The Transiting Multi-planet System HD15337: Two Nearly Equal-mass Planets Straddling the Radius Gap

We report the discovery of a super-Earth and a sub-Neptune transiting the star HD 15337 (TOI-402, TIC 120896927), a bright (V = 9) K1 dwarf observed by the Transiting Exoplanet Survey Satellite (TESS) in Sectors 3 and 4. We combine the TESS photometry with archival High Accuracy Radial velocity Planet Searcher spectra to confirm the planetary nature of the transit signals and derive the masses of the two transiting planets. With an orbital period of 4.8 days, a mass of ${7.51}_{-1.01}^{+1.09}\,{M}_{\oplus }$ and a radius of 1.64 ± 0.06 R ⊕, HD 15337 b joins the growing group of short-period super-Earths known to have a rocky terrestrial composition. The sub-Neptune HD 15337 c has an orbital period of 17.2 days, a mass of ${8.11}_{-1.69}^{+1.82}\,{{\rm{M}}}_{\oplus }$, and a radius of 2.39 ± 0.12 R ⊕, suggesting that the planet might be surrounded by a thick atmospheric envelope. The two planets have similar masses and lie on opposite sides of the radius gap, and are thus an excellent testbed for planet formation and evolution theories. Assuming that HD 15337 c hosts a hydrogen-dominated envelope, we employ a recently developed planet atmospheric evolution algorithm in a Bayesian framework to estimate the history of the high-energy (extreme ultraviolet and X-ray) emission of the host star. We find that at an age of 150 Myr, the star possessed on average between 3.7 and 127 times the high-energy luminosity of the current Sun

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-Onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification

Trends in Targeted Therapy Usage in Inflammatory Bowel Disease : TRENDY Study of ENEIDA

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment

Corrigendum: Cost-effective, safe, and personalized cell therapy for critical limb ischemia in type 2 diabetes mellitus (vol 10, 1151, 2019)

Reference 86 was also included as “Escacena N. Cellular medication as a therapeutic alternative in chronic critical limb ischemia in diabetic patients without the possibility of revascularization. Dissertation Thesis. Sevilla Spain: University of Sevilla. (2016)”. This reference should be included as number 107 “Escacena N. Cellular medication as a therapeutic alternative in chronic critical limb ischemia in diabetic patients without the possibility of revascularization (Dissertation Thesis). University of Sevilla, Seville, Spain (2016).

Cost-effective, safe, and personalized cell therapy for critical limb ischemia in type 2 diabetes mellitus

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI

Cost-effective, safe, and personalized cell therapy for critical limb ischemia in type 2 diabetes mellitus

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI

Corrigendum: Cost-effective, safe, and personalized cell therapy for critical limb ischemia in type 2 diabetes mellitus (vol 10, 1151, 2019)

Reference 86 was also included as “Escacena N. Cellular medication as a therapeutic alternative in chronic critical limb ischemia in diabetic patients without the possibility of revascularization. Dissertation Thesis. Sevilla Spain: University of Sevilla. (2016)”. This reference should be included as number 107 “Escacena N. Cellular medication as a therapeutic alternative in chronic critical limb ischemia in diabetic patients without the possibility of revascularization (Dissertation Thesis). University of Sevilla, Seville, Spain (2016).