bluuebunny/crossref_metadata_2025_split huggingface dataset:
Penerapan Pewarnaan Graf Menggunakan Algoritma Welch-Powell pada Penjadwalan Mata Pelajaran
Authors: Yusak Monica Yeyen , Putri Desi Febriani , Syaripuddin Syaripuddin 
Published: October 2024

Penjadwalan mata pelajaran adalah unsur penting dalam manajemen sekolah yang efisien. Pewarnaan graf digunakan sebagai pendekatan untuk menyelesaikan permasalahan pada proses penyusunan penjadwalan menggunakan algoritma welch-powell. Pada penelitian ini, dilakukan peenjadwalan penyusunan mata pelajaran di SMP Terpadu Rea Kaltim Kembang Janggut menggunakan pewarnaan graf. Algoritma yang digunakan adalah algoritma welch-powell, untuk menyusun penjadwalan yang meminimalkan bentrok antara mata pelajaran yang memiliki jadwal tumpang tindih. Penelitian ini bertujuan untuk mengetahui model mata pelajaran dan guru pengampu kedalam bentuk graf, serta untuk mengetahui hasil dari pewarnaan graf menggunakan algoritma welch-powell di SMP Terpadu Rea Kaltim Kembang Janggut. Penelitian ini berfokus pada pewarnaan titik menggunakan algoritma welch-powel, jadi untuk setiap titik yang bertetangga tidak boleh memiliki warna yang sama. Data pada penelitian ini mencakup informasi tentang guru pengampu mata pelajaran, jumlah kelas, dan jumlah mata pelajaran. Berdasarkan hasil penelitian diketahui bahwa pewarnaan graf dengan algoritma welch-powell dapat digunakan pada penyusunan penjadwalan mata pelajaran SMP Terpadu Rea Kaltim Kembang Janggut. Pada implementasi pewarnaan graf diperoleh bilangan kromatik adalah 5 atau yang terdiri dari warna merah, kuning, hijau, ungu, dan biru.
Priming from within: TLR2 dependent but receptor independent activation of the mammary macrophage inflammasome by Streptococcus uberis
Authors: Hinds Abbie , Ward Philip , Archer Nathan , Leigh James 
Published: October 2024

IntroductionStreptococcus uberis is a member of the pyogenic cluster of Streptococcus commonly associated with intramammary infection and mastitis in dairy cattle. It is a poorly controlled globally endemic pathogen responsible for a significant cause of the disease worldwide. The ruminant mammary gland provides an atypical body niche in which immune cell surveillance occurs on both sides of the epithelial tissue. S. uberis does not cause disease in non-ruminant species and is an asymptomatic commensal in other body niches. S. uberis exploits the unusual niche of the mammary gland to initiate an innate response from bovine mammary macrophage (BMMO) present in the secretion (milk) in which it can resist the host immune responses. As a result – and unexpectedly - the host inflammatory response is a key step in the pathogenesis of S.uberis, without which colonisation is impaired. In contrast to other bacteria pathogenic to the bovine mammary gland, S. uberis does not elicit innate responses from epithelial tissues; initial recognition of infection is via macrophages within milk.MethodsWe dissected the role of the bacterial protein SUB1154 in the inflammasome pathway using ex vivo bovine mammary macrophages isolated from milk, recombinant protein expression, and a panel of inhibitors, agonists, and antagonists. We combine this with reverse-transcription quantitative real-time PCR to investigate the mechanisms underlying SUB1154-mediated priming of the immune response.ResultsHere, we show that SUB1154 is responsible for priming the NLRP3 inflammasome in macrophages found in the mammary gland. Without SUB1154, IL-1β is not produced, and we were able to restore IL-1β responses to a sub1154 deletion S. uberis mutant using recombinant SUB1154. Surprisingly, only by blocking internalisation, or the cytoplasmic TIR domain of TLR2 were we able to block SUB1154-mediated priming.DiscussionTogether, our data unifies several contrasting past studies and provides new mechanistic understanding of potential early interactions between pyogenic streptococci and the host.
A rare homozygous variant of CHKB induced severe cardiomyopathy and a cardiac conduction disorder: a case report
Authors: Jing Siyuan , Liu Lu , Li Yifei , Liu Fuqiang , Hua Yimin , Duan Hongyu 
Published: October 2024

BackgroundThe CHKB (choline kinase beta) gene plays a crucial role in regulating mitochondrial function and choline metabolism. Mutations in CHKB lead to conditions such as megaconial congenital muscular dystrophy (MCMD), characterized by enlarged mitochondria and impaired mitochondrial function, inducing various clinical features in neurological and cardiac performance. Herein, we report a rare case presenting with dilated cardiomyopathy as the dominant feature with a homozygous nonsense variant of CHKB, and the related therapeutic strategy.Case presentationThe proband, a 13-year-old male, presented with a complex clinical profile characterized by mild intellectual disability and severe cardiac impairment, including reduced activity tolerance, suspected acute heart failure, significant cardiac enlargement, a left anterior fascicular block, and a complete right bundle branch block. Whole exome sequencing (WES) identified a homozygous nonsense variant, c.598delC (p.Q200Rfs*11) of the CHKB gene, that resulted in disease caused by amino acid sequence changes, a truncated protein, and splice site changes, as demonstrated by MutationTaster analysis. The protein structure of CHKB was built and named AF-Q9Y259-F1. The residue around 200 amino acid sites changed in CHKB p.Q200Rfs*11 with unaltered hydrogen bonds which indicated the pathogenicity of the variant mainly originated from a truncated protein induced by the nonsense mutation. The heart blocks in the proband were considered to be associated with choline metabolic impairment, and thus cardiac resynchronization therapy would benefit the patient. Furthermore, the missense homozygous or compound heterozygous variants of CHKB, as well as the combined compound heterozygous missense and nonsense variants of CHKB, usually lead to neurological impairments and muscular weakness.ConclusionThis study expands the spectrum of CHKB mutations and provides essential information for the genotype–phenotype map of a nonsense variant of the gene. It is important to confirm a differential diagnosis among such patients using WES analyses. Regular cardiac and musculoskeletal monitoring is recommended for MCMD patients. Patients with a CHKB deficiency presenting with heart blocks could benefit from the administration of cardiac resynchronization therapy. This therapeutic approach might improve cardiac function and conduction in patients with CHKB-related cardiomyopathies.
Association of body roundness index with abdominal aortic calcification among middle aged and elderly population: findings from NHANES
Authors: Wu Ji , Lu Daojun , Chen Xiang 
Published: October 2024

AimWe aim to investigate the association between body roundness index (BRI) and abdominal aortic calcification (AAC) among middle aged and elderly US residents.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 cycle, including 3,079 middle-aged and elderly participants aged 40 and above. AAC scores for these participants were assessed using dual-energy x-ray absorptiometry (DXA). BRI was calculated from participants’ height and waist circumference, with all measurements conducted by trained surveyors using standardized methods. The relationship between BRI and AAC was analyzed using weighted multivariate logistic regression, adjusting for confounding variable. Additionally, restricted cubic splines (RCS) analysis was also employed.ResultsWe found that those with AAC were significantly older and had a higher prevalence of smoking and chronic kidney disease (CKD) prevalence compared to those without AAC. Using weighted multivariable logistic regression, we determined that an increase of one unit in BRI was associated with a 22% higher risk of AAC. Additionally, higher BRI quartiles (Q2, Q3, Q4) showed significantly increased risks of AAC compared to the lowest quartile. Visualization using RCS indicated a gradual increase in AAC risk with higher BRI, which plateaued beyond a BRI of 7.2. This relationship was significant across different age and gender group.ConclusionThere is a positive association between abdominal obesity (as measured by BRI) and AAC in the middle-aged and elderly population. This suggests the impact of abdominal obesity on vascular health and that this factor should be considered in public health strategies.
Developmental language disorders and special educational needs: consideration of inclusion in the Norwegian school context
Authors: Chahboun Sobh , Wahl Hilde T. , Langner Jana , Vaags Agnete 
Published: October 2024

Children with language disorders face different challenges in their daily school routines. Accessing tools and having resources promoting a well-structured and inclusive environment is necessary to ensure a pleasant and successful passage through primary school.The current article seeks to highlight stimulating ideas, creating a foundation for involving everyone caring for and educating students with language disorders, particularly children with special needs. Moreover, experts need to prioritize educational initiatives aimed at language disorders, particularly emphasizing early detection, prevention, and specialized care. Balancing the need for students to get adequate attention while avoiding unequal treatment can be as difficult as dealing with a two-sided coin. Moreover, it is crucial to acknowledge that academic research should prioritize finding the best ways to support students with special needs who have language impairments. All professionals working with these students, such as speech therapists, psychopedagogical experts, and general therapists, need to focus on developing interventions and options to aid in their growth.
The expression of VDACs and Bcl2 family genes in pituitary adenomas: clinical correlations and postsurgical outcomes
Authors: Facundo AN , Magalhães M , Nascimento GC , Azulay RS , Santos RM , Freitas LA , Nascimento AGPAC , Rodrigues VP , Santos WC , Beckman AMGS , Abreu JMF , Silva RP , Carneiro EL , Oliveira Neto CP , Gil da Costa RM , Corcoy R , Mato E , Faria MS 
Published: October 2024

IntroductionPituitary adenomas (PAs) are benign tumors with high prevalence and, occasionally, aggressive course. The tumorigenesis of these lesions is not completely understood at the molecular level. BAK1 and BAX proteins play fundamental roles in apoptosis and seem to interact with VDAC proteins, whose expressions have been markedly altered in cancer, impacting their prognosis.Objectiveto evaluate the gene expression of VDAC1, VDAC2, BAK1 and BAX and their association with clinical and imaging characteristics in PA.MethodsClinical-epidemiological data were collected from 117 tumor samples from patients affected by PA. Invasiveness was assessed by the Knosp scale. Gene expression was examined by real-time PCR. Relative expression analysis was performed by 2^(-DDCt) method.ResultsThe sample was mainly composed of women (69/117 – 57.2%). Tumor subtypes observed were Non-Functioning (NF) (73/117 – 62.4%), Acromegaly (24/117 – 20.5%) and Cushing’s Disease (CD) (20/117 – 17.1%). Compared to normal tissue, there was a significant reduction in VDAC1 expression in the Acromegaly (p=0.029) and NF (p=0.002) groups. BAX expression was lower in all groups (p &lt;0.001; p=0.007; P =0.005). No difference was found in VDAC2 and BAK1 expression, compared to normal pituitary. Overexpression of VDAC2 occurred in PAs with post-surgical regrowth (p=0.042). A strongly negative correlation was observed in BAX and BAK1 expression in CD.ConclusionThe results indicated that downregulations of VDAC1 and BAX may be related to resistance to apoptosis. In contrast, overexpression of VDAC2 in regrowing PAs suggests an antiapoptotic role for this gene. In summary, the genes evaluated might be involved in the biopathology of PAs.
Association between Life’s Essential 8 and psoriasis in US adults: a cross-sectional study
Authors: Zhang Junjie , Ren Ci , Qin Zihan , Zhu Ling , Jin Zhoufeng , Yan Yuanyuan , Pan Xinghe , Luan Lan 
Published: October 2024

BackgroundPsoriasis is closely associated with cardiovascular disease (CVD). However, the current evidence on the correlation between Life’s Essential 8 and Psoriasis is insufficient. Our aim was to investigate the relationship between Life’s Essential 8 (LE8), a measure of cardiovascular health (CVH), and psoriasis.ObjectiveThis study aimed to clarify the impact of Life’s Essential 8 on Psoriasis and explore its implications.MethodsThis population-based cross-sectional study included 9,876 US adults aged 20 to 59 years from the National Health and Nutrition Examination Survey (NHANES) 2003–2006 and 2009–2014 cycles. The LE8 score comprises 8 metrics and was categorized into low, moderate, and high CVH. Logistic regression and restricted cubic splines (RCS) were used to assess the association between LE8 score and psoriasis.ResultsAmong the 9,876 participants, those with moderate and high CVH had higher risks of psoriasis compared to low CVH. Additionally, every 10-point increase in the LE8 score was associated with a 10% reduced risk of psoriasis. Interaction was observed between gender, age, education level, race/ethnicity, marital status, and PIR.ConclusionLE8 and its subscale scores were strongly negatively related to the risk of psoriasis. Encouraging optimal CVH levels may be advantageous in reducing the incidence of psoriasis.
Genetically stratified Parkinson’s disease with freezing of gait is related to specific pattern of cognitive impairment and non-motor dominant endophenotype
Authors: Pavelka Lukas , Rawal Rajesh , Sapienza Stefano , Klucken Jochen , Pauly Claire , Satagopam Venkata , Krüger Rejko 
Published: October 2024

BackgroundFreezing of gait (FOG) is an important milestone in the individual disease trajectory of people with Parkinson’s disease (PD). Based on the cognitive model of FOG etiology, the mechanism behind FOG implies higher executive dysfunction in PDFOG+. To test this model, we investigated the FOG-related phenotype and cognitive subdomains in idiopathic PD (iPD) patients without genetic variants linked to PD from the Luxembourg Parkinson’s study.MethodsA cross-sectional analysis comparing iPDFOG+ (n = 118) and iPDFOG− (n = 378) individuals was performed, followed by the application of logistic regression models. Consequently, regression models were fitted for a subset of iPDFOG+ (n = 35) vs. iPDFOG− (n = 126), utilizing a detailed neuropsychological battery to assess the association between FOG and cognitive subdomains. Both regression models were adjusted for sociodemographic confounders and disease severity.ResultsiPDFOG+ individuals presented with more motor complications (MDS-UPDRS IV) compared to iPDFOG- individuals. Moreover, iPDFOG+ individuals exhibited a higher non-motor burden, including a higher frequency of hallucinations, higher MDS-UPDRS I scores, and more pronounced autonomic dysfunction as measured by the SCOPA-AUT. In addition, iPDFOG+ individuals showed lower sleep quality along with lower quality of life (measured by PDSS and PDQ-39, respectively). The cognitive subdomain analysis in iPDFOG+ vs. iPDFOG− indicated lower scores in Benton’s Judgment of Line Orientation test and CERAD word recognition, reflecting higher impairment in visuospatial, executive function, and memory encoding.ConclusionWe determined a significant association between FOG and a clinical endophenotype of PD with higher non-motor burden. While our results supported the cognitive model of FOG, our findings point to a more widespread cortical impairment across cognitive subdomains beyond the executive domain in PDFOG+ with additional higher impairment in visuospatial function and memory encoding.
Roburic acid inhibits lung cancer metastasis and triggers autophagy as verified by network pharmacology, molecular docking techniques and experiments
Authors: Wang Luyao , Chen Huili , Deng Lili , Hu Mengling , Wang Ziqiang , Zhang Kai , Lian Chaoqun , Wang Xiaojing , Zhang Jing 
Published: October 2024

BackgroundRoburic acid (ROB) is a newly discovered tetracyclic triterpene acid extracted from oak galls, which has anti-inflammatory effects, but the mechanism of its anticancer effect is not clear. Our study focuses on exploring the potential mechanism of action of ROB in the treatment of lung cancer using a combination of network pharmacological prediction, molecular docking technique and experimental validation.MethodsA network pharmacology approach was used to screen the protein targets of ROB and lung cancer, and PPI network analysis and enrichment analysis were performed on the intersecting genes. The tissue and organ distribution of the targets was also evaluated based on the BioGPS database. To ensure the reliability of the network pharmacology prediction results, we proceeded to use molecular docking technique to determine the relationship between drugs and targets. Finally, in vitro experiments with cell lines were performed to further reveal the potential mechanism of ROB for the treatment of lung cancer.ResultsA total of 83 potential targets of ROB in lung cancer were collected and further screened by using Cytoscape software, and 7 targets of PTGS2, CYP19A1, PTGS1, AR, CYP17A1, PTGES and SRD5A1 were obtained as hub genes and 7 hub targets had good binding energy with ROB. GO and KEGG analysis showed that ROB treatment of lung cancer mainly involves Arachidonic acid metabolism, Notch signaling pathway, cancer pathway and PPAR signaling pathway. The results of in vitro experiments indicated that ROB may inhibit the proliferation and metastasis of lung cancer cells and activate the PPARγ signaling pathway, as well as induce cellular autophagy.ConclusionsThe results of this study comprehensively elucidated the potential targets and molecular mechanisms of ROB for the treatment of lung cancer, providing new ideas for further lung cancer therapy.
Chemotherapy combined with immune checkpoint inhibitors may overcome the detrimental effect of high neutrophil-to-lymphocyte ratio prior to treatment in esophageal cancer patients
Authors: Hirasawa Yuya , Kubota Yutaro , Mura Emiko , Suzuki Risako , Tsurui Toshiaki , Iriguchi Nana , Ishiguro Tomoyuki , Ohkuma Ryotaro , Shimokawa Masahiro , Ariizumi Hirotsugu , Horiike Atsushi , Wada Satoshi , Yamashita Takeshi , Ariyoshi Tomotake , Goto Satoru , Otsuka Koji , Murakami Masahiko , Kiuchi Yuji , Yoshimura Kiyoshi , Tsunoda Takuya 
Published: October 2024

IntroductionImmune checkpoint inhibitors (ICIs) have emerged as a promising treatment option for esophageal cancer (EC). Although ICIs enable long-term survival in some patients, the efficacy of ICIs varies widely among patients. Therefore, predictive biomarkers are necessary for identifying patients who are most likely to benefit from ICIs to improve the efficacy of the treatment. We retrospectively analyzed the outcomes of combination therapy, including nivolumab plus ipilimumab or chemotherapy plus anti-programmed cell death 1 (PD-1) antibodies in our institute to identify biomarkers.MethodsTwenty-seven patients received nivolumab plus ipilimumab, and thirty-six patients received chemotherapy plus anti-PD-1 antibodies were included in this study. We analyzed patient characteristics, efficacy, and safety. Multivariable analysis of biomarkers evaluated the correlation among overall survival (OS), progression-free survival (PFS), and the following variables: body mass index, performance status, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein level, and albumin level before treatment.ResultsIn multivariable analysis, albumin level was significantly correlated with PFS in the cisplatin plus 5-fluorouracil (CF) plus pembrolizumab group. NLR and albumin level were significantly correlated with OS in the nivolumab plus ipilimumab group. Other variables, including PS, BMI, and CRP did not correlate with any of the outcomes.ConclusionsHigh NLR in EC patients prior to treatment was significantly less effective for ICIs. In chemotherapy combined with ICIs, NLR before the treatment was not associated with treatment efficacy, suggesting combination chemotherapy may be beneficial for EC patients with high NLR. NLR may be an indicator of immunocompetence in anti-tumor immunity and a convenient predictive biomarker for selecting appropriate treatments including ICIs.
Association of mutation profiles with metastasis in patients with non-small cell lung cancer
Authors: Li Yingxue , Zheng Zheng , Wang Li , Han Lin , Du Ying , Zhang Xuedong , Liu Xia , Xie Jiaping 
Published: October 2024

ObjectiveThis study focused on the analysis of the correlation between common gene mutation types and metastatic sites in NSCLC patients.MethodsWe retrospectively studied 1586 NSCLC patients and used fluorescence Polymerase chain reaction (PCR) to detect EGFR, ALK, ROS1, RET, MET, BRAF, HER2, KRAS, NRAS, and PIK3CA gene mutations, and also investigated sex, smoking status, age at diagnosis, histological type and TNM stage. In addition, we analyzed the site of metastasis in patients with stage IV NSCLC.ResultsThe EGFR-mutation group more frequently metastasized to lung (18.9%, P = 0.004), brain (18.9%, P = 0.001) and bone (27.1%, P = 0.004) than wild-type patients. ALK-mutation group (71.0%, P &lt; 0.001), BRAF-mutation group (82.4%, P = 0.005) and NRAS-mutation group (100%, P = 0.025) were more likely to metastasize than the wild-type group. In the ALK mutation, lung metastasis (24.2%, P = 0.013), brain (24.2%, P = 0.007), bone metastasis (32.3%, P = 0.024), liver metastasis (19.4%, P = 0.001), and pleural metastasis (29.0%, P = 0.021) were common. In the KRAS-mutation group, lung metastasis (21.7%, P = 0.012) and brain metastasis (23.3%, P = 0.001) were more common. Less metastasis occurred in the HER2-mutation group (28.3%, P = 0.014). There was no difference in the RET, MET and PIK3CA mutations.ConclusionPatients with ALK mutant, BRAF mutant or NRAS mutant were more prone to metastasis, while the HER 2 mutation group was less metastatic. Patients with EGFR mutant NSCLC are more likely to develop bone, lung, or brain metastasis.
Development and validation of a clinical prognostic model for BRAF V600E-mutated colorectal cancer patients based on pathological stage, microsatellite status, and primary tumor site
Authors: Ou Kai , Liu Xiu , Ma Xiaoting , Yang Lin 
Published: October 2024

ObjectiveTo develop and validate a prognostic model for patients with BRAF V600E-mutated colorectal cancer.MethodsThe clinical and pathological information of 206 patients with BRAF V600E-mutated colorectal cancer diagnosed in Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from 2014 to 2021 was retrospectively collected. Least absolute shrinkage and selection operator (LASSO) regression, Cox regression, and nomograms were used to develop clinical prognostic models. The differentiation was measured using C-statistic, and the predicted variability was evaluated using the calibration curve. The prognostic model was externally validated using validation set data from 164 patients pooled from five studies.ResultsOur clinical prognostic model included three variables: pathological stage, microsatellite status, and primary tumor site. In internal validation, the model had a concordant index of 0.785 (95% CI [0.732–0.839]) and a concordant index of 0.754 (95% CI [0.698–0.810]) using pathological staging. External validation confirmed the robustness of the model with a consistency index of 0.670 (95% CI [0.617–0.724]) and a consistency index of 0.584 (95% CI [0.546–0.622]) using pathological staging. Likelihood ratio test results show that our model is better (internal validation, p = 5.141e−03; external validation, p = 2.728e−05). The calibration graph drawn based on the prediction and the actual situation is close to the 45° diagonal.ConclusionBy adding microsatellite status and primary tumor site on the basis of pathological stage, we improved the discriminability and prediction accuracy of the model and successfully established a prognosis model for patients with BRAF V600E mutation of colorectal cancer.