bluuebunny/crossref_metadata_2025_split huggingface dataset:
Niemann-Pick disease type-B: a unique case report with compound heterozygosity and complicated lipid management
Authors: Ordieres-Ortega L. , Galeano-Valle F. , Mallén-Pérez M. , Muñoz-Delgado C. , Apaza-Chavez J. E. , Menárguez-Palanca F. J. , Alvarez-Sala Walther L. A. , Demelo-Rodríguez P. 
Published: May 2020

Abstract
Background
Niemann-Pick disease (NPD) is a rare autosomal recessive hereditary disease characterized by deficient activity of acid sphingomyelinase.

Case presentation
We present a case of NPD type B with a unique compound heterozygosity for SMPD1 (NM_000543.4:c.[84delC];[96G > A]) in which both mutations that induce an early stop codon are located before the second in-frame initiation codon. The clinical presentation of the patient is compatible with NPD type B. She was initially diagnosed of Gaucher Disease, but her altered lipid profile led to a clinical suspicion of NPD.
Combined high doses of atorvastatin and ezetimibe were given to treat the severe hypercholesterolemia.

Conclusions
The pharmacological management of the lipid profile in these patients is important. A unique compound mutation in SMPD1 gene is described.
Deciphering genetic signatures by whole exome sequencing in a case of co-prevalence of severe renal hypouricemia and diabetes with impaired insulin secretion
Authors: Sekiya Motohiro , Matsuda Takaaki , Yamamoto Yuki , Furuta Yasuhisa , Ohyama Mariko , Murayama Yuki , Sugano Yoko , Ohsaki Yoshinori , Iwasaki Hitoshi , Yahagi Naoya , Yatoh Shigeru , Suzuki Hiroaki , Shimano Hitoshi 
Published: May 2020

Abstract
Background
Renal hypouricemia (RHUC) is a hereditary disorder where mutations in SLC22A12 gene and SLC2A9 gene cause RHUC type 1 (RHUC1) and RHUC type 2 (RHUC2), respectively. These genes regulate renal tubular reabsorption of urates while there exist other genes counterbalancing the net excretion of urates including ABCG2 and SLC17A1. Urate metabolism is tightly interconnected with glucose metabolism, and SLC2A9 gene may be involved in insulin secretion from pancreatic β-cells. On the other hand, a myriad of genes are responsible for the impaired insulin secretion independently of urate metabolism.

Case presentation
We describe a 67 year-old Japanese man who manifested severe hypouricemia (0.7 mg/dl (3.8–7.0 mg/dl), 41.6 μmol/l (226–416 μmol/l)) and diabetes with impaired insulin secretion. His high urinary fractional excretion of urate (65.5%) and low urinary C-peptide excretion (25.7 μg/day) were compatible with the diagnosis of RHUC and impaired insulin secretion, respectively. Considering the fact that metabolic pathways regulating urates and glucose are closely interconnected, we attempted to delineate the genetic basis of the hypouricemia and the insulin secretion defect observed in this patient using whole exome sequencing. Intriguingly, we found homozygous Trp258* mutations in SLC22A12 gene causing RHUC1 while concurrent mutations reported to be associated with hyperuricemia were also discovered including ABCG2 (Gln141Lys) and SLC17A1 (Thr269Ile). SLC2A9, that also facilitates glucose transport, has been implicated to enhance insulin secretion, however, the non-synonymous mutations found in SLC2A9 gene of this patient were not dysfunctional variants. Therefore, we embarked on a search for causal mutations for his impaired insulin secretion, resulting in identification of multiple mutations in HNF1A gene (MODY3) as well as other genes that play roles in pancreatic β-cells. Among them, the Leu80fs in the homeobox gene NKX6.1 was an unreported mutation.

Conclusion
We found a case of RHUC1 carrying mutations in SLC22A12 gene accompanied with compensatory mutations associated with hyperuricemia, representing the first report showing coexistence of the mutations with opposed potential to regulate urate concentrations. On the other hand, independent gene mutations may be responsible for his impaired insulin secretion, which contains novel mutations in key genes in the pancreatic β-cell functions that deserve further scrutiny.
Ancestry and frequency of genetic variants in the general population are confounders in the characterization of germline variants linked to cancer
Authors: Bobyn Anna , Zarrei Mehdi , Zhu Yuankun , Hoffman Mary , Brenner Darren , Resnick Adam C. , Scherer Stephen W. , Gallo Marco 
Published: May 2020

Abstract
Background
Pediatric high-grade gliomas (pHGGs) are incurable malignant brain cancers. Clear somatic genetic drivers are difficult to identify in the majority of cases. We hypothesized that this may be due to the existence of germline variants that influence tumor etiology and/or progression and are filtered out using traditional pipelines for somatic mutation calling.

Methods
In this study, we analyzed whole-genome sequencing (WGS) datasets of matched germlines and tumor tissues to identify recurrent germline variants in pHGG patients.

Results
We identified two structural variants that were highly recurrent in a discovery cohort of 8 pHGG patients. One was a ~ 40 kb deletion immediately upstream of the NEGR1 locus and predicted to remove the promoter region of this gene. This copy number variant (CNV) was present in all patients in our discovery cohort (n = 8) and in 86.3% of patients in our validation cohort (n = 73 cases). We also identified a second recurrent deletion 55.7 kb in size affecting the BTNL3 and BTNL8 loci. This BTNL3–8 deletion was observed in 62.5% patients in our discovery cohort, and in 17.8% of the patients in the validation cohort. Our single-cell RNA sequencing (scRNA-seq) data showed that both deletions result in disruption of transcription of the affected genes. However, analysis of genomic information from multiple non-cancer cohorts showed that both the NEGR1 promoter deletion and the BTNL3–8 deletion were CNVs occurring at high frequencies in the general population. Intriguingly, the upstream NEGR1 CNV deletion was homozygous in ~ 40% of individuals in the non-cancer population. This finding was immediately relevant because the affected genes have important physiological functions, and our analyses showed that NEGR1 expression levels have prognostic value for pHGG patient survival. We also found that these deletions occurred at different frequencies among different ethnic groups.

Conclusions
Our study highlights the need to integrate cancer genomic analyses and genomic data from large control populations. Failure to do so may lead to spurious association of genes with cancer etiology. Importantly, our results showcase the need for careful evaluation of differences in the frequency of genetic variants among different ethnic groups.
Effects of bodybuilding supplements on the kidney: A population-based incidence study of biopsy pathology and clinical characteristics among middle eastern men
Authors: Ali Alaa Abbas , Almukhtar Safaa E. , Sharif Dana A. , Saleem Zana Sidiq M. , Muhealdeen Dana N. , Hughson Michael D. 
Published: May 2020

Abstract
Background
The incidence of kidney diseases among bodybuilders is unknown.

Methods
Between January 2011 and December 2019, the Iraqi Kurdistan 15 to 39 year old male population averaged 1,100,000 with approximately 56,000 total participants and 25,000 regular participants (those training more than 1 year). Annual age specific incidence rates (ASIR) with (95% confidence intervals) per 100,000 bodybuilders were compared with the general age-matched male population.

Results
Fifteen male participants had kidney biopsies. Among regular participants, diagnoses were: focal segmental glomerulosclerosis (FSGS), 2; membranous glomerulonephritis (MGN), 2; post-infectious glomeruonephritis (PIGN), 1; tubulointerstitial nephritis (TIN), 1; and nephrocalcinosis, 2. Acute tubular necrosis (ATN) was diagnosed in 5 regular participants and 2 participants training less than 1 year. Among regular participants, anabolic steroid use was self-reported in 26% and veterinary grade vitamin D injections in 2.6%. ASIR for FSGS, MGN, PIGN, and TIN among regular participants was not statistically different than the general population. ASIR of FSGS adjusted for anabolic steroid use was 3.4 (− 1.3 to 8.1), a rate overlapping with FSGS in the general population at 2.0 (1.2 to 2.8). ATN presented as exertional muscle injury with myoglobinuria among new participants. Nevertheless, ASIR for ATN among total participants at 1.4 (0.4 to 2.4) was not significantly different than for the general population at 0.3 (0.1 to 0.5). Nephrocalcinosis was only diagnosed among bodybuilders at a 9-year cumulative rate of one per 314 vitamin D injectors.

Conclusions
Kidney disease rates among bodybuilders were not significantly different than for the general population, except for nephrocalcinosis that was caused by injections of veterinary grade vitamin D compounds.
Perinatal outcomes of frequent attendance in midwifery care in the Netherlands: a retrospective cohort study
Authors: Gitsels-van der Wal Janneke T. , Gitsels Lisanne A. , Hooker Angelo , Scholing Paula , Martin Linda , Feijen-de Jong Esther I. 
Published: May 2020

AbstractBackgroundOver the last decade, a trend towards high utilisation of primary maternity care was observed in high-income countries. There is limited research with contradictory results regarding frequent attendance (FA) and perinatal outcomes in midwifery care. Therefore, this study examined possible associations between FA in midwifery care and obstetric interventions and perinatal outcomes.MethodsA retrospective cohort study was performed in a medium-sized midwifery-led care practice in an urban region in the Netherlands. Frequent attenders (FAs) were categorised using the Kotelchuck-Index Revised. Regression analyses were executed to examine the relationship between FAs and perinatal outcomes, stratified by antenatal referral to an obstetrician. Main outcomes of interest were Apgar score ≤ 7 and perinatal death, birth weight, mode of delivery, haemorrhage, place of birth, transfer during labour, and a requirement for pain relief.ResultsThe study included 1015 women, 239 (24%) FAs and 776 (76%) non-FAs, 538 (53%) were not referred and 447 (47%) were referred to an obstetrician. In the non-referred group, FA was significantly associated with a requirement for pain relief (OR 1.98, 95% CI 1.24–3.17) and duration of dilatation (OR 1.20, 95% CI 1.04–1.38). In the referred group, FA was significantly associated with induction of labour (OR 1.86, 95% CI 1.17–2.95), ruptured perineum (OR 0.50, 95% CI 0.27–0.95) and episiotomy (OR 0.48, 95% CI 0.24–0.95). In the non-referred and the referred group, FA was not associated with the other obstetric and neonatal outcomes. Due to small numbers, we could not measure possible associations of FA with an Apgar score ≤ 7 and perinatal death.ConclusionIn our study, perinatal outcomes differed by FA and antenatal referral to an obstetrician. In the non-referred group, FA was significantly associated with medical pain relief and duration of dilatation. In the referred group, FA was significantly associated with induction of labour, ruptured perineum, and episiotomy. Further research with a larger study population is needed to look for a possible association between FA and primary adverse birth outcomes such as perinatal mortality.
Health management committee strengthening and community mobilisation through women’s groups to improve trained health worker attendance at birth in rural Nepal: a cluster randomised controlled trial
Authors: Morrison Joanna , Tumbahangphe Kirti , Sen Aman , Gram Lu , Budhathoki Bharat , Neupane Rishi , Thapa Rita , Dahal Kunta , Thapa Bidur , Manandhar Dharma , Costello Anthony , Osrin David 
Published: May 2020

Abstract
Background
Engaging citizens and communities to make services accountable is vital to achieving health development goals. Community participation in health management committees can increase public accountability of health services. We conducted a cluster randomised controlled trial to test the impact of strengthened health management committees (HMCs) and community mobilisation through women’s groups on institutional deliveries and deliveries by trained health workers in rural Nepal.

Methods
The study was conducted in all Village Development Committee clusters in the hills district of Makwanpur (population of 420,500). In 21 intervention clusters, we conducted three-day workshops with HMCs to improve their capacity for planning and action and supported female community health volunteers to run women’s groups. These groups met once a month and mobilised communities to address barriers to institutional delivery through participatory learning and action cycles. We compared this intervention with 22 control clusters. Prospective surveillance from October 2010 to the end of September 2012 captured complete data on 13,721 deliveries in intervention and control areas. Analysis was by intention to treat.

Results
The women’s group intervention was implemented as intended, but we were unable to support HMCs as planned because many did not meet regularly. The activities of community based organisations were systematically targeted at control clusters, which meant that there were no true ‘control’ clusters. 39% (5403) of deliveries were in health institutions and trained health workers attended most of them. There were no differences between trial arms in institutional delivery uptake (1.45, 0.76–2.78) or attendance by trained health workers (OR 1.43, 95% CI 0.74–2.74).

Conclusions
The absence of a true counterfactual and inadequate coverage of the HMC strengthening intervention impedes our ability to draw conclusions. Further research is needed to test the effectiveness of strengthening public accountability mechanisms on increased utilisation of services at delivery.

Trial registration
Current Controlled Trials ISRCTN99834806.
Date of registration:28/09/10.
Management of a pregnant patient with chylomicronemia from a novel mutation in GPIHBP1: a case report
Authors: Lin Min-Huan , Tian Xiao-Hui , Hao Xiu-Lan , Fei Hui , Yin Jian-Lan , Yan Dan-Dan , Li Tian 
Published: May 2020

Abstract
Background
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive lipid disorder often associated with recurrent episodes of pancreatitis. It is documented in most cases with FCS due to the mutations of key proteins in lipolysis, including LPL, APOC2, APOA5, LMF1 and GPIHBP1.

Case presentation
We report the successful management of a 35-year-old pregnant woman carrying a novel homozygous frameshift mutation c.48_49insGCGG (p.P17A fs*22) in the GPIHBP1 gene with previous severe episodes of acute pancreatitis triggered by pregnancy, resulting in adverse obstetrical outcomes. With careful monitoring, the patient underwent an uneventful pregnancy and delivered a baby with no anomalies.

Conclusions
The case report contributes to the understanding of GPIHBP1-deficient familial chylomicronemia syndrome (FCS) and highlights gestational management of FCS patient.
Is it home delivery or health facility? Community perceptions on place of childbirth in rural Northwest Tanzania using a qualitative approach
Authors: Konje Eveline T. , Hatfield Jennifer , Kuhn Susan , Sauve Reginald S. , Magoma Moke , Dewey Deborah 
Published: May 2020

Abstract
Background
In low and middle-income countries, pregnancy and delivery complications may deprive women and their newborns of life or the realization of their full potential. Provision of quality obstetric emergency and childbirth care can reduce maternal and newborn deaths. Underutilization of maternal and childbirth services remains a public health concern in Tanzania. The aim of this study was to explore elements of the local social, cultural, economic, and health systems that influenced the use of health facilities for delivery in a rural setting in Northwest Tanzania.

Methods
A qualitative approach was used to explore community perceptions of issues related to low utilization of health facilities for childbirth. Between September and December 2017, 11 focus group discussions were conducted with women (n = 33), men (n = 5) and community health workers (CHWs; n = 28); key informant interviews were conducted with traditional birth attendants (TBAs; n = 2). Coding, identification, indexing, charting, and mapping of these interviews was done using NVIVO 12 after manual familiarization of the data. Data saturation was used to determine when no further interviews or discussions were required.

Results
Four themes emerge; self-perceived obstetric risk, socio-cultural issues, economic concerns and health facility related factors. Health facility delivery was perceived to be crucial for complicated labor. However, the idea that childbirth was a “normal” process and lack of social and cultural acceptability of facility services, made home delivery appealing to many women and their families. In addition, out of pocket payments for suboptimal quality of health care was reported to hinder facility delivery.

Conclusion
Home delivery persists in rural settings due to economic and social issues, and the cultural meanings attached to childbirth. Accessibility to and affordability of respectful and culturally acceptable childbirth services remain challenging in this setting. Addressing barriers on both the demand and supply side could result in improved maternal and child outcomes during labor and delivery.
Massive splenic cyst in pregnancy: case report
Authors: Chung Philip , Swinson Ben , O’Rourke Nicholas , Schmidt Bart 
Published: May 2020

AbstractBackgroundPrimary splenic cysts are very rarely diagnosed in pregnancy, with only thirteen cases described in the literature. We examine the approach towards diagnosing and managing uniquely large abdominal masses that significantly complicate obstetric care.Case presentationA 37-year-old primigravida woman presented with abdominal distension and discomfort, yet otherwise asymptomatic. On ultrasound, an incidental pregnancy at 25 weeks of gestation and a large pelvic lesion were discovered. MRI defined a 28 × 29 cm lobulated, complex cystic mass in the upper abdomen. The patient underwent two ascitic drainages throughout her pregnancy. At 34 weeks of gestation, she had a classical caesarean section. Then at five-weeks postpartum, she underwent a laparotomy and total splenectomy with 16 L of fluid drained. Histopathological analysis revealed an epithelial cyst of the spleen. Her recovery was complicated by complete portal vein thrombosis.ConclusionThis case describes the largest splenic cyst ever reported in pregnancy and explores the diagnostic dilemmas and treatment challenges associated. We introduce the utility of serial ascitic drainages in prolonging the pregnancy and emphasise the reliance on imaging for surveillance of splenic size and fetal wellbeing.
“It is good, but I can’t afford it …” potential barriers to adequate prenatal care among Afghan women in Iran: a qualitative study in South Tehran
Authors: Dadras Omid , Taghizade Ziba , Dadras Fateme , Alizade Leyla , Seyedalinaghi Seyedahmad , Ono-Kihara Masako , Kihara Masahiro , Nakayama Takeo 
Published: May 2020

Abstract
Background
An estimated 96% of registered refugees in Iran are Afghan. Almost half of them are young women at the reproductive age. The adequate maternity care is crucial for healthy pregnancy. There is limited knowledge regarding the access and adequacy of maternity care among Afghan women in Iran. The reports from ministry of health (MOH) implicate higher prevalence of perinatal complications in Afghan population. This mainly attributed to the inadequate prenatal care during pregnancy. Therefore, this paper explores the potential barriers to prenatal care among Afghan women in Iran.

Methods
Using convenience sampling, thirty pregnant Afghan women were recruited at three community health centers with the highest number of Afghan visitors in Tehran, the capital city of Iran. Data were collected through face-to-face interviews in Persian language using an interview guide. The interviewers were two bilingual Afghan graduate midwifery students. Each interview lasted for an hour. The questions regarding the concerns and experienced obstacles in seeking prenatal care were asked. The interviews were transcribed into original language (Persian) and analyzed using content analysis and further translated back into English. The main themes were extracted grouping the similar codes and categories after careful consideration and consensus between the researchers.

Results
The financial constraints and lack of affordable health insurance with adequate coverage of prenatal care services, particularly the diagnostic and screening tests, were the most frequent reported obstacles by Afghan women. In addition, personnel behavior, transportation issues, stigma and discrimination, cultural concerns, legal and immigration issues were also mentioned as the source of disappointment and inadequate utilization of such services.

Conclusions
The findings of present study emphasize the necessity of available and most importantly, affordable prenatal care for Afghan women in Iran. Providing an affordable health insurance with adequate coverage of prenatal and delivery services, could reduce the financial burden, facilitate the access, and ensure the maternal and child health in this vulnerable population. The issues of fear and concern of deportation must be removed for at least illegal Afghan mothers to ensure their access to maternity care and improve the health of both mother and offspring.
Construction of an integrated human osteosarcoma database, HOsDb, based on literature mining, microarray analysis, and database retrieval
Authors: Sun Yifu , Wang Lishan , Li Changkuan , Gu Rui , Zang Weidong , Song Wei , Xia Peng 
Published: May 2020

Abstract
Background
Osteosarcoma (OS) is the most frequent primary malignancy of bone with a high incidence in adolescence. This study aimed to construct a publicly available, integrated database of human OS, named HOsDb.

Methods
Microarray data, current databases, and a literature search of PubMed were used to extract information relevant to human OS-related genes and their transcription factors (TFs) and single nucleotide polymorphisms (SNPs), as well as methylation sites and microRNAs (miRNAs). This information was collated for constructing the HOsDb.

Results
In total, we identified 7191 OS tumor-related genes, 763 OS metastasis-related genes, and 1589 OS drug-related genes, corresponding to 190,362, 21,131, and 41,135 gene-TF pairs, respectively, 3,749,490, 358,361, and 767,674 gene-miRNA pairs, respectively; and 28,386, 2532, and 3943 SNPs, respectively. Additionally, 240 OS-related miRNAs, 1695 genes with copy number variations in OS, and 18 genes with methylation sites in OS were identified. These data were collated to construct the HOsDb, which is available at www.hosdatabase.com. Users can search OS-related molecules using this database.

Conclusion
The HOsDb provides a platform that is comprehensive, quick, and easily accessible, and it will enrich our current knowledge of OS.