bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis Revealed the Potential Implications of m6A Regulators in Lung Adenocarcinoma
Authors: Xie Lingling , Dai Rongyang , Wang Xudong , Xie Guangfei , Gao Zhihua , Xu Xinxin 
Published: March 2022

Background: The biological significance of RNA N6-methyladenosine (m6A) decoration in tumorigenicity and progression has been highlighted in recent studies, but whether m6A modification plays a potential role in tumor microenvironment (TME) formation and immune regulation in lung adenocarcinoma (LUAD) remains unclear.Methods: m6A modification features were evaluated by analyzing the multi-omics features of 17 m6A regulators in over 1900 LUAD samples, and at the same time, the correlation between these modification patterns and TME characteristics was analyzed. An m6A score signature–based principal component analysis (PCA) algorithm was constructed to assess the prognosis and responses of individual patients to immunotherapeutic and targeted therapies.Results: Three different m6A modification patterns were determined in 1901 LUAD samples, which were found to be related to diverse clinical outcomes via different biological pathways. Based on the m6A score extracted from the m6A-associated signature genes, LUAD patients were separated into high- and low-m6A score groups. It was discovered that patients with high m6A scores had longer survival, lower tumor mutation loads, and low PD-L1/PDCD1/CTLA4/TAG3 expression level. In addition, LUAD patients with high m6A scores displayed lower IC50 to some targeted drugs, including nilotinib, erlotinib, imatinib, and lapatinib.Conclusion: m6A modification was significantly associated with the TME and clinical outcomes. These findings may help gain more insights into the role of m6A decoration in the molecular mechanism of LUAD, thus facilitating the development of more effective personalized treatment strategies.
Retinal Optical Coherence Tomography Angiography Parameters Between Patients With Different Causes of Chronic Kidney Disease
Authors: Yong Meng Hsien , Ong Ming Yean , Tan Kuan Sze , Hussein Siti Husna , Mohd Zain Ayesha , Mohd Rozita , Mustafar Ruslinda , Wan Abdul Halim Wan Haslina 
Published: March 2022

BackgroundChronic kidney disease (CKD) is a major public health issue because of the rising number of patients with the risk of progression to end-stage renal disease. The retinal micro-vasculatures provide a unique window to assess systemic microcirculation. Optical Coherence Tomography Angiography (OCTA) parameters may provide a non-invasive method for systemic correlation. This research aims to compare the association of OCTA parameters in different causes of CKD.MethodsThis is a single-center cross-sectional study on patients with CKD at the Universiti Kebangsaan Malaysia Medical Centre over 2 years. Patients with CKD were divided into three groups: DM group (diabetic CKD), HPT group (hypertensive CKD), and AG group (autoimmune-related glomerulonephritis CKD). The OCTA parameters, namely, the foveal avascular zone (FAZ), vascular density (VD), perfusion density (PD), and macular volume (MV), were measured and recorded using OCTA. Blood and urine analyses were taken as the patient’s CKD profile. The demographic data, the OCTA parameters and the CKD profiles, were analyzed using SPSS version 23.ResultsThe right eyes of 232 patients were included. The median age of the control and CKD subjects were 36 and 61 years old respectively. The proportion of the subjects under the control, diabetes mellitus (DM), HPT, and AG group were 30.6, 53.4, 5.6, and 10.4% respectively. There was no significant difference in FAZ, but there is a significant difference in the VD, PD, and MV between the control and CKD groups. There was a statistically significant difference between the three different causes of CKD in VD and PD (p &lt; 0.001, p = 0.001, respectively). When compared with the control group for VD and PD, there were significant differences between the DM-control group (p &lt; 0.001, p &lt; 0.001) even when the age variable was considered, but no significant difference when comparing the HPT-control and the AG-control. There was a significant correlation between age, FBS, and HbA1c with VD and PD. There was no significant association between CKD profile and FAZ.ConclusionOur study showed the meaningful reduction of VD and PD in patients with diabetes and CKD. However, the use of OCTA to screen or predict CKD in patients living with diabetes mellitus, hypertension, or autoimmune nephritis was not shown to be useful.
Adherence to the Vegetable-Fruit-Soy Dietary Pattern, a Reference From Mediterranean Diet, Protects Against Postmenopausal Breast Cancer Among Chinese Women
Authors: Cao Shang , Liu Linchen , Zhu Qianrang , Zhu Zheng , Zhou Jinyi , Wei Pingmin , Wu Ming 
Published: March 2022

BackgroundThe diet-center hypothesis has gained much support from the apparent protective effect of the Mediterranean diet on breast cancer. However, the evidence of the association between Mediterranean diet adherence and breast cancer molecular subtypes remains small, especially in non-Mediterranean populations.MethodsThe subjects from the Chinese Wuxi Exposure and Breast Cancer Study, a population-based case-control study, included 818 patients and 935 healthy controls. A validated food frequency questionnaire used for diet assessment and a modified version of the alternate Mediterranean Diet Score, which is called the alternate Chinese Diet Score, was developed to assess adherence to a migrated Chinese version of the Mediterranean diet, which we called the vegetable-fruit-soy dietary pattern. Soy foods, rapeseed oil, and coarse cereals replaced legumes, olive oil, and whole grains reflecting the cuisine of the region. We examined the association between the vegetable-fruit-soy diet adherence and breast cancer risk, stratified by menopause status (pre- or postmenopausal) and receptor status [estrogen-receptor (ER), progesterone-receptor (PR) status, and human epidermal growth factor 2 (HER2)] oncogene expression, followed by five specific combinations (ER+, ER–, ER+/PR+,ER–/PR–, and ER–/PR–/HER2–).ResultsThe results suggest that the vegetable-fruit-soy dietary pattern was inversely associated with postmenopausal breast cancer risk [4th vs. 1st quartile, odds ratio (OR) = 0.57, 95%CI = 0.41, 0.80;Ptrend &lt; 0.001] and that the inverse association was somewhat stronger to detect among ER- subtypes (OR = 0.63; 95%CI = 0.37, 0.94;Ptrend = 0.003) and ER–/PR–subtypes (OR = 0.64; 95%CI = 0.41, 0.93;Ptrend = 0.012). We did not observe any significant association between the vegetable-fruit-soy diet characteristics and ER+ subtype, as well as between PR+ and ER+/PR+ subtypes.ConclusionThe favorable influence from the Mediterranean diet may also apply to Chinese women. The vegetable-fruit-soy dietary pattern may reduce the risk of postmenopausal breast cancer, particularly among ER- subtype, and ER–/PR–subtype.
The GLIM Criteria Represent a More Appropriate Tool for Nutritional Assessment in Patients With Crohn's Disease
Authors: Li Yong , Peng Ziheng , Xu Duo , Peng Yu , Liu Xiaowei 
Published: March 2022

BackgroundThe early recognition of malnutrition is essential for improving the prognosis of patients with Crohn's disease (CD). The Global Leadership Initiative on Malnutrition (GLIM) criteria represent a new consensus for the diagnosis of malnutrition but need to be validated in CD. The aims were to explore the related factors of malnutrition in CD and explore whether GLIM-positive patients who did not meet the Nutritional Risk Screening 2002 (NRS 2002) would benefit from nutritional treatment.MethodsThis study retrospectively enrolled patients with CD at the Gastroenterology Department of Xiangya Hospital Central South University between March 2020 and March 2021. After bioelectrical impedance analysis, all patients underwent nutritional screening and diagnosis using the NRS 2002 and GLIM criteria, respectively. Multivariable analysis was performed to evaluate risk factors related to malnutrition in patients with CD. A multivariable Cox hazard model was used to assess the association between nutritional therapy and prognostic outcomes.ResultsOf the 118 patients included, fifty were classified as having a high malnutrition risk according to the NRS 2002, while 76 were diagnosed with malnutrition by the GLIM criteria. Multivariate analysis showed that a high malnutrition risk was independently associated with the L4 phenotype [odds ratio (OR) (95% confidence interval (CI)) = 4.718 (1.108, 20.10), p = 0.036] and Crohn's Disease Activity Index (CDAI) [OR (95% CI) = 1.018 (1.007, 1.029), p = 0.002] based on the NRS 2002. The age at onset [OR (95% CI) = 0.828 (0.699, 0.980), p = 0.028] and CDAI [OR (95% CI) = 1.111 (1.034, 1.195), p = 0.004] were regarded as independent risk factors related to malnutrition, as determined by the GLIM criteria. Among 26 GLIM+/NRS− patients, significantly more patients who received nutritional support achieved 6-week remission than patients who did not (100 vs. 71.4%, p &lt; 0.05). The 6-week remission risk in patients treated with nutrition therapy was more than 4-fold higher than those without nutritional therapy.ConclusionThe GLIM criteria could diagnose more malnourished patients with CD who are not positively screened by the NRS 2002, among whom nutritional support therapy would be beneficial for disease remission. The new criteria should be more appropriate for assessing the nutritional status of patients with CD.
Circulating Vitamin D Levels and the Risk of Atrial Fibrillation: A Two-Sample Mendelian Randomization Study
Authors: Yang Shengyi , Zhi Hong , Sun Ying , Wang Lina 
Published: March 2022

AimWe performed a two-sample Mendelian randomization (MR) analysis to evaluate the association between serum vitamin D levels and atrial fibrillation (AF) risks.MethodsData on the single-nucleotide polymorphisms (SNPs) related to vitamin D, 25-hydroxyvitamin D, and AF outcome were obtained from a UK Biobank study, SUNLIGHT consortium, and the latest meta-analysis of genome-wide association studies GWASs with six independent cohorts, respectively. MR analysis was performed to obtain the estimates, followed by the use of inverse variance weighted (IVW) method, weighted median method, maximum likelihood, MR-egger method, and MR-PRESSO methods.ResultsThe IVW estimate showed that genetically predicted vitamin D and 25-hydroxyvitamin D levels were not causally associated with the risk of AF with two models. The association was consistent in complementary analyses.ConclusionsOur MR finding suggested that no genetic evidence of serum vitamin D levels was significantly associated with AF risk. Further researches are necessary to explore the potential role and mechanisms of circulating serum vitamin D levels on AF.
Association of Four Nutritional Scores With All-Cause and Cardiovascular Mortality in the General Population
Authors: Fan Heze , Huang Yuzhi , Zhang Haoxuan , Feng Xueying , Yuan Zuyi , Zhou Juan 
Published: March 2022

Background and AimsMalnutrition is a well known risk factor for adverse outcomes in patients with cancer, cardiovascular disease (CVD) and chronic kidney disease, but epidemiological evidence on its relationship with the long-term risk of all-cause mortality and cardiovascular death is limited.MethodsA total of 20,116 adults from the United States National Health and Nutrition Examination Survey 2007–2014 were enrolled. The Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT) score, and Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI) were calculated at baseline. Cox regression and the Kaplan–Meier analysis were conducted when participants were divided into three groups according to the tertiles of objective nutritional scores. Restricted cubic spline was performed to further explore the shape of the relationship between all-cause mortality, cardiovascular death, and nutritional scores. In addition, the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were conducted to assess which nutritional scores have the greatest predictive value for all-cause death and cardiovascular death in the general population.ResultsThe cumulative incidence of all-cause death and cardiovascular death was significantly higher in participants with a higher CONUT score, lower GNRI, and lower PNI. TCBI showed the worst performance on grading and risk assessment. After adjusting confounding factors, the lowest PNI and GNRI tertile and highest COUNT score were independently and significantly associated with increased risk of all-cause death (all P &lt; 0.01) and cardiovascular death (all P &lt; 0.05) analyzed by a multivariate Cox regression model. An L-shaped association between the HR (hazard ratio) of all-cause mortality and nutritional scores (GNRI, PNI and TCBI) was observed in the overall populations. In addition, the PNI had the highest predictive value for all-cause mortality [AUC: 0.684, 95% confidence interval (CI): 0.667–0.701] and cardiovascular death (AUC: 0.710, 95% CI: 0.672–0.749) in the general population compared with other nutritional scores.ConclusionThe poorer the nutritional status of the general population, the higher the all-cause mortality and cardiovascular mortality. The PNI score may provide more useful predictive values than other nutritional scores.
The Effect of Ophiopogonin C in Ameliorating Radiation-Induced Pulmonary Fibrosis in C57BL/6 Mice: An Update Study
Authors: Fu Xiaobin , Li Tingting , Yao Qiwei 
Published: March 2022

BackgroundThe aim of this study was to assess and update the protective effects and underlying mechanisms of Ophiopogonin C (OP-C), a biologically active component separated and purified from Ophiopogon japonicus, in ameliorating radiation-induced pulmonary fibrosis in C57BL/6 mice administered thoracic radiation.Methods and MaterialsWe randomly divided 75 mice into five groups and administered a dose of 12-Gy whole thoracic radiation to establish a pulmonary fibrosis animal model. Mice were treated with OP-C or dexamethasone combined with or without cephalexin by daily gavage for 4 weeks. All mice were sacrificed after the completion of thoracic irradiation at 28 weeks. Serum levels of interleukin-6 and transforming growth factor-β1 (TGF-β1) were evaluated. Moreover, superoxide dismutase (SOD) levels in lung tissue were measured. The severity of fibrosis was evaluated using the hydroxyproline content of the lung tissue. The pathological changes in the five groups were detected by hematoxylin and eosin and Masson trichrome staining. Smooth muscle actin expression was detected using immunohistochemical staining. Matrix metalloproteinases-2 (MMP-2) and tissue inhibitors of metalloproteases-2 (TIMP-2) were examined by immunohistochemical staining of the lung sections, and semiquantitative analysis was used to calculate the expression of MMP-2 and TIMP-2.ResultsIrradiated mice treated with OP-C or DXE combined with or without cephalexin significantly reduced mortality in mice and fibrosis levels by 1) reducing the deposition of collagen and accumulation of inflammatory cells and fibroblasts, 2) downgrading levels of the promote-fibrosis cytokine TGF-β1, and 3) increasing SOD activity in the lung tissue compared with that of irradiated mice without treatment. However, there were no statistical differences in fibrosis levels among the irradiated mice treated with OP-C or DXE combined with or without cephalexin.ConclusionOP-C significantly ameliorates radiation-induced pulmonary fibrosis and may be a promising therapeutic strategy for this disorder.
Prognostic Relevance of Progesterone Receptor Levels in Early Luminal-Like HER2 Negative Breast Cancer Subtypes: A Retrospective Analysis
Authors: Diana Anna , Carlino Francesca , Buono Giuseppe , Antoniol Giuliano , Famiglietti Vincenzo , De Angelis Carmine , Carrano Simone , Piccolo Antonio , De Vita Ferdinando , Ciardiello Fortunato , Daniele Bruno , Arpino Grazia , Orditura Michele 
Published: March 2022

IntroductionIn luminal-like early breast cancer (BC), the lack of Progesterone Receptor (PR) expression generally correlates with more aggressive behavior but the clinical validity of low PR levels remains a debated issue.MethodsThe main aim of this retrospective analysis was to assess the survival outcome (Breast cancer specific survival, BCSS) in a cohort of 687 luminal-like HER2 negative early BC patients treated at our Institutions from January 2000 to December 2018, using a sub-classification of tumors in subgroup 1 (PR high/Ki67 low), subgroup 2 (PR high/Ki67 high), subgroup 3 (PR low/Ki67 low), subgroup 4 (PR low/Ki67 high) according to PR and Ki67 values.ResultsAt a median follow-up of 7 years, BCSS rates were 96.3%, 89%, 86.8% and 85% in the subgroup 1, 2, 3, 4 respectively. Overall, a statistically significant difference in BCSS rates was observed among the 4 subgroups (p=0.0036). On univariate analysis, post-menopause, older age (≥ 50 years), low PR and high Ki67 expression, poorly differentiated grade and size ≥ 2 cm as well as luminal B-like tumors (subgroups 2, 3, 4) were significantly associated with a worse BCSS. Multivariate analysis identified grade, size and subgroup classification of BC as independent prognostic markers of poorer outcome. In particular, subgroups 4, 3 and 2 displayed a significantly higher risk of BC-related death (HR=4.11; p=0.008; HR=3.43; p=0-007; HR=2.57; p=0.020, respectively) when compared to subgroup 1.ConclusionsOur results support the usefulness of PR and Ki67 levels as prognostic markers, corroborating their crucial role in the decision-making process of patients with luminal-like HER2 negative early BC. Clinical application of these parameters should be assessed prospectively.
Impact of New vs. Old International Children’s Continence Society Standardization on the Classification of Treatment Naïve Enuresis Children at Screening: The Value of Voiding Diaries and Questionnaires
Authors: Karamaria Sevasti , Ranguelov Nadejda , Hansen Pernille , De Boe Veerle , Verleyen Pieter , Segers Nathalie , Walle Johan Vande , Dossche Lien , Bael An 
Published: March 2022

Expert consensus papers recommend differentiating enuresis using questionnaires and voiding diaries into non- (NMNE) and monosymptomatic enuresis (MNE) is crucial at intake to decide the most appropriate workout and treatment. This national, Belgian, prospective study investigates the correlation, consistency, and added value of the two methods, the new against the old International Children’s Continence Society (ICCS) definitions, and documents the prevalence of the two enuresis subtypes in our population. Ninety treatment-naïve enuretic children were evaluated with the questionnaire, and the voiding diary and the two clinical management tools were compared. Almost 30% of the children had a different diagnosis with each method, and we observed inconsistencies between them in registering Lower Tract Symptoms (κ = –0.057–0.432 depending on the symptom). Both methods had a high correlation in identifying MNE (rs = 0.612, p = 0.001) but not for NMNE (rs = 0.127, p = 0.248). According to the latest ICCS definitions, the incidence of MNE was significantly lower (7 vs. 48%) with the old standardization.ConclusionThe voiding diary and the questionnaire, as recommended by the ICCS at the screening of treatment-naïve enuretic patients, are considerably inconsistent and have significantly different sensitivities in identifying LUTS and thus differentiating MNE from NMNE. However, the high incidence of LUTS and very low prevalence of MNE suggest that differentiating MNE from NMNE to the maximum might not always correlate with different therapy responses.
Hypernatremia During Intravenous Treatment With Fosfomycin: A Retrospective Medical Record Review Study and an Analysis of Spontaneous Reports in the EudraVigilance Database
Authors: Scavone Cristina , Mascolo Annamaria , Bernardi Francesca Futura , Aiezza Maria Luisa , Saturnino Paola , Morra Gaia , Simonelli Margherita , Massa Marida , Pomicino Andrea , Minei Giuseppina , Pisapia Raffaella , Spatarella Micaela , Trama Ugo , Guglielmi Gaspare , Capuano Annalisa , Perrella Alessandro 
Published: March 2022

Background: Hypernatremia is a serious event that can occur during intravenous (IV) treatment with fosfomycin, and it can also be caused by a wrong drug preparation. Considering the clinical significance of hypernatremia, we decided to carry out two studies by using two different data sources with the aim to evaluate cases of IV fosfomycin-induced hypernatremia.Methods: A retrospective medical record review was performed from June 2017 to June 2019 using data from two hospitals in Southern Italy. The information collected was related to the patients, the antibiotic treatment regimen, type of adverse drug reaction (ADR), hypernatremia severity classification, and drug withdrawal due to ADRs. Moreover, a pharmacovigilance study was performed from the date of the European marketing authorization of fosfomycin to October 11, 2021, using data reported on the European website of suspected ADRs. Information related to the patient characteristics, treatment, hypernatremia, and type of reporter was retrieved.Results: From the retrospective medical record review, a total of 62 patients (48 men and 14 women) in treatment with fosfomycin were identified, of which 17 experienced ADRs. Specifically, 11 patients experienced hypernatremia. During the period from June 2017 to June 2018, a total of 63.7% of hypernatremia events were related to the wrong reconstitution of the drug. According to these results, a surveillance and training campaign about the correct drug reconstitution was managed. However, from June 2018 to June 2019, we still had four new hypernatremia cases. Drug withdrawal occurred in only one patient with hypernatremia. From the pharmacovigilance study, a total of 25 cases of IV fosfomycin-induced hypernatremia were retrieved. No substantial difference was found for patients’ distribution by sex. Most cases were classified as serious (68%) and reported “Recovered/resolved” as the outcome (44%). In the majority of cases, fosfomycin was the only suspected drug reported (72%).Conclusion: Our results show that training campaigns on the correct drug preparation need to be strengthened to allow a reduction of hypernatremia cases. Moreover, when close monitoring and management is performed by the infectious disease (ID) specialist and hospital pharmacist, there also is a reduction in antibiotic withdrawal due to hypernatremia.