bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Mutation in AIMP2/P38, the Scaffold for the Multi-Trna Synthetase Complex, and Association With Progressive Neurodevelopmental Disorders
Authors: Mazaheri Mahta , Yavari Mahdie , Zare Marzouni Hadi , Stufano Angela , Lovreglio Piero , D'Amore Simona , Jahantigh Hamid Reza 
Published: January 2022

Background: Leukodystrophies constitute a heterogeneous group of inherited disorders primarily affecting the white matter of the central nervous system. Aminoacyl-tRNA synthetases (ARSs) catalyze the attachment of an amino acids to their cognate transfer RNAs (tRNAs). Pathogenic variants in both cytosolic and mitochondrial ARSs have been linked to a broad range of neurological disorders, including hypomyelinating leukodystrophies and pontocerebellar hypoplasias (PCH). Aminoacyl tRNA synthetase-interacting multifunctional protein 2 (AIMP2), one of the three non-catalytic components of multi ARS complex, harbors anti-proliferative activity and functions as a proapoptotic factor thus promoting cell death. We report a case of a 7-month-old infant with a complex clinical presentation, including weight loss, severe anemia, skeletal abnormalities, microcephaly and MR imaging features of leukodystrophy with a novel mutation in AIMP2.Methods: Whole-exome sequencing (WES) was performed on the proband. Parental samples were analyzed by PCR amplification and Sanger sequencing.Results: Whole-exome sequencing revealed a novel variant c.A463T in the homozygous state in exon 3 (NM_001,326,607) of AIMP2 [p.(K155X)] in the proband. Parental carrier status was confirmed by target sequencing.Conclusion: Here, we present an Iranian case with leukodystrophy with a novel AIMP2 mutation. This finding broadens the mutational and phenotypic spectra of AIMP2-related leukodystrophy and offers guidance for proper genetic counselling for pre- and post-natal screenings as well as for disease management.
Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study
Authors: Xu Qian , Ni Jing-Jing , Han Bai-Xue , Yan Shan-Shan , Wei Xin-Tong , Feng Gui-Juan , Zhang Hong , Zhang Lei , Li Bin , Pei Yu-Fang 
Published: January 2022

BackgroundGrowing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.ObjectiveTo reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis.Materials and MethodsWe assessed genome-wide association study (GWAS) summary statistics for gut microbiota and six common ADs, namely, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes (T1D), and celiac disease (CeD), from published GWASs. Two-sample MR analyses were first performed to identify causal bacterial taxa for ADs in discovery samples. Significant bacterial taxa were further replicated in independent replication outcome samples. A series of sensitivity analyses was performed to validate the robustness of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation.ResultsCombining the results from the discovery and replication stages, we identified one causal bacterial genus, Bifidobacterium. A higher relative abundance of the Bifidobacterium genus was associated with a higher risk of T1D [odds ratio (OR): 1.605; 95% CI, 1.339–1.922; PFDR = 4.19 × 10−7] and CeD (OR: 1.401; 95% CI, 1.139–1.722; PFDR = 2.03 × 10−3), respectively. Further sensitivity analyses validated the robustness of the above associations. The results of reverse MR analysis showed no evidence of reverse causality from T1D and CeD to the Bifidobacterium genus.ConclusionThis study implied a causal relationship between the Bifidobacterium genus and T1D and CeD, thus providing novel insights into the gut microbiota-mediated development mechanism of ADs.
Expression Profiles and Prognostic Value of Multiple Inhibitory Checkpoints in Head and Neck Lymphoepithelioma-Like Carcinoma
Authors: Zou Wen-Qing , Luo Wei-Jie , Feng Yan-Fen , Liu Fang , Liang Shao-Bo , Fang Xue-Liang , Liang Ye-Lin , Liu Na , Wang Ya-Qin , Mao Yan-Ping 
Published: January 2022

BackgroundInhibitory checkpoints are promising antitumor targets and predictive biomarkers in a variety of cancers. We aimed to identify the expression levels and prognostic value of multiple inhibitory checkpoints supported by preclinical and clinical evidence in head and neck lymphoepithelioma-like carcinoma (HNLELC).MethodsThe expression of seven inhibitory checkpoints were evaluated in the tumor nest (TN) and tumor stroma (TS) of 102 HNLELC specimens using immunohistochemistry and digital pathology, and an inhibitory checkpoint-based signature (ICS) was subsequently constructed using the LASSO Cox regression model.ResultsPD-L1, B7H3, and IDO-1 were mostly expressed in the TN, with median H-score of TN vs TS: 63.6 vs 14.6; 8.1 vs 1.0; 61.5 vs 34.7 (all P &lt; 0.001), whereas PD-1, TIM-3, LAG-3, and VISTA were mainly observed in the TS, with median H-score of TN vs TS: 0.2 vs 12.4, 3.4 vs 7.1, 6.2 vs 11.9, 16.4 vs 47.2 (all P &lt; 0.001), respectively. The most common simultaneously expressed combinations consisted of PD-L1 + B7H3 + IDO-1 + TIM-3 + LAG-3 + VISTA and B7H3 + IDO-1 + TIM-3 + LAG-3 in the TN (both occurring in 8.8% of patients) and PD-L1 + B7H3 + IDO-1 in the TS (4.9%). In addition, high-ICS patients had shorter 5-year disease-free (40.6% vs 81.7%; P &lt; 0.001), regional recurrence-free (63.5% vs 88.2%; P = 0.003), and overall survival (73.5% vs 92.9%; P = 0.006) than low-ICS patients. Multivariate analysis revealed that ICS represented an independent predictor, which could significantly complement the predictive performance of TNM stage for 3-year (AUC 0.724 vs 0.619, P = 0.014), 5-year (AUC 0.727 vs 0.640, P = 0.056), and 10-year disease-free survival (AUC 0.815 vs 0.709, P = 0.023).ConclusionsThe expression of inhibitory checkpoints and ICS classifier may increase the prognostic value of the TNM staging system and guide the rational design of personalized inhibitory checkpoint blockade therapy in HNLELC.
Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway
Authors: Zhang Biao , Xue Yi , Zhao Jin , Jiang Huojun , Zhu Jiaoli , Yin Hao , Qiu Yizhen , Hu Aihao , Xu Lingqi , Song Yi , Wang Xin 
Published: January 2022

BackgroundsTo date, there are no specific drugs approved for the treatment of sepsis associated acute kidney injury (AKI). Shionone is a natural component with anti-inflammatory activity. In this study, we sought to determine the functional role of Shionone in sepsis-induced AKI.MethodsAnimal models of AKI were constructed by cecum ligation and puncture (CLP) surgery. C57BL/6 mice were randomly assigned to the Sham, CLP, 10 mg/kg DXM, 50 mg/kg Shionone and 100 mg/kg Shionone groups. RAW264.7 treated with lipopolysaccharides (LPS) was used as anin vitrosepsis model and cells were divided into control, LPS, 1 μg/mL Shionone and 2 μg/mL Shionone groups. The pathological status was assessed by Hematoxylin-Eosin (HE) staining assay, protein expressions were detected by immunofluorescence staining and Western blot, macrophage typing was detected by flow, and the levels of pro-inflammatory factors (IL-6, IL-12, IL-1β, TNF-α) and anti-inflammatory factors (IL-10 and TGF-β) were measured using the corresponding kits.ResultsECM1 is highly expressed in tissue-infiltrating macrophages under inflammatory conditions. It has been observed that Shionone inhibits the expression of ECM1 and attenuates sepsis-induced injury in kidney and inflammatory factor levels in serum. In addition, Shionone may reduce inflammatory factor levels through the promotion of M2 macrophages by GM-CSF/STAT5/Arg1 pathway to alleviate sepsis induced inflammationin vitro.ConclusionThese findings demonstrate that Shionone can alleviate sepsis-induced AKI by promoting M2 macrophage polarization through regulating the ECM1/STAT5 pathway.
Different Types of Hyperfluorescence Observed in Post Anti-VEGF Fluorescein Angiographic Patterns in Retinopathy of Prematurity Patients
Authors: Jin Enzhong , Yin Hong , Liu Kailin , Liang Zhiqiao , Zhao Mingwei 
Published: January 2022

PurposeTo demonstrate that the demographic and treatment characteristics of retinopathy of prematurity (ROP) eyes showed different types of hyperfluorescence in fluorescein angiography (FA) initially treated with anti-vascular endothelial growth factor (VEGF) agents.MethodsA consecutive case series of ROP treated with anti-VEGF agents was retrospectively studied. All the patients underwent FA examinations at least 6 months later after treatment. The demographic and treatment characteristics of eyes with or without hyperfluorescence in FA were analyzed. The different types of hyperfluorescence were divided into three groups, including vascular leakage, fibrous membrane, and vascular abnormality.ResultsTwo hundred and forty-two eyes of 123 patients with treatment-required ROP were included. Hyperfluorescence was defined in 51/242 eyes, and 2.08 ± 1.11 injections were performed for them, while the eyes without hyperfluorescence received 1.65 ± 0.80 injections (P = 0.013). Vascular leakage was defined in 26/51 hyperfluorescence eyes. The postmenstrual age (PMA) of first injection for the hyperfluorescence group was 38.56 ± 3.24 weeks, which is earlier than that of infants without hyperfluorescence (P = 0.011). More additional treatments were performed in eyes with hyperfluorescence (23.53 vs. 3.66%, P = 0.000). Among them, the eyes with vascular leakage required more additional treatment than eyes without vascular leakage (42.31 vs. 4.00%, P = 0.004). For the 26 eyes with vascular leakage, 11 eyes of 8 patients received further treatments during further follow-up. No significant difference of refractive errors can be defined between different groups.ConclusionEyes with persistent hyperfluorescencein FA after treatment required more anti-VEGF and additional treatments, including laser and PPV. Not all hyperfluorescences were vascular leakage and required additional treatment.
Association of Novel Androgen Receptor Axis-Targeted Therapies With Diarrhea in Patients With Prostate Cancer: A Bayesian Network Analysis
Authors: Xiong Xingyu , Xu Hang , Wang Sheng , Liao Xinyang , Yi Xianyanling , Jin Kun , Lei Haoran , Bai Shengjiang , Qiu Shi , Yang Lu 
Published: January 2022

ObjectiveTo perform a systematic review and network meta-analysis to characterize the effect of novel androgen receptor axis-target (ARAT) agents on diarrhea and constipation.MethodsWe searched the Pubmed, Web of Science, and ClinicalTrials.gov up to September 2021 for phase 3 randomized controlled trials (RCTs) of patients receiving novel ARAT agents for prostate cancer (CaP). A Cochrane risk-of-bias tool was used to assess trial quality. The primary outcomes were risk ratio (RR) of any-grade diarrhea and constipation for patients receiving ARAT treatment. RRs of competing treatments were evaluated by pairwise and Bayesian network meta-analysis.ResultsIn this study, 13 trials with 15,117 participants comparing 5 treatments (abiraterone, enzalutamide, apalutamide, darolutamide, and placebo) were identified. Use of novel ARAT agents was associated with a significant increased risk of any-grade diarrhea (RR = 1.30, 95% CI [1.16, 1.44]). As for subgroup analysis, abiraterone, enzalutamide, and apalutamide were all associated with significant increased risk of any-grade diarrhea (abiraterone: RR = 1.40, 95% CI [1.09, 1.81]; enzalutamide: RR = 1.17, 95% CI [1.02, 1.35]; apalutamide: RR = 1.35, 95% CI [1.03, 1.76]). Based on Bayesian modeling, abiraterone and enzalutamide showed the highest and lowest probability to rank first in terms of increasing risk of any-grade diarrhea. There were no significant differences of risk in any-grade constipation, grade 3 or greater diarrhea, and constipation between ARAT and control group.ConclusionThe present study indicates that the use of novel ARAT agents is associated with a significantly higher risk of diarrhea. Across the four agents, abiraterone may relate to the highest risk of diarrhea among patients with metastatic hormone sensitive prostate cancer (mHSPC) and castration-resistant prostate cancer (CRPC).
Spontaneous Intramuscular Hemorrhage in Anti-MDA5 Positive Dermatomyositis: A Case Series and Literature Review
Authors: Xu Zhangling , Lv Xia , Xu Wenwen , Ye Yan , Wang Xiaodong , Ye Shuang , Ding Huihua , Wu Wanlong 
Published: January 2022

ObjectiveSpontaneous intramuscular hemorrhage (SIH) is a rare but life-threatening complication associated with dermatomyositis (DM). This study reported a case series of SIH associated with DM. In addition, the characteristics and prognostic effects for this complication were analyzed based on literature review.MethodsWe reported seven cases of anti-melanoma differentiation-associated gene five positive dermatomyositis (MDA5+DM) complicated by SIH in our single-center cohort, and a comprehensive literature review was performed. Clinical characteristics, treatment, and outcome data of all eligible reported cases were summarized. Potential prognostic effects were identified by comparisons between the deceased and survivors.ResultsAmong cumulatively reported patients with DM patients and SIH, the overall mortality was 60.9% (14/23) (including our cases). Fourteen out of nineteen (73.7%) hemorrhagic events occurred within 6 months of disease onset. Anti-MDA5 antibody predominated in those myositis-specific antibodies available cases (8/10), although patients with positive anti-NXP2 and anti-Mi2 have also been documented. Iliopsoas (52.2%, 12/23) was the most frequently involved bleeding location. Bleeding in deep muscles was identified to be associated with poorer prognosis. The mortality of patients with DM and deep muscular hematoma (non-palpable) (80%, 12/15) was significantly higher than that of patients with only superficial muscular hematoma (palpable) (25%, 2/8) (p =0.023).ConclusionSpontaneous hematoma in non-palpable deep muscles probably leads to excess mortality in dermatomyositis, particularly for those with anti-MDA5 antibody, which often occurs within 6 months of disease onset. Clinicians should be vigilant to this rare but potentially fatal complication and carefully balance the risks and benefits of prophylactic anti-thrombotic treatment.
High Expression of Long Non-Coding RNA TMCO1-AS1 is Associated With Poor Prognosis of Hepatocellular Carcinoma
Authors: Huang Xuelian , Zhu Sicong , Zhang Kelin , Tan Wenliang , Chen Yajin , Shang Changzhen 
Published: January 2022

Background: The molecular pathways along with the clinical significance of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) remain uncertain. Our study sought to identify and characterize lncRNAs associated with HCC.Methods: LncRNA TMCO1-AS1 was identified by differential expression analysis, receiver operating characteristic (ROC) analysis, and univariate analysis using RNA sequencing and clinical information of HCC from the public database. Then clinical correlations and survival analysis were conducted to further appraise the prognostic significance of lncRNA TMCO1-AS1 in HCC. Hepatoma and adjoining normal tissues from 66 patients who received surgical operation at our center were used to verify the results of the bioinformatics analysis. A survival prognostic model was established combining TMCO1-AS1 expression and other clinical characteristics.Results: Bioinformatics analysis showed the aberrant high expression of TMCO1-AS1 in HCC tissue. TMCO1-AS1 expression was positively correlated with alpha-fetoprotein (AFP) level, vascular invasion, tumor stage, as well as tumor differentiation. Moreover, survival analysis found a significant inverse association between the expression of TMCO1-AS1 and the survival of patients with HCC. Cox analysis indicated that TMCO1-AS1 was an independent factor for HCC prognosis. Analysis of the HCC tissues from patients at our center provided results similar to those of the bioinformatics analysis. Risk models for overall survival (OS) and recurrence-free survival (RFS) incorporating TMCO1-AS1 exhibited better sensitivity and specificity than using clinical characteristics alone.Conclusion: High TMCO1-AS1 expression is significantly correlated with the unfavorable poor prognosis of HCC, indicating its potential of being a novel prognostic marker for HCC.
Defining a Standard Set of Health Outcomes for Patients With Squamous Cell Carcinoma of the Head and Neck in Spain
Authors: Arrazubi Virginia , Cajaraville Gerardo , Cantero David , Giralt Jordi , Mesia Ricard , Monje Florencio , Rueda Antonio , Sistiaga Alexander , Suarez Jorge , Mut Alejandro , Comellas Marta , Lizán Luis 
Published: January 2022

PurposeA systematic, standardized collection of health outcomes during patient treatment and follow-up, relevant from the perspective of all stakeholders, is a crucial step toward effective and efficient disease management. This project aimed to define a standard set of health outcomes for patients with squamous cell carcinoma of the head and neck (SCCHN).MethodsThe project was led and coordinated by a scientific committee (SC). It comprised: (1) a literature review (to identify variables used during SCCHN management); (2) 1st-SC meeting (to select the variables for presentation during nominal groups-NG); (3) five NG (n=42 experts) and four interviews with patients (to reach consensus on the variables for inclusion); and (4) final-SC meeting (to review the results of NG ensuring consensus on the variables where consensus was not reached).ResultsExperts agreed to include the following variables in the standard set: treatment-related (treatment intent and type, response to treatment, treatment toxicity/complication, treatment completion), degree of health (performance status, patient-reported health status, pain, dysphonia, feeding and speech limitations, body image alteration, tracheotomy), survival (overall and progression-free survival, cause of death), nutritional (weight, nutritional intervention), other variables (smoking status, alcohol consumption, patient satisfaction with aftermath care, employment status), and case-mix variables (demographic, tumor-related, clinical and nutritional factors).ConclusionsThis project may pave the way to standardizing the collection of health outcomes in SCCHN and promote the incorporation of patients’ perspective in its management. The information provided through the systematic compilation of this standard set may define strategies to achieve high-quality, patient-centered care.
Seven Genes Associated With Lymphatic Metastasis in Thyroid Cancer That Is Linked to Tumor Immune Cell Infiltration
Authors: Wu Linfeng , Zhou Yuying , Guan Yaoyao , Xiao Rongyao , Cai Jiaohao , Chen Weike , Zheng Mengmeng , Sun Kaiting , Chen Chao , Huang Guanli , Zhang Xiaogang , Qian Ziliang , Shen Shurong 
Published: January 2022

ObjectiveSince there are few studies exploring genes associated with lymphatic metastasis of thyroid carcinoma (THCA), this study was conducted to explore genes associated with lymphatic metastasis of THCA and to investigate the relationship with immune infiltration.MethodsDifferentially expressed genes associated with THCA lymphatic metastasis were analyzed based on The Cancer Genome Atlas Program (TCGA) database; a protein-protein interaction(PPI)network was constructed to screen for pivotal genes. Based on the identified hub genes, their expression in THCA with and without lymphatic metastasis were determined. Functional enrichment analysis was performed. The correlation between the identified genes and immune cell infiltration was explored. LASSO logistic regression analysis was performed to determine the risk score of the most relevant gene constructs and multifactor COX regression analysis based on genes in the risk score formula.ResultsA total of 115 genes were differentially expressed in THCA with and without lymphatic metastasis, including 28 upregulated genes and 87 downregulated genes. The PPI network identified seven hub genes (EVA1A, TIMP1, SERPINA1, FAM20A, FN1, TNC, MXRA8); the expression of all seven genes was upregulated in the group with lymphatic metastasis; Immuno-infiltration analysis showed that all seven genes were significantly positively correlated with macrophage M1 and NK cells and negatively correlated with T-cell CD4+ and myeloid dendritic cells. LASSO logistic regression analysis identified the five most relevant genes (EVA1A, SERPINA1, FN1, TNC, MXRA8), and multi-factor COX regression analysis showed EVA1A, SERPINA1 and FN1 as independent prognostic factors.ConclusionSeven genes were associated with lymphatic metastasis of THCA and with tumor immune cell infiltration.
Thoracoscopic Lobectomy Versus Sublobar Resection for pStage I Geriatric Non-Small Cell Lung Cancer
Authors: Lin Young-Jen , Chiang Xu-Heng , Lu Tzu-Pin , Hsieh Min-Shu , Lin Mong-Wei , Hsu Hsao-Hsun , Chen Jin-Shing 
Published: January 2022

ObjectivesThe choice of resection method for geriatric patients with early-stage non-small cell lung cancer (NSCLC) remains contentious. This study aimed to evaluate survival and perioperative outcomes after thoracoscopic lobectomy resection (LR) or sublobar resection (SR) in patients aged ≥75 years with pathologic stage (pStage) I NSCLC.Materials and MethodsWe retrospectively examined 258 consecutive patients aged ≥75 years with pStage I NSCLC who underwent thoracoscopic tumor resection at our institute from 2011 to 2018. Propensity score matching (PSM) analysis identified 60 patients in each group for comparison of survival-related parameters, including disease-free survival (DFS), lung cancer-specific overall survival (OS), and non-lung cancer-specific OS, using the Kaplan-Meier analysis.ResultsLR and SR were performed in 84 (32.6%) and 174 (67.4%) patients aged ≥75 years, respectively. The LR group had younger patients, better performance status, larger tumor sizes, and deeper tumor location than the SR group. Multivariate studies showed that the resection method was not a prognostic factor for OS. The two PSM-matched groups were not significantly different with respect to lung cancer-specific OS (p = 0.116), non-lung cancer-specific OS (p = 0.408), and DFS (p = 0.597). SR helped achieve better perioperative outcomes than LR, including fewer postoperative complications (10.0% vs. 28.3%, p = 0.011), shorter operative times (p &lt; 0.001), decreased blood loss (p = 0.026), and shorter chest tube duration (p = 0.010) and hospital stays (p = 0.035).ConclusionsThoracoscopic SR may provide similar oncological outcomes to LR, but may be a safer and more feasible surgical method for geriatric patients with pStage I NSCLC.