bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome analysis reveals the pathogenesis of spontaneous tibial dyschondroplasia in broilers
Authors: Shi Kai , Wu Yongfu , Jiang Xusheng , Liu Xiangping , Du Yuesong , Feng Chungang , Li Dongfeng 
Published: July 2024

Tibial dyschondroplasia (TD) is a severe bone disease that affects fast-growing broiler chickens and causes economic loss. Despite previous studies, the regulatory mechanism of TD remains unclear and is thought to be primarily based on thiram induction, which may differ from that of naturally occurring diseases. To better understand TD, a digital X-ray machine was used in the present study to determine its incidence in four hundred yellow-feathered broiler chickens. The results showed that the incidence of TD was 22% after 6 weeks and gradually decreased after 8 and 10 weeks. The body weight of broilers with TD decreased significantly compared to that of NTD broilers. In addition, the length and density of the tibia were reduced after eight and 10 weeks, and the density of the tibia was reduced after 6 weeks compared with the NTD chickens. This study also examined tibial quality parameters from TD (n = 12) and NTD broilers (n = 12) and found that bone mineral content, bone mineral density, bone ash content, calcium content, and phosphorus content were significantly reduced in TD broilers. Transcriptome analysis revealed 849 differentially expressed genes (DEGs) in the growth plate between TD (n = 6) and NTD groups (n = 6). These genes were enriched in ECM-receptor interaction, cytokine-cytokine receptor interaction, calcium signaling pathway, and TGF-β signaling. Genes encoding the alpha chain of type XII collagen, that is, COL1A1, COL5A1, and COL8A1) were identified as critical in the regulatory network of TD. Gene set enrichment analysis (GSEA) revealed that the pathways of cartilage development, circulatory system development, and nervous system development were changed in the growth plates of TD birds. In the blood transcriptome, 12 DEGs were found in TD (n = 4) and NTD chickens (n = 4), and GSEA revealed that the pathways from TD broilers’ blood related to the phagosome, linoleic acid metabolism, monoatomic ion homeostasis, and calcium ion transport were downregulated. This study provides a comprehensive understanding of TD, including its effects on tibial quality, tibial changes, and the circulatory system, along with identifying important genes that may lead to the development of TD.
The distribution and maturation of tertiary lymphoid structures can predict clinical outcomes of patients with gastric adenocarcinoma
Authors: Sun Hui , Liu Yuxi , Cheng Wanjing , Xiong Rong , Gu Wenchao , Zhang Xiaoyan , Wang Xin , Wang Xu , Tan Cong , Weng Weiwei , Zhang Meng , Ni Shujuan , Huang Dan , Xu Midie , Sheng Weiqi , Wang Lei 
Published: July 2024

IntroductionTertiary lymphoid structures (TLSs) are analogues of secondary lymphoid organs that contain various immune cells. The spatial distribution, maturation and composition of TLSs have differential effects on prognosis, and the roles of TLSs in gastric adenocarcinoma (GA) have not been revealed.MethodsThus, we evaluated the prognostic value of TLSs in GA through analysis of bulk RNA sequencing(RNA-seq) data from public databases and validated our findings in tumour samples from the Fudan University Shanghai Cancer Center (FUSCC) cohort. The spatial distribution,maturation, and composition of TLSs in GA were analysed by reviewing H&amp;E-stained sections and by multiplex immunofluorescence (mIF) staining.ResultsWe found that TLSs, especially TLSs with germinal centres (GCs) and TLSs located in the invasive margin (IM), were correlated with prolonged overall survival (OS). Second, analysis of public RNA-seq data showed that high dendritic cell (DC) scores were a favourable prognostic factor in GA patients with high scores for both TLSs and GCs. In the FUSCC cohort, DC-LAMP+ DCs weresignificantly enriched in IM-TLSs with GCs, suggesting a potential correlation between the tumour immune activation milieu and the DC abundance. Third, compared to that in TLSs without GCs, the proportion of FOXP3+CD8+ Treg cells was significantly decreased in IM-TLSs with GCs, and the percentage of PD1+CD20+ B cells was significantly increased in TLSs with GCs.DiscussionOur results demonstrate that the spatial arrangement and maturation of TLSs significantly affect prognosis and indicate that TLSs could be a new additional factor for histopathological evaluation.
Case report: Effective treatment of rituximab-resistant minimal change disease with obinutuzumab in an adult
Authors: Wang Qiang , Lin Lin , Zhen Junhui , Jiang Bei , Liu Guangyi 
Published: July 2024

BackgroundMinimal change disease (MCD) is a common cause of adult nephrotic syndrome. Most adults with MCD achieve complete remission (CR) after initial steroid therapy. However, approximately 30% of adults who respond to steroids experience frequent relapses, becoming steroid-dependent and potentially developing refractory MCD. Treating refractory MCD in adults poses a significant challenge.Main bodyA 37-year-old woman presented to the nephrology department with a 6-year history of MCD. The diagnosis of MCD was confirmed via renal biopsy. She initially achieved CR with steroid treatment but experienced relapse during steroid tapering. Subsequent CR was achieved with a regimen of steroids and tacrolimus although multiple relapses occurred. Rituximab led to another CR, but its maintenance lasted only 6 months. The response to subsequent rituximab treatments was unsatisfactory. Ultimately, obinutuzumab was selected, resulting in the induction and maintenance of CR for 12 months.ConclusionsThis case demonstrates the successful treatment of frequently relapsed, steroid-dependent, and rituximab-resistant MCD with obinutuzumab. Obinutuzumab is a promising therapeutic option for rituximab-resistant MCD.
Ceramide metabolism alterations contribute to Tumor Necrosis Factor-induced melanoma dedifferentiation and predict resistance to immune checkpoint inhibitors in advanced melanoma patients
Authors: Dufau Carine , Genais Matthieu , Mucher Elodie , Jung Benjamin , Garcia Virginie , Montfort Anne , Tosolini Marie , Clarke Christopher J. , Medin Jeffrey A. , Levade Thierry , Delord Jean-Pierre , Meyer Nicolas , Pancaldi Vera , Andrieu-Abadie Nathalie , Ségui Bruno 
Published: July 2024

IntroductionAdvanced cutaneous melanoma is a skin cancer characterized by a poor prognosis and high metastatic potential. During metastatic spread, melanoma cells often undergo dedifferentiation toward an invasive phenotype, resulting in reduced expression of microphthalmia-associated transcription factor (MITF)-dependent melanoma antigens and facilitating immune escape. Tumor Necrosis Factor (TNF) is known to be a key factor in melanoma dedifferentiation. Interestingly, accumulating evidence suggests that TNF may play a role in melanoma progression and resistance to immunotherapies. Additionally, TNF has been identified as a potent regulator of sphingolipid metabolism, which could contribute to melanoma aggressiveness and the process of melanoma dedifferentiation.MethodsWe conducted RNA sequencing and mass spectrometry analyses to investigate TNF-induced dedifferentiation in two melanoma cell lines. In vitro experiments were performed to manipulate sphingolipid metabolism using genetic or pharmacologic alterations in combination with TNF treatment, aiming to elucidate the potential involvement of this metabolism in TNF-induced dedifferentiation. Lastly, to evaluate the clinical significance of our findings, we performed unsupervised analysis of plasma sphingolipid levels in 48 patients receiving treatment with immune checkpoint inhibitors, either alone or in combination with anti-TNF therapy.ResultsHerein, we demonstrate that TNF-induced melanoma cell dedifferentiation is associated with a global modulation of sphingolipid metabolism. Specifically, TNF decreases the expression and activity of acid ceramidase (AC), encoded by the ASAH1 gene, while increasing the expression of glucosylceramide synthase (GCS), encoded by the UGCG gene. Remarkably, knockdown of AC alone via RNA interference is enough to induce melanoma cell dedifferentiation. Furthermore, treatment with Eliglustat, a GCS inhibitor, inhibits TNF-induced melanoma cell dedifferentiation. Lastly, analysis of plasma samples from patients treated with immune checkpoint inhibitors, with or without anti-TNF therapy, revealed significant predictive sphingolipids. Notably, the top 8 predictive sphingolipids, including glycosphingolipids, were associated with a poor response to immunotherapy.DiscussionOur study highlights that ceramide metabolism alterations are causally involved in TNF-induced melanoma cell dedifferentiation and suggests that the evolution of specific ceramide metabolites in plasma may be considered as predictive biomarkers of resistance to immunotherapy.
Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer
Authors: Shao Wenwen , Lin Zhiheng , Xiahou Zhikai , Zhao Fu , Xu Jue , Liu Xinqi , Cai Pingping 
Published: July 2024

BackgroundOvarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease.Materials and methodsUtilizing single-cell RNA sequencing (scRNA-seq), we comprehensively investigated the cellular composition across six ovarian cancer patients with omental metastasis. Our focus centered on analysis of the malignant epithelial cells. Employing CytoTRACE and slingshot pseudotime analyses, we identified critical subpopulations and explored associated transcription factors (TFs) influencing ovarian cancer progression. Furthermore, by integrating clinical factors from a large cohort of bulk RNA sequencing data, we have established a novel prognostic model to investigate the impact of the tumor immune microenvironment on ovarian cancer patients. Furthermore, we have investigated the condition of immunological exhaustion.ResultsOur study identified a distinct and highly proliferative subgroup of malignant epithelial cells, known as C2 TOP2A+ TCs. This subgroup primarily consisted of patients who hadn’t received neoadjuvant chemotherapy. Ovarian cancer patients with elevated TOP2A expression exhibited heightened sensitivity to neoadjuvant chemotherapy (NACT). Moreover, the transcription factor MYBL2 in this subgroup played a critical role in ovarian cancer development. Additionally, we developed an independent prognostic indicator, the TOP2A TCs Risk Score (TTRS), which revealed a correlation between the High TTRS Group and unfavorable outcomes. Furthermore, immune infiltration and drug sensitivity analyses demonstrated increased responsiveness to Paclitaxel, Cisplatin, and Gemcitabine in the Low TTRS Group.ConclusionThis research deepens our understanding of malignant epithelial cells in ovarian cancer and enhances our knowledge of the ovarian cancer immune microenvironment and immune exhaustion. We have revealed the heightened susceptibility of the C2 TOP2A+ TCs subgroup to neoadjuvant chemotherapy and emphasized the role of MYBL2 within the C2 subgroup in promoting the occurrence and progression of ovarian cancer. These insights provide valuable guidance for the management of ovarian cancer treatment.
Diagnostic test performance of the Mentzer index in evaluating Saudi children with microcytosis
Authors: AlQarni Amani M. , Althumairi Arwa , Alkaltham Nourah K. , AlJishi Samaa , Hakami Amani Mohammed , Abdalla Leena Mohamed Osman Ali , Alawi Zahra Sayed Jalal , Alreedy Abdullah H. 
Published: July 2024

BackgroundAnemia is a global public health concern, affecting both developing and industrialized countries at a rate of 39.8%. It is defined by low hemoglobin concentration, and anemia varies in severity based on age: &lt;11 g/dL (6–59 months), &lt;11.5 g/dL (5–11 years), and &lt; 12 g/dL (12–14 years).AimThis study evaluates the Mentzer index’s reliability in differentiating iron deficiency anemia from the thalassemia trait.MethodsA total of 434 children (≤16 years) with hemoglobin electrophoresis previously screened for microcytosis (MCV &lt;80 FL) and an iron profile were included. Children with other hematological conditions were excluded.ResultsOut of 434 children, 181 were diagnosed with thalassemia, and 345 had iron deficiency anemia. The Mentzer index showed 74% sensitivity and 63% specificity for the beta-thalassemia trait, with 61% sensitivity and 36% specificity for iron deficiency anemia. The beta-thalassemia trait group had the highest negative predictive value (98%), while iron deficiency anemia had the highest positive predictive value (79%).ConclusionOur study, which is consistent with previous literature, suggests that the Mentzer index is not highly reliable in distinguishing iron deficiency anemia from the thalassemia trait among children in Saudi Arabia.
The one-year incidence of stroke in patients with atrial fibrillation in Jordan and its associated factors
Authors: Al-Shatanawi Tariq N. , Alkouri Osama , Khader Yousef , ALSalamat Husam , Qaladi Omar Aawadh , Jarrah Mohamad , Ababneh Anas , Al-Awaisheh Raed , Zamil Taqialdeen , Hammoudeh Ayman 
Published: July 2024

BackgroundAn elevated risk of stroke is linked to atrial fibrillation (AF). Effective care and prevention measures for individuals with AF require an understanding of the factors impacting the incidence of stroke in this population. Evidence regarding the incidence of stroke among patients with AF is insufficient in Jordan. This study aimed to determine the incidence of stroke and its associated factors among patients with AF in Jordan.MethodsThe Jordan Atrial Fibrillation Registry JoFib was used to identify a total of 2020 AF patients meeting the study inclusion and exclusion criteria. Demographics, clinical characteristics, and the CHA2DS2-VASc score-based evaluation of stroke risk were extracted from the registry.ResultsThis study encompassed 2020 participants diagnosed with AF, with 925 (45.8%) being men and 1,095 (54.2%) women. The one-year stroke incidence among the 2020 AF patients was 3.4%. Notably, stroke incidence significantly increased with age (p = 0.04) and was associated with the history of stroke (7.4% vs. 2.7%), hypertension (3.9% vs. 1.9%), and diabetes (5.1% vs. 2.1%). In the multivariate analysis, diabetes (OR = 2.6, 95% CI: 1.5–4.4, p = 0.001) and history of stroke (OR = 2.6, 95% CI: 1.5–4.6, p = 0.001) were significantly associated with stroke incidence.ConclusionThis study emphasizes Jordan’s high stroke rate among AF patients. Diabetes and prior stroke history are associated with increased odds of stroke, like all stroke patients. These results highlight the necessity for specialized management strategies among AF patients and highlight the significance of thorough risk assessment and focused interventions to reduce stroke risk in AF patients.
Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice
Authors: Cheng Jiahua , Wu Qiqi , Sun Rui , Li Wujuan , Wang Zhuoling , Zhou Min , Yang Tian , Wang Jing , Lyu Yuhong , Yue Changwu 
Published: July 2024

ObjectiveTo explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia.MethodsELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC–MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention.ResultsThe content of GABA and L-theanine in 7 L fermentation products was 12.555 μmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p &lt; 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p &lt; 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1β and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids.ConclusionProbiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.
Effect of chiral silver nanoparticles on prolyl-oligopeptidase binding and activity
Authors: Batista Carin C. S. , Toledo Victor H. , Ramos Marcos P. C. , Oliveira Vitor , Acuña Javier , Icimoto Marcelo Y. , Nantes Iseli L. 
Published: July 2024

Introduction: Silver nanoparticles have a diversity of applications both in biological and technological areas. More recently, studies conducted in the Nano/Bio interface have demonstrated that chiral nanocrystals grew in chiral templates, and nanostructures functionalized with chiral molecules present specific properties. These properties apply to advanced materials, energy, medicine, and pharmacology.Methodology: The present study synthesized silver nanoparticles on silver seeds using D- and L-histidine as templates and borohydride as a reducing agent.Results and Discussion: The nanoparticles were characterized by UV-visible spectroscopy and presented surface plasmon resonance (SPR) bands around 415 nm. CD spectra showed signals in the region of the SPR band, indicating the growth of nanocrystals with chiral distortion. Synthesized silver nanoparticles were also characterized by high-resolution transmission electron microscopy (HRTEM), which evidenced the presence of histidine corona. The silver nanoparticles were functionalized with prolyl-oligopeptidase (POP), a prolinespecific endopeptidase expressed in the brain. This enzyme cleaves neuroactive peptides involved in memory, learning, and neurodegeneration. The enzyme POP was expressed with a His-tag to provide competitive binding affinity to silver nanoparticles covered by D- and L-histidine. Considering the biological importance, POP was chosen as a model for studying the functionalization of chiral silver nanoparticles regarding the chiral discrimination for binding affinity and stabilization.
An internet-based self-help intervention for the reduction of consumption of ultra-processed products and increase of physical activity in Mexican university population: study protocol for a randomized controlled trial
Authors: González-Cantero Joel Omar , López-Torres Leyna Priscila , Alvarado-Avalos Itzel Refugio , López-Alcaraz Fátima , Gasca-Suarez Estefania , Cisneros-Hernández Adrian Antonio , Valadez Alexandra , Macías-Espinoza Fabiola , Dominguez-Rodriguez Alejandro 
Published: July 2024

IntroductionThe consumption of ultra-processed products has been associated with the etiology of various diseases, mainly metabolic diseases. On the other hand, physical activity acts as a protective factor that helps prevent the appearance of this type of disease. In addition to the physical effects, both the consumption of ultra-processed products (UPPs) and sedentary behaviors have been associated with a significant impact on people’s mental health. These problems occur significantly in university students. Online internet interventions are an alternative that has the advantage of reaching a broader sample size and adapting to various problems.MethodsA randomized controlled clinical superiority trial with two independent groups will be developed with 176 participants. Participants in both groups will be evaluated in 5 steps: (1) pretest, (2) middle of the intervention, (3) post-test, (4) follow-up at 3 months, and (5) follow-up at 6 months. In the experimental group (“UNISALUD”), participants will receive an intervention composed of 11 sessions with interactive elements such as videos, audio, and infographics created through the user experience (UX) principles and based on the health action process approach (HAPA). The participants in the control group will be on the waiting list and will receive treatment 27 days after fulfilling the inclusion criteria. Thus, participants will not receive the treatment immediately.DiscussionThe study is expected to establish the feasibility of a self-help internet-based intervention created based on the user experience methodology and the health action process model, leading to a significant decrease and increase in the consumption of UPPs, ultra-healthy products, and physical activity, respectively.ConclusionInternet-based interventions are scarce in Latin America. Due to their potential, this study will provide data about consumption of UPPs, physical activity, and mental health of the Mexican population, which will influence the reduction of health-related complications through prevention strategies or measures.Clinical Trial Registration:ClinicalTrials.gov, NCT05834842.