Jeppesenlynggaard1427

37, 95% CI 1.92, 21.17; P = 0.003) after adjusting for disease duration and antibodies.

We confirm a significant association between high PPI exposure with severity of calcinosis in SSc. Given the clinical impact of calcinosis and reflux in SSc, PPI exposure as a potentially modifiable risk factor for calcinosis requires further evaluation.

We confirm a significant association between high PPI exposure with severity of calcinosis in SSc. Given the clinical impact of calcinosis and reflux in SSc, PPI exposure as a potentially modifiable risk factor for calcinosis requires further evaluation.

Facilitated by technological advances and expeditious decrease in the sequencing costs, whole-genome sequencing is increasingly implemented to uncover variations in cultivars/accessions of many crop plants. In tomato (Solanum lycopersicum), the availability of the genome sequence, followed by the resequencing of tomato cultivars and its wild relatives, has provided a prodigious resource for the improvement of traits. A high-quality genome resequencing of 84 tomato accessions and wild relatives generated a dataset that can be used as a resource to identify agronomically important alleles across the genome. Converting this dataset into a searchable database, including information about the influence of single-nucleotide polymorphisms (SNPs) on protein function, provides valuable information about the genetic variations. The database will assist in searching for functional variants of a gene for introgression into tomato cultivars.

A recent release of better-quality tomato genome reference assembly SL3.0, and new annotation ITAG3.2 of SL3.0, dropped 3857 genes, added 4900 novel genes and updated 20766 genes. Using the above version, we remapped the data from the tomato lines resequenced under the '100 tomato genome resequencing project' on new tomato genome assembly SL3.0 and made an online searchable Tomato Genomic Variations (TGVs) database. The TGV contains information about SNPs and insertion/deletion events and expands it by functional annotation of variants with new ITAG3.2 using SIFT4G software. This database with search function assists in inferring the influence of SNPs on the function of a target gene. This database can be used for selecting SNPs, which can be potentially deployed for improving tomato traits.

TGV is freely available at http//psd.uohyd.ac.in/tgv.

TGV is freely available at http//psd.uohyd.ac.in/tgv.

In population-based cancer survival studies, the most common measure to compare population groups is age-standardized marginal relative survival, which under assumptions can be interpreted as marginal net survival; the probability of surviving if it was not possible to die of causes other than the cancer under study (if the age distribution was that of a common reference population). The hypothetical nature of this definition has led to confusion and incorrect interpretation. For any measure to be fair in terms of comparing cancer survival, then differences between population groups should depend only on differences in excess mortality rates due to the cancer and not differences in other-cause mortality rates or differences in the age distribution.

We propose using crude probabilities of death and all-cause survival which incorporate reference expected mortality rates. This makes it possible to obtain marginal crude probabilities and all-cause probability of death that only differ between population groups due to excess mortality rate differences. Choices have to be made regarding what reference mortality rates to use and what age distribution to standardize to.

We illustrate the method and some potential choices using data from England for men diagnosed with melanoma. Various marginal measures are presented and compared.

The new measures help enhance understanding of cancer survival and are a complement to the more commonly used measures.

The new measures help enhance understanding of cancer survival and are a complement to the more commonly used measures.

Remdesivir is a prodrug with in vitro activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Its clinical efficacy in patients with COVID-19 under mechanical ventilation remains to be evaluated.

This study includes patients under mechanical ventilation with confirmed SARS-CoV-2 infection admitted to the ICU of Pesaro hospital between 29 February and 20 March 2020. During this period, remdesivir was provided on a compassionate use basis. Clinical characteristics and outcome of patients treated with remdesivir were collected retrospectively and compared with those of patients hospitalized in the same time period.

A total of 51 patients were considered, of which 25 were treated with remdesivir. The median (IQR) age was 67 (59-75.5) years, 92% were men and symptom onset was 10 (8-12) days before admission to ICU. At baseline, there was no significant difference in demographic characteristics, comorbidities and laboratory values between patients treated and not treated with remdesivir. Median follow-up was 52 (46-57) days. Kaplan-Meier curves showed significantly lower mortality among patients who had been treated with remdesivir (56% versus 92%, P < 0.001). Cox regression analysis showed that the Charlson Comorbidity Index was the only factor that had a significant association with higher mortality (OR 1.184; 95% CI 1.027-1.365; P = 0.020), while the use of remdesivir was associated with better survival (OR 3.506; 95% CI 1.768-6.954; P < 0.001).

In this study the mortality rate of patients with COVID-19 under mechanical ventilation is confirmed to be high. The use of remdesivir was associated with a significant beneficial effect on survival.

In this study the mortality rate of patients with COVID-19 under mechanical ventilation is confirmed to be high. The use of remdesivir was associated with a significant beneficial effect on survival.

Can oocytes extracted from excised ovarian tissue and matured in vitro be a useful adjunct for urgent fertility preservation (FP)?

Ovarian tissue oocyte in-vitro maturation (OTO-IVM) in combination with ovarian tissue cryopreservation (OTC) is a valuable adjunct technique for FP.

Despite the impressive progress in the field, options for FP for cancer patients are still limited and, depending on the technique, clinical outcome data are still scarce.

This was a retrospective cohort study conducted at a university hospital-affiliated fertility clinic between January 2012 and May 2019.

The study included 77 patients who underwent unilateral oophorectomy for OTC. Cumulus-oocyte complexes (COCs) obtained during ovarian tissue processing were matured in vitro for 28-42 h. Oocytes reaching metaphase II stage were vitrified or inseminated for embryo vitrification.

Overall, 1220 COCs were collected. The mean oocyte maturation rate was 39% ± 23% (SD). There were 64 patients who had vitrification of oocytes ( The results of the study illustrate the added value of OTO-IVM in combination with OTC. We report the first live birth following the use of this appended technique combined with oocyte vitrification.

No external funding was used for this study. WAY-100635 in vivo M.D.V. reports honoraria for lectures in the last 2 years from MSD and Ferring, outside the submitted work, as well as grant support from MSD. The other authors have nothing to declare.

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What are the distributions and associated clinical characteristics of mediator complex subunit 12 (MED12), high mobility group AT-hook 2 (HMGA2) and fumarate hydratase (FH) aberrations in uterine leiomyomas from fertile-aged myomectomy patients?

These driver mutations account for the majority (83%) of tumours in fertile-aged patients.

Alterations affecting MED12, HMGA2 and FH account for 80-90% of uterine leiomyomas from middle-aged hysterectomy patients, while the molecular background of tumours from young myomectomy patients has not been systematically studied.

A retrospective series of 361 archival uterine leiomyoma samples from 234 women aged ≤45 years undergoing myomectomy in 2009-2014 was examined. Associations between the molecular data and detailed clinical information of the patients and tumours were analysed.

DNA was extracted from formalin-fixed paraffin-embedded samples and MED12 exons 1 and 2 were sequenced to identify mutations. Level of HMGA2 expression was evaluated by immunohistoche partly descriptive.

The contribution of driver mutations in leiomyomas from young myomectomy patients is comparable to tumours obtained from hysterectomies of mostly middle-aged women. Our results support the earlier findings that MED12 mutations are associated with multiple tumours, smaller tumour size and subserosal location. The study emphasizes the distinct molecular background of solitary leiomyomas, and more research is needed to clarify the underlying causes of the notable proportion of wild-type leiomyomas.

The study was supported by the Academy of Finland (307773), the Sigrid Jusélius Foundation, the Cancer Foundation Finland and the iCAN Digital Precision Cancer Medicine Flagship. The authors declare no conflicts of interest.

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N/A.Growing evidence suggests 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-positron emission tomography/computed tomography (PET/CT) is a useful imaging technique for the evaluation of fever of unknown origin (FUO). This imaging technique allows for accurate localization of foci of hypermetabolism based on 18FDG uptake in glycolytically-active cells that may represent inflammation, infection, or neoplasia. The presence of abnormal uptake can help direct further investigation that may yield a final diagnosis. A lack of abnormal uptake can be reasonably reassuring that these conditions are not present, thereby avoiding unnecessary additional testing. Insurers have not routinely covered outpatient 18FDG-PET/CT for the indication of FUO in the United States; however, data published since 2007 suggest early use in FUO diagnostic evaluations improves diagnostic efficiency and saves costs. Clinicians and insurers should consider 18FDG-PET/CTas a useful tool when preliminary studies are unrevealing.Th17 cells, a lymphocyte subpopulation that is characterized by the expression of the transcription factor "retinoic acid receptor-related orphan receptor gamma-t" (RORγt), plays an important role in the pathogenesis of autoimmune disease. The current study was set up to discover novel and non-steroidal small-molecule inverse agonists of RORγt and to determine their effects on autoimmune disease. Structure-based virtual screening (SBVS) was used to find compounds targeting RORγt. Flow cytometry was used to detect the Th17 cell differentiation. Inverse agonists were intraperitoneally administered to mice undergoing experimental autoimmune uveitis (EAU), experimental autoimmune encephalomyelitis (EAE) or type 1 diabetes. The effects of the inverse agonists were evaluated by clinical or histopathological scoring. Among 1.3 million compounds screened, CQMU151 and CQMU152 were found to inhibit Th17 cell differentiation without affecting the differentiation of Th1 and Treg lineages (both P = 0.001). These compounds also reduced the severity of EAU (P = 0.01 and 0.013) and functional studies showed that they reduced the number of Th17 cell and the expression of IL-17(Th17), but not IFN-γ(Th1) and TGF-β(Treg) in mouse retinas. Further studies showed that these compounds may reduce the expression of p-STAT3 by reducing the positive feedback loop of IL-17/IL-6/STAT3. These compounds also reduced the impaired blood-retinal barrier function by upregulating the expression of tight junction proteins. These compounds were also found to reduce the severity of EAE and type 1 diabetes. Our results showed that RORγt inverse agonists may inhibit the development of autoimmune diseases and may provide new clues for the treatment of Th17-mediated immune diseases.