bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction
Authors: Sierra-Marquez Juan , Schaller Lena , Sassenbach Lukas , Ramírez-Fernández Antonio , Alt Philipp , Rissiek Björn , Zimmer Béla , Schredelseker Johann , Hector Julia , Stähler Tobias , Koch-Nolte Friedrich , Staab-Weijnitz Claudia A. , Dietrich Alexander , Kopp Robin , Nicke Annette 
Published: June 2024

IntroductionP2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found. Most of this evidence stems, however, from in vitro model systems.MethodsHere, we used a P2X7-EGFP BAC transgenic mouse model as well as P2X4 and P2X7 knock-out mice to re-investigate a P2X4-P2X7 interaction in mouse lung by biochemical and immunohistochemical experiments as well as quantitative expression analysis.ResultsNo detectable amounts of P2X4 could be co-purified from mouse lung via P2X7-EGFP. In agreement with these findings, immuno-histochemical analysis using a P2X7-specific nanobody revealed only limited overlap in the cellular and subcellular localizations of P2X4 and P2X7 in both the native lung tissue and primary cells. Comparison of P2X4 and P2X7 transcript and protein levels in the respective gene-deficient and wild type mice showed no mutual interrelation between their expression levels in whole lungs. However, a significantly reduced P2rx7 expression was found in alveolar macrophages of P2rx4-/- mice.DiscussionIn summary, our detailed analysis of the cellular and subcellular P2X4 and P2X7 localization and expression does not support a physiologically relevant direct association of P2X4 and P2X7 subunits or receptors in vivo.
Minimum Service Package for the integration of female genital schistosomiasis into sexual and reproductive health and rights interventions
Authors: Pillay Leora N. , Umbelino-Walker Isis , Schlosser Delphine , Kalume Christine , Karuga Robinson 
Published: June 2024

IntroductionFemale genital schistosomiasis (FGS) is a manifestation of infection with schistosomes in the female genital area that affects an estimated 56 million women and girls in Africa. If untreated, FGS can result in severe sexual and reproductive health (SRH) complications. However, FGS is largely unrecognized by SRH providers, and there is no programmatic guidance for the integration of FGS and sexual and reproductive health and rights (SRHR) interventions in the way of a Minimum Service Package (MSP). Therefore, as part of a larger implementation study, an MSP was developed to guide program staff and health planners on how to integrate FGS and SRHR interventions in schistosomiasis-endemic countries.Materials and methodsIn collaboration with 35 experts from six sectors related to FGS, we conducted virtual workshops, engaging the participants within various specialties from around the world to identify a foundational framework for the MSP, as well as the integration points and activities for FGS and SRHR interventions. Several drafts of the MSP were developed, reviewed in virtual workshops, peer-reviewed, and then finalized by the participants.ResultsA participatory and consultative process led to the identification of a foundational framework for the integration of FGS and SRHR interventions, as well as the integration points and activities. This included identifying cadres of staff who would be needed to implement the MSP and the settings in which the service provision would take place.DiscussionDefining an MSP to guide the integration of a minimum package of FGS services in SRHR interventions is a critical step toward ensuring the prevention, screening, diagnosis, and treatment of women and girls in Africa. The MSP can now be rolled out and tested in a country context to start reducing the burden of this preventable and treatable neglected disease.
The exploration of perioperative hypotension subtypes: a prospective, single cohort, observational pilot study
Authors: Zhao Xu , Zhang Yuanjia , Kou Mengjia , Wang Zhongxing , He Qiulan , Wen Zhishuang , Chen Jingyuan , Song Yiyan , Wu Shihui , Huang Chanyan , Huang Wenqi 
Published: June 2024

BackgroundHypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension.MethodsThis is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored.ResultsSixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 [interquartile range, 3.1–23.3] minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury.ConclusionPerioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration.Clinical trial registrationhttps://www.chictr.org.cn/showprojEN.html?proj=134260, CTR2200055929.
D for dominant: porcine circovirus 2d (PCV-2d) prevalence over other genotypes in wild boars and higher viral flows from domestic pigs in Italy
Authors: Faustini Giulia , Poletto Francesca , Baston Riccardo , Tucciarone Claudia Maria , Legnardi Matteo , Dal Maso Mariangela , Genna Viviana , Fiorentini Laura , Di Donato Alessandra , Perulli Simona , Cecchinato Mattia , Drigo Michele , Franzo Giovanni 
Published: June 2024

IntroductionPorcine circovirus 2 (PCV-2) is a key pathogen for the swine industry at a global level. Nine genotypes, differing in epidemiology and potentially virulence, emerged over time, with PCV-2a, -2b, and -2d being the most widespread and clinically relevant. Conversely, the distribution of minor genotypes appears geographically and temporally restricted, suggesting lower virulence and different epidemiological drivers. In 2022, PCV-2e, the most genetically and phenotypically divergent genotype, was identified in multiple rural farms in North-eastern Italy. Since rural pigs often have access to outdoor environment, the introduction from wild boars was investigated.MethodsThrough a molecular and spatial approach, this study investigated the epidemiology and genetic diversity of PCV-2 in 122 wild boars across different provinces of North-eastern Italy.ResultsMolecular analysis revealed a high PCV-2 frequency (81.1%, 99/122), and classified the majority of strains as PCV-2d (96.3%, 78/81), with sporadic occurrences of PCV-2a (1.2%, 1/81) and PCV-2b (2.5%, 2/81) genotypes. A viral flow directed primarily from domestic pigs to wild boars was estimated by phylogenetic and phylodynamic analyses.DiscussionThese findings attested that the genotype replacement so far described only in the Italian domestic swine sector occurred also in wild boars. and suggested that the current heterogeneity of PCV-2d strains in Italian wild boars likely depends more on different introduction events from the domestic population rather than the presence of independent evolutionary pressures. While this might suggest PCV-2 circulation in wild boars having a marginal impact in the industrial sector, the sharing of PCV-2d strains across distinct wild populations, in absence of a consistent geographical pattern, suggests a complex interplay between domestic and wild pig populations, emphasizing the importance of improved biosecurity measures to mitigate the risk of pathogen transmission.
Generative AI unlocks PET insights: brain amyloid dynamics and quantification
Authors: Bossa Matías Nicolás , Nakshathri Akshaya Ganesh , Berenguer Abel Díaz , Sahli Hichem 
Published: June 2024

IntroductionStudying the spatiotemporal patterns of amyloid accumulation in the brain over time is crucial in understanding Alzheimer's disease (AD). Positron Emission Tomography (PET) imaging plays a pivotal role because it allows for the visualization and quantification of abnormal amyloid beta (Aβ) load in the living brain, providing a powerful tool for tracking disease progression and evaluating the efficacy of anti-amyloid therapies. Generative artificial intelligence (AI) can learn complex data distributions and generate realistic synthetic images. In this study, we demonstrate for the first time the potential of Generative Adversarial Networks (GANs) to build a low-dimensional representation space that effectively describes brain amyloid load and its dynamics.MethodsUsing a cohort of 1,259 subjects with AV45 PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we develop a 3D GAN model to project images into a latent representation space and generate back synthetic images. Then, we build a progression model on the representation space based on non-parametric ordinary differential equations to study brain amyloid evolution.ResultsWe found that global SUVR can be accurately predicted with a linear regression model only from the latent representation space (RMSE = 0.08 ± 0.01). We generated synthetic PET trajectories and illustrated predicted Aβ change in four years compared with actual progressionDiscussionGenerative AI can generate rich representations for statistical prediction and progression modeling and simulate evolution in synthetic patients, providing an invaluable tool for understanding AD, assisting in diagnosis, and designing clinical trials. The aim of this study was to illustrate the huge potential that generative AI has in brain amyloid imaging and to encourage its advancement by providing use cases and ideas for future research tracks.
Establishment and validation of a bad outcomes prediction model based on EEG and clinical parameters in prolonged disorder of consciousness
Authors: Liu Wanqing , Guo Yongkun , Xie Jingwei , Wu Yanzhi , Zhao Dexiao , Xing Zhe , Fu Xudong , Zhou Shaolong , Zhang Hengwei , Wang Xinjun 
Published: June 2024

ObjectiveThis study aimed to explore the electroencephalogram (EEG) indicators and clinical factors that may lead to poor prognosis in patients with prolonged disorder of consciousness (pDOC), and establish and verify a clinical predictive model based on these factors.MethodsThis study included 134 patients suffering from prolonged disorder of consciousness enrolled in our department of neurosurgery. We collected the data of sex, age, etiology, coma recovery scales (CRS-R) score, complications, blood routine, liver function, coagulation and other laboratory tests, resting EEG data and follow-up after discharge. These patients were divided into two groups: training set (n = 107) and verification set (n = 27). These patients were divided into a training set of 107 and a validation set of 27 for this study. Univariate and multivariate regression analysis were used to determine the factors affecting the poor prognosis of pDOC and to establish nomogram model. We use the receiver operating characteristic (ROC) and calibration curves to quantitatively test the effectiveness of the training set and the verification set. In order to further verify the clinical practical value of the model, we use decision curve analysis (DCA) to evaluate the model.ResultThe results from univariate and multivariate logistic regression analyses suggested that an increased frequency of occurrence microstate A, reduced CRS-R scores at the time of admission, the presence of episodes associated with paroxysmal sympathetic hyperactivity (PSH), and decreased fibrinogen levels all function as independent prognostic factors. These factors were used to construct the nomogram. The training and verification sets had areas under the curve of 0.854 and 0.920, respectively. Calibration curves and DCA demonstrated good model performance and significant clinical benefits in both sets.ConclusionThis study is based on the use of clinically available and low-cost clinical indicators combined with EEG to construct a highly applicable and accurate model for predicting the adverse prognosis of patients with prolonged disorder of consciousness. It provides an objective and reliable tool for clinicians to evaluate the prognosis of prolonged disorder of consciousness, and helps clinicians to provide personalized clinical care and decision-making for patients with prolonged disorder of consciousness and their families.
Optimized precipitation process for the treatment of radioactive effluents from Ni-alloy decontamination using a chemical oxidation reduction process
Authors: Robin Mathurin , Rivonkar Aditya , Suzuki-Muresan Tomo , Abdelouas Abdesselam , Mokili Marcel 
Published: June 2024

Nuclear power plays a major role in the generation of electricity with low carbon emissions. However, it generates significant amounts of radioactive waste, mainly from contaminated metallic components such as steam generators. Decontamination is essential for the safe handling and eventual recycling or disposal of these materials. Various decontamination techniques can be utilized but chemical processes are recommended for complex geometries such as the tubular parts of steam generators. COREMIX (Chemical Oxidation REduction using nitric permanganate and oxalic acid MIXture) is a process that is similar to the CORD (Chemical Oxidation Reduction Decontamination) process currently utilized in the industry which involves dissolving the contaminated oxide layers from metallic surfaces. This process generates a large quantity of radioactive effluent that requires appropriate treatment. The objective is to reduce metallic concentration and the radioactivity by precipitating metals in solution as hydroxides M(m-n)(OH)n (with m the oxidation number of the metal M). The optimization of a two-step precipitation protocol is presented here, with a study of the contact time (1–24 h) and the reagents used (NaOH and KOH). The resulting precipitates from this process are characterized using several techniques (FTIR, TGA and XRD). Tests were conducted on surrogate samples to demonstrate the viability of the process on more complex samples. Finally, the optimized protocols were implemented on radioactive Ni-alloy samples. Decontamination factors were calculated portraying the efficiency of both the COREMIX and the subsequent two-stage precipitation process. Characterization of the sludge produced during the process shows that the precipitate obtained at pH 8.5 consists mainly of iron (III) oxide-hydroxides, whereas the precipitate obtained at pH 12 is mainly composed of manganese (II,III) oxide. The optimization steps show that the contact time during the first precipitation and the choice of precipitants does not influence the efficiency of the protocol while the destruction of oxalic acid proves to be critical to quantitatively precipitate chromium. Ultimately, the COREMIX process can effectively decontaminate contaminated Ni-alloy samples, removing between 12% and 14% of the contamination in each cycle. Decontamination of effluent using the precipitation protocol results in a very high decontamination factor of between 3000 and 6000.
The global burden, trends, and inequalities of individuals with developmental and intellectual disabilities attributable to iodine deficiency from 1990 to 2019 and its prediction up to 2030
Authors: Yang Xuesong , Liu Cheng , Liu Yanbo , He Zhigang , Li Juan , Li Yijing , Wu Yanqiong , Manyande Anne , Feng Maohui , Xiang Hongbing 
Published: June 2024

ObjectiveThe objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019.MethodsUsing data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software.ResultsIn 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030.ConclusionThis research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.
Real-world TRAE association between niraparib and platinum-based chemotherapy
Authors: Wang Linli , Zhou Jieli , Wang Haibin , Han Wenling , Fang Chunyun 
Published: June 2024

BackgroundPre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated.MethodsPatients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher’s exact test were used for correlation analysis.Results1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p&lt;0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p&lt;0.001), red blood cell count decreased (57.5% vs 92.5%, p&lt;0.001), anemia (55% vs 87.5%, p&lt;0.001) and neutrophil count decreased (35% vs 85%, p&lt;0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified.Conclusion1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.
Large-scale, prospective observational study of regorafenib in Japanese patients with advanced gastrointestinal stromal tumors in a real-world clinical setting
Authors: Komatsu Yoshito , Muro Kei , Chosa Masayuki , Hirano Kazufumi , Sunaya Toshiyuki , Ayukawa Koichi , Hattori Kana , Nishida Toshirou 
Published: June 2024

BackgroundRegorafenib improves overall survival (OS) of patients with advanced progressive gastrointestinal stromal tumors (GISTs) after standard chemotherapy in phase III trials in the 3rd-line setting. This large-scale, prospective observational study evaluated the safety and effectiveness of regorafenib in Japanese patients with GIST in a real-world clinical setting.MethodsPatients with GIST received oral regorafenib at a maximum daily dose of 160 mg for weeks 1–3 of each 4-week cycle (dose could be modified at investigator’s discretion). The primary objective was to assess safety, particularly significant adverse drug reactions (ADRs), as well as the frequency of occurrence of ADRs, hand and foot syndrome (HFS), discontinuation of treatment due to disease progression and adverse events. A Cox proportional hazards model was used to evaluate associations between OS or time to treatment failure (TTF) and baseline characteristics or HFS.ResultsBetween August 2013 and March 2021, 143 evaluable patients were enrolled. ADRs occurred in 90.2% of patients and led to treatment discontinuation in 28.3%. The most frequent ADRs were HFS, hypertension, and liver injury. The overall response rate was 11.3% and disease control rate 56.5% (RECIST) based on investigators’ assessments. Median OS was 17.4 months (95% CI 14.24–23.68). Median TTF was 5.3 (95% CI 4.0–6.5) months. Improved OS and TTF responses occurred in patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1.ConclusionThe outcomes in this real-world study were consistent with those seen in clinical trials. No new safety concerns were identified.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT01933958.