bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNAH19 acts as a ceRNA of let-7 g to facilitate endothelial-to-mesenchymal transition in hypoxic pulmonary hypertension via regulating TGF-β signalling pathway
Authors: Yu Xin , Huang Jiabing , Liu Xu , Li Juan , Yu Miao , Li Minghui , Xie Yuliang , Li Ye , Qiu Junyu , Xu Zhou , Zhu Tiantian , Zhang Weifang 
Published: July 2024

Abstract
Background
Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined.

Methods
In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19.

Results
Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFβR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFβR1 induced similar effects to H19 deficiency.

Conclusions
In summary, our findings demonstrate that the H19/let-7 g/TGFβR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.
Six-month supplementation with high dose coenzyme Q10 improves liver steatosis, endothelial, vascular and myocardial function in patients with metabolic-dysfunction associated steatotic liver disease: a randomized double-blind, placebo-controlled trial
Authors: Vrentzos Emmanouil , Ikonomidis Ignatios , Pavlidis George , Katogiannis Konstantinos , Korakas Emmanouil , Kountouri Aikaterini , Pliouta Loukia , Michalopoulou Eleni , Pelekanou Emilia , Boumpas Dimitrios , Lambadiari Vaia 
Published: July 2024

Abstract
Backround
Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) has been associated with increased cardiovascular risk. The aim of this Randomized Double-blind clinical Trial was to evaluate the effects of coenzyme-Q10 supplementation in patients with MASLD in terms of endothelial, vascular and myocardial function.

Methods
Sixty patients with MASLD were randomized to receive daily 240 mg of coenzyme-Q10 or placebo. At baseline and at 6-months, the a)Perfused boundary region of sublingual vessels using the Sideview Darkfield imaging technique, b)pulse-wave-velocity, c)flow-mediated dilation of the brachial artery, d)left ventricular global longitudinal strain, e)coronary flow reserve of the left anterior descending coronary artery and f)controlled attenuation parameter for the quantification of liver steatosis were evaluated.

Results
Six months post-treatment, patients under coenzyme-Q10 showed reduced Perfused boundary region (2.18 ± 0.23vs.2.29 ± 0.18 μm), pulse-wave-velocity (9.5 ± 2vs.10.2 ± 2.3 m/s), controlled attenuation parameter (280.9 ± 33.4vs.304.8 ± 37.4dB/m), and increased flow-mediated dilation (6.1 ± 3.8vs.4.3 ± 2.8%), global longitudinal strain (-19.6 ± 1.6vs.-18.8 ± 1.9%) and coronary flow reserve (3.1 ± 0.4vs.2.8 ± 0.4) compared to baseline (p < 0.05). The placebo group exhibited no improvement during the 6-month follow-up period (p > 0.05). In patients under coenzyme-Q10, the reduction in controlled attenuation parameter score was positively related to the reduction in Perfused boundary region and pulse wave velocity and reversely related to the increase in coronary flow reserve and flow-mediated dilation (p < 0.05 for all relations).

Conclusions
Six-month treatment with high-dose coenzyme-Q10 reduces liver steatosis and improves endothelial, vascular and left ventricle myocardial function in patients with MASLD, demonstrating significant improvements in micro- and macro-vasculature function.

Trial Registration
NCT05941910
Automatic localization of cochlear implant electrodes using cone beam computed tomography images
Authors: Thormählen Jasmin , Krüger Benjamin , Nogueira Waldo 
Published: July 2024

Abstract
Background
Cochlear implants (CI) are implantable medical devices that enable the perception of sounds and the understanding of speech by electrically stimulating the auditory nerve in case of inner ear damage. The stimulation takes place via an array of electrodes surgically inserted in the cochlea. After CI implantation, cone beam computed tomography (CBCT) is used to evaluate the position of the electrodes. Moreover, CBCT is used in research studies to investigate the relationship between the position of the electrodes and the hearing outcome of CI user. In clinical routine, the estimation of the position of the CI electrodes is done manually, which is very time-consuming.

Results
The aim of this study was to optimize procedures of automatic electrode localization from CBCT data following CI implantation. For this, we analyzed the performance of automatic electrode localization for 150 CBCT data sets of 10 different types of electrode arrays. Our own implementation of the method by Noble and Dawant (Lecture notes in computer science (Including subseries lecture notes in artificial intelligence and lecture notes in bioinformatics), Springer, pp 152–159, 2015. https://doi.org/10.1007/978-3-319-24571-3_19) for automated electrode localization served as a benchmark for evaluation. Differences in the detection rate and the localization accuracy across types of electrode arrays were evaluated and errors were classified. Based on this analysis, we developed a strategy to optimize procedures of automatic electrode localization. It was shown that particularly distantly spaced electrodes in combination with a deep insertion can lead to apical–basal confusions in the localization procedure. This confusion prevents electrodes from being detected or assigned correctly, leading to a deterioration in localization accuracy.

Conclusions
We propose an extended cost function for automatic electrode localization methods that prevents double detection of electrodes to avoid apical–basal confusions. This significantly increased the detection rate by 11.15 percent points and improved the overall localization accuracy by 0.53 mm (1.75 voxels). In comparison to other methods, our proposed cost function does not require any prior knowledge about the individual cochlea anatomy.
Analysis and mapping of harm reduction research in the context of injectable drug use: identifying research hotspots, gaps and future directions
Authors: Sweileh Waleed M. 
Published: July 2024

Abstract
Background
Harm reduction is a crucial approach in addressing the multifaceted challenges of injectable drug use. This paper presents an analysis and mapping of the existing literature on harm reduction research in the context of injectable drug use. By reviewing a comprehensive set of scholarly articles, this study identifies research hotspots, knowledge gaps, and future directions in the field. The findings provide valuable insights for researchers, policymakers, and practitioners to guide future research efforts and inform evidence-based harm reduction interventions.

Methods
Data for the study was obtained from the Scopus database, using keywords and phrases related to harm reduction and injectable drug use. Validation methods were employed to verify the accuracy and comprehensiveness of the search strategy. Data analysis involved identifying growth patterns, key contributors, mapping frequent terms, identifying research hotspots, and identifying emerging research directions.

Results
A total of 971 articles were found, with a notable increase from 2015 to 2022. The International Journal of Drug Policy (n = 172, 17.7%) and the Harm Reduction Journal (n = 104, 10.7%) were the most prolific journals, and the United States (n = 558, 57.5%) had the highest number of publications. The Johns Hopkins University (n = 80, 8.5%) was the most prolific institution. Mapping of frequent author keywords revealed the main keywords, including harm reduction, HIV, hepatitis C, and opioid overdose. The highly cited articles cover a broad time span and focus on topics like naloxone distribution, HIV and hepatitis C transmission, while recent articles concentrate on emerging issues such as the impact of the COVID-19 pandemic, fentanyl-related concerns, stigma reduction, and needle and syringe programs. Both sets of articles share a common focus on harm reduction strategies, but recent publications highlight current challenges and developments in the field.

Conclusions
This study provides insights into research landscape on harm reduction in injectable drug use. Research is concentrated in high-income countries, emphasizing the need for more research in low- and middle-income countries. Recent publications focus on emerging challenges like COVID-19 and fentanyl. Research gaps highlight the need for studies in diverse populations, social determinants, program evaluation, and implementation strategies to enhance harm reduction interventions.
Identification and bioinformatic characterization of a serum miRNA signature for early detection of laryngeal squamous cell carcinoma
Authors: Falco Michela , Tammaro Chiara , Cossu Alessia Maria , Takeuchi Takashi , Tufano Rossella , Ceccarelli Michele , Scafuro Giuseppe , Zappavigna Silvia , Grimaldi Anna , Scrima Marianna , Ottaiano Alessandro , Savarese Giovanni , Fico Antonio , Mesolella Massimo , Fasano Morena , Motta Giovanni , Massimilla Eva Aurora , Addeo Raffaele , Ricciardiello Filippo , Caraglia Michele , Misso Gabriella 
Published: July 2024

Abstract
Background
The growing understanding of cancer biology and the establishment of new treatment modalities has not yielded the expected results in terms of survival for Laryngeal Squamous Cell Cancer (LSCC). Early diagnosis, as well as prompt identification of patients with high risk of relapse would ensure greater chance of therapeutic success. However, this goal remains a challenge due to the absence of specific biomarkers for this neoplasm.

Methods
Serum samples from 45 LSCC patients and 23 healthy donors were collected for miRNA expression profiling by TaqMan Array analysis. Additional 20 patients and 42 healthy volunteers were included for the validation set, reaching an equal number of clinical samples for each group. The potential diagnostic ability of the such identified three-miRNA signature was confirmed by ROC analysis. Moreover, each miRNA was analyzed for the possible correlation with HNSCC patients’ survival and TNM status by online databases Kaplan–Meier (KM) plotter and OncomiR. In silico analysis of common candidate targets and their network relevance to predict shared biological functions was finally performed by PANTHER and GeneMANIA software.

Results
We characterized serum miRNA profile of LSCC patients identifying a novel molecular signature, including miR-223, miR-93 and miR-532, as circulating marker endowed with high selectivity and specificity. The oncogenic effect and the prognostic significance of each miRNA was investigated by bioinformatic analysis, denoting significant correlation with OS. To analyse the molecular basis underlying the pro-tumorigenic role of the signature, we focused on the simultaneously regulated gene targets—IL6ST, GTDC1, MAP1B, CPEB3, PRKACB, NFIB, PURB, ATP2B1, ZNF148, PSD3, TBC1D15, PURA, KLF12—found by prediction tools and deepened for their functional role by pathway enrichment analysis. The results showed the involvement of 7 different biological processes, among which inflammation, proliferation, migration, apoptosis and angiogenesis.

Conclusions
In conclusion, we have identified a possible miRNA signature for early LSCC diagnosis and we assumed that miR-93, miR-223 and miR-532 could orchestrate the regulation of multiple cancer-related processes. These findings encourage the possibility to deepen the molecular mechanisms underlying their oncogenic role, for the desirable development of novel therapeutic opportunities based on the use of short single-stranded oligonucleotides acting as non-coding RNA antagonists in cancer.
CSF formation rate—a potential glymphatic flow parameter in hydrocephalus?
Authors: Qvarlander Sara , Sundström Nina , Malm Jan , Eklund Anders 
Published: July 2024

Abstract
Background
Studies indicate that brain clearance via the glymphatic system is impaired in idiopathic normal pressure hydrocephalus (INPH). This has been suggested to result from reduced cerebrospinal fluid (CSF) turnover, which could be caused by a reduced CSF formation rate. The aim of this study was to determine the formation rate of CSF in a cohort of patients investigated for INPH and compare this to a historical control cohort.

Methods
CSF formation rate was estimated in 135 (75 ± 6 years old, 64/71 men/women) patients undergoing investigation for INPH. A semiautomatic CSF infusion investigation (via lumbar puncture) was performed. CSF formation rate was assessed by downregulating and steadily maintaining CSF pressure at a zero level. During the last 10 min, the required outflow to maintain zero pressure, i.e., CSF formation rate, was continuously measured. The values were compared to those of a historical reference cohort from a study by Ekstedt in 1978.

Results
Mean CSF formation rate was 0.45 ± 0.15 ml/min (N = 135), equivalent to 27 ± 9 ml/hour. There was no difference in the mean (p = 0.362) or variance (p = 0.498) of CSF formation rate between the subjects that were diagnosed as INPH (N = 86) and those who were not (N = 43). The CSF formation rate in INPH was statistically higher than in the reference cohort (0.46 ± 0.15 vs. 0.40 ± 0.08 ml/min, p = 0.005), but the small difference was probably not physiologically relevant. There was no correlation between CSF formation rate and baseline CSF pressure (r = 0.136, p = 0.115, N = 135) or age (-0.02, p = 0.803, N = 135).

Conclusions
The average CSF formation rate in INPH was not decreased compared to the healthy reference cohort, which does not support reduced CSF turnover. This emphasizes the need to further investigate the source and routes of the flow in the glymphatic system and the cause of the suggested impaired glymphatic clearance in INPH.
TFscope: systematic analysis of the sequence features involved in the binding preferences of transcription factors
Authors: Romero Raphaël , Menichelli Christophe , Vroland Christophe , Marin Jean-Michel , Lèbre Sophie , Lecellier Charles-Henri , Bréhélin Laurent 
Published: July 2024

AbstractCharacterizing the binding preferences of transcription factors (TFs) in different cell types and conditions is key to understand how they orchestrate gene expression. Here, we develop TFscope, a machine learning approach that identifies sequence features explaining the binding differences observed between two ChIP-seq experiments targeting either the same TF in two conditions or two TFs with similar motifs (paralogous TFs). TFscope systematically investigates differences in the core motif, nucleotide environment and co-factor motifs, and provides the contribution of each key feature in the two experiments. TFscope was applied to > 305 ChIP-seq pairs, and several examples are discussed.
Oxygen uptake efficiency plateau is unaffected by fitness level - the NOODLE study
Authors: Kasiak Przemysław , Kowalski Tomasz , Rębiś Kinga , Klusiewicz Andrzej , Sadowska Dorota , Wilk Adrian , Wiecha Szczepan , Barylski Marcin , Poliwczak Adam Rafał , Wierzbiński Piotr , Mamcarz Artur , Śliż Daniel 
Published: July 2024

Abstract
Background
Endurance athletes (EA) are an emerging population of focus for cardiovascular health. The oxygen uptake efficiency plateau (OUEP) is the levelling-off period of ratio between oxygen uptake (VO2) and ventilation (VE). In the cohort of EA, we externally validated prediction models for OUEP and derived with internal validation a new equation.

Methods
140 EA underwent a medical assessment and maximal cycling cardiopulmonary exercise test. Participants were 55% male (N = 77, age = 21.4 ± 4.8 years, BMI = 22.6 ± 1.7 kg·m− 2, peak VO2 = 4.40 ± 0.64 L·min− 1) and 45% female (N = 63, age = 23.4 ± 4.3 years, BMI = 22.1 ± 1.6 kg·m− 2, peak VO2 = 3.21 ± 0.48 L·min− 1). OUEP was defined as the highest 90-second continuous value of the ratio between VO2 and VE. We used the multivariable stepwise linear regression to develop a new prediction equation for OUEP.

Results
OUEP was 44.2 ± 4.2 mL·L− 1 and 41.0 ± 4.8 mL·L− 1 for males and females, respectively. In external validation, OUEP was comparable to directly measured and did not differ significantly. The prediction error for males was − 0.42 mL·L− 1 (0.94%, p = 0.39), and for females was + 0.33 mL·L− 1 (0.81%, p = 0.59). The developed new prediction equation was: 61.37–0.12·height (in cm) + 5.08 (for males). The developed model outperformed the previous. However, the equation explained up to 12.9% of the variance (R = 0.377, R2 = 0.129, RMSE = 4.39 mL·L− 1).

Conclusion
OUEP is a stable and transferable cardiorespiratory index. OUEP is minimally affected by fitness level and demographic factors. The predicted OUEP provided promising but limited accuracy among EA. The derived new model is tailored for EA. OUEP could be used to stratify the cardiorespiratory response to exercise and guide training.
The effects of clays on bacterial community composition during arthropod decay
Authors: Corthésy Nora , Saleh Farid , Thomas Camille , Antcliffe Jonathan B. , Daley Allison C. 
Published: July 2024

AbstractFossilization, or the transition of an organism from the biosphere to the geosphere, is a complex mechanism involving numerous biological and geological variables. Bacteria are one of the most significant biotic players to decompose organic matter in natural environments, early on during fossilization. However, bacterial processes are difficult to characterize as many different abiotic conditions can influence bacterial efficiency in degrading tissues. One potentially important variable is the composition and nature of the sediment on which a carcass is deposited after death. We experimentally examined this by decaying the marine shrimp Palaemon varians underwater on three different clay sediments. Samples were then analyzed using 16S ribosomal RNA sequencing to identify the bacterial communities associated with each clay system. Results show that samples decaying on the surface of kaolinite have a lower bacterial diversity than those decaying on the surface of bentonite and montmorillonite, which could explain the limited decay of carcasses deposited on this clay. However, this is not the only role played by kaolinite, as a greater proportion of gram-negative over gram-positive bacteria is observed in this system. Gram-positive bacteria are generally thought to be more efficient at recycling complex polysaccharides such as those forming the body walls of arthropods. This is the first experimental evidence of sediments shaping an entire bacterial community. Such interaction between sediments and bacteria might have contributed to arthropods’ exquisite preservation and prevalence in kaolinite-rich Lagerstätten of the Cambrian Explosion.
Combining app-based behavioral therapy with electronic cigarettes for smoking cessation: a study protocol for a single-arm mixed-methods pilot trial
Authors: Schiek Helen , Esch Tobias , Michaelsen Maren M. , Hoetger Cosima 
Published: July 2024

Abstract
Background
Cigarette smoking remains a leading cause of preventable illness and death, underscoring the need for effective evidence-based smoking cessation interventions. Nuumi, a novel smoking cessation program integrating a digital behavioral therapy and an electronic cigarette, may provide a solution.

Objective
To investigate the initial efficacy, acceptability and psychological outcomes of an evidence-based smoking cessation intervention comprised of a mobile phone app and an electronic cigarette among adults who smoke and who are motivated to quit.

Methods
A prospective 6-month single-arm mixed-methods pilot study will be conducted. Seventy adults who smoke and who are motivated to quit will be recruited via web-based advertisements and flyers. Participants receive access to an app and an electronic cigarette with pods containing nicotine for temporary use of at least 3 months. The electronic cigarette is coupled with the app via Bluetooth, allowing for tracking of patterns of use. The behavioral therapy leverages evidence-based content informed by cognitive behavioral therapy and mindfulness-informed principles. Web-based self-report surveys will be conducted at baseline, at 4 weeks, at 8 weeks, at 12 weeks, and at 24 weeks post-baseline. Semi-structured interviews will be conducted at baseline and at 12 weeks post-baseline. Primary outcomes will be self-reported 7-day point prevalence abstinence from smoking at 12 weeks and 24 weeks. Secondary outcomes will include other smoking cessation-related outcomes, psychological outcomes, and acceptability of the nuumi intervention. Descriptive analyses and within-group comparisons will be performed on the quantitative data, and content analyses will be performed on the qualitative data. Recruitment for this study started in October 2023.

Discussion
As tobacco smoking is a leading cause of preventable morbidity and mortality, this research addresses one of the largest health burdens of our time. The results will provide insights into the initial efficacy, acceptability, and psychological outcomes of a novel mobile health intervention for smoking cessation. If successful, this pilot may generate an effective intervention supporting adults who smoke to quit smoking. The results will inform feasibility of a future randomized controlled trial.
Trial Registration German Clinical Trials Register DRKS00032652, registered 09/15/2023, https://drks.de/search/de/trial/DRKS00032652.