Abstract Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of chronic liver disease worldwide. Its prevalence has increased to more than 30% of adults in developed ...countries and its incidence is still rising. The majority of patients with NAFLD have simple steatosis but in up to one third of patients, NAFLD progresses to its more severe form nonalcoholic steatohepatitis (NASH). NASH is characterized by liver inflammation and injury thereby determining the risk to develop liver fibrosis and cancer. NAFLD is considered the hepatic manifestation of the metabolic syndrome. However, the liver is not only a passive target but affects the pathogenesis of the metabolic syndrome and its complications. Conversely, pathophysiological changes in other organs such as in the adipose tissue, the intestinal barrier or the immune system have been identified as triggers and promoters of NAFLD progression. This article details the pathogenesis of NAFLD along with the current state of its diagnosis and treatment.
In the past the main focus for improvements in power electronic modules was on chip technology. Therefore, looking at the cross section structure of modern modules, only small improvements have been ...made in recent decades.
The reason for this is that the design and joining technology satisfied the market requirements. Furthermore the power electronic market segment is smaller than the one for microelectronic devices. Therefore it had to use their existing production facilities, e.g. bond wire machines.
In the future this will change because of the following reasons:
1) Power electronic performance depends by a high ratio on package technology
2) The automotive industry has high requirements regarding cost efficiency, reliability and compactness. Furthermore they have big lever for innovations to make a product fit this requirement. Power electronic devices are used in (hybrid) electric vehicles ((H)EVs).
3) Dies in future will require new package technologies, especially when a wide band gap (WBG) material like silicon carbide (SiC) or gallium nitride (GaN) is used.
Therefore there is a need for a paradigm shift in package technology to make use of a junction temperature above 200°C possible while reliability and cost performance have increased. This article will give an overview of the current available technologies and present Fuji’s new package solution ideas.
•Power Electronic Module performance is highly dependent on chip, as well as package technology.•A paradigm shift in package technology is expected, due to high requirements in automotive apps.•A further paradigm shift is expected by new chip materials exceeding temperature limits of Silicon.
Ectomycorrhizal fungi are major ecological players in temperate forests, but they are rarely used in measures of forest condition because large‐scale, high‐resolution, standardized and replicated ...belowground data are scarce. We carried out an analysis of ectomycorrhizas at 22 intensively monitored long‐term oak plots, across nine European countries, covering complex natural and anthropogenic environmental gradients. We found that at large scales, mycorrhizal richness and evenness declined with decreasing soil pH and root density, and with increasing atmospheric nitrogen deposition. Shifts in mycorrhizas with different functional traits were detected; mycorrhizas with structures specialized for long‐distance transport related differently to most environmental variables than those without. The dominant oak‐specialist Lactarius quietus, with limited soil exploration abilities, responds positively to increasing nitrogen inputs and decreasing pH. In contrast, Tricholoma, Cortinarius and Piloderma species, with medium‐distance soil exploration abilities, show a consistently negative response. We also determined nitrogen critical loads for moderate (9.5–13.5 kg N/ha/year) and drastic (17 kg N/ha/year) changes in belowground mycorrhizal root communities in temperate oak forests. Overall, we generated the first baseline data for ectomycorrhizal fungi in the oak forests sampled, identified nitrogen pollution as one of their major drivers at large scales and revealed fungi that individually and/or in combination with others can be used as belowground indicators of environmental characteristics.
Frequent water table measurements are crucial for sustainable groundwater management in arid regions. Such monitoring is more important in areas that are already facing an acute problem with ...excessive groundwater withdrawal. In the majority of these locations, continuous readings of groundwater levels are lacking. Therefore, an approximate estimate of the rate of increase or decrease in water consumption over time may serve as a proxy for the missing data. This could be achieved by tracking the changes in vegetated areas that generally correlate with changes in the rate of water use. The technique proposed in this paper is based on two remote sensing datasets: Landsat 7 and 8 from 2001 to 2021, and Sentinel 2A from 2015 to 2021, as well as five vegetation indices: Normalized Difference Vegetation Index (NDVI), Renormalized Difference Vegetation Index (RDVI), Soil Adjusted Vegetation Index (SAVI), Enhanced Vegetation Index (EVI), and Transformed Vegetation Index (TVI). The findings have shown that the datasets chosen performed best for small-scale land farms at the research location, which was chosen to be the El-Qaa plain, in the southwestern corner of the Sinai Peninsula in Egypt. Landsat 7 data with a resolution of 30 m revealed a substantial increase in land farms from 2.9 km2 in 2001 to 23.3 km2 in 2021. By using the five indices based on Sentinel 2A data, vegetated areas were categorized as heavy, moderate, or light. In addition, the expansion of each class area from 2015 to 2021 was tracked. Additionally, the NDVI index was modified to better reflect the arid environment (subsequently naming this new index as the Arid Vegetation Index: AVI). Rough scenarios of the increase in water consumption rate at the research site were generated by observing the increase in vegetated areas and collecting rough information from the farmers regarding the crop types.
The importance of remote sensing in solving challenges in rural and undeveloped areas where there is a lack of in situ data or financial resources is undeniable ...
Inhibition of the RAS-RAF-ERK-pathway using sorafenib as a first-line and regorafenib as a second-line treatment approach is the only effective therapeutic strategy for advanced hepatocellular ...carcinoma (HCC). Recent studies suggest that wild-type KRAS and HRAS isoforms could majorly contribute to HCC progression and sorafenib resistance. In contrast, the role of neuroblastoma RAS viral oncogene homolog (NRAS) in HCC remained elusive. In this study, wild-type NRAS was found to be overexpressed in HCC cell lines, preclinical HCC models, and human HCC tissues. Moreover, NRAS overexpression correlated with poor survival and proliferation in vivo. However, si-RNA-pool–mediated NRAS knockdown showed only slight effects on HCC proliferation, clonogenicity, and AKT activity. We determined that KRAS upregulation served as a functional compensatory mechanism in the absence of NRAS, which was overcome by combined inhibition of NRAS and KRAS in HCC cells. Furthermore, NRAS expression was elevated in sorafenib-resistant compared to nonresistant HCC cells, and NRAS knockdown enhanced sorafenib efficacy in resistant cells. In summary, NRAS appears to be a prognostic marker in HCC and contributes to sorafenib resistance. Regarding potential therapeutic strategies, NRAS inhibition in HCC should be combined with KRAS inhibition to prevent KRAS-mediated rescue effects.
To characterize direct-to-consumer (DTC) men's health clinics by reviewing their online content. Increasing numbers of patients are seeking treatment for erectile dysfunction (ED) and hypogonadism ...from DTC “men's health” clinics. Treatments are often used off-label, with lack of transparency of provider credentials and qualifications.
We identified DTC Men's Health Clinics in the United States by internet search by state using the terms, “Men's Health Clinic,” and “Low T Center.” All stand-alone clinics were reviewed.
Two hundred and twenty-three clinics were reviewed, with 147 (65.9%) offered ED treatments and 196 (87.9%) offering testosterone replacement, and 120 (53.8%) offering both ED treatment and testosterone replacement. Of those clinics offering ED treatments, 93 (63.3%) advertised shockwave therapy and 84 (57.1%) PRP therapy. There were 56 (38%) who offered shockwave therapy and PRP. ICI was significantly more likely to be offered if there was a urologist on staff (p <.001).
Clinic providers represented 20 different medical and alternative medicine specialties. Internal medicine was most common (17.4%), followed by family medicine (11.1%). A nonphysician (nurse practitioner or physician assistant) was listed as the primary provider in 10 clinics (4.5%) and 45 clinics (20.1%) did not list their providers. Urologists were listed as the primary provider in 10.3% of clinics. A naturopathic provider was listed as a staff member in 22 (11.6%) of clinics.
There is significant heterogeneity and misinformation available to the public regarding men's health. Familiarity with and insight into practice patterns of “men's health” clinics will help provide informed patient care and counseling.
Positive plant diversity–productivity relationships are known to be driven by complementary resource use via differences in plant functional traits. Moreover, soil properties related to nutrient ...availability were shown to change with plant diversity over time; however, it is not well‐understood whether and how such plant diversity‐dependent soil changes and associated changes in functional traits contribute to positive diversity–productivity relationships in the long run. To test this, we investigated plant communities of different species richness (1, 2, 6, and 9 species) in a 15‐year‐old grassland biodiversity experiment. We determined community biomass production and biodiversity effects (net biodiversity NEs, complementarity CEs, and selection effects SEs), as well as community means of plant functional traits and soil properties. First, we tested how these variables changed along the plant diversity gradient and were related to each other. Then, we tested for direct and indirect effects of plant and soil variables influencing community biomass production and biodiversity effects. Community biomass production, NEs, CEs, SEs, plant height, root length density (RLD), and all soil property variables changed with plant diversity and the presence of the dominant grass species Arrhenatherum elatius (increase except for soil pH, which decreased). Plant height and RLD for plant functional traits, and soil pH and organic carbon concentration for soil properties, were the variables with the strongest influence on biomass production and biodiversity effects. Our results suggest that plant species richness and the presence of the dominant species, A. elatius, cause soil organic carbon to increase and soil pH to decrease over time, which increases nutrient availability favoring species with tall growth and dense root systems, resulting in higher biomass production in species‐rich communities. Here, we present an additional process that contributes to the strengthening positive diversity–productivity relationship, which may play a role alongside the widespread plant functional trait‐based explanation.
We sampled 15‐year‐old plant communities of a biodiversity experiment (Jena Experiment) and tested whether and how changes in plant functional traits and soil properties over time and along the plant species richness gradient contribute to variation in biomass production and biodiversity effects (i.e., net biodiversity, selection, and complementarity effects). We found that changes in soil properties influence plant functional traits, which can explain positive biodiversity effects. Therefore, soil properties and their association with plant functional traits, i.e., plant–soil interactions, should be considered to fully understand the mechanisms driving positive plant diversity–productivity relationships.
Immune-mediated inflammatory diseases (IMIDs) of the joints, gut and skin are treated with inhibitors of inflammatory cytokines. These cytokines are involved in the pathogenesis of coronavirus ...disease 2019 (COVID-19). Investigating anti-SARS-CoV-2 antibody responses in IMIDs we observe a reduced incidence of SARS-CoV-2 seroconversion in IMID patients treated with cytokine inhibitors compared to patients receiving no such inhibitors and two healthy control populations, despite similar social exposure. Hence, cytokine inhibitors seem to at least partially protect from SARS-CoV-2 infection.
PDF
