bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting a cancer-specific LYPD3 glycoform for tumor therapy
Authors: Neumann Theresa , Hartung Evelyn , Gellert Johanna , Weiß Lisa , Weiske Manon , Kast Naomi , Gurka Stephanie , Marinoff Sophie , Jäkel Anika , Danielczyk Antje , Kehler Patrik
Published: November 2023

Introduction: One of the most drastic changes in cancer is the altered glycosylation of proteins and lipids, giving rise to truncated O-glycans like the Thomsen Friedenreich (TF) or Thomsen nouvelle (Tn) antigen, which are almost absent on normal cells. Combined protein-carbohydrate epitopes comprising these specific glycans are ideal candidates for potent targeted therapies given their excellent tumor specificity and broad cancer expression.

Methods and results: We have generated GT-002, a monoclonal antibody specifically targeting the epithelial glycoprotein LYPD3 only in the presence of a TF glycosylation. It does not cross-react with non-glycosylated LYPD3 or TF on other glycoproteins in ELISA and flow cytometry. GT-002 binds to various tumor cell lines and stains tumor tissues of different cancer indications including squamous cell carcinoma of the head and neck. The remarkable tumor specificity was confirmed in an immunohistochemistry study on a normal human tissue panel including several LYPD3-positive organs, where GT-002 elicited almost completely abolished normal tissue binding. Consequently, we observed markedly reduced binding of GT-002 to normal human tissues compared to Lupartumab, a conventional anti-LYPD3 antibody previously in clinical development as antibody-drug conjugate (BAY1129980). Neuraminidase treatment of healthy tissues, resulting in cleavage of sialic acid residues, re-established binding of GT-002 comparable to Lupartumab, showing that the GT-002 epitope is masked by sialic acid in normal cells.

Discussion: We believe that GT-002 is a promising candidate for development of antibody-drug- and radio-conjugates as well as bispecific molecules and chimeric antigen receptor therapeutics and highlights the powerful potential of antibodies against combined protein-carbohydrate epitopes to reduce on-target/off-tumor cytotoxicity.
Patterns of engagement in digital mental health intervention for LGBTQ+ youth: a latent profile analysis
Authors: Choi Seul Ki , Bruehlman-Senecal Emma , Green Amy , Lavra Josh , Bauermeister José
Published: November 2023

Engagement is a key metric that researchers can use to assess whether participants received the intended dose of a digital health intervention. However, the prevailing approach has predominantly focused on individual paradata metrics, resulting in a fragmented understanding of overall engagement. To address this limitation, our study utilizes person-centered approaches that allow for the simultaneous capture of multiple engagement metrics within imi–a web application specifically designed to support the mental health of lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority youth (LGBTQ+ youth). This person-centered approach enabled us to explore the association between engagement patterns and stress appraisal outcomes within the imi intervention arm. Utilizing latent profile analysis, we classified users into two engagement forms: overall engagement (total number of sessions, pages visited, and external links clicked and their cumulative time spent using imi) and content engagement (number of pages viewed across imi's four core guides: gender, stress, queerness, and stigma). We identified two profiles for each form: a “high engagement” profile and an “average engagement” profile, with the majority of participants assigned to the “average engagement” profile. Our analyses revealed a significant association between overall engagement profiles and stress appraisals, with the “high engagement” profile demonstrating higher challenge appraisals and marginal improvements in threat appraisals compared to the “average engagement” profile. However, no such associations were observed for content engagement profiles and stress appraisal outcomes. The two person-centered approaches used were consistent with prior results utilizing a variable-centered approach, indicating a stronger intervention effect among individuals who exhibit higher engagement in digital health interventions. Although both methods yielded comparable findings, the person-centered approach mitigates concerns related to multi-collinearity and adds additional nuance and context to the study of digital engagement.
Recent and episodic activity of decoupled mud/fluid discharge at Sartori mud volcano in the Calabrian Arc, Mediterranean Sea
Authors: Doll Mechthild , Römer Miriam , Pape Thomas , Kölling Martin , Kaul Norbert , dos Santos Ferreira Christian , Bohrmann Gerhard
Published: November 2023

Mud volcanoes (MVs) are surface structures typically created by episodic discharge of fluids and solids, often associated to onshore and offshore accretionary prisms on convergent plate boundaries. Detailed investigations of ongoing activity and its associated morphological changes, as well as a better understanding of the temporal evolution of these highly dynamic systems, may improve the estimations of material fluxes from MVs drastically. Until today, approximately 70 individual MVs were discovered in the northern Ionian Sea in the Calabrian Arc (Central Mediterranean Sea), but only a few have been analyzed and described in detail. In this study, new evidence for recent recurring eruptive activity of the ∼45 m-high and 1 km-wide Sartori MV situated in the clastic wedge of the Calabrian Arc is presented. High-resolution seafloor mapping as well as sediment temperature, geochemical, and sedimentological data received from two research cruises in 2016 and 2020 are used. Bathymetric and seafloor backscatter data (1 m scale) indicate the presence of two active eruption centers at the flat-topped Sartori MV. Elevated sediment temperature gradients at both eruption centers show that currently heat is transferred to the surface sediments. Pore water analyses indicate that fluids rising below the eruption centers are CH4-rich, Cl−-poor, and SO42−-free. Stable C and H isotopic compositions of methane suggest that it originates from a mix of primary microbial, secondary microbial, and/or thermogenic sources. A relatively shallow position of the sulfate–methane interface at both eruption centers also indicates the presence of upward fluid migration in recent times. Pore water modeling suggests that seawater has penetrated the surface sediments to a greater extent within the last few years. In contrast, centimeter-thick layers of hemipelagic sediments overlying mud breccia in sediment cores taken from both eruption centers show that no solid material has been ejected in recent times. Sediment core analyses combined with high-resolution seafloor mapping show an absence of rim-passing mudflows over the past ∼10 ka. It is concluded that Sartori MV is an episodically active MV from which fluids with a comparatively low flux were released into the bottom water in recent times.
Tectonic and hydrothermal activity at the Yellow Lake fissure in response to the 2004 Dallol dyke intrusion event in Afar
Authors: Mège Daniel , Hauber Ernst , Dyment Jérôme , Allemand Pascal , Moors Hugo , De Craen Mieke , Choe Hanjin
Published: November 2023

The Danakil depression in Ethiopia, at the southern end of the Red Sea, has been the place of volcanic crises in 2004–10, with emplacement of at least 15 dykes. One of them, non-emergent, occurred in dry lake Asale next to Black Mountain and south of Mount Dallol during fall 2004. We report on the opening of a 4.5 km-long fissure in the ground at the same time the Black Mountain dyke was intruding the crust 2 km westward and parallel to it. The fissure, located north and south of Yellow Lake (Gaet’ale) and trending NNW-SSE, is still hydrothermally active. First, we describe the remarkable diversity of morphologic expressions of the fissure, made possible by development in an evaporite sequence. Satellite image monitoring reveals that its formation is coeval with the latest intrusion stage of the Black Mountain dyke. Hydrothermal activity in the fissure area is, however older than ∼60 years. It is suggested that hydrothermal activity is primarily a side effect of the igneous processes, probably sill intrusion, that resulted in the uplift of Mount Dallol area, in a ∼400 m thick, fluid-saturated evaporite pile. We suggest that, in 2004, emplacement of the Black Mountain dyke caused dilation within the evaporite pile overlying it, where extension was also facilitated by pressured pore fluids. This study documents the delicate intermingling of magmatic, tectonic, hydrothermal, and geomorphologic processes in evaporitic environments at the transition between continental rifting and oceanic spreading.
Correlation of executive functions, academic achievement, eating behavior and eating habits in university students of Mexico City
Authors: Chávez-Hernández María Elena
Published: November 2023

Introduction

Young adults between 18 and 25 years of age are in an important transitional time and university students are considered vulnerable given that they generally maintain an unhealthy lifestyle characterized by poor diet quality and meal skipping. The aim of the present study was to evaluate the relationship between executive functions, academic achievement, eating behavior, eating habits, and BMI in university students.

Methods

Undergraduate university students (18–25 years) who lived in Mexico City were included in the sample; executive function, eating habits, eating behavior and academic achievement were measured.

Results

1903 university students (1,038 women, 865 men), with a mean age of 20.65 years (SD ±1.66), participated in the study. Spearman’s r correlation analysis revealed that there is a significant correlation between all variables of interest, with the most significant correlations found with academic achievement, emotional eating, and eating habits.

Discussion

Our study confirms previous findings in the association between EF, eating habits, eating behavior, and academic achievement in university students, and also provides a first approach to the association between UP food intake, overall meal skipping (breakfast, lunch, and/or dinner) and EF.
Advantages of total parathyroidectomy in patients with secondary hyperparathyroidism induced by end stage renal disease
Authors: Iorga Cristian , Iorga Cristina Raluca , Andreiana Iuliana , Bengulescu Iustinian , Constantin Traian , Strambu Victor
Published: November 2023

Introduction

Secondary hyperparathyroidism, as a result of chronic kidney disease could be treated medically or surgically. When pharmacotherapy fails, patients undergo surgery - parathyroidectomy, the curative treatment of secondary hyperparathyroidism (SHPT). There are currently 3 accepted surgical techniques, each with supporters or opponents – total parathyroidectomy, subtotal parathyroidectomy and parathyroidectomy with immediate autotransplantation.

Methods

In this paper we described our experience on a series of 160 consecutive patients diagnosed with secondary hyperparathyroidism who underwent surgery, in 27 cases it was totalization of the intervention (patients with previously performed subtotal parathyroidectomy or with supernumerary glands and SHPT recurrence). We routinely perform total parathyroidectomy, the method that we believe offers the best results.

Results

The group of patients was studied according to demographic criteria, paraclinical balance, clinical symptomatology, pre- and postoperative iPTH (intact parathormone) values, SHPT recurrence, number of reinterventions. In 31 cases we found gland ectopy and in 15 cases we discovered supernumerary parathyroids. A percentage of 96.24% of patients with total parathyroidectomy did not show recurrence.

Discussions

After analyzing the obtained results, our conclusion was that total parathyroidectomy is the intervention of choice for patients suffering from secondary hyperparathyroidism when pharmacotherapy fails in order to prevent recurrence of the disease and to correct the metabolic parameters.
Multi-view information fusion using multi-view variational autoencoder to predict proximal femoral fracture load
Authors: Zhao Chen , Keyak Joyce H. , Cao Xuewei , Sha Qiuying , Wu Li , Luo Zhe , Zhao Lan-Juan , Tian Qing , Serou Michael , Qiu Chuan , Su Kuan-Jui , Shen Hui , Deng Hong-Wen , Zhou Weihua
Published: November 2023

Background

Hip fracture occurs when an applied force exceeds the force that the proximal femur can support (the fracture load or “strength”) and can have devastating consequences with poor functional outcomes. Proximal femoral strengths for specific loading conditions can be computed by subject-specific finite element analysis (FEA) using quantitative computerized tomography (QCT) images. However, the radiation and availability of QCT limit its clinical usability. Alternative low-dose and widely available measurements, such as dual energy X-ray absorptiometry (DXA) and genetic factors, would be preferable for bone strength assessment. The aim of this paper is to design a deep learning-based model to predict proximal femoral strength using multi-view information fusion.

Results

We developed new models using multi-view variational autoencoder (MVAE) for feature representation learning and a product of expert (PoE) model for multi-view information fusion. We applied the proposed models to an in-house Louisiana Osteoporosis Study (LOS) cohort with 931 male subjects, including 345 African Americans and 586 Caucasians. We performed genome-wide association studies (GWAS) to select 256 genetic variants with the lowest p-values for each proximal femoral strength and integrated whole genome sequence (WGS) features and DXA-derived imaging features to predict proximal femoral strength. The best prediction model for fall fracture load was acquired by integrating WGS features and DXA-derived imaging features. The designed models achieved the mean absolute percentage error of 18.04%, 6.84% and 7.95% for predicting proximal femoral fracture loads using linear models of fall loading, nonlinear models of fall loading, and nonlinear models of stance loading, respectively.

Conclusion

The proposed models are capable of predicting proximal femoral strength using WGS features and DXA-derived imaging features. Though this tool is not a substitute for predicting FEA using QCT images, it would make improved assessment of hip fracture risk more widely available while avoiding the increased radiation exposure from QCT.
Development and external validation of dual online tools for prognostic assessment in elderly patients with high-grade glioma: a comprehensive study using SEER and Chinese cohorts
Authors: Zhang Hongyu , Jiang Xinzhan , Ren Fubin , Gu Qiang , Yao Jiahao , Wang Xinyu , Zou Shuhuai , Gan Yifan , Gu Jianheng , Xu Yongji , Wang Zhao , Liu Shuang , Wang Xuefeng , Wei Baojian
Published: November 2023

Background

Elderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict overall survival (OS) and cancer-specific survival (CSS), assisting clinical decision-making.

Methods

We scrutinized data from the SEER database on 5,245 elderly patients diagnosed with high-grade glioma between 2000-2020, segmenting them into training (3,672) and validation (1,573) subsets. An additional external validation cohort was obtained from our institution. Prognostic determinants were pinpointed using Cox regression analyses, which facilitated the construction of the nomogram. The nomogram’s predictive precision for OS and CSS was gauged using calibration and ROC curves, the C-index, and decision curve analysis (DCA). Based on risk scores, patients were stratified into high or low-risk categories, and survival disparities were explored.

Results

Using multivariate Cox regression, we identified several prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with high-grade gliomas, including age, tumor location, size, surgical technique, and therapies. Two digital nomograms were formulated anchored on these determinants. For OS, the C-index values in the training, internal, and external validation cohorts were 0.734, 0.729, and 0.701, respectively. We also derived AUC values for 3-, 6-, and 12-month periods. For CSS, the C-index values for the training and validation groups were 0.733 and 0.727, with analogous AUC metrics. The efficacy and clinical relevance of the nomograms were corroborated via ROC curves, calibration plots, and DCA for both cohorts.

Conclusion

Our investigation pinpointed pivotal risk factors in elderly glioma patients, leading to the development of an instrumental prognostic nomogram for OS and CSS. This instrument offers invaluable insights to optimize treatment strategies.
Optimal decisions of closed-loop supply chain under government recycling subsidy and value co-creation
Authors: Liao Bifeng , Shang Yuanchao , Sun Yangyi
Published: November 2023

Several countries and regions have adopted recycling subsidy policies to encourage recycling activities and enacted recycling laws to improve the recycling rate of waste electrical and electronic equipment (WEEE). These initiatives are designed to reduce the damage to the environment and natural resource consumption caused the enterprise. In this study, we analyze how government recycling regulations, value co-creation activities, and recycling subsidies influence the pricing and output decisions of members of a closed-loop supply chain. We develop a Stackelberg game model led by manufacturers and followed by retailers to explore the impact of value co-creation activities and recycling subsidies on the quantity of new and remanufactured products, recyclers’ prices and prices of recycled electronic parts, manufacturers’ capacity to recycle, and environmental performance in the context of government recycling regulations. Manufacturers can choose from three recycling modes: mandatory minimum remanufacturing (SDWmodel), non-mandatory partial remanufacturing (SDOmodel), and full remanufacturing (SDBmodel). The results show that 1) higher recycling subsidies optimize the recycling capacity of manufacturers, increasing the number of remanufactured products and reducing the market share of new products, which affects the price of new products. 2) higher recycling subsidies reduce the price of recycled electronic parts purchased by manufacturers, strengthen the bargaining power of consumers, increase the price of recyclers, promote the active participation of consumers in value co-creation activities, and increase the level of value co-creation. 3) higher recycling subsidies help to increase the economic value of all parties in the closed-loop supply chain (manufacturers, recyclers, consumers), but stricter recycling constraints are not always beneficial to environmental performance; environmental taxes and fees above a certain threshold of recycling constraints reduce the negative impact of production activities on the environment. The novelties and contributions of this research include proposing a new application for the Value Co-creation and Government policy utilized to Supply Chain and their impact on sustainable supply chain. In addition, we proposed three new recycling strategies and analysed the impact of environmental tax on the environmental performance. Therefore, this study aims to provide some insights for government policymakers and for managers when facing a more complex business environment.
Frequency regulation strategy of direct drive permanent magnet synchronous wind power generation system based on RPC principle
Authors: Zhang Xiaoke , Xia Dawei , Zhang Hengyou , Wang Jinggang
Published: November 2023

The continuous integration of renewable energy into the grid has reduced its inertia and damping levels. When disturbances occur, the grid is prone to frequency excursion issues, which restrict the further utilization of renewable energy. Consequently, an increasing number of grid codes require active participation of renewable energy sources in the system’s frequency regulation (FR). Direct-drive permanent magnet synchronous wind power systems, characterized by their simple structure and high reliability, have gradually become the mainstream in wind power systems. By controlling the pitch angle to reserve surplus power, the wind turbines can actively engage in frequency regulation during disturbances. However, due to limited power reserve capacity, traditional FR methods struggle with parameters tuning, thus failing to achieve the desired effect. To this end, this paper proposes an FR strategy for direct-drive permanent magnet synchronous wind power systems based on the principle of rapid power compensation (RPC). It circumvents the challenges associated with parameter tuning, and achieves optimal FR performance for wind turbine inverter under power-limited conditions. Firstly, it is demonstrated that the proposed RPC control, when making full use of power reserves, can achieve FR effects equivalent to optimal PD control through rigorous mathematical analysis. Subsequently, the RPC control is divided into four operating modes to address FR requirements under different conditions. The transitions between these modes are explained, and the detailed implementation of the RPC control is provided. Finally, the effectiveness and superiority of the proposed control strategy are validated through simulation based on Matlab/Simulink.
Experimental study on flue gas foam-assisted steam flooding: investigating characteristics of enhanced oil recovery and gas storage
Authors: Cao Qiuying , Wei Tao , Wu Guanghuan , Yu Jianmei , Tian Kehan , Cao Aiqing
Published: November 2023

Steam flooding is one of the most widely used heavy oil thermal recovery technologies. Steam transfers heat to heavy oil to reduce viscosity and improve fluidity. The current problem is that steam loses a lot of heat in the formation, and there are serious carbon emissions in the whole production process. In this paper, flue gas and steam were combined to drive heavy oil in the form of composite thermal fluid, and foam was added on this basis. With the help of one-dimensional sandpack model, both single-model and parallel dual-model with permeability ratio experiments were conducted to investigate key characteristics such as steam heat transfer, heavy oil production and flue gas retention during the displacement process. The experimental results indicated that flue gas effectively inhibited steam condensation and reduced heat loss during the flow process. Compared to steam flooding, the sandpack model exhibited temperature rises of 4.4°C and 9.1°C at the middle and end, respectively. While flue gas foam fell slightly short of flue gas in terms of enhanced heat transfer, it outperforms in recovery factor, achieving a 10.4% improvement over flue gas-assisted steam flooding. The foam blocked gas channeling by accumulating and capturing along the flow path, resulting in a gas retention volume of 389 mL within the model. Furthermore, the flue gas foam facilitated steam flow to previously unswept low-permeability areas, thus enhancing oil recovery. In the parallel double-model experiment, the low-permeability model exhibited significantly improved oil displacement efficiency compared to flue gas-assisted steam flooding, and the remaining oil content in the end of the high permeability model was increased by 1.9%, while the remaining oil content in the front and end of the low-permeability model was reduced by 3.5% and 3.8% respectively.
Quarterly GDP forecast based on coupled economic and energy feature WA-LSTM model
Authors: Zhang Yaling , Shang Wenying , Zhang Na , Pan Xiao , Huang Bonan
Published: November 2023

Existing macroeconomic forecasting methods primarily focus on the characteristics of economic data, but they overlook the energy-related features concealed behind these economic characteristics, which may lead to inaccurate GDP predictions. Therefore, this paper meticulously analyzes the relationship between energy big data and economic data indicators, explores the coupling feature mining of energy big data and economic data, and constructs features coupling economic and energy data. Targeting the nonlinear variation coupling features in China’s quarterly GDP data and using the long short-term memory (LSTM) neural network model based on deep learning, we employ wavelet analysis technology (WA) to decompose selected macroeconomic variables and construct a prediction model combining LSTM and WA, which is further compared with multiple benchmark models. The research findings show that, in terms of quarterly GDP data prediction, the combined deep learning model and wavelet analysis significantly outperform other methods. When processing structurally complex, nonlinear, and multi-variable data, the LSTM and WA combined prediction model demonstrate better generalization capabilities, with its prediction accuracy generally surpassing other benchmark models.
Research on multilevel evaluations and zones of territorial spatial functions in Yibin, China
Authors: Meng Bao , Zhang Shaoyao , Deng Wei , Peng Li
Published: November 2023

Objectively evaluating and defining territorial spatial functions are important prerequisites for optimizing the use of territorial space. However, the results of the evaluation of functions at different levels may differ significantly. How to integrate the evaluation results and guide the spatial utilization at different levels more effectively is worth exploring. This study takes as the research area Yibin City, China, a node city along the Yangtze River in the upper reaches of the Yangtze River. In the study, 185 towns in that city were taken as the primary evaluation units for an indicator system of territorial spatial function constructed on the basis of multivariate data. Research methods such as the entropy method and cluster analysis were adopted to do multilevel evaluations and zoning of territorial spatial functions in Yibin City. The results suggest the following: 1) The distribution of agricultural production, rural living, and ecological regulation functions among the second-level production-living-ecological (PLE) functions of townships were relatively balanced in Yibin City. The production function of industry and mining, urban life function, and ecological product supply function showed spatial directivity. 2) The evaluation results of the first-level PLE functions of townships showed that the areas with substantial PLE functions accounted for approximately 20%, whereas the areas with insignificant functions accounted for approximately 80%, which reflected the “80/20 rule” of spatial functions. 3) In accordance with the cluster analysis of the multilevel evaluation results, the township functions in Yibin were divided into 5 functional areas: urban life-industrial production advantage areas (12%), urban life-rural life advantage areas (8%), rural life-agricultural production-ecological function product supply advantage areas (29%), rural life-agricultural production-ecological service function advantage areas (20%), and ecological service function-agricultural production function advantage areas (31%). 4) In the future, Yibin City should focus on 20% of the significant functional areas and attach importance to the relativity of spatial functions to form a high-quality territorial spatial protection and development pattern. Based on the objectives and requirements of the new territorial spatial planning in China, this study reconstructed the municipal territorial spatial functional areas through a multilevel functional evaluation, which has theoretical and practical significance for forming a new pattern of territorial spatial development and use with joint production, living, and ecological functions.
Diversity and soil chemical properties jointly explained the basal area in karst forest
Authors: Lu Lihong , Zeng Fuping , Zeng Zhaoxia , Du Hu , Zhang Chen , Zhang Hao
Published: November 2023

Introduction

Plant diversity and soil chemical properties are important factors affecting the plant growth. We sought to compare the explanatory rates of diversity and soil chemical properties in explaining the variation of basal area in karst forests, and also sought to compare the relative importance of the niche complementarity and mass ratio hypotheses.

Methods

On the basis of linear regression and structural equation modelling, we examined the correlation between the basal area of plant communities and species diversity, functional diversity, phylogenetic diversity, the community-weighted mean (CWM) of traits, and soil chemical properties, using data obtained from 35 monitoring plots in southwest China.

Results

Species, functional, and phylogenetic diversities were all significantly correlated with the basal area of the plant community, among the indices of which, Faith’s phylogenetic diversity was found to have the greatest explanatory power for basal area. These plant diversity indices can better explain the variation in basal area than the CWM of traits, suggesting the niche complementarity hypothesis is more applicable than the mass ratio hypothesis. Moreover, soil chemical properties also have an equal important impact. Different chemical properties were found to show significant positive correlations with basal area, and their total effects on basal area were shown to be greater than the CWM of traits.

Discussion

Attention should be paid to diversity and soil chemical properties. This study provides theoretical guidance for understanding biodiversity maintenance mechanisms and protecting karst forests.
Mixed Eucalyptus plantations in subtropical China enhance phosphorus accumulation and transformation in soil aggregates
Authors: Cui Yuhong , Yan Yu , Wang Shengqiang , Zhang Han , He Yaqin , Jiang Chenyang , Fan Rongyuan , Ye Shaoming
Published: November 2023

Introduction

The production of Eucalyptus, a principal economic tree genus in China, is faced with challenges related to soil phosphorus (P) limitations. In this study, we explore variations in phosphorus content, storage, and transformation in Eucalyptus forests. We hypothesize that mixed forests augment soil aggregate stability and P content and that microaggregates are pivotal in determining P differences between mixed and pure forests. Additionally, we posit that mixed forests foster P transformation, enhancing its efficacy in the soil. Current research on the distribution and transformation of soil total P (TP) and P fractions at the soil aggregate level is limited.

Methods

In this study, we selected soil from a Eucalyptus-Mytilaria laosensis Lecomte mixed forest, Eucalyptus-Erythrophleum fordii Oliv mixed forest, and pure Eucalyptus forest in Chongzuo County, Guangxi, China, as the research objects. Using a dry-sieving method, we divided the soil collected in situ from the 0–40 cm layer into aggregates of >2, 1–2, 0.25–1, and <0.25 mm particle sizes, measured the TP and P fractions (resin-extractable inorganic P, bicarbonate-extractable inorganic P, bicarbonate-extractable organic P, sodium hydroxide-extractable inorganic P, sodium hydroxide-extractable organic P, dilute hydrochloric acid-extractable P, concentrated hydrochloric acid extractable inorganic P, concentrated hydrochloric acid-extractable organic P and residue-P) in different aggregates, and used redundancy analysis and PLS SEM to reveal key factors affecting soil P accumulation and transformation.

Results

The results showed that compared to pure Eucalyptus forests, mixed Eucalyptus forests significantly enhanced the stability of soil aggregates and the content and storage of phosphorus, especially the Eucalyptus-Mytilaria laosensis mixed forest. The content of total soil phosphorus and its fractions decreased with increasing aggregate particle size, while the opposite trend was observed for stored P, with aggregates <0.25 mm being the main fraction influencing soil phosphorus accumulation. The transformation process of P fractions was primarily constrained by dissolution rates, mineralization rates, biological activity, including the action of microbes, fungi, and plant–root interactions, and other factors.

Discussion

Mixed forests increased the transformation of phosphorus in soil aggregates, effectivel enhancing the availability of soil phosphorus. In summary, this study provides important evidence for the systematic management of subtropical artificia Eucalyptus forests and the sustainable utilization of soil resources.
A comprehensive preimplantation genetic testing approach for SEA-type α-thalassemia by fluorescent gap-polymerase chain reaction combined with haplotype analysis
Authors: Wang Jing , Ma Yuanlin , Guo Jing , Li Rong , Zhou Canquan , Xu Yanwen
Published: November 2023

Introduction: This study aimed to evaluate the feasibility and necessity of using fluorescence Gap-polymerase chain reaction combined with haplotype analysis in preimplantation genetic testing for SEA-type α-thalassemia.

Methods: A total of 26 preimplantation genetic testing biopsy cycles were performed in 25 families from June 2021 to February 2022. All couples were carriers of SEA-type α-thalassemia. Fluorescent Gap-polymerase chain reaction was used for detecting fragment deletion. Subsequently, according to the results of polymerase chain reaction, reference embryos were identified to establish haplotype using single nucleotide polymorphism array, and aneuploidy was screened simultaneously. In cases wherein the polymerase chain reaction results were inconsistent with the haplotype results, the reasons were investigated, either by retest of the biopsied samples or rebiopsy of the embryo.

Results: Among the 172 embryos, 162 had consistent results when tested using both methods, resulting in a consistency rate of 94.2%. Conversely, 10 embryos had inconsistent results, mainly due to chromosome 16 aneuploidy (n = 7), allele dropout in Gap-polymerase chain reaction (n = 2), or incorrect haplotype due to poor sample amplification quality (n = 1). The clinical pregnancy rate of each frozen-thawed embryo transfer was 57.7% (15/26). Six families underwent prenatal diagnosis, which confirmed the results of preimplantation genetic testing.

Conclusion: Fluorescent Gap-polymerase chain reaction combined with haplotype analysis is feasible and necessary for SEA-type α-thalassemia preimplantation genetic testing.
Improving predictive ability in sparse testing designs in soybean populations
Authors: Persa Reyna , Canella Vieira Caio , Rios Esteban , Hoyos-Villegas Valerio , Messina Carlos D. , Runcie Daniel , Jarquin Diego
Published: November 2023

The availability of high-dimensional genomic data and advancements in genome-based prediction models (GP) have revolutionized and contributed to accelerated genetic gains in soybean breeding programs. GP-based sparse testing is a promising concept that allows increasing the testing capacity of genotypes in environments, of genotypes or environments at a fixed cost, or a substantial reduction of costs at a fixed testing capacity. This study represents the first attempt to implement GP-based sparse testing in soybeans by evaluating different training set compositions going from non-overlapped RILs until almost the other extreme of having same set of genotypes observed across environments for different training set sizes. A total of 1,755 recombinant inbred lines (RILs) tested in nine environments were used in this study. RILs were derived from 39 bi-parental populations of the Soybean Nested Association Mapping (NAM) project. The predictive abilities of various models and training set sizes and compositions were investigated. Training compositions included a range of ratios of overlapping (O-RILs) and non-overlapping (NO-RILs) RILs across environments, as well as a methodology to maximize or minimize the genetic diversity in a fixed-size sample. Reducing the training set size compromised predictive ability in most training set compositions. Overall, maximizing the genetic diversity within the training set and the inclusion of O-RILs increased prediction accuracy given a fixed training set size; however, the most complex model was less affected by these factors. More testing environments in the early stages of the breeding pipeline can provide a more comprehensive assessment of genotype stability and adaptation which are fundamental for the precise selection of superior genotypes adapted to a wide range of environments.
Case report: Neonatal-onset inflammatory bowel disease due to novel compound heterozygous mutations in DUOX2
Authors: Finocchi Andrea , Pacillo Lucia , Chiriaco Maria , Di Matteo Gigliola , Francalanci Paola , Angelino Giulia , Caldaro Tamara , Rivalta Beatrice , O’Mara Maurice , Zhang Suisheng , Lepri Francesca Romana , Novelli Antonio , De Angelis Paola , Knaus Ulla G. , Rea Francesca
Published: November 2023

Very Early Onset Inflammatory Bowel Disease (VEO-IBD) is potentially associated with genetic disorders of the intestinal epithelial barrier or inborn errors of immunity (IEI). Dual oxidase 2 (DUOX2), an H2O2-producing NADPH oxidase expressed at apical enterocyte membranes, plays a crucial role in innate defense response. Biallelic DUOX2 mutations have been described only in two patients with VEO-IBD to date. We report the case of a 1-month-old female infant who presented persistent high C-reactive protein (CRP) levels from birth and anemia. Positive occult blood and very high calprotectin in the stool were detected and abdominal ultrasound showed thickened last ileal loop. Full endoscopy evaluation revealed important colon stenosis with multiple pseudo-polyploidy formations that resulted refractory to steroid therapy, requiring a partial colic resection. Histological examination of biopsy samples showed morphological features of IBD. Whole Exome Sequencing (WES) disclosed compound heterozygous variants in the DUOX2 gene: the pathogenic c.2524C>T; p.Arg842Ter and the variant of uncertain significance (VUS) c.3175C>T; p.Arg1059Cys. Molecular and functional studies showed the presence of mutant DUOX2 in the intestinal epithelium of the patient, albeit with at least 50% decreased catalytic activity. In conclusion, we describe the third patient to date with compound heterozygous variants of DUOX2, responsible for monogenic neonatal-IBD. This case expands the knowledge about Mendelian causes of VEO-IBD and DUOX2 deficiency. We suggest that DUOX2 should be part of the diagnostic evaluation of patients with suspected monogenic VEO-IBD.
A two-sample Mendelian randomization analysis: causal association between chemokines and pan-carcinoma
Authors: Cui Kai , Song Na , Fan Yanwu , Zeng Liqun , Shi Pingyu , Wang Ziwei , Su Wei , Wang Haijun
Published: November 2023

Objective: According to the 2020 data from the World Health Organization (WHO), cancers stand as one of the foremost contributors to global mortality. Revealing novel cancer risk factors and protective factors is of paramount importance in the prevention of disease occurrence. Studies on the relationship between chemokines and cancer are ongoing; however, due to the coordination of multiple potential mechanisms, the specific causal association remains unclear.

Methods: We performed a bidirectional Mendelian randomization analysis to explore the causal association between serum chemokines and pan-carcinoma. All data is from the GWAS catalog and IEU Open GWAS database. The inverse-variance weighted (IVW) method is primarily employed for assessing the statistical significance of the findings. In addition, the significance threshold after the multiple hypothesis test (Bonferroni) was 0.0013, and the evidence of a potential association was considered if the p-value < 0.05, but remained greater than Bonferroni’s threshold.

Results: The results indicate that CCL1 (odds ratio, OR = 1.18), CCL2 (OR = 1.04), CCL8 (OR = 1.36), CCL14 (Colorectal, OR = 1.08, Small intestine, OR = 0.77, Lung, OR = 1.11), CCL15 (OR = 0.85), CCL18 (Breast, OR = 0.95, Prostate, OR = 0.96), CCL19 (Lung, OR = 0.66, Prostate, OR = 0.92), CCL20 (Lung, OR = 0.53, Thyroid, OR = 0.76), CCL21 (OR = 0.62), CCL22 (OR = 2.05), CCL23 (OR = 1.31), CCL24 (OR = 1.06), CCL27 (OR = 1.49), CCL28 (OR = 0.74), CXCL5 (OR = 0.95), CXCL9 (OR = 3.60), CXCL12 (Breast, OR = 0.87, Small intestine, OR = 0.58), CXCL13 (Breast, OR = 0.93, Lung, OR = 1.29), CXCL14 (Colon, OR = 1.40) and CXCL17 (OR = 1.07) are potential risk factors for cancers. In addition, there was a reverse causal association between CCL1 (OR = 0.94) and CCL18 (OR = 0.94) and breast cancer. Sensitivity analysis results were similar. The results of the other four MR Methods were consistent with the main results, and the leave-one-out method showed that the results were not driven by a Single nucleotide polymorphism (SNP). Moreover, there was no heterogeneity and pleiotropy in our analysis.

Conclusion: Based on the two-sample MR Analysis method, we found that chemokines might be upstream factors of cancer pathogenesis. These results might provide new insights into the future use of chemokines as potential targets for cancer prevention and treatment. Our results also provide important clues for tumor prevention, and changes of serum chemokine concentration may be recognized as one of the features of precancerous lesions in future clinical trials.
More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients
Authors: Joly Candie , Desjardins Delphine , Porcher Raphael , Péré Hélène , Bruneau Thomas , Zhang Qian , Bastard Paul , Cobat Aurélie , Resmini Léa , Lenoir Olivia , Savale Laurent , Lécuroux Camille , Verstuyft Céline , Roque-Afonso Anne-Marie , Veyer David , Baron Gabriel , Resche-Rigon Matthieu , Ravaud Philippe , Casanova Jean-Laurent , Le Grand Roger , Hermine Olivier , Tharaux Pierre-Louis , Mariette Xavier
Published: November 2023

Background

The clinical outcome of COVID-19 pneumonia is highly variable. Few biological predictive factors have been identified. Genetic and immunological studies suggest that type 1 interferons (IFN) are essential to control SARS-CoV-2 infection.

Objective

To study the link between change in blood IFN-α2 level and plasma SARS-Cov2 viral load over time and subsequent death in patients with severe and critical COVID-19.

Methods

One hundred and forty patients from the CORIMUNO-19 cohort hospitalized with severe or critical COVID-19 pneumonia, all requiring oxygen or ventilation, were prospectively studied. Blood IFN-α2 was evaluated using the Single Molecule Array technology. Anti-IFN-α2 auto-Abs were determined with a reporter luciferase activity. Plasma SARS-Cov2 viral load was measured using droplet digital PCR targeting the Nucleocapsid gene of the SARS-CoV-2 positive-strand RNA genome.

Results

Although the percentage of plasmacytoid dendritic cells was low, the blood IFN-α2 level was higher in patients than in healthy controls and was correlated to SARS-CoV-2 plasma viral load at entry. Neutralizing anti-IFN-α2 auto-antibodies were detected in 5% of patients, associated with a lower baseline level of blood IFN-α2. A longitudinal analysis found that a more rapid decline of blood IFN-α2 was observed in fatal versus surviving patients: mortality HR=3.15 (95% CI 1.14–8.66) in rapid versus slow decliners. Likewise, a high level of plasma SARS-CoV-2 RNA was associated with death risk in patients with severe COVID-19.

Conclusion

These findings could suggest an interest in evaluating type 1 IFN treatment in patients with severe COVID-19 and type 1 IFN decline, eventually combined with anti-inflammatory drugs.

Clinical trial registration

https://clinicaltrials.gov, identifiers NCT04324073, NCT04331808, NCT04341584.
Construction of an acute myeloid leukemia prognostic model based on m6A-related efferocytosis-related genes
Authors: Wang Ying , Bin Ting , Tang Jing , Xu Xiao-Jun , Lin Chao , Lu Bo , Sun Tian-Tian
Published: November 2023

Background

One of the most prevalent hematological system cancers is acute myeloid leukemia (AML). Efferocytosis-related genes (ERGs) and N6-methyladenosine (m6A) have an important significance in the progression of cancer, and the metastasis of tumors.

Methods

The AML-related data were collected from The Cancer Genome Atlas (TCGA; TCGA-AML) database and Gene Expression Omnibus (GEO; GSE9476, GSE71014, and GSE13159) database. The “limma” R package and Venn diagram were adopted to identify differentially expressed ERGs (DE-ERGs). The m6A related-DE-ERGs were obtained by Spearman analysis. Subsequently, univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) were used to construct an m6A related-ERGs risk signature for AML patients. The possibility of immunotherapy for AML was explored. The pRRophetic package was adopted to calculate the IC50 of drugs for the treatment of AML. Finally, the expression of characterized genes was validated by quantitative reverse transcription-PCR (qRT-PCR).

Results

Based on m6A related-DE-ERGs, a prognostic model with four characteristic genes (UCP2, DOCK1, SLC14A1, and SLC25A1) was constructed. The risk score of model was significantly associated with the immune microenvironment of AML, with four immune cell types, 14 immune checkpoints, 20 HLA family genes and, immunophenoscore (IPS) all showing differences between the high- and low-risk groups. A total of 56 drugs were predicted to differ between the two groups, of which Erlotinib, Dasatinib, BI.2536, and bortezomib have been reported to be associated with AML treatment. The qRT-PCR results showed that the expression trends of DOCK1, SLC14A1 and SLC25A1 were consistent with the bioinformatics analysis.

Conclusion

In summary, 4 m6A related- ERGs were identified and the corresponding prognostic model was constructed for AML patients. This prognostic model effectively stratified the risk of AML patients.
A2A adenosine receptor-driven cAMP signaling in olfactory bulb astrocytes is unaffected in experimental autoimmune encephalomyelitis
Authors: Wendlandt Marina , Kürten Alina J. , Beiersdorfer Antonia , Schubert Charlotte , Samad-Yazdtchi Kiana , Sauer Jessica , Pinto M. Carolina , Schulz Kristina , Friese Manuel A. , Gee Christine E. , Hirnet Daniela , Lohr Christian
Published: November 2023

Introduction

The cyclic nucleotide cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger, which is known to play an important anti-inflammatory role. Astrocytes in the central nervous system (CNS) can modulate inflammation but little is known about the significance of cAMP in their function.

Methods

We investigated cAMP dynamics in mouse olfactory bulb astrocytes in brain slices prepared from healthy and experimental autoimmune encephalomyelitis (EAE) mice.

Results

The purinergic receptor ligands adenosine and adenosine triphosphate (ATP) both induced transient increases in cAMP in astrocytes expressing the genetically encoded cAMP sensor Flamindo2. The A2A receptor antagonist ZM241385 inhibited the responses. Similar transient increases in astrocytic cAMP occurred when olfactory receptor neurons were stimulated electrically, resulting in ATP release from the stimulated axons that increased cAMP, again via A2A receptors. Notably, A2A-mediated responses to ATP and adenosine were not different in EAE mice as compared to healthy mice.

Discussion

Our results indicate that ATP, synaptically released by afferent axons in the olfactory bulb, is degraded to adenosine that acts on A2A receptors in astrocytes, thereby increasing the cytosolic cAMP concentration. However, this pathway is not altered in the olfactory bulb of EAE mice.