bluuebunny/crossref_metadata_2025 huggingface dataset:
AQI Predication Using Temporal Data Mining
Authors: Bhushan Shashi , Tiwari Sanjay Kumar
Published: November 2020

The Air Quality Index (AQI) is an air quality standards indicator based on air pollutants that have negative impacts on human health and the environment. Because of several human activities, air pollution is growing very quickly, and it is the introduction of chemicals, particulate matter or biological materials into the atmosphere that cause human suffering and also harms the natural environment. Indeed, air pollution in metropolitan and industrial cities is one of the major environmental problems. So predicting pollution and avoiding these issues is very crucial. One of the most exciting and difficult functions is the forecast of air pollution using data mining. Many systems are designed to help data storage, inventory management and convenient statistics generation. India's air quality indicator is a standard measure used to indicate pollution (so2, no2, rspm, spm, etc.) from time to time. The main purpose of the current study is to predict the temporal AQI used by the previous day AQI and climate change is used to predict and visualize the temporary data mine using a gradient break and an unreasonable forecasting process. In Navigation Forecast, we divide the database into 85% data and 15% data based on data testing and training to determine seasonal variations and styles. Balance problems are often exploited by problems and forecasting uses an unreasonable prediction process and gradient downtime. Air quality forecasts based on historical data of previous years and predictions for less than a year as a reputable gradient using a recurring problem.
Ensemble Machine Learning Approaches for Proteogenomic Cancer Studies
Authors: Liang Yulan , Gharipour Amin , Kelemen Erik , Kelemen Arpad
Published: November 2020

Background: The identification of important proteins is critical for medical diagnosis and prognosis in common diseases. Diverse sets of computational tools were developed for omics data reductions and protein selections. However, standard statistical models with single feature selection involve the multi-testing burden of low power with the available limited samples. Furthermore, high correlations among proteins with high redundancy and moderate effects often lead to unstable selections and cause reproducibility issues. Ensemble feature selection in machine learning may identify a stable set of disease biomarkers that could improve the prediction performance of subsequent classification models, and thereby simplify their interpretability. In this study, we developed a three-stage homogeneous ensemble feature selection approach for both identifying proteins and improving prediction accuracy. This approach was implemented and applied to ovarian cancer proteogenomics data sets: 1) binary putative homologous recombination deficiency positive or negative; and 2) multiple mRNA classes (differentiated, proliferative, immunoreactive, mesenchymal, and unknown). We conducted and compared various machine learning approaches with homogeneous ensemble feature selection including random forest, support vector machine, and neural network for predicting both binary and multiple class outcomes. Various performance criteria including sensitivity, specificity, kappa statistics were used to assess the prediction consistency and accuracy. Results: With the proposed three-stage homogeneous ensemble feature selection approaches, prediction accuracy can be improved with the limited sample through continuously reducing errors and redundancy, i.e. Treebag provided 83% prediction accuracy (85% sensitivity and 81% specificity) for binary ovarian outcomes. For mRNA multi-classes classification, our approach provided even better accuracy with increased sample size. Conclusions: Despite the different prediction accuracies from various models, homogeneous ensemble feature selection proposed identified consistent sets of top ranked important markers out of 9606 proteins linked to the binary disease and multiple mRNA class outcomes.
An Observational Cohort of First Episode Psychosis in Iran: The Azeri Recent Onset Acute Phase Psychosis Survey (ARAS Cohort) Study Protocol
Authors: Farhang Sara , Ghaemmaghami Mehrdad , Noorazar Gholamreza , Veling Wim , Malek Ayyoub , Shafiee-kandjani Alireza , Somi Mohammad Hossein , Alizadeh Behrooz Z , Bruggeman Richard
Published: November 2020

BackgroundMost of our knowledge about the etiology, course, treatment, and outcome of schizophrenia spectrum and other psychotic disorders stems from Western countries. Data from populations living in other geographical areas and low- and middle-income countries, with different genomes (ethnicity) and exposomes (e.g., culture and social support, drugs of abuse, religion), will add to our knowledge of this complex disorder.MethodsThe Azeri Acute phase/Recent onset psychosis Survey (ARAS) has been initiated to study the course of the disorder in patients with recent onset psychosis using validated diagnostic tools and a comprehensive outcome monitoring system, aiming to reveal indicators for understanding the risk and resilience factors and for choosing the best personalized treatment strategy. All participants will be evaluated for clinical signs and symptoms as well as risk and resilience factors and will be followed up for 1, 3, and 5 years for outcomes in several domains. A hierarchical cluster method will be applied to identify the number of clusters for each outcome. Defined models will be applied to assess the predictive value of cognition on symptomatic and functional outcomes at follow-up.DiscussionThe ARAS cohort will yield significant academic- (research and education) and care-related achievements. ARAS data and experience will have value both in being a useful model for other parts of this region and in expansion of the current available knowledge.
Breastfeeding support at an Australian Breastfeeding Association drop-in service: a descriptive survey
Authors: Burns Elaine , Duursma Louise , Triandafilidis Zoi
Published: November 2020

BackgroundIn Australia, during the early establishment phase of breastfeeding, women can access telephone peer support counselling provided by the Australian Breastfeeding Association (ABA) however options for face-to-face peer support are limited. The known factors which improve ongoing and exclusive breastfeeding include face-to-face support, peer and/or professional support, and trained personnel. This study aimed to examine women’s experiences of accessing one breastfeeding drop-in peer support service provided by trained peer support volunteer counsellors from the ABA.MethodsWomen who accessed the service were invited, in 2014, to participate in an anonymous online survey which collected both quantitative and qualitative data. Participants were asked about their experiences of breastfeeding support, as well as their experiences of the drop-in service. In total, 53 women completed the online survey, and subsequent analysis generated descriptive statistics and qualitative themes.ResultsResponses to the survey revealed that women attended the drop-in service with infants ranging in age from less than 1 week through to 12 months of age. Most women reported attending with infants aged 0-8 weeks of age (72%). The predominant presenting problems identified were sore/damaged nipples, difficulties with infant latching to the breast, or concerns about using nipple shields. Analysis of the open text qualitative responses revealed one overarching theme ‘Support to continue breastfeeding’ and four subthemes: ‘feeling listened to and not judged’; ‘emotional support and confidence building’; ‘the importance of face-to-face, practical support'; and ‘the need for ongoing, free access’.DiscussionIn this study many women were seeking support for ongoing breastfeeding difficulties. Health professionals who had limited breastfeeding knowledge and skills were identified as most unhelpful in providing support with ongoing breastfeeding difficulties. Women valued having access to trained peer counsellors, who had the capacity to provide non-judgemental, face-to-face support; who could sit through a feed; in a space that was ‘safe’; and who could enhance a woman’s confidence with breastfeeding over the course of her full breastfeeding journey.ConclusionReactive peer support, provided in response to need, at an Australian Breastfeeding Association drop-in service, was described by participants as pivotal to enabling their ongoing breastfeeding.
Do breastfeeding practices correlate with childhood diarrhoea? Multiple data analyses using national surveys in Ghana
Authors: Tampah-Naah Anthony Mwinilanaa
Published: November 2020

Background: Breastfeeding as a natural intervention tends to have a protective effect on the occurrence of diarrhoea in children. In environments where breastfeeding is suboptimal coupled with the early introduction of complementary foods, children are at a higher risk of experiencing diarrhoea. This study examined whether breastfeeding practices are associated with childhood diarrhoea in Ghana using multiple secondary datasets. Methods: The study used data from Ghana Demographic and Health Survey (GDHS) 2003, 2008 and 2014 individual datasets. These datasets contain data on women and issues related to children who were two years of age (0-23 months). An appended weighted sample of 4,675 mother-child pairs was used for the analyses. Thus, logistic regression analyses were performed to assess the effect of explanatory variables that were considered as potential confounders on the association between breastfeeding practices and childhood diarrhoea.Results: Univariate analysis revealed that children who were not exclusively breastfeeding had higher odds of experiencing diarrhoea. With the multilevel logistic analysis, breastfeeding practices and risks of diarrhoea among children revealed significant associations.Conclusions: Findings for this study further affirms to the protective effect breastfeeding has against childhood diarrhoea. Exclusive breastfeeding and at times predominant breastfeeding could prevent or minimize diarrhoea compare to non-practice of breastfeeding or partial breastfeeding.
Evaluating cochlear insertion trauma and hearing preservation after cochlear implantation (CIPRES): A study protocol for a randomised single blind controlled trial
Authors: Jwair Saad , Boerboom Ralf , Versnel Huib , Stokroos Robert , Thomeer Hans
Published: November 2020

BackgroundIn order to preserve residual hearing in patients with sensorineural hearing loss (SNHL) who receive a cochlear implant (CI), insertion trauma to the delicate structures of the cochlea needs to be minimized. The surgical approach comprises the conventional mastoidectomy-posterior tympanotomy (MPT) to arrive at the middle ear, followed by either a cochleostomy (CO) or the round window (RW) approach. Both techniques have their benefits and disadvantages. Another important aspect in structure preservation is the design of the electrode array. Two different designs are used: a ‘straight’ lateral wall lying electrode array (LW), or a ‘pre-curved’ perimodiolar lying electrode array (PM). Interestingly, until now, the best surgical approach and design of the implant is uncertain. Our hypothesis is that the combination of a RW approach and a LW lying electrode array minimizes insertion trauma, leading to better hearing outcome for SNHL patients. MethodsWe designed a monocenter, 2x2, randomized controlled trial to compare insertion trauma between four groups of patients, with each group having a unique combination of electrode array type (LW or PM) and surgical approach (RW or CO). In total, 48 patients will be randomized into one of these four intervention groups. Our primary objective is comparison of postoperative hearing preservation between these four groups. Secondly, we aim to assess structure preservation (i.e., scalar transposition, with basilar membrane disruption or tip fold-over of array) for each group. Thirdly, we will compare objective outcomes of hearing and structure preservation by way of electrocochleography (ECochG).DiscussionCochlear implantation by way of a cochleostomy or round window approach, using different electrode array types, is the standard medical care for patients with severe to profound bilateral sensorineural hearing loss, as it is a relative simple and low-risk procedure that greatly benefits patients. However, loss of residual hearing remains a problem. This trial is the first randomized controlled trial that evaluates the effect of cochlear insertion trauma of several CI treatment options on hearing preservation. Trial registrationThis trial is registered in the Netherlands Trial Register (NTR) (www.trialregister.nl): NL8586, date of registration: 4th of May 2020. Retrospectively registered; 3/48 participants were included before registration.
A mHealth-intervention to support the self-management of multimorbid patients in general practices in Germany (TelePraCMan) – Study protocol of a randomized pilot study
Authors: Wiezorreck Lars , Litke Nicola , Freund Tobias , Miksch Antje , Wensing Michel , Szecsenyi Joachim , Weis Aline
Published: November 2020

Background: Previously we developed a structured case management for patients with multiple chronic conditions in primary care (called ‘PraCMan’), delivered by Health Care Assistants in General Practice (VERAHs). The ‘TelePraCMan’ project aims to develop a supplementary web-based application to ‘PraCMan’, including a digital symptom diary in which patients can enter individual data via smartphone/tablet. This application is targeted at patients suffering from diabetes mellitus type 2, COPD, hypertension and/or chronic heart failure. Objective: The objective of this study is to evaluate this mHealth-intervention for patients with chronic diseases, focused on patients’ quality of life and self-management capabilities.Methods: A two-armed patient-randomized pilot trial is planned, involving 200 multimorbid patients in 20 GP-practices that use ‘PraCMan’ regularly. Participants are randomly assigned (1:1) to receive either standard ‘PracMan’ treatment or standard ‘PracMan’ treatment complemented with the mHealth-intervention (TelePraCMan). As primary outcome, the health-related quality of life is measured by the German version of the Short Form Health Questionnaire (SF-12). Secondary outcomes include self-management capabilities, technical affinity, and user experience of patient and practice staff. Outcomes are measured at baseline (T0) and at follow-up after 6 months (T1). For the evaluation of the implementation process, GPs, VERAHs and patients will be invited to participate in semi structured interviews afterwards.The outcomes will be compared between study arms using multilevel regression analysis. Qualitative interviews will be transcribed and analysed using qualitative content analysis based on the Tailored Implementation for Chronic Diseases Framework. Discussion: ‘TelePraCMan’ is one of the first mHealth-Interventions addressing multimorbid patients in primary care.Trial registration: DRKS, DRKS00017320, Registered 18 June 2019, http://www.drks.de/DRKS00017320
Helmet Continuous Positive Airway Pressure versus High-Flow Nasal Cannula in COVID-19: A pragmatic randomised clinical trial (COVID HELMET)
Authors: Tverring Jonas , Åkesson Anna , Nielsen Niklas
Published: November 2020

Background: Patients with COVID-19 and hypoxemia despite conventional low-flow oxygen therapy are often treated with High-flow Nasal Cannula (HFNC) in line with international guidelines. Oxygen delivery by Helmet Continuous Positive Airway Pressure (CPAP) is a feasible option that enables a higher positive end-expiratory pressure (PEEP) and may theoretically reduce the need for intubation compared to HFNC but direct comparative evidence is lacking. Methods: We plan to perform an investigator-initiated, pragmatic, randomised trial at an intermediate-level COVID-19 cohort ward in Helsingborg Hospital, southern Sweden. We have estimated a required sample size of 120 patients randomised 1:1 to HFNC or Helmet CPAP to achieve 90% power to detect superiority at a 0.05 significance level regarding the primary outcome of ventilator free days (VFD) within 28 days using a Mann-Whitney U test. Patient recruitment is planned to being June 2020 and be completed in the first half of 2021.Discussion: We hypothesize that the use of Helmet CPAP will reduce the need for invasive mechanical ventilation compared to the use of HFNC without having a negative effect on survival. This could have important implications during the current COVID-19 epidemic. Trial registration: ClinicalTrials.gov, NCT04395807, Registered 20 May 2020, https://clinicaltrials.gov/ct2/show/NCT04395807
Three-dimensional Construction of Micrometer Level in Rat Stomach by Synchrotron Radiation
Authors: Tao Qiang , Gao Chen-Chen , Tong Xue-Hong , Yuan Shi-Zhen , Xu Jingdong
Published: November 2020

Background: The structural changes of gastric mucosa are considered as an important window of early gastric lesions. This article shows an imaging method of the stomach that does not use imaging agents. X-ray phase-contrast images of different stages of gastric development were taken using micrometer level X-ray in-line phase-contrast imaging (XILPCI) technique on synchrotron radiation facility. The aim of the study was to demonstrate that the imaging technique is an appropriate method for micron imaging of the gastric structures.Methods: The stomachs of 4-, 6- and 12-week-old rats were removed and cleaned. XILPCI has 1000 times greater soft tissue contrast than that of X-ray traditional absorption radiography. The projection images of the rats stomachs were recorded by an XILPCI charge coupled device (CCD) at 9 μm image resolution.Results: The X-ray in-line phase-contrast images of the different stages of rats’ gastric specimens clearly showed the gastric architectures and the details of the gastro-duodenal region. 3-dimensional stomach anatomical structure images were reconstruction. Conclusion: The reconstructed gastric 3D images can clearly display the internal structure of the stomach. XILPCI may be a useful method for medical research in the future.
Evaluation of serum anti-Mullerian hormone levels in women with Hashimoto thyroiditis in the reproductive age
Authors: Unsal Ilknur Ozturk , Hepsen Sema , Akhanli Pinar , Calapkulu Murat , Sencar Muhammed Erkam , Yalcindag Ali , Cakal Erman
Published: November 2020

Background: Autoimmune thyroid disease in women is associated with subfertility and early pregnancy loss, and patients with primary ovarian insufficiency have a high prevalence of thyroid autoimmune disorders. The aim of this study was to investigate the association between Hashimoto thyroiditis (HT) and ovarian reserve.Methods: Levels of serum thyroid stimulating hormones, thyroid autoantibodies, and anti-Müllerian hormone (AMH) were measured in women with HT and a healthy control group between 2018 and 2019. Result: Evaluation was made of 108 premenopausal women with HT. A control group was formed of 172 healthy female subjects with normal anti-thyroid antibody levels and thyroid function. Serum AMH levels were determined to be significantly lower in the HT group compared to the control group.Conclusion: Ovarian reserve evaluated by serum AMH concentration is affected by thyroid autoimmunity independently of anti-thyroid antibodies type or titers.
Deep learning based DNA:RNA triplex forming potential prediction
Authors: ZHANG Yu , Long Yahui , Kwoh Chee Keong
Published: November 2020

Background: Long non-coding RNAs (lncRNAs) can exert functions via forming triplex with DNA. The current methods in predicting the triplex formation mainly rely on mathematic statistic according to the base paring rules. However, these methods have two main limitations: i) they identify a large number of triplex-forming lncRNAs, but the limited number of experimentally verified triplex-forming lncRNA indicates that maybe not all of them can form triplex in practice, and ii) their predictions only consider the theoretical relationship while lacking the features from the experimentally verified data. Results: In this work, we develop an integrated program named TriplexFPP (Triplex Forming Potential Prediction), which is the first machine learning model in DNA:RNA triplex prediction. TriplexFPP predicts the most likely triplex-forming lncRNAs and DNA sites based on the experimentally verified data, where the high-level features are learned by the convolutional neural networks. In the 5-fold cross validation, the average values of Area Under the ROC curves and PRC curves for removed redundancy triplex-forming lncRNA dataset with threshold 0.8 are 0.9649 and 0.9996, and these two values for triplex DNA sites prediction are 0.8705 and 0.9671, respectively. Besides, we also briefly summarise the cis and trans targeting of triplexes lncRNAs. Conclusions: The TriplexFPP is able to predict the most likely triplex-forming lncRNAs from all the lncRNAs with computationally defined triplex forming capacities and the potential of a DNA site to become a triplex. It may provide insights to the exploration of lncRNA functions.
DNA Barcoding Reveals Cryptic Diversity in the Underestimated Genus Triplophysa (Cypriniformes: Cobitidae, Nemacheilinae) from the Northeastern Qinghai-Tibet Plateau
Authors: wang tai , Zhang Yanping , Yang Zhuoyu , Liu Zhe , Du Yanyan
Published: November 2020

Background: The northeastern part of the Qinghai-Tibet Plateau (QTP) presents a high number of plateau loach species. As one of the three major groups of fishes distributed on the QTP, plateau loach has high ecological value. However, the taxonomy and systematics of these fish are still controversial, and a large number of new species have been reported. The reason for this phenomenon is that the degree of morphological variation is low, the phylogenetic information provided by morphological and anatomical features used for species identification is relatively poor, and many cryptic species are observed. Based on the high-density sampling points from the biodiversity hotspots surveyed, this study aims to evaluate the biodiversity of plateau loach in the northeastern part of the QTP and reveal the hidden diversity by comparing morphological species with molecular operational taxonomic units (MOTUs). Results: After careful identification and comparison of the morphology and DNA barcoding of 1,630 specimens, 22 species were identified, with 20 considered valid local species and two identified as new species that had not been previously described. Based on the combination of morphological and molecular methods, a total of 24 native species were found, two of which were cryptic species: Triplophysa robusta sp1 and Triplophysa minxianensis sp1. Fourteen of the 24 species form clusters of barcodes that allow them to be reliably identified. The remaining cases involved 10 closely related species, including rapidly differentiated species and species that seemed to have experienced incomplete lineage sorting or showed introgressions.Conclusions: The results highlight the need to combine traditional taxonomies with molecular methods to correctly identify species, especially closely related species, such as the plateau loach. This study provides a basis for protecting the biodiversity of plateau loach.
Age trajectories of disability in instrumental activities of daily living and disability-free life expectancy among middle-aged and older adults in Taiwan: an 11-year longitudinal study
Authors: Liao Wen-Ling , Chang Yu-Hung
Published: November 2020

Objectives: This study aims to identify the age trajectories of disability in instrumental activities of daily life (IADLs) over 11 years and their correlates, and to estimate disability-free life expectancy for identified trajectory groups in middle-aged and older adults.Methods: We included 3,118 participants aged 50 and over without IADL limitations at baseline from the Taiwan Longitudinal Study in Aging, followed across 1996-2007. We used group-based trajectory models to identify age trajectories of IADL disability, and multiple logistic regressions to examine their correlates. Sullivan method was used to compute IADL disability-free life expectancy for trajectory groups at different ages.Results: We identified two trajectories groups: 67.7% of participants classified as the late-onset group and 32.3% as the early-onset group. Female (adjusted odds ratio [aOR]: 1.93, 95% confidence interval [95% CI]: 1.54, 2.41), not being employed (aOR: 1.30, 95% CI: 1,08, 1,56), poor/fair self-rated health (aOR: 1.31, 95% CI:1.09, 1.58), hypertension (aOR: 1.32, 95% CI: 1.07, 1.63) , diabetes mellitus (aOR: 2.29, 95% CI: 1.72, 3.07), arthritis (aOR: 1.42, 95% CI: 1.11, 1.81), stroke (aOR: 2.21, 95% CI: 1.04, 4.70), and one-point increase in a 10-item depression scale (aOR: 1.04, 95% CI: 1.02, 1.06) were associated with early-onset of disability, whereas higher education (aOR: 0.59, 95% CI: 0.42, 0.81), regular exercise (aOR: 0.76, 95% CI: 0.62, 0.93), and participating voluntary or club activities (aOR: 0.78, 95% CI: 0.65, 0.93) related to the late-onset. IADL disability-free life expectancies at 65 years old in the late-onset group were 15.6 years for women and 14.4 for men, respectively, comprising 56.6% and 64.2% of their remaining life, whereas those of the early-onset group were 4.8 and 4.6 years for women and men respectively, comprising 22.5% and 27.2% of remaining life.Conclusions: Early-onset of IADLs disability may correlate to chronic conditions, and engagement in employment, exercise, and social participation were associated with a reduced risk of early disability in IADLs.
Comparison of oral glucose tolerance test and HbA1c in detection of disorders of glucose metabolism in patients with acute stroke
Authors: Matz Karl , Tuomilehto Jaakko , Teuschl Yvonne , Dachenhausen Alexandra , Brainin Michael
Published: November 2020

Background: Diabetes is an increasingly important risk factor for ischemic stroke and worsens stroke prognosis. Yet a large proportion of stroke patients who are eventually diabetic are undiagnosed. Therefore, it is important to have sensitive assessment of unrecognized hyperglycaemia in stroke patients. Design: Secondary outcome analysis of a randomized controlled trial focussing on parameters of glucose metabolism and detection of diabetes and prediabetes in patients with acute ischemic stroke (AIS). Methods: A total of 130 consecutively admitted patients with AIS without previously known type 2 diabetes mellitus (T2DM) were screened for diabetes or prediabetes as part of secondary outcome analysis of a randomized controlled trial that tested lifestyle intervention to prevent post-stroke cognitive decline. Patients had the oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) measurements in the second week after stroke onset and after one year. The detection rates of diabetes and prediabetes based on the OGTT or HbA1c values were compared.Results: By any of the applied tests at the second week after stroke onset 62 of 130 patients (48%) had prediabetes or T2DM. Seventy-five patients had results from both tests available, the OGTT and HbA1c; according to the OGTT 40 (53.3%) patients had normal glucose metabolism, 33 (44%) had prediabetes, two (2.7%) T2DM. In 50 (66.7%) patients the HbA1c results were normal, 24 (32%) in the prediabetic and one (1.3%) in the diabetic range. The detection rate for disorders of glucose metabolism was 10% higher (absolute difference; relative difference 29%) with the OGTT compared with HbA1c. After one year the detection rate for prediabetes or T2DM was 7% higher with the OGTT (26% relative difference).The study intervention led to a more favourable evolution of glycemic status after one year.Conclusion: The OGTT is a more sensitive screening tool than HbA1c for the detection of previously unrecognized glycemic disorders in patients with acute stroke with an at least a 25% relative difference in detection rate. Therefore, an OGTT should be performed in all patients with stroke with no history of diabetes.
Understanding the causes of errors in eukaryotic protein-coding gene prediction: a case study of primate proteomes
Authors: Meyer Corentin , Scalzitti Nicolas , Jeannin-Girardon Anne , Collet Pierre , Poch Olivier , Thompson Julie
Published: November 2020

Background: Recent advances in sequencing technologies have led to an explosion in the number of genomes available, but accurate genome annotation remains a major challenge. The prediction of protein-coding genes in eukaryotic genomes is especially problematic, due to their complex exon-intron structures. Even the best eukaryotic gene prediction algorithms can make serious errors that will significantly affect subsequent analyses. Results: We first investigated the prevalence of gene prediction errors in a large set of 176,478 proteins from ten primate proteomes available in public databases. Using the well-studied human proteins as a reference, a total of 82,305 potential errors were detected, including 44,001 deletions, 27,289 insertions and 11,015 mismatched segments where part of the correct protein sequence is replaced with an alternative erroneous sequence. We then focused on the mismatched sequence errors that cause particular problems for downstream applications. A detailed characterization allowed us to identify the potential causes for the gene misprediction in approximately half (5446) of these cases. As a proof-of-concept, we also developed a simple method which allowed us to propose improved sequences for 603 primate proteins. Conclusions: Gene prediction errors in primate proteomes affect up to 50% of the sequences. Major causes of errors include undetermined genome regions, genome sequencing or assembly issues, and limitations in the models used to represent gene exon-intron structures. Nevertheless, existing genome sequences can still be exploited to improve protein sequence quality. Perspectives of the work include the characterization of other types of gene prediction errors, as well as the development of a more comprehensive algorithm for protein sequence error correction.
Histone tail analysis reveals H3K36me2 and H4K16ac as epigenetic signatures of diffuse intrinsic pontine glioma
Authors: An Shejuan , Camarillo Jeannie , Huang Tina , Li Daphne , Morris Juliette , Zoltek Madeline , Qi Jin , Behbahani Mandana , Kelleher Neil , Nazarian Javad , Thomas Paul , Saratsis Amanda Muhs
Published: November 2020

Background: Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor. Most DIPGs harbor a histone H3 mutation, which alters histone post-translational modification (PTM) states and transcription. Here, we employed quantitative proteomic analysis to elucidate the impact of H3.3K27M mutation, as well as radiation and bromodomain inhibition (BRDi) with JQ1, on DIPG PTM profiles. Methods: We performed targeted mass spectroscopy on H3.3K27M mutant and wild-type tissues (n=12) and cell lines (n=7). Results: We found 29.2% and 26.4% of total H3.3K27 peptides were H3.3K27M in mutant DIPG tumor cell lines and tissue specimens, respectively. Significant differences in distinct PTMs were observed in H3.3K27M specimens, including at H3K27, H3K36, and H4K16 amino acid residues. In addition, H3.3K27me1 and H4K16ac were the most significantly distinct modifications in H3.3K27M mutant tumors relative to wild-type. Further, H3.3K36me2 was the most abundant modification co-occurring on the H3.3K27M mutant peptide in DIPG tissue, while H4K16ac was the most acetylated residue. Radiation treatment caused changes in PTM abundance in vitro , including increased H3K9me3. BRDi with JQ1 resulted in increased mono- and di-methylation of H3.1K27, H3.3K27, H3.3K36 and H4K20 in vitro . Conclusion: Taken together, our findings provide insight into the effects of the H3K27M mutation on Histone modification states and response to treatment, and suggest H3K36me2 and H4K16ac in DIPG may represent unique tumor epigenetic signatures for targeted therapy.
One-year Outcomes of Fixed-Dosing Aflibercept Therapy for pre treated and naive polypoidal choroidal vasculopathy patient
Authors: Choo Hun Gu , Lee Jin Hae , Oh Hyun Sub , You Yong Sung , Kim Soon Hyun , Kwon Oh Woong
Published: November 2020

Background: Polypoidal choroidal vasculopathy (PCV) is a type of age-related macular degeneration that can cause permanent vision loss. The purpose of this paper was to report the one-year outcomes of fixed-dosing aflibercept therapy for the treatment of PCV. Methods: This was a prospective, single-arm, interventional case series study of 25 PCV patients; 12 pre-treated and 13 treatment-naïve patients. The patients were treated and monitored for 12 months. Each patient was administered with an aflibercept (2.0 mg) injection every month for the first three months (the loading phase), and thereafter, once every two months. At every follow-up visit, best-corrected visual acuity (BCVA) test, fundus examination, and optical coherence tomography for measuring the central subfield macular thickness (CSMT) were performed. Fluorescein and indocyanine green angiography were conducted at baseline and at 4 and 12 months. Results: After 12 months of aflibercept therapy, the mean BCVA of the patients significantly improved from 65.48 letters at baseline to 69.91 letters (p=0.001), and the CSMT significantly decreased from 406.92 um at baseline to 276.12 um (p<0.001). Additionally, ten patients (40%) showed complete polyp regression. The treatment-naïve patients showed a statistically significant improvement in BCVA from 66.58 letters at baseline to 76.36 letters at 12 months, and a significant decrease in CSMT, from 462 to 243 um. In the pre-treated group, there was no change in BCVA (64.46 letters), and the decrease in CSMT from 356.08 to 303.69 um was not statistically significant. Conclusions: The fixed-dosing aflibercept regimen is effective for treating patients with PCV and is more effective in treatment-naïve patients than in pre-treated patients.
Corticosteroid use in COVID-19 patients: A systematic review and meta-analysis on clinical outcomes
Authors: Paassen Judith van , Vos Jeroen S. , Hoekstra Eva M. , Neumann Katinka M.I. , Boot Pauline C. , Arbous Sesmu M.
Published: November 2020

Background: In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed. Objectives: The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19. Methods: A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase, and Web of Science from 1st of December 2019 until 1 st of October 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, other oxygen therapy, length of hospital stay and secondary infections. Results: Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57-0.87). Furthermore, viral clearance time ranged from 10-29 days in the corticosteroid group and from 8-24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend towards more infections and antibiotic use was present. Conclusions: Our findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction of need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections.
Body mass index and cardiovascular outcomes in patients with acute coronary syndrome by diabetes status: the obesity paradox in a Korean national cohort study
Authors: Park Se-Jun , Ha Kyoung Hwa , Kim Dae Jung
Published: November 2020

Background: The “obesity paradox” has not been elucidated in the long-term outcomes of acute coronary syndrome (ACS). We investigated the association between obesity and cardiovascular (CV) outcomes in ACS patients with and without diabetes.Methods: We identified 6,978 patients with ACS aged 40–79 years from the Korean National Health Insurance Service-Health Screening Cohort between 2002 and 2015. Baseline body mass index (BMI) was categorized as underweight (<18.5 kg/m2), normal weight (18.5–22.9 kg/m2), overweight (23.0–24.9 kg/m2), obese class I (25.0–29.9 kg/m2), and obese class II (≥30.0 kg/m2). The primary outcome was major adverse CV events (MACE)—CV death, myocardial infarction (MI), and stroke. The secondary outcomes were the individual components of MACE, hospitalization for heart failure (HHF), and all-cause death. Results: After adjustment for confounding variables, compared to normal-weight patients without diabetes (reference group), obese class I patients with and without diabetes had a lower risk of MACE, but only significant in patients without diabetes (with diabetes: hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78–1.14; without diabetes: HR 0.78, 95% CI 0.62–0.97). Obese class II patient with diabetes had a higher risk of MACE with no statistical significance (HR 1.14, 95% CI 0.82–1.59). Underweight patients with and without diabetes had a higher risk of MACE, but only significant in patients with diabetes (with diabetes: HR 1.79, 95% CI 1.24–2.58; without diabetes: HR 1.23, 95% CI 0.77–1.97).Conclusion: In ACS patients, obesity had a protective effect on CV outcomes, especially in patients without diabetes.
Beyond standardized mortality ratios; some uses of smoothed age-specific mortality rates on small areas studies.
Authors: Perez-Panades Jordi , Botella-Rocamora Paloma , Martinez-Beneito Miguel Angel
Published: November 2020

Background: Most epidemiological risk indicators strongly depend on the age composition of populations, which makes the direct comparison of raw(unstandardized) indicators misleading because of the dierent age structures of the spatial units of study. Age-standardized rates (ASR) are a common solution for overcoming this confusing effect. The main drawback of ASRs is that they depend on age-specific rates which, when working with small areas, are often based on very few, or no, observed cases for most age groups. A similar effect occurs with life expectancy at birth and many more epidemiological indicators, which makes standardized mortality ratios (SMR) the omnipresent risk indicator for small areas epidemiologic studies.Methods: To deal with this issue, a multivariate smoothing model, the M-model, is proposed in order to t the age-specic probabilities of death (PoDs)for each spatial unit, which assumes dependence between closer age groups and spatial units. This age-space dependence structure enables information to be transferred between neighboring consecutive age groups and neighboring areas, at the same time, providing more reliable age-specific PoDs estimates.Results: Three case studies are presented to illustrate the wide range of applications that smoothed age specific PoDs have in practice . The first case study shows the application of the model to a geographical study of lung cancer mortality in women. This study illustrates the convenience of considering age-space interactions in geographical studies and to explore the different spatial risk patterns shown by the different age groups. Second, the model is also applied to the study of ischaemic heart disease mortality in women in two cities at the census tract level. Smoothed age-standardized rates are derived and compared for the census tracts of both cities, illustrating some advantages of this mortality indicator over traditional SMRs. In the latest case study, the model is applied to estimate smoothed life expectancy (LE), which is the most widely used syntheticindicator for characterizing overall mortality differences when (not so small) spatial units are considered.Conclusion: Our age-space model is an appropriate and flexible proposal that provides more reliable estimates of the probabilities of death, which allow the calculation of enhanced epidemiological indicators (smoothed ASR, smoothed LE), thus providing alternatives to traditional SMR-based studies of small areas.
HER2 gene assessment in liquid biopsy of gastric and esophagogastric junction cancer patients qualified for surgery
Authors: Grenda Anna , Wojas-Krawczyk Kamila , Skoczylas Tomasz , Krawczyk Paweł , Sierocińska-Sawa Jadwiga , Wallner Grzegorz , Milanowski Janusz
Published: November 2020

Background Amplification of HER2 gene (ERBB2) and overexpression of HER2 protein on cancer cells are found in 10-26% of gastric cancer (GC) and esophagogastric junction cancer (EGJC). Gene copy number variation (CNV) could be detected in these patients in liquid biopsy and in cancer cells.Methods We analysed HER2 gene CNV used qPCR method in 87 sera collected from GC and EGJC patients before surgical treatment and in 40 sera obtained from healthy donors. HER2 gene CNV was also assessed in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Furthermore, we assessed the number of HER2 gene copies and HER2 expression in cancer cells using the fluorescent in situ hybridization method (FISH) and immunohistochemistry (IHC).Results We found that the HER2 gene copy number in liquid biopsy was higher in GC and EGJC patients compared to healthy people (p=0.01). Moreover, EGJC patients had higher number of HER2 gene copies than healthy donors (p=0.0016). HER2 CNV examination could distinguish healthy individuals and patients with gastric or esophagogastric junction cancers with sensitivity and specificity of 58% and 98% (AUC=0.707, 95% CI: 0.593-0.821, p=0.004). We found that patients with a high copy number of the HER2 gene in the tumor tissue assessed by qPCR (but not by FISH) have significantly more often a high number of HER2 gene copies in liquid biopsy (p=0.04).Conclusions We suggested that HER2 testing in liquid biopsy could be used as an auxiliary method to analysis of HER2 status in tumor tissue in gastric or esophagogastric junction cancers.
Association between the non-HDL-cholesterol to HDL-cholesterol ratio and non-alcoholic fatty liver disease in Chinese children and adolescents: a large single-center cross-sectional study
Authors: Yang Shouxing , Zhong Jinwei , Ye Mengsi , Miao Lei , Lu Guangrong , Xu Changlong , Xue Zhanxiong , Zhou Xinhe
Published: November 2020

Background: The non-HDL-cholesterol to HDL-cholesterol (NHDLC/HDLC) ratio is closely related to a variety of dyslipidemia-related diseases. This study aimed to inspect the relationship between the NHDLC/HDLC ratio and non-alcoholic fatty liver (NAFLD) in children and adolescents.Methods: In this cross-sectional survey, a total of 7,759 eligible Chinese children and adolescents (5,692 boys and 2,067 girls) received routine medical examinations. The anthropometric and laboratory data of the subjects were collected. NAFLD was diagnosed by liver ultrasonography. Binary logistic regression analysis was performed on the NHDLC/HDLC ratio, NHDLC, HDLC and NAFLD. Receiver operating characteristic (ROC) curve analysis was exploited to compare the diagnostic significance of the above parameters for NAFLD.Results: The total prevalence of NAFLD was 4.36%, and the prevalence in boys was higher than that in girls (5.61% vs. 1.9%, P < 0.001). The prevalence of NAFLD was positively correlated with the NHDLC/HDLC ratio (P < 0.001). The binary logistic regression analysis demonstrated that the OR was 8.61 (95% CI, 5.90-12.57, P < 0.001) in tertile 3 (highest NHDLC/HDLC ratio) compared with tertile 1 (lowest NHDLC/HDLC ratio). After adjustment for age, sex, body mass index (BMI), alanine aminotransferase (ALT), uric acid (UA), total bilirubin (TB), fasting plasma glucose (FPG) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), the OR for tertile 3 (OR=1.83, 95% CI, 1.04-3.22, P = 0.035) was still significantly higher than that of tertile 1. The area under the curve (AUC) of the NHDLC/HDLC ratio of boys was 0.787, which was significantly greater than that of NHDLC and HDLC (0.719 and 0.726, P < 0.001). For girls, the AUC of the NHDLC/HDLC ratio was 0.763, which was also significantly greater than that of NHDLC (0.661, P < 0.001). Furthermore, the cutoff point of the NHDLC/HDLC ratio was 2.475 in boys and 2.695 in girls. In addition, the AUC of the NHDLC/HDLC ratio was 0.761 in subjects with normal ALT levels (ALT ≤ 40 U/L), which was significantly higher than that of NHDLC (0.680, P < 0.001) and HDLC (0.724, P = 0.007). For subjects with elevated ALT levels (ALT > 40 U/L), the AUC of the NHDLC/HDLC ratio (0.746) was also significantly greater than that of NHDLC (0.646, P < 0.001)Conclusions: The NHDLC/HDLC ratio was positively correlated with NAFLD in Chinese children and adolescents. It may serve as an effective indicator to help identify NAFLD in children and adolescents.
Determining electrocardiography training priorities for medical students using a modified Delphi method
Authors: Viljoen Charle Andre , Millar Rob Scott , Manning Kathryn , Burch Vanessa Celeste
Published: November 2020

BackgroundAlthough electrocardiography is considered a core learning outcome for medical students, there is currently little curricular guidance for undergraduate ECG training. Owing to the absence of expert consensus on undergraduate ECG teaching, curricular content is subject to individual opinion. The aim of this modified Delphi study was to establish expert consensus amongst content and context experts on an ECG curriculum for medical students.MethodsThe Delphi technique, an established method of obtaining consensus, was used to develop an undergraduate ECG curriculum. Specialists involved in ECG teaching were invited to complete three rounds of online surveys. An undergraduate ECG curriculum was formulated from the topics of ECG instruction for which consensus (i.e. ≥75% agreement) was achieved. ResultsThe panellists (n=131) had a wide range of expertise (42.8% Internal Medicine, 22.9% Cardiology, 16% Family Medicine, 13.7% Emergency Medicine and 4.6% Health Professions Education). Topics that reached consensus to be included in the undergraduate ECG curriculum were classified under technical aspects of performing ECGs, basic ECG analysis, recognition of the normal ECG and abnormal rhythms and waveforms and using electrocardiography as part of a clinical diagnosis. This study emphasises that ECG teaching should be framed within the clinical context. Course conveners should not overload students with complex and voluminous content, but rather focus on commonly encountered and life-threatening conditions, where accurate diagnosis impacts on patient outcome. A list of 23 “must know” ECG diagnoses is therefore proposed.ConclusionA multidisciplinary expert panel reached consensus on the ECG training priorities for medical students.