bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of corneal biomechanical behavior in vivo for healthy and keratoconic eyes using the stress–strain index
Authors: Padmanabhan Prema , Lopes Bernardo T. , Eliasy Ashkan , Abass Ahmed , Vinciguerra Riccardo , Vinciguerra Paolo , Ambrósio Renato , Elsheikh Ahmed
Published: March 2022

Purpose:

To evaluate the characteristics of corneal material properties in healthy individuals and keratoconic patients using the stress–strain index (SSI).

Setting:

Vincieye Clinic in Milan, Italy, and Instituto de Olhos Renato Ambrósio in Rio de Janeiro, Brazil.

Design:

Retrospective observational cross-sectional study.

Methods:

Records of 1221 patients were divided into 3 groups: healthy corneas (n = 728), bilateral keratoconus (KC, n = 388), and very asymmetric ectasia (VAE, n = 105) when patients presented with clinical ectasia in 1 eye and normal topography (VAE-NT) in the fellow eye. All patients were examined with Pentacam HR and Corvis ST. Severity of KC cases was stratified according to the Pentacam topographic KC classification. The SSI distribution across the different groups and its correlation with age, biomechanically corrected intraocular pressure (bIOP), and central corneal thickness (CCT) were assessed.

Results:

A statistically significant difference between healthy individuals and each of the keratoconic groups (P < .001) was observed, and a progressive reduction in the SSI was observed across the groups. A significant correlation was observed between the SSI and age in all groups (P < .010) but KC severe subgroup (P = .361). No correlation between the SSI and bIOP and CCT was observed in all KC subgroups and VAE-NT groups (P > .050). Among healthy eyes, there was only a mild correlation between the SSI and bIOP (R = 0.12, P = .002) and CCT (R = 0.13, P = .001).

Conclusions:

This study estimates the in vivo corneal material properties in healthy individuals and patients with KC using a new method. The SSI showed a progressive deterioration within the advance in disease stages while being relatively independent of bIOP and CCT but positively correlated with age.
Impact of Discharge Medication Reconciliation Across a Five-Hospital Health System
Authors: Lee Veronica , Kowalski Jaclyn , Liu Michael , Thayer Bailey
Published: March 2022

Purpose:

Hospital readmission of a primary diagnosis can have a substantial financial impact via reductions in reimbursement rates up to 3%, and have a negative impact on the lives of patients. Discharge medication reconciliation (DMR) can reduce medication errors that play a role in readmission. The objective of this study is to evaluate the impact of expanding pharmacist-led DMR across a four hospital health system on 30-day readmission rate for high risk of readmission disease groups.

Methods:

During the 3-month period, DMR was performed for patients with at least one of the disease states associated with a high risk for 30-day readmission, including chronic obstructive pulmonary disease, pneumonia, congestive heart failure, or acute myocardial infarction.

Results:

The 30-day readmission rate for patients with a high risk for readmission disease state significantly decreased from 17.5% to 15.5% in the pre-expansion to postexpansion phase, respectively (p = .003). Discharge medication reconciliation capture rate increased from 28% pre-expansion to 35% postexpansion. After expansion, the number of DMR interventions reported by pharmacists increased 2.93 times.

Conclusion:

Expansion of pharmacist-led DMR as a form of transitions of care significantly decreased 30-day readmission rate for high risk of readmission disease groups.
Clinician Perspectives on How to Hold Earlier Discussions About Palliative and End-of-Life Care With Chronic Obstructive Pulmonary Disease Patients
Authors: Tavares Nuno , Jarrett Nikki , Wilkinson Tom , Hunt Katherine
Published: March 2022

Chronic obstructive pulmonary disease is associated with progressive symptoms and increased treatment burden, especially at the end of life. However, most patients do not receive palliative care until late in their lives or discuss their end-of-life preferences with clinicians. This study explored clinicians' perspectives on the timing and nature of palliative care discussions.

Qualitative interviews were conducted with 7 physicians and 7 nurses working in primary and secondary care settings. Data were analyzed using a thematic analysis. Participants advocated for early, gradual, and informed palliative and future care discussions, because these discussions were thought to be less traumatic and better accepted by patients. Despite this, patient- and clinician-related barriers severely affected clinicians' ability to start discussions at earlier stages. Participants felt many patients were not ready for these discussions and feared damaging hope if the subject was broached. Therefore, clinicians delayed discussions until patients approached the end of life.

Stand-alone conversations about and near the end of life were described as current practice; however, clinicians believed these discussions reduced patients' hope and were potentially upsetting. Instead, individualized early, regular, and gradual discussions about immediate and long-term care plans were thought to be less negative and be better accepted.
Palliative Care Masterclass for Nurses in Central-Eastern Europe
Authors: Mitrea Nicoleta , Gerzevitz Diane , Mathe Teodora , Steller Julie , White Patricia , Ferszt Ginette , DeSanto-Madeya Susan
Published: March 2022

Given the increased need for palliative care services globally, the education of nurses has become paramount. In response, a group of nurses from Romania and the United States developed diverse nursing educational programs to meet the palliative care educational needs of nurses in Central-Eastern European countries. The purpose of this article is to describe a palliative nursing masterclass that was offered virtually to 59 participants, primarily nurses but also other health care professionals, from 11 Central-Eastern European countries.
Circulating Plasma Epstein-Barr Virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma
Authors: He Sha-sha , Wang Yan , Yang Yun-ying , Niu Shao-qing , Zhu Mei-yan , Lu Li-xia , Chen Yong
Published: March 2022

Background

Epstein-Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma (NPC), whereas the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival.

Methods

We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan-Meier estimates. Twelve- and 24-month landmark analyses for overall survival (OS) data were performed according to the EBV groups.

Results

Patients with post-EBV of less than 2500 copies/mL achieved better survival than did those with higher ones. Furthermore, patients with continuously elevated EBV DNA expressed significantly poorer OS (hazard ratio [HR], 2.542, 95% confidence interval [CI], 2.077–3.111; P < 0.001), distant metastasis-free survival (HR, 2.970; 95% CI, 2.392–3.687; P < 0.001), locoregional-free survival (HR, 1.699; 95% CI, 1.072–2.692; P = 0.013), and progression-free survival (HR, 2.535; 95% CI, 1.987–3.233; P < 0.001) than did patients with continuously normal EBV or those with elevated levels at any time point. The 5-year OS with elevated EBV was lower than that of the remission group by using the 12- and 24-month landmark analysis.

Conclusions

Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis, and unfavorable prognosis for NPC. In addition, there were consistent patterns of EBV DNA kinetics during long-term follow-up, which warrant further study.
Maritimibacter dapengensis sp. nov., a poly-β-hydroxyalkanoates-producing bacterium isolated from sediment of the Dapeng peninsula (Guangdong, China)
Authors: Yu Sheng-yang , Zheng Wei-shuang , Huang Yi
Published: March 2022

A Gram-negative, obligate aerobic, non-motile, rod-shaped bacterium lacking a flagellum, was isolated from sediment sampled at the Dapeng peninsula of Shenzhen, Guangdong, China, and designated strain DP4N28-5T. Growth of strain DP4N28-5T occurred at 15–45 °C (optimum at 30 °C), pH 6.0–8.0 (optimum at 6.0) and in 2.0–10.0 % NaCl (w/v; optimum at 2.0–3.0 %). The 16S rRNA gene sequence analysis revealed that strain DP4N28-5T was most closely related to

Maritimibacter alkaliphilus

DSM 100037T (97.6 %; sequence similarity). The strain synthesized a trace amount of poly-β-hydroxybutyrate. The dominant cellular fatty acids were summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c), C16 : 0, 11-mehtyl C18 : 1
 ω7c and C16 : 0 2-OH. The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmethylethanolamine, one unidentified aminophospholipid, three unidentified aminolipids and four unidentified lipids. The respiratory quinone was Q-10. The DNA G+C content was 62.0 mol% and the estimated genome size was 3.9 Mbp. The calculated average nucleotide value between strain DP4N28-5T and

M. alkaliphilus

DSM 100037T was 78.1 %. The phenotypic, genotypic and chemotaxonomic differences between strain DP4N28-5T and its phylogenetic relatives indicate that DP4N28-5T represents a novel species in the genus

Maritimibacter

, for which the name Maritimibacter dapengensis sp. nov. is proposed. The type strain is DP4N28-5T (=MCCC 1K05640T=KCTC 82805T). The description of genus

Maritimibacter

was emended to include this new species.
A paean to the ineffable Marjory Stephenson
Authors: Sargent Frank , Sawers R. Gary
Published: March 2022

It is now 75 years since Marjory Stephenson became the second President of the Society for General Microbiology (SGM). Around the time of her death at the end of 1948 many articles appeared extolling Marjory Stephenson’s contribution to the fields of Biochemistry and Microbiology. Not that much has been written about her since that time, which is unfortunate. Therefore, this brief review is intended as a form of redress and aims to highlight the role of this remarkable scientist in establishing the Society and in promoting Microbiology as a discipline. Notwithstanding the significance of these achievements, however, it is her overall impact on the field of ‘Chemical Microbiology’ and what she achieved through her research that are extraordinary, even by today’s standards. Marjory Stephenson recognized that in order to understand a biological system, the ‘whole’ organism must be considered and this can only be achieved by adopting an interdisciplinary approach: inorganic and organic chemistry, biochemistry, genetics, metabolism and ultimately physiology. Her scientific ethos serves today as a beacon for how scientific research should be conducted, and what we as scientists can learn about how to inspire and mentor the next generation. It is impossible to overstate Marjory Stephenson’s scientific legacy, or her overall contribution to Microbiology.
Positive selection in gamete interaction proteins inCarnivora
Authors: Pisciottano Francisco , Campos Clara , Penna Clementina , Bruque Carlos David , Gabaldón Toni , Saragüeta Patricia
Published: March 2022

The absence of robust interspecific isolation barriers among pantherines, including the iconic South American jaguar (Panthera onca), led us to study molecular evolution of typically rapidly evolving reproductive proteins within this subfamily and related groups. In this study, we delved into the evolutionary forces acting on the Zona Pellucida (ZP) gamete interaction protein family and the sperm-oocyte fusion protein pair IZUMO1-JUNO across theCarnivoraorder, distinguishing betweenCaniformiaandFeliformiasuborders and anticipating few significant diversifying changes in thePantherinaesubfamily. A chromosome-resolved jaguar genome assembly facilitated coding sequences, enabling the reconstruction of protein evolutionary histories. Examining sequence variability across more than 30 Carnivora species revealed thatFeliformiaexhibited significantly lower diversity compared to its sister taxa,Caniformia. Molecular evolution analyses of ZP2 and ZP3, subunits directly involved in sperm-recognition, unveiled diversifying positive selection inFeliformia,Caniformia, andPantherinae, although no significant changes were linked to sperm binding. Structural cross-linking ZP subunits, ZP4, and ZP1 exhibited lower levels or complete absence of positive selection. Notably, the fusion protein IZUMO1 displayed prominent positive selection signatures and sites in basal lineages of bothCaniformiaandFeliformia, extending along theCaniformiasubtree but absent inPantherinae. Conversely, JUNO did not exhibit any positive selection signatures across tested lineages and clades. Eight Caniformia-specific positive selected sites in IZUMO1 were detected within two JUNO-interaction clusters. Our findings provide for the first time insights into the evolutionary trajectories of ZP proteins and the IZUMO1-JUNO gamete interaction pair within theCarnivoraorder.
Global, regional, and cryptic population structure in a high gene-flow transatlantic fish
Authors: Jansson Eeva , Faust Ellika , Bekkevold Dorte , Quintela María , Durif Caroline , Halvorsen Kim Tallaksen , Dahle Geir , Pampoulie Christophe S. , Kennedy James , Whittaker Benjamin , Unneland Laila , André Carl , Glover Kevin A.
Published: March 2022

1

Lumpfish (Cyclopterus lumpus) is a transatlantic marine fish displaying large population sizes and a high potential for dispersal and gene-flow. These features are expected to result in weak population structure. Here, we investigated population genetic structure of lumpfish throughout its natural distribution in the North Atlantic using two approaches: I) 4393 genome wide SNPs and 95 individuals from 10 locations, and II) 139 discriminatory SNPs and 1,669 individuals from 40 locations. Both approaches identified extensive population genetic structuring with a major split between the East and West Atlantic and a distinct Baltic Sea population, as well as further differentiation of lumpfish from the English Channel, Iceland, and Greenland. The targeted discriminatory loci displayed ∼2-5 times higher divergence than the genome wide approach, revealing further evidence of local population substructures. Lumpfish from Isfjorden in Svalbard were highly distinct but resembled most fish from Greenland. The Kattegat area in the Baltic transition zone, formed a previously undescribed distinct genetic group. Also, further subdivision was detected within North America, Iceland, West Greenland, Barents Sea, and Norway. Although lumpfish have considerable potential for dispersal and gene-flow, the observed high levels of population structuring throughout the Atlantic suggests that this species displays natal homing and potentially local populations with adaptive differences. This fine-scale population structure calls for consideration when defining management units for lumpfish fishing stocks and in decisions related to sourcing and moving lumpfish for farming and cleaner fish use.
Geospatial analysis reveals distinct hotspots of severe mental illness
Authors: Song Janet , Ramírez Mauricio Castaño , Okano Justin , Service Susan K. , de la Hoz Juan , Díaz-Zuluaga Ana M , Upegui Cristian Vargas , Gallago Cristian , Arias Alejandro , Sánchez Alexandra Valderrama , Teshiba Terri , Sabatti Chiara , Gur Ruben C. , Bearden Carrie E. , Escobar Javier I. , Reus Victor I. , Jaramillo Carlos Lopez , Freimer Nelson B. , Olde Loohuis Loes M. , Blower Sally
Published: March 2022

Background

The identification of geographic variation in incidence can be an important step in the delineation of disease risk factors, but has mostly been undertaken in upper-income countries. Here, we use Electronic Health Records (EHR) from a middle-income country, Colombia, to characterize geographic variation in major mental disorders.

Method

We leveraged geolocated EHRs of 16,295 patients at a psychiatric hospital serving the entire state of Caldas, all of whom received a primary diagnosis of bipolar disorder, schizophrenia, or major depressive disorder at their first visit. To identify the relationship between travel time and incidence of mental illness we used a zero-inflated negative binomial regression model. We used spatial scan statistics to identify clusters of patients, stratified by diagnosis and severity: mild (outpatients) or severe (inpatients).

Results

We observed a significant association between incidence and travel time for outpatients (N = 11,077, relative risk (RR) = 0.80, 95% confidence interval (0.71, 0.89)), but not inpatients (N = 5,218). We found seven clusters of severe mental illness: the cluster with the most extreme overrepresentation of bipolar disorder (RR = 5.83, p < 0.001) has an average annual incidence of 8.7 inpatients per 10,000 residents, among the highest frequencies worldwide.

Conclusions

The hospital database reflects the geographic distribution of severe, but not mild, mental illness within Caldas. Each hotspot is a candidate location for further research to identify genetic or environmental risk factors for severe mental illness. Our analyses highlight how existing infrastructure from middle-income countries can be extraordinary resources for population studies.
Estimated Incidence of Respiratory Hospitalizations Attributable to RSV Infections across Age and Socioeconomic Groups
Authors: Zheng Zhe , Warren Joshua L. , Shapiro Eugene D. , Pitzer Virginia E. , Weinberger Daniel M.
Published: March 2022

Background

Surveillance for respiratory syncytial virus (RSV) likely captures just a fraction of the burden of disease. Understanding the burden of hospitalizations and disparities between populations can help to inform upcoming RSV vaccine programs and to improve surveillance.

Methods

We obtained monthly age-, ZIP code- and cause-specific hospitalizations in New York, New Jersey, and Washington from the US State Inpatient Databases (2005-2014). We estimated the incidence of respiratory hospitalizations attributable to RSV by age and by socioeconomic status using regression models. We compared the estimated incidence and the recorded incidence (based on ICD9-CM) of RSV hospitalizations to estimate the under-recorded rate in the different sub-populations.

Results

The estimated annual incidence of respiratory hospitalizations due to RSV was highest among infants <1 year of age with low socioeconomic status, (2700 per 100,000 people, 95% CrI [2600, 2900]) and were considerable in older adults that are ≥65 years of age across socioeconomic status, ranging from 130 to 970 per 100,000 people. The incidence of hospitalization recorded as being due to RSV represented a significant undercount, particularly in adults. Only <5% of the estimated RSV hospitalizations were captured for the older adults that are ≥65 years of age.

Conclusions

RSV causes a considerable burden of hospitalization in young children and in older adults in the U.S, with variation by socioeconomic group. Estimates of the incidence of hospitalizations due to RSV in older adults based on the recorded diagnoses likely represent an underestimate.

Key messages

What is already known on this topic?

Previous study suggested that the incidence of hospitalization for bronchiolitis (often caused by RSV) in infants varies greatly between communities of different socioeconomic levels. However, it is unclear whether these differences are associated with the admission criteria or the risk of RSV infection.

What this study adds?

The estimated annual incidence of respiratory hospitalizations due to RSV in infants residing in low socioeconomic areas was about twice as high as the incidence in infants residing in high socioeconomic areas. In older adults, a small fraction of the hospitalizations estimated to be caused by RSV were recorded as such in the inpatient database.

How this study might affect research, practice or policy?

With several vaccines and extended half-life monoclonal antibodies against RSV under active development, these estimates can help anticipate the impact of RSV prevention strategies in populations of different demographic characteristics.
Cell size and shape regulation of E. coli determines surface area scaling with volume
Authors: Kale Tanvi , Khatri Dhruv , Athale Chaitanya A.
Published: March 2022

The scaling of surface area and volume of cells has widespread consequences for cell physiology, growth and adaptation. While the surface area increases with volume as SA ~ Vγ the scaling exponent for proportional growth maintaining the shape and aspect is γ ~ 2/3 or 0.66. However most well-studied cellular systems deviate from this standard exponent. At the same time, a mechanism that could predict the biological or physical basis of these scaling relations remains unclear. Here, we quantify the surface area scaling with volume of Escherichia coli cells with varying growth rates and under different conditions and find the scaling exponent varies from γ ~ 0.7 to 0.9. A model of uncorrelated statistical variation of cell lengths and widths can reproduce the exponent observed in experiment. Average values of length and width on the other hand results in an impression of ‘ideal’ geometric scaling, as reported in some studies. Experimental data however suggests that E. coli cell width is strongly correlated with length and a model of saturation best explains the observations. We hypothesize this model of cell size and shape regulation could serve the function of optimizing flux of nutrients, within the constraints of the cell division machinery.
A novel oral GyrB/ParE dual binding inhibitor effective against multidrug resistant Neisseria gonorrhoeae and other high-threat pathogens
Authors: Park Steven , Russo Riccardo , Westfall Landon , Shrestha Riju , Zimmerman Matthew , Dartois Veronique , Kurepina Natalia , Kreiswirth Barry , Singleton Eric , Li Shao-Gang , Mittal Nisha , Ahn Yong-Mo , Bilotta Joseph , Connolly Kristie L. , Jerse Ann E. , Freundlich Joel S. , Perlin David S.
Published: March 2022

Drug resistant Neisseria gonorrhoeae is a serious global health concern. New drugs are needed that can overcome existing drug resistance, as well as limit development of new resistance. We describe the small molecule tricyclic pyrimidoindole JSF-2414 [8-(6- fluoro-8-(methylamino)-2-((2-methylpyrimidin-5-yl)oxy)-9H-pyrimido[4,5-b]indol-4-yl)-2- oxa-8-azaspiro[4.5]decan-3-yl)methanol], which simultaneously binds to ATP binding regions of DNA gyrase (GyrB) and topoisomerase (ParE). JSF-2414 displays potent activity against N. gonorrhoeae including drug-resistant strains. A phosphate prodrug JSF-2659 was developed to facilitate oral dosing. In two different animal models of Neisseria gonorrhoeae vaginal infection, JSF-2659 was highly efficacious in reducing microbial burdens to the limit of detection. The parent molecule also showed potent in vitro activity against high-threat Gram positive organisms, and JSF-2659 was shown in a deep tissue model of VRSA and a model of C. difficile-induced colitis to be highly efficacious and protective. JSF-2659 is a novel drug candidate against high-threat multidrug resistant organisms with low potential to develop new resistance.
Discovery of a Novel Inhibitor for Chikungunya Virus
Authors: Puhl Ana C. , Fernandes Rafaela S. , Godoy Andre S. , Gil Laura H. V. G. , Oliva Glaucius , Ekins Sean
Published: March 2022

Chikungunya virus (CHIKV) is the etiological agent of chikungunya fever, a (re)emerging arbovirus infection, that causes severe and often persistent arthritis, representing a serious health problem worldwide for which no antivirals are currently available. Despite the efforts over the last decade to identify and optimize new inhibitors or to reposition existing drugs, no compound has progressed to clinical trials and prophylaxis is based on vector control, which has shown limited success in containing the virus. Herein, we screened 36 compounds using a replicon system and ultimately identified 3-methyltoxoflavin with activity against CHIKV using cell assays (EC50 200 nM). We have additionally screened 3-methyltoxoflavin against a panel of viruses and showed that it also inhibits yellow fever virus (IC50 370 nM, SI=3.2 in Huh-7 cells). 3-methyltoxoflavin is a known protein disulfide isomerase (PDI) inhibitor, and inhibitor of alphaviruses which likely depends on this host protein to aid in facilitating disulfide bond formation and isomerization, since alphaviruses require conserved cysteine residues for proper folding and assembly of the E1 and E2 envelope glycoproteins. In summary we demonstrate that 3-methyltoxoflavin has activity against CHIKV and may represent a starting point for optimization to develop inhibitors to this and other viruses.
Urinary F plasmids reduce permissivity to coliphage infection
Authors: Hernandez Cesar Montelongo , Putonti Catherine , Wolfe Alan J.
Published: March 2022

The microbial community of the urinary tract (urinary microbiota or urobiota) has been associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacteria dynamics. While urinary E. coli, often associated with urinary tract infection (UTI), and their phages have been catalogued for the urobiome, the dynamics of their interactions have yet to be explored. In this study, we characterized urinary E. coli F plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Putative F plasmids were present in 47 of 67 urinary E. coli isolates, and most of these plasmids carry genes that encode for toxin-antitoxin (TA) modules, antibiotic resistance, and/or virulence. Two urinary E. coli F plasmids, from urinary microbiota (UMB) 0928 and 1284, were conjugated into E. coli K-12 strains; plasmids included genes for antibiotic resistance and virulence. These plasmids, pU0928 and pU1284, decreased permissivity to coliphage infection by the laboratory phage P1vir and the urinary phages Greed and Lust. Furthermore, pU0928 could be maintained in E. coli K-12 for up to ten days in the absence of antibiotic resistance selection; this included maintenance of the antibiotic resistance phenotype and decreased permissivity to phage. Finally, we discuss how F plasmids present in urinary E. coli could play a role in coliphage dynamics and maintenance of antibiotic resistance in urinary E. coli.

Importance

The microbial community of the urinary tract (urinary microbiota or urobiota) has been associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacteria dynamics. While urinary E. coli, often associated with urinary tract infection, and their phages have been catalogued for the urobiome, the dynamics of their interactions have yet to be explored. In this study, we characterized urinary E. coli F plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Two urinary E. coli F plasmids, each encoding antibiotic resistance and transferred by conjugation into naïve laboratory E. coli K-12 strains decreased permissivity to coliphage infection. We propose a model by which F plasmids present in urinary E. coli could help to maintain antibiotic resistance of urinary E. coli.
Prognostic factors for mortality, ICU and hospital admission due to SARS-CoV-2: A systematic review and meta-analysis of cohort studies in Europe
Authors: Vardavas Constantine I. , Mathioudakis Alexander G. , Nikitara Katerina , Stamatelopoulos Kimon , Georgiopoulos Georgios , Phalkey Revati , Leonardi-Bee Jo , Fernandez Esteve , Carnicer-Pont Dolors , Vestbo Jørgen , Semenza Jan C. , Deogan Charlotte , Suk Jonathan E. , Kramarz Piotr , Lamb Favelle , Penttinen Pasi
Published: March 2022

Background

As mortality from COVID-19 is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations.

Methods

We performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to SARS-CoV-2, including death, hospitalisation, Intensive Care Unit (ICU) admission, and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11thJune 2021 in Ovid Medline and Embase. Results are presented as Odds Ratios (ORs) with 95% confidence intervals (95%C.I.) and absolute risk differences (RD) in deaths per 1,000 COVID-19 patients.

Findings

We included 88 cohort studies with age/gender adjusted data from 6,653,207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease, and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes, and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke, and liver disease.

Interpretation

The results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of non-pharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions.

Funding

European Centre for Disease Prevention and Control (ECDC) under specific contract No. 10 ECD.11843 within Framework contract ECDC/2019/001 Lot 1B.
A Computational Pipeline to Identify and Characterize Binding Sites and Interacting Chemotypes in SARS-CoV-2
Authors: Sandholtz Sarah H. , Drocco Jeffrey A. , Zemla Adam T. , Torres Marisa W. , Silva Mary S. , Allen Jonathan E.
Published: March 2022

1

Minimizing the human and economic costs of the COVID-19 pandemic and of future pandemics requires the ability to develop and deploy effective treatments for novel pathogens as soon as possible after they emerge. To this end, we introduce a unique, computational pipeline for the rapid identification and characterization of binding sites in the proteins of novel viruses as well as the core chemical components with which these sites interact. We combine molecular-level structural modeling of proteins with clustering and cheminformatic techniques in a computationally efficient manner. Similarities between our results, experimental data, and other computational studies provide support for the effectiveness of our predictive framework. While we present here a demonstration of our tool on SARS-CoV-2, our process is generalizable and can be applied to any new virus, as long as either experimentally solved structures for its proteins are available or sufficiently accurate homology models can be constructed.
Reaction-diffusion patterning of DNA-based artificial cells
Authors: Leathers Adrian , Walczak Michal , Brady Ryan A. , Al Samad Assala , Kotar Jurij , Booth Michael J. , Cicuta Pietro , Di Michele Lorenzo
Published: March 2022

Biological cells display complex internal architectures, with distinct micro environments that establish the chemical heterogeneity needed to sustain cellular functions. The continued efforts to create advanced cell mimics –artificial cells– demands strategies to construct similarly heterogeneous structures with localized functionalities. Here, we introduce a platform for constructing membrane-less artificial cells from the self-assembly of synthetic DNA nanostructures, in which internal domains can be established thanks to prescribed reaction-diffusion waves. The method, rationalized through numerical modeling, enables the formation of up to five distinct, concentric environments, in which functional moieties can be localized. As a proof-of-concept, we apply this platform to build DNA-based artificial cells in which a prototypical nucleus synthesizes fluorescent RNA aptamers, which then accumulate in a surrounding storage shell, thus demonstrating spatial segregation of functionalities reminiscent of that observed in biological cells.
Growth Condition Dependent Differences in Methylation Implies Transiently Differentiated DNA Methylation States in E. coli
Authors: Breckell Georgia L , Silander Olin K
Published: March 2022

DNA methylation in bacteria frequently serves as a simple immune system, allowing recognition of DNA from foreign sources, such as phages or selfish genetic elements. It is not well established whether methylation also frequently serves a more general epigenetic function, modifying bacterial phenotypes in a heritable manner. To address this question, here we use Oxford Nanopore sequencing to profile DNA modification marks in three natural isolates of E. coli. We first identify the DNA sequence motifs targeted by the methyltransferases in each strain. We then quantify the frequency of methylation at each of these motifs across the genome in different growth conditions. We find that motifs in specific regions of the genome consistently exhibit high or low levels of methylation. Furthermore, we show that there are replicable and consistent differences in methylated regions across different growth conditions. This suggests that during growth, E. coli transiently differentiates into distinct methylation states that depend on the growth state, raising the possibility that measuring DNA methylation alone can be used to infer bacterial growth states without additional information such as transcriptome or proteome data. These results provide new insights into the dynamics of methylation during bacterial growth, and provide evidence of differentiated cell states, a transient analogue to what is observed in the differentiation of cell types in multicellular organisms.
Human Elp3/Kat9 is a mitochondrial tRNA modifying enzyme
Authors: Boutoual Rachid , Jo Hyunsun , Heckenbach Indra , Tiwari Ritesh , Kasler Herbert , Lerner Chad A. , Shah Samah , Schilling Birgit , Calvanese Vincenzo , Rardin Matthew J. , Scheibye-Knudsen Morten , Verdin Eric
Published: March 2022

Post-translational modifications, such as lysine acetylation, regulate the activity of diverse proteins across many cellular compartments. Protein deacetylation in mitochondria is catalyzed by the enzymatic activity of the NAD+-dependent deacetylase sirtuin 3 (SIRT3), however it remains unclear whether corresponding mitochondrial acetyltransferases exist. We used a bioinformatics approach to search for mitochondrial proteins with an acetyltransferase catalytic domain, and identified a novel splice variant of ELP3 (mt-ELP3) of the elongator complex, which localizes to the mitochondrial matrix in mammalian cells. Unexpectedly, mt-ELP3 does not mediate mitochondrial protein acetylation but instead induces a post-transcriptional modification of mitochondrial-transfer RNAs (mt-tRNAs). Overexpression of mt-ELP3 leads to the protection of mt-tRNAs against the tRNA-specific RNase angiogenin, increases mitochondrial translation, and furthermore increases expression of OXPHOS complexes. This study thus identifies mt-ELP3 as a non-canonical mt-tRNA modifying enzyme.
A microbiota membrane disrupter disseminates to the pancreas and increases β-cell mass
Authors: Hill Jennifer Hampton , Massaquoi Michelle Sconce , Sweeney Emily Goers , Wall Elena S. , Jahl Philip , Bell Rickesha , Kallio Karen , Derrick Daniel , Murtaugh L. Charles , Parthasarathy Raghuveer , Remington S. James , Round June L. , Guillemin Karen
Published: March 2022

Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. Here we report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β-cells during pancreatic development in gnotobiotic zebrafish and mice. BefA disseminates systemically via multiple anatomic routes to act directly on pancreatic islets. We report the structure of BefA, containing a lipid-binding SYLF domain, and demonstrate that it permeabilizes synthetic liposomes and bacterial membranes. A BefA mutant impaired in membrane disruption fails to expand β-cells whereas the pore-forming host defense protein, Reg3, stimulates β-cell proliferation. Our work demonstrates that membrane permeabilization by microbiome-derived and host defense proteins is necessary and sufficient for β-cell expansion during pancreas development, thereby connecting microbiome composition with diabetes risk.
SARS-CoV-2 harnesses host translational shutoff and autophagy to optimize virus yields: The role of the envelope (E) protein
Authors: Waisner Hope , Grieshaber Brandon , Saud Rabina , Henke Wyatt , Stephens Edward B , Kalamvoki Maria
Published: March 2022

The SARS-CoV-2 virion is composed of four structural proteins: spike (S), nucleocapsid (N), membrane (M), and envelope (E). E spans the membrane a single time and is the smallest, yet most enigmatic of the structural proteins. E is conserved among coronaviruses and has an essential role in virus-mediated pathogenesis. We found that ectopic expression of E had deleterious effects on the host cell as it activated stress responses, leading to phosphorylation of the translation initiation factor eIF2α and LC3 lipidation that resulted in host translational shutoff. During infection E is highly expressed although only a small fraction is incorporated into virions, suggesting that E activity is regulated and harnessed by the virus to its benefit. In support of this, we found that the γ1 34.5 protein of herpes simplex virus 1 (HSV-1) prevented deleterious effects of E on the host cell and allowed for E protein accumulation. This observation prompted us to investigate whether other SARS-CoV-2 structural proteins regulate E. We found that the N and M proteins enabled E protein accumulation, whereas S prevented E accumulation. While γ1 34.5 protein prevented deleterious effects of E on the host cells, it had a negative effect on SARS-CoV-2 replication. This negative effect of γ1 34.5 was most likely associated with failure of SARS-CoV-2 to divert the translational machinery and with deregulation of autophagy pathways. Overall, our data suggest that SARS-CoV-2 causes stress responses and subjugates these pathways, including host protein synthesis (phosphorylated eIF2α) and autophagy, to support optimal virus production.

Importance

In 2020, a new β-coronavirus, SARS-CoV-2, entered the human population that has caused a pandemic resulting in 6 million deaths worldwide. Although closely related to SARS-CoV, the mechanisms of SARS-CoV-2 pathogenesis are not fully understood. We found that ectopic expression of the SARS-CoV-2 E protein had detrimental effects on the host cell, causing metabolic alterations including shutoff of protein synthesis and mobilization of cellular resources through autophagy activation. Co-expression of E with viral proteins known to subvert host antiviral responses such as autophagy and translational inhibition, either from SARS-CoV-2 or from heterologous viruses increased cell survival and E protein accumulation. However, such factors were found to negatively impact SARS-CoV-2 infection, as autophagy contributes to formation of viral membrane factories, and translational control offers an advantage for viral gene expression. Overall, SARS-CoV-2 has evolved mechanisms to harness host functions that are essential for virus replication.
Motivations for social network site use and users' well-being: mediation of perceived social support, positive self-presentation and honest self-presentation
Authors: Gao Wen , Wei Jianhua , Li Yu , Wang Dongxue , Fang Lele
Published: March 2022

Purpose

This study aimed to investigate positive associations between three main motivations (social interaction, information and entertainment) for the use of social network sites (SNSs) and users' well-being, as well as the multiple mediating effects of perceived social support, positive and honest self-presentation.

Design/methodology/approach

A sample of 759 active users of SNSs (WeChat Moments, Qzone and Weibo) aged 14–43 years was measured with online questionnaires. Correlation analysis and structural equation modeling were implemented to examine the corresponding hypotheses.

Findings

The results showed the overall intensity of motivations was positively associated with users' well-being; perceived social support and positive self-presentation played intermediary roles and honest self-presentation and perceived social support had a chain mediation effect. However, the motivations of social interaction, information and entertainment indirectly affected users' well-being through three different mediation paths.

Originality/value

Although some studies have investigated the effects of motivations (including social interaction, information and entertainment) for SNS use on users' well-being, there has not been a consistent conclusion. The findings may shed light on the motivations for SNS use and how they may affect people's well-being in the digital era, thereby promoting their healthy use of SNSs as well as improved interface design and user management of SNSs.
What are job seekers attracted to? Examining the importance of organizational attributes across four types of job seekers in Poland and France
Authors: Mauger Yohann , Bryant-Lees Kinsey
Published: March 2022

Purpose

The current study has two major aims: (1) investigate the factor structure and importance ratings of attributes in France vs Poland and (2) compare the importance ratings of the attribute signals sent by potential employers during the recruiting process across four different types of job seekers (i.e. new entrants, short-term unemployed, long-term unemployed and currently employed).

Design/methodology/approach

First, using a confirmatory factor analysis (CFA), the authors compare the fit of several proposed models and identify the best fit using the combined job seeker sample. The authors then examine the fit of the selected model for the France and Poland samples separately. Finally, we compare the attribute importance rating factors across groups using a Country by Job Seeker multivariate analysis of variance (MANOVA).

Findings

The CFA results on the combined sample showed that a six factor-solution with two higher-order factors (organization- and job-attributes) provided the best fit and held for both France and Poland. MANOVA results showed a significant interaction between type of job seeker and country for organizational characteristics, and main effects of country and job seeker for work–life values and characteristics.

Originality/value

Most past research on the importance of job attribute factors focused on new entrants in the United States. This study provides the first examination of job attribute factors across different countries, France and Poland, and other types of job seekers.
Unleashing family firms' potential to do more with less: product innovation efficiency, family involvement in TMTs and technological collaborations
Authors: Martínez-Alonso Rubén , Martínez-Romero María J. , Rojo-Ramírez Alfonso A.
Published: March 2022

Purpose

This paper aims to examine the influence of family involvement in TMTs on product innovation efficiency and the contingent role of technological collaborations, combining insights from the resource-based view and the behavioral agency model.

Design/methodology/approach

This study empirically develops and tests the hypotheses using a longitudinal sample of 3,852 firm-year observations from Spanish manufacturing firms over the period 2006–2016.

Findings

The results reveal that family involvement in TMTs positively influences product innovation efficiency. The results also show that such positive effect is weakened as technological collaborations increase, and varies according to the partner type with whom the cooperation agreement is established. Specifically, the findings indicate that collaboration with suppliers appear to be the least detrimental for product innovation efficiency in family firms, followed by collaborations with customers and research organizations.

Practical implications

Family firms should consider appointing family members to their TMT to improve product innovation efficiency. Moreover, to enhance the effect of family management on product innovation efficiency, family managers should carefully select their technological partners.

Originality/value

This study is one of the first studies to theoretically explain and empirically demonstrate that family involvement in TMTs is a critical antecedent of product innovation efficiency and that technological collaborations moderate such link. Moreover, this study goes further in revealing that distinct types of partners have a differential moderating influence on the family involvement in TMTs-product innovation efficiency relationship. The results can be used to help managers and practitioners to boost innovation performance as well as to assist policymakers to design firm-level innovation policies to improve family firms' competitiveness.
Stakeholder engagement and SDGs: the role of social media in the European context
Authors: Mehmood Asad , Hajdini Johana , Iaia Lea , De Luca Francesco , Sakka Georgia
Published: March 2022

Purpose

The authors aim to investigate which social media posts' characteristics result in higher stakeholder engagement in the European context.

Design/methodology/approach

The authors apply chi-square automatic interaction detection (CHAID) method to categorize social media posts based on their engagement levels. The authors conduct analysis on the tweets published in 2019 by companies that draw up and publish a sustainability report on Global Reporting (www.globalreporting.org). The final sample is based on 3,045 tweets from 173 firms of different industries and countries.

Findings

The authors find that tweet characteristics, such as content type, industry type and country of a firm, significantly influence stakeholder engagement rate.

Practical implications

The findings are useful for practitioners and stakeholders. Firm management should consider the most important Sustainable Development Goals (SDGs) concerning their business activities for engaging stakeholders and contributing to sustainable development.

Originality/value

The authors consider stakeholder theory and contribute to stakeholder engagement and sustainability debate. For this purpose, the authors focus on firms' communication of SDGs through social media. To the best of the authors’ knowledge, this is the first study which considers the SDGs’ communication to determine the most significant SDGs resulting in higher stakeholder engagement.