bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining refractoriness in single atrial beats using autoencoder neural networks
Authors: Ruiperez-Campillo S , Deb B , Feng R , Ganesan P , Clopton P , Rogers AJ , Narayan SM 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIH

Background
Mapping atrial fibrillation (AF) is complicated by signals which may be local or far-field, but which cannot currently be separated. This could be clarified by a knowledge of atrial refractory periods, yet these are difficult to define from monophasic action potentials (MAP) in patients. We hypothesized that transfer learning using an autoencoder neural network (ANN), first trained with less-noisy ventricular signals, can be applied to de-noise and classify atrial MAPs.

Methods
We first developed an ANN to encode MAPs in 5706 ventricular MAPs from N=42 patients (age 65±13y) during pacing (fig1. A-B). This created a latent feature space. We now tuned the ANN to classify atrial MAPs in a different cohort of patients with AF. We used a statistical loss function based on mathematical optimization to evaluate the accuracy of final representations of the MAP and classify the different signals.

Results
The autoencoder ANN reconstructed ventricular MAPs with an average similarity of 0.85 (range 0-1) (an example is shown in fig 1.B). We tested on 3000 atrial MAPs in AF patients (N=21; 67±5y, 13 women). Atrial MAPs were accurately represented (fig 1.E-F) with similarity indices that were higher than those obtained by a panel of 3 experts. Fig. 1 shows the reconstruction of different signals: ventricular MAP (fig 1.A-B), ventricular MAP with pacing artifact (fig. 1.C-D), atrial MAP (transfer learning is assumed in here; fig 1.E-F) and noise or signals with morphologies of no interest (fig 1.G-H). Fig. 2 shows the classification of signals according to the similarity metric that allows distinguishing among the different types of signals without manual annotation (p&lt;0.05 between groups).

Conclusion
Atrial refractory periods can be defined in single beats in AF patients using autoencoder neural networks and transfer learning. This approach can separate atrial beats from far-field ventricular beats and other sources of noise. Future work can study if this approach can be used to improve AF mapping or define novel physiological phenotypes.
Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events
Authors: Linz B , Hesselkilde EM , Skarsfeldt MA , Hertel JN , Sattler SM , Yan Y , Tfelt-Hansen J , Diness JG , Bentzen BH , Linz D , Jespersen T 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): This work was supported by the Novo Nordisk Foundation (Tandem Programme; #31634).

Background
Obstructive sleep apnea (OSA) creates a complex substrate for atrial fibrillation (AF), which is refractory to many clinically available pharmacological interventions.

Purpose
To investigate atrial antiarrhythmogenic properties and ventricular electrophysiological safety of small-conductance Ca2+ -activated K+ (SK)- channel inhibition in a porcine model for obstructive respiratory events.

Methods
In spontaneously breathing pigs, obstructive respiratory events were simulated by intermittent negative upper airway pressure (INAP) applied via a pressure device connected to the intubation tube. INAP was applied for 75 seconds, every 10 minutes, three times before and three times during infusion of the SK-channel inhibitor AP14145. Atrial effective refractory periods (AERP) were acquired before (Pre-INAP), during (INAP) and after (Post-) INAP. AF-inducibility was determined by a S1S2 atrial pacing protocol. For the purpose of drug safety, ventricular arrhythmicity was evaluated by heart rate adjusted QT-interval duration (QT-paced) and electromechanical window (EMW) calculation.

Results
During vehicle infusion, INAP transiently shortened AERP (Pre-INAP: 135±10 ms vs. Post-INAP 101±11 ms; p=0.008) and increased AF-inducibility. QT-paced prolonged during INAP (Pre-INAP 270±7 ms vs. INAP 275±7 ms; p=0.04) and EMW shortened progressively throughout INAP and Post-INAP (Pre-INAP 80±4 ms; INAP 59±6 ms, Post-INAP 46±10 ms). AP14145 prolonged baseline AERP, partially prevented INAP-induced AERP-shortening and reduced AF-susceptibility. AP14145 did neither alter QT-paced (Pre-AP14145 270±7 ms vs. AP14145 268±6 ms, p=0.83) nor INAP-induced QT-paced prolongation, but blunted Post-INAP associated EMW-shortening.

Conclusion
In a pig model for obstructive respiratory events, the SK-channel-inhibitor AP14145 prevented INAP-associated AERP-shortening and AF-susceptibility without impairing ventricular electrophysiology. Hence, SK-channels may represent a promising target for OSA-related AF.
Differential effects of positive and negative upper airway pressure application on atrial electrophysiology: implications for CPAP-therapy in OSA-patients
Authors: Linz B , Hertel JN , Tfelt-Hansen J , Jespersen T , Linz D 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Novo nordisk foundation

Background
Obstructive sleep apnea (OSA) is closely associated with atrial fibrillation (AF) and OSA-treatment by continuous positive airway pressure (CPAP) is believed to reduce the AF burden in OSA-patients. While negative upper airway pressure during obstructive respiratory events have been shown to increase AF susceptibility, atrial electrophysiological effects of positive upper airway pressure during CPAP-therapy are unknown.

Purpose
In pigs, we investigated differential atrial electrophysiological effects of increasing levels of CPAP-applications compared to obstructive respiratory events.

Methods
In sedated and spontaneously breathing pigs, obstructive respiratory events were simulated by intermittent negative upper airway pressure (INAP) applied via a pressure device connected to the intubation tube. INAP was applied for 75 seconds with a 10 minute resting period in-between. After four INAP-applications, during which atrial electrophysiological responses to INAP were recorded, continuous positive airway pressure was applied in increasing pressure stages for a duration of 20 minutes for each pressure level (4, 8, 12 and 16 mbar). Atrial effective refractory periods (AERP) were recorded at the free wall of the right atrium (RA) and in the distal area of the coronary sinus (CS) before (Pre-INAP), during (INAP) and after (Post-) INAP and every 10 minutes throughout the stepwise increase of CPAP.

Results
AERP shortened due to INAP application in the RA (Pre-INAP 134±7ms vs. INAP 95±7ms; p=0.008, Fig.1.), but not in the CS (Pre-INAP 132±8ms vs. INAP 110±9ms; p=0.144, Fig.2). Stepwise increases of CPAP-application up until 12 mbar did neither result in changes of RA- nor CS-AERP. Only CPAP-application at 16 mbar (CPAP16) resulted in transiently shortened CS-AERP (CPAP-baseline 140±6ms versus CPAP16 115±10ms; p=0.0081, Fig.2.), but not RA-AERPs (p=0.31, Fig.1.).

Conclusion
While simulation of obstructive respiratory events by INAP were reproducibly associated with a predominantly right atrial shortening of refractoriness, high-pressure CPAP-application of 16 mbar was associated with an isolated moderate shortening of left atrial refractoriness. These findings may have important implications for CPAP treatment in patients with AF, which should be considered in the design of future clinical studies.
Consortin: a potential modulator of ventricular conduction
Authors: Marsman EMJ , Offerhaus JA , Bosada FM , Beekman L , Christoffels VM , Boukens BJ , Remme CA , Bezzina CR 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Consortin, encoded by the CNST gene, is a ubiquitously expressed protein putatively involved in trafficking of connexins to the plasma membrane. In the heart, connexins form gap junctions, which are essential for cardiac conduction. Reduced levels and abnormal cellular distribution of connexins have been found in patients with heart failure, atrial fibrillation, arrhythmogenic cardiomyopathy and Brugada syndrome.

Purpose
To decipher the role of Consortin in cardiac electrophysiology.

Methods
Homozygous Cnst knockout mice (Cnst-/-) were generated using CRISPR-Cas9 technology. Consortin expression was assessed by Western blot analysis. Cardiac conduction parameters were recorded by electrocardiography in anesthetized wild-type (WT) and Cnst-/- male and female littermates aged 3-6 months. Conduction velocity (CV) was determined in Langendorff-perfused hearts by optical mapping of the right ventricle (RV) at a pacing cycle length of 120 ms. Data were analyzed by Student’s t­-test and P values &lt; 0.05 were considered significant.

Results
Western blot analysis confirmed the presence of Consortin in WT mouse hearts, and its absence in Cnst-/- hearts. Heart rate, P-wave duration and PR-interval did not differ between groups, whereas QRS interval was significantly prolonged in Cnst-/- (mean±SEM 8.7±1.3 ms, n=13) compared to WT mice (7.9±1.1ms, n=13; (p=0.0009)). Hearts were structurally normal, and heart weight:body weight ratio was similar between groups. Preliminary optical mapping at the RV of Langendorff-perfused hearts demonstrated a lower, although not significantly different, transversal CV in Cnst-/- (56±4.3 cm/s, n=6) compared to WT (65±7.1 cm/s; n=3; p=0.31), whereas longitudinal CV was similar between groups (Cnst-/- 80±4.2 cm/s versus WT 83±9.1 cm/s; p=0.74). No differences were observed in RV effective refractory period (p=0.59).

Conclusion
These preliminary findings support a modulatory role of Consortin in ventricular conduction.
Current efforts are aimed at elucidating the underlying electrophysiological and molecular mechanisms, including the impact of Consortin on cardiac connexins.
Neuronal nitric oxide synthase inhibition exacerbates atrial electrical remodeling via small-conductance Ca2+-activated K+ channel activation
Authors: Koya T , Watanabe M , Natsui H , Kadosaka T , Koizumi T , Nakao M , Hagiwara H , Kamada R , Temma T , Anazai T 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): The Japan Society for the Promotion of Science KAKENHI

Background
The presence of atrial fibrillation (AF) is associated with electrical remodeling processes that promote a substrate for the maintenance of AF itself. Small conductance Ca2+-activated K+ (SK) channels; K+-selective and voltage-independent ion channels are key factors in the atrial electrical remodeling (2, 3). However, the mechanism of its activation remains unclear. A recent study showed that neuronal nitric oxide synthase (nNOS) expression and activity are reduced in AF patients and that nNOS depletion causes the abbreviation of action potential duration (APD), leading to increased AF inducibility in animal experiments (4). Decreased NO production, especially driven by nNOS inhibition, might play a key role in the atrial electrical remodeling, and the downstream alteration of SK channels might result from this process.

Purpose
We aimed to evaluate the potential of SK channel blocking to mitigate abnormal electrophysiological properties and the inducibility of atrial tachyarrhythmia (ATA) which was induced by nNOS depletion, and to describe the related mechanism.

Methods
Atrial tachyarrhythmia induction and optical mapping were performed in perfused rat hearts. nNOS was pharmacologically inhibited by S-methylthiocitrulline (SMTC, 100 nM). The influence of the SK channel was examined by a specific channel inhibitor, apamin (100 nM). APD, conduction velocity, and calcium transient (CaT) parameters (CaTD, rise time, time to 50% decay, and tau) were evaluated by voltage and calcium dual optical mapping. Dominant frequency was evaluated to analyze the wave dynamics of AF.

Results
SMTC increased the inducibility of ATA and apamin mitigated the nNOS inhibition-induced arrhythmogenicity (0% [0/7] vs 62% [8/13] vs 15% [2/13] in control, SMTC and SMTC + apamin). SMTC caused the abbreviation and enhanced spatial dispersion of APD, which were reversed by apamin. In contrast, conduction velocity was not affected by SMTC or apamin. Moreover, apamin reduced the dominant frequency of SMTC-induced ATA. In voltage and calcium optical mapping, STMC and apamin did not alter the parameters associated with CaT, however, SMTC caused the abbreviation of APD, which was reversed by apamin (APD80: 48.4 ± 2.7 msec in control group, 30.8 ± 1.5 msec in SMTC group, p &lt;0.0001 vs. control, 41.8 ± 1.5 msec in SMTC + apamin, p = 0.01 vs. SMTC by One-way ANOVA and Tukey’s multiple-comparison test) (Figure A-C).

Conclusion
Acute nNOS inhibition abbreviated APD via activating SK channels. A specific SK channel blocker mitigated APD abbreviation without the alteration of CaT, implying an underlying mechanism of post translational modification of SK channels.
A comprehensive review on classifying fast-acting and slow-acting antimalarial agents based on time of action and target organelle of Plasmodium sp
Authors: Mariebernard Monika , Mohanty Abhinab , Rajendran Vinoth 
Published: May 2022

Abstract
The clinical resistance towards malarial parasites has rendered many antimalarials ineffective, likely due to a lack of understanding of time of action and stage specificity of all life stages. Therefore, to tackle this problem a more incisive comprehensive analysis of the fast- and slow-acting profile of antimalarial agents relating to parasite time–kill kinetics and the target organelle on the progression of blood-stage parasites was carried out. It is evident from numerous findings that drugs targeting food vacuole, nuclear components, and endoplasmic reticulum mainly exhibit a fast-killing phenotype within 24 h affecting first-cycle activity. Whereas drugs targeting mitochondria, apicoplast, microtubules, parasite invasion, and egress exhibit a largely slow-killing phenotype within 96–120 h, affecting second-cycle activity with few exemptions as moderately fast-killing. It is essential to understand the susceptibility of drugs on rings, trophozoites, schizonts, merozoites, and the appearance of organelle at each stage of the 48-h intraerythrocytic parasite cycle. Therefore, these parameters may facilitate the paradigm for understanding the timing of antimalarials action in deciphering its precise mechanism linked with time. Thus, classifying drugs based on the time of killing may promote designing new combination regimens against varied strains of Plasmodium falciparum and evaluating potential clinical resistance.
Selling the Responsibility to Protect: The False Novelty but Real Impact of a Norm
Authors: Staunton Eglantine , Glanville Luke 
Published: May 2022

Abstract
The responsibility to protect (R2P) is often referred to as a new concept on the basis that it provides both states and the international community responsibilities, rather than merely rights, to protect populations from mass atrocities. As this article argues, this claim of novelty is overstated. And yet, R2P has comprised an important development in human protection over the past two decades: it has helped to generate a degree of consensus on how to prevent and address atrocity situations. If R2P is not as novel as is often suggested, why has it had such an impact on international discourse? After demonstrating R2P's overstated novelty, this article advances four key factors that help explain its meaningful international impact: the importance of previous and contiguous normative developments, the role played by norm entrepreneurs, the emphasis placed on prevention over intervention, and the concept's constructive mix of clarity and ambiguity. By doing so, it provides a stronger understanding of the norm.
The risks associated with percutaneous native kidney biopsies: a prospective study
Authors: Andrulli Simeone , Rossini Michele , Gigliotti Giuseppe , La Manna Gaetano , Feriozzi Sandro , Aucella Filippo , Granata Antonio , Moggia Elisabetta , Santoro Domenico , Manenti Lucio , Infante Barbara , Ferrantelli Angelo , Cianci Rosario , Giordano Mario , Giannese Domenico , Seminara Giuseppe , Di Luca Marina , Bonomini Mario , Spatola Leonardo , Bruno Francesca , Baraldi Olga , Micarelli David , Piemontese Matteo , Distefano Giulio , Mattozzi Francesca , De Giovanni Paola , Penna Davide , Garozzo Maurizio , Vernaglione Luigi , Abaterusso Cataldo , Zanchelli Fulvia , Brugnano Rachele , Gintoli Enrica , Sottini Laura , Quaglia Marco , Cavoli Gioacchino Li , De Fabritiis Marco , Conte Maria Maddalena , Manes Massimo , Battaglia Yuri , Fontana Francesco , Gesualdo Loreto ,   ITA-KID-BIO-Group
Published: May 2022

ABSTRACTBackgroundThe known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy.MethodsThe study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression.ResultsAnalysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08–1.17], liver disease (OR 2.27, 95% CI 1.21–4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07–1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92–0.99) were protective.ConclusionsThis is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.
Nightmares and Respite
Authors: Walker Michael L. 
Published: May 2022

Abstract
Rarely is the relationship between sleep hygiene and punishment explored; however, this chapter does just that. The author argues that dreams are not wholly individual experiences, but social ones shaped to one extent or another by shared social circumstances. It is not that people have the same dreams, but that they are more likely to have the same kinds of dreams. Chapter 8 explores the sociology of dreaming, but it is also an investigation of the inherent weaknesses of offering mental health treatment to penal residents who are hungry and sleep-deprived—especially mental health care that is so woefully underresourced. Still, residents learned to use trips to mental health for their nightmares and other sleep-related problems as endurance strategies of another kind: friendship and care among each other, access to a phone, and respite from the problems associated with the politics.
It Is What It Is
Authors: Walker Michael L. 
Published: May 2022

Abstract
In this chapter, the author explores two main philosophies of life that residents adopted as endurance strategies to make sense of their time in jail. Residents could situate the punishment they experienced as being outside of their hands, a philosophy best summarized as it is what it is. Or they could situate the punishment as being well within the hands of a divine personality who had a plan for their lives, which is best summarized as it is as it should be. Commensurate with organic ethnography, the author describes his own emotional stance to the study.
Introduction
Authors: Christie Douglas E. 
Published: May 2022

Abstract
The introduction provides a brief outline of the main questions and ideas of the book, including the question of the possible role ancient traditions of mystical darkness can play as we grapple with and respond deeply and honestly to our own losses and darkness. And whether our understanding of these mystical traditions of darkness and unknowing can be deepened by reading and thinking about them in light of our own dislocations and losses. It also describes the dialogical character of the book, in which questions about the meaning of darkness and unknowing and emptiness draw at once on mystical texts from apophatic mystical traditions and on voices of darkness and unknowing arising in contemporary literature, poetry, and film. And it describes how the ideas and language of spirituality, mysticism, and contemplative practice are employed in the book and what it means to retrieve and reinterpret them in light of the widespread experience of loss.
The Night Office
Authors: Christie Douglas E. 
Published: May 2022

Abstract
This chapter introduces the main themes and questions of the book, including the question of what it means to enter the night—in ordinary human experience and in moments of heightened awareness to which so many mystics and contemplatives bear witness. Drawing upon the monastic practice of the “night office,” or “nocturns,” the chapter considers different ways of imagining the night as a locus of spiritual experience and asks what it means to enter this space and keep vigil there. It examines also the bewildering sense of loss or absence that Michel de Certeau argues is a critical question for those mystics embarking upon journey into the night, something that continues to surface in much contemporary experience. And it explores the place of love in darkness and considers how the practice of spiritual relinquishment can foster a deeper sense of community—or what the mystics call “the common life.”
A Wild, Wide Oneness
Authors: Christie Douglas E. 
Published: May 2022

Abstract
This chapter considers what it means to enter the space that Flemish mystic Hadewijch of Antwerp describes as a “wild, wide oneness,” the deepest reaches of spiritual knowing where the poor of spirit live in purity, simplicity, and unity without end or beginning. This chapter takes up the question of how she and other Christian mystics (Francis of Assisi, Marguerite Porete, Thomas Merton), as well as certain modern and contemporary writers (Aldo Leopold, Lauret Savoy, Henry David Thoreau, Branka Arsić), understand the journey toward this wildness, within and without. It examines also how prolonged contact with wild places can help relinquish anthropocentric categories of identity and become open to the voice and presence of the wild other. It considers also how the reconfiguring of identity can contribute to a what Pope Francis, in Laudato Si’, calls ecological conversion.