bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimising whole body computed tomography doses for paediatric trauma patients: a Swiss retrospective analysis
Authors: Simma Leopold , Fornaro Juergen , Stahr Nikolai , Lehner Markus , Roos Justus E , Lima Thiago Viana Miranda
Published: March 2022

We aimed to evaluate the impact of a low-dose whole-body computed tomography (WBCT) protocol on radiation doses in paediatric major trauma patients. Retrospective cohort study of paediatric trauma patients (<16 years) at a national level 1 paediatric trauma centre (PTC) over a 6 year period prior and post introduction of a low-dose WBCT protocol (2014–2019). Demographic data, patient characteristics, CT device, and exposure information including scan range, dose-length product, and volume CT dose index were collected. Effective dose (ED) and exposure parameters were compared before and after protocol introduction. Forty-eight patients underwent WBCT during the study period. Prior to introduction of the low-dose protocol (n = 18), the ED was 20.6 mSv (median 20.1 ± 5.3 mSv [range 12.5–30.7]). After introduction of the low-dose WBCT protocol (n = 30), mean ED was 4.8 mSv (median 2.6 ± 5.0 [range: 0.8–19.1]). This resulted in a reduction of 77% in mean ED (p value <0.001). Significant radiation dose reduction of 77% can be achieved with low-dose WBCT protocols in PTCs.
Facile deposition of palladium oxide (PdO) nanoparticles on CoNi2S4 microstructures towards enhanced oxygen evolution reaction
Authors: Tahira Aneela , Aftab Umair , Solangi Muhammad Yameen , Gradone Alessandro , Morandi Vittorio , Medany Shymaa S , Kasry Amal , Infantes-Molina Antonia , Nafady Ayman , Ibupoto Zafar Hussain
Published: March 2022

Strong demand for renewable energy resources and clean environments have inspired scientists and researchers across the globe to carry out research activities on energy provision, conversion, and storage devices. In this context, development of outperform, stable, and durable electrocatalysts has been identified as one of the major objectives for oxygen evolution reaction (OER). Herein, we offer facile approach for the deposition of few palladium oxide (PdO) nanoparticles on the cobalt–nickel bi-metallic sulphide (CoNi2S4) microstructures represented as PdO@ CoNi2S4 using ultraviolet light (UV) reduction method. The morphology, crystalline structure, and chemical composition of the as-prepared PdO@ CoNi2S4 composite were probed through scanning electron microscopy, powder x-ray diffraction, high resolution transmission electron microscopy, energy dispersive spectroscopy and x-ray photoelectron spectroscopy techniques. The combined physical characterization results revealed that ultraviolet light (UV) light promoted the facile deposition of PdO nanoparticles of 10 nm size onto the CoNi2S4 and the fabricated PdO@ CoNi2S4 composite has a remarkable activity towards OER in alkaline media. Significantly, it exhibited a low onset potential of 1.41 V versus reversible hydrogen electrode (RHE) and a low overpotential of 230 mV at 10 mA cm−2. Additionally, the fabricated PdO@ CoNi2S4 composite has a marked stability of 45 h. Electrochemical impedance spectroscopy has shown that the PdO@CoNi2S4 composite has a low charge transfer resistance of 86.3 Ohms, which favours the OER kinetics. The PdO@ CoNi2S4 composite provided the multiple number of active sites, which favoured the enhanced OER activity. Taken together, this new class of material could be utilized in energy conversion and storage as well as sensing applications.
Evaluating the content accuracy of augmented reality applications on the Solar System
Authors: Aydin Mirac , Ozcan Ibrahim
Published: March 2022

Advancements in mobile technologies have accelerated mobile Augmented Reality (AR), and many applications have been developed and presented in online stores. This study aims to evaluate the accuracy of the AR model of the Solar System simulated in mobile AR applications located in the Google Play Store. The applications were examined in the store between 1 December 2020 and 1 January 2021. A criterion was developed and 23 applications were determined that met the criterion. The mobile AR applications were coded according to a coding scheme devoted to evaluating the content requirements of the Solar System. The results showed that the applications do not meet the requirements of the model of the Solar System. In addition, the applications are insufficient to accommodate the gravity, inertia, scale, and system formation that are the requirements of the teaching of the Solar System as a whole. The results also revealed that the applications have the potential to lead to similar misconceptions as mentioned in the literature. The results suggest that the applications should be developed or reviewed by specialists or teachers before using in science classrooms. In addition, research on AR should be more focused on the quality of mobile AR applications in online stores.
Enhancing cavitation dynamics and its mechanical effects with dual-frequency ultrasound
Authors: Li Zhangyong , Zou Qingqin , Qin Dui
Published: March 2022

Objective. Acoustic cavitation and its mechanical effects (e.g. stress and strain) play a primary role in ultrasound applications. Introducing encapsulated microbubbles as cavitation nuclei and utilizing dual-frequency ultrasound excitation are highly effective approaches to reduce cavitation thresholds and enhance cavitation effects. However, the cavitation dynamics of encapsulated microbubbles and the resultant stress/strain in viscoelastic tissues under dual-frequency excitation are poorly understood, especially for the enhancement effects caused by a dual-frequency approach. The goal of this study was to numerically investigate the dynamics of a lipid-coated microbubble and the spatiotemporal distributions of the stress and strain under dual-frequency excitation. Approach. The Gilmore–Zener bubble model was coupled with a shell model for the nonlinear changes of both shell elasticity and viscosity to accurately simulate the cavitation dynamics of lipid-coated microbubbles in viscoelastic tissues. Then, the spatiotemporal evolutions of the cavitation-induced stress and strain in the surrounding tissues were characterized quantitatively. Finally, the influences of some paramount parameters were examined to optimize the outcomes. Main results. We demonstrated that the cavitation dynamics and associated stress/strain were prominently enhanced by a dual-frequency excitation, highlighting positive correlations between the maximum bubble expansion and the maximum stress/strain. Moreover, the results showed that the dual-frequency ultrasound with smaller differences in its frequencies and pressure amplitudes could enhance the bubble oscillations and stress/strain more efficiently, whereas the phase difference manifested small influences under these conditions. Additionally, the dual-frequency approach seemed to show a stronger enhancement effect with the shell/tissue viscoelasticity increasing to a certain extent. Significance. This study might contribute to optimizing the dual-frequency operation in terms of cavitation dynamics and its mechanical effects for high-efficient ultrasound applications.
A two-step method to improve image quality of CBCT with phantom-based supervised and patient-based unsupervised learning strategies
Authors: Liu Yuxiang , Chen Xinyuan , Zhu Ji , Yang Bining , Wei Ran , Xiong Rui , Quan Hong , Liu Yueping , Dai Jianrong , Men Kuo
Published: March 2022

Objective. In this study, we aimed to develop deep learning framework to improve cone-beam computed tomography (CBCT) image quality for adaptive radiation therapy (ART) applications. Approach. Paired CBCT and planning CT images of 2 pelvic phantoms and 91 patients (15 patients for testing) diagnosed with prostate cancer were included in this study. First, well-matched images of rigid phantoms were used to train a U-net, which is the supervised learning strategy to reduce serious artifacts. Second, the phantom-trained U-net generated intermediate CT images from the patient CBCT images. Finally, a cycle-consistent generative adversarial network (CycleGAN) was trained with intermediate CT images and deformed planning CT images, which is the unsupervised learning strategy to learn the style of the patient images for further improvement. When testing or applying the trained model on patient CBCT images, the intermediate CT images were generated from the original CBCT image by U-net, and then the synthetic CT images were generated by the generator of CycleGAN with intermediate CT images as input. The performance was compared with conventional methods (U-net/CycleGAN alone trained with patient images) on the test set. Results. The proposed two-step method effectively improved the CBCT image quality to the level of CT scans. It outperformed conventional methods for region-of-interest contouring and HU calibration, which are important to ART applications. Compared with the U-net alone, it maintained the structure of CBCT. Compared with CycleGAN alone, our method improved the accuracy of CT number and effectively reduced the artifacts, making it more helpful for identifying the clinical target volume. Significance. This novel two-step method improves CBCT image quality by combining phantom-based supervised and patient-based unsupervised learning strategies. It has immense potential to be integrated into the ART workflow to improve radiotherapy accuracy.
Investigation of diethanolamine (DEA) as a chelating agent in the fabrication of fluorine-free propionate route YBa2Cu3O7 (YBCO) thin films
Authors: Daniel Andrada , Nasui Mircea , Petrisor Jr Traian , Sonher Ramona Bianca , Augieri Andrea , Pop Cornelia , Palau Anna , Vannozzi Angelo , Celentano Giuseppe , Ciontea Lelia , Petrisor Traian
Published: March 2022

The role of diethanolamine (DEA) as a chelating agent was investigated in a fluorine-free precursor solution for the growth of superconducting YBa2Cu3O7 (YBCO) thin films via chemical solution deposition. Infrared spectroscopy and thermal analyses were employed to elucidate the interactions between the chelating agent and propionate-based coating solution. The physical properties of the as-obtained YBCO films were investigated to assess the effect of DEA addition on film growth. Special emphasis was placed on the determination of superconducting transport properties. These have been investigated in wide magnetic field (0–18 T) and temperature (4.5–77 K) ranges to account for various possible application scenarios. The 100 nm thick YBCO film deposited on a (001) SrTiO3 single-crystal substrate exhibited a critical current density of 4 MA cm−2 at 77 K in self-field.
Status of the MUonE experiment
Authors: Abbiendi G
Published: March 2022

The MUonE experiment has been proposed to measure the differential cross section ofμe elastic scattering, by colliding the 160 GeV muons of the CERN M2 beam with atomic electrons of thin target plates. From a very precise measurement of the shape one can achieve a competitive determination of the leading hadronic contribution to the muon magnetic moment, independent from the other existing ones. In preparation for the Test Run with a reduced setup the detector geometry has been optimised. Expected yields for a first physics run with limited statistics are discussed, together with prospects for the assessment of the main systematic uncertainties.
The paradigm of warm quintessential inflation and spontaneous baryogenesis
Authors: Basak Soumen , Bhattacharya Sukannya , Gangopadhyay Mayukh R. , Jaman Nur , Rangarajan Raghavan , Sami M.
Published: March 2022

In this paper, we consider a scenario of spontaneous baryogenesis in a framework of warm quintessential inflation where the residual inflaton field, left out after warm inflation, plays the role of quintessence field at late times and is coupled to a non-conserved baryonic current. Assuming a four fermion (B – L) violating effective interaction, we have demonstrated that the required baryon asymmetry can be produced successfully in this case. We show that the post-inflationary evolution, with the underlying scalar field potential, V(ϕ) = V
0
4exp(–αϕ
n/M
4
Pl), n > 1 well suited to warm inflation, exhibits scaling behaviour soon after a brief kinetic regime. We show that the coupling of the scalar field to massive neutrino matter can give rise to exit from the scaling regime to cosmic acceleration at late times as massive neutrinos turn non-relativistic. The proposed model is shown to successfully describe the cosmic history from inflation to late time acceleration, with the evolution independent of initial conditions, along with the generation of baryon asymmetry during the post-inflationary era. A brief analysis of relic gravity waves produced in the scenario is presented.
Early sonographic response to a new medical therapy is associated with future treatment response or failure in patients with inflammatory bowel disease
Authors: Smith Rebecca L. , Taylor Kirstin M. , Friedman Antony B. , Gibson David J. , Con Danny , Gibson Peter R.
Published: March 2022

Objective

Gastrointestinal ultrasound (GIUS) accurately assesses inflammation and is responsive to changes in inflammatory bowel disease. This study aimed to determine the prognostic utility of sonographic response in the first 14 weeks of a newly-instituted therapy with therapeutic response at 46 weeks and to compare its performance with standard clinical assessment tools.

Methods

Patients with sonographic evidence of inflammation were assessed by GIUS, clinical activity, serum C-reactive protein and faecal calprotectin again 2, 6 and 14 weeks after commencing a new biologic or thiopurine. Treatment failure was defined as undergoing surgery, hospitalisation, escalation of dosage or introduction of new medication over 46-weeks’ follow-up. Sonographic response was defined as a decrease in bowel wall thickness and improved vascularity.

Results

In 31 patients (median age 49 years, 74% Crohn’s disease), sonographic response at 14 weeks [OR 19.3, 95% confidence interval (CI), 3.23–101.10; P = 0.0054] and faecal calprotectin (P = 0.018), but no clinical disease activity or C-reactive protein, were predictive of subsequent treatment response. Sonographic response alone was predictive at week 6 (P = 0.016), but not week 2. 16% reduction in bowel wall thickness at 6 weeks (area-under-the-receiver-operator-curve=0.86; P = 0.002; sensitivity 72%, specificity 90%), with similar performance for 10% at 14 weeks, was associated with treatment response.

Conclusion

Sonographic response as early as 6 weeks after initiation of a new therapy may accurately predict treatment outcomes over 46 weeks and is superior to other markers used to monitor disease activity.
Single-Center Retrospective Review of the Presentation and Initial Care of Esophageal Button Battery Impactions 2007–2020
Authors: Sinclair Elizabeth M. , Agarwal Maneesha , Santore Matthew T. , Sauer Cary G. , Riedesel Erica L.
Published: March 2022

Objective

The aims of this study were to characterize the patient population and initial presentation and care of esophageal button battery ingestion and provide descriptive data including factors affecting accurate diagnosis, duration of battery exposure, and battery removal.

Methods

This was a retrospective cohort study from 2007 to 2020 at a single-center, large-volume, urban academic pediatric hospital system. Included participants were children 6 months to 18 years old who underwent removal of an esophageal button battery impaction at our institution.

Results

Our cohort comprised 63 patients; ages ranged from 7 to 87 months with a median of 27 months. Median button battery size was 2.12 cm with 59% lodged in the proximal esophagus. A prolonged impaction, greater than 12 hours, occurred in 46% of patients. Risk ratio analysis demonstrated that lack of caregiver suspicion of ingestion was associated with prolonged impaction (risk ratio, 3.39; confidence interval, 2.15–5.34). Misdiagnosis of button battery ingestion occurred in 10% of cases. The majority of patients, 87%, required transfer from a referring facility with a median total distance of 37 miles (range, 1.4–160 miles) from home to facility where battery was removed.

Conclusion and Relevance

This study describes the initial presentation and care of a large cohort of pediatric esophageal button battery ingestion. It emphasizes the continued need for primary prevention, prompt identification, and removal of these batteries. There are many challenges in caring for these patients involving multiple pediatric disciplines, and guidelines encompassing a multidisciplinary approach would be beneficial.
Impact of the COVID-19 Pandemic on the Severity of Diabetic Ketoacidosis Presentations in a Tertiary Pediatric Emergency Department
Authors: Jafari Kaileen , Koves Ildiko , Rutman Lori , Brown Julie C.
Published: March 2022

Introduction:

More severe presentations of diabetic ketoacidosis (DKA) have been reported during the coronavirus disease 2019 (COVID-19) pandemic, possibly due to avoidance of healthcare settings or reduced access to care. To date, no studies have utilized statistical process control to relate temporal COVID-19 events with DKA severity. Our objectives were (1) to determine whether the severity of pediatric DKA presentations changed during COVID-19 and (2) to temporally relate changes in severity with regional pandemic events.

Methods:

This study was a retrospective chart review of 175 patients younger than 18 years with DKA presenting to a pediatric emergency department in the United States between 5/1/2019 and 8/15/2020. As part of our ongoing clinical standard work in ED management of DKA, DKA severity measures, including presenting pH, the proportion of PICU admissions, and admission length of stay, were analyzed using statistical process control.

Results:

During COVID-19, we found special cause variation with a downward shift in the mean pH on DKA presentation from 7.2 to 7.1 for all patients. The proportion of DKA patients requiring PICU admission increased from 34.2% to 54.6%. Changes temporally corresponded to the statewide bans on large events (3/11/2020), school closures (3/13/2020), and a reduction in our institution’s emergency department volumes. Admission length of stay was unchanged.

Conclusions:

Pediatric DKA presentations were more severe from March to June 2020, correlating with regional COVID-19 events. Future quality improvement interventions to reduce delayed presentations during COVID-19 surges or other natural disasters should target accessibility of care and public education regarding the importance of timely care for symptoms.
Minimizing the “Kitchen Sink” Approach: De-implementation of Unnecessary Care for Patients with Anaphylaxis in a Pediatric Emergency Department
Authors: Vanston Laura , Ogawa Kaleigh , Freeman Julia , Bauer Maureen , Carel Kirsten , Topoz Irina
Published: March 2022

Introduction:

Epinephrine is the only medication that prevents morbidity and mortality in anaphylaxis. Systemic corticosteroids and H2 receptor antagonists (H2RA) may benefit select cases but are not universally indicated. This study aims to de-implement the universal use of steroids and H2RAs and emphasize epinephrine-focused care for children with anaphylaxis during acute care visits. The study aims to reduce steroid and H2RA use from 81% and 60%, respectively, to 30% by December 2019.

Methods:

The primary outcome measures were the percent of patients receiving steroids and H2RAs in the emergency department (ED) or urgent care (UC). Process measure was the frequency of intravenous (IV) line placement. Balancing measures were ED/UC length of stay, admission rate, and ED/UC return visit rate. In addition, a multidisciplinary team designed the following interventions: (1) anaphylaxis clinical pathway to emphasize epinephrine-focused care, outline criteria for second-line therapies and a provider guideline for ED/UC observation; (2) standardize unit-based anaphylaxis medication kits; (3) optimize electronic medical record tools, including order sets and discharge instructions to be concordant with guideline recommendations.

Results:

The study included 870 patients. There was special cause variation in the use of steroids (81%–33%) and H2RAs (60%–11%), ED/UC Length of stay decreased (6.2–5.0 hours). There was no special cause variation in admission rates or ED/UC return visit rates.

Conclusion:

Universal use of systemic steroids and H2RAs can be safely de-implemented in pediatric patients with anaphylaxis using quality improvement methods.
The connection between the gut mycobiome community of natural black soldier fly populations and their environment
Authors: Vitenberg Tzach , Goldway Martin , Opatovsky Itai
Published: March 2022

In contrast to interactions between prokaryotic organisms (e.g. bacteria) and insects, an understanding of the interactions between eukaryotic microorganisms (e.g. fungi) and insects is lacking. In this study, black soldier fly larvae were collected from natural populations in household composts. The mycobiome composition of the larval gut and environment was identified using next generation sequencing. The nutrient composition of the larvae’s environment was analyzed. The mycobiome composition was divided into three groups: the first included larvae from Kfar HaHoresh that comprised mostlyMeyerozymaand were influenced by the fiber and carbohydrate composition of the compost; the second included the compost samples from Kfar HaHoresh and Misgav Am that mainly comprised the Dipodascaceae family and were influenced by the fiber composition of the compost. The third group contained all the remaining compost and larvae samples and mainly comprised the genusCandida.Candidaspp. are the most common in the environment and may thus affect their abundance in the insect gut. However, this species may be adapted to the insect’s gut, providing the insect with a benefit that allows the insect to disperseCandidato new resource patches and thereby help increase its abundance in the environment. In cases where dominant species are not present, it seems that the important factor determining fungal composition in the insect gut is its diet. Understanding the metabolic effect of fungi, e.g.Candida, on the BSF larvae is still a black box which requires further study.

IMPORTANCE

The research analyzed the mycobiome composition of BSF larvae from natural environments. It was found that the most dominant fungi in these communities is the Candida genus, which was found also dominant in the BSF environment (household compost) that differ in its nutrient composition. Understanding the metabolic effect of these fungi on the BSF larvae have the potential to dramatically affect the physiological condition of the insect. Revealing these metabolic interactions may help to increase the rearing efficiency of insects, such as the BSF, which is currently being reared at large scales as an alternative protein source.
Do amplifiers of selection maximise average fitness?
Authors: Sharma Nikhil , Traulsen Arne
Published: March 2022

Evolutionary dynamics on graphs has remarkable features: For example, it has been shown that amplifiers of selection exist that – compared to an unstructured population – increase the fixation probability of advantageous mutations, while they decrease the fixation probability of disadvantageous mutations. So far, the theoretical literature has focused on the case of a single mutant entering a graph structured population, asking how the graph affects the probability that a mutant takes over a population and the time until this typically happens. For continuously evolving systems, the more relevant case is when mutants constantly arise in an evolving population. Typically, such mutations occur with a small probability during reproduction events. We thus focus on the low mutation rate limit. The probability distribution for the fitness in this process converges to a steady-state at long times. Intuitively, amplifiers of selection are expected to increase the population’s mean fitness in the steady-state. Similarly, suppressors of selection are expected to decrease the population’s mean fitness in the steady-state. However, we show that another category of graphs, called suppressor of fixation, can attain the highest population mean fitness. The key reason behind this is their ability to efficiently reject deleterious mutants. This illustrates the importance of the deleterious mutant regime for the long-term evolutionary dynamics, something that seems to have been overlooked in the literature so far.
Modified double‐guidewire technique using a new double‐lumen catheter and 0.018‐inch guidewire for difficult biliary cannulation
Authors: Kawasaki Yuki , Hijioka Susumu , Saito Yutaka
Published: March 2022

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Intervention for swallowing problems in adults with cerebral palsy
Authors: Yi You Gyoung
Published: March 2022

This commentary is on the original article by McAllister et al. on pages 1017–1024 of this issue.
Psychometric properties of the Kessler psychological scales in a Swiss young‐adult community sample indicate poor suitability for community screening for mental disorders
Authors: Osman Naweed , Chow Winnie S. , Michel Chantal , Meisenzahl Eva , Schimmelmann Benno G. , Schultze‐Lutter Frauke
Published: March 2022

Aim

The Kessler psychological distress scales (K10 and K6) are used as screening tools to assess psychological distress related to the likely presence of a mental disorder. Thus, we studied the psychometric properties of their German versions in a Swiss community sample to evaluate their potential usefulness to screen for mental disorders or relevant mental problems in the community and, relatedly, for low threshold transdiagnostic German‐speaking services.

Methods

The sample consisted of 829 citizens of the Swiss canton Bern of age 19–43 years. K10/K6 were validated against mini‐international neuropsychiatric interview (M.I.N.I.) diagnoses, questionnaires about health status and quality of life. Receiver operating characteristic (ROC) curve analyses were used to test for general discriminative ability and to select optimal cut‐offs of the K10 and K6 for non‐psychotic full‐blown and subthreshold mental disorders.

Results

Cronbach's alphas were 0.81 (K10) and 0.70 (K6). ROC analyses indicated much lower optimal thresholds than earlier suggested; 10 for K10 and 6 for K6. At these thresholds, against M.I.N.I. diagnoses, Cohen's κ (≤0.173) and correspondence rates (≤58.14%) were insufficient throughout. Values were higher at the earlier suggested threshold, yet, at the cost of sensitivity that was below 0.5 in all but three, and below 0.3 in all but six cases.

Conclusions

For the lack of sufficient validity and sensitivity, respectively, our findings suggest that both K10 and K6 would only be of limited use in a low‐threshold transdiagnostic mental health service for young adults in Switzerland and likely other German‐speaking countries.
THE ENDLESS ACCUMULATION OF HISTORY IN FINANCIAL TIMES
Authors: Biltoft C. N.
Published: March 2022

This essay engages with Amin Samman's incisive 2019 text, History in Financial Times, which unfolds a philosophy of history for contemporary “financial times.” I turn first to Samman's concept of the strange loops of financial history, and so to the historical turn initiated by the subprime crisis of 2008. Then, I add the concept of strange portraiture to Samman's idea of strange history. Borrowing a metaphor from Oscar Wilde's The Picture of Dorian Gray, I trace the oscillating appearance of the linked faces of homo historia and homo economicus, which each offer distinct explanatory frameworks “under the sign of finance.” In this way, I suggest that we can also observe how capitalism transformed the meaning and possible trajectories of something like fate from invented origins to imagined destinies. In that frame, I explore how the loops that Samman underscores are also bound to the ways in which history and economics have competed and continue to compete for ascendency as modern sense‐making epistemes with different time‐binding effects.
Morphologic, immunophenotypic, and molecular genetic comparison study in patients with clonal cytopenia of undetermined significance, myelodysplastic syndrome, and acute myeloid leukemia with myelodysplasia‐related changes: A single institution experience
Authors: Gao Linlin , Hyter Stephen , Zhang Da , Kelting Sarah , Woodroof Janet , Abdallah Al‐Ola , Yacoub Abdulraheem , McGuirk Joseph , Abdelhakim Haitham , Godwin Andrew K. , Cui Wei
Published: March 2022

Introduction

Next‐generation sequencing (NGS) analysis showed clonal cytopenia of undetermined significance (CCUS) as an immediate precursor to myelodysplastic syndrome (MDS).

Methods

We evaluated and compared morphologic, multiparametric flow cytometry (MFC), and molecular genetic findings in patients with CCUS (n = 37), MDS (n = 75), and acute myeloid leukemia with myelodysplasia‐related changes (AML‐MRC, n = 24).

Results

CCUS patients showed variable MFC abnormalities including >2% CD34+ myeloblasts (5.8%), altered antigen expression on myeloblasts, monocytes, and granulocytes (1.2, 1.5, and 0.2/case), abnormal maturation of myeloblasts (45.8%), decreased hematogones (17.6%), and decreased side scatter (SSC) of granulocytes (11.4%). CCUS patients with high‐risk mutations showed significantly more MFC abnormalities. However, CCUS patients with >20% variant allelic fraction (VAF) did not show more MFC aberrations than the rest of the group. MDS patients showed significantly more MFC abnormalities compared with CCUS patients (p = 7.8E‐05–0.047). Low‐grade MDS patients showed significantly fewer MFC abnormalities compared with high‐grade MDS or AML‐MRC patients (p = 1.89E‐05–0.04). AML‐MRC patients showed significantly elevated blast counts, more antigen aberrations, decreased hematogones, and decreased SSC of granulocytes compared with CCUS patients (p = 2.0E‐05–0.01). CCUS patients carried predominantly TET2/DNMT3A/ASXL1 mutations. They harbored fewer mutations in gene coding splicing factors compared with MDS patients (p = .0001–.02) and fewer mutations in tumor suppressor and transcription factor genes compared with AML‐MRC patients (p = .0006–.02).

Conclusions

CCUS is an immediate precursor to low‐grade MDS. The progression from CCUS to MDS to AML‐MRC is a stepwise process that requires acquisition of mutations in splicing, transcription factor, and tumor suppressor genes with accumulations of additional MFC abnormalities.
Worth the risk? Contemporary indications, yield and complications of lumbar punctures in a metropolitan Australian health service
Authors: Cody Ross , Mohsenifard Mahsa , Yip Gary , Aldridge Emogene , Bridge Francesca , Datta Mineesh , Guy Stephen , Jordan Peter , Kyndt Chris , Newnham Evan , Ng Mark , Paul Elizabeth , Roodenburg Owen , Senanayake Channa , Sparham Sarah , Steele Michelle , Dewey Helen
Published: March 2022

Background

Performing lumbar punctures carries a risk of harm to the patient, but the information cerebrospinal fluid provides often makes this procedure necessary. Clinicians in the Australian setting would benefit from having more information on these procedures, in order to help them in a risk versus benefit analysis.

Aims

To describe the contemporary indications, cerebrospinal fluid findings and complications of lumbar punctures in a metropolitan Australian health service.

Methods

Retrospective electronic medical records audit of lumbar punctures performed on 525 adults within three acute hospitals between 1 July 2018 and 30 June 2019. Main outcome measures include frequency of indication for lumbar puncture by category, normal versus abnormal cerebrospinal fluid for each category, and frequency, severity and type of complications of lumbar punctures.

Results

Of 525 adult lumbar punctures that were assessed in this study, 466 were performed for a diagnostic indication. The most common diagnostic indications were acute severe headache (156 procedures; 33.5%) and encephalopathy (128 procedures; 27.5%). The yield of abnormal results varied by indication category, with the above indications yielding abnormal results in 85 (54.5%) and 72 (56.3%) cases respectively. A complication was recorded in 54 (10.3% of total) procedures. The majority (45; 8.6%) of complications were minor in severity and most frequently consisted of post‐dural puncture headache (PDPH).

Conclusions

In the era of an increased reliance on high quality neuroimaging, lumbar puncture has a high diagnostic yield with a low rate of major complications. The most common complication is PDPH, which is mild and self‐limiting in most cases.
Dual targeting of PI3K and BCL‐2 overcomes ibrutinib resistance in aggressive mantle cell lymphoma
Authors: Ye Haige , Huang Shengjian , Liu Yang , Chen Zhihong , Wang Michael , Jiang Vivian Changying
Published: March 2022

Despite significant efficacy of ibrutinib therapy in mantle cell lymphoma (MCL), about one‐third of MCL patients will display primary resistance. In time, secondary resistance occurs almost universally with an unlikely response to salvage chemotherapy afterwards. While intense efforts are being directed towards the characterization of resistance mechanisms, our focus is on identifying the signalling network rewiring that characterizes this ibrutinib resistant phenotype. Importantly, intrinsic genetic, epigenetic and tumour microenvironment‐initiated mechanisms have all been shown to influence the occurrence of the ibrutinib resistant phenotype. By using in vitro and in vivo models of primary and secondary ibrutinib resistance as well as post‐ibrutinib treatment clinical samples, we show that dual targeting of the BCL‐2 and PI3‐kinase signalling pathways results in synergistic anti‐tumour activity. Clinically relevant doses of venetoclax, a BCL‐2 inhibitor, in combination with duvelisib, a PI3Kδ/γ dual inhibitor, resulted in significant inhibition of these compensatory pathways and apoptosis induction. Our preclinical results suggest that the combination of venetoclax and duvelisib may be a therapeutic option for MCL patients who experienced ibrutinib failure and merits careful consideration for future clinical trial evaluation.
Structure-guided design enables development of a hyperpolarized molecular probe for the detection of aminopeptidase N activity in vivo
Authors: Saito Yutaro , Yatabe Hiroyuki , Tamura Iori , Kondo Yohei , Ishida Ryo , Seki Tomohiro , Hiraga Keita , Eguchi Akihiro , Takakusagi Yoichi , Saito Keisuke , Oshima Nobu , Ishikita Hiroshi , Yamamoto Kazutoshi , Krishna Murali C. , Sando Shinsuke
Published: March 2022

Dynamic nuclear polarization (DNP) is a cutting-edge technique that markedly enhances the detection sensitivity of molecules using nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI). This methodology enables real-time imaging of dynamic metabolic status in vivo using MRI. To expand the targetable metabolic reactions, there is a demand for developing exogenous, i.e., artificially designed, DNP-NMR molecular probes; however, complying with the requirements of practical DNP-NMR molecular probes is challenging because of the lack of established design guidelines. Here, we report Ala-[1-
13
C]Gly-
d
2
-NMe
2
as a DNP-NMR molecular probe for in vivo detection of aminopeptidase N activity. We developed this probe rationally through precise structural investigation, calculation, biochemical assessment, and advanced molecular design to achieve rapid and detectable responses to enzyme activity in vivo. With the fabricated probe, we successfully detected enzymatic activity in vivo. This report presents a comprehensive approach for the development of artificially derived, practical DNP-NMR molecular probes through structure-guided molecular design.
Dysfunctional breathing diagnosed by cardiopulmonary exercise testing in ‘long COVID’ patients with persistent dyspnoea
Authors: Frésard Isabelle , Genecand Léon , Altarelli Marco , Gex Grégoire , Vremaroiu Petrut , Vremaroiu-Coman Andreea , Lawi David , Bridevaux Pierre-Olivier
Published: March 2022

Background

‘Long COVID’-associated dyspnoea may persist for months after SARS-CoV-2 infection. Among the causes of persistent dyspnoea, dysfunctional breathing (DB), defined as an erratic or inappropriate ventilation at rest or exercise, has been observed, but little is known about its occurrence and pathophysiology among individuals with ‘long COVID’. We aimed to describe the occurrence and identify clinical predictors of DB among patients following SARS-CoV-2 infection.

Methods

Cardiopulmonary exercise testing (CPET) was performed in 51 SARS-CoV-2 patients (median age, 64 years (IQR, 15)); male, 66.7%) living with ‘long COVID’ and persistent dyspnoea. CPET was classified into three dominant patterns: respiratory limitation with gas exchange abnormalities (RL); normal CPET or O2delivery/utilisation impairment (D); and DB. Non-parametric and χ2tests were applied to analyse the association between CPET dominant patterns and demographics, pulmonary function tests and SARS-CoV-2 severity.

Results

Among 51 patients, DB mostly without hyperventilation was found in 29.4% (n=15), RL in 54.9% (n=28) and D in 15.7% (n=8). When compared with RL individuals, patients with DB were younger, had significantly less severe initial infection, a better transfer capacity for carbon monoxide (median 85% (IQR, 28)), higher oxygen consumption (22.9 mL/min/kg (IQR, 5.5)), a better ventilatory efficiency slope (31.6 (IQR, 12.8)), and a higher SpO2(95% (IQR, 3)).

Conclusions

Our findings suggest that DB without hyperventilation could be an important pathophysiological mechanism of disabling dyspnoea in younger outpatients following SARS-CoV-2 infection, which appears to be a feature of COVID-19 not described in other viral diseases.
Cancer risk among firefighters and police in the Ontario workforce
Authors: Sritharan Jeavana , Kirkham Tracy L , MacLeod Jill , Marjerrison Niki , Lau Ashley , Dakouo Mamadou , Logar-Henderson Chloë , Norzin Tenzin , DeBono Nathan L , Demers Paul A
Published: March 2022

Objective

Firefighters and police often work in high-stress, complex environments with known and suspected carcinogenic exposures. We aimed to characterise cancer incidence among firefighters and police.

Methods

The Occupational Disease Surveillance System (ODSS) was used to identify workers employed as firefighters or police in Ontario. A cohort of workers were identified using lost-time workers’ compensation claims data and followed for cancer in the Ontario Cancer Registry (1983–2020). Cox proportional hazard models were used to estimate HRs and 95% CIs for primary site-specific cancer diagnoses adjusted for age at start of follow-up, birth year and sex.

Results

A total of 13 642 firefighters and 22 595 police were identified in the cohort. Compared with all other workers in the ODSS, firefighters and police had increased risk of prostate cancer (firefighters: HR=1.43, 95% CI 1.31 to 1.57; police: HR=1.47, 95% CI 1.35 to 1.59), colon cancer (firefighters: HR=1.39, 95% CI 1.19 to 1.63; police: HR=1.39, 95% CI 1.21 to 1.60) and skin melanoma (firefighters: HR=2.38, 95% CI 1.99 to 2.84; police: HR=2.27, 95% CI 1.96 to 2.62). Firefighters also had increased risk of cancer of the pancreas, testis and kidney, as well as non-Hodgkin’s lymphoma and leukaemia. Police had increased risk of thyroid, bladder and female breast cancer. When compared directly with the police, firefighters had an elevated risk of mesothelioma and testicular cancer.

Conclusions

Firefighters and police demonstrated some similar as well as some unique cancer risks. Findings from this larger worker population may have important implications for workplace and policy-level changes to improve preventative measures and reduce potential exposures to known carcinogenic hazards.
Protein arginine N-methyltransferase 4 (PRMT4) contributes to lymphopenia in experimental sepsis
Authors: Lai Yandong , Li Xiuying , Li Tiao , Li Xiaoyun , Nyunoya Toru , Chen Kong , Kitsios Georgios , Nouraie Mehdi , Zhang Yingze , McVerry Bryan J , Lee Janet S , Mallmapalli Rama K , Zou Chunbin
Published: March 2022

Background

One hallmark of sepsis is the reduced number of lymphocytes, termed lymphopenia, that occurs from decreased lymphocyte proliferation or increased cell death contributing to immune suppression. Histone modification enzymes regulate immunity by their epigenetic and non-epigenetic functions; however, the role of these enzymes in lymphopenia remains elusive.

Methods

We used molecular biological approaches to investigate the high expression and function of a chromatin modulator protein arginine N-methyltransferase 4 (PRMT4)/coactivator-associated arginine methyltransferase 1 in human samples from septic patients and cellular and animal septic models.

Results

We identified that PRMT4 is elevated systemically in septic patients and experimental sepsis. Gram-negative bacteria and their derived endotoxin lipopolysaccharide (LPS) increased PRMT4 in B and T lymphocytes and THP-1 monocytes. Single-cell RNA sequencing results indicate an increase of PRMT4 gene expression in activated T lymphocytes. Augmented PRMT4 is crucial for inducing lymphocyte apoptosis but not monocyte THP-1 cells. Ectopic expression of PRMT4 protein caused substantial lymphocyte death via caspase 3-mediated cell death signalling, and knockout of PRMT4 abolished LPS-mediated lymphocyte death. PRMT4 inhibition with a small molecule compound attenuated lymphocyte death in complementary models of sepsis.

Conclusions

These findings demonstrate a previously uncharacterised role of a key chromatin modulator in lymphocyte survival that may shed light on devising therapeutic modalities to lessen the severity of septic immunosuppression.
Impact of antifibrotic therapy on lung cancer development in idiopathic pulmonary fibrosis
Authors: Naoi Hyogo , Suzuki Yuzo , Mori Kazutaka , Aono Yuya , Kono Masato , Hasegawa Hirotsugu , Yokomura Koshi , Inoue Yusuke , Hozumi Hironao , Karayama Masato , Furuhashi Kazuki , Enomoto Noriyuki , Fujisawa Tomoyuki , Nakamura Yutaro , Inui Naoki , Nakamura Hidenori , Suda Takafumi
Published: March 2022

Patients with idiopathic pulmonary fibrosis (IPF) are at a high risk of lung cancer (LC). Antifibrotic therapy slows disease progression and possibly prolongs survival. However, whether antifibrotic therapy affects LC development in patients with IPF remains unknown. This multicentre retrospective study evaluated 345 patients with IPF. The incidence and prevalence of LC were significantly lower in patients with IPF receiving antifibrotic therapy than those not receiving. Subsequently, LC-related mortality was significantly lower in patients with IPF receiving antifibrotic therapy. These results suggest that antifibrotic therapy was possibly associated with a reduced risk of LC development in patients with IPF, which may be partly associated with its survival benefit.
Joint patient and clinician priority setting to identify 10 key research questions regarding the long-term sequelae of COVID-19
Authors: Houchen-Wolloff Linzy , Poinasamy Krisnah , Holmes Kate , Tarpey Maryrose , Hastie Claire , Raihani Kelly , Rogers Natalie , Smith Nikki , Adams Dawn , Burgess Paul , Clark Jean , Cranage Clare , Desai Mahadev , Geary Nicola , Gill Rhyan , Mangwani Jitendra , Staunton Lily , Berry Colin , Bolton Charlotte E , Chalder Trudie , Chalmers James , De Soyza Anthony , Elneima Omer , Geddes John , Heller Simon , Ho Ling-Pei , Jacob Joseph , McAuley Hamish , Parmar Aarti , Quint Jennifer K , Raman Betty , Rowland Matthew , Singapuri Amisha , Singh Sally J , Thomas David , Toshner Mark R , Wain Louise V , Horsley Alex Robert , Marks Michael , Brightling Christopher E , Evans Rachael A
Published: March 2022

Given the large numbers of people infected and high rates of ongoing morbidity, research is clearly required to address the needs of adult survivors of COVID-19 living with ongoing symptoms (long COVID). To help direct resource and research efforts, we completed a research prioritisation process incorporating views from adults with ongoing symptoms of COVID-19, carers, clinicians and clinical researchers. The final top 10 research questions were agreed at an independently mediated workshop and included: identifying underlying mechanisms of long COVID, establishing diagnostic tools, understanding trajectory of recovery and evaluating the role of interventions both during the acute and persistent phases of the illness.
Relationship between asthma and severe COVID-19: a national cohort study
Authors: Dolby Ted , Nafilyan Vahe , Morgan Ann , Kallis Constantinos , Sheikh Aziz , Quint Jennifer K
Published: March 2022

Background

We aimed to determine whether children and adults with poorly controlled or more severe asthma have greater risk of hospitalisation and/or death from COVID-19.

Methods

We used individual-level data from the Office for National Statistics Public Health Data Asset, based on the 2011 census in England, and the General Practice Extraction Service data for pandemic planning and research linked to death registration records and Hospital Episode Statistics admission data. Adults were followed from 1 January 2020 to 30 September 2021 for hospitalisation or death from COVID-19. For children, only hospitalisation was included.

Results

Our cohort comprised 35 202 533 adults and 2 996 503 children aged 12–17 years. After controlling for sociodemographic factors, pre-existing health conditions and vaccine status, the risk of death involving COVID-19 for adults with asthma prescribed low dose inhaled corticosteroids (ICS) was not significantly different from those without asthma. Adults with asthma prescribed medium and high dosage ICS had an elevated risk of COVID-19 death; HRs 1.18 (95% CI 1.14 to 1.23) and 1.36 (95% CI 1.28 to 1.44), respectively. A similar pattern was observed for COVID-19 hospitalisation; fully adjusted HRs 1.53 (95% CI 1.50 to 1.56) and 1.52 (95% CI 1.46 to 1.56) for adults with asthma prescribed medium and high-dosage ICS, respectively. Risk of hospitalisation was greater for children with asthma prescribed one (2.58 (95% CI 1.82 to 3.66)) or two or more (3.80 (95% CI 2.41 to 5.95)) courses of oral corticosteroids in the year prior to the pandemic.

Discussion

People with mild and/or well-controlled asthma are neither at significantly increased risk of hospitalisation with nor more likely to die from COVID-19 than adults without asthma.
Electronic and magnetic properties of honeycomb arsenic–phosphorus nanoribbons via a first-principles study
Authors: Zhang Hui , Liu Qi-Chao
Published: March 2022

In this paper, the structural stability, electronic structure, and magnetic properties of single-layer honeycomb arsenic–phosphorus (AsP) nanoribbons are systematically investigated using density functional theory calculations. Zigzag AsP nanoribbons (ZNRs) possess magnetic moments on the edge atoms. In addition, the ferromagnetic and intraedge antiferromagnetic states of ZNRs can be randomly coupled because of their equal total energy and almost identical electronic band structures. Armchair AsP nanoribbons (ANRs) show clear edge reconstructions and are nonmagnetic. ZNRs and ANRs are indirect and direct semiconductors, respectively, and have significantly smaller bandgaps than that of two-dimensional single-layer AsP due to their edge states. More interestingly, when the edge atoms are saturated by hydrogen atoms, ZNRs change from an indirect bandgap to a direct bandgap. In addition, both the ZNRs and ANRs exhibit enlarged bandgaps and nonmagnetic ground states due to hydrogen saturation. This work indicates that AsP nanoribbons can possess quite different electronic structures from two-dimensional single-layer AsP, extending the application field of AsP nanostructures.