bluuebunny/crossref_metadata_2025 huggingface dataset:
161 Analysis of an ambulatory care pathway for patients with COVID-19 utilising remote pulse oximetry
Authors: Kyriakides Jonathon , Khani Aria , Kelly Charlotte , Coleman Reginald
Published: January 2021

Aims/Objectives/Background

The safe discharge of COVID-19 patients from the emergency department (ED) is difficult due to uncertainties surrounding the trajectory of the disease course. The infectivity of COVID-19 also limits follow-up options. A novel pathway consisting of home pulse oximetry with telephone follow-up was created to facilitate safe discharge from the ED of a London district general hospital. The primary objective was to utilise home pulse oximetry to prevent hospital admission. The secondary objective was to identify those requiring further care or investigation.

Methods/Design

Adult patients with confirmed or suspected COVID-19 with oxygen saturations of between 90–94% who were otherwise suitable for discharge were identified. These patients were discharged from the ED with a pulse oximeter. Oxygen saturations were measured three times a day for seven days. Patients received a structured telephone consultation on days two, five and seven post-discharge from the ED, and a decision was made as to whether further clinical assessment in the ED was necessary.

Results/Conclusions

Of the twenty patients discharged on the pathway, 85% avoided hospital admission, whilst 15% were re-assessed and subsequently admitted to hospital. 20% of patients required re-assessment in the ED but did not require admission.

Home pulse oximetry with telephone follow-up was used to prevent hospital admission in a considerable proportion of patients who would have otherwise been admitted in the absence of this pathway. Telephone follow-up effectively identified patients who required further clinical assessment. Increasing age, the presence of co-morbidities, and pulmonary infiltrates on chest radiograph were more common in the cohort who required re-assessment. This study demonstrates the potential for safe ambulation of a subgroup of patients with COVID-19, whilst identifying practical inclusion criteria which could be replicated in ambulatory units across the UK.
127 Fascia iliaca block in the emergency department-a quality improvement project, queen elizabeth hospital Birmingham
Authors: Browne Catherine , Hosein Riad , Jellinek Alistair
Published: January 2021

Aims/Objectives/Background

Fractured neck of femur is a common presentation and is associated with high rates of morbidity and mortality. RCEM Best Practice specifies that Fascia Iliaca Block should be available in Emergency Departments as part of the pain management strategy.

Aims

Improve compliance with RCEM guidance for safe administration, documentation and post-procedure monitoring following FIB.

Employ QIP methodology to create a FIB protocol.

Empower the junior SHO workforce to gain competence in FIB administration through structured teaching.

Improve understanding of post-block monitoring in nursing and medical staff.

Methods/Design

Data collection identified the number of blocks administered to those presenting with fractured neck of femur in November 2019. Documentation and post-procedure monitoring were evaluated.

Interventions were piloted in January 2020. These were: pre-made block packs, a block checklist sticker incorporating post-procedure monitoring chart and laminated ‘quick prompt’ guide.

Nurse champions facilitated MDT teaching sessions and junior SHOs were empowered to gain competence in block administration through teaching sessions.

Retrospective data from January 2020 was compared to November 2019, allowing us to establish the efficacy of changes.

Abstract 127 Figure 1

Results/Conclusions

October 2019 results demonstrated 59% of patients received a FIB, this increased to 78% in January 2020. Pre-intervention, 45% of patients had the correct dose of local anaesthetic. This increased to 79% post-intervention. Initially, documentation was correct in just 5% of cases, improving to 59% after re-auditing.

Feedback from teaching sessions was positive with nursing staff better understanding the need for post-procedure monitoring. SHOs gained increased confidence delivering FIBs, freeing up senior doctors for other tasks.

The new protocol has improved the administration of FIBs with better post-procedure care and standardised dosing of local anaesthetic. Interventions are embedded in departmental practice; this will be re-audited in 6 months. Following the transition to e-noting we are developing an electronic template to translate these successes onto the new system.
393 Reducing plastic waste in Paeds ED
Authors: Young Rona , Russell Fiona
Published: January 2021

Aims/Objectives/Background

Venepuncture and PVC insertion are common procedures in Children’s ED and often include blood cultures. Opening a universal dressing pack (udp) including a plastic tray, sterile swabs, gloves and 2 plastic sterile field drapes (sfd) is common practice. Our department was making a huge spend on udp’s. We aimed to determine if this was necessary and if we could reduce our plastic waste.

Methods/Design

A sample of 8 doctors across all grades demonstrated their set up for both procedures. We replaced udp in the IV trollies with x2 sfd pack (sfdp). Information was disseminated via weekly staff brief. Trollies are restocked each night using attached flashcards which were updated appropriately. The use and costs of dressing packs in ED was determined for April-June 2019. We planned to compare this for April-June 2020.

Results/Conclusions

All clinicians were opening a dressing pack for procedures but 87.5% only used the sfd and swabs. 100% discarded gloves due to inappropriate size and 100% discarded the tray. All staff adopted the new equipment with no problems identified. 3500 udps were being used in dept in 3 months. Udp v sfdp per item costs 32p v 8p, weight 65 g v 30 g. Due to CoVID-19 pandemic the number of ED attendances significantly reduced therefore costs were based on 2019 usage. In 3 months switching from udp to sfd would save £840 and 122.5 kg of refuse weight. Volumes of stocks were reduced from 0.05 m2 to 0.01 m2 for 50 udp v 50 sfdp which aids storage and restocking of IV trollies releasing staff time.

We demonstrated a significant reduction in unnecessary plastic waste while also reducing costs and need for storage and restocking whilst maintaining safe practice. This has been rolled out in the neighbouring Clinical Decision Unit with anticipation of being a permanent change in both areas.
In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis
Authors: Kim Seohyun , Kim Seong A , Nam Gi-Hoon , Hong Yeonsun , Kim Gi Beom , Choi Yoonjeong , Lee Seokyoung , Cho Yuri , Kwon Minsu , Jeong Cherlhyun , Kim Sehoon , Kim In-San
Published: January 2021

Background

Uveal melanoma (UM) is the most frequent intraocular malignancy and is resistant to immunotherapy. Nearly 50% of patients with UM develop metastatic disease, and the overall survival outcome remains very poor. Therefore, a treatment regimen that simultaneously targets primary UM and prevents metastasis is needed. Here, we suggest an immunotherapeutic strategy for UM involving a combination of local photodynamic therapy (PDT), rho-kinase (ROCK) inhibitor, and PD-1/PD-L1 immune checkpoint blockade.

Methods

The antitumor efficacy and immune response of monotreatment or combinational treatment were evaluated in B16F10-bearing syngeneic mouse models. Abscopal antitumor immune responses induced by triple-combinational treatment were validated in syngeneic bilateral B16F10 models. After each treatment, the immune profiles and functional examinations were assessed in tumors and tumor draining lymph nodes by flow cytometry, ELISA, and immunofluorescence assays. In orthotopic intraocular melanoma models, the location of the immune infiltrate in the tumor microenvironment (TME) was evaluated after each treatment by multiplex immunohistochemistry and metastatic nodules were monitored.

Results

PDT with Ce6-embedded nanophotosensitizer (FIC-PDT) elicited immunogenic cell death and stimulated antigen-presenting cells. In situ immunogenic clearance induced by a combination of FIC-PDT with ripasudil, a clinically approved ROCK inhibitor, stimulated antigen-presenting cells, which in turn primed tumor-specific cytotoxic T cells. Moreover, local immunogenic clearance sensitized PD-1/PD-L1 immune checkpoint blockade responses to reconstruct the TME immune phenotypes of cold tumors into hot tumors, resulting in recruitment of robust cytotoxic CD8+T cells in the TME, propagation of systemic antitumor immunity to mediate abscopal effects, and prolonged survival. In an immune-privileged orthotopic intraocular melanoma model, even low-dose FIC-PDT and ripasudil combined with anti-PD-L1 antibody reduced the primary tumor burden and prevented metastasis.

Conclusions

A combination of localized FIC-PDT and a ROCK inhibitor exerted a cancer vaccine-like function. Immunogenic clearance led to the trafficking of CD8+T cells into the primary tumor site and sensitized the immune checkpoint blockade response to evoke systemic antitumor immunity to inhibit metastasis, one of the major challenges in UM therapy. Thus, immunogenic clearance induced by FIC-PDT and ROCK inhibitor combined with anti-PD-L1 antibody could be a potent immunotherapeutic strategy for UM.
Intracellular homocysteine metabolites in SLE: plasma S-adenosylhomocysteine correlates with coronary plaque burden
Authors: Stojan George , Li Jessica , Liu Tian , Kane Maureen A , Petri Michelle A
Published: January 2021

Background and aims

We hypothesised that intracellular homocysteine and homocysteine metabolite levels in patients with SLE are disproportionately elevated compared with the levels seen in healthy subjects and that they are independently associated with coronary plaque in SLE.

Methods

A liquid chromatography–tandem mass spectrometry absolute quantification assay was used for the determination of six analytes in both plasma and peripheral blood mononuclear cells (PBMCs): homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), methionine (Met), cystathionine (Cysta) and 5-methyltetrahydrofolate (5m-THF). We then compared intracellular (PBMC) and extracellular (plasma) Hcy and Hcy metabolite (SAM, SAH, Met, Cysta and 5m-THF) concentrations in 10 patients with SLE and in 10 age, sex and ethnicity matched controls. Subjects with a history of diabetes mellitus, cardiovascular disease, hypertension, alcohol consumption in excess of 3 units per day, anaemia, renal insufficiency (serum creatinine >1.5 mg/dL) and pregnancy were excluded. All patients with SLE had two coronary CT angiography studies as screening for occult coronary atherosclerotic disease.

Results

Plasma from patients with SLE had higher levels of Hcy (p<0.0001), SAH (p<0.05), SAM (p<0.001) and lower levels of Met (p<0.05) and Cysta (p<0.001) compared with controls. PBMC intracellular concentrations from patients with SLE had higher levels of Cysta (p<0.05), SAH (p<0.05), SAM (p<0.001) and lower levels of 5m-THF (p<0.001). Plasma SAH showed a positive correlation with total coronary plaque, calcified plaque and non-calcified plaque (p<0.05).

Conclusion

Intracellular concentrations of Hcy metabolites were significantly different between patients with SLE and controls, despite similar intracellular Hcy levels. Plasma SAH was positively correlated with total coronary plaque, calcified plaque and non-calcified plaque.
Optimal thresholds to predict long-term outcome after complete endovascular recanalization in acute anterior ischemic stroke
Authors: Neuberger Ulf , Vollmuth Philipp , Nagel Simon , Schönenberger Silvia , Weyland Charlotte Sabine , Gumbinger Christoph , Ringleb Peter Arthur , Bendszus Martin , Pfaff Johannes Alex Rolf , Möhlenbruch Markus Alfred
Published: January 2021

Background

Despite complete endovascular recanalization, a significant percentage of patients with acute anterior stroke do not achieve a good clinical outcome. We analyzed optimal thresholds of relevant parameters to discern functional independence after successful endovascular recanalization and test their predictive performance.

Methods

Patients with acute anterior ischemic stroke undergoing endovascular treatment between April 2015 and November 2019 were retrospectively analyzed. Only patients with premorbid modified Rankin Scale (mRS) score <3 and complete recanalization (modified Thrombolysis In Cerebral Infarction 2c/3) were included. Optimal thresholds of the most important variables predicting functional independence (mRS 0–2 after 90 days) were calculated using receiver operating characteristic curves and their predictive performance was tested in an independent dataset using machine learning algorithms.

Results

Overall, 371 patients met the inclusion criteria. Optimal thresholds for the overall most important variables to predict functional independence were (1) National Institutes of Health Stroke Scale (NIHSS) score ≤5 after 24 hours (area under the curve (AUC) 0.88 (95% CI 0.84 to 0.92)); (2) Alberta Stroke Program Early CT Score (ASPECTS) ≥7 on follow-up CT (AUC 0.72 (95% CI 0.68 to 0.77)); and (3) change in NIHSS score ≥8 after 24 hours (AUC 0.70 (95% CI 0.65 to 0.74)). The performance of these thresholds to predict a good outcome using machine learning in the independent dataset was evaluated for (1) NIHSS score ≤5 after 24 hours (AUC 0.76 (95% CI 0.71 to 0.81)); (2) follow-up ASPECTS ≥7 (AUC 0.64 (95% CI 0.58 to 0.70)); (3) change in NIHSS score ≥8 after 24 hours (AUC 0.61 (95% CI 0.55 to 0.67)); and (4) the combination of all three parameters (AUC 0.84 (95% CI 0.80 to 0.88)).

Conclusions

After complete recanalization in acute anterior circulation ischemic stroke, a good long-term outcome could be accurately predicted reaching NIHSS score ≤5 after 24 hours.
Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands
Authors: van Voorst Henk , Kunz Wolfgang G , van den Berg Lucie A , Kappelhof Manon , Pinckaers Floor M E , Goyal Mayank , Hunink Myriam G M , Emmer Bart J , Mulder Maxim J H L , Dippel Diederik W J , Coutinho Jonathan M , Marquering Henk A , Boogaarts Hieronymus D , van der Lugt Aad , van Zwam Wim H , Roos Yvo B W E M , Buskens Erik , Dijkgraaf Marcel G W , Majoie Charles B L M
Published: January 2021

Background

The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population.

Methods

A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs.

Results

EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: −65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs.

Conclusion

One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs.
Older age, comorbidity, glucocorticoid use and disease activity are risk factors for COVID-19 hospitalisation in patients with inflammatory rheumatic and musculoskeletal diseases
Authors: Hasseli Rebecca , Mueller-Ladner Ulf , Hoyer Bimba F , Krause Andreas , Lorenz Hanns-Martin , Pfeil Alexander , Richter Jutta , Schäfer Martin , Schmeiser Tim , Strangfeld Anja , Schulze-Koops Hendrik , Voll Reinhard E , Specker Christof , Regierer Anne Constanze
Published: January 2021

Introduction

Whether patients with inflammatory rheumatic and musculoskeletal diseases (RMD) are at higher risk to develop severe courses of COVID-19 has not been fully elucidated. Aim of this analysis was to describe patients with RMD according to their COVID-19 severity and to identify risk factors for hospitalisation.

Methods

Patients with RMD with PCR confirmed SARS-CoV-2 infection reported to the German COVID-19 registry from 30 March to 1 November 2020 were evaluated. Multivariable logistic regression was used to estimate ORs for hospitalisation due to COVID-19.

Results

Data from 468 patients with RMD with SARS-CoV-2 infection were reported. Most frequent diagnosis was rheumatoid arthritis, RA (48%). 29% of the patients were hospitalised, 5.5% needed ventilation. 19 patients died. Multivariable analysis showed that age >65 years (OR 2.24; 95% CI 1.12 to 4.47), but even more>75 years (OR 3.94; 95% CI 1.86 to 8.32), cardiovascular disease (CVD; OR 3.36; 95% CI 1.5 to 7.55), interstitial lung disease/chronic obstructive pulmonary disease (ILD/COPD) (OR 2.79; 95% CI 1.2 to 6.49), chronic kidney disease (OR 2.96; 95% CI 1.16 to 7.5), moderate/high RMD disease activity (OR 1.96; 95% CI 1.02 to 3.76) and treatment with glucocorticoids (GCs) in dosages >5 mg/day (OR 3.67; 95% CI 1.49 to 9.05) were associated with higher odds of hospitalisation. Spondyloarthritis patients showed a smaller risk of hospitalisation compared with RA (OR 0.46; 95% CI 0.23 to 0.91).

Conclusion

Age was a major risk factor for hospitalisation as well as comorbidities such as CVD, ILD/COPD, chronic kidney disease and current or prior treatment with GCs. Moderate to high RMD disease activity was also an independent risk factor for hospitalisation, underlining the importance of continuing adequate RMD treatment during the pandemic.
First report of Phyllactinia chubutiana, nom. cons., on Vallesia glabra (Apocynaceae) in Mexico
Authors: Félix-Gastélum Rubén , Leyva-Madrigal Karla Yeriana , Quiroz-Figueroa Francisco Roberto , Rodriguez-Mora Norma , Maldonado-Mendoza Ignacio Eduardo , Espinosa-Matías Silvia , Mora-Romero Guadalupe Arlene
Published: January 2021

A new record of the powdery mildew Phyllactinia chubutiana, nom. cons. (= Oidium insolitum, Ovulariopsis insolita) was documented on pearl berry [Vallesia glabra (Cav.) Link]. No teleomorph was observed. This novel record was identified as a member of Ovulariopsis, based on the morphological characteristics of the anamorph (hyphae, conidiophores, and conidia), and its hemi-endophytic mycelium in V. glabra correspond to P. chubutiana, nom. cons. A Phyllactinia-specific primer pair was designed for the ITS region of the nuclear rDNA. Phylogenetic analyses confirmed the identity of the powdery mildew specimens found in V. glabra in Sinaloa, Mexico. This is the first ever report of this powdery mildew in V. glabra, and the second report world-wide on a member of the Apocynaceae.
Equation of motion truncation scheme based on partial orthogonalization
Authors: Catalano Francesco , Nilsson Johan
Published: January 2021

We introduce a general scheme to consistently truncate equations of motion for Green’s functions. Our scheme is guaranteed to generate physical Green’s functions with real excitation energies and positive spectral weights. There are free parameters in our scheme akin to mean field parameters that may be determined to get as good an approximation to the physics as possible. As a test case we apply our scheme to a two-pole approximation for the 2D Hubbard model. At half-filling we find an insulating solution with several interesting properties: it has low expectation value of the energy and it gives upper and lower Hubbard bands with the full non-interacting bandwidth in the large U limit. Away from half-filling, in particular in the intermediate interaction regime, our scheme allows for several different phases with different number of Fermi surfaces and topologies.

Graphic abstract
The Higgs field and the Jordan Brans Dicke cosmology
Authors: Dunya Onder , Akant Levent , Arik Metin , Kardas Yelda , Sahin Selale , Tok Tarik
Published: January 2021

We investigate a field theoretical approach to the Jordan–Brans–Dicke (JBD) theory extended with a particular potential term on a cosmological background by starting with the motivation that the Higgs field and the scale factor of the universe are related. Based on this relation, it is possible to come up with mathematically equivalent but two different interpretations. From one point of view while the universe is static, the masses of the elementary particles change with time. The other one, which we stick with throughout the manuscript, is that while the universe is expanding, particle masses are constant. Thus, a coupled Lagrangian density of the JBD field and the scale factor (the Higgs field), which exhibit a massive particle and a linearly expanding space in zeroth order respectively, is obtained. By performing a coordinate transformation in the field space for the reduced JBD action whose kinetic part is nonlinear sigma model, the Lagrangian of two scalar fields can be written as uncoupled for the Higgs mechanism. After this transformation, as a result of spontaneous symmetry breaking, the time dependent vacuum expectation value (vev) of the Higgs field and the Higgs bosons which are the particles corresponding to quantized oscillation modes about the vacuum, are found.
From high temporal resolution to synthetically enhanced radiometric resolution: insights from Night Thermal Gradient results
Authors: Piroddi L.
Published: January 2021

Electromagnetic emissions in thermal infrared bands are an important research topic on pre-earthquake studies. Satellite thermal data have been investigated by many independent research groups looking for their anomalous behaviour before main earthquake's occurrences. Among them, geosynchronous satellite data are reported as less prone to artefacts during data processing. In this work, the Night Thermal Gradient (NTG) algorithm is presented, which has been specifically proposed for geostationary thermal infrared data processing. NTG method relies on the exploitation of high temporal resolution data to find coherent low frequency components of a hypothetical precursory signal of seismic activity. In this paper, the method is presented by giving details about the applied procedures, steps, theoretical assumptions and results obtained during the studies of L'Aquila 2009 earthquake and the seismic activity of Central Italy and Sardinia.
Online Thread and Data Mapping Using a Sharing-Aware Memory Management Unit
Authors: Cruz Eduardo H. M. , Diener Matthias , Pilla Laércio L. , Navaux Philippe O. A.
Published: January 2021

Current and future architectures rely on thread-level parallelism to sustain performance growth. These architectures have introduced a complex memory hierarchy, consisting of several cores organized hierarchically with multiple cache levels and NUMA nodes. These memory hierarchies can have an impact on the performance and energy efficiency of parallel applications as the importance of memory access locality is increased. In order to improve locality, the analysis of the memory access behavior of parallel applications is critical for mapping threads and data. Nevertheless, most previous work relies on indirect information about the memory accesses, or does not combine thread and data mapping, resulting in less accurate mappings.

In this paper, we propose the Sharing-Aware Memory Management Unit (SAMMU), an extension to the memory management unit that allows it to detect the memory access behavior in hardware. With this information, the operating system can perform online mapping without any previous knowledge about the behavior of the application. In the evaluation with a wide range of parallel applications (NAS Parallel Benchmarks and PARSEC Benchmark Suite), performance was improved by up to 35.7% (10.0% on average) and energy efficiency was improved by up to 11.9% (4.1% on average). These improvements happened due to a substantial reduction of cache misses and interconnection traffic.
In Situ Surface-Enhanced Raman Spectroscopy Characterization of Electrocatalysis with Different Nanostructures
Authors: Wen Bao-Ying , Chen Qing-Qi , Radjenovic Petar M. , Dong Jin-Chao , Tian Zhong-Qun , Li Jian-Feng
Published: January 2021

As energy demands increase, electrocatalysis serves as a vital tool in energy conversion. Elucidating electrocatalytic mechanisms using in situ spectroscopic characterization techniques can provide experimental guidance for preparing high-efficiency electrocatalysts. Surface-enhanced Raman spectroscopy (SERS) can provide rich spectral information for ultratrace surface species and is extremely well suited to studying their activity. To improve the material and morphological universalities, researchers have employed different kinds of nanostructures that have played important roles in the development of SERS technologies. Different strategies, such as so-called borrowing enhancement from shell-isolated modes and shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS)-satellite structures, have been proposed to obtain highly effective Raman enhancement, and these methods make it possible to apply SERS to various electrocatalytic systems. Here, we discuss the development of SERS technology, focusing on its applications in different electrocatalytic reactions (such as oxygen reduction reactions) and at different nanostructure surfaces, and give a brief outlook on its development.
Graphene-like Graphite as a Novel Cathode Material with a Large Capacity and Moderate Operating Potential for Dual Carbon Batteries
Authors: Inamoto Junichi , Sekito Kazuhiro , Kobayashi Naoya , Matsuo Yoshiaki
Published: January 2021

Dual carbon batteries have recently attracted significant attention because of their ecofriendliness and reliability. In this study, graphene-like graphite (GLG) was prepared by thermal reduction of graphite oxide to be used as a cathode material, and the electrochemical PF6
− anion-intercalation reaction into GLG was investigated. Decreasing the heat-treatment temperature of GLGs from 900 °C to 600 °C resulted in increasing the reversible capacities and interlayer distances of GLG samples. Among them, GLG synthesized at 700 °C (GLG700) showed the largest discharge capacity of 137 mAh g−1, which was much larger than that of graphite (52 mAh g−1). Variations in the X-ray diffraction patterns and Raman spectra of GLG700 indicated that the stage number reached 1 at 4.8 V (vs Li+/Li) while that of graphite was 2 at the same potential. This indicates that GLG could store PF6
− anion in every interlayer, which is probably one of the main causes of the larger capacity. The charge–discharge cycling test of GLG700 showed that the capacity gradually increased during cycling, and the coulombic efficiency was approximately 97% at every cycle after the 5th cycle. These results clearly demonstrate that GLG can be used as a cathode material with a large capacity for dual carbon batteries.
Editors’ Choice—Diffusion Media for Cation Contaminant Transport Suppression into Fuel Cell Electrodes
Authors: Komini Babu Siddharth , O’Brien Thomas , Workman Michael J. , Wilson Mahlon , Mukundan Rangachary , Borup Rod
Published: January 2021

Polymer electrolyte membrane fuel cells provide an alternative option to fossil fuel-based energy conversion devices. However, the corrosion of fuel cell components, specifically the bipolar plates, introduces contaminants (e.g., Fe, Ni) into the membrane electrode assembly (MEA). These contaminants accelerate the ionomer degradation by acting as a Fenton’s reagent, decreasing the fuel cell’s durability. This study presents the mechanism and the diffusion media properties affecting the transport of cation contaminants into the MEA. Cation contaminant transport was studied after altering the gas diffusion layers (GDLs) wettability, emulating the GDL properties after prolonged operation, by ex situ hydrogen peroxide treatment or in situ electrochemical potential cycling. A GDL with crack-free microporous layer (MPL) showed a lower cation transport rate to the catalyst layer than MPL with cracks after both ex situ and in situ treatment. A novel GDL was developed from modification of the conventional GDL via the addition of a hydrophobic layer to the GDL substrate, which suppressed the contaminant cation transport significantly. This novel GDL also showed improved fuel cell performance.
A dynamic model of the body gas stores for carbon dioxide, oxygen, and inert gases that incorporates circulatory transport delays to and from the lung
Authors: Magor-Elliott Snapper R. M. , Fullerton Christopher J. , Richmond Graham , Ritchie Grant A. D. , Robbins Peter A.
Published: January 2021

A model for the body gas stores has been generated that is applicable to both respiratory gases (CO2 and O2) and inert gases. It is based on anatomical details for organ volumes and blood contents together with anatomical details of the large arteries. It can be scaled to the body size and composition of different individuals. The model enables mixed venous gas compositions to be predicted from the systemic arterial compositions.
Prognostic Impact of DNA‐Image‐Cytometry in Neuroendocrine (Carcinoid) Tumours
Authors: Raatz H. , Böcking A. , Hauptmann S.
Published: January 2021

Establishing prognosis proves particularly difficult with neuroendocrine tumours (NETs) as a benign looking histology can be associated with a malignant behaviour. In order to identify prognostic factors we examined 44 gastrointestinal and pulmonary, paraffin‐embedded NETs histologically and immunohistochemically. DNA‐image‐cytometry was used to examine 40 of these. We found that poor differentiation (corresponding to a Soga and Tazawa type D) and infiltrative growth correlated with a poorer prognosis. Moreover, parameters determined by diagnostic DNA cytometry like the 5c‐exceeding rate, the 2c‐deviation index, DNA‐grade of malignancy, DNA‐entropy and the type of DNA histogram were found to be of prognostic relevance. Morphometric parameters like the form factor and the mean nuclear area were relevant for survival, tumour recurrence and metastasis. However, in the multivariate analysis the only independent risk factor was the histological differentiation. The 5c‐exceeding rate is a good objective risk factor, which can be used particularly in cases in which only a fine needle biopsie is available. Direct comparison of the histology and the 5c‐exceeding rate in the multivariate analysis suggests that the 5c‐exceeding rate taken as sole prognostic factor might be of higher prognostic relevance than the histology but larger studies are needed to confirm this.
An Automated Method for the Quantification and Fractal Analysis of Immunostaining
Authors: Gerger Armin , Bergthaler Patrick , Smolle Josef
Published: January 2021

Aims. In tissue counter analysis (TCA) digital images of complex histologic sections are dissected into elements of equal size and shape, and digital information comprising grey level, colour and texture features is calculated for each element. In this study we assessed the feasibility of TCA for the quantitative description of amount and also of distribution of immunostained material. Methods. In a first step, our system was trained for differentiating between background and tissue on the one hand and between immunopositive and so‐called other tissue on the other. In a second step, immunostained slides were automatically screened and the procedure was tested for the quantitative description of amount of cytokeratin (CK) and leukocyte common antigen (LCA) immunopositive structures. Additionally, fractal analysis was applied to all cases describing the architectural distribution of immunostained material. Results. The procedure yielded reproducible assessments of the relative amounts of immunopositive tissue components when the number and percentage of CK and LCA stained structures was assessed. Furthermore, a reliable classification of immunopositive patterns was found by means of fractal dimensionality. Conclusions. Tissue counter analysis combined with classification trees and fractal analysis is a fully automated and reproducible approach for the quantitative description in immunohistology.
Diagnostic and Prognostic Value Of Ki67 Proliferation Fraction in Serous Effusions
Authors: Schönherr Alexandra , Bayer Mary , Böcking Alfred
Published: January 2021

The Ki67 proliferation rate of mesothelial cells was determined in 20 effusions due to malignant mesotheliomas and in 20 non‐neoplastic effusions, to investigate if this marker may be useful to identify neoplastic mesothelioma cells and if there is a correlation between proliferation rate and survival time. Using the ABC‐method, effusions were immunostained and the marker Ki67 was evaluated quantitatively. Ki67 proliferation fraction showed rates from 2.3% to 70% in malignant mesothelioma cells and from 1.8% to 25.5% in reactive mesothelial cells. A significant difference was found (p=0.05) between those two groups. Assuming a threshold at 26%, a sensitivity of 25% and specificity of 100% resulted. Yet, due to its low sensitivity this marker seems not to be useful for differential diagnosis. Plotting surviving period against Ki67 proliferation fraction a correlation was observed which was not significant. Long term survivors (>28 month) showed proliferation rates below 3.8%. Unexpectedly a highly significant difference (p=0.001) between Ki67 proliferation rates of mesothelial cells from patients with malignant tumors other than mesothelial origin (7.0% to 25.5%) and mesothelial cells of patients without any malignant disease (1.8% to 16.3%) were observed. Setting a threshold at 10% for identification of a malignant disease, a sensitivity of 77.8% and specificity of 90.9% resulted.
Genomic Alterations in Primary Gastric Adenocarcinomas Correlate with Clinicopathological Characteristics and Survival
Authors: Weiss Marjan M. , Kuipers Ernst J. , Postma Cindy , Snijders Antoine M. , Pinkel Daniel , Meuwissen Stefan G. M. , Albertson Donna , Meijer Gerrit A.
Published: January 2021

Background & aims: Pathogenesis of gastric cancer is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. In order to investigate the patterns of chromosomal aberrations in gastric carcinomas, we performed genome‐wide microarray based comparative genomic hybridisation (microarray CGH). With this recently developed technique chromosomal aberrations can be studied with high resolution and sensitivity. Methods: Array CGH was applied to a series of 35 gastric adenocarcinomas using a genome‐wide scanning array with 2275 BAC and P1 clones spotted in triplicate. Each clone contains at least one STS for linkage to the sequence of the human genome. These arrays provide an average resolution of 1.4 Mb across the genome. DNA copy number changes were correlated with clinicopathological tumour characteristics as well as survival. Results: All thirty‐five cancers showed chromosomal aberrations and 16 of the 35 tumours showed one or more amplifications. The most frequent aberrations are gains of 8q24.2, 8q24.1, 20q13.12, 20q13.2, 7p11.2, 1q32.3, 8p23.1–p23.3, losses of 5q14.1, 18q22.1, 19p13.12–p13.3, 9p21.3–p24.3, 17p13.1–p13.3, 13q31.1, 16q22.1, 21q21.3, and amplifications of 7q21–q22, and 12q14.1–q21.1. These aberrations were correlated to clinicopathological characteristics and survival. Gain of 1q32.3 was significantly correlated with lymph node status (p=0.007). Tumours with loss of 18q22.1, as well as tumours with amplifications were associated with poor survival (p=0.02, both). Conclusions: Microarray CGH has revealed several chromosomal regions that have not been described before in gastric cancer at this frequency and resolution, such as amplification of at 7q21–q22 and 12q14.1–q21.1, as well gains at 1q32.3, 7p11.2, and losses at 13q13.1. Interestingly, gain of 1q32.3 and loss of 18q22.1 are associated with a bad prognosis indicating that these regions could harbour gene(s) that may determine aggressive tumour behaviour and poor clinical outcome.
Chromosomal Instability, Aneuploidy, and Gene Mutations in Human Sporadic Colorectal Adenomas
Authors: Giaretti Walter , Molinu Silvia , Ceccarelli Jenny , Prevosto Claudia
Published: January 2021

Whether in vivo specific gene mutations lead to chromosomal instability (CIN) and aneuploidy or viceversa is so far not proven. We hypothesized that aneuploidy among human sporadic colorectal adenomas and KRAS2 and APC mutations were not independent. Additionally, we investigated if 1p34–36 deletions by dual target FISH were associated with aneuploidy. Among 116 adenomas, 29 were DNA aneuploid by flow cytometry (25%) and 29 were KRAS2 mutated (25%). KRAS2 mutations were associated with aneuploidy (P=0.02). However, while G–C and G–T transversions were strongly associated with DNA aneuploidy (P=0.007), G–A transitions were not. Within a second series of 61 adenomas, we found, instead, that APC mutational status and aneuploidy by flow cytometry were not associated. However, a statistically significant association was found with specific APC mutations, i.e., occurring in the mutation cluster region (MCR, codons 1200–1500) or downstream (P=0.016). Finally, the correlation of 1p34–36 deletions with flow cytometric and FISH detected aneuploidy was also significant (P=0.01). Specific KRAS2 and APC mutations and loss of genes in the 1p34–36 region appear associated with aneuploidy suggesting that these events are not independent and may cooperate in inducing human sporadic colorectal adenomas. A cause effect relationship between gene mutations and aneuploidy remains, however, to be demonstrated.
Microarray Data Analysis: From Hypotheses to Conclusions Using Gene Expression Data
Authors: Armstrong Nicola J. , van de Wiel Mark A.
Published: January 2021

We review several commonly used methods for the design and analysis of microarray data. To begin with, some experimental design issues are addressed. Several approaches for pre‐processing the data (filtering and normalization) before the statistical analysis stage are then discussed. A common first step in this type of analysis is gene selection based on statistical testing. Two approaches, permutation and model‐based methods are explained and we emphasize the need to correct for multiple testing. Moreover, powerful approaches based on gene sets are mentioned. Clustering of either genes or samples is frequently performed when analyzing microarray data. We summarize the basics of both supervised and unsupervised clustering (classification). The latter may be of use for creating diagnostic arrays, for example. Construction of biological networks, such as pathways, is a statistically challenging but complex task that is a relatively new development and hence mentioned only briefly. We finish with some remarks on literature and software. The emphasis in this paper is on the philosophy behind several statistical issues and on a critical interpretation of microarray related analysis methods.
Implementation of Accurate and Fast DNA Cytometry by Confocal Microscopy in 3D
Authors: Ploeger Lennert S. , Huisman André , van der Gugten Jurryt , van der Giezen Dionne M. , Beliën Jeroen A. M. , Abbaker Abdelhadi Y. , Dullens Hub F. J. , Grizzle William , Poulin Neal M. , Meijer Gerrit A. , van Diest Paul J.
Published: January 2021

Background: DNA cytometry is a powerful method for measuring genomic instability. Standard approaches that measure DNA content of isolated cells may induce selection bias and do not allow interpretation of genomic instability in the context of the tissue. Confocal Laser Scanning Microscopy (CLSM) provides the opportunity to perform 3D DNA content measurements on intact cells in thick histological sections. Because the technique is technically challenging and time consuming, only a small number of usually manually selected nuclei were analyzed in different studies, not allowing wide clinical evaluation. The aim of this study was to describe the conditions for accurate and fast 3D CLSM cytometry with a minimum of user interaction to arrive at sufficient throughput for pilot clinical applications. Methods: Nuclear DNA was stained in 14 μm thick tissue sections of normal liver and adrenal stained with either YOYO‐1 iodide or TO‐PRO‐3 iodide. Different pre‐treatment strategies were evaluated: boiling in citrate buffer (pH 6.0) followed by RNase application for 1 or 18 hours, or hydrolysis. The image stacks obtained with CLSM at microscope magnifications of ×40 or ×100 were analyzed off‐line using in‐house developed software for semi‐automated 3D fluorescence quantitation. To avoid sectioned nuclei, the top and bottom of the stacks were identified from ZX and YZ projections. As a measure of histogram quality, the coefficient of variation (CV) of the diploid peak was assessed. Results: The lowest CV (10.3%) was achieved with a protocol without boiling, with 1 hour RNase treatment and TO‐PRO‐3 iodide staining, and a final image recording at ×60 or ×100 magnifications. A sample size of 300 nuclei was generally achievable. By filtering the set of automatically segmented nuclei based on volume, size and shape, followed by interactive removal of the few remaining faulty objects, a single measurement was completely analyzed in approximately 3 hours. Conclusions: The described methodology allows to obtain a largely unbiased sample of nuclei in thick tissue sections using 3D DNA cytometry by confocal laser scanning microscopy within an acceptable time frame for pilot clinical applications, and with a CV small enough to resolve smaller near diploid stemlines. This provides a suitable method for 3D DNA ploidy assessment of selected rare cells based on morphologic characteristics and of clinical samples that are too small to prepare adequate cell suspensions.
Different DNA Loidy Patterns for the Differentiation of Common Subtypes of Renal Tumors
Authors: Li Guorong , Cottier Michèle , Sabido Odile , Gentil-Perret Anne , Lambert Claude , Genin Christian , Tostain Jacques
Published: January 2021

Objectives: The common subtypes of renal tumors are conventional or clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma. Each subtype has its distinct histogenesis and clinical evolution. DNA ploidy is viewed as a marker of gross genomic aberrations. The aim of this study is to evaluate the DNA ploidy in the common subtypes of renal tumors to increase our understanding of renal tumor biology and to broaden clinical application of DNA ploidy. Methods: 38 renal tumor samples (13 clear cell RCCs, 12 papillary RCCs, 7 chromophobe RCCs, and 6 oncocytomas) were studied. Five biopsies of different parts of each fresh tumor were subjected to a flow cytometric analysis of DNA ploidy. Results: All tumors except one papillary RCC generated interpretable DNA histograms. Flow cytometric analysis of oncocytomas showed the diploid pattern (29/30 frequencies) while the chromophobe RCC never showed the diploid pattern (0/55 frequencies) (p < 0.01). 3/7 chromopbobe RCCs possessed the hypodiploid stemline. The hypodiploid stemline appeared neither in conventional RCCs (0/63 frequencies) nor in papillary RCCs (0/50 frequencies). The diploid pattern was dominant in conventional and papillary RCCs. 10/13 (76.9%) of clear cell RCCs and 9/11 (81.8%) of papillary RCCs possessed a homogeneous DNA ploidy pattern while only 1/7 (14.3%) has a homogeneous DNA ploidy pattern. 6/7 chromophobe RCCs had multiple aneuploid stemlines. Conclusions: Flow cytometric analysis reveals that conventional and papillary RCCs are more homogeneous than chromophobe RCC. Each subtype of renal tumors possesses a specific DNA ploidy pattern. The analysis of DNA ploidy is useful for the differentiation of common subtypes of renal tumors in morphologically difficult cases.
Biphasic Chromatin Structure and FISH Signals Reflect Intranuclear Order
Authors: Chaudhuri Jyoti P. , Kasprzycki Eva , Battaglia Mathew , McGill John R. , Brøgger Anton , Walther Joachim-U. , Reith Albrecht
Published: January 2021

Background and Aim: One of the two parental allelic genes may selectively be expressed, regulated by imprinting, X‐inactivation or by other less known mechanisms. This study aims to reflect on such genetic mechanisms. Materials and Methods: Slides from short term cultures or direct smears of blood, bone marrow and amniotic fluids were hybridized with FISH probes singly, combined or sequentially. Two to three hundred cells were examined from each preparation. Results and Aignificance: A small number of cells (up to about 5%), more frequent in leukemia cases, showed the twin features: (1) nuclei with biphasic chromatin, one part decondensed and the other condensed; and (2) homologous FISH signals distributed equitably in those two regions. The biphasic chromatin structure with equitable distribution of the homologous FISH signals may correspond to the two sets of chromosomes, supporting observations on ploidywise intranuclear order. The decondensed chromatin may relate to enhanced transcriptions or advanced replications. Conclusions: Transcriptions of only one of the two parental genomes cause allelic exclusion. Genomes may switch with alternating monoallelic expression of biallelic genes as an efficient genetic mechanism. If genomes fail to switch, allelic exclusion may lead to malignancy. Similarly, a genome‐wide monoallelic replication may tilt the balance of heterozygosity resulting in aneusomy, initiating early events in malignant transformation and in predicting cancer mortality.
Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors
Authors: Bontkes Hetty J. , Ruizendaal Janneke J. , Schreurs Marco W. J. , Kramer Duco , Meijer Chris J. L. M. , Hooijberg Erik
Published: January 2021

Recombinant adenoviruses (RAd) and recombinant vaccinia viruses (RVV) expressing tumour‐associated antigens (TAA) are used as anti‐tumour vaccines. It is important that these vaccines deliver the TAA to dendritic cells (DC) for the induction of a strong immune response. Infection of myeloid DC (MDC) with RAd alone is relatively inefficient but CD40 retargeting significantly increases transduction efficiency and DC maturation. Infection with RVV is efficient without DC maturation. Plasmacytoid dendritic cells (PDC) play a role in the innate immune response to viral infections through the secretion of IFNα but may also play a role in specific T‐cell induction. The aim of our study was to investigate whether PDC are better targets for RAd and RVV based vaccines. RAd alone hardly infected PDC (2%) while CD40 retargeting did not improve transduction efficiency, but it did increase PDC maturation (25% CD83 positive cells). Accordingly, specific CTL activation by RAd infected PDC was limited (the number of IFNγ producing CTL was reduced by 75% compared to stimulation with peptide loaded PDC). RVV infected PDC specifically stimulated CTL but PDC were not activated. These Results indicate that PDC are not ideal targets for RAd and RVV based vaccines. However, PDC induced specific CTL activation after pulsing with recombinant protein, indicating that PDC can also cross‐present antigens released from surrounding infected cells.