bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular control of cellulosic fin morphogenesis in ascidians
Authors: Lanoizelet Maxence , Elkhoury Youhanna Christel , Roure Agnès , Darras Sébastien 
Published: April 2024

Abstract
Background
The tunicates form a group of filter-feeding marine animals closely related to vertebrates. They share with them a number of features such as a notochord and a dorsal neural tube in the tadpole larvae of ascidians, one of the three groups that make tunicates. However, a number of typical chordate characters have been lost in different branches of tunicates, a diverse and fast-evolving phylum. Consequently, the tunic, a sort of exoskeleton made of extracellular material including cellulose secreted by the epidermis, is the unifying character defining the tunicate phylum. In the larva of ascidians, the tunic differentiates in the tail into a median fin (with dorsal and ventral extended blades) and a caudal fin.

Results
Here we have performed experiments in the ascidian Phallusia mammillata to address the molecular control of tunic 3D morphogenesis. We have demonstrated that the tail epidermis medio-lateral patterning essential for peripheral nervous system specification also controls tunic elongation into fins. More specifically, when tail epidermis midline identity was abolished by BMP signaling inhibition, or CRISPR/Cas9 inactivation of the transcription factor coding genes Msx or Klf1/2/4/17, median fin did not form. We postulated that this genetic program should regulate effectors of tunic secretion. We thus analyzed the expression and regulation in different ascidian species of two genes acquired by horizontal gene transfer (HGT) from bacteria, CesA coding for a cellulose synthase and Gh6 coding for a cellulase. We have uncovered an unexpected dynamic history of these genes in tunicates and high levels of variability in gene expression and regulation among ascidians. Although, in Phallusia, Gh6 has a regionalized expression in the epidermis compatible with an involvement in fin elongation, our functional studies indicate a minor function during caudal fin formation only.

Conclusions
Our study constitutes an important step in the study of the integration of HGT-acquired genes into developmental networks and a cellulose-based morphogenesis of extracellular material in animals.
Real-world performance of indobufen versus aspirin after percutaneous coronary intervention: insights from the ASPIRATION registry
Authors: Dai Chunfeng , Liu Muyin , Yang Zheng , Li Youran , Zhou You , Lu Danbo , Xia Yan , Chen Ao , Li Chenguang , Lu Hao , Dai Yuxiang , Ma Jianying , Chen Zhangwei , Qian Juying , Ge Junbo 
Published: April 2024

Abstract
Background
Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population.

Methods
Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment.

Results
A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS.

Conclusions
Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS.

Trial registration
Chinese Clinical Trial Register (https://www.chictr.org.cn); Number: ChiCTR2300067274.
GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability
Authors: Barrett J. S. , Strauss J. A. , Chow L. S. , Shepherd S. O. , Wagenmakers A. J. M. , Wang Y. 
Published: April 2024

Abstract
Background
Insulin-stimulated glucose uptake into skeletal muscle occurs via translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. Elevated free fatty acid (FFA) availability via a lipid infusion reduces glucose disposal, but this occurs in the absence of impaired proximal insulin signalling. Whether GLUT4 localisation to the plasma membrane is subsequently affected by elevated FFA availability is not known.

Methods
Trained (n = 11) and sedentary (n = 10) individuals, matched for age, sex and body mass index, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0, 2 and 6 h) were analysed for GLUT4 membrane localisation and microvesicle size and distribution using immunofluorescence microscopy.

Results
At baseline, trained individuals had more small GLUT4 spots at the plasma membrane, whereas sedentary individuals had larger GLUT4 spots. GLUT4 localisation with the plasma membrane increased at 2 h (P = 0.04) of the hyperinsulinemic-euglycemic clamp, and remained elevated until 6 h, with no differences between groups or infusion type. The number of GLUT4 spots was unchanged at 2 h of infusion. However, from 2 to 6 h there was a decrease in the number of small GLUT4 spots at the plasma membrane (P = 0.047), with no differences between groups or infusion type.

Conclusion
GLUT4 localisation with the plasma membrane increases during a hyperinsulinemic-euglycemic clamp, but this is not altered by elevated FFA availability. GLUT4 appears to disperse from small GLUT4 clusters located at the plasma membrane to support glucose uptake during a hyperinsulinaemic-euglycaemic clamp.
Patient-reported outcome measures for primary hyperparathyroidism: a systematic review of measurement properties
Authors: Liang George , Kaur Manraj N. , Wade Carrie G. , Edelen Maria O. , Bates David W. , Pusic Andrea L. , Liu Jason B. 
Published: April 2024

Abstract
Background
The quality of patient-reported outcome measures (PROMs) used to assess the outcomes of primary hyperparathyroidism (PHPT), a common endocrine disorder that can negatively affect patients’ health-related quality of life due to chronic symptoms, has not been rigorously examined. This systematic review aimed to summarize and evaluate evidence on the measurement properties of PROMs used in adult patients with PHPT, and to provide recommendations for appropriate measure selection.

Methods
After PROSPERO registration (CRD42023438287), Medline, EMBASE, CINAHL Complete, Web of Science, PsycINFO, and Cochrane Trials were searched for full-text articles in English investigating PROM development, pilot studies, or evaluation of at least one PROM measurement property in adult patients with any clinical form of PHPT. Two reviewers independently identified studies for inclusion and conducted the review following the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) Methodology to assess risk of bias, evaluate the quality of measurement properties, and grade the certainty of evidence.

Results
From 4989 records, nine PROM development or validation studies were identified for three PROMs: the SF-36, PAS, and PHPQoL. Though the PAS demonstrated sufficient test-retest reliability and convergent validity, and the PHPQoL sufficient test-retest reliability, convergent validity, and responsiveness, the certainty of evidence was low-to-very low due to risk of bias. All three PROMs lacked sufficient evidence for content validity in patients with PHPT.

Conclusions
Based upon the available evidence, the SF-36, PAS, and PHPQoL cannot currently be recommended for use in research or clinical care, raising important questions about the conclusions of studies using these PROMs. Further validation studies or the development of more relevant PROMs with strong measurement properties for this patient population are needed.
The effectiveness of knowledge-sharing techniques and approaches in research funded by the National Institute for Health and Care Research (NIHR): a systematic review
Authors: Baxter Helen , Bearne Lindsay , Stone Tracey , Thomas Clare , Denholm Rachel , Redwood Sabi , Purdy Sarah , Huntley Alyson Louise 
Published: April 2024

Abstract
Background
The National Institute of Health and Care Research (NIHR), funds, enables and delivers world-leading health and social care research to improve people’s health and wellbeing. To achieve this aim, effective knowledge sharing (two-way knowledge sharing between researchers and stakeholders to create new knowledge and enable change in policy and practice) is needed. To date, it is not known which knowledge sharing techniques and approaches are used or how effective these are in creating new knowledge that can lead to changes in policy and practice in NIHR funded studies.

Methods
In this restricted systematic review, electronic databases [MEDLINE, The Health Management Information Consortium (including the Department of Health’s Library and Information Services and King’s Fund Information and Library Services)] were searched for published NIHR funded studies that described knowledge sharing between researchers and other stakeholders. One researcher performed title and abstract, full paper screening and quality assessment (Critical Appraisal Skills Programme qualitative checklist) with a 20% sample independently screened by a second reviewer. A narrative synthesis was adopted.

Results
In total 9897 records were identified. After screening, 17 studies were included. Five explicit forms of knowledge sharing studies were identified: embedded models, knowledge brokering, stakeholder engagement and involvement of non-researchers in the research or service design process and organisational collaborative partnerships between universities and healthcare organisations. Collectively, the techniques and approaches included five types of stakeholders and worked with them at all stages of the research cycle, except the stage of formation of the research design and preparation of funding application. Seven studies (using four of the approaches) gave examples of new knowledge creation, but only one study (using an embedded model approach) gave an example of a resulting change in practice. The use of a theory, model or framework to explain the knowledge sharing process was identified in six studies.

Conclusions
Five knowledge sharing techniques and approaches were reported in the included NIHR funded studies, and seven studies identified the creation of new knowledge. However, there was little investigation of the effectiveness of these approaches in influencing change in practice or policy.
Clinical significance of RNA methylation in hepatocellular carcinoma
Authors: Bao Qiongling , Zeng Yifan , Lou Qizhuo , Feng Xuewen , Jiang Shuwen , Lu Juan , Ruan Bing 
Published: April 2024

AbstractHepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.
Super enhancer lncRNAs: a novel hallmark in cancer
Authors: Song Ping , Han Rongyan , Yang Fan 
Published: April 2024

AbstractSuper enhancers (SEs) consist of clusters of enhancers, harboring an unusually high density of transcription factors, mediator coactivators and epigenetic modifications. SEs play a crucial role in the maintenance of cancer cell identity and promoting oncogenic transcription. Super enhancer lncRNAs (SE-lncRNAs) refer to either transcript from SEs locus or interact with SEs, whose transcriptional activity is highly dependent on SEs. Moreover, these SE-lncRNAs can interact with their associated enhancer regions in cis and modulate the expression of oncogenes or key signal pathways in cancers. Inhibition of SEs would be a promising therapy for cancer. In this review, we summarize the research of SE-lncRNAs in different kinds of cancers so far and decode the mechanism of SE-lncRNAs in carcinogenesis to provide novel ideas for the cancer therapy.
Primary left ventricular leiomyosarcoma: a case report
Authors: Balachandran Vipin , Young Vanessa , Baillie Tina , James Allen 
Published: April 2024

AbstractCardiac leiomyosarcomas are a rare subset of the already infrequent, primary malignant cardiac neoplasia spectrum. The most common site for a primary leiomyosarcoma of the ventricle is on the right with fewer than five globally reported cases in the left ventricle. Most present with non-specific symptoms but attention is usually sought after the appearance of compressive symptoms or arrhythmias. We present a case of a left ventricular leiomyosarcoma in a 50-year old female patient that had a delayed diagnosis and its subsequent surgical resection and oncological management with docetaxel and gemcitabine. This case highlights the need for a high index of suspicion for cardiac masses especially if there are competing chronic diseases with similar symptomatology. Given the rare presentation of left ventricular leiomyosarcomas, case reports may provide valuable information that is otherwise unavailable.
Transversotrema hafniensis n. sp. infection in Poecilia reticulata by cercariae released from Melanoides tuberculata in Denmark
Authors: Buchmann Kurt , Kania Per Walter 
Published: April 2024

Abstract
Background
Exotic and ornamental fish are highly popular companion animals resulting in a significant transcontinental trade of fish, invertebrates and aquatic plants. A major issue is the diseases associated with these organisms, as they have a major impact on health of the fish in both public and private household aquaria. A secondary issue is the trade with these products, which potentially may expand the distribution area and spread a range of diseases to new habitats.

Results
We here describe how Poecilia reticulata (guppy), produced in a private household aquarium, were invaded by cercariae of an exotic trematode released by imported Melanoides tuberculata snails. The fish presented with severe clinical signs (tremor, flashing, scraping of body against objects). A standard parasitological examination and morphometric identification showed scale pocket infections with a digenean trematode species within the genus Transversotrema. Molecular identification by PCR, sequencing and phylogenetic analyses of a 2646 bp sequence encoding ribosomal RNA (partial 18 S, ITS1, 5.8 S, ITS2, partial 28 S) was performed. The 1107 bp sequence of mitochondrial DNA (cox1) showed that the parasite differed from previously described Transversotrema species in M. tuberculata. Morphometrics of adult and larval specimens of this isolate also differed from previously described freshwater species within the genus. The new species was described and is named after Copenhagen, for its geographic origin.

Conclusions
The genus Transversotrema comprises a range of species, adapted to a microhabitat in scalepockets of teleosts. A combination of morphological and molecular characterization techniques has been shown to provide a good differentiation between species. The fish were not purchased from a pet shop but produced in the home aquarium. This indicated that an infection pressure existed in the aquarium, where the source of infection was found to be exotic intermediate host snails M. tuberculata, which originally were imported and purchased from a pet shop. The potential spread of fish diseases associated with trade of fish and snails to new geographic regions, where climate conditions are favourable, is discussed.
A phase I open-label, dose-escalation study of NUC-3373, a targeted thymidylate synthase inhibitor, in patients with advanced cancer (NuTide:301)
Authors: Spiliopoulou Pavlina , Kazmi Farasat , Aroldi Francesca , Holmes Thomas , Thompson David , Griffiths Lucinda , Qi Cathy , Parkes Matthew , Lord Simon , Veal Gareth J. , Harrison David J. , Coyle Vicky M. , Graham Jill , Jeffry Evans Thomas R. , Blagden Sarah P. 
Published: April 2024

Abstract
Purpose
5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), is associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 is a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed to overcome these limitations and replace fluoropyrimidines such as 5-FU.

Patients and methods
NUC-3373 was administered as monotherapy to patients with advanced solid tumors refractory to standard therapy via intravenous infusion either on Days 1, 8, 15 and 22 (Part 1) or on Days 1 and 15 (Part 2) of 28-day cycles until disease progression or unacceptable toxicity. Primary objectives were maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) and schedule of NUC-3373. Secondary objectives included pharmacokinetics (PK), and anti-tumor activity.

Results
Fifty-nine patients received weekly NUC-3373 in 9 cohorts in Part 1 (n = 43) and 3 alternate-weekly dosing cohorts in Part 2 (n = 16). They had received a median of 3 prior lines of treatment (range: 0–11) and 74% were exposed to prior fluoropyrimidines. Four experienced dose-limiting toxicities: two Grade (G) 3 transaminitis; one G2 headache; and one G3 transient hypotension. Commonest treatment-related G3 adverse event of raised transaminases occurred in < 10% of patients. NUC-3373 showed a favorable PK profile, with dose-proportionality and a prolonged half-life compared to 5-FU. A best overall response of stable disease was observed, with prolonged progression-free survival.

Conclusion
NUC-3373 was well-tolerated in a heavily pre-treated solid tumor patient population, including those who had relapsed on prior 5-FU. The MTD and RP2D was defined as 2500 mg/m2 NUC-3373 weekly. NUC-3373 is currently in combination treatment studies.

Trial registration
Clinicaltrials.gov registry number NCT02723240. Trial registered on 8th December 2015. https://clinicaltrials.gov/study/NCT02723240.
Comparison of a multiplex PCR with DNA barcoding for identification of container breeding mosquito species
Authors: Reichl Julia , Prossegger Christina , Petutschnig Sarah , Unterköfler Maria Sophia , Bakran-Lebl Karin , Markowicz Mateusz , Indra Alexander , Fuehrer Hans-Peter 
Published: April 2024

Abstract
Background
Identification of mosquitoes greatly relies on morphological specification. Since some species cannot be distinguished reliably by morphological methods, it is important to incorporate molecular techniques into the diagnostic pipeline. DNA barcoding using Sanger sequencing is currently widely used for identification of mosquito species. However, this method does not allow detection of multiple species in one sample, which would be important when analysing mosquito eggs. Detection of container breeding Aedes is typically performed by collecting eggs using ovitraps. These traps consist of a black container filled with water and a wooden spatula inserted for oviposition support. Aedes mosquitoes of different species might lay single or multiple eggs on the spatula. In contrast to Sanger sequencing of specific polymerase chain reaction (PCR) products, multiplex PCR protocols targeting specific species of interest can be of advantage for detection of multiple species in the same sample.

Methods
For this purpose, we adapted a previously published PCR protocol for simultaneous detection of four different Aedes species that are relevant for Austrian monitoring programmes, as they can be found in ovitraps: Aedes albopictus, Aedes japonicus, Aedes koreicus, and Aedes geniculatus. For evaluation of the multiplex PCR protocol, we analysed 2271 ovitrap mosquito samples from the years 2021 and 2022, which were collected within the scope of an Austrian nationwide monitoring programme. We compared the results of the multiplex PCR to the results of DNA barcoding.

Results
Of 2271 samples, the multiplex PCR could identify 1990 samples, while species determination using DNA barcoding of the mitochondrial cytochrome c oxidase subunit I gene was possible in 1722 samples. The multiplex PCR showed a mixture of different species in 47 samples, which could not be detected with DNA barcoding.

Conclusions
In conclusion, identification of Aedes species in ovitrap samples was more successful when using the multiplex PCR protocol as opposed to the DNA barcoding protocol. Additionally, the multiplex PCR allowed us to detect multiple species in the same sample, while those species might have been missed when using DNA barcoding with Sanger sequencing alone. Therefore, we propose that the multiplex PCR protocol is highly suitable and of great advantage when analysing mosquito eggs from ovitraps.

Graphical Abstract