bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutralization of S100A4 induces stabilization of atherosclerotic plaques: role of smooth muscle cells
Authors: Sakic Antonija , Chaabane Chiraz , Ambartsumian Noona , Klingelhöfer Jörg , Lemeille Sylvain , Kwak Brenda R , Grigorian Mariam , Bochaton-Piallat Marie-Luce
Published: October 2020

Aims

During atherosclerosis, smooth muscle cells (SMCs) accumulate in the intima where they switch from a contractile to a synthetic phenotype. From porcine coronary artery, we isolated spindle-shaped (S) SMCs exhibiting features of the contractile phenotype and rhomboid (R) SMCs typical of the synthetic phenotype. S100A4 was identified as a marker of R-SMCs in vitro and intimal SMCs, in pig and man. S100A4 exhibits intra- and extracellular functions. In this study, we investigated the role of extracellular S100A4 in SMC phenotypic transition.

Methods and results

S-SMCs were treated with oligomeric recombinant S100A4 (oS100A4), which induced nuclear factor (NF)-κB activation. Treatment of S-SMCs with oS100A4 in combination with platelet-derived growth factor (PDGF)-BB induced a complete SMC transition towards a pro-inflammatory R-phenotype associated with NF-κB activation, through toll-like receptor-4. RNA sequencing of cells treated with oS100A4/PDGF-BB revealed a strong up-regulation of pro-inflammatory genes and enrichment of transcription factor binding sites essential for SMC phenotypic transition. In a mouse model of established atherosclerosis, neutralization of extracellular S100A4 decreased area of atherosclerotic lesions, necrotic core, and CD68 expression and increased α-smooth muscle actin and smooth muscle myosin heavy chain expression.

Conclusion

We suggest that the neutralization of extracellular S100A4 promotes the stabilization of atherosclerotic plaques. Extracellular S100A4 could be a new target to influence the evolution of atherosclerotic plaques.
Risk factor management and atrial fibrillation
Authors: Hendriks Jeroen M , Gallagher Celine , Middeldorp Melissa E , Lau Dennis H , Sanders Prashanthan
Published: October 2020

The management of atrial fibrillation (AF) is multifaceted and treatment paradigms have changed significantly in the last century. The treatment of AF requires a comprehensive approach which goes beyond the treatment of the arrhythmia alone. Risk factor management has been introduced as a crucial pillar of AF management. As a result, the landscape of care delivery is changing as well, and novel models of comprehensive care delivery for AF have been introduced. This article reviews the evidence for the role of risk factor management in AF, how this can be integrated and implemented in clinical practice by applying novel models of care delivery, and finally identifies areas for ongoing research and potential healthcare reform to comprehensively manage the burgeoning AF population.
Compressible Euler equations on a sphere and elliptic–hyperbolic property
Authors: Holloway Ian , Sritharan Sivaguru S
Published: October 2020

In this work, we systematically derive the governing equations of supersonic conical flow by projecting the 3D Euler equations onto the unit sphere. These equations result from taking the assumption of conical invariance on the 3D flow field. Under this assumption, the compressible Euler equations reduce to a system defined on the surface of the unit sphere. This compressible flow problem has been successfully used to study the steady supersonic flow past cones of arbitrary cross section by reducing the number of spatial dimensions from three down to two while still capturing many of the relevant 3D effects. In this paper, the powerful machinery of tensor calculus is utilized to avoid reference to any particular coordinate system. With the flexibility to use any coordinate system on the surface of a sphere, the equations can be more readily solved numerically when a structured mesh is used by defining the mesh lines to be the coordinate lines. The type of the system of partial differential equations would be hyperbolic or elliptic based on whether the crossflow Mach number is supersonic or subsonic.
Counting Rational Curves on K3 Surfaces With Finite Group Actions
Authors: Zhan Sailun
Published: October 2020

Göttsche gave a formula for the dimension of the cohomology of Hilbert schemes of points on a smooth projective surface $S$. When $S$ admits an action by a finite group $G$, we describe the action of $G$ on the Hodge structure. In the case that $S$ is a K3 surface, each element of $G$ gives a trace on $\sum _{n=0}^{\infty }\sum _{i=0}^{\infty }(-1)^{i}H^{i}(S^{[n]},\mathbb{C})q^{n}$. When $G$ acts faithfully and symplectically on $S$, the resulting generating function is of the form $q/f(q)$, where $f(q)$ is a cusp form. We relate the Hodge structure of Hilbert schemes of points to the Hodge structure of the compactified Jacobian of the tautological family of curves over an integral linear system on a K3 surface as $G$-representations. Finally, we give a sufficient condition for a $G$-orbit of curves with nodal singularities not to contribute to the representation.
International survey of COVID-19 management strategies
Authors: Tartaglia Riccardo , La Regina Micaela , Tanzini Michela , Pomare Chiara , Urwin Rachel , Ellis Louise A , Fineschi Vittorio , Venneri Francesco , Seghieri Chiara , Lachman Peter , Westbrook Johanna , Braithwaite Jeffrey
Published: October 2020

Background

While individual countries have gained considerable knowledge and experience in coronavirus disease of 2019 (COVID-19) management, an international, comparative perspective is lacking, particularly regarding the measures taken by different countries to tackle the pandemic. This paper elicits the views of health system staff, tapping into their personal expertise on how the pandemic was initially handled.

Methods

From May to July 2020, we conducted a cross-sectional, online, purpose-designed survey comprising 70 items. Email lists of contacts provided by the International Society for Quality in Health Care, the Italian Network for Safety in Health Care and the Australian Institute of Health Innovation were used to access healthcare professionals and managers across the world. We snowballed the survey to individuals and groups connected to these organizations. Key outcome measures were attitudes and information about institutional approaches taken; media communication; how acute hospitals were re-organized; primary health organization; personal protective equipment; and staffing and training.

Results

A total of 1131 survey participants from 97 countries across the World Health Organization (WHO) regions responded to the survey. Responses were from all six WHO regions; 57.9% were female and the majority had 10 or more years of experience in healthcare; almost half (46.5%) were physicians; and all other major clinical professional groups participated. As the pandemic progressed, most countries established an emergency task force, developed communication channels to citizens, organized health services to cope and put in place appropriate measures (e.g. pathways for COVID-19 patients, and testing, screening and tracing procedures). Some countries did this better than others. We found several significant differences between the WHO regions in how they are tackling the pandemic. For instance, while overall most respondents (71.4%) believed that there was an effective plan prior to the outbreak, this was only the case for 31.9% of respondents from the Pan American Health Organization compared with 90.7% of respondents from the South-East Asia Region (SEARO). Issues with swab testing (e.g. delay in communicating the swab outcome) were less frequently reported by respondents from SEARO and the Western Pacific Region compared with other regions.

Conclusion

The world has progressed in its knowledge and sophistication in tackling the pandemic after early and often substantial obstacles were encountered. Most WHO regions have or are in the process of responding well, although some countries have not yet instituted widespread measures known to support mitigation, for example, effective swab testing and social control measures.
Antimicrobial stewardship in Australian hospitals: how does compliance with antimicrobial stewardship standards compare across key hospital classifications?
Authors: Jones Renee , Carville Kylie , James Rodney
Published: October 2020

Background

There is little information on the prevalence and type of antimicrobial stewardship (AMS) activities that are currently occurring in Australian hospitals.

Objectives

To determine what AMS activities are currently occurring in Australian hospitals, identify gaps in compliance with the Australian Commission on Safety and Quality in Health Care (ACSQHC) standards and determine perceived barriers and enablers for implementing AMS programmes.

Methods

A cross-sectional survey open to all Australian hospitals, conducted online and available to hospitals between November 2016 and July 2017.

Results

Responses were received from 254 hospitals. Compliance with ACSQHC AMS essential activities was high, except for essential activity 3 (post-prescription reviews), which was conducted by only 39% of respondent hospitals. Importantly, compliance varied by hospital remoteness classification for all activities except essential activity 1 (availability and endorsement of guidelines) and additional activity 4 (publishing antimicrobial susceptibility data annually), with major city hospitals having the highest compliance across all activities. The three most frequently reported barriers to implementing AMS programmes were a lack of training and education, lack of pharmacy resources and a lack of willingness from medical officers to change.

Conclusions

Due to low response rates from certain hospital groups, the survey results are not generalizable to all Australia hospitals. This survey has identified that several gaps in compliance still exist and outlines the need to address lower AMS compliance in hospitals located outside major cities. The key barriers and enablers for AMS programme implementation identified should be used to inform future strategies.
Evaluation of Infectious Disease Test Ordering and Positivity Rates in Illicit Fentanyl Users
Authors: Lloyd Matthew , Ransom Eric M , Anderson Neil W , Farnsworth Christopher W
Published: October 2020

Background

The emergence of illicit fentanyl use has resulted in considerable morbidity and mortality. Although illicit use of other opioids has been associated with transmission of viral and bacterial infections, limited data exist for the prevalence of infectious diseases among illicit fentanyl users. The purpose of this study was to assess the likelihood of infectious disease testing and infection prevalence among illicit fentanyl users.

Methods

Results from urine drug screens (UDSs) performed from August 13, 2019, to October 16, 2019, were obtained from the laboratory information system with concurrent microbial testing. Patients were categorized based on UDS results, and illicit drug use was inferred from physician encounter notes in the electronic medical record.

Results

Suspected illicit drugs users with fentanyl detected by UDS were more likely to be screened [odds ratio (OR): 1.7; 95% CI, 1.26–2.4] and test positive for hepatitis C virus (HCV) by immunoassay (OR: 5.89; 95% CI, 2.93–11.31) than patients without drugs detected. Patients with suspected illicit fentanyl use who were discharged from the emergency department (ED) were less likely to be tested for HCV than patients in outpatient settings (OR: 3.47; 95% CI, 1.05–10.4) and inpatient settings (OR: 17.43; 95% CI, 6.53–45.88). Patients with suspected illicit fentanyl use were more likely to have infected abscesses or wounds (OR: 5.12; 95% CI, 2.07–13.7) and Staphylococcus aureus infections (OR: 4.5; 95% CI, 1.59–12.28) than patients without drugs detected.

Conclusions

Patients with a positive UDS for fentanyl and suspected illicit use were more likely to test positive for HCV, were rarely screened for HCV in the ED, and had an increased risk of invasive S. aureus wound or abscess infection. These findings may represent considerable barriers to care for patients who use fentanyl illicitly.
Control Charting Genomic Data
Authors: Xu Jing , Crossley Eric , Wagenfuehr Jennifer , Mitui Midori , Londin Eric , Patel Khushbu , Park Jason Y
Published: October 2020

Background

Control charting is routine in the quality assurance of traditional clinical laboratory testing. Genomic tests are not typically managed by control charting. We examined control charting to monitor the performance of a clinical next-generation sequencing (NGS) assay.

Methods

We retrospectively examined 3 years of control material (NA12878) data from clinical genomic epilepsy testing. Levey-Jennings plots were used to visualize changes in control material depth of sequencing coverage in genomic regions of an epilepsy genomic panel. Changes in depth of coverage were correlated with changes in the manufactured lot of capture probe reagent. Depth of coverage was also correlated between quality control material and clinical samples.

Results

Fifty-seven sequencing runs of NA12878 were analyzed for 1811 genomic regions targeting 108 genes. Manufactured probe lot changes were associated with significant changes in the average coverage of 537 genomic regions and the lowest coverage of 173 regions (using a critical cut-off of P < 5.52 x 10−6). Genomic regions with the highest sensitivity to lot-to-lot variation by average sequencing depth of coverage were not the same regions with the highest sensitivity by lowest sequencing depth of coverage. Levey-Jennings plots displayed differences in genomic depth of coverage across capture probe reagent lot changes. There was moderate correlation between the changes in depth of sequencing across lot changes for control material and clinical cases (r2 = 0.45).

Conclusions

Genomic control charting can be used routinely by clinical laboratories to monitor assay performance and ensure the quality of testing.
Understanding parameter differences between analyses employing nested data subsets
Authors: Gratton Steven , Challinor Anthony
Published: October 2020

We provide an analytical argument for understanding the likely nature of parameter shifts between those coming from an analysis of a data set and from a subset of that data set, assuming differences are down to noise and any intrinsic variance alone. This gives us a measure against which we can interpret changes seen in parameters and make judgements about the coherency of the data and the suitability of a model in describing those data.
Redshift-space effects in voids and their impact on cosmological tests. Part I: the void size function
Authors: Correa Carlos M , Paz Dante J , Sánchez Ariel G , Ruiz Andrés N , Padilla Nelson D , Angulo Raúl E
Published: October 2020

Voids are promising cosmological probes. Nevertheless, every cosmological test based on voids must necessarily employ methods to identify them in redshift space. Therefore, redshift-space distortions (RSD) and the Alcock–Paczyński effect (AP) have an impact on the void identification process itself generating distortion patterns in observations. Using a spherical void finder, we developed a statistical and theoretical framework to describe physically the connection between the identification in real and redshift space. We found that redshift-space voids above the shot noise level have a unique real-space counterpart spanning the same region of space, they are systematically bigger and their centres are preferentially shifted along the line of sight. The expansion effect is a by-product of RSD induced by tracer dynamics at scales around the void radius, whereas the off-centring effect constitutes a different class of RSD induced at larger scales by the global dynamics of the whole region containing the void. The volume of voids is also altered by the fiducial cosmology assumed to measure distances, this is the AP change of volume. These three systematics have an impact on cosmological statistics. In this work, we focus on the void size function. We developed a theoretical framework to model these effects and tested it with a numerical simulation, recovering the statistical properties of the abundance of voids in real space. This description depends strongly on cosmology. Hence, we lay the foundations for improvements in current models of the abundance of voids in order to obtain unbiased cosmological constraints from redshift surveys.
G0.173−0.42: an X-ray and radio magnetized filament near the galactic centre
Authors: Yusef-Zadeh F , Wardle M , Heinke C , Heywood I , Arendt R , Royster M , Cotton W , Camilo F , Michail J
Published: October 2020

The detection of an X-ray filament associated with the radio filament G0.173–0.42 adds to four other non-thermal radio filaments with X-ray counterparts, amongst the more than 100 elongated radio structures that have been identified as synchrotron-emitting radio filaments in the inner couple of degrees of the Galactic centre. The synchrotron mechanism has also been proposed to explain the emission from X-ray filaments. However, the origin of radio filaments and the acceleration sites of energetic particles to produce synchrotron emission in radio and X-rays remain mysterious. Using MeerKAT, VLA, Chandra, WISE, and Spitzer, we present structural details of G0.173–0.42 which consists of multiple radio filaments, one of which has an X-ray counterpart. A faint oblique radio filament crosses the radio and X-ray filaments. Based on the morphology, brightening of radio and X-ray intensities, and radio spectral index variation, we argue that a physical interaction is taking place between two magnetized filaments. We consider that the reconnection of the magnetic field lines at the interaction site leads to the acceleration of particles to GeV energies. We also argue against the synchrotron mechanism for the X-ray emission due to the short ∼30 yr lifetime of TeV relativistic particles. Instead, we propose that the inverse Compton scattering mechanism is more likely to explain the X-ray emission by upscattering of seed photons emitted from a 106  L⊙ star located at the northern tip of the X-ray filament.
Optimal void finders in weak lensing maps
Authors: Davies Christopher T , Paillas Enrique , Cautun Marius , Li Baojiu
Published: October 2020

Cosmic voids are a key component of the large-scale structure that contain a plethora of cosmological information. Typically, voids are identified from the underlying galaxy distribution, which is a biased tracer of the total matter field. Previous works have shown that 2D voids identified in weak lensing (WL) maps – WL voids – correspond better to true underdense regions along the line of sight. In this work, we study how the properties of WL voids depend on the choice of void finder, by adapting several popular void finders. We present and discuss the differences between identifying voids directly in the convergence maps, and in the distribution of WL peaks. Particular effort has been made to test how these results are affected by galaxy shape noise (GSN), which is a dominant source of noise in WL observations. By studying the signal-to-noise ratios (S/N) for the tangential shear profile of each void finder, we find that voids identified directly in the convergence maps have the highest S/N but are also the ones most affected by GSN. Troughs are least affected by noise, but also have the lowest S/N. The tunnel algorithm, which identifies voids in the distribution of WL peaks, represents a good compromise between finding a large tangential shear S/N and mitigating the effect of GSN.
Magnetorotational core collapse of possible GRB progenitors – II. Formation of protomagnetars and collapsars
Authors: Aloy M Á , Obergaulinger M
Published: October 2020

We assess the variance of the post-collapse evolution remnants of compact, massive, low-metallicity stars, under small changes in the degrees of rotation and magnetic field of selected pre-supernova cores. These stellar models are commonly considered progenitors of long gamma-ray bursts. The fate of the protoneutron star (PNS) formed after the collapse, whose mass may continuously grow due to accretion, critically depends on the poloidal magnetic field strength at bounce. Should the poloidal magnetic field be sufficiently weak, the PNS collapses to a black hole (BH) within a few seconds. Models on this evolutionary track contain promising collapsar engines. Poloidal magnetic fields smooth over large radial scales (e.g. dipolar fields) or slightly augmented with respect to the original pre-supernova core yield long-lasting PNSs. In these models, BH formation is avoided or staved off for a long time, hence, they may produce protomagnetars (PMs). Some of our PM candidates have been run for $\lesssim 10\,$ s after core bounce, but they have not entered the Kelvin–Helmholtz phase yet. Among these models, some display episodic events of spin-down during which we find properties broadly compatible with the theoretical expectations for PMs ($M_\rm {\small PNS}\approx 1.85{-}2.5\, \mathrm{M}_{\odot }$, $\bar{P}_\rm {\small PNS}\approx 1.5 {-} 4\,$ ms, and $b^{\rm surf}_\rm {\small PNS}\lesssim 10^{15}\,$ G) and their very collimated supernova ejecta have nearly reached the stellar surface with (still growing) explosion energies $\gtrsim {2} \times 10^{51}\, \textrm {erg}$.
Identity Metaphysics
Authors: Strawson Galen
Published: October 2020

Identity metaphysics finds identity or unity where other metaphysical theories find difference or diversity. It denies the fundamentality of ontological distinctions that other theories treat as fundamental. It’s opposed to separatism, which mistakes natural conceptual distinctions for ground-floor ontological differences. It proposes that the distinctions between the concepts substance, object, quality, property, process, state, and event are metaphysically superficial; so too the distinctions between the concepts energy, lawsofnature, force, causation, power, and naturalnecessity. So too the distinction between these two sets of concepts. “Thinking takes apart what is really one” (Nietzsche 1885).
Nicotine Dependence in Dual Users of Cigarettes and E-Cigarettes: Common and Distinct Elements
Authors: Rest Eva C , Mermelstein Robin J , Hedeker Donald
Published: October 2020

Introduction

In a sample of dual users of cigarettes and electronic nicotine delivery systems (ENDS; e-cigarettes), we evaluated psychometric properties of ENDS versions of the Nicotine Dependence Syndrome Scale (NDSS), the brief Wisconsin Inventory of Smoking Dependence Motives (WISDM), and the Fagerström Test for Nicotine Dependence (FTND). Using the NDSS, we tested the hypothesis that there would be one common underlying factor of dependence across the cigarette and ENDS scales and other product-specific factors.

Aims and Methods

Adult dual users (N = 404) completed baseline cigarette and ENDS versions of the NDSS, WISDM, and FTND, and biweekly surveys of their smoking and vaping. Analyses included bifactor modeling, which helps to identify both a general and product-specific factor for each item, and exploratory factor analyses of the combined cigarette and ENDS NDSS items and examinations of concurrent and predictive validity.

Results

The bifactor model was not a good fit, suggesting the lack of one common underlying dependence factor. Factor analyses revealed separate, similar factors for both products, with only one factor (priority) showing overlap of cigarette and ENDS items. ENDS scales significantly predicted ENDS use over time, but not cigarette use. Cigarette scales did not predict ENDS use over time.

Conclusions

Although the cigarette and ENDS NDSS versions showed similar factor structure, there was not a primary common underlying factor reflecting drive or tolerance, but rather product-specific factors. The cigarette scales were not valid for predicting ENDS use. These results highlight the importance of separately assessing dependence for cigarettes and ENDS in dual users.

Implications

Although underlying dimensions of nicotine dependence may be similar for ENDS and cigarettes, separate, product-specific measures may be needed to understand differences in product-specific dependency and predict changes in use of each product over time.
Generating Infinite Digraphs by Derangements
Authors: Horsley Daniel , Iradmusa Moharram , Praeger Cheryl E
Published: October 2020

A set $\mathcal{S}$ of derangements (fixed-point-free permutations) of a set V generates a digraph with vertex set V and arcs $(x,x^{\,\sigma})$ for x ∈ V and $\sigma\in\mathcal{S}$. We address the problem of characterizing those infinite (simple loopless) digraphs which are generated by finite sets of derangements. The case of finite digraphs was addressed in an earlier work by the second and third authors. A criterion is given for derangement generation which resembles the criterion given by De Bruijn and Erdős for vertex colourings of graphs in that the property for an infinite digraph is determined by properties of its finite sub-digraphs. The derangement generation property for a digraph is linked with the existence of a finite 1-factor cover for an associated bipartite (undirected) graph.
Genetic Differentiation of Verticillium dahliae Populations Recovered from Symptomatic and Asymptomatic Hosts
Authors: Bautista-Jalón Laura S. , Frenkel Omer , Tsror (Lahkim) Leah , Malcolm Glenna M. , Gugino Beth K. , Lebiush Sara , Hazanovsky Marina , Milgroom Michael G. , del Mar Jiménez-Gasco María
Published: October 2020

Verticillium dahliae is a soilborne fungal pathogen affecting many economically important crops that can also infect weeds and rotational crops with no apparent disease symptoms. The main research goal was to test the hypothesis that V. dahliae populations recovered from asymptomatic rotational crops and weed species are evolutionarily and genetically distinct from symptomatic hosts. We collected V. dahliae isolates from symptomatic and asymptomatic hosts growing in fields with histories of Verticillium wilt of potato in Israel and Pennsylvania (United States), and used genotyping-by-sequencing to analyze the evolutionary history and genetic differentiation between populations of different hosts. A phylogeny inferred from 26,934 single-nucleotide polymorphisms (SNPs) in 126 V. dahliae isolates displayed a highly clonal structure correlated with vegetative compatibility groups, and isolates grouped in lineages 2A, 2B824, 4A, and 4B, with 77% of the isolates in lineage 4B. The lineages identified in this study were differentiated by host of origin; we found 2A, 2B824, and 4A only in symptomatic hosts but isolates from asymptomatic hosts (weeds, oat, and sorghum) grouped exclusively within lineage 4B, and were genetically indistinguishable from 4B isolates sampled from symptomatic hosts (potato, eggplant, and avocado). Using coalescent analysis of 158 SNPs of lineage 4B, we inferred a genealogy with clades that correlated with geographic origin. In contrast, isolates from asymptomatic and symptomatic hosts shared some of the same haplotypes and were not differentiated. We conclude that asymptomatic weeds and rotational hosts may be potential reservoirs for V. dahliae populations of lineage 4B, which are pathogenic to many cultivated hosts.
Divergence and Gene Flow Between Fusarium subglutinans and F. temperatum Isolated from Maize in Argentina
Authors: Fumero M. Veronica , Yue Wei , Chiotta María L. , Chulze Sofía N. , Leslie John F. , Toomajian Christopher
Published: October 2020

Fusarium subglutinans and F. temperatum are two important fungal pathogens of maize whose distinctness as separate species has been difficult to assess. We isolated strains of these species from commercial and native maize varieties in Argentina and sequenced >28,000 loci to estimate genetic variation in the sample. Our objectives were to measure genetic divergence between the species, infer demographic parameters related to their split, and describe the population structure of the sample. When analyzed together, over 30% of each species’ polymorphic sites (>2,500 sites) segregate as polymorphisms in the other. Demographic modeling confirmed the species split predated maize domestication, but subsequent between-species gene flow has occurred, with gene flow from F. subglutinans into F. temperatum greater than gene flow in the reverse direction. In F. subglutinans, little evidence exists for substructure or recent selective sweeps, but there is evidence for limited sexual reproduction. In F. temperatum, there is clear evidence for population substructure and signals of abundant recent selective sweeps, with sexual reproduction probably less common than in F. subglutinans. Both genetic variation and the relative number of polymorphisms shared between species increase near the telomeres of all 12 chromosomes, where genes related to plant−pathogen interactions often are located. Our results suggest that species boundaries between closely related Fusarium species can be semipermeable and merit further study. Such semipermeability could facilitate unanticipated genetic exchange between species and enable quicker permanent responses to changes in the agro-ecosystem, e.g., pathogen-resistant host varieties, new chemical and biological control agents, and agronomic practices.
Endosteal Vasculature Dominates Along the Tibial Cortical Diaphysis: A Quantitative Magnetic Resonance Imaging Analysis
Authors: Levack Ashley E. , Klinger Craig , Gadinsky Naomi E. , Dyke Jonathan P. , Fung Maggie M. , Helfet David L. , Lorich Dean G.
Published: October 2020

Objective:

Disrupted blood supply has been proposed as an underlying cause for delayed union in tibial shaft fractures (OTA/AO 42). Although tibial blood supply has been qualitatively evaluated, quantitative studies are lacking. The purpose of this project was to quantify the relative contribution of the endosteal supply to the tibial diaphysis.

Methods:

The superficial femoral artery of 8 fresh frozen cadaveric matched pair lower extremities was cannulated. The nutrient artery was ligated at its proximal branch point in experimental limbs. Pregadolinium and postgadolinium enhanced magnetic resonance imaging was performed with high resolution fat-suppressed ultrashort echo time magnetic resonance imaging sequences. Perfusion was assessed in 3 zones (outer, central, and inner cortex) for the proximal, middle, and distal diaphysis, respectively, using custom software to quantify and compare signal intensity between experimental and control limbs.

Results:

On average, the endosteal system supplied 91.4% (±3.9%) of the cortex and was the predominant blood supply for the inner, central, and outer thirds. The dominance of the endosteal contribution was most pronounced in the inner two-third of the cortex, with more than 97% loss of perfusion. Disruption of the nutrient artery also resulted in 76.3% (±11.2%) loss of perfusion of the outer one-third of the cortex.

Conclusion:

This quantitative study revealed a predominance of endosteal blood supply to all areas (inner, middle, and outer thirds) of the tibial diaphyseal cortex. To prevent delayed bone healing, surgeons should take care to preserve the remaining periosteal vascular network in fracture patterns in which the nutrient artery has likely been disrupted.
Systematic Review and Analysis of the Quality of Randomized Controlled Trials Comparing Reamed and Unreamed Intramedullary Nailing of Tibial Fractures
Authors: Clark DesRaj , Vo Loc-Uyen , Piscoya Andres S. , Chan Andrew , Dunn John C.
Published: October 2020

Objectives:

To evaluate the quality of research and reporting of randomized controlled trials comparing the use of reamed and unreamed intramedullary nails for tibial fractures with validated scoring systems.

Data Source:

PubMed using the search terms “tibia” AND “reamed OR unreamed” AND “intramedullary OR nail.” Filters were applied for the years 1991–2019, full articles, human subjects, and English language.

Study Selection:

Inclusion criteria were (1) prospective and randomized trials, (2) studies reported >80% follow-up, and (3) articles amenable to scoring with the chosen scoring systems. Exclusion criteria were (1) skeletally immature patients or (2) incomplete data sets.

Data Extraction:

Articles were assessed with the Coleman Methodology Score, the Consolidated Standards of Reporting Trials systems, and Cowan's Categorical Rating by 2 independent observers.

Data Synthesis:

Scores for individual articles were averaged for the 2 observers. The total and subcategory scores for all included articles were also averaged with SD from both observers. Categories from the 2 grading systems with deficient reporting were measured as a percentage based on grading from both observers. Data were analyzed using kappa statistic and correlation coefficient to assess agreement and reliability.

Conclusions:

All included articles supported the use of reamed tibial intramedullary nails, but the overall quality of the literature fell in the middle of both the modified Coleman Score and Consolidated Standards of Reporting Trials grading scheme ranges despite being Oxford Level 1.

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Automated Detection of Spinal Schwannomas Utilizing Deep Learning Based on Object Detection From Magnetic Resonance Imaging
Authors: Ito Sadayuki , Ando Kei , Kobayashi Kazuyoshi , Nakashima Hiroaki , Oda Masahiro , Machino Masaaki , Kanbara Shunsuke , Inoue Taro , Yamaguchi Hidetoshi , Koshimizu Hiroyuki , Mori Kensaku , Ishiguro Naoki , Imagama Shiro
Published: October 2020

Study Design.

A retrospective analysis of magnetic resonance imaging (MRI) was conducted.

Objective.

This study aims to develop an automated system for the detection of spinal schwannoma, by employing deep learning based on object detection from MRI. The performance of the proposed system was verified to compare the performances of spine surgeons.

Summary of Background Data.

Several MRI scans were conducted for the diagnoses of patients suspected to suffer from spinal diseases. Typically, spinal diseases do not involve tumors on the spinal cord, although a few tumors may exist at the unexpectable level or without symptom by chance. It is difficult to recognize these tumors; in some cases, these tumors may be overlooked. Hence, a deep learning approach based on object detection can minimize the probability of overlooking these tumors.

Methods.

Data from 50 patients with spinal schwannoma who had undergone MRI were retrospectively reviewed. Sagittal T1- and T2-weighted magnetic resonance imaging (T1WI and T2WI) were used in the object detection training and for validation. You Only Look Once version3 was used to develop the object detection system, and its accuracy was calculated. The performance of the proposed system was compared to that of two doctors.

Results.

The accuracies of the proposed object detection based on T1W1, T2W1, and both T1W1 and T2W1 were 80.3%, 91.0%, and 93.5%, respectively. The accuracies of the doctors were 90.2% and 89.3%.

Conclusion.

Automated object detection of spinal schwannoma was achieved. The proposed system yielded a high accuracy that was comparable to that of the doctors.

Level of Evidence: 4
Clinical Risk Prediction Scores in Coronavirus Disease 2019: Beware of Low Validity and Clinical Utility
Authors: Al Hassan Haamed , Cocks Eve , Jesani Lara , Lewis Sally , Szakmany Tamas
Published: October 2020

Several risk stratification tools were developed to predict disease progression in coronavirus disease 2019, with no external validation to date. We attempted to validate three previously published risk-stratification tools in a multicenter study. Primary outcome was a composite outcome of development of severe coronavirus disease 2019 disease leading to ICU admission or death censored at hospital discharge or 30 days. We collected data from 169 patients. Patients were 73 years old (59–82 yr old), 66 of 169 (39.1%) were female, 57 (33.7%) had one comorbidity, and 80 (47.3%) had two or more comorbidities. Area under the receiver operating characteristic curve (95% CI) for the COVID-GRAM score was 0.636 (0.550–0.722), for the CALL score 0.500 (0.411–0.589), and for the nomogram 0.628 (0.543–0.714).
Improvement of Cardiac Function in Rats With Myocardial Infarction by Low-Intensity to Moderate-Intensity Endurance Exercise Is Associated With Normalization of Klotho and SIRT1
Authors: Najafipour Hamid , Rostamzadeh Farzaneh , Yeganeh-Hajahmadi Mahboobeh , Joukar Siyavash
Published: October 2020

Exercise training (Ex) has beneficial effects on cardiovascular diseases by increasing Klotho and SIRT1. This study aimed to investigate whether the beneficial impact of Ex on myocardial infarction (MI) is mediated through Klotho and SIRT1. Fifty-six Wistar rats were divided into 4 main groups of Sham, MI, Ex, and MI + Ex. MI was induced by the closure of the left anterior descending. Animals were trained by endurance exercise for 4 weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of Klotho and SIRT1 in the serum and heart were measured by enzyme-linked immunosorbent assay and Western blot, respectively. The ADAM17 level in the heart and kidneys was assessed by enzyme-linked immunosorbent assay. The infarct size and fibrosis area were assessed by triphenyltetrazolium chloride and Masson trichrome staining, respectively. Ex recovered the reduction of dp/dt max and dp/dt min and decreased myocardial infarct size and fibrotic area in the MI group. Ex normalized the increase in heart rate, systolic blood pressure, left ventricular systolic pressure, and left ventricular end diastolic pressure in the MI group. Ex also normalized the reduction of the levels of Klotho and SIRT1 in serum and heart in the MI group. The changes of Klotho and SIRT1 in serum were positively correlated. Ex also restored ADAM17 levels in the MI group. Ex improved cardiac function in the MI group and is associated with reduction of the infarct size and normalization of Klotho and SIRT1 levels. Regarding unidirectional changes in Klotho and SIRT1, these proteins may play a role in beneficial effects of Ex on MI recovery.
Evaluation of Ocular Surface and Meibomian Glands in Patients With Scleroderma
Authors: Adiguzel Seyma , Palamar Melis , Yargucu Figen , Oksel Fahrettin , Yagci Ayse
Published: October 2020

Purpose:

To evaluate the prevalence of dry eye and meibomian gland dysfunction in patients with scleroderma.

Methods:

A total of 32 patients with scleroderma (study group) and 31 healthy subjects (control group) were enrolled. Besides routine ophthalmologic evaluation, Schirmer 1 test, tear break-up time, tear osmolarity, ocular surface staining with fluorescein (Oxford score), and Ocular Surface Disease Index (OSDI) score, meibomian gland dysfunction evaluation (foamy tears, telangiectasia of the eyelid, eyelid contour abnormalities, and meibomian plugs), and meibography were performed.

Results:

Sixty-four eyes of 32 patients with scleroderma and 62 eyes of 31 healthy individuals were evaluated. Mean ages of the study group was 48.34 ± 9.73 years (21–62 years) and of the control group was 45.84 ± 4.42 years (38–54 years) (P = 0.067). Mean duration of systemic sclerosis or scleroderma in study group was 9.78 ± 7.40 years (1–30 years). Mean tear break-up time was shorter in study group than that in the control group (P < 0.0005). No statistical differences were detected for osmolarity, OSDI score, and Schirmer 1 values between groups (P = 0.051, P = 0.053, and P = 0.358, respectively). The prevalence of grade 1 and higher Oxford score was higher in the study group (P < 0.0005). Upper meiboscores of grade 1 and higher were found to be more common in the study group than those in the control group (P = 0.036). The presence of foamy tears and telangiectasia of the eyelids were significantly higher in the study group (P = 0.002 and P = 0.002, respectively). OSDI score was the only significantly correlated data with disease duration (Spearman ρ coefficient = 0.396, P = 0.001).

Conclusions:

Evaporative type dry eye is more common in patients with scleroderma than the healthy population.
Orbital Compartment Syndrome After High-speed Air-Gasoline Blast Injury
Authors: Zhao Zhenyang , Malik Amina , Bhat Nita , Bindiganavile Shruthi Harish , Pandit Rahul T. , Kavoussi Shaheen C. , Lee Andrew G.
Published: October 2020

Orbital compartment syndrome is an ophthalmologic emergency that requires timely surgical intervention. The authors present a rare case of orbital compartment syndrome in a 30-year-old male injured by forceful entry of air-gasoline mixture into the orbit, secondary to inadvertent firing of the piston from running mechanical diagnostics on an automobile internal combustion engine. Orbital CT revealed extensive orbital emphysema with both pre- and postseptal involvement and diffuse chemical cellulitis. Serial exams revealed rapid deterioration of vision with elevated intraocular pressure and development of eyelid, corneal, and orbital edema; a relative afferent pupillary defect and optic nerve hypoperfusion. He was started on intravenous steroids and underwent an emergent lateral canthotomy with cantholysis, which temporarily reduced the intraocular pressure. However, a second rapid increase in soft tissue swelling resulted in another episode of ocular hypertension and compressive optic neuropathy, requiring emergent orbital bony decompression, which was followed by decreased intraocular and orbital pressure. The patient later developed progressive corneal opacification indicating delayed chemical injury. This was managed with a 10-day course of aggressive topical and systemic antiinflammatory agents with significant improvement in visual acuity. At last follow up, the vision was 20/30 and the corneal and eyelid edema had cleared.
Ambulatory surgery centers: possible solution to improve cataract healthcare in medical deserts
Authors: Bigoteau Maxime , Grammatico-Guillon Leslie , Massot Michel , Baudet Jean-Marie , Cook Ann-Rose , Duroi Quentin , Pichard Tiphanie , Slim Malek , Pisella Pierre-Jean , Khanna Raoul Kanav
Published: October 2020

Purpose:

To investigate the epidemiological impact of an ambulatory cataract surgery center providing a fast-track procedure without anesthetic evaluation on the access to cataract healthcare.

Setting:

French nationwide study.

Design:

Retrospective cross-sectional study.

Methods:

The study included individuals undergoing cataract surgery from the French national administrative database of medical information. Data analyses focused on patients living in the Cher and neighboring areas. Epidemiological indicators of patient flow and healthcare efficiency were calculated. A medicoeconomic analysis was performed.

Results:

Between 2012 and 2018, activity increased by +50.2% (3665 to 5506) interventions in the Cher area compared with a national increase of +22.7% (720 351/884 254), while maintaining a constant ophthalmologist workforce. The leakage ratio decreased by 5.9 points (26.3% to 20.4%), whereas the attractiveness and self-sufficiency ratios increased by 2.3 (8.6% to 10.9%) and 8.6 (80.6% to 89.2%) points, respectively. The age- and sex-standardized rate of healthcare utilization for cataract surgery increased by 4.3 points (11.6 to 15.9 cataract surgeries per 1000 inhabitants), making the Cher the second best French area in 2018 for the rate of cataract surgery despite ranking 96th of 109 French areas for ophthalmologist density. The cost of the cataract removal procedure was 523.99€ (666.22€ in the conventional operating room).

Conclusions:

An ambulatory cataract surgery center with a fast-track procedure could represent a solution in medical deserts to improve cataract healthcare without supplementary funding. Nonetheless, consulting activity should be optimized to detect eye disorders and schedule interventions.
Protein misfolding in combination with other risk factors in CEL-HYB1-mediated chronic pancreatitis
Authors: Tjora Erling , Gravdal Anny , Engjom Trond , Cnop Miriam , Johansson Bente B. , Dimcevski Georg G. , Molven Anders , Fjeld Karianne
Published: October 2020

Objectives

The hybrid allele of the carboxyl ester lipase gene (CEL-HYB1) is a genetic risk factor for chronic pancreatitis (CP) although the mechanism promoting disease development is largely unknown. Here, we aimed to clinically describe subjects carrying the CEL-HYB1 allele and to elucidate why the protein product is pathogenic by analyzing pancreatic secretions and cellular models.

Methods

Norwegian cases (n = 154) diagnosed with recurrent acute pancreatitis or CP were subjected to genetic screening by a CEL-HYB1-specific PCR assay followed by Sanger sequencing. For investigation of CEL-HYB1 protein secretion, duodenal juice samples from cases and controls were analyzed by western blotting. HEK293cells were transfected with constructs expressing CEL-HYB1 or the normal CEL protein (CEL-WT) and analyzed by qPCR, cell fractionation and western blotting.

Results

Two CEL-HYB1-positive families were identified. In both pedigrees, CEL-HYB1 did not fully co-segregate with disease. One proband had recurrent acute pancreatitis and was an active smoker. Her mother was a CEL-HYB1 carrier who had suffered from several attacks of acute pancreatitis until she stopped smoking. The other proband was diagnosed with CP and pancreas divisum. Her CEL-HYB1-positive parent was symptom-free but exhibited pancreatic imaging changes. When analyzing the CEL protein in duodenal juice, CEL-WT was readily detectable but no band corresponding to the risk variant was seen. In CEL-HYB1-transfected cells, we observed impaired protein secretion, protein aggregation and endoplasmic reticulum stress.

Conclusion

Our data suggest that CEL-HYB1, in combination with well-known pancreatitis risk factors, causes disease through the misfolding-dependent pathway of genetic CP risk.
Pathway-specific population attributable fractions
Authors: O’Connell Maurice , Ferguson John
Published: October 2020

A population attributable fraction (PAF) represents the relative change in disease prevalence that one might expect if a particular exposure was absent from the population. Often, one might be interested in what percentage of this effect acts through particular pathways. For instance, the effect of excessive alcohol intake on stroke risk may be mediated by blood pressure, body mass index and several other intermediate risk factors. In this situation, attributable fractions for each mediating pathway of interest can be defined as the relative change in disease prevalence from disabling the effect of the exposure through that mediating pathway.

This quantity is related to, but distinct from the recently proposed metrics of direct and indirect PAF by Sjölander. In particular, while differing pathway-specific PAF will each usually be less than total PAF, they may sum over differing mediating pathways to more than total PAF, whereas direct and indirect PAF must sum to total PAF. Here, we present definitions, identifiability conditions and estimation approaches for pathway-specific attributable fractions. We illustrate results, and comparisons to indirect PAF using INTERSTROKE, a case-control study designed to quantify disease burden attributable to a number of known causal risk factors.