bluuebunny/crossref_metadata_2025 huggingface dataset:
Meropenem extraction by ex vivo extracorporeal life support circuits
Authors: Honeycutt Christopher Cole , McDaniel Charles Griffin , McKnite Autumn , Hunt J. Porter , Whelan Aviva , Green Danielle J. , Watt Kevin M.
Published: September 2023

Background: Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. As many of these patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics. Based on the physicochemical properties of meropenem, it is expected that ECMO circuits will minimally extract meropenem, while CRRT circuits will rapidly clear meropenem. The present study seeks to determine the extraction of meropenem from ex vivo ECMO and CRRT circuits and elucidate the contribution of different ECMO circuit components to extraction. Methods: Standard doses of meropenem were administered to three different configurations (n = 3 per configuration) of blood-primed ex vivo ECMO circuits and serial sampling was conducted over 24 h. Similarly, standard doses of meropenem were administered to CRRT circuits (n = 4) and serial sampling was conducted over 4 h. Meropenem was administered to separate tubes primed with circuit blood to serve as controls to account for drug degradation. Meropenem concentrations were quantified, and percent recovery was calculated for each sample. Results: Meropenem was cleared at a similar rate in ECMO circuits of different configurations (n = 3) and controls (n = 6), with mean (standard deviation) recovery at 24 h of 15.6% (12.9) in Complete circuits, 37.9% (8.3) in Oxygenator circuits, 47.1% (8.2) in Pump circuits, and 20.6% (20.6) in controls. In CRRT circuits (n = 4) meropenem was cleared rapidly compared with controls (n = 6) with a mean recovery at 2 h of 2.36% (1.44) in circuits and 93.0% (7.1) in controls. Conclusion: Meropenem is rapidly cleared by hemodiafiltration during CRRT. There is minimal adsorption of meropenem to ECMO circuit components; however, meropenem undergoes significant degradation and/or plasma metabolism at physiological conditions. These ex vivo findings will advise pharmacists and physicians on the appropriate dosing of meropenem.
Multi-modal approach in management of vulvo-vaginal gingival syndrome − a rare variant of oral lichen planus
Authors: V. Shwetha , S. Sujatha , N. Rakesh , T. Pavan , Rathore Pooja
Published: September 2023

Lichen planus (LP) is a chronic autoimmune relapsing mucocutaneous disease that significantly affects the patient's quality of life (QoL) and is associated with several etiological factors. Vulvo-vaginal gingival syndrome (VVGS) is characterized as a clinical triad of gingival, vaginal and vulval LP. In previous literature, it has been described as a distinctive pattern of erosive plurimucosal LP. This condition if progressed can lead to multiple complications such as urethral and vaginal stenosis. This case report highlights the management of VVGS using a multidisciplinary strategy that includes dermatological consultation, oral hygiene maintenance, topical steroid application using custom-made trays and photodynamic therapy.
Unilateral Platysma Muscle Rupture as an Effect of Using a Hard Wooden Block for Facial Massage
Authors: Jung Kyu Hwa , Yang Eun-Jung , Lee Won
Published: September 2023

Facial massages are frequently performed to achieve a feeling of freshness, rejuvenation, skin tightening, and delayed onset of wrinkles. However, vigorous massages can induce unexpected symptoms. Here, we present a case of a woman who complained of an asymmetric facial appearance and a mass-like lesion following a long-term facial massage intervention. A facelift incision was performed. Platysma muscle rupture was observed intraoperatively, which was then repaired. To our knowledge, this is the first report of a vigorous facial massage-induced ipsilateral platysma rupture.
Cost-Effective and Scalable Synthesis of 4-Bromo-1,2-dimethyl-1H-imidazole: A Key Building Block for Bioactive Molecules
Authors: Vetrichelvan Muthalagu , Lanke Veeranjaneyulu , Chandu Bellam , Mathur Arvind , Gupta Anuradha
Published: September 2023

A cost-effective, scalable, high-yielding, and commercially viable synthesis of 4-bromo-1,2-dimethyl-1H-imidazole (1), an important building block to construct various bioactive molecules has been established. The main feature of this method includes the selection of appropriate starting material 1,2-dimethyl-1H-imidazole in which the existing issue of regioisomer formation is circumvented and the selective debromination is accomplished by using isopropyl magnesium chloride.
Comparison of Clinical and Pathological Staging in Patients with Head and Neck Cancer After Neck Dissection
Authors: Pinto João Viana , Sousa Mafalda Martins , Silveira Helena , Vales Fernando , Moura Carla Pinto
Published: September 2023

Introduction Clinical and pathological staging plays an important role on the prognosis of head and neck cancer (HNC) patients.

Objective The present study aims to compare clinical and pathological T, N and overall staging in patients with HNC, to identify factors associated with these discrepancies, and to analyze and compare survival or disease-free survival in staging disagreements.

Methods Retrospective cohort including every patient submitted to neck dissection from January 2010 to December 2020 in the department of Otorhinolaryngology of a tertiary hospital center.

Results A total of 79 patients were analyzed; their mean age was 58.52 ± 13.15 years old and 88.9% were male. Assessing overall staging, discrepancies were noted in 53% (36.4% upstaging and 16.6% downstaging) and were significantly associated with clinical overall staging (p = 0.006). Regarding T staging, differences were noted in 45.5% (30.3% upstaging and 15.2% downstaging) and were significantly associated with imaging modality (p = 0.016), clinical T staging (p = 0.049), and histology (p = 0.017). Discrepancies in N staging were noted in 38% (25.3% upstaging and 12.7% downstaging) and were significantly associated with age (p = 0.013), clinical N staging (p < 0.001), and presence of extranodal invasion (p < 0.001). Both in Overall, T, and N staging, the aforementioned disagreements were not associated with either higher mortality or higher disease relapse.

Conclusion Overall, T, and N staging disagree in an important number of cases, and the overall stage can disagree in up to 53% of the cases. These disagreements do not seem to influence overall and disease-free survival.
Extracorporeal Life Support in Pulmonary Hypertension: Practical Aspects
Authors: Hoeper Marius M.
Published: September 2023

Extracorporeal life support (ECLS), in particular veno-arterial extracorporeal membrane oxygenation, has emerged as a potentially life-saving treatment modality in patients presenting with pulmonary hypertension and right heart failure refractory to conventional treatment. Used mainly as a bridge to lung transplantation, ECLS is also being used occasionally as a bridge to recovery in patients with treatable causes of right heart failure. This review article describes indications, contraindications, techniques, and outcomes of the use of ECLS in patients with PH, focusing on practical aspects in the management of such patients.
Propelling an untethered microswimmer with explosive boiling
Authors: Palivela Ananya
Published: September 2023

A gliding microrobot employs electric discharge to reach high velocities while moving freely in water.
Outdoor stability testing of perovskite solar cells: Necessary step toward real-life applications
Authors: Ali Muhammad Umair , Mo Hongbo , Li Yin , Djurišić Aleksandra B.
Published: September 2023

Perovskite solar cells (PSCs) are among the most promising emerging photovoltaic technologies, due to their high efficiency, comparable to that of silicon solar cells. However, concerns about the stability of these devices remain, despite great progress achieved in recent years. To address these concerns, comprehensive investigations of their stability under realistic operating conditions are necessary. In this Perspective, we will discuss the outdoor testing of PSCs. We will first introduce degradation mechanisms relevant for intrinsic stability, as well as degradation mechanisms due to ambient exposure. Effective encapsulation of PSCs will then be discussed, followed by a summary of achieved progress and discussion of testing protocols and equipment to make outdoor testing more accessible. Finally, challenges and future outlook will be discussed.
A pragmatic and discourse analysis of hate words on social media
Authors: Retta Mattia
Published: September 2023

This paper studies some pragmatic and discursive properties of hate words employed in the comment chains of two Italian right-wing politicians’ social media accounts. The analysis focuses on hate speech directed towards two ethnic groups – African migrants and the Chinese – and an individual, the former minister of Agriculture Teresa Bellanova. Hate words are divided into two macrocategories: slurs and insulting epithets. Slurs are expressions that are consistently associated with derogatory attitudes against a group of people based on their origin/descent; insulting epithets are either offensive terms that do not attack specific identity traits or neutral words that, in certain contexts, can be offensive. Data indicate that the use of hate words is guided by pragmatic factors and discursive elements, and it changes according to the individual(s) or the groups being attacked. Hate speech on social media occurs mainly through insulting epithets, thus allowing the authors to avoid moderation and any responsibility for their utterance. The results support the idea that hate speech is a complex speech act that aims not only at derogating or expressing negative emotions but works within the framework of racist discourses as a means of creating and reinforcing political polarisation and in-group values.
Fast in the pandemic, durable after droughts, inequal during economic downturn. A 20 year multi-dimensional retrospective analysis of water demand change in Southern California
Authors: Gross Marie-Philine , Ajami Newsha K , Cominola Andrea
Published: September 2023

Determining changes in water consumption behavior due to recurring external stressors (e.g. droughts and socio-economic fluctuations) and previously unseen shocks like the COVID-19 pandemic can support future demand-side management (DSM) programs and identifying vulnerable social groups. Yet, most studies analyzing external drivers of water consumption change are noncomparative as they examine only one stressor at the time, mainly droughts. Here we develop a multi-dimensional retrospective analysis (MDRA) to quantify residential water consumption changes in Southern California over the last two decades under compound hydroclimatic, economic, and pandemic stressors. We then uncover what socio-economic groups relate to predominant behavioral changes under each stressor. We observe a long-lasting decreasing water consumption trend for more than 76% of the analyzed households. Socio-economically vulnerable households were more likely to reduce water consumption during the economic and pandemic stressors. Differently, affluent neighborhoods tended to increase water consumption during or after droughts and the pandemic. Our MDRA supports utilities and policy makers to discern the impacts of different stressors on water demand and helps to identify social and economic sensitivities across a service area to develop adaptive DSMs and assistance programs.
Physical mechanisms for the dominant summertime high-latitude atmospheric teleconnection pattern and the related Northern Eurasian climates
Authors: Kim Jin-Yong , Seo Kyong-Hwan
Published: September 2023

Summertime atmospheric teleconnection patterns over Eurasia have a significant influence on regional weather and climate. Despite extensive studies on the subtropical patterns, the high-latitude counterpart has received relatively less attention. This study proposes physical mechanisms for the formation and maintenance of the dominant high-latitude teleconnection pattern. The formation of the pattern is associated with variability in synoptic-scale eddy activity due to the meridional gradient of sea surface temperature anomalies in the vicinity of the Gulf Stream, causing a meridional shift of the central axis of storm track at the exit of Atlantic jet. The resultant convergence of transient vorticity fluxes to the west of the British Isles induces low-frequency cyclonic circulation anomalies and continued propagation of Rossby waves downstream along northern Eurasia. Once these circulation anomalies are formed, the subsequent latent heat-related diabatic anomalies over the northern Eurasian landmass act as another source of Rossby waves to maintain the teleconnection pattern. Regional temperature and precipitation variability is closely linked to the wave pattern along a route through northern Eurasia, and even precipitation over the East Asian summer monsoon region is influenced by the teleconnection pattern.
Evaluating the Accuracy of UAV and TLS for 3D Indoor Modelling in Large-Scale Building Environments
Authors: Zakiyon Ahmad Mirza Afiq Ahmad , Idris Ahmad Norhisyam , Hezri Razali M. , Ghani Muhammad Nasri Abdul , Syafuan Wan Mohamed
Published: September 2023

The accuracy of 3D indoor reconstructed models is critical in various applications such as indoor navigation, virtual reality (VR), and building information modelling (BIM). This research study aims to evaluate the accuracy of Unmanned Aerial Vehicles (UAV) and Terrestrial Laser Scanning (TLS) for 3D indoor modelling in large-scale building environments. To achieve this, several evaluations were made towards the number of point clouds, estimated costs and accuracy of the 3D indoor reconstructed model generated from dense point clouds acquired by Unmanned Aerial Vehicle (UAV) and Terrestrial Laser Scanner (TLS). A small indoor classroom was selected for this study approximately 100m2. In UAV data acquisition, three (3) flight missions were set up at the front, left and right views. Meanwhile, five (5) scanning stations were placed on-site for the TLS method. Due to various different flight mission views in the UAV dataset, the number of point clouds was quite higher compared to the TLS method. However, a better-quality visualization of the TLS model has been obtained as opposed to the UAV 3D model. For the required time to generate a 3D model, it showed that UAV processing time was more consuming lots of time than the TLS method, especially when georeferencing the overlapping photographs. In terms of accuracy, the RMSE value from TLS was better than UAV at 0.003m compared to UAV at 0.021m. Overall, this study provides insights into the accuracy and suitability of UAV and TLS for 3D indoor modelling in large-scale building environments. The results can inform decision-making processes in various industries such as architecture, engineering, and construction, where accurate and reliable 3D models are crucial for design, planning, and management purposes.
Mapping Oil Palm Plantations Using WorldView-2 Satellite Imagery and Machine Learning Algorithms
Authors: Marzuki F A A , Shafri H Z M , Ang Y , Shaharum N S N , Lee Y P , Bakar S A , Abidin H , Lim H S , Abdullah R
Published: September 2023

Currently, remote sensing has been used extensively in the agriculture industry for oil palm monitoring due to their large plantation area. Oil palm monitoring can be done by performing land cover classification using various classification methods and machine learning algorithms. This study was conducted to perform oil palm mapping using WorldView-2 satellite imagery and classify land cover features using machine learning algorithms such as Random Forest (RF) and Linear Support Vector Classifier (LSVC). A total of 58609 sampling points were classified into six classes which are water, built-up, bare soil, forest, mature oil palm (≥9 years) and young oil palm (3-8 years). The training and testing samples were split using 3-fold cross-validation. 67% of the total sampling points were used for training samples whereas the other 33% were used for testing samples. The methods used to validate the data in this study is by using spectral reflectance and Google Earth Pro. Accuracy assessment was conducted after obtaining the classification output such as Overall Accuracy (OA), Kappa Accuracy (KA), Precision, Recall and F1-score. As a result, the oil palm mapping using RF has a higher accuracy than LSVC which is 72.49% for OA and 62.98% for KA. The p-value obtained from the McNemar’s test conducted in this study is 0.683 (>0.05) which concludes that the predictive performance of the two models are equal.
The impact of computing infrastructure on carbon emissions: an empirical study based on china national supercomputing center
Authors: Yang Haodong , Wang Gaofeng
Published: September 2023

Digitalization is viewed as a potential solution to environmental sustainability issues. However, existing researches suggest that the environmental impact of digital technology is uncertain. This study focuses on the National Supercomputing Center (NSC) in China, a large-scale computing infrastructure, and expands the correlation between digital infrastructure and green development from a computing perspective. Based on the synthetic control method, we select non-supercomputing cities as the control group and assign appropriate weighting. Through the fitting of a synthetic control group (refer to as the synthetic city) with similar characteristics, the analysis is conducted to compare carbon emissions (CO2 emission) between NSC city and the synthetic city. The empirical results show that the NSC may worsen regional CO2 emissions, and this result still holds true after a series of robustness tests. Mechanism examinations show that the NSC does not exhibit significant composition effect (energy structure improvement) and technology effect (green technology innovation), while scale effect (increase in energy demand and consumption) dominate the NSC’s carbon emissions. Based on these findings, we consider that in addition to improving the energy efficiency of supercomputing centers, the adoption of cleaner renewable energy and the promotion of knowledge spillovers are crucial for achieving a green transformation for computing infrastructure.
Evaluation of different machine learning algorithms for LULC classification in heterogeneous landscape by using remote sensing and GIS techniques
Authors: Pokhariya Hemant Singh , Singh D P , Prakash Rishi
Published: September 2023

Remote sensing land cover classification plays a crucial role in detecting changes, urbanization planning, mapping and monitoring land cover on earth surface. It is very challenging to get accurate result in remote sensing data because different classifiers are very much area dependent. Different classifiers such as decision tree (DT), K-nearest neighbor (KNN), artificial neural network (ANN), support vector machine (SVM), boosted decision tree (BDT), random forest (RF), classification and regression tree (CART) and maximum likelihood classifiers (MLC), have different accuracies for the same classes. Several studies have utilized remote sensing and GIS tools to investigate changes in land use and land cover (LULC) using different classifiers. Seasonal rivers which should be classified as water bodies are mostly classified as urban area with the conventional land cover classification schemes because spectral reflectance of these river bodies is similar to urban area due to stones present in their river bed. It is very difficult to distinguish between these river beds (which are mostly found in various districts of Uttarakhand, India) and urban area in remote sensing images. In this paper, we present a new method to distinguish these river beds with the urban area and to separate other classes easily. First of all different spectral indices such as NDVI, NDBI, EVI and MNDWI are extracted from a high resolution Sentinel-2 MSI image then these indices are integrated with Sentinel-2 MSI image for classification of different land cover classes by using four different machine learning classifiers such as RF, SVM, DT and CART. The obtained results confirm the performance strength of the suggested method as there is much improvement in accuracy.
Bubbling and extinction for some fast diffusion equations in bounded domains
Authors: Jin Tianling , Xiong Jingang
Published: September 2023

We study a Sobolev critical fast diffusion equation in bounded domains with the Brézis-Nirenberg effect. We obtain extinction profiles of its positive solutions, and show that the convergence rates of the relative error in regular norms are at least polynomial. Exponential decay rates are proved for generic domains. Our proof makes use of its regularity estimates, a curvature type evolution equation, as well as blow up analysis. Results for Sobolev subcritical fast diffusion equations are also obtained.
mStrain: strain-level identification of Yersinia pestis using metagenomic data
Authors: Qian Xiuwei , Wu Yarong , Zuo Xiujuan , Peng Xin , Guo Yan , Yang Ruifu , Zhang Xianglilan , Cui Yujun
Published: September 2023

Motivation

High-resolution target pathogen detection using metagenomic sequencing data represents a major challenge due to the low concentration of target pathogens in samples. We introduced mStrain, a novel Yesinia pestis strain/lineage-level identification tool that utilizes metagenomic data. mStrain successfully identified Y. pestis at the strain/lineage level by extracting sufficient information regarding single-nucleotide polymorphisms (SNPs), which can therefore be an effective tool for identification and source tracking of Y. pestis based on metagenomic data during a plague outbreak.

Definition

 

Strain-level identification

Assigning the reads in the metagenomic sequencing data to an exactly known or most closely representative Y. pestis strain.

Lineage-level identification

Assigning the reads in the metagenomic sequencing data to a specific lineage on the phylogenetic tree.

canoSNPs

The unique and typical SNPs present in all representative strains.

Ancestor/derived state

An SNP is defined as the ancestor state when consistent with the allele of Yersinia pseudotuberculosis strain IP32953; otherwise, the SNP is defined as the derived state.

Availability and implementation

The code for running mStrain, the test dataset, and instructions for running the code can be found at the following GitHub repository: https://github.com/xwqian1123/mStrain.
Investigating the conformational landscape of AlphaFold2-predicted protein kinase structures
Authors: Al-Masri Carmen , Trozzi Francesco , Lin Shu-Hang , Tran Oanh , Sahni Navriti , Patek Marcel , Cichonska Anna , Ravikumar Balaguru , Rahman Rayees
Published: September 2023

Protein kinases are a family of signaling proteins, crucial for maintaining cellular homeostasis. When dysregulated, kinases drive the pathogenesis of several diseases, and are thus one of the largest target categories for drug discovery. Kinase activity is tightly controlled by switching through several active and inactive conformations in their catalytic domain. Kinase inhibitors have been designed to engage kinases in specific conformational states, where each conformation presents a unique physico-chemical environment for therapeutic intervention. Thus, modeling kinases across conformations can enable the design of novel and optimally selective kinase drugs. Due to the recent success of AlphaFold2 in accurately predicting the 3D structure of proteins based on sequence, we investigated the conformational landscape of protein kinases as modeled by AlphaFold2. We observed that AlphaFold2 is able to model several kinase conformations across the kinome, however, certain conformations are only observed in specific kinase families. Furthermore, we show that the per residue predicted local distance difference test can capture information describing structural flexibility of kinases. Finally, we evaluated the docking performance of AlphaFold2 kinase structures for enriching known ligands. Taken together, we see an opportunity to leverage AlphaFold2 models for structure-based drug discovery against kinases across several pharmacologically relevant conformational states.

Availability and implementation

All code used in the analysis is freely available at https://github.com/Harmonic-Discovery/AF2-kinase-conformational-landscape.
Advancements in computational modelling of biological systems: seventh annual SysMod meeting
Authors: Puniya Bhanwar Lal , Dräger Andreas
Published: September 2023

The Computational Modelling of Systems Biology (SysMod) Community of Special Interest (COSI) convenes annually at the Intelligent Systems for Molecular Biology (ISMB) conference to facilitate knowledge dissemination and exchange of research findings on systems modelling from interdisciplinary domains. The SysMod meeting 2022 was held in a hybrid mode in Madison, Wisconsin, spanning a 1-day duration centred on modelling techniques, applications, and single-cell technology implementations. The meeting showcased innovative approaches to modelling biological systems using cell-specific and multiscale modelling, multiomics data integration, and novel tools to develop systems models using single-cell and multiomics technology. The meeting also recognized outstanding research by awarding the three best posters. This report summarizes the key highlights and outcomes of the meeting.

Availability and implementation

All resources and further information are freely accessible at https://sysmod.info.
FrameD: framework for DNA-based data storage design, verification, and validation
Authors: Volkel Kevin D , Lin Kevin N , Hook Paul W , Timp Winston , Keung Albert J , Tuck James M
Published: September 2023

Motivation

DNA-based data storage is a quickly growing field that hopes to harness the massive theoretical information density of DNA molecules to produce a competitive next-generation storage medium suitable for archival data. In recent years, many DNA-based storage system designs have been proposed. Given that no common infrastructure exists for simulating these storage systems, comparing many different designs along with many different error models is increasingly difficult. To address this challenge, we introduce FrameD, a simulation infrastructure for DNA storage systems that leverages the underlying modularity of DNA storage system designs to provide a framework to express different designs while being able to reuse common components.

Results

We demonstrate the utility of FrameD and the need for a common simulation platform using a case study. Our case study compares designs that utilize strand copies differently, some that align strand copies using multiple sequence alignment algorithms and others that do not. We found that the choice to include multiple sequence alignment in the pipeline is dependent on the error rate and the type of errors being injected and is not always beneficial. In addition to supporting a wide range of designs, FrameD provides the user with transparent parallelism to deal with a large number of reads from sequencing and the need for many fault injection iterations. We believe that FrameD fills a void in the tools publicly available to the DNA storage community by providing a modular and extensible framework with support for massive parallelism. As a result, it will help accelerate the design process of future DNA-based storage systems.

Availability and implementation

The source code for FrameD along with the data generated during the demonstration of FrameD is available in a public Github repository at https://github.com/dna-storage/framed, (https://dx.doi.org/10.5281/zenodo.7757762).
Multidisciplinary cardiogenic shock team approach improves the long-term outcomes of patients suffering from refractory cardiogenic shock treated with short-term mechanical circulatory support
Authors: Hérion François-Xavier , Beurton Antoine , Oddos Claire , Nubret Karine , Aguerreche Clément , Quessard Astrid , Faure Maxime , Gerbaud Edouard , Pernot Mathieu , Imbault Julien , Ouattara Alexandre
Published: September 2023

Aims

Short-term mechanical circulatory support (STMCS) may be used as an intentional escalation strategy to treat refractory cardiogenic shock (rCS). However, with growing technical possibilities, making the right choice at the right time can be challenging. We established a shock team in January 2013 comprising a cardiac anaesthetist–intensivist, an interventional cardiologist, and a cardiac surgeon. Since then, a diagnosis of rCS has triggered a multidisciplinary team meeting based on a common algorithm. This study aimed to compare the decision-making process for STMCS for rCS before (2007–2013) and after (2013–2019) the creation of the shock team.

Methods and results

This before-and-after cohort study was conducted over a 156-month period. Post-cardiotomy rCS were excluded. The primary outcome was a 1-year survival rate. In total, 250 consecutive adult patients were included in the analysis (84 in the control group and 166 in the shock team group). At baseline, the CardShock score was not different between the two groups (5[3–5] vs. 5[4–6], P = 0.323). The 1-year survival rate was significantly higher in the shock team group compared with the control group (59% vs. 45%, P = 0.043). After a Cox regression analysis, the shock team intervention was independently associated with a significantly improved 1-year survival rate (HR: 0.592, 95% CI: 0.398–0.880, P = 0.010).

Conclusion

A multidisciplinary shock team-based decision for STMCS device implantation in rCS is associated with better 1-year survival rates.
Quantification of myocardial extracellular volume without blood sampling
Authors: Chen Wensu , Faragli Alessandro , Goetze Collin , Zieschang Victoria , Weiss Karl Jakob , Hashemi Djawid , Beyer Rebecca , Hafermann Lorena , Stawowy Philipp , Kelle Sebastian , Doeblin Patrick
Published: September 2023

Aims

Cardiac magnetic resonance (CMR) T1 relaxation time mapping is an established technique primarily used to identify diffuse interstitial fibrosis and oedema. The myocardial extracellular volume (ECV) can be calculated from pre- and post-contrast T1 relaxation times and is a reproducible parametric index of the proportion of volume occupied by non-cardiomyocyte components in myocardial tissue. The conventional calculation of the ECV requires blood sampling to measure the haematocrit (HCT). Given the high variability of the HCT, the blood collection is recommended within 24 h of the CMR scan, limiting its applicability and posing a barrier to the clinical routine use of ECV measurements. In recent years, several research groups have proposed a method to determine the ECV by CMR without blood sampling. This is based on the inverse relationship between the T1 relaxation rate (R1) of blood and the HCT. Consequently, a ‘synthetic’ HCT could be estimated from the native blood R1, avoiding blood sampling.

Methods and results

We performed a review and meta-analysis of published studies on synthetic ECV, as well as a secondary analysis of previously published data to examine the effect of the chosen regression modell on bias. While, overall, a good correlation and little bias between synthetic and conventional ECV were found in these studies, questions regarding its accuracy remain.

Conclusion

Synthetic HCT and ECV can provide a ‘non-invasive’ quantitative measurement of the myocardium’s extracellular space when timely HCT measurements are not available and large alterations in ECV are expected, such as in cardiac amyloidosis. Due to the dependency of T1 relaxation times on the local setup, calculation of local formulas using linear regression is recommended, which can be easily performed using available data.
Quality of life and societal costs in patients with dilated cardiomyopathy
Authors: Wiethoff Isabell , Sikking Maurits , Evers Silvia , Gabrio Andrea , Henkens Michiel , Michels Michelle , Verdonschot Job , Heymans Stephane , Hiligsmann Mickaël
Published: September 2023

Aims

Dilated cardiomyopathy (DCM) is a major cause of heart failure impairing patient wellbeing and imposing a substantial economic burden on society, but respective data are missing. This study aims to measure the quality of life (QoL) and societal costs of DCM patients.

Methods and results

A cross-sectional evaluation of QoL and societal costs of DCM patients was performed through the 5-level EuroQol and the Medical Consumption Questionnaire and Productivity Cost Questionnaire, respectively. QoL was translated into numerical values (i.e. utilities). Costs were measured from a Dutch societal perspective. Final costs were extrapolated to 1 year, reported in 2022 Euros, and compared between DCM severity according to NYHA classes. A total of 550 DCM patients from the Maastricht cardiomyopathy registry were included. Mean age was 61 years, and 34% were women. Overall utility was slightly lower for DCM patients than the population mean (0.840 vs. 0.869, P = 0.225). Among EQ-5D dimensions, DCM patients scored lowest in ‘usual activities’. Total societal DCM costs were €14 843 per patient per year. Cost drivers were productivity losses (€7037) and medical costs (€4621). Patients with more symptomatic DCM (i.e. NYHA class III or IV) had significantly higher average DCM costs per year compared to less symptomatic DCM (€31 099 vs. €11 446, P < 0.001) and significantly lower utilities (0.631 vs. 0.883, P < 0.001).

Conclusion

DCM is associated with high societal costs and reduced QoL, in particular with high DCM severity.
Inactivation of TRPM7 Kinase Targets AKT Signaling and Cyclooxygenase-2 Expression in Human CML Cells
Authors: Hoeger Birgit , Nadolni Wiebke , Hampe Sarah , Hoelting Kilian , Fraticelli Marco , Zaborsky Nadja , Madlmayr Anna , Sperrer Viktoria , Fraticelli Laura , Addington Lynda , Steinritz Dirk , Chubanov Vladimir , Geisberger Roland , Greil Richard , Breit Andreas , Boekhoff Ingrid , Gudermann Thomas , Zierler Susanna
Published: September 2023

Cyclooxygenase-2 (COX-2) is a key regulator of inflammation. High constitutive COX-2 expression enhances survival and proliferation of cancer cells, and adversely impacts antitumor immunity. The expression of COX-2 is modulated by various signaling pathways. Recently, we identified the melastatin-like transient-receptor-potential-7 (TRPM7) channel-kinase as modulator of immune homeostasis. TRPM7 protein is essential for leukocyte proliferation and differentiation, and upregulated in several cancers. It comprises of a cation channel and an atypical α-kinase, linked to inflammatory cell signals and associated with hallmarks of tumor progression. A role in leukemia has not been established, and signaling pathways are yet to be deciphered. We show that inhibiting TRPM7 channel-kinase in chronic myeloid leukemia (CML) cells results in reduced constitutive COX-2 expression. By utilizing a CML-derived cell line, HAP1, harboring CRISPR/Cas9-mediated TRPM7 knockout, or a point mutation inactivating TRPM7 kinase, we could link this to reduced activation of AKT serine/threonine kinase and mothers against decapentaplegic homolog 2 (SMAD2). We identified AKT as a direct in vitro substrate of TRPM7 kinase. Pharmacologic blockade of TRPM7 in wildtype HAP1 cells confirmed the effect on COX-2 via altered AKT signaling. Addition of an AKT activator on TRPM7 kinase-dead cells reconstituted the wildtype phenotype. Inhibition of TRPM7 resulted in reduced phosphorylation of AKT and diminished COX-2 expression in peripheral blood mononuclear cells derived from CML patients, and reduced proliferation in patient-derived CD34+ cells. These results highlight a role of TRPM7 kinase in AKT-driven COX-2 expression and suggest a beneficial potential of TRPM7 blockade in COX-2-related inflammation and malignancy.
Firearm violence exposure and health in 2 national samples of Black and American Indian/Alaska Native adults
Authors: Semenza Daniel C , Baker Nazsa , Ziminski Devon
Published: September 2023

Exposure to firearm violence is widespread and disproportionately experienced by communities of color, with implications for broad health disparities. Survey data were collected from 2 nationally representative samples of Black (n = 3015) and American Indian/Alaska Native (AI/AN) (n = 527) adults in the United States in April and May 2023. The exposure measures were 4 types of firearm violence exposure. The outcome measures were self-rated health, number of poor physical health days, and number of poor mental health days. Regression results demonstrate that being threatened with a firearm and hearing about or witnessing a shooting were associated with poorer self-rated, mental, and physical health across both samples. Cumulative exposure to firearm violence was particularly associated with increasing harms to health for all outcomes. In general, individual and cumulative firearm violence exposures are linked to poorer health among Black and AI/AN adults in the United States. Significant enhancements and long-term investment are needed for firearm violence prevention to yield improvements to population health, particularly among communities burdened with high levels of exposure to firearm violence.
Ratio analysis 2: liquidity, working capital and long-term financial stability
Authors: Scott Peter
Published: September 2023

This chapter discusses the other ratios related to liquidity, working capital, and long-term financial stability. It begins with the definition of liquidity and the cash flow cycle. It discusses aspects critical to an organization’s liquidity, solvency, cash flow generating capacity, and its ability to raise additional funds with which to finance operations. It considers how an entity’s capital structure contributes to an assessment of that entity’s long-term financial stability. In addition, it looks at the key ratios in the assessment of an entity’s capital structures as well as evaluating an organization’s ability to survive with high levels of borrowings.
Introduction to Immunology and the Immune System
Authors: Juris Stephen
Published: September 2023

This chapter provides a background on how the body keeps infections at bay. It explores the two major branches of the immune system (the innate immune system and the adaptive immune system) and the cells, molecules, and tissues that drive their responses to provide protection from infectious disease. It also reviews a vast array of mechanisms that the human body relies on to keep them healthy in spite of all the challenges the immune system faces daily. The chapter explains immunology as the study of immunity from diseases and the mechanisms used by the immune system to provide protection against pathogens. It explains that pathogens have the ability to cause disease, either via bacteria, viruses, fungi, protozoa, or parasites.
B-Cell-Mediated Adaptive Immunity
Authors: Juris Stephen
Published: September 2023

This chapter explores the function of B cells in the adaptive immune system. It analyses the molecular mechanisms that drive clonal selection and expansion of B cells to understand the means by which immunoglobulins act in a humoral immune response. It also notes how B cells can only become activated upon engagement of their cell-surface immunoglobulin with the antigen they are capable of recognizing. The chapter talks about the migration of B cells into secondary lymphoid tissues to monitor the presence of antigens, which is where they test for the presence of the antigen their immunoglobulin can recognize in the T-cell zone. It covers secreted immunoglobulins that have a variety of functions within the humoral adaptive immune response, including neutralization, activation of innate immune cells, protection of internal tissues, complement activation, and clearance of small immune complexes.
Immunological Memory and Vaccination
Authors: Juris Stephen
Published: September 2023

This chapter highlights the mechanisms of action of the primary and secondary adaptive immune responses. It shows how the adaptive immune response works to combat a pathogen and produces cells that enable the immune system to remember the pathogen. It also emphasizes how the understanding of the adaptive immune response has resulted in treatments that promote healthy pregnancy and childbirth and in vaccines that protect against deadly pathogens. The chapter talks about memory cells produced during an adaptive immune response that include memory B cells, T memory stem cells, central memory T cells, effector memory T cells, and resident memory T cells. It looks at a variety of vaccination strategies that have been employed as means to promote effective protection against different viral and bacterial pathogens.
Autoimmune Diseases
Authors: Juris Stephen
Published: September 2023

This chapter explores problems that occur when tolerance to self-antigens is lost, noting that cells of the adaptive immune system undergo somatic recombination events to provide a diverse array of receptors at their surfaces. It analyses similarities between autoimmune diseases and hypersensitivity responses. While the antigens recognized in hypersensitivity reactions differ from those recognized in autoimmune, recognition prompts activation of adaptive immune responses that can be damaging and life-threatening. The chapter describes how autoimmune diseases are induced due to a lack of central or peripheral tolerance of the adaptive immune system. It highlights the failure of central and peripheral tolerance, which drives the onset of autoimmune disease and caused by both genetic and environmental factors.
Cancer and the Immune System
Authors: Juris Stephen
Published: September 2023

This chapter investigates the interaction of the immune system with cancer cells, noting that cancer are the result of mutations within cells that affect the ability of the body to control the cell cycle and cell division. It considers proto-oncogenes and tumor suppressor genes as two key gene families that work to promote progression through the cell cycle. These are targets for mutations that can lead to the onset of cancer. It also highlights the battle that ensues between cancer cells, which aim to continue to survive and divide, and immune mechanisms, which aim to recognize and target harmful pathogens and cells. The chapter demonstrates how cancer cells avoid destruction by immune system effect or mechanisms by avoiding detection or manipulating the immune response that would normally target these cells. It talks about the recognition of the adaptive immune system of cancer cells through tumor-associated or tumor-specific antigens expressed by these cells.
Antigen Recognition by T Lymphocytes
Authors: Juris Stephen
Published: September 2023

This chapter explores the important interactions between T cells and antigen-presenting cells, noting how through these interactions the adaptive immune system is able to recognize an infection. It explains the defining features of the T-cell receptor structure and shows how this allows it to be both diverse and to function in recognizing an MHC-peptide complex. It also reviews what are the molecular mechanisms of antigen processing and presentation by MHC class I and class II molecules. The chapter looks at the diversity in MHC molecules, which is a result of different MHC genes in the population. It shows that the maintenance of MHC diversity promotes organism survival in the evolutionary arms race against pathogens and causes problems for medical breakthroughs, such as tissue and hematopoietic stem cell transplantation.
T-Cell-Mediated Adaptive Immunity
Authors: Juris Stephen
Published: September 2023

This chapter examines the role of T cells in the adaptive immune system. It addresses how T cells are activated when they recognize an MHC-peptide complex via their receptor. It looks at the effect or functions of T cells in the cellular arm of the adaptive immune system. T cells can migrate to secondary lymphoid tissue, where they assess various antigens presented by antigen-presenting cells via MHC class I and class II molecules. The chapter highlights the recognition of the T cells of a specific MHC-peptide complex which undergoes clonal selection, causing signalling events that drive clonal expansion via cell division and allow the expanded T cells to differentiate into effector T cells. It points out that the effector T cells produced during clonal expansion and differentiation will match what is required to combat the specific pathogen whose antigen was presented.
Stochastic methods
Authors: Baker Daniel H.
Published: September 2023

This chapter looks into stochastic methods used to model different situations, which often involve using random numbers in one way or another. Methods like resampling and bootstrapping illustrate how flexible and widespread stochastic methods are. The main advantage of stochastic methods revolves around how it can allow working out useful stuff without requiring formal equations. The chapter explores ways of generating random numbers, citing that using a complex algorithm to generate sequences of numbers that appear random to a first approximation is the most common method and the method used by R. It also elaborates on the concept of resampling.
Correcting for multiple comparisons
Authors: Baker Daniel H.
Published: September 2023

This chapter tackles the notion of correcting for multiple comparisons. It considers the idea of a higher probability of significance when more statistical tests are being run to investigate a given hypothesis, even if there is no true effect. Traditionally, the solution to this problem has been to correct the criterion for significance to account for the number of comparisons. The chapter elaborates on the approach of false discovery rate and cluster correction that deal with multiple comparisons in a principled way while maintaining statistical power at higher levels than older methods. It looks into the process of correcting for multiple comparisons in R.
Reproducible data analysis
Authors: Baker Daniel H.
Published: September 2023

This chapter argues for making data and scripts open and accessible. It explains that making code and data available will improve the integrity and progress of science, and this is worthwhile for researchers in all disciplines and at all career stages. Computer scientists and professional programmers most often use a system called git to keep track of changes within the code. Then the chapter considers how to interface with platforms called Git Hub, R Markdown, and Open Science Framework. The common data sharing issue of data acquisition devices' proprietary native file format can be solved by either converting the data to a standard format or converting the data into a generic data format that is not specific to a particular scientific field or data type.
The Diversity of Benthic Marine Invertebrates
Authors: Levinton Jeffrey S.
Published: September 2023

This chapter explores the diversity of marine benthic invertebrates. It focuses on the Cambrian explosion of animal life about 540 million years ago, which resulted in some evolutionary changes that allowed for the development of morphological and behavioral complexity. Benthic invertebrates with radial symmetry have a center of symmetry, and bilateral symmetry is often associated with directional movement and anterior sense organs. Complexity and different degrees of evolutionary transformation can be found in terms of symmetry and organ types. The chapter considers the characteristics and structure of various invertebrates, such as Cnidaria, Platyhelminthes, Nemertea, and Protists. It also looks into mollusks, arthropods, echinodermata, and urochordata.