bluuebunny/crossref_metadata_2025 huggingface dataset:
Are telocytes related to maintenance of vascular homeostasis in normal and pathological aorta?
Authors: Borges L , Falcao R S P , Taboga S R , Gutierrez P S , Michel J B
Published: May 2024

Funding Acknowledgements 

None.

The telocyte (TC) is a new interstitial cell type described in a wide variety of organs and loose connective tissues around small vessels, but its presence in large arteries remains unexplored. TCs have small cell bodies and remarkably thin, long, moniliform processes called telopods (Tps). Using transmission electron microscopy and immunofluorescence, we identified TCs in normal human thoracic aortas and in those with aneurysm and acute dissection (TAAD). In normal aortas the TCs were distributed throughout the connective tissue of the adventitial layer, in its innermost portion and at the zone of transition with the medial layer, with their long axes oriented parallel to the external elastic lamellae, forming a three-dimensional network, without prevalence in the media layer. In contrast, TAAD TCs were present in the medial layer and in regions of neovascularization. The most important feature of the adventitia of diseased aortas was the presence of numerous contacts between TCs and stem cells, including vascular progenitor cells. Although the biologically functional correlations need to be elucidated, the morphological observations presented here provide strong evidence of the involvement of TCs in maintaining vascular homeostasis in pathological situations of tissue injury.
Exploring the role of air pollution on the development of atherosclerosis disorder in human endothelial cells
Authors: Alenany R , Shawkat T , Korashy H
Published: May 2024

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): QU - NSPP

Introduction

Atherosclerosis, the main cause of cardiovascular and cerebrovascular diseases, is a global health threat. Rising cardiovascular disease prevalence, unexplained by traditional risk factors, prompts exploration of the impact of occupational exposure to environmental toxins as a risk factor. benzo[a]pyrene (BaP) is a polyaromatic compound that mediate its toxicity through activation of the Aryl hydrocarbon receptor (AhR). The molecular mechanisms of involvement of environmental toxins and the role of AhR/CYP1A pathway in atherosclerosis development remain not fully investigated.

Purpose

The current study explores the AhR pathway activation in endothelial cells upon exposure to environmental toxins in order to elucidate the molecular mechanisms of atherosclerotic cardiovascular diseases and plaque formation through investigating pro-inflammatory (CYP1A1, CYP1B1, TNF-a) and pro-apoptotic markers (BCL-2, Caspase-3).

Methods

EA. hy926 cell line underwent treatment with increasing concentrations of BaP (0-20 microM), as well as 10nm of TCDD, to confirm the results. DSMO was used as a control. Total RNA and protein were isolated to investigate mRNA expression and protein expression of AhR, CYP1A1, CYP1B1, as well as caspase-3, Bcl-2, and TNF-α using RT-PCR and Western Blot analysis. Statistical analysis was done using one-way ANOVA.

Results

The results showed that BaP induce significant dose-dependent upregulation of AhR and target genes (CYP1A1, CYP1B1). At 20uM, expression of AhR (3-fold), CYP1A1 (2.5-fold) and CYP1B1 (2-fold) was significantly high as compared to their respective controls and low doses. As for apoptotic markers, Bcl-2 was significantly downregulated at the highest concentrations 10uM and 20uM (0.7- and 0.6-fold, respectively). Caspase-3 showed no significant change but exhibited upregulation across all doses. TCDD 10nM significantly upregulated AhR (2.0-fold), CYP1A1 (1.5-fold), CYP1B1 (1.7-fold). Bcl-2 downregulated (0.6-fold), TNF-α significantly upregulated (1.8-fold) at 10nM. Caspase-3 increased 2-folds but was not statistically significant.

Conclusion

This study illustrated that AhR inducers, such as BaP, can accelerate the pathological progress of atherosclerosis by evoking oxidative stress and inflammation response molecules in human endothelial cells, demonstrated by the reduced expression of anti-apoptotic markers and the increased expression of inflammatory markers.
Estrogen and the estrogen receptor in ZSF1 rats with heart failure with preserved ejection fraction
Authors: Buettner P , Werner S , Thiele H
Published: May 2024

Funding Acknowledgements

None.

Background

Heart failure with preserved ejection fraction (HFpEF) is more prevalent in women, so declining estrogen levels after menopause may be involved in genesis of the disease. Estrogen is cardio-protective, affecting blood pressure and vasodilatation and endothelial dysfunction is discussed as HFpEF pathomechanism. However, the potential connection between HFpEF and estrogen levels remains poorly understood. The well-established HFpEF ZSF1 rat model was used to analyze endothelial dysfunction, and a pronounced imbalance of the NO synthase substrates arginine and homoarginine was observed. Of note, estrogen levels in woman are directly and positively associated to homoarginine levels.

Purpose

We characterized serum estrogen levels and the expression of the estrogen receptor alpha (ERα) in the hearts of female ZSF1 HFpEF rats to investigate a possible contribution of estrogen signaling in HFpEF manifestation and to evaluate the suitability of this animal model in the context of estrogen and HFpEF.

Methods

In total, 12 obese ZSF1 rats with HFpEF (O-ZSF1) and 12 lean healthy ZSF1 rats (L-ZSF1) at 20 weeks of age and 5 animals of either phenotype aged 32 weeks were analyzed. Further, six O-ZSF1 rats were supplemented with homoarginine (hArg) when HFpEF was manifest and were observed up to 32 weeks of age. The manifestation of HFpEF was confirmed by echocardiography and determination of NT-proBNP by ELISA. Circulating estradiol (E2) in serum was determined using ELISA. Expression of the estrogen receptor alpha was determined by Western Blot analysis in the left ventricle (LV), septum and right ventricle (RV).

Results

Serum estradiol levels were similar in age-matched L-ZSF1 and O-ZSF1, but were ~2-fold increased at an age of 32 weeks compared to 20 weeks (p=0.002). The canonical ERα-66kDa was very weakly expressed in all tissues. ERα-45kDa expression in the LV was lower in O-ZSF1 at an age of 20 weeks (-46%, p=0.008) and at 32 weeks (-46%, p=0.002).

ERα-45kDa expression in LV was 2-fold higher than in septum and 5-fold higher than in RV in rats aged 20 weeks (p<0.001). In RV, no differences in ERα-45kDa expression were observed. Supplementation of O-ZSF1 with hArg reestablished the ERα-45kDa expression in the LV (p=0.005 vs. O-ZSF1 without supplementation).

Conclusion

The manifestation and progression of HFpEF in ZSF1 rats is accompanied by a decrease of the ERα-45kDa expression in the LV, whereas the RV is not affected. Supplementation with homoarginine normalizes ERα-45kDa expression. The ERα-45kDa isoform was found to suppress the transcriptional activity of the classical ERα-66kDa isoform and to be an acute regulator of endothelial NO synthase in response to estrogen. These results suggest that altered ERα expression in the LV may represent a novel pathomechanism in HFpEF. In combination with decreasing estrogen levels in woman, adverse consequences for NO production in the LV seem likely.
The maximally selected likelihood ratio test in random coefficient models
Authors: Horváth Lajos , Trapani Lorenzo , VanderDoes Jeremy
Published: May 2024

In a recent contribution, we developed a family of cumulative sum-based change-point tests in the context of a random coefficient autoregressive model of order 1. In the current paper, we complement the results in that contribution by studying the (maximally selected) likelihood ratio statistic. We show that this has power versus breaks occurring even as close as periods from the beginning/end of sample; moreover, the use of quasi-maximum likelihood-based estimates yields better power properties, with the added bonus of being nuisance-free. Our test statistic has the same distribution—of the Darling–Erdős type—irrespective of whether the data are stationary or not, and can therefore be applied with no prior knowledge of this. Our simulations show that our test has very good power and, when applying a suitable correction to the asymptotic critical values, the correct size. We illustrate the usefulness and generality of our approach through applications to economic and epidemiological time series.
A Novel Dual-Language Touch-Screen Intervention to Slow Down Cognitive Decline in Older Adults: A Randomized Controlled Trial
Authors: Yow Wei Quin , Sou Ka Lon , Wong Alina Clarise
Published: May 2024

Background and Objectives

Bilingualism has been suggested to protect older adults from cognitive aging and delay the onset of dementia. However, no studies have systematically explored bilingual usage as a tool to mitigate age-related cognitive decline. We developed the Dual-Language Intervention in Semantic memory—Computerized (DISC), a novel cognitive training program with three training tasks (object categorization, verbal fluency, and utility of things) designed specifically for older adults that featured two modes: single-language (SL) exposure mode and dual-language (DL) exposure mode.

Research Design and Methods

The final sample included 50 cognitively healthy (CH; 33 female, Mage = 72.93 years, range = 53.08–87.43 years) and 48 cognitively impaired (CI; 35 female, Mage = 80.93 years, range = 62.31–96.67 years) older adults, randomly assigned them into one of three groups: SL group, DL group, and control group (no training). Participants in SL and DL groups used DISC in either SL mode (i.e., training instructions were spoken in only one language throughout the entire training) or DL mode (i.e., training instructions alternated between two languages), respectively, for 24 sessions. Participants in the control group were asked to continue with their normal daily activities (e.g., playing bingo and reading newspapers).

Results

For CH older adults, we found significant improvements in the Rey Auditory Verbal Learning Test (RAVLT) Trial 5 score and the Clock Drawing Test score in the DL group but not in the SL and control groups posttraining compared with pretraining. For CI older adults, there was a delayed improvement in the RAVLT Trial 1, six months later.

Discussion and Implications

Our findings provided novel evidence that implementing DL cognitive training benefits CH older adult’s late verbal learning and visuospatial construction skills, and a delayed improvement in CI older adults’ early verbal learning abilities.
Evolution of Litter Size: Proximate and Ultimate Mechanisms
Authors: Wilsterman Kathryn , Bautista Anna Isabel , Butler Chloe E , Juergens Makenna Y , Larson Ashley M
Published: May 2024

Synopsis

Relative reproductive success and failure are the ultimate determinants of Darwinian fitness. As such, reproductive traits and variations therein have an immediate and considerable impact on the evolutionary trajectory of lineages. Historically, significant attention has been paid to the ecological and evolutionary processes (ultimate factors) that shape the diversity and canalization of reproductive traits within groups to better our understanding of organismal diversity and population or species resilience. In contrast, the physiological systems that mediate variation within and among species (i.e., the proximate factors) in reproductive traits remain a significant black box. To date, there is comparatively little information about how proximate mechanisms constrain or promote evolutionary potential in reproductive traits. In this mini-review, we focus on litter size in Eutherian mammals as a trait with relatively well-defined diversity (litter sizes are well-described both within and across species) and for which some genetic determinants have been identified. We discuss both the ultimate and potential proximate determinants of litter size with special attention to the breadth of physiological traits that may act as “toggle” switches for evolution of litter size. We close with a brief discussion of the role that physiological plasticity may play in the evolution of litter size and lay out several forward-looking areas for future research.
Robust estimation of smooth graph signals from randomized space–time samples
Authors: Huang Longxiu , Needell Deanna , Tang Sui
Published: May 2024

Heat diffusion processes have found wide applications in modelling dynamical systems over graphs. In this paper, we consider the recovery of a $k$-bandlimited graph signal that is an initial signal of a heat diffusion process from its space–time samples. We propose three random space–time sampling regimes, termed dynamical sampling techniques, that consist in selecting a small subset of space–time nodes at random according to some probability distribution. We show that the number of space–time samples required to ensure stable recovery for each regime depends on a parameter called the spectral graph weighted coherence, which depends on the interplay between the dynamics over the graphs and sampling probability distributions. In optimal scenarios, as little as $\mathcal{O}(k \log (k))$ space–time samples are sufficient to ensure accurate and stable recovery of all $k$-bandlimited signals. Dynamical sampling typically requires much fewer spatial samples than the static case by leveraging the temporal information. Then, we propose a computationally efficient method to reconstruct $k$-bandlimited signals from their space–time samples. We prove that it yields accurate reconstructions and that it is also stable to noise. Finally, we test dynamical sampling techniques on a wide variety of graphs. The numerical results on synthetic and real climate datasets support our theoretical findings and demonstrate the efficiency.
Nutrition facts, drug facts, and model facts: putting AI ethics into practice in gun violence research
Authors: Zhu Jessica , Cukier Michel , Richardson Joseph
Published: May 2024

Objective

Firearm injury research necessitates using data from often-exploited vulnerable populations of Black and Brown Americans. In order to reduce bias against protected attributes, this study provides a theoretical framework for establishing trust and transparency in the use of AI with the general population.

Methods

We propose a Model Facts template that is easily extendable and decomposes accuracy and demographics into standardized and minimally complex values. This framework allows general users to assess the validity and biases of a model without diving into technical model documentation.

Examples

We apply the Model Facts template on 2 previously published models, a violence risk identification model and a suicide risk prediction model. We demonstrate the ease of accessing the appropriate information when the data are structured appropriately.

Discussion

The Model Facts template is limited in its current form to human based data and biases. Like nutrition facts, it will require educational programs for users to grasp its full utility. Human computer interaction experiments should be conducted to ensure model information is communicated accurately and in a manner that improves user decisions.

Conclusion

The Model Facts label is the first framework dedicated to establishing trust with end users and general population consumers. Implementation of Model Facts into firearm injury research will provide public health practitioners and those impacted by firearm injury greater faith in the tools the research provides.
Designing interactive visualizations for analyzing chronic lung diseases in a user-centered approach
Authors: Warnking René Pascal , Scheer Jan , Becker Franziska , Siegel Fabian , Trinkmann Frederik , Nagel Till
Published: May 2024

Objectives

Medical practitioners analyze numerous types of data, often using archaic representations that do not meet their needs. Pneumologists who analyze lung function exams must often consult multiple exam records manually, making comparisons cumbersome. Such shortcomings can be addressed with interactive visualizations, but these must be designed carefully with practitioners’ needs in mind.

Materials and Methods

A workshop with experts was conducted to gather user requirements and common tasks. Based on the workshop results, we iteratively designed a web-based prototype, continuously consulting experts along the way. The resulting application was evaluated in a formative study via expert interviews with 3 medical practitioners.

Results

Participants in our study were able to solve all tasks in accordance with experts’ expectations and generally viewed our system positively, though there were some usability and utility issues in the initial prototype. An improved version of our system solves these issues and includes additional customization functionalities.

Discussion

The study results showed that participants were able to use our system effectively to solve domain-relevant tasks, even though some shortcomings could be observed. Using a different framework with more fine-grained control over interactions and visual elements, we implemented design changes in an improved version of our prototype that needs to be evaluated in future work.

Conclusion

Employing a user-centered design approach, we developed a visual analytics system for lung function data that allows medical practitioners to more easily analyze the progression of several key parameters over time.
Burns Resulting From Electric Vehicle Manufacturing in Silicon Valley
Authors: Silverstein Max L , Karanas Yvonne , Sheckter Clifford C
Published: May 2024

The development of electric vehicles (EVs) has introduced novel technologies and manufacturing processes that expose workers to new risks of burn injury. We identified 6 patients who were admitted to our burn center for injuries that occurred while working in EV manufacturing facilities. The burns fell into 3 categories: flash flame burns due to lithium-ion battery explosions, high-voltage electrical injuries, and burns caused by contact with molten metal. Recognizing these recurrent patterns of injury should inform future prevention efforts and prepare health systems to evaluate and treat patients burned in EV manufacturing.
Elastic reverse time migration based on nested triangular mesh in 2D isotropic media
Authors: Lu Yongming , Lei Tao , Liu Qiancheng , Zhang Jianfeng , Zang Nan
Published: May 2024

Reverse time migration (RTM) based on a two-way wave equation is an important imaging tool that has been widely used in exploration geophysics. It offers distinct advantages in handling complex geological structures. Moreover, elastic reverse time migration (ERTM) can produce more physically meaningful images for subsurface and has received increasing attention in recent years. However, rugged topography presents challenges in the reconstruction of subsurface structures for ERTM. To overcome this problem, we introduce the grid method for topography ERTM, which is an unstructured mesh-based algorithm. However, the conventional gird method for RTM is implementing by discretizing the model into small meshes, leading to high computational cost. To address this problem, we introduce the grid method based on nested unstructured meshes to implement ERTM with complex surface topography. Low-order small meshes, due to their fine scale, can accurately depict complex surface topography. However, their generation process is relatively time consuming. By contrast, high-order large meshes contain many similar small meshes internally, which can be processed in parallel, resulting in higher computational efficiency. Therefore, we propose the following strategy: for the receiver wavefield, several layers on surface discretized by the small meshes are used to place receivers and remaining layers discretized by the large meshes to improve computational efficiency. For the source wavefield, only the large meshes are used because the spacing of the shot is relatively large. In this way, we ensure the accurate description of complex surface topography for the implementation of ERTM with high computational efficiency. Finally, the effectiveness of our method is validated through experiments on three models with complex topography.
Searching for gamma-ray emission from stellar flares
Authors: Song Yuzhe , Paglione Timothy A D , Ilin Ekaterina
Published: May 2024

Flares from magnetically active dwarf stars should produce relativistic particles capable of creating γ-rays. So far, the only isolated main-sequence star besides the Sun to have been detected in γ-rays is TVLM 513−46546. Detecting γ-ray flares from more dwarf stars can improve our understanding of their magnetospheric properties, and could also indicate a diminished likelihood of their planets’ habitability. In this work, we stack data from the Fermi Gamma-ray Space Telescope during a large number of events identified from optical and X-ray flare surveys. We report an upper limit of γ-ray emission from the population of flare stars. Stacking results towards control positions are consistent with a non-detection. We compare these results to observed solar γ-ray flares and against a model of emission from neutral pion decay. The upper limit is consistent with solar flares when scaled to the flare energies and distances of the target stars. As with solar flares, the neutral pion decay mechanism for γ-ray production is also consistent with these results.
Prospects for constraining quasar ages with fibre spectrographs: quasar-induced Ly α emission from the intergalactic medium
Authors: Hada Ryuichiro , Takada Masahiro , Inoue Akio K
Published: May 2024

We present a theoretical framework for linking quasar properties, such as quasar age, to the surrounding Ly α emission intensity. In particular, we focus on a method for mapping the large-scale structure of Ly α emission intensity with galaxy spectra from wide-field spectroscopic surveys, e.g. the Subaru Prime Focus Spectrograph (PFS) or the Dark Energy Spectroscopic Instrument (DESI), and consider the quasar-induced Ly α emission from the intergalactic medium (IGM). To do this, we construct a theoretical model based on two physical processes: resonant scattering of quasar Ly α photons and fluorescence due to quasar ionizing photons, finding that the fluorescence contribution due to optically thick gas clouds is dominant. Taking into account the light-cone effect and assuming a typical quasar spectrum, we calculate the fluorescence contribution to the spectrum stacked within each bin of the separation angle from the quasar as a function of quasar age. Furthermore, we compute the quasar-Ly α emission cross-correlation and its SNR for the planned PFS survey. The predicted signal can only account for $\sim 10~{{\ \rm per\ cent}}$ of the measurements indicated from the BOSS and eBOSS surveys in the outer region of $\gtrsim 10\ \rm {cMpc}\ \rm {h}^{-1}$, and the predicted SNR is not sufficient to detect the quasar-induced contribution. However, we found that our model, combined with the contribution of star-forming galaxies, is not in conflict with these measurements. We discuss other possible contributions to the Ly α emission excess around quasars, the efficiency of using spectroscopic fibres, and the redshift dependence of our model.
Spin-configuration of emission states in zero-dimensional metal halides
Authors: Kuang Zhiyuan , Huang Xinyu , Wang Xing , Wang Chengcheng , Wang Xinrui , Huang Wei , Peng Qiming , Wang Jianpu
Published: May 2024

Understanding the spin-configuration of excited states in a luminescent material is essential for tailoring its properties for many applications such as light-emitting diodes and spin-optoelectronic devices. Zero-dimensional organic-inorganic metal halide (0D-OIMH) materials have demonstrated remarkable potential in diverse applications owing to their captivating optoelectronic characteristics. However, the electronic structure and spin-configuration of the frequently observed dual-peak emission in these materials remains a subject of intensive debate. In this study, we employ low-temperature magneto-optical measurements to investigate the excited state structure of a representative 0D-OIMH, namely (Bmpip)2SnBr4. The spin-configurations of the dark and bright states are clearly elucidated by measuring the magneto-polarization of the emissions. Our results reveal that the high-energy peak arises from bright excited states within a higher energy band, whilst the low-energy peak originates from a combination of triplet-bright states and singlet-dark states. These findings provide an unambiguous understanding of the exciton structures of the distinctive 0D-OIMHs.
Conversion-type anode chemistry with interfacial compatibility toward Ah-level near-neutral high-voltage zinc ion batteries
Authors: Guo Shan , Qin Liping , Wu Jia , Liu Zhexuan , Huang Yuhao , Xie Yiman , Fang Guozhao , Liang Shuquan
Published: May 2024

High-voltage aqueous zinc ion batteries (AZIBs) with a high-safety near-neutral electrolyte is of great significance for practical sustainable application; however, they suffer from anode and electrode/electrolyte interfacial incompatibility. Herein, a conversion-type anode chemistry with a low anodic potential, which is guided by the Gibbs free energy change of conversion reaction, was designed for high-voltage near-neutral AZIBs. A reversible conversion reaction between ZnC2O4·2H2O particles and three-dimensional Zn metal networks well-matched in CH3COOLi-based electrolyte was revealed. This mechanism can be universally validated in the battery systems with sodium or iodine ions. More importantly, a cathodic crowded micellar electrolyte with a water confinement effect was proposed in which lies the core for the stability and reversibility of the cathode under an operating platform voltage beyond 2.0 V, obtaining a capacity retention of 95% after 100 cycles. Remarkably, the scientific and technological challenges from the coin cell to Ah-scale battery, sluggish kinetics of the solid-solid electrode reaction, capacity excitation under high loading of active material, and preparation complexities associated with large-area quasi-solid electrolytes, were explored, successfully achieving an 88% capacity retention under high loading of more than 20 mg cm−2 and particularly a practical 1.1 Ah-level pouch cell. This work provides a path for designing low-cost, eco-friendly and high-voltage aqueous batteries.
Revisiting the diagnostic and prognostic significance of high-frequency QRS analysis in cardiovascular diseases: a comprehensive review
Authors: Qiu Shifeng , Liu Tinghui , Zhan Zijin , Li Xue , Liu Xuewei , Xin Xiaoyu , Lu Junyan , Wu Lipei , Wang Li , Cui Kai , Xiu Jiancheng
Published: May 2024

Cardiovascular diseases (CVDs) present a significant global public health threat, contributing to a substantial number of cases involving morbidity and mortality. Therefore, the early and accurate detection of CVDs plays an indispensable role in enhancing patient outcomes. Decades of extensive research on electrocardiography at high frequencies have yielded a wealth of knowledge regarding alterations in the QRS complex during myocardial ischemia, as well as the methodologies to assess and quantify these changes. In recent years, the analysis of high-frequency QRS (HF-QRS) components has emerged as a promising non-invasive approach for diagnosing various cardiovascular conditions. Alterations in HF-QRS amplitude and morphology have demonstrated remarkable sensitivity as diagnostic indicators for myocardial ischemia, often surpassing measures of ST-T segment changes. This comprehensive review aims to provide an intricate overview of the current advancements, challenges, and prospects associated with HF-QRS analysis in the field of CVDs.
Anti-HMGCR myopathy: estimated five-fold higher incidence in Polynesian compared with European populations in Aotearoa/New Zealand
Authors: Chow Ke Li , Keating Paula Elizabeth , O’Donnell John Liston
Published: May 2024

Objective

In 2014 the incidence of anti-3-hydroxy-3-methylglutaryl-CoA-reductase (HMGCR) myopathy in New Zealand was ∼1.7 case/million persons/year. This study aimed to re-estimate the population incidence and assess ethnic variation in those aged >40 years old.

Methods

An incidence cohort was defined by seropositivity for immunoprecipitating anti-HMGCR autoantibodies tested at a national reference laboratory between 1 October 2019 and 30 September 2021. Separately, ethnicity standardized incidence in >40 year olds discharged from New Zealand public hospitals for idiopathic and unspecified myopathy [International Statistical Classification of Disease and Related Health Problems Tenth Revision Australian Modification (ICD-10 AM) codes M60.8/M60.9], was examined for concordance.

Results

The 40 patients identified in the incidence cohort were all >40 years old and all had a prior history of statin use. Annual incidence was 4 cases/million/year (95% CI 2.8–5.5). In those >40 years old the incidence in Polynesians (Māori and Pacific Peoples combined) was 25 cases/million/year (95% CI 15.9–40.1), in Asians 5.7 cases/million/year (95% CI 0.7–20.5) and in Europeans 7 cases/million/year (95% CI 3.1–8.4). The risk in statin users aged >40 years was ∼1/9000 in Polynesians and ∼1/48 000 in Europeans. Ethnic difference in incidence of idiopathic and unspecified myopathy (ICD AM codes M60.8/M60.9) was also found in hospital discharges.

Conclusion

In the past half decade the estimated incidence of anti-HMGCR myopathy in New Zealand has doubled. Polynesian peoples of New Zealand >40 years old have an estimated 5-fold higher risk compared with European and Asian peoples. The estimated absolute risk in statin users >40 years old was 108 cases/million/year in Polynesians vs 21 cases/million/year in Europeans.
Extracorporeal membrane oxygenation for acute lung injury in idiopathic inflammatory myopathies—a potential lifesaving intervention
Authors: Zheng Boyang , Eline Ellen , Xu Lillian , Huang Kun , Hermans Greet , Perch Michael , Samoukovic Gordan , De Langhe Ellen , Dastmalchi Maryam , Christopher-Stine Lisa , Diederichsen Louise Pyndt , Leclair Valérie
Published: May 2024

Objectives

Idiopathic inflammatory myopathies (IIM) can present with acute IIM-related lung injury and respiratory failure, leading to a high mortality risk in intensive care units (ICU). Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome can be lifesaving. We aimed to report a case series of IIM patients that received ECMO.

Methods

Patients with IIM from tertiary care centres in Belgium, Canada, Denmark, USA and Sweden who underwent ECMO were reviewed to describe clinical characteristics, disease outcomes and hospitalization course. Clinical characteristics at admission and during ICU stay including ECMO complications and mortality causes were summarized.

Results

The study included 22 patients (50% female, mean ± SD age at admission 47 ± 12 years) with anti-MDA5 positive dermatomyositis (68%), anti-synthetase syndrome (14%), polymyositis (9%), overlap myositis (5%) and non-MDA5 dermatomyositis (5%). Patients had low comorbidity scores and 46% had received immunosuppression before their ICU admission. Eight (36%) patients died in the ICU, six (27%) were bridged to recovery and eight (36%) were bridged to transplant. When comparing patients bridged to recovery and those who died in the ICU, those who died were older (P = 0.03) and had higher median Charlson comorbidity index scores (P = 0.05). Both groups had similar frequencies of ECMO-related complications (33% vs 50%, P = 0.94).

Conclusion

In the patients exposed to ECMO in this case series, 14 were successfully bridged to recovery or transplant, while 8 died in the ICU. Large studies are needed to collect data on clinical outcomes in patients with IIM-ILD exposed to ECMO to identify the best candidates for the intervention.
Lecturers don’t know everything: students listening to the thought processes of lecturers on unfamiliar ground
Authors: Steckles Katie , Ketnor Claire , Porter Ros , Shukie Alex , Corner Alexander S
Published: May 2024

Due to the nature of the teaching environment, students may often develop perceptions of their lecturers’ ability as mathematicians, based on the pre-prepared and well-rehearsed content they present. In reality, performing mathematical calculations and solving problems is a difficult skill, and students may compare their own experiences unfavourably with the ease they see lecturers display. To interrogate this disparity, an exercise was included in an undergraduate maths session during which lecturers attempted unseen problems from A-level maths papers, so the students could see them describing the process of problem-solving—including making mistakes, applying helpful strategies and techniques, correcting their own errors and identifying gaps in their knowledge. As well as describing these positive behaviours for students, the session aimed to develop the students’ understanding that their own experiences of struggling with maths are normal and healthy. The activity formed part of a broader session on making mistakes in maths, which also included some advice and opportunities to find mistakes in mathematical working-out. The students were invited to participate in questionnaires and focus groups to explore their perceptions and attitudes towards their lecturers’ knowledge and capacity to make mistakes, and in this paper we analyse these responses and consider how this relates to teaching, and to students’ personal development.
Peer Mentorship: Career Support in Full Bloom
Authors: Dong Sara W. , Huang Grace C. , Farid Huma
Published: May 2024

Peer mentorship, referring to interactions among colleagues at similar career stages for the purpose of bidirectional career development, is a powerful tool to promote personal and professional growth. While dyadic mentoring has traditionally been the norm in academia, the needs of junior faculty may span multiple domains that a single senior mentor may not be able to address.1,2 A vibrant community garden of peer mentors can help to harvest ideas, encourage mutual collaboration, increase personal satisfaction, and promote career advancement.
Xinyang flavivirus, from Haemaphysalis flava ticks in Henan Province, China, defines a basal, likely tick-only Orthoflavivirus clade
Authors: Wang Lan-Lan , Cheng Qia , Newton Natalee D. , Wolfinger Michael T. , Morgan Mahali S. , Slonchak Andrii , Khromykh Alexander A. , Cheng Tian-Yin , Parry Rhys H.
Published: May 2024

Tick-borne orthoflaviviruses (TBFs) are classified into three conventional groups based on genetics and ecology: mammalian, seabird and probable-TBF group. Recently, a fourth basal group has been identified in Rhipicephalus ticks from Africa: Mpulungu flavivirus (MPFV) in Zambia and Ngoye virus (NGOV) in Senegal. Despite attempts, isolating these viruses in vertebrate and invertebrate cell lines or intracerebral injection of newborn mice with virus-containing homogenates has remained unsuccessful. In this study, we report the discovery of Xinyang flavivirus (XiFV) in Haemaphysalis flava ticks from Xìnyáng, Henan Province, China. Phylogenetic analysis shows that XiFV was most closely related to MPFV and NGOV, marking the first identification of this tick orthoflavivirus group in Asia. We developed a reverse transcriptase quantitative PCR assay to screen wild-collected ticks and egg clutches, with absolute infection rates of 20.75 % in adult females and 15.19 % in egg clutches, suggesting that XiFV could be potentially spread through transovarial transmission. To examine potential host range, dinucleotide composition analyses revealed that XiFV, MPFV and NGOV share a closer composition to classical insect-specific orthoflaviviruses than to vertebrate-infecting TBFs, suggesting that XiFV could be a tick-only orthoflavivirus. Additionally, both XiFV and MPFV lack a furin cleavage site in the prM protein, unlike other TBFs, suggesting these viruses might exist towards a biased immature particle state. To examine this, chimeric Binjari virus with XIFV-prME (bXiFV) was generated, purified and analysed by SDS-PAGE and negative-stain transmission electron microscopy, suggesting prototypical orthoflavivirus size (~50 nm) and bias towards uncleaved prM. In silico structural analyses of the 3′-untranslated regions show that XiFV forms up to five pseudo-knot-containing stem-loops and a prototypical orthoflavivirus dumbbell element, suggesting the potential for multiple exoribonuclease-resistant RNA structures.
OPTIMIZATION OF DRIED BLOOD SPOT ASSAYS FOR HEPATITIS B VIRUS SURFACE ANTIBODY QUANTIFICATION
Authors: Motshosi Patience , Phinius Bonolo B. , Jongman Mosimanegape , Baruti Kabo , Bhebhe Lynnette , Choga Wonderful T. , Moyo Sikhulile , Gaseitsiwe Simani , Anderson Motswedi
Published: May 2024

Dried blood spot (DBS) cards can be used as an alternative sample collection method to plasma, however, there is no optimized elution protocol for DBS cards specifically for hepatitis B surface antibody (anti-HBs) testing. The study aimed to develop a DBS elution protocol for anti-HBs quantification. Our study sought to determine the ideal phosphate-buffered saline (PBS) buffer volume to use by comparing three PBS volumes (300uL, 450uL, and 500uL), and the optimal time to agitate DBS discs on a plate shaker (1hr, 2hrs, 3hrs, and 4hrs) to yield DBS anti-HBs concentrations that are comparable to corresponding plasma anti-HBs concentrations. The optimal DBS storage temperature (25°C, -20°C, and -80°C) was investigated to determine the ideal longterm storage temperature of the cards. Residual samples were used for optimization (2019-2021). A total of 50 DBS-plasma pairs was used throughout the study, with plasma anti-HBs concentrations being used as the golden standard to compare. The analysis of results was carried out by determining the p-values of the Wilcoxon sign rank. A two-way analysis of variance (ANOVA) was also performed to determine the impact of PBS elution volumes, elution time, and storage temperature on the anti-HBs concentration of DBS samples on STATA Version 15.0. No statistically significant difference between the DBS-plasma anti-HBs pairs was observed when using 450 or 500uL of PBS buffer and when samples were agitated for 3 hours (p=0.594, p=0.499 respectively). The optimal storage temperature for DBS cards was 25°C because the results showed no statistically significant difference between DBS-plasma anti-HBs titers (p=0.594). The two-way ANOVA analysis showed that elution volumes and time had no statistically significant impact on the DBS anti-HBs concentrations, p=0.948 and p=0.381 respectively. Storage temperature had a statistically significant impact on the DBS anti-HBs concentrations, p=0.002. The optimized DBS elution protocol for anti-HBs quantification will help monitor vaccine efficacy in infants due to the low sample volumes required compared to plasma and also can be used for anti-HBs testing in resource-limited areas around the country.
Structural and functional analysis of TREM2 interactions with amyloid beta reveal molecular mechanisms that mediate phagocytosis of oligomeric amyloid beta
Authors: Greven Jessica A. , Osario Omar , Nix Jay C. , Alexander-Brett Jennifer M. , Brett Tom J.
Published: May 2024

The TREM2 receptor is expressed on microglia in the brain, where it plays critical roles regulating microglia function. TREM2 engages a number of ligands involved in Alzheimer’s disease, and consequent signaling triggers phagocytosis, activation, survival, and proliferation. TREM2 has emerged as a drug target for AD, however very little is known regarding the structural basis for TREM2 microglial functions. Here we investigated the engagement of oligomeric amyloid beta (oAβ42) with TREM2. Using familial variants of amyloid beta, we show that mutations in the N-terminal portion of Aβ, notably residues H6 and D7, disrupt binding to TREM2. We then co-crystallized TREM2 with Aβ(1-8) peptide and determined the high resolution crystal structure. The structure revealed the peptide binds to the hydrophobic site of TREM2, closest to CDR1. Mutational and binding studies using BLI confirmed that mutations to the hydrophobic site ablate binding to oAβ42. Finally, we show that these interactions are critical to triggering phagocytosis of oAβ42, as oAβ42 variants H6R and D7N are not phagocytosed. Altogether, these data indicate that TREM2 engages oAβ42 using the hydrophobic site on TREM2 and the N-terminal portion of Aβ, and that this interaction is critical to trigger signaling and phagocytosis.
Spatial modeling algorithms for reactions and transport (SMART) in biological cells
Authors: Francis Emmet A. , Laughlin Justin , Dokken Jørgen S. , Finsberg Henrik , Lee Christopher T. , Rognes Marie E. , Rangamani Padmini
Published: May 2024

Biological cells rely on precise spatiotemporal coordination of biochemical reactions to control their many functions. Such cell signaling networks have been a common focus for mathematical models, but they remain challenging to simulate, particularly in realistic cell geometries. Herein, we present our software, Spatial Modeling Algorithms for Reaction and Transport (SMART), a package that takes in high-level user specifications about cell signaling networks and molecular transport, and then assembles and solves the associated mathematical and computational systems. SMART uses state-of-the-art finite element analysis, via the FEniCS Project software, to efficiently and accurately resolve cell signaling events over discretized cellular and subcellular geometries. We demonstrate its application to several different biological systems, including YAP/TAZ mechanotransduction, calcium signaling in neurons and cardiomyocytes, and ATP generation in mitochondria. Throughout, we utilize experimentally-derived realistic cellular geometries represented by well-conditioned tetrahedral meshes. These scenarios demonstrate the applicability, flexibility, accuracy and efficiency of SMART across a range of temporal and spatial scales.
Performance comparison of ten state-of-the-art machine learning algorithms for outcome prediction modeling of radiation-induced toxicity
Authors: Salazar Ramon M. , Nair Saurabh S. , Leone Alexandra O. , Xu Ting , Mumme Raymond P. , Duryea Jack D. , De Brian , Corrigan Kelsey L. , Rooney Michael K. , Ning Matthew S. , Das Prajnan , Holliday Emma B. , Liao Zhongxing , Court Laurence E. , Niedzielski Joshua S.
Published: May 2024

Purpose

To evaluate the efficacy of prominent machine learning algorithms in predicting normal tissue complication probability utilizing clinical data obtained from two distinct disease sites, and to create a software tool that facilitates the automatic determination of the optimal algorithm to model any given labeled dataset.

Methods and Materials

We obtained 3 sets of radiation toxicity data (478 patients) from our clinic, gastrointestinal toxicity (GIT), radiation pneumonitis (RP), and radiation esophagitis (RE). These data comprised clinicopathological and dosimetric information for patients diagnosed with non-small cell lung cancer and anal squamous cell carcinoma. Each dataset was modeled using ten commonly employed machine learning algorithms (elastic net, LASSO, random forest, regression forest, support vector machine, XGBoost, k-nearest- neighbors, neural network, Bayesian-LASSO, and Bayesian neural network) by randomly dividing the dataset into a training and test set. The training set was used to create and tune the model, and the test set served to assess it by calculating performance metrics. This process was repeated 100 times by each algorithm for each dataset. Figures were generated to visually compare the performance of the algorithms. A graphical user interface was developed to automate this whole process.

Results

LASSO achieved the highest area under the precision-recall curve (AUPRC) (0.807±0.067) for RE, random forest for GIT (0.726±0.096), and the neural network for RP (0.878±0.060). Area-under-the-curve was 0.754±0.069, 0.889±0.043, and 0.905±0.045, respectively. The graphical user interface was used to compare all algorithms for each dataset automatically. When averaging AUPRC across all toxicities, Bayesian-LASSO was the best model.

Conclusion

Our results show that there is no best algorithm for all datasets. Therefore, it is important to compare multiple algorithms when training an outcome prediction model on a new dataset. The graphical user interface created for this study automatically compares the performance of these ten algorithms for any dataset.
Targeted Sequencing of CTX-M Alleles in Seattle Area Wastewater
Authors: Ong Angelo Q. , Philo Sarah E. , Taylor Anysiah , Hu Ruohan , Meschke John Scott , Fuhrmeister Erica R.
Published: May 2024

Extended-spectrum-beta-lactamases (ESBLs) are a growing group of antimicrobial resistance (AMR) enzymes that can result in severe clinical outcomes. The CTX-M gene, which encodes for ESBLs in bacteria, confers resistance to third generation cephalosporins and is of high clinical concern. We developed a targeted, long-read sequencing method utilizing unique molecular identifiers to generate accurate, full length CTX-M gene sequences from wastewater. We characterized CTX-M in 36 samples from three Seattle area wastewater treatment plants from April 2020 to March 2021. We identified a core community of alleles that persisted across time and treatment plant. The CTX-M-15 containing protein variant (CTX-M-15/216/28) was detected in all but three samples and made up, at most, 30% of detected CTX-M alleles. We observed significant diversity across the CTX-M gene at the nucleic acid level, although most nucleotide mutations were synonymous - resulting in two to three amino acid variants across 19 loci. By average relative abundance, 23% of protein variants were novel, defined as those not represented in the CARD database. This method provides information (full length gene sequences) that cannot be obtained through other culture-independent methods. This flexible approach can be expanded to additional targets and implemented in settings where AMR surveillance is a priority, such as hospital wastewater.
Percutaneous rheolytic thrombectomy of thrombosed arteriovenous dialysis access using the AngioJet catheter- A Systematic Review
Authors: Lee Quinncy , Ho Dominic Lap Hin , Ng Jun Jie , Choong Andrew MTL
Published: May 2024

Introduction

The endovascular removal of thrombi in occluded arteriovenous (AV) access sites has been increasingly accepted by surgeons as an alternative to surgical thrombectomy and revision [1,2]. This systematic review documents the experiences and outcomes of using the AngioJet Rheolytic Thrombectomy Device for salvaging thrombosed arteriovenous fistulas (AVFs) or grafts (AVGs).

Methods

Electronic databases, such as PubMed, Embase, and the Cochrane Library, were searched from their establishment until May 2024. Initially, 549 articles were reviewed for potential inclusion, and only 10 studies fulfilled our inclusion criteria. Our final dataset included 771 patients who underwent 996 thrombectomies to treat 338 thrombosed AVFs and 457 AVGs.

Results

The demographics, technical and procedural success, patency rates, and complications were evaluated to examine the effectiveness and safety of AngioJet thrombectomy. The mean primary patency rates at 3, 6, and 12 months were 64.09 ± 10.12, 50.36 ± 11.73, and 40.81 ± 15.13 (p < 0.05). The mean assisted primary patency rates at 3, 6, and 12 months were 75.37 ± 13.98, 59.58 ± 14.26 and 40.88 ± 18.81 (p < 0.05). Finally, the mean secondary patency rates at 3, 6, and 12 months were 84.03 ± 8.38, 77.93 ± 9.07, and 65.81 ± 12.12 (p < 0.05). A total of 92 complications were recorded; most were minor complications, thereby being transient and self-limiting. Additionally, 5 total deaths were reported; however, all were not considered related to the AngioJet device.

Discussion

Our study deemed devices such as AngioJet efficacious in performing pharmacomechanical thrombectomies, as promising results in terms of safeness and effectiveness to re-establish patency in occluded AVFs and AVGs have been reported.