bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal and child health service delivery in conflict-affected settings: a case study example from Upper Nile and Unity states, South Sudan
Authors: Sami Samira , Mayai Augustino , Sheehy Grace , Lightman Nicole , Boerma Ties , Wild Hannah , Tappis Hannah , Ochan Wilfred , Wanyama James , Spiegel Paul 
Published: May 2020

Abstract
Background
Decades of war left the Republic of South Sudan with a fragile health system that has remained deprived of resources since the country’s independence. We describe the coverage of interventions for women’s and children’s health in Upper Nile and Unity states, and explore factors that affected service provision during a protracted conflict.

Methods
We conducted a case study using a desk review of publicly available literature since 2013 and a secondary analysis of intervention coverage and conflict-related events from 2010 to 2017. During June through September 2018, we conducted 26 qualitative interviews with technical leads and 9 focus groups among health workers working in women and children’s health in Juba, Malakal, and Bentiu.

Results
Coverage for antenatal care, institutional delivery, and childhood vaccines were low prior to the escalation of conflict in 2013, and the limited data indicate that coverage remained low through 2017. Key factors that determined the delivery of services for women and children in our study sites were government leadership, coordination of development and humanitarian efforts, and human resource capacity. Participants felt that national and local health officials had a limited role in the delivery of services, and financial tracking data showed that funding stagnated or declined for humanitarian health and development programming during 2013–2014. Although health services were concentrated in camp settings, the availability of healthcare providers was negatively impacted by the protracted nature of the conflict and insecurity in the region.

Conclusions
Health care for women and children should be prioritized during acute and protracted periods of conflict by strengthening surveillance systems, coordinating short and long term activities among humanitarian and development organizations, and building the capacity of national and local government officials to ensure sustainability.
Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples
Authors: Russano Marco , Napolitano Andrea , Ribelli Giulia , Iuliani Michele , Simonetti Sonia , Citarella Fabrizio , Pantano Francesco , Dell’Aquila Emanuela , Anesi Cecilia , Silvestris Nicola , Argentiero Antonella , Solimando Antonio Giovanni , Vincenzi Bruno , Tonini Giuseppe , Santini Daniele 
Published: May 2020

AbstractIn a large number of cancer types, treatment selection depends on the presence of specific tumor biomarkers. Due to the dynamic nature of cancer, very often these predictive biomarkers are not uniformly present in all cancer cells. Tumor heterogeneity represents indeed one of the main causes of therapeutic failure, and its decoding remains a major ongoing challenge in the field.Liquid biopsy is the sampling and analysis of non-solid biological tissue often through rapid and non-invasive methods, which allows the assessment in real-time of the evolving landscape of cancer. Samples can be obtained from blood and most other bodily fluids. A blood-based liquid biopsy can capture circulating tumor cells and leukocytes, as well as circulating tumor-derived nucleic acids.In this review, we discuss the current and possibly future applications of blood-based liquid biopsy in oncology, its advantages and its limitations in clinical practice. We specifically focused on its role as a tool to capture tumor heterogeneity in metastatic cancer patients.
Prediction of in-hospital mortality in patients with post traumatic brain injury using National Trauma Registry and Machine Learning Approach
Authors: Abujaber Ahmad , Fadlalla Adam , Gammoh Diala , Abdelrahman Husham , Mollazehi Monira , El-Menyar Ayman 
Published: May 2020

Abstract
Background
The use of machine learning techniques to predict diseases outcomes has grown significantly in the last decade. Several studies prove that the machine learning predictive techniques outperform the classical multivariate techniques. We aimed to build a machine learning predictive model to predict the in-hospital mortality for patients who sustained Traumatic Brain Injury (TBI).

Methods
Adult patients with TBI who were hospitalized in the level 1 trauma center in the period from January 2014 to February 2019 were included in this study. Patients’ demographics, injury characteristics and CT findings were used as predictors. The predictive performance of Artificial Neural Networks (ANN) and Support Vector Machines (SVM) was evaluated in terms of accuracy, Area Under the Curve (AUC), sensitivity, precision, Negative Predictive Value (NPV), specificity and F-score.

Results
A total of 1620 eligible patients were included in the study (1417 survival and 203 non-survivals). Both models achieved accuracy over 91% and AUC over 93%. SVM achieved the optimal performance with accuracy 95.6% and AUC 96%.

Conclusions
for prediction of mortality in patients with TBI, SVM outperformed the well-known classical models that utilized the conventional multivariate analytical techniques.
A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial
Authors:   on behalf of the PD COMM Collaborative Group, Sackley C. M. , Rick C. , Au P. , Brady M. C. , Beaton G. , Burton C. , Caulfield M. , Dickson S. , Dowling F. , Hughes M. , Ives N. , Jowett S. , Masterson-Algar P. , Nicoll A. , Patel S. , Smith C. H. , Woolley R. , Clarke C. E. 
Published: May 2020

Abstract
Background
Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive.

Methods/design
PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation.
Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation.
The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK.

Discussion
The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions.

Trial registration
International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016.
Single-cell RNA sequencing reveals the tumor microenvironment and facilitates strategic choices to circumvent treatment failure in a chemorefractory bladder cancer patient
Authors: Lee Hye Won , Chung Woosung , Lee Hae-Ock , Jeong Da Eun , Jo Areum , Lim Joung Eun , Hong Jeong Hee , Nam Do-Hyun , Jeong Byong Chang , Park Se Hoon , Joo Kyeung-Min , Park Woong-Yang 
Published: May 2020

AbstractBackgroundTumor cell-intrinsic mechanisms and complex interactions with the tumor microenvironment contribute to therapeutic failure via tumor evolution. It may be possible to overcome treatment resistance by developing a personalized approach against relapsing cancers based on a comprehensive analysis of cell type-specific transcriptomic changes over the clinical course of the disease using single-cell RNA sequencing (scRNA-seq).MethodsHere, we used scRNA-seq to depict the tumor landscape of a single case of chemo-resistant metastatic, muscle-invasive urothelial bladder cancer (MIUBC) addicted to an activating Harvey rat sarcoma viral oncogene homolog (HRAS) mutation. In order to analyze tumor evolution and microenvironmental changes upon treatment, we also applied scRNA-seq to the corresponding patient-derived xenograft (PDX) before and after treatment with tipifarnib, a HRAS-targeting agent under clinical evaluation.ResultsIn the parallel analysis of the human MIUBC and the PDX, diverse stromal and immune cell populations recapitulated the cellular composition in the human and mouse tumor microenvironment. Treatment with tipifarnib showed dramatic anticancer effects but was unable to achieve a complete response. Importantly, the comparative scRNA-seq analysis between pre- and post-tipifarnib-treated PDX revealed the nature of tipifarnib-refractory tumor cells and the tumor-supporting microenvironment. Based on the upregulation of programmed death-ligand 1 (PD-L1) in surviving tumor cells, and the accumulation of multiple immune-suppressive subsets from post-tipifarnib-treated PDX, a PD-L1 inhibitor, atezolizumab, was clinically applied; this resulted in a favorable response from the patient with acquired resistance to tipifarnib.ConclusionWe presented a single case report demonstrating the power of scRNA-seq for visualizing the tumor microenvironment and identifying molecular and cellular therapeutic targets in a treatment-refractory cancer patient.
The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues
Authors: Muyas Francesc , Zapata Luis , Guigó Roderic , Ossowski Stephan 
Published: May 2020

Abstract
Background
Mosaic mutations acquired during early embryogenesis can lead to severe early-onset genetic disorders and cancer predisposition, but are often undetectable in blood samples. The rate and mutational spectrum of embryonic mosaic mutations (EMMs) have only been studied in few tissues, and their contribution to genetic disorders is unknown. Therefore, we investigated how frequent mosaic mutations occur during embryogenesis across all germ layers and tissues.

Methods
Mosaic mutation detection in 49 normal tissues from 570 individuals (Genotype-Tissue Expression (GTEx) cohort) was performed using a newly developed multi-tissue, multi-individual variant calling approach for RNA-seq data. Our method allows for reliable identification of EMMs and the developmental stage during which they appeared.

Results
The analysis of EMMs in 570 individuals revealed that newborns on average harbor 0.5–1 EMMs in the exome affecting multiple organs (1.3230 × 10−8 per nucleotide per individual), a similar frequency as reported for germline de novo mutations. Our multi-tissue, multi-individual study design allowed us to distinguish mosaic mutations acquired during different stages of embryogenesis and adult life, as well as to provide insights into the rate and spectrum of mosaic mutations. We observed that EMMs are dominated by a mutational signature associated with spontaneous deamination of methylated cytosines and the number of cell divisions. After birth, cells continue to accumulate somatic mutations, which can lead to the development of cancer. Investigation of the mutational spectrum of the gastrointestinal tract revealed a mutational pattern associated with the food-borne carcinogen aflatoxin, a signature that has so far only been reported in liver cancer.

Conclusions
In summary, our multi-tissue, multi-individual study reveals a surprisingly high number of embryonic mosaic mutations in coding regions, implying novel hypotheses and diagnostic procedures for investigating genetic causes of disease and cancer predisposition.
Therapeutic abortion in Iran: an epidemiologic study of legal abortion in 2 years
Authors: Mahdavi Seyed Amirhosein , Jafari Asieh , Azimi Khadijeh , Dehghanizadeh Nikoo , Barzegar Abdolrazagh 
Published: May 2020

AbstractObjectivesUnsafe abortion is one of the most important causes of death and disability among mothers in countries where abortion is illegal. These conditions have changed since then. The present study has investigated the cases who were referred to the legal medicine organization to receive abortion permission. This country level secondary patient data analysis, investigated all the cases who were referred to the legal medicine centers of Iran for abortion permission during 2015 to 2017.ResultsFrom 21,477 applicants, 15,617 (72.71%) received permission including 14,367 (91.99%) for fetal abnormalities and 1250 (8.01%) for maternal diseases. The most common fetal abnormalities/disorders were nervous system malformations (26.4%), chromosomal abnormalities (18.4%) and of maternal diseases were circulatory system diseases (43.9%), neoplasms (13.4%) and genitourinary system diseases (9.9%). The most common reasons for not permission were lack of supplementary documents to prove (38.8%), not competency with the criteria (33.9%), and gestational age of more than 19 weeks (25.8%).
Expression patterns of SLIT/ROBO mRNAs reveal a characteristic feature in the entorhinal-hippocampal area of macaque monkeys
Authors: Sasaki Tetsuya , Komatsu Yusuke , Yamamori Tetsuo 
Published: May 2020

Abstract
Objective
SLITs are secreted glycoproteins that bind to Roundabouts (ROBOs) which are a family member of transmembrane receptors. SLIT signaling has well-conserved roles in mediating axon repulsion in a developing nervous system. We previously reported that SLIT1 mRNA is enriched in middle layers of the prefrontal cortex of macaque monkeys in a developmentally regulated manner. Other SLIT (SLIT2 and SLIT3) mRNAs showed preferential expressions in the prefrontal cortex with a distinct laminar pattern. To obtain further clues to the role of SLIT signaling in the organization of the primate brain, we performed ISH analysis of SLIT and ROBO mRNAs using adult macaque brain tissues.

Results
In this study, we examined the expression patterns of SLITs and ROBOs (ROBO1 and ROBO2) in other brain regions, and found intense and characteristic expression patterns of these genes in the entorhinal-hippocampal area. In situ hybridization analysis revealed that SLIT1 and SLIT2 mRNAs showed marked complementary distribution in the entorhinal cortex. SLIT and ROBO mRNAs were widely expressed in the hippocampus with modest regional preference. These findings suggest that each SLIT gene has a specialized role that is particularly important for prefrontal as well as hippocampal connectivity in the primate cortex.
Co-occurrence between C1 esterase inhibitor deficiency and autoimmune disease: a systematic literature review
Authors: Levy Donald , Craig Timothy , Keith Paul K. , Krishnarajah Girishanthy , Beckerman Rachel , Prusty Subhransu 
Published: May 2020

AbstractBackgroundHereditary angioedema (HAE) is caused by a SERPING1 gene defect resulting in decreased (Type I) or dysfunctional (Type II) C1 esterase inhibitor (C1-INH). The prevalence of autoimmune diseases (ADs) in patients with HAE appears to be higher than the general population. A systematic literature review was conducted to examine the co-occurrence between HAE and ADs.MethodsPubMed/EMBASE were searched for English-language reviews, case reports, observational studies, retrospective studies, and randomized controlled trials up to 04/15/2018 (04/15/2015-04/15/2018 for EMBASE) that mentioned patients with HAE Type I or II and comorbid ADs. Non-human or in vitro studies and publications of C1-INH deficiency secondary to lymphoproliferative disorders or angiotensin-converting-enzyme inhibitors were excluded.ResultsOf the 2880 records screened, 76 met the eligibility criteria and 155 individual occurrences of co-occurring HAE and AD were mentioned. The most common ADs were systemic lupus erythematosus (30 mentions), thyroid disease (21 mentions), and glomerulonephritis (16 mentions). When ADs were grouped by MedDRA v21.0 High Level Terms, the most common were: Lupus Erythematosus and Associated Conditions, n = 52; Endocrine Autoimmune Disorders, n = 21; Gastrointestinal Inflammatory Conditions, n = 16; Glomerulonephritis and Nephrotic Syndrome, n = 16; Rheumatoid Arthritis and Associated Conditions, n = 11; Eye, Salivary Gland and Connective Tissue Disorders, n = 10; and Immune and Associated Conditions Not Elsewhere Classified, n = 5.ConclusionsBased on literature reports, systemic lupus erythematosus is the most common AD co-occurring with HAE Type I and II. Cause and effect for co-occurring HAE and AD has not been clinically established but could be related to lack of sufficient C1-INH function.
Identification of amygdala-expressed genes associated with autism spectrum disorder
Authors: Herrero Maria Jesus , Velmeshev Dmitry , Hernandez-Pineda David , Sethi Saarthak , Sorrells Shawn , Banerjee Payal , Sullivan Catherine , Gupta Abha R. , Kriegstein Arnold R. , Corbin Joshua G. 
Published: May 2020

Abstract
Background
Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development.

Methods
Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20 years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD.

Results
Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline.

Limitations
We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages.

Conclusions
Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala.
Intravenous infusion of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells as a potential treatment for patients with COVID-19 pneumonia
Authors: Zhang Yingxin , Ding Jie , Ren Shaoda , Wang Weihua , Yang Yapei , Li Shuangjing , Meng Min , Wu Tiejun , Liu Daliang , Tian Suochen , Tian Hui , Chen Shuangfeng , Zhou Changhui 
Published: May 2020

AbstractThe novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency since patients were first detected in Wuhan, China. Thus far, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. The immune system and inflammation are proposed to play a central role in COVID-19 pathogenesis. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. Intravenous infusion of MSCs has shown promising results in COVID-19 treatment. Here, we report a case of a severe COVID-19 patient treated with human umbilical cord Wharton’s jelly-derived MSCs (hWJCs) from a healthy donor in Liaocheng People’s Hospital, China, from February 24, 2020. The pulmonary function and symptoms of the patient with COVID-19 pneumonia was significantly improved in 2 days after hWJC transplantation, and recovered and discharged in 7 days after treatment. After treatment, the percentage and counts of lymphocyte subsets (CD3+, CD4+, and CD8+ T cell) were increased, and the level of IL-6, TNF-α, and C-reactive protein is significantly decreased after hWJC treatment. Thus, the intravenous transplantation of hWJCs was safe and effective for the treatment of patients with COVID-19 pneumonia, especially for the patients in a critically severe condition. This report highlights the potential of hWJC infusions as an effective treatment for COVID-19 pneumonia.
Role of CD133 in human embryonic stem cell proliferation and teratoma formation
Authors: Wang Hua , Gong Peng , Li Jie , Fu Yudong , Zhou Zhongcheng , Liu Lin 
Published: May 2020

AbstractBackgroundPluripotent stem cells (PSCs), including human embryonic stem cells (hESCs), hold great potential for regenerative medicine and cell therapy. One of the major hurdles hindering the clinical development of PSC-based therapy is the potential risk of tumorigenesis. CD133 (Prominin 1, PROM1) is a transmembrane protein whose mRNA and glycosylated forms are highly expressed in many human cancer cell types. CD133 also serves as a cancer stem cell (CSC) marker associated with cancer progression and patient outcome. Interestingly, CD133 is highly expressed in hESCs as well as in human preimplantation embryos, but its function in hESCs has remained largely unknown.MethodsCD133 knockout hESC WA26 cell line was generated with CRISPR/Cas9. CD133 knockout and wide type hESC lines were subjected to pluripotency, proliferation, telomere biology, and teratoma tests; the related global changes and underlying mechanisms were further systemically analyzed by RNA-seq.ResultsCD133 deficiency did not affect hESC pluripotency or in vivo differentiation into three germ layers but significantly decreased cell proliferation. RNA-seq revealed that CD133 deficiency dysregulated the p53, PI3K-Akt, AMPK, and Wnt signaling pathways. Alterations in these pathways have been implicated in tumor proliferation and apoptotic escape.ConclusionsOur data imply that CD133 could be an additional target and used as a selective marker to sort and eliminate undifferentiated cells in reducing potential teratoma formation risk of hESCs in regenerative medicine.