An integrated approach to characterize transcription factor and microRNA regulatory networks involved in Schwann cell response to peripheral nerve injury

BACKGROUND: The regenerative response of Schwann cells after peripheral nerve injury is a critical process directly related to the pathophysiology of a number of neurodegenerative diseases. This SC injury response is dependent on an intricate gene regulatory program coordinated by a number of transcription factors and microRNAs, but the interactions among them remain largely unknown. Uncovering the transcriptional and post-transcriptional regulatory networks governing the Schwann cell injury response is a key step towards a better understanding of Schwann cell biology and may help develop novel therapies for related diseases. Performing such comprehensive network analysis requires systematic bioinformatics methods to integrate multiple genomic datasets. RESULTS: In this study we present a computational pipeline to infer transcription factor and microRNA regulatory networks. Our approach combined mRNA and microRNA expression profiling data, ChIP-Seq data of transcription factors, and computational transcription factor and microRNA target prediction. Using mRNA and microRNA expression data collected in a Schwann cell injury model, we constructed a regulatory network and studied regulatory pathways involved in Schwann cell response to injury. Furthermore, we analyzed network motifs and obtained insights on cooperative regulation of transcription factors and microRNAs in Schwann cell injury recovery. CONCLUSIONS: This work demonstrates a systematic method for gene regulatory network inference that may be used to gain new information on gene regulation by transcription factors and microRNAs

Sex differences in authorship in cardiothoracic surgery during the early coronavirus disease 2019 pandemic.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic negatively impacted cardiothoracic (CT) surgery, with changes in clinical, academic, and personal responsibilities. We hypothesized that the pandemic may disproportionately impact female academic CT surgeons, accentuating preexisting sex disparities. This study assessed sex differences in authorship of 2 major CT surgery journals during the early part of the COVID-19 pandemic. METHODS: All accepted submissions to The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular Surgery between April and August of 2019 and the same period in 2020 were reviewed. Article type and author characteristics were obtained from the journals. Author sex was predicted using a validated multinational database (Genderize.io) and verified with authors institutional and public professional profiles. RESULTS: In total, 1106 submissions were accepted during the 2019 period, whereas 900 articles (18.6% decrease) were accepted during the same period in 2020. Original research articles comprised 33.3% of the 2019 articles but only 4.9% of the 2020 articles. Female authors contributed to 39.3% (23.1% original research and 16.2% nonoriginal articles) and 29.4% (3.3% original research and 26.1% nonoriginal articles) of articles during the 2019 and 2020 periods, respectively. This represents a marked change in the type of articles that female authors contributed to. CONCLUSIONS: Early on during the COVID-19 pandemic, the type of articles accepted, and authorship demographic changed. There was a decrease in contribution of female-authored CT surgery articles submitted to both journals, especially for original research. Future research will elucidate the long-term impact of the pandemic on sex disparities in academic productivity

Vertical variance analysis of geomagnetic disturbance during solar cycle 23

300-309The geomagnetic field consists of temporal variations induced primarily by the variations in the solar wind and embedded interplanetary magnetic field. 34 stations across the Earth have been categorized in this paper on the basis of their geomagnetic disturbance during solar cycle 23 (1997-2008). The Vertical Variance (VV) disturbance quantifier has been used to develop such profile. The latitude profile of geomagnetic disturbance has been found to exhibit a typical ‘Knee’ behaviour, with the fluctuation content seen to rise sharply beyond this critical latitude determined near 52° latitude. The increasing trend in geomagnetic fluctuation content however is seen to end around the auroral oval beyond where abrupt variations has been observed indicating the transition from closed to open magnetic field lines. The physical mechanism behind this trend has also been explored. The VV analysis of geomagnetic disturbance has revealed prominent features of solar wind – magnetosphere coupling

Vertical variance analysis of geomagnetic disturbance during solar cycle 23

The geomagnetic field consists of temporal variations induced primarily by the variations in the solar wind and embedded interplanetary magnetic field. 34 stations across the Earth have been categorized in this paper on the basis of their geomagnetic disturbance during solar cycle 23 (1997-2008). The Vertical Variance (VV) disturbance quantifier has been used to develop such profile. The latitude profile of geomagnetic disturbance has been found to exhibit a typical 'Knee' behaviour, with the fluctuation content seen to rise sharply beyond this critical latitude determined near 52° latitude. The increasing trend in geomagnetic fluctuation content however is seen to end around the auroral oval beyond where abrupt variations has been observed indicating the transition from closed to open magnetic field lines. The physical mechanism behind this trend has also been explored. The VV analysis of geomagnetic disturbance has revealed prominent features of solar wind – magnetosphere coupling

Mapping of variations in child stunting, wasting and underweight within the states of India: the Global Burden of Disease Study 2000–2017

Background To inform actions at the district level under the National Nutrition Mission (NNM), we assessed the prevalence trends of child growth failure (CGF) indicators for all districts in India and inequality between districts within the states. Methods We assessed the trends of CGF indicators (stunting, wasting and underweight) from 2000 to 2017 across the districts of India, aggregated from 5 × 5 km grid estimates, using all accessible data from various surveys with subnational geographical information. The states were categorised into three groups using their Socio-demographic Index (SDI) levels calculated as part of the Global Burden of Disease Study based on per capita income, mean education and fertility rate in women younger than 25 years. Inequality between districts within the states was assessed using coefficient of variation (CV). We projected the prevalence of CGF indicators for the districts up to 2030 based on the trends from 2000 to 2017 to compare with the NNM 2022 targets for stunting and underweight, and the WHO/UNICEF 2030 targets for stunting and wasting. We assessed Pearson correlation coefficient between two major national surveys for district-level estimates of CGF indicators in the states. Findings The prevalence of stunting ranged 3.8-fold from 16.4% (95% UI 15.2–17.8) to 62.8% (95% UI 61.5–64.0) among the 723 districts of India in 2017, wasting ranged 5.4-fold from 5.5% (95% UI 5.1–6.1) to 30.0% (95% UI 28.2–31.8), and underweight ranged 4.6-fold from 11.0% (95% UI 10.5–11.9) to 51.0% (95% UI 49.9–52.1). 36.1% of the districts in India had stunting prevalence 40% or more, with 67.0% districts in the low SDI states group and only 1.1% districts in the high SDI states with this level of stunting. The prevalence of stunting declined significantly from 2010 to 2017 in 98.5% of the districts with a maximum decline of 41.2% (95% UI 40.3–42.5), wasting in 61.3% with a maximum decline of 44.0% (95% UI 42.3–46.7), and underweight in 95.0% with a maximum decline of 53.9% (95% UI 52.8–55.4). The CV varied 7.4-fold for stunting, 12.2-fold for wasting, and 8.6-fold for underweight between the states in 2017; the CV increased for stunting in 28 out of 31 states, for wasting in 16 states, and for underweight in 20 states from 2000 to 2017. In order to reach the NNM 2022 targets for stunting and underweight individually, 82.6% and 98.5% of the districts in India would need a rate of improvement higher than they had up to 2017, respectively. To achieve the WHO/UNICEF 2030 target for wasting, all districts in India would need a rate of improvement higher than they had up to 2017. The correlation between the two national surveys for district-level estimates was poor, with Pearson correlation coefficient of 0.7 only in Odisha and four small north-eastern states out of the 27 states covered by these surveys. Interpretation CGF indicators have improved in India, but there are substantial variations between the districts in their magnitude and rate of decline, and the inequality between districts has increased in a large proportion of the states. The poor correlation between the national surveys for CGF estimates highlights the need to standardise collection of anthropometric data in India. The district-level trends in this report provide a useful reference for targeting the efforts under NNM to reduce CGF across India and meet the Indian and global targets. Keywords Child growth failureDistrict-levelGeospatial mappingInequalityNational Nutrition MissionPrevalenceStuntingTime trendsUnder-fiveUndernutritionUnderweightWastingWHO/UNICEF target

A search using GEO600 for gravitational waves coincident with fast radio bursts from SGR 1935+2154

The magnetar SGR 1935+2154 is the only known Galactic source of fast radio bursts (FRBs). FRBs from SGR 1935+2154 were first detected by the Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB and the Survey for Transient Astronomical Radio Emission 2 in 2020 April, after the conclusion of the LIGO, Virgo, and KAGRA Collaborations' O3 observing run. Here, we analyze four periods of gravitational wave (GW) data from the GEO600 detector coincident with four periods of FRB activity detected by CHIME/FRB, as well as X-ray glitches and X-ray bursts detected by NICER and NuSTAR close to the time of one of the FRBs. We do not detect any significant GW emission from any of the events. Instead, using a short-duration GW search (for bursts ≤1 s) we derive 50% (90%) upper limits of 1048 (1049) erg for GWs at 300 Hz and 1049 (1050) erg at 2 kHz, and constrain the GW-to-radio energy ratio to ≤1014−1016. We also derive upper limits from a long-duration search for bursts with durations between 1 and 10 s. These represent the strictest upper limits on concurrent GW emission from FRBs

Search for continuous gravitational waves from known pulsars in the first part of the fourth LIGO-Virgo-KAGRA observing run

Continuous gravitational waves (CWs) emission from neutron stars carries information about their internal structure and equation of state, and it can provide tests of general relativity. We present a search for CWs from a set of 45 known pulsars in the first part of the fourth LIGO–Virgo–KAGRA observing run, known as O4a. We conducted a targeted search for each pulsar using three independent analysis methods considering single-harmonic and dual-harmonic emission models. We find no evidence of a CW signal in O4a data for both models and set upper limits on the signal amplitude and on the ellipticity, which quantifies the asymmetry in the neutron star mass distribution. For the single-harmonic emission model, 29 targets have the upper limit on the amplitude below the theoretical spin-down limit. The lowest upper limit on the amplitude is 6.4 × 10−27 for the young energetic pulsar J0537−6910, while the lowest constraint on the ellipticity is 8.8 × 10−9 for the bright nearby millisecond pulsar J0437−4715. Additionally, for a subset of 16 targets, we performed a narrowband search that is more robust regarding the emission model, with no evidence of a signal. We also found no evidence of nonstandard polarizations as predicted by the Brans–Dicke theory

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years