bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eliminating viral hepatitis C in Belgium: the micro-elimination approach
Authors: Busschots Dana , Toghanian Samira , Bielen Rob , Salomonsson Stina , Koc Özgür M. , Hendrickx Greet , Jadoul Michel , Nevens Frederik , Sokal Etienne , Brixko Christian , Peerlinck Kathelijne , Apers Ludwig , Robaeys Geert , Lazarus Jeffrey V. 
Published: February 2020

AbstractBackgroundHepatitis C virus is one of the leading causes of chronic liver disease and liver-related deaths worldwide. The estimated prevalence of chronic hepatitis C viral infection among the general Belgian population was 0.57% (n = 64,000) in 2015. Although Belgium has had a ‘Hepatitis C Plan’ since 2014, elimination efforts are unclear. This study employs the best available data and modelling estimates to define the burden of hepatitis C viral infection among key subgroups in Belgium, identify information gaps and propose potential approaches to screening, linkage to care and treatment, and cure.MethodsWe examined the peer-reviewed and grey literature since 2012 for data on the prevalence of hepatitis C viral infection in Belgium in key subgroups identified by national experts and in the literature. Ultimately, this research is primarily based on data provided by the key stakeholders themselves due to a lack of reliable data in the literature. Based on this, we modelled the treatment rates required to reach elimination of hepatitis C in several subgroups.ResultsEleven potential subgroups were identified. There were no data available for two subgroups: generational cohorts and men who have sex with men. In six subgroups, fewer than 3000 people were reported or estimated to have hepatitis C infection. Migrants and people who inject drugs were the most affected subgroups, and children were the least affected subgroup. Only two subgroups are on target to achieve elimination by 2030: patients living with haemophilia and transplant recipients.ConclusionsRemoving Belgian treatment reimbursement restrictions in January 2019 was a big step towards eliminating HCV. In addition, increasing surveillance, including with a national registry, treatment prescription by other health-care providers and availability of treatment in local pharmacies are central to improving the current situation and getting on track to reach the 2030 WHO hepatitis C elimination targets in Belgium.
Case report: a synonymous VHL mutation (c.414A > G, p.Pro138Pro) causes pathogenic familial hemangioblastoma through dysregulated splicing
Authors: Liu Fang , Calhoun Barbara , Alam Md. Suhail , Sun Miaomiao , Wang Xuechun , Zhang Chao , Haldar Kasturi , Lu Xin 
Published: February 2020

Abstract
Background
von Hippel-Lindau (VHL) disease is a familial neoplasia syndrome that results from the germline mutation of VHL. Pathogenic VHL mutations include deletion, frameshift, nonsense and missense mutations. Synonymous mutations are expected to be phenotypically silent and their role in VHL disease remains poorly understood.

Case presentation
We report a Caucasian male with a family history of pheochromocytoma and the synonymous VHL mutation c.414A > G (p.Pro138Pro). At 47-years, MRI revealed pheochromocytoma in the left adrenal gland and hemangioblastomas in the spine and brain. Pheochromocytoma was treated by adrenalectomy. Radiotherapy, followed by craniotomy and resection were needed to reduce hemangioblastomas to residual lesions. Two of three of the proband’s children inherited the mutation and both presented with retinal hemangioblastomas without pheochromocytoma at age 7: one twin needed four laser treatments. Primary skin fibroblasts carrying the heterozygous mutation or wild type VHL were established from the family. Mutant fibroblasts downregulated full-length VHL mRNA and protein, and upregulated the short VHL mRNA isoform (a result of exon 2 skipping in splicing) at the mRNA level but not at the protein level.

Conclusions
Our study shows that the synonymous VHL mutation c.414A > G can within 7 years induce pediatric retinal hemangioblastoma in absence of pheochromocytoma. This highlights the need to include splicing-altering synonymous mutations into the screening for VHL disease. This is also the first report on detecting and validating a synonymous VHL mutation using patient-derived fibroblasts. The mutation c.414A > G translates to p.Pro138Pro, yet it is not functionally silent, because it causes aberrant splicing by skipping exon 2. The reduced but not completely abolished pVHL protein in a loss-of-heterozygosity genetic backdrop may underlie the etiology of VHL disease.
The joint effect of maternal smoking during pregnancy and maternal pre-pregnancy overweight on infants’ term birth weight
Authors: Chattrapiban Thanin , Smit Henriette A. , Wijga Alet H. , Brunekreef Bert , Vonk Judith M. , Gehring Ulrike , van Rossem Lenie 
Published: February 2020

Abstract
Background
It is well known that maternal smoking during pregnancy and maternal pre-pregnancy overweight have opposite effects on the infants’ birth weight. We report on the association of the combination between both risk factors and the infants’ birth weight.

Methods
We studied 3241 infants born at term in the PIAMA birth cohort. Maternal smoking during pregnancy and pre-pregnancy height and weight were self-reported. Multivariable regression analysis was performed to assess the associations between infants of mothers who only smoked during pregnancy, who only had pre-pregnancy overweight and who had both risk factors simultaneously, on term birth weight and the risk of being SGA or LGA.

Results
Of 3241 infants, 421 infants (13%) were born to smoking, non-overweight mothers, 514 (15.8%) to non-smoking, overweight mothers, 129 (4%) to smoking and overweight mothers and 2177 (67%) to non-smoking, non-overweight mothers (reference group). Infants of mothers who smoked and also had pre-pregnancy overweight had similar term birth weight (− 26.6 g, 95%CI: − 113.0, 59.8), SGA risk (OR = 1.06, 95%CI: 0.56, 2.04), and LGA risk (OR = 1.09, 95%CI: 0.61, 1.96) as the reference group.

Conclusions
Our findings suggested that the effects of maternal smoking during pregnancy and maternal pre-pregnancy overweight on infants’ birth weight cancel each other out. Therefore, birth weight may not be a good indicator of an infant’s health status in perinatal practice because it may mask potential health risks due to these maternal risk factors when both present together.
Risk factors for severe rash with use of vemurafenib alone or in combination with cobimetinib for advanced melanoma: pooled analysis of clinical trials
Authors: Hopkins Ashley M. , Rathod Akash D. , Rowland Andrew , Kichenadasse Ganessan , Sorich Michael J. 
Published: February 2020

Abstract
Background
Rash is one of the most common severe adverse events associated with use of vemurafenib for the treatment of melanoma, either as monotherapy or in combination with cobimetinib. The study aimed to identify pre-treatment patient characteristics predictive of developing severe rash with vemurafenib therapy.

Methods
This was a secondary pooled analysis of individual patient data from the BRIM-2, BRIM-3 and coBRIM clinical trials, including all patients treated with vemurafenib alone and vemurafenib plus cobimetinib. Patient age, sex, performance status, body weight, body mass index, liver function markers and estimated glomerular filtration rate were assessed for association with development of severe (grade 3 or 4) rash using logistic regression.

Results
Of 962 patients treated with vemurafenib, 150 (16%) patients experienced severe rash. Female sex was identified as a significant risk factor for severe rash development (P < 0.001), having a two-fold increased risk compared to males (22% vs 11%, odds ratio [OR] 2.17; 95% CI 1.52 to 3.09). Low body weight was also associated with increased risk of severe rash (P = 0.002), but this association was not significant after adjustment for sex. The association between sex and risk of severe rash was consistent across clinical trials and treatments (vemurafenib monotherapy, vemurafenib plus cobimetinib).

Conclusion
Females had approximately two-fold increased risk of developing severe rash compared to males in clinical trials of vemurafenib alone or in combination with cobimetinib.
Evaluation of posterior capsule opacification of the Alcon Clareon IOL vs the Alcon Acrysof IOL using a human capsular bag model
Authors: Hillenmayer Anna , Wertheimer Christian M. , Kassumeh Stefan , von Studnitz Annabel , Luft Nikolaus , Ohlmann Andreas , Priglinger Siegfried , Mayer Wolfgang J. 
Published: February 2020

AbstractBackgroundPosterior capsule opacification (PCO) after cataract surgery is influenced by intraocular lens (IOL) design and material. The following is an ex vivo comparison of PCO between the Clareon vs. the AcrySof IOL in human capsular bags.MethodsTwenty cadaver capsular bags from 10 human donors were used, with the novel hydrophobic IOL (Clareon, CNA0T0) being implanted in one eye and the other eye of the same donor receiving the AcrySof IOL (SN60WF) following phacoemulsification cataract surgery. Five capsular bags of 3 donors served as controls without IOL. Cellular growth of lens epithelial cells was photo-documented daily. The primary endpoint was the time until full coverage of the posterior capsule by cells. Furthermore, immunofluorescence staining of capsular bags for the fibrotic markers f-actin, fibronectin, alpha smooth muscle actin, and collagen type 1 were performed.ResultsThe new Clareon IOL did not show any disadvantages in terms of days until full cell coverage of the posterior capsule in comparison to the AcrySof (p > 0.99). Both, the Clareon (p = 0.01, 14.8 days) and the AcrySof IOL (p = 0.005, 15.7 days) showed a slower PCO development in comparison to the control (8.6 days). The fibrotic markers f-actin, fibronectin, alpha smooth muscle actin, and collagen type 1 were equally distributed between the two IOLs and differed from the control.ConclusionsA comparable performance has been found in the ex vivo formation of PCO between the two IOLs. Long-term clinical studies are necessary to reach final conclusions.
Perceived barriers to early diagnosis of breast Cancer in south and southwestern Ethiopia: a qualitative study
Authors: Getachew Sefonias , Tesfaw Aragaw , Kaba Mirgissa , Wienke Andreas , Taylor Lesley , Kantelhardt Eva J. , Addissie Adamu 
Published: February 2020

Abstract
Background
Early diagnosis is a key determinant of breast cancer prognosis and survival. More than half of breast cancer cases are diagnosed at an advanced stage in Ethiopia, and the barriers to early diagnosis in this country are not well understood. We aimed to identify the perceived barriers to early diagnosis of breast cancer from the perspective of patients and health care providers in south and southwestern Ethiopia.

Methods
A qualitative study was conducted from March to April 2018 using in-depth interviews of breast cancer patients and breast cancer health care providers from six public hospitals located in urban and rural areas of south and southwestern Ethiopia. All participants provided verbal consent before participating. A thematic analysis was performed using Open Code 4.02.

Results
Twelve breast cancer patients and thirteen health care providers were included in the study. Patient and health-system related barriers to early diagnosis of breast cancer were identified. Patient-related barriers were lack of knowledge and awareness of breast cancer, belief in traditional medicine and religious practices for treatment, and lack of social and financial support to seek care at a medical facility. Health-system related barriers were misdiagnosis of breast cancer, long distance to referral facilities, high cost of diagnostic services, long waiting time for diagnostic tests, and lack of screening and diagnostic tests in local facilities.

Conclusions
Early diagnosis of breast cancer is affected by multiple barriers in south and southwestern Ethiopia. Awareness campaigns and education about the disease, prevention, and early detection are needed to increase early diagnosis of breast cancer. Opportunities exist to improve early diagnosis and timely treatment in rural areas.
Acute care pathways for patients calling the out-of-hours services
Authors: Søvsø Morten Breinholt , Huibers Linda , Bech Bodil Hammer , Christensen Helle Collatz , Christensen Morten Bondo , Christensen Erika Frischknecht 
Published: February 2020

Abstract
Background
In Western countries, patients with acute illness or injury out-of-hours (OOH) can call either emergency medical services (EMS) for emergencies or primary care services (OOH-PC) in less urgent situations. Callers initially choose which service to contact; whether this choice reflect the intended differences in urgency and severity is unknown. Hospital diagnoses and admission rates following an OOH service contact could elucidate this. We aimed to investigate and compare the prevalence of patient contacts, subsequent hospital contacts, and the age-related pattern of hospital diagnoses following an out-of-hours contact to EMS or OOH-PC services in Denmark.

Methods
Population-based observational cohort study including patients from two Danish regions with contact to EMS or OOH-PC in 2016. Hospital contacts were defined as short (< 24 h) or admissions (≥24 h) on the date of OOH service contact. Both regions have EMS, whereas the North Denmark Region has a general practitioner cooperative (GPC) as OOH-PC service and the Capital Region of Copenhagen the Medical Helpline 1813 (MH-1813), together representing all Danish OOH service types. Calling an OOH service is mandatory prior to a hospital contact outside office hours.

Results
OOH-PC handled 91% (1,107,297) of all contacts (1,219,963). Subsequent hospital contacts were most frequent for EMS contacts (46–54%) followed by MH-1813 (41%) and GPC contacts (9%). EMS had more admissions (52–56%) than OOH-PC. For both EMS and OOH-PC, short hospital contacts often concerned injuries (32–63%) and non-specific diagnoses (20–45%). The proportion of circulatory disease was almost twice as large following EMS (13–17%) compared to OOH-PC (7–9%) in admitted patients, whereas respiratory diseases (11–14%), injuries (15–22%) and non-specific symptoms (22–29%) were more equally distributed. Generally, admitted patients were older.

Conclusions
EMS contacts were fewer, but with a higher percentage of hospital contacts, admissions and prevalence of circulatory diseases compared to OOH-PC, perhaps indicating that patients more often contact EMS in case of severe disease. However, hospital diagnoses only elucidate severity of diseases to some extent, and other measures of severity could be considered in future studies. Moreover, the socio-demographic pattern of patients calling OOH needs exploration as this may play an important role in choice of entrance.
Delirium misdiagnosis risk in psychiatry: a machine learning-logistic regression predictive algorithm
Authors: Hercus Catherine , Hudaib Abdul-Rahman 
Published: February 2020

Abstract
Background
Delirium is a frequent diagnosis made by Consultation-Liaison Psychiatry (CLP). Numerous studies have demonstrated misdiagnosis prior to referral to CLP. Few studies have considered the factors underlying misdiagnosis using multivariate approaches.

Objectives
To determine the number of cases referred to CLP, which are misdiagnosed at time of referral, to build an accurate predictive classifier algorithm, using input variables related to delirium misdiagnosis.

Method
A retrospective observational study was conducted at Alfred Hospital in Melbourne, collecting data from a record of all patients seen by CLP for a period of 5 months. Data was collected pertaining to putative factors underlying misdiagnosis. A Machine Learning-Logistic Regression classifier model was built, to classify cases of accurate delirium diagnosis vs. misdiagnosis.

Results
Thirty five of 74 new cases referred were misdiagnosed. The proposed predictive algorithm achieved a mean Receiver Operating Characteristic (ROC) Area under the curve (AUC) of 79%, an average 72% classification accuracy, 77% sensitivity and 67% specificity.
CONCLUSIONS: Delirium is commonly misdiagnosed in hospital settings. Our findings support the potential application of Machine Leaning-logistic predictive classifier in health care settings.
Relationship between placenta malaria and mother to child transmission of HIV infection in pregnant women in South East Nigeria
Authors: Mbachu Ikechukwu I. , Ejikunle Samson D. , Anolue Frederick , Mbachu Chioma N. , Dike Ephraim , Ejikem Eke , Okeudo Chijioke 
Published: February 2020

Abstract
Background
This study determined the rate of mother-to-child transmission (MTCT) of HIV among HIV positive women with placenta malaria and factors associated with placenta malaria.

Methods
This was a prospective observational study of booked HIV positive pregnant women in labour. A smear for malaria parasite was made from blood taken from the placental tissue post-delivery. The baby HIV testing was done with DNA polymerase chain reaction at 6 weeks postpartum. Data on age, parity, gestational age, religion, address, highest educational attainment and knowledge about malaria prevention in pregnancy was obtained with questionnaires and analysed using SPSS version 20. The P-value was set at 0.05 providing a confidence interval of 95%.

Results
A total of 174 booked HIV women participated in this study. The placental malaria parasitaemia prevalence was 44.8%. Overall rate of MTCT of HIV infection was 17.2%. Number of infants with HIV infection among women with maternal placental malarial parasitaemia was 30/78 (38.5%), while it was 0/96 (0%) for women without placenta malaria. There was significant relationship between placenta malaria density and infant HIV status (P-value = 0.001). The relative risk for MTCT of HIV for women with placenta malaria Density > 5000 was 25% with 95% confidence interval of 11.41–54.76%.

Conclusion
The mother-to-child transmission rate of HIV was high among HIV positive women with placental malaria parasitaemia. There is the need to review the malarial treatment and prophylactic measures at least in this group of women and to establish the nature of relationship between placenta malaria and MTCT of HIV infection.
m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2–mediated YAP activity in NSCLC
Authors: Jin Dan , Guo Jiwei , Wu Yan , Yang Lijuan , Wang Xiaohong , Du Jing , Dai Juanjuan , Chen Weiwei , Gong Kaikai , Miao Shuang , Li Xuelin , Sun Hongliang 
Published: February 2020

Abstract
Background
The importance of mRNA methylation erased by ALKBH5 in mRNA biogenesis, decay, and translation control is an emerging research focus. Ectopically activated YAP is associated with the development of many human cancers. However, the mechanism whereby ALKBH5 regulates YAP expression and activity to inhibit NSCLC tumor growth and metastasis is not clear.

Methods
Protein and transcript interactions were analyzed in normal lung cell and NSCLC cells. Gene expression was evaluated by qPCR and reporter assays. Protein levels were determined by immunochemical approaches. Nucleic acid interactions and status were analyzed by immunoprecipitation. Cell behavior was analyzed by standard biochemical tests. The m6A modification was analyzed by MeRIP.

Results
Our results show that YAP expression is negatively correlated with ALKBH5 expression and plays an opposite role in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. ALKBH5 reduced m6A modification of YAP. YTHDF3 combined YAP pre-mRNA depending on m6A modification. YTHDF1 and YTHDF2 competitively interacted with YTHDF3 in an m6A-independent manner to regulate YAP expression. YTHDF2 facilitated YAP mRNA decay via the AGO2 system, whereas YTHDF1 promoted YAP mRNA translation by interacting with eIF3a; both these activities are regulated by m6A modification. Furthermore, ALKBH5 decreased YAP activity by regulating miR-107/LATS2 axis in an HuR-dependent manner. Further, ALKBH5 inhibited tumor growth and metastasis in vivo by reducing the expression and activity of YAP.

Conclusions
The presented findings suggest m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2–mediated YAP activity in NSCLC. Moreover, effective inhibition of m6A modification of ALKBH5 might constitute a potential treatment strategy for lung cancer.
Preparation of antibacterial and osteoconductive 3D-printed PLGA/Cu(I)@ZIF-8 nanocomposite scaffolds for infected bone repair
Authors: Zou Fei , Jiang Jianyuan , Lv Feizhou , Xia Xinlei , Ma Xiaosheng 
Published: February 2020

Abstract
Background
The repair of large bone defects is a great challenge in clinical practice. In this study, copper-loaded-ZIF-8 nanoparticles and poly (lactide-co-glycolide) (PLGA) were combined to fabricate porous PLGA/Cu(I)@ZIF-8 scaffolds using three-dimensional printing technology for infected bone repair.

Methods
The surface morphology of PLGA/Cu(I)@ZIF-8 scaffolds was investigated by transmission electron microscopy and scanning electron microscopy. The PLGA/Cu(I)@ZIF-8 scaffolds were co-cultured with bacteria to determine their antibacterial properties, and with murine mesenchymal stem cells (MSCs) to explore their biocompatibility and osteoconductive properties. The bioactivity of the PLGA/Cu(I)@ZIF-8 scaffolds was evaluated by incubating in simulated body fluid.

Results
The results revealed that the PLGA/Cu(I)@ZIF-8 scaffolds had porosities of 80.04 ± 5.6% and exhibited good mechanical properties. When incubated with H2O2, Cu(I)@ZIF-8 nanoparticles resulted generated reactive oxygen species, which contributed to their antibacterial properties. The mMSCs cultured on the surface of PLGA/Cu(I)@ZIF-8 scaffolds were well-spread and adherent with a high proliferation rate, and staining with alkaline phosphatase and alizarin red was increased compared with the pure PLGA scaffolds. The mineralization assay showed an apatite-rich layer was formed on the surface of PLGA/Cu(I)@ZIF-8 scaffolds, while there was hardly any apatite on the surface of the PLGA scaffolds. Additionally, in vitro, Staphylococcus aureus cultured on the PLGA/Cu(I)@ZIF-8 scaffolds were almost all dead, while in vivo inflammatory cell infiltration and bacteria numbers were dramatically reduced in infected rats implanted with PLGA/Cu@ZIF-8 scaffolds.

Conclusion
All these findings demonstrate that PLGA/Cu(I)@ZIF-8 scaffolds possess excellent antibacterial and osteoconductive properties, as well as good biocompatibility and high bioactivity. This study suggests that the PLGA/Cu(I)@ZIF-8 scaffolds could be used as a promising biomaterial for bone tissue engineering, especially for infected bone repair.