bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a CT-TA nomogram for preoperatively differentiating thymic epithelial tumor histologic subtypes
Authors: Ren Caiyue , Li Mingli , Zhang Yunyan , Zhang Shengjian 
Published: February 2020

Abstract
Background: Thymic epithelial tumors (TETs) are the most common primary tumors in the anterior mediastinum with considerable histologic heterogeneity. This study aimed to develop and validate a nomogram based on computed tomography (CT) and texture analysis (TA) for preoperatively predicting pathological classification for TET patients.Methods: Totally 172 patients with pathologically confirmed TET after surgery were retrospectively analyzed and randomly divided into a training cohort (n=120) and a validation cohort (n=52). Preoperative clinical demographic, CT signs and texture features of each patient were analyzed and prediction models were developed using the least absolute shrinkage and selection operator (LASSO) regression. The performance of models was evaluated and compared by the area under receiver operating characteristic (ROC) curve (AUC) and DeLong test. The clinical application value of models was determined through the decision curve analysis (DCA). Then a nomogram was developed based on the model with the best predictive accuracy and clinical utility and validated using the calibration plots.Results: Totally 87 patients with low-risk TET (LTET) (types A, AB, B1) and 85 patients with high-risk TET (HTET) (types B2, B3, C) were enrolled in this study. We separately constructed 4 prediction models for differentiating LTET from HTET using clinical, CT, texture features and their combination. These 4 prediction models achieved AUC values of 0.66, 0.79, 0.82, 0.88 in the training cohort and 0.64, 0.82, 0.86, 0.94 in the validation cohort, respectively. DeLong test and DCA analysis showed that the Combined model consisting of 2 CT signs and 2 texture parameters held the highest predictive efficiency and clinical utility ( p <0.05). A prediction nomogram was subsequently developed using the combined model’s 4 independently risk factors. The calibration curves indicated a good consistency between the actual observation and nomogram prediction for differentiating TET classifications.Conclusion: A prediction nomogram incorporating both the CT and texture parameters was constructed and validated in our study, which was conveniently used to facilitate the preoperative individualized prediction of simplified histologic subtypes in TET patients, assisting in clinical treatment decision making and achieving precision treatment.
Fatty acid synthase (FASN), a novel signature for visceral adipose tissues, regulates proliferation, migration and predicts prognosis of clear cell renal cell carcinoma
Authors: Xu Wen-Hao , Anwaier Aihetaimujiang , Wang Hong-Kai , Wang Jun , Zhu Wen-Kai , Tian Xi , Ma Chung-Guang , Wan Fang-Ning , Cao Da-Long , Shi Guo-Hai , Qu Yuan-Yuan , Zhang Hai-Liang , Ye Ding-Wei 
Published: February 2020

Abstract
Background: Growing evidence has indicated obesity one of the important etiological indicators of clear cell renal cell carcinoma (ccRCC). This study aims to investigated FASN mRNA expression in anthropometric adipose tissue, and elucidate prognostic value and potential functions in ccRCC patients. Methods: Transcriptional expression profiles was obtained from 380 paired ccRCC and adjacent normal tissues from Fudan University Shanghai Cancer Center (FUSCC) and 533 ccRCC samples from the Cancer Genome Atlas (TCGA) cohort. The visceral adipose tissue (VAT) and the subcutaneous adipose tissue (SAT) at the level of the umbilicus were measured using magnetic resonance imaging. The Kaplan-Meier method and log-rank test, with cooperation from Cox regression analysis, were used in survival analysis. Subsequently, we transiently transfected FASN plasmid into A498 and 786O cells, and investigated the role of FASN in ccRCC cell proliferation, apoptosis and migration in vitro. Related hub gens, functional annotations and significant signal pathways were predicted using integrated bioinformatics. Results: FASN mRNA expression was significantly higher in tumor than normal tissues in 913 ccRCC patients from FUSCC and TCGA cohorts. In addition, increased FASN mRNA expression was significantly relevant to advanced T stage ( p <0.001), N stage ( p =0.019), and AJCC stage ( p =0.002). Pearson’s correlation coefficient indicated that FASN amplification positively correlated with VAT% ( r =0.772, p <0.001). VAT% was significantly correlated with poor PFS and OS, with hazard ratios of 2.066 (1.113-7.261, p =0.028) and 2.773 (1.168-8.974, p =0.023) in FUSCC. Meanwhile, ccRCC patients with elevated FASN expression significantly responded for poor PFS and OS, with hazard ratios of 1.529 (1.135-2.061, p =0.005) and 1.450 (1.030-2.041, p =0.033). Next, after transfection efficiency was verified in A498 and 786O cells, we found transient inhibition and overexpression of FASN significantly regulates cells proliferation and migration abilities, and inhibition of FASN displayed higher apoptotic rate in ccRCC cells. Conclusion: In conclusion, this study demonstrated that FASN mRNA expression is positively related with aggressive proliferation, migration progression and predicts prognosis of ccRCC. In addition, we first reveal that elevated FASN mRNA expression is significantly correlated with abdominal obesity distribution, especially VAT%, which also is a significant predictor of poor prognosis in patients with ccRCC.
A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility
Authors: Onwuka Justina Ucheojor , Li Dapeng , Liu Yupeng , Huang Hao , Xu Jing , Liu Ying , Zhao Yashuang , Zhang Yuanyuan 
Published: February 2020

Abstract
Background Differential DNA methylation panel derived from peripheral blood could serve as biomarkers of CRC susceptibility. However, most of the previous studies utilized post-diagnostic blood DNA which may be markers of disease rather than susceptibility. In addition, to date no study has evaluated the predictive potential of such markers in a prospective cohort and on a genome-wide basis. The aim of this study was to identify potential panel of DNA methylation biomarkers in peripheral blood that are associated with CRC risk and therefore serve as epigenetic biomarkers of disease susceptibility. Methods DNA methylation profile of a nested case-control study with 166 CRC and 424 healthy normal subjects were obtained from Gene Expression Omnibus (GEO) database. The differentially methylated markers were identified by moderated t-statistics. The DNA methylation panel were constructed by stepwise logistic regression and least absolute shrinkage and selection operator in training dataset. A methylation risk score (MRS) model was constructed and the association between MRS and CRC risk assessed. Results We identified 48 differentially methylated CpGs sites, of which 33 were hypomethylated. Of these, sixteen-CpG based MRS that was associated with CRC risk (OR = 2.68, 95% CI: 2.13, 3.38, P < 0.0001) was constructed. This association is confirmed in the testing dataset (OR = 2.02, 95% CI: 1.48, 2.74, P < 0.0001) and persisted in both males and females, younger and older subjects, short and long time-to-diagnosis. The MRS also predicted CRC with AUC 0.82 (95% CI: 0.76, 0.88), indicating high accuracy. Conclusions Our study has identified a novel DNA methylation panel that is associated with CRC and could be-useful for the prediction of CRC risk in the future.
Farnesal-loaded pH-sensitive polymeric micelles provided effective prevention and treatment on dental caries
Authors: Yi Youping , Wang Lujun , Chen Lin , Lin Yan , Luo Zhongling , Chen Zhenyu , Li Ting , Wu Jianming , Zhong Zhirong 
Published: February 2020

Abstract
Background: Farnesol is a sesquiterpene from propolis and citrus fruit that shows promising anti-bacterial activity for caries treatment and prevention, but its hydrophobicity limits the clinical application. We aimed to develop the novel polymeric micelles (PMs) containing a kind of derivative of farnesol and a ligand of pyrophosphate (PPi) that mediated PMs to adhere tightly with the tooth enamel.Results: Farnesal (Far) was derived from farnesol and successfully linked to PEG via an acid-labile hydrazone bond to form PEG-hyd-Far, which was then conjugated to PPi and loaded into PMs to form the aimed novel drug delivery system, PPi-Far-PMs. The in vitro test about the binding of PPi-Far-PMs to hydroxyapatite showed that PPi-Far-PMs could bind rapidly to hydroxyapatite and quickly release Far under the acidic conditions. Results from the mechanical testing and the micro-computed tomography indicated that PPi-Far-PMs could restore the microarchitecture of teeth with caries. Moreover, PPi-Far-PMs diminished the incidence and severity of smooth and sulcal surface caries in rats that were infected with Streptococcus mutans while being fed with a high-sucrose diet . The anti-caries efficacy of free Far can be improved significantly by PPi-Far-PMs through the effective binding of it with tooth enamel via PPi.Conclusions: This novel drug-delivery system may be useful for the treatment and prevention of dental caries as well as the targeting therapy of anti-bacterial drugs in the oral disease.
Ovarian inguinal hernia – a possibility in MURCS syndrome
Authors: Saini Rahul , Bains Lovenish , Kaur Tarangpreet , Lal Pawan , Pal Veer , Beg Mohd Yasir , Kaur Daljit 
Published: February 2020

Abstract
Background Inguinal hernia containing ovary can be found in paediatric population and is a rare finding in women of reproductive age group. Most of the cases are associated with congenital abnormalities of the female genital tract. Case Presentation A 20 year old female presented with right reducible inguinal hernia, primary amenorrhea and normal secondary sexual characteristics. Clinical examination revealed scoliosis with convexity towards left side, prominence of left rib cage with sprengel deformity and right sided heart sounds. Ultrasound of the inguinal swelling revealed right ovary within the hernial sac, Chest X-ray revealed right lung collapse and dextrocardia. Further Magnetic resonance imaging (MRI) of pelvis revealed inguinal hernia with right ovary as its content, normal left ovary and absent uterus. Computed tomography (CT) revealed complete collapse of right lung with compensatory left lung hyperinflation and absent right kidney. Karyotyping of the patient was normal, 46XX. A diagnosis of MURCS syndrome with right ovarian hernia was made. The hernia was surgically managed with repositioning of ovary into the pelvis. Discussion Ovary in inguinal hernia is rare in women of reproductive age group. MRKH syndrome, a mullerian duct anomaly, is the congenital aplasia of uterus and upper two-thirds of vagina in a female with normal ovaries, fallopian tube, secondary sexual characteristics and 46XX karyotype. MURCS is a subtype of MRKH type 2 having mullerian duct agenesis with renal, cardiac, muscular & vertebral defects. General physical examination and primary investigations if yields abnormal findings; the patient must undergo an array of investigations to rule out MRKH/MURCS, or other congenital abnormality. Early diagnosis is essential to prevent its incarceration or torsion. The primary treatment of ovary in inguinal hernia is repositioning the ovary back to pelvis to preserve fertility and repair of inguinal hernia. A multidisciplinary team is required to deal with various abnormalities present in a patient with MURCS.
Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of Phase 3 studies in participants with migraine
Authors: Stauffer Virginia , Wang Shufang , Bonner Jo , Kim ByungKun , Bhandari Rohit , Day Kathleen A. , Camporeale Angelo 
Published: February 2020

Abstract
Background: Injection-site reactions have been reported with biologicals. In this post hoc analysis of Phase 3 studies in participants with migraine, we provide a comprehensive overview and detailed summary of injection-site reaction with galcanezumab.Methods: Data were obtained from two randomised clinical studies in participants with episodic migraine (EVOLVE-1 and EVOLVE-2), one randomised study in participants with chronic migraine (REGAIN) and one open-label study (Study CGAJ) in participants with episodic or chronic migraine. The injection-site reactions were measured for two different cohorts: 1) six-month double-blind treatment phase in the EVOLVE-1 and EVOLVE-2 studies and three-month double-blind treatment phase in the REGAIN study, where participants received placebo and galcanezumab (placebo-controlled analysis set); 2) three month double-blind (Month 0 to Month 3; 1:1:placebo:galcanezumab) + nine months open-label extension phase (Month 3 to Month 12) of REGAIN and twelve month open-label phase of Study CGAJ, where participants received only galcanezumab (galcanezumab exposure analysis set).Results: A total of 477 participants in the placebo-controlled analysis set (galcanezumab 240 mg, 166/730 [22.7%]; galcanezumab 120 mg, 128/705 [18.2%]; placebo, 183/1451 [12.6%]) reported at least one injection-site reaction. Most of the injection-site reactions were reported as injection-site pain, unspecified injection-site reaction, injection-site erythema, and injection-site pruritus. The incidence of injection-site pain was highest among all reported Injection-site reactions and were reported with similar frequency by participants receiving galcanezumab (galcanezumab 120mg, 10.1%; galcanezumab 240 mg, 11.6%) and placebo (9.5%) and was the most common injection-site reaction reported within 60 minutes of injection (~86% of participants). The frequency of unspecified injection-site reaction, injection-site erythema and injection-site pruritus was significantly (P<0.001) higher in participant receiving galcanezumab versus placebo. In the galcanezumab exposure analysis set participants received up to 12 doses and the frequency of injection-site reactions reported for both doses combined was 21.8%. The reporting of injection-site reactions did not increase with the number of doses received. No ISR-related serious adverse events were reported in both the placebo-controlled and galcanezumab exposure analysis sets.Conclusions: The most common adverse event of galcanezumab is injection-site reactions. However, these events were generally mild-to-moderate in severity, non-serious, resolved spontaneously, and discontinuations due to injection-site reactions were low (1%).Trial registration: Clinicaltrials.gov identifier: NCT02614183, NCT02614196, NCT02614261, NCT02614287.
The Joint External Evaluation process in Cameroon: Assessing the country’s capacity for health security
Authors: Fossouo Viviane Ndoungue Viviane , Mouiche Mohamed Moctar Mouliom , Tiwoda Christie , Gnigninanjouena Oumarou , Sadeuh-Mba Serge alain , Kimbi Roland WANGO , Ngapana Arouna Njayou 
Published: February 2020

Abstract
Objectives: The objective of this study was to present the JEE process in Cameroon’s as well as the country capacities to prevent, detect and respond to public health threats in accordance with the IHR (2005). Data for the 48 indicators within the 19 technical areas of the Joint External Evaluation (JEE) tool was examined. Results: Cameroon's overall median score was 2 (Min =1, Max=4) and 34/48 indicators (71%) had scores less than 2 on a 1 to 5 scale. The weakest technical areas in the “Prevent” category were antimicrobial resistance, biosafety and biosecurity, and National legislation, policy and financing. In the “Detect” category, the median score was 2. Technical areas with the lowest median scores were Reporting and National Laboratory System. Emergency Response Operations, Preparedness, Medical Countermeasures and Personnel Deployment had the lowest scores in the “Respond” category. Chemical Events and Points of Entry had the lowest score in “Other IHR-related hazards and Point of Entry” category. Recommendations from the JEE to address the gaps will be aligned in a costed National Action Plan for Health Security (NAPHS) and implemented using national resources, external donors and multilateral agencies. Key words: International Health Regulation, Joint External Evaluation, Health security, Cameroon.
Optimized vs. Standard Automated Peritoneal Dialysis Regimens (OptiStAR): Study Protocol for a Randomized Controlled Trial
Authors: Bergling Karin , de Arteaga Javier , Ledesma Fabián , Öberg Carl Mikael 
Published: February 2020

Abstract
Background: It has been estimated that automated peritoneal dialysis (APD) is currently the fastest growing renal replacement therapy in the world. However, in light of the growing number of diabetic patients on peritoneal dialysis (PD), the unwanted glucose absorption during APD remains problematic. Recent results, using an extended 3-pore model of APD, indicated that large reductions in glucose absorption are possible by using optimized bi-modal treatment regimens, having “UF cycles” using a higher glucose concentration and “Clearance cycles” using a low concentration or, preferentially, no glucose. The present study is designed to test the theoretical prediction of a lower glucose absorption using these novel regimes. Methods: This study is a randomized single-center, open-label, prospective study. Prevalent PD patients between 18 to 75 years old without known catheter problems or recent peritonitis are eligible for inclusion. Patients are allocated to a first treatment session of either Standard APD (6 × 2 L 1.36% over 9 hours) or Optimized APD (7 × 2 L 2.27% + 5 × 2 L 0.1% over 8 hours). A second treatment session using the other treatment will be performed in a crossover fashion. Samples of the dialysis fluid will be taken before and after the treatment and the volume of the dialysate before and after the treatment will be carefully assessed. The primary endpoint is difference in glucose absorption between the Optimized and Standard treatment. Secondary endpoints are ultrafiltration, sodium removal, Kt/V urea and Kt/V Creatinine. The study will be closed when a total of 20 patients have successfully completed the interventions or terminated according to interim analysis. A Monte Carlo power analysis shows that the study has 80% power to detect a difference of 10 g (in line with that of theoretical results) in glucose absorption between the two treatments in 10 patients. Discussion: The present study is the first clinical investigation of optimized bi-modal treatments proposed by recent theoretical studies.
Expression of mitochondrial protein genes encoded by nuclear and mitochondrial genomes correlate with energy metabolism in dairy cattle
Authors: Dorji Jigme , Jagt Christy J. Vander , Garner Josie B. , Marett Leah C. , Mason Brett , Reich Coralie M. , Xiang Ruidong , Clark Emily L. , Cocks Benjamin J. , Chamberlain Amanda J. , MacLeod Iona M. , Daetwyler Hans D. 
Published: February 2020

Abstract
Background Mutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterised by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MPs) from both the nuclear ( Nu MP) and mitochondrial ( Mt MP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses. Results MP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DE Nu MP genes in varying proportions of over-expression and under-expression. On the other hand, DE of Mt MP genes was observed in <50% of tissues and notably Mt MP genes within a tissue was either all over-expressed or all under-expressed . A high proportion of Nu MP (up to 60%) and Mt MP (up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% of Nu MP, 77% of Mt MP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of all Mt MP genes in the direction of dominant Nu MP genes expression. The Nu MP and Mt MP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathways. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets. Conclusions This study demonstrated the biological interaction of MP genes from the mitochondrial and nuclear genomes and their over-expression in tissues with high energy demand. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism.
Strain-level analysis of microbial community and detection of mutually exclusive relationships uncover complexity of inflammatory bowel disease
Authors: Shin Sunguk , Kim Jihyun F. 
Published: February 2020

Abstract
Background

Despite intraspecies variation in ecological interaction and cellular function, most analytical methods for microbial communities that use the 16S rRNA gene are employed at the taxonomic level. Further, methods that detect positive or negative relationships between microbes such as Pearson correlation coefficient are generally applicable for linear correlations.

Results

We present METATEA for the analysis of community members with identical 16S rDNA sequences to define intraspecies groups, and for the calculation of exclusive correlation coefficient (ECC) to detect mutually exclusive relationships. Proportional variation of identical sequence groups in each disease subtype was revealed using a 16S rDNA data set of inflammatory bowel disease (IBD) samples.

Conclusions

Results at the identical sequence level complied with and outperformed those at the species or genus levels. Intraspecies variation was prevalent within Faecalibacterium prausnitzii , suggesting that some strains might be associated with diseases although it is known to be abundant in the human gut microbiota of healthy adults. IBD samples were categorized into two groups based on the ratios of certain Bacteroides vulgatus -like sequences. ECC identified strains antagonistic to disease-associated bacteria, thus proving their potential as probiotics in precision medicine. Klebsiella pneumoniae showed exclusive relationships with various bacteria, and its proportion was associated with bacterial diversity and Crohn’s disease. We expect METATEA to allow high resolution analysis of microbial communities and easy identification of pathogen-antagonistic probiotic microbes.