bluuebunny/crossref_metadata_2025 huggingface dataset:
Pleiotropic roles of N-glycans for enzyme activities and stabilities of MIPC synthases, Csh1 and Sur1/Csg1, inSaccharomyces cerevisiae
Authors: Uemura Satoshi , Moriguchi Takashi
Published: June 2022

Mannosyl phosphorylceramide (MIPC) is a membrane lipid classified as a complex sphingolipid in Saccharomyces cerevisiae. MIPC is synthesized by 2 redundant enzymes, Sur1/Csg1 and Csh1, in the Golgi lumen. MIPC consists of 5 subtypes (A, B′, B, C, and D-type) according to the position and number of hydroxyl groups on the ceramide moiety. Sur1 exerts higher impact on synthesis of MIPC-B and MIPC-C than Csh1. In this study, we elucidated the roles played by N-glycans attached to Sur1 and Csh1, and dissected the mechanisms underlying substrate recognition by these 2 enzymes. Sur1 carries an N-glycan on Asn-224, whereas Csh1 has N-glycans on Asn-51 and Asn-247. Although intracellular proteins usually harbor core-type N-glycans, the N-glycan on Asn-51 of Csh1 exhibited a unique mannan-like structure containing a long backbone of mannose. Sur1 N224Q and Csh1 N51Q mutants exhibited a decrease in the activity to synthesize specific MIPC subtypes for each enzyme, suggesting that these N-glycans play a role in substrate recognition through their catalytic domains. Moreover, ectopic insertion of an N-glycosylation consensus sequence (NST) at codon 51 of Sur1 (Sur1-NST51) resulted in an artificial modification with mannan, which markedly decreased protein stability. Our results suggest that the diminished stability of the Sur1-NST51 mutant protein could be attributable to potential structural alterations by the mannan. Collectively, the present study reveals essential luminal domains of Sur1 and Csh1 that dictate substrate specificity and/or the protein stabilities via mannan modification.
What are the tools available for the job? Coordination instruments at Uganda’s national government level and their implications for multisectoral action for health
Authors: Ssennyonjo Aloysius , Criel Bart , Van Belle Sara , Ssengooba Freddie , Titeca Kristof
Published: June 2022

Managing sectoral interdependences requires functional tools that facilitate coordinated multisectoral efforts. The pursuit of multisectoral action for health is intrinsically linked to broader efforts in many governments to achieve greater internal coordination. This research explores the nature of coordination instruments for multisectoral action at the national level in Uganda and the complexities of how these tools play out in implementation. Data was collected through 26 purposive in-depth interviews with national-level stakeholders, including government officials and non-state actors, and a review of selected government strategic documents. A typology of coordination instruments was developed and used to break them down into structural and management tools, and infer their underlying coordination mechanisms based on their design and operational features. A multitheoretical framework guided the analysis of the factors influencing the implementation dynamics and functioning of the tools. The study found that the Government of Uganda uses a range of structural and management instrument mixes mutually influencing each other and mainly based on hierarchy and network mechanisms These instruments constitute and generate the resources that structure interorganizational relationships across vertical and horizontal boundaries. The instrument mixes also create hybrid institutional configurations that generate complementary but at times conflicting influences. This study demonstrated that a contextualized examination of specific coordination tools can be enhanced by delineating the underlying institutional forms of ideal type mechanisms. Such an approach can inspire more complex analysis and comparisons of coordination instruments within and across government levels, policy domains or issues over time. Health policy and systems research needs to pay attention to the instrument mixes in government systems and their dynamic interaction across policy issues and over time.
Managing Inflammatory Bowel Disease in Pregnancy: Health Care Professionals’ Involvement, Knowledge, and Decision Making
Authors: Liu Eleanor , Laube Robyn , Leong Rupert W , Fraser Aileen , Selinger Christian , Limdi Jimmy K
Published: June 2022

Background

The management of pregnant women with inflammatory bowel disease (IBD) is complex. We aimed to assess health care professionals’ (HCPs) theoretical and applied knowledge of pregnancy-related IBD issues.

Methods

A cross-sectional international survey was distributed to HCPs providing IBD care between October 2020 and March 2021. Knowledge was assessed using the validated Crohn’s and Colitis Pregnancy Knowledge Score (CCPKnow; range, 0-17). Decision-making was assessed by free text responses to 3 clinical scenarios scored against predetermined scoring criteria (maximum score 70).

Results

Among 81 participants, median CCPKnow score was 16 (range, 8-17), and median total scenario score was 29 (range, 9-51). Health care professionals who treat >10 IBD patients per week (CCPKnow P = .03; scenarios P = .003) and are more regularly involved in pregnancy care (CCPKnow P = .005; scenarios P = .005) had significantly better scores. Although CCPKnow scoring was consistently high (median score ≥15) across all groups, consultants scored better than trainees and IBD nurses (P = .008 and P = .031). Median scenario scores were higher for consultants (32) and IBD nurses (33) compared with trainees (24; P = .018 and P = .022). There was a significant positive correlation between caring for greater numbers of pregnant IBD patients and higher CCPKnow (P = .001, r = .358) and scenario scores (P = .001, r = .377). There was a modest correlation between CCPKnow and scenario scores (r = .356; P < 0.001).

Conclusions

Despite “good” theoretical pregnancy-related IBD knowledge as assessed by CCPKnow, applied knowledge in the scenarios was less consistent. There is need for further HCP education and clinical experience to achieve optimal standardized care for IBD in pregnancy.
Reflection on modern methods: constructing directed acyclic graphs (DAGs) with domain experts for health services research
Authors: Rodrigues Daniela , Kreif Noemi , Lawrence-Jones Anna , Barahona Mauricio , Mayer Erik
Published: June 2022

Directed acyclic graphs (DAGs) are a useful tool to represent, in a graphical format, researchers’ assumptions about the causal structure among variables while providing a rationale for the choice of confounding variables to adjust for. With origins in the field of probabilistic graphical modelling, DAGs are yet to be widely adopted in applied health research, where causal assumptions are frequently made for the purpose of evaluating health services initiatives. In this context, there is still limited practical guidance on how to construct and use DAGs. Some progress has recently been made in terms of building DAGs based on studies from the literature, but an area that has received less attention is how to create DAGs from information provided by domain experts, an approach of particular importance when there is limited published information about the intervention under study. This approach offers the opportunity for findings to be more robust and relevant to patients, carers and the public, and more likely to inform policy and clinical practice. This article draws lessons from a stakeholder workshop involving patients, health care professionals, researchers, commissioners and representatives from industry, whose objective was to draw DAGs for a complex intervention—online consultation, i.e. written exchange between the patient and health care professional using an online system—in the context of the English National Health Service. We provide some initial, practical guidance to those interested in engaging with domain experts to develop DAGs.
Factors Associated With Human IgG Antibody Response to Anopheles albimanus Salivary Gland Extract, Artibonite Department, Haiti, 2017
Authors: Jaramillo-Underwood Alicia , Impoinvil Daniel , Sutcliff Alice , Hamre Karen E S , Joseph Vena , Hoogen Lotus van den , Lemoine Jean Frantz , Ashton Ruth A , Chang Michelle A , Existe Alexandre , Boncy Jacques , Drakeley Chris , Stresman Gillian , Druetz Thomas , Eisele Thomas , Rogier Eric
Published: June 2022

Serological data can provide estimates of human exposure to both malaria vector and parasite based on antibody responses. A multiplex bead-based assay was developed to simultaneously detect IgG to Anopheles albimanus salivary gland extract (SGE) and 23 Plasmodium falciparum antigens among 4185 participants enrolled in Artibonite department, Haiti in 2017. Logistic regression adjusted for participant- and site-level covariates and found children under 5 years and 6–15 years old had 3.7- and 5.4-fold increase in odds, respectively, of high anti-SGE IgG compared to participants >15 years. Seropositivity to P. falciparum CSP, Rh2_2030, and SEA-1 antigens was significantly associated with high IgG response against SGE, and participant enrolment at elevations under 200 m was associated with higher anti-SGE IgG levels. The ability to approximate population exposure to malaria vectors through SGE serology data is very dependent by age categories, and SGE antigens can be easily integrated into a multiplex serological assay.
Assessment of the Stability of Midregional Proadrenomedullin in Different Biological Matrices
Authors: Angeletti Silvia , Legramante Jacopo M , Lia Maria Stella , D’Amico Loreta , Fogolari Marta , Cella Eleonora , De Cesaris Marina , De Angelis Fabio , Pieri Massimo , Terrinoni Alessandro , Bernardini Sergio , Minieri Marilena
Published: June 2022

Midregional proadrenomedullin (MR-proADM) has been shown to play a key role in endothelial dysfunction, with increased levels helping to prevent early stages of organ dysfunction. Recent clinical evidence has demonstrated MR-proADM to be a helpful biomarker to identify disease severity in patients with sepsis as well as pneumonia. This biomarker is helpful at triage in emergency departments to assess risk level of patients. The aim of this study is to evaluate the stability of MR-proADM in different biological matrices. The results, obtained by Bland-Altman and scatter plot analyses, demonstrate that deviation of MR-proADM concentration in serum compared to EDTA plasma unequivocally shows that serum should not be used as a sample matrix. Instead, the excellent correlation of heparin plasma vs EDTA plasma samples shows that heparin plasma can be used without reservation in clinical routine and emergency samples.
Occultation portal: A web-based platform for data collection and analysis of stellar occultations
Authors: Kilic Y , Braga-Ribas F , Kaplan M , Erece O , Souami D , Dindar M , Desmars J , Sicardy B , Morgado B E , Shameoni M N , Rommel F L , Gomes-Júnior A R
Published: June 2022

Recording a stellar occultation is one powerful method that gives direct information about the physical properties of the occulting Solar system object. In order to obtain reliable and accurate results, simultaneous observations from different locations across-track of the projected path are of great importance. However, organizing all the observing stations, aggregating, and analysing the data is time-consuming and not that easy. We have developed a web portal named Occultation Portal (OP) to manage all those occultation observation campaigns from a central server. With this portal, the instrumental and observational information of all observers participating in a stellar occultation campaign and the concerned data are archived systematically in a standard format. The researchers can then visualize the archived data on an event basis. The investigators can also extract the light curve for each data set with the added reduction pipeline to the portal base. This paper describes in detail the portal structure and the developed features.
Evolution mapping: a new approach to describe matter clustering in the non-linear regime
Authors: Sánchez Ariel G , Ruiz Andrés N , Jara Jenny Gonzalez , Padilla Nelson D
Published: June 2022

We present a new approach to describe statistics of the non-linear matter density field that exploits a degeneracy in the impact of different cosmological parameters on the linear dimensionless matter power spectrum, $\Delta ^2_{\rm L}(k)$. We classify all cosmological parameters into two groups, shape parameters, which determine the shape of $\Delta ^2_{\rm L}(k)$, and evolution parameters, which only affect its amplitude at any given redshift. With this definition, the time evolution of $\Delta ^2_{\rm L}(k)$ in models with identical shape parameters but different evolution parameters can be mapped from one to the other by relabelling the redshifts that correspond to the same clustering amplitude, which we characterize by the linear mass fluctuation in spheres of radius $12\, {\rm Mpc}$, σ12(z). We use N-body simulations to show that the same evolution-mapping relation gives a good description of the non-linear power spectrum, the halo mass function, or the full density field. The deviations from the exact degeneracy are the result of the different structure formation histories experienced by each model to reach the same clustering amplitude and can be accurately described in terms of differences in the suppression factor g(a) = D(a)/a. These relations can be used to drastically reduce the number of parameters required to describe the cosmology dependence of the power spectrum. We show how this can help to speed up the inference of parameter constraints from cosmological observations. We also present a new design of an emulator of the non-linear power spectrum whose predictions can be adapted to an arbitrary choice of evolution parameters and redshift.
A 5 per cent measurement of the Hubble–Lemaître constant from Type II supernovae
Authors: de Jaeger T , Galbany L , Riess A G , Stahl B E , Shappee B J , Filippenko A V , Zheng W
Published: June 2022

The most stringent local measurement of the Hubble–Lemaître constant from Cepheid-calibrated Type Ia supernovae (SNe Ia) differs from the value inferred via the cosmic microwave background radiation (Planck+ΛCDM) by ∼5σ. This so-called Hubble tension has been confirmed by other independent methods, and thus does not appear to be a possible consequence of systematic errors. Here, we continue upon our prior work of using Type II supernovae to provide another, largely independent method to measure the Hubble–Lemaître constant. From 13 SNe II with geometric, Cepheid, or tip of the red giant branch (TRGB) host-galaxy distance measurements, we derive H$_0= 75.4^{+3.8}_{-3.7}$ km s−1 Mpc−1 (statistical errors only), consistent with the local measurement but in disagreement by ∼2.0σ with the Planck+ΛCDM value. Using only Cepheids (N = 7), we find H$_0 = 77.6^{+5.2}_{-4.8}$ km s−1 Mpc−1, while using only TRGB (N = 5), we derive H$_0 = 73.1^{+5.7}_{-5.3}$ km s−1 Mpc−1. Via 13 variants of our data set, we derive a systematic uncertainty estimate of 1.5 km s−1 Mpc−1. The median value derived from these variants differs by just 0.3 km s−1 Mpc−1 from that produced by our fiducial model. Because we only replace SNe Ia with SNe II – and we do not find statistically significant difference between the Cepheid and TRGB H0 measurements – our work reveals no indication that SNe Ia or Cepheids could be the sources of the ‘H0 tension.’ We caution, however, that our conclusions rest upon a modest calibrator sample; as this sample grows in the future, our results should be verified.
Towards a classification scheme for the rocky planets based on equilibrium thermodynamic considerations
Authors: Bertolami Orfeu , Francisco Frederico
Published: June 2022

A classification scheme for rocky planets is proposed, based on a description of the Earth System in terms of the Landau–Ginzburg Theory of phase transitions. Three major equilibrium states can be identified and the associated planetary states or phases are: Earth-like Holocene state; hot Venus-like state; cold Mars-like state. The scheme is based on an approach proposed to understand the Earth transition from the Holocene to the Anthropocene, driven by the impact of the human action on the Earth System. In this work, we identity the natural conditions that cause transformations on the planets forcing them into one of the states identified above. We discuss how the parameters that describe these transformations can be related with exoplanets observables. In analysing the relevant physical parameters, we were stroke by the similarities between Earth and Venus, and how likely is that the Anthropocene transition may lead to hot-house Earth scenario.
Multiple giant eruptions and X-ray emission in the recoiling AGN/LBV candidate SDSS1133
Authors: Kokubo Mitsuru
Published: June 2022

We present a comprehensive analysis of 20 yr worth of multicolour photometric light curves, multiepoch optical spectra, and X-ray data of an off-nuclear variable object SDSS1133 in Mrk 177 at z = 0.0079. The UV-optical light curves reveal that SDSS1133 experienced four outbursts in 2001, 2014, 2019, and 2021. The persistent UV-optical luminosity in the non-outbursting state is ∼1041 erg s−1 with small-scale flux variations, and peak luminosities during the outbursts reach ∼1042 erg s−1. The optical spectra exhibit enduring broad hydrogen Balmer P-Cygni profiles with the absorption minimum at ∼−2000 km s−1, indicating the presence of fast-moving ejecta. Chandra detected weak X-ray emission at a 0.3−10-keV luminosity of LX = 4 × 1038 erg s−1 after the 2019 outburst. These lines of evidence suggests that SDSS1133 is an extreme luminous blue variable (LBV) star experiencing multiple giant eruptions with interactions of the ejected shell with different shells and/or circumstellar medium (CSM), and disfavours the recoiling active galactic nuclei scenario suggested in the literature. We suggest that pulsational pair-instability may provide a viable explanation for the multiple energetic eruptions in SDSS1133. If the current activity of SDSS1133 is a precursor of a supernova explosion, we may be able to observe a few additional giant eruptions and then the terminal supernova explosion or collapse to a massive black hole in future observations.
Functional Divergence of thebag-of-marblesGene in theDrosophila melanogasterSpecies Group
Authors: Bubnell Jaclyn E , Ulbing Cynthia K S , Fernandez Begne Paula , Aquadro Charles F
Published: June 2022

In Drosophila melanogaster, a key germline stem cell (GSC) differentiation factor, bag of marbles (bam) shows rapid bursts of amino acid fixations between sibling species D. melanogaster and Drosophila simulans, but not in the outgroup species Drosophila ananassae. Here, we test the null hypothesis that bam’s differentiation function is conserved between D. melanogaster and four additional Drosophila species in the melanogaster species group spanning approximately 30 million years of divergence. Surprisingly, we demonstrate that bam is not necessary for oogenesis or spermatogenesis in Drosophila teissieri nor is bam necessary for spermatogenesis in D. ananassae. Remarkably bam function may change on a relatively short time scale. We further report tests of neutral sequence evolution at bam in additional species of Drosophila and find a positive, but not perfect, correlation between evidence for positive selection at bam and its essential role in GSC regulation and fertility for both males and females. Further characterization of bam function in more divergent lineages will be necessary to distinguish between bam’s critical gametogenesis role being newly derived in D. melanogaster, D. simulans, Drosophila yakuba, and D. ananassae females or it being basal to the genus and subsequently lost in numerous lineages.
Genome-wide CRISPR/Cas9 transcriptional activation screen identifies a histone acetyltransferase inhibitor complex as a regulator of HIV-1 integration
Authors: Zhang Qiong , Wang Shaobo , Li Wanyu , Yau Edwin , Hui Hui , Singh Parmit Kumar , Achuthan Vasudevan , Young Karris Maile Ann , Engelman Alan N , Rana Tariq M
Published: June 2022

The retrovirus human immunodeficiency virus-1 (HIV-1) is the causative agent of AIDS. Although treatment of HIV/AIDS with antiretroviral therapy provides suppression of viremia, latent reservoirs of integrated proviruses preclude cure by current antiviral treatments. Understanding the mechanisms of host–viral interactions may elucidate new treatment strategies. Here, we performed a CRISPR/Cas9 transcriptional activation screen using a high-complexity, genome-wide sgRNA library to identify cellular factors that inhibit HIV-1 infection of human CD4+ T cells. MT4 cells were transduced with a CRISPR/Cas9 sgRNA library and infected with nef-deficient HIV-1NL4-3 expressing ganciclovir-sensitive thymidine kinase, thus enabling selection of HIV-1-resistant cells for analysis of enriched sgRNAs. After validation of screen hits, multiple host factors essential for HIV-1 infection were identified, including SET (SET nuclear proto-oncogene) and ANP32A (acidic nuclear phosphoprotein 32A, PP32A), which together form a histone acetylase inhibitor complex. Using multiple human cell lines and peripheral blood mononuclear cells (PBMCs) from healthy donors and HIV-1-infected individuals, we demonstrate that SET depletion increased HIV-1 infectivity by augmenting DNA integration without significantly changing sites of integration. Conversely, SET overexpression decreased HIV-1 integration and infectivity. SET protein expression was significantly reduced in PBMCs from HIV-1-infected individuals and was downregulated by HIV-1 infection of healthy donor cells in vitro. Notably, HIV-1-induced downregulation of SET could be alleviated by inhibition of the protease granzyme A. Altogether, we have identified cellular inhibitors of HIV-1 infection on a genome-wide scale, which affords new insight into host–virus interactions and may provide new strategies for HIV-1 treatment.
Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression
Authors: Portuguez Avital Sarusi , Grbesa Ivana , Tal Moran , Deitch Rachel , Raz Dana , Kliker Limor , Weismann Ran , Schwartz Michal , Loza Olga , Cohen Leslie , Marchenkov-Flam Libi , Sung Myong-Hee , Kaplan Tommy , Hakim Ofir
Published: June 2022

The rapid transcriptional response to the transcription factor, glucocorticoid receptor (GR), including gene activation or repression, is mediated by the spatial association of genes with multiple GR binding sites (GBSs) over large genomic distances. However, only a minority of the GBSs have independent GR-mediated activating capacity, and GBSs with independent repressive activity were rarely reported. To understand the positive and negative effects of GR we mapped the regulatory environment of its gene targets. We show that the chromatin interaction networks of GR-activated and repressed genes are spatially separated and vary in the features and configuration of their GBS and other non-GBS regulatory elements. The convergence of the KLF4 pathway in GR-activated domains and the STAT6 pathway in GR-repressed domains, impose opposite transcriptional effects to GR, independent of hormone application. Moreover, the ROR and Rev-erb transcription factors serve as positive and negative regulators, respectively, of GR-mediated gene activation. We found that the spatial crosstalk between GBSs and non-GBSs provides a physical platform for sequestering the Ep300 co-activator from non-GR regulatory loci in both GR-activated and -repressed gene compartments. While this allows rapid gene repression, Ep300 recruitment to GBSs is productive specifically in the activated compartments, thus providing the basis for gene induction.
DeNovoCNN: a deep learning approach to de novo variant calling in next generation sequencing data
Authors: Khazeeva Gelana , Sablauskas Karolis , van der Sanden Bart , Steyaert Wouter , Kwint Michael , Rots Dmitrijs , Hinne Max , van Gerven Marcel , Yntema Helger , Vissers Lisenka , Gilissen Christian
Published: June 2022

De novo mutations (DNMs) are an important cause of genetic disorders. The accurate identification of DNMs from sequencing data is therefore fundamental to rare disease research and diagnostics. Unfortunately, identifying reliable DNMs remains a major challenge due to sequence errors, uneven coverage, and mapping artifacts. Here, we developed a deep convolutional neural network (CNN) DNM caller (DeNovoCNN), that encodes the alignment of sequence reads for a trio as 160$ \times$164 resolution images. DeNovoCNN was trained on DNMs of 5616 whole exome sequencing (WES) trios achieving total 96.74% recall and 96.55% precision on the test dataset. We find that DeNovoCNN has increased recall/sensitivity and precision compared to existing DNM calling approaches (GATK, DeNovoGear, DeepTrio, Samtools) based on the Genome in a Bottle reference dataset and independent WES and WGS trios. Validations of DNMs based on Sanger and PacBio HiFi sequencing confirm that DeNovoCNN outperforms existing methods. Most importantly, our results suggest that DeNovoCNN is likely robust against different exome sequencing and analyses approaches, thereby allowing the application on other datasets. DeNovoCNN is freely available as a Docker container and can be run on existing alignment (BAM/CRAM) and variant calling (VCF) files from WES and WGS without a need for variant recalling.
Body temperature variation controls pre-mRNA processing and transcription of antiviral genes and SARS-CoV-2 replication
Authors: Los Bruna , Preußner Marco , Eschke Kathrin , Vidal Ricardo Martin , Abdelgawad Azza , Olofsson Didrik , Keiper Sandra , Paulo-Pedro Margarida , Grindel Alica , Meinke Stefan , Trimpert Jakob , Heyd Florian
Published: June 2022

Antiviral innate immunity represents the first defense against invading viruses and is key to control viral infections, including SARS-CoV-2. Body temperature is an omnipresent variable but was neglected when addressing host defense mechanisms and susceptibility to SARS-CoV-2 infection. Here, we show that increasing temperature in a 1.5°C window, between 36.5 and 38°C, strongly increases the expression of genes in two branches of antiviral immunity, nitric oxide production and type I interferon response. We show that alternative splicing coupled to nonsense-mediated decay decreases STAT2 expression in colder conditions and suggest that increased STAT2 expression at elevated temperature induces the expression of diverse antiviral genes and SARS-CoV-2 restriction factors. This cascade is activated in a remarkably narrow temperature range below febrile temperature, which reflects individual, circadian and age-dependent variation. We suggest that decreased body temperature with aging contributes to reduced expression of antiviral genes in older individuals. Using cell culture and in vivo models, we show that higher body temperature correlates with reduced SARS-CoV-2 replication, which may affect the different vulnerability of children versus seniors toward severe SARS-CoV-2 infection. Altogether, our data connect body temperature and pre-mRNA processing to provide new mechanistic insight into the regulation of antiviral innate immunity.
Determining states of consciousness in the electroencephalogram based on spectral, complexity, and criticality features
Authors: Walter Nike , Hinterberger Thilo
Published: June 2022

This study was based on the contemporary proposal that distinct states of consciousness are quantifiable by neural complexity and critical dynamics. To test this hypothesis, it was aimed at comparing the electrophysiological correlates of three meditation conditions using nonlinear techniques from the complexity and criticality framework as well as power spectral density. Thirty participants highly proficient in meditation were measured with 64-channel electroencephalography (EEG) during one session consisting of a task-free baseline resting (eyes closed and eyes open), a reading condition, and three meditation conditions (thoughtless emptiness, presence monitoring, and focused attention). The data were analyzed applying analytical tools from criticality theory (detrended fluctuation analysis, neuronal avalanche analysis), complexity measures (multiscale entropy, Higuchi’s fractal dimension), and power spectral density. Task conditions were contrasted, and effect sizes were compared. Partial least square regression and receiver operating characteristics analysis were applied to determine the discrimination accuracy of each measure. Compared to resting with eyes closed, the meditation categories emptiness and focused attention showed higher values of entropy and fractal dimension. Long-range temporal correlations were declined in all meditation conditions. The critical exponent yielded the lowest values for focused attention and reading. The highest discrimination accuracy was found for the gamma band (0.83–0.98), the global power spectral density (0.78–0.96), and the sample entropy (0.86–0.90). Electrophysiological correlates of distinct meditation states were identified and the relationship between nonlinear complexity, critical brain dynamics, and spectral features was determined. The meditation states could be discriminated with nonlinear measures and quantified by the degree of neuronal complexity, long-range temporal correlations, and power law distributions in neuronal avalanches.
Measurement Properties of Remotely or Self-Administered Lower Extremity Mobility Performance Measures in Adults: A Systematic Review
Authors: Morgan Ashley , Bégin Diane , Heisz Jennifer , Tang Ada , Thabane Lehana , Richardson Julie
Published: June 2022

Objective

For individuals who face barriers to care assessment, there is a need for remote administration or self-administration of physical performance measures that assess mobility to determine current functional status and to monitor and predict future changes in functional status. The primary purpose of this review is to evaluate the available measurement properties of scores for remotely or self-administered lower extremity mobility performance measures in adults. This review also outlines the test procedures and population suitability of these measures.

Methods

Data sources were Ovid MEDLINE, Ovid Embase, EBSCOhost CINAHL, Ovid AMED, and Cochrane CENTRAL—which were searched from inception to January 26, 2021—and the reference lists of relevant studies. Two individuals independently screened studies that assessed at least 1 prespecified measurement property of scores for a remote and/or self-administered lower extremity physical performance measure assessing mobility in an adult population. Two individuals independently extracted data on study characteristics, measurement properties, feasibility, and interpretability using piloted extraction forms. The COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) Risk of Bias tool was used to assess methodological quality. Data were qualitatively summarized, and results were compared against COSMIN’s criteria for good measurement properties. Level of evidence was determined using COSMIN’s modified GRADE approach.

Results

Fourteen studies detailing 19 outcome measures were included. Many studies displayed “sufficient” measurement properties based on COSMIN’s criteria; however, risk of bias for most of the included studies was rated adequate or doubtful.

Conclusion

Clinicians and researchers can consider the measurement properties of scores and feasibility of different approaches presented in this review when determining how to assess or monitor mobility in adult populations.

Impact

Assessing mobility via remote or self-administered physical performance measures in adult populations appears to be feasible using a variety of methods including simple tools (chair, stopwatch), videoconferencing, and smartphone applications. This strategy may be particularly valuable for self-management of chronic conditions and decreasing barriers to accessing care.
How Do People With Knee Osteoarthritis Conceptualize Knee Confidence? A Qualitative Study
Authors: Binnie Tara , O’Sullivan Peter , Bunzli Samantha , Campbell Amity , Ng Leo , Kent Peter , Smith Anne
Published: June 2022

Objective

Reduced knee confidence is common in people with knee osteoarthritis (OA) and is likely to influence how people with knee OA engage with movement and activities. However, there is conflicting evidence surrounding the association between confidence and function. This may be because knee confidence has been assessed via a single questionnaire item that was not developed for people with knee OA and thus may not provide an accurate or comprehensive assessment of confidence in this population. A better understanding of knee confidence could inform a more thorough assessment of the construct both in clinical and research contexts. Therefore, the aim of this study was to explore the meaning of knee confidence from the perspective of people with knee OA.

Methods

Fifty-one people with a clinical diagnosis of knee OA took part in a one-to-one semistructured interview. Interviews explored how each participant conceptualized knee confidence. Reflexive thematic analysis was selected as a flexible approach for identifying patterns of meaning across cases through a combination of data-driven and theory-informed coding of the transcribed data.

Results

People with knee OA conceptualized confidence with reference to 1 or more of 4 themes: (1) symptoms, (2) functional ability, (3) the internal structure of the knee, and (4) knowledge about knee OA and its management. Each conceptualization of confidence was associated with present and future concerns.

Conclusion

Because people with knee OA conceptualize knee confidence in different ways, a single-item measure is unlikely to capture all of the aspects of this construct in this population. This may explain the conflicting evidence around the association between reduced knee confidence and function in people with knee OA.

Impact

This study showed that a multi-item measure is needed to measure knee confidence in people with knee OA. Clinicians and researchers need to understand what knee confidence means to people with knee OA, because it is likely to influence how these individuals engage with movement and activities. Understanding this relationship can enable more targeted education and functional rehabilitation for people with knee OA.
Validation of the parent global assessment as a health-related quality of life measure in juvenile idiopathic arthritis: results from ReACCh-Out
Authors: Oen Kiem , Toupin-April Karine , Feldman Brian M , Berard Roberta A , Duffy Ciẚran M , Tucker Lori B , Tian Jiahao , Rumsey Dax G , Guzman Jaime ,   ReACCh-Out investigators, Bolaria Roxana , Cabral David , Gross Katherine , Houghton Kristin , Morishita Kimberly , Petty Ross , Turvey Stuart E , Ellsworth Janet , Benseler Susanne , Johnson Nicole , Miettunen Paivi , Schmeling Heinrike , Larche Maggie , Cameron Bonnie , Laxer Ronald M , Spiegel Lynn , Schneider Rayfel , Silverman Earl , Yeung Rae S M , Levy Deborah M , Tse Shirley , Gibbon Michele , Roth Johannes , Duffy Karen Watanabe , Chetaille Anne-Laure , Dorval Jean , Boire Gilles , Bruns Alessandra , Campillo Sarah , Chedeville Gaelle , LeBlanc Claire , Scuccimarri Rosie , Haddad Elie , Cyr Claire St , Feldman Debbie , Lang Bianca , Ramsey Suzanne E , Stringer Elizabeth , Huber Adam M , Dancey Paul
Published: June 2022

Objectives

To (i) validate the JIA parent global assessment (parent global) as a health-related quality of life (HRQoL) instrument; (ii) evaluate measurement properties of accepted HRQoL measures relative to those of the parent global; and (iii) assess causal pathways determining parent global scores.

Methods

Data from the Research in Arthritis in Canadian Children emphasizing outcomes (ReACCh-Out) cohort were used. Measurement properties were assessed in 344 patients at enrolment and 6 months later. Causal pathways were tested by structural equation modelling to understand root causes and mediators leading to parent global scores.

Results

Construct validity was supported by Spearman correlations of 0.53–0.70 for the parent global with the Juvenile Arthritis Quality of Life Questionnaire, Quality of My Life health scale (HRQoML), Pediatric Quality of Life Inventory (PedsQL)-Parent, and Child Health Questionnaire (CHQ)-Physical. Exceptions were PedsQL-Child (0.44) and CHQ-Psychosocial (0.31). Correlations were lower (0.14–0.49) with disease activity measures (physician global assessment of disease activity, active joint count, ESR). Responsiveness of the parent global to improvement according to parent ratings (0.51) was acceptable and within the range (0.32–0.71) of that of other measures. Reliability estimates and measurement errors for all measures were unsatisfactory, likely due to the prolonged time between assessments. Causal pathways for the parent global matched those previously reported for HRQoML.

Conclusions

Our results offer support for the parent global as a valid measure of HRQoL for JIA. If confirmed, existing studies using the parent global may be re-interpreted, enhancing our knowledge of HRQoL in children with JIA.
The democratic paradox: are national elections always good for satisfaction with democracy in Europe?
Authors: Krishnarajan Suthan
Published: June 2022

This article challenges the widespread notion that national elections are unequivocally good for people’s satisfaction with democracy. Instead, it argues that elections have enduring and disparate effects on democratic satisfaction, depending on the economic situation in which they take place; that is the election economy. When held during economic upturns, national elections increase subsequent satisfaction with democracy during most of the following electoral term—regardless of election results and economic growth after the election. When held during economic downturns, elections reduce democratic satisfaction until the next election—again, regardless of such post-election developments. An analysis of 29 European democracies in the period 1973–2019 supports these propositions and suggests that the disparate effects of national elections endure during most of the electoral term. These findings are robust to an array of model specifications, including when accounting for several pre-election and post-election developments.
Social participation restriction among persons with leprosy discharged from a multidrug therapy clinic in northern Nigeria
Authors: Dahiru Tahir , Iliyasu Zubairu , Aliyu Muktar H
Published: June 2022

Background

The burden of leprosy-related disability, stigma and social participation after completing treatment is not well documented in Nigeria. We assessed the extent of disability, level of stigma and predictors of activity limitation and social participation restriction after completing multidrug therapy (MDT) for leprosy in Kano, Nigeria.

Methods

A consecutively recruited cross-section of 354 persons discharged from MDT and 360 community members were interviewed. The Eyes, Hands and Feet sum score, Screening of Activity Limitation and Safety Awareness scale, Participation scale and Jacoby Stigma scale were used for affected persons. The Exploratory Model Interview Catalogue scale was used to assess community-perceived stigma. Levels of disability, activity limitation, participation restriction and stigma were scored. Adjusted ORs for predictors were generated from logistic regression models.

Results

Most (91.5%, n=324) respondents had a disability; (8.2%, n=29) and (83.3%, n=295) were WHO grades 1 and 2, respectively. Similarly, 321 participants (90.7%) had activity limitation and 316 respondents (89.3%) experienced participation restriction. Further, 88.7% of participants (n=314) anticipated stigma. Activity limitation was higher among unemployed participants, men, persons with disability and those who anticipated stigma. Participation restriction was higher among low income earners (≤1000 Nigerian Naira per month (equivalent to US$2.50 per month)) and persons with disability, limited activity and anticipated stigma.

Conclusion

Leprosy-related disability, stigma, activity limitation and social participation restriction are high after treatment. We recommend community-based rehabilitation to sustain self-care, reduce stigma and ensure social inclusion.
SGLT2 inhibitor dapagliflozin attenuates cardiac fibrosis and inflammation by reverting the HIF‐2α signaling pathway in arrhythmogenic cardiomyopathy
Authors: Yang Zhe , Li Tengling , Xian Jianzhong , Chen Jia , Huang Yin , Zhang Qin , Lin Xiufang , Lu Hongyun , Lin Yubi
Published: June 2022

Excessive cardiac fibrosis and inflammation aberrantly contribute to the progressive pathogenesis of arrhythmogenic cardiomyopathy (ACM). Whether sodium‐glucose cotransporter‐2 inhibitor (SGLT2i), as a new hypoglycemic drug, benefits ACM remains unclear. Cardiomyocyte‐specific Dsg2 exon‐11 knockout and wild‐type (WT) littermate mice were used as the animal model of ACM and controls, respectively. Mice were administered by gavage with either SGLT2i dapagliflozin (DAPA, 1 mg/kg/day) or vehicle alone for 8 weeks. HL‐1 cells were treated with DAPA to identify the molecular mechanism in vitro. All mice presented normal glucose homeostasis. DAPA not only significantly ameliorated cardiac dysfunction, adverse remodeling, and ventricular dilation in ACM but also attenuated ACM‐associated cardiac fibrofatty replacement, as demonstrated by the echocardiography and histopathological examination. The protein expressions of HIF‐2α and HIF‐1α were decreased and increased respectively in cardiac tissue of ACM, which were compromised after DAPA treatment. Additionally, NF‐κB P65 and IκB phosphorylation, as well as fibrosis indicators (including TGF‐β, α‐SMA, Collagen I, and Collagen III) were increased in ACM. However, these trends were markedly suppressed by DAPA treatment. Consistent with these results in vitro, DAPA alleviated the IκB phosphorylation and NF‐κB p65 transcriptional activity in DSG2‐knockdown HL‐1 cells. Interestingly, the elective HIF‐2α inhibitor PT2399 almost completely blunted the DAPA‐mediated downregulation of indicators concerning cardiac fibrosis and inflammation. SGLT2i attenuated the ACM‐associated cardiac dysfunction and adverse remodeling in a glucose‐independent manner by suppressing cardiac fibrosis and inflammation via reverting the HIF‐2α signaling pathway, suggesting that SGLT2i is a novel and available therapy for ACM.
Assessment of Occupational Exposure to Eye Lens Dosimetry for Interventional Radiology Workers in China During 2017–2019
Authors: Li Mengxue , Fan Shengnan , Zhang Xianpeng , Hao Shuxia , Zhao Yu , Deng Jun , Sun Quanfu
Published: June 2022

The eye lens is a sensitive tissue to ionizing radiation and recently has been recognized as more radiosensitive than previously considered. The International Commission on Radiological Protection (ICRP) has recommended a considerable reduction in the equivalent dose limit of eye lens from 150 mSv y−1 to 20 mSv y−1, averaged over a defined period of 5 y. In this paper, the eye lens dose of interventional radiology workers in China during 2017–2019 is analyzed to understand the current status of eye lens occupational exposure and to provide decision-making suggestions for health supervision departments using data obtained from the National Radiological Health Information Platform in China. A total of 3,026 eye lens dose records of interventional radiology workers were collected. The average annual eye lens dose (AAELD) for interventional radiology workers ranged from 1.07 to 1.51 mSv during 2017-2019 and was 1.44 mSv for all monitored interventional radiology workers, with 2,973 records (98.2%) lower than the public limit of 15 mSv and 33 records (1.1%) exceeding the newly revised occupational eye lens dose limit of 20 mSv y−1. During the period of 2017-2019, the AAELDs of interventional radiologists (1.61 mSv) and of interventional cardiologists (1.59 mSv) were significantly higher than that of other interventional workers (0.62 mSv); the AAELD of doctors (1.50 mSv) was significantly higher than that of nurses (1.01 mSv); the AAELD of western China (2.00 mSv) was significantly higher than that of eastern (1.11 mSv) and central China (1.27 mSv); and the AAELD of males (1.59 mSv) was significantly higher than that of females (0.84 mSv). The eye lens dose of interventional radiology workers meets the Chinese standard limit of 150 mSv y−1, while some cases exceed the one recommended by ICRP. The study shows that the interventional radiology workers’ eye lens dosimetry data complied with the existing Chinese eye lens dose limits. However, education, training, and supervision of radiation protection also should be strengthened continuously for interventional radiology workers, especially for the interventional radiologists and interventional cardiologists. Significant attention should be paid to the radiation protection of underdeveloped regions in China in future works.
Complete and long-lasting response to immunotherapy
Authors: Silva Diogo J. , Mesquita Alexandra
Published: June 2022

Introduction:

Bladder cancer is the tenth most common cancer worldwide, with Europe having the highest incidence rates. Regarding the treatment of metastatic disease, first-line treatment for fit patients is cisplatin-containing combination chemotherapy. However, a significant percentage of patients are ineligible for platinum-based chemotherapy, or progress under these regimens. Recently, immune checkpoint blockade has become a treatment option for this group of patients. In this report, we present the case of a male patient diagnosed with metastatic bladder cancer who did not tolerate cisplatin-containing chemotherapy and achieved complete response after treatment with pembrolizumab.

Patient concerns:

A 58 years-old Caucasian man with a medical history of high-grade urothelial carcinoma pT3bN0R0 under a watchful waiting strategy for 6 months presented to the Medical Oncology appointment with two axillary and cervical adenopathies.

Diagnosis:

Cervicothoracoabdominal computed tomography confirmed the presence of two large necrotic lymphadenopathies in the cervical and axillary lymphatic chains, and bone scintigraphy revealed dorsal (D11) and lumbar (L5) metastatic lesions. Ultrasonography-guided biopsy of the axillary nodule revealed the presence of metastatic tissue of primary urothelial origin.

Interventions:

The patient was initiated on a palliative chemotherapy regimen of carboplatin area under the curve 5 plus gemcitabine (1000 mg/m2). During the first cycle of chemotherapy, acute kidney failure akin 2 developed due to nonobstructive toxic acute tubular necrosis with progressive deterioration of kidney function. Therefore, palliative chemotherapy with carboplatin plus gemcitabine was changed to 200 mg of pembrolizumab every 21 days.

Outcomes:

Overal survival of 57 months with an immune complete response according to the immune Response Evaluation Criteria in Solid Tumours criteria and an excellent quality of life.

Conclusion:

This case illustrates that second-line therapy with ICIs (pembrolizumab or atezolizumab) has favourable results in achieving an immune complete response after intolerance to cisplatin-based regimens. ICIs provide durable responses that improve overall survival and quality of life.