bluuebunny/crossref_metadata_2025 huggingface dataset:
ExoBCD: a comprehensive database for exosomal biomarker discovery in breast cancer
Authors: Wang Xuanyi , Chai Zixuan , Pan Guizhi , Hao Youjin , Li Bo , Ye Ting , Li Yinghong , Long Fei , Xia Lixin , Liu Mingwei
Published: April 2020

Effective and safe implementation of precision oncology for breast cancer is a vital strategy to improve patient outcomes, which relies on the application of reliable biomarkers. As ‘liquid biopsy’ and novel resource for biomarkers, exosomes provide a promising avenue for the diagnosis and treatment of breast cancer. Although several exosome-related databases have been developed, there is still lacking of an integrated database for exosome-based biomarker discovery. To this end, a comprehensive database ExoBCD (https://exobcd.liumwei.org) was constructed with the combination of robust analysis of four high-throughput datasets, transcriptome validation of 1191 TCGA cases and manual mining of 950 studies. In ExoBCD, approximately 20 900 annotation entries were integrated from 25 external sources and 306 exosomal molecules (49 potential biomarkers and 257 biologically interesting molecules). The latter could be divided into 3 molecule types, including 121 mRNAs, 172 miRNAs and 13 lncRNAs. Thus, the well-linked information about molecular characters, experimental biology, gene expression patterns, overall survival, functional evidence, tumour stage and clinical use were fully integrated. As a data-driven and literature-based paradigm proposed of biomarker discovery, this study also demonstrated the corroborative analysis and identified 36 promising molecules, as well as the most promising prognostic biomarkers, IGF1R and FRS2. Taken together, ExoBCD is the first well-corroborated knowledge base for exosomal studies of breast cancer. It not only lays a foundation for subsequent studies but also strengthens the studies of probing molecular mechanisms, discovering biomarkers and developing meaningful clinical use.
miRactDB characterizes miRNA–gene relation switch between normal and cancer tissues across pan-cancer
Authors: Tan Hua , Kim Pora , Sun Peiqing , Zhou Xiaobo
Published: April 2020

It has been increasingly accepted that microRNA (miRNA) can both activate and suppress gene expression, directly or indirectly, under particular circumstances. Yet, a systematic study on the switch in their interaction pattern between activation and suppression and between normal and cancer conditions based on multi-omics evidences is not available. We built miRactDB, a database for miRNA–gene interaction, at https://ccsm.uth.edu/miRactDB, to provide a versatile resource and platform for annotation and interpretation of miRNA–gene relations. We conducted a comprehensive investigation on miRNA–gene interactions and their biological implications across tissue types in both tumour and normal conditions, based on TCGA, CCLE and GTEx databases. We particularly explored the genetic and epigenetic mechanisms potentially contributing to the positive correlation, including identification of miRNA binding sites in the gene coding sequence (CDS) and promoter regions of partner genes. Integrative analysis based on this resource revealed that top-ranked genes derived from TCGA tumour and adjacent normal samples share an overwhelming part of biological processes, which are quite different than those from CCLE and GTEx. The most active miRNAs predicted to target CDS and promoter regions are largely overlapped. These findings corroborate that adjacent normal tissues might have undergone significant molecular transformations towards oncogenesis before phenotypic and histological change; and there probably exists a small yet critical set of miRNAs that profoundly influence various cancer hallmark processes. miRactDB provides a unique resource for the cancer and genomics communities to screen, prioritize and rationalize their candidates of miRNA–gene interactions, in both normal and cancer scenarios.
Reduction of spontaneous cortical beta bursts in Parkinson’s disease is linked to symptom severity
Authors: Vinding Mikkel C , Tsitsi Panagiota , Waldthaler Josefine , Oostenveld Robert , Ingvar Martin , Svenningsson Per , Lundqvist Daniel
Published: April 2020

Parkinson’s disease is characterized by a gradual loss of dopaminergic neurons, which is associated with altered neuronal activity in the beta-band (13–30 Hz). Assessing beta-band activity typically involves transforming the time-series to get the power of the signal in the frequency domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine- and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical features in the beta-band—for example, that the beta-band exhibits transient bursts of high-amplitude activity. In an exploratory study, we used magnetoencephalography to record beta-band activity from the sensorimotor cortex, to characterize how spontaneous cortical beta bursts manifest in Parkinson’s patients on and off dopaminergic medication, and compare this to matched healthy controls. We extracted the time-course of beta-band activity from the sensorimotor cortex and characterized bursts in the signal. We then compared the burst rate, duration, inter-burst interval and peak amplitude between the Parkinson’s patients and healthy controls. Our results show that Parkinson’s patients off medication had a 5–17% lower beta bursts rate compared to healthy controls, while both the duration and the amplitude of the bursts were the same for healthy controls and medicated state of the Parkinson’s patients. These data thus support the view that beta bursts are fundamental underlying features of beta-band activity, and show that changes in cortical beta-band power in Parkinson’s disease can be explained—primarily by changes in the underlying burst rate. Importantly, our results also revealed a relationship between beta burst rate and motor symptom severity in Parkinson’s disease: a lower burst rate scaled with increased severity of bradykinesia and postural/kinetic tremor. Beta burst rate might thus serve as a neuromarker for Parkinson’s disease that can help in the assessment of symptom severity in Parkinson’s disease or in the evaluation of treatment effectiveness.
Sex Differences in Variability of Brain Structure Across the Lifespan
Authors: Forde Natalie J , Jeyachandra Jerrold , Joseph Michael , Jacobs Grace R , Dickie Erin , Satterthwaite Theodore D , Shinohara Russell T , Ameis Stephanie H , Voineskos Aristotle N
Published: April 2020

Several brain disorders exhibit sex differences in onset, presentation, and prevalence. Increased understanding of the neurobiology of sex-based differences in variability across the lifespan can provide insight into both disease vulnerability and resilience. In n = 3069 participants, from 8 to 95 years of age, we found widespread greater variability in males compared with females in cortical surface area and global and subcortical volumes for discrete brain regions. In contrast, variance in cortical thickness was similar for males and females. These findings were supported by multivariate analysis accounting for structural covariance, and present and stable across the lifespan. Additionally, we examined variability among brain regions by sex. We found significant age-by-sex interactions across neuroimaging metrics, whereby in very early life males had reduced among-region variability compared with females, while in very late life this was reversed. Overall, our findings of greater regional variability, but less among-region variability in males in early life may aid our understanding of sex-based risk for neurodevelopmental disorders. In contrast, our findings in late life may provide a potential sex-based risk mechanism for dementia.
Iso-osmolar hyponatremia from polyethylene glycol
Authors: Tucker Bryan M , Pirkle James L , Stefi Erinda , Sheikh-Hamad David , DuBose Thomas
Published: April 2020

Understanding and applying pathophysiological concepts to patient care is an important skill for physicians in the clinical setting. Here, we present a case that demonstrates how the application of common physiological concepts relating to the widely accepted hyponatremia algorithm led to an accurate diagnosis of hyponatremia. This case documents iso-osmolar hyponatremia caused by orally administered polyethylene glycol absorption in the gastrointestinal tract. Herein, we discuss the workup and differential diagnosis for iso-osmolar hyponatremia in juxtaposition with the pathophysiological mechanisms unique to this case. We discuss these pathophysiological mechanisms based on the patients’ laboratory data and responses to therapeutic interventions.
Intrinsic cardiac elastography in patients with primary mitral regurgitation: predictive role after mitral valve repair
Authors: De Jesus Tais , Alashry Mahmoud M , Padang Ratnasari , Pislaru Sorin V , Nkomo Vuyisile T , Pellikka Patricia A , Pislaru Cristina
Published: April 2020

Aims 

Chronic volume-overload can impair systolic and diastolic myocardial properties. We tested the hypothesis that Intrinsic Cardiac Elastography may detect alterations in passive myocardial elasticity in patients with chronic severe mitral regurgitation (MR) and predict worsening left ventricular (LV) function after mitral valve repair (MVr).

Methods and results 

Comprehensive transthoracic echocardiography and cardiac elastography were performed in 80 patients with primary MR (prolapse and/or flail leaflets) of varying severity and compared with 40 normal subjects. In patients who underwent MVr (n = 51), elastography measurements were related to changes in left ventricular ejection fraction (LVEF) at short-term (3–4 days post-op) and mid-term (1 year) follow-up. Most patients were asymptomatic or mildly symptomatic and had preserved LVEF (>60%). Intrinsic velocity propagation (iVP) of myocardial stretch, a direct measure of myocardial stiffness, was higher in patients with severe MR {median 2.0 [interquartile range (IQR) 1.5–2.2] m/s, range 1.1–3.4 m/s; n = 56} compared to normal subjects [median 1.7 (IQR 1.5–1.8) m/s; n = 40; P = 0.0005], but not in those with mild or moderate MR [median 1.7 (IQR 1.4–1.9) m/s; n = 24]. A higher iVP was associated with more severe LV volume-overload and LV and left atrial enlargement (P < 0.05 for all). In patients undergoing MVr, a higher iVP independently predicted a larger drop in LVEF post-intervention (short-term, P = 0.001; 1 year, P = 0.007), incrementally to pre-operative LVEF (P < 0.05).

Conclusion 

Non-invasive measurements of myocardial stiffness were able to predict functional deterioration after MVr for chronic primary MR. Further studies should investigate the mechanisms and practical utility of this novel measurement.
Left ventricular reverse remodeling after successful subannular mitral valve repair in end-stage heart failure: a case report
Authors: Pausch Jonas , Sequeira Gross Tatiana , Reichenspurner Hermann , Girdauskas Evaldas
Published: April 2020

Background

Due to ongoing left ventricular (LV) remodeling and consecutive geometric displacement of both papillary muscles, end-stage heart failure is frequently associated with relevant functional mitral regurgitation (FMR) Type IIIb. Treatment strategies of FMR and their prognostic impact are still controversial.

Case summary

We present a case of an 80-year-old patient who suffered from recurrent symptoms of congestive heart failure due to dilated cardiomyopathy and concomitant severe FMR. To specifically address severe tethering of both mitral leaflets heart team decision was to perform minimally invasive mitral valve repair (MVR) including a subannular LV remodeling procedure, instead of an interventional edge-to-edge repair (MitraClip® procedure). In addition to mitral valve ring annuloplasty, standardized relocation of both papillary muscles was performed successfully, leading to a complete resolution of mitral leaflet tethering. There were no procedural complications and the patient was discharged with an excellent functional result without residual mitral regurgitation. Furthermore, after 12 and 24 months, he reported an increase of his functional exercise capacity and a remarkable reverse LV remodeling could be demonstrated.

Discussion

Novel subannular repair techniques, especially the relocation of both papillary muscles, specifically address severe leaflet tethering in FMR and have an obvious potential to improve long-term competence of MVR. Therefore, they could be considered as a viable therapeutic option even in elderly patients presenting with end-stage cardiomyopathy and severe leaflet tenting.
The antifungal pipeline: the need is established. Are there new compounds?
Authors: Li Dongmei , She Xiaodong , Calderone Richard
Published: April 2020

Our review summarizes and compares the temporal development (eras) of antifungal drug discovery as well as antibacterial ventures. The innovation gap that occurred in antibacterial discovery from 1960 to 2000 was likely due to tailoring of existing compounds to have better activity than predecessors. Antifungal discovery also faced innovation gaps. The semi-synthetic antibiotic era was followed closely by the resistance era and the heightened need for new compounds and targets. With the immense contribution of comparative genomics, antifungal targets became part of the discovery focus. These targets by definition are absolutely required to be fungal- or even lineage (clade) specific. Importantly, targets need to be essential for growth and/or have important roles in disease and pathogenesis. Two types of antifungals are discussed that are mostly in the FDA phase I–III clinical trials. New antifungals are either modified to increase bioavailability and stability for instance, or are new compounds that inhibit new targets. One of the important developments in incentivizing new antifungal discovery has been the prolific number of publications of global and country-specific incidence. International efforts that champion global antimicrobial drug discovery are discussed. Still, interventions are needed. The current pipeline of antifungals and alternatives to antifungals are discussed including vaccines.
Are there viable chemical and non-chemical alternatives to the use of conventional insecticides for the protection of young trees from damage by the large pine weevil Hylobius abietis L. in UK forestry?
Authors: Willoughby Ian H , Moore Roger , Moffat Andrew J , Forster Jack , Sayyed Imam , Leslie Kerstin
Published: April 2020

In UK forestry, the synthetic pyrethroid insecticides alpha-cypermethrin and cypermethrin have been used for many years to provide protection for young trees planted on restock sites from damage by the large pine weevil, Hylobius abietis L. However, concerns over the toxicity of these insecticides to aquatic life if misused have led to a search for alternative forms of protection. This paper describes a detailed programme of efficacy experiments undertaken between 2009 and 2015 to find replacements for these products. Over 50 combinations of chemical and non-chemical approaches were tested on 16 different sites. Of the alternative synthetic insecticides tested, applications of 0.037 g a.i. stem−1 acetamiprid provided high levels of protection from Hylobius browsing damage on young Sitka spruce (Picea sitchensis (Bong.) Carrière) trees, without causing any phytotoxic symptoms, and gave comparable levels of protection to those achievable using alpha-cypermethrin or cypermethrin. Acetamiprid is less toxic to aquatic life than alpha-cypermethrin or cypermethrin and has not been linked to bee decline. Applications of 0.0129 g a.i. stem−1 chlorantraniliprole also showed promise, and this relatively low toxicity non-neonicotinoid insecticide merits further study. Although imidacloprid and thiacloprid also provided good levels of protection, their use in forests is not now permitted due to concerns over their potential impacts on bees and drinking water, respectively. Whilst the natural product insecticide spinosad, and the entomopathogenic fungal control agent Metarhizium anisopliae (Metschn.) Sorokin, gave only limited protection in our work, they may have some future potential if methods of deployment can be improved. Other chemical and non-chemical approaches tested, but found to be largely ineffective in UK conditions, included the natural product insecticides azadirachtin, maltodextrin and pyrethrins, the synthetic insecticides lambda-cyhalothrin and spirotetramat and a wide range of repellents, flexible stem coatings and physical barrier products. However, we conclude that physical barrier sleeves such as MultiPro® and BioSleeve® may have a limited role as a partial substitute for the use of insecticides in the UK in some circumstances, but only if on-site populations of Hylobius are predicted to be low.
The Effects of Housing Cost Burden and Housing Tenure on Moves to a Nursing Home Among Low- and Moderate-Income Older Adults
Authors: Jenkins Morales Meghan , Robert Stephanie A
Published: April 2020

Background and Objectives

In the United States, a growing number of older adults struggle to find affordable housing that can adapt to their changing needs. Research suggests that access to affordable housing is a significant barrier to reducing unnecessary nursing home admissions. This is the first empirical study we know of to examine whether housing cost burden (HCB) is associated with moves to nursing homes among older adults.

Research Design and Methods

Data include low- and moderate-income community-dwelling older adults (N = 3,403) from the nationally representative 2015 National Health and Aging Trends Study. HCB (≥30% of income spent on mortgage/rent) and housing tenure (owner/renter) are combined to create a 4-category housing typology. Multinomial logistic regression models test (a) if renters with HCB are most likely (compared with other housing types) to move to a nursing home over 3 years (2015–2018) and (b) if housing type interacts with health and functioning to predict moves to a nursing home.

Results

Across all models, renters with HCB had the greatest likelihood of moving to a nursing home. Moreover, self-rated health, physical capacity, and mental health were weaker predictors of nursing home moves for renters with HCB.

Discussion and Implications

Results suggest that older renters with HCB are most likely to experience unnecessary nursing home placement. The growing population of older renters experiencing HCB may not only signal a housing crisis, but may also challenge national efforts to shift long-term care away from nursing homes and toward community-based alternatives.
Studying human reproductive biology through single-cell analysis and in vitro differentiation of stem cells into germ cell-like cells
Authors: Li Lin , Yang Risako , Yin Chenghong , Kee Kehkooi
Published: April 2020

BACKGROUND

Understanding the molecular and cellular mechanisms of human reproductive development has been limited by the scarcity of human samples and ethical constraints. Recently, in vitro differentiation of human pluripotent stem cells into germ cells and single-cell analyses have opened new avenues to directly study human germ cells and identify unique mechanisms in human reproductive development.

OBJECTIVE AND RATIONALE

The goal of this review is to collate novel findings and insightful discoveries with these new methodologies, aiming at introducing researchers and clinicians to the use of these tools to study human reproductive biology and develop treatments for infertility.

SEARCH METHODS

PubMed was used to search articles and reviews with the following main keywords: in vitro differentiation, human stem cells, single-cell analysis, spermatogenesis, oogenesis, germ cells and other key terms related to these subjects. The search period included all publications from 2000 until now.

OUTCOMES

Single-cell analyses of human gonads have identified many important gene markers at different developmental stages and in subpopulations of cells. To validate the functional roles of these gene markers, researchers have used the in vitro differentiation of human pluripotent cells into germ cells and confirmed that some genetic requirements are unique in human germ cells and are not conserved in mouse models. Moreover, transcriptional regulatory networks and the interaction of germ and somatic cells in gonads were elucidated in these studies.

WIDER IMPLICATIONS

Single-cell analyses allow researchers to identify gene markers and potential regulatory networks using limited clinical samples. On the other hand, in vitro differentiation methods provide clinical researchers with tools to examine these newly identify gene markers and study the causative effects of mutations previously associated with infertility. Combining these two methodologies, researchers can identify gene markers and networks which are essential and unique in human reproductive development, thereby producing more accurate diagnostic tools for assessing reproductive disorders and developing treatments for infertility.
Quantitative Analysis of Food Additives in a Beverage using High Performance Liquid Chromatography and Diode Array Detection Coupled with Chemometrics
Authors: Aksu Dönmez Özlem , Dinç-Zor Şule , Aşçı Bürge , Bozdoğan Abdürrezzak E
Published: April 2020

Background

In many countries, the levels of synthetic food additives causing harm to humans have been determined and their use has been controlled by legal regulations. Sensitive, accurate and low-cost analysis methods are required for food additive determination.

Objective

In this study, a fast high performance liquid chromatography-diode array detection (HPLC-DAD) analytical methodology for quantification of sodium benzoate, potassium sorbate, ponceau 4R, and carmoisine in a beverage was proposed.

Methods

Partial least squares (PLS) and principal component regression (PCR) multivariate calibration methods applied to chromatograms with overlapped peaks were used to establish a green and smart method with short isocratic elution. A series of synthetic solutions including different concentrations of analytes were used to test the prediction ability of the developed methods.

Conclusions

The average recoveries for all target analytes were in the range of 98.27–101.37% with average relative prediction errors of less than 3%. The proposed chemometrics-assisted HPLC-DAD methods were implemented to a beverage successfully. Analysis results from sodium benzoate, potassium sorbate, ponceau 4R, and carmoisine in a beverage by PLS-2 and PCR were statistically compared with conventional HPLC.

Highlights

The HPLC methods coupled with the PLS-2 and PCR algorithm could provide a simple, quick and accurate strategy for simultaneous determination of sodium benzoate, potassium sorbate, ponceau 4R, and carmoisine in a beverage sample.
Gastroenterology Practitioner and Trainee Numbers in Canada 2018: Annual Report From the Canadian Association of Gastroenterology
Authors: Leddin Desmond , Carroll Matthew , Gillis Cory , Cehovin Adria
Published: April 2020

Background

It is necessary for health planners, educators and physician and patient organizations to be aware of trends in gastroenterologist (GI) numbers in order to ensure that patients have timely access to care.

Methods

The number of GIs in practice and the number of trainees in the specialty was determined for 2018 using three national databases compared with previous years.

Results

In 2018, there were 787 GIs in Canada, which equated to 2.1 GIs per 100,000 population. There are marked differences between provinces with numbers ranging from 1.1 to 2.9 per 100,000. There are 53 GIs specializing in pediatric GI care. Forty-six per cent of practitioners under the age of 35 years are female. Seventy-two residents are training in adult GI and six in pediatrics. Approximately 75% of fellows in adult and pediatric GI are training on temporary visas. The number of adult GIs is decreasing despite increasing national population growth and service demand. The numbers of trainees in both adult and pediatric GI are lower than in 2010. If these trends continue, wait times for GI care, which are already poor, will likely increase further.

Conclusions

Continued monitoring of human resource numbers, patient access to care and validation of current data is required.

The purpose of this report is to present the number of gastroenterologists (GIs), both in practice and in training, in Canada for 2018. We also wished to examine the 2018 numbers by province and gender, compare the 2018 numbers with those of previous years and describe the practice settings and organization.
The United Kingdom’s Coronavirus Act, deprivations of liberty, and the right to liberty and security of the person
Authors: Pugh Jonathan
Published: April 2020

In response to the SARS-CoV-2 coronavirus pandemic the UK government has passed the Coronavirus Act 2020 (CA). Among other things, this act extends existing statutory powers to impose restrictions of liberty for public health purposes. The extension of such powers naturally raises concerns about whether their use will be compatible with human rights law. In particular, it is unclear whether their use will fall within the public heath exception to the Article 5 right to liberty and security of the person in the European Convention of Human Rights. In this paper, I outline key features of the CA, and briefly consider how the European Court of Human Rights has interpreted the public health exception to Article 5 rights. This analysis suggests two grounds on which restrictions of liberty enforced some under the CA might be vulnerable to claims of Article 5 rights violations. First, the absence of specified time limits on certain restrictions of liberty means that they may fail the requirement of legal certainty championed by the European Court in its interpretation of the public health exception. Second, the Coronavirus Act’s extension of powers to individuals lacking public health expertise may undermine the extent to which the act will ensure that deprivations of liberty are necessary and proportionate.
Impact of the Withdrawal of Palivizumab Immunoprophylaxis on the Incidence of Respiratory Syncytial Virus (RSV) Hospitalizations Among Infants Born at 33 to 35 Weeks’ Gestational Age in the Province of Quebec, Canada: The RSV-Quebec Study
Authors: Papenburg Jesse , Defoy Isabelle , Massé Edith , Caouette Georges , Lebel Marc H
Published: April 2020

Background

Infants born at 33–35 completed weeks’ gestational age (wGA) aged <6 months at the start of or born during respiratory syncytial virus (RSV) season and classified as moderate/high risk of severe RSV disease were included in a palivizumab RSV prophylaxis program in the province of Quebec, Canada, until 2014–2015. We assessed the impact of withdrawal of this indication on lower respiratory tract infection (LRTI)/RSV hospitalizations (H) in this population.

Methods

We conducted a 4-year, retrospective, cohort study in 25 Quebec hospitals (2 seasons with and 2 without palivizumab prophylaxis for moderate- to high-risk infants). Our primary outcome was LRTI/RSV-H incidence. We compared LRTI/RSV-H incidence before (2013–2015; seasons 1 + 2 [S1/2]) and after (2015–2017; S3/4) the change in indication.

Results

We identified 6457 33–35 wGA births. LRTI/RSV-H occurred in 105/3353 infants (3.13%) in S1/2 and 130/3104 (4.19%) in S3/4. Among LRTI/RSV-H, 86.4% were laboratory-confirmed RSV-H. Adjusting for sex, wGA, and birth month, S3/4 was significantly associated with increased LRTI/RSV-H incidence (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.04–1.76) but not with laboratory-confirmed RSV-H (aOR, 1.19; 95% CI, 0.90–1.58). Mean duration of LRTI/RSV-H was 5.6 days; 22.6% required intensive care unit admission. Comparing S3/4 with S1/2, infant percentage with LRTI/RSV-H classified as moderate/high risk increased from 27.8% to 41.9% (P = .11).

Conclusions

In a province-wide study, we observed a significant increase in LRTI/RSV-H incidence among infants born at 33–35 wGA in the 2 years after withdrawal of RSV prophylaxis.
The Effects of Limited Work Opportunities on Transitions to Adulthood among Young Refugees in Uganda and Jordan
Authors: Shand Wayne , van Blerk Lorraine , Prazeres Laura , Bukenya Badru , Ibrahim Rawan , Hunter Janine , Essaid Aida A , Kasirye Rogers
Published: April 2020

Young people constitute more than half of global refugee populations, yet there is limited research into the impact of displacement on transitions into adult life. With the average period of protracted displacement extending beyond 20 years, insight is needed into how the experience of being a refugee shapes the expectations and lives of young people. This article examines the effects of weak and restricted labour markets on the transitions of young refugees into adulthood. Drawing from research undertaken with displaced children and youth in Uganda and Jordan, the article explores how a lack of work opportunities affects individual ability to achieve financial independence and, more widely, to obtain the social recognition associated with adulthood. The research finds how a dependence on precarious work and the effects of legal restrictions on employment curtail transitions to adulthood, highlighting the importance of national and humanitarian policy support to help young refugees establish stable livelihoods.
The use of dorsoradial forearm flap for the treatment of dorsal hand defect
Authors: Karakol Perçin , Sezgiç Melihcan , Tatar Burak Ergün , Gelbal Caner , Uslu Can
Published: April 2020

Generally dorsal hand defects are often closed with a flap. Dorsoradial forearm artery flap has generally been used in thumb defects; however, it can also be used in the reconstruction of dorsal hand defects thanks to its wide rotation arc and appropriate pedicle length. In this case report, we presented the outcome of a case where the dorsoradial forearm flap was applied to treat the dorsal hand defect. A 27-year-old patient was admitted to emergency room with trauma on hand. Fixation of metacarpal bone fractures was performed. The dorsoradial forearm flap was elevated and inserted in order to close an opening exposing bones and tendons in the dorsum of hand. There was no complication with flap viability in the postoperative period. Patient’s joint range of motion and vital functions were acceptable. Dorsoradial forearm flap, which is generally used in thumb reconstruction, can also be used in dorsal hand defects.
Who wrote Wuthering Heights?
Authors: McCarthy Rachel , O'Sullivan James
Published: April 2020

Emily Brontë published Wuthering Heights in 1847 under the pseudonym Ellis Bell. It was not until the later second edition, published after Emily’s death, that she was credited as the novel’s author. Those Victorian attitudes towards women which compelled Brontë to publish as Bell have not been wholly eradicated, with her legitimacy as the sole author being called into question by male commentators at several junctures since. Their claim is that Emily’s brother Branwell is the real author of Wuthering Heights. Using stylometry, a computer-assisted technique which measures the likely author of a text, this brief experiment demonstrates that it is highly unlikely that Branwell Brontë contributed to the writing of Wuthering Heights, and that Emily, as generally considered, is the novel’s sole author. Furthermore, considering a number of limitations with the corpus being tested, this study provides a good and necessary example of stylometry in practice, and how such an experiment should be conducted in less-than-ideal circumstances.
Low-frequency observations of the Giant Radio Galaxy NGC 6251
Authors: Cantwell T M , Bray J D , Croston J H , Scaife A M M , Mulcahy D D , Best P N , Brüggen M , Brunetti G , Callingham J R , Clarke A O , Hardcastle M J , Harwood J J , Heald G , Heesen V , Iacobelli M , Jamrozy M , Morganti R , Orrú E , O’Sullivan S P , Riseley C J , Röttgering H J A , Shulevski A , Sridhar S S , Tasse C , Van Eck C L
Published: April 2020

We present LOFAR observations at 150 MHz of the borderline FRI/FRII giant radio galaxy NGC 6251. This paper presents the most sensitive and highest-resolution images of NGC 6251 at these frequencies to date, revealing for the first time a low-surface-brightness extension to the northern lobe, and a possible backflow associated with the southern lobe. The integrated spectra of components of NGC 6251 are consistent with previous measurements at higher frequencies, similar to results from other LOFAR studies of nearby radio galaxies. We find the outer structures of NGC 6251 to be either at equipartition or slightly electron dominated, similar to those of FRII sources rather than FRIs; but this conclusion remains tentative because of uncertainties associated with the geometry and the extrapolation of X-ray measurements to determine the external pressure distribution on the scale of the outer lobes. We place lower limits on the ages of the extension of the northern lobe and the backflow of the southern lobe of t ≳ 250 Myr and t ≳ 210 Myr respectively. We present the first detection of polarisation at 150 MHz in NGC 6251. Taking advantage of the high Faraday resolution of LOFAR, we place an upper limit on the magnetic field in the group of B < 0.2 (ΛB/10 kpc)−0.5 μG for a coherence scale of ΛB < 60 kpc and B < 13 μG for ΛB = 240 kpc.
LOFAR detectability of prompt low-frequency radio emission during gamma-ray burst X-ray flares
Authors: Starling R L C , Rowlinson A , van der Horst A J , Wijers R A M J
Published: April 2020

The prompt emission in long gamma-ray bursts (GRBs) arises from within relativistic outflows created during the collapse of massive stars, and the mechanism by which radiation is produced may be either magnetically or matter dominated. In this work, we suggest an observational test of a magnetically dominated Poynting flux model that predicts both γ-ray and low-frequency radio pulses. A common feature among early light curves of long GRBs are X-ray flares, which have been shown to arise from sites internal to the jet. Ascribing these events to the prompt emission, we take an established Swift XRT flare sample and apply a magnetically dominated wind model to make predictions for the timing and flux density of corresponding radio pulses in the ∼100–200 MHz band observable with radio facilities such as LOFAR. We find that 44 per cent of the X-ray flares studied would have had detectable radio emission under this model, for typical sensitivities reached using LOFAR’s rapid response mode and assuming negligible absorption and scattering effects in the interstellar and intergalactic medium. We estimate the rate of Swift GRBs displaying X-ray flares with detectable radio pulses, accessible to LOFAR, of order seven per year. We determine that LOFAR triggered observations can play a key role in establishing the long debated mechanism responsible for GRB prompt emission.
Measuring the eccentricity of binary black holes in GWTC-1 by using the inspiral-only waveform
Authors: Wu Shichao , Cao Zhoujian , Zhu Zong-Hong
Published: April 2020

In this article, we estimate the eccentricity of 10 binary black holes (BBHs) in the Gravitational-Wave Transient Catalog GWTC-1 by using the inspiral-only BBH waveform template EccentricFD. First, we test our method with simulated eccentric BBHs. Afterwards we apply the method to real BBH gravitational-wave data. We find that the BBHs in GWTC-1, with the exception of GW151226, GW170608 and GW170729, show very small eccentricity. Their upper limits on eccentricity range from 0.033–0.084 with 90 per cent credible interval at a reference frequency of 10 Hz. For GW151226, GW170608 and GW170729, the upper limits are higher than 0.1. The relatively large eccentricity of GW151226 and GW170729 is probably due to ignoring χeff and the low signal-to-noise ratio, and GW170608 is worthy of follow-up research. We also point out the limitations of the inspiral-only non-spinning waveform template in eccentricity measurement. Measurement of BBH eccentricity helps us to understand its formation mechanism. With an increase in the number of BBH gravitational-wave events and a more complete eccentric BBH waveform template, this will become a viable method in the near future.
The impact of scatter in the galaxy UV luminosity to halo mass relation on Ly α visibility during the epoch of reionization
Authors: Whitler Lily R , Mason Charlotte A , Ren Keven , Dijkstra Mark , Mesinger Andrei , Pentericci Laura , Trenti Michele , Treu Tommaso
Published: April 2020

The reionization of hydrogen is closely linked to the first structures in the Universe, so understanding the timeline of reionization promises to shed light on the nature of these early objects. In particular, transmission of Lyman alpha (Ly α) from galaxies through the intergalactic medium (IGM) is sensitive to neutral hydrogen in the IGM, so can be used to probe the reionization timeline. In this work, we implement an improved model of the galaxy UV luminosity to dark matter halo mass relation to infer the volume-averaged fraction of neutral hydrogen in the IGM from Ly α observations. Many models assume that UV-bright galaxies are hosted by massive dark matter haloes in overdense regions of the IGM, so reside in relatively large ionized regions. However, observations and N-body simulations indicate that scatter in the UV luminosity–halo mass relation is expected. Here, we model the scatter (though we assume the IGM topology is unaffected) and assess the impact on Ly α visibility during reionization. We show that UV luminosity–halo mass scatter reduces Ly α visibility compared to models without scatter, and that this is most significant for UV-bright galaxies. We then use our model with scatter to infer the neutral fraction, $\overline{x}_{\mathrm{ H}\,{\small I}}$, at z ∼ 7 using a sample of Lyman-break galaxies in legacy fields. We infer $\overline{x}_{\mathrm{ H}\,{\small I}} = 0.55_{-0.13}^{+0.11}$ with scatter, compared to $\overline{x}_{\mathrm{ H}\,{\small I}} = 0.59_{-0.14}^{+0.12}$ without scatter, a very slight decrease and consistent within the uncertainties. Finally, we place our results in the context of other constraints on the reionization timeline and discuss implications for future high-redshift galaxy studies.
CRISPR–Cas12a system in fission yeast for multiplex genomic editing and CRISPR interference
Authors: Zhao Yu , Boeke Jef D
Published: April 2020

The CRISPR–Cas12a is a class II, type V clustered regularly interspaced short palindromic repeat (CRISPR) system with both RNase and DNase activity. Compared to the CRISPR–Cas9 system, it recognizes T-rich PAM sequences and has the advantage of multiplex genomic editing. Here, in fission yeast Schizosaccharomyces pombe, we successfully implemented the CRISPR–Cas12a system for versatile genomic editing and manipulation. In addition to the rrk1 promoter, we used new pol II promoters from endogenous coding genes to express crRNA for Cas12a and obtained a much higher editing efficiency. This new design expands the promoter choices for potential applications in fission yeast and other organisms. In addition, we expressed a gRNA array using a strong constitutive pol II promoter. The array transcript is processed by Cas12a itself to release multiple mature crRNAs. With this construct, multiplex genomic editing of up to three loci was achieved from a single yeast transformation. We also built a CRISPR interference system using a DNase-dead Cas12a to significantly repress endogenous gene expression. Our study provides the first CRISPR-Cas12a toolkit for efficient and rapid genomic gene editing and regulation in fission yeast.
FGviewer: an online visualization tool for functional features of human fusion genes
Authors: Kim Pora , Yiya Ke , Zhou Xiaobo
Published: April 2020

Among the diverse location of the breakpoints (BPs) of structural variants (SVs), the breakpoints of fusion genes (FGs) are located in the gene bodies. This broken gene context provided the aberrant functional clues to study disease genesis. Many tumorigenic fusion genes have retained or lost functional or regulatory domains and these features impacted tumorigenesis. Full annotation of fusion genes aided by the visualization tool based on two gene bodies will be helpful to study the functional aspect of fusion genes. To date, a specialized tool with effective visualization of the functional features of fusion genes is not available. In this study, we built FGviewer, a tool for visualizing functional features of human fusion genes, which is available at https://ccsmweb.uth.edu/FGviewer. FGviewer gets the input of fusion gene symbols, breakpoint information, or structural variants from whole-genome sequence (WGS) data. For any combination of gene pairs/breakpoints to be involved in fusion genes, the users can search the functional/regulatory aspect of the fusion gene in the three bio-molecular levels (DNA-, RNA-, and protein-levels) and one clinical level (pathogenic-level). FGviewer will be a unique online tool in disease research communities.
The Parliamentarisation of Security in the UK and Australia
Authors: Neal Andrew W
Published: April 2020

This article examines the parliamentarisation of security through four decades of committee activity in the UK and Australia. Security governance has expanded since the Cold War from defence and secret intelligence to an array of problematisations that could arise in almost any policy area. This has driven parliamentary activity, with the effect that a much wider range of committees have done substantive work on security issues. The UK and Australia display similar levels of security parliamentarisation but of a different character due to differences in executive/legislative relations, party discipline, parliamentary rules and geopolitical circumstance.
Maintaining High-Quality Multidisciplinary Pain Medicine Fellowship Programs: Part I: Innovations in Pain Fellows’ Education, Research, Applicant Selection Process, Wellness, and ACGME Implementation During the COVID-19 Pandemic
Authors: Kohan Lynn , Moeschler Susan , Spektor Boris , Przkora Rene , Sobey Christopher , Brancolini Scott , Wahezi Sayed , Anitescu Magdalena
Published: April 2020

Background

Pain fellowship programs are facing unique challenges during the COVID-19 pandemic. Restrictions from state governments and the Centers for Disease Control and Prevention have resulted in a rapidly changing and evolving learning environment for todays’ fellows. Innovative solutions must be sought to guarantee that proper education is maintained and to ensure the well-being of our trainees.

Methods

We assembled a panel of pain program directors who serve as officers/board members of the Association of Pain Program Directors to provide guidance and formulate recommendations to pain fellowship directors nationally. This guidance is based on reviewing current changes to the Accreditation Council for Graduate Medical Education (ACGME) and American Board of Anesthesiology policies and best available evidence and expert opinion on the use of remote educational activities, research endeavors, and trainee wellness.

Conclusions

The country is in the midst of an unprecedented pandemic. The impact on pain management fellowships has been severe and will likely last for months, resulting in extraordinary challenges to the administration of pain fellowship programs and the education of our fellows. Understanding revisions to ACGME policies, using technology to promote remote learning opportunities, and providing trainees with opportunities to alleviate their anxiety and encourage mental health are beneficial strategies to implement. Together, we can implement innovative solutions to help overcome these challenges.
Foreign trusts in the Czech Republic: mostly recognized and (sometimes) registered
Authors: Ronovská Kateřina , Pihera Vlastimil
Published: April 2020

In connection with the recodification of private law in effect from 2014, several innovations have appeared in the Czech legal system. Among them were trust funds, i.e. Czech trust-like instruments, as well as rules for recognizing foreign trust structures. Although their position has significantly improved as a result, the operation of foreign trust structures in the Czech Republic still gives rise to some questions to which the current Czech law does not have any clear answers. Drawing attention to those issues, the aim of this article is to suggest some measures that can be taken in order to limit the risks arising in relation to foreign trusts.
Respirometric Screening and Characterization of Mitochondrial Toxicants Within the ToxCast Phase I and II Chemical Libraries
Authors: Hallinger Daniel R , Lindsay Hayley B , Paul Friedman Katie , Suarez Danielle A , Simmons Steven O
Published: April 2020

Mitochondrial toxicity drives several adverse health outcomes. Current high-throughput screening assays for chemically induced mitochondrial toxicity typically measure changes to mitochondrial structure and may not detect known mitochondrial toxicants. We adapted a respirometric screening assay (RSA) measuring mitochondrial function to screen ToxCast chemicals in HepG2 cells using a tiered testing strategy. Of 1042 chemicals initially screened at a singlemaximal concentration, 243 actives were identified and rescreened at 7 concentrations. Concentration-response data for 3 respiration phases confirmed activity and indicated a mechanism for 193 mitochondrial toxicants: 149 electron transport chain inhibitors (ETCi), 15 uncouplers and 29 adenosine triphosphate synthase inhibitors. Subsequently, an electron flow assay was used to identify the target complex for 84 of the 149 ETCi. Sixty reference chemicals were used to compare the RSA to existing ToxCast and Tox21 mitochondrial toxicity assays. The RSA was most predictive (accuracy = 90%) of mitochondrial toxicity. The Tox21 mitochondrial membrane potential assay was also highly predictive (accuracy = 87%) of bioactivity but underestimated the potency of well-known ETCi and provided no mechanistic information. The tiered RSA approach accurately identifies and characterizes mitochondrial toxicants acting through diverse mechanisms and at a throughput sufficient to screen large chemical inventories. The electron flow assay provides additional confirmation and detailed mechanistic understanding for ETCi, the most common type of mitochondrial toxicants among ToxCast chemicals. The mitochondrial toxicity screening approach described herein may inform hazard assessment and the in vitro bioactive concentrations used to derive relevant doses for screening level chemical assessment using new approach methodologies.
Burnout and satisfaction with work-life integration among PAs relative to other workers
Authors: Dyrbye Lotte N. , West Colin P. , Halasy Michael , O'Laughlin Danielle J. , Satele Daniel , Shanafelt Tait
Published: April 2020

Objective:

To evaluate burnout and satisfaction with work-life integration among physician assistants (PAs) compared with other US workers.

Methods:

We surveyed PAs and a probability-based sample of US workers. The survey included the Maslach Burnout Inventory and an item on satisfaction with work-life integration.

Results:

Overall, 41.4% of PAs had burnout symptoms and 65.3% were satisfied with their work-life integration. In multivariable analysis, working in emergency medicine and dissatisfaction with control of workload and work-life integration were independently associated with having higher odds of burnout. PAs were more likely to have burnout than other workers but did not have greater struggles with work-life integration.

Conclusion:

Findings from this study suggest burnout and dissatisfaction with work-life integration are common. PAs appear at higher risk for burnout than workers in other fields.
Guiding patients to appropriate vaccination during pregnancy
Authors: Heavey Elizabeth
Published: April 2020

This article focuses on the two universally recommended vaccines during pregnancy—Tdap and influenza—and how NPs can advocate for the appropriate vaccination of this patient population.