Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study

Background: HSK21542, a novel selective peripherally-restricted κ-opioid receptor agonist has been proven to be a safe and effective analgesic and antipruritic drug in both in vitro and in vivo studies. We aimed to evaluate its safety, pharmacokinetics and efficacy in hemodialysis patients over a 1-week treatment period, and to establish the optimal dosage for a further 12-week stage 2 trial.Methods: In this multiple ascending dose study, hemodialysis patients were randomly assigned to receive HSK21542 (0.05–0.80 μg/kg), or a placebo three times within 2.5 h at the end of each dialysis session for 1 week. Safety evaluations included reports of treatment-emergent adverse events (TEAEs); pharmacokinetics and efficacy outcomes were also assessed.Results: Among the 44 screened patients, 41 were enrolled and completed the trial. The overall incidence of TEAEs was higher in the HSK21542 group compared to the placebo group, with an incidence of 75.0%, 50.0%, 75.0%, and 88.9% in the range of 0.05–0.80 μg/kg. All TEAEs were grade 1 or 2 in severity. HSK21542 exhibited linear pharmacokinetics characteristics within the dose range 0.05–0.80 μg/kg, without drug accumulation after multiple-doses. Compared to the placebo, a significant decrease of the weekly mean Worst Itching Intensity Numerical Rating Scale was found in the HSK21542-0.30 μg/kg group (p = 0.046), but without significant improvement in the Skindex-16 score.Conclusion: HSK21542 was well tolerated in the dose range 0.05–0.80 μg/kg in hemodialysis patients. HSK21542-0.3 μg/kg exhibited promising efficacy in patients with moderate to severe pruritus and warrants a further Stage 2 trial.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT04470154

TOI-132 b: A short-period planet in the Neptune desert transiting a V=11.3 G-type star

The Neptune desert is a feature seen in the radius-period plane, whereby a notable dearth of short period, Neptune-like planets is found. Here, we report the Transiting Exoplanet Survey Satellite (TESS) discovery of a new short-period planet in the Neptune desert, orbiting the G-type dwarf TYC 8003-1117-1 (TOI-132). TESS photometry shows transit-like dips at the level of similar to 1400 ppm occurring every similar to 2.11 d. High-precision radial velocity follow-up with High Accuracy Radial Velocity Planet Searcher confirmed the planetary nature of the transit signal and provided a semi-amplitude radial velocity variation of 11.38(-0.85)(+0.84) m s(-1), which, when combined with the stellar mass of 0.97 +/- 0.06 M-circle dot, provides a planetary mass of 22.40(-1.92)(+1.90) M-circle plus. Modelling the TESS light curve returns a planet radius of 3.42(-0.14)(+0.13) R-circle plus , and therefore the planet bulk density is found to be 3.08(-0.46)(+0.44) g cm(-3). Planet structure models suggest that the bulk of the planet mass is in the form of a rocky core, with an atmospheric mass fraction of 4.3(-2.3)(+1.2) percent. TOI-132 b is a TESS Level 1 Science Requirement candidate, and therefore priority follow-up will allow the search for additional planets in the system, whilst helping to constrain low-mass planet formation and evolution models, particularly valuable for better understanding of the Neptune desert

The Magellan-TESS Survey I: Survey Description and Mid-Survey Results

One of the most significant revelations from Kepler is that roughly one-third of Sun-like stars host planets which orbit their stars within 100 days and are between the size of Earth and Neptune. How do these super-Earth and sub-Neptune planets form, what are they made of, and do they represent a continuous population or naturally divide into separate groups? Measuring their masses and thus bulk densities can help address these questions of their origin and composition. To that end, we began the Magellan-TESS Survey (MTS), which uses Magellan II/PFS to obtain radial velocity (RV) masses of 30 transiting exoplanets discovered by TESS and develops an analysis framework that connects observed planet distributions to underlying populations. In the past, RV measurements of small planets have been challenging to obtain due to the faintness and low RV semi-amplitudes of most Kepler systems, and challenging to interpret due to the potential biases in the existing ensemble of small planet masses from non-algorithmic decisions for target selection and observation plans. The MTS attempts to minimize these biases by focusing on bright TESS targets and employing a quantitative selection function and multi-year observing strategy. In this paper, we (1) describe the motivation and survey strategy behind the MTS, (2) present our first catalog of planet mass and density constraints for 25 TESS Objects of Interest (TOIs; 20 in our population analysis sample, five that are members of the same systems), and (3) employ a hierarchical Bayesian model to produce preliminary constraints on the mass-radius (M-R) relation. We find qualitative agreement with prior mass-radius relations but some quantitative differences (abridged). The the results of this work can inform more detailed studies of individual systems and offer a framework that can be applied to future RV surveys with the goal of population inferences.Comment: 101 pages (39 of main text and references, the rest an appendix of figures and tables). Submitted to AAS Journal

Identification of the top TESS objects of interest for atmospheric characterization of transiting exoplanets with JWST

Funding: Funding for the TESS mission is provided by NASA's Science Mission Directorate. This work makes use of observations from the LCOGT network. Part of the LCOGT telescope time was granted by NOIRLab through the Mid-Scale Innovations Program (MSIP). MSIP is funded by NSF. This paper is based on observations made with the MuSCAT3 instrument, developed by the Astrobiology Center and under financial support by JSPS KAKENHI (grant No. JP18H05439) and JST PRESTO (grant No. JPMJPR1775), at Faulkes Telescope North on Maui, HI, operated by the Las Cumbres Observatory. This paper makes use of data from the MEarth Project, which is a collaboration between Harvard University and the Smithsonian Astrophysical Observatory. The MEarth Project acknowledges funding from the David and Lucile Packard Fellowship for Science and Engineering, the National Science Foundation under grant Nos. AST-0807690, AST-1109468, AST-1616624 and AST-1004488 (Alan T. Waterman Award), the National Aeronautics and Space Administration under grant No. 80NSSC18K0476 issued through the XRP Program, and the John Templeton Foundation. C.M. would like to gratefully acknowledge the entire Dragonfly Telephoto Array team, and Bob Abraham in particular, for allowing their telescope bright time to be put to use observing exoplanets. B.J.H. acknowledges support from the Future Investigators in NASA Earth and Space Science and Technology (FINESST) program (grant No. 80NSSC20K1551) and support by NASA under grant No. 80GSFC21M0002. K.A.C. and C.N.W. acknowledge support from the TESS mission via subaward s3449 from MIT. D.R.C. and C.A.C. acknowledge support from NASA through the XRP grant No. 18-2XRP18_2-0007. C.A.C. acknowledges that this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). S.Z. and A.B. acknowledge support from the Israel Ministry of Science and Technology (grant No. 3-18143). The research leading to these results has received funding from the ARC grant for Concerted Research Actions, financed by the Wallonia-Brussels Federation. TRAPPIST is funded by the Belgian Fund for Scientific Research (Fond National de la Recherche Scientifique, FNRS) under the grant No. PDR T.0120.21. The postdoctoral fellowship of K.B. is funded by F.R.S.-FNRS grant No. T.0109.20 and by the Francqui Foundation. H.P.O.'s contribution has been carried out within the framework of the NCCR PlanetS supported by the Swiss National Science Foundation under grant Nos. 51NF40_182901 and 51NF40_205606. F.J.P. acknowledges financial support from the grant No. CEX2021-001131-S funded by MCIN/AEI/ 10.13039/501100011033. A.J. acknowledges support from ANID—Millennium Science Initiative—ICN12_009 and from FONDECYT project 1210718. Z.L.D. acknowledges the MIT Presidential Fellowship and that this material is based upon work supported by the National Science Foundation Graduate Research Fellowship under grant No. 1745302. P.R. acknowledges support from the National Science Foundation grant No. 1952545. This work is partly supported by JSPS KAKENHI grant Nos. JP17H04574, JP18H05439, JP21K20376; JST CREST grant No. JPMJCR1761; and Astrobiology Center SATELLITE Research project AB022006. This publication benefits from the support of the French Community of Belgium in the context of the FRIA Doctoral Grant awarded to M.T. D.D. acknowledges support from TESS Guest Investigator Program grant Nos. 80NSSC22K1353, 80NSSC22K0185, and 80NSSC23K0769. A.B. acknowledges the support of M.V. Lomonosov Moscow State University Program of Development. T.D. was supported in part by the McDonnell Center for the Space Sciences. V.K. acknowledges support from the youth scientific laboratory project, topic FEUZ-2020-0038.JWST has ushered in an era of unprecedented ability to characterize exoplanetary atmospheres. While there are over 5000 confirmed planets, more than 4000 Transiting Exoplanet Survey Satellite (TESS) planet candidates are still unconfirmed and many of the best planets for atmospheric characterization may remain to be identified. We present a sample of TESS planets and planet candidates that we identify as “best-in-class” for transmission and emission spectroscopy with JWST. These targets are sorted into bins across equilibrium temperature Teq and planetary radius Rp and are ranked by a transmission and an emission spectroscopy metric (TSM and ESM, respectively) within each bin. We perform cuts for expected signal size and stellar brightness to remove suboptimal targets for JWST. Of the 194 targets in the resulting sample, 103 are unconfirmed TESS planet candidates, also known as TESS Objects of Interest (TOIs). We perform vetting and statistical validation analyses on these 103 targets to determine which are likely planets and which are likely false positives, incorporating ground-based follow-up from the TESS Follow-up Observation Program to aid the vetting and validation process. We statistically validate 18 TOIs, marginally validate 31 TOIs to varying levels of confidence, deem 29 TOIs likely false positives, and leave the dispositions for four TOIs as inconclusive. Twenty-one of the 103 TOIs were confirmed independently over the course of our analysis. We intend for this work to serve as a community resource and motivate formal confirmation and mass measurements of each validated planet. We encourage more detailed analysis of individual targets by the community.Peer reviewe

GJ 1252 b: A 1.2 R⊕ Planet Transiting an M3 Dwarf at 20.4 pc

We report the discovery of GJ 1252 b, a planet with a radius of 1.193 ± 0.074 R and an orbital period of 0.52 days around an M3-type star (0.381 ± 0.019 M, 0.391 ± 0.020 R) located 20.385 ± 0.019 pc away. We use Transiting Exoplanet Survey Satellite (TESS) data, ground-based photometry and spectroscopy, Gaia astrometry, and high angular resolution imaging to show that the transit signal seen in the TESS data must originate from a transiting planet. We do so by ruling out all false-positive scenarios that attempt to explain the transit signal as originating from an eclipsing stellar binary. Precise Doppler monitoring also leads to a tentative mass measurement of 2.09 ± 0.56 M ⊕. The host star proximity, brightness (V = 12.19 mag, K = 7.92 mag), low stellar activity, and the system's short orbital period make this planet an attractive target for detailed characterization, including precise mass measurement, looking for other objects in the system, and planet atmosphere characterization

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

TOI-332 b : a super dense Neptune found deep within the Neptunian desert

To date, thousands of planets have been discovered, but there are regions of the orbital parameter space that are still bare. An example is the short period and intermediate mass/radius space known as the “Neptunian desert”, where planets should be easy to find but discoveries remain few. This suggests unusual formation and evolution processes are responsible for the planets residing here. We present the discovery of TOI-332 b, a planet with an ultra-short period of 0.78 d that sits firmly within the desert. It orbits a K0 dwarf with an effective temperature of 5251 ± 71 K. TOI-332 b has a radius of 3.20+ 0.16 −0.12 R⊕, smaller than that of Neptune, but an unusually large mass of 57.2 ± 1.6 M⊕. It has one of the highest densities of any Neptune-sized planet discovered thus far at 9.6+ 1.1 −1.3 g cm−3 . A 4-layer internal structure model indicates it likely has a negligible hydrogen-helium envelope, something only found for a small handful of planets this massive, and so TOI-332 b presents an interesting challenge to planetary formation theories. We find that photoevaporation cannot account for the mass loss required to strip this planet of the Jupiter-like envelope it would have been expected to accrete. We need to look towards other scenarios, such as high-eccentricity migration, giant impacts, or gap opening in the protoplanetary disc, to try and explain this unusual discovery

Transit timings variations in the three-planet system : TOI-270

We present ground- and space-based photometric observations of TOI-270 (L231-32), a system of three transiting planets consisting of one super-Earth and two sub-Neptunes discovered by TESS around a bright (K-mag = 8.25) M3V dwarf. The planets orbit near low-order mean-motion resonances (5:3 and 2:1) and are thus expected to exhibit large transit timing variations (TTVs). Following an extensive observing campaign using eight different observatories between 2018 and 2020, we now report a clear detection of TTVs for planets c and d, with amplitudes of ∼10 min and a super-period of ∼3 yr, as well as significantly refined estimates of the radii and mean orbital periods of all three planets. Dynamical modelling of the TTVs alone puts strong constraints on the mass ratio of planets c and d and on their eccentricities. When incorporating recently published constraints from radial velocity observations, we obtain masses of Mb=1.48±0.18M⊕⁠, Mc=6.20±0.31M⊕⁠, and Md=4.20±0.16M⊕ for planets b, c, and d, respectively. We also detect small but significant eccentricities for all three planets : eb = 0.0167 ± 0.0084, ec = 0.0044 ± 0.0006, and ed = 0.0066 ± 0.0020. Our findings imply an Earth-like rocky composition for the inner planet, and Earth-like cores with an additional He/H2O atmosphere for the outer two. TOI-270 is now one of the best constrained systems of small transiting planets, and it remains an excellent target for atmospheric characterization

Identification the genetic influence of SARS-CoV-2 infections on IgA nephropathy based on bioinformatics method.

Introduction: Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. It was initially detected in Wuhan, China, in December 2019. In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. Compared to healthy individuals, patients with IgA nephropathy (IgAN) are at a higher risk of SARS-CoV-2 infection. However, the potential mechanisms remain unclear. This study explores the underlying molecular mechanisms and therapeutic agents for the management of IgAN and COVID-19 using the bioinformatics and system biology way. Methods: We first downloaded GSE73953 and GSE164805 from the Gene Expression Omnibus (GEO) database to obtain common differentially expressed genes (DEGs). Then, we performed the functional enrichment analysis, pathway analysis, protein-protein interaction (PPI) analysis, gene regulatory networks analysis, and potential drug analysis on these common DEGs. Results: We acquired 312 common DEGs from the IgAN and COVID-19 datasets and used various bioinformatics tools and statistical analyses to construct the PPI network to extract hub genes. Besides, we performed gene ontology (GO) and pathway analyses to reveal the common correlation between IgAN and COVID-19. Finally, on the basis of common DEGs, we determined the interactions between DEGs-miRNAs, the transcription factor-genes (TFs-genes), protein-drug, and gene-disease networks. Discussion/Conclusion: We successfully identified hub genes that may act as biomarkers of COVID-19 and IgAN and also screened out some potential drugs to provide new ideas for COVID-19 and IgAN treatment