bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene signature characteristic of elevated stromal infiltration and activation is associated with increased risk of hematogenous and lymphatic metastasis in serous ovarian cancer
Authors: Yue Huiran , Wang Jieyu , Chen Ruifang , Hou Xiaoman , Li Jun , Lu Xin 
Published: December 2019

Abstract
Background
The clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer.

Methods
Since lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases.

Results
We observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer.

Conclusions
Our findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.
Reliable cell and tissue morphology-based diagnosis of endemic Burkitt lymphoma in resource-constrained settings in Ghana
Authors: Smith-Togobo Cecilia , Pedersen Mette Ø. , Jensen Steffen G. , Duduyemi Babatunde , Gyasi Richard K. , Ofori Michael F. , Paintsil Vivian , Renner Lorna , Nørgaard Peter , Hviid Lars 
Published: December 2019

AbstractBackgroundEndemic Burkitt lymphoma (eBL) is an aggressive B-cell lymphoma, which is a common childhood cancer in areas with intense transmission ofPlasmodium falciparumparasites. Early and accurate diagnosis is a prerequisite for successful therapy, but it optimally involves advanced laboratory investigations. These are technologically demanding, expensive, and often difficult to implement in settings where eBL is prevalent. Diagnosis is thus generally based on clinical assessment and morphological examination of tumour biopsies or fine-needle aspirates (FNAs).MethodsThe purpose of the present study was to assess the accuracy of eBL diagnosis at two tertiary hospitals in Ghana. To that end, we studied FNAs from 29 eBL patients and 21 non-eBL lymphoma patients originally diagnosed in 2018. In addition, we examined 111 archival formalin-fixed and paraffin-embedded (FFPE) biopsies from Ghanaian patients originally diagnosed as eBL (N = 55) or non-eBL (N = 56) between 2010 and 2017. Availability-based subsets of samples were subjected to haematoxylin-eosin or Giemsa staining, C-MYC immunohistochemistry, and fluorescence in situ hybridisation (FISH) analysis ofc-mycrearrangements.ResultsWe found a good correlation between original diagnosis and subsequent retrospective assessment, particularly for FNA samples. However, evidence of intactc-mycgenes and normal C-MYC expression in samples from some patients originally diagnosed as eBL indicates that morphological assessment alone can lead to eBL over-diagnosis in our study area. In addition, several FFPE samples could not be assessed retrospectively, due to poor sample quality. Therefore, the simpler FNA method of obtaining tumour material is preferable, particularly when careful processing of biopsy specimens cannot be guaranteed.ConclusionWe conclude that the accuracy of eBL diagnostic tools available in Ghana is generally adequate, but could be improved by implementation of additional pathology laboratory investigations. Improved attention to adequate preservation of archival samples is recommended.
Association between ESR1, ESR2, HER2, UGT1A4, and UGT2B7 polymorphisms and breast Cancer in Jordan: a case-control study
Authors: AL-Eitan Laith N. , Rababa’h Doaa M. , Alghamdi Mansour A. , Khasawneh Rame H. 
Published: December 2019

Abstract
Background
Breast cancer risk, development, and treatment are influenced by genetic variation in certain genes, namely those involved in cell proliferation, tumor suppression, and drug metabolism. In turn, the relevance of the aforementioned genetic variation to cancer depends on the ethnic group in question, highlighting the need for population-specific association studies. Therefore, the objective of the present study was to investigate the association between certain ESR1, ESR2, HER2, UGT1A4, and UGT2B7 single nucleotide polymorphisms and breast cancer.

Methods
Blood samples were collected from 437 Jordanian-Arab breast cancer patients and healthy volunteers and subject to genotyping using the Sequenom MassARRAY® system (iPLEX GOLD).

Results
Our findings show a significant association between breast cancer and the allelic (P = 0.02486879) and genotypic (P = 0.04793066) frequencies of the ESR1 polymorphism rs3798577, a result which was confirmed in different genetic models. No other investigated polymorphism showed a significant association with breast cancer itself in Jordanian Arabs, but the Rare Hz (GG) vs Het (AG) genetic model revealed an association of the disease with the ESR1 polymorphism rs3798577. However, several associations were found between certain polymorphisms and breast cancer’s prognostic factors.

Conclusion
This study suggests that certain polymorphisms may increase the risk of breast cancer in the Jordanian-Arab population. Future research and clinical translation could incorporate the current results in preventative breast cancer approaches tailored for Jordanian-Arab patients.
Improvements in visual acuity and macular morphology following cessation of anti-estrogen drugs in a patient with anti-estrogen maculopathy resembling macular telangiectasia type 2: a pathogenic hypothesis
Authors: Shinkai Akihiro , Saito Wataru , Hashimoto Yuki , Ishida Susumu 
Published: December 2019

Abstract
Background
The relationship between anti-estrogen drugs and macular telangiectasia type 2 (MacTel-2) remains unknown. Here we report a case with anti-estrogen maculopathy resembling MacTel-2 with improved visual function and macular morphology following cessation of anti-estrogen drugs.

Case presentation
A 53-year-old woman presented with a 5-month history of central vision loss and anorthopia in both eyes. She had received oral tamoxifen followed by toremifene for 69 months. Funduscopy, fluorescein angiography, and optical coherence tomography (OCT) revealed MacTel-2-like findings OU. Fundus autofluorescence (FAF) showed hyper-autofluorescence at the fovea OU. Visual acuity, macular morphology on OCT, and FAF findings gradually improved after cessation of anti-estrogen drugs.

Conclusions
In the present case, visual acuity, macular morphology, and impairment of the retinal pigment epithelium (RPE) improved following cessation of anti-estrogen drugs, suggesting the relationship between retinal toxicity of anti-estrogen drugs and the development of MacTel-2-like findings. From these results and the previous observations, toxicity of both photoreceptor and RPE cells caused by anti-estrogen drugs may contribute to the development of anti-estrogen maculopathy similar to MacTel-2.
Repeated intravitreal injections of antivascular endothelial growth factor in patients with neovascular age-related macular degeneration may increase the risk of ischemic optic neuropathy
Authors: Chen Yu-Yen , Chou Pesus , Huang Yu-Fang , Chien Hung-Jen , Wu Yu-Chieh , Lee Chia-Chi , Huang Li-Ying , Chen Hsin-Hua 
Published: December 2019

Abstract
Background
Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD).

Methods
A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10–15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma).

Results
In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32–2.76) and 2.20 (95% CI, 1.42–3.43), respectively, compared with those in the first-level group.

Conclusions
Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.
Watch out for the special location of intraventricular silicone oil following an intraocular tamponade - a 10-year follow-up case report based on CT/MRI
Authors: Cao Juntao , Bian Lianlong , Zhou Pengpeng , Tu Jianchun 
Published: December 2019

Abstract
Background
Intraventricular silicone oil is a relatively rare complication resulted from silicone oil tamponade to treat retinal detachment. It is occasionally reported in previous literature. To the best of our knowledge, the long-term longitudinal comparisons of silicone oil both in the brain and in the postoperative eyeball based on CT/MRI were lacking, and intraventricular silicone oil accumulation beside lesions has been reported rarely.

Case presentation
A 63-year-old male patient underwent an intraocular tamponade with silicone oil in June 2009. Eight CT examinations and 2 MRI examinations were acquired between 2011 and 2018.The changes of silicone oil in the brain in CT/MRI as below: Silicone oil initially migration to bilateral lateral ventricular anterior horn was found in November 2011, it was aslo found at right side of suprasellar cisterna, and there was no change in location 6 h later; Silicone oil at the anterior horn of right lateral ventricle disappeared but remained at left lateral ventricle and right side of suprasellar cisterna in July 2014, and there was no change in location in a short-term reexamination. It was found at the middle of left lateral ventricle (adjacent to the real cause) in march 2018, but disappeared 3 months later, while remained at anterior horn of left lateral ventricular and right side of suprasellar cisterna all the time. There was no change in location in the next 2 follow-up (September and October in 2018). The CT values of silicone oil distributed throughout the brain were dynamically changed with time.

Conclusion
It is important to recognize intraventricular silicone oil in a particular location.More important is to discover “the real murderer”, which is the main cause of symptoms in the vicinity of special location. Moreover, the migration of silicone oil between eyeball and brain may not be always in a single direction.
Study protocol: The Dutch 20|30 Postmeningitis study: a cross-sectional follow-up of two historical childhood bacterial meningitis cohorts on long-term outcomes
Authors: El Tahir O. , de Jonge R. C. J. , Ouburg S. , Morré S. A. , van Furth A. M. 
Published: December 2019

AbstractBackgroundBacterial meningitis (BM) is a serious, life-threatening infectious disease of the central nervous system that often occurs in young children. The most common severe to moderate sequelae following BM are sensorineural hearing loss, neuromotor disabilities and mental retardation, while subtle sequelae include academic and behavioral disabilities. It is largely unknown whether these more subtle sequelae persist into adolescence and adulthood. Therefore, this study will investigate the very long-term effects of childhood BM in later life. Better understanding of long-term effects and early identification of adverse outcomes after BM are essential for more timely interventions. Additionally, certain single nucleotide polymorphisms (SNPs) are associated with disease severity and might predict adverse sequelae. These include SNPs in genes encoding for pathogen recognition and immune response upon infection. Accordingly, a secondary objective of this study is to investigate the role of genetic variation in BM and use any insights to predict short- and long-term outcomes.MethodsIn the Dutch 20|30 Postmeningitis study, adolescents and young adults (n = 947) from two historical cohorts with a prior episode of BM during childhood will be enrolled into a cross-sectional follow-up investigation using mainly questionnaires that examine executive and behavioral functioning, health-related quality of life, subjective hearing, mood and sleeping disorders, academic performance, and economic self-sufficiency. The results will be compared to normative data by one-sample t-tests. Multivariable regression analysis will be used to assess for any associations with causative pathogens and severity of BM. Participants that complete the questionnaires will be approached to provide a swab for buccal DNA and subsequent sequencing analyses. Logistic regression models will be used to predict sequelae.DiscussionThe unique follow-up duration of this cohort will enable us to gain insights into the possible very long-term adverse effects of childhood BM and how these might impact on quality of life. The investigation of host genetic factors will contribute to the development of prediction models which will serve as prognostic tools to identify children who are at high risk of adverse outcome after BM.Trial RegistrationDutch Trial RegisterNTR-6891. Retrospectively registered 28 December 2017.
How do community-based eye care practitioners approach depression in patients with low vision? A mixed methods study
Authors: Nollett Claire , Bartlett Rebecca , Man Ryan , Pickles Timothy , Ryan Barbara , Acton Jennifer H. 
Published: December 2019

AbstractBackgroundClinically significant depressive symptoms are prevalent in people attending low vision clinics and often go undetected. The Low Vision Service Wales (LVSW) plans to introduce depression screening and management pathways. Prior to implementation there is an unmet need to understand how eye care practitioners providing the service currently address depression with patients, and the characteristics and beliefs that influence their practice.MethodsA mixed methods convergent design was employed. Twelve low vision practitioners were purposively selected to engage in individual semi-structured interviews which were analysed using thematic analysis. A further 167 practitioners were invited to complete a questionnaire assessing professional background, current practice, confidence and perceived barriers in working with people with low vision and suspected depression. Multiple regression analyses were performed to determine the characteristics related to the Rasch-transformed questionnaire scores.ResultsOf the 122 practitioners that responded to the questionnaire, 33% aimed to identify depression in patients, and those who were more confident were more likely to do so. Those who scored higher on the perceived barriers scale and lower on confidence were less likely to report acting in response to suspected depression (allp < 0.05). Three qualitative themes were identified; depression is an understandable response to low vision, patients themselves are a barrier to addressing depression and practitioners lacked confidence in their knowledge and skills to address depression. The qualitative data largely expanded the quantitative findings.ConclusionsPractitioners viewed their own lack of knowledge and confidence as a barrier to the identification and management of depression and expressed a need for training prior to the implementation of service changes. The study findings will help to inform the development of a training programme to support low vision practitioners and those working with other chronic illness in Wales, and internationally, in the identification and management of people with depression.
The impact of depression and anxiety treatment on biological aging and metabolic stress: study protocol of the Mood treatment with antidepressants or running (MOTAR) study
Authors: Lever-van Milligen Bianca A. , Verhoeven Josine E. , Schmaal Lianne , van Velzen Laura S. , Révész Dóra , Black Catherine N. , Han Laura K. M. , Horsfall Melany , Batelaan Neeltje M. , van Balkom Anton J. L. M. , van Schaik Digna J. F. , van Oppen Patricia , Penninx Brenda W. J. H. 
Published: December 2019

Abstract
Background
Depressive and anxiety disorders have shown to be associated to premature or advanced biological aging and consequently to adversely impact somatic health. Treatments with antidepressant medication or running therapy are both found to be effective for many but not all patients with mood and anxiety disorders. These interventions may, however, work through different pathophysiological mechanisms and could differ in their impact on biological aging and somatic health. This study protocol describes the design of an unique intervention study that examines whether both treatments are similarly effective in reducing or reversing biological aging (primary outcome), psychiatric status, metabolic stress and neurobiological indicators (secondary outcomes).

Methods
The MOod Treatment with Antidepressants or Running (MOTAR) study will recruit a total of 160 patients with a current major depressive and/or anxiety disorder in a mental health care setting. Patients will receive a 16-week treatment with either antidepressant medication or running therapy (3 times/week). Patients will undergo the treatment of their preference and a subsample will be randomized (1:1) to overcome preference bias. An additional no-disease-no-treatment group of 60 healthy controls without lifetime psychopathology, will be included as comparison group for primary and secondary outcomes at baseline. Assessments are done at week 0 for patients and controls, and at week 16 and week 52 for patients only, including written questionnaires, a psychiatric and medical examination, blood, urine and saliva collection and a cycle ergometer test, to gather information about biological aging (telomere length and telomerase activity), mental health (depression and anxiety disorder characteristics), general fitness, metabolic stress-related biomarkers (inflammation, metabolic syndrome, cortisol) and genetic determinants. In addition, neurobiological alterations in brain processes will be assessed using structural and functional Magnetic Resonance Imaging (MRI) in a subsample of at least 25 patients per treatment arm and in all controls.

Discussion
This intervention study aims to provide a better understanding of the impact of antidepressant medication and running therapy on biological aging, metabolic stress and neurobiological indicators in patients with depressive and anxiety disorders in order to guide a more personalized medicine treatment.

Trial registration
Trialregister.nl Number of identification: NTR3460, May 2012.
Longitudinal associations between perceptions of the neighbourhood environment and physical activity in adolescents: evidence from the Olympic Regeneration in East London (ORiEL) study
Authors: Berger Nicolas , Lewis Daniel , Quartagno Matteo , Njagi Edmund Njeru , Cummins Steven 
Published: December 2019

Abstract
Background
Most UK adolescents do not achieve recommended levels of physical activity. Previous studies suggested that perceptions of the neighbourhood environment could contribute to explain differences in physical activity behaviours. We aimed to examine whether five measures of perceptions – perceived bus stop proximity, traffic safety, street connectivity, enjoyment of the neighbourhood for walking/cycling, and personal safety – were longitudinally associated with common forms of physical activity, namely walking to school, walking for leisure, and a composite measure of outdoor physical activity. We further aimed to investigate the moderating role of gender.

Methods
We used longitudinal data from the Olympic Regeneration in East London (ORiEL) study, a prospective cohort study. In 2012, 3106 adolescents aged 11 to 12 were recruited from 25 schools in 4 deprived boroughs of East London. Adolescents were followed-up in 2013 and 2014. The final sample includes 2260 adolescents surveyed at three occasions. We estimated logistic regression models using Generalised Estimating Equations to test the plausibility of hypotheses on the nature of the longitudinal associations (general association, cumulative effect, co-varying trajectories), adjusting for potential confounders. Item non-response was handled using multiple imputation.

Results
Longitudinal analyses indicate little evidence that perceptions of the neighbourhood are important predictors of younger adolescent physical activity. There was weak evidence that greater perceived proximity to bus stops is associated with a small decrease in the probability of walking for leisure. Results also indicate that poorer perception of personal safety decreases the probability of walking for leisure. There was some indication that better perception of street connectivity is associated with more outdoor physical activity. Finally, we found very little evidence that the associations between perceptions of the neighbourhood and physical activity differed by gender.

Conclusions
This study suggests that younger adolescents’ perceptions of their neighbourhood environment, and changes in these perceptions, did not consistently predict physical activity in a deprived and ethnically diverse urban population. Future studies should use situation-specific measures of the neighbourhood environment and physical activity to better capture the hypothesised processes and explore the relative roles of the objective environment, parental and adolescents’ perceptions in examining differences in types of physical activity.