bluuebunny/crossref_metadata_2025 huggingface dataset:
Dapagliflozin decreases atherosclerotic plaque instability via regulating macrophage pyroptosis
Authors: Xu L , Dai Y , Yao K , Yang H , Sun A , Qian J , Ge J
Published: October 2021

Background

Vulnerable plaques are characterized by infiltration of inflammatory cells, playing a key role in the progression of acute coronary events. It's important to clarify the inflammatory mechanism of unstable plaque formation. Several clinical trials have demonstrated that dapagliflozin could reduce major adverse cardiac events in whether diabetic or non-diabetic patients. However, the underlying cardioprotective mechanism of dapagliflozin remains unclear. This study was aimed to investigate the role of dapagliflozin in regulating macrophage pyroptosis and vulnerable plaque formation.

Methods

20 ApoE−/− mice (control) were fed with high fat diet while another 20 ApoE−/− mice were challenged with high fat diet plus dapagliflozin for 12 weeks. The extent and instability of atherosclerotic plaque was determined by oil-red staining, HE staining, immunofluorescence staining and electron microscopy. Changes in subsets of immune cells were evaluated by flow cytometry. Plasma cytokines were assessed by ELISA. Microarray analysis was applied to detect gene expressions while Western blot and real-time PCR was used to assess gene expression levels.

Results

Morphology studies revealed that dapagliflozin could inhibit plaque formation and reduce instability in ApoE−/− mice. FACS data showed that dapagliflozin could decrease CD11b+Ly6Chigh M1 macrophages differentiation and inhibit foam cells formation in ApoE−/− mice. Microarray analysis and in vitro studies exhibited that dapagliflozin could induce the down regulation of NLRP3, caspase-1, IL-1β, IL-18 and MMP-7/10/12/14 to retard macrophage pyroptosis and foam cell formation.

Conclusions

We have characterized a novel role for dapagliflozin in modulating atherosclerotic lesion development and progression. We envision that this study may provide several potential therapeutic targets for treatment of acute coronary syndromes.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Shanghai Sailing Program
Deficiency of myeloid prolyl hydroxylase domain proteins aggravates atherogenesis via macrophage apoptosis and paracrine fibrotic signaling
Authors: Sluimer J , Van Kuijk K , Demandt J A F , Perales-Paton J , Kuppe C , Jin H , Matic L , Mees B , Hedin U , Biessen E A L , Carmeliet P , Baker A H , Kramann R K , Schurgers L J , Saez-Rodriguez J
Published: October 2021

Background

Atherosclerotic plaque hypoxia is detrimental for macrophage function. Prolyl hydroxylases (PHDs) initiate cellular hypoxic responses, possibly influencing macrophage function in plaque hypoxia. Thus, we aimed to elucidate the role of myeloid PHDs in atherosclerosis.

Methods

Myeloid specific PHD knockout (PHDko) mice were fed high cholesterol diet for 6–12 weeks to induce atherosclerosis. Plaque parameters, e.g. plaque size and macrophage content, were analyzed. Bulk and single cell RNA sequencing was performed on PHD2 BMDMs and plaque macrophages, respectively.

Results

Aortic root plaque size was augmented 2.6fold in PHD2cko, and 1.4-fold in PHD3ko, but not in PHD1ko mice compared to controls. Macrophage apoptosis was promoted in PHD2cko and PHD3ko mice in vitro and in vivo, via the HIF1α/BNIP3 axis. Bulk and single cell RNA data of PHD2cko bone-marrow-derived macrophages (BMDM) and plaque macrophages, respectively, confirmed these findings and were validated by siRNA silencing. Human plaque BNIP3 mRNA associated with plaque necrotic core, suggesting similar adverse effects. Further, PHD2cko plaques displayed enhanced fibrosis, independent of macrophage MMP activity, collagen secretion or proliferation and of SMC collagen production, or proliferation. Rather, PHD2cko BMDMs enhanced fibroblast collagen secretion in a paracrine manner. Nichenet in silico analysis of macrophage-fibroblast communication predicted SPP1 signaling as regulator, in line with enhanced plaque SPP1 protein content, and SPP1 mRNA in TREM2-foamy plaque macrophages, but not in neutrophils.

Conclusion

Myeloid PHD2cko and PHD3ko enhanced plaque growth, macrophage apoptosis, and PHD2cko activated paracrine collagen secretion by fibroblasts.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO, Leducq
Endothelial progenitor cells modulate the phenotype of smooth muscle cells and increase their neointimal accumulation following vascular injury
Authors: Mause S , Ritzel E , Deck A , Vogt F , Liehn E
Published: October 2021

Background

Smooth muscle cells (SMCs) are the main driver of neointima formation and restenosis following vascular injury. In animal models, endothelial progenitor cells (EPCs) accelerate endothelial regeneration and reduce neointima formation after arterial injury, however EPC-capture stents do not to reduce target vessel failure compared to conventional stents. Here we examined the influence of EPCs on features of SMCs pivotal for their impact on neointima formation including proliferation, migration and phenotype switch.

Methods and results

EPCs, their conditioned medium and EPC-derived microparticles induced proliferation of SMCs while limiting their apoptosis. In transwell membrane experiments and scratch assays EPCs stimulated migration of SMCs and accelerated their recovery from scratch-induced injury. Treatment of SMCs with EPC-derived conditioned medium or microparticles triggered transformation of SMCs towards a synthetic phenotype. However, co-cultivation of EPCs and SMCs enabling direct cell-cell contacts preserved their original phenotype and protected from the transformative effect of SMC cholesterol-loading. Adhesion of EPCs to SMCs was stimulated by SMC injury and reduced by blocking CXCR2 and CCR5. Interaction of EPCs with SMCs modulated their secretome and synergistically increased the release of selected chemokines. Following carotid wire injury in athymic mice, injection of EPCs resulted not only in reduced neointima formation but also in altered cellular composition of the neointima with augmented accumulation of SMCs.

Conclusion

EPCs stimulate proliferation and migration of SMCs and increase their neointimal accumulation following vascular injury. Furthermore, EPCs modify the SMC phenotype with protection from the transformative effect of cholesterol when direct cell-cell contact is established.

Funding Acknowledgement

Type of funding sources: None.
Infrared study and computational simulations of coronary arteries atherosclerotic lesions for early diagnosis of disease progression
Authors: Mamarelis I , Mamareli C H R , Mylonas E , Mamareli V , Spilopoulos K , Kotoulas S , Kolovou P , Subramaniyan P , Muthukumaran P , Badilescu S , Koui M , Theophanides T , Kotoulas C H R , Anastassopoulou J
Published: October 2021

Introduction

Coronary artery atherosclerotic disease is the most common cardiovascular disease and bypass grafting surgery (CABG) is an effective treatment. However, the pathogenic mechanism of coronary arteries atherosclerosis and disease progression is not yet clear.

Purpose

The use of FT-IR spectroscopy, hyperspectral microscope and mathematical simulation models are some of the tools to predict the morphological and elasticity disorders in the vessel wall due to molecular structure changes.

Methods

Biopsies of atherosclerotic native coronary arteries from 54 patients (44–85 years), who underwent coronary endarterectomy during bypass grafting surgery (CABG), were examined ex vivo. The FT-IR-spectra were recorded with a Nicolet-6700 spectrometer. Morphological changes of atheromatic plaques were performed with SEM-EDX, Fei-Co. CytoVita-Olympus hyperspectral microscope was used to obtain the cells.

Results

FT-IR spectroscopy (Figure 1A) showed that the disease affects the protein folding, leading to amyloid formation (beta-sheets), lipid peroxidation and AGEs (Advanced Glycation end products) production. The detection of amorphous CaCO3 (1415 and 872 cm–1) deposits in high lipophilic regions was of high importance. Increased mineral concentration leads to increased formation of crystalline deposits, consisting of CaCO3, CaHPO4, Ca3(PO4)2 and inorganic hydroxyapatite, resulting in arterial stenosis. Hyperspectral images confirmed the formation of micelles (1) due to amyloidosis and calcified cells (2), in agreement with FT-IR, ImageJ analysis data. Mathematical simulation model based on finite element method (Figure 1E) showed that arterial wall damage and elasticity changes were not homogenous. This model provides the time of crystallization of the calcium salts, which play crucial role to stenosis.

Conclusions

FT-IR spectra showed that the formation of amorphous CaCO3 in the presence of Mg2+, in reach of oxidized lipids regions, inhibit the development of coronary artery stenosis. Excessive of Ca2+ efflux promotes the crystallinity of CaCO3 and Ca3(PO4)2 deposits, leading to the development of atherosclerotic plaques and coronary artery stenosis. Mathematical models approach in a much better way the progression of arterial atherosclerosis.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Integrative single cell RNA-sequencing descrambles a substantial divergence of adaptive immune cell identities and transcriptional programs in mouse and human atherosclerosis
Authors: Horstmann H , Anto Michel N , Sheng X S , Hansen S , Lindau A , Klymiuk I , Marchini T , Winkels H , Verheyen N , Gerhardt T , Oswald W , Conhert T , Bode C , Zirlik A , Wolf D ,   Vascular Immunology lab
Published: October 2021

Aims

The distinct function of immune cells in human atherosclerosis has been mostly defined by preclinical mouse studies. Contrastingly, the immune cell composition of human atherosclerotic plaques and their contribution to disease progression is only poorly understood. It remains uncertain whether genetic animal models allow for valuable translational approaches.

Methods and results

We performed single cell RNA-sequencing (scRNAseq) to define the immune cell landscape in human carotid atherosclerotic plaques. The human immune cell repertoire was dominated by T cells with a considerable inter-patient variability and an unexpected heterogeneity. We performed bioinformatical integration with 7 mouse data sets and discovered a total of 38 cellular identities, of which some were not conserved between species and exclusively found in mice or humans. Locations, frequencies, and transcriptional programs of immune cells in preclinical mouse models did not resemble the immune cell landscape in human atherosclerosis. In contrast to mice, human plaques were not myeloid- and B cell-dominated and instead contained several T cell phenotypes with hallmarks of T cell memory, dysregulation, exhaustion, and activation. Human immune cells were predominantly enriched for transcriptional programs of hypoxia, glucose, and autoimmunity. In a validation cohort of 43 patients activated immune cell subsets defined by multi-colour flow cytometry associated with cerebral ischemia and coronary artery disease.

Conclusion

Here, we uncover yet undefined immune cell types associating with clinical disease. This leukocyte atlas of human atherosclerosis builds the conceptual basis for subsequent identification of cellular targets for clinical immunomodulatory therapies and risk prediction.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ERC Starting Grant
High-density lipoprotein lipid peroxidation in association with presence of coronary artery disease and atrial fibrillation in a large cross-sectional study
Authors: Pagonas N , Sasko B , Mueller R , Jaensch M , Dammermann W , Hillmeister P , Buschmann I , Ritter O , Westhoff T H , Kelesidis T
Published: October 2021

Background

The function of high-density lipoprotein (HDL) cholesterol may play a more important role in the prevention of cardiovascular disease compared to the concentration of the HDL. Cardiovascular diseases such as coronary artery disease (CAD) and atrial fibrillation (AF) have been linked to impaired HDL function.

Purpose

The aim of the present study is to assess a biochemical measure of the antioxidant function of HDL and its association with presence of CAD and AF.

Methods

Patients admitted for elective cardiac catheterization were recruited in this cross-sectional study. Out of 1231 participants that were included in the analyses, 727 patients had confirmed CAD (CAD group), 369 patients had no CAD (no CAD group) and 129 persons were included as a control group. HDL function was measured in sera by determination of HDL-lipid peroxidation content (HDLox) assessed by a validated fluorometric cell-free biochemical assay and was normalized for the levels of HDL cholesterol (normalized HDLox/HDL-C ratio or nHDLox; no units). Results are expressed as median with interquartile range. Associations of nHDLox with presence of CAD and AF were assessed by univariate and multivariate analyses.

Results

Participants in the CAD group had higher levels of nHDLox (0.80, 0.61–1.03) compared to the no CAD (0.70, 0.55–0.93) and control (0.66, 0.55–1.03, no units, p<0.001) group. Out of 1206 participants, 233 (19%) had AF and 973 (81%) had no AF. Patients with AF have also higher nHDLox (0.82, 0.60–10.03) compared to persons without AF (0.73, 0.58–0.98, p=0.03). In univariate analysis nHDLox was associated with CAD (p<0.001). In multivariate analysis adjusted for age, gender, CAD, BMI and hypertension, nHDLox was a strong independent predictor of atrial fibrillation (p=0.015) but was not an independent predictor of CAD (p>0.05)

Conclusions

Reduced antioxidant function of HDL (increased HDLox measured by a biochemical assay), a metric of HDL function, is increased in patients with atherosclerosis and manifested CAD and is also associated with the presence of atrial fibrillation independent of the presence of CAD.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Medical School of Brandenburg-MHB Fontane
Diploid genome assembly of Kluyveromyces marxianus NRRL Y-50883 (SLP1)
Authors: Gómez-Márquez Carolina , Sandoval-Nuñez Dania , Gschaedler Anne , Romero-Gutiérrez Teresa , Amaya-Delgado Lorena , Morales J Alejandro
Published: October 2021

The yeast Kluyveromyces marxianus SLP1 has the potential for application in biotechnological processes because it can metabolize several sugars and produce high-value metabolites. K. marxianus SLP1 is a thermotolerant yeast isolated from the mezcal process, and it is tolerant to several cell growth inhibitors such as saponins, furan aldehydes, weak acids, and phenolics compounds. The genomic differences between dairy and nondairy strains related to K. marxianus variability are a focus of research attention, particularly the pathways leading this species toward polyploidy. We report the diploid genome assembly of K. marxianus SLP1 nonlactide strain into 32 contigs to reach a size of ∼12 Mb (N50 = 1.3 Mb) and a ∼39% GC content. Genome size is consistent with the k-mer frequency results. Genome annotation by Funannotate estimated 5000 genes in haplotype A and 4910 in haplotype B. The enriched annotated genes by ontology show differences between alleles in biological processes and cellular component. The analysis of variants related to DMKU3 and between haplotypes shows changes in LAC12 and INU1, which we hypothesize can impact carbon source performance. This report presents the first polyploid K. marxianus strain recovered from nonlactic fermenting medium.
Germany's relations with the United States and China from a strategic triangle perspective
Authors: Biba Sebastian
Published: October 2021

As the Sino-American Great Power competition continues to intensify, newly-elected US President Joe Biden's administration now seeks to enlist the support of its allies and partners around the world. As Europe's largest economy and a, if not the, leading voice within the European Union, Germany represents an important puzzle-piece for Biden. But Germany, at least under outgoing chancellor Angela Merkel, has been reluctant to take sides. It is against this backdrop that this article looks into Germany's past and present trilateral relationships with the US and China through the theoretical lens of the so-called strategic triangle approach. Applying this approach, the article seeks to trace and explain German behaviour, as well as to elucidate the opportunities and pitfalls that have come with it. The article demonstrates that Germany's recently gained position as a ‘pivot’ (two positive bilateral relationships) between the US and Chinese ‘wings’ (positive bilateral relations with Germany and negative bilateral relations with each other) is desirable from the perspective of the strategic triangle. At the same time, being pivot is also challenging and hard to maintain. Alternative options, such as entering a US–German ‘marriage’ directed against China, are also problematic. The article therefore concludes that Germany has tough decisions to take going forward.
Effect of automated unit dose dispensing with barcode scanning on medication administration errors: an uncontrolled before-and-after study
Authors: Jessurun Janique Gabriëlle , Hunfeld Nicole Geertruida Maria , Van Rosmalen Joost , Van Dijk Monique , Van Den Bemt Patricia Maria Lucia Adriana
Published: October 2021

Background

Medication administration errors (MAEs) occur frequently in hospitals and may compromise patient safety. Preventive strategies are needed to reduce the risk of MAEs.

Objective

The primary aim of this study was to assess the effect of central automated unit dose dispensing with barcode-assisted medication administration on the prevalence of MAEs. Secondary aims were to assess the effect on the type and potential severity of MAEs. Furthermore, compliance with procedures regarding scanning of patient and medication barcodes and nursing staff satisfaction with the medication administration system were assessed.

Methods

We performed a prospective uncontrolled before-and-after study in six clinical wards in a Dutch university hospital from 2018 to 2020. MAE data were collected by observation. The primary outcome was the proportion of medication administrations with one or more MAEs. Secondary outcomes were the type and potential severity of MAEs, rates of compliance with patient identification and signing of administered medication by scanning and nursing staff satisfaction with the medication administration system. Multivariable mixed-effects logistic regression analyses were used for the primary outcome to adjust for confounding and for clustering on nurse and patient level.

Results

One or more MAEs occurred in 291 of 1490 administrations (19.5%) pre-intervention and in 258 of 1630 administrations (15.8%) post-intervention (adjusted odds ratio 0.70, 95% confidence interval 0.51–0.96). The rate of omission fell from 4.6% to 2.0% and of wrong dose from 3.8% to 2.1%, whereas rates of other MAE types were similar. The rate of potentially harmful MAEs fell from 3.0% (n = 44) to 0.3% (n = 5). The rates of compliance with scanning of patient and medication barcode post-intervention were 13.6% and 55.9%, respectively.

The median overall satisfaction score of the nurses with the medication administration system on a 100-point scale was 70 (interquartile range 63–75, n = 193) pre-intervention and 70 (interquartile range 60–78, n = 145) post-intervention (P = 0.626, Mann–Whitney U test).

Conclusion

The implementation of central automated unit dose dispensing with barcode-assisted medication administration was associated with a lower probability of MAEs, including potentially harmful errors, but more compliance with scanning procedures is needed. Nurses were moderately satisfied with the medication administration system, both before and after implementation. In conclusion, despite low compliance with scanning procedures, this study shows that this intervention contributes to the improvement of medication safety in hospitals.
Safety and Cost-Effectiveness of Outpatient Surgery in Acute Burn Care
Authors: Zhang Zach , Golin Andrew P , Papp Anthony
Published: October 2021

Outpatient burn surgery is increasingly used in acute burn care. Reports of its safety and efficacy are limited. This study aims to evaluate the safety and cost reduction associated with outpatient burn surgery and to describe our center’s experience. This was a single-center, retrospective cohort study of consecutive patients who underwent outpatient burn surgery requiring split-thickness skin graft or dermal regenerative template from January 2010 to December 2018. Patient demographics, comorbidities, burn etiologies, operative data, and postoperative care were reviewed. The primary outcome is complications involving major graft loss requiring reoperation. One hundred and sixty-five patients and 173 procedures met the inclusion criteria. The average age was 44 years and 60.6% (100/165) were male. Annual outpatient procedure volume increased 48% from 23 to 34 cases over the 9-year period. The median (interquartile range) grafted percentage total body surface area was 1.0 (1.0)%. Rate of major graft loss requiring reoperation was 5.2% (9/172) and the most common site was the lower extremity (8/9, 88.9%). Age, sex, comorbidities, total body surface area, and procedure types were not significantly associated with postoperative complication rates. The outpatient burn surgery model was estimated to save CA$8170 per patient from inpatient costs. Demonstration of the safety and cost savings associated with outpatient acute burn surgery is compelling for further utilization. Our experience found the adoption of improved dressing care, appropriate patient selection, increased patient education, adequate pain control, and regimented outpatient multidisciplinary care to be fundamental for effective outpatient surgical burn care.
Outcomes of Early Surgical vs Nonsurgical Management of Pediatric Hand Friction Injuries Caused by Treadmills
Authors: Ridelman Elika , Abbas Paulette I , Angst Beth A , Klein Justin D , Shanti Christina M
Published: October 2021

Pediatric hand friction injuries caused by running treadmills are ever more prevalent due to the increasing presence of home exercise equipment. These and other related injuries have received recent attention in the media, leading to mass product recalls in some cases. These friction injuries are similar to deep thermal burns, and these patients are usually cared for in the pediatric burn unit at our institution. We sought to describe our recent experience managing 22 patients with these injuries. Patients were queried from our urban pediatric burn center database. After Institutional Review Board approval, a retrospective chart review of all patients admitted for a treadmill-related hand injury over a 5-year period was performed. Data collected included patient demographics, initial treatment methods (surgical vs nonoperative), type of dressing used, hospital length of stay (LOS), and compliance with follow-up. We collected patient-centered outcomes included the time to healing and the need for subsequent surgical and/or nonsurgical interventions to treat the sequelae of these injuries. Our center treated 22 hand friction injuries caused by treadmills over the 5-year period. Five patients (23%) underwent early surgical intervention (<30 days from injury), with a median time from injury of 7 days (interquartile range 1.75–13.5). This cohort required additional interventions to treat postoperative sequelae with 2 (40%) requiring additional surgery and 3 (60%) managed nonsurgically. Of the 17 (77%) who were initially treated nonoperatively, 5 (29%) healed completely with dressing changes only and required no further treatment. Eleven (65%) had injury-related sequelae and were managed successfully with nonsurgical interventions. Only 1 patient (6%) required scar modification by Z-plasty. Average LOS was 14 hours and the median number of weekly follow-up visits was 4 until complete healing. Given the excellent outcomes observed in patients treated without acute surgical intervention in this case series, nonoperative management appears to be feasible, safe, and may reduce the need for operative intervention. These injuries, although small, are deep and require a prolonged period of dressing changes and aggressive therapy including posthealing time commitment to scar management in order to achieve best outcomes. Our study supports the need for increased community awareness of this type of injury.
A Geographic Information System Approach to Map Tick Exposure Risk at a Scale for Public Health Intervention
Authors: Baldwin Harper , Landesman William J , Borgmann-Winter Benjamin , Allen David
Published: October 2021

Tick-borne disease control and prevention have been largely ineffective compared to the control of other vector-borne diseases. Although control strategies exist, they are costly or ineffective at large spatial scales. We need tools to target these strategies to places of highest tick exposure risk. Here we present a geographic information system (GIS) method for mapping predicted tick exposure risk at a 200 m by 200 m resolution, appropriate for public health intervention. We followed the approach used to map tick habitat suitability over large areas. We used drag-cloth sampling to measure the density of nymphal blacklegged ticks (Ixodes scapularis, Say (Acari: Ixodidae)) at 24 sites in Addison and Rutland Counties, VT, United States. We used a GIS to average habitat, climatological, land-use/land-cover, and abiotic characteristics over 100 m, 400 m, 1,000 m, and 2,000 m buffers around each site to evaluate which characteristic at which buffer size best predicted density of nymphal ticks (DON). The relationships between predictor variables and DON were determined with random forest models. The 100 m buffer model performed best and explained 37.7% of the variation in DON, although was highly accurate at classifying sites as having below or above average DON. This model was applied to Addison County, VT, to predict tick exposure risk at a 200 m resolution. This GIS approach to map predicted DON over a small area with fine resolution, could be used to target public health campaigns and land management practices to reduce human exposure to ticks.
Initial Work on Sex-Specific Growth Curve Guidelines for Forensically Important Blow Flies Using Chrysomya megacephala (Diptera: Calliphoridae) Entire Age Cohorts
Authors: Smith Joshua L , Adams Derek J
Published: October 2021

Sex is a factor influencing development in many insect species, but is not widely studied in forensically important blow flies. If sex influences blow fly development, knowing the sex of a larva from a corpse can increase precision in estimates of that larva’s age. The improved prediction of larval age will make estimates of time since death using entomological evidence better. Larvae lack sexually dimorphic morphological characteristics, so sex is not immediately known visually. To generate sexually dimorphic reference growth curves, a subsample must be large enough to ensure enough males and females are present for comparison. Using two entire age Chrysomya megacephala (Fabricius) cohorts, we evaluated the minimum sample number needed to have enough individuals of both sexes for comparison using 95% prediction intervals. Through a simulation of three trials of 1000 random replicates, we determined that a sample size of 19 would prevent any instance of a comparison not occurring because of insufficient sampling from one sex. As the current method for molecular sex determination can be expensive, we also compared how the results of various subsampling percentages compare those of the entire age cohorts. We found that subsampling at least 50% of an entire cohort leads to almost identical results in comparison to the entire age cohort. Together, these findings will help establish guidelines for generating sex-specific reference growth curves. A uniform approach to generating these sex-specific growth curves will lead to more consistency in age estimates made from them.
Diagnosis and Clinical Development of Sporadic Inclusion Body Myositis and Polymyositis With Mitochondrial Pathology: A Single-Center Retrospective Analysis
Authors: Winkler Maren , von Landenberg Christina , Kappes-Horn Karin , Neudecker Stephan , Kornblum Cornelia , Reimann Jens
Published: October 2021

To review our diagnostic and treatment approaches concerning sporadic inclusion body myositis (sIBM) and polymyositis with mitochondrial pathology (PM-Mito), we conducted a retrospective analysis of clinical and histological data of 32 patients diagnosed as sIBM and 7 patients diagnosed as PM-Mito by muscle biopsy. Of 32 patients identified histologically as sIBM, 19 fulfilled the 2011 European Neuromuscular Center (ENMC) diagnostic criteria for “clinico-pathologically defined sIBM” at the time of biopsy. Among these, 2 patients developed sIBM after years of immunosuppressive treatment for organ transplantation. Of 11 patients fulfilling the histological but not the clinical criteria, including 3 cases with duration <12 months, 8 later fulfilled the criteria for clinico-pathologically defined sIBM. Of 7 PM-Mito patients, 4 received immunosuppression with clinical improvement in 3. One of these later developed clinico-pathologically defined sIBM; 1 untreated patient progressed to clinically defined sIBM. Thus, muscle histology remains important for this differential diagnosis to identify sIBM patients not matching the ENMC criteria and the PM-Mito group. In the latter, we report at least 50% positive, if occasionally transient, response to immunosuppressive treatments and progression to sIBM in a minority. The mitochondrial abnormalities defining PM-Mito do not seem to define the threshold to immunosuppression unresponsiveness.
Returned traveller presenting with anaemia: clinical challenge of post-artesunate delayed haemolysis
Authors: Matsee Wasin , Hiranrusme Thanyapat , Pisutsan Phimphan , Hanboonkunupakarn Borimas , Chotivanich Kesinee
Published: October 2021

Although malaria is one of the differential diagnoses among travellers to endemic area, delayed haemolysis following malaria treatment with artemisinin-derivative drugs during travel should be aware. We highlight the clinical perspective for clinicians to consider this clinical phenomenon to detect any delayed haemolytic event early and prevent potentially serious consequences.
Proto-magnetar jets as central engines for broad-lined Type Ic supernovae
Authors: Shankar Swapnil , Mösta Philipp , Barnes Jennifer , Duffell Paul C , Kasen Daniel
Published: October 2021

A subset of Type Ic supernovae (SNe Ic), broad-lined SNe Ic (SNe Ic-bl), show unusually high kinetic energies (∼1052 erg) that cannot be explained by the energy supplied by neutrinos alone. Many SNe Ic-bl have been observed in coincidence with long gamma-ray bursts (GRBs) that suggests a connection between SNe and GRBs. A small fraction of core-collapse supernovae form a rapidly rotating and strongly magnetized protoneutron star (PNS), a proto-magnetar. Jets from such magnetars can provide the high kinetic energies observed in SNe Ic-bl and also provide the connection to GRBs. In this work, we use the jetted outflow produced in a 3D general relativistic magnetohydrodynamic CCSN simulation from a consistently formed proto-magnetar as the central engine for full-star explosion simulations. We extract a range of central engine parameters and find that the extracted engine energy is in the range of 6.231 × 1051−1.725 × 1052 erg, the engine time-scale in the range of 0.479−1.159 s and the engine half-opening angle in the range of ∼9°−19°. Using these as central engines, we perform 2D special relativistic (SR) hydrodynamic (HD) and radiation transfer simulations to calculate the corresponding light curves and spectra. We find that these central engine parameters successfully produce SNe Ic-bl that demonstrates that jets from proto-magnetars can be viable engines for SNe Ic-bl. We also find that only the central engines with smaller opening angles (∼11°) form a GRB implying that GRB formation is likely associated with narrower jet outflows and Ic-bl’s without GRBs may be associated with wider outflows.
Optimized localization for gravitational waves from merging binaries
Authors: You Zhi-Qiang , Ashton Gregory , Zhu Xing-Jiang , Thrane Eric , Zhu Zong-Hong
Published: October 2021

The Advanced LIGO and Virgo gravitational-wave observatories have opened a new window with which to study the inspiral and mergers of binary compact objects. These observations are most powerful when coordinated with multimessenger observations. This was underlined by the first observation of a binary neutron star merger GW170817, coincident with a short gamma-ray burst, GRB170817A, and the identification of the host galaxy NGC 4993 from the optical counterpart AT2017gfo. Finding the fast-fading optical counterpart critically depends on the rapid production of a sky map based on LIGO/Virgo data. Currently, a rapid initial sky map is produced, followed by a more accurate, high-latency, ${\gtrsim}{12}\, {\rm h}$ sky map. We study optimization choices of the Bayesian prior and signal model, which can be used alongside other approaches such as reduced order quadrature. We find these yield up to a $60{{\ \rm per\ cent}}$ reduction in the time required to produce the high-latency localization for binary neutron star mergers.
VLBI properties of compact interplanetary scintillators detected by the Murchison Widefield Array
Authors: Jaiswal Sumit , An Tao , Wang Ailing , Tingay Steven
Published: October 2021

Interplanetary scintillation (IPS) provides an approach for identifying the presence of sub-arcsec structures in radio sources, and very long baseline interferometry (VLBI) technique can help verify whether the IPS sources have fine structures on milli-arcsec (mas) scales. We searched the available VLBI archive for the 244 IPS sources detected by the Murchison Widefield Array at 162 MHz and found 63 cross-matches. We analysed the VLBI data of the 63 sources and characterised the compactness index in terms of the ratio R of the VLBI-measured flux density at 4.3 GHz to the flux density estimated using the Very Large Array Sky Survey (VLASS) at 3 GHz and NRAO VLA Sky Survey (NVSS) at 1.4 GHz (SVLBI/SSA). Eleven sources are identified as blazars according to their flat spectra and strong variability. They show high compactness indices with R > 0.4, compact core-jet structure, and a broad distribution of normalised scintillation index (NSI). Other sources show diverse morphologies (compact core, core and one-sided jet, core and two-sided jets), but there is a correlation between R and NSI with a correlation coefficient r = 0.47. A similar R–NSI correlation is found in sources showing single steep power-law or convex spectra. After excluding blazars (which are already known to be compact sources) from the VLBI-detected IPS sources, a strong correlation is found between the compactness and scintillation index of the remaining samples, indicating that stronger scintillating sources are more compact. This pilot study shows that IPS offers a convenient method to identify compact radio sources without the need to invoke high-resolution imaging observations, which often require significant observational time.
Deprojection of external barred galaxies from photometry
Authors: Tahmasebzadeh Behzad , Zhu Ling , Shen Juntai , Gerhard Ortwin , Qin Yujing
Published: October 2021

The observations of external galaxies are projected to the 2D sky plane. Reconstructing the 3D intrinsic density distribution of a galaxy from the 2D image is challenging, especially for barred galaxies, but is a critical step for constructing galactic dynamical models. Here, we present a method for deprojecting barred galaxies and we validate the method by testing against mock images created from an N-body simulation with a peanut-shaped bar. We decompose a galaxy image into a bulge (including a bar) and a disc. By subtracting the disc from the original image a barred bulge remains. We perform multi-Gaussian expansion (MGE) fit to each component, then we deproject them separately by considering the barred bulge is triaxial while the disc is axisymmetric. We restrict the barred bulge to be aligned in the disc plane and has a similar thickness to the disc in the outer regions. The 3D density distribution is thus constructed by combining the barred bulge and the disc. Our model can generally recover the 3D density distribution of disc and inner barred bulge regions, although not a perfect match to the peanut-shaped structure. By using the same initial conditions, we integrate the orbits in our model-inferred potential and the true potential by freezing the N-body simulation. We find that $85{{\ \rm per\ cent}}$ of all these orbits have similar morphologies in these two potentials, and our model supports the orbits that generate a boxy/peanut-shaped structure and an elongated bar similar to these in the true potential.
Central sensitisation in primary Sjögren Syndrome and its effect on sleep quality
Authors: Metin Ökmen Burcu , Ayar Koray , Altan Lale , Yeşilöz Özgür
Published: October 2021

Objective

The aim of the present study is to evaluate the presence and frequency of central sensitisation (CS) in primary Sjögren Syndrome (pSS) and to determine the effect of CS on sleep quality.

Materials and Methods

In this cross-sectional study, 50 patients diagnosed with pSS between the ages of 18 and 75 were included. The healthy control group was composed of 43 healthcare workers. Each participant underwent a physical examination, and demographic data and the medications they used were recorded. Central sensitisation inventory and Pittsburgh Sleep Quality Index questionnaires were filled in to garner data on CS and sleep quality, respectively, from all participants.

Results

While central sensitisation inventory  >40 was detected in 74% of pSS patients, it was 25.6% in healthy controls, and there is a statistically significant difference between the groups (p < .05). A correlation analysis of the central sensitisation inventory and Pittsburgh Sleep Quality Index values of all participants revealed a statistically significant correlation between all parameters other than the duration of sleep (p < .05).

Conclusions

CS was found to have a negative effect on sleep quality in patients with pSS. We suggest that the cause of widespread pain seen in patients with pSS as the possible development of CS should be considered.
Vanadate inhibits Feo-mediated iron transport inVibrio cholerae
Authors: Shin Minhye , Gomez-Garzon Camilo , Payne Shelley M
Published: October 2021

Iron is an essential element for Vibrio cholerae to survive, and Feo, the major bacterial system for ferrous iron transport, is important for growth of this pathogen in low-oxygen environments. To gain insight into its biochemical mechanism, we evaluated the effects of widely used ATPase inhibitors on the ATP hydrolysis activity of the N-terminal domain of V. cholerae FeoB. Our results showed that sodium orthovanadate and sodium azide effectively inhibit the catalytic activity of the N-terminal domain of V. cholerae FeoB. Further, sodium orthovanadate was the more effective inhibitor against V. cholerae ferrous iron transport in vivo. These results contribute to a more comprehensive biochemical understanding of Feo function, and shed light on designing effective inhibitors against bacterial FeoB proteins.
Apical amplification—a cellular mechanism of conscious perception?
Authors: Marvan Tomáš , Polák Michal , Bachmann Talis , Phillips William A
Published: October 2021

We present a theoretical view of the cellular foundations for network-level processes involved in producing our conscious experience. Inputs to apical synapses in layer 1 of a large subset of neocortical cells are summed at an integration zone near the top of their apical trunk. These inputs come from diverse sources and provide a context within which the transmission of information abstracted from sensory input to their basal and perisomatic synapses can be amplified when relevant. We argue that apical amplification enables conscious perceptual experience and makes it more flexible, and thus more adaptive, by being sensitive to context. Apical amplification provides a possible mechanism for recurrent processing theory that avoids strong loops. It makes the broadcasting hypothesized by global neuronal workspace theories feasible while preserving the distinct contributions of the individual cells receiving the broadcast. It also provides mechanisms that contribute to the holistic aspects of integrated information theory. As apical amplification is highly dependent on cholinergic, aminergic, and other neuromodulators, it relates the specific contents of conscious experience to global mental states and to fluctuations in arousal when awake. We conclude that apical dendrites provide a cellular mechanism for the context-sensitive selective amplification that is a cardinal prerequisite of conscious perception.
Needs of Children and Families during Spring 2020 COVID-19 School Closures: Findings from a National Survey
Authors: Watson Kate R , Astor Ron Avi , Benbenishty Rami , Capp Gordon , Kelly Michael S
Published: October 2021

Despite extensive reports during the COVID-19 pandemic of the academic challenges facing students, and the effects of online learning on academic achievements, we have little information regarding the needs and difficulties of K–12 students and their families from a social work perspective. The present article shares findings from a nationwide survey of 1,275 school social workers (SSWs) reporting on their clients—schools, children, and families—during the spring 2020 COVID-19 school closures. SSWs indicated that the children and families they served had significant unmet basic needs, including for food, healthcare, and housing. Poverty and mental health compounded pandemic difficulties, which were associated with the sociodemographic makeup of schools. Student engagement in social work services during the closures was significantly lower than prepandemic levels, generally due to unmet material needs. Several policy and practice implications arise from these findings, including a need for additional services for students and families, a plan to address structural inequities in our schools and communities, coordinated outreach to reengage missing students, and recognition of the strong work being done by school staff coupled with a need for additional supports and resources to combat persistent inequality.
Nucleotide Substitutions during Speciation may Explain Substitution Rate Variation
Authors: Janzen Thijs , Bokma Folmer , Etienne Rampal S
Published: October 2021

Although molecular mechanisms associated with the generation of mutations are highly conserved across taxa, there is widespread variation in mutation rates between evolutionary lineages. When phylogenies are reconstructed based on nucleotide sequences, such variation is typically accounted for by the assumption of a relaxed molecular clock, which is a statistical distribution of mutation rates without much underlying biological mechanism. Here, we propose that variation in accumulated mutations may be partly explained by an elevated mutation rate during speciation. Using simulations, we show how shifting mutations from branches to speciation events impacts inference of branching times in phylogenetic reconstruction. Furthermore, the resulting nucleotide alignments are better described by a relaxed than by a strict molecular clock. Thus, elevated mutation rates during speciation potentially explain part of the variation in substitution rates that is observed across the tree of life. [Molecular clock; phylogenetic reconstruction; speciation; substitution rate variation.]
Assessment of bovine respiratory disease progression in calves challenged with bovine herpesvirus 1 and Mannheimia haemolytica using point-of-care and laboratory-based blood leukocyte differential assays
Authors: Baruch Joaquin , Cernicchiaro Natalia , Cull Charley A , Lechtenberg Kelly F , Nickell Jason S , Renter David G
Published: October 2021

Blood leukocyte differentials can be useful for understanding changes associated with bovine respiratory disease (BRD) progression. By improving turnaround time, point-of-care leukocyte differential assays (PCLD) may provide logistical advantages to laboratory-based assays. Our objective was to assess BRD progression in steers challenged with bovine herpesvirus 1 and Mannheimia haemolytica using point-of-care and laboratory-based blood leukocyte differentials. Thirty Holstein steers (average body weight of 211 kg + 2.4 kg) were inoculated intranasally on day 0 with bovine herpesvirus 1 and intrabronchially on day 6 with Mannheimia haemolytica. Blood leukocytes differentials were measured using both assays from study days 0 to 13. Linear mixed models were fitted to evaluate the associations between: (1) the type of assay (laboratory-based or PCLD) with respect to leukocyte, lymphocyte, and neutrophil concentrations; (2) study day with cell concentrations; and (3) cell concentrations with lung consolidation measured at necropsy. Point-of-care leukocyte, lymphocyte, and neutrophil concentrations were significantly associated (P < 0.05) with the respective cell concentrations obtained from the laboratory-based leukocyte differential. Cell concentrations reported by both assays differed significantly (P < 0.05) over time, indicating shifts from healthy to viral and bacterial disease states. Lymphocyte concentrations, lymphocyte/neutrophil ratios obtained from both assays, and band neutrophil concentrations from the laboratory-based assay were significantly associated (P < 0.05) with lung consolidation, enhancing assessments of disease severity. The PCLD may be a useful alternative to assess BRD progression when laboratory-based leukocyte differentials are impractical.
The Attitude of Practitioners Towards Endoscopic Sleeve Gastroplasty
Authors: Badurdeen Dilhana , Farha Jad , Fayad Lea , Abbarh Shahem , Singh Gagandeep , Jovani Manol , Hedjoudje Abdellah , Adam Atif , Alqahtani Aayed , Neto Manoel G. , Kumbhari Vivek
Published: October 2021

Background and Aim:

Despite widespread adoption and encouraging results seen over the last 5 years, no consensus exists regarding the endoscopic sleeve gastroplasty (ESG) technique, training, or preprocedure and postprocedure management of the patient. The aim of our survey was to assess practice trends and preferences of bariatric endoscopists with respect to ESG.

Methods:

Using a digital platform, we conducted a worldwide survey by emailing a link with an electronic questionnaire to 1200 bariatric endoscopists trained to perform endoscopic suturing using the Apollo Overstitch suturing device (Apollo Endosurgery).

Results:

We received 221 responses that were included in the analysis. Fifty-one responders (36.4%) required 1 to 10 procedures, and 37 (26.4%) needed 11 to 20 procedures to become proficient at ESG. Ninety-six (68.6%) stated that lower body mass index thresholds should be adopted for Asian and Arab patients. There was no consensus on the ideal number of sutures, with 45 (32.1%), 42 (30%), 36 (25.7%), 13 (9.3%), and 4 (2.9%) recommending 4 to 6, 5 to 7, 6 to 8, 7 to 9, and 8 to 12 sutures, respectively. The primary barriers to establishing an endobariatric program were the inability to establish a cash pay model, 77 (95.1%); lack of institutional support, 61 (75.3%); and difficulty in establishing an ambulatory surgical center/hospital to perform ESG, 73 (90.1%).

Conclusions:

ESG practice trends remain heterogenous among practitioners in regard to indication, technique, and preprocedure and postprocedure management. Specific ESG guidelines are warranted, and this survey will assist in providing the framework for these guidelines to be written.