bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of different energy levels in low-protein diet on liver lipid metabolism in the late-phase laying hens through the gut-liver axis
Authors: Hu Hong , Huang Ying , Li Anjian , Mi Qianhui , Wang Kunping , Chen Liang , Zhao Zelong , Zhang Qiang , Bai Xi , Pan Hongbin 
Published: July 2024

Abstract
Background
The energy/protein imbalance in a low-protein diet induces lipid metabolism disorders in late-phase laying hens. Reducing energy levels in the low-protein diet to adjust the energy-to-protein ratio may improve fat deposition, but this also decreases the laying performance of hens. This study investigated the mechanism by which different energy levels in the low-protein diet influences liver lipid metabolism in late-phase laying hens through the enterohepatic axis to guide feed optimization and nutrition strategies. A total of 288 laying hens were randomly allocated to the normal-energy and normal-protein diet group (positive control: CK) or 1 of 3 groups: low-energy and low-protein diet (LL), normal-energy and low-protein diet (NL), and high-energy and low-protein diet (HL) groups. The energy-to-protein ratios of the CK, LL, NL, and HL diets were 0.67, 0.74, 0.77, and 0.80, respectively.

Results
Compared with the CK group, egg quality deteriorated with increasing energy intake in late-phase laying hens fed low-protein diet. Hens fed LL, NL, and HL diets had significantly higher triglyceride, total cholesterol, acetyl-CoA carboxylase, and fatty acid synthase levels, but significantly lower hepatic lipase levels compared with the CK group. Liver transcriptome sequencing revealed that genes involved in fatty acid beta-oxidation (ACOX1, HADHA, EHHADH, and ACAA1) were downregulated, whereas genes related to fatty acid synthesis (SCD, FASN, and ACACA) were upregulated in LL group compared with the CK group. Comparison of the cecal microbiome showed that in hens fed an LL diet, Lactobacillus and Desulfovibrio were enriched, whereas riboflavin metabolism was suppressed. Cecal metabolites that were most significantly affected by the LL diet included several vitamins, such as riboflavin (vitamin B2), pantethine (vitamin B5 derivative), pyridoxine (vitamin B6), and 4-pyridoxic acid.

Conclusion
A lipid metabolism disorder due to deficiencies of vitamin B2 and pantethine originating from the metabolism of the cecal microbiome may be the underlying reason for fat accumulation in the liver of late-phase laying hens fed an LL diet. Based on the present study, we propose that targeting vitamin B2 and pantethine (vitamin B5 derivative) might be an effective strategy for improving lipid metabolism in late-phase laying hens fed a low-protein diet.
Anti-TIM3 chimeric antigen receptor-natural killer cells preferentially target primitive acute myeloid leukemia cells with minimal fratricide and exhaustion
Authors: Klaihmon Phatchanat , Samart Parinya , Rojanasakul Yon , Issaragrisil Surapol , Luanpitpong Sudjit 
Published: July 2024

AbstractAcute myeloid leukemia (AML) is an aggressive and genetically heterogeneous disease with poor clinical outcomes. Refractory AML is common, and relapse remains a major challenge, attributable to the presence of therapy-resistant leukemic stem cells (LSCs), which possess self-renewal and repopulating capability. Targeting LSCs is currently the most promising avenue for long-term management of AML. Likewise, chimeric antigen receptor (CAR)-natural killer (NK) cells have emerged as a promising alternative to CAR-T cells due to their intrinsic potential as off-the-shelf products and safer clinical profiles. Here, we introduced a third-generation CAR harboring TIM3 scFv, CD28, 4-1BB, and CD3ζ (CAR-TIM3) into human NK-92 cells, the only FDA-approved NK cell line for clinical trials. TIM3 was chosen as a target antigen owing to its differential expression in LSCs and normal hematopoietic stem/progenitor cells (HSPCs). The established CAR-TIM3 NK-92 cells effectively targeted TIM3 and displayed potent anti-tumor activity against various primitive AML cells, subsequently causing a reduction in leukemic clonogenic growth in vitro, while having minimal effects on HSPCs. CAR-TIM3 NK-92 cells significantly reduced leukemic burden in vivo and interestingly suppressed the engraftment of AML cells into the mouse liver and bone marrow. Surprisingly, we found that CAR-TIM3 NK-92 cells expressed relatively low surface TIM3, leading to a low fratricidal effect. As TIM3 and PD-1 are immune checkpoints involved in NK cell dysfunction, we further tested and found that CAR-TIM3 NK-92 cells are beneficial for alleviating NK cell exhaustion. Our findings highlight the potential application of CAR-TIM3 NK cells for cellular immunotherapy for TIM3+ AML.
Does using artificial intelligence assistance accelerate skill decay and hinder skill development without performers’ awareness?
Authors: Macnamara Brooke N. , Berber Ibrahim , Çavuşoğlu M. Cenk , Krupinski Elizabeth A. , Nallapareddy Naren , Nelson Noelle E. , Smith Philip J. , Wilson-Delfosse Amy L. , Ray Soumya 
Published: July 2024

AbstractArtificial intelligence in the workplace is becoming increasingly common. These tools are sometimes used to aid users in performing their task, for example, when an artificial intelligence tool assists a radiologist in their search for abnormalities in radiographic images. The use of artificial intelligence brings a wealth of benefits, such as increasing the efficiency and efficacy of performance. However, little research has been conducted to determine how the use of artificial intelligence assistants might affect the user’s cognitive skills. In this theoretical perspective, we discuss how artificial intelligence assistants might accelerate skill decay among experts and hinder skill acquisition among learners. Further, we discuss how AI assistants might also prevent experts and learners from recognizing these deleterious effects. We then discuss the types of questions: use-inspired basic cognitive researchers, applied researchers, and computer science researchers should seek to answer. We conclude that multidisciplinary research from use-inspired basic cognitive research, domain-specific applied research, and technical research (e.g., human factors research, computer science research) is needed to (a) understand these potential consequences, (b) design artificial intelligence systems to mitigate these impacts, and (c) develop training and use protocols to prevent negative impacts on users’ cognitive skills. Only by answering these questions from multidisciplinary perspectives can we harness the benefits of artificial intelligence in the workplace while preventing negative impacts on users’ cognitive skills.
Using learning analytics to explore peer learning patterns in asynchronous gamified environments
Authors: Moon Jewoong , McNeill Laura , Edmonds Christopher Thomas , Banihashem Seyyed Kazem , Noroozi Omid 
Published: July 2024

AbstractThis study explored the dynamics of students' knowledge co-construction in an asynchronous gamified environment in higher education, focusing on peer discussions in college business courses. Utilizing epistemic network analysis, sequence pattern mining, and automated coding, we analyzed the interactions of 1,319 business students. Our findings revealed that externalization and epistemic activity were prevalent, demonstrating a strong link between problem-solving and conceptual understanding. Three primary discussion types were observed: argumentative, epistemic, and social, each with unique patterns of engagement and idea integration. Effective knowledge co-construction patterns included open-ended questions with an epistemic focus, debates serving as intense knowledge co-construction arenas, and social interactions fostering a supportive and collaborative learning environment. The introduction of gamification elements led to increased student engagement and participation. Our findings emphasize the significance of structured analysis, collaboration, and argumentation in promoting effective knowledge co-construction in peer learning settings. This study offers insights into the temporal interplay of discourse dimensions and their potential for collaborative learning, enhancing our understanding of how learning analytics can be employed to discover ways in which students co-construct knowledge in asynchronous gamified environments.
Effects of normal saline versus isotonic balanced crystalloid on acid–base balance and renal functions in patients undergoing intracranial tumor resection surgeries
Authors: Bala Renu , Akanksha  , Arora Vandna , Yadav Divyansh , Singh Ankur 
Published: July 2024

Abstract
Background
Normal saline (NS) infusion in large volumes may result in hyperchloremic metabolic acidosis and renal compromise. Balanced crystalloid (BC) with physiochemical composition akin to that of plasma may avoid these problems associated with NS. The present study aimed to evaluate effects of NS versus BC on acid–base balance and renal functions in patients undergoing intracranial tumor resection surgeries.

Methods
Fifty adult patients scheduled to undergo elective neurosurgery for intracranial tumor resection were randomized to receive either NS or BC as intraoperative or maintenance fluid. Metabolic and renal parameters were estimated prior to induction (baseline), at 1 h and 2 h after induction, at the end of surgery and 4 h after extubation. Serum neutrophil gelatinase-associated lipocalin (NGAL) was measured postoperatively. Brain relaxation score was assessed by the operating surgeon.

Results
Baseline values of variables were similar between the groups. At rest of the observed time-points, pH was significantly lower, while blood urea, serum creatinine, sodium, chloride, NGAL and plasma osmolality were significantly higher in the NS group as compared to the BC group. Brain relaxation score, serum bicarbonate and base excess were comparable between the two groups.

Conclusion
Use of balanced crystalloid (plasmalyte) resulted in better metabolic and renal profile as compared to normal saline in neurosurgical patients.
Introduction of novel intravascular ultrasound preceding with angled guiding catheter (I-PAD) technique to treat chronic total occlusions in peripheral artery disease
Authors: Sobajima Mitsuo , Imamura Teruhiko , Ueno Yohei , Onoda Hiroshi , Ushijima Ryuichi , Ueno Hiroshi , Kinugawa Koichiro 
Published: July 2024

Abstract
Background
The optimal endovascular treatment (EVT) for chronic total occlusion (CTO) lesions in patients with peripheral artery disease (PAD) has remained unestablished. We encountered a patient with PAD in whom CTO was successfully treated using a novel technique that involved intravascular ultrasound (IVUS) and angled guiding catheter: IVUS Preceding with Angled guiDing catheter (I-PAD) technique.

Case presentation
A 74-year-old male presented with intermittent claudication attributed to CTO of the right external iliac artery. EVT was performed via the right common femoral artery. We retrogradely advanced the I-PAD system (i.e. partially extending the IVUS transducer portion from the tip of the angled guiding catheter) in the CTO lesion under the real-time guidance of IVUS imaging. We successfully traversed the CTO lesion without the use of a guidewire in approximately three minutes. The procedure concluded successfully without any procedure-related complications, following optimal stenting.

Conclusions
The I-PAD might be an effective technique to accurately, quickly, and safely pass through CTO lesions.
Evaluation of the diagnostic value of different serum biomarkers in girls with central precocious puberty
Authors: Abdelmeguid Yasmine , Abdelkarem Omneya , Raafat Shaymaa 
Published: July 2024

Abstract
Background
Alarming trends show an increase in referrals of girls with suspected early puberty. However, variations in defining precocious puberty exist. GnRH stimulation test is the gold standard diagnostic test, which is expensive and challenging to interpret. Moreover, intravenous GnRH might not be available. Therefore, we sought to evaluate the diagnostic performance of basal serum Luteinizing Hormone and Anti-Mullerian hormone in girls with central precocious puberty, as an easier alternative to GnRH stimulation test. The study was conducted on 26 Egyptian girls presenting with early puberty at age < 8 years. Several evaluations including Tanner staging and GnRH stimulation test were performed. Basal serum luteinizing hormone, follicle stimulating hormone, and anti-Mullerian hormone were analyzed, and ROC curve was performed.

Results
The mean age of the patients at diagnosis was 5 ± 2.8 years. Most patients had breast Tanner 3 (76.9%). Bone age was advanced in 65.4% of patients. Basal luteinizing hormone level significantly differed between central precocious puberty and controls (p < 0.001), with an area under the curve of 0.840. A cut-off of 0.29 IU/L provided 84.62% sensitivity and 76.92% specificity.

Conclusions
Basal luteinizing hormone out-performs follicle-stimulating hormone and anti-Mullerian hormone as a screening tool and valuable indicator of central precocious puberty, potentially reducing the necessity of GnRH stimulation test.
Study on the spatial relationship between road network and the diversity of urban public facilities: the case of the central area of Changsha City
Authors: Hu Yiwen , Liang Chao 
Published: July 2024

AbstractIn the context of contemporary urbanization, the significance of diversifying urban public facilities has attracted significant attention. This study examines the relationship between road network and the diversity of urban public facilities in Changsha City. These factors are measured through the Shannon-Weiner Index and Space Syntax method. To provide greater specificity, the study employs Random Forest and Geographically Weighted Regression models to analyze the relationship between road networks and the diversity of urban public facilities. The results identify a nonlinear relationship between these variables. In addition, high accessibility exhibits a stronger association with diversity than accessibility alone, and this correlation is reflected in varying degrees of inconsistency across different study areas. Finally, the cartographic depiction of diversity clusters is overlaid on the road network, demonstrating a significant relationship between the configuration of the road network and diversity patterns. In conclusion, this research emphasizes the robust correlation between the roadway network and the diversity of urban public facilities. It prompts local governments to focus beyond mere equality, with a greater commitment to enhancing the quality of life for residents through diversity.
Exploration of microRNA biomarker panel as a predictor of evolution of pancreatitis to pancreatic ductal adenocarcinoma.
Authors: Nuthakki Mira 
Published: July 2024

e16343 Background: PDAC (pancreatic ductal adenocarcinoma) is 3rd most common cause of cancer deaths, and is projected to become the 2nd leading cause of cancer death by 2030 even as it comprises only 3.2% of all cancer cases. The most important predictor of survival is resection of early stage cancer. Currently, screening for early detection of PDAC via annual MRI or endoscopic ultrasound (EUS) is recommended only in the 10% of total cases, that have hereditary/ genetic associations. PDAC risk is doubled even 5 years after acute pancreatitis and is 15-16 fold for chronic pancreatitis. Biomarkers such as CA19-9, peptide panels, tumor-associated autoantibodies and microRNAs have been studied for early diagnosis of PDAC. However, biomarkers that can predict risk of PDAC following pancreatitis have not been well studied. This study aims to identify, compare, and extract a differentially expressed microRNA (DEM) panel in serum, that could predict risk of progression to PDAC from pancreatitis. Methods: Two microarray Genomic Spatial Event (GSE) datasets containing pancreatitis (n = 75), PDAC (90), and control samples (164) were used to extract DEM (n = 22), common to both pancreatitis and PDAC. 8 smaller subgroups of DEM (for cost benefit) were derived from bioinformatics methods such as ROC/AUC of expression values, up and downregulated clustering, correlation analysis, miRNA interaction networks, target gene prediction tools, target gene interaction and functional enrichment analysis for all target genes and top modules, as well as decision tree/cross-validated random forest machine learning models. Results: The DEM main group (n = 22) and the smaller subgroups were trained on the original datasets, and were used to predict the risk of pancreatic cancer vs control in a validation set consisting of six other GSE datasets. The main 22miRNA panel had the highest accuracy (0.928), F1(0.976), precision and recall, followed by subgroup 6 (accuracy 0.910, F1 0.968) derived from the target hub genes with the highest interaction (hsa-miR-28-3p, 320b, 320c, 320d, 532-5p, and 423-5p). The associated main pathways were ubi-conjugation and ubiquitin pathway, mRNA splicing/processing/binding, and endocytosis. Conclusions: A new serum 22 microRNA biomarker panel predicting evolution of pancreatitis to pancreatic ductal adenocarcinoma, and it’s associated pathways, has been identified, that also performed very well in distinguishing pancreatic cancer (with or without pancreatitis risk factor) from control. A smaller subpanel of 6 microRNA may have a cost benefit. Further studies with larger samples, specifically differentiating PDAC vs all pancreatic cancer, and acute vs chronic pancreatitis among the samples are needed.
Pancreatoblastoma: A study of demographic and socioeconomic factors.
Authors: Bitar Gabriel Anthony , Tade Yanick , Tandon Nikhita , Sadighian Assal , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: July 2024

e16345 Background: Pancreatoblastoma (PB) is a rare tumor originating from pancreatic epithelial exocrine cells with a very poor prognosis. At diagnosis, it often presents with large lesions encompassing overlapping regions and may involve the entire pancreas. PB is frequently associated with distant metastasis and often occurs in children under the age of 10. An optimal treatment strategy has yet to be established. Analyzing trends in diagnoses may yield valuable information about its epidemiology. The National Cancer Database (NCDB) was utilized to uncover the demographic factors in patients diagnosed with PB. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 82 patients were found with a histologically confirmed diagnosis of PB (ICD-8971-3). Race, gender, Hispanic origin, type of treatment facility, insurance coverage, and distance from patient residence to treatment facility were analyzed via descriptive statistics. Trends in incidence were interpreted using regression analysis. Results: A total of 82 individuals in the NCDB were confirmed to be diagnosed with pancreatoblastoma between 2004-2020. The incidence rate of patients diagnosed per year is steady (R² =0.0). The average age of diagnosis was 55.3 years (SD = 15.4, range = 19-90) with women (89%) being more likely to be diagnosed compared to men (11%). None of the observed patients utilized palliative care, and from this population, 87% received surgery, and 28% received chemotherapy as their primary treatment. The majority of the patients were non-Hispanic (89%) and White (87%). Most patients were privately insured (52%) and lived in metropolitan areas with a population greater than 1 million (51%). More patients were in the highest quartile of income earners (33%), compared to those in the second, third, or fourth quartiles. Fewer patients were treated at a comprehensive community cancer program (28%) than in an academic/research program (37%). Most patients (79%) had a Charlson/Deyo comorbidity scores of 0 and were applicable to Stage I group (49%). Conclusions: This represents the first analysis of pancreatoblastoma within the NCDB to our knowledge, addressing a notable knowledge gap. Pancreatoblastoma is predominantly treated by surgery, consistent with previous case reports. Notably, our study pioneers the exploration of socioeconomic aspects among pancreatoblastoma patients. Findings reveal a higher likelihood of these patients belonging to the highest income quartile, residing in densely populated metropolitan areas, and receiving treatment within academic/research programs. Further investigation is warranted to comprehend the influence of demographic and socioeconomic variables on the diagnosis, treatment approaches, and overall survival of individuals with pancreatoblastoma.
Phase 1 dose-finding study to evaluate safety and tolerability of CVGBM in patients with newly diagnosed and surgically resected MGMT-unmethylated glioblastoma.
Authors: Tabatabai Ghazaleh , Von Baumgarten Louisa , Van Den Bent Martin J. , Burger Michael C , Freres Pierre , Glas Martin , Hau Peter , Herrlinger Ulrich , Mildenberger Iris , Neyns Bart , Schafer Henning Sebastian , Seidel Clemens , Galot Rachel , Wick Antje , Falk Martin H. , de Freitas Chama Laura Leticia , Kelemen Peter , Koch Sven D , Romer Roche Paula , Gnad-Vogt Senta Ulrike ,   CV-GBLM-001 Study Group
Published: July 2024

TPS2095 Background: Glioblastoma (GBM) is characterized by a low mutational burden limiting the number of neoantigen targets for cancer vaccines. Vaccination against tumor-associated antigens over-presented via MHC class I and II in GBM is an alternative that has shown promise in previous trials. A previous cancer vaccine containing peptides presented by HLA-A*02:01 (class I) and some DR alleles (class II), showed evidence of peripheral and intratumoral vaccine-induced immune response against these peptides in patients with GBM. Our study will assess the safety and immunogenicity of the messenger ribonucleic acid (mRNA)-based multiepitope vaccine CVGBM, an investigational therapeutic mRNA vaccine, encoding eight of these peptides that have demonstrated immunogenicity as peptide vaccines. CVGBM consists of a mRNA with unmodified nucleotides formulated with lipid nanoparticles. Methods: CV-GBLM-001 (NCT05938387) is a first-in-human, open-label, international, dose-escalation phase 1 trial. HLA-A*02:01-positive patients with newly diagnosed MGMT-unmethylated GBM (CNS WHO Grade 4), including IDH-wildtype astrocytoma with a molecular signature of unmethylated glioblastoma who have had a gross total or partial resection and who completed post-surgery radiotherapy with or without chemotherapy, are eligible to receive CVGBM. The trial comprises a dose-escalation part (Part A) followed by a dose-expansion part (Part B). In Part A, mRNA dose levels between 12 and 100 µg are being investigated and dose escalation is guided by a Bayesian logistic regression model. Patients will receive 7 doses of CVGBM by intramuscular injection on Days 1, 8, 15, 29, 43, 57, and 71, followed by 6 optional doses at 6-week intervals, up to 1 year after the first dose or until disease progression or intolerable toxicity. An independent Data and Safety Monitoring Board will recommend the dose for expansion in Part B and about 20 patients will be enrolled. Biomarkers and vaccine-induced innate and adaptive immunogenicity, including, but not limited to, systemically induced cytokines and chemokines and antigen-specific CD4+ and CD8+ T cells, will be monitored in the blood, and optionally in vaccine-draining lymph nodes and progressive tumors. In addition to the primary safety objectives, secondary objectives of efficacy (progression-free survival, overall survival) and patient-reported quality of life outcomes will be assessed. Trial sponsor: CureVac SE, Germany. Clinical trial information: NCT05938387 .