bluuebunny/crossref_metadata_2025 huggingface dataset:
Naimark dilations of qubit POVMs and joint measurements
Authors: Pellonpää Juha-Pekka , Designolle Sébastien , Uola Roope
Published: March 2023

Measurement incompatibility is one of the cornerstones of quantum theory. This phenomenon appears in many forms, of which the concept of non-joint measurability has received considerable attention in the recent years. In order to characterise this non-classical phenomenon, various analytical and numerical methods have been developed. The analytical approaches have mostly concentrated on the qubit case, as well as to scenarios involving sets of measurements with symmetries, such as position and momentum or sets of mutually unbiased bases. The numerical methods can, in principle, decide any finite-dimensional and discrete joint measurability problem, but they naturally have practical limitations in terms of computational power. These methods exclusively start from a given set of measurements and ask whether the set possesses incompatibility. Here, we take a complementary approach by asking which measurements are compatible with a given measurement. It turns out, that this question can be answered in full generality through a minimal Naimark dilation of the given measurement: the set of interest is exactly those measurements that have a block-diagonal representation in such dilation. We demonstrate the use of the technique through various qubit examples, leading to an alternative characterisation of all compatible pairs of binary qubit measurements, which retrieves the celebrated Busch criterion. We further apply the technique to special examples of trinary and continuous qubit measurements.
Hybrid quantum-classical dynamics of pure-dephasing systems
*
Authors: Manfredi Giovanni , Rittaud Antoine , Tronci Cesare
Published: March 2023

We consider the interaction dynamics of a classical oscillator and a quantum two-level system for different pure-dephasing Hamiltonians of the type

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. This type of systems represents a severe challenge for popular hybrid quantum–classical descriptions. For example, in the case of the common Ehrenfest model, the classical density evolution is shown to decouple entirely from the pure-dephasing quantum dynamics. We focus on a recently proposed hybrid wave equation that is based on Koopman’s wavefunction description of classical mechanics. This model retains quantum–classical correlations whenever a coupling potential is present. Here, several benchmark problems are considered and the results are compared with those arising from fully quantum dynamics. A good agreement is found for a series of study cases involving harmonic oscillators with linear and quadratic coupling, as well as time-varying coupling parameters. In all these cases the classical evolution coincides exactly with the oscillator dynamics resulting from the fully quantum description. In the special case of time-independent coupling involving a classical oscillator with varying frequency, the quantum Bloch rotation exhibits peculiar features that escape from the hybrid description. In addition, nonlinear corrections to the harmonic Hamiltonian lead to an overall growth of decoherence at long times, which is absent in the fully quantum treatment.
Information parity increases on functional brain networks under influence of a psychedelic substance
Authors: Viol Aline , Viswanathan Gandhimohan M , Soldatkina Oleksandra , Palhano-Fontes Fernanda , Onias Heloisa , de Araujo Draulio , Hövel Philipp
Published: March 2023

The physical basis of consciousness is one of the most intriguing open questions that contemporary science aims to solve. By approaching the brain as an interactive information system, complex network theory has greatly contributed to understand brain process in different states of mind. We study a non-ordinary state of mind by comparing resting-state functional brain networks of individuals in two different conditions: before and after the ingestion of the psychedelic brew Ayahuasca. In order to quantify the functional, statistical symmetries between brain region connectivity, we calculate the pairwise information parity of the functional brain networks. Unlike the usual approach to quantitative network analysis that considers only local or global scales, information parity instead quantifies pairwise statistical similarities over the entire network structure. We find an increase in the average information parity on brain networks of individuals under psychedelic influences. Notably, the information parity between regions from the limbic system and frontal cortex is consistently higher for all the individuals while under the psychedelic influence. These findings suggest that the resemblance of statistical influences between pair of brain regions activities tends to increase under Ayahuasca effects. This could be interpreted as a mechanism to maintain the network functional resilience.
ResNetKhib: a novel cell type-specific tool for predicting lysine 2-hydroxyisobutylation sites via transfer learning
Authors: Jia Xiaoti , Zhao Pei , Li Fuyi , Qin Zhaohui , Ren Haoran , Li Junzhou , Miao Chunbo , Zhao Quanzhi , Akutsu Tatsuya , Dou Gensheng , Chen Zhen , Song Jiangning
Published: March 2023

Lysine 2-hydroxyisobutylation (Khib), which was first reported in 2014, has been shown to play vital roles in a myriad of biological processes including gene transcription, regulation of chromatin functions, purine metabolism, pentose phosphate pathway and glycolysis/gluconeogenesis. Identification of Khib sites in protein substrates represents an initial but crucial step in elucidating the molecular mechanisms underlying protein 2-hydroxyisobutylation. Experimental identification of Khib sites mainly depends on the combination of liquid chromatography and mass spectrometry. However, experimental approaches for identifying Khib sites are often time-consuming and expensive compared with computational approaches. Previous studies have shown that Khib sites may have distinct characteristics for different cell types of the same species. Several tools have been developed to identify Khib sites, which exhibit high diversity in their algorithms, encoding schemes and feature selection techniques. However, to date, there are no tools designed for predicting cell type-specific Khib sites. Therefore, it is highly desirable to develop an effective predictor for cell type-specific Khib site prediction. Inspired by the residual connection of ResNet, we develop a deep learning-based approach, termed ResNetKhib, which leverages both the one-dimensional convolution and transfer learning to enable and improve the prediction of cell type-specific 2-hydroxyisobutylation sites. ResNetKhib is capable of predicting Khib sites for four human cell types, mouse liver cell and three rice cell types. Its performance is benchmarked against the commonly used random forest (RF) predictor on both 10-fold cross-validation and independent tests. The results show that ResNetKhib achieves the area under the receiver operating characteristic curve values ranging from 0.807 to 0.901, depending on the cell type and species, which performs better than RF-based predictors and other currently available Khib site prediction tools. We also implement an online web server of the proposed ResNetKhib algorithm together with all the curated datasets and trained model for the wider research community to use, which is publicly accessible at https://resnetkhib.erc.monash.edu/.
Development of a TMErisk model based on immune infiltration in tumour microenvironment to predict prognosis of immune checkpoint inhibitor treatment in hepatocellular carcinoma
Authors: Yan Zi-Jun , Yu Chu-Ting , Chen Lei , Wang Hong-Yang
Published: March 2023

Immune checkpoint inhibitor (ICI) treatment has created the opportunity of improved outcome for patients with hepatocellular carcinoma (HCC). However, only a minority of HCC patients benefit from ICI treatment owing to poor treatment efficacy and safety concerns. There are few predictive factors that precisely stratify HCC responders to immunotherapy. In this study, we developed a tumour microenvironment risk (TMErisk) model to divide HCC patients into different immune subtypes and evaluated their prognosis. Our results indicated that virally mediated HCC patients who had more common tumour protein P53 (TP53) alterations with lower TMErisk scores were appropriate for ICI treatment. HCC patients with alcoholic hepatitis who more commonly harboured catenin beta 1 (CTNNB1) alterations with higher TMErisk scores could benefit from treatment with multi-tyrosine kinase inhibitors. The developed TMErisk model represents the first attempt to anticipate tumour tolerance of ICIs in the TME through the degree of immune infiltration in HCCs.
Machine learning on protein–protein interaction prediction: models, challenges and trends
Authors: Tang Tao , Zhang Xiaocai , Liu Yuansheng , Peng Hui , Zheng Binshuang , Yin Yanlin , Zeng Xiangxiang
Published: March 2023

Protein–protein interactions (PPIs) carry out the cellular processes of all living organisms. Experimental methods for PPI detection suffer from high cost and false-positive rate, hence efficient computational methods are highly desirable for facilitating PPI detection. In recent years, benefiting from the enormous amount of protein data produced by advanced high-throughput technologies, machine learning models have been well developed in the field of PPI prediction. In this paper, we present a comprehensive survey of the recently proposed machine learning-based prediction methods. The machine learning models applied in these methods and details of protein data representation are also outlined. To understand the potential improvements in PPI prediction, we discuss the trend in the development of machine learning-based methods. Finally, we highlight potential directions in PPI prediction, such as the use of computationally predicted protein structures to extend the data source for machine learning models. This review is supposed to serve as a companion for further improvements in this field.
NGenomeSyn: an easy-to-use and flexible tool for publication-ready visualization of syntenic relationships across multiple genomes
Authors: He Weiming , Yang Jian , Jing Yi , Xu Lian , Yu Kang , Fang Xiaodong
Published: March 2023

Large-scale comparative genomic studies have provided important insights into species evolution and diversity, but also lead to a great challenge to visualize. Quick catching or presenting key information hidden in the vast amount of genomic data and relationships among multiple genomes requires an efficient visualization tool. However, current tools for such visualization remain inflexible in layout and/or require advanced computation skills, especially for visualization of genome-based synteny. Here, we developed an easy-to-use and flexible layout tool, NGenomeSyn [multiple (N) Genome Synteny], for publication-ready visualization of syntenic relationships of the whole genome or local region and genomic features (e.g. repeats, structural variations, genes) across multiple genomes with a high customization. NGenomeSyn provides an easy way for its users to visualize a large amount of data with a rich layout by simply adjusting options for moving, scaling, and rotation of target genomes. Moreover, NGenomeSyn could be applied on the visualization of relationships on non-genomic data with similar input formats.

Availability and implementation

NGenomeSyn is freely available at GitHub (https://github.com/hewm2008/NGenomeSyn) and Zenodo (https://doi.org/10.5281/zenodo.7645148).
The logarithmic transformation in bivariate allometry
Authors: Packard Gary C
Published: March 2023

The field of biological allometry has been dominated since early in the last century by the logarithmic transformation, which is widely perceived to be necessary for the proper analysis of bivariate data relating the size of a structure or the intensity of a process to some measure of body size. Some investigators argue that transformation is needed to align the analysis with underlying theory; others assert that transformation is required to describe multiplicative growth in living substance; and still other workers believe that transformation is necessary to accommodate multiplicative variation in the response variable (heteroscedasticity) and/or a lognormal distribution for residuals from the fitted equation. None of these beliefs is true. Moreover, constraints imposed by logarithmic transformation typically result in data being ‘fitted’ to a predetermined statistical model instead of a model being fitted to the data, thereby leading in many instances to erroneous perceptions of pattern in the data, misinterpretation of the findings and misdirection for future research. Robust statistical models with different functional form and different assumptions about random error can be fitted directly to the original data by non-linear regression, thereby obviating transformation altogether. The utility of the regression protocol is illustrated in a re-analysis of published data.
Climate change and the brain
Authors: Sisodiya Sanjay M
Published: March 2023

Heatwaves are becoming more common as a result of climate change. Sanjay Sisodiya discusses some of the potential impacts of climate change on the nervous system, particularly in individuals with neurological disorders, and emphasizes the need to take action now to help mitigate these effects.
Loss of age-related laminar differentiation of intracortical myelin in bipolar disorder
Authors: Suh Jee Su , Rowley Christopher D , Sehmbi Manpreet , Tardif Christine L , Minuzzi Luciano , Bock Nicholas A , Frey Benicio N
Published: March 2023

Age-related changes of intracortical myelin in bipolar disorder (BD) have been observed to deviate from the quadratic age curve observed in healthy controls (HC), but it is unclear if this holds at varying cortical depths. From BD (n = 44; age range = 17.6–45.5 years) and HC (n = 60; age range = 17.1–45.8 years) participants, we collected 3T T1-weighted (T1w) images with strong intracortical contrast. Signal values were sampled from 3 equivolume cortical depths. Linear mixed models were used to compare age-related changes in the T1w signal between depths and between groups at each depth. In HC, the age-related changes were significantly different between the superficial one-fourth depth and the deeper depths in the right ventral somatosensory (t = −4.63; FDRp = 0.00025), left dorsomedial somatosensory (t = −3.16; FDRp = 0.028), left rostral ventral premotor (t = −3.16; FDRp = 0.028), and right ventral inferior parietal cortex (t = −3.29; FDRp = 0.028). BD participants exhibited no differences in the age-related T1w signal between depths. Illness duration was negatively correlated with the T1w signal at the one-fourth depth in the right anterior cingulate cortex (rACC; rho = −0.50; FDRp = 0.029). Physiological age-related and depth-specific variation in the T1w signal were not observed in BD. The T1w signal in the rACC may reflect lifetime disease burden in the disorder.
A fast algorithm to approximate the spectral density of locally tree-like networks with assortativity
Authors: Guzman Grover E C , Fujita André
Published: March 2023

Graphs have become crucial for representing and examining biological, social and technological interactions. In this context, the graph spectrum is an exciting feature to be studied because it encodes the structural and dynamic characteristics of the graph. Hence, it becomes essential to efficiently compute the graph’s spectral distribution (eigenvalue’s density function). Recently, some authors proposed degree-based methods to obtain the spectral density of locally tree-like networks in linear time. The bottleneck of their approach is that they assumed that the graph’s assortativity is zero. However, most real-world networks, such as social and biological networks, present assortativity. Consequently, their spectral density approximations may be inaccurate. Here, we propose a method that considers assortativity. Our algorithm’s time and space complexities are $\mathscr{O}(d_{\max}^{2})$, where $d_{\max}$ is the largest degree of the graph. Finally, we show our method’s efficacy in simulated and empirical networks.
Overcoming professional barriers encountered by women in interventional cardiology: an EAPCI statement
Authors: Buchanan Gill Louise , Paradies Valeria , Karam Nicole , Holmvang Lene , Mamas Mamas A , Mehilli Julinda , Capodanno Davide , Capranzano Piera , Appelman Yolande , Manzo-Silberman Stéphane , Kunadian Vijay , Mauri Josepa , Shuepke Stefanie , Petronio Anna Sonia , Kaluzna-Oleksy Marta , Gilard Martine , Morice Marie Claude , Barbato Emanuele , Dudek Dariusz , Chieffo Alaide
Published: March 2023

Despite the increasing proportion of female medical and nursing students, there is still a significant under-representation of women working as healthcare providers in interventional cardiology, with very few of them reaching senior leadership, academic positions, or acting principal investigators, as well as actively involved in company advisory boards. In this position paper, we will describe the current status of women working in interventional cardiology across Europe. We will also provide an overview of the most relevant determinants of the under-representation of women at each stage of the interventional cardiology career path and offer practical suggestions for overcoming these challenges.
Circulating ketone bodies and cardiovascular outcomes: the MESA study
Authors: Shemesh Elad , Chevli Parag Anilkumar , Islam Tareq , German Charles A , Otvos James , Yeboah Joseph , Rodriguez Fatima , deFilippi Christopher , Lima Joao A C , Blaha Michael , Pandey Ambarish , Vaduganathan Muthiah , Shapiro Michael D
Published: March 2023

Aims

Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD).

Methods and results

This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) [hazard ratio, HR (95% confidence interval, CI): 1.54 (1.12–2.12) and 1.37 (1.04–1.80) per 10-fold increase in total KB, respectively]. Participants also experienced an 87% (95% CI: 1.17–2.97) increased rate of CVD mortality and an 81% (1.45–2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB [1.68 (1.07–2.65), per 10-fold increase in total KB].

Conclusion

The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment.
Iron deficiency in pulmonary vascular disease: pathophysiological and clinical implications
Authors: Martens Pieter , Yu Shilin , Larive Brett , Borlaug Barry A , Erzurum Serpil C , Farha Samar , Finet J Emanuel , Grunig Gabriele , Hemnes Anna R , Hill Nicholas S , Horn Evelyn M , Jacob Miriam , Kwon Deborah H , Park Margaret M , Rischard Franz P , Rosenzweig Erika B , Wilcox Jennifer D , Tang Wai Hong Wilson ,   the PVDOMICS Study Group
Published: March 2023

Aims

Iron deficiency is common in pulmonary hypertension, but its clinical significance and optimal definition remain unclear.

Methods and results

Phenotypic data for 1028 patients enrolled in the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics study were analyzed. Iron deficiency was defined using the conventional heart failure definition and also based upon optimal cut-points associated with impaired peak oxygen consumption (peakVO2), 6-min walk test distance, and 36-Item Short Form Survey (SF-36) scores. The relationships between iron deficiency and cardiac and pulmonary vascular function and structure and outcomes were assessed. The heart failure definition of iron deficiency endorsed by pulmonary hypertension guidelines did not identify patients with reduced peakVO2, 6-min walk test, and SF-36 (P > 0.208 for all), but defining iron deficiency as transferrin saturation (TSAT) <21% did. Compared to those with TSAT ≥21%, patients with TSAT <21% demonstrated lower peakVO2 [absolute difference: −1.89 (−2.73 to −1.04) mL/kg/min], 6-min walk test distance [absolute difference: −34 (−51 to −17) m], and SF-36 physical component score [absolute difference: −2.5 (−1.3 to −3.8)] after adjusting for age, sex, and hemoglobin (all P < 0.001). Patients with a TSAT <21% had more right ventricular remodeling on cardiac magnetic resonance but similar pulmonary vascular resistance on catheterization. Transferrin saturation <21% was also associated with increased mortality risk (hazard ratio 1.63, 95% confidence interval 1.13–2.34; P = 0.009) after adjusting for sex, age, hemoglobin, and N-terminal pro-B-type natriuretic peptide.

Conclusion

The definition of iron deficiency in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines does not identify patients with lower exercise capacity or functional status, while a definition of TSAT <21% identifies patients with lower exercise capacity, worse functional status, right heart remodeling, and adverse clinical outcomes.
Lifelong endurance exercise and its relation with coronary atherosclerosis
Authors: De Bosscher Ruben , Dausin Christophe , Claus Piet , Bogaert Jan , Dymarkowski Steven , Goetschalckx Kaatje , Ghekiere Olivier , Van De Heyning Caroline M , Van Herck Paul , Paelinck Bernard , Addouli Haroun El , La Gerche André , Herbots Lieven , Willems Rik , Heidbuchel Hein , Claessen Guido
Published: March 2023

Aims

The impact of long-term endurance sport participation (on top of a healthy lifestyle) on coronary atherosclerosis and acute cardiac events remains controversial.

Methods and results

The Master@Heart study is a well-balanced prospective observational cohort study. Overall, 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile, were included. Peak oxygen uptake quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on computed tomography coronary angiography. Analyses were corrected for multiple cardiovascular risk factors. The median age was 55 (50–60) years in all groups. Lifelong and late-onset athletes had higher peak oxygen uptake than non-athletes [159 (143–177) vs. 155 (138–169) vs. 122 (108–138) % predicted]. Lifelong endurance sports was associated with having ≥1 coronary plaque [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.17–2.94], ≥ 1 proximal plaque (OR 1.96, 95% CI 1.24–3.11), ≥ 1 calcified plaques (OR 1.58, 95% CI 1.01–2.49), ≥ 1 calcified proximal plaque (OR 2.07, 95% CI 1.28–3.35), ≥ 1 non-calcified plaque (OR 1.95, 95% CI 1.12–3.40), ≥ 1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39–5.65), and ≥1 mixed plaque (OR 1.78, 95% CI 1.06–2.99) as compared to a healthy non-athletic lifestyle.

Conclusion

Lifelong endurance sport participation is not associated with a more favourable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum.
An artificial intelligence–based model for prediction of atrial fibrillation from single-lead sinus rhythm electrocardiograms facilitating screening
Authors: Hygrell Tove , Viberg Fredrik , Dahlberg Erik , Charlton Peter H , Kemp Gudmundsdottir Katrin , Mant Jonathan , Hörnlund Josef Lindman , Svennberg Emma
Published: March 2023

Aims

Screening for atrial fibrillation (AF) is recommended in the European Society of Cardiology guidelines. Yields of detection can be low due to the paroxysmal nature of the disease. Prolonged heart rhythm monitoring might be needed to increase yield but can be cumbersome and expensive. The aim of this study was to observe the accuracy of an artificial intelligence (AI)-based network to predict paroxysmal AF from a normal sinus rhythm single-lead ECG.

Methods and results

A convolutional neural network model was trained and evaluated using data from three AF screening studies. A total of 478 963 single-lead ECGs from 14 831 patients aged ≥65 years were included in the analysis. The training set included ECGs from 80% of participants in SAFER and STROKESTOP II. The remaining ECGs from 20% of participants in SAFER and STROKESTOP II together with all participants in STROKESTOP I were included in the test set. The accuracy was estimated using the area under the receiver operating characteristic curve (AUC). From a single timepoint ECG, the artificial intelligence–based algorithm predicted paroxysmal AF in the SAFER study with an AUC of 0.80 [confidence interval (CI) 0.78–0.83], which had a wide age range of 65–90+ years. Performance was lower in the age-homogenous groups in STROKESTOP I and STROKESTOP II (age range: 75–76 years), with AUCs of 0.62 (CI 0.61–0.64) and 0.62 (CI 0.58–0.65), respectively.

Conclusion

An artificial intelligence–enabled network has the ability to predict AF from a sinus rhythm single-lead ECG. Performance improves with a wider age distribution.
Combination of an implantable defibrillator multi-sensor heart failure index and an apnea index for the prediction of atrial high-rate events
Authors: Bertini Matteo , Vitali Francesco , D’Onofrio Antonio , Vitulano Gennaro , Calò Leonardo , Savarese Gianluca , Santobuono Vincenzo Ezio , Dello Russo Antonio , Mattera Agostino , Santoro Amato , Calvanese Raimondo , Arena Giuseppe , Amellone Claudia , Ziacchi Matteo , Palmisano Pietro , Santini Luca , Mazza Andrea , Campari Monica , Valsecchi Sergio , Boriani Giuseppe
Published: March 2023

Aims

Patients with atrial fibrillation frequently experience sleep disorder breathing, and both conditions are highly prevalent in presence of heart failure (HF). We explored the association between the combination of an HF and a sleep apnoea (SA) index and the incidence of atrial high-rate events (AHRE) in patients with implantable defibrillators (ICDs).

Methods and results

Data were prospectively collected from 411 consecutive HF patients with ICD. The IN-alert HF state was measured by the multi-sensor HeartLogic Index (>16), and the ICD-measured Respiratory Disturbance Index (RDI) was computed to identify severe SA. The endpoints were as follows: daily AHRE burden of ≥5 min, ≥6 h, and ≥23 h. During a median follow-up of 26 months, the time IN-alert HF state was 13% of the total observation period. The RDI value was ≥30 episodes/h (severe SA) during 58% of the observation period. An AHRE burden of ≥5 min/day was documented in 139 (34%) patients, ≥6 h/day in 89 (22%) patients, and ≥23 h/day in 68 (17%) patients. The IN-alert HF state was independently associated with AHRE regardless of the daily burden threshold: hazard ratios from 2.17 for ≥5 min/day to 3.43 for ≥23 h/day (P < 0.01). An RDI ≥ 30 episodes/h was associated only with AHRE burden ≥5 min/day [hazard ratio 1.55 (95% confidence interval: 1.11–2.16), P = 0.001]. The combination of IN-alert HF state and RDI ≥ 30 episodes/h accounted for only 6% of the follow-up period and was associated with high rates of AHRE occurrence (from 28 events/100 patient-years for AHRE burden ≥5 min/day to 22 events/100 patient-years for AHRE burden ≥23 h/day).

Conclusions

In HF patients, the occurrence of AHRE is independently associated with the ICD-measured IN-alert HF state and RDI ≥ 30 episodes/h. The coexistence of these two conditions occurs rarely but is associated with a very high rate of AHRE occurrence.

Clinical trial registration

URL: http://clinicaltrials.gov/Identifier: NCT02275637.
A targeted genetic modifier screen in Drosophila uncovers vulnerabilities in a genetically complex model of colon cancer
Authors: Datta Ishwaree , Vassel Tajah , Linkous Benjamin , Odum Tyler , Drew Christian , Taylor Andrew , Bangi Erdem
Published: March 2023

Received on 16 January 2023; accepted on 21 February 2023Kinases are key regulators of cellular signal transduction pathways. Many diseases, including cancer, are associated with global alterations in protein phosphorylation networks. As a result, kinases are frequent targets of drug discovery efforts. However, target identification and assessment, a critical step in targeted drug discovery that involves identifying essential genetic mediators of disease phenotypes, can be challenging in complex, heterogeneous diseases like cancer, where multiple concurrent genomic alterations are common. Drosophila is a particularly useful genetic model system to identify novel regulators of biological processes through unbiased genetic screens. Here, we report 2 classic genetic modifier screens focusing on the Drosophila kinome to identify kinase regulators in 2 different backgrounds: KRAS TP53 PTEN APC, a multigenic cancer model that targets 4 genes recurrently mutated in human colon tumors and KRAS alone, a simpler model that targets one of the most frequently altered pathways in cancer. These screens identified hits unique to each model and one shared by both, emphasizing the importance of capturing the genetic complexity of human tumor genome landscapes in experimental models. Our follow-up analysis of 2 hits from the KRAS-only screen suggests that classical genetic modifier screens in heterozygous mutant backgrounds that result in a modest, nonlethal reduction in candidate gene activity in the context of a whole animal—a key goal of systemic drug treatment—may be a particularly useful approach to identify the most rate-limiting genetic vulnerabilities in disease models as ideal candidate drug targets.
Social Media Use May Not Be As Bad As Some Suggest: Implication for Older Adults
Authors: Cotten Shelia R , Ghaiumy Anaraky Reza , Schuster Amy M
Published: March 2023

Background and Objectives

Social media use (SMU) has increased over the past decade among older adults. Cross-sectional studies report SMU is related to negative mental health outcomes (i.e., depression). Given depression is the most common mental health issue for older adults and increases the risk of morbidity and mortality, determining longitudinally whether SMU is related to increased depression is critical. This study examined the longitudinal relationship between SMU and depression.

Research Design and Methods

Data from 6 waves (2015–20) of the National Health and Aging Trends Study (NHATS) were analyzed. Participants included a nationally representative sample of U.S. older adults, aged 65 years and older (N = 7,057). We used a Random Intercept Cross-Lagged Panel Modeling (RI-CLPM) framework to examine the relationship between primary outcomes of SMU and depression symptoms.

Results

No pattern was found of SMU predicting depression symptoms, or depression symptoms predicting SMU. The major driver of SMU in each wave was SMU in the previous wave. On average, our model accounted for 3.03% of the variance in SMU. The major predictor of depression in each wave was the pre-existing depression. Our model accounted for an average of 22.81% of the variance in depressive symptoms.

Discussion and Implications

The results suggest that SMU and depressive symptoms are driven by the previous patterns of SMU and depression, respectively. We did not find any patterns of SMU and depression influencing each other. NHATS measures SMU with a binary instrument. Future longitudinal research should employ measures that account for SMU duration, type, and purpose. These findings suggest that SMU may not be related to negative health outcomes, in this case, depression, for older adults.
Setting thresholds for good ecosystem state in marine seabed systems and beyond
Authors: Hiddink J G , Valanko S , Delargy A J , van Denderen P D
Published: March 2023

One of the aims of environmental management is to achieve good ecosystem state. Assessing the state needs to be informed by thresholds above which state is defined as “good” for both the quality that defines good state, and the extent of the habitat that needs to be in such a quality. Operationalizing such thresholds has been carried out using a wide variety of approaches, with, often, haphazard and subjective outcomes. Here, we review approaches for setting “good-state” thresholds and evaluate their strengths and weaknesses for application to marine seabed ecosystems. Only two approaches defined a current ecologically meaningful good state and estimated thresholds quantitatively from data, while two other approaches (“avoid collapse” and “allow recovery”) would result in a state that could recover to good in the future. Other methods were subjective in the choice of threshold or based on statistically detectable thresholds rather than thresholds between good and not good or degraded state. We argue that the most objective method for setting a good-state threshold is based on maintaining the state within the range of natural variation in undisturbed systems. Preliminary time-series analyses of marine seabed community biomass suggest this threshold is located between 54 and 79% of the undisturbed state.
Regularity analysis for SEEs with multiplicative fBms and strong convergence for a fully discrete scheme
Authors: Ding Xiao-Li , Wang Dehua
Published: March 2023

One of the open problems in the study of stochastic differential equations is regularity analysis and approximations to stochastic partial differential equations driven by multiplicative fractional Brownian motions (fBms), especially for the case $H\in (0,\frac {1}{2})$. In this paper, we address this problem by considering a class of stochastic evolution equations (SEEs) driven by multiplicative fBms. We analyze the well-posedness and regularity of mild solutions to such equations with $H\in (0,\frac {1}{2})$ and $H\in (\frac {1}{2},1)$ under the Lipschitz conditions and linear growth conditions. The two cases are treated separately. Compared with the standard Brownian motion case, the main difficulty is that fBm is neither a Markov process nor a semimartingale such that some classical stochastic calculus theories are unavailable. As a consequence, we need to explore some new strategies to complete the existence and uniqueness and regularity analysis of the solutions. Especially for the case $H\in (0,\frac {1}{2})$, we utilize some delicate techniques to overcome the difficulties from the singularity of the covariance of fBms. In addition, we give a fully discrete scheme for such equations, carried out by the spectral Galerkin method in space and a time-stepping method in time. The obtained regularity results of the equations help us to examine the strong convergence of the discrete scheme. In final, several numerical examples are done to substantiate the theoretical findings.
(0,2) Mirror Symmetry on Homogeneous Hopf Surfaces
Authors: Álvarez-Cónsul Luis , De Arriba De La Hera Andoni , Garcia-Fernandez Mario
Published: March 2023

In this work, we find the first examples of (0,2) mirror symmetry on compact non-Kähler complex manifolds. For this, we follow Borisov’s approach to mirror symmetry using vertex algebras and the chiral de Rham complex. Our examples of (0,2) mirrors are given by pairs of Hopf surfaces endowed with a Bismut-flat pluriclosed metric. Requiring that the geometry is homogeneous, we reduce the problem to the study of Killing spinors on a quadratic Lie algebra and the construction of embeddings of the $N=2$ superconformal vertex algebra in the superaffine vertex algebra, combined with topological T-duality.
Piperacillin/tazobactam versus cefepime or carbapenems for cefoxitin-non-susceptibleEnterobacter cloacae,Klebsiella aerogenes,Citrobacter freundii,Serratia marcescensandMorganella morganiibacteraemia in immunocompromised patients
Authors: Lu Brian , Wong Miranda , Ha David , Bounthavong Mark , Banaei Niaz , Deresinski Stanley , Diep Calvin
Published: March 2023

Background

The role of piperacillin/tazobactam for treatment of serious infections due to AmpC-producing organisms remains debatable, particularly in immunocompromised patients.

Methods

This was a retrospective cohort study in immunocompromised patients that investigated the effect of definitive treatment with either piperacillin/tazobactam versus cefepime or carbapenems for bacteraemia caused by cefoxitin-non-susceptible Enterobacterales. The primary endpoint was a composite of clinical and microbiological failure. A logistic regression model was constructed to assess the impact of definitive treatment choice on the primary endpoint.

Results

A total of 81 immunocompromised patients with blood cultures positive for cefoxitin-non-susceptible Enterobacterales were included for analysis. There was more microbiological failure in the piperacillin/tazobactam arm compared with the cefepime/carbapenem arm (11.4% versus 0.0%, P = 0.019). Definitive treatment with cefepime or a carbapenem was associated with a decreased odds of clinical or microbiological failure (OR 0.303, 95% CI 0.093–0.991, P = 0.048) when controlling for baseline characteristics.

Conclusions

In immunocompromised patients with bacteraemia due to cefoxitin-non-susceptible Enterobacterales, definitive treatment with piperacillin/tazobactam was associated with an increased risk of microbiological failure and higher odds of clinical or microbiological failure compared with cefepime or carbapenems.
Comparing efficacy and safety of high-dose and standard-dose rifampicin in the treatment of brucellosis: a randomized clinical trial
Authors: Salehi Mohammadreza , Farbod Farnaz , Khalili Hossein , Rahmani Hamid , Jafari Sirous , Abbasi Ali
Published: March 2023

Background

In a few studies, higher doses of rifampicin improved the outcome of patients with TB. There is no information regarding efficacy and safety of higher doses of rifampicin in patients with brucellosis.

Objectives

To compare efficacy and safety of higher and standard doses of rifampicin, each with doxycycline, in the treatment of patients with brucellosis.

Methods

Within a randomized clinical trial, clinical response and adverse events of high-dose rifampicin (900–1200 mg/day) plus doxycycline 100 mg twice daily were compared with standard-dose rifampicin (600 mg/day) plus doxycycline 100 mg twice daily in 120 patients with brucellosis.

Results

Clinical response occurred in 57 (95%) of patients in the high-dose group and 49 (81.66%) of patients in the standard-dose group (P = 0.04). The most common adverse events of the treatment were nausea (37.5%), skin rash (13.33%), vomiting (10%) and transaminitis (7.22%). Incidence of these events was comparable between the groups.

Conclusions

The rate of clinical response in patients with brucellosis who were treated with high-dose rifampicin plus standard-dose doxycycline was significantly higher than in the patients who received the standard doses of rifampicin and doxycycline, without further adverse events. The high-dose rifampicin therefore improved clinical response in patients with brucellosis with a similar safety profile to the standard dose. If these findings are confirmed in future studies, higher doses of rifampicin may be recommended for treatment of patients with brucellosis.
Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program
Authors: Lorman Vitaly , Rao Suchitra , Jhaveri Ravi , Case Abigail , Mejias Asuncion , Pajor Nathan M , Patel Payal , Thacker Deepika , Bose-Brill Seuli , Block Jason , Hanley Patrick C , Prahalad Priya , Chen Yong , Forrest Christopher B , Bailey L Charles , Lee Grace M , Razzaghi Hanieh
Published: March 2023

Objectives

Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC.

Materials and Methods

We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N = 1309) to children with (N = 6545) and without (N = 6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls.

Results

We found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise.

Discussion

Our study addresses methodological limitations of prior studies that rely on prespecified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes.

Conclusion

We identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.
Artificial Intelligence in Breast Imaging: Challenges of Integration Into Clinical Practice
Authors: Ozcan B Bersu , Patel Bhavika K , Banerjee Imon , Dogan Basak E
Published: March 2023

Artificial intelligence (AI) in breast imaging is a rapidly developing field with promising results. Despite the large number of recent publications in this field, unanswered questions have led to limited implementation of AI into daily clinical practice for breast radiologists. This paper provides an overview of the key limitations of AI in breast imaging including, but not limited to, limited numbers of FDA-approved algorithms and annotated data sets with histologic ground truth; concerns surrounding data privacy, security, algorithm transparency, and bias; and ethical issues. Ultimately, the successful implementation of AI into clinical care will require thoughtful action to address these challenges, transparency, and sharing of AI implementation workflows, limitations, and performance metrics within the breast imaging community and other end-users.
A9 INTESTINAL ORGANOID TRANSPLANTATION REVERSED THE INTESTINAL EPITHELIUM DAMAGE IN EXPERIMENTAL NECROTIZING ENTEROCOLITIS
Authors: Li B , Lee C , Cadete M , Lee D , Zhu H , Sherman P , Pierro A
Published: March 2023

NOT PUBLISHED AT AUTHOR’S REQUEST

Please acknowledge all funding agencies by checking the applicable boxes below

CIHR

Disclosure of Interest

None Declared
A51 INTESTINAL MICROBIOTA DETERMINES ARYL HYDROCARBON RECEPTOR ACTIVATION AND SUSCEPTIBILITY TO COLITIS
Authors: Rondeau L , Haas D , Wang X , Caminero A
Published: March 2023

Background

Intestinal microbiota, diet, and the immune system have been proposed to contribute to the development of inflammatory bowel diseases (IBD). The aryl hydrocarbon receptor (AhR) is a critical regulator of intestinal immunity and mucosal barrier homeostasis that is activated by agonists such as host and microbial tryptophan metabolites. IBD patients have altered microbiota and reduced AhR agonists in intestinal content resulting in the downregulation of AhR. These findings necessitate further study to understand how diet-microbiota interactions contribute to intestinal inflammation.

Purpose

To study the influence of intestinal microbiota on tryptophan metabolism, AhR activation, and colitis severity.

Method

8- to 10-week-old germ-free C57BL/6 mice were colonized with cecal content of mice harbouring specific pathogen-free (SPF) or a limited and well-defined altered Schaedler flora (ASF) microbiota. Germ-free mice were used as controls. Three weeks following colonization, mucosal injury was induced in a subset of mice with dextran sulfate sodium (DSS) in drinking water for five days followed by two days of water recovery. Activation of AhR was measured in stool using an in vitro AhR luciferase reporter assay. Stool AhR agonists were determined using high-performance liquid chromatography coupled to high-resolution mass spectrometry. Colonic expression of AhR pathway genes Cyp1a1, Il22, Ahrr, Ahr, and Il17 was evaluated by RT-qPCR. Susceptibility to colitis was assessed by analysing stool consistency and stool blood, colonic microscopic damage, immune infiltration by immunohistochemistry, and pro-inflammatory gene expression (NanoString). Fecal microbiota was analysed by 16S rRNA gene sequencing (Illumina).

Result(s)

AhR agonists, AhR activation in vitro, and AhR pathway gene expression were elevated in mice colonized with SPF microbiota in comparison to mice colonized with ASF microbiota and germ-free mice. In ASF-colonized mice, DSS induced more severe inflammation than in SPF-colonized mice, as demonstrated by worsened mucosal injury, greater weight loss, and softer stools. SPF-colonized mice developed less mucosal immune cell infiltration and pro-inflammatory gene signaling.

Conclusion(s)

Our findings suggest that intestinal microbiota composition determines the metabolic capacity to degrade tryptophan into agonists that homeostatically activate AhR. When mucosal injury is induced, mice with elevated microbiota-derived AhR agonists and AhR activation develop less severe mucosal injury and signs of colitis. This study presents a useful tool for evaluating dietary and microbial therapies in the context of a microbiota with impaired tryptophan metabolism.

Please acknowledge all funding agencies by checking the applicable boxes below

CCC, CIHR

Disclosure of Interest

None Declared