bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of the EphB6 receptor ectodomain
Authors: Mason Emilia O. , Goldgur Yehuda , Robev Dorothea , Freywald Andrew , Nikolov Dimitar B. , Himanen Juha P.
Published: March 2021

Eph receptors are the largest group amongst the receptor tyrosine kinases and are divided into two subgroups, A and B, based on ligand binding specificities and sequence conservation. Through ligand-induced and ligand-independent activities, Ephs play central roles in diverse biological processes, including embryo development, regulation of neuronal signaling, immune responses, vasculogenesis, as well as tumor initiation, progression, and metastasis. The Eph extracellular regions (ECDs) are constituted of multiple domains, and previous structural studies of the A class receptors revealed how they interact with ephrin ligands and simultaneously mediate Eph-Eph clustering necessary for biological activity. Specifically, EphA structures highlighted a model, where clustering of ligand-bound receptors relies on two distinct receptor/receptor interfaces. Interestingly, most unliganded A class receptors also form an additional, third interface, between the ligand binding domain (LBD) and the fibronectin III domain (FN3) of neighboring molecules. Structures of B-class Eph ECDs, on the other hand, have never been reported. To further our understanding of Eph receptor function, we crystallized the EphB6-ECD and determined its three-dimensional structure using X-ray crystallography. EphB6 has important functions in both normal physiology and human malignancies and is especially interesting because this atypical receptor innately lacks kinase activity and our understanding of the mechanism of action is still incomplete. Our structural data reveals the overall EphB6-ECD architecture and shows EphB6-LBD/FN3 interactions similar to those observed for the unliganded A class receptors, suggesting that these unusual interactions are of general importance to the Eph group. We also observe unique structural features, which likely reflect the atypical signaling properties of EphB6, namely the need of co-receptor(s) for this kinase-inactive Eph. These findings provide new valuable information on the structural organization and mechanism of action of the B-class Ephs, and specifically EphB6, which in the future will assist in identifying clinically relevant targets for cancer therapy.
Accuracy and reliability of the InBody 270 multi-frequency body composition analyser in 10-12-year-old children
Authors: Larsen Malte Nejst , Krustrup Peter , Araújo Póvoas Susana Cristina , Castagna Carlo
Published: March 2021

The aim of this study was at examining the validity and reliability of a marketed bioimpedance (BIA) scale for body composition assessment, in children engaged in an educational football project (FIFA 11 for Health). One-hundred and twenty-seven children (70 boys and 57 girls; age 10.7±0.5 years, body mass 41.2±9.0 kg, Body mass index 18.5±3.3 kg·m-2and stature 149±7 cm) were evaluated for total body mass, lean body mass, muscle mass, using BIA (InBody 270, Biospace, California, USA) and dual-energy X-ray absorptiometry (DEXA, Lunar Prodigy, GE Medical Systems, Madison, Wisconsin, USA), at baseline conditions. Data analyses were carried out separately for girls and boys. Nearly perfect associations (r = 0.97−0.99) and excellent absolute (TEM = 0.04−1.9%) and relative (ICC = 0.98−1.00) inter-device reliability were found between DEXA and BIA variables. Fat and lean body mass bias (p < .0001) were practically relevant both for the boys (2.56 and 11.22 kg, respectively) and the girls (2.33 and 10.49 kg, respectively). Muscle mass and body fat were underestimated and overestimated, respectively, for the boys and girls. InBody 270 is a valid BIA system for estimating body composition with an excellent inter-device relative and absolute reliability. However, the remarkable measurements bias of BIA fat and muscle mass values discourage its use for clinical prescription. The BIA body composition biases were sex dependent.
Identification and characterization of genes related to salt stress tolerance within segregation distortion regions of genetic map in F2 population of upland cotton
Authors: Shehzad Muhammad , Zhou Zhongli , Ditta Allah , Khan Majid , Cai Xiaoyan , Xu Yanchao , Maqbool Amir , Khalofah Ahlam , Shaban Muhammad , Naeem Muhammad , Ansari Mohammad Javed , Wang Kunbo , Liu Fang
Published: March 2021

Segregation distortion (SD) is a genetic mechanism commonly found in segregating or stable populations. The principle behind this puzzles many researchers. The F2generation developed from wildGossypium darwiniiandG.hirsutumCCRI12 species was used to investigate the possible transcription factors within the segregation distortion regions (SDRs). The 384 out of 2763 markers were distorted in 29 SDRs on 18 chromosomes. Good collinearity was observed among genetic and physical maps ofG.hirsutumandG.barbadensesyntenic blocks. Total 568 genes were identified from SDRs of 18 chromosomes. Out of these genes, 128 belonged to three top-ranked salt-tolerant gene families. The DUF597 contained 8 uncharacterized genes linked to Pkinase (PF00069) gene family in the phylogenetic tree, while 15 uncharacterized genes clustered with the zinc finger gene family. Two hundred thirty four miRNAs targeted numerous genes, including ghr-miR156, ghr-miR399 and ghr-miR482, while others targeted top-ranked stress-responsive transcription factors. Moreover, these genes were involved in the regulation of numerous stress-responsive cis-regulatory elements. The RNA sequence data of fifteen upregulated genes were verified through the RT-qPCR. The expression profiles of two highly upregulated genes (Gh_D01G2015andGh_A01G1773) in salt-tolerantG.darwiniishowed antagonistic expression inG.hirsutum. The results indicated that salt-tolerant genes have been possibly transferred from the wildG.darwiniispecies. A detailed functional analysis of these genes can be carried out which might be helpful in the future for gene cloning, transformation, gene editing and the development of salt-resistant cotton varieties.
An emergency system for monitoring pulse oximetry, peak expiratory flow, and body temperature of patients with COVID-19 at home: Development and preliminary application
Authors: Motta Leonardo Pereira , Silva Pedro Paulo Ferreira da , Borguezan Bruno Max , Amaral Jorge Luis Machado do , Milagres Lucimar Gonçalves , Bóia Márcio Neves , Ferraz Marcos Rochedo , Mogami Roberto , Nunes Rodolfo Acatauassú , Melo Pedro Lopes de
Published: March 2021

Background

COVID-19 is characterized by a rapid change in the patient’s condition, with major changes occurring over a few days. We aimed to develop and evaluate an emergency system for monitoring patients with COVID-19, which may be useful in hospitals where more severe patients stay in their homes.

Methodology/Principal findings

The system consists of the home-based patient unit, which is set up around the patient and the hospital unit, which enables the medical staff to telemonitor the patient’s condition and help to send medical recommendations. The home unit allows the data transmission from the patient to the hospital, which is performed using a cell phone application. The hospital unit includes a virtual instrument developed in LabVIEW® environment that can provide a real-time monitoring of the oxygen saturation (SpO2), beats per minute (BPM), body temperature (BT), and peak expiratory flow (PEF). Abnormal events may be fast and automatically identified. After the design details are described, the system is validated by a 30-day home monitoring study in 12 controls and 12 patients with COVID-19 presenting asymptomatic to mild disease. Patients presented reduced SpO2 (p<0.0001) and increased BPM values (p<0.0001). Three patients (25%) presented PEF values between 50 and 80% of the predicted. Three of the 12 monitored patients presented events of desaturation (SpO2<92%). The experimental results were in close agreement with the involved pathophysiology, providing clear evidence that the proposed system can be a useful tool for the remote monitoring of patients with COVID-19.

Conclusions

An emergency system for home monitoring of patients with COVID-19 was developed in the current study. The proposed system allowed us to quickly respond to early abnormalities in these patients. This system may contribute to conserving hospital resources for those most in need while simultaneously enabling early recognition of patients under acute deterioration, requiring urgent assessment.
Transient changes in white matter microstructure during general anesthesia
Authors: Tang Cheuk Y. , Wang Victoria X. , Lun Min Yin , Mincer Joshua S. , Ng Johnny C. , Brallier Jess W. , Schwartz Arthur E. , Ahn Helen , McCormick Patrick J. , Nir Tommer , Delman Bradley , Sano Mary , Deiner Stacie G. , Baxter Mark G.
Published: March 2021

Cognitive dysfunction after surgery under general anesthesia is a well-recognized clinical phenomenon in the elderly. Physiological effects of various anesthetic agents have been studied at length. Very little is known about potential effects of anesthesia on brain structure. In this study we used Diffusion Tensor Imaging to compare the white matter microstructure of healthy control subjects under sevoflurane anesthesia with their awake state. Fractional Anisotropy, a white mater integrity index, transiently decreases throughout the brain during sevoflurane anesthesia and then returns back to baseline. Other DTI metrics such as mean diffusivity, axial diffusivity and radial diffusivity were increased under sevoflurane anesthesia. Although DTI metrics are age dependent, the transient changes due to sevoflurane were independent of age and sex. Volumetric analysis shows various white matter volumes decreased whereas some gray matter volumes increased during sevoflurane anesthesia. These results suggest that sevoflurane anesthesia has a significant, but transient, effect on white matter microstructure. In spite of the transient effects of sevoflurane anesthesia there were no measurable effects on brain white matter as determined by the DTI metrics at 2 days and 7 days following anesthesia. The role of white matter in the loss of consciousness under anesthesia will need to be studied and MRI studies with subjects under anesthesia will need to take these results into account.
Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: A systematic review of the literature and meta-analysis
Authors: Eraso Isabel , Sangiovanni Saveria , Morales Eliana I. , Fernández-Trujillo Liliana
Published: March 2021

Background

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) might benefit from aspirin desensitization (AD) as an alternative treatment to standard care. However, there is conflicting evidence regarding its role in bronchial symptoms and asthma exacerbations.

Objective

To analyze the clinical effects of AD in terms of lung function, systemic and inhaled steroid use, the frequency of acute asthma exacerbations, and adverse effects in patients with NERD and asthma.

Methodology

We identified randomized clinical trials (RCTs) from PubMed, EMBASE, SCOPUS, and EBSCO. We also searched the RCT references for additional studies. Studies comparing AD to placebo in patients with a previous history of pulmonary symptoms triggered by ASA or other NSAIDs or with a positive provocation test to ASA were included.

Primary results

Five studies with 210 participants with NERD were included in this review. The study duration ranged from 3 to 6 months. Overall, the risk of bias across the included RCTs was low. We identified 3 studies evaluating lung function, 2 of which reported a significant improvement in FEV1 in the AD group after 6 months, while the other reported no difference among the treatments. Due to high heterogeneity, we did not pool the results. The remaining primary outcomes were reported only in a single study each, hindering their interpretation. Secondary outcomes revealed reduced symptom and medication scores in patients with AD.

Conclusions

Due to the small number of studies included in this systematic review, conclusions should be made with caution. AD shows a trend towards improving lung function (FEV1) following 6 months of treatment, although no conclusions can be made regarding the use of corticosteroids or the frequency of acute exacerbations. AD appears to reduce both symptom and medication scores. Additional RCTs are needed to fully assess the efficacy of AD in reducing bronchial symptoms in patients with NERD.
Hydroclimatic and cultural instability in northeastern North America during the last millennium
Authors: Stager J. Curt , Wiltse Brendan , Cumming Brian F. , Messner Timothy C. , Robtoy Joshua , Cushing Sidney
Published: March 2021

Long-term, large-scale perspectives are necessary for understanding climate variability and its effects on ecosystems and cultures. Tree ring records of the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA) have documented major hydroclimatic variability during the last millennium in the American West, but fewer continuous, high-resolution hydroclimate records of the MCA-LIA period are available for eastern North America, particularly during the transition from the MCA to the LIA (ca. A.D. 1250–1400). Diatoms (micro-algae with silica cell walls) in sediment cores from three Adirondack (NY, USA) lakes and a hiatus in a wetland peat deposit in the Adirondack uplands provide novel insights into the late Holocene hydroclimate history of the Northeast. These records demonstrate that two of the region’s most extreme decadal-scale droughts of the last millennium occurred ca. A.D. 1260–1330 and ca. A.D. 1360–1390 during a dry-wet-dry (DWD) oscillation in the Adirondacks that contributed to forest fires and desiccation of wetlands in New York and Maine. The bimodal drying was probably related to more extreme droughts farther west and coincided with major events in Iroquoian and Abenaki cultural history. Although the causes of the DWD oscillation in the Adirondacks remain uncertain, changing sea-surface temperatures and solar variability are likely to have played a role.
Modelling glucose dynamics during moderate exercise in individuals with type 1 diabetes
Authors: Alkhateeb Haneen , El Fathi Anas , Ghanbari Milad , Haidar Ahmad
Published: March 2021

The artificial pancreas is a closed-loop insulin delivery system that automatically regulates glucose levels in individuals with type 1 diabetes. In-silico testing using simulation environments accelerates the development of better artificial pancreas systems. Simulation environments need an accurate model that captures glucose dynamics during exercise to simulate real-life scenarios. We proposed six variations of the Bergman Minimal Model to capture the physiological effects of moderate exercise on glucose dynamics in individuals with type 1 diabetes. We estimated the parameters of each model with clinical data using a Bayesian approach and Markov chain Monte Carlo methods. The data consisted of measurements of plasma glucose, plasma insulin, and oxygen consumption collected from a study of 17 adults with type 1 diabetes undergoing aerobic exercise sessions. We compared the models based on the physiological plausibility of their parameters estimates and the deviance information criterion. The best model features (i) an increase in glucose effectiveness proportional to exercise intensity, and (ii) an increase in insulin action proportional to exercise intensity and duration. We validated the selected model by reproducing results from two previous clinical studies. The selected model accurately simulates the physiological effects of moderate exercise on glucose dynamics in individuals with type 1 diabetes. This work offers an important tool to develop strategies for exercise management with the artificial pancreas.
Efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of pneumocystis pneumonia in human immunodeficiency virus-negative immunodeficient patients: A systematic review and meta-analysis
Authors: Li Rui , Tang Zhiyong , Liu Fu , Yang Ming
Published: March 2021

Background

Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine.

Methods

A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported.

Results

Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03).

Conclusions

TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.
Impact of elevated air temperature and drought on pollen characteristics of major agricultural grass species
Authors: Jung Stephan , Estrella Nicole , Pfaffl Michael W. , Hartmann Stephan , Ewald Franziska , Menzel Annette
Published: March 2021

Grass pollen allergens are known to be one of the major triggers of hay fever with an increasing number of humans affected by pollen associated health impacts. Climate change characterized by increasing air temperature and more frequent drought periods might affect plant development and pollen characteristics. In this study a one-year (2017) field experiment was conducted in Bavaria, Germany, simulating drought by excluding rain and elevated air temperature by installing a heating system to investigate their effects primarily on the allergenic potential of eight selected cultivars of the two grass species timothy and perennial ryegrass. It could be shown for timothy that especially under drought and heat conditions the allergen content is significantly lower accompanied by a decrease in pollen weight and protein content. In perennial ryegrass the response to drought and heat conditions in terms of allergen content, pollen weight, and protein content was more dependent on the respective cultivar probably due to varying requirements for their growth conditions and tolerance to drought and heat. Results support recommendations which cultivars should be grown preferentially. The optimal choice of grass species and respective cultivars under changing climate conditions should be a major key aspect for the public health sector in the future.
Moral foundations theory, political identity, and the depiction of morality in children’s movies
Authors: Gehman Rachel , Guglielmo Steve , Schwebel David C.
Published: March 2021

Children’s movies often provide messages about morally appropriate and inappropriate conduct. In two studies, we draw on Moral Foundations Theory (MFT) to derive predictions about actual depictions of morality, and people’s preferences for different moral depictions, within children’s movies. According to MFT, people’s moral concerns include individualizing foundations of care and fairness and binding foundations of loyalty, authority, and sanctity. Prior work reveals that although there are political differences in the endorsement of these two broad categories—whereby stronger political conservatism predicts stronger binding concerns and weaker individualizing concerns—there nonetheless is broad agreement across political identity in the importance of individualizing concerns. We therefore predicted that heroes would value individualizing foundations more than villains, and that despite political differences in preferences for moral messages, there would be more agreement in the importance of messages promoting individualizing concerns. In Study 1, we coded heroes and villains from popular children’s movies for their valuation of moral foundations. Heroes valued individualizing concerns more, and binding concerns less, than villains did. Participants in Study 2 considered moral dilemmas faced by children’s movie characters, and rated their preferences for resolutions that promoted either individualizing or binding foundations. Although liberals preferred individualizing-promoting resolutions and conservatives preferred binding-promoting resolutions, there was stronger agreement across political identity in the importance of individualizing concerns. Despite political differences in moral preferences, popular depictions of children’s movie characters and people’s self-reported moral endorsement suggest a shared belief in the importance of the individualizing moral virtues of care and fairness.

Movies are often infused with moral messages. From their exploration of overarching themes, their ascription of particular traits to heroic and villainous characters, and their resolution of pivotal moral dilemmas, movies provide viewers with depictions of morally virtuous (and morally suspect) behavior. Moral messaging in children’s movies is of particular importance, since it is targeted at an audience for which morality is actively developing. What moral messages do filmmakers (and consumers, including parents) want children’s movies to depict? Are these preferences related to people’s political identity? And what are the actual moral depictions presented in movies? In the present two studies, we draw on an influential theory of moral judgment—Moral Foundations Theory—to develop and test predictions about the depiction of morality in children’s movies.
How to bring residents’ psychosocial well-being to the heart of the fight against Covid-19 in Belgian nursing homes—A qualitative study
Authors: Kaelen Sanne , van den Boogaard Wilma , Pellecchia Umberto , Spiers Sofie , De Cramer Caroline , Demaegd Gwennin , Fouqueray Edouard , Van den Bergh Rafael , Goublomme Stephanie , Decroo Tom , Quinet Muriel , Van Hoof Elke , Draguez Bertrand
Published: March 2021

Background

Nursing homes (NH) for the elderly have been particularly affected by the Covid-19 pandemic mainly due to their hosted vulnerable populations and poor outbreak preparedness. In Belgium, the medical humanitarian organization Médecins Sans Frontières (MSF) implemented a support project for NH including training on infection prevention and control (IPC), (re)-organization of care, and psychosocial support for NH staff. As psychosocial and mental health needs of NH residents in times of Covid-19 are poorly understood and addressed, this study aimed to better understand these needs and how staff could respond accordingly.

Methods

A qualitative study adopting thematic content analysis. Eight focus group discussions with direct caring staff and 56 in-depth interviews with residents were conducted in eight purposively and conveniently selected NHs in Brussels, Belgium, June 2020.

Results

NH residents experienced losses of freedom, social life, autonomy, and recreational activities that deprived them of their basic psychological needs. This had a massive impact on their mental well-being expressed in feeling depressed, anxious, and frustrated as well as decreased meaning and quality of life. Staff felt unprepared for the challenges posed by the pandemic; lacking guidelines, personal protective equipment and clarity around organization of care. They were confronted with professional and ethical dilemmas, feeling ‘trapped’ between IPC and the residents’ wellbeing. They witnessed the detrimental effects of the measures imposed on their residents.

Conclusion

This study revealed the insights of residents’ and NH staff at the height of the early Covid-19 pandemic. Clearer outbreak plans, including psychosocial support, could have prevented the aggravated mental health conditions of both residents and staff. A holistic approach is needed in NHs in which tailor-made essential restrictive IPC measures are combined with psychosocial support measures to reduce the impact on residents’ mental health impact and to enhance their quality of life.
Ungovernable systems: The strength of informal institutions in the sea cucumber fishery in Yucatan, Mexico
Authors: Pedroza-Gutiérrez Carmen , López-Rocha Jorge A.
Published: March 2021

Formal and informal institutions govern fisheries around the world. Yucatan’s sea cucumber fishery is not an exemption, the sudden and fast development of the fishery in 2010 has motivated the creation of informal and illegal forms of organization. The prices, buyers’ interest and the fishing effort substantially increased, being followed by illegal fishing-fishers and traders, creating informal fishing-trade channels and severe social and biological concerns. This article aims to give account of the emergence and dynamics of the informal institutions which currently dominate this fishery. It was sought to identify the extent to which rules and regulations are not being respected and how they are affecting fish resources and coastal communities. We considered the case of the port of Sisal, Yucatan, Mexico to illustrate our argument and here we applied a mixture of qualitative and quantitative methodologies including informal and in-depth interviews applied to 17 key informants, a questionnaire applied to 47 fishers and an estimation of the degree of compliance from three of the main management measures. Socio-biological negative impacts were identified in Yucatan’s coastal communities and its fisheries. Foreign buyers and local middlemen exert high pressure on fishers to exceed the quota and catch the highest possible volumes facilitating the fisheries decline. This and the growing economic interest motivated the development of strong informal institutions supporting illegal fishing and informal trade. Social problems emerged and women were particularly affected. The economic power of the fishery is likely to overcome any type of governance structure. The enforcement of entry rules was not effective, so the governance base was around informality and illegal actions. Local and foreign buyers are exerting pressure to increase the catch volume thus it is recommended that rules and regulations be directed at buyers and exporting companies rather than at fishers.
Feasibility and potential significance of rapid in vitro qualitative phenotypic antimicrobial susceptibility testing of gram-negative bacilli with the ProMax system
Authors: Chen Jade , Tomasek Michael , Cruz Amorina , Faron Matthew L. , Liu Dakai , Rodgers William H. , Gau Vincent
Published: March 2021

The emergence and evolution of antibiotic resistance has been accelerated due to the widespread use of antibiotics and a lack of timely diagnostic tests that guide therapeutic treatment with adequate sensitivity, specificity, and antimicrobial susceptibility testing (AST) accuracy. Automated AST instruments are extensively used in clinical microbiology labs and provide a streamlined workflow, simplifying susceptibility testing for pathogenic bacteria isolated from clinical samples. Although currently used commercial systems such as the Vitek2 and BD Phoenix can deliver results in substantially less time than conventional methods, their dependence on traditional AST inoculum concentrations and optical detection limit their speed somewhat. Herein, we describe the GeneFluidics ProMax lab automation system intended for a rapid 3.5-hour molecular AST from clinical isolates. The detection method described utilizes a higher starting inoculum concentration and automated molecular quantification of species-specific 16S rRNA through the use of an electrochemical sensor to assess microbiological responses to antibiotic exposure. A panel of clinical isolates consisting of species of gram-negative rods from the CDC AR bank and two hospitals, New York-Presbyterian Queens and Medical College of Wisconsin, were evaluated against ciprofloxacin, gentamicin, and meropenem in a series of reproducibility and clinical studies. The categorical agreement and reproducibility for Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, and Pseudomonas aeruginosa were 100% and 100% for ciprofloxacin, 98.7% and 100% for gentamicin and 98.5% and 98.5% for meropenem, respectively.
Intermediate monocytes correlate with CXCR3+ Th17 cells but not with bone characteristics in untreated early rheumatoid arthritis
Authors: Drevinge Christina , Scheffler Julia M , Koro-Arvidsson Catalin , Sundh Daniel , Carlsten Hans , Gjertsson Inger , Lindholm Catharina , Lorentzon Mattias , Rudin Anna , Ekwall Anna-Karin Hultgård , Islander Ulrika
Published: March 2021

Background

Rheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients.

Methods

78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4+ helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT.

Results

Flow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3+ Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3+ Th17 cells were associated with bone density or bone microarchitecture measurements.

Conclusions

Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3+ Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.
The effect of intraocular pressure elevation and related ocular biometry changes on corneal OCT speckle distribution in porcine eyes
Authors: Niemczyk Marcela , Danielewska Monika E. , Kostyszak Malgorzata A. , Lewandowski Daniel , Iskander D. Robert
Published: March 2021

The aim of this study was to evaluate the influence of increase in intraocular pressure (IOP) and cooccurring changes in ocular biometry parameters on the corneal optical coherence tomography (OCT) speckle distribution in ex-vivo experiments on porcine intact eyes. Twenty-three eyeballs were used in the inflation test where IOP in the anterior chamber was precisely set from 10 mmHg to 40 mmHg in steps of 5 mmHg and where eye biometry was utilized (IOL Master 700). To assess the influence of the duration of the experiment on the OCT speckle statistics, the second experiment was performed with 10 eyeballs at the constant IOP of 15 mmHg. Based on the OCT scans of central cornea (Copernicus REVO), spatial maps of the scale parameter (a) and the shape parameter (v) of the gamma distribution speckle model were estimated. The means of both parameters for each spatial map were computed within the 2 mm of the central stroma. Both distributional parameters statistically significantly varied with IOP and time (one way repeated measures ANOVA, all p-values < 0.001). The a parameter revealed a faster statistically significant increase in IOP up to 25 mmHg, regardless of time. Central corneal thickness (CCT), the anterior chamber depth, and the mean equivalent spherical power varied significantly with IOP, whereas CCT and axial length changed statistically significantly with time. Statistically significant correlation was found between CCT and the a parameter, after removing IOP as a confounding factor (r = −0.576, p < 0.001). The parameters of the gamma distribution can be used not only for identifying IOP induced changes in the optical scattering within the corneal stroma, but also in corneal geometry. The approach of corneal speckle analysis could be potentially utilized for an indirect and noninvasive assessment of some properties of corneal stroma.
Sex- and age-specific clinical and immunological features of coronavirus disease 2019
Authors: Jin Shengwei , An Hui , Zhou Tong , Li Ting , Xie Mengzhen , Chen Saijing , Chen Chengshui , Ying Binyu , Xu Zhangye , Li Xiaokun , Li Ming
Published: March 2021

To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8+T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8+T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8+T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.
Deconvolution of intergenic polymorphisms determining high expression of Factor H binding protein in meningococcus and their association with invasive disease
Authors: Spinsanti Marco , Brignoli Tarcisio , Bodini Margherita , Fontana Lucia Eleonora , De Chiara Matteo , Biolchi Alessia , Muzzi Alessandro , Scarlato Vincenzo , Delany Isabel
Published: March 2021

Neisseria meningitidisis a strictly human pathogen and is the major cause of septicemia and meningitis worldwide. Factor H binding protein (fHbp) is a meningococcal surface-exposed lipoprotein that binds the human Complement factor H allowing the bacterium to evade the host innate immune response. FHbp is also a key antigen in two vaccines againstN.meningitidisserogroup B. Although thefHbpgene is present in most circulating meningococcal strains, level of fHbp expression varies among isolates and has been correlated to differences in promoter sequences upstream of the gene. Here we elucidated the sequence determinants that control fHbp expression in globally circulating strains. We analyzed the upstreamfHbpintergenicregion (fIR) of more than 5800 strains representative of the UK circulating isolates and we identified eleven fIR sequence alleles which represent 88% of meningococcal strains. By engineering isogenic recombinant strains where fHbp expression was under the control of each of the eleven fIR alleles, we confirmed that the fIR sequence determines a specific and distinct level of expression. Moreover, we identified the molecular basis for variation in expression through polymorphisms within key regulatory regions that are known to affect fHbp expression. We experimentally established three expression groups, high–medium–low, that correlated directly with the susceptibility to killing mediated by anti-fHbp antibodies and the ability of the meningococcal strain to survive within human serum. By using this sequence classification and information about the variant, we predicted fHbp expression in the panel of UK strains and we observed that strains with higher expressing fIR alleles are more likely associated with invasive disease. Overall, our findings can contribute to understand and predict vaccine coverage mediated by fHbp as well as to shed light on the role of this virulence factor in determining an invasive phenotype.
Host cystathionine-γ lyase derived hydrogen sulfide protects against Pseudomonas aeruginosa sepsis
Authors: Renieris Georgios , Droggiti Dionysia-Eirini , Katrini Konstantina , Koufargyris Panagiotis , Gkavogianni Theologia , Karakike Eleni , Antonakos Nikolaos , Damoraki Georgia , Karageorgos Athanasios , Sabracos Labros , Katsouda Antonia , Jentho Elisa , Weis Sebastian , Wang Rui , Bauer Michael , Szabo Csaba , Platoni Kalliopi , Kouloulias Vasilios , Papapetropoulos Andreas , Giamarellos-Bourboulis Evangelos J.
Published: March 2021

Hydrogen sulfide (H2S) has recently been recognized as a novel gaseous transmitter with several anti-inflammatory properties. The role of host- derived H2S in infections by Pseudomonas aeruginosa was investigated in clinical and mouse models. H2S concentrations and survival was assessed in septic patients with lung infection. Animal experiments using a model of severe systemic multidrug-resistant P. aeruginosa infection were performed using mice with a constitutive knock-out of cystathionine-γ lyase (Cse) gene (Cse-/-) and wild-type mice with a physiological expression (Cse+/+). Experiments were repeated in mice after a) treatment with cyclophosphamide; b) bone marrow transplantation (BMT) from a Cse+/+ donor; c) treatment with H2S synthesis inhibitor aminooxyacetic acid (ΑΟΑΑ) or propargylglycine (PAG) and d) H2S donor sodium thiosulfate (STS) or GYY3147. Bacterial loads and myeloperoxidase activity were measured in tissue samples. The expression of quorum sensing genes (QS) was determined in vivo and in vitro. Cytokine concentration was measured in serum and incubated splenocytes. Patients survivors at day 28 had significantly higher serum H2S compared to non-survivors. A cut- off point of 5.3 μΜ discriminated survivors with sensitivity 92.3%. Mortality after 28 days was 30.9% and 93.7% in patients with H2S higher and less than 5.3 μΜ (p = 7 x 10−6). In mice expression of Cse and application of STS afforded protection against infection with multidrug-resistant P. aeruginosa. Cyclophosphamide pretreatment eliminated the survival benefit of Cse+/+ mice, whereas BMT increased the survival of Cse-/- mice. Cse-/- mice had increased pathogen loads compared to Cse+/+ mice. Phagocytic activity of leukocytes from Cse-/- mice was reduced but was restored after H2S supplementation. An H2S dependent down- regulation of quorum sensing genes of P.aeruginosa could be demonstrated in vivo and in vitro. Endogenous H2S is a potential independent parameter correlating with the outcome of P. aeruginosa. H2S provides resistance to infection by MDR bacterial pathogens.
Fashioning Prince: Bikini briefs, trench coats and zoot suits, 1978–91
Authors: Ritchie Casci
Published: March 2021

Minneapolis-born Prince Rogers Nelson is often revered as one of the most influential figures in twenty-first-century popular culture. A true provocateur, Prince consistently challenged perceptions of gender and sexuality throughout his career, which spanned over four decades. Since his untimely passing on 21 April 2016, not only have fans around the world celebrated the musician’s life, but his oeuvre, representation and style have garnered increasing critical academic attention. This article will contribute to this burgeoning body of academic work on Prince and his lasting legacy, through a focus upon tracing the development of Prince’s iconic sartorial style, from his debut release For You () to the worldwide success of his thirteenth studio album, Diamonds and Pearls (1991). Throughout this period, Prince aroused, entertained and shocked audiences simultaneously. Whilst critical attention has been paid to his music, background and identity, there remains comparatively little academic work focusing specifically and in detail upon his garments and style. This article will chart the emerging custom designed and created style of Prince through sequential album eras, focusing on important garments worn throughout music videos, concerts and album art.
From emo kid to stylish GQ Gent and back again: Matty Healy and hybrid masculinity
Authors: Morgan Ashley
Published: March 2021

This article examines the evolution of the appearance of British musician, Matty Healy, lead singer of contemporary band The 1975, in his performance as a hybrid man in style and fashion magazines. Hybrid masculinity is often used by young white men as a form of assimilating aspects from marginalized groups into performing their identities. This is to distance themselves from the narrow confines of hegemonic masculinity through transgression. Healy’s performances of gay and feminized hybrid masculinities have emerged through his clothing, from early national success as a typical ‘emo’ kid ‘dressed in black from head to toe’ to a fully groomed, suited and booted Englishman, cover star ofGQand in demand as a model. Prior to global fame, Healy’s style referenced rock stars of the past and he was admired for his simple black clothing, boyish emo good looks and curly hair; style blog IdleMan.com refers to him as a ‘gothic hipster’. Yet in concert with his stylist, Patricia Villirillo, Healy has begun to play on the more feminized aspects of emo fashion such as performing in women’s skirts and dresses, and arguably has produced a twenty-first-century emo aesthetic. Moreover, he also adopts the appearance of a powerful man in a suit or for performances as well as photoshoots. Healy might now be dressed in a suit or tie for performing, as easily as he might wear a skirt, as many men in music have before him. Wearing skirts as an act of transgression highlights the lack of diversity in men’s clothing in its mundanity, and despite advances in acceptance of dynamic masculine identities through performing gay identities, performing hybrid masculinities through femininity, is still highly problematic.
Diachronic investigation of learner language
Authors: Horváth József
Published: March 2021

Corpus linguistics studies have by now become a staple of linguists and teachers worldwide. Even practitioners who are not directly involved with corpus development or analysis are increasingly aware of this domain and its results. Thus, we can say that the time has come to investigate the long-term effects of the findings connected to corpus linguistics. This paper focuses on a specific sort of corpus: the learner corpus. It argues that what used to be a more traditional approach represented in the EFL (English as a foreign language) discipline has evolved into a perhaps more appropriate one represented in ELF (English as a lingua franca) partly because of the work of learner corpus research. To demonstrate any existing long-term effects of work with learner corpora on language education, an L2 corpus, the JPU Corpus, is presented. Five of the ten hypotheses originally set up in the early 2000s are revisited and critiqued by applying both quantitative and qualitative investigations. The results indicate that a diachronic learner corpus approach further establishes the shift from EFL to ELF approaches, a potentially useful and relevant change for students and their teachers across the world, especially within the framework of writing pedagogy.
Management of Neonatal Sepsis with Intravenous Immunoglobulin as an Adjunctive Therapy in Preterm Newborn
Authors: Mishra Kripanath , Gaurav Prashant , Kumar Pankaj
Published: March 2021

BACKGROUND Neonatal sepsis refers to systemic infections affecting infants within 28 days of life, 1 characterised by invasion of bloodstream by pathogens and possible involvement of multiple organ systems. Neonatal sepsis can present as bloodstream infections (BSI) or septicaemia, pneumonia, meningitis, urinary tract, and bone / joint infections but does not as superficial infections. We wanted to evaluate the rationale of administering intravenous immune globulin (IVIG) with antimicrobials to improve the therapeutic significance of sepsis in preterm neonates. METHODS One hundred preterm neonates with sepsis were randomly assigned into study and control categories at SNCU, Department of Paediatrics, Darbhanga Medical College and Hospital, Laheriasarai, Darbhanga, Bihar, India. Study-category was given IVIG in addition to standard treatment. RESULTS Total 100 sick new-borns were registered, 50 in study, and 50 in control categories. There were no differences in sex ratio (male 50 %, female 50 %) of sick new-borns who were registered. This was also apparent in the study (males 47.7 %, females 52.3 %) and control category (males 52.3 %, females 47.7 %). CONCLUSIONS The cause of increased morbidity and mortality in severe infection of preterm neonates was the low level of immunity. IVIG use in conjunction with the antimicrobials and other sympathetic therapy can change the end result. KEY WORDS IVIG, Neonatal Sepsis, Preterm Babies