the host range factors of ASFV, exhibit divergent selection among the paralogous members, conferring sequence pools for genetic diversification and adaptive capability. By integrating the genes with selection signatures into a unified framework of interactions between ASFV and hosts, we showed that the genes are involved in multiple processes of host immune interaction and virus life cycles, and may play crucial roles in circumventing host defense systems and enhancing adaptive fitness. Our findings will allow enhanced understanding of genetic basis of rapid spreading and adaptation of ASFV among the hosts.
Precise Prediction of COVID-19 in Chest X-Ray Images Using KE Sieve Algorithm
Authors: Thejeshwar S Sai , Chokkareddy Chaitanya , Eswaran K
Published: August 2020

The novel coronavirus (COVID-19) pandemic is pressurizing the healthcare systems across the globe and few of them are on the verge of failing. The detection of this virus as early as possible will help in contaminating the spread of it as the virus is mutating itself as fast as possible and currently there are about 4,300 strains of the virus according to the reports. Clinical studies have shown that most of the COVID-19 patients suffer from a lung infection similar to influenza. So, it is possible to diagnose lung infection using imaging techniques. Although a chest computed tomography (CT) scan has been shown to be an effective imaging technique for lung-related disease diagnosis, chest X-ray is more widely available across the hospitals due to its considerably lower cost and faster imaging time than CT scan. The advancements in the area of machine learning and pattern recognition has resulted in intelligent systems that analyze CT Scans or X-ray images and classify between pneumonia and normal patients. This paper proposes KE Sieve Neural Network architecture, which helps in the rapid diagnosis of COVID-19 using chest X-ray images. This architecture is achieving an accuracy of 98.49%. This noninvasive prediction method can assist the doctors in this pandemic and reduce the stress on health care systems.
The Mehler reaction site is the Phylloquinone within Photosystem I
Authors: Kozuleva Marina , Petrova Anastasia , Milrad Yuval , Semenov Alexey , Ivanov Boris , Redding Kevin E. , Yacoby Iftach
Published: August 2020

Photosynthesis is a vital process, responsible for fixing carbon dioxide, and producing most of the organic matter on the planet. However, photosynthesis has some inherent limitations in utilizing solar energy. Up to a third of the energy absorbed is lost in the reduction of O2to produce the superoxide radical (O2•−), which occurs principally within photosystem I (PSI)viathe Mehler reaction. Strikingly, the precise location as well as the evolutionary role of the reaction have long been a matter of debate. For decades, O2reduction was assumed to take place solely in the distal iron-sulfur clusters of PSI rather than within the two asymmetrical cofactor branches. Here we demonstrate that under high irradiance, O2photoreduction by PSI takes place at the phylloquinone of one of the branches (the A-branch). This conclusion derives from the light dependency of the O2photoreduction rate constant, and from the high rates of O2photoreduction in PSI complexes lacking iron-sulfur clusters and in a mutant PSI, in which the lifetime of this phyllosemiquinone state is extended 100-fold. On these grounds, we suggest that the Mehler reaction serves as a release valve, functioning only when needed, under conditions where both the distal iron-sulfur clusters of PSI and the mobile ferredoxin pool are over reduced.

SIGNIFICANCE STATEMENT

Photosynthesis is the process responsible for the oxygenation of the ancient anoxic atmosphere, and the transformation of inorganic carbon to most of the organic matter on Earth. However, it is less commonly appreciated that the appearance of oxygen in the atmosphere led to the unavoidable opposite process in which oxygen is consumed, thereby producing deleterious oxygen radicals such as the superoxide radical. For almost half a decade, the location of the main site of superoxide radical production in chloroplasts has been a matter of debate. We now provide conclusive evidence that it is located in the phylloquinones(s) within photosystem I.
Temporal instability of lake charr phenotypes: synchronicity of growth rates and morphology linked to environmental variables?
Authors: Chavarie L. , Voelker Steve , Hansen M.J. , Bronte C.R. , Muir A.M. , Zimmerman M.S. , Krueger C.C.
Published: August 2020

Pathways through which phenotypic variation arises among individuals arise can be complex. One assumption often made in relation to intraspecific diversity is that the stability or predictability of the environment will interact with expression of the underlying phenotypic variation. To address biological complexity below the species level, we investigated variability across years in morphology and annual growth increments between and within two sympatric lake charr ecotypes in Rush Lake, USA. We found a rapid phenotypic shift in body and head shape within a decade. The magnitude and direction of the observed phenotypic change was consistent in both ecotypes, which suggests similar pathways caused the temporal variation over time. Over the same time period, annual growth increments declined for both lake charr ecotypes and corresponded with a consistent phenotypic shift of each ecotype. Despite ecotype-specific annual growth changes in response to winter conditions, the observed annual growth shift for both ecotypes was linked, to some degree, with variation in the environment. Particularly, a declining trend in regional cloud cover was associated with an increase of early stage (age 1-3) annual growth for lake charr of Rush Lake. Underlying mechanisms causing reduced growth rates and constrained morphological modulation are not fully understood. An improved knowledge of the biology hidden within the expression of phenotypic variation promises to clarify our understanding of temporal morphological diversity and instability.
The Macerprep: a minimalist kit- and enzyme-free high-yield miniprep utilising alkaline lysis and alkaline hydrolysis principles
Authors: Hu Ian
Published: August 2020

The commercialisation of miniprep kits supplanted the original alkaline lysis method for plasmid DNA preparation, and had remained relatively unchanged for almost two decades. The Miraprep substantially improved the yields of miniprep kits. However, the method still relies on commercial kits, which can be a burden financially to certain projects. Additionally, Pronobis et al. also identified loss of RNAse activities in miniprep kits over time. The present novel plasmid DNA isolation protocol addresses the two issues mentioned above utilising alkaline lysis and alkaline hydrolysis principles. With a largely identical workflow and operation time, the Macerprep will significantly reduce costs of establishing new laboratories as well as maintenance of running molecular biology laboratories.
D-graph clusters flaviviruses and β-coronaviruses according to their hosts, disease type and human cell receptors
Authors: Braun Benjamin A. , Schein Catherine H. , Braun Werner
Published: August 2020

Motivation

There is a need for rapid and easy to use, alignment free methods to cluster large groups of protein sequence data. Commonly used phylogenetic trees based on alignments can be used to visualize only a limited number of protein sequences. DGraph, introduced here, is a dynamic programming application developed to generate 2D-maps based on similarity scores for sequences. The program automatically calculates and graphically displays property distance (PD) scores based on physico-chemical property (PCP) similarities from an unaligned list of FASTA files. Such “PD-graphs” show the interrelatedness of the sequences, whereby clusters can reveal deeper connectivities.

Results

PD-Graphs generated for flavivirus (FV), enterovirus (EV), and coronavirus (CoV) sequences from complete polyproteins or individual proteins are consistent with biological data on vector types, hosts, cellular receptors and disease phenotypes. PD-graphs separate the tick- from the mosquito-borne FV, clusters viruses that infect bats, camels, seabirds and humans separately and the clusters correlate with disease phenotype. The PD method segregates the β-CoV spike proteins of SARS, SARS-CoV-2, and MERS sequences from other human pathogenic CoV, with clustering consistent with cellular receptor usage. The graphs also suggest evolutionary relationships that may be difficult to determine with conventional bootstrapping methods that require postulating an ancestral sequence.

Availability and implementation

DGraph is written in Java, compatible with the Java 5 runtime or newer. Source code and executable is available from the GitHub website (https://github.com/bjmnbraun/DGraph/releases). Documentation for installation and use of the software is available from the Readme.md file at (https://github.com/bjmnbraun/DGraph).

Contact

bjmnbraun@gmail.comorwebraun@utmb.edu

Supplementary information

Supplementary information Table S1 and Fig. S1 are online available.
Single position substitution of hairpin pyrrole-imidazole polyamides imparts distinct DNA-binding profiles across the human genome
Authors: Finn Paul B. , Bhimsaria Devesh , Ali Asfa , Eguchi Asuka , Ansari Aseem Z. , Dervan Peter B.
Published: August 2020

Regulating desired loci in the genome with sequence-specific DNA-binding molecules is a major goal for the development of precision medicine. Pyrrole–imidazole (Py–Im) polyamides are synthetic molecules that can be rationally designed to target specific DNA sequences to both disrupt and recruit transcriptional machinery. Whilein vitrobinding has been extensively studied,in vivoeffects are often difficult to predict using current models of DNA binding. Determining the impact of genomic architecture and the local chromatin landscape on polyamide-DNA sequence specificity remains an unresolved question that impedes their effective deploymentin vivo. In this report we identified polyamide–DNA interaction sites across the entire genome, by covalently crosslinking and capturing these events in the nuclei of human LNCaP cells. This method, termed COSMIC-seq, confirms the ability of hairpin-polyamides, with similar architectures but differing at a single ring position, to retainin vitrospecificities and display distinct genome-wide binding profiles. These results underpin the development of Py-Im polyamides as DNA-targeting molecules that mediate their regulatory or remedial functions at desired genomic loci.
Structure Basis of Cav1.1 Modulation by Dihydropyridine Compounds
Authors: Gao Shuai , Yan Nieng
Published: August 2020

1,4-Dihydropyridines (DHP), the most commonly used antihypertensives, function by inhibiting the L-type voltage-gated Ca2+(Cav) channels. DHP compounds exhibit chirality-specific antagonistic or agonistic effects. Recent structural elucidation of rabbit Cav1.1 bound to an achiral drug nifedipine reveals the general binding mode for DHP drugs, but the molecular basis for chiral specificity remains elusive. Here, we report five cryo-EM structures of nanodisc-embedded Cav1.1 in the presence of the bestselling drug amlodipine, a DHP antagonist (R)-(+)-Bay K8644, and a titration of its agonistic enantiomer (S)-(-)-Bay K8644 at resolutions of 2.9-3.4 Å. The amlodipine-bound structure reveals the molecular basis for the high efficacy of the drug. All structures with the addition of the Bay K8644 enantiomers exhibit similar inactivated conformations, suggesting that the agonistic effect of (S)-(-)-Bay K8644 might be transient. The similarity of these structures to that obtained in detergent micelles alleviates the concerns about potential structural perturbation by detergents.
Somatic structural variation targets neurodevelopmental genes and identifies SHANK2 as a tumor suppressor in neuroblastoma
Authors: Lopez Gonzalo , Conkrite Karina L. , Doepner Miriam , Rathi Komal S. , Modi Apexa , Vaksman Zalman , Farra Lance M. , Hyson Eric , Noureddine Moataz , Wei Jun S. , Smith Malcolm A. , Asgharzadeh Shahab , Seeger Robert C. , Khan Javed , Auvil Jaime Guidry , Gerhard Daniela S. , Maris John M. , Diskin Sharon J.
Published: August 2020

Neuroblastoma is a malignancy of the developing sympathetic nervous system that accounts for 12% of childhood cancer deaths. Like many childhood cancers, neuroblastoma shows a relative paucity of somatic single-nucleotide variants (SNVs) and small insertions and deletions (indels) compared to adult cancers. Here, we assessed the contribution of somatic structural variation (SV) in neuroblastoma using a combination of whole-genome sequencing (WGS) of tumor-normal pairs (n = 135) and single-nucleotide polymorphism (SNP) genotyping of primary tumors (n = 914). Our study design allowed for orthogonal validation and replication across platforms. SV frequency, type, and localization varied significantly among high-risk tumors. MYCN nonamplified high-risk tumors harbored an increased SV burden overall, including a significant excess of tandem duplication events across the genome. Genes disrupted by SV breakpoints were enriched in neuronal lineages and associated with phenotypes such as autism spectrum disorder (ASD). The postsynaptic adapter protein-coding gene, SHANK2, located on Chromosome 11q13, was disrupted by SVs in 14% of MYCN nonamplified high-risk tumors based on WGS and 10% in the SNP array cohort. Expression of SHANK2 was low across human-derived neuroblastoma cell lines and high-risk neuroblastoma tumors. Forced expression of SHANK2 in neuroblastoma cells resulted in significant growth inhibition (P = 2.6 × 10−2 to 3.4 × 10−5) and accelerated neuronal differentiation following treatment with all-trans retinoic acid (P = 3.1 × 10−13 to 2.4 × 10−30). These data further define the complex landscape of somatic structural variation in neuroblastoma and suggest that events leading to deregulation of neurodevelopmental processes, such as inactivation of SHANK2, are key mediators of tumorigenesis in this childhood cancer.
X-ray phase-contrast topography to measure the surface stress and bulk strain in a silicon crystal
Authors: Massa E. , Sasso C. P. , Fretto M. , Martino L. , Mana G.
Published: August 2020

The measurement of the Si lattice parameter by X-ray interferometry assumes the use of strain-free crystals, which might not be true because of intrinsic stresses due to surface relaxation, reconstruction and oxidation. X-ray phase-contrast topography was used to investigate the strain sensitivity to the finishing, annealing and coating of interferometer crystals. The topography capabilities were assessed by measuring the lattice strain due to films of copper deposited on the interferometer mirror crystal. A by-product has been the measurement of the surface stresses after complete relaxation of the coatings.
Exemplary followership. Part 2: impact of organizational citizenship behavior
Authors: Peterson Tim O. , Peterson Claudette M.
Published: August 2020

Purpose

The purpose of this study is to determine to what extent there is a predictive relationship between organizational citizenship behaviors (OCB) and followership behaviors within medical organizations in the USA. This is the second part of a two-part paper. It uses a revised followership instrument and an OCB instrument to determine if there is a predictive relationship between OCB and followership behaviors.

Design/methodology/approach

Part 1 of this quantitative survey-based empirical study used confirmatory factor analysis on an existing instrument and exploratory factor analysis on a revised instrument. Part 2 used regression analysis to explore the predictive relationship between followership and organizational citizenship.

Findings

The overall findings of this two-part paper show that organizational citizenship has a significant predictive impact on followership behaviors.

Research limitations/implications

Participants in this study work exclusively in the health care industry; future research should expand to other industries and other large organizations that have many followers but few managerial leaders.

Practical implications

As organizational citizenship can be developed and there is a predictive relationship between organizational citizenship and followership, organizations can develop professional development for individual followers. Managers and other leaders can learn how to develop OCB, and thus followership in several ways: onboarding, coaching, mentoring and executive development.

Originality/value

Part 2 of this paper demonstrates the predictive impact that OCB can have in developing high performing followers.
Preventive maintenance optimization of sugarcane harvester machine based on FT-Bayesian network reliability
Authors: Afsharnia Fatemeh , Marzban Afshin , Asoodar Mohammadamin , Abdeshahi Abas
Published: August 2020

Purpose

The purpose of this paper is to optimize the preventive maintenance based on fault tree (FT)–Bayesian network (BN) reliability for sugarcane harvester machine as a fundamental machine in the sugar industry that must be operated failure-free during a given period of the harvesting process.

Design/methodology/approach

To determine machine reliability using the algorithm developed based on mapping FTs into BNs, the common failures of 168 machines were carefully investigated over 12 years (2007–2019). This algorithm was then used to predict the harvester reliability, estimate delays by machine downtimes and their consequences on white sugar production losses that can be reduced by optimizing the preventive maintenance scheduling.

Findings

The optimization of preventive maintenance scheduling based on estimated reliability of sugarcane harvester machines using FT–BNs can reduce white sugar production losses, the operation-stopping breakdowns and the downtime costs as a crisis that the sugar industry is facing.

Practical implications

Machine reliability gradually decreased by 31.08% approximately, which resulted in a working time loss of 26% in the 2018–19 harvesting season. In total, the white sugar losses were estimated as 204.17 tons for burnt canes and 114.53 tons for green canes. The losses of the 2018–19 harvesting season have been 11.85 times greater than the first harvesting season. The proposed maintenance interval for critical subsystems including the hydraulic, chopper and base cutter were obtained as 1.815, 1.12 and 1.05 h, respectively.

Originality/value

In this study, a new approach was used to optimize preventive maintenance to reduce delays and their implications upon costs in time, inconvenience and white sugar losses. The FT–BNs algorithm was found a useful tool that was over-fitting of failure occurrence probabilities data for sugarcane harvester machine.
Institutions and economic growth in ECOWAS: an investigation into the hierarchy of institution hypothesis (HIH)
Authors: Olaoye Olumide , Aderajo Oluwatosin
Published: August 2020

Purpose

The purpose of this paper is to examine the relationship between the quality of different dimensions of institutional and economic growth in a panel of 15 member ECOWAS.

Design/methodology/approach

The study adopts Driscoll and Kraay′s nonparametric covariance matrix estimator, and the spatial error model to account for cross-section dependency, cross-country heterogeneity and spatial dependence inherent in empirical modelling, which has largely been ignored in previous studies. This is because, the likelihood that corruption and human capital cluster in space is very high because factors that affect these phenomena disperse across borders. Similarly, to test the threshold effect, the study adopts the more refined and more appropriate dynamic panel data which models a nonlinear asymmetric dynamics and cross-sectional heterogeneity, simultaneously, in a dynamic threshold panel data framework.

Findings

The empirical evidence supports findings by previous researchers that better-quality political and economic institutions can have positive effects on economic growth. Similarly, our results support a nonlinear relationship between political institutions and economic institution, confirming the “hierarchy of institution hypothesis” in ECOWAS. Specifically, the findings show that economic institutions will only have the desired economic outcome in ECOWAS, only when political institution is above a certain threshold.

Originality/value

Unlike previous studies which assume cross-sectional and spatial independence, the authors account for cross-section dependency and cross-country heterogeneity inherent in empirical modelling.

Peer review

The peer review history for this article is available at:https://publons.com/publon/10.1108/IJSE-10-2019-0630
Vitality among university students: exploring the role of gratitude and resilience
Authors: Garg Naval , Sarkar Ayatakshee
Published: August 2020

Purpose

Vitality is an occurrence of having extremely high energy, stamina, physical or mental vigor. This study tends to investigate whether gratitude and resilience lead to vitality. In particular, it tends to examine the necessity and sufficiency of gratitude and resilience for vitality among Indian university students.

Design/methodology/approach

The collected data are analyzed with the help of different statistical tools like the measure of central tendency, standard deviation, correlation, linear and multiple regression, and necessary condition analysis.

Findings

The results establish both gratitude and resilience as sufficient and necessary conditions for the occurrence of vitality among students. Theoretical and practical implications, along with scope for future researchers, are also elaborated.

Practical implications

Though universities are the active change agents and change-makers in the lives of the students, the onus of positive transformation lies on both students and the university administration. Hence these prosocial measures like gratitude and resilience, which are self-regulating, self-professed and competent, help to build internal psychological resources to promote sustainable vitality.

Originality/value

The present study is probably the first study that explores sufficiency and necessity of resilience and gratitude for vitality among students. The findings suggest that university administration may rely on gratitude and resilience-based interventions to enhance vitality of students.
Consumer buying behaviour and purchase intention of organic food: a conceptual framework
Authors: Dangi Neeraj , Gupta Sandeep Kumar , Narula Sapna A.
Published: August 2020

Purpose

The paper aims to investigate existing research in factors impacting organic food purchase with special reference to eco-labels and identify the relative influence of various determinants.

Design/methodology/approach

A conceptual framework is proposed of organic food buying behaviour after analysing a sample of 154,072 consumers reported in 91 research studies from 2001–2020. The factors are categorised into four categories on the basis of relatedness. In addition, the factors were analysed based on time, region and national economic status.

Findings

The impact of consumer psychographics, socio-demographic and product-related factor categories were found to be more pronounced compared to supply-related factor category. The results show that among individual factors like health concern, environment concern, knowledge and awareness, eco-labels and price followed by trust in organic food are the most important factors in organic food purchase. The findings suggest that eco-labels increase trust in organic food by reducing information asymmetry in consumers. However, there were differences in perception and factors importance between high-income economies and emerging economies.

Originality/value

The study is unique, as it analyses secondary research based on criteria of high-income economies and emerging economies. The conceptual framework can also be incorporated further into different cognitive models like the theory of planned behaviour.
Usefulness of 2‐D shear wave elastography for the diagnosis of inguinal lymph node metastasis of malignant melanoma and squamous cell carcinoma
Authors: Kawahara Yu , Togawa Yaei , Yamamoto Yosuke , Wakabayashi Seiichiro , Matsue Hiroyuki , Inafuku Kazuhiro
Published: August 2020

We used 2‐D shear wave elastography to quantify lymph node hardness, from the shear wave velocity, to determine the presence or absence of metastatic lymphadenopathy in the inguinal lymph nodes of five patients with malignant melanoma and squamous cell carcinoma. The shear wave velocity accurately identified all cases of metastasis confirmed by histology, compared with two false‐positive and one false‐negative finding with positron emission tomography/computed tomography. 2‐D shear wave elastography would be useful to evaluate inguinal lymph node metastasis.
More than words: the chemistry behind the interactions in the plant holobiont
Authors: Berlanga‐Clavero María Victoria , Molina‐Santiago Carlos , de Vicente Antonio , Romero Diego
Published: August 2020

Plants and microbes have evolved sophisticated ways to communicate and coexist. The simplest interactions that occur in plant‐associated habitats, i.e., those involved in disease detection, depend on the production of microbial pathogenic and virulence factors and the host's evolved immunological response. In contrast, microbes can also be beneficial for their host plants in a number of ways, including fighting pathogens and promoting plant growth. In order to clarify the mechanisms directly involved in these various plant–microbe interactions, we must still deepen our understanding of how these interkingdom communication systems, which are constantly modulated by resident microbial activity, are established and, most importantly, how their effects can span physically separated plant compartments. Efforts in this direction have revealed a complex and interconnected network of molecules and associated metabolic pathways that modulate plant–microbe and microbe–microbe communication pathways to regulate diverse ecological responses. Once sufficiently understood, these pathways will be biotechnologically exploitable, for example, in the use of beneficial microbes in sustainable agriculture. The aim of this review is to present the latest findings on the dazzlingly diverse arsenal of molecules that efficiently mediate specific microbe–microbe and microbe–plant communication pathways during plant development and on different plant organs.