Notes

Your Polycomb team health proteins MEDEA controls mobile proliferation as well as embryonic patterning throughout Arabidopsis.
Can a combination of the focussed protein kinase assays and a wide-scale proteomic screen pinpoint novel, clinically relevant players in decidualization in vitro and in vivo?

Rho-dependent protein kinase (ROCK) activity is elevated in response to the combined treatment with progesterone and 8-Br-cAMP during in vitro decidualization, mirrored by increase of ROCK2 mRNA and protein levels and the phosphorylation levels of its downstream target Cofilin-1 (CFL1) in secretory versus proliferative endometrium.

Decidualization is associated with extensive changes in gene expression profile, proliferation, metabolism and morphology of endometrium, yet only a few underlying molecular pathways have been systematically explored. In vitro decidualization of endometrial stromal cells (ESCs) can be reportedly induced using multiple protocols with variable physiological relevance. In our previous studies, cyclic AMP (cAMP)/cAMP-dependent protein kinase (PKA)/prolactin axis that is classically upregulated during deciduaian Ministry of Education and Research, and the Estonian Research Council (PRG1076, PRG454, PSG230 and PSG608), Enterprise Estonia (EU48695), Horizon 2020 innovation grant (ERIN, Grant no. EU952516) of the European Commission, the COMBIVET ERA Chair, H2020-WIDESPREAD-2018-04 (Grant agreement no. 857418), the Academy of Finland (Project grants 315921 and 321763), the Finnish Medical Foundation and The Sigrid Juselius Foundation. The authors confirm that they have no conflict of interest with respect to the content of this article.
Phaeochromocytoma is sometimes not diagnosed before surgery and may present as an adrenal incidentaloma. The aim of this study was to investigate differences in clinical presentation and perioperative outcome in patients with subclinical and symptomatic phaeochromocytoma, and in patients operated with and without preoperative α-blockade.

This was a retrospective observational study of patients with a histopathological diagnosis of phaeochromocytoma registered in Eurocrine®, the European registry for endocrine tumours, between 1 January 2015 and 31 March 2020. Patient characteristics, clinical presentation, tumour detection, and perioperative variables were analysed.

Some 551 patients were included. Of these, 486 patients (88.2 per cent) had a preoperative diagnosis of phaeochromocytoma. Tumours were detected as incidentalomas in 239 patients (43.4 per cent) and 265 (48.1 per cent) had a preoperative diagnosis of hypertension. Preoperative α-blockade was more frequently used in patients with a known phaeochromocytoma (350, 90.9 per cent) than in patients with other indications for adrenalectomy (16, 31 per cent). Complications did not differ between patients who had surgery because of catecholamine excess compared with those who had other indications for surgery (19 (3.9 per cent) versus 2 (3 per cent); P = 0.785), nor did the conversion rate from minimally invasive to open surgery differ between the groups. There were no obvious differences in complications, according to the Clavien-Dindo classification, based on preoperative α-blockade or not.

Subclinical phaeochromocytoma detected incidentally is common. A significantproportion of patients with phaeochromocytoma did not have α-blockade before surgery, without an apparent effect on complications.
Subclinical phaeochromocytoma detected incidentally is common. A significantproportion of patients with phaeochromocytoma did not have α-blockade before surgery, without an apparent effect on complications.
To propose an algorithm that utilizes only timestamps of longitudinal electronic health record data to classify clinical deterioration events.

This retrospective study explores the efficacy of machine learning algorithms in classifying clinical deterioration events among patients in intensive care units using sequences of timestamps of vital sign measurements, flowsheets comments, order entries, and nursing notes. We design a data pipeline to partition events into discrete, regular time bins that we refer to as timesteps. Logistic regressions, random forest classifiers, and recurrent neural networks are trained on datasets of different length of timesteps, respectively, against a composite outcome of death, cardiac arrest, and Rapid Response Team calls. Then these models are validated on a holdout dataset.

A total of 6720 intensive care unit encounters meet the criteria and the final dataset includes 830 578 timestamps. The gated recurrent unit model utilizes timestamps of vital signs, order entries, flowsheet comments, and nursing notes to achieve the best performance on the time-to-outcome dataset, with an area under the precision-recall curve of 0.101 (0.06, 0.137), a sensitivity of 0.443, and a positive predictive value of 0. 092 at the threshold of 0.6.

This study demonstrates that our recurrent neural network models using only timestamps of longitudinal electronic health record data that reflect healthcare processes achieve well-performing discriminative power.
This study demonstrates that our recurrent neural network models using only timestamps of longitudinal electronic health record data that reflect healthcare processes achieve well-performing discriminative power.
Cardiogenic shock is a life-threatening situation with high mortality rates. Mechanical unloading of the left ventricle may be achieved via left ventricular assist device (LVAD) implantation. Postoperative right ventricular (RV) failure, however, has very limited therapeutic options and is associated with increased postoperative mortality. In this paper, we describe a percutaneous right heart bypass for temporary postoperative RV support.

We retrospectively examined all patients receiving percutaneous RV mechanical support after LVAD implantation. All patients receiving trans-jugular mechanical right heart bypass during or after LVAD implantation in our tertiary medical centre between November 2014 and December 2019 were examined retrospectively. The venous draining cannula was placed in the femoral vein; the pulmonary cannula was placed in the pulmonary artery using fluoroscopy.

In total, 14 patients received RV support using the trans-jugular technique. Mean age was 48.4 ± 14.9 years. Nine patients were treated with mechanical circulatory support before LVAD implantation. Biventricular support was done in 7 patients. Navitoclax in vitro All patients were treated with an HVAD. Mean postoperative intensive care unit stay was 46.3 ± 32.4 days. Mean right heart bypass support time was 10.6 ± 4.3 days. Twelve patients (86%) could be bridged to RV recovery, RV assist device implantation or heart transplantation.

Percutaneous RV mechanical support is feasible, safe and shows acceptable outcome. Early implantation of RV support may contribute to successful outcome after LVAD implantation.
Percutaneous RV mechanical support is feasible, safe and shows acceptable outcome. Early implantation of RV support may contribute to successful outcome after LVAD implantation.Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by severe, progressive muscle wasting. Cardiomyopathy has emerged as a leading cause of death in patients with DMD. The mechanisms contributing to DMD cardiac disease remain under investigation and specific therapies available are lacking. Our prior work has shown that DMD-iPSC derived cardiomyocytes (DMD-iCMs) are vulnerable to oxidative stress injury and chronic exposure to DMD secreted exosomes impaired the cell's ability to protect against stress. In this study, we sought to examine a mechanism by which DMD cardiac exosomes impair cellular response through altering important stress-responsive genes in the recipient cells. Here, we report that DMD-iCMs secrete exosomes containing altered microRNA (miR) profiles in comparison to healthy controls. In particular, miR-339-5p was upregulated in DMD-iCMs, DMD exosomes, and in mdx mouse cardiac tissue. Restoring dystrophin in DMD-iCMs improved the cellular response to stress and was associated with downregulation of miR-339-5p, suggesting that it is disease-specific. Knockdown of miR-339-5p was associated with increased expression of MDM2, GSK3A and MAP2K3, which are genes involved in important stress-responsive signaling pathways. Finally, knockdown of miR-339-5p led to mitochondrial protection and a reduction in cell death in DMD-iCMs, indicating miR-339-5p is involved in direct modulation of stress-responsiveness. Together, these findings identify a potential mechanism by which exosomal miR-339-5p may be modulating cell signaling pathways which are important for robust stress responses. Additionally, these exosomal miRs may provide important disease specific targets for future therapeutic advancements for the management and diagnosis of DMD cardiomyopathy.
The factors contributing to long-term remission in axial spondyloarthritis (axSpA) are unclear. We aimed to characterize individuals with axSpA at 5-year follow-up to identify baseline factors associated with remission.

We included all patients from the DESIR cohort (recent onset axSpA) with available Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) at 5-year follow-up. Patients in remission (ASDAS-CRP<1.3) were compared to those with active disease by demographic, clinical, biological and imaging characteristics. A logistic model stratified on tumor necrosis factor inhibitor (TNFi) exposure was used.

Overall, 111/449 (25%) patients were in remission after 5 years. Among those never exposed to TNFi, 31% (77/247) were in remission compared to 17% (34/202) of those exposed to TNFi. Patients in remission after 5-years were more likely to be male, HLA-B27+, have a lower body mass index (BMI), and a higher education level. Baseline factors associated with 5-year remission in patients never exposed to TNFi, included lower BASDAI (adjusted odds ratio [ORa] 0.9, 95% confidence interval [95%CI] 0.8-0.9) and history of peripheral arthritis (ORa 2.1, 95%CI 1.2-5.3). In those exposed to TNFi, remission was associated with higher education level (ORa 2.9, 95%CI 1.6-5.1), lower enthesitis index (ORa 0.8, 95%CI 0.7-0.9), lower BASDAI (ORa 0.9, 95%CI 0.9-0.9), and lower BMI (ORa 0.8, 95%CI 0.7-0.9).

This study highlights the difficulty in achieving 5-year remission in those with recent onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.
This study highlights the difficulty in achieving 5-year remission in those with recent onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.Numerous genome-wide association studies (GWASs) have been conducted for the identification of genetic variants involved with human height. The vast majority of these studies, however, have been conducted in populations of European ancestry. Here, we report the first GWAS of adult height in the Taiwan Biobank using a discovery sample of 14 571 individuals and an independent replication sample of 20 506 individuals. From our analysis we generalize to the Taiwanese population genome-wide significant associations with height and 18 previously identified genes in European and non-Taiwanese East Asian populations. We also identify and replicate, at the genome-wide significance level, associated variants for height in four novel genes at two loci that have not previously been reported RASA2 on chromosome 3 and NABP2, RNF41, and SLC39A5 at 12q13.3 on chromosome 12. RASA2 and RNF41 are strong candidates for having a role in height with copy number and loss of function variants in RASA2 previously found to be associated with short stature disorders, and decreased expression of the RNF41 gene resulting in insulin resistance in skeletal muscle.
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