bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amelioration of Atherosclerosis by lycopene is linked to the modulation of gut microbiota dysbiosis and related gut-heart axis activation in high-fat diet-fed ApoE−/− mice
Authors: Tu Tengcan , Liu Hao , Liu Zhenhao , Liang Yunyi , Tan Chujun , Feng Dan , Zou Jun 
Published: December 2023

Abstract
Background
Interplay between gut microbiota and heart, termed “gut-heart” axis, has a crucial role in the pathogenesis of atherosclerosis. Our previous study showed that lycopene possesses anti-inflammatory and anti-atherosclerotic effects, but its link to the gut microbiota is poorly understood. Herein, we surmised that lycopene could regulate the gut microbiota, exert anti-atherosclerotic effect by regulating the “gut-heart” axis.

Methods
Male ApoE−/− mice were fed a high-fat diet (HFD) with or without lycopene (0.1% w/w) for 19 weeks. Gut microbiota was analyzed by 16 S rRNA sequencing, the protein levels of zonula occludens-1 (ZO-1), occludin, toll-like receptor 4 (TLR4) and phospho-nuclear factor-κB (NF-κB) p65 were measured by Western blotting, the levels of serum inflammatory factors including monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were assayed using ELISA kits. Also, the concentrations of serum lipopolysaccharide (LPS), D-lactic acid (D-LA) and diamine peroxidase (DAO) were measured through ELISA method.

Results
The aortic sinus sections revealed that lycopene supplementation significantly reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development caused by HFD. The analysis of gut microbiota showed that lycopene reduced the ratio of Firmicutes/Bacteroides and increased the relative abundance of Verrucomicrobia, Akkermansia and Alloprevotella, which were related to elevated intestinal barrier function and reduced inflammation. Moreover, lycopene up-regulated the expression of intestinal ZO-1 and occludin and decreased serum LPS, D-LA and DAO levels. In addition, lycopene inhibited the expression of TLR4 and phospho-NF-κB p65 in aortic sinus plaque, serum MCP-1, TNF-α, IL-1β, and IL-6 levels were also lowered by lycopene treatment.

Conclusions
Our results indicated the protective effect of lycopene against atherosclerosis induced by HFD and further revealed that its mechanism might be its prebiotic effect on maintaining gut microbiota homeostasis and improving intestinal barrier function, consequently reducing serum LPS-triggered inflammatory response in the heart.
A novel visual marker to distinguish haploids from doubled haploids in rice (Oryza sativa, L) at early growth stages
Authors: Ghalagi Chaitanya , Namratha Malavalli Rajashekar , Kotyal Kavita , Prakash Shiva , Raju Basavaiah Mohan 
Published: December 2023

AbstractDoubled haploid technology, which enables the generation of homozygous lines in a single step, is one of the modern tools being employed for accelerating breeding processes in different crops. In rice, a globally important staple food crop, doubled haploid production through androgenesis is increasingly being employed in breeding programs. Amongst the androgenic rice lines, doubled haploids are formed spontaneously at about 50–60%, while the remaining 40–50% of plants remain as haploids. As haploids cannot be easily identified, it is routine to grow all the rice androgenic lines till maturity and harvest the seeds from the fertile doubled haploids. Therefore, the methods that facilitate easy identification of haploids at an early developmental stage in rice would enable treatment of such haploid lines with colchicine, to increase the efficiency of doubled haploid production. Further, it would also help in eliminating the operational cost involved in maintaining them till maturity. In the above context, a systematic study to identify easily observable physiological and morphological differences between haploid and doubled haploid rice lines was undertaken. Rice haploids were found to be noticeably different from doubled haploids in photosynthetic rate, transpiration rate, stomatal conductance, and morphology of lodicules, stigma and style, features which have not been reported before. Most importantly, rice haploids invariably have acute leaf apex which is easily distinguishable from the doubled haploids that have attenuated leaf apex shape. Very high per cent accuracy in the prediction of ploidy level was observed when haploids were identified at an early developmental stage based on leaf apex shape, and the results verified with flow cytometry perfectly matches with leaf apex shape. The study establishes ‘acute leaf apex’ shape as an accurate visual marker to rapidly identify haploid rice lines at an early developmental stage in a cost-effective manner.
Inhibition of miR-96-5p alleviates intervertebral disc degeneration by regulating the peroxisome proliferator-activated receptor γ/nuclear factor-kappaB pathway
Authors: Li Xusheng , Hou Qian , Yuan Wenqi , Zhan Xuehua , Yuan Haifeng 
Published: December 2023

Abstract
Background
Intervertebral disc degeneration (IDD) is the main pathogenesis of low back pain. MicroRNAs (miRNAs) have been found to exert regulatory function in IDD. This study aimed to investigate the effect and potential mechanism of miR-96-5p in IDD.

Methods
In vitro cell model of IDD was established by treating human nucleus pulposus cells (HNPCs) with interleukin-1β (IL-1β). The level of peroxisome proliferator-activated receptor γ (PPARγ) was examined in the IDD cell model by Western blot and quantification real-time reverse transcription-polymerase chain reaction (qRT-PCR). The expression level of miR-96-5p was detected by RT-qPCR. Effects of PPARγ or/and PPARγ agonist on inflammatory factors, extracellular matrix (ECM), apoptosis, and nuclear factor-kappaB (NF-κB) nuclear translocation were examined through enzyme-linked immunosorbent assay (ELISA), Western blot, flow cytometry assay, and immunofluorescence staining. The Starbase database and dual luciferase reporter assay were used to predict and validate the targeting relationship between miR-96-5p and PPARγ, and rescue assay was performed to gain insight into the role of miR-96-5p on IDD through PPARγ/NF-κB signaling.

Results
PPARγ expression reduced with concentration and time under IL-1β stimulation, while miR-96-5p expression showed the reverse trend (P < 0.05). Upregulation or/and activation of PPARγ inhibited IL-1β-induced the increase in inflammatory factor levels, apoptosis, degradation of the ECM, and the nuclear translocation of NF-κB (P < 0.05). MiR-96-5p was highly expressed but PPARγ was lowly expressed in IDD, while knockdown of PPARγ partially reversed remission of IDD induced by miR-96-5p downregulation (P < 0.05). MiR-96-5p promoted NF-κB entry into the nucleus but PPARγ inhibited this process.

Conclusion
Inhibition of miR-96-5p suppressed IDD progression by regulating the PPARγ/NF-κB pathway. MiR-96-5p may be a promising target for IDD treatment clinically.
Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa (ADAP-TIV): study protocol for an adaptive randomized controlled trial
Authors: Ross Jesse , Perumal Rubeshan , Wolf Allison , Zulu Mbali , Guzman Kevin , Seepamore Boitumelo , Reis Karl , Nyilana Hlengiwe , Hlathi Senzo , Narasimmulu Radhamoney , Cheung Ying Kuen K. , Amico K. Rivet , Friedland Gerald , Daftary Amrita , Zelnick Jennifer R. , Naidoo Kogieleum , O’Donnell Max R. 
Published: December 2023

Abstract
Background
Highly effective, short-course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.

Methods
This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include (1) enhanced standard of care, (2) psychosocial support, (3) mHealth using cellular-enabled electronic dose monitoring, and (4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will include survival, negative TB culture, retention in care, and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes.

Discussion
This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO-recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support.

Trial registration
ClinicalTrials.gov NCT05633056. Registered on 1 December 2022
Effectiveness and mediators of change of an online CBT intervention for students with adjustment disorder—study protocol for a randomized controlled trial
Authors: Juszczyk-Kalina A. , Holas P. , Farchione T. J. 
Published: December 2023

Abstract
Background
Adjustment problems and disorders are highly prevalent among university students worldwide. These problems can cause significant interference in academic and social functioning and increase vulnerability to other mental health disorders. Unfortunately, only half of students in need receive psychological help. Furthermore, few studies have evaluated psychological interventions for adjustment disorders in students. New, more scalable forms of treatment for students with an adjustment disorder need to be developed, evaluated, and implemented. The study aims to determine the effectiveness of an online transdiagnostic cognitive behavioural intervention for students experiencing adjustment disorder and to assess mediators of change.

Method/design
In this three-arm randomized controlled trial, we plan to recruit 214 Polish students diagnosed with an adjustment disorder. Participants who meet initial eligibility criteria will be randomly assigned to one of three 6-week conditions: (1) online cognitive behavioural therapy intervention based on an existing, empirically supported transdiagnostic protocol, the unified protocol; (2) online progressive muscle relaxation training as an active control group; or (3) waiting-list control group. Both interventions are asynchronous, interactive, and include minimal amount of therapist support. Assessments will consist of self-report questionnaires, daily diary measures, and neurocognitive tasks for evaluating cognitive functioning. These will be conducted at baseline, post-treatment, and 1-month follow-up. Daily diary measures will be taken during the first and last week of treatment (or waitlist period). Primary outcome measures will include adjustment disorder severity; secondary outcome measures will consist of other negative (psychopathology: depression, anxiety, and stress) and positive (life satisfaction) indexes of mental health as well as process measures (e.g. mindfulness, experiential avoidance, cognitive fusion).

Discussion
To our knowledge, the current study is the first to evaluate the effectiveness of a psychological intervention for students with adjustment disorder. Therefore, it may have important practical implications for students with this disorder. It can potentially guide the development of a scalable, validated treatment option.

Trial registration
Clinical Trials, NCT05768308, registered 14 March 2023, https://www.clinicaltrials.gov/ct2/show/NCT05768308
Differential interactome mapping of aggregation prone/prion-like proteins under stress: novel links to stress granule biology
Authors: Younas Neelam , Zafar Saima , Saleem Tayyaba , Fernandez Flores Leticia Camila , Younas Abrar , Schmitz Matthias , Zerr Inga 
Published: December 2023

Abstract
Background
Aberrant stress granules (SGs) are emerging as prime suspects in the nucleation of toxic protein aggregates. Understanding the molecular networks linked with aggregation-prone proteins (prion protein, synuclein, and tau) under stressful environments is crucial to understand pathophysiological cascades associated with these proteins.

Methods
We characterized and validated oxidative stress-induced molecular network changes of endogenous aggregation-prone proteins (prion protein, synuclein, and tau) by employing immunoprecipitation coupled with mass spectrometry analysis under basal and oxidative stress conditions. We used two different cell models (SH-SY5Y: human neuroblastoma and HeLa cell line) to induce oxidative stress using a well-known inducer (sodium arsenite) of oxidative stress.

Results
Overall, we identified 597 proteins as potential interaction partners. Our comparative interactome mapping provides comprehensive network reorganizations of three aggregation-prone hallmark proteins, establish novel interacting partners and their dysregulation, and validates that prion protein and synuclein localize in cytoplasmic SGs. Localization of prion protein and synuclein in TIA1-positive SGs provides an important link between SG pathobiology and aggregation-prone proteins. In addition, dysregulation (downregulation) of prion protein and exportin-5 protein, and translocation of exportin-5 into the nucleus under oxidative stress shed light on nucleocytoplasmic transport defects during the stress response.

Conclusions
The current study contributes to our understanding of stress-mediated network rearrangements and posttranslational modifications of prion/prion-like proteins. Localization of prion protein and synuclein in the cytoplasmic SGs provides an important link between stress granule pathobiology and aggregation-prone proteins. In addition, our findings demonstrate nucleocytoplasmic transport defects after oxidative stress via dysregulation and nuclear accumulation of exportin-5.
Predictive and prognostic biomarkers of bone metastasis in breast cancer: current status and future directions
Authors: Wang Shenkangle , Wu Wenxin , Lin Xixi , Zhang Kevin Matthew , Wu QingLiang , Luo Mingpeng , Zhou Jichun 
Published: December 2023

AbstractThe most common site of metastasis in breast cancer is the bone, where the balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation is disrupted. This imbalance causes osteolytic bone metastasis in breast cancer, which leads to bone pain, pathological fractures, spinal cord compression, and other skeletal-related events (SREs). These complications reduce patients' quality of life significantly and have a profound impact on prognosis. In this review, we begin by providing a brief overview of the epidemiology of bone metastasis in breast cancer, including current diagnostic tools, treatment approaches, and existing challenges. Then, we will introduce the pathophysiology of breast cancer bone metastasis (BCBM) and the animal models involved in the study of BCBM. We then come to the focus of this paper: a discussion of several biomarkers that have the potential to provide predictive and prognostic value in the context of BCBM—some of which may be particularly compatible with more comprehensive liquid biopsies. Beyond that, we briefly explore the potential of new technologies such as single-cell sequencing and organoid models, which will improve our understanding of tumor heterogeneity and aid in the development of improved biomarkers. The emerging biomarkers discussed hold promise for future clinical application, aiding in the prevention of BCBM, improving the prognosis of patients, and guiding the implementation of personalized medicine.
Effective acoustic parameters for automatic classification of performed and synthesized Guzheng music
Authors: Xue Huiwen , Sun Chenxin , Tang Mingcheng , Hu Chenrui , Yuan Zhengqing , Huang Min , Xiao Zhongzhe 
Published: December 2023

AbstractThis study focuses on exploring the acoustic differences between synthesized Guzheng pieces and real Guzheng performances, with the aim of improving the quality of synthesized Guzheng music. A dataset with consideration of generalizability with multiple sources and genres is constructed as the basis of analysis. Classification accuracy up to 93.30% with a single feature put forward the fact that although the synthesized Guzheng pieces in subjective perception evaluation are recognized by human listeners, there is a very significant difference to the performed Guzheng music. With features compensating to each other, a combination of only three features can achieve a nearly perfect classification accuracy of 99.73%, with the essential two features related to spectral flux and an auxiliary feature related to MFCC. The conclusion of this work points out a potential future improvement direction in Guzheng synthesized algorithms with spectral flux properties.
Data extraction and comparison for complex systematic reviews: a step-by-step guideline and an implementation example using open-source software
Authors: Afifi Mohamed , Stryhn Henrik , Sanchez Javier 
Published: December 2023

AbstractBackgroundData extraction (DE) is a challenging step in systematic reviews (SRs). Complex SRs can involve multiple interventions and/or outcomes and encompass multiple research questions. Attempts have been made to clarify DE aspects focusing on the subsequent meta-analysis; there are, however, no guidelines for DE in complex SRs. Comparing datasets extracted independently by pairs of reviewers to detect discrepancies is also cumbersome, especially when the number of extracted variables and/or studies is colossal. This work aims to provide a set of practical steps to help SR teams design and build DE tools and compare extracted data for complex SRs.MethodsWe provided a 10-step guideline, from determining data items and structure to data comparison, to help identify discrepancies and solve data disagreements between reviewers. The steps were organised into three phases: planning and building the database and data manipulation. Each step was described and illustrated with examples, and relevant references were provided for further guidance. A demonstration example was presented to illustrate the application of Epi Info and R in the database building and data manipulation phases. The proposed guideline was also summarised and compared with previous DE guidelines.ResultsThe steps of this guideline are described generally without focusing on a particular software application or meta-analysis technique. We emphasised determining the organisational data structure and highlighted its role in the subsequent steps of database building. In addition to the minimal programming skills needed, creating relational databases and data validation features of Epi info can be utilised to build DE tools for complex SRs. However, two R libraries are needed to facilitate data comparison and solve discrepancies.ConclusionsWe hope adopting this guideline can help review teams construct DE tools that suit their complex review projects. Although Epi Info depends on proprietary software for data storage, it can still be a potential alternative to other commercial DE software for completing complex reviews.
PPO-based deployment and phase control for movable intelligent reflecting surface
Authors: Zhao Yikun , Zhou Fanqin , Liu Huaide , Feng Lei , Li Wenjing 
Published: December 2023

AbstractIntelligent reflecting surface (IRS) stands as a promising technology to revolutionize wireless communication by manipulating incident signal amplitudes and phases to enhance system performance. While existing research primarily centers around optimizing the phase shifts of IRS, the deployment of IRS on movable platforms introduces a new degree of freedom in the design of IRS-assisted systems. Leveraging flexible deployment strategies for IRS holds the potential to further amplify network throughput and extend coverage. This paper addresses the challenging non-convex joint optimization problem of the movable IRS and proposes a dynamic optimization algorithm based on proximal policy optimization (PPO) for dynamically optimizing the aerial position and phase configuration of IRS. Simulation results show the effectiveness of the proposed approach, demonstrating significant performance improvements compared to communication schemes without IRS assistance and conventional static IRS-assisted methods.
A study on a political system for the advance in green hydrogen technology: a South Korea case study
Authors: Yun Minyoung , Jang Wooseok , Lim Jongyeon , Yun Bitnari 
Published: December 2023

Abstract
Background
Hydrogen energy, a type of renewable energy if produced without fossil fuel, has a critical issue in that most of it is still produced from carbon footprint heavy industries such as the fossil fuel industry. It is imperative to produce hydrogen from renewable sources on a global level so that the carbon footprint can be curbed. South Korea, along with other global economies such as the US, the EU, Japan and China, has shown its resolution to build a hydrogen economy with green hydrogen produced only from renewable sources. Since 2017, South Korea has been actively shaping its political actions and policies to develop the necessary technology for this transition. This study focuses on South Korea's actions and policies, using a political system model to better understand the shift towards a green hydrogen economy.

Results
The analysis shows that budgeting for R&D projects has had a significant impact on scientific breakthroughs, advancements, and product development in the field of green hydrogen in South Korea. These actions have also affected market performance, resulting in increased interest and investment in green hydrogen. Although there have been significant advancements in the field of green hydrogen in South Korea, the current state of technology remains in its early stages of development. Most of the breakthroughs have been in water-to-hydrogen and biomass-to-hydrogen technologies. However, these technologies show promise as the foundation of a thriving hydrogen economy in South Korea. The analysis also indicates a strong market demand for green hydrogen technology. To support these efforts, the political system has focused its financial support on water-to-hydrogen technology and projects at the TRL 1–3 stage.

Conclusions
The study concludes that ongoing financial and political support is necessary for areas showing outstanding performance to vitalize the hydrogen economy and facilitate the transition to a green hydrogen society in the future. Additionally, a robust legal framework is crucial to ensure steady growth of the green hydrogen economy, similar to those in other major hydrogen economies such as the US and Germany. This study serves as a case study of South Korea, showcasing the impact of political actions on the advancement of scientific technology.