bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of COVID-19 lockdown on heart rate variability
Authors: Bourdillon Nicolas , Yazdani Sasan , Schmitt Laurent , P.Millet Grégoire
Published: August 2020

Introduction

Strict lockdown rules were imposed to the French population from 17 March to 11 May 2020, which may result in limited possibilities of physical activity, modified psychological and health states. This report is focused on HRV parameters kinetics before, during and after this lockdown period.

Methods

95 participants were included in this study, who underwent regular orthostatic tests (a 5-minute supine followed by a 5-minute standing recording of heart rate (HR)) on a regular basis before, during and after the lockdown (BSL, CFN and RCV, respectively). HR, power in low- and high-frequency bands (LF, HF, respectively) and root mean square of the successive differences (RMSSD) were computed for each orthostatic test, and for each positions. Subjective well-being was assessed on a 0-10 visual analogic scale (VAS).

Results

Out of the 95 participants, 19 (WB+) reported an improved well-being (i.e., increase >2 in VAS score) during CFN, contradictory to the 76 other participants (WB-). There was an increase in HR and a decrease in RMSSD when measured supine in CFN and RCV, compared to BSL in WB-, whilst opposite results were found in WB+ (i.e. decrease in HR and increase in RMSSD in CFN and RCV; increase in LF and HF in RCV). There was a moderate significant correlation between VAS and HR, RMSSD, HF, respectively, in the supine position; the higher the VAS score (i.e., subjective well-being), the higher the RMSSD and HF and the lower the HR. In standing position, HRV parameters were not modified during CFN.

Conclusion

The strict COVID-19 lockdown likely had opposite effects on French population as 20% of participants improved parasympathetic activation (RMSSD, HF) and rated positively this period, whilst 80% showed altered responses and deteriorated well-being. The changes in HRV parameters during and after the lockdown period were in line with subjective well-being responses. These results confirmed the usefulness of HRV as a non-invasive means for monitoring well-being and health in the general population.
Development and Evaluation of MADDIE: Method to Acquire Delivery Date Information from Electronic Health Records
Authors: Canelón Silvia P. , Burris Heather H. , Levine Lisa D. , Boland Mary Regina
Published: August 2020

Objective

To develop an algorithm that infers patient delivery dates (PDDs) and delivery-specific details from Electronic Health Records (EHRs) with high accuracy.

Materials and Methods

We obtained EHR data from 1,060,100 female patients treated at Penn Medicine hospitals or outpatient clinics between 2010-2017. We developed an algorithm called MADDIE: Method to Acquire Delivery Date Information from Electronic Health Records that infers a PDD for distinct deliveries based on EHR encounter dates assigned a delivery code, the frequency of code usage, and the time differential between code assignments. We validated MADDIE’s PDDs against a birth log independently maintained by the Department of Obstetrics and Gynecology.

Results

MADDIE identified 50,560 patients having 63,334 distinct deliveries. MADDIE was 98.6% accurate (F1-score 92.1%) when compared to the birth log. The PDD was on average 0.68 days earlier than the true delivery date for patients with only one delivery (± 1.43 days) and 0.52 days earlier for patients with more than one delivery episode (± 1.11 days).

Discussion

MADDIE is the first algorithm to successfully infer PDD information using only structured delivery codes and identify multiple deliveries per patient. MADDIE is also the first to validate the accuracy of the PDD using an external gold standard of known delivery dates as opposed to manual chart review of a sample.

Conclusion

MADDIE infers delivery dates and delivery-specific details from the EHR with high accuracy and relies only on structured EHR elements while harnessing temporal information and the frequency of code usage to identify accurate PDDs.
Loneliness, physical activity and mental health during Covid-19: a longitudinal analysis of depression and anxiety between 2015 and 2020
Authors: Creese Byron , Khan Zunera , Henley William , O’Dwyer Siobhan , Corbett Anne , Da Silva Miguel Vasconcelos , Mills Kathryn , Wright Natalie , Testad Ingelin , Aarsland Dag , Ballard Clive
Published: August 2020

Background

Loneliness and physical activity are important targets for research into the impact of COVID-19 because they have established links with mental health, could be exacerbated by social distancing policies and are potentially modifiable.

Method

We analysed mental health data collected during COVID-19 from adults aged 50 and over alongside comparable annual data collected between 2015 and 2019 from the same sample. Trajectories of depression (PHQ-9) and anxiety (GAD-7) were analysed with respect to loneliness, physical activity levels and a number of socioeconomic and demographic characteristics using zero-inflated negative binomial regression.

Results

3,281 people completed the COVID-19 mental health questionnaire, all had at least one data point prior to 2020. In 2020, the adjusted PHQ-9 score for loneliness was 3.2. (95% CI: 3.0-3.4), an increase of one point on previous years and 2 points higher than people not rated lonely, whose score did not change in 2020 (1.2, 95% CI: 1.1-1.3). PHQ-9 was 2.6 (95% CI: 2.4-2.8) in people with decreased physical activity, an increase of 0.5 on previous years. In contrast, PHQ-9 in 2020 for people whose physical activity had not decreased was 1.7 (95% CI: 1.6-1.8), similar to previous years. A similar relationship was observed for GAD-7 though the differences were smaller and the absolute burden of symptoms lower.

Conclusions

After accounting for pre-COVID-19 trends, we show that experiencing loneliness and decreased physical activity are risk factors for worsening mental health during the pandemic. Our findings highlight the need to examine policies which target these potentially modifiable risk factors.
Microbial contamination of powered air purifying respirators (PAPR) used during the COVID-19 pandemic: an in situ microbiological study
Authors: Chakladar Abhijoy , Jones Claire G , Siu Jimmy , Hassan-Ibrahim Mohammed Osman , Khan Mansoor
Published: August 2020

OBJECTIVE

To determine whether internal components of powered air purifying respirators (PAPR) used during the Corona virus 2019 disease (COVID-19) pandemic are contaminated with bacteria, fungi and/or any viral material.

DESIGN & SETTING

In situ microbiological study. Single NHS Trust, UK.

OUTCOME MEASURES

Growth of any bacteria or fungi, or positive polymerase chain reaction results for common respiratory viruses and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

RESULTS

25 PAPR hoods were swabbed; ten (40%) returned positive results. Bacterial growth was detected on six hoods (bacillus simplex, kocuria rhizophilia, bacillus weihenstephensis, microcccus luteus and staphylococcus epidermidis); five of the hoods were positive for fungal growth (non-sporulating environmental mould, NSEM); all sampled hoods tested negative for both SARS-CoV-2 and an expanded panel of respiratory viruses. There was wide variation in the storage of cleaned hoods.

CONCLUSION

Despite following recommended cleaning procedures, bacteria and fungi can remain on the internal components of PAPR hoods, at levels significant enough to be swabbed and cultured. PAPR hoods have the potential to cross-infect wearers and patients and are used primarily by clinicians who fail to fit disposable FFP3 respirators; the female sex and non-Caucasian people are less likely to fit FFP3 respirators. The hoods tested cannot be adequately cleaned for use in high risk healthcare environments, PAPR hoods and tubes can act as fomites, and there are evident shortcomings in their provision.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Prior to this study there had been no similar investigations looking at the microbiological contamination of PAPR hoods in situ in the real work place hospital environment.

SARS-CoV-2 is able to persist in an infective state on surfaces for up to 72 hours.

The possibility of internal contamination of PAPR had never been addressed by manufacturers as the hoods were not designed for shared usage.

WHAT THIS PAPER ADDS

PAPR hoods in their current form risk transmitting infection between users, and do not protect patients from infected healthcare workers

It is possible to detect biological agents within the PAPR hoods despite cleaning as per guidelines

An infected asymptomatic carrier is at risk of infecting those around them due to contaminated exhalation
NAD modulates DNA methylation and cell differentiation
Authors: Ummarino Simone , Bassal Mahmoud A. , Zhang Yanzhou , Seelam Andy Joe , Kobayashi Ikei S. , Borchiellini Marta , Ebralidze Alexander K. , Trinh Bon Q. , Kobayashi Susumu S. , Di Ruscio Annalisa
Published: August 2020

Nutritional intake impacts the human epigenome by directing epigenetic pathways in normal cell development via as yet unknown molecular mechanisms. Consequently, imbalance in the nutritional intake is able to dysregulate the epigenetic profile and drive cells towards malignant transformation. Herein, we present a novel epigenetic effect of the essential nutrient, NAD. We demonstrate that impairment of DNMT1 enzymatic activity by NAD-promoted ADP-ribosylation, leads to demethylation and transcriptional activation ofCEBPAgene, suggesting the existence of an unknown NAD-controlled region within the locus. In addition to the molecular events, NAD treated cells exhibit significant morphological and phenotypical changes that correspond to myeloid differentiation.

Collectively, these results delineate a novel role for NAD in cell differentiation and indicate novel nutri-epigenetic strategy to regulate and control gene expression in human cells.
Engineered ACE2 receptor traps potently neutralize SARS-CoV-2
Authors: Glasgow Anum , Glasgow Jeff , Limonta Daniel , Solomon Paige , Lui Irene , Zhang Yang , Nix Matthew A. , Rettko Nicholas J. , Lim Shion A. , Zha Shoshana , Yamin Rachel , Kao Kevin , Rosenberg Oren S. , Ravetch Jeffrey V. , Wiita Arun P. , Leung Kevin K. , Zhou Xin X. , Hobman Tom C. , Kortemme Tanja , Wells James A.
Published: August 2020

An essential mechanism for SARS-CoV-1 and -2 infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). Here we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human Fc domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2 pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50) in the 10-100 ng/ml range. Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-utilizing coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be pre-designed for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies isolated or generated from convalescent patients.
The distribution of plasmid fitness effects explains plasmid persistence in bacterial communities
Authors: Valle Aida Alonso-del , León-Sampedro Ricardo , Rodríguez-Beltrán Jerónimo , DelaFuente Javier , Hernández-García Marta , Ruiz-Garbajosa Patricia , Cantón Rafael , Peña-Miller Rafael , Millán Álvaro San
Published: August 2020

Introductory paragraph

Plasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the distribution of fitness effects (DFE) for the major antibiotic resistance plasmid pOXA-48 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48 produced an overall reduction in bacterial fitness, the DFE was dominated by quasi-neutral effects, and beneficial effects were observed in several isolates. Incorporating these data into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. Moreover, genomic results showed a link between plasmid fitness effects and bacterial phylogeny, helping to explain pOXA-48 epidemiology. Our results provide a simple and general explanation for plasmid persistence in natural bacterial communities.
High-Spatial-Resolution Multi-Omics Atlas Sequencing of Mouse Embryos via Deterministic Barcoding in Tissue
Authors: Liu Yang , Yang Mingyu , Deng Yanxiang , Su Graham , Enninful Archibald , Guo Cindy C. , Tebaldi Toma , Zhang Di , Kim Dongjoo , Bai Zhiliang , Norris Eileen , Pan Alisia , Li Jiatong , Xiao Yang , Halene Stephanie , Fan Rong
Published: August 2020

This manuscript has been withdrawn due to a duplicate posting on our website. Please visit DOI: 10.1101/788992 to access the current version of this preprint on bioRxiv.
Circular RNA expression profiles in pediatric ependymomas
Authors: Ahmadov Ulvi , Bendikas Meile M. , Ebbesen Karoline K. , Sehested Astrid M. , Kjems Jørgen , Broholm Helle , Kristensen Lasse S.
Published: August 2020

Pediatric brain tumors frequently develop in the cerebellum, where ependymoma, medulloblastoma and pilocytic astrocytoma are the most prevalent subtypes. These tumors are currently treated using non-specific therapies, in part because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) have recently emerged as a large class of primarily non-coding RNAs with important roles in tumorigenesis, but so far they have not been described in pediatric brain tumors. To advance our understanding of these tumors, we performed high-throughput sequencing of ribosomal RNA-depleted total RNA from 10 primary ependymoma and 3 control samples. CircRNA expression patterns were determined using two independent bioinformatics algorithms, and correlated to disease stage, outcome, age, and gender. We found a profound global downregulation of circRNAs in ependymoma relative to control samples. Many differentially expressed circRNAs were discovered and circSMARCA5 and circ-FBXW7, which are described as tumor suppressors in glioma and glioblastomas in adults, were among the most downregulated. Moreover, patients with a dismal outcome clustered separately from patients with a good prognosis in unsupervised hierarchical cluster analyses. Next, we performed NanoString nCounter experiments using a custom-designed panel including 66 selected circRNA targets and analyzed formalin-fixed paraffin-embedded (FFPE) samples from a larger cohort of ependymoma patients as well as patients diagnosed with medulloblastoma or pilocytic astrocytoma. These experiments were used to validate our findings and, in addition, indicated that circRNA expression profiles are different among distinct pediatric brain tumor subtypes. In particular, circRMST and a circRNA derived from the LRBA gene were specifically upregulated in ependymomas. In conclusion, circRNAs have profoundly different expression profiles in ependymomas relative to controls and other pediatric brain tumor subtypes.
Validation of multiplex steroid hormone measurements in prostate cancer using plasma for multimodality biomarker studies
Authors: Snaterse Gido , van Dessel Lisanne F , Taylor Angela E , Visser Jenny A , Arlt Wiebke , Lolkema Martijn P , Hofland Johannes
Published: August 2020

Background

Steroid hormones are essential signalling molecules in prostate cancer (PC). However, many studies focusing on liquid biomarkers fail to take the hormonal status of these patients into account. Steroid measurements are sensitive to bias caused by matrix effects, thus assessing potential matrix effects is an important step in combining circulating tumour DNA analysis with hormone status.

Methods

We investigated the accuracy of multi-steroid hormone profiling in mechanically-separated plasma (MSP) samples and in plasma from CellSave Preservative (CS) tubes, that are typically used to obtain circulating tumour DNA (ctDNA), compared to measurements in serum. We performed multiplex steroid profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in samples obtained from ten healthy controls and ten castration-resistant prostate cancer (CRPC) patients.

Results

Steroid measurements were comparable between MSP and serum. A small but consistent decrease of 8 – 21% compared to serum was observed when using CS plasma, which was considered to be within the acceptable margin. The minimal residual testosterone levels of CRPC patients could be sensitively quantified in both MSP and CS samples.

Conclusions

We validated the use of MSP and CS samples for multi-steroid profiling by LC-MS/MS. The optimised use of these samples in clinical trials will allow us to gain further insight into the steroid metabolism in PC patients.
The Trend of Neutralizing Antibody Response Against SARS-CoV-2 and the Cytokine/Chemokine Release in Patients with Differing Severities of COVID-19: All Individuals Infected with SARS-CoV-2 Obtained Neutralizing Antibody
Authors: Tjan Lidya Handayani , Nagano Tatsuya , Furukawa Koichi , Nishimura Mitsuhiro , Arii Jun , Fujinaka Sayo , Iwata Sachiyo , Nishimura Yoshihiro , Mori Yasuko
Published: August 2020

Background

COVID-19 patients show a wide clinical spectrum ranging from mild respiratory symptoms to severe and fatal disease, and older individuals are known to be affected more severely. Neutralizing antibody for viruses is critical for their elimination, and increased cytokine/chemokine levels are thought to be related to COVID-19 severity. However, the trend of the neutralizing antibody production and cytokine/chemokine levels during the clinical course of COVID-19 patients with differing levels of severity has not been established.

Methods

We serially collected 45 blood samples from 12 patients with different levels of COVID-19 severity, and investigated the trend of neutralizing antibody production using authentic SARS-CoV-2 and cytokine/chemokine release in the patients’ clinical courses.

Results

All 12 individuals infected with SARS-CoV-2 had the neutralizing antibody against it, and the antibodies were induced at approx. 4-10 days after the patients’ onsets. The antibodies in the critical and severe cases showed high neutralizing activity in all clinical courses. Most cytokine/chemokine levels were clearly high in the critical patients compared to those with milder symptoms.

Conclusion

Neutralizing antibodies against SARS-CoV-2 were induced at a high level in the severe COVID-19 patients, indicating that abundant virus replication occurred. Cytokines/chemokines were expressed more in the critical patients, indicating that high productions of cytokines/chemokines have roles in the disease severity. These results may indicate that plasma or neutralizing antibody therapy could be a first-line treatment for older patients to eliminate the virus, and corticosteroid therapy could be effective to suppress the cytokine storm after the viral genome’s disappearance.
Groundbreaking predictions about COVID-19 pandemic duration, number of infected and dead: A novel mathematical approach never used in epidemiology
Authors: Garcia Garcia de Alcaniz Javier , Lopez-Rodas Victoria , Costas Eduardo
Published: August 2020

Hundreds of predictions about the duration of the pandemic and the number of infected and dead have been carried out using traditional epidemiological tools (i.e. SIR, SIRD models, etc.) or new procedures of big-data analysis. However, the extraordinary complexity of the disease and the lack of knowledge about the pandemic (i.e. R value, mortality rate, etc.) create uncertainty about the accuracy of these estimates. However, several elegant mathematical approaches, based on physics and probability principles, like the Delta-t argument, Lindy's Law or the Doomsday principle-Carter's catastrophe, which have been successfully applied by scientists to unravel complex phenomena characterized by their great uncertainty (i.e. Human race's longevity; How many more humans will be born before extinction) allow predicting parameters of the Covid-19 pandemic. These models predict that the COVID-19 pandemic will hit us until at least September-October 2021, but will likely last until January-September 2022, causing a minimum of 36,000,000 infected and most likely 60,000,000, as well as 1,400,000 dead at best and most likely 2,333,000.
An information management approach for supply chain disruption recovery
Authors: Messina Dario , Barros Ana Cristina , Soares António Lucas , Matopoulos Aristides
Published: August 2020

Purpose

To study how supply chain decision makers gather, process and use the available internal and external information when facing supply chain disruptions.

Design/methodology/approach

The paper reviews relevant supply chain literature to build an information management model for disruption management. Afterwards, three case studies in the vehicle assembly sector, namely cars, trucks and aircraft wings, bring the empirical insights to the information management model.

Findings

This research characterises the phases of disruption management and identifies the information companies use to recover from a variety of disruptive events. It presents an information management model to enhance supply chain visibility and support disruption management at the operational level. Moreover, it arrives at two design propositions to help companies in the redesign of their disruption discovery and recovery processes.

Originality/value

This research studies how companies manage operational disruptions. The proposed information management model allows to provide visibility to support the disruption management process. Also, based on the analysis of the disruptions occurring at the operational level we propose a conceptual model to support decision makers in the recovery from daily disruptive events.
Assessing the reliability and validity of an outcomes star
Authors: Sweet Daryl , Winter Karen , Neeson Laura , Connolly Paul
Published: August 2020

Purpose

This paper aims to assess the reliability, validity and use of the Family Star Plus, one of several Outcomes Stars increasingly used as part of outcomes-based accountability approaches in the delivery of family support services. The Family Star Plus measures progress towards effective parenting but a lack of evidence exists on its psychometric properties and suitability for use as an outcomes tool.

Design/methodology/approach

Based on data from 1,255 families receiving a pilot support service, Cronbach’s alpha was used to assess the internal reliability of the 10-item scale, while principal component analysis (PCA) examined the number of constructs in the tool. Using matched data from evaluation of 80 families, correlations between the Family Star Plus and psychometrically validated tools were used to assess concurrent validity. Findings from a process evaluation explore practical issues around use of the tool.

Findings

Cronbach’s alpha indicated sufficient internal reliability of the Family Star Plus; however, the PCA raised questions concerning the internal validity the Star. Correlations between the Star and validated tools were not strong enough to support concurrent validity of the Star. Process evaluation findings highlight inconsistencies in Family Star Plus data capture, which may explain these differences.

Practical implications

Further work is required before the Family Star Plus can be considered for use as an outcome measure.

Originality/value

To the best of authors’ knowledge, this is the first peer-reviewed analysis of the psychometric qualities of the Family Star Plus.
Earnings momentum meets short‐term return reversal
Authors: Zhu Zhaobo , Sun Licheng , Tu Jun
Published: August 2020

This paper evaluates the effectiveness of a joint strategy that exploits fundamental‐based momentum and return‐based reversal anomalies. This joint strategy is motivated by two considerations. First, reversal can serve as a natural hedge to momentum. Second, both fundamental and price‐related information can contribute to stock return predictability. Consequently, we propose a new joint strategy that synthesises both earnings momentum and short‐term reversal. We find that this joint strategy generates considerable economic gains and outperforms the sum of profits from two individual anomalies. Moreover, the proposed strategy appears to be quite robust, generating stable and persistent profits across different market conditions.
Current landscape attributes and landscape stability in breeding grounds explain genetic differentiation in a long‐distance migratory bird
Authors: García J. , Morán‐Ordóñez A. , García J. T. , Calero‐Riestra M. , Alda F. , Sanz J. , Suárez‐Seoane S.
Published: August 2020

Numerous studies have highlighted a major role of isolation by both geographic distance and current landscape resistance in controlling bird population genetic differentiation. However, the importance of past landscape features or landscape temporal stability in shaping population genetic structure remains undervalued, particularly in birds. We assessed the role of isolation by landscape resistance – derived from current landscape attributes and measures of landscape stability –, in comparison to geographic isolation, as drivers of genetic differentiation of the Iberian bluethroat (Luscinia svecica azuricollis), a migratory bird whose populations breed in fragmented and dynamic landscapes affected by land use change. First, we characterized bluethroat genetic structure using microsatellite genotypes and evaluated genetic distances. Then, we built species distribution models using as a predictor a time series (two decades) of values of the Normalized Difference Vegetation Index as proxies of recent past landscape stability and current landscape features to ultimately generate landscape resistance values through different functions. Finally, we used maximum‐likelihood population effects models to evaluate the relationships between genetic distances and both geographic and landscape resistance distances. We found a genetic structure of four clusters in the Iberian bluethroats populations, as well as a high level of genetic differentiation. Genetic structure was better associated with landscape resistance, rather than with geographic distance. The highest values of habitat suitability corresponded to areas where vegetation remained mostly stable during the two decades prior to bird surveys, with low annual precipitation and spring temperature, being the relationship between gene flow and presence of intervenient habitat among populations linear or quasi‐linear. Our results suggest that conservation policies and land management practices that promote the maintenance of semi‐open pasture‐shrub mosaics (e.g. through extensive livestock grazing) can strongly benefit Iberian bluethroat populations, improving gene flow and population connectivity.
Cocaine attenuates acid sphingomyelinase activity during establishment of addiction‐related behavior—A translational study in rats and monkeys
Authors: Frankowska Małgorzata , Jesus Fernando M. , Mühle Christiane , Pacheco Jéssica V.N. , Maior Rafael S. , Sadakierska‐Chudy Anna , Smaga Irena , Piechota Marcin , Kalinichenko Liubov S. , Gulbins Erich , Kornhuber Johannes , Filip Małgorzata , Müller Christian P. , Barros Marilia
Published: August 2020

Cocaine addiction is a severe psychiatric condition for which currently no effective pharmacotherapy is available. Brain mechanisms for the establishment of addiction‐related behaviors are still not fully understood, and specific biomarkers for cocaine use are not available. Sphingolipids are major membrane lipids, which shape neuronal membrane composition and dynamics in the brain. Here, we investigated how chronic cocaine exposure during establishment of addiction‐related behaviors affects the activity of the sphingolipid rheostat controlling enzymes in the brain of rats. As we detected specific effects on several enzymes in the brain, we tested whether the activity of selected enzymes in the blood may serve as potential biomarker for cocaine exposure in non‐human primates (Callithrix penicillata). We found that intravenous cocaine self‐administration led to a reduced mRNA expression of Cers1, Degs1 and Degs2, and Smpd1 in the prefrontal cortex of rats, as well as a reduction of Cers4 expression in the striatum. These effects reversed after 10 days of abstinence. Monkeys showed a robust cocaine‐induced place preference (CPP). This coincided with a reduction in blood acid sphingomyelinase (ASM) activity after CPP establishment. This effect normalized after 15 days of abstinence. Altogether, these findings suggest that the establishment of cocaine addiction‐related behaviors coincides with changes in the activity of sphingolipid controlling enzymes. In particular, blood ASM levels may serve as a translational biomarker for recent cocaine exposure.
Comparing dentinal tubule penetration of conventional and ‘HiFlow’ bioceramic sealers with resin‐based sealer: An in vitro study
Authors: Reynolds John Z. , Augsburger Robert A. , Svoboda Kathy K.H. , Jalali Poorya
Published: August 2020

This study compared the depth and percentage of dentinal tubule penetration for single‐cone (SC) and warm vertical (WV) obturation techniques with two different bioceramic sealers (BC Sealer [BCS], BC Sealer HiFlow [BCSHF]) and an epoxy resin‐based sealer (2Seal easymiX). Fifty canals were filled with BCS, BCSHF or resin‐based sealer (RBS). Teeth in BCS and BCSHF groups were filled with SC or WV techniques, and teeth in the control group (RBS) filled with WV technique only. The roots were sectioned at 3 mm and 6 mm levels from the apex and evaluated with a confocal laser microscope. There was significantly greater depth and percentage of sealer penetration at the 6 mm section compared to 3 mm (P < 0.05). No statistically significant difference was found in sealer type or obturation technique at the examined levels (P > 0.05). In conclusion, dentinal tubule penetration was similar comparing BC Sealer, BC Sealer HiFlow and RBS using SC and WV techniques.
Green Innovation and Finance in Asia
Authors: Tolliver Clarence , Fujii Hidemichi , Keeley Alexander Ryota , Managi Shunsuke
Published: August 2020

Green innovation and green finance are two key components of sustainable development. In the most populous, fastest‐growing region in the world, Asian countries are pressed to maintain economic growth while addressing climate change and environmental externalities. Japan, South Korea, and China have each implemented policies to promote green innovation and finance conducive to such ends. While each country possesses unique capabilities, the extent to which they can promote environmentally adjusted multifactor productivity growth, green patent registrations, green bond issuances, green foreign direct investment, and environmental, social, and governance information disclosures stands to impact on their shifts to sustainable growth paradigms.
Sputum macrophage diversity and activation in asthma: Role of severity and inflammatory phenotype
Authors: Tiotiu Angelica , Zounemat Kermani Nazanin , Badi Yusef , Pavlidis Stelios , Hansbro Philip M. , Guo Yi‐Ke , Chung Kian Fan , Adcock Ian M. ,   the U‐BIOPRED consortium project team
Published: August 2020

Background

Macrophages control innate and acquired immunity, but their role in severe asthma remains ill‐defined. We investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U‐BIOPRED cohort.

Methods

Forty‐nine gene signatures (modules) for differentially stimulated macrophages, one to assess lung tissue‐resident cells (TR‐Mφ) and two for their polarization (classically and alternatively activated macrophages: M1 and M2, respectively) were studied using gene set variation analysis. We calculated enrichment scores (ES) across severity and previously identified asthma transcriptome‐associated clusters (TACs).

Results

Macrophage numbers were significantly decreased in severe asthma compared to mild‐moderate asthma and healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll‐like receptors via NF‐κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL‐2 biosynthesis (all P < .01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll‐like and TNF receptor activation and arachidonic acid metabolism (P < .001) and in TAC2 for the inflammasome and interferon signalling pathways (P < .001). Data were validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR‐Mφ were enriched in TAC3 and associated with mitochondrial function.

Conclusions

Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterized by distinct inflammatory pathways.
Expression and roles of system L amino acid transporters in human embryonal carcinoma cells
Authors: Chatsirisupachai Kasit , Kitdumrongthum Sarunya , Panvongsa Wittaya , Janpipatkul Keatdamrong , Worakitchanon Wittawin , Lertjintanakit Sarat , Wongtrakoongate Patompon , Chairoungdua Arthit
Published: August 2020

Background

Testicular germ cell tumors (TGCTs) are the most common malignant cancer in young men. Although TGCTs are generally responsive to platinum‐based chemotherapy particularly cisplatin, acquired resistance in patients with metastasis still occurs resulting in poor prognosis. Specifically, differentiation of embryonal carcinoma (EC) cells, the stem cells of TGCTs, can lead to the reduction of cisplatin responsiveness. Therefore, novel therapeutic strategies for TGCTs are needed. System L amino acid transporters have been reported to be up‐regulated and to play an important role in tumorigenesis. However, expression and role of system L amino acid transporters in TGCTs remain elusive.

Materials and methods

Expression of system L amino acid transporters was analyzed in TGCT samples from The Cancer Genome Atlas (TCGA). Expression of LAT1, LAT2, and 4F2hc was examined in human embryonal carcinoma cell line NTERA2. Roles of system L amino acid transporters on NTERA2 cell survival, cell proliferation, pluripotency, and cisplatin sensitivity were evaluated.

Results

Based upon TCGA datasets, we found that two isoforms of system L (LAT1 and LAT2) and their chaperone protein 4F2hc are highly expressed in EC samples compared with other groups. Treatment with the system L inhibitor BCH significantly suppressed leucine uptake into the pluripotent EC cell line NTERA2. The malignant phenotypes including cell viability, cell proliferation, and clonal ability were decreased following BCH treatment. Nonetheless, system L inhibition did not alter expression of stemness genes in NTERA2 cells. After NTERA2 differentiation, expressions of LAT1 and LAT2 were decreased. Finally, co‐administration of BCH enhanced cisplatin sensitivity in both undifferentiated and differentiated cells. These effects were associated with the reduction in p70S6K phosphorylation.

Conclusion

Taken together, these results shed light on the roles of system L amino acid transporters in TGCTs. Therefore, system L amino acid transporters could provide novel therapeutic targets for treatment against TGCTs.
Mucinous appendiceal neoplasms with or without pseudomyxoma peritonei: a review
Authors: Soucisse Mikael L. , Lansom Joshua , Alshahrani Mohammad S. , Morris David L.
Published: August 2020

Mucinous appendiceal neoplasms (MANs) are rare tumours and the primary cause of pseudomyxoma peritonei. These tumours have a much more benign course than typical colorectal cancers, generally growing for many years before giving any clinical signs. The spectrum of presentations, tumour stages and the underlying cytology is very wide, warranting from the simplest operation like an appendicectomy to the most complicated operation like a complete cytoreduction surgery and hyperthermic intraperitoneal chemotherapy. Fortunately, most patients can be offered a curative treatment, but limiting operative morbidity without compromising oncologic outcomes is the biggest challenge in managing these patients. Histopathology is the cornerstone of decision making for MANs, but is also subject to ongoing debate because of a lack of terminology consensus amongst pathologists. Combined with the rarity of this disease, the multiple histopathologic classification updates of MANs explain the ongoing confusion amongst clinicians in regard to individual optimal treatment. This review will cover the most recent histological classification of MANs and attempt to clarify optimal management of patients with different clinical presentation and histologic combinations.
Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma
Authors: Wagner Katy , Abraham Earl , Tran Bryan , Roshan David , Wykes James , Campbell Peter , Ebrahimi Ardalan
Published: August 2020

Background

Lymphovascular invasion (LVI) is an established adverse prognostic factor in many cancers, however, there are few studies assessing its significance in papillary thyroid carcinoma (PTC). We aimed to determine if LVI is an independent prognostic factor in PTC.

Methods

We conducted a single institution retrospective analysis of 610 patients with PTC treated between 1987 and 2016. LVI was defined as the presence or absence of cancer cells in blood vessels and/or lymphatics on histopathology. Multivariate Cox regression analysis was used to evaluate the association between LVI and recurrence‐free survival (RFS).

Results

The study cohort included 481 (78.9%) females and 129 (21.1%) males, with a median age of 47.6 years and median follow‐up of 3.4 years. LVI was present in 56 (9.2%) patients and was associated with nodal metastases (P < 0.001), extrathyroidal extension (P < 0.001), extranodal extension (P < 0.001), multifocality (P = 0.018) and microscopic positive margins (P < 0.001). On univariate analysis, LVI was associated with reduced RFS (hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.3–4.3; P = 0.007). However, after adjusting for nodal stage (pN0, pN1a, pN1b) there was no association between LVI and RFS (HR 1.3; 95% CI 0.7–2.5; P = 0.398). Similar results were obtained in full multivariate models adjusting for additional prognostic factors (HR 1.2; 95% CI 0.6–2.4; P = 0.627).

Conclusion

LVI is strongly associated with other adverse prognostic factors in PTC, particularly the presence and extent of nodal metastases. However, after adjusting for these, LVI is not an independent predictor of recurrence.
Necrotising enterocolitis–A 15‐year outcome report from a UK specialist centre
Authors: Calvert William , Sampat Keerthika , Jones Matthew , Baillie Colin , Lamont Graham , Losty Paul D.
Published: August 2020

Aims

Necrotising enterocolitis (NEC) is a disease associated with high mortality and morbidity, low birthweight and prematurity are risk factors. This study reports outcomes of babies having emergency laparotomy for NEC, examining institutional trends and exploring impact of multiple variables on mortality at 30 days and 1 year post‐operatively.

Methods

Case records of babies with ICD coding for NEC were examined from 2000 to 2015. After exclusions, 243 cases were identified—confirmed by operative findings and histology. Cohort demographics and trends in mortality were investigated, and the relationship of common variables to mortality was modelled with univariate and multivariate logistic regression to generate a mortality prediction tool.

Results

Mean gestational age was 28 + 4 weeks. A 30‐day mortality was 18.9%. Gestation, birthweight and area of bowel affected were significant of outcome (mortality), and the presence of pre‐operative pneumoperitoneum was strongly correlated. Year of surgery and congenital cardiac pathology requiring intervention were not significant. Using multivariate regression modelling, a mortality outcome prediction tool has been developed.

Conclusion

Good survival following operation for NEC (>70%) is feasible, even in those babies born extremely premature (<28 weeks) and post‐operatively re‐located to tertiary NICUs. With increasing gestational age (>32 weeks), mortality is uncommon.
Retzius‐sparing robot‐assisted radical prostatectomy improves early recovery of urinary continence: a randomized, controlled, single‐blind trial with a 1‐year follow‐up
Authors: Qiu Xuefeng , Li Youjian , Chen Mengxia , Xu Linfeng , Guo Suhan , Marra Giancarlo , Elliot Rosenberg Joel , Ma Haoxin , Li Xiaogong , Guo Hongqian
Published: August 2020

Objective

To evaluate the impact of Retzius‐sparing robot‐assisted radical prostatectomy (posterior approach) on early recovery of urinary continence (UC) compared to the conventional approach (anterior approach) for the treatment of clinically localized prostate cancer (PCa).

Methods

A total of 110 consecutive patients with clinically localized PCa were prospectively randomized in a 1:1 ratio to an anterior group (n = 55) or a posterior group (n = 55). The primary outcome was immediate UC, defined as freedom from any pad use within 1 week after removal of the urinary catheter. The UC rate following surgery was also calculated with Kaplan–Meier curves, and the log‐rank test was used for statistical comparison. Intra‐operative outcomes, pathological data and oncological outcomes, including positive surgical margin (PSM) status and biochemical recurrence‐free survival (BCRFS), were also compared between the two groups. The comparison of the two approaches was also analysed in subgroups after risk stratification.

Results

Of the patients who underwent the posterior approach, 69.1% achieved immediate UC compared with 30.9% in the anterior group (relative risk 2.24, 95% confidence interval [CI] 1.48–3.51; P = 0.000). The relative Kaplan–Meier curves for UC during the 12‐month follow‐up revealed statistically better recovery in the posterior group when compared with the anterior group (hazard ratio [HR] 1.51, 95% CI 1.01–2.24; log‐rank P = 0.007). No statistically significant differences were observed between the groups regarding complications (P = 0.399), PSM status (P = 0.225) or BCRFS (HR 4.80, 95% CI 0.97–23.78; log‐rank P = 0.111). In sub‐analyses, no significant difference between the two approaches with regard to UC recovery in patients with high‐risk PCa was observed (HR 1.26, 95% CI 0.63–2.51; log‐rank P = 0.415).

Conclusions

The Retzius‐sparing approach significantly improved early recovery of UC compared to the conventional approach. Further prospective studies are needed to confirm the benefits of the Retzius‐sparing approach for clinically localized PCa, especially for high‐risk cases.
From Theory to Methodology: Using Ecological Engagement to Study Development in Context
Authors: Koller Silvia H. , Raffaelli Marcela , de Morais Normanda Araujo
Published: August 2020

Urie Bronfenbrenner’s groundbreaking work on development in context has made an enduring impact on the field of developmental science. However, translating his theoretical concepts in empirical studies has proved challenging. In this article, we describe a methodological approach—ecological engagement methodology (EEM)—that was designed to operationalize key elements of Bronfenbrenner’s bioecological theory in studies of development in context. In particular, we describe the development of EEM, illustrate the approach using examples from qualitative and quantitative studies of vulnerable youth, provide a brief guide to implementing EEM, and discuss its major strengths and challenges. We conclude that EEM offers a flexible and powerful way to apply Bronfenbrenner’s theoretical propositions in studies of development in context, yielding data that are of high quality; ecologically valid; and relevant to researchers, practitioners, and policymakers.
Emergency airway training: “Who are you going to FONA?”
Authors: Bhalla Sanjana , Beegun Issa , Hogan Chris , Awad Zaid , Tolley Neil
Published: August 2020

Objectives

To demonstrate face and content validity of a home‐made simulation model as a training tool for front of neck access (FONA) procedures.

Design

This was a prospective evaluation study, in which experienced otolaryngologists and trainees were recruited to complete 3 tasks using our FONA model.

Setting

The study was completed during regular simulation training days and international conferences.

Participants

A total of 52 participants completed the questionnaire and were included in the study; 25 were experts and 27 were trainees.

Main outcome measures

All participants completed a validated 15‐item questionnaire using a 5‐point likert scale to assess the model across 4 domains: face validity (FV), global content (GC), task‐specific content (TSC) and curriculum applicability (CTR).

Results

There were no statistically significant differences between the groups ratings for FV, GC, TSC or CTR (P = .76, .13, .4 and .67, respectively). The model achieved a median FV of 4 (IQR 4‐5) with the agreement of experienced and trainee groups (68.9% and 92%, respectively). The median GC validity score was 5 (IQR 4‐5) with the agreement of 87.6% and 98.4% in respected groups. The model achieved a median TSC of 4.8 (IQR 4‐5) with the agreement of 54.5% and 99% in respected groups. The median CTR score was 5 (IQR 4‐5) with the agreement of 54.4% and 100% in respected groups.

Conclusion

Our home‐made FONA model achieved face and content validity for training and is safe and affordable for teaching basic front of neck access skills to otolaryngology trainees.
A case of tumor‐to‐tumor metastasis of cutaneous malignant melanoma
Authors: Straker Richard J. , Modi Mitul B. , Elder David E. , LiVolsi Virginia A. , Fraker Douglas L. , Xu Xiaowei , Karakousis Giorgos C.
Published: August 2020

We report a case of tumor‐to‐tumor metastasis of a cutaneous malignant melanoma to a synchronous thyroid Hurthle cell carcinoma. A 42‐year‐old male underwent a biopsy of right inguinal lymphadenopathy which showed metastatic melanoma. The primary lesion was identified on his right posterior leg, and staging workup discovered a synchronous left thyroid lobe nodule concerning for a follicular neoplasm. He underwent excision of the primary melanoma, right inguinal lymphadenectomy, and total thyroidectomy. The resected thyroid contained a 6.6‐cm, well‐encapsulated left‐sided nodule, red‐brown in color and homogenous in consistency, with areas of focal hemorrhage and no grossly identifiable calcification. Microscopically, large tumor cells with distinct cell borders were present, with deeply eosinophilic and granular cytoplasm, large nuclei with prominent nucleoli, and loss of polarity consistent with oncocytes. A microscopic single focus of vascular invasion was identified, and a diagnosis of angioinvasive Hurthle cell carcinoma was made. Within the Hurthle cell carcinoma, multiple deposits of metastatic melanoma were seen. These findings were indicative of tumor‐to‐tumor metastasis of the cutaneous melanoma to the angioinvasive Hurthle cell carcinoma. Our findings show the ability of melanoma to metastasize to a pre‐existing neoplasm.