Notes

Whole-genome sequencing associated with follicular thyroid carcinomas expose repeated strains in microRNA digesting subunit DGCR8.
Osteosarcoma (OSA) arising from the digits, metatarsal and metacarpal bones is rare and may carry a better prognosis compared with other locations. The aim of this study was to retrospectively evaluate the biological behaviour, the progression free interval (PFI), the survival time (ST) and evaluate the effect of adjuvant chemotherapy for OSA affecting these bones. Medical records from two academic institutions were reviewed and 15 cases were included. Descriptive statistics were used for signalment and history. For estimation of median PFI and median ST, the Kaplan-Meier method was utilized. The prognostic effect of chemotherapy, lymphocyte and monocyte count was investigated. Log-rank analysis was used to compare PFI and ST between groups. The overall median PFI and median ST were 377 and 687 days, respectively. No significant differences were noted for any of the variables evaluated. In this study, dogs affected by OSA of digits, metacarpal and metatarsal bones appear to have a longer ST compared with dogs with OSA of other appendicular locations. A study with a larger number of patients is needed to confirm these results and investigate the potential benefit of adjuvant chemotherapy.Publication bias is a well-known threat to the validity of meta-analyses and, more broadly, the reproducibility of scientific findings. When policies and recommendations are predicated on an incomplete evidence base, it undermines the goals of evidence-based decision-making. Great strides have been made in the last 50 years to understand and address this problem, including calls for mandatory trial registration and the development of statistical methods to detect and correct for publication bias. We offer an historical account of seminal contributions by the evidence synthesis community, with an emphasis on the parallel development of graph-based and selection model approaches. We also draw attention to current innovations and opportunities for future methodological work.Late-stage functionalization (LSF) aids drug discovery efforts by introducing functional groups onto C-H bonds on pre-existing skeletons. We adopted the LSF strategy to synthesize analogues of the abundantly available triterpenoid, glycyrrhetinic acid (GA), by introducing aryl groups in the A-ring, expanding the A-ring and selectively activating one methyl group of the gem-dimethyl groups. Intriguingly, two compounds were found to preferentially accumulate in the mitochondrial compartment of MDA-MB-231 breast cancer cells, to cause depolarization of mitochondrial membrane potential and to induce antiproliferative and anti-invasive effects through enhanced mitochondrial superoxide production with parallel depletion of GSH levels. Furthermore, intraperitoneal administration of these two compounds, in comparison with GA, greatly regressed breast tumor growth and metastasis in a SCID mouse model bearing labeled MDA-MB-231 cells.Submerged macrophytes are of key importance for the structure and functioning of shallow lakes and can be decisive for maintaining them in a clear water state. The ongoing climate change affects the macrophytes through changes in temperature and precipitation, causing variations in nutrient load, water level and light availability. To investigate how these factors jointly determine macrophyte dominance and growth, we conducted a highly standardized pan-European experiment involving the installation of mesocosms in lakes. The experimental design consisted of mesotrophic and eutrophic nutrient conditions at 1 m (shallow) and 2 m (deep) depth along a latitudinal temperature gradient with average water temperatures ranging from 14.9 to 23.9°C (Sweden to Greece) and a natural drop in water levels in the warmest countries (Greece and Turkey). We determined percent plant volume inhabited (PVI) of submerged macrophytes on a monthly basis for 5 months and dry weight at the end of the experiment. Over the temperature gradient, PVI was highest in the shallow mesotrophic mesocosms followed by intermediate levels in the shallow eutrophic and deep mesotrophic mesocosms, and lowest levels in the deep eutrophic mesocosms. We identified three pathways along which water temperature likely affected PVI, exhibiting (a) a direct positive effect if light was not limiting; (b) an indirect positive effect due to an evaporation-driven water level reduction, causing a nonlinear increase in mean available light; and (c) an indirect negative effect through algal growth and, thus, high light attenuation under eutrophic conditions. We conclude that high temperatures combined with a temperature-mediated water level decrease can counterbalance the negative effects of eutrophic conditions on macrophytes by enhancing the light availability. While a water level reduction can promote macrophyte dominance, an extreme reduction will likely decrease macrophyte biomass and, consequently, their capacity to function as a carbon store and food source.
Aberrant salience has been considered as a predisposing factor during prodromal phases of psychosis and in ultra high-risk subjects. Most studies investigated the presence of aberrant salience in general population as a measure of vulnerability to psychosis. This study aimed atinvestigating the level of aberrant salience in a sample of Italian high-school students.

Aberrant salience was measured with the Aberrant Salience Inventory (ASI) and its association with measures of general psychopathology (Youth Self Report [YSR]) was tested. A sample of 312 high school students (115 boys, 197 girls; age range 14 to 19) was recruited.

Within the ASI and the YSR, the subscales did associate with each other at medium to large effect size, while the associations of the ASI subscales to the YRS scales had small effect sizes, indicating that the two tools measure different constructs. Latent Class Analysis revealed a distribution of aberrant salience across three classes with the intermediate class corresponding to more than half of the sample (58.3%). The class with the highest endorsement of the ASI items included 101 subjects (32.4%). Greater differences by classes were found in the "increased significance" and the "impending understanding" subscales. Higher aberrant salience was found on the anxious/depressed, the somatic complaints, and the thought problems scales of the YSR.

Aberrant salience represents a common experience in the adolescent population and is associated with various psychopathological disorders, in particular, thought disorder. Aberrant salience might be involved in proneness to psychosis.
Aberrant salience represents a common experience in the adolescent population and is associated with various psychopathological disorders, in particular, thought disorder. Aberrant salience might be involved in proneness to psychosis.
Macrophage polarization affects tumor growth, metabolism, and many other tumor processes. M1 macrophages can promote antitumor immunity response. Signal transducer and activator of transcription 1 (STAT1) is one of the critical transcription factors in this process, which promotes the expression of a series of inflammatory molecules. STAT1 has been reported as a potential target of reactive oxygen species (ROS)-induced glutathionylation, while the glutathionylation of STAT1 in macrophages and its underlying regulatory mechanism remains unclear. Glutaredoxin 1 (Grx1) functions as a deglutathionylation enzyme, which regulates the activities of many proteins through reversing glutathionylation.

GeneChip and RT-qPCR was first applied to test the mRNA level of Grx1 in M1 macrophages. Western blot was then used to evaluate the variations of the Grx1 protein expression in M1 macrophages. Next, immunoprecipitation was used to investigate the glutathionylated STAT1 in both wild-type and Grx1
mouse macrophages. Finally, the induced alterations of STAT1 activity and function by Grx1 in M1 macrophage were examined by western blot and RT-qPCR.

In M1-type macrophages, the levels of Grx1 were elevated. TNG260 Glutathionylation of STAT1 was negatively regulated by Grx1. Furthermore, depletion of Grx1 increased the activity of STAT1, and thereby promoted the mRNA level of C-X-C motif chemokine ligand 9 (CXCL9) during M1-type polarization of macrophages.

Grx1 controlled deglutathionylation of STAT1, which in turn might regulate M1-type polarization of macrophages.
Grx1 controlled deglutathionylation of STAT1, which in turn might regulate M1-type polarization of macrophages.
To present historical and contemporary hypotheses on the pathogenesis of benign prostatic hyperplasia (BPH), and the potential implications for current medical therapies.

The literature on BPH was reviewed. BPH is a prevalent disease with significant health and economic impacts on patients and health organisations across the world, whilst the cause/initiation of the disease process has still not been fully determined.

In BPH, pathways involving androgens, oestrogens, insulin, inflammation, proliferative reawakening, stem cells and telomerase have been hypothesised in the pathogenesis of the disease. A number of pathways first described >40years ago have been first rebuked and then have come back into favour. A system of an inflammatory process within the prostate, which leads to growth factor production, stem cell activation, and cellular proliferation encompassing a number of pathways, is currently in vogue. This review also highlights the physiology of the prostate cell subpopulations and how this may account for the delay/failure in treatment response for certain medical therapies.

BPH is an important disease, and as the pathogenesis is not fully understood it impacts the effectiveness of medical therapies. This impacts patients, with further research potentially highlighting novel therapeutic avenues.
BPH is an important disease, and as the pathogenesis is not fully understood it impacts the effectiveness of medical therapies. This impacts patients, with further research potentially highlighting novel therapeutic avenues.Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotypegenotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross-referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.
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