bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of synaptic transmission through O-GlcNAcylation
Authors: Han Seunghyo , Kim Jun-Nyeong , Park Chan Ho , Byun Jin-Seok , Kim Do-Yeon , Ko Hyoung-Gon 
Published: January 2024

AbstractO-GlcNAcylation is a posttranslational modification where N-acetylglucosamine (O-GlcNAc) is attached and detached from a serine/threonine position by two enzymes: O-GlcNAc transferase and O-GlcNAcase. In addition to roles in diabetes and cancer, recent pharmacological and genetic studies have revealed that O-GlcNAcylation is involved in neuronal function, specifically synaptic transmission. Global alteration of the O-GlcNAc level does not affect basal synaptic transmission while the effect on synaptic plasticity is unclear. Although synaptic proteins that are O-GlcNAcylated are gradually being discovered, the mechanism of how O-GlcNAcylated synaptic protein modulate synaptic transmission has only been reported on CREB, synapsin, and GluA2 subunit of AMPAR. Future research enabling the manipulation of O-GlcNAcylation in individual synaptic proteins should reveal hidden aspects of O-GlcNAcylated synaptic proteins as modulators of synaptic transmission.
EIF4A3-mediated biogenesis of circSTX6 promotes bladder cancer metastasis and cisplatin resistance
Authors: Wei Wenjie , Liu Kan , Huang Xing , Tian Shuo , Wang Hanfeng , Zhang Chi , Ye Jiali , Dong Yuhao , An Ziyan , Ma Xin , Wang Baojun , Huang Yan , Zhang Xu 
Published: January 2024

Abstract
Background
Cisplatin (CDDP)-based chemotherapy is a standard first-line treatment for metastatic bladder cancer (BCa) patients, and chemoresistance remains a major challenge in clinical practice. Circular RNAs (circRNAs) have emerged as essential regulators in carcinogenesis and cancer progression. However, the role of circRNAs in mediating CDDP chemosensitivity has yet to be well elucidated in BCa.

Methods
CircSTX6 (hsa_circ_0007905) was identified by mining the public circRNA datasets and verified by Sanger sequencing, agarose gel electrophoresis, RNase R treatment and qRT-PCR assays. Then, function experiments were performed to evaluate the effects of circSTX6 on BCa metastasis. Luciferase reporter assay, RNA pull-down, RNA immunoprecipitation (RIP), RNA stability assay, Fluorescence in situ hybridization (FISH) and Immunofluorescence (IF) were conducted to evaluate the interaction among circSTX6, miR-515-3p, PABPC1 and SUZ12. Animal experiments were performed to explore the function of circSTX6 in tumor metastasis and CDDP sensitivity.

Results
We identified that circSTX6 was significantly upregulated in clinical samples and cells of BCa. Functionally, circSTX6 promoted cell migration and invasion both in vitro and in vivo. Mechanistically, circSTX6 could act as a miR-515-3p sponge and abolish its effect on SUZ12. Moreover, circSTX6 was confirmed to increase the stability of SUZ12 mRNA by interacting with a mRNA stabilizer PABPC1 and subsequently promote the expression of SUZ12. Importantly, silencing of circSTX6 improved the chemosensitivity of CDDP-resistant bladder cancer cells to CDDP. Furthermore, in vivo analysis supported that knockdown of circSTX6 attenuated CDDP resistance in BCa tumors.

Conclusion
These studies demonstrate that circSTX6 plays a pivotal role in BCa metastasis and chemoresistance, and has potential to serve as a therapeutic target for treatment of BCa.
Video versus direct laryngoscopy in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials
Authors: Araújo Beatriz , Rivera André , Martins Suzany , Abreu Renatha , Cassa Paula , Silva Maicon , Gallo de Moraes Alice 
Published: January 2024

Abstract
Background
The utilization of video laryngoscopy (VL) has demonstrated superiority over direct laryngoscopy (DL) for intubation in surgical settings. However, its effectiveness in the intensive care unit and emergency department settings remains uncertain.

Methods
We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) comparing VL versus DL in critically ill patients. Critical setting was defined as emergency department and intensive care unit. This systematic review and meta-analysis followed Cochrane and PRISMA recommendations. R version 4.3.1 was used for statistical analysis and heterogeneity was examined with I2 statistics. All outcomes were submitted to random-effect models.

Results
Our meta-analysis of 14 RCTs, compromising 3981 patients assigned to VL (n = 2002) or DL (n = 1979). Compared with DL, VL significantly increased successful intubations on the first attempt (RR 1.12; 95% CI 1.04–1.20; p < 0.01; I2 = 82%). Regarding adverse events, VL reduced the number of esophageal intubations (RR 0.44; 95% CI 0.24–0.80; p < 0.01; I2 = 0%) and incidence of aspiration episodes (RR 0.63; 95% CI 0.41–0.96; p = 0.03; I2 = 0%) compared to DL.

Conclusion
VL is a more effective and safer strategy compared with DL for increasing successful intubations on the first attempt and reducing esophageal intubations in critically ill patients. Our findings support the routine use of VL in critically ill patients.
Registration CRD42023439685 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439685. Registered 6 July 2023.
Accounting for diverse transposable element landscapes is key to developing and evaluating accurate de novo annotation strategies
Authors: Gozashti Landen , Hoekstra Hopi E. 
Published: January 2024

AbstractTransposable elements (TEs) are important drivers of genome evolution. Nonetheless, TE annotation remains a complex and challenging task. As more genomes from phylogenetically diverse species are published, a comprehensive pipeline for accurate annotation of diverse TEs is increasingly important. Recently, (Ou et al. Genome Biol. 20:275, 2019) developed a new comprehensive pipeline, Extensive De novo Transposable element Annotator (EDTA), and benchmarked its performance on the genomes of three species: maize, wheat, and fruit fly. Because TE landscapes can vary tremendously across species, we tested EDTA’s performance on four additional genomes with different TE landscapes: mouse, zebrafish, zebra finch, and chicken. Our analysis reveals that EDTA faces challenges with repeat classification in these genomes and underperforms overall relative to its benchmark dataset. Notably, EDTA consistently misclassifies nonLTR retrotransposons as DNA transposons, resulting in erroneous TE annotations for species with considerable repertoires of nonLTR retrotransposons. Overall, we set expectations for EDTA’s performance on genomes spanning additional diversity, urge caution when using EDTA on genomes with divergent TE repertoires from the species on which it was initially benchmarked, and hope to motivate the development of methods that are robust to both the diversity of TEs and TE landscapes observed across species.
FORGEdb: a tool for identifying candidate functional variants and uncovering target genes and mechanisms for complex diseases
Authors: Breeze Charles E. , Haugen Eric , Gutierrez-Arcelus María , Yao Xiaozheng , Teschendorff Andrew , Beck Stephan , Dunham Ian , Stamatoyannopoulos John , Franceschini Nora , Machiela Mitchell J. , Berndt Sonja I. 
Published: January 2024

AbstractThe majority of disease-associated variants identified through genome-wide association studies are located outside of protein-coding regions. Prioritizing candidate regulatory variants and gene targets to identify potential biological mechanisms for further functional experiments can be challenging. To address this challenge, we developed FORGEdb (https://forgedb.cancer.gov/; https://forge2.altiusinstitute.org/files/forgedb.html; and https://doi.org/10.5281/zenodo.10067458), a standalone and web-based tool that integrates multiple datasets, delivering information on associated regulatory elements, transcription factor binding sites, and target genes for over 37 million variants. FORGEdb scores provide researchers with a quantitative assessment of the relative importance of each variant for targeted functional experiments.
Efficacy and safety of heparin for sepsis-induced disseminated intravascular coagulation (HepSIC): study protocol for a multicenter randomized controlled trial
Authors: Sun Yini , Ding Renyu , Sun Hao , Liang Yingjian , Ma Xiaochun 
Published: January 2024

Abstract
Background
Disseminated intravascular coagulation (DIC) occurs in 30–50% of septic patients and contributes to high mortality in the intensive care unit (ICU). However, there are few proven interventions for coagulation disorder management in sepsis. Experimental and clinical data have demonstrated that sepsis could benefit from unfractionated heparin (UFH) treatment. To date, there are no large multicenter trials to determine the safety and efficacy of UFH in septic patients with suspected DIC.

Methods
A multicenter, double-blinded, placebo-controlled randomized trial is designed to recruit 600 patients who met sepsis 3.0 criteria and suspected DIC. Participants will be randomized (1:1) to receive UFH or saline via continuous intravenous administration for 7 days within 6 h of enrolment. The primary outcome is ICU mortality. The secondary outcome includes 28-day all-cause mortality, the improvement of Sequential Organ Failure Assessment scores, and the incidence of major hemorrhage. Investigators, participants, and statisticians will be blinded to the allocation.

Discussion
The HepSIC trial is to evaluate the efficacy and safety of UFH on sepsis-related DIC across different areas of China. The small dosage of UFH administration would offer a new potential approach for treating sepsis-related coagulation disorders.

Ethics and dissemination
Ethical approval was granted by all the ethics committees of 20 participant centers. Results will be disseminated via peer-reviewed publications and presented at conferences.

Trial registration
ClinicalTrials.gov NCT02654561. Registered on 13 January 2016.
Experiences and challenges with the new European Clinical Trials Regulation
Authors: Patrick-Brown Thale D. J. H. , Bourner Josephine , Kali Sabrina , Trøseid Marius , Yazdanpanah Yazdan , Olliaro Piero , Olsen Inge Christoffer 
Published: January 2024

Abstract
Background
The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure.

Methods
We report the time to approval, size of the application dossier, and number of requests for information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments.

Results
While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles.

Conclusions
CTIS promised to lower the administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the value of multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. This report is relevant to both regulators and clinical researchers. It is hoped that these findings can help improve pan-European clinical trials, especially for the purpose of epidemic preparedness and response.

Trial registration
This paper references experiences gained during management of three pan-European trials: EU-SolidAct’s Bari-SolidAct (CT No. 2022-500385-99-00 - 15 March 2022) and AXL-SolidAct (CT No. 2022-500363-12-00 - 19 April 2022), and MOSAIC (CT No. 2022-501132-42-00 - 22 June 2022).
Ectoparasites of European hedgehogs (Erinaceus europaeus) in Germany and their health impact
Authors: Schütte Karolin , Springer Andrea , Brandes Florian , Reuschel Maximilian , Fehr Michael , Strube Christina 
Published: January 2024

Abstract
Background
The European hedgehog (Erinaceus europaeus) is known for high levels of ectoparasitism that not only represents a health risk for the animals themselves, but also for pet animals and humans as hedgehogs are frequently taken into human care. In the present study, patterns of ectoparasite infestation were assessed in hedgehogs taken into care at northern German animal rehabilitation centres.

Methods
Ectoparasites (ticks, fleas and mites) of 498 hedgehogs were collected over a period of 3 years from July 2018 to May 2021. Species were identified based on morphological characteristics and also via amplification and sequencing of the partial cytochrome c oxidase subunit 2 (COX-2) gene for fleas of the family Ceratophyllidae. Seasonal changes in infestation patterns as well as correlations with animal age, body weight and health status were assessed using generalised linear models.

Results
Infestation with ticks, fleas and mites occurred throughout the year. Overall, 86.5% (431/498) of the examined hedgehogs were infested with ticks, 91.4% (455/498) with fleas and 17.7% (88/498) with mites.Ixodes ricinus and Ixodes hexagonus/Ixodes canisuga were the most common tick species detected, with the additional occurrence of one Ixodes frontalis. Significant seasonal changes were observed for I. ricinus, but not for I. hexagonus/I. canisuga. Additionally, I. ricinus nymph prevalence declined significantly as of 2020, probably as a consequence of the climate change-related drought as of 2018. In hedgehogs with flea infestations, Archaeopsylla erinacei, Ceratophyllus sciurorum, Nosopsyllus fasciatus and Ctenocephalides felis were identified. In all cases of mite infestation, Caparinia tripilis was detected, in addition to specimens of the family Macronyssidae and free-living mites of the family Acaridae. Statistical analyses showed correlations regarding the factors month, year, body weight and age, but no correlation was evident regarding the health status of the animals.

Conclusions
With a detected infestation rate of 98.6%, almost all of the examined hedgehogs were infested with at least one ectoparasite species. The seasonal activity patterns of the different ectoparasite species together with the complex annual cycle of hedgehogs lead to different seasonal patterns in ectoparasite prevalence and infestation intensities. Due to the risk of transmission of zoonotic pathogens as well as the possible negative impact on the host itself, hedgehogs should be treated against ectoparasites when taken into care facilities.

Graphical Abstract
Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors
Authors: Yan Nan , Xie Weiyan , Wang Dongfang , Fang Qiuyue , Guo Jing , Chen Yiyuan , Li Xinqi , Gong Lei , Wang Jialin , Guo Wenbo , Zhang Xuegong , Zhang Yazhuo , Gu Jin , Li Chuzhong 
Published: January 2024

AbstractBackgroundPituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood.MethodsWe performed single-cell RNA sequencing (scRNA-seq) on 4 normal samples and 24 PitNET samples for comprehensive bioinformatics analysis. Findings regarding the function ofPBKin the aggressive tumor cells were validated by siRNA knockdown, overexpression, and transwell experiments.ResultsWe first constructed a reference cell atlas of the human pituitary. Subsequent scRNA-seq analysis of PitNET samples, representing major tumor subtypes, shed light on the intrinsic cellular heterogeneities of the tumor cells and tumor microenvironment (TME). We found that the expression of hormone-encoding genes defined the major variations of the PIT1-lineage tumor cell transcriptomic heterogeneities. A sub-population of TPIT-lineage tumor cells highly expressingGZMKsuggested a novel subtype of corticotroph tumors. In immune cells, we found two clusters of tumor-associated macrophages, which were both highly enriched in PitNETs but with distinct functional characteristics. In PitNETs, the stress response pathway was significantly activated in T cells. While a majority of these tumors are benign, our study unveils a common existence of aggressive tumor cells in the studied samples, which highly express a set of malignant signature genes. The following functional experiments confirmed the oncogenic role of selected up-regulated genes. The over-expression ofPBKcould promote both tumor cell proliferation and migration, and it was also significantly associated with poor prognosis in PitNET patients.ConclusionsOur data and analysis manifested the basic cell types in the normal pituitary and inherent heterogeneity of PitNETs, identified several features of the tumor immune microenvironments, and found a novel epithelial cell sub-population with aggressive signatures across all the studied cases.
Inhibitory effects of Acanthopanax sessiliflorus Harms extract on the etiology of rheumatoid arthritis in a collagen-induced arthritis mouse model
Authors: Kim Dahye , Heo Yunji , Kim Mangeun , Suminda Godagama Gamaarachchige Dinesh , Manzoor Umar , Min Yunhui , Kim Minhye , Yang Jiwon , Park Youngjun , Zhao Yaping , Ghosh Mrinmoy , Son Young-Ok 
Published: January 2024

Abstract
Background
The biological function of Acanthopanax sessiliflorus Harm (ASH) has been investigated on various diseases; however, the effects of ASH on arthritis have not been investigated so far. This study investigates the effects of ASH on rheumatoid arthritis (RA).

Methods
Supercritical carbon dioxide (CO2) was used for ASH extract preparation, and its primary components, pimaric and kaurenoic acids, were identified using gas chromatography-mass spectrometer (GC–MS). Collagenase-induced arthritis (CIA) was used as the RA model, and primary cultures of articular chondrocytes were used to examine the inhibitory effects of ASH extract on arthritis in three synovial joints: ankle, sole, and knee.

Results
Pimaric and kaurenoic acids attenuated pro-inflammatory cytokine-mediated increase in the catabolic factors and retrieved pro-inflammatory cytokine-mediated decrease in related anabolic factors in vitro; however, they did not affect pro-inflammatory cytokine (IL-1β, TNF-α, and IL-6)-mediated cytotoxicity. ASH effectively inhibited cartilage degradation in the knee, ankle, and toe in the CIA model and decreased pannus development in the knee. Immunohistochemistry demonstrated that ASH mostly inhibited the IL-6-mediated matrix metalloproteinase. Gene Ontology and pathway studies bridge major gaps in the literature and provide insights into the pathophysiology and in-depth mechanisms of RA-like joint degeneration.

Conclusions
To the best of our knowledge, this is the first study to conduct extensive research on the efficacy of ASH extract in inhibiting the pathogenesis of RA. However, additional animal models and clinical studies are required to validate this hypothesis.
Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis
Authors: Qiu Yulu , Feng Xiaoke , Liu Chang , Shi Yumeng , Xu Lingxiao , You Hanxiao , Wang Lei , Lv Chengyin , Wang Fang , Tan Wenfeng 
Published: January 2024

Abstract
Background
Anti-melanoma differentiation-associated gene five antibody positive (MDA5+) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5+ DM patients.

Methods
Plasma samples from 20 MDA5+ DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5+ DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA).

Results
A total of 413 differentially expressed proteins (DEPs) were detected between the MDA5+ DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5+ DM.

Conclusion
This study provides novel insights into the pathogenesis of RP-ILD development in MDA5+ DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.
Autoimmune congenital heart block: a case report and review of the literature related to pathogenesis and pregnancy management
Authors: Huang Ying , Deng Jialin , Liu Jinghua , Yang Fangyuan , He Yi 
Published: January 2024

AbstractAutoimmune congenital heart block (ACHB) is a passively acquired immune-mediated disease characterized by the presence of maternal antibodies against components of the Ro/SSA and La/SSB ribonucleoprotein complex that mainly affects the cardiac conducting system. ACHB occurs in 2% of women with positive anti-Ro/SSA and anti-La/SSB antibodies and causes a high risk of intrauterine fetal death, neonatal mortality, and long-term sequelae. In this review, we first describe a case of ACHB to provide preliminary knowledge. Then, we discuss the possible pathogenic mechanisms of ACHB; summarize the pregnancy management of patients with positive anti-Ro/SSA and anti-La/SSB antibodies and/or rheumatic diseases, the prevention of ACHB, and the treatment of ACHB fetuses; and propose routine screening of these antibodies for the general population. Careful follow-up, which consists of monitoring the fetal heart rate, is feasible and reassuring for pregnant women with positive anti-Ro/SSA and/or anti-La/SSB antibodies to lower the risk of ACHB in fetuses. Moreover, maternal administration of hydroxychloroquine may be useful in preventing ACHB in pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies.