bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world management and outcomes of 7 million patients with acute coronary syndrome according to clinical research trial enrolment status: a propensity matched analysis
Authors: Matetic Andrija , Mohamed Mohamed O , Roberts Derek J , Rana Jamal S , Alraies M Chadi , Patel Brijesh , Sauer Andrew J , Diaz-Arocutipa Carlos , Sattar Yasar , Van Spall Harriette G C , Mamas Mamas A
Published: December 2021

Aims

We aimed to determine whether clinical outcomes and invasive care of acute coronary syndrome (ACS) patients participating in trials differed from those of non-participants, particularly including those who were trial eligible.

Methods and results

We included all hospitalizations with a principal diagnosis of ACS in the US National Inpatient Sample between January 2004 and September 2015, stratified by trial enrolment and eligibility using the International Classification of Diseases, ninth revision. We conducted propensity score matching to investigate the following outcomes: all-cause mortality; major bleeding; stroke; composite of mortality, stroke, and cardiac complications [major adverse cardiovascular and cerebrovascular events (MACCEs)]; coronary angiography (CA); and percutaneous coronary intervention (PCI). A total of 7 091 179 weighted ACS hospitalizations were analysed, including 19 684 (0.3%) trial participants and 7 071 495 non-participants (3 485 514 of whom were trial eligible). Trial participants were more likely to receive CA [Δ% 28.73%, 95% confidence interval (CI) 27.22–30.24, P < 0.001] and PCI (Δ% 27.13%, 95% CI 24.86–29.41, P < 0.001), with decreased mortality (Δ% −3.51%, 95% CI −4.72 to −2.31, P < 0.001), MACCEs (Δ% −3.04%, 95% CI −4.55 to −1.53, P < 0.001), and bleeding (Δ% −0.89%, 95% CI −1.59 to −0.19, P = 0.013) compared with non-participants. After accounting for eligibility, trial participants were more likely to undergo CA (Δ% 22.78%, 95% CI 21.58–23.99, P < 0.001) and PCI (Δ% 23.95%, 95% CI 21.77–26.13, P < 0.001), and had no difference in mortality (Δ% −0.21%, 95% CI −0.65 to 0.24, P = 0.362).

Conclusion

Among ACS patients, trial enrolment was associated with significantly greater invasive care and lower mortality than among matched non-participants. Trial participants were more likely to be invasively managed even when compared with eligible non-participants, even though there was no difference in mortality.
Thoracic bilateral sympathectomy attenuates oxidative stress and prevents ventricular remodelling in experimental pulmonary hypertension
Authors: Coutinho e Silva Raphael dos Santos , Wiggenhauser Lucas Moritz , Simas Rafael , Zanoni Fernando Luiz , Medeiros Geisla , da Silva Fernanda Beatriz , Ogata Daniel Cury , Breithaupt-Faloppa Ana Cristina , Krenning Guido , Moreira Luiz Felipe Pinho
Published: December 2021

OBJECTIVES

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease that affects the pulmonary vasculature, leading to increased afterload and eventually right ventricular (RV) remodelling and failure. Bilateral sympathectomy (BS) has shown promising results in dampening cardiac remodelling and dysfunction in several heart failure models. In the present study, we investigated whether BS reduces pulmonary arterial remodelling and mitigates RV remodelling and failure.

METHODS

PAH was induced in male Wistar rats by intraperitoneal injection of monocrotaline. Rats were divided into 3 groups, involving untreated PAH (n = 15), BS-treated PAH (n = 13) and non-manipulated control rats (n = 13). Three weeks after PAH induction, the rats were anaesthetized and RV function was assessed via the pressure-volume loop catheter approach. Upon completion of the experiment, the lungs and heart were harvested for further analyses.

RESULTS

BS was found to prevent pulmonary artery remodelling, with a clear reduction in α-smooth muscle actin and endothelin-1 expression. RV end-systolic pressure was reduced in the BS group, and preload recruitable stroke work was preserved. BS, therefore, mitigated RV remodelling and cardiomyocyte hypertrophy and diminished oxidative stress.

CONCLUSIONS

We showed that thoracic BS may be an important treatment option for PAH patients. Blockade of the sympathetic pathway can prevent pulmonary remodelling and protect the RV from oxidative stress, myocardial remodelling and function decay.
An external validation study of the Utah Bleeding Risk Score
Authors: Peivandi Armin , Welp Henryk , Scherer Mirela , Sindermann Jürgen R , Wagner Nana-Maria , Dell’Aquila Angelo M
Published: December 2021

OBJECTIVES

Gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices (CF-LVAD) impairs quality of life and increases hospitalization rate. The Utah Bleeding Risk Score (UBRS) has been created to predict gastrointestinal bleeding (GIB) in patients on left ventricular assist device. We here aimed to externally validate UBRS on our cohort of CF-LVAD patients.

METHODS

Utah Bleeding Risk Score was calculated, GIB events summarized on follow-up and patients stratified into 3 risk groups. Predictive ability of UBRS was examined at 3 years and during whole support time and person time incidence rates correlated to UBRS. In a sub-analysis, single effects of UBRS variables on freedom from GIB were assessed.

RESULTS

A total of 111 CF-LVAD patients were included. The median UBRS was 2 (3–1). Receiver operating characteristic curve analysis showed an area under the curve of 0.519 (P = 0.758, 95% confidence interval = 0.422–0.615) at 3 years and an area under the curve of 0.515 (P = 0.797, 95% confidence interval = 0.418–0.611) during whole support time. No significant difference was observed in UBRS between bleeders and non-bleeders (P = 0.80). No significant difference in freedom from GIB was observed (P3 years = 0.7; Psupport-time = 0.816) and no independent significance regarding the freedom from bleeding at 3 years for any variable was observed. Coronary artery disease was associated with higher risk of GIB beyond the 3rd year (P = 0.048).

CONCLUSIONS

UBRS was not able to predict GIB and therefore not applicable in our cohort of patients. Coronary artery disease could lead to a higher risk for GIB during support time. An additional validation in a larger cohort is advisable.
‘Reform or revolution’, redux: Eduard Bernstein on the 1918–19 German Revolution
Authors: Ostrowski Marius S
Published: December 2021

The 1918–19 German Revolution forced an abrupt moment of decision among German socialists on the question of ‘social reform or revolution’. This article traces the arguments of Eduard Bernstein, the founder of ‘reformism’, on the lessons social democracy should draw from the events of the Revolution and the transition from the Kaiserreich to the Weimar Republic. It argues that Bernstein makes significant advances on his early reformism in his post-Revolution writings, and explores his refinement of the concept of ‘revolution’ as well as his critique of Bolshevism and the U.S.S.R. as a new ideological rival within the socialist movement.
Are NOACs as safe and efficient as VKA regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?
Authors: Magro Pedro Lamares , Sousa-Uva Miguel
Published: December 2021

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: ‘Are NOACs as safe and efficient as vitamin K antagonist regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?’ Altogether more than 324 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The RIVER and ENAVLE trials showed non-inferiority of rivaroxaban (regarding mean time free from composite of death, major cardiovascular events or major bleeding at 12 months) and edoxaban (composite of death, clinical thromboembolic events or asymptomatic intracardiac thrombosis; and major bleeding) when compared with vitamin K antagonist. These studies include a low number of patients within 3 months of index surgery and overall low statistical power regarding this particular subgroup of patients. Data derived from lower evidence studies are compatible with the aforementioned findings. The available evidence suggests that non-vitamin K antagonist anticoagulants are as safe and as efficient as vitamin K antagonist regarding thromboembolic prophylaxis and bleeding event rates in patients with surgical bioprosthesis and atrial fibrillation within 3 months of bioprosthesis implantation. However, this evidence is derived from a limited number of studies with important methodological limitations. Expanding non-vitamin K antagonist anticoagulant recommendation to the early postoperative period warrants more confirmatory research.
Thoracoscopic pneumonectomy in patient with unilateral absence of the left pulmonary artery accompanied by the left lung cancer
Authors: Kononets Pavel V , Akhmedov Parvin I , Topol Konstantin Y
Published: December 2021

Unilateral absence of the pulmonary artery is a rare congenital cardiovascular anomaly. Unilateral absence of the pulmonary artery is often accompanied by cardiovascular disorders but also can occur in an isolated manner. We present a case of female patient, in which the absence of the left pulmonary artery was revealed and the left lower lobe adenocarcinoma was diagnosed.
Evaluation of the Association of Length of Stay in Hospital and Outcomes
Authors: Han Thang S , Murray Paul , Robin Jonathan , Wilkinson Peter , Fluck David , Fry Christopher H
Published: December 2021

Background

There exist wide variations in healthcare quality within the National Health Service (NHS). A shorter hospital length of stay (LOS) has been implicated as premature discharge, that may in turn lead to adverse consequences. We tested the hypothesis that a short LOS might be associated with increased risk of readmissions within 28 days of hospital discharge and also post-discharge mortality.

Methods

We conducted a single-centred study of 32,270 (46.1% men) consecutive alive-discharge episodes (mean age = 64.0 years, standard deviation = 20.5, range = 18-107 years), collected between 01/04/2017 and 31/03/2019. Associations of LOS tertiles (middle tertile as a reference) with readmissions and mortality were assessed using observed/expected ratios, and logistic and Cox regressions to estimate odds (OR) and hazard ratios (HR) (adjusted for age, sex, patients’ severity of underlying health status and index admissions), with 95% confidence intervals (CI).

Results

The observed numbers of readmissions within 28 days of hospital discharge or post-discharge mortality were lower than expected (observed: expected ratio <1) in patients in the bottom tertile (<1.2 days) and middle tertile (1.2-4.3 days) of LOS, whilst higher than expected (observed: expected ratio >1) in patients in the top tertile (>4.3 days), amongst all ages. Patients in the top tertile of LOS had increased risks for one readmission: OR = 2.32 (95%CI = 1.86-2.88) or ≥2 readmissions: OR = 6.17 (95%CI = 5.11-7.45), death within 30 days: OR = 2.87 (95%CI = 2.34-3.51), and within six months of discharge: OR = 2.52 (95%CI = 2.23-2.85), and death over a 2-year period: HR = 2.25 (95%CI = 2.05-2.47). The LOS explained 7.4% and 15.9% of the total variance (r2) in one readmission and ≥2 readmissions, and 9.1% and 10.0% of the total variance in mortality with 30 days and within six months of hospital discharge, respectively. Within the bottom, middle and top tertiles of the initial LOS, the median duration from hospital discharge to death progressively shortened from 136, 126 to 80 days, whilst LOS during readmission lengthened from 0.4, 0.9 to 2.8 days, respectively.

Conclusion

Short LOS in hospital was associated with favourable post-discharge outcomes such as early readmission and mortality, and with a delay in time interval from discharge to death and shorter LOS in hospital during readmission. These findings indicate that timely discharge from our hospital meets the aims of the NHS-generated national improvement programme, Getting It Right First Time (GIFTR).
A national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004–20 in Spain
Authors: Sempere Julio , González-Camacho Fernando , Domenech Mirian , Llamosí Mirella , Del Río Idoia , López-Ruiz Beatriz , Gimeno Mercedes , Coronel Pilar , Yuste Jose
Published: December 2021

Background

Surveillance studies including antibiotic resistance and evolution of pneumococcal serotypes are critical to evaluate the susceptibility of commonly used antibiotics and the contribution of conjugate vaccines against resistant strains.

Objectives

To determine the susceptibility of clinical isolates of Streptococcus pneumoniae with reduced susceptibility to penicillin to a panel of antibiotics during the period 2004–20 and characterize the impact of pneumococcal conjugate vaccines in the evolution of resistant serotypes.

Methods

We selected 3017 clinical isolates in order to determine the minimal inhibitory concentration to penicillin, amoxicillin, cefotaxime, erythromycin, levofloxacin and oral cephalosporins, including cefditoren, cefixime and cefpodoxime.

Results

The antibiotics with the lowest proportion of resistant strains from 2004 to 2020 were cefditoren (<0.4%), followed by cefotaxime (<5%), penicillin (<6.5%) and levofloxacin (<7%). Among oral cephalosporins, cefixime was the cephalosporin with the highest MIC90 (32 mg/L) and MIC50 (8–16 mg/L) throughout the study, followed by cefpodoxime with highest values of MIC90 (4 mg/L) and MIC50 (2 mg/L) for the majority of the study period. In contrast, cefditoren was the cephalosporin with the lowest MIC90 (1 mg/L) and MIC50 (0.25–0.5 mg/L).

Conclusions

Cefditoren was the antibiotic with the highest proportion of susceptible strains. Hence, more than 80% of the clinical strains were susceptible to cefditoren throughout the period 2004–20. The proportion of resistant isolates to cefditoren and cefotaxime was scarce, being less than 0.4% for cefditoren and lower than 5% for cefotaxime, despite the increased rates of serotypes not covered by the 13-valent pneumococcal conjugate vaccine.
Basic structure and cytocompatibility of giant membrane vesicles derived from paraformaldehyde-exposed human cells
Authors: Okada Saya , Fukai Yuta , Tanoue Yuki , Nasser Hesham , Fukuda Takaichi , Ikeda Terumasa , Saitoh Hisato
Published: December 2021

Exposure of cultured mammalian cells to paraformaldehyde (PFA) is an effective approach to induce membrane blebs, which is followed by their detachment from the cellular cortex to yield giant membrane vesicles in extracellular spaces. Although PFA-induced giant vesicles have attracted significant interest in the field of cell membrane dynamics, their biochemical components and cytocompatibility remain largely unknown. In this report, we exposed human cervical cancer HeLa cells to PFA under metal-free buffer conditions to produce giant vesicles. We analyzed the components and structure of the purified PFA-induced giant vesicles. Co-culturing PFA-induced giant vesicles with exponentially growing HeLa cells resulted in docking of a significant number of the giant vesicles to the cell surface with seemingly no cytotoxicity. Intriguingly, we found that pre-treatment of HeLa cells with peptide-N-glycosidase and neuraminidase was effective in facilitating cellular uptake of constituents residing inside the vesicles. The results revealed further details about the effect of PFA on cell membranes and provide insights for studying the interaction between PFA-induced giant vesicles and cultured cells.
Professions, work, and digitalization: Technology as means to connective professionalism
Authors: Pareliussen Bjarne , Æsøy Vilmar , Giskeødegård Marte F
Published: December 2021

Developments within digital technology are often seen as an enabler, allowing professions to connect to outside players for competence and new ways of performing their professional work. At the same time, it is often seen as a threat, challenging professional claims to competence and status. This article explores how the implementation of new digital technology affects a profession. The empirical data are from a case study from the maritime industry that focuses on ship engineers and the implementation of an advanced sustainable fuel system and a subsequent new business model to enable its operationalization. Our findings indicate that digital technology created pressure on the profession when their existing competencies did not cover the maintenance of this new technology. The solution for the shipowner to mend the competency gap was more digital technology, specifically technology that enabled more connectivity toward the outside world. This article shows how the profession of the ship engineer was able to connect to outside partners so they could gain competence and incorporate the new digital technology in their professional work. These relations shape the professional work of the ship engineers and move the profession toward connective professionalism. The contribution of this paper is the identification of mechanisms like the pressure to connect to outside actors, removal of barriers, and the observed value of the professional work. These mechanisms are essential to understanding connective professionalism.
Sustainable development goals and the European Cohesion Policy: an application to the autonomous Region of Sardinia
Authors: Cavalli Laura , Sanna Sandro , Alibegovic Mia , Arras Filippo , Cocco Gianluca , Farnia Luca , Manca Emanuela , Mulas Luisa F , Onnis Marco , Ortu Sandro , Romani Ilenia G , Testa Marta
Published: December 2021

Paramount to the implementation of the 2030 Agenda and the effective tackling of the 17 sustainable development goals (SDGs) is the cooperation and coordination of the different levels of government—i.e. the supranational, national and local levels. This is due to the very nature of the SDGs, which are multi-dimensional and intended to guide and boost sustainable development at multiple scales. The European Union (EU) demonstrated a full commitment to the Agenda, making sustainable development a top priority. In fact, the five strategic objectives of the EU are modelled on the principles of the 2030 Agenda and the Cohesion Policy, EU’s most transversal policy, is designed to give a direct contribution to the tackling of the 17 SDGs. Introducing a new methodology to evaluate the sustainability of operational programmes co-financed by the EU, the following paper aims to contribute to the building literature around the question of monitoring public investments regarding sustainability criteria. By matching the 169 targets of the 2030 Agenda with the 143 intervention fields of the Cohesion Policy, with specific reference to Sardinia’s European Regional Development Fund and European Social Fund 2014–2020 Regional Operational Programmes, the present work introduces the key features of the model developed and its first results. The model could be of valuable support to policymakers who now have an innovative tool to monitor investments’ coherence with the sustainability standards of the 2030 Agenda.
Detectability of electromagnetic counterparts from neutron star mergers: prompt emission versus afterglow
Authors: Mohan Sreelekshmi , Saleem M , Resmi Lekshmi
Published: December 2021

Electromagnetic observations of the first binary neutron star (BNS) merger detected in gravitational waves, GW170817, have established that relativistic jets can be successfully launched in BNS mergers. Typically, such jets produce emission in two phases: γ-ray prompt emission and multiwavelength afterglow. Because of relativistic beaming and the jet’s angular structure, the detectability of both these counterparts is dependent on the angle (θ${\rm v}$) between the observer’s line of sight and the jet axis. We compare the detectability of prompt and afterglow emission from off-axis jets, assuming standard detector thresholds such as that of Fermi Gamma-ray Burst Monitor (GBM), Chandra, and Jansky Very Large Array (VLA). We find that for top-hat jets, afterglow is a more likely counterpart than the prompt emission even with unfavourable afterglow parameters. For structured jets with a Gaussian profile, prompt emission is more promising than the afterglows at extreme viewing angles, under the assumption that the total energy emitted in the prompt phase equals the kinetic energy of the outflow. Assuming a Gaussian jet profile, we forecast the population of γ-ray detections and find that extreme viewing angle events like GRB 170817A will be rare. In our simulated sample, the observed isotropic equivalent energy in γ-rays is moderately correlated with the viewing angle, such that a low Eiso,γ is almost always associated with a high off-axis viewing angle.
Planet Hunters TESS IV: a massive, compact hierarchical triple star system TIC 470710327
Authors: Eisner N L , Johnston C , Toonen S , Frost A J , Janssens S , Lintott C J , Aigrain S , Sana H , Abdul-Masih M , Arellano-Córdova K Z , Beck P G , Bordier E , Cannon E , Escorza A , Fabry M , Hermansson L , Howell S B , Miller G , Sheyte S , Alhassan S , Baeten E M L , Barnet F , Bean S J , Bernau M , Bundy D M , Di Fraia M Z , Emralino F M , Goodwin B L , Hermes P , Hoffman T , Huten M , Janíček R , Lee S , Mazzucato M T , Rogers D J , Rout M P , Sejpka J , Tanner C , Terentev I A , Urvoy D
Published: December 2021

We report the discovery and analysis of a massive, compact, hierarchical triple system (TIC 470710327) initially identified by citizen scientists in data obtained by NASA’s Transiting Exoplanet Survey Satellite (TESS). Spectroscopic follow-up observations obtained with the hermes spectrograph, combined with eclipse-timing variations (ETVs), confirm that the system is comprised of three OB stars, with a compact 1.10 d eclipsing binary and a non-eclipsing tertiary on a 52.04 d orbit. Dynamical modelling of the system (from radial velocity and ETVs) reveal a rare configuration wherein the tertiary star (O9.5-B0.5V; 14–17 M⊙) is more massive than the combined mass of the inner binary (10.9–13.2 M⊙). Given the high mass of the tertiary, we predict that this system will undergo multiple phases of mass transfer in the future, and likely end up as a double neutron star gravitational wave progenitor or an exotic Thorne–Żytkow object. Further observational characterization of this system promises constraints on both formation scenarios of massive stars as well as their exotic evolutionary end-products.
On accretion in the eclipsing polar BS Tri
Authors: Kolbin Alexander I , Borisov N V , Serebriakova N A , Shimansky V V , Katysheva N A , Gabdeev M M , Shugarov S Yu
Published: December 2021

We analyse spectroscopic and photometric observations of the eclipsing polar BS Tri. The polar’s light-curve-shape variations can be interpreted by changing contributions of the accretion stream to the integral radiation of the system. Based on the radial-velocity curves of the irradiated part of the secondary, we refine the masses of the system components, M1 = 0.60 ± 0.04 M⊙ and M2 ≈ 0.12 M⊙, and the orbital inclination, i = 85 ± 0.5°. The polar’s spectra reveal cyclotron harmonics forming in an accretion spot with a magnetic field strength of B = 22.7 ± 0.4 MG and an average temperature of T ∼ 10 keV. In addition to the cyclotron harmonics, the BS Tri spectra contain Zeeman components of H α line, which are probably formed in the cool halo near the accretion spot. The orientation of the magnetic dipole and the coordinates of the accretion spot are estimated by modelling the light curves of the polar. We show that for a satisfactory description of the BS Tri light curves we have to take into account the variability of the spot’s optical depth along the line of sight. Doppler maps of BS Tri show a part of the accretion stream with a trajectory close to ballistic near the Lagrange point L1, and another part of the stream moving along the magnetic field lines. The estimate of the stagnation region position found from the Doppler tomograms is consistent with the photometric estimates of the accretion spot position.
On the synthesis of N–O bearing species in astrophysical ices – an infrared spectroscopic study using heavy-ion irradiation of solid N2:CO samples
Authors: Bergantini A , de Barros A L F , Domaracka A , Rothard H , Boduch P , da Silveira E F
Published: December 2021

The interstellar chemistry of nitrogen is considerably less understood than the chemistry of other common elements, such as carbon and oxygen. Even though a relatively large number of species containing nitrogen atoms have already been detected in the interstellar medium, only six of them bear a nitrogen–oxygen (N–O) bond. Some astrophysical and primeval Earth models suggest that N–O species, such as hydroxylamine (NH2OH), are potential precursors of prebiotic amino acids, and even peptides. In this work, we have analyzed an apolar ice mixture of N2:CO of astrophysical interest to investigate possible formation mechanisms of N–O bearing molecules due to processing of the sample by 64Ni24+ 538 MeV ions (8.4 MeV/u) at 14 K. The results show the formation of simple nitrogen oxides ($\rm {N_{1 - 2}}{O_y})$, but no CN–O species of any kind. We have also determined the formation cross-sections of some of the products, as well as the destruction cross-sections of precursors and products. The results presented here are discussed in light of our previous work on the processing of a NH3:CO ice mixture, which have found no N–O bearing molecules at all.
Neutron star oscillations in pseudo-Newtonian gravity
Authors: Tang Yat-To , Lin Lap-Ming
Published: December 2021

We investigate the oscillations of neutron stars using a purely Newtonian approach and three other pseudo-Newtonian formulations. Our work is motivated by the fact that pseudo-Newtonian formulations are commonly used in core-collapse supernova (CCSN) simulations. We derive and solve numerically the radial and non-radial perturbation equations for neutron star oscillations using different combinations of modified Newtonian hydrodynamics equations and gravitational potentials. We pay special attention to the formulation proposed recently by Zha et al. that implements the standard Case A effective potential in CCSN simulations with an additional lapse-function correction to the hydrodynamics equations. We find that this ‘Case A + lapse’ formulation can typically approximate the frequency of the fundamental radial mode of a 1.4-M⊙ neutron star computed in general relativity to about a few tens of per cent for our chosen EOS models. For the non-radial quadrupolar f mode, which is expected to contribute strongly to the gravitational waves emitted from a protoneutron star, the Case A + lapse formulation performs much better and can approximate the f-mode frequency to within about a few per cent even for the maximum-mass configuration in general relativity.
Accretion of a clumped wind from a red supergiant donor on to a magnetar is suggested by the analysis of the XMM–Newton and NuSTAR observations of the X-ray binary 3A 1954+319
Authors: Bozzo E , Ferrigno C , Oskinova L , Ducci L
Published: December 2021

3A 1954+319 has been classified for a long time as a symbiotic X-ray binary, hosting a slowly rotating neutron star and an aged M red giant. Recently, this classification has been revised thanks to the discovery that the donor star is an M supergiant. This makes 3A 1954+319 a rare type of high-mass X-ray binary consisting of a neutron star and a red supergiant donor. In this paper, we analyse two archival and still unpublished XMM–Newton and NuSTAR observations of the source. We perform a detailed hardness ratio-resolved spectral analysis to search for spectral variability that could help investigating the structures of the inhomogeneous M supergiant wind from which the neutron star is accreting. We discuss our results in the context of wind-fed supergiant X-ray binaries and show that the newest findings on 3A 1954+319 reinforce the hypothesis that the neutron star in this system is endowed with a magnetar-like magnetic field strength (≳ 1014 G).
Development of RIKEN Plant Metabolome MetaDatabase
Authors: Fukushima Atsushi , Takahashi Mikiko , Nagasaki Hideki , Aono Yusuke , Kobayashi Makoto , Kusano Miyako , Saito Kazuki , Kobayashi Norio , Arita Masanori
Published: December 2021

The advancement of metabolomics in terms of techniques for measuring small molecules has enabled the rapid detection and quantification of numerous cellular metabolites. Metabolomic data provide new opportunities to gain a deeper understanding of plant metabolism that can improve the health of both plants and humans that consume them. Although major public repositories for general metabolomic data have been established, the community still has shortcomings related to data sharing, especially in terms of data reanalysis, reusability and reproducibility. To address these issues, we developed the RIKEN Plant Metabolome MetaDatabase (RIKEN PMM, http://metabobank.riken.jp/pmm/db/plantMetabolomics), which stores mass spectrometry-based (e.g. gas chromatography–MS-based) metabolite profiling data of plants together with their detailed, structured experimental metadata, including sampling and experimental procedures. Our metadata are described as Linked Open Data based on the Resource Description Framework using standardized and controlled vocabularies, such as the Metabolomics Standards Initiative Ontology, which are to be integrated with various life and biomedical science data using the World Wide Web. RIKEN PMM implements intuitive and interactive operations for plant metabolome data, including raw data (netCDF format), mass spectra (NIST MSP format) and metabolite annotations. The feature is suitable not only for biologists who are interested in metabolomic phenotypes, but also for researchers who would like to investigate life science in general through plant metabolomic approaches.
Interfered chromosome pairing at high temperature promotes meiotic instability in autotetraploid Arabidopsis
Authors: Fu Huiqi , Zhao Jiayi , Ren Ziming , Yang Ke , Wang Chong , Zhang Xiaohong , Elesawi Ibrahim Eid , Zhang Xianhua , Xia Jing , Chen Chunli , Lu Ping , Chen Yongxing , Liu Hong , Yu Guanghui , Liu Bing
Published: December 2021

Changes in environmental temperature affect multiple meiotic processes in flowering plants. Polyploid plants derived from whole-genome duplication (WGD) have enhanced genetic plasticity and tolerance to environmental stress but face challenges in organizing and segregating doubled chromosome sets. In this study, we investigated the impact of increased environmental temperature on male meiosis in autotetraploid Arabidopsis (Arabidopsis thaliana). Under low to mildly increased temperatures (5°C–28°C), irregular chromosome segregation universally occurred in synthetic autotetraploid Columbia-0 (Col-0). Similar meiotic lesions occurred in autotetraploid rice (Oryza sativa L.) and allotetraploid canola (Brassica napus cv Westar), but not in evolutionarily derived hexaploid wheat (Triticum aestivum). At extremely high temperatures, chromosome separation and tetrad formation became severely disordered due to univalent formation caused by the suppression of crossing-over. We found a strong correlation between tetravalent formation and successful chromosome pairing, both of which were negatively correlated with temperature elevation, suggesting that increased temperature interferes with crossing-over predominantly by impacting homolog pairing. We also showed that loading irregularities of axis proteins ASY1 and ASY4 co-localize on the chromosomes of the syn1 mutant and the heat-stressed diploid and autotetraploid Col-0, revealing that heat stress affects the lateral region of synaptonemal complex (SC) by impacting the stability of the chromosome axis. Moreover, we showed that chromosome axis and SC in autotetraploid Col-0 are more sensitive to increased temperature than those in diploid Arabidopsis. Taken together, our data provide evidence suggesting that WGD negatively affects the stability and thermal tolerance of meiotic recombination in newly synthetic autotetraploid Arabidopsis.
Characteristics and Risk Factors of Persistent Neuropathic Pain in Recovered COVID-19 Patients
Authors: Magdy Rehab , Eid Ragaey A , Fathy Wael , Abdel-Aziz Manar M , Ibrahim Raghda E , Yehia Ahmed , Sheemy Mostafa S , Hussein Mona
Published: December 2021

Objectives

To assess risk factors for persistent neuropathic pain in subjects recovered from coronavirus disease 2019 (COVID-19) and to study the serum level of neurofilament light chain (NFL) in those patients.

Design

Case-control study.

Setting

Persistent post-COVID-19 pain.

Subjects

In total, 45 patients with post-COVID-19 pain and another 45 age and sex-matched healthcare workers who recovered from COVID-19 without pain.

Methods

The included participants were subjected to medical history taking, screening for depressive disorders, comprehensive neurological examination, and pain evaluation using the Douleur Neuropathique en 4 questions (DN4). All patients who had a score at least 4/10 on DN4 were included. The serum NFL level was measured for both groups at the time of patients’ enrollment.

Results

The frequency of depression, moderate and severe COVID-19 cases, disease duration and serum ferritin were significantly higher in the cases with post-COVID-19 pain than controls. Binary logistic regression revealed that depression, azithromycin use, moderate and severe COVID-19 increased the odds of post-COVID-19 pain by 4.462, 5.444, 4.901, and 6.276 times, respectively. Cases with post-COVID-19 pain had significantly higher NFL (11.34 ± 9.7, 95% confidence interval [CI]: 8.42–14.25) than control group (7.64 ± 5.40, 95% CI: 6.02–9.27), (P value = .029). Patients with allodynia had significantly higher NFL (14.96 ± 12.41, 95% CI: 8.58–21.35) compared to those without (9.14 ± 6.99, 95% CI: 6.43–11.85) (P value = .05).

Discussion

Depression, azithromycin, and moderate and severe COVID-19 are independent predictors of persistent post-COVID-19 pain. Serum NFL may serve as a potential biomarker for persistent neuropathic pain after COVID-19.
White Matter Metabolite Relaxation and Diffusion Abnormalities in First-Episode Psychosis: A Longitudinal Study
Authors: Chen Xi , Fan Xiaoying , Song Xiaopeng , Gardner Margaret , Du Fei , Öngür Dost
Published: December 2021

Microstructural abnormalities in the white matter (WM) are implicated in the pathophysiology of psychosis. In vivo magnetic resonance spectroscopy (MRS) can probe the brain’s intracellular microenvironment through the measurement of transverse relaxation and diffusion of neurometabolites and possibly provide cell-specific information. In our previous studies, we observed differential metabolite signal abnormalities in first episode and chronic stages of psychosis. In the present work, longitudinal data were presented for the first time on white matter cell-type specific abnormalities using a combination of diffusion tensor spectroscopy (DTS), T2 MRS, and diffusion tensor imaging (DTI) from a group of 25 first episode psychosis patients and nine matched controls scanned at baseline and one and two years of follow-up. We observed significantly reduced choline ADC in the year 1 of follow-up (0.194 µm2/ms) compared to baseline (0.229 µm2/ms), followed by a significant increase in NAA ADC in the year 2 follow-up (0.258 µm2/ms) from baseline (0.222 µm2/ms) and year 1 follow-up (0.217 µm2/ms). In contrast, NAA T2 relaxation, reflecting a related but different aspect of microenvironment from diffusion, was reduced at year 1 follow-up (257 ms) compared to baseline (278 ms). These abnormalities were observed in the absence of any abnormalities in water relaxation and diffusion at any timepoint. These findings indicate that abnormalities are seen in in glial-enriched (choline) signals in early stages of psychosis, followed by the subsequent emergence of neuronal-enriched (NAA) diffusion abnormalities, all in the absence of nonspecific water signal abnormalities.
3D Microtissues Mimic the Architecture, Estradiol Synthesis, and Gap Junction Intercellular Communication of the Avascular Granulosa
Authors: Ip Blanche C , Leary Elizabeth , Knorlein Benjamin , Reich David , Van Vivian , Manning Joshua , Morgan Jeffrey R
Published: December 2021

Humans are consistently exposed to thousands of untested chemicals that have been detected in the follicular fluid of the ovaries, and can disrupt reproductive health. Human granulosa cells (GCs) are the functional unit of the ovarian follicle with steroidogenic and signaling activities, and play a pivotal role in oocyte development. During follicle progression, GCs multiply to form a 3D avascular structure, and establish gap junction intercellular communication (GJIC) that is critical to maintaining optimal viability and function. We developed a high-throughput in vitro platform of human GCs for the screening of chemicals that can impact GJIC and estradiol (E2) production of human granulosa. Our granulosa 3D microtissues fabricated with human ovarian granulosa-like tumor KGN cells are multicell-layered structures that mimic the avascular granulosa layers surrounding the oocyte. These microtissues robustly expressed the steroidogenic CYP19 aromatase enzyme and GJIC intercellular membrane channel, connexin 43. Granulosa microtissues produced E2 at rates comparable to primary human GCs as previously reported. E2 production was suppressed by the CYP19 inhibitor, letrozole, and induced by CYP19 activators, bisphenol A at 100 µM, and genistein at 100 µM. Granulosa microtissues displayed active GJIC function, as demonstrated by the connexin 43-dependent diffusion of calcein fluorescent dye from microtissue surface to the core using high-throughput confocal microscopy in conjunction with our open-sourced automated image analysis tool. Overall, our 3D human granulosa screening platform is highly promising for predictive and efficient in vitro toxicity testing to screen for chemicals that contaminate follicular fluid and may affect fertility.
Epidemiology and Outcome of Sepsis in Adults and Children in a Rural, Sub-Sahara African Setting
Authors: Kwizera Arthur , Urayeneza Olivier , Mujyarugamba Pierre , Baelani Inipavudu , Meier Jens , Mer Mervyn , Musa Ndidiamaka , Kissoon Niranjan , Patterson Andrew J. , Farmer Joseph C. , Dünser Martin W. ,   For the “Sepsis in Resource-Limited Nations” Task Force of the Surviving Sepsis Campaign
Published: December 2021

OBJECTIVES:

To identify the epidemiology and outcome of adults and children with and without sepsis in a rural sub-Sahara African setting.

DESIGN:

A priori planned substudy of a prospective, before-and-after trial.

SETTING:

Rural, sub-Sahara African hospital.

PATIENTS:

One-thousand four-hundred twelve patients (adults, n = 491; children, n = 921) who were admitted to hospital because of an acute infection.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Demographic, clinical, laboratory data, danger signs, and the presence of sepsis (defined as a quick Sequential Organ Failure Assessment score count ≥ 2) at admission were extracted. Sepsis was observed in 69 adults (14.1%) and 248 children (26.9%). Sepsis patients differed from subjects without sepsis in several demographic and clinical aspects. Malaria was the most frequent type of infection in adults (66.7%) and children (63.7%) with sepsis, followed by suspected bacterial and parasitic infections other than malaria. Adults with sepsis more frequently developed respiratory failure (8.7% vs 2.1%; p = 0.01), had a higher in-hospital mortality (17.4% vs 8.3%; p < 0.001), were less often discharged home (81.2% vs 92.2%; p = 0.007), and had higher median (interquartile range) costs of care (30,300 [19,400–49,900] vs 42,500 Rwandan Francs [27,000–64,400 Rwandan Francs]; p = 0.004) than adults without sepsis. Children with sepsis were less frequently discharged home than children without sepsis (93.1% vs 96.4%; p = 0.046). Malaria and respiratory tract infections claimed the highest absolute numbers of lives. The duration of symptoms before hospital admission did not differ between survivors and nonsurvivors in adults (72 [24–168] vs 96 hr [72–168 hr]; p = 0.27) or children (48 [24–72] vs 36 [24–108 hr]; p = 0.8). Respiratory failure and coma were the most common causes of in-hospital death.

CONCLUSIONS:

In addition to suspected bacterial, viral, and fungal infections, malaria and other parasitic infections are common and important causes of sepsis in adults and children admitted to a rural hospital in sub-Sahara Africa. The in-hospital mortality associated with sepsis is substantial, primarily in adults.
Postnatal exposure to PM2.5 and weight trajectories in early childhood
Authors: Vanoli Jacopo , Coull Brent A. , Ettinger de Cuba Stephanie , Fabian Patricia M. , Carnes Fei , Massaro Marisa A. , Poblacion Ana , Bellocco Rino , Kloog Itai , Schwartz Joel , Laden Francine , Zanobetti Antonella
Published: December 2021

Background:

Inconsistent evidence has assessed the impact of air pollution exposure on children’s growth trajectories. We investigated the role of 90-day average postnatal fine particulate matter (PM2.5) exposures by estimating the magnitude of effects at different ages, and the change in child weight trajectory by categories of exposure.

Methods:

We obtained weight values from electronic health records at each hospital visit (males = 1859, females = 1601) from birth to 6 years old children recruited into the Boston-based Children’s HealthWatch cohort (2009–2014). We applied mixed models, adjusting for individual and maternal confounders using (1) varying-coefficient models allowing for smooth non-linear interaction between age and PM2.5, (2) factor-smooth interaction between age and PM2.5 quartiles. Additionally, we stratified by sex and low birthweight (LBW) status (≤2500 g).

Results:

Using varying-coefficient models, we found that PM2.5 significantly modified the association between age and weight in males, with a positive association in children younger than 3 years and a negative association afterwards. In boys, for each 10 µg/m3 increase in PM2.5 we found a 2.6% increase (95% confidence interval = 0.8, 4.6) in weight at 1 year of age and a −0.6% (95% confidence interval = −3.9, 2.9) at 5 years. We found similar but smaller changes in females, and no differences comparing growth trajectories across quartiles of PM2.5. Most of the effects were in LBW children and null for normal birthweight children.

Conclusions:

This study suggests that medium-term postnatal PM2.5 may modify weight trajectories nonlinearly in young children, and that LBW babies are more susceptible than normal-weight infants.
Early environmental quality and life-course mental health effects: The Equal-Life project
Authors: Kamp Irene van , Persson Waye Kerstin , Kanninen Katja , Gulliver John , Bozzon Alessandro , Psyllidis Achilleas , Boshuizen Hendriek , Selander Jenny , van den Hazel Peter , Brambilla Marco , Foraster Maria , Julvez Jordi , Klatte Maria , Jeram Sonja , Lercher Peter , Botteldooren Dick , Ristovska Gordana , Kaprio Jaakko , Schreckenberg Dirk , Hornikx Maarten , Fels Janina , Weber Miriam , Braat-Eggen Ella , Hartmann Julia , Clark Charlotte , Vrijkotte Tanja , Brown Lex , Bolte Gabriele ,   Equal-Life Scientific Team
Published: December 2021

Background:

There is increasing evidence that a complex interplay of factors within environments in which children grows up, contributes to children’s suboptimal mental health and cognitive development. The concept of the life-course exposome helps to study the impact of the physical and social environment, including social inequities, on cognitive development and mental health over time.

Methods:

Equal-Life develops and tests combined exposures and their effects on children’s mental health and cognitive development. Data from eight birth-cohorts and three school studies (N = 240.000) linked to exposure data, will provide insights and policy guidance into aspects of physical and social exposures hitherto untapped, at different scale levels and timeframes, while accounting for social inequities. Reasoning from the outcome point of view, relevant stakeholders participate in the formulation and validation of research questions, and in the formulation of environmental hazards. Exposure assessment combines GIS-based environmental indicators with omics approaches and new data sources, forming the early-life exposome. Statistical tools integrate data at different spatial and temporal granularity and combine exploratory machine learning models with hypothesis-driven causal modeling.

Conclusions:

Equal-Life contributes to the development and utilization of the exposome concept by (1) integrating the internal, physical and social exposomes, (2) studying a distinct set of life-course effects on a child’s development and mental health (3) characterizing the child’s environment at different developmental stages and in different activity spaces, (4) looking at supportive environments for child development, rather than merely pollutants, and (5) combining physical, social indicators with novel effect markers and using new data sources describing child activity patterns and environments.
Prevalence and risk factors of musculoskeletal pain symptoms as long-term post-COVID sequelae in hospitalized COVID-19 survivors: a multicenter study
Authors: Fernández-de-las-Peñas César , de-la-Llave-Rincón Ana I. , Ortega-Santiago Ricardo , Ambite-Quesada Silvia , Gómez-Mayordomo Víctor , Cuadrado María L. , Arias-Navalón José A. , Hernández-Barrera Valentín , Martín-Guerrero José D. , Pellicer-Valero Oscar J. , Arendt-Nielsen Lars
Published: December 2021

This study investigated the prevalence of long-term musculoskeletal post-COVID pain and their risk factors in a large cohort of COVID-19 survivors. A multicenter cohort study including patients hospitalised because of COVID-19 in 5 hospitals of Madrid (Spain) during the first wave of the pandemic was conducted. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview after hospital discharge for collecting data about the musculoskeletal post-COVID pain. Anxiety/depressive levels and sleep quality were likewise assessed. From 2000 patients recruited, a total of 1969 individuals (46.4% women, age: 61 years, SD: 16 years) were assessed on average at 8.4 (SD: 1.5) months after discharge. At the time of the study, 887 (45% women) reported musculoskeletal post-COVID pain. According to the presence of previous pain symptoms, the prevalence of “de novo” (new-onset) musculoskeletal post-COVID pain was 74.9%, whereas 25.1% experienced an increase in previous symptoms (exacerbated COVID-related pain). Female sex (odds ratio [OR]: 1.349, 95% confidence interval [CI]: 1.059-1.720), history of musculoskeletal pain (OR 1.553, 95% CI 1.271-1.898), presence of myalgia (OR 1.546, 95% CI 1.155-2.070) and headache (1.866, 95% CI 1.349-2.580) as COVID-19–associated onset symptoms, and days at hospital (OR 1.013, 95% CI 1.004-1.022) were risk factors associated with musculoskeletal post-COVID pain. In conclusion, musculoskeletal post-COVID pain is present in 45.1% of COVID-19 survivors at 8 months after hospital discharge with most patients developing de novo post-COVID pain. Female sex, history of musculoskeletal pain, presence of myalgia and headache as COVID-19 symptoms at the acute phase, and days at hospital were risk factors associated with musculoskeletal post-COVID pain.