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This report adds to the genotype-phenotype correlation, highlighting the clinical importance of considering MAP3K1 gene defects as part of the differential diagnosis for complete or partial gonadal dysgenesis especially with multiple affected family members.Science and medicine have become increasingly "human-centric" over the years. A growing shift away from the use of animals in basic research has led to the development of sophisticated in vitro models of various tissues utilizing human-derived cells to study physiology and disease. The human cornea has likewise been modeled in vitro using primary cells derived from corneas obtained from cadavers or post-transplantation. learn more By utilizing a cell's intrinsic ability to maintain its tissue phenotype in a pre-designed microenvironment containing the required growth factors, physiological temperature, and humidity, tissue-engineered corneas can be grown and maintained in culture for relatively long periods of time on the scale of weeks to months. Due to its transparency and avascularity, the cornea is an optimal tissue for studies of extracellular matrix and cell-cell interactions, toxicology and permeability of drugs, and underlying mechanisms of scarring and tissue regeneration. This paper describes methods for the cultivation of corneal keratocytes, fibroblasts, epithelial, and endothelial cells for in vitro applications. We also provide detailed, step-by-step protocols for assembling and culturing 3D constructs of the corneal stroma, epithelial- and endothelial-stromal co-cultures and isolation of extracellular vesicles. © 2020 Wiley Periodicals LLC. Basic Protocol 1 Isolating and culturing human corneal keratocytes and fibroblasts Basic Protocol 2 Isolating and culturing human corneal epithelial cells Basic Protocol 3 Isolating and culturing human corneal endothelial cells Basic Protocol 4 3D corneal stromal construct assembly Basic Protocol 5 3D corneal epithelial-stromal construct assembly Basic Protocol 6 3D corneal endothelial-stromal construct assembly Basic Protocol 7 Isolating extracellular vesicles from corneal cell conditioned medium Support Protocol Cryopreserving human corneal fibroblasts, corneal epithelial cells, and corneal endothelial cells.Invited for this month's cover is the group of Prof. Pavel Hobza, Czech Academy of Sciences, Prague. The cover picture shows a powerful automated quantum mechanics based SQM/COSMO approach to protein-ligand scoring. It comprises thorough preparation of ligand structures, extensive generation of binding complexes, fast geometry relaxation and reliable affinity prediction. Read the full text of the Minireview at 10.1002/cplu.202000120.

Lung adenocarcinoma (ADC) is the main cause of death related to lung cancer. The aim of this study was to identify poor prognostic factors for overall survival (OS) in patients with stage IV lung ADC in real-world clinical practice.

Patients were selected from the Surveillance Epidemiology and End Results (SEER) database. Chi-square bivariate analysis was used for the association of binary qualitative variables. A multivariate Cox regression analysis was performed to determine the impact of these prognostic factors on OS.

A total of 46 030 patients were included (51.3% men, mean age 67.03 ± 11.6), of whom 41.3% presented with metastases in bone, 28.9% in brain, 17.1% in liver and 31.8% in lung. Patients with liver metastases presented with two or more metastatic sites more frequently than patients without liver metastases (P < 0.001). Male sex (HR 0.78, 95% CI 0.76-0.80), age ≥ 65 years (HR 1.37, 95% CI 1.33-1.40), lack of family support (HR 0.80, 95% CI 0.78-0.81) and presence of liver (HR 1.45, 95%reatments including immunotherapy.

SIGNIFICANT FINDINGS OF THE STUDY Regression analysis identified poor prognostic factors for overall survival. Factors were male sex, age ≥ 65 years, lack of family support and presence of liver, bone and brain metastases. Patients with liver metastasis showed the highest HR (HR = 1.45 95% CI 1.40-1.50). This study included the highest number of adenocarcinoma patients analyzed so far (N = 46 030). What this study adds The presence of liver metastases should be considered as a stratification factor for future studies evaluating new cancer treatments including immunotherapy.Reliably determining the physical properties of ice (e.g., crystal structure, adhesion strength, interfacial state, and molecular orientation) has proven to be both challenging and highly dependent on experiment-specific conditions, including surface roughness, ice formation, water purity, and measurement method. Here, non-destructive measurements of single-layer graphene (SLG) interfaced with bulk ice are used to determine temperature-dependent, ice-induced strain and estimate ice-created strain elastic density in SLG. The use of SLG enables the precise study of interfacial strain by monitoring the 2D Raman mode. Upon ice formation, a clear, ≈2 cm-1 decrease in the 2D mode frequency is observed, which is ascribed to a 0.012% biaxial tensile shear strain at the ice-SLG interface. From this shear strain value, the ice-created SLG elastic strain energy density is estimated to be 2.4 μJ m-2 . In addition to these Raman strain measurements, intentionally ionized water is used to show that water-mediated charging of the SLG surface manifests itself in a distinctly different manner than ice-induced strain. Finally, the localized nature of the Raman probe is used to map SLG regions with and without ice, suggesting that this method cannot only determine ice-induced interfacial strain, but also correlate ice adhesion properties with surface roughness and topology.

Image registration and delineation of organs at risk (OARs) are key components of three-dimensional conformal (3DCRT) and intensity-modulated radiotherapy (IMRT) treatment planning. This study hypothesized that image registration and OAR delineation are often performed by medical physicists and/or dosimetrists and are not routinely reviewed by treating physicians.

An anonymous, internet-based survey of medical physicists and dosimetrists was distributed via the MEDPHYS and MEDDOS listserv groups. Participants were asked to characterize standard practices for completion and review of OAR contouring, target volume contouring, and image registration at their institution along with their personal training in these areas and level of comfort performing these tasks. Likert-type scales are reported as Median [Interquartile range] with scores ranging from 1="Extremely/All of the time" to 5="Not at all/Never."

Two hundred and ninety-seven individuals responded to the survey. Overall, respondents indicated significantly less frequent physician review (3 [2-4] vs 2 [1-3]), and less confidence in the thoroughness of physician review (3 [2-4] vs 2 [1-3], P<0.

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