bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of an immune-related lncRNA signature pair for predicting oncologic outcomes and the sensitivity of immunosuppressor in treatment of lung adenocarcinoma
Authors: Zhuang Jinman , Chen Zhongwu , Chen Zishan , Chen Jin , Liu Maolin , Xu Xinying , Liu Yuhang , Yang Shuyan , Hu Zhijian , He Fei 
Published: May 2022

Abstract
Background
Although immunotherapy has shown clinical activity in lung adenocarcinoma (LUAD), LUAD prognosis has been a perplexing problem. We aimed to construct an immune-related lncRNA pairs (IRLPs) score for LUAD and identify what immunosuppressor are appropriate for which group of people with LUAD.

Methods
Based on The Cancer Genome Atlas (TCGA)-LUAD cohort, IRLPs were identified to construct an IRLPs scoring system by Cox regression and validated in the Gene Expression Omnibus (GEO) dataset using log-rank test and the receiver operating characteristic curve (ROC). Next, we used spearman’s correlation analysis, t-test, signaling pathways analysis and gene mutation analysis to explore immune and molecular characteristics in different IRLP subgroups. The “pRRophetic” package was used to predict the sensitivity of immunosuppressant.

Results
The IRLPs score was constructed based on eight IRLPs calculated as 2.12 × (MIR31HG|RRN3P2) + 0.43 × (NKX2-1-AS1|AC083949.1) + 1.79 × (TMPO-AS1|LPP-AS2) + 1.60 × (TMPO-AS1|MGC32805) + 1.79 × (TMPO-AS1|PINK1-AS) + 0.65 × (SH3BP5-AS1|LINC01137) + 0.51 × (LINC01004|SH3PXD2A-AS1) + 0.62 × (LINC00339|AGAP2-AS1). Patients with a lower IRLPs risk score had a better overall survival (OS) (Log-rank test PTCGA train dataset < 0.001, PTCGA test dataset = 0.017, PGEO dataset = 0.027) and similar results were observed in the AUCs of TCGA dataset and GEO dataset (AUC TCGA train dataset = 0.777, AUC TCGA test dataset = 0.685, AUC TCGA total dataset = 0.733, AUC GEO dataset = 0.680). Immune score (Cor = -0.18893, P < 0.001), stoma score (Cor = -0.24804, P < 0.001), and microenvironment score (Cor = -0.22338, P < 0.001) were significantly decreased in the patients with the higher IRLP risk score. The gene set enrichment analysis found that high-risk group enriched in molecular changes in DNA and chromosomes signaling pathways, and in this group the tumor mutation burden (TMB) was higher than in the low-risk group (P = 0.0015). Immunosuppressor methotrexate sensitivity was higher in the high-risk group (P = 0.0052), whereas parthenolide (P < 0.001) and rapamycin (P = 0.013) sensitivity were lower in the high-risk group.

Conclusions
Our study established an IRLPs scoring system as a biomarker to help in the prognosis, the identification of molecular and immune characteristics, and the patient-tailored selection of the most suitable immunosuppressor for LUAD therapy.
Extracellular vesicles from the inflammatory microenvironment regulate the osteogenic and odontogenic differentiation of periodontal ligament stem cells by miR-758-5p/LMBR1/BMP2/4 axis
Authors: Yan Chaoting , Li Na , Xiao Tong , Ye Xiaying , Fu Lin , Ye Yu , Xu Tao , Yu Jinhua 
Published: May 2022

Abstract
Background
Extracellular vesicles (EVs) play a key role in constructing a microenvironment that favors the differentiation of stem cells. The present work aimed to determine the molecular mechanisms by which EV derived from inflammatory dental pulp stem cell (iDPSC-EV) influence periodontal ligament stem cells (PDLSCs) and provide a potential strategy for bone and dental pulp regeneration.

Methods
The osteogenic and odontogenic differentiation was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, alkaline phosphatase (ALP) activity assay, ALP staining, alizarin red S (ARS) staining, and immunofluorescence staining. To detect proliferation, the Cell Counting Kit-8 (CCK-8) assay, and flow cytometry analysis were used. EVs were isolated by the Exoperfect kit and ultrafiltration and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. The expression profile of miRNAs in EVs was studied using miRNA sequence and bioinformatics, and one of the upregulated miRNAs was evaluated on PDLSCs.

Results
The inflammatory microenvironment stimulated osteogenic and odontogenic differentiation of DPSCs and iDPSC-EV behaved alike on PDLSCs. MiR-758-5p was upregulated in iDPSC-EV and was demonstrated to play a significant role in the osteogenic and odontogenic commitment of PDLSCs. A dual-luciferase reporter assay confirmed the binding site between miR-758-5p and limb development membrane protein 1 (LMBR1). The knockdown of LMBR1 also enhanced the above potential. Mechanically, bone morphogenetic protein (BMP) signaling was activated.

Conclusions
EVs from the inflammatory microenvironment enhanced the osteogenic and odontogenic differentiation of PDLSCs partly by shuttering LMBR1-targeting miR-758-5p via BMP signaling.
Identification of mutation patterns and circulating tumour DNA-derived prognostic markers in advanced breast cancer patients
Authors: Liao Hao , Zhang Jiayang , Zheng Tiantian , Liu Xiaoran , Zhong Jianxin , Shao Bin , Dong Xiaoxi , Wang Xiaohong , Du Pan , King Bonnie L. , Jia Shidong , Yu Jianjun , Li Huiping 
Published: May 2022

AbstractBackgroundThe correlations between circulating tumour DNA (ctDNA)-derived genomic markers and treatment response and survival outcome in Chinese patients with advanced breast cancer (ABC) have not been extensively characterized.MethodsBlood samples from 141 ABC patients who underwent first-line standard treatment in Peking University Cancer Hospital were collected. A next-generation sequencing based liquid biopsy assay (PredicineCARE) was used to detect somatic mutations and copy number variations (CNVs) in ctDNA. A subset of matched blood samples and tumour tissue biopsies were compared to evaluate the concordance.ResultsOverall, TP53 (44.0%) and PIK3CA (28.4%) were the top two altered genes. Frequent CNVs included amplifications of ERBB2 (24.8%) and FGFR1 (8.5%) and deletions of CDKN2A (3.5%). PIK3CA/TP53 and FGFR1/2/3 variants were associated with drug resistance in hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-positive (HER2 +) patients. The comparison of genomic variants across matched tumour tissue and ctDNA samples revealed a moderate to high concordance that was gene dependent. Triple-negative breast cancer (TNBC) patients harbouring TP53 or PIK3CA alterations had a shorter overall survival than those without corresponding mutations (P = 0.03 and 0.008). A high ctDNA fraction was correlated with a shorter progression-free survival (PFS) (P = 0.005) in TNBC patients. High blood-based tumor mutation burden (bTMB) was associated with a shorter PFS for HER2 + and TNBC patients (P = 0.009 and 0.05). Moreover, disease monitoring revealed several acquired genomic variants such as ESR1 mutations, CDKN2A deletions, and FGFR1 amplifications.ConclusionsThis study revealed the molecular profiles of Chinese patients with ABC and the clinical validity of ctDNA-derived markers, including the ctDNA fraction and bTMB, for predicting treatment response, prognosis, and disease progression.Trial registration: ClinicalTrials.gov ID: NCT03792529. Registered January 3rd 2019,https://clinicaltrials.gov/ct2/show/NCT03792529.
Z-DNA binding protein 1 mediates necroptotic and apoptotic cell death pathways in murine astrocytes following herpes simplex virus-1 infection
Authors: Jeffries Austin M. , Suptela Alexander J. , Marriott Ian 
Published: May 2022

Abstract
Background
The mechanisms by which glia respond to viral central nervous system (CNS) pathogens are now becoming apparent with the demonstration that microglia and astrocytes express an array of pattern recognition receptors that include intracellular RNA and DNA sensors. We have previously demonstrated that glia express Z-DNA binding protein 1 (ZBP1) and showed that this cytosolic nucleic acid sensor contributes to the inflammatory/neurotoxic responses of these cells to herpes simplex virus-1 (HSV-1). However, the relative contribution made by ZBP1- to HSV-1-mediated cell death in glia has not been determined.

Methods
We have investigated the relative contribution made by ZBP1- to HSV-1-mediated cell death in primary astrocytes derived from mice genetically deficient in this sensor. We have used capture ELISAs and immunoblot analysis to assess inflammatory cytokine production and ZBP1 and phosphorylated mixed lineage kinase domain-like protein (MLKL) expression levels, respectively, following HSV-1 challenge. Furthermore, we have used a commercially available cell viability assay to determine the proportion and rate of cell death in cells following infection with laboratory and neuroinvasive clinical strains of HSV-1, and pharmacological inhibitors of necroptotic and apoptotic pathway components to assess the relative role of each.

Results
We show that the loss of ZBP1 in astrocytes results in an increase in the number of viral particles released following HSV-1 infection. Importantly, we have confirmed that HSV-1 induces necroptosis in astrocytes and have established the ability of ZBP1 to mediate this cell death pathway. Interestingly, while ZBP1 is best known for its role in necroptotic signaling, our findings indicate that this sensor can also contribute to virally induced apoptosis in these glia.

Conclusions
Our findings indicate that ZBP1 serves as a restriction factor for HSV-1 infection and is associated with the induction of both necroptotic and apoptotic cell death pathways in primary murine astrocytes. While it remains to be seen whether ZBP1-mediated activation of cell death in astrocytes contributes significantly to host protection or, rather, exacerbates HSV-1 encephalitis pathology, the identification of such a role in resident CNS cells may represent a novel target for therapeutic intervention to reduce HSV encephalitis-associated morbidity and mortality.
The correlation between cutout and eccentric distance (ED) of the cephalic fixator tip in geriatric intertrochanteric fractures with internal fixation
Authors: Yang Yun-fa , Huang Jian-wen , Gao Xiao-sheng , Xu Zhong-he 
Published: May 2022

Abstract
Background
The location of cephalic fixator tip with different eccentric distance (ED) should have different risks of cutout. This study aims to evaluate the cephalic fixator tip position by measuring ED of the cephalic fixator tip in geriatric ITF patients with single-screw cephalomedullary nail (SCMN) fixation and analyze the correlation between the cutout and the ED.

Methods
Firstly, we assumed all the femoral head was a regular sphere and standardized the radius of the femoral head (RFD) as “3” no matter how big the RFD was for complete match of the Cleveland zone system and convenient identification of artificial intelligence. Secondly, we measured the ED of the cephalic fixator tip by calculating the distances from the cephalic fixator tip to the geometric central axis of the femoral neck and head on both AP view and lateral view radiographs. Thirdly, we evaluated all the ED of the cephalic fixator tip in the eligible 123 geriatric ITF patients and analyzed the correlation between the cutout and the ED.

Results
The ED in cutout group (1.25 ± 0.43) is much bigger than that in non-cutout group (0.64 ± 0.34) with significant difference (OR = 50.01, 95% CI 8.42–297.19, p < 0.001). The probability of cutout increased with ED increasing, especially when “ED ≥ 1.” The best cutoff value of ED for predicting cutout was “1.022” (“1.022” was just a little bit more than 1/3 times of RFD because “RFD = 3,” sensitivity = 73.3%, specificity = 86.1%, and AUC = 0.867, p < 0.001).

Conclusion
ED is suitable for evaluation of the cephalic fixator tip position for predicting cutout in geriatric ITF patients with SCMN fixation, and ED can potentially be used as artificial intelligence application during surgery. The smaller the ED, the lower the cutout rate. For avoiding cutout, the ED of the cephalic fixator tip should be less than one-third times of the radius of the femoral head.
Microdeletions in 1q21 and 8q12.1 depict two additional molecular subgroups of Silver-Russell syndrome like phenotypes
Authors: Baba Naomi , Lengyel Anna , Pinti Eva , Yapici Elzem , Schreyer Isolde , Liehr Thomas , Fekete György , Eggermann Thomas 
Published: May 2022

Abstract
Background
Silver-Russell syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction, relative macrocephaly at birth, body asymmetry and typical facial features. Clinical and molecular heterogeneity is described in SRS. Common causes are loss of methylation of the imprinting center 1 in 11p15 and maternal uniparental disomy of chromosome 7. Other genetic alterations include disturbances of imprinted regions in 14q32, 7q32 and 11p15 as well as submicroscopic deletions and duplications. Single nucleotide variants in genes like IGF2, HMGA2, PLAG1, CDKN1C have also been identified in patients with SRS phenotypes. However, routine molecular diagnostics usually focus on 11p15 and chromosome 7, while less frequent causes are not systematically addressed.

Results
Here we report two patients with SRS features in which molecular karyotyping revealed microdeletions in 1q21 and 8q12.1 respectively. In a 3.5-year-old girl with postnatal growth restriction, feeding difficulties, relative macrocephaly and distinct SRS features a 2 Mb deletion in 1q21.1q21.2 was identified. Our second case is a 1.5-year-old boy with intrauterine and postnatal growth restriction, feeding difficulties and distinct facial features with a 77 kb deletion in 8q12.1 affecting PLAG1 as the only protein-encoding gene with known function.

Conclusions
The 1q21 region has not yet been assigned as an SRS region, although six patients with the same deletion and SRS features including relative macrocephaly have been described before. This new case adds to the evidence that distal 1q21 should be annotated as an SRS candidate region. The PLAGL1 alteration is the smallest deletion in 8q12.1 ever reported in a patient with SRS phenotype and it finally confirms that PLAG1 is the SRS causing gene in 8q12.1. To increase the diagnostic yield in patients with suspected SRS, we recommend both molecular karyotyping and next generation sequencing-based approaches.
Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations
Authors: Eckardt Jan-Niklas , Stölzel Friedrich , Kunadt Desiree , Röllig Christoph , Stasik Sebastian , Wagenführ Lisa , Jöhrens Korinna , Kuithan Friederike , Krämer Alwin , Scholl Sebastian , Hochhaus Andreas , Crysandt Martina , Brümmendorf Tim H. , Naumann Ralph , Steffen Björn , Kunzmann Volker , Einsele Hermann , Schaich Markus , Burchert Andreas , Neubauer Andreas , Schäfer-Eckart Kerstin , Schliemann Christoph , Krause Stefan W. , Herbst Regina , Hänel Mathias , Hanoun Maher , Kaiser Ulrich , Kaufmann Martin , Rácil Zdenek , Mayer Jiri , Kroschinsky Frank , Berdel Wolfgang E. , Ehninger Gerhard , Serve Hubert , Müller-Tidow Carsten , Platzbecker Uwe , Baldus Claudia D. , Schetelig Johannes , Bornhäuser Martin , Thiede Christian , Middeke Jan Moritz 
Published: May 2022

Abstract
Background
Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed.

Methods
We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM.

Results
AML patients with EM presented with significantly higher counts of white blood cells (p < 0.0001), peripheral blood blasts (p < 0.0001), bone marrow blasts (p = 0.019), and LDH (p < 0.0001). Regarding molecular genetics, EM AML was associated with mutations of NPM1 (OR: 1.66, p < 0.001), FLT3-ITD (OR: 1.72, p < 0.001) and PTPN11 (OR: 2.46, p < 0.001). With regard to clinical outcomes, EM AML patients were less likely to achieve complete remissions (OR: 0.62, p = 0.004), and had a higher early death rate (OR: 2.23, p = 0.003). Multivariable analysis revealed EM as an independent risk factor for reduced overall survival (hazard ratio [HR]: 1.43, p < 0.001), however, for patients who received allogeneic hematopoietic cell transplantation (HCT) survival did not differ. For patients bearing EM AML, multivariable analysis unveiled mutated TP53 and IKZF1 as independent risk factors for reduced event-free (HR: 4.45, p < 0.001, and HR: 2.05, p = 0.044, respectively) and overall survival (HR: 2.48, p = 0.026, and HR: 2.63, p = 0.008, respectively).

Conclusion
Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM.
DNA methylation may affect beef tenderness through signal transduction in Bos indicus
Authors: de Souza Marcela Maria , Niciura Simone Cristina Méo , Rocha Marina Ibelli Pereira , Pan Zhangyuan , Zhou Huaijun , Bruscadin Jennifer Jessica , da Silva Diniz Wellison Jarles , Afonso Juliana , de Oliveira Priscila Silva Neubern , Mourão Gerson B. , Zerlotini Adhemar , Coutinho Luiz Lehmann , Koltes James E. , de Almeida Regitano Luciana Correia 
Published: May 2022

Abstract
Background
Beef tenderness is a complex trait of economic importance for the beef industry. Understanding the epigenetic mechanisms underlying this trait may help improve the accuracy of breeding programs. However, little is known about epigenetic effects on Bos taurus muscle and their implications in tenderness, and no studies have been conducted in Bos indicus.

Results
Comparing methylation profile of Bos indicus skeletal muscle with contrasting beef tenderness at 14 days after slaughter, we identified differentially methylated cytosines and regions associated with this trait. Interestingly, muscle that became tender beef had higher levels of hypermethylation compared to the tough group. Enrichment analysis of predicted target genes suggested that differences in methylation between tender and tough beef may affect signal transduction pathways, among which G protein signaling was a key pathway. In addition, different methylation levels were found associated with expression levels of GNAS, PDE4B, EPCAM and EBF3 genes. The differentially methylated elements correlated with EBF3 and GNAS genes overlapped CpG islands and regulatory elements. GNAS, a complex imprinted gene, has a key role on G protein signaling pathways. Moreover, both G protein signaling pathway and the EBF3 gene regulate muscle homeostasis, relaxation, and muscle cell-specificity.

Conclusions
We present differentially methylated loci that may be of interest to decipher the epigenetic mechanisms affecting tenderness. Supported by the previous knowledge about regulatory elements and gene function, the methylation data suggests EBF3 and GNAS as potential candidate genes and G protein signaling as potential candidate pathway associated with beef tenderness via methylation.
Effect of legumes in energy reduced dietary approaches to stop hypertension (DASH) diet on blood pressure among overweight and obese type 2 diabetic patients: a randomized controlled trial
Authors: Hosseinpour-Niazi Somayeh , Hadaegh Farzad , Mirmiran Parvin , Daneshpour Maryam S. , Mahdavi Maryam , Azizi Fereidoun 
Published: May 2022

AbstractBackgroundThis study aimed to investigate the effects of legumes in dietary approaches to stop hypertension (DASH) on blood pressure and urinary sodium and potassium in participants with type 2 diabetes. We further investigated whether changes in individual dietary food groups in the DASH diet contribute to blood pressure.MethodsParticipants were randomized to the traditional DASH diet (n = 150) or the legume-based DASH diet (n = 150). Blood pressure and urinary sodium and potassium were measured at baseline and after 16-week interventions. An intention-to-treat approach with multiple imputations of missing data was applied. The restricted cubic spline (RCS) was applied to assess the linearity and explore the shape of the relationship between the changes in food groups and systolic blood pressure (SBP) in the two intervention groups.ResultsA reduction in SBP and urinary sodium was observed at week 16 in both dietary interventions, and this reduction was more significant in the legume-based DASH diet, than in the DASH diet. In the legume-based DASH diet, SBP decreased with the legume intake of more than 95.8 g/day (Pnonlinear < 0.001). The multivariable RCS analysis showed a U-shaped relationship of refined grains, an L-shaped relationship of fruits, and a linear relationship of sweet, energy, sodium and vegetables intake with SBP.ConclusionsThe DASH diet, enriched in legumes, could improve SBP in participants with type 2 diabetes. In DASH diet, the balance of consumption of refined grains and fruits along with higher vegetable consumption and lower sweet, sodium and energy intake reduced the SBP.Trial registration:IRCT20090203001640N17.
Influence of combined action observation and motor imagery of walking on lower limb reflex modulation in patients after stroke–preliminary results
Authors: Behrendt Frank , Le-Minh Monika , Schuster-Amft Corina 
Published: May 2022

Abstract
Objective
The combined use of action observation and motor imagery (AOMI) is a promising technique in neurorehabilitation that can be usefully applied in addition to conventional forms of therapy. Previous studies with healthy participants showed that the mere passive observation of walking results in a phase-dependent reflex modulation in the tibialis anterior muscle that resembles the pattern occurring when walking. In patients after stroke, a similar reflex modulation was found in several lower limb muscles during the real execution of walking, but responses were blunted. To clarify whether and how lower limb reflex responses are also modulated in such patients during the combined synchronous observation and imagery of walking, medium-latency cutaneous reflexes from the tibialis anterior muscle were measured. We compared the reflex responses of seven patients after stroke during the AOMI of walking from two different conditions: (a) elicited during the end stance phase and (b) during the end swing phase, both normalized to a baseline condition.

Results
So far, using the identical methodological set-up as in our study with healthy individuals, we could not find any noteworthy reflex response modulation. The study was registered with the German Clinical Trials Register (DRKS00028255).
Trial registration : The study was registered with the German Clinical Trials Register: DRKS00028255.