bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptidergic Modulation of the Lobster Cardiac System Has Opposing Action on Neurons and Muscles
Authors: Petropoulos I S , Jordan A E , Dickinson P S , Powell D J 
Published: January 2025

Synopsis
Modulation of neuronal networks, primarily through neuropeptides, generates variations in motor patterns that allow organisms to adapt to environmental changes or sensory inputs. Modulation is complex, with receptors for neuromodulators expressed at various locations within a nervous system; neuromodulators can thus alter muscle dynamics peripherally via the neuromuscular junction (NMJ) and the muscle itself. The neurogenic cardiac neuromuscular system of the American lobster (Homarus americanus) is a well-characterized model for investigating peptidergic modulation. Myosuppressin (pQDLDHVFLRFamide) is an endogenous peptide that interestingly decreases contraction frequency while also increasing contraction force by acting at both the lobster heart central pattern generator (CPG; the cardiac ganglion) and the periphery (cardiac muscles). Myosuppressin decreases heartbeat frequency by decreasing the burst frequency of the cardiac ganglion. Here, we investigated the remaining question, does myosuppressin exert its peripheral effects directly on the cardiac muscle, the NMJ, or both? To elucidate myosuppressin's effects on the cardiac muscle, the muscle was isolated from the CPG, and contractions were evoked using focal application of the endogenous neurotransmitter, l-glutamate, while superfusing myosuppressin over the heart. Myosuppressin increased glutamate-evoked contraction amplitude in the isolated muscle, suggesting that myosuppressin exerts its peripheral effects directly on the cardiac muscle. To examine effects on the NMJ, excitatory junction potentials were evoked by stimulating the motor nerve and recording the intracellular membrane voltage from a single muscle fiber both in control saline and in the presence of myosuppressin. Myosuppressin did not modulate the amplitude of excitatory junction potentials suggesting that myosuppressin acts directly on the muscle and not via the NMJ, to cause an increase in contraction force.
Machine learning-based risk prediction of outcomes in patients hospitalized with COVID-19 in Australia: the AUS-COVID Score
Authors: Sritharan Hari P , Nguyen Harrison , van Gaal William , Kritharides Leonard , Chow Clara K , Bhindi Ravinay 
Published: January 2025

Abstract

Objectives
We aimed to develop a highly interpretable and effective, machine learning (ML)-based risk prediction algorithm to predict in-hospital mortality, intubation, and adverse cardiovascular events in patients hospitalized with coronavirus disease 2019 (COVID-19) in Australia (AUS-COVID Score).

Materials and Methods
This prospective study across 21 hospitals included 1714 consecutive patients aged ≥ 18 in their index hospitalization with COVID-19. The dataset was separated into training (80%) and test sets (20%). Eight supervised ML methods were used: least absolute shrinkage and selection operator (LASSO), ridge, elastic net (EN), decision tree, support vector machine, random forest, AdaBoost, and gradient boosting. A feature selection method was used to establish informative variables, which were considered in groups of 5/10/15/20/all. The final model was selected by balancing the optimal area under the curve (AUC) score with interpretability, through the number of included variables. The coefficients of the final models were used to build the AUS-COVID Score.

Results and Discussion
Among the patients, 181 (10.6%) died in-hospital, 148 (8.6%) required intubation, and 90 (5.3%) had adverse cardiovascular events. The LASSO model performed best for predicting in-hospital mortality (AUC 0.85) using 5 variables: age, respiratory rate, COVID-19 features on chest X-ray, troponin elevation, and COVID-19 vaccination (≥1 dose). The EN model performed best for predicting intubation (AUC 0.75) and adverse cardiovascular events (AUC 0.64), each with 5 variables. A user-friendly web-based application was built for clinician use at the bedside.

Conclusion
The AUS-COVID Score is an accurate and practical, ML-based risk score to predict in-hospital mortality, intubation, and adverse cardiovascular events in hospitalized COVID-19 patients.
Improving Wellness Through Reading Room Design and Flexible Scheduling Options
Authors: Muhammad Hamad , Puglia Millie , Colvin Stephanie , Zalasin Stefanie , Yalniz Ceren , Zamora Kathryn W , Woodard Stefanie 
Published: January 2025

Abstract
Breast radiologists have high rates of burnout. Some contributing factors include the sedentary nature of the occupation, reading room design and isolation associated with higher volumes, and increased remote interpretation. Reading rooms can also be filled with numerous distractions and produce conditions that do not support optimal workflow. Identifying and addressing these issues may help prolong physician careers and increase overall productivity. This article presents approaches to improve wellness for breast imaging radiologists and reduce the overall rate of burnout.
Anatomic reconstruction of isolated left main coronary artery ostial stenosis using a right internal mammary artery patch
Authors: Bara Albaraa , Izzat Ahmad Walid , Izzat Mohammad Bashar 
Published: January 2025

Abstract
Surgical patch angioplasty is an alternative to classic coronary artery bypass grafting for patients with isolated coronary ostial stenosis and normal distal coronary arteries. We present a case where we successfully used an arterial patch from the right internal mammary artery to restore patency of an isolated ostial left main coronary artery stenosis. This technique is likely to offer more physiological antegrade myocardial perfusion, mimic normal vascular anatomy, and may be associated with an improved outcome.
The Arabidopsis eATP receptor, DORN1 and CNGC19 channel act in tandem to regulate plant defense upon Spodoptera litura herbivory
Authors: Kundu Pritha , Kumari Misha , Meena Mukesh Kumar , Mishra Shruti , Vadassery Jyothilakshmi 
Published: January 2025

Abstract
Plants deploy cellular Ca2+ elevation as a signal for environmental stress signaling. Extracellular ATP (eATP) is released into the extracellular matrix when cells are wounded. DOES NOT RESPOND TO NUCLEOTIDES 1 (DORN1), a key legume-type lectin receptor, senses and binds eATP and activates Ca2+ signaling. No evidence directly links calcium-mediated eATP signaling to resistance against insect herbivores. Here, we report upregulation of DORN1 transcripts upon wounding and Spodoptera litura feeding in Arabidopsis. Loss-of-function of DORN1 resulted in increased S. litura feeding compared to that on wildtype. Plant immunity is compromised in dorn1 mutants as they show reduced S. litura oral secretion mediated Ca2+ elevation, jasmonic acid accumulation, and expression of jasmonate responsive genes. The herbivory-induced calcium channel, CYCLIC NUCLEOTIDE GATED CHANNEL 19 (CNGC19), co-expresses with DORN1. We found that eATP-induced Ca2+ elevation requires functional CNGC19. Loss-of-function of DORN1 and CNGC19 highly increased the susceptibility to S. litura, mediated by reduced accumulation of jasmonates. We also demonstrate a plausible interaction of CNGC19 with DORN1. The data implicate the role of damage-released eATP and its receptor DORN1 in herbivory-induced defense signaling. DORN1 together with the Ca2+ channel CNGC19 generate the eATP-induced Ca2+ elevation, leading to the activation of immune signaling.
AGN feedback in isolated galaxies with a SMUGGLE multiphase ISM
Authors: Sivasankaran Aneesh , Blecha Laura , Torrey Paul , Kelley Luke Zoltan , Bhowmick Aklant , Vogelsberger Mark , Hernquist Lars , Marinacci Federico , Sales Laura V 
Published: January 2025

ABSTRACT
Feedback from active galactic nuclei (AGNs) can strongly impact the host galaxies by driving high-velocity winds that impart substantial energy and momentum to the interstellar medium (ISM). In this work, we study the impact of these winds in isolated galaxies using high-resolution hydrodynamics simulations. Our simulations use the explicit ISM and stellar evolution model called Stars and MUltiphase Gas in GaLaxiEs. Additionally, using a super-Lagrangian refinement scheme, we resolve AGN feedback coupling to the ISM at $\sim$10–100 pc scales. We find that AGN feedback efficiently regulates the growth of supermassive black holes. However, its effect on star formation and outflows depends strongly on the relative strengths of AGN versus local stellar feedback and the geometrical structure of the gas disc. When the energy injected by AGN is subdominant to that of stellar feedback, there are no significant changes in the star formation rates or mass outflow rates of the host galaxy. Conversely, when the energy budget is dominated by the AGN, we see a significant decline in the star formation rates accompanied by an increase in outflows. Galaxies with thin gas discs like the Milky Way allow feedback to escape easily into the polar directions without doing much work on the ISM. In contrast, galaxies with thick and diffuse gas discs confine the initial expansion of the feedback bubble within the disc, resulting in more work done on the ISM. Phase space analysis indicates that outflows primarily comprise hot and diffuse gas, with a lack of cold and dense gas.
Pro-cumulin addition in a biphasic in vitro oocyte maturation system modulates human oocyte and cumulus cell transcriptomes
Authors: Cava-Cami Berta , Galvao Antonio , Van Ranst Heidi , Stocker William A , Harrison Craig A , Smitz Johan , De Vos Michel , Kelsey Gavin , Anckaert Ellen 
Published: January 2025

Abstract
Biphasic IVM can be offered as a patient-friendly alternative to conventional ovarian stimulation in IVF patients predicted to be hyper-responsive to ovarian stimulation. However, cumulative live birth rates after IVM per cycle are lower than after conventional ovarian stimulation for IVF. In different animal species, supplementation of IVM media with oocyte-secreted factors (OSFs) improves oocyte developmental competence through the expression of pro-ovulatory genes in cumulus cells. Whether the addition of OSFs in human biphasic IVM culture impacts the transcriptome of oocytes and cumulus cells retrieved from small antral follicles in minimally stimulated non-hCG-triggered IVM cycles remains to be elucidated. To answer this, human cumulus–oocyte complexes (COCs) that were fully surrounded by cumulus cells or partially denuded at the time of retrieval were cultured in a biphasic IVM system either without or with the addition of pro-cumulin, a GDF9:BMP15 heterodimer. Oocytes and their accompanying cumulus cells were collected separately, and single-cell RNA-seq libraries were generated. The transcriptomic profile of cumulus cells revealed that pro-cumulin upregulated the expression of genes involved in cumulus cell expansion and proliferation while downregulating steroidogenesis, luteinization, and apoptosis pathways. Moreover, pro-cumulin modulated the immature oocyte transcriptome during the pre-maturation step, including regulating translation, apoptosis, and mitochondria remodeling pathways in the growing germinal vesicle oocytes. The addition of pro-cumulin also restored the transcriptomic profile of matured metaphase II oocytes that were partially denuded at collection. These results suggest that cumulus cell and oocyte transcriptome regulation by pro-cumulin may increase the number of developmentally competent oocytes after biphasic IVM treatment. Future studies should assess the effects of pro-cumulin addition in human biphasic IVM at the proteomic level and the embryological outcomes, particularly its potential to enhance outcomes of oocytes that are partially denuded at COC collection.
AAV vector transduction restriction and attenuated toxicity in hESCs via a rationally designed inverted terminal repeat
Authors: Song Liujiang , Hasegawa Tomoko , Brown Nolan J , Bower Jacquelyn J , Samulski Richard J , Hirsch Matthew L 
Published: January 2025

Abstract
Adeno-associated virus (AAV) inverted terminal repeats (ITRs) induce p53-dependent apoptosis in human embryonic stem cells (hESCs). To interrogate this phenomenon, a synthetic ITR (SynITR), harboring substitutions in putative p53 binding sites was generated and evaluated for vector production and gene delivery. Replication of SynITR flanked transgenic genome was similar compared to wild type (wt) ITR, with a modest increase in vector titers. Packaged in the AAV2 capsid, wtITR and SynITR vectors demonstrated similar transduction efficiencies of human cells without toxicity. Following AAV2-wtITR vector infection of hESCs, rapid apoptosis was observed as reported. In contrast, infection by AAV2 vectors packaged with SynITRs attenuated the wtITR-induced hESC toxicity. While hESC particle entry and the abundance of double stranded circular episomes was similar for the ITR contexts, reporter expression was inhibited from transduced SynITR genomes. Mechanistically, infection of hESCs induced γH2AX in an ITR-independent manner, however, canonical activation of p53α was uncoupled using AAV-SynITR. Further investigations in hESCs revealed additional novel findings: (i) p53β is uniquely and constitutively active and (ii) AAV vector infection, independent of the ITR sequence, induces activation of p53ψ. The data herein reveal an ITR-dependent AAV vector transduction restriction specific to hESCs and manipulation of the DNA damage response via ITR engineering.
Transcription near arrested DNA replication forks triggers ribosomal DNA copy number changes
Authors: Sasaki Mariko , Kobayashi Takehiko 
Published: January 2025

Abstract
DNA copy number changes via chromosomal rearrangements or the production of extrachromosomal circular DNA. Here, we demonstrate that the histone deacetylase Sir2 maintains the copy number of budding yeast ribosomal RNA gene [ribosomal DNA (rDNA)] by suppressing end resection of DNA double-strand breaks (DSBs) formed upon DNA replication fork arrest in the rDNA and their subsequent homologous recombination (HR)-mediated rDNA copy number changes during DSB repair. Sir2 represses transcription from the regulatory promoter E-pro located near the fork arresting site. When Sir2 is absent, this transcription is stimulated but terminated by arrested replication forks. This transcription–replication collision induces DSB formation, DSB end resection and the Mre11-Rad50-Xrs2 complex-dependent DSB repair that is prone to chromosomal rDNA copy number changes and the production of extrachromosomal rDNA circles. Therefore, repression of transcription near arrested replication forks is critical for the maintenance of rDNA stability by directing DSB repair into the HR-independent, rearrangement-free pathway.
Methyl-dependent auto-regulation of the DNA N6-adenine methyltransferase AMT1 in the unicellular eukaryote Tetrahymena thermophila
Authors: Duan Lili , Li Haicheng , Ju Aili , Zhang Zhe , Niu Junhua , Zhang Yumiao , Diao Jinghan , Liu Yongqiang , Song Ni , Ma Honggang , Kataoka Kensuke , Gao Shan , Wang Yuanyuan 
Published: January 2025

Abstract
DNA N6-methyladenine (6mA) is a potential epigenetic mark involved in gene transcription in eukaryotes, yet the regulatory mechanism governing its methyltransferase (MTase) activity remains obscure. Here, we exploited the 6mA MTase AMT1 to elucidate its auto-regulation in the unicellular eukaryote Tetrahymena thermophila. The detailed endogenous localization of AMT1 in vegetative and sexual stages revealed a correlation between the 6mA reestablishment in the new MAC and the occurrence of zygotically expressed AMT1. Catalytically inactive AMT1 reduced 6mA level on the AMT1 gene and its expression, suggesting that AMT1 modulated its own transcription via 6mA. Furthermore, AMT1-dependent 6mA regulated the transcription of its target genes, thereby affecting cell fitness. Our findings unveil a positive feedback loop of transcriptional activation on the AMT1 gene and highlight the crucial role of AMT1-dependent 6mA in gene transcription.
Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis
Authors: Cheng Jinmei , Gu Yimin , Wang Yueming , Xun Junjie , Wang Guishuan , Wang Yu , Wang Jianyu , Li Yinchuan , Sun Fei 
Published: January 2025

Abstract
Chromatin remodeling, which involves the histone-to-protamine exchange process during spermiogenesis, is crucial for sperm nuclear condensation and male fertility. However, the key regulators and underlying molecular mechanisms involved in this process remain largely unexplored. In this study, we discovered that deficiency in the family with sequence similarity 170 member A (Fam170a) led to abnormal sperm nuclear morphology and male infertility in mice, mirroring the observation of very low Fam170a transcription levels in sperm of infertile men with teratozoospermia. Further investigation revealed that Fam170a plays a significant role in the histone-to-protamine chromatin remodeling process. This was evidenced by the earlier core histone removal, accelerated translation and degradation of transition proteins, and reduced protamine incorporation during spermiogenesis in Fam170a-deleted mice. Mechanistically, we found that Fam170a interacts with chromatin remodeling-associated proteins and regulates the transcription of genes related to chromatin remodeling. Notably, Fam170a directly interacts with the deubiquitinating enzyme Usp7 and facilitates its nuclear translocation in elongating sperm, enhancing the deubiquitinating activity of Usp7 on testis-specific histone H2A and H2B variants. Collectively, our findings identify Fam170a as a previously unrecognized key regulator of sperm chromatin remodeling and suggest that histone deubiquitination may play an essential role in the histone-to-protamine exchange process.
Oxidative damage within alternative DNA structures results in aberrant mutagenic processing
Authors: Zewail-Foote Maha , del Mundo Imee M A , Klattenhoff Alex W , Vasquez Karen M 
Published: January 2025

Abstract
Genetic instability is a hallmark of cancer, and mutation hotspots in human cancer genomes co-localize with alternative DNA structure-forming sequences (e.g. H-DNA), implicating them in cancer etiology. H-DNA has been shown to stimulate genetic instability in mammals. Here, we demonstrate a new paradigm of genetic instability, where a cancer-associated H-DNA-forming sequence accumulates more oxidative lesions than B-DNA under conditions of oxidative stress (OS), often found in tumor microenvironments. We show that OS results in destabilization of the H-DNA structure and attenuates the fold increase in H-DNA-induced mutations over control B-DNA in mammalian cells. Furthermore, the mutation spectra revealed that the damaged H-DNA-containing region was processed differently compared to H-DNA in the absence of oxidative damage in mammalian cells. The oxidatively modified H-DNA elicits differential recruitment of DNA repair proteins from both the base excision repair and nucleotide excision repair mechanisms. Altogether, these results suggest a new model of genetic instability whereby H-DNA-forming regions are hotspots for DNA damage in oxidative microenvironments, resulting in its altered mutagenic processing. Our findings provide valuable insights into the role of OS in DNA structure-induced genetic instability and may establish H-DNA-forming sequences as promising genomic biomarkers and potential therapeutic targets for genetic diseases.
Effect of Haemodiafiltration Versus Haemodialysis on Vascular Access Patency when Starting Haemodialysis
Authors: Yoshida Mahoko , Maeoka Yujiro , Takahashi Akira , Ishiuchi Naoki , Osaki Yosuke , Sasaki Kensuke , Masaki Takao 
Published: January 2025

Abstract

Background
Haemodiafiltration (HDF) therapy improves the prognosis by reducing inflammation and oxidative stress, and improving endothelial function. These factors contribute to vascular access (VA) stenosis, one of the most common complications in patients on haemodialysis (HD) or HDF. This study aimed to assess the efficacy of HDF on VA patency.

Methods
This multicentre, prospective, observational study with post-hoc analysis included 612 patients among 643 who underwent VA procedures and started dialysis between April 2012 and March 2021. Five hundred and sixteen patients were on HD from starting dialysis, while 96 switched to HDF after starting dialysis. One-to-one propensity score matching was performed to compare the 24-month patency rates of VA between groups by Kaplan–Meier and log-rank tests, and a Cox proportional hazard regression analysis was used to identify factors affecting patency rates.

Results
There were 87 patients in each group. The 24-month primary patency rates were 74.2% for HDF and 47.7% for HD (P &lt; 0.001). A multivariate Cox proportional hazards analysis showed that a history of cardiovascular disease (hazard ratio [HR] 2.29; 95% confidence interval [CI] 1.21–4.34, P = 0.01) and higher haemoglobin A1c values (HR 1.37; 95% CI 1.00–1.82, P = 0.04) were associated with poor 24-month primary patency. However, HDF (HR 0.30; 95% CI 0.16–0.56, P &lt; 0.001) and use of statins (HR 0.50; 95% CI 0.27–0.94, P = 0.03) were associated with better patency. A stratified analysis showed that HRs for loss of VA patency were lower in patients with HDF than in those with HD in the subgroups of ≥ 65 years, male sex, radiocephalic arteriovenous fistula, a history of diabetes mellitus or cardiovascular disease, haemoglobin concentrations &lt;10 g/dL, and albumin concentrations &lt; 3.5 g/dL.

Conclusions
HDF potentially improves VA patency rates compared with HD, even in patients with cardiovascular disease or diabetes, commonly associated with poor patency.
Porous covalent organic framework liquid for boosting CO2 adsorption and catalysis via dynamically expanding effect
Authors: Chen Zi-Ao , Zou Lei , Cao Rong , Huang Yuan-Biao 
Published: January 2025

Abstract
The features of intrinsic porosity and fluidity endow porous liquids (PLs) unique properties and performances but the preparation of PLs remains challenging due to the difficulty in liquefying and keeping porous features at the same time. Herein, we develop a stepwise surface functionalization and ion exchange strategy to achieve a rare example of flexible covalent organic framework (COF) based porous liquid (COF-PLs). By coating the outer surface of the judiciously selected three-dimensional flexible COF-301 with an imidazolium salt corona, followed by liquefaction using the anion canopy potassium poly(ethylene glycol) sulfonate (PEGS) via electrostatic interactions to obtain the flexible porous liquid COF-301-PL. Theoretical calculations and CO2 adsorption experiments reveal that the cavities of COF-301-PL undergo dynamic adjustments in response to changes in CO2 pressure. The dynamic expansion effect not only can provide additional gas adsorption capacity (7.04 mmol/g at 40 bar) but also facilitate the mass transfer of gas molecules during the catalytic process. Consequently, COF-301-PL exhibits superior catalytic efficiency for the conversion of CO2 into cyclic carbonate by a factor of 24 and 17 compared to those of PEGS and COF-301 solid counterpart, respectively. The optimization of substrate adsorption and mass transfer conditions consequently improves the overall efficiency of catalytic reactions. This work offers a new perspective on the preparation of PLs and their large potential application for gas adsorption and catalysis.