bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era
Authors: Zelt Jason G.E. , Sugarman Jordan , Weatherald Jason , Partridge Arun C.R. , Liang Jiaming (Calvin) , Swiston John , Brunner Nathan , Chandy George , Stewart Duncan J. , Contreras-Dominguez Vladimir , Thakrar Mitesh , Helmersen Doug , Varughese Rhea , Hirani Naushad , Umar Fraz , Dunne Rosemary , Doyle-Cox Caroyln , Foxall Julia , Mielniczuk Lisa 
Published: October 2021

BackgroundThe evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH.MethodsWe performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e.monotherapyversuscombination therapy).ResultsThere was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53).ConclusionsThere was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.
Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures
Authors: Kulasinghe Arutha , Tan Chin Wee , Ribeiro dos Santos Miggiolaro Anna Flavia , Monkman James , SadeghiRad Habib , Bhuva Dharmesh D. , Motta Junior Jarbas da Silva , Busatta Vaz de Paula Caroline , Nagashima Seigo , Baena Cristina Pellegrino , Souza-Fonseca-Guimaraes Paulo , de Noronha Lucia , McCulloch Timothy , Rossi Gustavo Rodrigues , Cooper Caroline , Tang Benjamin , Short Kirsty R. , Davis Melissa J. , Souza-Fonseca-Guimaraes Fernando , Belz Gabrielle T. , O'Byrne Ken 
Published: October 2021

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies.MethodsHere, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients.ResultsHost transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient–patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated geneIFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza.ConclusionCollectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.
Temporal trends in pulmonary arterial hypertension: results from the COMPERA registry
Authors: Hoeper Marius M. , Pausch Christine , Grünig Ekkehard , Staehler Gerd , Huscher Doerte , Pittrow David , Olsson Karen M. , Vizza Carmine Dario , Gall Henning , Distler Oliver , Opitz Christian , Gibbs J. Simon R. , Delcroix Marion , Ghofrani H. Ardeschir , Rosenkranz Stephan , Park Da-Hee , Ewert Ralf , Kaemmerer Harald , Lange Tobias J. , Kabitz Hans-Joachim , Skowasch Dirk , Skride Andris , Claussen Martin , Behr Juergen , Milger Katrin , Halank Michael , Wilkens Heinrike , Seyfarth Hans-Jürgen , Held Matthias , Dumitrescu Daniel , Tsangaris Iraklis , Vonk-Noordegraaf Anton , Ulrich Silvia , Klose Hans 
Published: October 2021

BackgroundSince 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extent this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival.MethodsWe analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we looked at annualised data and at cumulated data comparing the periods 2010–2014 and 2015–2019.ResultsA total of 2531 patients were included. The use of early combination therapy (within 3 months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1 year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010–2014 and 2015–2019 periods, 1-year survival estimates were similar (89.0% (95% CI 87.2–90.9%) and 90.8% (95% CI 89.3–92.4%), respectively), whereas there was a slight but nonsignificant improvement in 3-year survival estimates (67.8% (95% CI 65.0–70.8%) and 70.5% (95% CI 67.8–73.4%), respectively).ConclusionsThe use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1 year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed.
Pilot study on nocturnal monitoring of crackles in children with pneumonia
Authors: Nikolaizik Wilfried , Wuensch Lisa , Bauck Monika , Gross Volker , Sohrabi Keywan , Weissflog Andreas , Hildebrandt Olaf , Koehler Ulrich , Weber Stefanie 
Published: October 2021

BackgroundThe clinical diagnosis of pneumonia is usually based on crackles at auscultation, but it is not yet clear what kind of crackles are the characteristic features of pneumonia in children. Lung sound monitoring can be used as a “longtime stethoscope”. Therefore, it was the aim of this pilot study to use a lung sound monitor system to detect crackles and to differentiate between fine and coarse crackles in children with acute pneumonia. The change of crackles during the course of the disease shall be investigated in a follow-up study.Patients and methodsCrackles were recorded overnight from 22:00 to 06:00 h in 30 children with radiographically confirmed pneumonia. The data for a total of 28 800 recorded 30-s epochs were audiovisually analysed for fine and coarse crackles.ResultsFine crackles and coarse crackles were recognised in every patient with pneumonia, but the number of epochs with and without crackles varied widely among the different patients: fine crackles were detected in 40±22% (mean±sd), coarse crackles in 76±20%. The predominant localisation of crackles as recorded during overnight monitoring was in accordance with the radiographic infiltrates and the classical auscultation in most patients. The distribution of crackles was fairly equal throughout the night. However, there were time periods without any crackle in the single patients so that the diagnosis of pneumonia might be missed at sporadic auscultation.ConclusionNocturnal monitoring can be beneficial to reliably detect fine and coarse crackles in children with pneumonia.
Lung cancer mortality in Europe and the USA between 2000 and 2017: an observational analysis
Authors: Jani Chinmay , Marshall Dominic C. , Singh Harpreet , Goodall Richard , Shalhoub Joseph , Al Omari Omar , Salciccioli Justin D. , Thomson Carey C. 
Published: October 2021

BackgroundThe lung is the most common site for cancer and has the highest worldwide cancer-related mortality. Our study reports and compares trends in lung cancer mortality in the USA and 26 European countries.Study design and methodsLung cancer mortality data were extracted for males and females for each of the years 2000–2017 from the World Health Organization (WHO) Mortality and the Centers for Disease Control and Prevention (CDC) WONDER databases. Lung cancer mortality trends were compared using Joinpoint regression analysis, and male-to-female mortality ratios were calculated.ResultsDown-trending lung cancer mortality rates were observed in males in all countries except Cyprus and Portugal between 2000 and 2017. In females, increasing mortality rates were observed in 22 of the 27 countries analysed. Latvia had the highest estimated annual percentage change (EAPC) in male mortality (−9.6%) between 2013 and 2015. In the USA, EAPCs were −5.1% for males and −4.2% for females between 2014 and 2017. All countries had an overall decrease in the ratio of male-to-female lung cancer mortality. The most recent observation of median male-to-female mortality was 2.26 (IQR 1.92–4.05). The countries with the greatest current sex disparity in lung cancer mortality were Lithuania (5.51) and Latvia (5.00).ConclusionBetween 2000 and 2017, lung cancer mortality rates were decreasing for males in Europe and the USA, whereas increasing lung cancer mortality rates were generally observed in females. There is a persistent but decreasing sex-mortality gap, with men having persistently greater lung cancer mortality but with rates decreasing faster than women.
Health outcomes after stopping long-term mepolizumab in severe eosinophilic asthma: COMET
Authors: Liu Mark C. , Bel Elisabeth H. , Kornmann Oliver , Moore Wendy C. , Kaneko Norihiro , Smith Steven G. , Martin Neil , Price Robert G. , Yancey Steven W. , Humbert Marc 
Published: October 2021

Asthma worsening and symptom control are clinically important health outcomes in patients with severe eosinophilic asthma. This analysis of COMET evaluated whether stoppingversuscontinuing long-term mepolizumab therapy impacted these outcomes.Patients with severe eosinophilic asthma with ≥3 years continuous mepolizumab treatment (viaCOLUMBA (NCT01691859) or COSMEX (NCT02135692) open-label studies) were eligible to enter COMET (NCT02555371), a randomised, double-blind, placebo-controlled study. Patients were randomised 1:1 to continue mepolizumab 100 mg subcutaneous every 4 weeks or to stop mepolizumab, plus standard of care asthma treatment. Patients could switch to open-label mepolizumab following an exacerbation. Health outcome endpoints included time to first asthma worsening (composite endpoint: rescue use, symptoms, awakening at night and morning peak expiratory flow (PEF)), patient and clinician assessed global rating of asthma severity and overall perception of response to therapy, and unscheduled healthcare resource utilisation.Patients who stopped mepolizumab showed increased risk of and shorter time to first asthma worsening compared with those who continued mepolizumab (hazard ratio (HR) 1.71; 95% CI 1.17–2.52; p=0.006), including reduced asthma control (increased risk of first worsening in rescue use (HR 1.36; 95% CI 1.00–1.84; p=0.047) and morning PEF (HR 1.77; 95% CI 1.21–2.59; p=0.003). There was a higher probability of any unscheduled healthcare resource use (HR 1.81; 95% CI 1.31–2.49; p<0.001), and patients and clinicians reported greater asthma severity and less favourable perceived response to therapy for patients who stoppedversuscontinued mepolizumab.These data suggest that patients with severe eosinophilic asthma continuing long-term mepolizumab treatment sustain clinically important improvements in health outcomes.
Global shifts in species richness have shaped carpet shark evolution
Authors: Boyd Bret M. , Seitz Jason C. 
Published: October 2021

Abstract
Background
The evolutionary processes that shape patterns of species richness in marine ecosystems are complex and may differ between organismal groups. There has been considerable interest in understanding the evolutionary processes that led to marine species richness being concentrated in specific geographical locations. In this study we focus on the evolutionary history of a group of small-to-medium sized sharks known as carpet sharks. While a few carpet shark species are widespread, the majority of carpet shark species richness is contained within a biodiversity hotspot at the boundary of the Indian and Pacific oceans. We address the significance of this biodiversity hotspot in carpet shark evolution and speciation by leveraging a rich fossil record and molecular phylogenetics to examine the prehistoric distribution of carpet sharks.

Results
We find that carpet sharks species richness was greatest in shallow seas connected to the Atlantic Ocean during the Late Cretaceous, but that there was a subsequent loss of biodiversity in Atlantic waters. Fossil evidence from sites in close geographic proximity to the current center of carpet shark diversity are generally restricted to younger geologic strata.

Conclusions
From this data we conclude that (1) center of carpet shark biodiversity has shifted during the last 100 million years, (2) carpet sharks have repeatedly dispersed to nascent habitat (including to their current center of diversity), and (3) the current center of carpet shark biodiversity conserves lineages that have been extirpated from this prehistoric range and is a source of new carpet shark species. Our findings provide insights into the roles of marine biodiversity hotspots for higher-tropic level predators and the methods applied here can be used for additional studies of shark evolution.
Sensitivity and specificity of self-reported psychiatric diagnoses amongst patients treated for opioid use disorder
Authors: Leung Kelly , Xu Emily , Rosic Tea , Worster Andrew , Thabane Lehana , Samaan Zainab 
Published: October 2021

Abstract
Background
Patients with opioid use disorder (OUD) frequently present with comorbid psychiatric illnesses which have significant implications for their treatment outcomes. Notably, these are often identified by self-report. Our study examined the sensitivity and specificity of self-reported psychiatric diagnoses against a structured diagnostic interview in a cohort of patients receiving outpatient pharmacological treatment for OUD.

Methods
Using cross-sectional data from adults receiving outpatient opioid agonist treatment for OUD in clinics across Ontario, Canada, we compared participants’ self-reported psychiatric diagnoses with those identified by the Mini Neuropsychiatric Interview (MINI) Version 6.0 administered at the time of study entry. Sensitivity and specificity were calculated for self-report of psychiatric diagnoses.

Results
Amongst a sample of 683 participants, 24% (n = 162) reported having a comorbid psychiatric disorder. Only 104 of these 162 individuals (64%) reporting a comorbidity met criteria for a psychiatric disorder as per the MINI; meanwhile, 304 (75%) participants who self-reported no psychiatric comorbidity were in fact identified to meet MINI criteria for a psychiatric disorder. The sensitivity and specificity for any self-reported psychiatric diagnoses were 25.5% (95% CI 21.3, 30.0) and 78.9% (95% CI 73.6, 83.6), respectively.

Conclusions
Our findings raise questions about the utility of self-reported psychiatric comorbidity in patients with OUD, particularly in the context of low sensitivity of self-reported diagnoses. Several factors may contribute to this including remittance and relapse of some psychiatric illnesses, underdiagnosis, and the challenge of differentiating psychiatric and substance-induced disorders. These findings highlight that other methods should be considered in order to identify comorbid psychiatric disorders in patients with OUD.
Prediction of gold stage in patients hospitalized with COPD exacerbations using blood neutrophils and demographic parameters as risk factors
Authors: Chen Jing , Yang Zhao , Yuan Qun , Guo Li-quan , Xiong Da-xi 
Published: October 2021

Abstract
Background
Patients hospitalized with chronic obstructive pulmonary disease (COPD) exacerbations are unable to complete the pulmonary function test reliably due to their poor health conditions. Creating an easy-to-use instrument to identify the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage will offer valuable information that assists clinicians to choose appropriate clinical care to decrease the mortality in these patients. The objective of this study was to develop a prediction model to identify the GOLD stage in the hospitalized exacerbation of chronic obstructive pulmonary disease (ECOPD) patients.

Methods
This prospective study involved 155 patients hospitalized for ECOPD. All participants completed lung function tests and the collection of blood neutrophils and demographic parameters. Receiver operating characteristic (ROC) curve was plotted based on the data of 155 patients, and was used to analyze the disease severity predictive capability of blood neutrophils and demographic parameters. A support vector regression (SVR) based GOLD stage prediction model was built using the training data set (75%), whose accuracy was then verified by the testing data set (25%).

Results
The percentage of blood neutrophils (denoted as NEU%) combined with the demographic parameters was associated with a higher risk to severe episode of ECOPD. The area under the ROC curve was 0.84. The SVR model managed to predict the GOLD stage with an accuracy of 90.24%. The root-mean-square error (RMSE) of the forced expiratory volume in one second as the percentage of the predicted value (denoted as FEV1%pred) was 8.84%.

Conclusions
The NEU% and demographic parameters are associated with the pulmonary function of the hospitalized ECOPD patients. The established prediction model could assist clinicians in diagnosing GOLD stage and planning appropriate clinical care.
Functionalized nanoparticles with monocyte membranes and rapamycin achieve synergistic chemoimmunotherapy for reperfusion-induced injury in ischemic stroke
Authors: Wang Yanyun , Wang Yi , Li Shuyu , Cui Yuliang , Liang Xiping , Shan Juanjuan , Gu Wei , Qiu Juhui , Li Yiliang , Wang Guixue 
Published: October 2021

AbstractBackgroundIschemic stroke is an acute and severe neurological disease, and reperfusion is an effective way to reverse brain damage after stroke. However, reperfusion causes secondary tissue damage induced by inflammatory responses, called ischemia/reperfusion (I/R) injury. Current therapeutic strategies that control inflammation to treat I/R are less than satisfactory.ResultsWe report a kind of shield and sword nano-soldier functionalized nanoparticles (monocyte membranes-coated rapamycin nanoparticles, McM/RNPs) that can reduce inflammation and relieve I/R injury by blocking monocyte infiltration and inhibiting microglia proliferation. The fabricated McM/RNPs can actively target and bind to inflammatory endothelial cells, which inhibit the adhesion of monocytes to the endothelium, thus acting as a shield. Subsequently, McM/RNPs can penetrate the endothelium to reach the injury site, similar to a sword, and release the RAP drug to inhibit the proliferation of inflammatory cells. In a rat I/R injury model, McM/RNPs exhibited improved active homing to I/R injury areas and greatly ameliorated neuroscores and infarct volume. Importantly, in vivo animal studies revealed good safety for McM/RNPs treatment.ConclusionThe results demonstrated that the developed McM/RNPs may serve as an effective and safe nanovehicles for I/R injury therapy.Graphic abstract
COVID19 infection in a patient undergoing treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH) with Ravulizumab
Authors: Shikdar Sufana , Borogovac Azra , Mohamad Elabdallah , Khawandanah Mohamad 
Published: October 2021

Abstract
Background
In the recent COVID19 pandemic, patients with hematological disorders were considered at high risk for severe disease. Limited data is available regarding the course of COVID19 infection in this subgroup.

Case Presentation
We describe a case of a 32-year-old man with paroxysmal nocturnal hemoglobinuria (PNH) undergoing treatment with ravulizumab (Ultomiris) who presented with COVID19 infection. He experienced only mild symptoms and had a rapid recovery from COVID19 infection.

Conclusion
This case may demonstrate the beneficial effects of ravulizumab on complement mediated inflammatory damage linked with COVID19 infection especially in PNH patients.
Non-circular signal DOA estimation based on coprime array MIMO radar
Authors: Zhang Fei , Ji Chuantang , Zhang Zijing , Yin Dayu , Wang Yi 
Published: October 2021

AbstractAiming at the problems of low degree of freedom, small array aperture, and phase ambiguity in traditional coprime array direction-of-arrival estimation methods, a non-circular signal DOA estimation method based on expanded coprime array MIMO radar is proposed. Firstly, this method combines the coprime array and the MIMO radar to form transmitter and receiver array. Secondly, the array is expanded using the non-circular signal characteristics to reconstruct the received signal matrix. Then the dimensionality reduction is performed. The two-dimensional spectral peak search is converted into an optimization problem, and the optimization of the two-dimensional MUSIC algorithm is reconstructed using constraints, and a cost function is constructed to solve the problem. In addition, use the power series of the noise eigenvalues to correct the noise subspace to further improve the accuracy of the algorithm. Finally, the problem of no phase ambiguity in the method in this article is derived. Simulation experiments show that the method in this article can effectively avoid phase ambiguity, greatly improve the degree of freedom, and expand the array aperture. Compared with the traditional MUSIC algorithm and the mutual prime array MUSIC algorithm, it has better resolution and DOA estimation accuracy.