bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of full-length transcriptomes based on hybrid population reveals regulatory mechanisms of anthocyanin biosynthesis in sweet potato (Ipomoea batatas (L.) Lam)
Authors: Qin Zhen , Hou Fuyun , Li Aixian , Dong Shuxu , Huang Chengxing , Wang Qingmei , Zhang Liming 
Published: June 2020

Abstract
Background
Sweet potato (Ipomoea batatas (L.) Lam.) is a highly heterozygous autohexaploid crop with high yield and high anthocyanin content. Purple sweet potato is the main source of anthocyanins, and the mechanism of anthocyanin biosynthesis in storage roots has not been fully revealed.

Results
In order to reveal the mechanism of anthocyanin biosynthesis and identify new homologous genes involved in anthocyanin biosynthesis in the storage roots of sweet potato, we used Ningzishu 1 and Jizishu 2 as parents to construct a F1 hybrid population. Seven anthocyanin-containing lines and three anthocyanin-free lines were selected for full-length and second-generation transcriptome analyses. A total of 598,375 circular consensus sequencing reads were identified from full-length transcriptome sequencing. After analysis and correction of second-generation transcriptome data, 41,356 transcripts and 18,176 unigenes were obtained. Through a comparative analysis between anthocyanin-containing and anthocyanin-free groups 2329 unigenes were found to be significantly differentially expressed, of which 1235 were significantly up-regulated and 1094 were significantly down-regulated. GO enrichment analysis showed that the differentially expressed unigenes were significantly enriched in molecular function and biological process. KEGG enrichment analysis showed that the up-regulated unigenes were significantly enriched in the flavonoid biosynthesis and phenylpropanoid biosynthesis pathways, and the down-regulated unigenes were significantly enriched in the plant hormone signal transduction pathway. Weighted gene co-expression network analysis of differentially expressed unigenes revealed that anthocyanin biosynthesis genes were co-expressed with transcription factors such as MYB, bHLH and WRKY at the transcription level.

Conclusions
Our study will shed light on the regulatory mechanism of anthocyanin biosynthesis in sweet potato storage roots at the transcriptome level.
Characterization of Brazilian hospital admissions due to cardiovascular diseases: a longitudinal study
Authors: de Araújo Fonseca Luiza Gabriela , Lima Illia Nadinne Dantas Florentino , Gualdi Lucien Peroni 
Published: June 2020

Abstract
Background
Cardiovascular diseases (CVD) are the main cause of death and comorbidities worldwide. It is estimated that three quarters of all deaths related to CVD occur in low and middle income countries such as Brazil. Furthermore, it is estimated that emerging countries will present the highest worldwide prevalence of such diseases by 2050. In view of the above, this study aims to characterize Brazilian hospital admission distribution classified by the ICD-10 in adults between 2008 and 2017 in Brazil.

Methods
This is a longitudinal descriptive study in which all data regarding hospital admissions registered in the Brazilian Hospital Information System of “Sistema Único de Saúde” (SIH/SUS) due to cardiovascular diseases (ICD-10) were included. All admissions from private or public services linked to the SUS from 2008 and 2017 were evaluated. The following variables were collected: number of hospital admissions, place of hospitalization classified by the ICD-10 and mortality rate at the federal level and according to regions. Absolute values and frequency of hospital admissions were grouped according to sex, age and living region as well as the number of deaths. The extracted data was stored in a Microsoft Excel 2013 program spreadsheet. Statistical analysis was performed by GraphPad Prism version 5.0 software.

Results
There was a total of 11,345,821 hospital admissions due to CVD registered between 2008 and 2017. Individuals from 50 to 79 years old were the most affected. Heart failure (21.3%), other ischemic heart diseases (13.3%) and stroke (11.4%) were responsible for almost half of the hospital admissions associated to CVD. The number of registered deaths caused by any CVD was 867,838 and the national mortality rate was 7.82.

Conclusion
CVD were responsible for around 10% of all hospital admissions in Brazil between 2008 and 2017. Moreover, it was possible to observe a decrease in hospital admissions as well as mortality rate over time after implementing governmental strategies to prevent cardiovascular diseases.
Modeling observations with a detection limit using a truncated normal distribution with censoring
Authors: Williams Justin R. , Kim Hyung-Woo , Crespi Catherine M. 
Published: June 2020

Abstract
Background
When data are collected subject to a detection limit, observations below the detection limit may be considered censored. In addition, the domain of such observations may be restricted; for example, values may be required to be non-negative.

Methods
We propose a method for estimating population mean and variance from censored observations that accounts for known domain restriction. The method finds maximum likelihood estimates assuming an underlying truncated normal distribution.

Results
We show that our method, tcensReg, has lower bias, Type I error rates, and mean squared error than other methods commonly used for data with detection limits such as Tobit regression and single imputation under a range of simulation settings from mild to heavy censoring and truncation. We further demonstrate the consistency of the maximum likelihood estimators. We apply our method to analyze vision quality data collected from ophthalmology clinical trials comparing different types of intraocular lenses implanted during cataract surgery. All of the methods yield similar conclusions regarding non-inferiority, but estimates from the tcensReg method suggest that there may be greater mean differences and overall variability.

Conclusions
In the presence of detection limits, our new method tcensReg provides a way to incorporate known domain restrictions in dependent variables that substantially improves inferences.
A conceptual framework for prognostic research
Authors: Kent Peter , Cancelliere Carol , Boyle Eleanor , Cassidy J. David , Kongsted Alice 
Published: June 2020

Abstract
Background
Prognostic research has many important purposes, including (i) describing the natural history and clinical course of health conditions, (ii) investigating variables associated with health outcomes of interest, (iii) estimating an individual’s probability of developing different outcomes, (iv) investigating the clinical application of prediction models, and (v) investigating determinants of recovery that can inform the development of interventions to improve patient outcomes. But much prognostic research has been poorly conducted and interpreted, indicating that a number of conceptual areas are often misunderstood. Recent initiatives to improve this include the Prognosis Research Strategy (PROGRESS) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) Statement. In this paper, we aim to show how different categories of prognostic research relate to each other, to differentiate exploratory and confirmatory studies, discuss moderators and mediators, and to show how important it is to understand study designs and the differences between prediction and causation.

Main text
We propose that there are four main objectives of prognostic studies – description, association, prediction and causation. By causation, we mean the effect of prediction and decision rules on outcomes as determined by intervention studies and the investigation of whether a prognostic factor is a determinant of outcome (on the causal pathway). These either fall under the umbrella of exploratory (description, association, and prediction model development) or confirmatory (prediction model external validation and investigation of causation). Including considerations of causation within a prognostic framework provides a more comprehensive roadmap of how different types of studies conceptually relate to each other, and better clarity about appropriate model performance measures and the inferences that can be drawn from different types of prognostic studies. We also propose definitions of ‘candidate prognostic factors’, ‘prognostic factors’, ‘prognostic determinants (causal)’ and ‘prognostic markers (non-causal)’. Furthermore, we address common conceptual misunderstandings related to study design, analysis, and interpretation of multivariable models from the perspectives of association, prediction and causation.

Conclusion
This paper uses a framework to clarify some concepts in prognostic research that remain poorly understood and implemented, to stimulate discussion about how prognostic studies can be strengthened and appropriately interpreted.
Transarterial chemoembolization combined with iodine 125 seeds versus transarterial chemoembolization combined with radiofrequency ablation in the treatment of early- and intermediate-stage hepatocellular carcinoma
Authors: Chen Lei , Kan Xuefeng , Sun Tao , Ren Yanqiao , Cao Yanyan , Yan Liangliang , Liang Bin , Xiong Bin , Zheng Chuansheng 
Published: June 2020

Abstract
Background
Transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and iodine 125 seeds implantation are optional treatments for hepatocellular carcinoma (HCC). The aim of this study is to compare the efficacy of the combined treatment of TACE with iodine 125 seeds implantation (TACE-iodine 125) with TACE with RFA (TACE-RFA) in patients with early- and intermediate-stage HCC.

Methods
The study included 112 patients who were diagnosed with early- and intermediate-stage HCC from January 1, 2014, to May 31, 2018. Among them, 38 patients were treated with TACE-Iodine 125, and 74 with TACE-RFA. The efficacy of the two treatment groups was retrospectively analyzed. To reduced the selective bias, a propensity score matching (PSM) analysis and inverse probability of treatment weighting (IPTW) method were used to compare the outcomes between the two groups.

Results
In the absence of PSM and IPTW, the median overall survival (OS) and progression-free survival (PFS) of the TACE-RFA group were slightly longer than those of the TACE-Iodine 125 group (OS: 41 months vs. 36 months; PFS: 18 months vs. 15 months). However, there were no statistically significant differences in the median OS, PFS, and objective response rate (ORR) between the two groups (P > 0.05). After adjusting the age, gender, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and Alpha-fetoprotein (AFP), TACE-Iodine 125 treatment was not associated with a significant increasing the risks of death (HR: 0.763; 95%CI: 0.403,1.345, P = 0.320) and recurrence (HR: 1.020; 95%CI: 0.645,1.611, P = 0.934). After PSM, 35 matched pairs of patients were obtained, and there were no statistically significant differences in the median OS and PFS between the two groups. After IPTW, similar results presented.

Conclusions
The combination of TACE with iodine 125 seeds implantation may represent an effective treatment for patients with early- and intermediate-stage HCC.
Asymptomatic central line-associated bloodstream infections in children implanted with long term indwelling central venous catheters in a teaching hospital, Sri Lanka
Authors: Jayaweera J. A. A. S. , Sivakumar D. 
Published: June 2020

Abstract
Background
Indwelling central venous catheters (CVC) are used to provide long term hemodialysis. The commonest and the severe complication of CVC is the central line-associated bloodstream infection (CLABSI). This study was done to assess the etiology and infectious complications of CVC in children on long term hemodialysis.

Methods
Children newly undergoing hemodialysis and having indwelling CVC were included. They were followed up to a period of 2-years to assess infectious complications. Catheter bundle care approach was employed to prevent infections and other complications. Automated culture from the central catheter and peripheral vein and 2D echocardiography were done in each hemodialysis. Serial procalcitonin (PCT) was measured. Differential time of positivity (DTP) was used to detect CLABSI. During homestay in weekly telephone conversations were done to assess features of infection, and whenever having, we have asked to admit to the tertiary care unit. Logistic regression was performed, and the significant outcome variable was considered following multivariable analysis as a risk factor.

Results
Blood cultures were positive in 1090 (74.5%) out of 1462 children. According to DTP, 410 (28%) were having CLABSI, while 520 (35.6%) were having bacteremia without CLABSI. Out of 410 CLABSI patients, 79 (19.2%) were asymptomatic. Coagulase-negative Staphylococcus spp. (CoNS) bacteremia was significantly associated with asymptomatic CLABSI. Right-sided infective endocarditis (RS-IE) was significantly associated with asymptomatic CLABSI and asymptomatic bacteremia without CLABSI. CoNS was associated significantly in RS-IE following asymptomatic CLABSI and asymptomatic bacteremia. PCT was in asymptomatic CLABSI was 1.8 ± 0.9 ng/mL while in symptomatic CLABSI was 11.3 ± 2.5 ng/ml (P = 0.02). CoNS bloodstream infection, tunneled CVC, peripherally inserted central catheter, femoral site, the number of line days > 90, receipt of vancomycin, meropenem, or linezolid in the 5 days before CLABSI diagnosis and recurrent bacteremia were risk factors for asymptomatic CLABSI.

Conclusions
Asymptomatic CLABSI could be a rare occurrence. CoNS was predominantly isolated in patients with asymptomatic CLABSI. RS- IE is a well-known complication in long term indwelling CVC. CoNS was significantly associated with RS-IE following asymptomatic CLABSI. Regular procalcitonin, microbiological, and imaging studies would be essential to detect infectious complications in both symptomatic and asymptomatic patients implanted with long term indwelling CVCs.
Comparison of the clinical and MRI features of patients with hepatic hemangioma, epithelioid hemangioendothelioma, or angiosarcoma
Authors: Liu Zhuangsheng , Yi Lilei , Chen Junhao , Li Ruqiong , Liang Keming , Chen Xiangmeng , Li Ronggang , Long Wansheng 
Published: June 2020

Abstract
Background
Comparisons of hepatic epithelioid hemangioendothelioma (HEHE), hepatic hemangioma, and hepatic angiosarcoma (HAS) have rarely been reported. The purpose of our study was to analyze the clinical and magnetic resonance imaging (MRI) findings of these conditions.

Methods
A total of 57 patients (25 with hemangioma, 13 with HEHE, and 19 with HAS) provided hepatic vascular endothelial cell data between June 2006 and May 2017.

Results
The proportions of cases with circumscribed margins were 88% (22/25), 84.6% (11/13), and 31.6% (6/19) for hemangioma, HEHE, and HAS, respectively (P < 0.001). HAS lesions were less likely to have circumscribed margins. The proportions of lesions with hemorrhaging were 4% (1/25), 30.8% (4/13), and 36.8% (7/19) for hemangioma, HEHE, and HAS, respectively (P = 0.014). HEHE and HAS cases were more likely to show heterogeneous signals on T1-weighted (T1WI) MRI. HEHE and HAS cases were more likely to show heterogeneous signals on T2-weighted (T2WI) MRI. Centripetal enhancement was the most common pattern in vascular tumors, with proportions of 100, 46.2% (6/13), and 68.4% (13/19) for hemangioma, HEHE, and HAS, respectively. The difference in enhancement pattern between HEHE and HAS was not significant, but rim enhancement was more common for HEHE (46.2%, 6/13).

Conclusions
Our study revealed clinical and imaging differences between HEHE and HAS. The platelet count (PLT) and coagulation function of the HAS group decreased, whereas the alpha-fetoprotein (AFP) level increased. The 5-year survival rate for HAS was significantly lower than that of HEHE. A higher malignancy degree indicated a more blurred lesion margin, easier occurrence of hemorrhaging, and more heterogeneous T1WI and T2WI signals.
Prospective study of stress, depression and personality in myasthenia gravis relapses
Authors: Bogdan Anca , Barnett Carolina , Ali Abdulrahman , AlQwaifly Mohammed , Abraham Alon , Mannan Shabber , Ng Eduardo , Bril Vera 
Published: June 2020

Abstract
Background
Psychopathology and personality traits may influence the course of autoimmune disorders. With this prospective longitudinal cohort study, we aimed to assess personality, stress and depression in myasthenia patients who relapse and those who remain stable or improve (non-relapsers).

Method
We collected data from 155 consecutive adult patients with confirmed MG attending the Neuromuscular Clinic, Toronto General Hospital, between March 2017 and July 2018, for this study. Patients were assessed at baseline and 6 months, or at the time of MG relapse. At both visits, the patients were assessed clinically and were asked to complete self-administered questionnaires for disease severity, chronic stress and depression. Personality type was assessed at baseline only. Relapsing patients were defined as those patients with MGII score increasing by more than 5.5 points from visit 1 to visit 2.

Results
Relapsers had higher baseline scores for depression (p = 0.01) and the change in disease severity correlated with the change in depression score (r = 0.2534, p = 0.0015, 95% CI: 0.098 0.3961). Higher levels of stress at baseline and neuroticism predicted higher relapse rates (p = 0.01 and p < .0001, respectively). In the linear regression model, with change of the MGII score as the dependent variable, change in depression scores (p = 0.0004) and age (p = 0.03) predicted change in disease severity.

Conclusions
Since emotional factors and personality type may influence MG, attention to these factors might improve care in MG patients.
A novel POLR3A genotype leads to leukodystrophy type-7 in two siblings with unusually late age of onset
Authors: Campopiano Rosa , Ferese Rosangela , Zampatti Stefania , Giardina Emiliano , Biagioni Francesca , Colonnese Claudio , Centonze Diego , Storto Marianna , Buttari Fabio , Fraviga Edoardo , Broccoli Vania , Fanelli Mirco , Fornai Francesco , Gambardella Stefano 
Published: June 2020

Abstract
Background
Leukodystrophies are familial heterogeneous disorders primarily affecting the white matter, which are defined as hypomyelinating or demyelinating based on disease severity as assessed at MRI. Recently, a group of clinically overlapping hypomyelinating leukodystrophies (HL) has been associated with mutations in RNA polymerase III enzymes (Pol III) subunits.

Case presentation
In this manuscript, we describe two Italian siblings carrying a novel POLR3A genotype. MRI imaging, genetic analysis, and clinical data led to diagnosing HL type 7. The female sibling, at the age of 34, is tetra-paretic and suffers from severe cognitive regression. She had a disease onset at the age of 19, characterized by slow and progressive cognitive impairment associated with gait disturbances and amenorrhea. The male sibling was diagnosed during an MRI carried out for cephalalgia at the age of 41. After 5 years, he developed mild cognitive impairment, dystonia with 4-limb hypotonia, and moderate dysmetria with balance and gait impairment.

Conclusions
The present study provides the first evidence of unusually late age of onset in HL, describing two siblings with a novel POLR3A genotype which showed the first symptoms at the age of 41 and 19, respectively. This provides a powerful insight into clinical heterogeneity and genotype-phenotype correlation in POLR3A related HL.
Associations of malaria, HIV, and coinfection, with anemia in pregnancy in sub-Saharan Africa: a population-based cross-sectional study
Authors: Ssentongo Paddy , Ba Djibril M. , Ssentongo Anna E. , Ericson Jessica E. , Wang Ming , Liao Duanping , Chinchilli Vernon M. 
Published: June 2020

AbstractBackgroundMalaria and HIV are common infections in Africa and cause substantial morbidity and mortality in pregnant women. We aimed to assess the association of malaria with anemia in pregnant women and to explore the joint effects of malaria and HIV infection on anemia in pregnant women.MethodsWe used nationally representative, cross-sectional demographic and health surveys (DHS) that were conducted between 2012 and 2017 across 7 countries of sub-Saharan Africa (Burundi, the Democratic Republic of the Congo, Gambia, Ghana, Mali, Senegal and Togo). The outcome variables were anemia (defined as a hemoglobin concentration < 110 g/L), and hemoglobin concentration on a continuous scale, in pregnant women at the time of the interview. We used generalized linear mixed-effects models to account for the nested structure of the data. We adjusted models for individual covariates, with random effects of the primary sampling unit nested within a country.ResultsA total of 947 pregnant women, ages, 15–49 y, were analyzed.Prevalence of malaria only, HIV only, and malaria- HIV coinfection in pregnant women was 31% (95% CI: 28.5 to 34.5%,n = 293), 1.3% (95% CI: 0.77 to 2.4%,n = 13) and 0.52% (95% CI: 0.02 to 1.3%,n = 5) respectively. Overall prevalence of anemia was 48.3% (95% CI: 45.1 to 51.5%). The anemia prevalence in pregnant women with malaria infection only was 56.0% (95% CI: 50.1 to 61.7%); HIV infection only, 62.5% (95% CI: 25.9 to 89.8%); malaria- HIV coinfection, 60.0 (95% CI: 17.0–92.7%) and without either infection, 44.6% (95% CI: 40.7 to 48.6%). In the fully adjusted models, malaria infection was associated with 27% higher prevalence of anemia (95% CI of prevalence ratio: 1.12 to 1.45;p = 0.004), and 3.4 g/L lower hemoglobin concentration (95% CI: - 5.01 to − 1.79;p = 0.03) compared to uninfected pregnant women. The prevalence of HIV infection and malaria-HIV coinfection was too low to allow meaningful analysis of their association with anemia or hemoglobin concentration.ConclusionMalaria was associated with an increased prevalence of anemia during pregnancy.
Absence of lymphatic vessels in term placenta
Authors: Becker Jürgen , Tchagou Tchangou Gilles E. , Schmidt Sonja , Zelent Christina , Kahl Fritz , Wilting Jörg 
Published: June 2020

Abstract
Background
There has been debate about the existence of lymphatic vessels in placenta. Lymphatic endothelial cell (LEC) markers such as LYVE-1 and podoplanin/D2–40 have been found, although PROX1 has not been detected. The most reliable marker for LECs is the double staining for CD31 and PROX1, which has not been performed yet.

Methods
We studied three term placentas and dissected them into three areas: i.) basal plate area, ii.) intermediate area, and iii.) chorionic plate area. We used immunofluorescence single and double staining with antibodies against CD31, PROX1, LYVE-1, VEGFR-3, D2–40/PDPN, CD34, CCBE-1, and vimentin, as well as nested PCR, qPCR, Western blot and transmission electron microscopy (TEM).

Results
At TEM level we observed structures that have previously mistakenly been interpreted as lymphatics, however, we did not find any CD31/PROX1 double-positive cells in placenta. Absence of PROX1 was also noted by nested PCR, qPCR and Western blot. Also, LEC marker VEGFR-3 was expressed only in a small number of scattered leukocytes but was absent from vessels. The LEC marker D2–40/PDPN was expressed in most stromal cells, and the LEC marker LYVE-1 was found in a considerable number of stromal cells, but not in endothelial cells, which were positive for CD31, CD34, CCBE-1 and vimentin. Additionally, vimentin was found in stromal cells.

Conclusions
Our studies clearly show absence of lymphatics in term placenta. We also show that the functional area of the mother’s endometrium is not penetrated by lymphatics in term pregnancy.