bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitin Deacetylases Are Required for Epichloë festucae Endophytic Cell Wall Remodeling During Establishment of a Mutualistic Symbiotic Interaction with Lolium perenne
Authors: Noorifar Nazanin , Savoian Matthew S. , Ram Arvina , Lukito Yonathan , Hassing Berit , Weikert Tobias W. , Moerschbacher Bruno M. , Scott Barry
Published: June 2021

Epichloë festucae forms a mutualistic symbiotic association with Lolium perenne. This biotrophic fungus systemically colonizes the intercellular spaces of aerial tissues to form an endophytic hyphal network and also grows as an epiphyte. However, little is known about the cell wall–remodeling mechanisms required to avoid host defense and maintain intercalary growth within the host. Here, we use a suite of molecular probes to show that the E. festucae cell wall is remodeled by conversion of chitin to chitosan during infection of L. perenne seedlings, as the hyphae switch from free-living to endophytic growth. When hyphae transition from endophytic to epiphytic growth, the cell wall is remodeled from predominantly chitosan to chitin. This conversion from chitin to chitosan is catalyzed by chitin deacetylase. The genome of E. festucae encodes three putative chitin deacetylases, two of which (cdaA and cdaB) are expressed in planta. Deletion of either of these genes results in disruption of fungal intercalary growth in the intercellular spaces of plants infected with these mutants. These results establish that these two genes are required for maintenance of the mutualistic symbiotic interaction between E. festucae and L. perenne.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Comparison of Patient Preference, Understanding, and Sentiment for Minimally Invasive Versus Open Spine Surgery
Authors: White Christopher A. , Patel Akshar V. , Butler Liam R. , Amakiri Uchechukwu O. , Yeshoua Brandon J. , Steinberger Jeremy M. , Cho Samuel K. , Kim Jun S.
Published: May 2021

Study Design.

Retrospective questionnaire analysis.

Objective.

The goal of this study was to analyze patients’ understanding and preferences for minimally invasive spine (MIS) versus open spine surgery.

Summary of Background Data.

MIS surgery is increasing in prevalence. However, there is insufficient literature to evaluate how the availability of MIS surgery influences the patients’ decision-making process and perceptions of spine procedures.

Methods.

A survey was administered to patients who received a microdiscectomy or transforaminal lumbar interbody fusion between 2016 and 2020. All eligible patients were stratified into two cohorts based on the use of minimally invasive techniques. Each cohort was administered a survey that evaluated patient preferences, perceptions, and understanding of their surgery.

Results.

One hundred fifty two patients completed surveys (MIS: 88, Open: 64). There was no difference in time from surgery to survey (MIS: 2.1 ± 1.4 yrs, Open: 1.9 ± 1.4 yrs; P = 0.36) or sex (MIS: 56.8% male, Open: 53.1% male; P = 0.65). The MIS group was younger (MIS: 53.0 ± 16.9 yrs, Open: 58.2 ± 14.6 yrs; P = 0.05). More MIS patients reported that their technique influenced their surgeon choice (MIS: 64.0%, Open: 37.5%; P 
< 0.00001) and increased their preoperative confidence (MIS: 77.9%, Open: 38.1%; P 
< 0.00001). There was a trend towards the MIS group being less informed about the intraoperative specifics of their technique (MIS: 35.2%, Open: 23.4%; P = 0.12). More of the MIS cohort reported perceived advantages to their surgical technique (MIS: 98.8%, Open: 69.4%; P < 0.00001) and less reported disadvantages (MIS: 12.9%, Open: 68.8%; P < 0.00001). 98.9% and 87.1% of the MIS and open surgery cohorts reported a preference for MIS surgery in the future.

Conclusion.

Patients who received a MIS approach more frequently sought out their surgeons, were more confident in their procedure, and reported less perceived disadvantages following their surgery compared with the open surgery cohort. Both cohorts would prefer MIS surgery in the future. Overall, patients have positive perceptions of MIS surgery.

Level of Evidence: 3
Myocardial strain in hypertension: a meta-analysis of two-dimensional speckle tracking echocardiographic studies
Authors: Tadic Marijana , Sala Carla , Carugo Stefano , Mancia Giuseppe , Grassi Guido , Cuspidi Cesare
Published: May 2021

Aim:

Available evidence on systolic dysfunction in systemic hypertension, as assessed by left ventricular (LV) mechanics, is still based on single studies. Thus, we performed a systematic meta-analysis of two-dimensional speckle-tracking studies in order to provide an updated comprehensive information on this issue.

Methods:

The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English language articles published from the inception up to 31 December 2020. Studies were identified by using MeSH terms and crossing the following search items: ‘myocardial strain’, ‘left ventricular mechanics’, ‘speckle tracking echocardiography’, ‘systolic dysfunction’, ‘hypertensive heart disease’, ‘systemic hypertension’, ‘essential hypertension’.

Results:

Data from 4276 individuals (2089 normotensive controls and 2187 mostly uncomplicated hypertensive patients) were included. Left ventricular (LV) mass index, relative wall thickness, left atrial volume index and E/e’ ratio were significantly higher in hypertensive patients than in normotensive controls. LV ejection fraction did not differ in the two pooled groups (SMD −0.048 ± 0.054, 95% CI −0.20 to 0.10, P = 0.30), whereas LV global longitudinal strain (GLS) was significantly impaired in the hypertensive group (SMD: 1.07 ± 0. 15, 95% CI 0.77–1.36, P < 0.0001). Similar findings were obtained in a sub-analysis restricted to 15 studies in which mean age was similar in cases and controls (SMD 1.21 ± 0.23, 95% CI 0.76–1.67, P = 0.002).

Conclusion:

The present meta-analysis suggests that GLS assessment unmasks systolic dysfunction undetected by conventional ejection fraction in the uncomplicated hypertension setting and that this parameter should be incorporated into routine work-up aimed to identify hypertension-mediated cardiac damage.
Novel Treatment of a Diffuse Infantile Hepatic Hemangioma With a Selective Beta-1 Antagonist
Authors: Tanguay Julia K. , Erdemir Huseyin H. , Onimoe Grace
Published: June 2021

Propranolol has been the new standard-of-care treatment for infantile hepatic hemangioma (IHH) cases necessitating medical treatment based on a case series in 2008 that reported how propranolol resulted in involution of cutaneous infantile hemangioma in 2 patients with heart failure. The mechanism of action of propranolol on cutaneous infantile hemangiomas and IHHs is not well-understood, although new research suggests that hemangiomas and other vascular tumors express high amounts of β1 to β3 receptors, and thus explains why these vascular tumors are susceptible to beta-antagonists. However, there are reports of adverse side effects with the use of propranolol, including hypoglycemia, bronchial hyperreactivity, and sleep disturbances. There has been an interest in utilizing selective beta-antagonists to avoid potential side effects of propranolol in treating vascular tumors. We report the first documented case of a 4-month-old patient with diffuse IHH successfully treated with atenolol.
Autoimmune Cytopenia as an Early and Initial Presenting Manifestation in Activated PI3 Kinase Delta Syndrome: Case Report and Review
Authors: Schworer Stephen A. , Francis Olivia L. , Johnson Steven M. , Smith Benjamin D. , Gold Stuart H. , Smitherman Andrew B. , Wu Eveline Y.
Published: May 2021

Activated PI3 kinase delta syndrome (APDS) is a combined immunodeficiency characterized by recurrent sinopulmonary infections, increased risk of herpesvirus infections, lymphoproliferation, autoimmunity, and increased risk of lymphoid malignancies. Gain-of-function mutations in PIK3CD and PIK3R1 result in increased phosphoinositide-3-kinase-delta activity which causes hyperactivation of lymphocytes and abnormal development and activation of T and B cells. Cytopenias are the most common autoimmune process occurring in patients with APDS and typically occur as a later manifestation of the disease. Here we present a female patient with an early autoimmune hemolytic anemia, hepatosplenomegaly, and frequent infections presenting in infancy, followed by development of significant lymphadenopathy before her diagnosis with APDS type 1. She had significant improvement in her infectious history with immunoglobulin replacement, and control of autoimmune hemolytic anemia with initiation of sirolimus after her diagnosis with APDS type 1. We utilize this case to review the literature on APDS and present the novel finding of early-onset autoimmune disease in the setting of APDS. Autoimmune cytopenias are seen in many primary immunodeficiencies, and workup of autoimmune cytopenias in young patients should include evaluation for underlying immune disorder.
Management of Hyperleukocytosis in Childhood Acute Leukemia Without Leukapheresis and Rasburicase Prophylaxis
Authors: Aylan Gelen Sema , Sarper Nazan , Zengin Emine , Azizoğlu Mehmet
Published: May 2021

Indications of leukapheresis (LPh) and the prophylactic use of rasburicase in tumor lysis syndrome (TLS) of patients with acute leukemia with hyperleukocytosis are not clear. In this retrospective single-center pediatric study, the outcomes of patients with hyperleukocytosis were reviewed. There were 48 patients with acute lymphoblastic leukemia (ALL) and 13 patients with acute myeloblastic leukemia (AML). The treatment strategies included hyperhydration, allopurinol administration, strict monitoring, and early initiation of induction chemotherapy (CT). No patient underwent LPh because it was not available. Rasburicase was used only in 3 ALL patients with hyperuricemia when the drug was available. Laboratory and clinical TLS developed in 54.16% and 14.58% of patients with ALL, respectively. Laboratory and clinical TLS developed in 76.92% and 15.38% of patients with AML, respectively. No patient developed grade III to V TLS requiring dialysis. Thirteen patients (21.3%) had pulmonary leukostasis on admission, but recovered with CT and nasal oxygen. During the first 14 days of presentation, cerebral leukostasis/coagulopathy-related early death (ED) was 4.2% and 7.7% in patients with ALL and AML, respectively, and all of these patients had a white blood cell count ≥400,000/µL. There was also 1 infection-related death. Patients with hyperleukocytosis can be treated without LPh and liberal use of rasburicase. Renal failure is no longer a cause of ED. Intracranial hemorrhage is the main cause of ED, especially in patients already presenting with this complication. LPh may be performed in patients with leukostasis, if it is not possible to start induction CT early. When resources are limited, rasburicase should be administered in patients presenting with or developing hyperuricemia and/or renal dysfunction.
Using the Delphi Method to Construct a Promotion Plan for Clinical Nurse Specialists
Authors: Zhao Han , Li Weihua , Gao Mingrong , Shi Lei
Published: June 2021

Purpose

The aim of this study was to design a quantitative evaluation of the promotion plan for clinical nurse specialists in China.

Design

The evaluation indexes were selected and established by inquiring 22 experts and using the analytic hierarchy process. The promotion plan was sent to 22 specialized nurses. The reference value was established by comparing the results from predictions made by experts and the self-evaluation of specialized nurses.

Methods

This study used the Delphi method and mixed qualitative and quantitative methods, which not only determined the entry of the promotion plan but also calculated its weight, and obtained the baseline score through a small range of empirical studies.

Results

This promotion plan included basic promotion conditions, 5 primary indicators, 15 secondary indicators, and 61 tertiary indicators and was designed by experts who had a high degree of authority in this field. The self-evaluation results of 19 specialist nurses showed a reference value of 30 points per 3 years using the promotion plan. For clinical nursing managers, it is a management tool to evaluate specialist nurses, which can provide a basis for the promotion of specialist nurses.

Conclusions

The promotion plan for clinical nurse specialists in China formed by this research is quantifiable, scientific, and instructive.
Driving Pressure and Normalized Energy Transmission Calculations in Mechanically Ventilated Children Without Lung Disease and Pediatric Acute Respiratory Distress Syndrome*
Authors: Díaz Franco , González-Dambrauskas Sebastián , Cristiani Federico , Casanova Daniel R. , Cruces Pablo
Published: May 2021

OBJECTIVES:

To compare the new tools to evaluate the energy dissipated to the lung parenchyma in mechanically ventilated children with and without lung injury. We compared their discrimination capability between both groups when indexed by ideal body weight and driving pressure.

DESIGN:

Post hoc analysis of individual patient data from two previously published studies describing pulmonary mechanics.

SETTING:

Two academic hospitals in Latin-America.

PATIENTS:

Mechanically ventilated patients younger than 15 years old were included. We analyzed two groups, 30 children under general anesthesia (ANESTH group) and 38 children with pediatric acute respiratory distress syndrome.

INTERVENTIONS:

Respiratory mechanics were measured after intubation in all patients.

MEASUREMENTS AND MAIN RESULTS:

Mechanical power and derived variables of the equation of motion (dynamic power, driving power, and mechanical energy) were computed and then indexed by ideal body weight. Driving pressure was higher in pediatric acute respiratory distress syndrome group compared with ANESTH group. Receiver operator curve analysis showed that driving pressure had the best discrimination capability compared with all derived variables of the equation of motion indexed by ideal body weight. The same results were observed when the subgroup of patients weighs less than 15 kg. There was no difference in unindexed mechanical power between groups.

CONCLUSIONS:

Driving pressure is the variable that better discriminates pediatric acute respiratory distress syndrome from nonpediatric acute respiratory distress syndrome in children than the calculations derived from the equation of motion, even when indexed by ideal body weight. Unindexed mechanical power was useless to differentiate against both groups. Future studies should determine the threshold for variables of the energy dissipated by the lungs and their association with clinical outcomes.
Blindness Secondary to Orbital Giant Cell Granuloma Mass-Effect in Noonan Syndrome With Return of Vision Following Surgical Decompression
Authors: Anderson Spencer R. , Mancho Salim N.
Published: May 2021

Noonan syndrome is a rare, autosomal dominant disorder encompassing multiple congenital defects, as well as association with solid tumor and lesion development. The authors present a 26-year-old female with known Noonan syndrome and ongoing complaint of worsening unilateral vision, progressing to vision loss due to lesion mass effect. Decompressive surgery was performed, restoring patient's vision to baseline immediately postoperative. The lesion was confirmed to be giant cell granuloma. In this paper we discuss the unique presentation of vision loss due to orbital giant cell granuloma in Noonan syndrome with postoperative return of vision; the importance of a multi-disciplinary team evaluation, thorough preoperative clinical and image-based work up, intraoperative findings, postoperative outcome, and complexity of definitive management.
Unicoronal Craniosynostosis: Is There a Lateral Difference in Retinal Morphology?
Authors: Kalmar Christopher L. , Carlson Anna R. , Zapatero Zachary D. , Kosyk Mychajlo S. , Aleman Tomas S. , Bartlett Scott P. , Liu Grant T. , Avery Robert A. , Taylor Jesse A. , Swanson Jordan W.
Published: May 2021

Background:

Craniosynostosis is the premature fusion of cranial sutures in pediatric patients, which may lead to elevated intracranial pressure due to cerebro-cephalic disproportion between a growing brain and constricted skull. It is unknown whether this increased pressure is distributed equally throughout the cranial vault, or whether certain areas of the brain experience greater pressure at these regions of premature osseous fusion.

Methods:

Optical coherence tomography (OCT) is a noninvasive modality for detecting elevated intracranial pressure. Optical coherence tomography was utilized to measure the peripapillary retinal nerve fiber layer (RNFL) thickness in patients undergoing surgical correction of craniosynostosis. Retinal nerve fiber layer in the eye ipsilateral to the unicoronal suture fusion was compared to the RNFL in the eye contralateral to the unicoronal suture fusion.

Results:

During the study interval, 21 patients met inclusion criteria. Median age at operative intervention was 8.0 months, and 28.6% patients presented with left-sided unicoronal craniosynostosis, whereas 71.4% of patients presented with right-sided unicoronal craniosynostosis. Rather than universal increase on the affected side of coronal suture fusion, retinal nerve fiber layer thickness parameters showed a rotation phenomenon, such that the patterns of elevation had a 45° circumferential rotation in the direction of intorsion.

Conclusions:

The explanation for these results remains elusive, but they likely indicate either intracranial changes transmitted differentially to the peripapillary retina, or differing retinal morphology, between the ipsilateral and contralateral eyes in unicoronal craniosynostosis.
Concurrency measures in the era of temporal network epidemiology: a review
Authors: Masuda Naoki , Miller Joel C. , Holme Petter
Published: June 2021

Diseases spread over temporal networks of interaction events between individuals. Structures of these temporal networks hold the keys to understanding epidemic propagation. One early concept of the literature to aid in discussing these structures is concurrency—quantifying individuals’ tendency to form time-overlapping ‘partnerships’. Although conflicting evaluations and an overabundance of operational definitions have marred the history of concurrency, it remains important, especially in the area of sexually transmitted infections. Today, much of theoretical epidemiology uses more direct models of contact patterns, and there is an emerging body of literature trying to connect methods to the concurrency literature. In this review, we will cover the development of the concept of concurrency and these new approaches.
Optimal use of simplified social information in sequential decision-making
Authors: Mann Richard P.
Published: June 2021

Social animals can improve their decisions by attending to those made by others. The benefit of this social information must be balanced against the costs of obtaining and processing it. Previous work has focused on rational agents that respond optimally to a sequence of prior decisions. However, full decision sequences are potentially costly to perceive and process. As such, animals may rely on simpler social information, which will affect the social behaviour they exhibit. Here, I derive the optimal policy for agents responding to simplified forms of social information. I show how the behaviour of agents attending to the aggregate number of previous choices differs from those attending to just the most recent prior decision, and I propose a hybrid strategy that provides a highly accurate approximation to the optimal policy with the full sequence. Finally, I analyse the evolutionary stability of each strategy, showing that the hybrid strategy dominates when cognitive costs are low but non-zero, while attending to the most recent decision is dominant when costs are high. These results show that agents can employ highly effective social decision-making rules without requiring unrealistic cognitive capacities, and indicate likely ecological variation in the social information different animals attend to.
Suction feeding by elephants
Authors: Schulz Andrew K. , Ning Wu Jia , Ha Sung Yeon Sara , Kim Greena , Braccini Slade Stephanie , Rivera Sam , Reidenberg Joy S. , Hu David L.
Published: June 2021

Despite having a trunk that weighs over 100 kg, elephants mainly feed on lightweight vegetation. How do elephants manipulate such small items? In this experimental and theoretical investigation, we filmed elephants at Zoo Atlanta showing that they can use suction to grab food, performing a behaviour that was previously thought to be restricted to fishes. We use a mathematical model to show that an elephant’s nostril size and lung capacity enables them to grab items using comparable pressures as the human lung. Ultrasonographic imaging of the elephant sucking viscous fluids show that the elephant’s nostrils dilate up to30%in radius, which increases the nasal volume by64%. Based on the pressures applied, we estimate that the elephants can inhale at speeds of over 150 m s−1, nearly 30 times the speed of a human sneeze. These high air speeds enable the elephant to vacuum up piles of rutabaga cubes as well as fragile tortilla chips. We hope these findings inspire further work in suction-based manipulation in both animals and robots.
The relationship between brain injury criteria and brain strain across different types of head impacts can be different
Authors: Zhan Xianghao , Li Yiheng , Liu Yuzhe , Domel August G. , Alizadeh Hossein Vahid , Raymond Samuel J. , Ruan Jesse , Barbat Saeed , Tiernan Stephen , Gevaert Olivier , Zeineh Michael M. , Grant Gerald A. , Camarillo David B.
Published: June 2021

Multiple brain injury criteria (BIC) are developed to quickly quantify brain injury risks after head impacts. These BIC originated from different head impact types (e.g. sports and car crashes) are widely used in risk evaluation. However, the accuracy of using the BIC on brain injury risk estimation across head impact types has not been evaluated. Physiologically, brain strain is often considered the key parameter of brain injury. To evaluate the BIC's risk estimation accuracy across five datasets comprising different head impact types, linear regression was used to model 95% maximum principal strain, 95% maximum principal strain at the corpus callosum and cumulative strain damage (15%) on 18 BIC. The results show significantly different relationships between BIC and brain strain across datasets, indicating the same BIC value may suggest different brain strain across head impact types. The accuracy of brain strain regression is generally decreasing if the BIC regression models are fitted on a dataset with a different type of head impact rather than on the dataset with the same type. Given this finding, this study raises concerns for applying BIC to estimate the brain injury risks for head impacts different from the head impacts on which the BIC was developed.
Techniques for RNA extraction from cells cultured in starPEG–heparin hydrogels
Authors: Jaeschke Anna , Harvey Nicholas R. , Tsurkan Mikhail , Werner Carsten , Griffiths Lyn R. , Haupt Larisa M. , Bray Laura J.
Published: June 2021

Three-dimensional (3D) cell culture models that provide a biologically relevant microenvironment are imperative to investigate cell–cell and cell–matrix interactions
in vitro
. Semi-synthetic star-shaped poly(ethylene glycol) (starPEG)–heparin hydrogels are widely used for 3D cell culture due to their highly tuneable biochemical and biomechanical properties. Changes in gene expression levels are commonly used as a measure of cellular responses. However, the isolation of high-quality RNA presents a challenge as contamination of the RNA with hydrogel residue, such as polymer or glycosaminoglycan fragments, can impact template quality and quantity, limiting effective gene expression analyses. Here, we compare two protocols for the extraction of high-quality RNA from starPEG–heparin hydrogels and assess three subsequent purification techniques. Removal of hydrogel residue by centrifugation was found to be essential for obtaining high-quality RNA in both isolation methods. However, purification of the RNA did not result in further improvements in RNA quality. Furthermore, we show the suitability of the extracted RNA for cDNA synthesis of three endogenous control genes confirmed via quantitative polymerase chain reaction (qPCR). The methods and techniques shown can be tailored for other hydrogel models based on natural or semi-synthetic materials to provide robust templates for all gene expression analyses.
A spatial model of COVID-19 transmission in England and Wales: early spread, peak timing and the impact of seasonality
Authors: Danon Leon , Brooks-Pollock Ellen , Bailey Mick , Keeling Matt
Published: May 2021

An outbreak of a novel coronavirus was first reported in China on 31 December 2019. As of 9 February 2020, cases have been reported in 25 countries, including probable human-to-human transmission in England. We adapted an existing national-scale metapopulation model to capture the spread of COVID-19 in England and Wales. We used 2011 census data to inform population sizes and movements, together with parameter estimates from the outbreak in China. We predict that the epidemic will peak 126 to 147 days (approx. 4 months) after the start of person-to-person transmission in the absence of controls. Assuming biological parameters remain unchanged and transmission persists from February, we expect the peak to occur in June. Starting location and model stochasticity have a minimal impact on peak timing. However, realistic parameter uncertainty leads to peak time estimates ranging from 78 to 241 days following sustained transmission. Seasonal changes in transmission rate can substantially impact the timing and size of the epidemic. We provide initial estimates of the epidemic potential of COVID-19. These results can be refined with more precise parameters. Seasonal changes in transmission could shift the timing of the peak into winter, with important implications for healthcare capacity planning.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK.
Optimizing time-limited non-pharmaceutical interventions for COVID-19 outbreak control
Authors: Morgan Alex L. K. , Woolhouse Mark E. J. , Medley Graham F. , van Bunnik Bram A. D.
Published: May 2021

Retrospective analyses of the non-pharmaceutical interventions (NPIs) used to combat the ongoing COVID-19 outbreak have highlighted the potential of optimizing interventions. These optimal interventions allow policymakers to manage NPIs to minimize the epidemiological and human health impacts of both COVID-19 and the intervention itself. Here, we use a susceptible–infectious–recovered (SIR) mathematical model to explore the feasibility of optimizing the duration, magnitude and trigger point of five different NPI scenarios to minimize the peak prevalence or the attack rate of a simulated UK COVID-19 outbreak. An optimal parameter space to minimize the peak prevalence or the attack rate was identified for each intervention scenario, with each scenario differing with regard to how reductions to transmission were modelled. However, we show that these optimal interventions are fragile, sensitive to epidemiological uncertainty and prone to implementation error. We highlight the use of robust, but suboptimal interventions as an alternative, with these interventions capable of mitigating the peak prevalence or the attack rate over a broader, more achievable parameter space, but being less efficacious than theoretically optimal interventions. This work provides an illustrative example of the concept of intervention optimization across a range of different NPI strategies.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Leafy greens as a potential source of multidrug-resistant diarrhoeagenic Escherichia coli and Salmonella
Authors: Priyanka  , Meena Prem Raj , Meghwanshi Keshav Kumar , Rana Anuj , Singh Arvind Pratap
Published: June 2021

A continued rise in leafy green-linked outbreaks of disease caused by pathogenic

Escherichia coli

or

Salmonella

, particularly strains exhibiting multidrug resistance (MDR), has emerged as a major threat to human health and food safety worldwide. Thus, the present study was conducted to examine antimicrobial resistance, including MDR, in diarrhoeagenic

E. coli

(DEC) and

Salmonella

isolates obtained from leafy greens from rural and urban areas of India. Of the collected samples (830), 14.1 and 6.5% yielded 117

E. coli

(40 DEC and 77 non-DEC) and 54

Salmonella

isolates, respectively. Among the DEC pathotypes, enteroaggregative

E. coli

was the most prevalent (10.2 %), followed by enteropathogenic

E. coli

(9.4 %), enteroinvasive

E. coli

(7.6 %) and enterohemorrhagic

E. coli

(6.8 %). Antimicrobial susceptibility testing of all bacterial isolates with respect to drugs categorized as critically or highly important in both human and veterinary medicine revealed moderate to high (30–90%) resistance for amoxicillin/clavulanic acid, ampicillin, gentamycin and colistin, but relatively low resistance (>30 %) for ciprofloxacin, trimethoprim/sulfamethoxazole and fosfomycin. Notably, all DEC and more than 90% non-DEC or

Salmonella

isolates were found to be multidrug-resistant to drugs of both human and animal importance. Overall, the results of the present study suggest that leafy greens are potential reservoirs or sources of multidrug-resistant DEC and

Salmonella

strains in the rural or urban areas of India.
Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination
Authors: Caniels Tom G. , Bontjer Ilja , van der Straten Karlijn , Poniman Meliawati , Burger Judith A. , Appelman Brent , Lavell Ayesha H.A. , Oomen Melissa , Godeke Gert-Jan , Valle Coralie , Mögling Ramona , van Willigen Hugo D.G. , Wynberg Elke , Schinkel Michiel , van Vught Lonneke A. , Guerra Denise , Snitselaar Jonne L. , Chaturbhuj Devidas N. , Martin Isabel Cuella ,   Amsterdam UMC COVID-19 S3/HCW study group, Moore John P. , de Jong Menno D. , Reusken Chantal , Sikkens Jonne J. , Bomers Marije K. , de Bree Godelieve J. , van Gils Marit J. , Eggink Dirk , Sanders Rogier W.
Published: June 2021

Emerging SARS-CoV-2 variants pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three variants of concern (B.1.1.7, B.1.351 and P.1) in cohorts of COVID-19 patients ranging in disease severity (n = 69) and recipients of the Pfizer/BioNTech vaccine (n = 50). Spike binding and neutralization against all three VOC was substantially reduced in the majority of samples, with the largest 4-7-fold reduction in neutralization being observed against B.1.351. While hospitalized COVID-19 patients and vaccinees maintained sufficient neutralizing titers against all three VOC, 39% of non-hospitalized patients did not neutralize B.1.351. Moreover, monoclonal neutralizing antibodies (NAbs) show sharp reductions in their binding kinetics and neutralizing potential to B.1.351 and P.1, but not to B.1.1.7. These data have implications for the degree to which pre-existing immunity can protect against subsequent infection with VOC and informs policy makers of susceptibility to globally circulating SARS-CoV-2 VOC.
Prevalence of Returnable Genetic Results Based on Recognizable Phenotypes among Children with Autism Spectrum Disorder
Authors: Bishop Somer L. , Thurm Audrey , Robinson Elise , Sanders Stephan J
Published: June 2021

The importance of extensive genetic testing of autism spectrum disorder (ASD) cases has been demonstrated repeatedly in research settings but such testing in clinical settings remains sporadic. Determining which individuals should be prioritized for expensive tests remains a challenge. Several guidelines have been released relating to clinical genetic evaluations and testing in the context of ASD and these guidelines may be informed by the results of genetic testing in large research cohorts. The current study summarizes findings from over 2,000 individuals with ASD who received genetic testing, including microarray and exome testing, through the Simons Simplex Consortium. A returnable genetic result is identified in 10% of cases, however, this yield increases based on four readily accessible phenotypes: female sex and the presence of intellectual disability, seizures or delayed walking. Combinations of these factors increase return rate further, with some combinations yielding a return rate over 50%. In conclusion, these four phenotypes provide a simple approach to prioritize genetic testing in a clinical setting and inform future clinical guidelines. Providing a systematic approach to decisions about who to test removes barriers for, and therefore decrease disparities in, reimbursable genetic testing for individuals diagnosed with ASD.
Infectious SARS-CoV-2 Virus in Symptomatic COVID-19 Outpatients: Host, Disease, and Viral Correlates
Authors: Mollan Katie R. , Eron Joseph J. , Krajewski Taylor J. , Painter Wendy , Duke Elizabeth R. , Morse Caryn G. , Goecker Erin A. , Premkumar Lakshmanane , Wolfe Cameron R. , Szewczyk Laura J. , Alabanza Paul L. , Loftis Amy James , Degli-Angeli Emily J. , Brown Ariane J. , Dragavon Joan A. , Won John J. , Keys Jessica , Hudgens Michael G. , Fang Lei , Wohl David A. , Cohen Myron S. , Baric Ralph S. , Coombs Robert W. , Sheahan Timothy P. , Fischer William A.
Published: June 2021

Background

While SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection.

Methods

COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay.

Results

Among 204 participants with mild-to-moderate symptomatic COVID19, the median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (IgA, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001).

Conclusions

The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion.

ClinicalTrials.gov Identifier

NCT04405570

Key Points (Summary)

Among COVID-19 outpatients within 7 days of symptom onset, the presence of SARS-CoV-2-specific antibodies was strongly associated with clearance of infectious virus. Seropositivity appears to be more reliable marker of infectious virus clearance than subjective measure of COVID-19 symptoms.
Robust Characterization of Non-Invasive Post-Traumatic Osteoarthritis Mouse Model
Authors: Bhatti Fazal-Ur-Rehman , Jeong Yong-Hoon , Kim Do-Gyoon , Brand David D. , Hasty Karen A. , Cho Hongsik
Published: May 2021

Objective

Biochemical and molecular changes involved in the pathophysiology of post-traumatic arthritis (PTOA) have not been fully understood. This study used non-invasive mouse models to study biochemical, biomechanical and pain-related behavior changes induced in mice following repetitive mechanical knee loading. Mouse models were used to reflect the effects of the early stages of PTOA in humans.

Methods

Forty-eight twelve week old male mice were obtained for three groups: normal control without mechanical loading, trauma (24 hours after loading), and PTOA (early OA) groups. For the non-invasive PTOA mouse model, cyclic comprehensive loading (9 N) was applied on the left knee joint of each mouse. Biochemical and molecular changes induced by mechanical loading were analyzed after loading was completed. Blood and cartilage were collected and further examined using gene expression analysis. Grading of the tissue sections was completed using the osteoarthritis research society international (OARSI) scale. Biomechanical features of mechanically loaded knee joints were determined after 24 hours (Trauma) and three weeks (PTOA) post-mechanical loading sessions to examine the development of PTOA, respectively.

Results

The loaded left knee joint showed a greater ROS/RNS signal than the right knee that was not loaded. There was an increase in cartilage damage and MMP activity in the affected knee as the intensity of MabCII680 and MMP750 signal increased in the mechanical loaded joints as compared to unloaded control knee joints. There was also an increase in the difference of viscoelastic energy dissipation ability (tan δ) in PTOA. The OA score increased significantly in mechanically loaded knee joints.

Conclusion

This study showed that biomechanical, biochemical, and behavioral characteristics of the murine PTOA groups are significantly different from the control group. These results validate that the current mouse model can be used for translational studies to examine PTOA.
Association between individual and country-level socioeconomic factors and work participation in spondyloarthritis including psoriatic arthritis: analysis of the ASAS-perSpA study
Authors: Zhao Sizheng Steven , Nikiphorou Elena , Boonen Annelies , López-Medina Clementina , Dougados Maxime , Ramiro Sofia
Published: June 2021

Objective

To examine whether associations between socioeconomic factors and work outcomes in spondyloarthritis (SpA) differ across axial (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA), and whether associations for individual-level socioeconomic factors are modified by country-level factors.

Methods

Patients with a physician diagnosis of SpA within working age (18-65 years) were included. Associations between individual- (age, gender, education, marital status) and country-level factors (Human Development Index, Health Care Expenditure (HCE), Gross Domestic Product, percentage unemployed) with work outcomes (employment status, absenteeism, presenteeism) were assessed using multivariable mixed-effects models. Associations between individual factors and outcomes were compared according to SpA phenotypes and country-level factors using interaction terms.

Results

A total of 3835 patients (mean age 42 years, 61% males) from 23 countries worldwide were included (66% axSpA, 10% pSpA, 23% PsA). Being employed was associated with gender (male vs. female OR 2.5; 95%CI 1.9-3.2), education (university vs. primary OR 3.7; 2.9-4.7), marital status (married vs. single OR 1.3; 1.04-1.6), and age in a non-linear manner. University (vs primary) education was associated with lower odds of absenteeism (OR 0.7; 0.5-0.96) and presenteeism (OR 0.5; 0.3-0.7). Associations were similar across SpA phenotypes. Higher HCE was associated with more favourable work outcomes, e.g., higher odds of employment (OR 2.5; 1.5-4.1). Gender discrepancy in odds of employment was greater in countries with lower socioeconomic development.

Conclusion

Higher educational attainment and higher HCE were associated with more favourable work outcomes, independently of SpA phenotype. The disadvantageous effect of female gender on employment is particularly strong in countries with lower socioeconomic development.
Eosinophils are an integral component of the pulmonary granulocyte response in Tuberculosis and promote host resistance in mice
Authors: Bohrer Andrea C. , Castro Ehydel , Hu Zhidong , Queiroz Artur T.L. , Tocheny Claire E. , Assmann Maike , Sakai Shunsuke , Nelson Christine , Baker Paul J. , Ma Hui , Wang Lin , Zilu Wen , du Bruyn Elsa , Riou Catherine , Kauffman Keith D. ,   Tuberculosis Imaging Program, Moore Ian N. , Nonno Franca Del , Petrone Linda , Goletti Delia , Martineau Adrian R. , Lowe David M. , Cronan Mark R. , Wilkinson Robert J. , Barry Clifton E. , Via Laura E. , Barber Daniel L. , Klion Amy D. , Andrade Bruno B. , Song Yanzheng , Wong Ka-Wing , Mayer-Barber Katrin D.
Published: June 2021

Host resistance to Mycobacterium tuberculosis infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. Influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, employing complementary genetic models of eosinophil deficiency, we demonstrate that, in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice.
Biofouling Characteristics of Graphene Oxide Membrane in a Protein-rich Environment
Authors: Rode Richard , Moghaddam Saeed
Published: May 2021

Membrane biofouling has inhibited permselective separation processes for decades, requiring frequent membrane backwash treatment or replacement to maintain efficacy. However, frequent treatment is not viable for devices with a continuous blood flow such as a wearable or implantable dialyzer. In this study, the biofouling characteristics of a highly hemocompatible graphene oxide (GO) membrane developed through a novel self-assembly process is studied in a protein-rich environment and compared with performance of a state-of-the-art commercial polymer membrane dialyzer. The studies are conducted in phosphate-buffered saline (PBS) environment using human serum albumin (HSA), which represents 60% of the blood protein, at the nominal blood protein concentration of 1 g L-1. Protein aggregation on the membrane surface is evaluated by monitoring the change in the membrane flux and SEM imaging. The GO membrane water flux declined only ~10% over a week-long test whereas the polymer membrane flux declined by 50% during the same period. The SEM images show that HSA primarily aggerates over the graphitic regions of nanoplatelets, away from the charged hydrophilic edges. This phenomenon leaves the open areas of the membrane formed between the nanoplatelets edges, through which the species pass, relatively intact. In contrast, HSA completely plugs the polymer membrane pores resulting in a steady decline in membrane permeability.
Aerosol SARS-CoV-2 in hospitals and long-term care homes during the COVID-19 pandemic
Authors: Mallach Gary , Kasloff Samantha B. , Kovesi Tom , Kumar Anand , Kulka Ryan , Krishnan Jay , Robert Benoit , McGuinty Michaeline , Otter-Moore Sophia den , Yazji Bashour , Cutts Todd
Published: June 2021

Background

Few studies have quantified aerosol concentrations of SARS-CoV-2 in hospitals and long-term care homes, and fewer still have examined samples for viability. This information is needed to clarify transmission risks beyond close contact.

Methods

We deployed particulate air samplers in rooms with COVID-19 positive patients in hospital ward and ICU rooms, rooms in long-term care homes experiencing outbreaks, and a correctional facility experiencing an outbreak. Samplers were placed between 2 and 3 meters from the patient. Aerosol (small liquid particles suspended in air) samples were collected onto gelatin filters by Ultrasonic Personal Air Samplers (UPAS) fitted with <2.5µm (micrometer) and <10 µm size-selective inlets operated for 16 hours (total 1.92m3), and with a Coriolis Biosampler over 10 minutes (total 1.5m3). Samples were assayed for viable SARS-CoV-2 virus and for the viral genome by multiplex PCR using the E and N protein target sequences. We validated the sampling methods by inoculating gelatin filters with viable vesicular stomatitis virus (VSV), and with three concentrations of viable SARS-CoV-2, operating personal samplers for 16hrs, and quantifying viable virus recovery by TCID50 assay.

Results

In total, 138 samples were collected from 99 rooms. RNA samples were positive in 9.1% (6/66) of samples obtained with the UPAS 2.5µm samplers, 13.5% (7/52) with the UPAS 10µm samplers, and 10.0% (2/20) samples obtained with the Coriolis samplers. Culturable virus was not recovered in any samples. Viral RNA was detected in 10.9% of the rooms sampled. There was no significant difference in viral RNA recovery between the different room locations or samplers. Method development experiments indicated minimal loss of SARS-CoV-2 viability via the personal air sampler operation.

Key Findings

Although a subset of aerosol samples exhibited detectable SARS-CoV-2 RNA at low titres, the presence of viable SARS-CoV-2 virus in aerosols appears to be infrequent at >2m distance.
Mediobasal hypothalamic FKBP51 acts as a molecular switch linking autophagy to whole-body metabolism
Authors: Häusl Alexander S. , Brix Lea M. , Bajaj Thomas , Pöhlmann Max L. , Hafner Kathrin , De Angelis Meri , Nagler Joachim , Balsevich Georgia , Schramm Karl-Werner , Giavalisco Patrick , Chen Alon , Schmidt Mathias V. , Gassen Nils C.
Published: June 2021

The mediobasal hypothalamus (MBH) is the central region in the physiological response to metabolic stress. The FK506-binding protein 51 (FKBP51) is a major modulator of the stress response and has recently emerged as a scaffolder regulating metabolic and autophagy pathways. However, the detailed protein-protein interactions linking FKBP51 to autophagy upon metabolic challenges remain elusive. We performed mass spectrometry-based metabolomics of FKBP51 knockout (KO) cells revealing an increased amino acid and polyamine metabolism. We identified FKBP51 as a central nexus for the recruitment of the LKB1/AMPK complex to WIPI4 and TSC2 to WIPI3, thereby regulating the balance between autophagy and mTOR signaling in response to metabolic challenges. Furthermore, we demonstrated that MBH FKBP51 deletion strongly induces obesity, while its overexpression protects against high-fat diet (HFD) induced obesity. Our study provides an important novel regulatory function of MBH FKBP51 within the stress-adapted autophagy response to metabolic challenges.
Correlation of vaccine-elicited antibody levels and neutralizing activities against SARS-CoV-2 and its variants
Authors: Liu Jinbiao , Bodnar Brittany H , Wang Xu , Wang Peng , Meng Fengzhen , Khan Adil I , Saribas A Sami , Padhiar Nigam H , McCluskey Elizabeth , Shah Sahil , Luo Jin Jun , Hu Wen-Hui , Ho Wen-Zhe
Published: June 2021

Both Pfizer-BNT162b2 and Moderna-mRNA-1273 vaccines can elicit an effective immune response against SARS-CoV-2 infection. However, the elicited serum antibody levels vary substantially and longitudinally decrease after vaccination. We examined the correlation of vaccination-induced IgG levels and neutralization titers against newly emerged variants remains and demonstrate a significant reduction of neutralization activities against the variants (B.1.1.7, B.1.525, and B.1.351) in Pfizer or Moderna vaccined sera. There was a significant and positive correlation between serum IgG levels and ID50 titers for not only SARS-CoV-2 WT but also the variants. These findings indicate that a high level of anti-spike IgG may offer better protection against infection from SARS-CoV-2 and its variants. Therefore, it is necessary to longitudinally monitor specific serum IgG level for evaluating the protective efficacy of the vaccines against SARS-CoV-2 and its new variants.