bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenine base editing-mediated exon skipping restores dystrophin in humanized Duchenne mouse model
Authors: Lin Jiajia , Jin Ming , Yang Dong , Li Zhifang , Zhang Yu , Xiao Qingquan , Wang Yin , Yu Yuyang , Zhang Xiumei , Shao Zhurui , Shi Linyu , Zhang Shu , Chen Wan-jin , Wang Ning , Wu Shiwen , Yang Hui , Xu Chunlong , Li Guoling 
Published: July 2024

AbstractDuchenne muscular dystrophy (DMD) affecting 1 in 3500–5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient’s DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.
Engineering a nanoscale liposome-in-liposome for in situ biochemical synthesis and multi-stage release
Authors: Pilkington Colin P. , Gispert Ignacio , Chui Suet Y. , Seddon John. M. , Elani Yuval 
Published: July 2024

AbstractSoft-matter nanoscale assemblies such as liposomes and lipid nanoparticles have the potential to deliver and release multiple cargos in an externally stimulated and site-specific manner. Such assemblies are currently structurally simplistic, comprising spherical capsules or lipid clusters. Given that form and function are intertwined, this lack of architectural complexity restricts the development of more sophisticated properties. To address this, we have devised an engineering strategy combining microfluidics and conjugation chemistry to synthesize nanosized liposomes with two discrete compartments, one within another, which we term concentrisomes. We can control the composition of each bilayer and tune both particle size and the dimensions between inner and outer membranes. We can specify the identity of encapsulated cargo within each compartment, and the biophysical features of inner and outer bilayers, allowing us to imbue each bilayer with different stimuli-responsive properties. We use these particles for multi-stage release of two payloads at defined time points, and as attolitre reactors for triggered in situ biochemical synthesis.
Adherence and persistence to tafamidis treatment among Medicare beneficiaries in the presence of a patient assistance program
Authors: Chung Haechung , Cantu Cera , Pankratova Cindi , Kemner Jason , Alvir Jose , Prasad Sapna , Chen Yong 
Published: July 2024

AbstractTafamidis is the only disease-modifying therapy approved to treat patients in the United States with transthyretin amyloid cardiomyopathy (ATTR-CM), which most commonly affects patients aged ≥ 65 years. The manufacturer operates a patient assistance program (PAP) to support access to tafamidis. This study conducted Privacy Preserving Record Linking (PPRL) using Datavant tokens to match patients across Medicare prescription drug plan (PDP) and PAP databases to evaluate the impact of PAPs on treatment exposure classification, adherence, and persistence determined using Medicare PDP data alone. We found 35% of Medicare PDP patients received tafamidis through the PAP only; 14% through both Medicare PDP and the PAP, and 51% through Medicare PDP only. Adherence and persistence were comparable between these cohorts but underestimated among patients who received ≥ 2 prescriptions through Medicare PDP and ≥ 1 through the PAP when solely using Medicare data versus pooled Medicare and PAP data (modified Medication Possession Ratio: 84% [69% ≥ 80% adherent] vs. 96% [93%]; Proportion of Days Covered: 77% [66% ≥ 80% adherent] vs. 88% [88%]; mean days to discontinuation: 186 vs. 252; total discontinuation: 13% vs. 11%). Cross-database PPRL is a valuable method to build more complete treatment journeys and reduce the risk of exposure misclassification in real-world analyses.
Stochastic journeys of cell progenies through compartments and the role of self-renewal, symmetric and asymmetric division
Authors: Dreiwi Hanan , Feliciangeli Flavia , Castro Mario , Lythe Grant , Molina-París Carmen , López-García Martín 
Published: July 2024

AbstractDivision and differentiation events by which cell populations with specific functions are generated often take place as part of a developmental programme, which can be represented by a sequence of compartments. A compartment is the set of cells with common characteristics; sharing, for instance, a spatial location or a phenotype. Differentiation events are transitions from one compartment to the next. Cells may also die or divide. We consider three different types of division events: (i) where both daughter cells inherit the mother’s phenotype (self-renewal), (ii) where only one of the daughters changes phenotype (asymmetric division), and (iii) where both daughters change phenotype (symmetric division). The self-renewal probability in each compartment determines whether the progeny of a single cell, moving through the sequence of compartments, is finite or grows without bound. We analyse the progeny stochastic dynamics with probability generating functions. In the case of self-renewal, by following one of the daughters after any division event, we may construct lifelines containing only one cell at any time. We analyse the number of divisions along such lines, and the compartment where lines terminate with a death event. Analysis and numerical simulations are applied to a five-compartment model of the gradual differentiation of hematopoietic stem cells and to a model of thymocyte development: from pre-double positive to single positive (SP) cells with a bifurcation to either SP4 or SP8 in the last compartment of the sequence.
The impact of tertiary lymphoid structures on tumor prognosis and the immune microenvironment in non-small cell lung cancer
Authors: Weng Yiming , Yuan Jingping , Cui Xue , Wang Jinsong , Chen Honglei , Xu Li , Chen Xinyi , Peng Min , Song Qibin 
Published: July 2024

AbstractNon-small cell lung cancer (NSCLC) is a common malignancy whose prognosis and treatment outcome are influenced by many factors. Some studies have found that tertiary lymphoid structures (TLSs) in cancer may contribute to prognosis and the prediction of immunotherapy efficacy However, the combined role of TLSs in NSCLC remains unclear. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to obtain mRNA sequencing data and clinical information as the TCGA cohort, and used our own sample of 53 advanced NSCLC as a study cohort. The samples were divided into TLS+ and TLS- groups by pathological tissue sections. Patients of the TLS+ group had a better OS (p = 0.022), PFS (p = 0.042), and DSS (p = 0.004) in the TCGA cohort, and the results were confirmed by the study cohort (PFS, p = 0.012). Furthermore, our result showed that the count and size of TLSs are closely associated with the efficacy of immunotherapy. In addition, the TLS+ group was associated with better immune status and lower tumor mutation load. In the tumor microenvironment (TME), the expression levels of CD4+ T cells and CD8+ T cells of different phenotypes were associated with TLSs. Overall, TLSs are a strong predictor of survival and immunotherapeutic efficacy in advanced NSCLC, and T cell-rich TLSs suggest a more ordered and active immune response site, which aids in the decision-making and application of immunotherapy in the clinic.
Prevalence and trends in overactive bladder among men in the United States, 2005–2020
Authors: Cheng Yu , Chen Tao , Zheng Guanghao , Song Zhen , Zhang Gan , Rao Xuepeng , Zeng Tao , Yuan Changfei 
Published: July 2024

AbstractThe purpose of present study was to examine the current prevalence and recent trends of overactive bladder (OAB) among US adult men and examine the correlations between OAB and several potential risk factors. The study used the nationally representative data between 2005 and 2020 from the National Health and Nutrition Examination Survey in the US. A total of 18,386 participants aged ≥ 20 years were included in the study. We divided the data into three groups: 2005–2008, 2009–2014 and 2015–2020 to investigate the trends in OAB prevalence. The weighted prevalence and corresponding 95% confidence intervals (CI) of OAB were calculated. The differences (95% CI) in prevalence between the surveys were calculated and multivariate-adjusted weighted logistic regression analysis was performed to determine the correlates of OAB. Among all US adult men, the overall prevalence of OAB increased slightly from 11.3% in 2005–2008 to 11.7% in 2009–2014 and significantly increased to 14.5% in 2015–2020 (difference, 3.2% [95% CI (1.9–4.4%)]; P < 0.05). Increases in OAB prevalence especially concentrated on those who were 40–59 years, non-Hispanic White, non-Hispanic Black and those who were overweight and obese. Older age, non-Hispanic Black, lower educational level and family poverty ratio, diabetes, depression, sleep disorder, other chronic comorbidities, less intense recreational activity, poorer health condition and unsafe food were independent risk factors of OAB. The contemporary prevalence of OAB was high, affecting 14.5% US men and the estimated overall prevalence significantly increased from 2005 to 2020. Therefore, future research should be focused to prevent and remedy this growing socioeconomic and individually troublesome malady.
Integrating plasma proteomics with genome-wide association data to identify novel drug targets for inflammatory bowel disease
Authors: Bai Zhongyuan , Hao Jiawei , Chen Miaoran , Yao Kaixin , Zheng Leilei , Liu Liu , Hu Jingxi , Guo Kaiqing , Lv Yongqiang , Li Feng 
Published: July 2024

AbstractInflammatory bowel disease (IBD) is a chronic disease that includes Crohn’s disease (CD) and ulcerative colitis (UC). Although genome-wide association studies (GWASs) have identified many relevant genetic risk loci, the impact of these loci on protein abundance and their potential utility as clinical therapeutic targets remain uncertain. Therefore, this study aimed to investigate the pathogenesis of IBD and identify effective therapeutic targets through a comprehensive and integrated analysis. We systematically integrated GWAS data related to IBD, UC and CD (N = 25,305) by the study of de Lange KM with the human blood proteome (N = 7213) by the Atherosclerosis Risk in Communities (ARIC) study. Proteome-wide association study (PWAS), mendelian randomisation (MR) and Bayesian colocalisation analysis were used to identify proteins contributing to the risk of IBD. Integrative analysis revealed that genetic variations in IBD, UC and CD affected the abundance of five (ERAP2, RIPK2, TALDO1, CADM2 and RHOC), three (VSIR, HGFAC and CADM2) and two (MST1 and FLRT3) cis-regulated plasma proteins, respectively (P < 0.05). Among the proteins identified via Bayesian colocalisation analysis, CADM2 was found to be an important common protein between IBD and UC. A drug and five druggable target genes were identified from DGIdb after Bayesian colocalisation analysis. Our study's findings from genetic and proteomic approaches have identified compelling proteins that may serve as important leads for future functional studies and potential drug targets for IBD (UC and CD).
Fabrication of SrTiO3 anchored rGO/g-C3N4 photocatalyst for the removal of mixed dye from wastewater: dual photocatalytic mechanism
Authors: Gopal Venkatesh , Palanisamy Govindasamy , Lee Jintae , Abu-Yousef Imad A. , Majdalawieh Amin F. , Mahasneh Amjad , Prabu Kattupatti M. , Kanan Sofian 
Published: July 2024

AbstractA metal-free combination of rGO/g-C3N4-coupled SrTiO3 (SRN) ternary nanocomposite prepared via a wet impregnation method for UV–Vis light photocatalytic applications. Various physicochemical properties of the samples were investigated by several spectroscopic techniques including X-ray diffraction (XRD), FT-IR, Raman, field emission scanning electron microscopy with energy dispersive X-ray spectroscopy (FE-SEM-EDX), high-resolution transmission electron microscopy (HR-TEM), UV–Vis, photoluminescence (PL), X-ray photoelectron spectroscopy (XPS) and Brunauer–Emmett–Teller (BET) surface area analysis. The data suggest agglomerated SRT nanoparticles are dispersed and distributed throughout the surface of the rGO sheets and GCN nanostructures. The photocatalytic performance of the SRN towards combined mixed dye and its degradation activities were evaluated towards the most common industrial effluents, Rhodamine B (RhB) and Methylene blue (MB), under UV–Vis light illumination. The results revealed that the degradation efficiency of the SRN photocatalyst shows excellent performance compared with that of the binary composition and the pure SrTiO3 (SRT) sample. The reaction rate constant for RhB was estimated to be 0.0039 min−1 and for MB to be 0.0316 min−1, which are 3.26 (RhB) and 4.21 (MB) times faster than the pure SRT sample. The enhanced degradation efficiency was attained not only by interfacial formation but also by the speedy transportation of electrons across the heterojunction. After 5 runs of the photocatalytic recylic process, the SRN photocatalyst exhibited ultimate stability without structural changes, and no noticeable degradation was observed. The outcomes of the ternary SRN nanocomposite manifest a dual photocatalytic scheme, the photocatalytic enrichment could be caused by the Z-scheme charge transfer process between GCN, SRT, and rGO nanocomposite, which helps effectual charge separation and keeps a high redox potential. From the results, SRN sample provides insight into the integration of an effective and potential photocatalyst for wastewater treatment toward real-time environmental remediation applications.
Prognostic value of cardiopulmonary exercise test in patients with acute myocardial infarction after percutaneous coronary intervention
Authors: Li Zhengyan , Fan Baochao , Wu Yifan , Rui Haomiao , Hu Yongcun , Gu Yingchun , Bai Juncai , Lu Liming , Wang Dongwei 
Published: July 2024

AbstractTo determine the independent risk factors of cardiopulmonary exercise test (CPET) parameters related to adverse prognostic events within 5 years in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and establish a prediction model for the occurrence of adverse events within 5 years to provide a reference for cardiac rehabilitation training. From August 2015 to December 2021, patients who underwent PCI for AMI and completed CPET within 1–2 weeks after surgery before discharge from the Department of Cardiovascular Medicine of Zhengzhou Central Hospital Affiliated to Zhengzhou University, Henan Provincial Hospital of Traditional Chinese Medicine, and Anyang District Hospital were selected as participants. Univariate and multivariate analyses were used to screen for independent risk factors associated with 5-year adverse events. Feature importance was interpreted using SHapley Additive exPlanations (SHAP), and a logistic regression model was established for prediction. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the prediction model. Calibration was assessed by the Hosmer–Lemeshow test and the calibration curve. In total, 375 patients met the inclusion criteria. Based on whether adverse events occurred during the 5-year follow-up period, the patients were divided into two groups: the event group (n = 53) and the non-event group (n = 322). Peak oxygen uptake (peakVO2), carbon dioxide ventilation equivalent slope (VE/VCO2slop), and peak end-tidal carbon dioxide partial pressure (PETCO2) were three independent risk factors for re-acute myocardial infarction (re-AMI), heart failure (HF), and even death after PCI for AMI (P < 0.05). The SHAP plots demonstrated that the significant contributors to model performance were related to peakVO2, VE/VCO2slop, and PETCO2. The risk of adverse events was significantly reduced when the peakVO2 was ≥ 20 mL/kg/min and the VE/VCO2slop was < 33. The ROC curves of the three models were drawn, including the no-event and event groups, re-AMI group, and HF group, which performed well, with AUC of 0.894, 0.760, and 0.883, respectively. The Hosmer–Lemeshow test showed that the three models were a good fit (P > 0.05). The calibration curve of the three models was close to the ideal diagonal lines. CPET parameters can predict the prognosis of adverse events within 5 years after PCI in patients with AMI and provide a theoretical basis for cardiac rehabilitation training.
High gain quasi-omnidirectional dipole array fed by radial power divider for millimeter-wave IoT sensing
Authors: Sufian Md. Abu , Hussain Niamat , Choi Domin , Lee Sang-Min , Gil Sang-Keun , Kim Nam 
Published: July 2024

AbstractThis article presents the design and implementation of a dipole array antenna based on a radial waveguide power divider for millimeter-wave IoT sensing applications. The dipole array and radial waveguide power divider techniques are used in tandem to achieve high gain with omnidirectional radiation properties. The proposed antenna is comprised of eight non-uniform array dipole structures, a circular radiating loop, and shorting vias. The one-to-eight power divider is created with the shorting vias to feed the circularly arranged eight non-uniform dipole arrays simultaneously. The proposed antenna is simulated and manufactured on Rogers-RO3003C substrate with a thickness of 8 mils. Both simulated and tested results confirm that the proposed method enables the antenna to offer a quasi-omnidirectional pattern with a high peak gain of 5.42 dBi. The antenna offers an impedance bandwidth (S11 < ‒ 10 dB) of more than 1 GHz ranging from 27.93 to 29.13 GHz. Moreover, by optimizing the parameters of the power divider network the proposed antenna can be tuned between a wide bandwidth range of 14.53 GHz as the designed dipole array offering the operating bandwidth from 25.56 to 40.09 GHz. Due to its comprehensive set of performance attributes, particularly for the quasi-omnidirectional radiation characteristics, the presented antenna is a viable candidate for the 5G millimeter wave wireless IoT sensing applications. Additionally, this work will accommodate other researchers to explore the proposed method for developing high-gain omnidirectional antennas for millimeter-wave applications.
Oxidative and carbonyl stress induced AMD and Codonopsis lanceolata ameliorates AMD via controlling oxidative and carbonyl stress
Authors: Lee Soon-Young , Cho Yeon-Kyoung , Bae Chun-Sik , Kim Gyeyeop , Lee Min-Jae , Cho Seung-Sik , Jeon In-Chul , Park Dae-Hun 
Published: July 2024

AbstractAge-related macular degeneration (AMD) is one of the leading causes of blindness. AMD is currently incurable; the best solution is to prevent its occurrence. To develop drugs for AMD, it is crucial to have a model system that mimics the symptoms and mechanisms in patients. It is most important to develop safer and more effective anti-AMD drug. In this study, the dose of A2E and the intensity of blue light were evaluated to establish an appropriate atrophic in vitro model of AMD and anti-AMD effect and therapeutic mechanism of Codonopsis lanceolata. The experimental groups included a control group an AMD group treated with A2E and blue light, a lutein group treated with 25 μM lutein after AMD induction, and three groups treated with different doses of C. lanceolata (10, 20, and 50 μg/mL) after AMD induction. Intrinsic apoptotic pathway (Bcl-2 family), anti-oxidative system (Keap1/Nrf2/HO-1 antioxidant response element), and anti-carbonyl effect (4-hydroxynonenal [4-HNE]) were evaluated using immunofluorescence, MTT, TUNEL, FACS, and western blotting analyses. A2E accumulation in the cytoplasm of ARPE-19 cells depending on the dose of A2E. Cell viability of ARPE-19 cells according to the dose of A2E and/or blue light intensity. The population of apoptotic or necrotic cells increased based on the A2E dose and blue light intensity. Codonopsis lanceolata dose-dependently prevented cell death which was induced by A2E and blue light. The antiapoptotic effect of that was caused by activating Keap1/Nrf2/HO-1 pathway, suppressing 4-HNE, and modulating Bcl-2 family proteins like increase of antiapoptotic proteins such as Bcl-2 and Bcl-XL and decrease of proapoptotic protein such as Bim. Based on these findings, 30 μM A2E and 20 mW/cm2 blue light on adult retinal pigment epithelium-19 cells was an appropriate condition for AMD model and C. lanceolata shows promise as an anti-AMD agent.
A fusion approach using GIS, green area detection, weather API and GPT for satellite image based fertile land discovery and crop suitability
Authors: Balasundaram Ananthakrishnan , Abdul Aziz A. B. , Gupta Aman , Shaik Ayesha , Kavitha Muthu Subash 
Published: July 2024

AbstractProper utilization of agricultural land is a big challenge as they often laid over as waste lands. Farming is a significant occupation in any country and improving it further by promoting more farming opportunities will take the country towards making a huge leap forward. The issue in achieving this would be the lack of knowledge of cultivable land for food crops. The objective of this work is to utilize modern computer vision technology to identify and map cultivable land for agricultural needs. With increasing population and demand for food, improving the farming sector is crucial. However, the challenge lies in the lack of suitable land for food crops cultivation. To tackle this issue, we propose to use sophisticated image processing techniques on satellite images of the land to determine the regions that are capable of growing food crops. The solution architecture includes enhancement of satellite imagery using sophisticated pan sharpening techniques, notably the Brovey transformation, aiming to transform dull satellite images into sharper versions, thereby improving the overall quality and interpretability of the visual data. Making use of the weather data on the location observed and taking into factors like the soil moisture, weather, humidity, wind, sunlight times and so on, this data is fed into a generative pre-trained transformer model which makes use of it and gives a set of crops that are suitable to be grown on this piece of land under the said conditions. The results obtained by the proposed fusion approach is compared with the dataset provided by the government for different states in India and the performance was measured. We achieved an accuracy of 80% considering the crop suggested by our model and the predominant crop of the region. Also, the classification report detailing the performance of the proposed model is presented.