bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of neurological diseases using multi-dimensional CSF analysis
Authors: Gross Catharina C , Schulte-Mecklenbeck Andreas , Madireddy Lohith , Pawlitzki Marc , Strippel Christine , Räuber Saskia , Krämer Julia , Rolfes Leoni , Ruck Tobias , Beuker Carolin , Schmidt-Pogoda Antje , Lohmann Lisa , Schneider-Hohendorf Tilman , Hahn Tim , Schwab Nicholas , Minnerup Jens , Melzer Nico , Klotz Luisa , Meuth Sven G , Meyer zu Hörste Gerd , Baranzini Sergio E , Wiendl Heinz
Published: April 2021

Although CSF analysis routinely enables the diagnosis of neurological diseases, it is mainly used for the gross distinction between infectious, autoimmune inflammatory, and degenerative disorders of the CNS. To investigate, whether a multi-dimensional cellular blood and CSF characterization can support the diagnosis of clinically similar neurological diseases, we analysed 546 patients with autoimmune neuroinflammatory, degenerative, or vascular conditions in a cross-sectional retrospective study. By combining feature selection with dimensionality reduction and machine learning approaches we identified pan-disease parameters that were altered across all autoimmune neuroinflammatory CNS diseases and differentiated them from other neurological conditions and inter-autoimmunity classifiers that subdifferentiate variants of CNS-directed autoimmunity. Pan-disease as well as diseases-specific changes formed a continuum, reflecting clinical disease evolution. A validation cohort of 231 independent patients confirmed that combining multiple parameters into composite scores can assist the classification of neurological patients. Overall, we showed that the integrated analysis of blood and CSF parameters improves the differential diagnosis of neurological diseases, thereby facilitating early treatment decisions.
A passive and objective measure of recognition memory in Alzheimer’s disease using Fastball memory assessment
Authors: Stothart George , Smith Laura J , Milton Alexander , Coulthard Elizabeth
Published: April 2021

Earlier diagnosis of Alzheimer’s disease requires biomarkers sensitive to associated structural and functional changes. While considerable progress has been made in the development of structural biomarkers, functional biomarkers of early cognitive change, unconfounded by effort, practice and level of education, are still needed. We present Fastball, a new EEG method for the passive and objective measurement of recognition memory, that requires no behavioural memory response or comprehension of the task . Younger adults, older adults and Alzheimer’s disease patients (n = 20 per group) completed the Fastball task, lasting just under 3 min. Participants passively viewed rapidly presented images and EEG assessed their automatic ability to differentiate between images based on previous exposure, i.e. old/new. Participants were not instructed to attend to previously seen images and provided no behavioural response. Following the Fastball task, participants completed a two-alternative forced choice (2AFC) task to measure their explicit behavioural recognition of previously seen stimuli. Fastball EEG detected significantly impaired recognition memory in Alzheimer’s disease compared to healthy older adults (P < 0.001, Cohen’s d = 1.52), whereas behavioural recognition was not significantly different between Alzheimer’s disease and healthy older adults. Alzheimer’s disease patients could be discriminated with high accuracy from healthy older adult controls using the Fastball measure of recognition memory (AUC = 0.86, P < 0.001), whereas discrimination performance was poor using behavioural 2AFC accuracy (AUC = 0.63, P = 0.148). There were no significant effects of healthy ageing, with older and younger adult controls performing equivalently in both the Fastball task and behavioural 2AFC task. Early diagnosis of Alzheimer’s disease offers potential for early treatment when quality of life and independence can be retained through disease modification and cognitive enhancement. Fastball provides an alternative way of testing recognition responses that holds promise as a functional marker of disease pathology in stages where behavioural performance deficits are not yet evident. It is passive, non-invasive, quick to administer and uses cheap, scalable EEG technology. Fastball provides a new powerful method for the assessment of cognition in dementia and opens a new door in the development of early diagnosis tools.
Tumour immune landscape of paediatric high-grade gliomas
Authors: Ross James L , Velazquez Vega Jose , Plant Ashley , MacDonald Tobey J , Becher Oren J , Hambardzumyan Dolores
Published: April 2021

Over the past decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumours. It has become evident that paediatric high-grade gliomas differ from those in adults with respect to multiple defining aspects including: DNA copy number, gene expression profiles, tumour locations within the CNS and genetic alterations such as somatic histone mutations.

Despite these advances, clinical trials for children with gliomas have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Additionally, although our knowledge of the intrinsic cellular mechanisms driving tumour progression has considerably expanded, little is known about the dynamic tumour immune microenvironment in paediatric high-grade gliomas.

In this review, we explore the genetic and epigenetic landscape of these gliomas and how this drives the creation of specific tumour subgroups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the paediatric high-grade glioma tumour immune microenvironment and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumours.
Nosocomial Outbreak of Coronavirus Disease 2019 by Possible Airborne Transmission Leading to a Superspreading Event
Authors: Cheng Vincent Chi-Chung , Fung Kitty Sau-Chun , Siu Gilman Kit-Hang , Wong Shuk-Ching , Cheng Lily Shui-Kuen , Wong Man-Sing , Lee Lam-Kwong , Chan Wan-Mui , Chau Ka-Yee , Leung Jake Siu-Lun , Chu Allen Wing-Ho , Chan Wai-Shan , Lu Kelvin Keru , Tam Kingsley King-Gee , Ip Jonathan Daniel , Leung Kenneth Siu-Sing , Lung David Christopher , Tse Herman , To Kelvin Kai-Wang , Yuen Kwok-Yung
Published: April 2021

Background

Nosocomial outbreaks with superspreading of coronavirus disease 2019 due to a possible airborne transmission have not been reported.

Methods

Epidemiological analysis, environmental samplings, and whole-genome sequencing (WGS) were performed for a hospital outbreak.

Results

A superspreading event that involved 12 patients and 9 healthcare workers (HCWs) occurred within 9 days in 3 of 6 cubicles at an old-fashioned general ward with no air exhaust built within the cubicles. The environmental contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was significantly higher in air grilles (>2 m from patients’ heads and not within reach) than on high-touch clinical surfaces (36.4%, 8 of 22 vs 3.4%, 1 of 29, P = .003). Six (66.7%) of 9 contaminated air exhaust grilles were located outside patient cubicles. The clinical attack rate of patients was significantly higher than of HCWs (15.4%, 12 of 78 exposed patients vs 4.6%, 9 of 195 exposed HCWs, P = .005). Moreover, the clinical attack rate of ward-based HCWs was significantly higher than of nonward-based HCWs (8.1%, 7 of 68 vs 1.8%, 2 of 109, P = .045). The episodes (mean ± standard deviation) of patient-care duty assignment in the cubicles was significantly higher among infected ward-based HCWs than among noninfected ward-based HCWs (6.0 ± 2.4 vs 3.0 ± 2.9, P = .012) during the outbreak period. The outbreak strains belong to SARS-CoV-2 lineage B.1.36.27 (GISAID clade GH) with the unique S-T470N mutation on WGS.

Conclusions

This nosocomial point source superspreading event due to possible airborne transmission demonstrates the need for stringent SARS-CoV-2 screening at admission to healthcare facilities and better architectural design of ventilation systems to prevent such outbreaks. Portable high-efficiency particulate filters were installed in each cubicle to improve ventilation before resumption of clinical service.
Early impact of the COVID-19 pandemic and social restrictions on ambulance missions
Authors: Laukkanen Lauri , Lahtinen Sanna , Liisanantti Janne , Kaakinen Timo , Ehrola Ari , Raatiniemi Lasse
Published: April 2021

Background

The SARS-CoV-2 coronavirus disease 2019 (COVID-19) has had a major impact on health care services globally. Recent studies report that emergency departments have experienced a significant decline in the number of admitted patients in the early phase of the pandemic. To date, research regarding the influence of COVID-19 on emergency medical services (EMS) is limited. This study investigates a change in the number and characteristics of EMS missions in the early phase of the pandemic.

Methods

All EMS missions in the Northern Ostrobothnia region, Finland (population 295 500) between 1 March to 30 June 2020 were screened and analyzed as the study group. A control group was composed from the EMS calls between the corresponding months in the years 2016–19.

Results

A total of 74 576 EMS missions were screened for the study. Within the first 2 months after the first COVID-19 cases in the study area, the decline in the number of EMS missions was 5.7–13% compared with the control group average. EMS time intervals (emergency call to dispatch, dispatch, en-route, on-scene and hospital handover) prolonged in the COVID-19 period. Dispatches concerning mental health problems increased most in the study period (+1.2%, P < 0.001). Only eleven confirmed COVID-19 infections were encountered by EMS in the study period.

Conclusion

Our findings suggest that the present COVID-19 pandemic and social restrictions lead to changes in the EMS usage. These preliminary findings emphasize the importance of developing new strategies and protocols in response to the oncoming pandemic waves.
Numerical comparison of time-, frequency- and wavelet-domain methods for coda wave interferometry
Authors: Yuan Congcong , Bryan Jared , Denolle Marine
Published: April 2021

Temporal changes in subsurface properties, such as seismic wave speeds, can be monitored by measuring phase shifts in the coda of two seismic waveforms that share a similar source–receiver path but that are recorded at different times. These nearly identical seismic waveforms are usually obtained either from repeated earthquake waveforms or from repeated ambient noise cross-correlations. The five algorithms that are the most popular to measure phase shifts in the coda waves are the windowed cross correlation (WCC), trace stretching (TS), dynamic time warping (DTW), moving window cross spectrum (MWCS) and wavelet cross spectrum (WCS). The seismic wave speed perturbation is then obtained from the linear regression of phase shifts with their respective lag times under the assumption that the velocity perturbation is homogeneous between (virtual or active) source and receiver. We categorize these methods into the time domain (WCC, TS, DTW), frequency domain (MWCS) and wavelet domain (WCS). This study complements this suite of algorithms with two additional wavelet-domain methods, which we call wavelet transform stretching (WTS) and wavelet transform DTW, wherein we apply traditional stretching and DTW techniques to the wavelet transform. This work aims to verify, validate, and test the accuracy and performance of all methods by performing numerical experiments, in which the elastic wavefields are solved for in various 2-D heterogeneous half-space geometries. Through this work, we validate the assumption of a linear increase in phase shifts with respect to phase lags as a valid argument for fully homogeneous and laterally homogeneous velocity changes. Additionally, we investigate the sensitivity of coda waves at various seismic frequencies to the depth of the velocity perturbation. Overall, we conclude that seismic wavefields generated and recorded at the surface lose sensitivity rapidly with increasing depth of the velocity change for all source–receiver offsets. However, measurements made over a spectrum of seismic frequencies exhibit a pattern such that wavelet methods, and especially WTS, provide useful information to infer the depth of the velocity changes.
Mapping lithospheric seismic structure beneath the Shillong plateau (India) and adjoining regions by jointly fitting receiver functions and surface wave dispersion
Authors: Agrawal Mohit , Das Mukesh Kumar , Kumar Sachin , Pulliam Jay
Published: April 2021

The northeastern Indian region is characterized by complex lithospheric structure that developed due to collision between the Indian and Eurasian tectonic plates, in the north, and to subduction beneath the Burmese arc, in the east. We report results from joint modelling of Ps and Sp receiver functions and Rayleigh wave group velocity dispersion curves in which a broad search for acceptable models is performed via simulated annealing. We identify three tectonic domains, the Shillong plateau, Brahmaputra valley and Indo-Burma convergence zone (IBCZ), sampled by teleseismic earthquake data recorded by nine broad-band seismic stations. Our results reveal that the region's thinnest crust lies beneath the Shillong plateau, where it increases slightly from the plateau's eastern edge to its centre and reaches a maximum at the western edge of the plateau. Crustal Vp/Vs ratios range between 1.69 and 1.75 for the Shillong plateau, which is consistent with a felsic composition. Deeper Moho depths beneath the Brahmaputra valley, adjacent to the northern front of the Shillong plateau, may be due to the flexure of Indian lithosphere subducting beneath Asia. Low velocity zones are indicated at ∼5–10 km depth beneath the Brahmaputra valley, which may have been developed by NE–SW trending compressional stresses from the collision at the Himalayan arc and subduction at the Burmese arc. The crust is thickest in Kohima, beneath the Naga thrust in the IBCZ, where a high velocity zone is observed for both Vp and Vs at a depth of 25–40 km. This anomaly may be associated with a high velocity slab, trending N–NE to S–SW, that comprises the subducting Indian lithosphere in the IBCZ.
From detente to containment: the emergence of Iran's new Saudi strategy
Authors: Ahmadian Hassan , Mohseni Payam
Published: April 2021

Iran's strategy with respect to Saudi Arabia is a key factor in the complex balance of power of the Middle East as the Iranian–Saudi rivalry impacts the dynamics of peace and conflict across the region from Yemen to Syria, Lebanon, Iraq and Bahrain. What is Iranian strategic thinking on Saudi Arabia? And what have been the key factors driving the evolution of Iranian strategy towards the Kingdom? In what marks a substantive shift from its previous detente policy, we argue that Tehran has developed a new containment strategy in response to the perceived threat posed by an increasingly pro-active Saudi Arabia in the post-Arab Spring period. Incorporating rich fieldwork and interviews in the Middle East, this article delineates the theoretical contours of Iranian containment and contextualizes it within the framework of the Persian Gulf security architecture, demonstrating how rational geopolitical decision-making factors based on a containment strategy, rather than the primacy of sectarianism or domestic political orientations, shape Iran's Saudi strategy. Accordingly, the article traces Iranian strategic decision-making towards the Kingdom since the Islamic Revolution of 1979 and examines three cases of Iran's current use of containment against Saudi Arabia in Syria, Yemen and Qatar.
Study of chemical looping co-gasification of lignite and rice husk with Cu-Ni oxygen carrier
Authors: Wang Mengxin , Li Tianle , Xiao Yupeng , Wang Wenju
Published: April 2021

Coal is the dominant composition of fossil fuel but, with the accompanying gaseous products, causes environmental pollution. Here, we report a methodology to improve C conversion in co-gasification. The steam gasification and chemical looping gasification (CLG) of lignite and rice husk with oxygen uncoupling over 5% NiO/CuO oxygen carrier were conducted by non-isothermal kinetics method in a fixed-bed reactor. The gasification results showed that the yields of gas products in CLG of lignite or rice husk are higher than that in steam gasification. The yields of gases in chemical looping co-gasification (CLCG) are higher than that in steam co-gasification. In the co-gasification, the complementation of reactivity between fuels facilitated the C conversion rate, so the yields in co-gasification were higher than in individual gasification. The C conversion in CLCG of lignite and rice husk is 14.51% higher than that in steam co-gasification.
On a subdiffusive tumour growth model with fractional time derivative
Authors: Fritz Marvin , Kuttler Christina , Rajendran Mabel L , Wohlmuth Barbara , Scarabosio Laura
Published: April 2021

In this work, we present and analyse a system of coupled partial differential equations, which models tumour growth under the influence of subdiffusion, mechanical effects, nutrient supply and chemotherapy. The subdiffusion of the system is modelled by a time fractional derivative in the equation governing the volume fraction of the tumour cells. The mass densities of the nutrients and the chemotherapeutic agents are modelled by reaction diffusion equations. We prove the existence and uniqueness of a weak solution to the model via the Faedo–Galerkin method and the application of appropriate compactness theorems. Lastly, we propose a fully discretized system and illustrate the effects of the fractional derivative and the influence of the fractional parameter in numerical examples.
Two-Sample Mendelian Randomization Analysis of Associations Between Periodontal Disease and Risk of Cancer
Authors: Corlin Laura , Ruan Mengyuan , Tsilidis Konstantinos K , Bouras Emmanouil , Yu Yau-Hua , Stolzenberg-Solomon Rachael , Klein Alison P , Risch Harvey A , Amos Christopher I , Sakoda Lori C , Vodička Pavel , Rish Pai K , Beck James , Platz Elizabeth A , Michaud Dominique S
Published: April 2021

Background

Observational studies indicate that periodontal disease may increase the risk of colorectal, lung, and pancreatic cancers. Using a 2-sample Mendelian randomization (MR) analysis, we assessed whether a genetic predisposition index for periodontal disease was associated with colorectal, lung, or pancreatic cancer risks.

Methods

Our primary instrument included single nucleotide polymorphisms with strong genome-wide association study evidence for associations with chronic, aggressive, and/or severe periodontal disease (rs729876, rs1537415, rs2738058, rs12461706, rs16870060, rs2521634, rs3826782, and rs7762544). We used summary-level genetic data for colorectal cancer (n = 58 131 cases; Genetics and Epidemiology of Colorectal Cancer Consortium, Colon Cancer Family Registry, and Colorectal Transdisciplinary Study), lung cancer (n = 18 082 cases; International Lung Cancer Consortium), and pancreatic cancer (n = 9254 cases; Pancreatic Cancer Consortia). Four MR approaches were employed for this analysis: random-effects inverse-variance weighted (primary analyses), Mendelian Randomization-Pleiotropy RESidual Sum and Outlier, simple median, and weighted median. We conducted secondary analyses to determine if associations varied by cancer subtype (colorectal cancer location, lung cancer histology), sex (colorectal and pancreatic cancers), or smoking history (lung and pancreatic cancer). All statistical tests were 2-sided.

Results

The genetic predisposition index for chronic or aggressive periodontitis was statistically significantly associated with a 3% increased risk of colorectal cancer (per unit increase in genetic index of periodontal disease; P = .03), 3% increased risk of colon cancer (P = .02), 4% increased risk of proximal colon cancer (P = .01), and 3% increased risk of colorectal cancer among females (P = .04); however, it was not statistically significantly associated with the risk of lung cancer or pancreatic cancer, overall or within most subgroups.

Conclusions

Genetic predisposition to periodontitis may be associated with colorectal cancer risk. Further research should determine whether increased periodontitis prevention and increased cancer surveillance of patients with periodontitis is warranted.
A Systematic Review of Benefit-Finding and Growth in Pediatric Medical Populations
Authors: Kritikos Tessa K , Stiles-Shields Colleen , Winning Adrien M , Starnes Meredith , Ohanian Diana M , Clark Olivia E , del Castillo Allison , Chavez Patricia , Holmbeck Grayson N
Published: April 2021

Objective

This review synthesizes the literature on benefit-finding and growth (BFG) among youth with medical illnesses and disabilities and their parents. Specifically, we summarized: (a) methods for assessing BFG; (b) personal characteristics, personal, and environmental resources, as well as positive outcomes, associated with BFG; (c) interventions that have enhanced BFG; and (d) the quality of the literature.

Methods

A medical research librarian conducted the search across PubMed, Scopus, PsycInfo, Google Scholar, and Cochrane Library. Studies on BFG among children ages 0–18 with chronic illnesses and disabilities, or the parents of these youth were eligible for inclusion. Articles were uploaded into Covidence; all articles were screened by two reviewers, who then extracted data (e.g., study characteristics and findings related to BFG) independently and in duplicate for each eligible study. The review was based on a systematic narrative synthesis framework and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number: CRD42020189339).

Results

In total, 110 articles were included in this review. Generally, BFG capabilities were present across a range of pediatric health conditions and disabilities. Correlates of both youth and parent BFG are presented, including personal and environmental resources, coping resources, and positive outcomes. In addition, studies describing interventions aimed at enhancing BFG are discussed, and a quality assessment of the included studies is provided.

Conclusions

Recommendations are provided regarding how to assess BFG and with whom to study BFG to diversify and extend our current literature.
Experiencing Enumeration: Local Reactions and Resistance to Censuses in Imperial Russia, 1863–81
Authors: Gibson Catherine
Published: April 2021

During the second half of the nineteenth century, statistics attracted significant attention from government officials and educated elites as a method of quantifying socioeconomic change and rendering human and natural resources visible through data. However, we still know little about how local communities responded to changing methods of gathering statistical data during the gradual shift away from forms of enumeration based on legal estates and households toward modern methods of individual enumeration by census. Rarely do we approach the history of censuses from the perspective of the census subjects to consider the experiences of those being counted. This article analyzes interactions between census organizers and local populations in the three Russian imperial Baltic provinces (Estland, Livland, and Kurland) in the second half of the nineteenth century. As a form of administrative intervention, censuses opened up a space for local populations to articulate opinions and question the overlapping layers of authority within the empire between local elites, the provincial administration, and tsarist government. Examining the history of censuses from the perspective of local communities in the Russian Empire demonstrates how attitudes and resistance to censuses were closely tied to particular local issues and concerns. The Baltic case study adds nuance to existing discussions on forms of census resistance by broadening the focus beyond identity politics and conflict over forms of confessional, linguistic, and national classification. Instead, census subjects in the Baltic voiced concerns about how the local authorities might use individual enumeration as a form of administrative surveillance and social control.
Cell identity specification in plants: lessons from flower development
Authors: Xu Xiaocai , Smaczniak Cezary , Muino Jose M , Kaufmann Kerstin
Published: April 2021

Multicellular organisms display a fascinating complexity of cellular identities and patterns of diversification. The concept of ‘cell type’ aims to describe and categorize this complexity. In this review, we discuss the traditional concept of cell types and highlight the impact of single-cell technologies and spatial omics on the understanding of cellular differentiation in plants. We summarize and compare position-based and lineage-based mechanisms of cell identity specification using flower development as a model system. More than understanding ontogenetic origins of differentiated cells, an important question in plant science is to understand their position- and developmental stage-specific heterogeneity. Combinatorial action and crosstalk of external and internal signals is the key to cellular heterogeneity, often converging on transcription factors that orchestrate gene expression programs.
LINC00205 Promotes Tumor Malignancy of Lung Adenocarcinoma Through Sponging miR-185-5p
Authors: Li Yongqiang , Hu Yahui , Wu Yuting , Zhang Deming , Huang Dongwei
Published: April 2021

The emerging role of long noncoding RNAs (lncRNAs) in cancer, especially in lung adenocarcinoma (LUAD), is attracting increasingly more attention as a potential therapeutic target. However, whether lncRNA LINC00205 regulates the malignancy of LUAD has not been characterized. In this study, we discovered that LINC00205 was markedly upregulated in LUAD tissues and cell lines and correlated with poor prognosis of patients with LUAD. Our data showed that LINC00205 promoted the migration and proliferation of LUAD cells in vitro and tumor growth in vivo. Notably, the tumor suppressor miR-185-5p was found to be a direct target of LINC00205. In addition, miR-185-5p diminished the promotion of cell proliferation and migration mediated by LINC00205, whereas miR-185-5p inhibition had the opposite effect. In summary, our results show that LINC00205 contributes to LUAD malignancy by sponging miR-185-5p, which provides new insight into LUAD progression.
Recovering the origins of the lenticular galaxy NGC 3115 using multiband imaging
Authors: Buzzo Maria Luisa , Cortesi Arianna , Hernandez-Jimenez Jose A , Coccato Lodovico , Werle Ariel , Beraldo e Silva Leandro , Grossi Marco , Vika Marina , Barbosa Carlos Eduardo , Lucatelli Geferson , Santana-Silva Luidhy , Bamford Steven , Debattista Victor P , Forbes Duncan A , Overzier Roderik , Romanowsky Aaron J , Ferrari Fabricio , Brodie Jean P , Mendes de Oliveira Claudia
Published: April 2021

A detailed study of the morphology of lenticular galaxies is an important way to understand how this type of galaxy is formed and evolves over time. Decomposing a galaxy into its components (disc, bulge, bar, ...) allows recovering the colour gradients present in each system, its star formation history, and its assembly history. We use galfitm to perform a multiwavelength structural decomposition of the closest lenticular galaxy, NGC 3115, resulting in the description of its stellar light into several main components: a bulge, a thin disc, a thick disc, and also evidence of a bar. We report the finding of central bluer stellar populations in the bulge, as compared to the colour of the galaxy outskirts, indicating either the presence of an active galactic nucleus (AGN) and/or recent star formation activity. From the spectral energy distribution results, we show that the galaxy has a low luminosity AGN component, but even excluding the effect of the nuclear activity, the bulge is still bluer than the outer-regions of the galaxy, revealing a recent episode of star formation. Based on all of the derived properties, we propose a scenario for the formation of NGC 3115 consisting of an initial gas-rich merger, followed by accretions and feedback that quench the galaxy, until a recent encounter with the companion KK084 that reignited the star formation in the bulge, provoked a core displacement in NGC 3115 and generated spiral-like features. This result is consistent with the two-phase formation scenario, proposed in previous studies of this galaxy.
Stellar flares detected with the Next Generation Transit Survey
Authors: Jackman James A G , Wheatley Peter J , Acton Jack S , Anderson David R , Bayliss Daniel , Briegal Joshua T , Burleigh Matthew R , Casewell Sarah L , Gänsicke Boris T , Gill Samuel , Gillen Edward , Goad Michael R , Günther Maximilian N , Henderson Beth A , Hodgkin Simon T , Jenkins James S , Pugh Chloe , Queloz Didier , Raynard Liam , Tilbrook Rosanna H , Watson Christopher A , West Richard G
Published: April 2021

We present the results of a search for stellar flares in the first data release from the Next Generation Transit Survey (NGTS). We have found 610 flares from 339 stars, with spectral types between F8 and M6, the majority of which belong to the Galactic thin disc. We have used the 13-s cadence NGTS light curves to measure flare properties such as the flare amplitude, duration, and bolometric energy. We have measured the average flare occurrence rates of K and early to mid-M stars and present a generalized method to measure these rates while accounting for changing detection sensitivities. We find that field age K and early M stars show similar flare behaviour, while fully convective M stars exhibit increased white-light flaring activity, which we attribute to their increased spin-down time. We have also studied the average flare rates of pre-main-sequence K and M stars, showing they exhibit increased flare activity relative to their main-sequence counterparts.
In the mouse, prostaglandin D2 signalling protects the endometrium against adenomyosis
Authors: Philibert Pascal , Déjardin Stéphanie , Pirot Nelly , Pruvost Alain , Nguyen Anvi Laetitia , Bernex Florence , Poulat Francis , Boizet-Bonhoure Brigitte
Published: April 2021

Adenomyosis is characterised by epithelial gland and mesenchymal stroma invasion of the uterine myometrium. Adenomyosis is an oestrogen-dependent gynaecological disease in which a number of factors, such as inflammatory molecules, prostaglandins (PGs), angiogenic factors, cell proliferation and extracellular matrix remodelling proteins, also play a role as key disease mediators. In this study, we used mice lacking both lipocalin and hematopoietic-PG D synthase (L- and H-Pgds) genes in which PGD2 is not produced to elucidate PGD2 roles in the uterus. Gene expression studied by real-time PCR and hormone dosages performed by ELISA or liquid chromatography tandem mass spectroscopy in mouse uterus samples showed that components of the PGD2 signalling pathway, both PGDS and PGD2-receptors, are expressed in the mouse endometrium throughout the oestrus cycle with some differences among uterine compartments. We showed that PGE2 production and the steroidogenic pathway are dysregulated in the absence of PGD2. Histological analysis of L/H-Pgds−/− uteri, and immunohistochemistry and immunofluorescence analyses of proliferation (Ki67), endothelial cell (CD31), epithelial cell (pan-cytokeratin), myofibroblast (α-SMA) and mesenchymal cell (vimentin) markers, identify that 6-month-old L/H-Pgds−/− animals developed adenomyotic lesions, and that disease severity increased with age. In conclusion, this study suggests that the PGD2 pathway has major roles in the uterus by protecting the endometrium against adenomyosis development. Additional experiments, using for instance transcriptomic approaches, are necessary to fully determine the molecular mechanisms that lead to adenomyosis in L/H-Pgds−/− mice and to confirm whether this strain is an appropriate model for studying the human disease.
Dynamically elongated associative toehold for tuning DNA circuit kinetics and thermodynamics
Authors: Ang Yan Shan , Yung Lin-Yue Lanry
Published: April 2021

Associative toehold is a powerful concept enabling efficient combinatorial computation in DNA circuit. A longer association length boosts circuit kinetics and equilibrium signal but results in higher leak rate. We reconcile this trade-off by using a hairpin lock design to dynamically elongate the effective associative toehold length in response to the input target. Design guidelines were established to achieve robust elongation without incurring additional leakages. Three hairpin initiators with different combinations of elongated associative toehold (4 → 6 nt, 5 → 8 nt and 6 → 9 nt) were shortlisted from the design framework for further discussion. The circuit performance improved in terms of reaction kinetics, equilibrium signal generated and limit of detection. Overall, the elongated associative toehold served as a built-in function to stabilize and favour the forward, desired reaction when triggered.
The multi-functionality of UHRF1: epigenome maintenance and preservation of genome integrity
Authors: Mancini Monica , Magnani Elena , Macchi Filippo , Bonapace Ian Marc
Published: April 2021

During S phase, the cooperation between the macromolecular complexes regulating DNA synthesis, epigenetic information maintenance and DNA repair is advantageous for cells, as they can rapidly detect DNA damage and initiate the DNA damage response (DDR). UHRF1 is a fundamental epigenetic regulator; its ability to coordinate DNA methylation and histone code is unique across proteomes of different species. Recently, UHRF1’s role in DNA damage repair has been explored and recognized to be as important as its role in maintaining the epigenome. UHRF1 is a sensor for interstrand crosslinks and a determinant for the switch towards homologous recombination in the repair of double-strand breaks; its loss results in enhanced sensitivity to DNA damage. These functions are finely regulated by specific post-translational modifications and are mediated by the SRA domain, which binds to damaged DNA, and the RING domain. Here, we review recent studies on the role of UHRF1 in DDR focusing on how it recognizes DNA damage and cooperates with other proteins in its repair. We then discuss how UHRF1’s epigenetic abilities in reading and writing histone modifications, or its interactions with ncRNAs, could interlace with its role in DDR.
Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation
Authors: Letunic Ivica , Bork Peer
Published: April 2021

The Interactive Tree Of Life (https://itol.embl.de) is an online tool for the display, manipulation and annotation of phylogenetic and other trees. It is freely available and open to everyone. iTOL version 5 introduces a completely new tree display engine, together with numerous new features. For example, a new dataset type has been added (MEME motifs), while annotation options have been expanded for several existing ones. Node metadata display options have been extended and now also support non-numerical categorical values, as well as multiple values per node. Direct manual annotation is now available, providing a set of basic drawing and labeling tools, allowing users to draw shapes, labels and other features by hand directly onto the trees. Support for tree and dataset scales has been extended, providing fine control over line and label styles. Unrooted tree displays can now use the equal-daylight algorithm, proving a much greater display clarity. The user account system has been streamlined and expanded with new navigation options and currently handles >1 million trees from >70 000 individual users.
Sofosbuvir-based hepatitis C therapies in patients with chronic and end-stage kidney disease
Authors: Sise Meghan E , McQuaid Thomas , Martin Paul
Published: April 2021

Sofosbuvir (SOF), a nucleotide inhibitor of the hepatitis C virus (HCV) polymerase, is a component of several all-oral HCV therapies. GS-331007, SOF’s predominant metabolite, is renally eliminated and accumulates 5- to 20-fold in patients with advanced chronic kidney disease (CKD) or undergoing hemodialysis (HD), respectively. Preclinical data did not determine whether these exposures represented a risk for toxicity. Therefore subjects with advanced CKD were not included in registrational studies and SOF was not initially approved for use in advanced CKD. Nevertheless, after initial licensing, off-label use of SOF at full or reduced doses was reported in patients with kidney disease. Two clinical trials of SOF-containing therapies were conducted in patients with end-stage kidney disease, demonstrating safety and efficacy. These led to expanded US Food and Drug Administration approval in 2019 for the use of SOF-containing regimens in patients with advanced CKD, including dialysis dependence. Even so, given the availability of protease inhibitor–containing direct-acting antiviral regimens, there was a reluctance by some practitioners to use SOF-containing regimens in moderate to severe kidney disease. Here we review the existing data on SOF’s pharmacokinetics, toxicology, efficacy and safety in patients with kidney disease. Data from both clinical trials and real-world practice settings indicate that in patients with moderate to severe kidney disease, full-dose SOF-based regimens have high rates of efficacy and acceptable safety and tolerability profiles, without increased risk for cardiac adverse events or clinically meaningful changes in kidney function. SOF-based regimens are safe and effective in patients who have moderate to severe kidney disease, including those undergoing HD.
Lymphopaenia at diagnosis of anti-neutrophil cytoplasmic antibody-vasculitis with renal involvement is correlated with severity and renal prognosis
Authors: Wacrenier Samuel , Riou Jérémie , Jourdain Pierre , Guibert Fanny , Henry Nicolas , Djema Assia , Coindre Jean-Philippe , Crochette Romain , Cousin Maud , Croue Anne , Subra Jean-François , Piccoli Giorgina , Augusto Jean-François , Brilland Benoit
Published: April 2021

Background

Lymphopaenia is commonly observed in autoimmune diseases, where it has been associated with disease activity or prognosis. However, in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) only a few small-scale studies have been targeted towards this issue. Research has not yet focused on AAV with renal involvement (AAV-RI). Thus the aim of this study was to analyse the association between lymphocyte counts and outcomes in a large cohort of AAV-RI patients.

Methods

We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French nephrology centres, recorded since January 2000. We analysed clinical, biological and histological data at diagnosis of AAV-RI. Risk factors for end-stage kidney disease (ESKD) were analysed. Event-free survival was also assessed.

Results

Among the 145 patients included in the study, those with lymphopaenia at diagnosis had a lower renal function at baseline [estimated glomerular filtration rate (eGFR) 13 versus 26 mL/min; P = 0.002] and were more likely to require kidney replacement therapy (51% versus 25%; P = 0.003). Lymphopaenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (P = 0.0027). ESKD-free survival was lower in lymphopaenic patients (P < 0.0001). In multivariate Cox analysis, lymphopaenia was an independent risk factor for ESKD [hazard ratio 4.47 (95% confidence interval 2.06–9.72), P < 0.001].

Conclusions

Lymphopaenia correlates with the severity of AAV glomerulonephritis at diagnosis and predicts poor renal outcome. In this view, lymphopaenia could be used as a simple and cost-effective biomarker to assess renal prognosis at AAV-RI diagnosis.
A large-scale experiment demonstrates that line marking reduces power line collision mortality for large terrestrial birds, but not bustards, in the Karoo, South Africa
Authors: Shaw Jessica M , Reid Tim A , Gibbons Bradley K , Pretorius Matt , Jenkins Andrew R , Visagie Ronelle , Michael Michael D , Ryan Peter G
Published: April 2021

Line markers are widely used to mitigate bird collisions with power lines, but few studies have robustly tested their efficacy. Power line collisions are an escalating problem for several threatened bird species endemic to southern Africa, so it is critical to know whether or not marking works to adequately manage this problem. Over 8 yr, a large-scale experiment was set up on 72 of 117 km of monitored transmission power lines in the eastern Karoo, South Africa, to assess whether line markers reduce bird collision mortality, particularly for Blue Cranes (Grus paradisea) and Ludwig’s Bustards (Neotis ludwigii). We tested the 2 marking devices commonly used in South Africa: bird flappers and static bird flight diverters. Using a before-after-control-impact design, we show that line marking reduced collision rates for Blue Cranes by 92% (95% confidence interval [CI]: 77–97%) and all large birds by 51% (95% CI: 23–68%), but had no effect on bustards. Both marker types appeared similarly effective. Given that monitoring at this site also confirmed high levels of mortality of a range of species of conservation concern, we recommend that marking be widely installed on new power lines. However, other options need to be explored urgently to reduce collision mortality of bustards. Five bustard species were in the top 10 list of most frequently found carcasses, and high collision rates of Ludwig’s Bustards (0.68 birds km–1 yr–1 uncorrected for survey biases) add to wider concerns about population-level effects for this range-restricted and Endangered species.
Army-ant following in Neotropical birds: A review and prospectus
Authors: Martínez Ari E , Pollock Henry S , Rodrigues Patricia F , Touchton Janeene M
Published: April 2021

Army-ants (particularly swarm-raiding species Eciton burchellii and Labidus praedator) are keystone predators in Neotropical forests. Hundreds of associated species from diverse taxa depend on them for survival, the most conspicuous of which are the ant-following birds. These birds forage on cryptic arthropods and vertebrates as they attempt to escape raiding army-ants. Despite capturing the attention of tropical biologists for centuries, research on ant-following birds has been largely limited to natural history observations until more recently. Here, we argue that this complex system provides unique and underappreciated opportunities for testing hypotheses in 5 main areas of interest: (1) competitive interactions among attendant birds, (2) cognitive and behavioral adaptations for locating swarms, (3) evolution of ant-following behavior, (4) biogeography of ant-following behavior, and (5) conservation of ant-following birds. For each research area, we review the current state of knowledge and make suggestions for fruitful research avenues that we believe will help address important questions in the fields of ecology, evolution, and behavior.
Police Accountability in the United States: A View from the UK
Authors: McDaniel John L M
Published: April 2021

In the article entitled ‘Police Accountability in the United States: Gaining Traction or Spinning Wheels?’, Professor Carol Archbold addresses many of the obstacles facing police reformers in the USA; this commentary reflects upon two of the areas from a UK perspective: (1) the use of civilian arbiters of police misconduct and (2) the release of police misconduct data to the public.
The impact of economic crisis on mortality due to mental health illnesses
Authors: Zilidis C , Angelopoulos N V
Published: April 2021

Background

The financial crisis affected several aspects of health. The aim of this study is to explore the impact of the crisis on mortality of mental illnesses in Greece and the socioeconomic determinants of mortality trends.

Methods

Mortality data of 2000–16 were analyzed and sex-and-age-standardized death rates (SDRs) were calculated. The Average Annual Percent Change (AAPC) before and after the time point of slope change was computed. The crisis impact on SDRs was explored with interrupted time series analyses and standardized rate ratios (SRRs). The correlation of mortality with socioeconomic and healthcare-related variables was investigated with correlation and regression analyses.

Results

A significant change in SDR trend was observed after 2012. The AAPC reversed from −2.9% to 94.5%, while the SRR was calculated at 6.1 (5.5–6.7). Income reduction, unemployment rise and health budget cuts were found to be significantly correlated with mortality rise.

Conclusions

Financial crisis had a significant impact on mortality due to mental illnesses, especially in females and elderly. The findings indicate that mortality increase is more driven by socioeconomic and healthcare-related factors that affect access to appropriate healthcare than by morbidity trends. The findings have implications in planning interventions to provide appropriate healthcare to patients living with mental illness.
Individual and organizational health literacies: moderating psychological distress for individuals with chronic conditions
Authors: Li Ang
Published: April 2021

Background

People with chronic conditions experience high psychological distress.

Methods

Using the National Health Survey in Australia during 2017–18, the study assessed whether and which health literacies moderated the relationship between chronic conditions and psychological distress for diabetes, chronic kidney disease (CKD), cardiovascular disease (CVD), arthritis, other musculoskeletal conditions, asthma, other chronic lower respiratory diseases and cancer. Psychological distress was regressed on chronic diseases, health literacy domains and their interactions, controlling for demographic, socioeconomic and health factors.

Results

Of 5790 adults, 4212 (72.75%) aged 18–64; 846 (14.6%) had high or very high psychological distress, 1819 (31.4%) had diabetes, CKD or CVD, 2645 (45.7%) musculoskeletal conditions, and 910 (15.7%) lower respiratory conditions. Having sufficient information from healthcare providers was associated with the lowest level of psychological distress for CKD and cancer. Social support was associated with significantly lower levels of psychological distress for cardiovascular, musculoskeletal and lower respiratory conditions. Understanding health information was associated with the largest improvement in psychological distress for diabetes.

Conclusions

Higher health literacies were associated with reduced risks of psychological distress among individuals managing chronic conditions. Interventions for improving self-management and health inequalities should incorporate disease-specific health literacy enhancement strategies at individual and organizational levels.
Responding to the fear of dying alone during COVID-19 pandemic
Authors: Corpuz Jeff Clyde G
Published: April 2021

A recent correspondence published in this journal rightly argues the meaning of creative ritual practices during the coronavirus disease 2019 (COVID-19) pandemic. Recent researches revealed the ‘creative ways’ to augment the need for spiritual and religious longing, complicated grief and different ways of coping with loss and coping mental health issues during the COVID-19 pandemic. This paper further adds the ways on how to mitigate the reality of dying alone during COVID-19 pandemic.