bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consequences of Ignoring Clustering in Linear Regression
Authors: Ntani Georgia , Inskip Hazel , Osmond Clive , Coggon David 
Published: November 2020

Abstract
BackgroundClustering of observations is a common phenomenon in epidemiological and clinical research. Previous studies have highlighted the importance of using multilevel analysis to account for such clustering, but in practice, methods ignoring clustering are often used. We used simulated data to explore the circumstances in which failure to account for clustering in linear regression analysis could lead to importantly erroneous conclusions. MethodsWe simulated data following the random-intercept model specification under different scenarios of clustering of a continuous outcome and a single continuous or binary explanatory variable. We fitted random-intercept (RI) and cluster-unadjusted ordinary least squares (OLS) models and compared the derived estimates of effect, as quantified by regression coefficients, and their estimated precision. We also assessed the extent to which coverage by 95% confidence intervals and rates of Type I error were appropriate. ResultsWe found that effects estimated from OLS linear regression models that ignored clustering were on average unbiased. The precision of effect estimates from the OLS model was overestimated when both the outcome and explanatory variable were continuous. By contrast, in linear regression with a binary explanatory variable, in most circumstances, the precision of effects was somewhat underestimated by the OLS model. The magnitude of bias, both in point estimates and their precision, increased with greater clustering of the outcome variable, and was influenced also by the amount of clustering in the explanatory variable. The cluster-unadjusted model resulted in poor coverage rates by 95% confidence intervals and high rates of Type I error especially when the explanatory variable was continuous. ConclusionsIn this study we identified situations in which an OLS regression model is more likely to affect statistical inference, namely when the explanatory variable is continuous, and its intraclass correlation coefficient is higher than 0.01. Situations in which statistical inference is less likely to be affected have also been identified.
Osteoarthritic Infrapatellar Fat Pad Aggravates Cartilage Degradation via Activation of p38MAPK and ERK1/2 Pathways
Authors: Zhou Zuoqing , Tang Su'an , Nie Xiaoyu , Zhang Yiqun , Li Delong , Zhao Yang , Cao Yumei , Yin Jianwen , Chen Tianyu , Ruan Guangfeng , Zhu Zhaohua , Bai Xiaochun , Han Weiyu , Ding Changhai 
Published: November 2020

Abstract
Background: Although existing studies have suggested the involvement of the infrapatellar fat pad (IPFP) during the development of knee osteoarthritis (OA), the role of IPFP is still controversial. This study aimed to investigate the biochemical effects of osteoarthritic IPFP on cartilage and the underlying mechanisms.Methods: Human IPFP and articular cartilage were collected from end-stage OA patients during total knee arthroplasty. IPFP derived fat-conditioned medium (FCM) was used to stimulate human primary chondrocytes and cartilage explants. CCK8 was used to detect the viability of human chondrocyte. qRT-PCR and western blotting was performed to evaluate the balance of extracellular matrix (ECM) catabolism and anabolism in human chondrocytes with FCM stimulation. Functional effect of osteoarthritic IPFP was also demonstrated in human articular cartilage by ex vivo assay. Activation of relative pathways and its effects on chondrocytes were assessed through immunoblotting and inhibition experiments, respectively. Neutralization test was performed to identify the main factors and their associated pathways responsible for the effects of IPFP. Results: Osteoarthritic IPFP-derived FCM significantly induced extracellular matrix (ECM) degradation in both human primary chondrocytes and cartilage explants. Several pathways, such as NF-κB, mTORC1, p38MAPK, JNK, and ERK1/2 signaling were significantly activated in human chondrocytes with osteoarthritic IPFP-derived FCM stimulation. Interestingly, inhibition of p38MAPK and ERK1/2 signaling pathway could alleviate the detrimental effects of FCM on chondrocytes while inhibition of other signaling pathways had no similar results. In addition, IL-1β and TNF-α instead of IL-6 in osteoarthritic IPFP-derived FCM played a key role in cartilage degradation via activating p38MAPK rather than ERK1/2 signaling pathway.Conclusions: Osteoarthritic IPFP induces the degradation and inflammation of cartilage via activation of p38MAPK and ERK1/2 pathways, in which IL-1β and TNF-α act as the key factors. Our study suggests that modulating the effects of IPFP on cartilage may be a promising strategy for knee OA intervention.
Association of the X-chromosomal hsa_circ_0140271 with Female Rheumatoid Arthritis
Authors: Chen Yufeng , XU Xianghe , Li Xuegang , Shang Jie , Jiang Ning , Wang Bin , Wu Biao , Zhong Junlong , Zhong Shuping , Lu Huading 
Published: November 2020

Abstract
Background:Rheumatoid arthritis (RA) commonly affects women. Circular RNAs (circRNAs) have been reported to be related RA progress. However, it is still unknown the role of circRNA in female RA. Methods: In this study, we extracted total RNA of peripheral blood mononuclear cells (PBMC) from four RA patients and four healthy control donors, then performed RNA sequencing analysis. To validation, we recruited PBMC samples from 47 RA patients and 47 healthy control donors. The diagnosis ability of candidate circRNA in female RA was explored by Receiver Operating Characteristic (ROC) curve analysis. Levels of inflammation factors in serum, such as IL-1α, IL-1β, IL-6, IL-8,TNF-α and INF-γ, were detected in female RA patients and female healthy donors to analysis the correlation between those factors and candidate circRNA. KEGG pathway enrichment analyses were also performed to predict function of candidate circRNA.Resuluts: By analyzing circRNA expression profiles, we identified hsa_circ_0140271, generated from X chromosome gene-MED14, was specifically expressed in female RA patients. We verified hsa_circ_0140271 expression in PBMC samples from a cohort of 47 RA patients and 47 healthy control subjects via RT-qPCR and found hsa_circ_0140271 was also specifically highly expressed in female RA. In addition, ROC curve analysis indicated that the specificity of hsa_circ_0140271 in female RA patients was 1 comparing to female healthy subjects, osteoarthritis (OA) patients or Ankylosing spondylitis (AS) patients. Levels of IL-6, IL-8 and TNF-α was higher in serum from female RA patients than that from female healthy subjects. Furthermore, KEGG analysis indicated that hsa_circ_0140271 might regulate fatty acid metabolism in female RA patients.Conclusion:Our results suggested that hsa_circ_0140271 has a potential role in detect female RA and may contribute RA progress by fatty acid metabolism.
Thread Migration After Polydioxanone Thread Lift
Authors: Jeong Tae Kwang , Chung Chang Ho , Min Kyung Hee 
Published: November 2020

Abstract
Background: The thread-lift has gained popular interest as a minimally invasive procedure because it is simple and reliable. Additionally, it has shorter recovery time and fewer complications than facelift surgery. However, complications including hematoma, infection, facial asymmetry, thread exposure, thread migration, dimpling, alopecia, parotid gland injury, and scarring can occur. We report a case of thread migration after a polydioxanone (PDO) thread lift.Case presentation: A 40-year-old woman underwent a thread lift using a PDO cogged thread. Insertion sites were marked along the temporal hairline. The expected distal ends of threads were marked at least 1.5 cm apart from the nasolabial and marionette folds and 2.5 cm apart from the mandibular border. All threads were inserted into the deep subcutaneous plane. After 1 month, she complained of a foreign body sensation and pain just lateral to the left mouth corner. She showed a linear elevation with oblique direction, and a linear material was palpated with little mobility. The removed material was confirmed to be a part of the inserted thread.Conclusion:During thread lift, it is important to remove the cannula gently and straightly to avoid breaking the thread. Also, it is better to avoid strong manual massage on the path of the thread.
Clinical Evidence of Vestibular Dysregulation in Colicky Babies Before and After Chiropractic Treatment Compared to Non-Colicky Babies.
Authors: Hoeve Jan 
Published: November 2020

Abstract
Aim: to present a five-point clinical index of vestibular (hyper)activity and its application as a tool to investigate vestibular dysregulation in colicky and non-colicky babies.Methods: 120 consecutive colicky babies, before and after treatment, were evaluated using this index and compared to 117 non-colicky babies.Results. Before treatment out of 120 colicky babies 118 (98.3%) scored 1-5 and only 2 (1.7%) scored 0. Out of 117 non-colicky babies 89 (76,1%) scored 0 and 28 (23.9%) scored 1-3, none scored 4-5. Odds ratios are OR (CI 95%) 187.54 (43.52-808.09). After treatment 111 (92.5%) scored 0 and 9 (7.5%) scored 1-3, none scored 4-5. A McNemar test showed the difference before and after to be significant (χ² = 109.00, p < .001). For colicky babies the mean vestibular score is 2.88(SD 1.22), compared to 0.37(SD 0.73) for non-colicky babies, a difference of 87.2%. After treatment the score decreased from 2.88 (SD 1.12) to 0.10 (SD 0.40), or 96.5%. Conclusion: colicky babies are not just infants who cry a lot. They also show clinical evidence of vestibular dysregulation. The vestibular index opens the prospect that it could be developed into a tool towards an objective clinical diagnosis of infantile colic.
NPAS4 Polymorphisms Contribute to Coronary Heart Disease (CHD) Risk
Authors: Yan Yuping , Yin Xiangli , Li Jingjie , Sun Yao , Wu Jiamin , Xiong Zichao , Tian Gang 
Published: November 2020

Abstract
Background: As genetic inheritance is an inevitable risk factor in the development of coronary heart disease (CHD), it is critical to identify the single-nucleotide polymorphism (SNP) locus of CHD risk. This case-control study exported whether the NPAS4 polymorphisms are related to the CHD risk in the Chinese Han population. Methods: The Agena MassARRAY platform was used to genotype the five SNPs in NPAS4 from 499 CHD patients and 500 healthy controls. We used χ2 test to compare the distributions of gender, allele and genotypes frequencies between cases and controls. The logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: The rs4466842 in NPAS4 was found to be correlated with an increased risk of CHD in overall, males and age ≤ 60. The rs117186164 and rs12785321 in NPAS4 were significantly related to an increased risk of CHD in the male and the age ≤ 60, respectively. Moreover, the haplotype AC (rs117186164 and rs4466842) in NPAS4 was significantly correlated with an increased risk of CHD. Conclusions: Our results indicated that polymorphisms (rs117186164, rs12785321, and rs4466842) in NPAS4 were significantly correlated with increased the risk of CHD in the Chinese Han population. Further association and functional studies are required to confirm the results and investigate the role of this SNP in the development of CHD.
Echocardiographic Characteristics and Prognosis of the Fetuses with Ebstein Anomaly in Pregnancy
Authors: Wu Yuduo , Gu Xiaoyan , Zhang Hongjia , He Yihua 
Published: November 2020

Abstract
Objective: This study aimed to describe the fetal echocardiographic features of Ebstein anomaly (EA) and evaluate the prognosis of those fetuses.Methods: We retrospectively reviewed the clinical records of 53 fetuses with EA. They were enrolled from January 2011 to December 2018 in Beijing Anzhen Hospital and analyzed the fetuses' ultrasonic features and prognosis. Results: In this single-institutional study, we screened 53 fetuses during 23~39 weeks of gestation with EA. In these fetuses, patients with complications accounted for a more significant percentage (69.81%). Ultrasound imaging showed that the posterior lobe shifted down further than the septal leaflets, and the anterior lobe changed less than 50%. Severe tricuspid valve (TV) regurgitation showed the highest proportion in these fetuses (56.60%). Among the enrolled fetuses, 20 cases were classified into grade -Ⅱ, 40 cases (75.47%) were inducted, and 13 cases (24.5%) were continued pregnancy. However, only one of those fetuses successful delivery. Conclusion: Echocardiography has become an essential diagnostic tool in identifying fetuses with EA. The prognosis of the fetuses with EA is relatively low in our center. Therefore, understanding the echocardiographic characteristics and the prognosis of the fetuses with EA is of great value for pregnancy consultations during the perinatal period.
Anxiety and Depression Among Pregnant Women in Plain and Plateaus&nbsp;Areas: A Cross-sectional Study
Authors: Chen Jiebing , Zou Qiaojian , Jiang Cheng , Huang Jiaming , Liu Xiaochen , Zhou Jun , Ding Sha , Wang Ganlu , Yao Shuzhong 
Published: November 2020

Abstract
Background: Perinatal anxiety and depression can severely damage both maternal and infant’s health and result in negative effects. In this study, we investigated the current state of anxiety and depression among pregnant women in Tibet and Guangzhou and identified its risk factors, which would provide guidance for clinical daily work.Methods: From September 2018 to May 2019, 169 pregnant women in Tibet and 199 of them in Guangzhou were selected. Zung's Self Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to assess the degree of anxiety and depression, respectively. All the data were collected by the questionnaire.Results: The SAS and SDS scores in Guangzhou were 42.4±8.5 and 48.0±9.5 respectively, while the same score became 46.6±8.0 and 54.7±8.9 in Tibet. Scores of pregnant women in Tibet were significantly higher than in Guangzhou (P < 0.05). Trimester, nationality, delivery times and educational experience were considered to be influence factors for anxiety and depression among pregnant women.Conclusions: Pregnant women living in plateaus areas of China have higher SAS and SDS scores than in plain areas, especially for those with a low level of educational experience. More attention should be paid in future work.
Incidence and Risk Factors for Deep Venous Thrombosis of Lower Extremity After Surgical Treatment of Isolated Patella Fractures
Authors: Tan Zhanchao , Hu Hongzhi , Deng Xiangtian , Zhu Jian , Zhu Yanbin , Ye Dandan , Cheng Xiaodong , Zhang Yingze 
Published: November 2020

Abstract
Background: Limited information exists on the incidence of postoperative deep venous thromboembolism (DVT) in patients with isolated patella fractures. The objective of this study was to investigate the postoperative incidence and locations of deep venous thrombosis (DVT) of the lower extremity in patients underwent isolated patella fractures and to identify the associated risk factors.Methods: We collected the medical data of 716 hospitalized patients with acute isolated patella fracture who presented at the 3rd Hospital of Hebei Medical University between January 1, 2016, and February 31, 2019 and all patients met the inclusion criteria. Medical data were collected using the inpatient record system, including the patient demographics, patient’s bad hobbies, comorbidities, past medical history, fracture and surgery-related factors, and hematological biomarkers, total hospital stay, preoperative stay. Doppler examination was conducted for the diagnosis of DVT, Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors.Results: Among the 716 patients, DVT was confirmed in 29 cases, indicating an incidence of 4.1%. DVT involved bilateral limbs (injured and uninjured) in one patient (3.4%). DVT involved superficial femoral common vein in 1 case (3.4%), popliteal vein in 6 cases (20.7%), posterior tibial vein in 11 cases (37.9%), and peroneal vein in 11 cases (37.9%). The median of the interval between surgery and diagnosis of DVT was 4.0 days (range: 1.0 to 8.0 days). Six variables were identified to be independent risk factors for DVT, including age category (>65 years old), OR, 4.44 (1.34 - 14.71), arrhythmia, OR, 4.41(1.20 - 16.15), intra-operative blood loss, OR, 1.01 (1.00 - 1.02), preoperative stay (delay of each day), OR, 1.43 (1.15 - 1.78). Surgical duration, OR, 1.04 (1.03 - 1.06), LDL-C (> 3.37 mmol/L), OR, 2.98 (1.14 - 7.76).Conclusion: Incidence of postoperative DVT in patients with isolated patella fractures is not low. More attentions should be paid on postoperative DVT prophylaxis in patients with isolated patella fractures. Identification of associated risk factors can help clinicians recognize the risk population, assess the risk of DVT and develop personalized prophylaxis strategies.
Surgical excision of complex lipoma from the foot: a case report&nbsp;
Authors: Uddin Akram , Flanagan George , Reilly Ian 
Published: November 2020

Abstract
Background: Soft tissue malignant tumours of the foot and ankle are rare. Diagnostic imaging and interventional biopsy are vital to establish the nature and grading of a suspicious tumour prior to surgical intervention. The purpose of the study is to provide an account on how a symptomatic mass to the plantar aspect of the foot warranted a referral to a sarcoma centre, highlighting the importance of having urgent access to diagnostic imaging and a pathway to refer suspected cases to specialist centres. Method: A single patient with a symptomatic soft tissue tumour of the plantar foot was referred from our service to the regional sarcoma centre. It was considered to be benign and therefore open surgical resection was performed under local anaesthesia by our team, and the lesion sent for histopathological examination. Results: Histopathological analysis identified the excised mass as a lipoma to show no atypia or necrosis and mature adipose tissue with fibrous bands. At 2 years postoperatively there was no recurrence and the patient presented an asymptomatic foot. Favourable patient reported outcomes measures were observed. Conclusion: United Kingdom (UK) Guidelines suggest that all soft tissue masses of suspicious nature, greater than 50mm, deep seated irrespective of size, or fast growing should be referred to a sarcoma unit prior to surgical management. European guidance identifies a threshold of 15mm for a mass in the foot. Patients presenting with red flag symptoms irrespective of size of mass should be referred to a sarcoma centre. Advanced imaging and multidisciplinary input to enable appropriate surgical planning is recommended for these soft tissue tumours that present to the foot and ankle surgeon.Level of evidence: V case study.
An Integrated mRNA-lncRNA Signature for Overall Survival Prediction in Cholangiocarcinoma
Authors: Zeng Liping , Mukiibi Robert , Xu Derong , Xin Hongbo , Zhang Feng 
Published: November 2020

Abstract
BackgroundThe incidence and mortality rate of cholangiocarcinoma (CCA) have been rising globally. Patients with CCA have extremely poor prognosis, partly due to the silent clinical character and hence diagnosed at advantage stage without effective treatments. There is growing evidence showing that aberrant expression of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) are involved in tumorigenesis and development of CCA. It is essential to establish an integrated mRNA-lncRNA signature to improve the ability of prognostic prediction in CCA patients.MethodsWe collected a training dataset of 45 patients from The Cancer Genome Atlas dataset and a validation cohort (GSE107943) of 57 patients from Gene Expression Omnibus. An integrated mRNA-lncRNA risk score was established by a univariate and a multivariate Cox regression analyses. Time-dependent receiver operating characteristic (ROC) analysis was used to evaluate prognostic performance. Moreover, we conducted a correlation analysis between the signature and different clinical characteristics, and preformed weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis to investigate functional roles of the integrated signature.ResultsA total of two mRNAs (CFHR3 and PIWIL4) and two lncRNAs (AC007285.1 and AC134682.1) were identified to construct the integrated signature through a univariate Cox regression (P-value = 1.35E-02) and a multivariable Cox analysis (P-value = 1.12E-02). The ROC curve suggested the integrated mRNA-lncRNA signature possessed a high specificity and sensitivity of prognostic prediction with an area under the curve (AUC) of 0.872 and 0.790 at 1-year and 3-years, respectively. Subsequently, the signature was validated in GSE107943 cohort and combined dataset, and an area under the ROC curve reached up to 0.750 and 0.819 at 1-year. The signature was not only independent from different clinical features (P-value= 1.12E-02), but also outperformed other clinical characteristics as prognostic biomarkers with AUC of 0.781 at 3 years. These molecules in the integrated signature may associated with metabolic-related biological process and lipid metabolism pathway, which was highly involved in CCA carcinogenesis. ConclusionThese results showed that the integrated mRNA-lncRNA signature had an independent prognostic value for risk stratification, and further facilitated personalized treatment for CCA patients.
The Efficacy of Corticosteroid Therapy in Fibrotic Hypersensitivity Pneumonitis: A Propensity Score-matched Cohort Analysis
Authors: Ejima Masaru , Okamoto Tsukasa , Suzuki Takafumi , Anzai Tatsuhiko , Takahashi Kunihiko , Miyazaki Yasunari 
Published: November 2020

Abstract
Background: Fibrotic hypersensitivity pneumonitis (HP) is a chronic interstitial lung disease caused by allergic responses to repeated exposures to a causative antigen. Therapeutic evidence of corticosteroid for fibrotic HP remains lacking, although corticosteroid is recognized as a major treatment option. The purpose of this study was to evaluate the efficacy of corticosteroid for patients with fibrotic HP in a propensity score-matched cohort.Methods: Retrospective medical record review from 2005 to 2019 in a single center was conducted to identify 144 patients with fibrotic HP. Semiquantitative scores of lung abnormalities on HRCT were evaluated. Patients with corticosteroid treatment (PDN group) and without the treatment (non-PDN group) were matched using a propensity score method. Survival rates and serial changes in pulmonary function, and annual changes in HRCT scores werecompared between pair-matched patients. Results: In the matched analysis, 30 of the PDN group were matched with 30 of the non-PDN group, the majority of which comprised ILD without extensive fibrosis. The survival rate was significantly better in the PDN group (P = 0.032for the stratified Cox proportional hazards model; HR, 0.250). Absolute changes in %FVC at 6, 12, and 24 months from baseline were significantly better in the PDN group. Fewer cases experienced annual deterioration in HRCT scores in the non-PDN group for ground-glass attenuation, consolidation, reticulation, traction bronchiectasis and honeycombing. Conclusions: Fibrotic HP without extensive fibrosis may receive benefits from corticosteroid treatment in terms of improvements in survival rate and pulmonary function decline and inhibition of fibrotic progression. We propose that early initiation of corticosteroid be considered for fibrotic HP when worsening fibrosis is observed.