bluuebunny/crossref_metadata_2025 huggingface dataset:
nf-core/nanostring: a pipeline for reproducible NanoString nCounter analysis
Authors: Peltzer Alexander , Mohr Christopher , Stadermann Kai B , Zwick Matthias , Schmid Ramona
Published: January 2024

Motivation

The NanoString™ nCounter® technology platform is a widely used targeted quantification platform for the analysis of gene expression of up to ∼800 genes. Whereas the software tools by the manufacturer can perform the analysis in an interactive and GUI driven approach, there is no portable and user-friendly workflow available that can be used to perform reproducible analysis of multiple samples simultaneously in a scalable fashion on different computing infrastructures.

Results

Here, we present the nf-core/nanostring open-source pipeline to perform a comprehensive analysis including quality control and additional features such as expression visualization, annotation with additional metadata and input creation for differential gene expression analysis. The workflow features an easy installation, comprehensive documentation, open-source code with the possibility for further extensions, a strong portability across multiple computing environments and detailed quality metrics reporting covering all parts of the pipeline. nf-core/nanostring has been implemented in the Nextflow workflow language and supports Docker, Singularity, Podman container technologies as well as Conda environments, enabling easy deployment on any Nextflow supported compatible system, including most widely used cloud computing environments such as Google GCP or Amazon AWS.

Availability and implementation

The source code, documentation and installation instructions as well as results for continuous tests are freely available at https://github.com/nf-core/nanostring and https://nf-co.re/nanostring.
Targeted deletion of NR2F2 and VCAM1 in theca cells impacts ovarian follicular development: insights into polycystic ovary syndrome?
Authors: Candelaria Nicholes R , Richards JoAnne S
Published: January 2024

Defining features of polycystic ovary syndrome (PCOS) include elevated expression of steroidogenic genes, theca cell androgen biosynthesis, and peripheral levels of androgens. In previous studies, we identified vascular cell adhesion molecule 1 (VCAM1) as a selective androgen target gene in specific NR2F2/SF1 (+/+) theca cells. By deleting NR2F2 and VCAM1 selectively in CYP17A1 theca cells in mice, we documented that NR2F2 and VCAM1 impact distinct and sometimes opposing theca cell functions that alter ovarian follicular development in vivo: including major changes in ovarian morphology, steroidogenesis, gene expression profiles, immunolocalization images (NR5A1, CYP11A1, NOTCH1, CYP17A1, INSL3, VCAM1, NR2F2) as well as granulosa cell functions. We propose that theca cells impact follicle integrity by regulating androgen production and action, as well as granulosa cell differentiation/luteinization in response to androgens and gonadotropins that may underlie PCOS.
Identification of novel biomarkers in the early diagnosis of malignant melanoma by untargeted liquid chromatography coupled to high-resolution mass spectrometry-based metabolomics: a pilot study
Authors: Peña-Martín Jesús , Belén García-Ortega María , Palacios-Ferrer José Luis , Díaz Caridad , Ángel García María , Boulaiz Houria , Valdivia Javier , Jurado José Miguel , Almazan-Fernandez Francisco M , Arias Santiago Salvador , Vicente Francisca , del Val Coral , Pérez del Palacio José , Marchal Juan Antonio
Published: January 2024

Background

Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge.

Objectives

To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management.

Methods

In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM.

Results

We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample.

Conclusions

These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.
Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study
Authors: Li Zheng-yan , Wei Bo , Zhou Yan-bing , Li Tai-yuan , Li Ji-peng , Zhou Zhi-wei , She Jun-jun , Qin Xin-gan , Hu Jian-kun , Li Yong-Xiang , Qian Feng , Shi Yan , Cui Hao , Tian Yu-long , Gao Geng-mei , Gao Rui-zi , Liang Cheng-cai , Shi Fei-yu , Yu Li-Jun , Yang Kun , Zhang Shang-xin , Yu Pei-wu , Zhao Yong-liang
Published: January 2024

Background

The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer.

Methods

Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence.

Results

Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39–58) months for the RG group and 39 (38–56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups.

Conclusion

RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.
TREM2 variants that cause early dementia and increase Alzheimer’s disease risk affect gene splicing
Authors: Kiianitsa Kostantin , Lukes Maria E , Hayes Brian J , Brutman Julianna N , Valdmanis Paul N , Bird Thomas D , Raskind Wendy H , Korvatska Olena
Published: January 2024

Loss-of-function variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are responsible for a spectrum of neurodegenerative disorders. In the homozygous state, they cause severe pathologies with early onset dementia, such as Nasu-Hakola disease and behavioural variants of frontotemporal dementia (FTD), whereas heterozygous variants increase the risk of late-onset Alzheimer’s disease (AD) and FTD. For over half of TREM2 variants found in families with recessive early onset dementia, the defect occurs at the transcript level via premature termination codons or aberrant splicing. The remaining variants are missense alterations thought to affect the protein; however, the underlying pathogenic mechanism is less clear. In this work, we tested whether these disease-associated TREM2 variants contribute to the pathology via altered splicing.

Variants scored by SpliceAI algorithm were tested by a full-size TREM2 splicing reporter assay in different cell lines. The effect of variants was quantified by qRT-/RT-PCR and western blots. Nanostring nCounter was used to measure TREM2 RNA in the brains of NHD patients who carried spliceogenic variants. Exon skipping events were analysed from brain RNA-Seq datasets available through the Accelerating Medicines Partnership for Alzheimer’s Disease Consortium.

We found that for some Nasu-Hakola disease and early onset FTD-causing variants, splicing defects were the primary cause (D134G) or likely contributor to pathogenicity (V126G and K186N). Similar but milder effects on splicing of exons 2 and 3 were demonstrated for A130V, L133L and R136W enriched in patients with dementia. Moreover, the two most frequent missense variants associated with AD/FTD risk in European and African ancestries (R62H, 1% in Caucasians and T96K, 12% in Africans) had splicing defects via excessive skipping of exon 2 and overproduction of a potentially antagonistic TREM2 protein isoform. The effect of R62H on exon 2 skipping was confirmed in three independent brain RNA-Seq datasets.

Our findings revealed an unanticipated complexity of pathogenic variation in TREM2, in which effects on post-transcriptional gene regulation and protein function often coexist. This necessitates the inclusion of computational and experimental analyses of splicing and mRNA processing for a better understanding of genetic variation in disease.
Longitudinal flortaucipir, metabolism and volume differ between phonetic and prosodic speech apraxia
Authors: Tetzloff Katerina A , Martin Peter R , Duffy Joseph R , Utianski Rene L , Clark Heather M , Botha Hugo , Machulda Mary M , Thu Pham Nha Trang , Schwarz Christopher G , Senjem Matthew L , Jack Clifford R , Lowe Val J , Josephs Keith A , Whitwell Jennifer L
Published: January 2024

Progressive apraxia of speech (PAOS) is a neurodegenerative motor-speech disorder that most commonly arises from a four-repeat tauopathy. Recent studies have established that progressive apraxia of speech is not a homogenous disease but rather there are distinct subtypes: the phonetic subtype is characterized by distorted sound substitutions, the prosodic subtype by slow and segmented speech and the mixed subtype by a combination of both but lack of predominance of either. There is some evidence that cross-sectional patterns of neurodegeneration differ across subtypes, although it is unknown whether longitudinal patterns of neurodegeneration differ.

We examined longitudinal patterns of atrophy on MRI, hypometabolism on 18F-fluorodeoxyglucose-PET and tau uptake on flortaucipir-PET in a large cohort of subjects with PAOS that had been followed for many years. Ninety-one subjects with PAOS (51 phonetic, 40 prosodic) were recruited by the Neurodegenerative Research Group. Of these, 54 (27 phonetic, 27 prosodic) returned for annual follow-up, with up to seven longitudinal visits (total visits analysed = 217). Volumes, metabolism and flortaucipir uptake were measured for subcortical and cortical regions, for all scans. Bayesian hierarchical models were used to model longitudinal change across imaging modalities with PAOS subtypes being compared at baseline, 4 years from baseline, and in terms of rates of change.

The phonetic group showed smaller volumes and worse metabolism in Broca’s area and the striatum at baseline and after 4 years, and faster rates of change in these regions, compared with the prosodic group. There was also evidence of faster spread of hypometabolism and flortaucipir uptake into the temporal and parietal lobes in the phonetic group. In contrast, the prosodic group showed smaller cerebellar dentate, midbrain, substantia nigra and thalamus volumes at baseline and after 4 years, as well as faster rates of atrophy, than the phonetic group. Greater hypometabolism and flortaucipir uptake were also observed in the cerebellar dentate and substantia nigra in the prosodic group. Mixed findings were observed in the supplementary motor area and precentral cortex, with no clear differences observed across phonetic and prosodic groups.

These findings support different patterns of disease spread in PAOS subtypes, with corticostriatal patterns in the phonetic subtype and brainstem and thalamic patterns in the prosodic subtype, providing insight into the pathophysiology and heterogeneity of PAOS.
The significance and limited influence of cerebrovascular reactivity on age and sex effects in task- and resting-state brain activity
Authors: Chen Donna Y , Di Xin , Yu Xin , Biswal Bharat B
Published: January 2024

Functional MRI measures the blood-oxygen-level dependent signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state blood-oxygen-level dependent activity and may confound inter-individual effects, such as those related to aging and biological sex. We examined a large dataset containing breath-holding, checkerboard, and resting-state tasks. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and quantified resting-state activity with amplitude of low-frequency fluctuations and regional homogeneity. We hypothesized that cerebrovascular reactivity would be correlated with blood-oxygen-level dependent measures and that accounting for these correlations would result in better estimates of age and sex effects. We found that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with amplitude of low-frequency fluctuations and regional homogeneity in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in amplitude of low-frequency fluctuations and regional homogeneity. However, correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.
Resting heart rate causally affects the brain cortical structure: Mendelian randomization study
Authors: Zhong Yinsheng , Li Jun , Hong Yinghui , Yang Shujun , Pei Liying , Chen Xuxiang , Wu Haidong , Wang Tong
Published: January 2024

Resting heart rate (RHR) has been linked to impaired cortical structure in observational studies. However, the extent to which this association is potentially causal has not been determined. Using genetic data, this study aimed to reveal the causal effect of RHR on brain cortical structure. A Two-Sample Mendelian randomization (MR) analysis was conducted. Sensitivity analyses, weighted median, MR Pleiotropy residual sum and outlier, and MR-Egger regression were conducted to evaluate heterogeneity and pleiotropy. A causal relationship between RHR and cortical structures was identified by MR analysis. On the global scale, elevated RHR was found to decrease global surface area (SA; P < 0.0125). On a regional scale, the elevated RHR significantly decreased the SA of pars triangularis without global weighted (P = 1.58 × 10−4) and the thickness (TH) of the paracentral with global weighted (P = 3.56 × 10−5), whereas it increased the TH of banks of the superior temporal sulcus in the presence of global weighted (P = 1.04 × 10−4). MR study provided evidence that RHR might be causally linked to brain cortical structure, which offers a different way to understand the heart–brain axis theory.
Distinct mechanisms underlying cross-modal semantic conflict and response conflict processing
Authors: Xu Honghui , Yang Guochun , Wu Haiyan , Xiao Jing , Li Qi , Liu Xun
Published: January 2024

Interference from task-irrelevant stimuli can occur during the semantic and response processing stages. Previous studies have shown both common and distinct mechanisms underlying semantic conflict processing and response conflict processing in the visual domain. However, it remains unclear whether common and/or distinct mechanisms are involved in semantic conflict processing and response conflict processing in the cross-modal domain. Therefore, the present electroencephalography study adopted an audiovisual 2-1 mapping Stroop task to investigate whether common and/or distinct mechanisms underlie semantic conflict and response conflict. Behaviorally, significant cross-modal semantic conflict and significant cross-modal response conflict were observed. Electroencephalography results revealed that the frontal N2 amplitude and theta power increased only in the semantic conflict condition, while the parietal N450 amplitude increased only in the response conflict condition. These findings indicated that distinct neural mechanisms were involved in cross-modal semantic conflict and response conflict processing, supporting the domain-specific cognitive control mechanisms from a cross-modal multistage conflict processing perspective.
Short- and long-term neuroplasticity interact during the perceptual learning of concurrent speech
Authors: MacLean Jessica , Stirn Jack , Sisson Alexandria , Bidelman Gavin M
Published: January 2024

Plasticity from auditory experience shapes the brain’s encoding and perception of sound. However, whether such long-term plasticity alters the trajectory of short-term plasticity during speech processing has yet to be investigated. Here, we explored the neural mechanisms and interplay between short- and long-term neuroplasticity for rapid auditory perceptual learning of concurrent speech sounds in young, normal-hearing musicians and nonmusicians. Participants learned to identify double-vowel mixtures during ~ 45 min training sessions recorded simultaneously with high-density electroencephalography (EEG). We analyzed frequency-following responses (FFRs) and event-related potentials (ERPs) to investigate neural correlates of learning at subcortical and cortical levels, respectively. Although both groups showed rapid perceptual learning, musicians showed faster behavioral decisions than nonmusicians overall. Learning-related changes were not apparent in brainstem FFRs. However, plasticity was highly evident in cortex, where ERPs revealed unique hemispheric asymmetries between groups suggestive of different neural strategies (musicians: right hemisphere bias; nonmusicians: left hemisphere). Source reconstruction and the early (150–200 ms) time course of these effects localized learning-induced cortical plasticity to auditory-sensory brain areas. Our findings reinforce the domain-general benefits of musicianship but reveal that successful speech sound learning is driven by a critical interplay between long- and short-term mechanisms of auditory plasticity, which first emerge at a cortical level.
Time Trends in Causes of Death in People With HIV: Insights From the Swiss HIV Cohort Study
Authors: Weber M S R , Duran Ramirez J J , Hentzien M , Cavassini M , Bernasconi E , Hofmann E , Furrer H , Kovari H , Stöckle M , Schmid P , Haerry D , Braun D L , Günthard H F , Kusejko K ,   the Swiss HIV Cohort Study, Abela I , Aebi-Popp K , Anagnostopoulos A , Battegay M , Bernasconi E , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Hachfeld A , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Jackson-Perry D , Kahlert C R , Keiser O , Klimkait T , Kouyos R D , Kusejko K , Labhardt N , Leuzinger K , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nemeth J , Nicca D , Notter J , Paioni P , Pantaleo G , Perreau M , Rauch A , Salazar-Vizcaya L , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Wandeler G , Weisser M , Yerly S
Published: January 2024

Background

Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in AIDS-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years are scarce.

Methods

We investigated all reported deaths in the Swiss HIV Cohort Study between 2005 and 2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death.

Results

In total, 1630 deaths were reported, with 23.7% of individuals assigned female sex at birth. These deaths included 147 (9.0%) HIV/AIDS-related deaths, 373 (22.9%) due to non-AIDS, non-hepatic cancers, 166 (10.2%) liver-related deaths, and 158 (9.7%) cardiovascular-related deaths. The median age at death (interquartile range) increased from 45.0 (40.0–53.0) years in 2005–2007 to 61.0 (56.0–69.5) years in 2020–2022. HIV/AIDS- and liver-related deaths decreased, whereas deaths from non-AIDS, non-hepatic cancers increased and cardiovascular-related deaths remained relatively stable.

Conclusions

The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus coinfection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non–AIDS-related comorbid conditions, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.
Formylated Peptide Receptor-1-Mediated Gut Inflammation as a Therapeutic Target in Inflammatory Bowel Disease
Authors: McAllister Milly J , Hall Rebecca , Whelan Robert J , Fischer Lena J , Chuah Cher S , Cartlidge Peter D , Drury Broc , Rutherford Duncan G , Duffin Rodger M , Cartwright Jennifer A , Dorward David A , Rossi Adriano G , Ho Gwo-tzer
Published: January 2024

Background

Formylated peptide receptor (FPR)-1 is a G-coupled receptor that senses foreign bacterial and host-derived mitochondrial formylated peptides (FPs), leading to innate immune system activation.

Aim

We sought to investigate the role of FPR1-mediated inflammation and its potential as a therapeutic target in inflammatory bowel disease (IBD).

Methods

We characterized FPR1 gene and protein expression in 8 human IBD (~1000 patients) datasets with analysis on disease subtype, mucosal inflammation, and drug response. We performed in vivo dextran-sulfate sodium (DSS) colitis in C57/BL6 FPR1 knockout mice. In ex vivo studies, we studied the role of mitochondrial FPs and pharmacological blockade of FPR1 using cyclosporin H in human peripheral blood neutrophils. Finally, we assess mitochondrial FPs as a potential mechanistic biomarker in the blood and stools of patients with IBD.

Results

Detailed in silico analysis in human intestinal biopsies showed that FPR1 is highly expressed in IBD (n = 207 IBD vs 67 non-IBD controls, P < .001), and highly correlated with gut inflammation in ulcerative colitis (UC) and Crohn’s disease (CD) (both P < .001). FPR1 receptor is predominantly expressed in leukocytes, and we showed significantly higher FPR1+ve neutrophils in inflamed gut tissue section in IBD (17 CD and 24 UC; both P < .001). Further analysis in 6 independent IBD (data available under Gene Expression Omnibus accession numbers GSE59071, GSE206285, GSE73661, GSE16879, GSE92415, and GSE235970) showed an association with active gut inflammation and treatment resistance to infliximab, ustekinumab, and vedolizumab. FPR1 gene deletion is protective in murine DSS colitis with lower gut neutrophil inflammation. In the human ex vivo neutrophil system, mitochondrial FP, nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) is a potent activator of neutrophils resulting in higher CD62L shedding, CD63 expression, reactive oxygen species production, and chemotactic capacity; these effects are inhibited by cyclosporin H. We screened for mitochondrial ND6 in IBD (n = 54) using ELISA and detected ND6 in stools with median values of 2.2 gg/mL (interquartile range [IQR] 0.0–4.99; range 0–53.3) but not in blood. Stool ND6 levels, however, were not significantly correlated with paired stool calprotectin, C-reactive protein, and clinical IBD activity.

Conclusions

Our data suggest that FPR1-mediated neutrophilic inflammation is a tractable target in IBD; however, further work is required to clarify the clinical utility of mitochondrial FPs as a potential mechanistic marker for future stratification.
Perilipin 1: a systematic review on its functions on lipid metabolism and atherosclerosis in mice and humans
Authors: Desgrouas Camille , Thalheim Tabea , Cerino Mathieu , Badens Catherine , Bonello-Palot Nathalie
Published: January 2024

The function of perilipin 1 in human metabolism was recently highlighted by the description of PLIN1 variants associated with various pathologies. These include severe familial partial lipodystrophy and early onset acute coronary syndrome. Additionally, certain variants have been reported to have a protective effect on cardiovascular diseases. The role of this protein remains controversial in mice and variant interpretation in humans is still conflicting. This literature review has two primary objectives (i) to clarify the function of the PLIN1 gene in lipid metabolism and atherosclerosis by examining functional studies performed in cells (adipocytes) and mice and (ii) to understand the impact of PLIN1 variants identified in humans based on the variant’s location within the protein and the type of variant (missense or frameshift). To achieve these objectives, we conducted an extensive analysis of the relevant literature on perilipin 1, its function in cellular models and mice, and the consequences of its mutations in humans. We also utilized bioinformatics tools and consulted the Human Genetics Cardiovascular Disease Knowledge Portal to enhance the pathogenicity assessment of PLIN1 missense variants.
Evaluation of a digital patient education programme for Chinese immigrants after a heart attack
Authors: Shi Wendan , Zhang Ling , Ghisi Gabriela L M , Panaretto Lise , Oh Paul , Gallagher Robyn
Published: January 2024

Aims

To evaluate a self-administered digital education resource for patients after a heart attack (adapted simplified Chinese version of Cardiac College™) on secondary prevention knowledge and health behaviour change outcomes.

Methods and results

Chinese immigrants recovering from a heart attack were recruited from cardiac rehabilitation programmes at four metropolitan tertiary hospitals. Participants provided access to Cardiac College™ (adapted simplified Chinese version), a self-learning secondary prevention virtual education resource over 4 weeks. The web-based resources include 9 booklets and 10 pre-recorded video education sessions. Assessments included health literacy, secondary prevention knowledge, self-management behaviours, self-reported physical activity, and a heart-healthy diet. Satisfaction, acceptability, and engagement were also assessed.

From 81 patients screened, 67 were recruited, and 64 (95.5%) completed the study. The participants’ mean age was 67.2 ± 8.1 years old, 81.2% were males, and the majority had no English proficiency (65.6%). Following the intervention, significant improvements were observed for secondary prevention knowledge overall and in all subdomains, with the most improvement occurring in medical, exercise, and psychological domains (P < 0.001). Dietary and self-management behaviours also improved significantly (P < 0.05). According to participants, the educational materials were engaging (100%), and the content was adequate (68.8%); however, 26.6% found the information overwhelming. Overall, 46.9% were highly satisfied with the resources.

Conclusion

A self-learning virtual patient-education package improved secondary prevention knowledge and self-care behaviour in Chinese immigrants after a heart attack. The culturally adapted version of Cardiac College™ offers an alternative education model where bilingual staff or translated resources are limited.
Three-dimensional intracardiac echocardiography for left atrial appendage sizing and percutaneous occlusion guidance
Authors: Della Rocca Domenico G , Magnocavallo Michele , Gianni Carola , Mohanty Sanghamitra , Al-Ahmad Amin , Bassiouny Mohamed , Denora Marialessia , La Fazia Vincenzo Mirco , Lavalle Carlo , Gallinghouse Gerald J , Santangeli Pasquale , Polselli Marco , Sarkozy Andrea , Vetta Giampaolo , Ahmed Adnan , Sanchez Javier E , Pannone Luigi , Chierchia Gian-Battista , Tschopp David R , de Asmundis Carlo , Di Biase Luigi , Lakkireddy Dhanunjaya , Burkhardt David J , Horton Rodney P , Natale Andrea
Published: January 2024

Aims

Left atrial appendage (LAA) imaging is critical during percutaneous occlusion procedures. 3D-intracardiac echocardiography (ICE) features direct visualization of LAA from multiple cross-sectional planes at a time. We aimed at reporting procedural success of 3D-ICE-guided LAA occlusion and the correlation between pre-procedural transoesophageal echocardiography (TEE) and intraprocedural 3D-ICE for LAA sizing.

Methods and results

Among 274 patients undergoing left atrial appendage occlusion (LAAO) with a Watchman FLX, periprocedural ICE guidance was achieved via a commercially available 2D-ICE catheter (220 patients) or a novel (NUVISION™) 3D-ICE one (54 patients). Primary endpoint was a composite of procedural success and LAA sealing at follow-up TEE. Secondary endpoint was a composite of periprocedural device recapture/resizing plus presence of leaks ≥ 3 mm at follow-up TEE. 3D-ICE measurements of maximum landing zone correlated highly with pre-procedural TEE reference values [Pearson’s: 0.94; P < 0.001; bias: −0.06 (−2.39, 2.27)]. The agreement between 3D-ICE-based device selection and final device size was 96.3% vs. 79.1% with 2D-ICE (P = 0.005). The incidence of the primary endpoint was 98.1% with 3D-ICE and 97.3% with 2D-ICE (P = 0.99). 2D-ICE patients had a trend towards a higher incidence of periprocedural device recapture/redeployment (31.5% vs. 44.5%; P = 0.09). The secondary endpoint occurred in 31.5% of 3D-ICE patients vs. 45.9% of 2D-ICE ones (P = 0.065).

Conclusion

Intracardiac echocardiography-guided LAAO showed a very high success, with no major adverse events. A very high level of agreement for LAA sizing was found between pre-procedural TEE and periprocedural 3D-ICE. 3D-ICE performed significantly better than 2D-ICE for FLX size selection and may provide better guidance during device deployment.
Incoherent noise-induced distortions of Rayleigh wave ellipticity measurements obtained with three-component beamforming
Authors: Wathelet Marc
Published: January 2024

For site characterization, the elliptic particle motion of Rayleigh waves and its frequency dependence is a well-known property that aroused less interest than the frequency dependence of the phase velocity. More than 50 yr ago, ellipticity was already recognized as providing information independent from phase velocity, despite the difficulties inherent to its accurate and precise measurement. Several techniques were developed during the last two decades to extract the ellipticity curve from ambient vibration recordings, with a single three-component (3C) station, with pairs of 3C stations and more recently with 3C arrays. The latter has the advantage over the other approaches that the sign of the ellipticity can be retrieved. Moreover, higher order mode separation is possible under certain conditions. Nevertheless, Rayleigh Three-component BeamForming (RTBF) proposed by Wathelet et al. encounters difficulties in the presence of significant levels of incoherent noise when the true ellipticity is vanishing or when it has a high absolute value. In this work, the analytical expressions of the beam power for a single source wavefield are revised under more realistic assumptions for the incoherent noise azimuthal distribution. The proposed model also includes an asymmetric distribution of the incoherent noise between vertical and horizontal components, which was not the case in the original publication. Switching from ellipticity to angular ellipticity drastically simplifies the formalism. Moreover, it naturally leads to a new steering matrix (all-component ellipticity steering) which solves the limitation around zero and infinity observed for RTBF. Interestingly, the accuracy of the ellipticity is no longer influenced by the absolute level of incoherent noise but by the difference between the incoherent noise ratio on vertical and horizontal components. A method based on the second derivative of the beam power versus the radial wavenumber is finally proposed to experimentally measure the noise ratio difference, which allows experimental values to be corrected. The methodology is compared with classical vertical beamforming and RTBF for a synthetic case and three experimental data sets.
Earthquake or blast? Classification of local-distance seismic events in Sweden using fully connected neural networks
Authors: Eggertsson Gunnar , Lund Björn , Roth Michael , Schmidt Peter
Published: January 2024

Distinguishing between different types of seismic events is a task typically performed manually by expert analysts and can thus be both time and resource expensive. Analysts at the Swedish National Seismic Network (SNSN) use four different event types in the routine analysis: natural (tectonic) earthquakes, blasts (e.g. from mines, quarries and construction) and two different types of mining-induced events associated with large, underground mines. In order to aid manual event classification and to classify automatic event definitions, we have used fully connected neural networks to implement classification models which distinguish between the four event types. For each event, we bandpass filter the waveform data in 20 narrow-frequency bands before dividing each component into four non-overlapping time windows, corresponding to the P phase, P coda, S phase and S coda. In each window, we compute the root-mean-square amplitude and the resulting array of amplitudes is then used as the neural network inputs. We compare results achieved using a station-specific approach, where individual models are trained for each seismic station, to a regional approach where a single model is trained for the whole study area. An extension of the models, which distinguishes spurious phase associations from real seismic events in automatic event definitions, has also been implemented. When applying our models to evaluation data distinguishing between earthquakes and blasts, we achieve an accuracy of about 98 per cent for automatic events and 99 per cent for manually analysed events. In areas located close to large underground mines, where all four event types are observed, the corresponding accuracy is about 90 and 96 per cent, respectively. The accuracy when distinguishing spurious events from real seismic events is about 95 per cent. We find that the majority of erroneous classifications can be traced back to uncertainties in automatic phase picks and location estimates. The models are already in use at the SNSN, both for preliminary type predictions of automatic events and for reviewing manually analysed events.
A Two-color Single-molecule Sequencing Platform and Its Clinical Applications
Authors: Chen Fang , Liu Bin , Chen Meirong , Jiang Zefei , Zhou Zhiliang , Wu Ping , Zhang Meng , Jin Huan , Li Linsen , Lu Liuyan , Shang Huan , Liu Lei , Chen Weiyue , Xu Jianfeng , Sun Ruitao , Wang Guangming , Zheng Jiao , Qi Jifang , Yang Bo , Zeng Lidong , Li Yan , Lv Hui , Zhao Nannan , Wang Wen , Cai Jinsen , Liu Yongfeng , Luo Weiwei , Zhang Juan , Zhang Yanhua , Fan Jicai , Dan Haitao , He Xuesen , Huang Wei , Sun Lei , Yan Qin
Published: January 2024

DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.
An Inverse Spectral Problem for Non-Self-Adjoint Jacobi Matrices
Authors: Pushnitski Alexander , Štampach František
Published: January 2024

We consider the class of bounded symmetric Jacobi matrices $J$ with positive off-diagonal elements and complex diagonal elements. With each matrix $J$ from this class, we associate the spectral data, which consists of a pair $(\nu ,\psi )$. Here $\nu $ is the spectral measure of $|J|=\sqrt {J^{*}J}$ and $\psi $ is a phase function on the real line satisfying $|\psi |\leq 1$ almost everywhere with respect to the measure $\nu $. Our main result is that the map from $J$ to the pair $(\nu ,\psi )$ is a bijection between our class of Jacobi matrices and the set of all spectral data.
Stability Analysis of Two-Dimensional Ideal Flows With Applications to Viscous Fluids and Plasmas
Authors: Arsénio Diogo , Houamed Haroune
Published: January 2024

We are interested in the stability analysis of two-dimensional incompressible inviscid fluids. Specifically, we revisit a known recent result on the stability of Yudovich’s solutions to the incompressible Euler equations in $L^{\infty }([0,T];H^{1})$ by providing a new approach to its proof based on the idea of compactness extrapolation and by extending it to the whole plane. This new method of proof is robust and, when applied to viscous models, leads to a remarkable logarithmic improvement on the rate of convergence in the vanishing viscosity limit of two-dimensional fluids. Loosely speaking, this logarithmic gain is the result of the fact that, in appropriate high-regularity settings, the smoothness of solutions to the Euler equations at times $t\in [0,T)$ is strictly higher than their regularity at time $t=T$. This “memory effect” seems to be a general principle that is not exclusive to fluid mechanics. It is therefore likely to be observed in other setting and deserves further investigation. Finally, we also apply the stability results on Euler systems to the study of two-dimensional ideal plasmas and establish their convergence, in strong topologies, to solutions of magnetohydrodynamic systems, when the speed of light tends to infinity. The crux of this asymptotic analysis relies on a fine understanding of Maxwell’s system.
Single-Cell Profiling of the Differential In Vivo Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Lung Tissue Cell Subtypes at the Protein Level
Authors: Fotooh Abadi Leila , Sharma Madhav B , Kelesidis Theodoros
Published: January 2024

The complexity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its variants in lung cells can truly be characterized only at the tissue and protein levels among unique cell subtypes. However, in vivo data are limited due to lack of accessible human tissues. Using a transgenic mouse model of SARS-CoV-2 infection and flow cytometry, we provide in vivo novel insight at the protein level that the differential impact of SARS-CoV-2 (Wuhan strain) and its B.1.617.2 (Delta) and BA.1 (Omicron) variants on lung may be attributed to differential patterns of viral protein levels among ciliated airway cells, alveolar types 1 and 2 cells, immune cells, and endothelial lung cells.
Vaccine-Boosted CCP Decreases Virus Replication and Hastens Resolution of Infection Despite Transiently Enhancing Disease in SARS-CoV-2–Infected Hamsters
Authors: Carroll Timothy D , Wong Talia , Morris Mary Kate , Di Germanio Clara , Ma Zhong-min , Stone Mars , Ball Erin , Fritts Linda , Rustagi Arjun , Simmons Graham , Busch Michael , Miller Christopher J
Published: January 2024

Definitive data demonstrating the utility of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) for treating immunocompromised patients remains elusive. To better understand the mechanism of action of CCP, we studied viral replication and disease progression in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–infected hamsters treated with CCP obtained from recovered COVID-19 patients that were also vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. Vaxplas transiently enhanced disease severity and lung pathology in hamsters treated near peak viral replication due to immune complex and activated complement deposition in pulmonary endothelium, and recruitment of M1 proinflammatory macrophages into the lung parenchyma. However, aside from one report, transient enhanced disease has not been reported in CCP recipient patients, and the transient enhanced disease in Vaxplas hamsters may have been due to mismatched species IgG-FcR interactions, infusion timing, or other experimental factors. Despite transient disease enhancement, Vaxplas dramatically reduced virus replication in lungs and improved infection outcome in SARS-CoV-2–infected hamsters.
Activity of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against clinical Gram-negative isolates—SMART United States 2019–21
Authors: Karlowsky James A , Lob Sibylle H , Bauer Karri A , Esterly John , Siddiqui Fakhar , Young Katherine , Motyl Mary R , Sahm Daniel F
Published: January 2024

Background

Ongoing national and international surveillance efforts are critical components of antimicrobial stewardship, resistance monitoring, and drug development programs. In this report, we summarize the results of ceftolozane/tazobactam, imipenem/relebactam, ceftazidime/avibactam and comparator agent testing against 10 509 Enterobacterales and 2524 Pseudomonas aeruginosa collected by USA clinical laboratories in 2019–21 as part of the SMART global surveillance programme.

Methods

MICs were determined by CLSI broth microdilution and interpreted using 2023 CLSI M100 breakpoints.

Results

Most Enterobacterales were ceftazidime/avibactam susceptible (>99%), meropenem susceptible (99%) and ceftolozane/tazobactam susceptible (94%). Non-Morganellaceae Enterobacterales were also highly susceptible to imipenem/relebactam (99%). Ceftolozane/tazobactam inhibited 94% of Escherichia coli and 89% of Klebsiella pneumoniae with ceftriaxone non-susceptible/non-carbapenem-resistant phenotypes. Against P. aeruginosa, ceftolozane/tazobactam (97% susceptible) was more active than ceftazidime/avibactam (95%) and imipenem/relebactam (91%). MDR and difficult-to-treat resistance (DTR) phenotypes were identified in 13% and 7% of P. aeruginosa isolates, respectively. Ceftolozane/tazobactam remained active against 78% of MDR P. aeruginosa (13% and 23% higher than ceftazidime/avibactam and imipenem/relebactam, respectively) and against 74% of DTR P. aeruginosa (24% and 37% higher than ceftazidime/avibactam and imipenem/relebactam, respectively). Length of hospital stay at the time of specimen collection, ward type and infection type resulted in percent susceptible value differences of >5% across isolate demographic strata for some antimicrobial agent/pathogen combinations.

Conclusions

We conclude that in the USA, in 2019–21, carbapenem (meropenem) resistance remained uncommon in Enterobacterales and ceftolozane/tazobactam was more active than both ceftazidime/avibactam and imipenem/relebactam against P. aeruginosa.
Antifungal mechanism of rose, mustard, and their blended essential oils against Cladosporium allicinum isolated from Xinjiang naan and its storage application
Authors: Yuan Yu-Han , Lin Xiang-Na , Xu Xiao-Mei , Liu Ling-Xiao , Li Xing-Jiang , Liu Yun-Guo
Published: January 2024

Aims

To reveal the inhibition mechanism of rose, mustard, and blended essential oils against Cladosporium allicinum isolated from Xinjiang naan, and investigate the effect of the three essential oils on oxidative damage and energy metabolism.

Methods and results

Rose and mustard essential oils significantly inhibited mycelial growth and spore viability in a dose-dependent relationship. After essential oil treatment, the cell membrane permeability was altered, and significant leakage of intracellular proteins and nucleic acids occurred. SEM observations further confirmed the disruption of cell structure. ROS, MDA, and SOD measurements indicated that essential oil treatment induced a redox imbalance in C. allicinum, leading to cell death. As for energy metabolism, essential oil treatment significantly reduced Na+K+-ATPase, Ca2+Mg2+-ATPase, MDH activity, and CA content, impairing metabolic functions. Finally, storage experiments showed that all three essential oils ensured better preservation of naan, with mustard essential oil having the best antifungal effect.

Conclusions

Rose and mustard essential oils and their blends can inhibit C. allicinum at multiple targets and pathways, destroying cell morphological structure and disrupting metabolic processes.
An economic evaluation of the expansion of electronic case reporting in an academic healthcare setting
Authors: Hartsell Joel , Wilson Fernando A , Shoaf Kimberley , Dunn Angela , Samore Matthew H , Staes Catherine Janes
Published: January 2024

Objectives

Determine the economic cost or benefit of expanding electronic case reporting (eCR) for 29 reportable conditions beyond the initial eCR implementation for COVID-19 at an academic health center.

Materials and methods

The return on investment (ROI) framework was used to quantify the economic impact of the expansion of eCR from the perspective of an academic health system over a 5-year time horizon. Sensitivity analyses were performed to assess key factors such as personnel cost, inflation, and number of expanded conditions.

Results

The total implementation costs for the implementation year were estimated to be $5031.46. The 5-year ROI for the expansion of eCR for the 29 conditions is expected to be 142% (net present value of savings: $7166). Based on the annual ROI, estimates suggest that the savings from the expansion of eCR will cover implementation costs in approximately 4.8 years. All sensitivity analyses yielded a strong ROI for the expansion of eCR.

Discussion and conclusion

Our findings suggest a strong ROI for the expansion of eCR at UHealth, with the most significant cost savings observed implementing eCR for all reportable conditions. An early effort to ensure data quality is recommended to expedite the transition from parallel reporting to production to improve the ROI for healthcare organizations. This study demonstrates a positive ROI for the expansion of eCR to additional reportable conditions beyond COVID-19 in an academic health setting, such as UHealth. While this evaluation focuses on the 5-year time horizon, the potential benefit could extend further.