bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early respiratory diagnosis: benefits of enhanced lung function assessment
Authors: Sylvester Karl P , Youngs Luke , Rutter M A , Beech Ross , Mahadeva Ravi 
Published: July 2021

IntroductionThe National Health Service for England Long Term Plan identifies respiratory disease as one of its priority workstreams. To assist with earlier and more accurate diagnosis of lung disease they recommend improvement in delivery of quality-assured spirometry. However, there is a likelihood that patients will present with abnormal gas exchange when spirometry results are normal and therefore there will be a proportion of patients whose time to diagnosis is still protracted. We wished to determine the incidence rate of this occurring within our Trust.MethodsA retrospective review of all patients attending the lung function laboratory for their first pulmonary function assessment from June 2006 to December 2020 was undertaken. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) >−1.64 standardised residual (SR) was used to confirm no obstructive lung function abnormality and FVC >−1.64 SR to confirm no suggestion of a restrictive lung function abnormality. Lung gas transfer for carbon monoxide (TLCO) and transfer coefficient of the lung for carbon monoxide (KCO) <−1.64 SR confirmed the presence of a gas exchange abnormality. Spirometry and gas transfer reference values generated by the Global Lung Initiative were used to determine normality.ResultsOf 12 835 eligible first visits with normal FEV1/FVC and FVC, 4856 (37.8%) were identified as having an abnormally low TLCO and 3302 (25.7%) presenting with an abnormally low KCO. Of 3494 with FEV1/FVC SR <−1.64, 3316 also had a ratio of <0.70, meaning 178 (5%) of patients in this cohort would have been misclassified as having obstructive lung disease using the 0.70 cut-off recommended by the Global Initiative for Chronic Obstructive Lung Disease for diagnosing obstructive lung disease.DiscussionIn conclusion, to assist with ensuring more accurate and timely diagnosis of lung disease and enhance patients’ diagnostic pathway, we recommend the performance of lung gas transfer measurements alongside spirometry in all healthcare settings. To assess and monitor gas transfer at the earliest opportunity we recommend this is implemented into new models being developed within community hubs. This will increase the identification of lung function abnormalities and provide patients with a definitive diagnosis earlier.
Performance of the Hull Salford Cambridge Decision Rule (HSC DR) for early discharge of patients with findings on CT scan of the brain: a CENTER-TBI validation study
Authors: Marincowitz Carl , Gravesteijn Benjamin , Sheldon Trevor , Steyerberg Ewout , Lecky Fiona 
Published: July 2021

BackgroundThere is international variation in hospital admission practices for patients with mild traumatic brain injury (TBI) and injuries on CT scan. Only a small proportion of patients require neurosurgical intervention, while many guidelines recommend routine admission of all patients. We aim to validate the Hull Salford Cambridge Decision Rule (HSC DR) and the Brain Injury Guidelines (BIG) criteria to select low-risk patients for discharge from the emergency department.MethodA cohort from 18 countries of Glasgow Coma Scale 13–15 patients with injuries on CT imaging was identified from the multicentre Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) Study (conducted from 2014 to 2017) for secondary analysis. A composite outcome measure encompassing need for ongoing hospital admission was used, including seizure activity, death, intubation, neurosurgical intervention and neurological deterioration. We assessed the performance of our previously derived prognostic model, the HSC DR and the BIG criteria at predicting deterioration in this validation cohort.ResultsAmong 1047 patients meeting the inclusion criteria, 267 (26%) deteriorated. Our prognostic model achieved a C-statistic of 0.81 (95% CI: 0.78 to 0.84). The HSC DR achieved a sensitivity of 100% (95% CI: 97% to 100%) and specificity of only 4.7% (95% CI: 3.3% to 6.5%) for deterioration. Using the BIG criteria for discharge from the ED achieved a higher specificity (13.3%, 95% CI: 10.9% to 16.1%) and lower sensitivity (94.6%, 95% CI: 90.5% to 97%), with 12/105 patients recommended for discharge subsequently deteriorating, compared with 0/34 with the HSC DR.ConclusionOur decision rule would have allowed 3.5% of patients to be discharged, none of whom would have deteriorated. Use of the BIG criteria may select patients for discharge who have too high a risk of subsequent deterioration to be used clinically. Further validation and implementation studies are required to support use in clinical practice.
Stool microRNA profiles reflect different dietary and gut microbiome patterns in healthy individuals
Authors: Tarallo Sonia , Ferrero Giulio , De Filippis Francesca , Francavilla Antonio , Pasolli Edoardo , Panero Valentina , Cordero Francesca , Segata Nicola , Grioni Sara , Pensa Ruggero Gaetano , Pardini Barbara , Ercolini Danilo , Naccarati Alessio 
Published: July 2021

ObjectivesMicroRNA (miRNA) profiles have been evaluated in several biospecimens in relation to common diseases for which diet may have a considerable impact. We aimed at characterising how specific diets are associated with the miRNome in stool of vegans, vegetarians and omnivores and how this is reflected in the gut microbial composition, as this is still poorly explored.DesignWe performed small RNA and shotgun metagenomic sequencing in faecal samples and dietary recording from 120 healthy volunteers, equally distributed for the different diets and matched for sex and age.ResultsWe found 49 miRNAs differentially expressed among vegans, vegetarians and omnivores (adj. p <0.05) and confirmed trends of expression levels of such miRNAs in vegans and vegetarians compared with an independent cohort of 45 omnivores. Two miRNAs related to lipid metabolism, miR-636 and miR-4739, were inversely correlated to the non-omnivorous diet duration, independently of subject age. Seventeen miRNAs correlated (|rho|>0.22, adj. p <0.05) with the estimated intake of nutrients, particularly animal proteins, phosphorus and, interestingly, lipids. In omnivores, higherPrevotellaandRoseburiaand lowerBacteroidesabundances than in vegans and vegetarians were observed. Lipid metabolism-related miR-425-3p and miR-638 expression levels were associated with increased abundances of microbial species, such asRoseburiasp. CAG 182 andAkkermansia muciniphila,specific of different diets. An integrated analysis identified 25 miRNAs, 25 taxa and 7 dietary nutrients that clearly discriminated (area under the receiver operating characteristic curve=0.89) the three diets.ConclusionStool miRNA profiles are associated with specific diets and support the role of lipids as a driver of epigenetic changes and host-microbial molecular interactions in the gut.
Carotid webs produce greater hemodynamic disturbances than atherosclerotic disease: a DSA time–density curve study
Authors: Park Charlie C , El Sayed Retta , Risk Benjamin B , Haussen Diogo C , Nogueira Raul G , Oshinski John N , Allen Jason W 
Published: July 2021

BackgroundCarotid webs (CaWs) are associated with ischemic strokes in younger patients without degrees of stenosis that are traditionally considered clinically significant.ObjectiveTo compare the hemodynamic parameters in the internal carotid artery (ICA) bulbar segment in patients with CaW with those in patients with atherosclerotic lesions using time–density curve (TDC) analysis of digital subtraction angiography (DSA) images.MethodsWe retrospectively assessed DSA images of 47 carotid arteries in 41 adult patients who underwent ICA catheter angiography for evaluation after ischemic stroke. Hemodynamic parameters, including full width at half maximum (FWHM) and area under the time–density curve (AUC) as proxies for increased flow stasis, were calculated using TDC analyses of a region of interest (ROI) in the ICA bulb immediately rostral to the web/atherosclerotic plaque, relative to a standardized ROI in the ipsilateral distal common carotid artery (eg, relative FWHM (rFWHM)). Hemodynamic parameters were compared using non-parametric Kruskal-Wallis tests. Logistic regression was used to predict CaW versus mild/moderate atherosclerosis for each hemodynamic parameter, adjusting for degree of stenosis.ResultsMean age of patients was 56.0±13 years, with 22 (53.7%) women. 17 CaWs, 22 atherosclerotic plaques (15 mild/moderate and 7 severe), and eight normal carotid arteries were assessed. Significant between-group differences were present in the relative total AUC (p<0.001), relative AUC at wash out (p=0.031), and relative FWHM (p=0.001). Logistic regression to predict CaW versus mild/moderate atherosclerosis showed that rAUC total had the highest predictive value (pAUC=0.96, 95% CI 0.90 to 1.00), followed by rFWHM (0.87, 95% CI 0.74 to 1.00), and rAUC WO (0.74, 95% CI (0.57 to 0.91).ConclusionCaW results in larger local hemodynamic disruption, characterized by flow stasis, than mild/moderate carotid atherosclerotic lesions, suggesting that CaWs may produce larger regions of thrombogenic flow stasis.
Who is providing HIV diagnostic testing? Comparing HIV testing by general practitioners and sexual health centres in five regions in the Netherlands, 2011−2018
Authors: Bogers Saskia J , Twisk Denise E , Beckers Loes M , Götz Hannelore M , Meima Bram , Kroone Michelle , Hoornenborg Elske , Ott Alewijn , Luning-Koster Marleen N , Dukers-Muijrers Nicole H T M , Hoebe Christian J P A , Kampman Carolina J G , Bosma Froukje , Schim van der Loeff Maarten , Geerlings Suzanne , van Bergen Jan 
Published: July 2021

ObjectivesGeneral practitioners (GPs) and sexual health centres (SHCs) are the main providers of HIV testing and diagnose two-thirds of HIV infections in the Netherlands. We compared regional HIV testing and positivity by GPs versus SHCs to gain insight into strategies to improve HIV testing, to enable timely detection of HIV infections.MethodsLaboratory data (2011–2018) on HIV testing by GPs and SHCs in five Dutch regions with varying levels of urbanisation were evaluated. Regional HIV testing rates per 10 000 residents ≥15 years (mean over period and annual) were compared between providers using negative binomial generalised additive models and additionally stratified by sex and age (15–29 years, 30–44 years, 45–59 years, ≥60 years). χ2 tests were used to compare positivity percentage between the two groups of providers.ResultsIn the study period, 505 167 HIV tests (GP 36%, SHC 64%) were performed. The highest HIV testing rates were observed in highly urbanised regions, with large regional variations. The HIV testing rates ranged from 28 to 178 per 10 000 residents by GPs and from 30 to 378 per 10 000 by SHCs. Testing rates by GPs were lower than by SHCs in three regions and comparable in two. In all regions, men were tested less by GPs than by SHCs; for women, this varied by region. Among those aged 15–29 years old, GPs’ testing rates were lower than SHCs’, while this was reversed in older age categories in four out of five regions. The overall mean HIV positivity was 0.4%. In contrast to other regions, positivity in Amsterdam was significantly higher among individuals tested by GPs than by SHCs.ConclusionsThis retrospective observational study shows that besides SHCs, who perform opt-out testing for key groups, GPs play a prominent role in HIV testing, especially in non-key populations, such as women and older individuals. Large regional variation exists, requiring region-specific interventions to improve GPs’ HIV testing practices.
MadFlow: automating Monte Carlo simulation on GPU for particle physics processes
Authors: Carrazza Stefano , Cruz-Martinez Juan , Rossi Marco , Zaro Marco 
Published: July 2021

AbstractWe present , a first general multi-purpose framework for Monte Carlo (MC) event simulation of particle physics processes designed to take full advantage of hardware accelerators, in particular, graphics processing units (GPUs). The automation process of generating all the required components for MC simulation of a generic physics process and its deployment on hardware accelerator is still a big challenge nowadays. In order to solve this challenge, we design a workflow and code library which provides to the user the possibility to simulate custom processes through the MadGraph5_aMC@NLO framework and a plugin for the generation and exporting of specialized code in a GPU-like format. The exported code includes analytic expressions for matrix elements and phase space. The simulation is performed using the VegasFlow and PDFFlow libraries which deploy automatically the full simulation on systems with different hardware acceleration capabilities, such as multi-threading CPU, single-GPU and multi-GPU setups. The package also provides an asynchronous unweighted events procedure to store simulation results. Crucially, although only Leading Order is automatized, the library provides all ingredients necessary to build full complex Monte Carlo simulators in a modern, extensible and maintainable way. We show simulation results at leading-order for multiple processes on different hardware configurations.
Fabrication of N-Doped Carbon Quantum Dots/BiOI Nanocomposite and Its Efficient Photocatalytic Activity Under Visible-Light Irradiation
Authors: Yu Yichang , Zheng Ziyuyang , Liao Weiling , Yao Yuan , Peng Feng , Chen Tingting , Wu Jin , Feng Li 
Published: July 2021

A novel spherical N-CQDs/BiOI photocatalyst was successfully synthesized through a facile solvothermal method. The optimization experiments of hydrothermal time and temperature were carried out. The effect of ammonium citrate addition was investigated. The as-synthesized photocatalysts were characterized via X-ray diffraction, scanning and transmission electron microscopy, Fourier transform infrared spectrum and elemental analysis. The adsorption and photocatalytic performance of as-synthesized photocatalysts were studied, 0.2N-CQDs/BiOI showed the best performance. For the removal of anionic dye RhB, adsorption occupied a major position. The maximum adsorption capacity was 97.09[Formula: see text]mg/g for RhB. For the removal of cationic dyes X3B, photocatalysis occupied a major position. The photocatalytic activity of 0.2N-CQDs/BiOI was superior to that of nano-TiO2 under the simulate sunlight irradiation. Different scavengers were used to analyze the effect of active species and photocatalytic degradation mechanism of X3B. The outstanding stability and performance make 0.2N-CQDs/BiOI has highly potential applications in wastewater treatment.
Improvement of Presbyopia Using a Mixture of Traditional Chinese Herbal Medicines, Including Cassiae Semen, Wolfberry, and Dendrobium huoshanense
Authors: Horng Chi-Ting , Ma Jui-Wen , Shieh Po-Chuen 
Published: July 2021

Background. Presbyopia is a primary cause of a decline in near vision. In this study, we developed a new mixed herbal medicine to retard presbyopic progression and increase the amplitude of accommodation (AA), which is beneficial for near vision. Methods. A total of 400 participants between the ages of 45 and 70 years were recruited. We designed the mixed herbal drug to include Cassiae Semen (200 mg), wolfberry (200 mg), and Dendrobium huoshanense (DD) (40 mg) in one capsule. In experiment 1, the recruited subjects were directed to perform a push-up test to measure their AA; this was then converted to the additional diopters of reading glasses. In experiment 2, 240 subjects took three capsules daily for six months and then stopped medical therapy for a six-month follow-up. In experiment 3, 160 subjects were randomly categorized into four groups: a placebo group, low-dose group (LDG) (1 capsule daily), middle-dose group (MDG) (two capsules daily), and high-dose group (HDG) (three capsules daily). The 160 volunteers took different doses for six months and then stopped treatment, accompanied by another six-month follow-up. In experiments 2 and 3, the change in AA, uncorrected far visual acuity (UFVA), and uncorrected near visual acuity (UNVA) were recorded each month for one year. Results. In experiment 1, AA was found to decrease with age and a great deal of additional power was needed in older individuals. In experiment 2, the mean AA reached a maximum value of 2.1D (

P

< 0.05) after six months, while the UNVA improved by about two to three lines of a Jaeger chart in most of the subjects. At nine months, all the means decreased slightly to 2.0 D (

P

< 0.05). This meant that the mixed herbal medicine could still maintain AA for another three months because the herbal therapy was stopped at the seventh month. In experiment 3, the maximal AA was 2.8D, 2.9D, and 3.2D (

P

< 0.05) in the LDG, MDG, and HDG after six-month treatments, respectively. Experiment 3 showed that AA gain occurred in a dose-dependent manner; the higher the dose, the greater the AA value. Conclusion. Only two studies on the use of herbal drugs for presbyopia have been reported in PubMed. In our study, we found that taking a mixed herbal drug caused an excellent gain in AA. This is the first study to report that the characteristics of the new herbal regimen could retard and even ameliorate presbyopia.
Preclinical and Early Clinical Development of PTC596, a Novel Small-Molecule Tubulin-Binding Agent
Authors: Jernigan Finith , Branstrom Arthur , Baird John D. , Cao Liangxian , Dali Mandar , Furia Bansri , Kim Min Jung , O'Keefe Kylie , Kong Ronald , Laskin Oscar L. , Colacino Joseph M. , Pykett Mark , Mollin Anna , Sheedy Josephine , Dumble Melissa , Moon Young-Choon , Sheridan Richard , Mühlethaler Tobias , Spiegel Robert J. , Prota Andrea E. , Steinmetz Michel O. , Weetall Marla 
Published: July 2021

Abstract

PTC596 is an investigational small-molecule tubulin-binding agent. Unlike other tubulin-binding agents, PTC596 is orally bioavailable and is not a P-glycoprotein substrate. So as to characterize PTC596 to position the molecule for optimal clinical development, the interactions of PTC596 with tubulin using crystallography, its spectrum of preclinical in vitro anticancer activity, and its pharmacokinetic–pharmacodynamic relationship were investigated for efficacy in multiple preclinical mouse models of leiomyosarcomas and glioblastoma. Using X-ray crystallography, it was determined that PTC596 binds to the colchicine site of tubulin with unique key interactions. PTC596 exhibited broad-spectrum anticancer activity. PTC596 showed efficacy as monotherapy and additive or synergistic efficacy in combinations in mouse models of leiomyosarcomas and glioblastoma. PTC596 demonstrated efficacy in an orthotopic model of glioblastoma under conditions where temozolomide was inactive. In a first-in-human phase I clinical trial in patients with cancer, PTC596 monotherapy drug exposures were compared with those predicted to be efficacious based on mouse models. PTC596 is currently being tested in combination with dacarbazine in a clinical trial in adults with leiomyosarcoma and in combination with radiation in a clinical trial in children with diffuse intrinsic pontine glioma.
Design of a Cytotoxic Neuroblastoma-Targeting Agent Using an Enzyme Acting on Polysialic Acid Fused to a Toxin
Authors: Lehti Timo A. , Pajunen Maria I. , Jokilammi Anne , Korja Miikka , Lilie Hauke , Vettenranta Kim , Finne Jukka 
Published: July 2021

Abstract
Polysialic acid, an abundant cell surface component of the developing nervous system, which declines rapidly postnatally to virtual absence in the majority of adult tissues, is highly expressed in some malignant tumors including neuroblastoma. We found that the binding of a noncatalytic endosialidase to polysialic acid causes internalization of the complex from the surface of neuroblastoma kSK-N-SH cells, a subline of SK-N-SH, and leads to a complete relocalization of polysialic acid to the intracellular compartment. The binding and uptake of the endosialidase is polysialic acid–dependent as it is inhibited by free excess ligand or removal of polysialic acid by active endosialidase, and does not happen if catalytic endosialidase is used in place of inactive endosialidase. A fusion protein composed of the noncatalytic endosialidase and the cytotoxic portion of diphtheria toxin was prepared to investigate whether the cellular uptake observed could be used for the specific elimination of polysialic acid–containing cells. The conjugate toxin was found to be toxic to polysialic acid–positive kSK-N-SH with an IC50 of 1.0 nmol/L. Replacing the noncatalytic endosialidase with active endosialidase decreased the activity to the level of nonconjugated toxin. Normal nonmalignant cells were selectively resistant to the toxin conjugate. The results demonstrate that noncatalytic endosialidase induces a quantitative removal and cellular uptake of polysialic acid from the cell surface which, by conjugation with diphtheria toxin fragment, can be exploited for the selective elimination of polysialic acid–containing tumor cells.
Novel Humanized Mesothelin-Expressing Genetically Engineered Mouse Models Underscore Challenges in Delivery of Complex Therapeutics to Pancreatic Cancers
Authors: Hagerty Brendan , O'Sullivan T. Norene , Zhang Xianyu , Collins N. Keith , Custer Lawrence Wendi , Bassel Laura L. , Pate Nathan , Xu Jian , Guerin Theresa M. , Kozlov Serguei , Alewine Christine 
Published: July 2021

Abstract
Antibody-based therapies designed for human use frequently fail to cross-react with the murine isoform of their target. Because of this problem, preclinical studies of antibody-based mesothelin (Msl)-targeted therapeutics in immunocompetent systems have been limited by the lack of suitable mouse models. Here, we describe two immunocompetent humanized mesothelin transgenic mouse lines that can act as tolerant hosts for C57Bl/6-syngeneic cell lines expressing the human isoform of mesothelin. Thyroid peroxidase (TPO) mice have thyroid-restricted human mesothelin expression. Mesothelin (Msl) mice express human mesothelin in the typical serosal membrane distribution and can additionally be utilized to assess on-target, off-tumor toxicity of human mesothelin–targeted therapeutics. Both transgenic strains shed human mesothelin into the serum like human mesothelioma and patients with ovarian cancer, and serum human mesothelin can be used as a blood-based surrogate of tumor burden. Using these models, we examined the on-target toxicity and antitumor activity of human mesothelin–targeted recombinant immunotoxins. We found that immunotoxin treatment causes acute and chronic histologic changes to serosal membranes in Msl mice, while human mesothelin-expressing thyroid follicular cells in TPO mice are resistant to immunotoxin despite excellent drug delivery. Furthermore, poor delivery of immunotoxin to syngeneic orthotopic human mesothelin-expressing pancreatic adenocarcinoma limits antitumor activity both alone and in combination with immune checkpoint inhibition. In summary, we have developed two high-fidelity, immunocompetent murine models for human cancer that allow for rigorous preclinical evaluation of human mesothelin–targeted therapeutics.