bluuebunny/crossref_metadata_2025_split huggingface dataset:
Switching of hypertrophic signalling towards enhanced cardiomyocyte identity and maturity by a GATA4-targeted compound
Authors: Pohjolainen Lotta , Kinnunen Sini M. , Auno Samuli , Kiriazis Alexandros , Pohjavaara Saana , Kari-Koskinen Julia , Zore Matej , Jumppanen Mikael , Yli-Kauhaluoma Jari , Talman Virpi , Ruskoaho Heikki , Välimäki Mika J. 
Published: January 2024

Abstract
Background
The prevalence of heart failure is constantly increasing, and the prognosis of patients remains poor. New treatment strategies to preserve cardiac function and limit cardiac hypertrophy are therefore urgently needed. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used as an experimental platform for cardiac in vitro studies. However, in contrast to adult cardiomyocytes, hiPSC-CMs display immature morphology, contractility, gene expression and metabolism and hence express a naive phenotype that resembles more of a foetal cardiomyocyte.

Methods
A library of 14 novel compounds was synthesized in-house and screened for GATA4-NKX2-5 reporter activity and cellular toxicity. The most potent compound, 3i-1262, along with previously reported GATA4-acting compounds, were selected to investigate their effects on hypertrophy induced by endothelin-1 or mechanical stretch. Morphological changes and protein expression were characterized using immunofluorescence staining and high-content analysis. Changes in gene expression were studied using qPCR and RNA sequencing.

Results
The prototype compound 3i-1262 inhibited GATA4-NKX2-5 synergy in a luciferase reporter assay. Additionally, the isoxazole compound 3i-1262 inhibited the hypertrophy biomarker B-type natriuretic peptide (BNP) by reducing BNP promoter activity and proBNP expression in neonatal rat ventricular myocytes and hiPSC-CMs, respectively. Treatment with 3i-1262 increased metabolic activity and cardiac troponin T expression in hiPSC-CMs without affecting GATA4 protein levels. RNA sequencing analysis revealed that 3i-1262 induces gene expression related to metabolic activity and cell cycle exit, indicating a change in the identity and maturity status of hiPSC-CMs. The biological processes that were enriched in upregulated genes in response to 3i-1262 were downregulated in response to mechanical stretch, and conversely, the downregulated processes in response to 3i-1262 were upregulated in response to mechanical stretch.

Conclusions
There is currently a lack of systematic understanding of the molecular modulation and control of hiPSC-CM maturation. In this study, we demonstrated that the GATA4-interfering compound 3i-1262 reorganizes the cardiac transcription factor network and converts hypertrophic signalling towards enhanced cardiomyocyte identity and maturity. This conceptually unique approach provides a novel structural scaffold for further development as a modality to promote cardiomyocyte specification and maturity.
Nodal solutions for Neumann systems with gradient dependence
Authors: Saoudi Kamel , Alzahrani Eadah , Repovš Dušan D. 
Published: January 2024

AbstractWe consider the following convective Neumann systems: $$ ( \mathrm{S} ) \quad \textstyle\begin{cases} -\Delta _{p_{1}}u_{1}+ \frac{ \vert \nabla u_{1} \vert ^{p_{1}}}{u_{1}+\delta _{1} }=f_{1}(x,u_{1},u_{2}, \nabla u_{1},\nabla u_{2}) & \text{in } \Omega , \\ -\Delta _{p_{2}}u_{2}+ \frac{ \vert \nabla u_{2} \vert ^{p_{2}}}{u_{2}+\delta _{2} }=f_{2}(x,u_{1},u_{2}, \nabla u_{1},\nabla u_{2}) & \text{in } \Omega , \\ \vert \nabla u_{1} \vert ^{p_{1}-2}\frac{\partial u_{1}}{\partial \eta }=0= \vert \nabla u_{2} \vert ^{p_{2}-2}\frac{\partial u_{2}}{\partial \eta } & \text{on } \partial \Omega ,\end{cases} $$
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Timed-release encryption anonymous interaction protocol based on smart contract
Authors: Yuan Ke , Wang Zilin , Chen Keyan , Zhou Bingcai , Li Zheng , Jia Chunfu 
Published: January 2024

AbstractTimed-release encryption (TRE) is a cryptographic primitive that can control the decryption time and has significant application value in time-sensitive scenarios. To solve the reliability issue of nodes in existing TRE anonymous interaction schemes, we propose a blockchain-based TRE protocol for anonymous query time trapdoors. In our protocol, the recipient divides the encrypted trapdoor request information intonciphertext fragments using secret sharing technology near the decryption time, and employs the idea of onion routing to perform layer-by-layer encryption, creating onion-type data transmitted through middlemen selected from the smart contract. After receiving the ciphertext fragments, the time server integrates them to obtain the trapdoor request information and returns the corresponding time trapdoor to the recipient. This allows the recipient to query any time trapdoor anonymously. Our protocol provides a normative design for the smart contract and specific constraints on the participants’ behavior. Compared with the related anonymous query trapdoor schemes, our protocol improves the probability of successful queries. Security analysis shows that our protocol can resist release-ahead attack, interruption attack, eavesdropping attack, and replacement attack. Performance analysis shows that our protocol outperforms related protocols regarding anonymity, efficiency, and flexibility, achieving highly efficient anonymous interactions. Finally, we conducted an experiment in the EthereumRinkebytest network. For the settings of ciphertext fragment number$$n=3$$n=3and ciphertext fragment threshold$$t=2$$t=2, the gas consumption for a user to execute the contract was $5.66, which was higher than the contract cost of related schemes, but the contract execution cost was within an acceptable range.
Enhancing trust transfer in supply chain finance: a blockchain-based transitive trust model
Authors: Shu Chang , Chen Yuling , Tan Chaoyue , Luo Yun , Dou Hui 
Published: January 2024

AbstractArtificial intelligence and blockchain technology have become indispensable in the era of the digital economy, particularly in the field of financial financing. However, when it comes to supply chain finance (SCF), existing models primarily focus on risk identification and credit evaluation, neglecting the critical aspects of trust transfer continuity and reliability within the chain. To address this issue, this paper proposes a blockchain-based transitive trust model for SCF, which ensures seamless trust transfer from core enterprises to bottom suppliers during financing enterprise credit evaluation. The model utilizes multi-layer metrics to calculate the comprehensive trust value of underlying suppliers, serving as the basis for credit delivery. Additionally, the model stores transitive signature receivable warrants on the blockchain and utilizes splittable delivery of warrants to underlying suppliers. The model’s rationality and correctness are verified through experimental analysis, with results demonstrating that the transitive trust model enhances Small and Medium-Sized Enterprises’ (SMEs) trust at the bottom of the supply chain, thus alleviating financing difficulties for SMEs.
“Cigarettes play the equalizer”: discrimination experiences and readiness to quit cigarette smoking among African Americans experiencing homelessness: a qualitative analysis
Authors: Jones-Patten Alexandria , Shin Sanghyuk S. , Nyamathi Adeline , Bounds Dawn 
Published: January 2024

Abstract
Background
Approximately 70–80% of people experiencing homelessness in the United States use tobacco. Smoking cessation programs specifically for this population have been found to be less effective for African American participants. The purpose of this study was to explore discrimination experiences and their impact on smoking habits and readiness to quit cigarette smoking while experiencing homelessness.

Methods
In the qualitative phase of this mixed methods study, five focus groups were conducted for African Americans residing in a homeless shelter in Skid Row, Los Angeles, CA. Using a semi-structured interview guide, we asked participants about discrimination experiences, how smoking habits were impacted by these experiences, and tools needed to successfully abstain from cigarette smoking. Qualitative descriptive content analysis was used to explore discrimination experiences and its association with readiness to quit cigarette smoking.

Results
Of the 17 participants, 14 (82.4%) were male, and the average age was 46.8 years. Using a qualitative In Vivo coding method, three themes were revealed: “Experiencing Discrimination while Black”, “The Psychosocial Fabric—Why Quitting Cigarette Smoking is a Challenge”, and “The Lesser of Two Evils—Choosing to Smoke over More Harmful Options.” Participants discussed working in the blue-collar workforce while Black, identifying as a double minority, smoking to cope with stress, early exposure to cigarettes, smoking being a central part of one’s belonging to a group, and the legality of cigarette smoking.

Discussion
Our findings show that African Americans experiencing homelessness (1) may experience discrimination in multiple settings, regardless of housing status, (2) could have grown up around cigarette smoking and remain surrounded by it while experiencing homelessness, and (3) may experience a calming effect with smoking, which slows some from reacting negatively to adverse situations.

Conclusion
Barriers to successfully abstaining from smoking are multifactorial among African Americans experiencing homelessness and should be addressed individually. Future research should explore the cultural tailoring of interventions that support cessation efforts unique to minoritized populations to improve smoking cessation programs offered to this population.
A literature review and meta-analysis of the optimal factors study of repetitive transcranial magnetic stimulation in post-infarction aphasia
Authors: Tan Yang , Zhang Lin-Ming , Liang Xing-ling , Xiong Guei-fei , Xing Xuan-lin , Zhang Qiu-juan , Zhang Bing-ran , Yang Zi-bin , Liu Ming-wei 
Published: January 2024

Abstract
Background
The existing literature indicates that repetitive transcranial magnetic stimulation (rTMS) can potentially enhance the prognosis of poststroke aphasia (PSA). Nevertheless, these investigations did not identify the most effective parameters or settings for achieving optimal treatment outcomes. This study involved a meta-analysis aimed to identify the optimal variables for rTMS in treating post-infarction aphasia to guide the use of rTMS in rehabilitating PSA.

Methods
PubMed, Embase, and Cochrane Library databases were searched from inception to May 2023, and articles were reviewed manually using subject words and free words and supplemented with references from the included literature to obtain additional relevant literature. The search terms included “poststroke aphasia” and “repetitive transcranial magnetic stimulation (rTMS)” repetitive transcranial magnetic stimulation. Additionally, a review of the reference lists of previously published systematic reviews identified through the Cochrane Database of Systematic Reviews (search terms: poststroke aphasia, rTMS; restrictions: none) and PubMed (search terms: poststroke aphasia, rTMSs; restrictions: systematic review or meta-analysis) was performed. Information from studies involving different doses of rTMS in PSA was independently screened and extracted by 2 researchers.

Results
This meta-analysis included 387 participants with PSA across 18 randomized controlled trials. The results showed that the total pulse had a trend toward a significant correlation with the treatment effect (P = 0.088), while all other variables did not correlate significantly. When rTMS was not grouped by stimulus parameter and location, our nonlinear results showed that when the total pulses were 40,000 (standardized mean difference (SMD):1.86, 95% credible interval (CrI) 0.50 to 3.33), the pulse/session was 1000 (SMD:1.05, 95% CrI 0.55–1.57), and an RMT of 80% (SMD:1.08, 95% CrI 0.60–1.57) had the best treatment effect. When rTMS was grouped by stimulus parameters and location, our nonlinear results showed that when the total low-frequency (LF)-rTMS-right inferior frontal gyrus (RIFG) pulse was 40,000 (SMD:1.76, 95% CrI:0.36–3.29), the pulse/session was 1000 (SMD:1.06, 95% CrI:0.54–1.59). Optimal results were obtained with an RMT of 80% (SMD:1.14, 95% CrI 0.54 − 1.76).

Conclusions
The optimal treatment effects of rTMS for PSA may be obtained with a total pulse of 40,000, a pulse/session of 1000, and an RMT of 80%. Further rigorous randomized controlled studies are required to substantiate the validity of these results.
Use of machine learning techniques for identifying ischemic stroke instead of the rule-based methods: a nationwide population-based study
Authors: Lim Hyunsun , Park Youngmin , Hong Jung Hwa , Yoo Ki-Bong , Seo Kwon-Duk 
Published: January 2024

Abstract
Background
Many studies have evaluated stroke using claims data; most of these studies have defined ischemic stroke using an operational definition following the rule-based method. Rule-based methods tend to overestimate the number of patients with ischemic stroke.

Objectives
We aimed to identify an appropriate algorithm for identifying stroke by applying machine learning (ML) techniques to analyze the claims data.

Methods
We obtained the data from the Korean National Health Insurance Service database, which is linked to the Ilsan Hospital database (n = 30,897). The performance of prediction models (extreme gradient boosting [XGBoost] or gated recurrent unit [GRU]) was evaluated using the area under the receiver operating characteristic curve (AUROC), the area under precision–recall curve (AUPRC), and calibration curve.

Results
In total, 30,897 patients were enrolled in this study, 3145 of whom (10.18%) had ischemic stroke. XGBoost, a tree-based ML technique, had the AUROC was 94.46% and AUPRC was 92.80%. GRU showed the highest accuracy (99.81%), precision (99.92%) and recall (99.69%).

Conclusions
We proposed recurrent neural network-based deep learning techniques to improve stroke phenotyping. This can be expected to produce rapid and more accurate results than the rule-based methods.
May I come in? A probe into the contributions of self-esteem, teacher support, and critical thinking to anxiety and shyness in language classes
Authors: Li Lei , Heydarnejad Tahereh 
Published: January 2024

AbstractMany students feel uncomfortable when obliged to communicate in English. Students’ fear of speaking English is influenced by psychological reasons such as the fear of failing, being misunderstood, and making grammatical errors. Students’ active participation in English class discussions might be hindered by shyness, nervousness, lack of confidence, and motivation. Helping these reserved students gain self-assurance and perfect their spoken English is a top priority for all English language instructors. In the classroom, teachers may use some simple methods to encourage their reserved students to open up and speak English with more ease and confidence. The existing literature on students’ shyness shows that the gap in this realm is great and a critical look is needed. To this end, the current research intended to gauge the effects of self-esteem, teacher support, and critical thinking on anxiety and shyness in language classes. 385 language learners attending English language institutions took part in this research. They were at intermediate and upper intermediate levels. The findings of both confirmatory factor analysis (CFA) and structural equation modeling (SEM) point to the fact that improving students’ self-esteem, teacher support, and critical thinking may have a moderating effect on students ‘anxiety and shyness in language learning. The implications of this inquiry may be advantageous for language learners, language instructors, as well as policymakers.
Pharmacokinetics and pharmacodynamics of perfluoropropane after intra-venous bolus injection of perflutren lipid microsphere injection (DEFINITY®) in healthy Chinese volunteers
Authors: Li Pengfei , Du Ping , Peng Jun , Zhao Zhixia , Li Huiling , Yu Weiyue , Wang Shumin , Liu Lihong 
Published: January 2024

Abstract
Background and objective
Definity is an ultrasound contrast agent consisting of phospholipids-encapsulated perfluoropropane (PFP), also known as perflutren, microspheres, which is initially designed to enhance echocardiographic ultrasound images. With no pharmacologic action, Definity can increase the backscatter of ultrasound resulting enhanced ultrasound signals. The objective of this study was to determine the pharmacokinetics (PKs), Pharmacodynamics (PDs) and safety of Definity in healthy male and female Chinese volunteers.

Methods
A simple GC-MS method was developed and applied to simultaneously quantify PFP both in human whole blood and in expired air using Perfluorobutane (PFB) as internal standard. Meanwhile, the blood microbubble Doppler intensities were continuously monitored as companion PDs by a Doppler ultrasonography system using a non-imaging method.

Results
After intravenous infusion of 10 µL/kg of PFP within 30 seconds, the mean AUClast of the pharmacokinetic analysis set was 0.000653 (uL/mL)*min, the average AUC∞ was 0.001051 (uL/mL)*min. The main coefficient of variation of parameters were within 30%. In this trial, the blood drug concentration of female subjects was lower than that of males. Female Cmax, AUClast and AUC∞ were lower than males’, Tmax and t1/2 was close to males’, Vss and CL were slightly higher than males’. The concentration of PFP in the expired air of the subject reached the maximum value 1–2 min after administration and the PFP accumulation curve in the expired air began to become flat at 9.5–11 min after administration. The PFP in the expired air at the last sampling point of most subjects was still measurable. The results of the analysis showed that female subjects had slightly more and faster PFP excretion via the lungs than males. The change of blood drug concentration in this trial was related to the change process of Doppler signal intensity. The trend of the two was close, but the peak time of blood drug concentration was slightly delayed compared with the peak time of the Doppler signal intensity. The results showed that female tmax−pd, t10 was earlier than male, and women have lower AUCpd than men.

Conclusion
The pharmacokinetics and pharmacodynamics of Definity in blood and expired air were systematically evaluated for the first time in this study. The PK/PD analysis results of this trial showed that the change of blood concentration was related to the change process of Doppler signal intensity, the trend of the two was close and expired air are the main excretion pathways of Definity. Definity was well tolerated by all subjects in the trial.

Trial registration
This study was registered on 08 December 2017 at the Chinese Clinical Trial Registry (CTR20171087).
Automatic damage identification of Sanskrit palm leaf manuscripts with SegFormer
Authors: Wang Yue , Wen Ming , Zhou Xiao , Gao Feng , Tian Shuai , Jue Dan , Lu Hongmei , Zhang Zhimin 
Published: January 2024

Abstract
Palm leaf manuscripts (PLMs) are of great importance in recording Buddhist Scriptures, medicine, history, philosophy, etc. Some damages occur during the use, spread, and preservation procedure. The comprehensive investigation of Sanskrit PLMs is a prerequisite for further conservation and restoration. However, current damage identification and investigation are carried out manually. They require strong professional skills and are extraordinarily time-consuming. In this study, PLM-SegFormer is developed to provide an automated damage segmentation for Sanskrit PLMs based on the SegFormer architecture. Firstly, a digital image dataset of Sanskrit PLMs (the PLM dataset) was obtained from the Potala Palace in Tibet. Then, the hyperparameters for pre-processing, model training, prediction, and post-processing phases were fully optimized to make the SegFormer model more suitable for the PLM damage segmentation task. The optimized segmentation model reaches 70.1% mHit and 51.2% mIoU. The proposed framework automates the damage segmentation of 10,064 folios of PLMs within 12 h. The PLM-SegFormer framework will facilitate the preservation state survey and record of the Palm-leaf manuscript and be of great value to the subsequent preservation and restoration. The source code is available at https://github.com/Ryan21wy/PLM_SegFormer.