bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of epicardial adipose tissue in children with type 1 diabetes
Authors: Trabzon Gül , Güngör Şükrü , Güllü Şeyma Demiray , Çalışkan Osman Fırat , Güllü Ufuk Utku 
Published: June 2024

Abstract

Introduction
Epicardial adipose tissue (EAT), the visceral fat surrounding the heart between the myocardium and visceral pericardium, intersects with Type 1 diabetes (T1D). This review aims to elucidate the intricate association between EAT and childhood T1D.

Materials and methods
In this retrospective study, two pediatric groups were involved children with type 1 diabetes, and healthy children. Epicardial fat thickness was measured appropriately, and the study documented HbA1c levels and time to diabetes diagnosis for comprehensive analysis.

Results
Encompassing 51 children with T1D and 69 healthy controls, revealed that children with type 1 diabetes had a mean HbA1c level of 9.4 ± 0.2, and a mean insulin dose of 0.94 units/kg/day. Epicardial adipose tissue (EAT) values were significantly higher in the Type 1 DM group. It has been shown that epicardial fat thickness may have a specific and sensitive value in type 1 diabetics.

Discussion
The increased presence of epicardial fat tissue in children with type 1 diabetes is highlighted, prompting the consideration of various mechanisms. However, the complexity of this relationship underscores the need for further studies to provide a more comprehensive understanding of the underlying factors. Ongoing research in this area is crucial for advancing our knowledge and potential therapeutic interventions.

Impacts

Cardiac complications are one of the most important causes of morbidity and mortality in people with type 1 diabetes.

Being able to detect cardiological complications of diabetes at an early stage contributes to morbidity.

We found that epicardial fat tissue thickness was thicker in children with type 1 diabetes than in healthy children.

Epicardial fat tissue thickness may be associated with poor control in children with type 1 diabetes and maybe a guide in terms of cardiac risks.
Efficacy and safety of outpatient fludarabine, cyclophosphamide, and rituximab based allogeneic hematopoietic cell transplantation in adults with severe aplastic anemia
Authors: Gilmore Rachel M. , Abernathy Karin , Shultes Kendall , Eplin Dwight D. , Orton Lindsay , Kassim Adetola , Sengsayadeth Salyka , Chinratanalab Wichai , Kim Tae Kon , Dholaria Bhagirathbhai , Jayani Reena V. , Savani Bipin N. , McNeer Elizabeth , Choi Leena , Gatwood Katie 
Published: June 2024

AbstractThe age effect in severe aplastic anemia (SAA) following allogeneic hematopoietic cell transplantation (HCT) favors the use of reduced intensity conditioning (RIC) regimens in older adults. We implemented a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and rituximab (FCR) to improve HCT outcomes in SAA. Patients who underwent first HCT for SAA utilizing an FCR regimen between January 2016 and May 2022 were included. Outcomes analyzed included time to engraftment, incidence of graft failure, GVHD, viral reactivation, disease recurrence, and GVHD-free, relapse-free survival (GRFS). Among 24 patients included, median age was 43.5 years (22–62) and a variety of donor types and stem cell sources were represented. At median follow-up of 26.9 months (2.4–72.7), no cases of grade III-IV acute (aGVHD) or severe chronic GVHD (cGVHD) were recorded. Viral reactivation was minimal, and there were no cases of graft failure or PTLD, with 100% disease-free and overall survival at last follow up. The estimate of 1-year GRFS was 86.3% (95% CI: 72.8–100%), with moderate cGVHD accounting for all events. The FCR regimen in SAA was well tolerated, even in older adults, with 100% disease-free survival with low GVHD and infection rates. These encouraging findings should be validated in larger prospective trials.
Lactylation of NAT10 promotes N4‐acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation
Authors: Yan Qin , Zhou Jing , Gu Yang , Huang Wenjing , Ruan Mingpeng , Zhang Haoran , Wang Tianjiao , Wei Pengjun , Chen Guochun , Li Wan , Lu Chun 
Published: June 2024

AbstractN4-acetylcytidine (ac4C), a conserved but recently rediscovered RNA modification on tRNAs, rRNAs and mRNAs, is catalyzed by N-acetyltransferase 10 (NAT10). Lysine acylation is a ubiquitous protein modification that controls protein functions. Our latest study demonstrates a NAT10-dependent ac4C modification, which occurs on the polyadenylated nuclear RNA (PAN) encoded by oncogenic DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV), can induce KSHV reactivation from latency and activate inflammasome. However, it remains unclear whether a novel lysine acylation occurs in NAT10 during KSHV reactivation and how this acylation of NAT10 regulates tRNAs ac4C modification. Here, we showed that NAT10 was lactylated by α-tubulin acetyltransferase 1 (ATAT1), as a writer at the critical domain, to exert RNA acetyltransferase function and thus increase the ac4C level of tRNASer-CGA-1-1. Mutagenesis at the ac4C site in tRNASer-CGA-1-1 inhibited its ac4C modifications, translation efficiency of viral lytic genes, and virion production. Mechanistically, KSHV PAN orchestrated NAT10 and ATAT1 to enhance NAT10 lactylation, resulting in tRNASer-CGA-1-1 ac4C modification, eventually boosting KSHV reactivation. Our findings reveal a novel post-translational modification in NAT10, as well as expand the understanding about tRNA-related ac4C modification during KSHV replication, which may be exploited to design therapeutic strategies for KSHV-related diseases.
Interleukin-1β induces and accelerates human endometrial stromal cell senescence and impairs decidualization via the c-Jun N-terminal kinase pathway
Authors: Taylor Robert N. , Berga Sarah L. , Zou Eric , Washington Jacara , Song Sunyangzi , Marzullo Brandon J. , Bagchi Indrani C. , Bagchi Milan K. , Yu Jie 
Published: June 2024

AbstractAs the mean age of first-time mothers increases in the industrialized world, inquiries into causes of human reproductive senescence have followed. Rates of ovulatory dysfunction and oocyte aneuploidy parallel chronological age, but poor reproductive outcomes in women older than 35 years are also attributed to endometrial senescence. The current studies, using primary human endometrial stromal cell (ESC) cultures as an in vitro model for endometrial aging, characterize the proinflammatory cytokine, IL-1β-mediated and passage number-dependent effects on ESC phenotype. ESC senescence was accelerated by incubation with IL-1β, which was monitored by RNA sequencing, ELISA, immunocytochemistry and Western blotting. Senescence associated secreted phenotype (SASP) proteins, IL-1β, IL-6, IL-8, TNF-α, MMP3, CCL2, CCL5, and other senescence-associated biomarkers of DNA damage (p16, p21, HMGB1, phospho-γ-histone 2 A.X) were noted to increase directly in response to 0.1 nM IL-1β stimulation. Production of the corresponding SASP proteins increased further following extended cell passage. Using enzyme inhibitors and siRNA interference, these effects of IL-1β were found to be mediated via the c-Jun N-terminal kinase (JNK) signaling pathway. Hormone-induced ESC decidualization, classical morphological and biochemical endocrine responses to estradiol, progesterone and cAMP stimulation (prolactin, IGFBP-1, IL-11 and VEGF), were attenuated pari passu with prolonged ESC passaging. The kinetics of differentiation responses varied in a biomarker-specific manner, with IGFBP-1 and VEGF secretion showing the largest and smallest reductions, with respect to cell passage number. ESC hormone responsiveness was most robust when limited to the first six cell passages. Hence, investigation of ESC cultures as a decidualization model should respect this limitation of cell aging. The results support the hypotheses that “inflammaging” contributes to endometrial senescence, disruption of decidualization and impairment of fecundity. IL-1β and the JNK signaling pathway are pathogenetic targets amenable to pharmacological correction or mitigation with the potential to reduce endometrial stromal senescence and enhance uterine receptivity.
Nicotine-induced activation of cholinergic receptor nicotinic alpha 5 subunit mediates the malignant behaviours of laryngeal squamous epithelial cells by interacting with RABL6
Authors: Shen Yujie , Huang Qiang , Yuan Xiaohui , Gong Hongli , Xu Chengzhi , Du Huaidong , Hsueh Chi-Yao , Zhou Liang 
Published: June 2024

AbstractNicotine, a crucial constituent of tobacco smoke, can bind to and activate nicotinic acetylcholine receptors (nAChRs), thereby regulating various biological functions. However, the specific mechanisms through which nicotine mediates nAChRs to regulate the metastasis of laryngeal squamous cell carcinoma (LSCC) remain elusive. In this study, smoking status was found to be closely associated with metastasis in patients with LSCC. In addition, nicotine exposure potentiated the hematogenous and lymphatic metastatic capacity of LSCC cells. Nicotine activates membrane-bound CHRNA5, promoting cell migration and invasion, EMT and cell–ECM adhesion in LSCC. Furthermore, this study demonstrated that the Ras superfamily protein RABL6 directly interacted with CHRNA5, which preferentially binds to the RABL6-39-279aa region, and this interaction was enhanced by nicotine. Nicotine-mediated activation of CHRNA5 enhanced its interaction with RABL6, triggering the JAK2/STAT3 signalling pathway and eventually augmenting the metastatic potential of LSCC cells. This study reveals a novel mechanism through which nicotine-mediated CHRNA5–RABL6 interaction promotes the metastasis of LSCC. The findings of this study may help to develop effective strategies for improving the outcome of patients with LSCC in clinical settings.
The roles of Th cells in myocardial infarction
Authors: Liu Jun , Liu Feila , Liang Tingting , Zhou Yue , Su Xiaohan , Li Xue , Zeng Jiao , Qu Peng , Wang Yali , Chen Fuli , Lei Qian , Li Gang , Cheng Panke 
Published: June 2024

AbstractMyocardial infarction, commonly known as a heart attack, is a serious condition caused by the abrupt stoppage of blood flow to a part of the heart, leading to tissue damage. A significant aspect of this condition is reperfusion injury, which occurs when blood flow is restored but exacerbates the damage. This review first addresses the role of the innate immune system, including neutrophils and macrophages, in the cascade of events leading to myocardial infarction and reperfusion injury. It then shifts focus to the critical involvement of CD4+ T helper cells in these processes. These cells, pivotal in regulating the immune response and tissue recovery, include various subpopulations such as Th1, Th2, Th9, Th17, and Th22, each playing a unique role in the pathophysiology of myocardial infarction and reperfusion injury. These subpopulations contribute to the injury process through diverse mechanisms, with cytokines such as IFN-γ and IL-4 influencing the balance between tissue repair and injury exacerbation. Understanding the interplay between the innate immune system and CD4+ T helper cells, along with their cytokines, is crucial for developing targeted therapies to mitigate myocardial infarction and reperfusion injury, ultimately improving outcomes for cardiac patients.
In-tube micro-pyramidal silicon nanopore for inertial-kinetic sensing of single molecules
Authors: Yang Jianxin , Pan Tianle , Xie Zhenming , Yuan Wu , Ho Ho-Pui 
Published: June 2024

AbstractElectrokinetic force has been the major choice for driving the translocation of molecules through a nanopore. However, the use of this approach is limited by an uncontrollable translocation speed, resulting in non-uniform conductance signals with low conformational sensitivity, which hinders the accurate discrimination of the molecules. Here, we show the use of inertial-kinetic translocation induced by spinning an in-tube micro-pyramidal silicon nanopore fabricated using photovoltaic electrochemical etch-stop technique for biomolecular sensing. By adjusting the kinetic properties of a funnel-shaped centrifugal force field while maintaining a counter-balanced state of electrophoretic and electroosmotic effect in the nanopore, we achieved regulated translocation of proteins and obtained stable signals of long and adjustable dwell times and high conformational sensitivity. Moreover, we demonstrated instantaneous sensing and discrimination of molecular conformations and longitudinal monitoring of molecular reactions and conformation changes by wirelessly measuring characteristic features in current blockade readouts using the in-tube nanopore device.
Roadblocks confronting widespread dissemination and deployment of Organs on Chips
Authors: Alver Charles G. , Drabbe Emma , Ishahak Matthew , Agarwal Ashutosh 
Published: June 2024

AbstractOrgan on Chip platforms hold significant promise as alternatives to animal models or traditional cell cultures, both of which poorly recapitulate human pathophysiology and human level responses. Within the last 15 years, we have witnessed seminal scientific developments from academic laboratories, a flurry of startups and investments, and a genuine interest from pharmaceutical industry as well as regulatory authorities to translate these platforms. This Perspective identifies several fundamental design and process features that may act as roadblocks that prevent widespread dissemination and deployment of these systems, and provides a roadmap to help position this technology in mainstream drug discovery.
Deep cell phenotyping and spatial analysis of multiplexed imaging with TRACERx-PHLEX
Authors: Magness Alastair , Colliver Emma , Enfield Katey S. S. , Lee Claudia , Shimato Masako , Daly Emer , Moore David A. , Sivakumar Monica , Valand Karishma , Levi Dina , Hiley Crispin T. , Hobson Philip S. , van Maldegem Febe , Reading James L. , Quezada Sergio A. , Downward Julian , Sahai Erik , Swanton Charles , Angelova Mihaela 
Published: June 2024

AbstractThe growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations. PHLEX was developed using imaging mass cytometry (IMC) in the TRACERx study, validated using published Co-detection by indexing (CODEX), IMC and orthogonal data and benchmarked against state-of-the-art approaches. We evaluated its use on different tissue types, tissue fixation conditions, image sizes and antibody panels. As PHLEX is an automated and containerised Nextflow pipeline, manual assessment, programming skills or pathology expertise are not essential. PHLEX offers an end-to-end solution in a growing field of highly multiplexed data and provides clinically relevant insights.
Oceanic Anoxic Event 2 triggered by Kerguelen volcanism
Authors: Walker-Trivett C. A. , Kender S. , Bogus K. A. , Littler K. , Edvardsen T. , Leng M. J. , Lacey J. , Riding J. B. , Millar I. L. , Wagner D. 
Published: June 2024

AbstractLarge Igneous Provinces (LIPs) are associated with global warming and carbon cycle perturbations during Oceanic Anoxic Event 2 (OAE2, ~94 Ma) and the Mid-Cenomanian Event (MCE, ~96.5 Ma). However, there is still no consensus on the role volcanism played as a trigger, or its source – previously ascribed to the Caribbean LIP or High Arctic LIP. Here, we use Mentelle Basin sedimentary mercury (Hg) concentrations to determine the timing of volcanism, and neodymium (Nd) and strontium (Sr) isotopes for sedimentary provenance. High Hg concentrations compared to Northern Hemisphere records, and a shift to radiogenic Nd isotopes, indicates Kerguelen LIP volcanic activity and plateau uplift occurred in the lead up to and within OAE2. Whilst we find limited evidence that a volcanic event caused the MCE, pulsed Hg spikes before and during OAE2 imply volcanic emissions were key in driving climate and carbon cycle changes and triggering OAE2.
m5C methylated lncRncr3–MeCP2 interaction restricts miR124a-initiated neurogenesis
Authors: Zhang Jing , Li Huili , Niswander Lee A. 
Published: June 2024

AbstractCoordination of neuronal differentiation with expansion of the neuroepithelial/neural progenitor cell (NEPC/NPC) pool is essential in early brain development. Our in vitro and in vivo studies identify independent and opposing roles for two neural-specific and differentially expressed non-coding RNAs derived from the same locus: the evolutionarily conserved lncRNA Rncr3 and the embedded microRNA miR124a-1. Rncr3 regulates NEPC/NPC proliferation and controls the biogenesis of miR124a, which determines neuronal differentiation. Rncr3 conserved exons 2/3 are cytosine methylated and bound by methyl-CpG binding protein MeCP2, which restricts expression of miR124a embedded in exon 4 to prevent premature neuronal differentiation, and to orchestrate proper brain growth. MeCP2 directly binds cytosine-methylated Rncr3 through previously unrecognized lysine residues and suppresses miR124a processing by recruiting PTBP1 to block access of DROSHA-DGCR8. Thus, miRNA processing is controlled by lncRNA m5C methylation along with the defined m5C epitranscriptomic RNA reader protein MeCP2 to coordinate brain development.
Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue
Authors: Baek Sewoom , Ha Hyun-Su , Park Jeong Su , Cho Min Jeong , Kim Hye-Seon , Yu Seung Eun , Chung Seyong , Kim Chansik , Kim Jueun , Lee Ji Youn , Lee Yerin , Kim Hyunjae , Nam Yujin , Cho Sungwoo , Lee Kyubae , Yoon Ja Kyung , Choi Jin Sub , Han Dai Hoon , Sung Hak-Joon 
Published: June 2024

AbstractHepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.
Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology
Authors: Mastenbroek Sophie E. , Vogel Jacob W. , Collij Lyduine E. , Serrano Geidy E. , Tremblay Cécilia , Young Alexandra L. , Arce Richard A. , Shill Holly A. , Driver-Dunckley Erika D. , Mehta Shyamal H. , Belden Christine M. , Atri Alireza , Choudhury Parichita , Barkhof Frederik , Adler Charles H. , Ossenkoppele Rik , Beach Thomas G. , Hansson Oskar 
Published: June 2024

AbstractLewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer’s disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.
Stabilized ε-Fe2C catalyst with Mn tuning to suppress C1 byproduct selectivity for high-temperature olefin synthesis
Authors: Qian Fei , Bai Jiawei , Cai Yi , Yang Hui , Cao Xue-Min , Liu Xingchen , Liu Xing-Wu , Yang Yong , Li Yong-Wang , Ma Ding , Wen Xiao-Dong 
Published: June 2024

AbstractAccurately controlling the product selectivity in syngas conversion, especially increasing the olefin selectivity while minimizing C1 byproducts, remains a significant challenge. Epsilon Fe2C is deemed a promising candidate catalyst due to its inherently low CO2 selectivity, but its use is hindered by its poor high-temperature stability. Herein, we report the successful synthesis of highly stable ε-Fe2C through a N-induced strategy utilizing pyrolysis of Prussian blue analogs (PBAs). This catalyst, with precisely controlled Mn promoter, not only achieved an olefin selectivity of up to 70.2% but also minimized the selectivity of C1 byproducts to 19.0%, including 11.9% CO2 and 7.1% CH4. The superior performance of our ε-Fe2C-xMn catalysts, particularly in minimizing CO2 formation, is largely attributed to the interface of dispersed MnO cluster and ε-Fe2C, which crucially limits CO to CO2 conversion. Here, we enhance the carbon efficiency and economic viability of the olefin production process while maintaining high catalytic activity.
Hebbian priming of human motor learning
Authors: Bjørndal Jonas Rud , Beck Mikkel Malling , Jespersen Lasse , Christiansen Lasse , Lundbye-Jensen Jesper 
Published: June 2024

AbstractMotor learning relies on experience-dependent plasticity in relevant neural circuits. In four experiments, we provide initial evidence and a double-blinded, sham-controlled replication (Experiment I-II) demonstrating that motor learning involving ballistic index finger movements is improved by preceding paired corticospinal-motoneuronal stimulation (PCMS), a human model for exogenous induction of spike-timing-dependent plasticity. Behavioral effects of PCMS targeting corticomotoneuronal (CM) synapses are order- and timing-specific and partially bidirectional (Experiment III). PCMS with a 2 ms inter-arrival interval at CM-synapses enhances learning and increases corticospinal excitability compared to control protocols. Unpaired stimulations did not increase corticospinal excitability (Experiment IV). Our findings demonstrate that non-invasively induced plasticity interacts positively with experience-dependent plasticity to promote motor learning. The effects of PCMS on motor learning approximate Hebbian learning rules, while the effects on corticospinal excitability demonstrate timing-specificity but not bidirectionality. These findings offer a mechanistic rationale to enhance motor practice effects by priming sensorimotor training with individualized PCMS.