bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meis transcription factors regulate cardiac conduction system development and adult function
Authors: Muñoz-Martín Noelia , Simon-Chica Ana , Díaz-Díaz Covadonga , Cadenas Vanessa , Temiño Susana , Esteban Isaac , Ludwig Andreas , Schormair Barbara , Winkelmann Juliane , Olejnickova Veronika , Sedmera David , Filgueiras-Rama David , Torres Miguel 
Published: December 2024

Abstract

Aims
The cardiac conduction system (CCS) is progressively specified during development by interactions among a discrete number of transcription factors (TFs) that ensure its proper patterning and the emergence of its functional properties. Meis genes encode homeodomain TFs with multiple roles in mammalian development. In humans, Meis genes associate with congenital cardiac malformations and alterations of cardiac electrical activity; however, the basis for these alterations has not been established. Here, we studied the role of Meis TFs in cardiomyocyte development and function during mouse development and adult life.

Methods and results
We studied Meis1 and Meis2 conditional deletion mouse models that allowed cardiomyocyte-specific elimination of Meis function during development and inducible elimination of Meis function in cardiomyocytes of the adult CCS. We studied cardiac anatomy, contractility, and conduction. We report that Meis factors are global regulators of cardiac conduction, with a predominant role in the CCS. While constitutive Meis deletion in cardiomyocytes led to congenital malformations of the arterial pole and atria, as well as defects in ventricular conduction, Meis elimination in cardiomyocytes of the adult CCS produced sinus node dysfunction and delayed atrio-ventricular conduction. Molecular analyses unravelled Meis-controlled molecular pathways associated with these defects. Finally, we studied in transgenic mice the activity of a Meis1 human enhancer related to an single-nucleotide polymorphism (SNP) associated by Genome-wide association studies (GWAS) to PR (P and R waves of the electrocardiogram) elongation and found that the transgene drives expression in components of the atrio-ventricular conduction system.

Conclusion
Our study identifies Meis TFs as essential regulators of the establishment of cardiac conduction function during development and its maintenance during adult life. In addition, we generated animal models and identified molecular alterations that will ease the study of Meis-associated conduction defects and congenital malformations in humans.
Transjugular transcatheter edge-to-edge mitral valve repair in a patient with functional mitral regurgitation: a case report
Authors: Enta Yusuke , Munehisa Yoshiko , Satomi Natsuko , Hayatsu Yukihiro , Tada Norio 
Published: December 2024

Abstract

Background
Transcatheter edge-to-edge mitral valve repair (M-TEER) using the MitraClip system is primarily performed using the transfemoral approach. However, when this approach is not feasible, the transjugular approach can be used as an alternative.

Case summary
A 57-year-old man presented with heart failure and persistent New York Heart Association class IV symptoms, refractory to guideline-directed medical therapy, intravenous therapy, and intra-aortic balloon pumping. His medical history included pulmonary embolism secondary to deep vein thrombosis, which occluded the inferior vena cava (IVC). Transthoracic echocardiography (TTE) revealed severe functional mitral regurgitation (FMR). The IVC occlusion made the transfemoral approach impossible; hence, transjugular M-TEER was planned. Transseptal puncture was performed via the right internal jugular (RIJ), 32 mm above the mitral annulus. A Confida wire was positioned in the left ventricle, and a steerable guiding catheter was introduced with 180° clockwise rotation of the +knob for septal crossing through the stiff wire. The MitraClip XTW was inserted into the catheter with a 90° counterclockwise rotation. After adjusting to a straddle position to move the clip laterally, additional knob rotations were performed to position the clip at A2/P2. Once the clip was placed, only trivial mitral regurgitation (MR) remained. No complications occurred, and the patient improved, allowing discharge. Transthoracic echocardiography at 1-year post-procedure demonstrated sustained MR reduction.

Discussion
We have described the successful completion of M-TEER using the RIJ approach in a patient with severe FMR. Technical considerations in M-TEER require special attention because of limited reports on the M-TEER procedure via the RIJ.
Comparative cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter-2 inhibitors in atherosclerotic cardiovascular disease phenotypes: a systematic review and meta-analysis
Authors: Lin Yu-Min , Wu Jheng-Yan , Lee Mei-Chuan , Su Chen-Lun , Toh Han Siong , Chang Wei-Ting , Chen Sih-Yao , Kuo Fang-Hsiu , Tang Hsin-Ju , Liao Chia-Te 
Published: December 2024

Abstract

Background
Atherosclerotic cardiovascular disease (ASCVD) encompasses various phenotypes with elevated risks of major adverse cardiovascular events (MACEs). This study aimed to assess the comparative cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium–glucose cotransporter-2 inhibitors (SGLT2is) across diverse ASCVD phenotypes.

Methods and results
We conducted a systematic review and meta-analysis of randomized controlled trials evaluating GLP-1 RAs or SGLT2is against placebo or standard care in ASCVD patients. Primary outcomes included MACE, defined as cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Risk ratios (RRs) with 95% confidence interval (CI) were calculated using a random-effects model.
Twenty-six trials (151 789 patients) were included. Both GLP-1 RAs and SGLT2is significantly reduced MACE rates in ASCVD patients (RR 0.85; 95% CI 0.80–0.91 for both). GLP-1 RAs showed significant effectiveness in peripheral artery disease (RR 0.86; 95% CI 0.76–0.98) and post-acute cardiovascular events (RR 0.90; 95% CI 0.83–0.97). In ASCVD with heart failure, both drug classes reduced MACE (GLP-1 RAs: RR 0.73; 95% CI 0.63–0.84; SGLT2is: RR 0.86; 95% CI 0.78–0.95). SGLT2is significantly reduced MACE in ASCVD with chronic kidney disease (RR 0.84; 95% CI 0.72–0.99), particularly in severe albuminuria (RR 0.61; 95% CI 0.37–0.99).

Conclusion
GLP-1 RAs and SGLT2is exhibit distinct cardiovascular effectiveness profiles across ASCVD phenotypes. GLP-1 RAs show particular benefits in peripheral artery disease and post-acute cardiovascular events, while SGLT2is demonstrate unique advantages in ASCVD with comorbid chronic kidney disease. Both are effective in heart failure. These findings support tailored treatment strategies for diverse ASCVD participants based on specific comorbidities and risk factors.
Deep learning model to diagnose cardiac amyloidosis from haematoxylin/eosin-stained myocardial tissue
Authors: Tohyama Takeshi , Iwasaki Takeshi , Ikeda Masataka , Katsuki Masato , Watanabe Tatsuya , Misumi Kayo , Shinohara Keisuke , Fujino Takeo , Hashimoto Toru , Matsushima Shouji , Ide Tomomi , Kishimoto Junji , Todaka Koji , Oda Yoshinao , Abe Kohtaro 
Published: December 2024

Abstract

Aims
Amyloid deposition in myocardial tissue is a definitive feature for diagnosing cardiac amyloidosis, though less invasive imaging modalities such as bone tracer cardiac scintigraphy and cardiac magnetic resonance imaging have been established as first steps for its diagnosis. This study aimed to develop a deep learning model to support the diagnosis of cardiac amyloidosis from haematoxylin/eosin (HE)-stained myocardial tissue.

Methods and results
This single-centre retrospective observational study enrolled 166 patients who underwent myocardial biopsies between 2008 and 2022, including 76 patients diagnosed with cardiac amyloidosis and 90 with other diagnoses. A deep learning model was developed to output the probabilities of cardiac amyloidosis for all the small patches cutout from each myocardial specimen. The developed model highlighted the area in the stained images as highly suspicious, corresponding to where Dylon staining marked amyloid deposition, and discriminated the patches in the evaluation dataset with an area under the curve of 0.965. Provided that the diagnostic criterion for cardiac amyloidosis was defined as a median probability of cardiac amyloidosis &gt;50% in all patches, the model achieved perfect performance in discriminating patients with cardiac amyloidosis from those without it, with an area under the curve of 1.0.

Conclusion
A deep learning model was developed to diagnose cardiac amyloidosis from HE-stained myocardial tissue accurately. Although further prospective validation of this model using HE-stained myocardial tissues from multiple centres is needed, it may help minimize the risk of missing cardiac amyloidosis and maximize the utility of histological diagnosis in clinical practice.
What’s the cardiac rhythm at the time of cardiac arrest? Disputed dogma or true fact?
Authors: Maury Philippe , Marimpouy Nathan , Beneyto Maxime 
Published: December 2024

Abstract
It was widely accepted that malignant ventricular arrhythmias (VA) are the main direct initial cause for cardiac arrest and sudden cardiac death (SCD), but diverging data tended to demonstrate that asystole or pulseless activity were becoming the most prevalent cardiac rhythms at the time of cardiac arrest. We challenge here these conceptions and reinforce the persisting prominent role of VA in SCD.
French socialism in the Argentine Partido Socialista: political dimensions of an uncomfortable presence (1890–1915)
Authors: Herrera Carlos M , Reyes Francisco J 
Published: December 2024

Abstract
The presence of French socialism in the Argentine Socialist Party is something of a paradox: the cultural weight of France in Argentina’s intellectual and artistic life from the nineteenth century until the first decades of the twentieth century had no equivalent impact on Argentine socialism. This is even more striking if we consider the intensity of personal exchanges, including a visit by Jean Jaurès to Buenos Aires in 1911. Of course, Francophilia was not unknown to these socialists, but their main leaders adopted a mostly critical approach towards French traditions, and later towards the Section française de l’Internationale ouvrière (SFIO), at least when compared to the Belgian and German socialist parties. This difference becomes even more perceptible when we compare the Partido Socialista (PS) in Argentina to other socialist parties from the same region. The thesis of this article is that the influence of French socialism served, in the early years of the PS in Argentina, to feed the leftist currents that opposed the leadership, promoting a revolutionary attitude on its part instead of its integration into the political system. At the same time, Jaurès’ immense international status as a socialist meant that his 1911 visit would facilitate the eventual integration of the Argentine party into the political system.
Detecting gene expression in Caenorhabditis elegans
Authors: Calarco John A , Taylor Seth R , Miller David M 
Published: December 2024

Abstract
Reliable methods for detecting and analyzing gene expression are necessary tools for understanding development and investigating biological responses to genetic and environmental perturbation. With its fully sequenced genome, invariant cell lineage, transparent body, wiring diagram, detailed anatomy, and wide array of genetic tools, Caenorhabditis elegans is an exceptionally useful model organism for linking gene expression to cellular phenotypes. The development of new techniques in recent years has greatly expanded our ability to detect gene expression at high resolution. Here, we provide an overview of gene expression methods for C. elegans, including techniques for detecting transcripts and proteins in situ, bulk RNA sequencing of whole worms and specific tissues and cells, single-cell RNA sequencing, and high-throughput proteomics. We discuss important considerations for choosing among these techniques and provide an overview of publicly available online resources for gene expression data.
Characterizing selection on complex traits through conditional frequency spectra
Authors: Patel Roshni A , Weiß Clemens L , Zhu Huisheng , Mostafavi Hakhamanesh , Simons Yuval B , Spence Jeffrey P , Pritchard Jonathan K 
Published: December 2024

Abstract
Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of its frequency and effect size – but for traits under selection, the effect size of a variant determines the strength of selection against it, constraining its frequency. Recognizing the biases inherent to GWAS ascertainment, we propose studying the joint distribution of allele frequencies across populations, conditional on the frequencies in the GWAS cohort. Before considering these conditional frequency spectra, we first characterized the impact of selection and non-equilibrium demography on allele frequency dynamics forwards and backwards in time. We then used these results to understand conditional frequency spectra under realistic human demography. Finally, we investigated empirical conditional frequency spectra for GWAS variants associated with 106 complex traits, finding compelling evidence for either stabilizing or purifying selection. Our results provide insights into polygenic score portability and other properties of variants ascertained with GWAS, highlighting the utility of conditional frequency spectra.
Motor pool selectivity of neuromuscular degeneration in type I spinal muscular atrophy is conserved between human and mouse
Authors: Lee Justin C , Chung Wendy K , Pisapia David J , Henderson Christopher E 
Published: December 2024

Abstract
Spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein. Even though SMN is ubiquitously expressed, the disease selectively affects motor neurons, leading to progressive muscle weakness. Even among motor neurons, certain motor units appear more clinically resistant to SMA. To quantitatively survey selective resistance, we studied extensive neuromuscular autopsies of Type I SMA patients and age-matched controls. We found highly divergent degrees of degeneration of neighboring motor units, even within individual cranial nerves or a single anatomical area such as the neck. Examination of a Type I SMA patient maintained on life support for 17 years found that most muscles were atrophied, but the diaphragm was strikingly preserved. Nevertheless, some resistant human muscles with preserved morphology displayed nearly complete conversion to slow Type I myofibers. Remarkably, a similar pattern of selective resistance was observed in the SMNΔ7 mouse model. Overall, differential motor unit vulnerability in human Type I SMA suggests the existence of potent, motor unit-specific disease modifiers. Mechanisms that confer selective resistance to SMA may represent therapeutic targets independent of the SMN protein, particularly in patients with neuromuscular weakness refractory to current treatments.
Marine heatwaves in the Subarctic and the effect of acute temperature change on the key grazer Strongylocentrotus droebachiensis (Echinoidea, Echinodermata)
Authors: Koch Marie , Jungblut Simon , Götze Sandra , Bock Christian , Saborowski Reinhard 
Published: December 2024

Abstract
Subarctic fjord systems are facing a continuous temperature increase as well as more frequent and more intense marine heatwaves (MHWs). MHWs are periods of exceptionally high temperatures above the long-term average. In the Porsangerfjord (Northern Norway), the average water temperature ranges from 2.5°C in March to 10°C in August. MHWs frequently exceed the summer maximum by up to 6°C with so far unknown ecological effects. The green sea urchin, Strongylocentrotus droebachiensis, is a key grazer on habitat-forming kelp in Subarctic fjord systems. At high abundances, sea urchins transform productive kelp beds through pronounced grazing into depleted sea urchin barrens. In a laboratory experiment, we investigated the influence of acute temperature change on the grazing activity and the metabolic performance of the green sea urchin. Grazing rates increased continuously from 2 to 10°C but decreased again at 14°C. At 22°C, rapid decay of sea urchins were associated with changes of the metabolic energy state from aerobiosis to anaerobiosis. We propose two scenarios: Moderate warming might lead to the proliferation of the sea urchin population and increased grazing pressure on kelp forests, while extreme warming, as predicted by the end of the century, as well as the occurrence of extreme MHWs, may severely impair the sea urchin population and, in turn, might favour the proliferation of adaptable kelp species.
The weighted and shifted seven-step BDF method for parabolic equations
Authors: Akrivis Georgios , Chen Minghua , Yu Fan 
Published: December 2024

Abstract
Stability of the BDF methods of order up to 5 for parabolic equations can be established by the energy technique via Nevanlinna–Odeh multipliers. The nonexistence of Nevanlinna–Odeh multipliers makes the six-step BDF method special; however, the energy technique was recently extended by the authors in Akrivis et al. (2021, SIAM J. Numer. Anal., 59, 2449–2472) and covers all six stable BDF methods. The seven-step BDF method is unstable for parabolic equations, since it is not even zero-stable. In this work, we construct and analyze a stable linear combination of two non zero-stable schemes, the seven-step BDF method and its shifted counterpart, referred to as WSBDF7 method. The stability regions of the WSBDF$q, q\leqslant 7$, with a weight $\vartheta \geqslant 1$, increase as $\vartheta $ increases and are larger than the stability regions of the classical $q$-step BDF methods, corresponding to $\vartheta =1$. We determine novel and suitable multipliers for the WSBDF7 method and establish stability for parabolic equations by the energy technique. The proposed approach is applicable for mean curvature flow, gradient flows, fractional equations and nonlinear equations.
Dynamic quinone repertoire accompanied the diversification of energy metabolism in Pseudomonadota
Authors: Chobert Sophie-Carole , Roger-Margueritat Morgane , Flandrin Laura , Berraies Safa , Lefèvre Christopher T , Pelosi Ludovic , Junier Ivan , Varoquaux Nelle , Pierrel Fabien , Abby Sophie S 
Published: December 2024

Abstract
It is currently unclear how Pseudomonadota, a phylum that originated around the time of the Great Oxidation Event, became one of the most abundant and diverse bacterial phyla on Earth, with metabolically versatile members colonizing a wide range of environments with different O2 concentrations. Here, we address this question by studying isoprenoid quinones, which are central components of energy metabolism covering a wide range of redox potentials. We demonstrate that a dynamic repertoire of quinone biosynthetic pathways accompanied the diversification of Pseudomonadota. The low potential menaquinone (MK) was lost in an ancestor of Pseudomonadota while the high potential ubiquinone (UQ) emerged. We show that the O2-dependent and O2-independent UQ pathways were both present in the last common ancestor of Pseudomonadota, and transmitted vertically. The O2-independent pathway has a conserved genetic organization and displays signs of positive regulation by the master regulator “fumarate and nitrate reductase” (FNR), suggesting a conserved role for UQ in anaerobiosis across Pseudomonadota. The O2-independent pathway was lost in some lineages but maintained in others, where it favoured a secondary reacquisition of low potential quinones (MK or rhodoquinone), which promoted diversification towards aerobic facultative and anaerobic metabolisms. Our results support that the ecological success of Pseudomonadota is linked to the acquisition of the largest known repertoire of quinones, which allowed adaptation to oxic niches as O2 levels increased on Earth, and subsequent diversification into anoxic or O2-fluctuating environments.
High prevalence of reverse transcriptase inhibitors associated resistance mutations among people living with HIV on dolutegravir-based antiretroviral therapy in Francistown, Botswana
Authors: Choga Ontlametse T , Lemogang Goitseone M , Choga Wonderful T , Muzanywa Gaonyadiwe , Shadreck Thembinkosi M , Ralegoreng Charity , Maruapula Dorcas , Moraka Natasha O , Koofhethile Catherine K , Mokgethi Patrick T , Seru Kedumetse , Zuze Boitumelo J L , Montshosi Patience , Gobe Irene , Motswaledi Modisa S , Musonda Rosemary , Mbulawa Mpaphi B , Makhema Joseph , Shapiro Roger , Lockman Shahin , Chebani Tony , Nawa Judith , Bochena Lindani , Moyo Sikhulile , Gaseitsiwe Simani 
Published: December 2024

Abstract

Objectives
We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.

Methods
The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana’s national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200–999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL). HIV-1 protease, reverse transcriptase and integrase genes were sequenced using an in-house next-generation sequencing Oxford nanopore technology. HIV-1 drug resistance mutations (DRMs) were identified using the HIVdb Program in the Stanford HIV drug resistance database and compared between VL groups.

Results
Among 100 participants, 83.0% were on dolutegravir-based, 10.0% were on non-dolutegravir-based ART and 7.0% had unknown/undocumented ART regimens. Thirty (30%) participants had LLV and 70 (70%) had VF. Among 58 successfully sequenced, 32.8% [95% Confidence Interval (CI): 21.8–46.0] had DRMs to any drug class, 33.3% (4/12) in the LLV group and 32.6% (15/46) in the VF group. Among individuals on dolutegravir-based ART, the overall HIV DRMs were 34.8% (95% CI: 22.7–49.2). By VL groups, 40.0% (95% CI: 16.8–68.7) and 33.3% (95% CI: 20.2–50.0) had DRMs at LLV and VF, respectively.

Conclusions
A high but similar prevalence of any DRMs was observed among individuals with LLV and those with VF on dolutegravir-based therapy. Monitoring DRMs in individuals with detectable VL is crucial for preserving dolutegravir-based ART.