bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome sequencing identified two novel COL10A1 heterozygous mutations in two irregular dominance Chinese pedigrees with Schmid-type metaphyseal chondrodysplasia
Authors: Kong Lingchi , Shi Li , Wang Wenbo , Zuo Rongtai , Wang Mengwei , Kang Qinglin 
Published: August 2019

Abstract
Background
Schmid-type metaphyseal chondrodysplasia (MCDS) is an autosomal dominant disorder caused by COL10A1 mutations, which is characterized by short stature, waddling gait, coxa vara and bowing of the long bones. However, the research about unusual phenotype features of MCDS is rare.

Methods
Two probands and available family members affected with MCDS were subjected to clinical and radiological examination. Genomic DNA of all affected individuals underwent whole-exome sequencing, and candidate mutations were verified by Sanger sequencing in all available family members and 250 donors. Then the spatial model of type X collagen (α1) C-terminal noncollagenous (NC1) domain was further constructed.

Results
We found that the affected family members exhibited evident irregular dominance. Mutation analysis indicated that there were two novel heterozygous missense mutations [c.1765T>A (p.Phe589Ile)] and [c.1846A>G (p.Lys616Glu)] in the COL10A1 gene in family 1 and 2, respectively. The two novel substitution sites were highly conserved and the mutations were predicted to be remarkably deleterious in silico analysis. Furthermore, protein modeling revealed that the two substitutions located in the NC1 domain of collagen X (α1), which potentially impacted the trimerization of collagen X (α1) and combination with molecules in pericellular matrix.

Conclusion
Two novel mutations were identified in the present study, which facilitated to diagnose MCDS and further expanded the spectrum of the COL10A1 mutations associated with MCDS patients. In addition, our research preliminarily elaborated the phenotype features and heredity characteristics of MCDS based on the two Chinese pedigrees.
Association of PD-1 polymorphisms with the risk and prognosis of lung adenocarcinoma in the northeastern Chinese Han population
Authors: huang Kun , Hu Erqiang , Li Wan , Lv Junjie , He Yuehan , Deng Gui , Xiao Jinling , Yang Chengcheng , Zhao Xinyu , Chen Lina , Wang Xinyan 
Published: August 2019

Abstract
Introduction
Lung cancer is a leading cause of death from cancer worldwide, especially non-small cell lung cancer (NSCLC). The marker of progression in lung adenocarcinoma has been rarely studied. PD-1 is an effective drug target for the treatment of non-small cell lung cancer. The study of the effect of polymorphism on the progression of lung adenocarcinoma in the Han population of Northeast China may provide a valuable reference for the research and application of these drugs.
Methods
Chi-square test, Wilcoxon rank sum test, and classification efficacy assessment were used to teste SNPs of PD-1 in 287 patients and combined with clinical information.
Results
We successfully identified biomarkers (rs2227981, rs2227982, and rs3608432) that could distinguish the early stages and late stages of lung adenocarcinoma. Multiple clinical indicators showed significant differences among different SNP typing and cancer stages. Furthermore, this gene was confirmed to effectively distinguish the staging of lung adenocarcinoma with RNA-seq data in TCGA.
Conclusions
This indicated that the PD-1 gene and the SNPs on it could be used as markers for distinguishing lung adenocarcinoma staging in the Northeast Han population.
Compound heterozygous LPIN2 pathogenic variants in a Majeed Syndrome patient with recurrent fever and severe neutropenia: case report
Authors: liu jun , Hu Xu-Yun , Zhao Zhi-Peng , Guo Ruo-Lan , Guo Jun , Li Wei , Hao Chan-Juan , Xu Bao-Ping 
Published: August 2019

Abstract
Background

Majeed syndrome is a rare, autosomal recessive autoinflammatory disorder first described in 1989. The syndrome starts during infancy with recurrent relapses of osteomyelitis typically associated with fever, congenital dyserythropoietic anemia (CDA) and often neutrophilic dermatosis. Mutations in the LPIN2 gene located on the short arm of chromosome 18 have been identified as being responsible for the Majeed syndrome.

Case presentation

We report a 8-month old boy, who presented with recurrent fever, mild to moderate anemia and severe neutropenia. Erythrocyte sedimentation rate and C-reactive protein were elevated. Molecular studies identified a paternal splicing donor site variant c.2327+1G>C and a maternal frameshift variant c.1691_1694delGAGA (Arg564Lysfs*3)in LPIN2.

Conclusions

Up to now, only a few cases with LPIN2 mutation have been reported, mainly in the Middle East with homozygous variants. Our patient exhibited a mild clinical phenotype and severe neutropenia, distinct from previously reported.
Spatio-temporal variation of malaria hotspots in central Senegal, 2008-2012
Authors: DIENG Sokhna , Ba El Hadj , Cissé Badara , Sallah Kankoe , Guindo Abdoulaye , Ouedraogo Boukary , Piarroux Martine , Rebaudet Stanislas , Piarroux Renaud , Landier Jordi , Sokhna Cheikh , Gaudart Jean 
Published: August 2019

Abstract
Background

In malaria endemic areas, identifying spatio-temporal hotspots is becoming an important element of innovative control strategies targeting transmission bottlenecks. The aim of this work was to describe the spatio-temporal variation of malaria hotspots in central Senegal, and to identify the meteorological, environmental, and preventive factors that influence this variation.

Methods

The weekly incidence of malaria cases recorded from 2008 to 2012 in 575 villages of central Senegal (total population 523,908) during a trial of Seasonal Malaria Chemoprevention (SMC), were analysed. Data on weekly rainfall and annual vegetation types were obtained for each village from remote sensing data. The time series of weekly cumulative malaria incidence for the entire study area was divided into periods of high and low transmission using change-point analysis. Malaria hotspots were detected for each period with the SaTScan method. The effects of rainfall, vegetation type, and SMC intervention on the spatio-temporal variation of malaria hotspots were assessed using a General Additive Mixed Model.

Results

The cumulative malaria incidence rate for the entire area ranged from 0 to 115.34 cases/100,000 person weeks during the study period. During high transmission periods, the cumulative malaria incidence rate varied between 7.53 and 38.1 cases/100,000 person-weeks, and the number of hotspot villages varied between 62 and 147. During low transmission periods, the cumulative malaria incidence rate varied between 0.83 and 2.73 cases/100,000 person-weeks, and the number of hotspot villages varied between 10 and 43. Villages with SMC were less likely to be hotspots (OR=0.48, IC95%: 0.33-0.68). According to the spatial interpolation, 2 zones located in the south of the study area had the highest risk of being a hotspot (ORmin=1.90, 95%CI: 1.02-3.56; ORmax=60.65, 95%CI: 26.86-136.95). The association between rainfall and hotspot status was non-linear and depended on vegetation type and the amount of rainfall.

Conclusion

In our study, malaria hotspots varied over space and time according to a combination of meteorological, environmental, and preventive factors. Our analysis shows also the importance of adapting control strategies to the local context and dynamic patterns. Moreover, the issue of spatial hotspots and foci of malaria persistence during LTPs needs to be further addressed.
Global trends in survival from brain tumours in adolescents and young adults: a systematic review.
Authors: Girardi Fabio , Allemani Claudia , Coleman Michel P 
Published: August 2019

Abstract
Background
Brain tumours represent an important cause of cancer-related death in adolescents and young adults. Most are diagnosed in low-income and middle-income countries. We aimed to conduct the first systematic review of time trends and geographical variation in survival in this age group.

Methods
We included observational studies describing population-based survival from astrocytic tumours in patients aged 15-39 years. We queried six electronic databases from database inception to 30 September 2018. This review is registered with PROSPERO, number CRD42018111981.

Results
Among 5,245 retrieved records, 20 studies fulfilled the inclusion criteria. Only one study was partly conducted in middle-income countries. Five-year survival from astrocytoma (broad morphology group) varied between 48% and 71% (1973-2004), without clear trends or geographic differences. Adolescents with astrocytoma had better outcomes than young adults, but survival values were similar when non-malignant tumours were excluded.

During 2002-2007, five-year survival for WHO grade I-II tumours was in the range 75-93% in England, Germany, and the US, but lower in South-Eastern Europe (59%).

Five-year survival for anaplastic astrocytoma varied between 40% and 55% (2002-2007). Five-year survival from glioblastoma was in the range 15-23% (1991-2009).

Conclusions
Survival from astrocytic tumours remained somewhat steady over time, with little change between 1973 and 2009. Survival disparities were difficult to examine, because nearly all the studies were conducted in affluent countries. Studies often adopted the International Classification of Childhood Cancer, which, however, did not allow to accurately describe variation in survival. Larger studies are warranted, including under-represented populations and providing more recent survival estimates.

Keywords
Population-based survival, brain tumours, adolescents, young adults, time trends.
Clinicopathological characteristics and cancer-specific survival prediction of Large cell lung cencer: a population-based study
Authors: Shi Yafei , Chen Wei , Li Chunyu , Qi Shuya , Zhou Xiaowei , Zhang Yujun , Li Ying , Li Guohui 
Published: August 2019

Abstract
Background:The features and survival outcome large cell lung cancer(LCLC) are scarce reported due to its low incidence,as a result, the prognoses of LCLC remain unclear.The aim of this study was to describe the demographic and clinical characteristics of large cell lung cancer with a population-base database and find the prognosis factors for cancer-specific survival(CSS) of the LCLC patients.Besides,a nomogram would be developed and independently validated to predict the CSS for LCLC based on the found prognosis factors.
Methods: We extracted LCLC patients information from the Surveillance, Epidemiology, and End Results(SEER) database(2005-2014) and summarized the characteristic of the extracted factors.We used the Cox proportional hazards regression to find the prognosis factors for LCLC patients and develop the nomogram based on these in a splitted train cohort from the extracted data.The validation of the developed nomogram would be performed in an independent validation cohort from the extracted data, in which the C-index and the average of the time-dependent area under the receiver operating characteristic curve(time-dependent AUC) for CSS in 1-year, 3-year and 5-year would be calculated.The calibration curves would be drawn to visualize the performance of the established nomogram.
Results: In result,4936 patients with LCLC were identified from the SEER database. Nearly half of LCLC patients were diagnosis with stage IV,only approximately 20% of patients was performed surgery.The prognosis factors influence the LCLC patients included age, sex,American Joint Committee on Cancer (AJCC) stage,race,surgery, tumour size and marital status.The calculated C-index was 0.701±0.01,mean time-dependent AUC for CSS in 1-year, 3-year and 5-year was 0.88.The calibrate curve showed that the gap between the predicted and observed CSS for 1-year, 3-year and 5-year was small.
Conclusions:Sex,age,race,marital status,AJCC stage, surgery and tumour size are all the independent prognostic factors for CSS of the LCLC.The established nomogram can provide more precise evaluation for the survival of LCLC patients,and help the clinicians to make individual management.
Cardiac biomarkers for early detection of cardiac involvement in children with Kawasaki disease: a cross-sectional study
Authors: Molaei Akbar , Khomahani Azizollah , Ghaffari Shamsi , Sadeghi-Shabestari Mahnaz , Sadat-Ebrahimi Seyyed-Reza 
Published: August 2019

Abstract
Background

Kawasaki disease (KD), which is the second most prevalent vasculitis disease in children after IgA vasculitis, can cause serious cardiovascular complications. Early detection of cardiac involvement in KD is an essential part in managing and preventing the cardiac sequels. Although some cardiac biomarkers such as cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) have recently been suggested for early diagnosis of cardiac involvement in patients with KD, their applicability is still unclear. Thus, this study aimed to compare the levels of cTnI and NT-proBNP in KD child patients with or without cardiac involvement.

Methods

In this cross sectional study, 32 children with KD who were admitted to the children teaching hospital of Tabriz University of Medical Sciences between April 2015 and April 2018, were consecutively included in the study. For all involved children, the coronary artery involvement defined as coronary artery aneurysm or perivascular brightness of coronary arteries was examined by transthoracic echocardiography, and their serum levels of NT-proBNP and cTnI were measured.

Results

Of 32 enrolled patients, 4 (9.4%) had cardiac involvement including 3 patients with perivascular brightness of coronary arteries and 1 patient with small aneurysm of the coronary arteries. In all study patients, the cTnI levels were lower than 0.35 and the NT-proBNP assessments revealed an average of 678.5 pg/ml. Children with cardiac involvement had significantly higher NT-proBNP (p-value, 0.001). ROC analysis for power of the NT-proBNP in predicting the cardiac involvement, revealed an excellent power for NT-proBNP (AUC=1.000, p=0.001). Both sensitivity and specificity of NT-proBNP at the optimum cut-off point of 1354 pg/ml were 100 percent.

Conclusion

Unlike the cTnI, the NT-proBNP can serve as an excellent objective test for early detection of cardiac involvement. Therefore, in KD-patients with high levels of NT-proBNP additional therapy and closer follow up should be considered.
Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan: evidence from two longitudinal cohort studies 15 years apart
Authors: Hansen Chelsea L , McCormick Benjamin JJ , Azam Syed Iqbal , Ahmed Khalil , Baker Julia M , Hussain Ejaz , Jahan Assis , Jamison Alexandra F , Knobler Stacey L , Samji Nahida , Shah Wasiat , Spiro David , Thomas Elizabeth D , Viboud Cecile , Rasmussen Zeba A 
Published: August 2019

Abstract
Background

Oshikhandass is a rural village in northern Pakistan where a verbal autopsy study from 1989-1991 showed that diarrhea and pneumonia were the top causes of under-5 mortality. Intensive surveillance, active community health education and child health interventions were delivered in 1989-1996; here we assess if any improvements in under-5 mortality, diarrhea, and pneumonia over this period continued 15 years later.

Methods

Two open-cohort studies in Oshikhandass from 1989-1996 (Study 1) and 2011-2014 (Study 2) enrolled all children under age 60 months. Study staff trained using WHO guidelines conducted weekly household surveillance and promoted knowledge on causes and management of diarrhea and pneumonia. Information about household characteristics and socioeconomic status was collected. Hurdle models were constructed to examine putative risk factors for diarrhea and pneumonia.

Results

Against a backdrop of considerable change in the socioeconomic status of the community, under-5 mortality, which declined over the course of Study 1 (from 114.3 to 79.5 deaths/1000 live births between 1989 and 1996), exceeded Sustainable Development Goal 3 by Study 2 (19.6 deaths/ 1000 live births). Reductions in diarrhea prevalence (20.3 to 2.2 days/ Child Year [CY]), incidence (2.1 to 0.5 episodes/ CY), and number of bloody diarrhea episodes (18.6% to 5.2%) seen during Study 1, were sustained in Study 2. Pneumonia incidence was 0.5 episodes /CY in Study 1 and 0.2/CY in Study 2; only 5% of episodes were categorized as severe or very severe in both studies. While no individual factors predicted a statistically significant difference in diarrhea or pneumonia episodes, the combined effect of water, toilet and house construction was associated with a significant decrease in diarrhea; higher household income was the most protective factor for pneumonia.

Conclusions

We report a 2-3-fold decrease in childhood morbidity and mortality from diarrhea and pneumonia in a remote rural village in Pakistan. Household water and sanitation predicted small differences in diarrhea morbidity, but the decrease in disease burden over the first study suggests that promoting tight linkages between health workers and the community to increase knowledge and management of child health can lead to sustainable reductions in child morbidity and mortality.
Prenatal sFlt-1/PlGF value for prediction of adverse neonatal outcome of isolated ultrasonic small-for-gestational-age fetus in normotensive pregnant women: A prospective cohort study
Authors: Shim So Hyun , Jeon Haeng Jun , Ryu Hye Jin , Kim So Hyun , Min Seung Gi , Kang Min Kyu , Park Hee Jin , Cha Dong Hyun 
Published: August 2019

Abstract
Background

Not only preeclampsia but also small-for-gestational-age (SGA) neonates in the absence of preeclampsia are at increased risk of morbidity and mortality. Early recognition of fetuses at increased risk of being growth-restricted enables more appropriate surveillance and optimization of management for reduced risk of adverse neonatal outcomes. We investigated potential value of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio, estimated in late-second and early-third trimester respectively, for prediction of SGA neonates with poor neonatal outcome.

Methods

Included in this case control study were 530 singleton pregnant women who had attended the prenatal screening program at single institution between January 2011 and March 2012. The maternal serum levels of sFlt-1 and PlGF at 24 to 28+6weeks and 29 to 36+6weeks of gestation were measured for comparing control and SGA group.

Results

After excluding 22 preeclampsia cases, 47 SGA group and 461 control-group were included. Mean gestational age at delivery in SGA group was 37.76 ± 2.05weeks, which showed no significant difference comparing to control group (38.43 ± 2.1weeks, p=0.122). The sFlt-1/PlGF ratios at late-second trimester and early-third trimester were both higher in the SGA group than control group (7.62 vs 3.74, p=0.63; 28.62 vs 14.42, p=0.037) and especially sFlt-1/PlGF ratio at early-third trimester was significantly higher in the SGA group. Among SGA group, 17 neonates had adverse neonatal outcome (36.1%, 17/47). Both sFlt-1/PlGF ratios in each trimester were also higher in poor SGA group than control group (6.73 vs 3.77, p = 0.379; 109.12 vs 15.27, p=0.002). As gestational age advances, rapid increase in sflt-1/PlGF ratio detected in poor SGA group comparing to SGA group with no adverse outcome. A cutoff value of 28.15 for the sFlt-1/PlGF ratio at 29 to 36+6weeks significantly predicted SGA neonates who had adverse outcome, with sensitivity and specificity of 76.9% and 88%, respectively.

Conclusion

In this study, sFlt-1/PlGF ratio of SGA with adverse neonatal outcome group was significantly higher than control group. This study suggests the feasibility of the sFlt-1/PlGF ratio as helpful objective measurement for predicting the adverse SGA neonatal outcome by providing sFlt-1/PlGF cutoff value, besides ultrasound biometry measurement.
The First Study of Successful Pregnancies in Chinese patients with Phenylketonuria
Authors: Lin Wang , Fang Ye , Hui Zou , Kundi Wang , Zhihua Chen , Qin Hui , Bingjuan Han , Weimin Yu , Chun He , Xiaowen Li , Ming Shen 
Published: August 2019

Abstract
Since the inception of newborn screening programs in China in the 1990s, pregnancy among patients with inherited, metabolic disorders has become more common. This study explores the management and outcomes of planned, full-term pregnancies in patients with phenylketonuria (PKU). Married patients from 2012 to 2017 were enrolled to receive prenatal counseling and their partners were screened for heterozygous genes of phenylalanine hydroxylase (PAH). Daily intake of phenylalanine (Phe), blood Phe, obstetrical data, and offspring outcomes (e.g. developmental quotients [DQs]) were recorded. None of the paternal parents were heterozygous for PAH. A total of 6 neonates were successfully delivered, 5 males and 1 female. The mean ±SD (range) age of the mother at delivery was 26.3±4.7 (range:21.1-32.5) years old. The mean duration of Phe control before pregnancy was 5.5±1.3 (range:3.1-6.5) months. During pregnancy, the proportion of time during which blood Phe concentrations were within the clinically-recommended target range (120–360 μmol/L) was 63.2-83.5%. For the two babies born to patients with <70% of their pregnancy within the blood Phe target range, both birth weight and DQs were lower than the other four births. This is the first report of women in China with PKU who successfully gave birth to clinically healthy babies. Infant outcomes were related to maternal blood Phe management prior to and during pregnancy. In maternal PKU patients with poor compliance to dietary treatment, sapropterin dihydrochloride（6R-BH4）may be an option to improve the management of blood Phe levels.
Knowledge of Preconception Care and Associated Factors among Pregnant Mothers with Pre-existing Diabetes Mellitus in selected Governmental Hospitals, Addis Ababa Ethiopia
Authors: Kassie Aychew , Gebretensaye Tigistu Gebreyohannis , Abebe Mesfin 
Published: August 2019

Abstract
Background: Many women with diabetes mellitus experience high rates of unintended pregnancies, infant morbidity and mortality and preventable birth defects.Thus, preconception care offers the potential for earlier risk assessment and intervention that can benefit women before pregnancy and ensure the healthiest possible start for the newborn child. The aim of this study is to assess the knowledge and experience of preconception care and associated factors among pregnant mothers with pre-existing diabetes mellitus.
Methods: Facility based quantitative cross-sectional study design was employed among 142 conveniently selected pregnant women between March 11and April 12, 2018. Logistic regression including bivariate and multivariate analysis considering 95% CI was utilized to examine association between dependent and independent variables. P-value < 0.05 was considered statistically significant.
Result: this study found that 67(42.7%) of pregnant women with pre-existing diabetes mellitus had good knowledge on preconception care. Educational level, occupation and duration of diabetes was associated with knowledge about preconception care AOR= 0.24 [0.065, 0.828], AOR= 0.042[0.102(0.011-0.918] and AOR= 0.035 [3.599(.095-11.833] respectively.
Conclusion: women’s knowledge on preconception care in this study is low. Education, occupation and duration of diabetes were factors associated with knowledge of preconception care. Establishment of preconception care strategies addressing all components of the care and increasing women’s knowledge about preconception care is an important component to ensure prevention of potential risks.