bluuebunny/crossref_metadata_2025_split huggingface dataset:
A critical systematic review of extracellular vesicle clinical trials
Authors: Mizenko Rachel R. , Feaver Madison , Bozkurt Batuhan T. , Lowe Neona , Nguyen Bryan , Huang Kuan‐Wei , Wang Aijun , Carney Randy P. 
Published: September 2024

AbstractThis systematic review examines the landscape of extracellular vesicle (EV)‐related clinical trials to elucidate the field's trends in clinical applications and EV‐related methodologies, with an additional focus on the acknowledgement of EV subpopulations. By analysing data from public reporting repositories, we catalogued 471 EV‐related clinical trials to date, with indications for over 200 diseases. Diagnostics and companion diagnostics represented the bulk of EV‐related clinical trials with cancer being the most frequent application. EV‐related therapeutics trials mainly utilized mesenchymal stromal cell (MSC) EVs and were most frequently used for treatment of respiratory illnesses. Ultracentrifugation and RNA‐sequencing were the most common isolation and characterization techniques; however, methodology for each was not frequently reported in study records. Most of the reported characterization relied on bulk characterization of EV isolates, with only 11% utilizing EV subpopulations in their experimental design. While this may be connected to a lack of available techniques suitable for clinical implementation, it also highlights the opportunity for use of EV subpopulations to improve translational efforts. As academic research identifies more chemically distinct subpopulations and technologies for their enrichment, we forecast to more refined EV trials in the near future. This review emphasizes the need for meticulous methodological reporting and consideration of EV subpopulations to enhance the translational success of EV‐based interventions, pointing towards a paradigm shift in personalized medicine.
Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
Authors: Palviainen Mari , Puutio Johanna , Østergaard Rikke Halse , Eble Johannes A. , Maaninka Katariina , Butt Umar , Ndika Joseph , Kari Otto K. , Kamali‐Moghaddam Masood , Kjaer‐Sorensen Kasper , Oxvig Claus , Aransay Ana M. , Falcon‐Perez Juan M. , Federico Antonio , Greco Dario , Laitinen Saara , Hayashi Yuya , Siljander Pia R.‐M. 
Published: September 2024

AbstractRenowned for their role in haemostasis and thrombosis, platelets are also increasingly recognized for their contribution in innate immunity, immunothrombosis and inflammatory diseases. Platelets express a wide range of receptors, which allows them to reach a variety of activation endpoints and grants them immunomodulatory functions. Activated platelets release extracellular vesicles (PEVs), whose formation and molecular cargo has been shown to depend on receptor‐mediated activation and environmental cues.This study compared the immunomodulatory profiles of PEVs generated via activation of platelets by different receptors, glycoprotein VI, C‐type lectin‐like receptor 2 and combining all thrombin‐collagen receptors. Functional assays in vivo in zebrafish and in vitro in human macrophages highlighted distinct homing and secretory responses triggered by the PEVs. In contrast, omics analyses of protein and miRNA cargo combined with physicochemical particle characterization found only subtle differences between the activated PEV types, which were insufficient to predict their different immunomodulatory functions. In contrast, constitutively released PEVs, formed in the absence of an exogenous activator, displayed a distinct immunomodulatory profile from the receptor‐induced PEVs.Our findings underscore that PEVs are tunable through receptor‐mediated activation. To truly comprehend their role(s) in mediating platelet functions among immune cells, conducting functional assays is imperative.
MAP kinase kinase 1 (MEK1) within extracellular vesicles inhibits tumour growth by promoting anti‐tumour immunity
Authors: Searles Stephen C. , Chen Wei‐Shan , Yee Jarrod D. , Lee Preston , Lee Calvin K. , Caron Christine , Mousovich‐Neto Felippe , Matei Irina , Lyden David , Bui Jack D. 
Published: September 2024

AbstractExtracellular vesicles (EVs) mediate intercellular communication in many physiologic processes and can modulate immune responses in individuals with cancer. Most studies of EVs in cancer have focused on their tumour promoting properties. Whether and how EVs might mediate tumour regression besides carrying antigens has not been well characterized. Using a mouse model of highly immunogenic regressor versus poorly immunogenic progressor tumour cells, we have characterized the role of EVs in activating macrophages and promoting tumour rejection. We found that the signalling molecule MAP2K1 (MEK1) is enriched in EVs secreted by regressor relative to progressor cells. Progressor EVs engineered to have levels of MEK1 similar to regressor EVs could inhibit tumour growth by indirectly promoting adaptive immunity in both syngeneic and 3rd party tumours. This effect required MEK1 activity and could occur by activating macrophages to promote adaptive immune responses against the tumour via the cytokine interferon‐gamma. Our results suggest that MEK inhibition may be deleterious to cancer treatment, since MEK1 plays an important cell‐extrinsic, tumour‐suppressive role within EVs. Moreover, the delivery of MEK1 to tumour‐associated macrophages, either by EVs, nanoparticles, or some other means, could be a useful strategy to treat cancer via the activation of anti‐tumour immunity.
Palladium‐Catalyzed Synthesis of Pyrrolo[1,2‐α]Pyrazines From N‐Phenacyl Pyrrole‐2‐Carbonitriles and Aryl Boronic Acids
Authors: Park Hyejun , Shim Seunghwan , Jeon Hayoung , Lee Hwayoung , Lee Kiho , Lee Kyeong , Lee Jae Kyun , Jalani Hitesh B. , Choi Yongseok 
Published: September 2024

ABSTRACTHerein, we have developed palladium‐trifluoroacetate‐catalyzed carbo‐palladation reaction of pyrrole‐2‐carbonitriles and aryl boronic acids leading to functionally diverse pyrrolo[1,2‐α]pyrazines under thoroughly optimized reaction conditions. The reaction proceeded smoothly and allowed the diversity‐oriented synthesis of pyrrolo[1,2‐α]pyrazines with broad substrate scope with respect to pyrrole‐2‐carbonitriles and aryl boronic acids.
Benzenediazonium Tetrafluoroborate‐Catalyzed Formal [3 + 3] Cyclization of 4‐Hydroxycoumarins With Propargylicalcohols
Authors: Chen Rongxiang , Li Xingshuo , Xiao Jutuan , Zhu Mingli , Sun Aili , Wang Kai‐Kai 
Published: September 2024

ABSTRACTA formal [3 + 3] cycloaddition of 4‐hydroxycoumarins with propargylicalcohols was established under mild conditions. This strategy utilizes diazonium tetrafluoroborate as the Lewis acid catalyst and provides a practical approach for delivering pyranocoumarin derivatives in moderate to high yield. The structure of the cycloadduct was unequivocally confirmed by single‐crystal x‐ray diffraction. The potential synthetic applications of this strategy were also highlighted by the scale‐up experiment and further synthetic transformation.
Cost‐effectiveness of Micra™ VR leadless pacemaker in patients with bradycardia and atrial fibrillation in Australia
Authors: Makino Koji , Mudge Mia , Hill Michelle , Zaunmayr Chelsea , Tilden Dominic 
Published: September 2024

AbstractBackgroundMicra™ VR Transcatheter Pacing System (Micra VR) is a single‐chamber transcatheter leadless pacemaker. Absence of leads and subcutaneous pocket reduces or completely eliminates the risk of complications associated with the conventional transvenous pacemakers (TVPM). When compared with TVPM, the leadless technology provides a quicker postimplantation recovery and causes less cosmetic concerns/discomfort providing better patient experiences in the long run. We performed a modeled cost‐utility analysis of Micra VR versus TVPM for the management of patients with bradycardia.MethodsWe developed a Markov model comparing Micra VR to TVPM over the device battery life of 17 years. Key data inputs were drawn from the MICRA Coverage with Evidence Development (CED) study. Costs were obtained from Australian sources. The analysis is from the perspective of the Australian healthcare system.ResultsThe risks of complications, including device‐related events, in real‐world clinical practice were relatively low for TVPM. The magnitude of cost savings arising from risk reductions provided by Micra VR was however sizable, offsetting roughly a quarter of its additional device cost. Over the 17‐year model period, Micra VR was associated with an estimated incremental cost of A$4277 and an incremental quality‐adjusted life years (QALYs) of 0.09 when compared with TVPM, yielding an incremental cost‐effectiveness ratio of A$47 379 per QALY gain.ConclusionsMicra VR is likely to offer a cost‐effective alternative to the conventional TVPM technology for the management of patients with bradycardia.
PARIOplus—A reliable method for determining soil texture?
Authors: Leemhuis Svenja , Hüttner Florian , Göttlein Axel 
Published: September 2024

AbstractThe new PARIOplus soil texture measuring system, based on the integral suspension pressure method, a modification of the PARIOclassic, is a method in which the suspension pressure curve measured with a high‐precision sensor is adapted to the modelled Stokes' law of sedimentation by means of inverse modelling. In order to validate the method, soil samples were mixed from artificial material to cover the entire grain size triangle. The results were also compared with those of the burette. This study shows that PARIOplus provides reliable and comparable results with R2 > 0.99 in all texture classes.
Management and outcomes of histoplasmosis in youth with inflammatory bowel disease in an endemic area
Authors: Wright Jonathan C. , Ardura Monica I. , Dotson Jennifer L. , Boyle Brendan , Maltz Ross M. , Michel Hilary K. 
Published: September 2024

AbstractObjectivePatients with inflammatory bowel disease (IBD) prescribed immunosuppressive therapies including antitumor necrosis factor (aTNF) therapies are at increased risk of histoplasmosis. We aim to evaluate the presentation, management, and outcomes of youth with IBD and concurrent histoplasmosis.MethodsSingle center, retrospective review of youth with IBD diagnosed with histoplasmosis from January 12, 2007 to January 1, 2022. Management and outcomes were followed for up to 2 years after diagnosis.ResultsNineteen patients (10 male, median age 16 years, range 8–22) with IBD were diagnosed with histoplasmosis: disseminated (N = 15/19; 79%), pulmonary (N = 3/19; 16%), lymph node (N = 1/19; 5%). At the time of histoplasmosis diagnosis, patients were predominantly receiving aTNF therapy (N = 17/19; 89%, median duration 21.9 months (interquartile range 8.5–52.0). Thirteen (13/19, 68%) patients required hospitalization and 2/19 (11%) required intensive care. All achieved antigen clearance with no recurrences. At the time of histoplasmosis diagnosis, aTNF was stopped in 15/17 (88%) patients and the following IBD therapies were initiated: 5‐aminosalicylates (N = 4/19; 21%), 6‐mercaptopurine (N = 3/19; 16%), enteral therapy (N = 2/19; 11%), and vedolizumab (N = 2/19; 11%); 6 of 19 (32%) received no IBD therapy and 2 of 19 (11%) patients continued aTNF. During follow‐up, 6 of 19 (32%) patients had an emergency department (ED) visit and/or hospitalization for symptoms attributed to active IBD, all of whom had discontinued aTNF; one patient required colectomy.ConclusionsSevere histoplasmosis infection in youth with IBD was rare. IBD treatment was modified by reducing immunosuppression. Histoplasmosis outcomes were favorable, but multiple patients required hospitalization or ED visits for IBD symptoms. The optimal approach to managing IBD during histoplasmosis treatment is challenging and requires further study.
Highly efficient green‐emissive organic light emitting diodes based on multiple‐resonance boron‐nitrogen materials
Authors: Cao Xudong , Liang Xiao , Xu Kai , Li Chong , Zhang Zhaochao , Duan Lian 
Published: September 2024

AbstractGreen‐emission phosphor‐sensitized OLEDs were demonstrated to achieve extremely high performance. SY‐FGD8‐based sensitized top‐emission devices achieved current efficiency of 232.8 cd/A@10 mA/cm2, LT95@50 mA/cm2, room temperature of 71 h and LT80@20 mA/cm2, 85°C of 187 h, which are greatly improved by 28%, 29%, and 65%, respectively, compared to phosphorescent devices. Notably, SY‐FGD8 exhibited excellent compatibility with different host and phosphorescent sensitizers.
Characteristics and Drivers of Soil Ecological Stoichiometry in Saline–Alkali Areas of Western Jilin Province, Northeast China
Authors: Li Yuefen , Zhong Jingfa , Chang Lei 
Published: September 2024

ABSTRACTSoil ecological stoichiometry (SES) provides an important approach in exploring chemical element balance relationships and ecosystem structure and function, but the characterization, significance, and drivers of SES in saline–alkali areas have not been well studied. Soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) were measured and their SES ratios were calculated from 155 soil samples collected at a depth of 20 cm in the saline–alkali soil zone of western Jilin Province, China. The results showed that SOC, TN, and TP contents and SES ratios (52:4:3) were lower in this region than in terrestrial ecosystems both in China as a whole and globally. The distribution of SOC, TN, and TP in saline–alkali soil varied significantly across land use types, with high concentrations mainly in woodland, grassland, and cropland. SOC, TN, and TP were tightly coupled, with significant positive correlations (p < 0.01), and C:N was significantly negatively correlated (p < 0.01) with the other SES ratios, indicating that saline–alkali soils are susceptible to carbon and nitrogen limitation. The distribution patterns of SOC, TN, TP, and their eco‐chemometrics on the environmental gradient were variable, mainly in the form of significant decreases with increasing mean annual precipitation, mean annual temperature, and elevation. Cropland was most affected by environmental factors, and all SES except TP were affected by environmental factors. Soil nutrient (44.9%) and soil texture (9.8%) contributed the most to explaining SES in the saline–alkali soil zone, while climate (1.6%) and vegetation (0.4%) contributed the least to the explanation. All land use types were most explained by AN, except for woodland SES, which was most explained by AP. Elevation (17.4%) possessed a high degree of explanation for SES on underutilized land, except for the soil itself. Grassland is the land category most affected by climatic factors (12.7%). By applying biochar, nitrogen fertilizer, and planting saline‐tolerant crops such as Leymus chinensis, the soil structure can be effectively improved and the content of carbon and nitrogen in the soil can be increased, which has a positive effect on the improvement of saline–alkali soil. The results of the study provide information that can be used to help saline–alkali areas cope with environmental and climate change and restore degraded ecosystems.
Controlling Soil Erosion of Tailings From Rare Earth Mines With Paspalum wettsteinii and Soil Amendments
Authors: He Yanzi , Tian Zhiyuan , Gu Zhujun , Wu Bingxiao , Liang Yin 
Published: September 2024

ABSTRACTRare earth elements are crucial for applications in aerospace, electronics, petrochemicals, and metallurgical industries. However, as rare earth mining expands, their tailings accumulate, leading to severe soil erosion and threatening of the local ecology. This study aimed to investigate the impact of planting Paspalum wettsteinii and soil amendments, including superabsorbent polymers (SAPs), organics, minerals, and urea, in controlling soil erosion. Six treatments, each with four replicates, were implemented on micro‐runoff plots on rare earth tailings: (1) bare slopes, (2) bare slopes repaired with composite soil amendments, (3) grass slopes, (4) grass slopes repaired with SAPs, and grass slopes repaired with (5) low or (6) high amounts of composites. Over 11 months, natural rainfall patterns, vegetation coverage, runoff yield, and sediment yield were monitored on the tailings' slope. Initially, plant growth was slow on bare slopes (56% vegetation coverage at 130 days), but it significantly improved with soil amendments (74% vegetation coverage on grass slopes repaired with SAPs and 97% vegetation coverage on grass slopes repaired with composites at 52 days). Adding composites onto bare slopes marginally reduced runoff and sediment yields by 3% and 16%, respectively. Vegetation, especially when combined with composites, significantly reduced runoff by 77% and sediment by 96%, while supplementing planting with SAPs decreased runoff by 41% and sediment by 88%. Planting without any amendments resulted in lower reductions of 26% in runoff and 81% in sediment. The results of the structural equation model showed that SAPs and fertilizers indirectly reduce sediment yield by increasing vegetation cover, with fertilizers also exercising a positive direct effect on sediment regulation. Our findings highlight how SAPs coupled with organic and inorganic fertilizers promote plant growth and erosion control, as applying these composites alone is less effective in controlling erosion on bare slopes. These results have promising implications for the ecological restoration of rare earth tailings.
Suppressing Ion Migration in MAPbI3 Polycrystalline Wafer with BMIMBF4 Ionic Liquid for X‐ray Detection and Imaging
Authors: Liu Dan , Wang Hongbing , Liao Feiyi , Di Haipeng , Li Haibin , Zhao Jianwei , Zhao Xiaochong , Song Jiangfeng , Lei Lin , Chen Changan 
Published: September 2024

Abstract3D lead‐halide perovskite wafers, recognized for their superior photoelectronic properties and robust fabrication, are promising candidates for advanced X‐ray detectors. However, severe ion migration in 3D perovskite wafers leads to dark current baseline drift and long‐term operational instability, hindering their further development. Herein, 3D MAPbI3 polycrystalline wafers with suppressed ion migration are prepared using the ionic liquid 1‐butyl‐3‐methylimidazolium tetrafluoroborate (BMIMBF4) and systematically investigated for X‐ray detection. The BMIMBF4‐passivated MAPbI3 wafers exhibit a low defect trap density (ntrap) of 9.45 × 109 cm−3, a high ion activation energy (Ea) of 0.51 eV, a notable iodide ion migration energy barrier of 0.65 eV, and a decreased dark current drift (Idrift) of 3.56 × 10−4 nA cm−1 s−1 V−1. The optimized MAPbI3 wafer‐based detectors exhibit a high sensitivity of 12088.8 µC Gyair−1 cm−2, a low detection limit (LoD) of 107.8 nGyair s−1, and strong operational stability in X‐ray detection. Moreover, these detectors demonstrate outstanding X‐ray imaging capabilities, achieving a high spatial resolution of 5.17 lp mm−1. Consequently, the utilization of ionic liquids with pseudo‐halide anions and polarized electron density distribution provides an innovative strategy for passivating 3D perovskite, advancing the field of powder‐pressed perovskite wafer X‐ray detection.
High‐Speed Hemodynamic Imaging with Low‐Fluence Photoacoustic Microscopy and Self‐Supervised Single Volume Denoising
Authors: Zhong Fenghe , Huang Xin , Sun Minglu , Li Dongyu , Fei Peng 
Published: September 2024

AbstractPhotoacoustic microscopy (PAM) enables label‐free imaging of the 3D vasculature and functional information with 2D lateral scan. The unique capacity in probing metabolism makes it ideal for animal research and clinical application. However, the high‐excitation power impedes the high‐speed monitoring of hemodynamics due to thermal accumulation and photon damage. To address this challenge, a self‐supervised photoacoustic single volume denoising (PSVD) approach, which combines 3D random sampling and noise augmentation to achieve 6 dB signal‐to‐noise‐ratio and contrast‐to‐noise‐ratio increases for the customized optical‐resolution photoacoustic microscope, is developed. Using PSVD, high‐quality PAM images of the mouse ear are acquired with only 10% fluence of normal excitation. Functional imaging is validated with this PSVD‐empowered low‐fluence PAM. Accurate oxygen saturation maps and high‐contrast flow kymographs are obtained. Moreover, the capability of this approach in the live mouse ear under hypercapnia is demonstrated. Further transformation into clinical imaging with low fluence will broaden the application of PAM.
SYT7 as a Potential Prognostic Marker Promotes the Metastasis of Epithelial Ovarian Cancer Cells by Activating the STAT3 Pathway
Authors: Li Yinguang , Shao Fengping , Huang Ying , Yin Qian , Liu Jun , Zhao Yunhe , Yuan Linjing 
Published: September 2024

ABSTRACTThe study aimed to investigate the impact of synaptotagmin 7 (SYT7) on the metastasis of epithelial ovarian cancer (EOC) and its potential mechanisms. This was achieved through the analysis of SYT7 expression levels and clinical relevance in EOC using bioinformatics analysis from TCGA. Additionally, the study examined the influence of SYT7 on the migration and invasion of EOC cells, as well as explored its molecular mechanisms using in vitro EOC cell lines and in vivo mouse xenograft models. Our research revealed that human EOC tissues exhibit significantly elevated levels of SYT7 compared to normal ovarian tissues, and that SYT7 expression is inversely correlated with overall survival. Suppression of SYT7 effectively impeded the migratory and invasive capabilities of CAOV3 cells, whereas overexpression of SYT7 notably accelerated tumor progression in A2780 cells. Mechanistic investigations demonstrated that SYT7 upregulates p‐STAT3 and MMP2 in EOC cells. Importantly, treatment with the STAT3 inhibitor niclosamide effectively counteracted the oncogenic effects of SYT7 in EOC. The inhibition of SYT7 was found to significantly reduce in vivo tumor metastasis in a nude mouse xenograft model. Our findings suggest that the upregulation of SYT7 in EOC is associated with a negative prognosis, as it enhances tumor migration and invasion by activating the STAT3 signaling pathway. Thus, SYT7 might be utilized as a EOC prognostic marker and treatment target.