bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial
Authors: Rojas-Serrano Jorge , Thirion-Romero Angelica Margarita Portillo-Vásquez , Vázquez-Pérez Joel , Ramírez-Venegas Fidencio Mejía-Nepomuceno Alejandra , Pérez-Kawabe Karla Midori , Pérez-Padilla Rogelio
Published: May 2021

Health care workers are at high risk of being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Our aim is to evaluate the efficacy and safety of hydroxychloroquine (HCQ) for prophylaxis of COVID19 in health personnel exposed to patients infected by SARS-COV-2.

Methods

Double-blind randomized, placebo-controlled single center clinical trial. Included subjects were health care workers caring for severe COVD19 patients. Main outcome was time to symptomatic SARS-CoV2 infection.

Results

127 subjects with a confirmed baseline negative RT-PCR SARS-CoV2 test were included in the trial, 62 assigned to HCQ and 65 to placebo. One subject (1.6%) in the HCQ group and 6 (9,2%) subjects in the placebo group developed COVID-19. (Log Rank test p = 0.09). No severe COVID19 cases were observed. The study was suspended because of a refusal to participate and losses to follow up after several trials reported lack of effectiveness of hydroxychloroquine in hospitalized patients with COVID-19.

CONCLUSION

Although the number of symptomatic infections in health personnel was lower in the HCQ group, the difference was not statistically significant. The trial is underpowered due to the failure to complete the estimated sample size.
Evaluation of SARS-CoV-2 rapid antigen diagnostic tests for saliva samples
Authors: Hagbom Marie , Carmona-Vicente Noelia , Sharma Sumit , Olsson Henrik , Jämtberg Mikael , Nilsdotter-Augustinsson Åsa , Sjöwall Johanna , Nordgren Johan
Published: May 2021

Background

The COVID-19 pandemic has highlighted the need for rapid, cost effective and easy-to-use diagnostic tools for SARS-CoV-2 rapid antigen detection (RAD) for use in point of care settings or as self-tests, to limit disease transmission. Using saliva samples would further greatly facilitate sample collection, diagnostic feasibility, and mass screening.

Objective

We tested two rapid antigen immunochromatographic tests designed for detection of SARS-CoV-2 in saliva: Rapid Response™ COVID-19 Antigen Rapid Test Cassette for oral fluids (Rapid Response) and DIAGNOS™ COVID-19 Antigen Saliva Test (DIAGNOS). Evaluation of detection limit was performed with purified SARS-CoV-2 nucleocapsid protein and titrated live SARS-CoV-2 virus and compared to Abbott Panbio™ COVID-19 Ag Rapid Test (Panbio) designed for nasopharyngeal samples. Sensitivity and specificity were further evaluated on RT-qPCR positive and negative saliva samples from individuals hospitalized with COVID-19 (n=34); and asymptomatic health care personnel (n=20).

Results

The limit of detection of the saliva test from DIAGNOS was comparable with the Panbio test and showed higher sensitivity than Rapid Response for both nucleocapsid protein and diluted live viruses. DIAGNOS and Rapid Response further detected seven (47%) and five (33%), respectively, of the 15 RT-qPCR positive saliva samples in individuals hospitalized with COVID-19. Of the 39 RT-qPCR negative samples, all were negative with both tests (specificity 100%; 95% c.i. 0.91-1.00). Only one of the RT-qPCR positive saliva samples (Ct 21.6) contained infectious virus as determined by cell culture and was also positive using the saliva RADs.

Conclusion

The results show that the DIAGNOS test exhibit a similar limit of detection as the Panbio RAD and may be an important and easy-to-use saliva RAD complement to detect infectious individuals.
CovidExpress: an interactive portal for intuitive investigation on SARS-CoV-2 related transcriptomes
Authors: Djekidel Mohamed Nadhir , Rosikiewicz Wojciech , Peng Jamy C. , Kanneganti Thirumala-Devi , Hui Yawei , Jin Hongjian , Hedges Dale , Schreiner Patrick , Fan Yiping , Wu Gang , Xu Beisi
Published: May 2021

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans could cause coronavirus disease 2019 (COVID-19). Since its first discovery in Dec 2019, SARS-CoV-2 has become a global pandemic and caused 3.3 million direct/indirect deaths (2021 May). Amongst the scientific community’s response to COVID-19, data sharing has emerged as an essential aspect of the combat against SARS-CoV-2. Despite the ever-growing studies about SARS-CoV-2 and COVID-19, to date, only a few databases were curated to enable access to gene expression data. Furthermore, these databases curated only a small set of data and do not provide easy access for investigators without computational skills to perform analyses. To fill this gap and advance open-access to the growing gene expression data on this deadly virus, we collected about 1,500 human bulk RNA-seq datasets from publicly available resources, developed a database and visualization tool, named CovidExpress (https://stjudecab.github.io/covidexpress). This open access database will allow research investigators to examine the gene expression in various tissues, cell lines, and their response to SARS-CoV-2 under different experimental conditions, accelerating the understanding of the etiology of this disease to inform the drug and vaccine development. Our integrative analysis of this big dataset highlights a set of commonly regulated genes in SARS-CoV-2 infected lung and Rhinovirus infected nasal tissues, including OASL that were under-studied in COVID-19 related reports. Our results also suggested a potential FURIN positive feedback loop that might explain the evolutional advantage of SARS-CoV-2.
The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies
Authors: Tada Takuya , Zhou Hao , Dcosta Belinda M. , Samanovic Marie I. , Mulligan Mark J. , Landau Nathaniel R.
Published: May 2021

Highly transmissible SARS-CoV-2 variants recently identified in India designated B.1.617 and B.1.618 have mutations within the spike protein that may contribute to their increased transmissibility and that could potentially result in re-infection or resistance to vaccine-elicited antibody. B.1.617 encodes a spike protein with mutations L452R, E484Q, D614G and P681R while the B.1.618 spike has mutations Δ145-146, E484K and D614G. We generated lentiviruses pseudotyped by the variant proteins and determined their resistance to neutralization by convalescent sera, vaccine-elicited antibodies and therapeutic monoclonal antibodies. Viruses with B.1.617 and B.1.618 spike were neutralized with a 2-5-fold decrease in titer by convalescent sera and vaccine-elicited antibodies. The E484Q and E484K versions were neutralized with a 2-4-fold decrease in titer. Virus with the B.1.617 spike protein was neutralized with a 4.7-fold decrease in titer by the Regeneron monoclonal antibody cocktail as a result of the L452R mutation. The modest neutralization resistance of the variant spike proteins to vaccine elicited antibody suggests that current vaccines will remain protective against the B.1.617 and B.1.618 variants.
Atto 465 derivative is a nuclear stain with unique excitation and emission spectra for multiplex immunofluorescence histochemistry
Authors: Dodge Joshua T. , Costa-da-Silva Ana C. , Hogden Christopher T. , Mezey Eva , Mays Jacqueline W.
Published: May 2021

The architecture of a biologic response is inextricably linked with the tissue architecture of the target site. Multiplex immunofluorescence (mIF) is an effective technique for the maximal visualization of multiple target proteins in situ. This powerful tool is limited by the spectral overlap separation of the currently available synthetic fluorescent dyes. The fluorescence excitation wavelengths ranging between 405nm and 488nm are rarely used in mIF imaging and serve as a logical additional slot for a fluorescent probe. In the present study, we demonstrate that Atto 465-pentafluoroaniline (Atto 465-p), a derivative of the fluorescent dye Atto 465, can serve as a nuclear stain in the violet-blue region of the visible spectrum. This opens the 405nm channel, traditionally used for nuclear stain, for detection of another experimental target. This increases the flexibility of the mIF panel and, with appropriate staining and microscopy, enables the quantitative analysis of at least six targets in one tissue section.
Fatal breakthrough infection after anti-BCMA CAR-T therapy highlights suboptimal immune response to SARS-CoV-2 vaccination in myeloma patients
Authors: Aleman Adolfo , Van Oekelen Oliver , Upadhyaya Bhaskar , Agte Sarita , Kappes Katerina , Beach Katherine , Srivastava Komal , Gleason Charles R. ,   PVI study group, Wang Bo , Mouhieddine Tarek H. , Tuballes Kevin , Geanon Daniel , Khan Zenab , Gonzalez-Reiche Ana S. , van Bakel Harm , Simons Nicole W. , Mouskas Konstantinos , Charney Alexander W. , Rahman Adeeb , Kim-Schulze Seunghee , Sordillo Emilia M. , Krammer Florian , Cordon-Cardo Carlos , Bhardwaj Nina , Gnjatic Sacha , Merad Miriam , Brown Brian D. , Sanchez Larysa , Chari Ajai , Jagannath Sundar , Simon Viviana , Wajnberg Ania , Parekh Samir
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly effective in healthy individuals. Patients with multiple myeloma (MM) are immunocompromised due to defects in humoral and cellular immunity as well as immunosuppressive therapies. The efficacy after two doses of SARS-CoV-2 mRNA vaccination in MM patients is currently unknown. Here, we report the case of a MM patient who developed a fatal SARS-CoV-2 infection after full vaccination while in remission after B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T treatment. We show that the patient failed to generate antibodies or SARS-CoV-2-specific B and T cell responses, highlighting the continued risk of severe coronavirus disease 2019 (COVID-19) in vaccine non-responders. In the largest cohort of vaccinated MM patients to date, we demonstrate that 15.9% lack SARS-CoV-2 spike antibody response more than 10 days after the second mRNA vaccine dose. The patients actively receiving MM treatment, especially on regimens containing anti-CD38 and anti-BCMA, have lower antibody responses compared to healthy controls. Thus, it is of critical importance to monitor this patient population for serological responses. Non-responders may benefit from ongoing public health measures and from urgent study of prophylactic treatments to prevent SARS-CoV-2 infection.
Toxoplasmosis: An important risk factor for acquiring SARS-CoV-2 infection and a severe course of Covid-19 disease
Authors: Flegr Jaroslav
Published: May 2021

Background

Latent toxoplasmosis, i.e. a lifelong infection with the protozoan parasiteToxoplasmagondii, affects about a third of human population worldwide. In the past ten years, numerous studies had shown that infected subjects have a significantly higher incidence of mental and physical health problems and are more prone to exhibiting the adverse effects of various diseases.

Methods

A cross-sectional internet study was performed on a population of 4,499Toxoplasma-free and 786Toxoplasma-infected subjects and looked for factors which positively or negatively affect the risk of SARS-CoV-2 infection and likelihood of a severe course of Covid-19.

Findings

Logistic regression and partial Kendall correlation controlled for sex, age, and size of the place of residence showed that latent toxoplasmosis had the strongest effect on the risk of infection (OR = 1·50) before sport (OR = 1·30), and borreliosis (1·27). It also had the strongest effect on the risk of severe course of infection (Tau = 0·146), before autoimmunity, immunodeficiency, male sex, keeping a cat, being overweight, borreliosis, higher age, or chronic obstructive pulmonary disease. Toxoplasmosis augmented the adverse effects of other risk factors but was not the proximal cause of the effect of cat keeping (in the form of higher likelihood of Covid infection and higher severity of the course of infection), which was observed especially in a subset ofToxoplasma-infected subjects (Tau = 0·153). Effects of keeping a cat were detected only in subjects from multi-member families, suggesting that a cat could a vector for the transmission of SARS-CoV-2 within a family.

Interpretations

Toxoplasmosis is currently not considered a risk factor for Covid-19 andToxoplasma- infected subjects are neither informed about their higher risks nor prioritised in vaccination programs. Because toxoplasmosis affects a large segment of the human population, its impact on Covid-19-associated effects on public health could be considerable.
Fc-independent neutralization of SARS-CoV-2 by recombinant human monoclonal antibodies
Authors: Noy-Porat Tal , Edri Avishay , Alcalay Ron , Makdasi Efi , Gur David , Aftalion Moshe , Evgy Yentl , Beth-Din Adi , Levy Yinon , Epstein Eyal , Radinsky Olga , Zauberman Ayelet , Lazar Shirley , Yitzhaki Shmuel , Marcus Hadar , Porgador Angel , Rosenfeld Ronit , Mazor Ohad
Published: May 2021

The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficaciousin vivoneutralization of SARS-CoV-2 is not yet clear. Delineating the role this process plays in antibody-mediated protection will have a great impact on the design of such therapeutics. Here, the Fc of two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, targeting distinct domains of the spike, was engineered to abrogate their Fc-dependent functions. The protective activity of these antibodies was tested against lethal SARS-CoV-2 infections in K18-hACE2 transgenic mice, both before or two days post-exposure in comparison to their original, Fc-active antibodies. Antibody treatment with both Fc-variants similarly rescued the mice from death, reduced viral load and prevented signs of morbidity. In addition, surviving animals developed a significant endogenous immune response towards the virus. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in antibody-mediated protection, which should aid in future design of effective antibody-based therapies.
Anticancer pan-ErbB inhibitors reduce inflammation and tissue injury and exert broad-spectrum antiviral effects
Authors: Saul Sirle , Karim Marwah , Ghita Luca , Huang Pei-Tzu , Chiu Winston , Durán Verónica , Lo Chieh-Wen , Kumar Sathish , Bhalla Nishank , Leyssen Pieter , Alem Farhang , Boghdeh Niloufar A. , Tran Do HN , Cohen Courtney A. , Brown Jacquelyn A. , Huie Kathleen E. , Tindle Courtney , Sibai Mamdouh , Ye Chengjin , Khalil Ahmed Magdy , Martinez-Sobrido Luis , Dye John M. , Pinsky Benjamin A. , Ghosh Pradipta , Das Soumita , Solow-Cordero David E. , Jin Jing , Wikswo John P. , Jochmans Dirk , Neyts Johan , Jonghe Steven De , Narayanan Aarthi , Einav Shirit
Published: May 2021

Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib suppressed SARS-CoV-2 entry and later stages of the viral life cycle and showed synergistic effect with the direct-acting antiviral nirmatrelvir. We discovered that ErbB1, 2 and 4 bind SARS-CoV-2 S1 protein and regulate viral and ACE2 internalization, and they are required for VEEV infection. In human lung organoids, lapatinib protected from SARS-CoV-2-induced activation of ErbB-regulated pathways implicated in non-infectious lung injury, pro-inflammatory cytokine production, and epithelial barrier injury. Lapatinib suppressed VEEV replication, cytokine production and disruption of the blood-brain barrier integrity in microfluidic-based human neurovascular units, and reduced mortality in a lethal infection murine model. We validated lapatinib-mediated inhibition of ErbB activity as an important mechanism of antiviral action. These findings reveal regulation of viral replication, inflammation, and tissue injury via ErbBs and establish a proof-of-principle for a repurposed, ErbB-targeted approach to combat emerging viruses.
SETDB1 regulates microtubule dynamics
Authors: Hernandez-Vicens Rosari , Pernicone Nomi , Listovsky Tamar , Gerlitz Gabi
Published: May 2021

SETDB1 is a methyltransferase responsible for the methylation of histone H3-lysine-9, which is mainly related to heterochromatin formation. SETDB1 is overexpressed in various cancer types and is associated with an aggressive phenotype. In agreement with its activity, it mainly exhibits a nuclear localization; however, in several cell types a cytoplasmic localization was reported. Here we show that a substantial cytoplasmic pool of SETDB1 is colocalized with microtubules. Significantly, silencing of SETDB1 led to faster polymerization and reduced rate of catastrophe events of microtubules in parallel to reduced proliferation rate and slower mitotic kinetics. Interestingly, over-expression of either wild-type or catalytic dead SETDB1 altered microtubule polymerization rate to the same extent, suggesting that SETDB1 affects MT dynamics by a methylation-independent mechanism. Finding interaction between SETDB1 and the tubulin deacetylase HDAC6 and increased tubulin acetylation levels upon silencing of SETDB1 suggest a model in which SETDB1 affects microtubule dynamics by interacting with both microtubules and HDAC6 to enhance tubulin deacetylation. Overall, our results suggest a novel cytoplasmic role for SETDB1 in the regulation of microtubule dynamics.
Stabilization of the SARS-CoV-2 Spike receptor-binding domain using deep mutational scanning and structure-based design
Authors: Ellis Daniel , Brunette Natalie , Crawford Katharine H. D. , Walls Alexandra C. , Pham Minh N. , Chen Chengbo , Herpoldt Karla-Luise , Fiala Brooke , Murphy Michael , Pettie Deleah , Kraft John C. , Malone Keara D. , Navarro Mary Jane , Ogohara Cassie , Kepl Elizabeth , Ravichandran Rashmi , Sydeman Claire , Ahlrichs Maggie , Johnson Max , Blackstone Alyssa , Carter Lauren , Starr Tyler N. , Greaney Allison J. , Lee Kelly K. , Veesler David , Bloom Jesse D. , King Neil P.
Published: May 2021

The unprecedented global demand for SARS-CoV-2 vaccines has demonstrated the need for highly effective vaccine candidates that are thermostable and amenable to large-scale manufacturing. Nanoparticle immunogens presenting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S) in repetitive arrays are being advanced as second-generation vaccine candidates, as they feature robust manufacturing characteristics and have shown promising immunogenicity in preclinical models. Here, we used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the RBD. The selected mutations fill a cavity in the RBD that has been identified as a linoleic acid binding pocket. Screening of several designs led to the selection of two lead candidates that expressed at higher yields than the wild-type RBD. These stabilized RBDs possess enhanced thermal stability and resistance to aggregation, particularly when incorporated into an icosahedral nanoparticle immunogen that maintained its integrity and antigenicity for 28 days at 35-40°C, while corresponding immunogens displaying the wild-type RBD experienced aggregation and loss of antigenicity. The stabilized immunogens preserved the potent immunogenicity of the original nanoparticle immunogen, which is currently being evaluated in a Phase I/II clinical trial. Our findings may improve the scalability and stability of RBD-based coronavirus vaccines in any format and more generally highlight the utility of comprehensive DMS data in guiding vaccine design.
Safety, immunogenicity and protection provided by unadjuvanted and adjuvanted formulations of recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in non-human primates
Authors: Pillet Stéphane , Arunachalam Prabhu S. , Andreani Guadalupe , Golden Nadia , Fontenot Jane , Aye Pyone , Röltgen Katharina , Lehmick Gabrielle , Dubé Charlotte , Gobeil Philipe , Trépanier Sonia , Charland Nathalie , D’Aoust Marc-André , Russell-Lodrigue Kasi , Blair Robert V. , Boyd Scott , Bohm Rudolph B. , Rappaport Jay , Villinger François , Ward Brian J. , Pulendran Bali , Landry Nathalie
Published: May 2021

Although antivirals are important tools to control the SARS-CoV-2 infection, effective vaccines are essential to control the current pandemic. Plant-derived virus-like particle (VLP) vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza. Here we report the immunogenicity and protection induced in macaques by intramuscular injections of VLP bearing SARS-CoV-2 spike protein (CoVLP) vaccine candidate formulated with or without Adjuvant System 03 (AS03) or cytosine phosphoguanine (CpG) 1018. Although a single dose of unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses, booster immunization (at 28 days after prime) and adjuvants significantly improved both responses with a higher immunogenicity and protection provided by AS03 adjuvanted CoVLP. Fifteen microgram CoVLP adjuvanted with AS03 induced a balanced IL-2 driven response along with IL-4 expression in CD4 T cells and mobilization of CD4 follicular helper cells (Tfh). Animals were challenged by multiple routes (i.e. intratracheal, intranasal and ocular) with a total viral dose of 106 plaque forming units of SARS-CoV-2. Lower viral replication in nasal swabs and broncho-alveolar lavage (BAL) as well as fewer SARS-CoV-2 infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of pro-inflammatory cytokines and chemotactic factors in BAL were observed in the animals immunized with CoVLP adjuvanted with AS03. No clinical, pathologic or virologic evidences of vaccine associated enhanced disease (VAED) were observed in vaccinated animals. CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.
Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome
Authors: Mösbauer Kirstin , Fritsch Verena Nadin , Adrian Lorenz , Bernhardt Jörg , Gruhlke Martin Clemens Horst , Slusarenko Alan John , Niemeyer Daniela , Antelmann Haike
Published: May 2021

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is a major health burden. Volatile garlic organosulfur compounds, such as the thiol-reactive allicin (diallyl thiosulfinate) exert strong antimicrobial activity against various respiratory pathogens. Here, we investigated the antiviral activity of allicin against SARS-CoV-2 in infected Vero E6 and Calu-3 lung cells. Calu-3 cells showed greater allicin tolerance due >4-fold increased GSH levels compared to Vero E6. However, biocompatible allicin doses efficiently inhibited viral replication in both cell lines. Proteome analyses of SARS-CoV-2 infected Calu-3 cells revealed a strong induction of the antiviral interferon-stimulated gene (ISG) signature (e.g. cGAS, Mx1, IFIT, IFIH, IFI16, IFI44, 2’5’OAS and ISG15), pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTC1, ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin abrogated the ISG host response and reverted the host cellular pathways to levels of uninfected Calu-3 cells, confirming the antiviral and immunomodulatory activity of allicin in the host proteome. Thus, biocompatible doses of allicin could be promising for protection of lung cells against SARS-CoV-2.
An innovative approach for determining composite wheat quality index to identify quality enriched genotypes - insights and implications
Authors: Mohan D , Sendhil R , Gupta Om Prakash , Pandey Vanita , Gopalareddy K , Singh Gyanendra Pratap
Published: May 2021

Ranking test entries or test sites on a quality basis is very difficult in wheat as value addition is perceived by several grain properties and end-products. Here, a novel approach has been developed and tested by deriving wheat quality index based on principal component analysis of 13 physico-chemical grain parameters and 3 end products of 45 wheat varieties. Depending upon the observed index range (0.15 to 0.71), the cultivars were assorted into 3 distinct classesi.e. elite, moderate and poor. The top group ascertained high quality standards of grain suited for bread andchapatiwhereas bottom group assured better cookies quality. This technique was also tested to differentiate quality enriched test sites within a zone or demarcate the most suited production environments to harness good quality wheat. The index will have an implication on farmers (premium price for varietal segregation), industry (product specific quality cultivars), and consumers (superior quality products).
Clinical Strains of Pseudomonas aeruginosa secret LasB protease to induce hemorrhagic diffused alveolar damage and acute lung injury in mice
Authors: Zhu Yajie , Ge Xiaoli , Xie Di , Wang Shangyuan , Chen Feng , Pan Shuming
Published: May 2021

Background

Acute lung injury and acute respiratory distress syndrome are most often caused by bacterial pneumonia, characterized by severe dyspnea and high mortality. Knowledge about the lung injury effects of current clinical bacteria strains is lacking. The aim of this study was to investigate the ability of representative pathogenic bacteria isolated from patients to cause ALI/ARDS in mice and identify the virulent factors.

Method

7 major bacteria species were isolated from clinical sputum and instilled in to mice airway unilaterally. Histology study was used to judge the lung injury effect. Virulence genes were examined by PCR. Sequence type of P. aeruginosa strains were identified by MLST. LC-MS/MS was used to identify the suspicious protein bands. LasB was purified through DEAE-cellulose column and its toxicity was tested both in vitro and in vivo.

Results

Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus agalactiae, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli were randomly separated and tested 3 times. Among them, gram-negative bacteria are more potential than gram-positive bacteria to cause acute lung injury. However, P. aeruginosa is the only pathogen which induced diffused alveolar damage, hemorrhage and hyaline membrane in the lung of mice. The lung injury effect is associated to the excreted matrix metalloproteinase LasB of P. aeruginosa. Purified LasB recapitulated hemorrhagic acute lung injury identical to P. aeruginosa infection in vivo. We found this was due to the powerful degradation effect of LasB on both lung extracellular matrix and key proteins in coagulation cascade without inducing cellular apoptosis.

Conclusion

P. aeruginosa strains are most capable to induce ALI/ARDS among major clinical pathogenic bacteria, this ability is specifically attributed to their LasB production.
Night warming alters mean warming effects on predator–prey interactions by modifying predator demographics and interaction strengths
Authors: Ma Gang , Bai Chun‐Ming , Rudolf Volker H. W. , Ma Chun‐Sen
Published: May 2021

Temperatures are increasing globally, but this increase is not symmetrical; instead, night‐time minimum air temperatures increase faster than daytime maximum temperatures. However, we still know little about when and how this differential increase in maximum versus minimum air temperatures affects ecological interactions between species. Understanding the connection between different types (night vs. day) of warming and interspecific interactions is essential to predict the ecological consequences of climate change for natural ecosystems.

Here we used experiments in a common predator (lady beetle)–prey (aphid) system to examine how night warming, thermal regime (constant vs. fluctuating) and prey density influence demographic rates and per capita feeding rate and thus predation pressure. We mainly focused on the demographic variables and prey consumption as well as energy‐related variables of the predators to understand how changes in night‐time temperature, temperature regime and prey density affect predator performances and to differentiate these effects between constant and fluctuating thermal conditions.

We found that warming effects on most of the individual demographic rates and per capita consumption rates of the predator differed between constant and fluctuating regimes. These differences scaled up to alter population stage structure and population growth rate of the predator and ultimately the predation pressure in our system. Furthermore, warming had stronger and negative consequences on predator population growth and thus predation pressure in constant regime, but little or even positive effects under fluctuating conditions. Importantly, these results are consistent across prey densities.

Our results suggest that compared to night warming, predictions based on mean warming can under‐ or overestimate species demographic rates and per capita predation effects, causing inaccurate or even misleading expectations on population structure, long‐term population growth and interspecific interactions. These results emphasize the importance of accounting for both ecologically relevant diurnal temperature cycle and lifelong demographics and per capita consumption when assessing how warming affects interspecific interactions. Our findings thus provide better understanding of how night warming will affect predator–prey interactions and energy flux within trophic cascades and also have implications for predicting the consequences of top‐down control in natural and agricultural ecosystems under climate change.

A free Plain Language Summary can be found within the Supporting Information of this article.
Why Firms Announce Good News Late: Earnings Management and Financial Reporting Timeliness*
Authors: Kim Mark P. , Pierce Spencer R. , Yeung Ira
Published: May 2021

Prior studies find that delayed earnings announcements tend to communicate unfavorable news, and investors react negatively when firms delay earnings announcements. However, these findings do not explain why investors discount delayed earnings, even after controlling for the earnings news, and why firms sometimes announce good news late. Motivated by theory from Trueman (1990) that attempts to explain these phenomena, we examine whether announcement delays indicate earnings management. We predict and find that good news firms with higher discretionary accruals are more likely to announce earnings late. Consistent with post fiscal year‐end activities driving announcement delays, we fail to find a relation between measures of real earnings management and late announcements. Using a last‐chance earnings management measure based on tax expense manipulation, we also predict and find strong evidence that good news firms engaging in last‐chance earnings management are more likely to delay earnings announcements. Consistent with Trueman's (1990) theory that earnings management explains why investors discount delayed earnings announcements, we find that, on average, earnings announcement returns are 1.4% lower for late announcers relying on last‐chance earnings management to report good news. Overall, our findings suggest that announcement delays provide information about not only the sign of the earnings news but also the potential for earnings management.
A cascade of care for alcohol use disorder: Using 2015–2019 National Survey on Drug Use and Health data to identify gaps in past 12‐month care
Authors: Mintz Carrie M. , Hartz Sarah M. , Fisher Sherri L. , Ramsey Alex T. , Geng Elvin H. , Grucza Richard A. , Bierut Laura J.
Published: May 2021

Background

Although effective treatments exist, alcohol use disorder (AUD) is undertreated. We used a cascade of care framework to understand gaps in care for persons with AUD.

Methods

Using 2015–2019 National Survey on Drug Use and Health data, we evaluated the following steps in the cascade of care: (1) adult prevalence of AUD; (2) proportion of adults with AUD who utilized health care in the past 12 months; (3) proportion with AUD screened about their alcohol use; (4) proportion with AUD who received a brief intervention about their alcohol misuse; (5) proportion with AUD who received information about treatment for alcohol misuse; and (6) proportion with AUD who received treatment. Analyses were stratified by AUD severity.

Results

Of the 214,505 persons included in the sample, the weighted prevalence of AUD was 7.8% (95% CI 7.6–8.0%). Cascades of care showed the majority of individuals with AUD utilized health care in the past 12 months [81.4% (95% CI 80.7–82.1%)] and were screened about alcohol use [69.9% (95% CI 68.9–70.8%)]. However, only a minority of individuals received subsequent steps of care, including 11.6% (95% CI 11.0–12.2%) who reported receiving a brief intervention, 5.1% (95% CI 4.6–5.6%) who were referred to treatment, and 5.8% (95% CI 5.4–6.3%) who received treatment. Similar patterns were observed when cascades of care were stratified by AUD severity.

Conclusions

Persons with AUD commonly utilize health care and are often screened about alcohol use, but few receive treatment. Healthcare settings—particularly primary care settings—represent a prime opportunity to implement AUD treatment to improve outcomes in this high‐risk population.
The effect of group size on reproduction in cooperatively breeding gray wolves depends on density
Authors: Ausband D. E. , Mitchell M. S.
Published: May 2021

In cooperatively breeding species, large group size is often positively related to reproductive success and group persistence. We have a poor understanding, however, of how group sizes within a population affect reproduction particularly as density varies. We hypothesized that at low densities, wolves in both small and large groups would have similar reproductive rates. At high densities, however, wolves in small groups would have lower reproductive rates compared to those in large groups. Using empirical data from radio‐collared wolves in Idaho and Yellowstone National Park, WY, USA (1996–2012), we compared reproductive rates (i.e. proportion reproducing, litter size, pup survival) among small and large groups of wolves as density fluctuated within the populations. Reproductive rates were generally lower for individuals in small groups compared to those in large groups, particularly as density increased. Pup survival, however, was slightly higher for wolves in small groups compared to large groups except at very high densities. Polygamy increased with density regardless of group size, suggesting a polygamy threshold for wolves. Large group size resulted in less parturition failure, more breeding females per group, larger litter sizes, and ultimately more pups recruited per group. Large group size appears advantageous for several, but not all, aspects of reproduction particularly when population density is high.
An assessment of the current status of children’s toothpaste in Australia
Authors: Smith BD , MacPhail C , Russell J
Published: May 2021

Background

Despite recommendations that pre‐school children use toothpaste containing 500–550 ppm of fluoride, there has been an increase in non‐fluoridated toothpastes marketed for children. This study investigated children’s toothpaste in Australia.

Methods

A comprehensive audit of all toothpastes marketed for pre‐school children and available in store in the Macarthur region of NSW, Australia, was carried out. All toothpastes available for purchase were obtained and examined; size and price were catalogued, along with ingredient lists and fluoride levels.

Results

One hundred and seven individual toothpastes were identified in the audit, with 67 (62.6%) containing no fluoride. Of the 40 fluoridated toothpastes, only 11 (10.3%) contained the recommended level of fluoride of 500–550 ppm. Twenty‐two (20.6%) of all toothpastes were made in Australia, all of which were non‐fluoridated. Six (5.6%) of the toothpastes studied contained excessive levels of fluoride (1350–1500 ppm). Seventeen of the 20 least expensive toothpastes contained fluoride, while 18 of the 20 most expensive toothpastes were non‐fluoridated.

Conclusions

Despite expert recommendations, the majority of children’s toothpaste available in Australia contains either no fluoride or the wrong levels of fluoride. Further study is needed to determine why this change is occurring and what is influencing the increase in non‐fluoride toothpastes on the market.
Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS‐52 is unaffected by eosinophilic status
Authors: Fujieda Shigeharu , Matsune Shoji , Takeno Sachio , Ohta Nobuo , Asako Mikiya , Bachert Claus , Inoue Tomoyuki , Takahashi Yoshinori , Fujita Hiroyuki , Deniz Yamo , Rowe Paul , Ortiz Benjamin , Li Yongtao , Mannent Leda P.
Published: May 2021

Background

The human monoclonal antibody dupilumab blocks interleukin (IL)‐4 andIL‐13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS‐52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS‐52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy.

Methods

Patients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund‐Mackay score assessed by CT (LMK‐CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm.

Results

Dupilumab significantly improved NPS, NC, and LMK‐CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non‐/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK‐CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups.

Conclusion

Dupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP.
The gift of hospitality and the (un)welcoming of Syrian migrants in Turkey
Authors: ALKAN HILAL
Published: May 2021

As of 2020, Turkey was home to 3.6 million Syrian migrants who fled violence in their country after the uprisings of 2011. Although they are not recognized as refugees, Syrian migrants have been granted the right to self‐settlement in Turkey. The Turkish state has promoted this reception as
a form of hospitality and generosity. The state's elevation of hospitality has
been criticized, however, for reinforcing inequalities. More broadly, the concept of hospitality itself has been scrutinized for its immediate affinity to
hostility. But as revealed by ethnographic work with Istanbul's neighborhood
aid networks, “hospitality” at ​the grassroots level is governed by principles of the gift. In everyday interactions, it can catalyze a cycle of reciprocal returns that may lead to long‐term relationships. Countering the argument that hospitality is always paired with hostility, this ethnography shows that it can also turn strangers into relatable Others. [gift, hospitality, neighborhoods, reciprocity, Syrian refugees, Istanbul, Turkey]
Living arrangements after parental separation have minimal impact on mental health at age 7 years
Authors: Hjern Anders , Bergström Malin , Fransson Emma , Kjaer Urhoj Stine
Published: May 2021

Aim

This study compared mental health after parental separation in 7‐year‐old children living in joint physical custody with sole physical custody family arrangements.

Methods

The study population included 39 661 children from the Danish National Birth Cohort, living in a nuclear family at age 6 months. Child mental health was measured at age 7 years with maternal reports of the Strength and Difficulties Questionnaire (SDQ) operationalised as a high total score. Associations between living arrangements and mental health were analysed using logistic regression models, taking into account early childhood indicators of family relations, parental mental health and socioeconomic conditions.

Results

There were no statistically significant differences between the living arrangements after parental separation with joint physical custody having an odds ratio (OR) of 1.37 (95% CI 1.10–1.70), sole physical custody without a new partner OR 1.33 (95% CI 1.19–1.47) and OR 1.55 (95% CI 1.30–1.84) for sole physical custody with new partner, with children in a nuclear family as reference.

Conclusion

This study indicates that living arrangements after parental separation have a minimal influence on child mental health at age 7 years.
Laparoscopic intraperitoneal mesh repair of a large incisional hernia in a kidney transplantation patient: A case report
Authors: Kaida Daisuke , Miyata Takashi , Kin Ryosuke , Nishiki Hisashi , Hashimoto Akifumi , Fujii Yoritaka , Miura Seiko , Fujita Jun , Tomita Yasuto , Nakamura Naohiko , Miyashita Tomoharu , Fujita Hideto , Ueda Nobuhiko , Takamura Hiroyuki
Published: May 2021

A 73‐year‐old woman presented to our hospital because of painful bulging in the right lower abdomen, and developed a 17 × 12 cm incisional hernia after kidney transplantation using right oblique incision. Laparoscopic intraperitoneal onlay mesh (IPOM) repair was performed. Since a transplanted kidney is close to the abdominal wall defect, the space between the transplanted kidney and the abdominal wall was peeled off to secure enough space for the mesh to be place. After that the fascial defect was detected precisely, and the polypropylene‐polyglycolic acid composite mesh was fixed with 3 cm overlapping of the hernia ring by non‐absorbable tacks. The patient was discharged 9 days after surgery. In general, abdominal incisional hernias after kidney transplantation are relatively large with boundary defect of abdominal wall ensuing between the abdominal and allograft. However, laparoscopic IPOM repair of incisional hernia after kidney transplantation can be performed safely and effectively.
Anthropogenic disturbance modifies long‐term changes of boreal mountain vegetation under contemporary climate warming
Authors: Maliniemi Tuija , Virtanen Risto
Published: May 2021

Aims

Accelerating high‐latitude climate warming drives shrub expansion in open landscapes and alters species distributions and compositions of plant communities. Simultaneously, various land use practices cause disturbance to the vegetation. However, not much documentation exists on how long‐term intensive land use disturbance modifies high‐latitude vegetation under climate warming. Here, we study how the composition of boreal mountain plant communities has changed during three decades in response to heavy land use disturbance, related to ski resort construction and management, and how these changes compare to those observed in adjacent less disturbed communities.

Location

Iso‐Syöte, Finland.

Methods

We resurveyed vegetation along four elevational gradients (240–426 m a.s.l.) on a boreal mountain in 2013–14. After the original study in 1980, half of the gradients were subjected to continuous heavy land use disturbance, while the other half remained only slightly disturbed. All the gradients experienced a similar amount of macroclimatic warming over time. We analysed temporal changes in plant group covers, species richness and species’ elevational range means in relation to disturbance levels and elevation.

Results

Under slight disturbance, the cover of shrubs increased on the originally open upper slopes and elevational range means of several species shifted upward. In contrast, heavy disturbance resulted in a uniform, yet modest, shrub cover increase along the whole elevational gradient and promoted both up‐ and downward shifts of species. Bryophyte cover decreased considerably over time, regardless of the disturbance level. Species richness increased throughout, yet more under heavy disturbance.

Conclusions

Long‐term changes in boreal mountain vegetation are substantially influenced by heavy land use disturbance compared to less disturbed sites where the vegetation changes are more comparable to those expected under a warmer climate. Therefore, along with the climatic effects, land use effects on vegetation are important to consider in management actions and in projections of future vegetation.
Plant quality and primary productivity modulate plant biomass responses to the joint effects of grazing and fertilization in a mesic grassland
Authors: Campana Sofía , Yahdjian Laura
Published: May 2021

Questions: Human activities are increasing the density of domestic grazers and global nutrient loads, modifying the main determinants of vegetation community dynamics. Grazing (top‐down control) and nutrient availability (bottom‐up control) may interactively modify plant biomass, which is particularly important in grasslands devoted to livestock production. Here, we aim to understand the interactive effects of grazing and fertilization on grassland plant biomass. We hypothesized that the joint effects of nutrient addition and domestic grazing on above‐ground plant biomass are not additive, but they modify each other through changes in ground‐level light, leaf nutritional quality, above‐ground net primary productivity (ANPP), and below‐ground plant allocation.

Location: Flooding Pampa (Buenos Aires, Argentina).

Methods: We carried out a factorial experiment of grazing exclusion and fertilization with nitrogen, phosphorus, and potassium + micronutrients during ​several years in a mesic grassland devoted to livestock production.

Results: After four years, grazing reduced live above‐ground plant biomass by 52%, and when combined with fertilization this reduction was 70%. Nutrient addition in the grazed grassland increased ANPP and leaf nutrient concentration. These changes in turn intensified grazing pressure and cattle’s plant consumption. By contrast, fertilization did not produce any significant effect on plant biomass or ANPP inside the exclosures, where ground‐level light was low. A structural equation model revealed that the increase in ANPP fostered above‐ground and reduced below‐ground plant biomass.

Conclusions: This is the first study conducted in the Pampas grasslands that evaluated the effect of cattle grazing and fertilization on plant communities under field conditions over several years. Grazing and nutrient addition synergistically controlled grassland plant biomass, as the reduction in above‐ground biomass by cattle consumption was greater in fertilized plots. Our results provided empirical evidence that leaf nitrogen and ANPP modulated plant biomass dynamics in grasslands devoted to livestock production in the context of increased nutrient loads in terrestrial ecosystems.