bluuebunny/crossref_metadata_2025 huggingface dataset:
”Jag fick verkligen skrika på hjälp"
Authors: Andersson Sandra , Olsson Helén , Rantakeisu Ulla
Published: November 2024

”I actually had to scream for help” – abused women’s survival work before, during and after their shelter stay
In this interview study, we apply institutional ethnography and the ‘generous’ concept of work to analyse the survival work of ten women who have stayed in domestic violence shelters due to male partner violence. The analysis shows that survival work - the work the women do to gain access to protection and support - can take many forms. For instance, in order to access a shelter, women had to navigate the fragmented organisation of social services and articulate their experiences of violence to a range of different caseworkers. Once in a shelter, the women tried to manage and make sense of the safety rules they encountered. Moreover, they worked to increase their autonomy and freedom by trying to bridge the safety restrictions without jeopardizing the protection provided by the shelter. During the shelter stay, the women also worked to gain access to psychosocial support. The pursuit of support continued after leaving the shelter; with the purpose of establishing a new life in the municipality. This included the work to protect themselves from further violence.
Uso problemático del Internet y su Relación con Ansiedad y Depresión en Adultos Puertorriqueños
Authors: Cruz Santos Andres , Rosario Rodríguez Adam , Colón Negrón Miguel
Published: November 2024

Esta investigación fue conocer cuánto tiempo los participantes pasan conectados al internet, cuál es el dispositivo que más utilizan y en qué actividades pasan el tiempo mientras utilizan el internet. Se evaluó si existen correlaciones entre la Escala de Uso Problemático del Internet (EUPI-6) y los datos sociodemográficos y los cuestionarios Ansiedad Generalizada (GAD-7) y Cuestionario de Salud del Paciente (PHQ-8). También, se exploró si existen diferencias entre el género de la muestra en función a los instrumentos. Por último, se exploró si la EUPI-6 sirve como variable moderadora/mediadora de las demás variables. La muestra estuvo compuesta mayormente por mujeres (80.6%). Se utilizó un diseño no experimental transversal exploratorio-descriptivo. Los hallazgos principales indican que el 30% de los participantes consumen de dos a tres horas en el internet, y existe una correlación significativa entre las escalas. También se observó que hubo diferencias entre el género y las puntuaciones de las escalas. Por último, se observó que el uso problemático del internet no modera la relación entre la ansiedad y la depresión en la muestra de participantes. Sin embargo, sí media parcialmente la relación entre ansiedad y depresión en los participantes. Esperamos que esta investigación abra paso a explorar este fenómeno y sus efectos más adelante en los niños y adolescentes, además, de que sirva para que los profesionales de la salud mental lo incluyan en sus procesos de evaluación, utilizando la escala EUPI-6, con la creación de protocolos y política pública con el fin de maximizar la calidad de vida y un uso óptimo del internet. 
Palabras Claves: Uso Problemático del Internet; Ciberpsicología; Depresión; Ansiedad,  Internet.
Case Report: Anaphylaxis caused by traditional Chinese medicine in a patient with pollinosis
Authors: Pan Zhouxian , Zhan Mengyuan , Wang Qing , Liu Jun , Li Yu , Zhi Fan , Zhang Jing , Liu Jinhe , Guan Kai , Wen Liping
Published: November 2024

This case describes a patient with anaphylaxis caused by traditional Chinese medicine. Skin prick test with the traditional Chinese medicine decoction indicates that he was allergic to Suan Zao Ren. The patient had pollinosis and had never taken Suan Zao Ren before, thus we need to think the possibility of pollen food allergy syndrome. This paper also proposes a procedure for doctors to identify the specific culprit of traditional Chinese medicine decoction.
Case Report: Dual monoclonal antibody therapy in chronic rhinosinusitis with nasal polyps and severe eosinophilic asthma—a proteome analysis
Authors: Blauwblomme Manon , Gevaert Philippe , Van Nevel Sharon , Riemann Sebastian , Vandewalle Elke , Holtappels Gabriele , De Ruyck Natalie , Derycke Lara , Eeckels Anne-Sophie , Vanhee Stijn , Lambrecht Bart N. , Brusselle Guy , Van Zele Thibaut
Published: November 2024

Context

Recent insights into type 2 inflammation have led to the development of monoclonal antibody therapies for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Despite add-on therapy with a monoclonal antibody, some individuals remain uncontrolled in terms of upper and/or lower airway symptoms, prompting an exploration of the efficacy of combining biological therapies and their impact on inflammatory pathways.

Objectives

In this article, we present a distinctive case of a patient with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, who experienced substantial clinical and local inflammatory improvements through dual monoclonal antibody therapy.

Methods

We provide a detailed case description and analysis of the patient's nasal tissue and secretions to gain insights into the local nasal inflammation under this unique therapeutic approach.

Results

The addition of an anti-IL-4Rα antibody led to an improvement in upper airway symptoms and a reduction in both eosinophilic and neutrophilic inflammation, despite prior anti-IL-5 therapy. These effects were consistently observed in both polyp tissue and nasal secretions.

Conclusion

Our patient, with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, experienced substantial improvement with dual monoclonal antibody therapy, without major complications or side effects.
Evaluating animal welfare on broiler and turkey farms using either normative values or descriptive benchmarks
Authors: Michaelis Sarina , Gieseke Daniel , Knierim Ute
Published: November 2024

For the welfare assessment on commercial broiler and turkey farms, not only the recording of animal-based indicators but also the evaluation of the resulting prevalence or rate is essential. Two evaluation methods were compared using data on welfare indicators collected over 1 year from 11 broiler and 11 turkey farms in Germany: the application of normative values from an evaluation framework and the calculation of a benchmark. The evaluation framework had recently been developed in a participatory process that provided an evaluation with target and alarm values. The target range was predominantly based on ethical considerations, while the alarm range was aligned with the current status quo from farm investigations. The 25th percentile and the 75th percentile of the benchmarking were similarly classified as target and alarm. When applying the evaluation framework across all indicators and flocks, 30.6% of broiler flocks were in the target range, while 41.4% were in the alarm range, mostly for indicators such as footpad dermatitis, weight uniformity, and mortality. For turkeys at week 5 or at the end of the fattening period, 51.6% and 32.9%, respectively, were in the target range and 12.3% and 14.4% were in the alarm range. Most alarm classifications were related to footpad dermatitis, low-weight uniformity, plumage damage, and skin injuries. The application of normative values led to a significantly worse average welfare rank over all indicators and flocks for broilers compared to the benchmark, while no difference was observed for turkeys. The farm selection process may have favored turkey farms with better management practices, resulting in a more rigorous benchmark than in broilers. In addition, the farm data used to set the normative values had indicated a poorer status quo in turkeys for certain indicators, resulting in less stringent limits for the alarm range. This highlights the challenges associated with both evaluation methods: normative values are affected by the process and criteria used to set them, while benchmarks are affected by the reference population, which calls for large databases with regular updates. Also, for normative values, developments in the sector and the latest scientific evidence should be used for recurrent validation.
Key factors for increased tip-apex distance when treating intertrochanteric fractures with InterTAN nails
Authors: Zhu Naifeng , Wu Lianxia , Han Xiaofeng , Qian Zhonglai
Published: November 2024

Background

The tip-apex distance is a key factor in predicting implant cut-out after intramedullary fixation for intertrochanteric fractures. This study aimed to evaluate the factors associated with an increased tip-apex distance when treating intertrochanteric fractures using an InterTAN nail.

Methods and Material

We retrospectively analyzed patients with intertrochanteric fractures who underwent InterTAN nail insertion between January 2017 and March 2022 at our hospital. Medical and radiological data were collected. Measurements of preoperative factors and postoperative factors were performed accordingly. Multivariate logistic regression analysis was performed to determine the statistically significant variables of the tip-apex distance.

Results

This study included 102 patients with intertrochanteric fractures. The average tip-apex distance measured 22.4 ± 7.1 mm, ranging from 9.3 to 48.0 mm. The length of the femoral neck on the non-fractured side, lag screw placement in the sagittal plane (center-inferior, superior) and coronal plane (posterior), and the angle between the line of the proximal nail axis and the femoral long axis were identified to be statistically significant factors for the tip-apex distance.

Conclusion

To obtain a shorter tip-apex distance, we recommend a medial trochanteric entry point to minimize the angle between the line of the proximal nail axis and the femoral long axis. Additionally, sufficiently deep central insertion of the lag screw was advised in both the sagittal and coronal planes.
Attachment promoting compounds significantly enhance cell proliferation and purity of bovine satellite cells grown on microcarriers in the absence of serum
Authors: Bodiou Vincent , Kumar Anitha Ajith , Massarelli Edoardo , van Haaften Tessa , Post Mark J. , Moutsatsou Panagiota
Published: November 2024

Introduction

To bring cultivated beef to the market, a scalable system that can support growth of bovine satellite cells (bSCs) in a serum-free and preferably also animal-free medium is of utmost importance. The use of microcarriers (MCs) is, at the moment, one of the most promising technologies for scaling up. MCs offer a large surface to volume ratio, they can be used in scalable stirred tank bioreactors, where the culture conditions can be tightly controlled to meet the cells’ requirements (temperature, pH, dissolved oxygen). The inherent capacity of the cells to migrate from one MC to another, also known as bead-to-bead transfer, facilitates a scale-up strategy involving MCs. Previous studies have shown growth of bSCs on three commercially available MCs in serum containing media. Unfortunately there is currently no information available regarding their growth on MCs in serum-free conditions.

Methods

In this study, we aimed to find suitable serum-free media, MCs and attachment promoting compounds (APCs) supporting the growth of bSCs. Initially, six commercial MCs and three serum-free media were evaluated. The effects of three APCs were compared (vitronectin, laminin and fibronectin). Subsequently, the effects of different concentrations and modes of addition of the best performing APC were investigated.

Results and Discussion

Our results showed that Cytodex 1, Synthemax II and CellBIND supported bSCs’ growth in all serum-free media. Overall, better growth was observed with Cytodex 1 in serum-free proliferation media. We showed that the use of laminin or vitronectin with Cytodex 1 can significantly improve cell growth and purity. Laminin also allowed attachment and growth of bSCs on Plastic MCs which had been previously unsuccessful without APCs. Finally, we optimized the use of vitronectin from a sustainability and process perspective, and showed that it can be used solely as a coating for Cytodex 1 (16–100 ng/cm2) MCs, instead of as a medium supplement, enhancing cell attachment and proliferation.
Development and evaluation of a pH-sensitive, naturally crosslinked alginate-chitosan hydrogel for drug delivery applications
Authors: Khatibi Negin , Naimi-Jamal M. Reza , Balalaie Saeed , Shokoohmand Ali
Published: November 2024

The development of safe and efficient delivery systems for targeted and controlled release of therapeutic agents has become a major focus in pharmacotherapy. The colon is one organ that serves as an optimal site for the absorption of protein and peptide drugs, offering significant potential for both localized and systemic therapies. However, effective drug delivery is challenged by the need to protect these drugs from premature absorption and maintain their stability across the varying pH levels of the gastrointestinal tract. In this study, we introduce, for the first time, a fully natural hydrogel system composed of N-acetylated chitosan and alginate, crosslinked using a phenylalanine-phenylalanine dipeptide. The hydrogel demonstrates a unique swelling behavior, allowing for a solvent-free drug-loading method and pH-sensitive release properties. In a colon-simulated pH environment, the hydrogel achieved a high drug release efficiency, with 77.6% of the tested drug sulfasalazine and 51% of hydrocortisone over 5 hours. These findings underscore hydrogel’s potential as a promising drug delivery carrier for targeted gastrointestinal treatments, with the capacity to enhance the efficacy of current therapeutic options.
Global, regional, and national time trends in ischaemic heart disease incidence over three decades (1990–2019): an age-period-cohort analysis of the global burden of disease study 2019
Authors: Tang Juan , Hu Shaobo , Liu Xiaozhu , Li Huan , Kuang Lirong , Zhang Lei , Cao Wenzhai , Zhang Ting , Guan Xiaoyan , Li Lang , Zhang Yutao , Peng Shengxian , Zhang Qingwei , Zhou Xiaoqian
Published: November 2024

Introduction

To assess the prevailing trends in the incidence of ischemic heart disease (IHD) across 204 countries and territories from 1990 to 2019, and to elucidate their correlations with age, period, and birth cohort, a comprehensive analysis was conducted.

Methods

From 1990 to 2019, we employed the Global Burden of Disease Study (GBD) Results Tool in conjunction with an age-period-cohort model. This approach facilitated the estimation of annual percentage changes in incidence, referred to as net drifts, encompassing the overall population. Additionally, we calculated annual percentage changes spanning ages 15 - 19 to 95 + years, denoted as local drifts. Furthermore, our analysis involved determining period and cohort relative risks, elucidating the effects associated with distinct periods and birth cohorts.

Results

Globally, 21,203,479 [95% uncertainty interval (UI): 18,799,322 − 23,704,124] cases of IHD occurred in 2019. There were 33 countries with at least 100000 cases. Between 1990 and 2019, the net drift of IHD incidence exhibited a range from −1.7% per year [95% confidence interval (CI): −1.79, −1.61] in countries with a high socio-demographic index (SDI) to 0.08% per year (95% CI: 0.05, 0.11) in countries with a low SDI. Age effects across all countries and genders demonstrated an increasing trend over time, indicating age as a significant risk factor for IHD. Moreover, period and cohort effects in higher SDI countries exhibited a more rapid decline in both genders compared to lower SDI countries. The findings indicated that nations with a higher SDI manifested overall favorable trends in the relative risk of IHD incidence, both across time and in successive younger birth cohorts.

Discussion

The incidence of IHD serves as a valuable and accessible indicator for assessing trends in IHD provision, spanning from early youth through later life. Enhancements in IHD prevention have the potential to mitigate risks for successively younger cohorts and, over time, redistribute the risk across all age groups. Despite global declines in IHD incidence over the last three decades, decreasing trends in incidence have slowed and, in some countries, flattened. Many countries have experienced unfavorable period and cohort effects.
Personalized risk prediction of mortality and rehospitalization for heart failure in patients undergoing mitral valve repair surgery
Authors: Zhou Ning , Zhang Kui , Qiao Bokang , Chen Cong , Guo Xiaobo , Fu Wei , Zheng Jubing , Du Jie , Dong Ran
Published: November 2024

Background

Accurately assessing the postoperative mortality and rehospitalization for heart failure risks in patients undergoing mitral valve repair surgery is of significant importance for individualized medical strategies.

Objective

We sought to develop and validate a risk assessment system for the prediction of mortality and rehospitalization for heart failure.

Methods

Personalized risk prediction system of mortality and rehospitalization for heart failure was developed. For developing a prediction system with death as the outcome, there were 965 patients (70%) and 413 patients (30%) were included in the the derivation cohort and the validation cohort. For developing a prediction system with rehospitalization for heart failure as the outcome, there were 927 patients (70%) and 398 patients (30%) were included in the derivation cohort and the validation cohort. There were 42 routine clinical variables used to develop the models. The performance evaluation of the model is based on the area under the curve (AUC). Evaluate the improvement with Euro Score II according to NRI and IDI net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results

The median follow-up time was 685 days, the incidence of death was 3.85% (n = 53), and the incidence of rehospitalization for heart failure was 10.01% (n = 138). The AUC values of the mortality prediction model in the derivation and validation cohorts were 0.825 (0.764–0.886) and 0.808 (0.699–0.917), respectively. The AUC values of the rehospitalization for heart failure prediction model in the derivation and validation cohorts were 0.794 (0.756–0.832) and 0.812 (0.758–0.866), respectively. NRI and IDI showed that the mortality prediction model exhibited superior performance than the Euro Score II. The mortality and rehospitalization for heart failure risk prediction models effectively stratified patients into different risk subgroups.

Conclusion

The developed and validated models exhibit satisfactory performance in prediction of all-cause mortality and rehospitalization for heart failure after mitral valve repair surgery.

Clinical Trial Registration

http://www.clinicaltrials.gov, Unique identifier: (NCT05141292).
Identification of key genes for cuproptosis in carotid atherosclerosis
Authors: Wu Xize , Kang Jian , Pan Xue , Xue Chentian , Pan Jiaxiang , Quan Chao , Ren Lihong , Gong Lihong , Li Yue
Published: November 2024

Background

Atherosclerosis is a leading cause of cardiovascular disease worldwide, while carotid atherosclerosis (CAS) is more likely to cause ischemic cerebrovascular events. Emerging evidence suggests that cuproptosis may be associated with an increased risk of atherosclerotic cardiovascular disease. This study aims to explore the potential mechanisms linking cuproptosis and CAS.

Methods

The GSE100927 and GSE43292 datasets were merged to screen for CAS differentially expressed genes (DEGs) and intersected with cuproptosis-related genes to obtain CAS cuproptosis-related genes (CASCRGs). Unsupervised cluster analysis was performed on CAS samples to identify cuproptosis molecular clusters. Weighted gene co-expression network analysis was performed on all samples and cuproptosis molecule clusters to identify common module genes. CAS-specific DEGs were identified in the GSE100927 dataset and intersected with common module genes to obtain candidate hub genes. Finally, 83 machine learning models were constructed to screen hub genes and construct a nomogram to predict the incidence of CAS.

Results

Four ASCRGs (NLRP3, SLC31A2, CDKN2A, and GLS) were identified as regulators of the immune infiltration microenvironment in CAS. CAS samples were identified with two cuproptosis-related molecular clusters with significant biological function differences based on ASCRGs. 220 common module hub genes and 1,518 CAS-specific DEGs were intersected to obtain 58 candidate hub genes, and the machine learning model showed that the Lasso + XGBoost model exhibited the best discriminative performance. Further external validation of single gene differential analysis and nomogram identified SGCE, PCDH7, RAB23, and RIMKLB as hub genes; SGCE and PCDH7 were also used as biomarkers to characterize CAS plaque stability. Finally, a nomogram was developed to assess the incidence of CAS and exhibited satisfactory predictive performance.

Conclusions

Cuproptosis alters the CAS immune infiltration microenvironment and may regulate actin cytoskeleton formation.
Cognitive warfare: a conceptual analysis of the NATO ACT cognitive warfare exploratory concept
Authors: Deppe Christoph , Schaal Gary S.
Published: November 2024

This study evaluates NATO ACT's cognitive warfare concept from a political science perspective, exploring its utility beyond military applications. Despite its growing presence in scholarly discourse, the concept's interdisciplinary nature has hindered a unified definition. By analyzing NATO's framework, developed with input from diverse disciplines and both military and civilian researchers, this paper seeks to assess its applicability to political science. It aims to bridge military and civilian research divides and refine NATO's cognitive warfare approach, offering significant implications for enhancing political science research and fostering integrated scholarly collaboration.
Study on the mining response law and coal burst risk assessment of an isolated working face
Authors: Liu Guojun , Lei Ruide , Huang Ling , Li Menglai , Zhou Jiankun
Published: November 2024

With the increasing demand for coal resources and the unreasonable arrangement of subsequent working faces, mining activities in isolated working faces are more likely to induce coal burst accidents. In this study, the minimum distance principle is utilized as the risk assessment indicator and the quantitative theory is introduced to evaluate coal burst risk in isolated working faces. Through a case study in 1,304 isolated working face of Yangcheng Coal Mine, the key factors affecting the risk of coal burst were identified, and a three-dimensional coal burst risk assessment model was constructed to evaluate the risk of the isolated working face. The results show that as the working face advances, the abutment pressure and elastic strain energy density in front of the working face increase to the peak value in a positive exponential relationship at first and then decrease to in situ stress, which presents an upward convex trend. Under different excavation steps, the concentration coefficient of the peak stress gradually increases. The influence range of the abutment pressure of the working face gradually increases. Compared with one-dimensional and two-dimensional evaluation functions, the three-dimensional function significantly improves the accuracy of risk assessment and successfully identifies strong coal and gas outburst risks. Additionally, the model not only enhances the precision of risk assessment but also quantifies the assessment parameters.
Mapping the interconnections: a systematic review and network analysis of factors influencing teachers' technology acceptance
Authors: Galimova Elvira G. , Oborsky Alexey Yu. , Khvatova Maria A. , Astakhov Dmitry V. , Orlova Ekaterina V. , Andryushchenko Irina S.
Published: November 2024

This paper uses the Technology Acceptance Model (TAM) framework to examine elements affecting technology acceptance in teacher education. By means of network and cluster analysis, we investigate the distribution, interactions, and importance of components influencing technology adoption among pre-service and in-service teachers. Following the PRISMA method, a thorough search of Scopus and Web of Science databases produced 32 publications for in-depth study. Key interactions among TAM variables were found using network analysis done in RStudio with the igraph tool. Our results underline in teacher education settings the importance of perceived utility, attitudes toward technology, and perceived ease of use. The study revealed certain topic groups including psychological and social elements, knowledge and occupational relevance, and pragmatic uses in learning environments. While pointing up possible study gaps in this field, the network analysis offers insights into important factors and relationships impacting instructors' technology uptake. This study helps to create efficient professional development programs meant to improve instructors' technological integration skills and enable the successful application of instructional technologies in their respective fields. Our results provide insightful direction for teachers and legislators creating focused initiatives to increase technology acceptance in learning environments.
An intragenic duplication in the AFF2 gene associated with Cornelia de Lange syndrome phenotype
Authors: Lucia-Campos Cristina , Parenti Ilaria , Latorre-Pellicer Ana , Gil-Salvador Marta , Bestetti Ilaria , Finelli Palma , Larizza Lidia , Arnedo María , Ayerza-Casas Ariadna , Del Rincón Julia , Trujillano Laura , Morte Beatriz , Pérez-Jurado Luis A. , Lapunzina Pablo , Leitão Elsa , Beygo Jasmin , Lich Christina , Kilpert Fabian , Kaya Sabine , Depienne Christel , Kaiser Frank J. , Ramos Feliciano J. , Puisac Beatriz , Pié Juan
Published: November 2024

Cornelia de Lange syndrome (CdLS, OMIM #122470, #300590, #300882, #610759, and #614701) is a rare congenital disorder that affects the development of multiple organs and is characterized by physical abnormalities and cognitive and behavioral disabilities. Its molecular basis is mainly based on alterations in genes encoding structural and regulatory proteins related to the cohesin complex. Moreover, other transcriptional regulatory factors have been linked to this syndrome. However, additional causative genes are still unknown, since many patients still lack a molecular diagnosis. Herein, we describe a case with multiple affected family members presenting with an intragenic duplication in the AFF2 gene. The direct tandem intragenic duplication of exons 10, 11 and 12 was detected through high-resolution array Comparative Genomic Hybridization and next-generation sequencing technologies. Confirming the X-linked inheritance pattern, the duplication was found in the patient, his mother and his maternal aunt affected (dizygotic twins). Targeted sequencing with Oxford Nanopore Technologies revealed an aberrant transcript which is predominantly expressed in the patient and his aunt. Along with these results, a significant reduction in AFF2 gene expression levels was detected in these two individuals. Clinically both subjects exhibit a classic CdLS phenotype, whereas the mother is mostly unaffected. Consistent with the phenotypical differences observed between the mother and the aunt, there is a marked difference in X-inactivation patterns skewing. Given the crucial role of AFF2 in transcriptional regulation, it is not surprising that AFF2 variants can give rise to CdLS phenotypes. Therefore, the AFF2 gene should be considered for the molecular diagnosis of this syndrome.
An integrated transcriptome and physiological analysis of nitrogen use efficiency in rice (Oryza sativa L. ssp. indica) under drought stress
Authors: Wang Yu , Zhang Yufan , Qiao Han , Zheng Yutong , Hou Xin , Shi Liangsheng
Published: November 2024

Nitrogen is a critical nutrient vital for crop growth. However, our current understanding of nitrogen use efficiency (NUE) under drought remains inadequate. To delve into the molecular mechanisms underlying NUE under drought, a transcriptome and physiological co-expression analysis was performed in rice, which is particularly sensitive to drought. We conducted a pot experiment using rice grown under normal irrigation, mild drought stress, and severe drought stress. Compared to the normal treatment, drought stress led to a significant reduction in NUE across growth stages, with decreases ranging from 2.18% to 31.67%. Totals of 4,424 and 2,452 genes were identified as NUE-related DEGs that showed differential expressions (DEGs) and significantly correlated with NUE (NUE-related) under drought in the vegetative and reproductive stages, respectively. Interestingly, five genes involved in nitrogen metabolism were found in the overlapped genes of these two sets. Furthermore, the two sets of NUE-related DEGs were enriched in glyoxylate and dicarboxylate metabolism, as well as carbon fixation in photosynthetic organisms. Several genes in these two pathways were identified as hub genes in the two sets of NUE-related DEGs. This study offers new insights into the molecular mechanism of rice NUE under drought in agricultural practices and provides potential genes for breeding drought-resistant crops with high NUE.
Molecular markers and molecular basis of plant type related traits in maize
Authors: Zhao Xinghua , Wang Changbiao , Liu Jiang , Han Bin , Huang Jinling
Published: November 2024

Maize, belonging to the Poaceae family and the Zea L. genus, stands as an excellent food crop. The plant type has a significant impact on crop growth, photosynthesis, lodging resistance, planting density, and final yield. In this study, 160 maize inbred lines were selected as experimental materials to conduct molecular markers research on maize plant type traits through the measurement of plant type-related traits, population structure, and genome-wide association analysis. The phenotypic data revealed differences in plant type-related traits among maize inbred lines grown in the Xinzhou and Jinzhong regions. The frequency distribution of plant height, ear height, spindle length of tassel, and first-order branch number of tassel traits in the 160 maize inbred lines previously studied generally conformed to a normal distribution. We identified 42,240 high-quality single nucleotide polymorphisms (SNPs) using the Affymetrix Axiom chip. The 160 maize inbred lines were categorized into six subgroups, each exhibiting an average gene diversity of 0.356 and an average polymorphism information content of 0.245. We identified 9, 23, 18, 8 and 32 loci that were significantly associated with first-order branch number of tassel, spindle length of tassel, ear height, plant height, and ear height/plant height ratio, respectively. At the same time, 6, 22, 14, 2, and 37 genes were identified as significantly associated with first-order branch number of tassel, spindle length of tassel, ear height, plant height, and ear height/plant height ratio, respectively. This study comprehensively delved into the genetic information of maize plant type-related traits, offering valuable genetic resources and a solid theoretical foundation for the breeding of novel maize varieties with optimized plant types.
Neutrophil extracellular traps in tumor progression of gynecologic cancers
Authors: Chen Hong , Zhou Ying , Tang Yaling , Lan Jianfa , Lin Chao , Chen Qionghua , Kuang Hongying
Published: November 2024

This article delves into the intricate interplay between tumors, particularly gynecologic malignancies, and neutrophil extracellular traps (NETs). The relationship between tumors, specifically gynecologic malignancies, and NETs is a multifaceted and pivotal area of study. Neutrophils, pivotal components of the immune system, are tasked with combating foreign invaders. NETs, intricate structures released by neutrophils, play a vital role in combating systemic infections but also play a role in non-infectious conditions such as inflammation, autoimmune diseases, and cancer. Cancer cells have the ability to attract neutrophils, creating tumor-associated neutrophils, which then stimulate the release of NETs into the tumor microenvironment. The impact of NETs within the tumor microenvironment is profound and intricate. They play a significant role in influencing cancer development and metastasis, as well as modulating tumor immune responses. Through the release of proteases and pro-inflammatory cytokines, NETs directly alter the behavior of tumor cells, increasing invasiveness and metastatic potential. Additionally, NETs can trigger epithelial-mesenchymal transition in tumor cells, a process associated with increased invasion and metastasis. The interaction between tumors and NETs is particularly critical in gynecologic malignancies such as ovarian, cervical, and endometrial cancer. Understanding the mechanisms through which NETs operate in these tumors can offer valuable insights for the development of targeted therapeutic interventions. Researchers are actively working towards harnessing this interaction to impede tumor progression and metastasis, opening up new avenues for future treatment modalities. As our understanding of the interplay between tumors and NETs deepens, it is anticipated that novel treatment strategies will emerge, potentially leading to improved outcomes for patients with gynecologic malignancies. This article provides a comprehensive overview of the latest research findings on the interaction between NETs and cancer, particularly in gynecologic tumors, serving as a valuable resource for future exploration in this field.
Analysis of immunogenic cell death in periodontitis based on scRNA-seq and bulk RNA-seq data
Authors: Wu Erli , Yin Xuan , Liang Feng , Zhou Xianqing , Hu Jiamin , Yuan Wanting , Gu Feihan , Zhao Jingxin , Gao Ziyang , Cheng Ming , Yang Shouxiang , Zhang Lei , Wang Qingqing , Sun Xiaoyu , Shao Wei
Published: November 2024

Background

Recent studies have suggested that cell death may be involved in bone loss or the resolution of inflammation in periodontitis. Immunogenic cell death (ICD), a recently identified cell death pathway, may be involved in the development of this disease.

Methods

By analyzing single-cell RNA sequencing (scRNA-seq) for periodontitis and scoring gene set activity, we identified cell populations associated with ICD, which were further verified by qPCR, enzyme linked immunosorbent assay (ELISA) and immunofluorescence (IF) staining. By combining the bulk transcriptome and applying machine learning methods, we identified several potential ICD-related hub genes, which were then used to build diagnostic models. Subsequently, consensus clustering analysis was performed to identify ICD-associated subtypes, and multiple bioinformatics algorithms were used to investigate differences in immune cells and pathways between subtypes. Finally, qPCR and immunohistochemical staining were performed to validate the accuracy of the models.

Results

Single-cell gene set activity analysis found that in non-immune cells, fibroblasts had a higher ICD activity score, and KEGG results showed that fibroblasts were enriched in a variety of ICD-related pathways. qPCR, Elisa and IF further verified the accuracy of the results. From the bulk transcriptome, we identified 11 differentially expressed genes (DEGs) associated with ICD, and machine learning methods further identified 5 hub genes associated with ICD. Consensus cluster analysis based on these 5 genes showed that there were differences in immune cells and immune functions among subtypes associated with ICD. Finally, qPCR and immunohistochemistry confirmed the ability of these five genes as biomarkers for the diagnosis of periodontitis.

Conclusion

Fibroblasts may be the main cell source of ICD in periodontitis. Adaptive immune responses driven by ICD may be one of the pathogenesis of periodontitis. Five key genes associated with ICD (ENTPD1, TLR4, LY96, PRF1 and P2RX7) may be diagnostic biomarkers of periodontitis and future therapeutic targets.
The enhancement of immunoactivity induced by immunogenic cell death through serine/threonine kinase 10 inhibition: a potential therapeutic strategy
Authors: Xia Xiaoli , Wang Yixin , Wang Minghui , Lin Jian , Wang Ruiheng , Xie Shufeng , Yu Yaoyifu , Long Jinlan , Huang Zixuan , Xian Huajian , Zhang Wenjie , Lu Chaoqun , Wang Wenfang , Liu Han
Published: November 2024

Introduction

Immunogenic cell death (ICD) is capable of activating the anti-tumor immune response of the organism; however, it is concurrently a complex process involving multiple factors. The specific factors that impact the occurrence of ICD remain undefined.

Methods

Through cluster analysis, patient specimens retrieved from the TARGET, TCGA, and GEO AML databases were categorized into two subtypes based on the expression levels of ICD-related genes: ICD-high and ICD-low. We compared the prognostic survival outcomes, pathway enrichment analysis, and immune cell infiltration between these two subtypes. Additionally, we identified factors related to AML development from multiple databases and verified the role of these factors both in vivo and in vitro in activating the immune response during the occurrence of ICD.

Results and discussion

In the ICD-high subtype, there was a notable increase in the abundance of immune cell populations, along with the enrichment of pathways pertinent to the activation of various immune cells. Despite these immunological enhancements, this subgroup demonstrated a poorer prognosis. This phenomenon was consistently observed across various additional AML datasets, leading us to hypothesize that elevated expression of ICD genes does not invariably correlate with a favorable prognosis. Notably, STK10 exhibited elevated expression in AML, was associated with a poor prognosis, and showed synchronous expression patterns with ICD genes. Inhibition of STK10 led to the activation of ICD and the induction of an antitumor response. Moreover, when combined with other ICD inducers, it produced a synergistic anti-tumor effect. Our results reveal the impact of STK10 on ICD and underscore its key role in initiating ICD.
Effects of early intervention in neuromyelitis optica spectrum disorder patients with seropositive AQP4 antibodies
Authors: Xue Binbin , Li Jia , Xie Dewei , Weng Yiyun , Zhang Xu , Li Xiang , Xia Junhui , Lin Jie
Published: November 2024

Background

The impact of early intervention with immunosuppressive treatment (IST) in anti-Aquaporin4-antibody (AQP4-ab) seropositive neuromyelitis optica spectrum disorder (NMOSD) has not been thoroughly evaluated.

Objective

This study aims to assess the effects of early IST intervention in patients with NMOSD.

Methods

This retrospective cohort study included 174 treatments from 137 NMOSD patients seropositive for AQP4-antibody, treated with ISTs such as rituximab, mycophenolate mofetil, azathioprine, or tacrolimus. Multiple statistical analyses, including regression discontinuity design (RDD), kaplan-meier analyze, Cox proportional hazards regression model, were employed to evaluate the effects of early IST intervention on annualized relapse rate (ARR) change, Expanded Disability Status Scale (EDSS) change, and time to next relapse.

Results

A total of 174 treatments from 137 patients were analyzed. Patients exhibited significant improvement in ARR[1.95 vs.0, IQR (0.70-6.0 vs. 0-0.42), p<0.001] and EDSS [3.0 vs. 2.5, IQR (2.0-4.0 vs. 1.0-3.0) p<0.001]after IST, although the ARR change was not significant in patients treated with TAC. Early IST initiation was associated with greater improvements in both ARR and EDSS compared to later initiation. RDD analysis demonstrated a time-dependent effect of ARR-change, indicating greater efficacy with early IST intervention.

Conclusions

Early intervention with ISTs in AQP4-antibody-positive NMOSD patients is associated with better outcomes in terms of reducing relapse rate and improving disability. These findings underscore the importance of early treatment in NMOSD.
Predictive value of bowel dose-volume for severe radiation-induced lymphopenia and survival in cervical cancer
Authors: Li Jingjing , Chen Qingqing , Liu Zhengcao , Xu Yingying , Ji Shengjun
Published: November 2024

Background

Radiation-induced lymphopenia (RIL) is closely related to the prognosis of cervical cancer patients and may affect the efficacy of immune checkpoint inhibitors (ICIs). However, the factors influencing RIL are not very clear. In addition to bone marrow (BM) dose-volume, animal studies indicate radiation-induced bowel injury may be a more crucial factor. Further clarification of the correlation between RIL and bowel dose-volume is important for cervical cancer treatment.

Methods

Cervical cancer patients treated with postoperative radiotherapy or radical radiotherapy were eligible for this retrospective study. Clinical characteristics, dose parameters of bowel and BM, planning target volume (PTV) size, overall survival (OS) and progression-free survival (PFS) were recorded. The absolute lymphocyte count<0.5×109/L at radiotherapy end was defined as severe RIL (sRIL). Hazard ratio (HR) and 95% confidence interval (Cl)were estimated using Cox regression models. Survival curve was plotted using the Kaplan-Meier method. On this basis, the receiver operating characteristics (ROC) curve was used to calculate the area under the curve (AUC) for radiation parameters with sRIL as the state variable.

Result

A total of 118 cervical cancer patients were included in this study, with a median follow-up time of 57.6 months. In multivariable Cox regression analysis, international Federation of Gynecology and obstetrics (FIGO) stage (HR, 11.806; 95% CI, 3.256-42.809; p<0.001), concurrent chemotherapy (HR, 0.200; 95% CI, 0.054-0.748; p=0.017), sRIL after radiotherapy (HR, 6.009; 95% CI, 1.361-26.539; p=0.018), and pathological type (HR, 2.261; 95% CI, 1.043-4.901; p=0.039) were significantly correlated with OS. Patients with sRIL had significantly decreased OS (79.1% vs 94.1%; HR, 3.81; 95%CI, 1.46-9.92; p=0.023). In binary logistic regression analysis, sRIL was significantly correlated with bowel V45 (Odds radio (OR), 1.025; 95%CI, 1.007-1.044; p=0.007), BM V10 (OR, 0.987; 95%CI, 0.978-0.997; p=0.011), BM V20 (OR, 1.017; 95%CI, 1.002-1.031, p=0.027), and PTV size (OR, 0.998; 95%CI, 0.996-1.000; p=0.026). The ROC curve showed, bowel V45 (AUC=0.787, p<0.001) was the best indicator for predicting sRIL.

Conclusion

SRIL after radiotherapy could significantly predict decreased OS. In addition, sRIL is associated with higher bowel, BM dose-volume, PTV size, indicating that the bowel may be an important organ leading to an increased risk of sRIL.
Role of immune dysregulation in peri-implantitis
Authors: Huang Mingshu , Wang Chao , Li Ping , Lu Hongye , Li An , Xu Shulan
Published: November 2024

Peri-implantitis, a complex condition that can lead to dental implant failure, is characterized by inflammatory destruction resulting from immune dysregulation. Oral microbial dysbiosis and foreign body stimulation are the main factors contributing to such dysregulation, impairing immune cell function and triggering an inflammatory response. Immune dysregulation plays a critical role in the pathophysiology of peri-implantitis, impacting the balance of T cell subsets, the production of inflammatory factors, and immune-related molecular signaling pathways. Understanding the relationship between immune dysregulation and peri-implantitis is crucial for developing targeted strategies for clinical diagnosis and individualized treatment planning. This review explores the similarities and differences in the immune microenvironment of oral bacterial infections and foreign body rejection, analyzes the relevant molecular signaling pathways, and identifies new key targets for developing innovative immunotherapeutic drugs and effective and personalized treatment modalities for peri-implantitis. Additionally, it addresses the challenges and potential directions for translating immunotherapy into clinical practice for peri-implantitis, offering insights that bridge the gaps in current literature and pave the way for future research.
Bulk- and single cell-RNA sequencing reveal KIF20A as a key driver of hepatocellular carcinoma progression and immune evasion
Authors: Su Zhixiong , Zhong Yaqi , He Yufang , You Lijie , Xin Fuli , Wang Lei , Liu Zhihua
Published: November 2024

Introduction

Kinesin family member 20A (KIF20A) is essential for cell proliferation and is implicated in promoting tumor progression, but its role in hepatocellular carcinoma (HCC) remains poorly studied.

Methods

Through the analysis of bulk RNA-sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) data, the expression of KIF20A and its relationship with diagnosis, prognosis, and the immune microenvironment were examined. The association between KIF20A and the malignant progression and metastasis of HCC was confirmed through in vitro and in vivo experiments. Furthermore, patient re-staging was performed using Recursive Partitioning Analysis (RPA) to enhance clinical benefit.

Results

In this study, we firstly found KIF20A was overexprerssed in HCC both by bulk RNA-seq and scRNA-seq, and then the overexpression of KIF20A significantly promoted the proliferation, invasion, and metastasis in vitro. In vivo, the overexpression of KIF20A promoted the growth and lung metastasis of HCC. Furthermore, gene set variation analysis of bulk RNA-seq and scRNA-seq revealed that KIF20A might be associated with cell cycle related signaling pathways of E2F and G2M, and overexpression of KIF20A inhibited the activity of p21 and bax, as well as shortened G2 phase. Importantly, we found that KIF20A could induce T cell exhaustion via the SPP1-CD44 axe using scRNA-seq. Additionally, KIF20A was also correlated with the expression of immune checkpoint inhibitors (ICIs), and KIF20Ahigh subgroup might be benefited from the ICIs therapy.

Conclusion

KIF20A emerges as a pivotal driver of HCC progression, intricately regulating cell cycle pathways and modulating immune responses, which position KIF20A as a promising target for HCC management.
The CRAFITY score emerges as a paramount prognostic indicator in hepatocellular carcinoma patients received Lenvatinib and Pembrolizumab
Authors: Wu Weijie , Yang Zhenyun , Zou Hao , Long Teng , Zhou Zhongguo , Zhang Yaojun , Chen Minshan , Hu Dandan
Published: November 2024

Background

Levels of C-reactive protein (CRP) and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) scores are associated with the prognosis of patients with hepatocellular carcinoma (HCC). This study aimed to explore the efficacy of lenvatinib and pembrolizumab (Len-P) based on the CRAFITY score.

Methods

In this study, 228 patients with HCC who received Len-P in Sun Yat-sen University Cancer Center were included. CRAFITY 0 score was defined as AFP level below 100 ng/ml, CRP level below 1 mg/dl, CRAFITY 1 score was defined as AFP level at least 100 ng/ml or CRP level at least 1 mg/dl. CRAFITY 2 scores were defined as AFP levels exceeding 100 ng/ml and CRP levels exceeding 100 ng/ml. The primary outcome was overall survival (OS). The second outcome was tumor response rate.

Results

The survival time of CRAFITY 0 is significantly longer than that of CRAFITY 1 and CRAFITY 2 (p =.044). Univariate analysis showed that largest tumor size (HR = 2.149; 95% CI 1.129 - 4.091; p =.02), lymph node metastasis (HR = 2.012; 95% CI 1.132- 3.579; p = .017), and CRAFITY (HR = 0.372; 95% CI 0.168-0.824; p = .015) were important risk determinants of OS in all patients. The results of multivariate analysis show that CRAFITY score is an independent risk factors for OS (HR = 0.719; 95% CI 0.377-1.374; p =.048). The ORR of CRAFITY 0, 1 and 2 scores were 36.4%, 32% and 27.4%, respectively (p = .556). The ORR of intrahepatic lesions by CRAFITY 0, 1 and 2 were 37.9%, 35%, 30.6% (p= .688).

Conclusion

CRAFITY score is a good predictor of prognosis in HCC patients receiving Len-P.