bluuebunny/crossref_metadata_2025 huggingface dataset:
A branded bandage is worth a thousand words: blood branded bandages signal men’s generosity and morality
Authors: Lam Michael , Masser Barbara M. , Dixson Barnaby J.W.
Published: October 2020

Background and Objective

Recruiting and retaining male donors remain an ongoing challenge for blood collection agencies. Research suggests that interventions based on costly signalling theory that allows donors to unobtrusively but publicly signal their donor status may be effective. However, what functions as such a signal and how it is interpreted has not been determined.

Materials and Methods

A total of 242 Australian residents (127 female; 115 male) recruited through an online research platform rated their perceptions of a male target wearing (a) no bandage, (b) a regular unmarked bandage or (c) a blood donor branded bandage.

Results

The target wearing a blood donor branded bandage was rated as significantly more generous by female participants and moral compared to both the target who wore no bandage and the target wearing a regular unmarked bandage. The target wearing the unmarked bandage was perceived as significantly less healthy and competent compared to the target not wearing a bandage.

Conclusion

A public signal of public donor status conveys the generosity and morality of the wearer. The bandage applied to donors after they have donated can act as such an effective signal, but only when these bandages are clearly branded as resulting from donating blood.
Blood supply management in times of SARS‐CoV‐2 pandemic – challenges, strategies adopted, and the lessons learned from the experience of a hospital‐based blood centre
Authors: Pandey Hem Chandra , Coshic Poonam , C S Chippy , Arcot Priyadarsini Jayachandran , Kumar Karan
Published: October 2020

Introduction

Numerous concerns regarding maintenance of blood inventory have been raised after SARS‐CoV‐2 pandemic outbreak. These concerns were based on the experience of blood centres in previous pandemics where shortage of blood components was reported. The present study had tried to understand the impact of SARS‐CoV‐2 pandemic on blood collection and demand as well as the impact of disaster planning in maintaining an adequate inventory.

Methods

Data related to blood supply and demand were collected retrospectively using blood bank management software for pre‐COVID‐19 and COVID‐19 time period and compared. Strategies adopted and effects of changes in existing disaster plans to maintain an adequate inventory were studied.

Results

A drastic fall in the red cell inventory was observed as compared to pre‐COVID‐19 time period was observed due to disproportionate decrease in blood collection (1/6 to 1/9 of the previous collection) and demand (1/2 of the previous demand). The buffer stock fell gradually over a period of three weeks with cancellation of planned blood donation drives. A buffer stock equivalent to 2‐week inventory led to adequate inventory in the initial lockdown periods. Similar fall was observed in the platelet inventory with reduction in the blood collection but almost a proportionate reduction in the platelet demand led to adequate inventory. No increase in wastage was observed for both red cells and platelets during this period.

Discussion

A buffer stock of blood and blood components, strict adherence to the transfusion triggers, good coordination with the clinical staff and a prospective review of blood transfusion requests to ensure rational blood transfusion were some of the steps which helped us to successfully maintain transfusion requirements in the initial phases of the COVID‐19 pandemic. Use of first‐in‐first‐out policy prevented any wastage due to outdating of blood.
A three‐dimensional computed tomographic volume rendering methodology to measure the tibial torsion angle in dogs
Authors: Longo Federico , Nicetto Tommaso , Pozzi Antonio , Contiero Barbara , Isola Maurizio
Published: October 2020

Objective

To describe a three‐dimensional (3D) computed tomographic (CT) methodology to measure the tibial torsion angle (TTa) and to evaluate intrarater and interrater agreements and accuracy through comparison with anatomic measurements.

Study design

Ex vivo cadaveric study.

Sample population

Thirty‐six tibiae from 18 dogs.

Methods

Tibial torsion angle of each tibia was measured by using two CT techniques (axial and 3D volume rendering) by three raters who blindly measured TTa in duplicate. A semitransparent bone filter was used to enhance the visibility of the target anatomical landmarks for the 3D volume rendering CT technique. Tibial torsion angle was also quantitated in tibial specimens. Intrarater and interrater agreements were analyzed by using intraclass coefficients (ICC). Accuracy was evaluated by using adjusted R2 coefficients (R2 > 80% was considered acceptable).

Results

The 3D volume rendering CT technique had excellent intrarater and interrater agreements (ICC > 0.94) and an R2 value of 97%. The axial CT technique had good to excellent intrarater and interrater agreements (0.8 < ICC < 0.95) and an R2 of 86%. No difference was found between axial and 3D CT techniques. A mean internal TT angle of approximately −6° was found with CT and anatomic measurements.

Conclusion

The 3D volume rendering and axial CT techniques were precise and accurate for measuring TTa in dogs unaffected by patellar luxation.

Clinical relevance

Combining 3D bone manipulation with application of a semitransparent filter allows simultaneous visualization of anatomic landmarks, which may facilitate the evaluation of complex bone deformations. Internal tibial torsion may be present in nonchondrodystrophic dogs without patella luxation.
Deep anterior lamellar keratoplasty with cross‐linked acellular porcine corneal stroma to manage fungal keratitis
Authors: Zheng Qinxiang , Zhang Yueqin , Ren Yueping , Zhao Zelin , Hua Shanshan , Li Jinyang , Wang Haiou , Ye Cong , Kim Andy D. , Wang Liya , Chen Wei
Published: October 2020

Purpose

To evaluate the effects of deep anterior lamellar keratoplasty (DALK) with cross‐linked acellular porcine corneal stroma (APCS) and post‐operative topical tacrolimus treatment in patients with fungal keratitis.

Methods

This multicenter prospective study involved 25 cases of fungal keratitis that were treated by DALK with cross‐linked APCSs and post‐operative topical tacrolimus from December 2013 to November 2014 at the Wenzhou Eye Hospital and the Henan provincial Eye Hospital. Signs of post‐operative inflammation, corneal reepithelialization, corneal neovascularization, and graft rejection were assessed, and best corrected visual acuity (BCVA), intraocular pressure (IOP), and APCS graft transparency were monitored for the 12‐month follow‐up period.

Results

All 25 patients underwent DALK without Descemet's membrane perforation. Corneal epithelium recovered completely in 17 patients in the first week, and APCS grafts maintained transparency in 18 patients at 1‐year follow‐up. The mean BCVA significantly improved from 2.16 ± 0.32 (LogMAR) at baseline to 1.56 ± 0.70 at 1‐week (P < .001), 0.95 ± 0.57 at 1‐month (P < .001), and 0.70 ± 0.51 at 3‐month follow‐ups (P < .001). The BCVA kept stable at 6‐month and 12‐month follow‐ups. Post‐operative topical tacrolimus alleviated the ciliary injection, except in one case which acute stromal rejection occurred. One patient developed fungal reinfection and underwent penetrating keratoplasty. Graft rejection occurred in three patients. No case was noted with graft splitting, elevated IOP or tacrolimus intolerance.

Conclusions

DALK using cross‐linked APCS combining topical tacrolimus treatment is safe and effective in managing fungal keratitis. It may ameliorate the shortage of corneal donation globally.
Lifelong voluntary aerobic exercise prevents age‐ and Western diet‐ induced vascular dysfunction, mitochondrial oxidative stress and inflammation in mice
Authors: Gioscia‐Ryan Rachel A. , Clayton Zachary S. , Zigler Melanie C. , Richey James J. , Cuevas Lauren M. , Rossman Matthew J. , Battson Micah L. , Ziemba Brian P. , Hutton David A. , VanDongen Nicholas S. , Seals Douglas R.
Published: October 2020

Key points

The results of the present study establish the temporal pattern of age‐related vascular dysfunction across the adult lifespan in sedentary mice consuming a non‐Western diet, and the underlying mechanisms

The results demonstrate that consuming a Western diet accelerates and exacerbates vascular ageing across the lifespan in sedentary mice

They also show that lifelong voluntary aerobic exercise has remarkable protective effects on vascular function throughout the lifespan, in the setting of ageing alone, as well as ageing compounded by Western diet consumption

Overall, the results indicate that amelioration of mitochondrial oxidative stress and inflammation are key mechanisms underlying the voluntary aerobic exercise‐associated preservation of vascular function across the lifespan in both the presence and absence of a Western dietary pattern

Advancing age is the major risk factor for cardiovascular diseases, driven largely by vascular endothelial dysfunction (impaired endothelium‐dependent dilatation, EDD) and aortic stiffening (increased aortic pulse wave velocity, aPWV). In humans, vascular ageing occurs in the presence of differences in diet and physical activity, but the interactive effects of these factors are unknown. We assessed carotid artery EDD and aPWV across the lifespan in mice consuming standard (normal) low‐fat chow (NC) or a high‐fat/high‐sucrose Western diet (WD) in the absence (sedentary, SED) or presence (voluntary wheel running, VWR) of aerobic exercise. Ageing impaired nitric oxide‐mediated EDD (peak EDD 88 ± 12% 6 monthsP = 0.003vs. 59 ± 9% 27 months NC‐SED), which was accelerated by WD (60 ± 18% 6 months WD‐SED). In NC mice, aPWV increased 32% with age (423 ± 13 cm/s at 24 monthsP < 0.001vs. 321 ± 12 cm/s at 6 months) and absolute values were an additional ∼10% higher at any age in WD mice (P = 0.042vs. NC‐SED). Increases in aPWV with age in NC and WD mice were associated with 30–65% increases in aortic intrinsic wall stiffness (6vs. 19–27 months,P = 0.007). Lifelong aerobic exercise prevented age‐ and WD‐related vascular dysfunction across the lifespan, and this protection appeared to be mediated by mitigation of vascular mitochondrial oxidative stress and inflammation. Our results depict the temporal impairment of vascular function over the lifespan in mice, acceleration and exacerbation of that dysfunction with WD consumption, the remarkable protective effects of voluntary aerobic exercise, and the underlying mechanisms.
Inhibitory interneurons in a brainstem circuit adjust their inhibitory motifs to process multimodal input
Authors: Wu Calvin , Shore Susan E.
Published: October 2020

Key points

Inhibitory‐interneuron networks, consisting of multiple forms of circuit motifs including reciprocal (inhibitory interneurons inhibiting other interneurons) and feedforward (inhibitory interneurons inhibiting principal neurons) connections, are crucial in processing sensory information.

The present study applies a statistical method to in vivo multichannel spike trains of dorsal cochlear nucleus neurons to disentangle reciprocal and feedforward‐inhibitory motifs.

After inducing input‐specific plasticity, reciprocal and feedforward inhibition are found to be differentially regulated, and the combined effect synergistically modulates circuit output.

The findings highlight the interplay among different circuit motifs as a key element in neural computation.

Inhibitory interneurons play an essential role in neural computations by utilizing a combination of reciprocal (interneurons inhibiting each other) and feedforward (interneuron inhibiting the principal neuron) inhibition to process information. To disentangle the interplay between the two inhibitory‐circuit motifs and understand their effects on the circuit output, in vivo recordings were made from the guinea pig dorsal cochlear nucleus, a cerebellar‐like brainstem circuit. Spikes from inhibitory interneurons (cartwheel cell) and principal output neurons (fusiform cell) were compared before and after manipulating their common multimodal input. Using a statistical model based on the Cox method of modulated renewal process of spike train influence, reciprocal‐ and feedforward‐inhibition motifs were quantified. In response to altered multimodal input, reciprocal inhibition was strengthened while feedforward inhibition was weakened, and the two motifs combined to modulate fusiform cell output and acoustic‐driven responses. These findings reveal the cartwheel cell's role in auditory and multimodal processing, as well as illustrated the balance between different inhibitory‐circuit motifs as a key element in neural computation.
Modelling the impacts of lockdown and isolation on the eradication of COVID-19
Authors: Ndam Joel N.
Published: October 2020

A model describing the dynamics of COVID-19 is formulated and examined. The model is meant to address the impacts of lockdown and social isolation as strategies for the eradication of the pandemic. Local stability analysis indicate that the equilibria are locally-asymptotically stable for R0<1 and R_0>1 for the disease-free equilibrium and the endemic equilibrium respectively. Numerical simulations of the model equations show that lockdown is a more effective strategy in the eradication of the disease than social isolation. However, strict enforcement of both strategies is the most effective means that could end the disease within a shorter period of time.
Flow Regime Identification in Vertical Upward Gas–Liquid Flow Using an Optical Sensor With Linear and Quadratic Discriminant Analysis
Authors: Sarkodie Kwame , Fergusson-Rees Andrew
Published: October 2020

The accurate identification of gas–liquid flow regimes in pipes remains a challenge for the chemical process industries. This paper proposes a method for flow regime identification that combines responses from a nonintrusive optical sensor with linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) for vertical upward gas–liquid flow of air and water. A total of 165 flow conditions make up the dataset, collected from an experimental air–water flow loop with a transparent test section (TS) of 27.3 mm inner diameter and 5 m length. Selected features extracted from the sensor response are categorized into feature group 1, average sensor response and standard deviation, and feature group 2 that also includes percentage counts of the calibrated responses for water and air. The selected features are used to train, cross validate, and test four model cases (LDA1, LDA2, QDA1, and QDA2). The LDA models produce higher average test classification accuracies (both 95%) than the QDA models (80% QDA1 and 45% QDA2) due to misclassification associated with the slug and churn flow regimes. Results suggest that the LDA1 model case is the most stable with the lowest average performance loss and is therefore considered superior for flow regime identification. In future studies, a larger dataset may improve stability and accuracy of the QDA models, and an extension of the conditions and parameters would be a useful test of applicability.
Computer simulations of the interaction between SARS-CoV-2 spike glycoprotein and different surfaces
Authors: Malaspina David C. , Faraudo Jordi
Published: October 2020

A prominent feature of coronaviruses is the presence of a large glycoprotein spike protruding from a lipidic membrane. This glycoprotein spike determines the interaction of coronaviruses with the environment and the host. In this paper, we perform all atomic molecular dynamics simulations of the interaction between the SARS-CoV-2 trimeric glycoprotein spike and surfaces of materials. We considered a material with high hydrogen bonding capacity (cellulose) and a material capable of strong hydrophobic interactions (graphite). Initially, the spike adsorbs to both surfaces through essentially the same residues belonging to the receptor binding subunit of its three monomers. Adsorption onto cellulose stabilizes in this configuration, with the help of a large number of hydrogen bonds developed between cellulose and the three receptor-binding domains of the glycoprotein spike. In the case of adsorption onto graphite, the initial adsorption configuration is not stable and the surface induces a substantial deformation of the glycoprotein spike with a large number of adsorbed residues not pertaining to the binding subunits of the spike monomers.
Reflection of audio sounds generated by a parametric array loudspeaker
Authors: Zhong Jiaxin , Wang Shuping , Kirby Ray , Qiu Xiaojun
Published: October 2020

The reflection of audio sounds generated by a parametric array loudspeaker (PAL) is investigated in this paper. The image source method and the non-paraxial PAL radiation model under the quasilinear approximation are used to calculate the reflected audio sound from an infinitely large surface with an arbitrary incident angle. The effects of the surface absorption in the ultrasound frequency range are studied, and the simulation and experiment results show that the reflection behavior of audio sounds generated by a PAL is different from those generated by traditional audio sources. The reason is that the reflected sound generated by the PAL consists of the reflection of audio sounds generated by incident ultrasounds and the audio sounds generated by the reflected ultrasound, and it is the latter that determines the directivity of the reflected audio sound.
High Prevalence of Clostridium difficile in Home Gardens in Western Australia
Authors: Shivaperumal Nirajmohan , Chang Barbara J. , Riley Thomas V.
Published: October 2020

Recently, community-associated
Clostridium difficile
infection (CA-CDI) has emerged as a significant problem, accounting for ∼50% of all CDI cases and reported to affect a younger population without traditional risk factors. Possible sources of CA-CDI are soil, food, and water contaminated by animal feces, and recent reports show overlapping ribotypes of
C. difficile
in animals, humans, and the environment; however, the epidemiology of CA-CDI and related risk factors need to be better understood. Our research aimed to determine the prevalence of
C. difficile
in home gardens and on the shoe soles of homeowners in Perth, Western Australia. There were high rates of contamination with
C. difficile
in gardens, and some of the ribotypes identified had been isolated from human cases of CDI in Western Australia. This study shows that home gardens and shoes may be a source of
C. difficile
in CA-CDI.
Simple Phenotypic Tests To Improve Accuracy in Screening Chromosomal and Plasmid-Mediated Colistin Resistance in Gram-Negative Bacilli
Authors: Pasteran Fernando , Danze Diego , Menocal Alejandra , Cabrera Carla , Castillo Ignacio , Albornoz Ezequiel , Lucero Celeste , Rapoport Melina , Ceriana Paola , Corso Alejandra
Published: October 2020

CLSI and EUCAST recommend that only broth microdilution (BMD) should be used for routine colistin susceptibility testing; however, this technique can be difficult to perform in resource-poor settings. The purpose of this study was to evaluate the accuracy of a colistin agar spot test (COL-AS) and a colistin drop test (COL-DT) compared to BMD. COL-AS and COL-DT were assessed with a collection of 271 Gram-negative bacilli clinical isolates: 195
Enterobacterales
(including 63
mcr-1
positive strains), 37
Acinetobacter
spp.
Isolation and Characterization of Porcine Astrovirus 5 from a Classical Swine Fever Virus-Infected Specimen
Authors: Mi Shijiang , Guo Shibang , Xing Chaonan , Xiao Chaoting , He Biao , Wu Bin , Xia Xianzhu , Tu Changchun , Gong Wenjie
Published: October 2020

Porcine astroviruses are mainly associated with gastroenteritis and neurological diseases in pigs, and five genotypes have been identified (PAstV1-5). However, the clinical manifestations of genotypes other than PAstV1 have not yet been determined because of the failure of
in vitro
virus isolation. Here, we report a surprising isolation of a PAstV5 strain from a clinical classical swine fever virus (CSFV)-infected tissue sample, which can stably passage in PK-15 cells, and coinfection with CSFV significantly enhanced the replication of PAstV5, possibly through suppression of beta interferon production. Thus, the first isolated PAstV5 strain will be useful for investigating the biological and pathogenic properties of this virus, and the findings obtained in this study provide new insights into defining the interaction mechanism between CSFV and PAstV5.
Precise Triggering and Chemical Control of Single-Virus Fusion within Endosomes
Authors: Haldar Sourav , Okamoto Kenta , Dunning Rebecca A. , Kasson Peter M.
Published: October 2020

Many enveloped viruses infect cells via fusion to endosomes, but controlling this process within living cells has been challenging. We studied the fusion of influenza virus virions to endosomes in a chemically controllable manner. Extracting virus:endosome conjugates from cells and exogenously triggering fusion permits precise study of virus:endosome fusion kinetics. Surprisingly, endosomal curvature does not grossly alter fusion kinetics, although membrane deformability does. This supports a model for influenza virus entry where cells restrict or permit membrane fusion by changing deformability, for instance, using interferon-induced proteins.
Tell Me Where You’ve Been and I’ll Tell You How You’ll Evolve
Authors: Fumasoni Marco
Published: October 2020

The reproducibility of adaptive evolution is a long-standing debate in evolutionary biology. Kempher et al. (M. L. Kempher, X. Tao, R. Song, B. Wu, et al., mBio 11:e00569-20, 2020,
https://doi.org/10.1128/mBio.00569-20
) used experimental evolution to investigate the effect of previous evolutionary trajectories on the ability of microbial populations to adapt to high temperatures. Despite the divergence caused by adaptation to previous environments, all populations reproducibly converged on similar final levels of fitness.
Biotic Interactions Are More Important than Propagule Pressure in Microbial Community Invasions
Authors: Albright Michaeline B. N. , Sevanto Sanna , Gallegos-Graves La Verne , Dunbar John
Published: October 2020

With increasing frequency, humans are introducing new microbes into preexisting microbiomes to alter functioning. Example applications include modification of microflora in human guts for better health and those of soil for food security and/or climate management. Probiotic applications are often approached as trial-and-error endeavors and have mixed outcomes. We propose that increased success in microbiome engineering may be achieved with a better understanding of microbial invasions. We conducted a microbial community invasion experiment to test the relative importance of propagule pressure and biotic interactions in driving microbial community composition and ecosystem functioning in microcosms. We found that biotic interactions were more important than propagule pressure in determining the impact of microbial invasions. Furthermore, the principles for community engineering vary among organismal groups (bacteria versus fungi).
HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
Authors: Yang Yang , Liu Weiyong , Hu Dan , Su Rui , Ji Man , Huang Yuqing , Shereen Muhammad Adnan , Xu Xiaodi , Luo Zhen , Zhang Qi , Liu Fang , Wu Kailang , Liu Yingle , Wu Jianguo
Published: October 2020

The ubiquitin-proteasome system (UPS) is essential for the degradation of damaged proteins, which takes place in the proteasome. Upon activation by cytokines, the catalytic subunits of the proteasome are replaced by distinct isoforms resulting in the formation of an immunoproteasome (iProteasome). iProteasome generates peptides used by major histocompatibility complex class I (MHC-I) for antigen presentation and is essential for immune responses. HIV-1 is the causative agent of AIDS, and HIV-1-specific cytotoxic T lymphocytes (CTLs) provide immune responses limiting viral replication. This study identifies a distinct mechanism by which HIV-1 promotes immune evasion. The viral protein negative regulatory factor (Nef) interacts with a component of iProteasome, LMP7, attenuating iProteasome formation and protein degradation function, and thus repressing the MHC-I antigen presentation activity of MHC-I. Therefore, HIV-1 targets LMP7 to inhibit iProteasome activation, and LMP7 may be used as the target for the development of anti-HIV-1/AIDS therapy.
Discovery of a New Neisseria gonorrhoeae Type IV Pilus Assembly Factor, TfpC
Authors: Hu Linda I. , Yin Shaohui , Ozer Egon A. , Sewell Lee , Rehman Saima , Garnett James A. , Seifert H Steven
Published: October 2020

Most bacterial species express one or more extracellular organelles called pili/fimbriae that are required for many properties of each bacterial cell. The
Neisseria gonorrhoeae
type IV pilus is a major virulence and colonization factor for the sexually transmitted infection gonorrhea. We have discovered a new protein of
Neisseria gonorrhoeae
called TfpC that is required to maintain type IV pili on the bacterial cell surface. There are similar proteins found in other members of the
Neisseria
genus and many other bacterial species important for human health.
Humidity and Deposition Solution Play a Critical Role in Virus Inactivation by Heat Treatment of N95 Respirators
Authors: Rockey Nicole , Arts Peter J. , Li Lucinda , Harrison Katherine R. , Langenfeld Kathryn , Fitzsimmons William J. , Lauring Adam S. , Love Nancy G. , Kaye Keith S. , Raskin Lutgarde , Roberts William W. , Hegarty Bridget , Wigginton Krista R.
Published: October 2020

Shortages of personal protective equipment, including N95 respirators, during the coronavirus (CoV) disease 2019 (COVID-19) pandemic have highlighted the need to develop effective decontamination strategies for their reuse. This is particularly important in health care settings for reducing exposure to respiratory viruses, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Although several treatment methods are available, a widely accessible strategy will be necessary to combat shortages on a global scale. We demonstrate that the combination of heat and humidity inactivates a range of RNA viruses, including both viral pathogens and common viral pathogen surrogates, after deposition on N95 respirators and achieves the necessary virus inactivation detailed by the U.S. Food and Drug Administration guidelines to validate N95 respirator decontamination technologies. We further demonstrate that depositing viruses onto surfaces when suspended in culture media can greatly enhance observed inactivation, adding caution to how heat and humidity treatment methods are validated.
Morphology of vascular ring arch anomalies influences prognosis and management
Authors: Ctori Elena , Crucean Adrian , Pinkey Benjamin , McGuirk Simon P , Anderson Robert H , Stickley John , Jones Timothy J , Seale Anna N
Published: October 2020

Objective

This study aimed to explore the anatomical features of aortic arch anomalies associated with vascular rings, hoping to identify those which may increase the risk of symptomatic presentation and surgical intervention.

Methods

This was a retrospective observational study at a single cardiac unit. Individuals diagnosed with an aortic arch anomaly, either isolated or non-isolated, between June 2014 and September 2018 were included. The morphology of the aortic arch was established via analysis of postnatal echocardiography, CT or MRI scans. CT and magnetic resonance studies were evaluated for the presence of a Kommerell diverticulum in those with aberrant vessels. Case notes were reviewed for relevant clinical data.

Results

Of those with aberrant subclavian arteries, 24/79 (30.4%) were shown to have a Kommerell diverticulum. Additional forms of congenital heart disease were present in 133/227 (58.6%) individuals. Surgical division of the vascular ring was performed in 30/227 (13.2%), most commonly in the setting of a double aortic arch (70.8%). In those with aberrant subclavian arteries, no children without a Kommerell diverticulum were referred for surgery. In those with a Kommerell diverticulum confirmed on imaging, 11/24 underwent surgery.

Conclusion

Individuals with a double aortic arch, or an aberrant subclavian artery arising from a Kommerell diverticulum, have the highest requirement for surgical intervention, especially in isolated anomalies. These individuals should remain under monitoring. The subjective nature of symptoms remains problematic. Longitudinal research is required further to understand the natural history of vascular rings and how it links to morphology.
Comparative effectiveness of treatments for patellofemoral pain: a living systematic review with network meta-analysis
Authors: Winters Marinus , Holden Sinéad , Lura Carolina Bryne , Welton Nicky J , Caldwell Deborah M , Vicenzino Bill T , Weir Adam , Rathleff Michael Skovdal
Published: October 2020

Objective

To investigate the comparative effectiveness of all treatments for patellofemoral pain (PFP).

Design

Living systematic review with network meta-analysis (NMA).

Data sources

Sensitive search in seven databases, three grey literature resources and four trial registers.

Eligibility criteria

Randomised controlled trials evaluating any treatment for PFP with outcomes ‘any improvement’, and pain intensity.

Data extraction

Two reviewers independently extracted data and assessed risk of bias with Risk of Bias Tool V.2. We used Grading of Recommendations, Assessment, Development and Evaluation to appraise the strength of the evidence.

Primary outcome measure

‘Any improvement’ measured with a Global Rating of Change Scale.

Results

Twenty-two trials (with forty-eight treatment arms) were included, of which approximately 10 (45%) were at high risk of bias for the primary outcome. Most comparisons had a low to very low strength of the evidence. All treatments were better than wait and see for any improvement at 3 months (education (OR 9.6, 95% credible interval (CrI): 2.2 to 48.8); exercise (OR 13.0, 95% CrI: 2.4 to 83.5); education+orthosis (OR 16.5, 95% CrI: 4.9 to 65.8); education+exercise+patellar taping/mobilisations (OR 25.2, 95% CrI: 5.7 to 130.3) and education+exercise+patellar taping/mobilisations+orthosis (OR 38.8, 95% CrI: 7.3 to 236.9)). Education+exercise+patellar taping/mobilisations, with (OR 4.0, 95% CrI: 1.5 to 11.8) or without orthosis (OR 2.6, 95% CrI: 1.7 to 4.2), were superior to education alone. At 12 months, education or education+any combination yielded similar improvement rates.

Summary/conclusion

Education combined with a physical treatment (exercise, orthoses or patellar taping/mobilisation) is most likely to be effective at 3 months. At 12 months, education appears comparable to education with a physical treatment. There was insufficient evidence to recommend a specific type of physical treatment over another. All treatments in our NMA were superior to wait and see at 3 months, and we recommend avoiding a wait-and-see approach.

PROSPERO registeration number

PROSPERO registration CRD42018079502.
Trends in prevalence of pre-existing diabetes and perinatal outcomes: a large, population-based study in Catalonia, Spain, 2006–2015
Authors: Gortazar Lucia , Goday Albert , Flores-Le Roux Juana Antonia , Sarsanedas Eugènia , Payà Antonio , Mañé Laura , Pedro-Botet Juan , Benaiges David
Published: October 2020

Introduction

This study aims to assess trends in the prevalence of pre-existing diabetes and whether the risk of adverse perinatal outcomes decreased in women between 2006 and 2015 in Catalonia, Spain.

Research design and methods

A population-based study of 743 762 singleton deliveries between 2006 and 2015 in Catalonia, Spain, was conducted using data from the Spanish Minimum Basic Data Set. Cases of type 1 diabetes (T1DM) and ‘type 2 diabetes and other pre-existing diabetes’ (‘T2DM and other PGD’) were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Crude and age-adjusted annual prevalences were calculated. Poisson regression model was used to assess trends in prevalence and perinatal outcomes during the study period.

Results

Overall prevalences of pre-existing diabetes, T1DM and ‘T2DM and other PGD’ were 0.52% (95% CI 0.51 to 0.54), 0.17% (95% CI 0.17 to 0.18) and 0.35% (95% CI 0.33 to 0.36), respectively. From 2006 to 2015, rates increased for pre-existing diabetes (from 0.43 (95% CI 0.39 to 0.48) to 0.56% (0.50 to 0.62), p<0.001), T1DM (from 0.14 (0.11 to 0.17) to 0.20% (0.17 to 0.23), p<0.001) and ‘T2DM and other PGD’ (from 0.29 (0.25 to 0.33) to 0.36% (0.31 to 0.40), p<0.001). Pre-eclampsia rose in women with pre-existing diabetes (from 4.38% to 8.97%, adjusted p<0.001), T1DM (from 3.85% to 12.88%, p=0.005) and ‘T2DM and other PGD’ (from 4.63% to 6.78%, adjusted p=0.01). Prevalence of prematurity, cesarean section and small for gestational age remained stable in all diabetes groups. However, the prevalence of macrosomia fell in women with pre-existing diabetes (from 18.18% to 11.9%, adjusted p=0.011) and ‘T2DM and other PGD’ (from 14.71% to 11.06%, non-adjusted p=0.022, adjusted p=0.305) and large for gestational age decreased in all diabetes groups (from 39.73% to 30.25% in pre-existing diabetes, adjusted p=0.004).

Conclusions

The prevalence of pre-existing diabetes increased significantly in Catalonia between 2006 and 2015. Despite improvements in outcomes related to excessive birth weight, pre-eclampsia rates are rising and overall perinatal outcomes in women with pre-existing diabetes continue to be markedly worse than in the population without diabetes.
Validation analysis of Global Health Security Index (GHSI) scores 2019
Authors: Boyd Matthew J , Wilson Nick , Nelson Cassidy
Published: October 2020

Introduction

The COVID-19 pandemic powerfully demonstrates the consequences of biothreats. Countries will want to know how to better prepare for future events. The Global Health Security Index (GHSI) is a broad, independent assessment of 195 countries’ preparedness for biothreats that may aid this endeavour. However, to be useful, the GHSI’s external validity must be demonstrated. We aimed to validate the GHSI against a range of external metrics to assess how it could be utilised by countries.

Methods

Global aggregate communicable disease outcomes were correlated with GHSI scores and linear regression models were examined to determine associations while controlling for a number of global macroindices. GHSI scores for countries previously exposed to severe acute respiratory syndrome (SARS), Middle East respiratory syndrome and Ebola and recipients of US Global Health Security Agenda (GHSA) investment were compared with matched control countries. Possible content omissions in light of the progressing COVID-19 pandemic were assessed.

Results

GHSI scores for countries had strong criterion validity against the Joint External Evaluation ReadyScore (rho=0.82, p<0.0001), and moderate external validity against deaths from communicable diseases (−0.56, p<0.0001). GHSI scores were associated with reduced deaths from communicable diseases (F(3, 172)=22.75, p<0.0001). The proportion of deaths from communicable diseases decreased 4.8% per 10-point rise in GHSI. Recipient countries of the GHSA (n=31) and SARS-affected countries (n=26), had GHSI scores 6.0 (p=0.0011) and 8.2 (p=0.0010) points higher than matched controls, respectively. Biosecurity and biosafety appear weak globally including in high-income countries, and health systems, particularly in Africa, are not prepared. Notably, the GHSI does not account for all factors important for health security.

Conclusion

The GHSI shows promise as a valid tool to guide action on biosafety, biosecurity and systems preparedness. However, countries need to look beyond existing metrics to other factors moderating the impact of future pandemics and other biothreats. Consideration of anthropogenic and large catastrophic scenarios is also needed.
QRS complex characteristics and patient outcomes in out-of-hospital pulseless electrical activity cardiac arrest
Authors: Kim Jung Ho , Ryoo Hyun Wook , Kim Jong-yeon , Ahn Jae Yun , Moon Sungbae , Lee Dong Eun , Mun You Ho , Son Jang Won
Published: October 2020

Background

Pulseless electrical activity (PEA) is increasingly observed in out-of-hospital cardiac arrest (OHCA), but outcomes are still poor. We aimed to assess the relationship between QRS characteristics and outcomes of patients with OHCA with initial PEA (OHCA-P).

Methods

This prospective observational study included patients aged at least 18 years who developed OHCA-P between 1 January 2016 and 31 December 2018, and were enrolled in the Daegu Emergency Medical Services registry, South Korea. We performed multivariable logistic regression analyses to identify the associations between QRS characteristics and OHCA-P outcomes, in which QRS complexes were considered separately (model 1) and simultaneously (model 2). The primary outcome was survival to hospital discharge and the secondary outcome was a favourable neurological outcome.

Results

Of the 3659 patients with OHCA, 576 were enrolled (median age 73 years; 334 men). A higher QRS amplitude was associated with survival to hospital discharge and a favourable neurological outcome in model 1 (adjusted OR (aOR) 1.077 and 1.106, respectively; 95% CI 1.021 to 0.136 and 1.029 to 1.190, respectively) and model 2 (aOR 1.084 and 1.123, respectively; 95% CI 1.026 to 1.145 and 1.036 to 1.216, respectively). A QRS width of <120 ms was associated with survival to hospital discharge and a favourable neurological outcome in model 1 (aOR 3.371 and 4.634, respectively; 95% CI 1.633 to 6.960 and 1.562 to 13.144, respectively) and model 2 (aOR 3.213 and 5.103, respectively; 95% CI 1.568 to 6.584 and 1.682 to 15.482, respectively). Survival to hospital discharge and neurological outcome were not associated with QRS frequency.

Conclusion

OHCA-P outcomes were better when the initial QRS complex showed a higher amplitude or narrower width.
Discovery of biomarker candidates associated with the risk of short-term and mid/long-term relapse after infliximab withdrawal in Crohn’s patients: a proteomics-based study
Authors: Pierre Nicolas , Baiwir Dominique , Huynh-Thu Vân Anh , Mazzucchelli Gabriel , Smargiasso Nicolas , De Pauw Edwin , Bouhnik Yoram , Laharie David , Colombel Jean-Frédéric , Meuwis Marie-Alice , Louis Edouard
Published: October 2020

Objective

A subset of Crohn’s disease (CD) patients experiences mid/long-term remission after infliximab withdrawal. Biomarkers are needed to identify those patients.

Design

New biomarkers of relapse were searched in the baseline serum of CD patients stopping infliximab when they were under combined therapy (antimetabolite and infliximab) and stable clinical remission (diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors cohort, n=102). From shotgun proteomics experiment (discovery step), biomarker candidates were identified and further targeted by selected reaction monitoring (verification step). The dataset was stratified to search for markers of short-term (<6 months) or mid/long-term relapse (>6 months). The risk of relapse and the predicting capacity associated with biomarker candidates were evaluated using univariate Cox model and log-rank statistic, respectively. To test their complementary predicting capacity, biomarker candidates were systematically combined in pairs.

Results

Distinct biomarker candidates were associated with the risk (HR) of short-term (15 proteins, 2.9<HR<16.1, p<0.05) and mid/long-term (17 proteins, 2.1<HR<4.7, p<0.05) relapse, they reflect different pathophysiological processes. In stratified and non-stratified datasets, novel marker combinations exhibited a high predicting capacity as shown by their higher Z-scores (false discovery rate <0.001) than C reactive protein and faecal calprotectin (current references in predicting relapse).

Conclusion

We identified for the first time circulating biomarker candidates associated with the risk of mid/long-term relapse in CD patients stopping infliximab. We also highlight a sequence of pathophysiological processes leading to relapse, this could help to better understand the disease progression. Our findings may pave the way for a better non-invasive evaluation of the risk of relapse when contemplating antitumour necrosis factor α withdrawal in CD patients.
Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma
Authors: Barsoumian Hampartsoum B , Ramapriyan Rishab , Younes Ahmed I , Caetano Mauricio S , Menon Hari , Comeaux Nathan I , Cushman Taylor R , Schoenhals Jonathan E , Cadena Alexandra P , Reilly Timothy P , Chen Dawei , Masrorpour Fatemeh , Li Ailin , Hong David S , Diab Adi , Nguyen Quynh-Nhu , Glitza Isabella , Ferrarotto Renata , Chun Stephen G , Cortez Maria Angelica , Welsh James
Published: October 2020

Background

Despite some successes with checkpoint inhibitors for treating cancer, most patients remain refractory to treatment, possibly due to the inhibitory nature of the tumor stroma that impedes the function and entry of effector cells. We devised a new technique of combining immunotherapy with radiotherapy (XRT), more specifically low-dose XRT, to overcome the stroma and maximize systemic outcomes.

Methods

We bilaterally established 344SQ lung adenocarcinoma tumors in 129Sv/Ev mice. Primary and secondary tumors were irradiated with either high-dose or low-dose of XRT with systemic anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte associated protein 4 administration. Survival and tumor growth were monitored for the various groups, and secondary tumors were phenotyped by flow cytometry for immune populations. Tumor growth factor-beta (TGF-β) cytokine levels were assessed locally after low-dose XRT, and specific immune-cell depletion experiments were conducted to identify the major contributors to the observed systemic antitumor effect.

Results

Through our preclinical and clinical studies, we observed that when tumor burden was high, there was a necessity of combining high-dose XRT to ‘prime’ T cells at the primary tumor site, with low-dose XRT directed to secondary (metastatic) tumors to ‘modulate the stroma’. Low-dose XRT improved the antitumor outcomes of checkpoint inhibitors by favoring M1 macrophage polarization, enhancing natural killer (NK) cell infiltration, and reducing TGF-β levels. Depletion of CD4+T cells and NK cells abrogated the observed antitumor effect.

Conclusion

Our data extend the benefits of low-dose XRT to reprogram the tumor environment and improve the infiltration and function of effector immune cells into secondary tumors.
Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia
Authors: Díaz-González Francisca , Wadhwa Saruchi , Rodriguez-Zabala Maria , Kumar Somesh , Aza-Carmona Miriam , Sentchordi-Montané Lucia , Alonso Milagros , Ahmad Istaq , Zahra Sana , Kumar Deepak , Kushwah Neetu , Shamim Uzma , Sait Haseena , Kapoor Seema , Roldán Belen , Nishimura Gen , Offiah Amaka C , Faruq Mohammed , Heath Karen E.
Published: October 2020

Background

C-type natriuretic peptide (CNP), its endogenous receptor, natriuretic peptide receptor-B (NPR-B), as well as its downstream mediator, cyclic guanosine monophosphate (cGMP) dependent protein kinase II (cGKII), have been shown to play a pivotal role in chondrogenic differentiation and endochondral bone growth. In humans, biallelic variants in NPR2, encoding NPR-B, cause acromesomelic dysplasia, type Maroteaux, while heterozygous variants in NPR2 (natriuretic peptide receptor 2) and NPPC (natriuretic peptide precursor C), encoding CNP, cause milder phenotypes. In contrast, no variants in cGKII, encoded by the protein kinase cGMP-dependent type II gene (PRKG2), have been reported in humans to date, although its role in longitudinal growth has been clearly demonstrated in several animal models.

Methods

Exome sequencing was performed in two girls with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones. Functional characterisation was undertaken for the identified variants.

Results

Two homozygous PRKG2 variants, a nonsense and a frameshift, were identified. The mutant transcripts are exposed to nonsense-mediated decay and the truncated mutant cGKII proteins, partially or completely lacking the kinase domain, alter the downstream mitogen activation protein kinase signalling pathway by failing to phosphorylate c-Raf 1 at Ser43 and subsequently reduce ERK1/2 activation in response to fibroblast growth factor 2. They also downregulate COL10A1 and upregulate COL2A1 expression through SOX9.

Conclusion

In conclusion, we have clinically and molecularly characterised a new acromesomelic dysplasia, acromesomelic dysplasia, PRKG2 type (AMDP).
Prior antiplatelet therapy and haematoma expansion after primary intracerebral haemorrhage: an individual patient-level analysis of CLEAR III, MISTIE III and VISTA-ICH
Authors: Murthy Santosh , Roh David J , Chatterjee Abhinaba , McBee Nichol , Parikh Neal S , Merkler Alexander E , Navi Babak B , Falcone Guido J , Sheth Kevin N , Awad Issam , Hanley Daniel , Kamel Hooman , Ziai Wendy C
Published: October 2020

Objective

To evaluate the relationship between prior antiplatelet therapy (APT) and outcomes after primary intracerebral haemorrhage (ICH), and assess if it varies by haematoma location.

Methods

We pooled individual patient data from the Virtual International Stroke Trials Archive-ICH trials dataset, Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III trial. The exposure was APT preceding ICH diagnosis. The primary outcome was haematoma expansion at 72 hours. Secondary outcomes were admission haematoma volume, all-cause mortality, death or major disability (modified Rankin Scale (mRS) score ≥4) and shift in mRS distribution. Mixed-effects models were used to assess the relationship between APT and outcomes. Secondary analyses were stratified by ICH location and study cohort.

Results

Among 1420 patients with ICH, there were 782 (55.1%) lobar and 596 (42.0%) deep haemorrhages. APT was reported in 284 (20.0%) patients. In adjusted regression models, prior APT was not associated with haematoma expansion (OR, 0.97; 95% CI 0.60 to 1.57), major disability or death (OR, 1.05; 95% CI 0.61 to 1.63), all-cause mortality (OR, 0.89; 95% CI 0.47 to 1.85), admission haematoma volume (beta, −0.17; SE, 0.09; p=0.07) and shift in mRS (p=0.43). In secondary analyses, APT was associated with admission haematoma volume in lobar ICH (beta, 0.25; SE, 0.12; p=0.03), but there was no relationship with other ICH outcomes when stratified by haematoma location or study cohort.

Conclusions

In a large heterogeneous cohort of patients with ICH, prior APT was not associated with haematoma expansion or functional outcomes after ICH, regardless of haematoma location. APT was associated with admission haematoma volumes in lobar ICH.
Dilemma for appeals to the moral significance of birth
Authors: Bobier Christopher A , Omelianchuk Adam
Published: October 2020

Giubilini and Minerva argue that the permissibility of abortion entails the permissibility of infanticide. Proponents of what we refer to as the Birth Strategy claim that there is a morally significant difference brought about at birth that accounts for our strong intuition that killing newborns is morally impermissible. We argue that strategy does not account for the moral intuition that late-term, non-therapeutic abortions are morally impermissible. Advocates of the Birth Strategy must either judge non-therapeutic abortions as impermissible in the later stages of pregnancy or conclude that they are permissible on the basis of premises that are far less intuitively plausible than the opposite conclusion and its supporting premises.