bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent, mobile and toxic (PMT) and very persistent and very mobile (vPvM) substances pose an equivalent level of concern to persistent, bioaccumulative and toxic (PBT) and very persistent and very bioaccumulative (vPvB) substances under REACH
Authors: Hale Sarah E. , Arp Hans Peter H. , Schliebner Ivo , Neumann Michael 
Published: December 2020

Abstract
Background
Under the EU chemicals regulation REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals EC 1907/2006), registrants are not obliged to provide information related to intrinsic substance properties for substances that pose a threat to the drinking water resources. In 2019, perfluorobutane sulfonic acid (PFBS) and 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoic acid (HFPO-DA trade name GenX) were demonstrated to have an equivalent level of concern (ELoC) to persistent, bioaccumulative and toxic or very persistent and very bioaccumulative (PBT/vPvB) substances owing to their persistent, mobile and toxic (PMT) substance properties and very persistent and very mobile (vPvM) substance properties, respectively. They were both subsequently identified as substances of very high concern (SVHC) applying Article 57(f) in REACH. This work follows up on this regulatory decision by presenting a science based, conceptual level comparison that all PMT/vPvM substances pose an ELoC to PBT/vPvB substances. Using the two cases named above, as well as 1,4-dioxane, 16 categories were developed to evaluate a) serious effects on human health, b) serious effects on the environment and c) additional effects. 1,4-dioxane has recently been proposed to be classified as Carcinogenic 1B by the Committee for Risk Assessment (RAC). The aim was to enable an objective and scientifically justified conclusion that these classes of substances have an equivalent level of concern for the environment and human health.

Results
In all of the categories related to human health, the environment and other effects, the PMT/vPvM case study substances exhibited comparable effects to PBT/vPvB substances. A difference in the human and environmental exposure pathways of PMT/vPvM and PBT/vPvB substances exists as they vary temporally and spatially. However, effects and impacts are similar, with PMT/vPvM substances potentially accumulating in (semi-)closed drinking water cycles and pristine aquatic environments, and PBT/vPvB substances accumulating in humans and the food chain. Both PMT/vPvM and PBT/vPvB substances share the common difficulty that long term and long-range transport and risk of exposure is very difficult to determine in advance and with sufficient accuracy.

Conclusion
The registration process of substances under REACH should reflect that PMT/vPvM substances pose an equivalent level of concern to PBT/vPvB substances.
NIMO-CKD-UK: a real-world, observational study of iron isomaltoside in patients with iron deficiency anaemia and chronic kidney disease
Authors: Kalra Philip A. , Bhandari Sunil , Spyridon Michael , Davison Rachel , Lawman Sarah , Mikhail Ashraf , Reaich David , Pritchard Nick , McCafferty Kieran , Moore Jason 
Published: December 2020

Abstract
Background
Intravenous iron is often used to treat iron deficiency anaemia in non-dialysis chronic kidney disease (ND-CKD), but the optimal dosing regimen remains unclear. We evaluated the impact of high- versus low-dose intravenous iron isomaltoside on the probability of retreatment with intravenous iron in iron-deficient ND-CKD patients.

Methods
This real-world, prospective, observational study collected data from 256 ND-CKD patients treated for anaemia in the UK. Following an initial course of iron isomaltoside, patients were followed for ≥12 months. Iron dose and the need for retreatment were determined at the investigators’ discretion. The primary study outcome was the need for retreatment at 52 weeks compared between patients who received >1000 mg of iron during Course 1 and those who received ≤1000 mg. Safety was evaluated through adverse drug reactions.

Results
The probability of retreatment at Week 52 was significantly lower in the >1000 mg iron group (n = 58) versus the ≤1000 mg group (n = 198); hazard ratio (95% confidence interval [CI]): 0.46 (0.20, 0.91); p = 0.012. Mean (95% CI) haemoglobin increased by 6.58 (4.94, 8.21) g/L in the ≤1000 mg group and by 10.59 (7.52, 13.66) g/L in the >1000 mg group (p = 0.024). Changes in other blood and iron parameters were not significantly different between the two groups. Administering >1000 mg of iron isomaltoside saved 8.6 appointments per 100 patients compared to ≤1000 mg. No serious adverse drug reactions were reported. Of the patients who received ≤1000 mg of iron in this study, 82.3% were eligible for a dose >1000 mg.

Conclusions
The >1000 mg iron isomaltoside regimen reduced the probability of retreatment, achieved a greater haemoglobin response irrespective of erythropoiesis-stimulating agent treatment, and reduced the total number of appointments required, compared to the ≤1000 mg regimen. Many of the patients who received ≤1000 mg of iron were eligible for >1000 mg, indicating that there was considerable underdosing in this study.

Trial registration
ClinicalTrials.gov NCT02546154, 10 September 2015.
Rare concurrent ocular myasthenia gravis and Graves’ ophthalmopathy in a man with Poland syndrome: a case report
Authors: Tang Jingqun , Qin Chao 
Published: December 2020

Abstract
Background
Ocular myasthenia gravis and Graves’ ophthalmopathy are autoimmune diseases that are mediated by membrane receptors and share many identical clinical processes. Poland syndrome is a rare congenital deformity characterized by defects of the ipsilateral hand and the chest wall, and it is usually associated with hypoplasia of ipsilateral pectoral muscles and homolateral breast. However, to the best of our knowledge, the co-occurrence of these diseases has never been reported. In this study, we present a man with Poland syndrome who was diagnosed with Graves’ ophthalmopathy and ocular myasthenia gravis in succession.

Case presentation
A 43-year-old man presented with bilateral upper eyelid ptosis, bilateral eye protrusion, bilateral eye movement disorder and malformation of the right hand. Asymmetrical malformation of the chest wall and ipsilateral hand deformity were shown as Poland syndrome. He was diagnosed with ocular myasthenia gravis and Graves’ ophthalmopathy on the basis of clinical manifestations and laboratory examinations, including bilateral exophthalmos and progressive asymmetrical ophthalmoparesis without pupillary dysfunction, positive autoantibody tests, repetitive nerve stimulation tests, and computed tomography scans. Treatments with pyridostigmine bromide, thymectomy, and prednisone led to partial clinical improvement. After 13 months of follow-up, the symptoms of drooping eyelids were partially improved, but the eyeball protrusion and right hand deformity remained unchanged.

Conclusions
We report the first case of co-occurrence of ocular myasthenia gravis, Graves’ ophthalmopathy, and Poland syndrome. Genetic predisposition and immune dysregulation might be the pathogenesis of the association.
The global, regional, and national burden of pancreatitis in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017
Authors: Ouyang Guoqing , Pan Guangdong , Liu Qiang , Wu Yongrong , Liu Zhen , Lu Wuchang , Li Shuai , Zhou Zheng , Wen Yu 
Published: December 2020

Abstract
Background
Pancreatitis is a critical public health problem, and the burden of pancreatitis is increasing. We report the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) for pancreatitis at the global, regional, and national levels in 195 countries and territories from 1990 to 2017, stratified by sex, age, and sociodemographic index (SDI).

Methods
Data on pancreatitis were available from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Numbers and age-standardized prevalence, incidence, and YLDs’ rates per 100,000 population were estimated through a systematic analysis of modeled data from the 2017 GBD study. Both acute and chronic pancreatitis are being modeled separately in the GBD 2017; however, our data show acute and chronic pancreatitis together. Estimates were reported with uncertainty intervals (UIs).

Results
Globally, in 2017, the age-standardized rates were 76.2 (95% UIs 68.9 to 83.4), 20.6 (19.2 to 22.1), and 4.5 (2.3 to 7.6) per 100,000 population for the point prevalence, incidence, and YLDs, respectively. From 1990 to 2017, the percent changes in the age-standardized prevalence and YLDs rates increased, whereas the age-standardized incidence rate decreased. The global prevalence increased with age up to 60–64 years and 44–49 years in females and males, respectively, and then decreased, with no significant difference between females and males. The global prevalence rate increased with age, peaking in the 95+ age group, with no difference between sexes. Generally, positive correlation between age-standardized YLDs and SDIs at the regional and national levels was observed. Slovakia (297.7 [273.4 to 325.3]), Belgium (274.3 [242.6 to 306.5]), and Poland (266.7 [248.2 to 284.4]) had the highest age-standardized prevalence rates in 2017. Taiwan (Province of China) (104.2% [94.8 to 115.2%]), Maldives (72.4% [66.5 to 79.2%]), and Iceland (64.8% [57.2 to 72.9%]) had the largest increases in age-standardized prevalence rates from 1990 to 2017.

Conclusions
Pancreatitis is a major public health issue worldwide. The age-standardized prevalence and YLDs rates increased, but the age-standardized incidence rate decreased from 1990 to 2017. Improving the quality of pancreatitis health data in all regions and countries is strongly recommended for better monitoring the burden of pancreatitis.
Hypoxic exosomes orchestrate tumorigenesis: molecular mechanisms and therapeutic implications
Authors: Jafari Reza , Rahbarghazi Reza , Ahmadi Mahdi , Hassanpour Mehdi , Rezaie Jafar 
Published: December 2020

AbstractThe solid tumor microenvironment possesses a hypoxic condition, which promotes aggressiveness and resistance to therapies. Hypoxic tumor cells undergo broadly metabolic and molecular adaptations and communicate with surrounding cells to provide conditions promising for their homeostasis and metastasis. Extracellular vesicles such as exosomes originating from the endosomal pathway carry different types of biomolecules such as nucleic acids, proteins, and lipids; participate in cell-to-cell communication. The exposure of cancer cells to hypoxic conditions, not only, increases exosomes biogenesis and secretion but also alters exosomes cargo. Under the hypoxic condition, different signaling pathways such as HIFs, Rab-GTPases, NF-κB, and tetraspanin are involved in the exosomes biogenesis. Hypoxic tumor cells release exosomes that induce tumorigenesis through promoting metastasis, angiogenesis, and modulating immune responses. Exosomes from hypoxic tumor cells hold great potential for clinical application and cancer diagnosis. Besides, targeting the biogenesis of these exosomes may be a therapeutic opportunity for reducing tumorigenesis. Exosomes can serve as a drug delivery system transferring therapeutic compounds to cancer cells. Understanding the detailed mechanisms involved in biogenesis and functions of exosomes under hypoxic conditions may help to develop effective therapies against cancer.
Designing architecture of soothing labor–delivery–recovery–postpartum unit: a study protocol
Authors: Esfeh Behnam Kazemi , Kazemi Ashraf , Shamsaie Aida 
Published: December 2020

Abstract
Background
The physical environment profoundly affects women's well-being during childbirth in family-centered unit. A LDRP, which is an acronym for labor, delivery, recovery, and postpartum that describes a maternity unit designed for family-centered care. This study aimed to design soothing LDRP healing architecture based on recognizing the emotional elements of Iranian women.

Methods
This study will be conducted in four consecutive phases; including review of literature to provide documentation based on architectural knowledge and the effects of each architectural component on the parturient psychological conditions, qualitative study to extract women's needs and suggestions for physiological childbirth, architectural designing of the soothing LDRP based on the results of the first and second phases and qualitative study for evaluation of the designed program.

Discussion
Designing soothing LDRP architecture based on safe child birth unit standards and favorable psychological environment will provide a positive childbirth experience for Iranian women and their family. But, the preferences and demands of families will be based on Iranian socio-cultural context, therefore the using of this design will be limited in other societies with different cultures.
CD83 expression regulates antibody production in response to influenza A virus infection
Authors: Akauliya Madhav , Gautam Avishekh , Maharjan Sony , Park Byoung Kwon , Kim Jinsoo , Kwon Hyung-Joo 
Published: December 2020

AbstractBackgroundCD83 is known to regulate lymphocyte maturation, activation, homeostasis, and antibody response to immunization and infection. While CD83 has a major part in B cell function, its role in influenza A virus infection has not yet been investigated.MethodsWe investigated the role of CD83 using C57BL/6J wild type mice and CD83 knockout (KO) mice after intraperitoneal administration of the influenza A/WSN/1933 virus. We analyzed cells of the peritoneal cavity, splenocytes, and cells of the bone marrow with FACS to investigate CD83 expression and cell population change in response to the virus infection. ELISA was performed with sera and peritoneal cavity fluids to detect A/WSN/1933 virus-specific IgG and the subclasses of IgG.ResultsFACS analysis data showed a transient but distinct induction of CD83 expression in the peritoneal B cells of wild type mice. CD83 KO mice exhibited a delayed recovery of B cells in the bone marrow after influenza virus infection and overall, a smaller T cell population compared to wild type mice. The peritoneal cavity and serum of the wild type mice contained a high titer of IgG within 14 days after infection, whereas the CD83 KO mice had a very low titer of IgG.ConclusionsThese results show the importance of CD83 in lymphocytes homeostasis and antibody production during influenza A virus infection.
A systematic review of surgical procedures on thoracic myelopathy
Authors: Zhu Shiqi , Wang Yu , Yin Peng , Su Qingjun 
Published: December 2020

Abstract
Purpose
The surgical treatment of thoracic myelopathy is still controversial and also a challenge for spine surgeons. Therefore, the objective of this study was to review the related literature on the surgical treatment of thoracic myelopathy and try to define treatment guidelines for spine surgeons on thoracic myelopathy.

Methods
Relevant literatures were searched based on the PubMed, EMBASE, and Cochrane Library between January 2008 and December 2018. Some data on the characteristics of patients were extracted, including number of patients, mean age, surgical procedures, blood loss, complications, and pre-/post-operation modified JOA score. Recovery rate was used to assess the effect of surgery outcome, and the safety was evaluated by blood loss and incidence of complications.

Results
Thirty-five studies met the inclusion criteria and were retrieved. A total of 2183 patients were included in our systematic review, with the average age of 55.2 years. There were 69.8% patients diagnosed as ossification of ligamentum flavum (OLF), 20.0% as ossification of posterior longitudinal ligament (OPLL), 9.3% as disk herniation (DH), and 0.9% as others including diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS). The volume of blood loss was more in the treatment of circumferential decompression (CD) than posterior decompression (PD), and the incidence of complications was higher in CD (P < 0.05). The volume of blood loss in minimally invasive surgery (MIS) was lowest and the incidence of complications was 19.2%. Post-operation recovery rate was 0.49 in PD, 0.35 in CD, and 0.29 in MIS while the recovery rate was 0.54 in PD, 0.55 in CD, and 0.49 in MIS at the last follow-up. When focusing on the OLF specifically, incidence of complications in PD was much lower than CD, with less blood loss and higher recovery rate. Focusing on the OPLL specifically, incidence of complications in PD was much lower than CD, with less blood loss while there was no statistical difference in recovery rate between these two methods.

Conclusions
This systematic review showed that posterior decompression for thoracic myelopathy is safer and better than circumferential decompression according to the complication rate and surgical outcome. And we should also consider the location of compression before the operation.
Dysregulation of lnc-SNHG1 and miR-216b-5p correlate with chemoresistance and indicate poor prognosis of serous epithelial ovarian cancer
Authors: Pei Mei Li , Zhao Zong Xia , Shuang Ting 
Published: December 2020

Abstract
Aim
This study aimed to explore whether the dysregulation of lnc-small nucleolar RNA host gene 1 (SNHG1) and miR-216b-5p correlated with chemoresistance and indicated poor prognosis of serous epithelial ovarian cancer (EOC).

Methods and results
The expression of lnc-SNHG1 was upregulated, while miR-216b-5p showed low expression in patients with chemoresistant EOC compared with patients with chemosensitive EOC. The multivariate Cox regression analysis showed that the expression of miR-216b-5p and FIGO stage were independent prognostic factors for the overall survival (OS) of patients with serous EOC. Kaplan–Meier curves revealed a significant association of the increased expression level of lnc-SNHG1 with shorter OS and disease-free survival (DFS). Patients with a low expression level of miR-216b-5p also had shorter OS and DFS. The biological functions were tested using CCK-8 assay, colony formation assay, wound healing assay, and cell apoptosis. The knockdown of SNHG1 and the overexpression of miR-216b-5p stimulated paclitaxel sensitivity in A2780/Taxol cells through inhibiting cell growth and migration and promoting apoptosis. The inhibition of miR-216b-5p could rescue the effect of lnc-SNHG1 inhibition on the sensitivity of A2780/Taxol cells to paclitaxel. Luciferase reporter assay, RNA Binding Protein Immunoprecipitation Assay (RIP), and quantitative reverse transcription–polymerase chain reaction (qRT-PCR) indicated that lnc-SNHG1 acted as a sponge of miR-216b-5p in A2780/Taxol cells.

Conclusions
This study showed that the overexpression of lnc-SNHG1 and decreased expression level of miR-216b-5p correlated with the chemoresistance of patients with serous EOC and indicated shorter OS and DFS. Lnc-SNHG1 functioned as a ceRNA with miR-216b-5p, which was critical in modulating the paclitaxel sensitivity of ovarian cancer cells.
Systematic evaluation of supervised machine learning for sample origin prediction using metagenomic sequencing data
Authors: Chen Julie Chih-yu , Tyler Andrea D. 
Published: December 2020

AbstractBackgroundThe advent of metagenomic sequencing provides microbial abundance patterns that can be leveraged for sample origin prediction. Supervised machine learning classification approaches have been reported to predict sample origin accurately when the origin has been previously sampled. Using metagenomic datasets provided by the 2019 CAMDA challenge, we evaluated the influence of variable technical, analytical and machine learning approaches for result interpretation and novel source prediction.ResultsComparison between 16S rRNA amplicon and shotgun sequencing approaches as well as metagenomic analytical tools showed differences in normalized microbial abundance, especially for organisms present at low abundance. Shotgun sequence data analyzed using Kraken2 and Bracken, for taxonomic annotation, had higher detection sensitivity. As classification models are limited to labeling pre-trained origins, we took an alternative approach using Lasso-regularized multivariate regression to predict geographic coordinates for comparison. In both models, the prediction errors were much higher in Leave-1-city-out than in 10-fold cross validation, of which the former realistically forecasted the increased difficulty in accurately predicting samples from new origins. This challenge was further confirmed when applying the model to a set of samples obtained from new origins. Overall, the prediction performance of the regression and classification models, as measured by mean squared error, were comparable on mystery samples. Due to higher prediction error rates for samples from new origins, we provided an additional strategy based on prediction ambiguity to infer whether a sample is from a new origin. Lastly, we report increased prediction error when data from different sequencing protocols were included as training data.ConclusionsHerein, we highlight the capacity of predicting sample origin accurately with pre-trained origins and the challenge of predicting new origins through both regression and classification models. Overall, this work provides a summary of the impact of sequencing technique, protocol, taxonomic analytical approaches, and machine learning approaches on the use of metagenomics for prediction of sample origin.
Measles-mumps-rubella vaccine at 6 months of age, immunology, and childhood morbidity in a high-income setting: study protocol for a randomized controlled trial
Authors: Vittrup Dorthe Maria , Laursen Anne Cathrine Lund , Malon Michelle , Soerensen Jesper Kiehn , Hjort Jakob , Buus Soren , Svensson Jannet , Stensballe Lone Graff 
Published: December 2020

AbstractBackgroundMeasles is a highly contagious and serious infection. Before the introduction of vaccination, measles caused yearly epidemics putting vulnerable children at risk of brain damage and death. Despite safe and cost-effective vaccines, measles remains a leading cause of death in children globally. Due to insufficient vaccine coverage and low levels of in utero transferred antibodies from vaccinated mothers, outbreaks of measles in Denmark and other high-income countries are observed at increasing frequency.The current vaccine was introduced in Denmark in 1987 as a one-shot measles-mumps-rubella vaccine at 15 months, a timing chosen to avoid inhibition of the infant’s immune response by maternal antibodies. One generation later, the MMR vaccinated mothers have lower antibody levels compared to the naturally infected, and their infants are already susceptible at 6 months of age or earlier, thus increasing the risk of epidemics.MethodsThe Danish MMR trial is a double-blind randomized clinical trial recruiting between March 2019 and December 2021 with last patient last visit in February 2022. AltogetherN = 6500 infants aged 6 months will be randomly assigned to intramuscular vaccination with routine MMR (M-M-R VaxPro) or placebo (solvent only). According to the Danish Childhood vaccination program, all infants will receive a routine MMR vaccination at 15 months of age. At randomization, 1 month later, and 1 month after routine MMR vaccination at 15 months of age, a blood sample is drawn from app. 10% (N = 600) of the population. Additionally, hair, saliva, and urine are sampled at randomization. The co-primary study outcomes are immunogenicity 1 month after MMR vaccination at 6 months of age assessed as plaque-reduction neutralization test, and incidence of infectious disease hospitalizations from randomization to 12 months of age. Six weeks post randomization, all participants are interviewed regarding adverse events.Trial registrationThe trial is registered in the EU Clinical Trials Registry. EudraCT registration number:2016-001901-18. Registered on 14 February 2017.