Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination

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Review: Gastric cancer—Clinical aspects

Gastric cancer (GC) was responsible for over 1 000 000 new cases in 2018 and an estimated 783 000 deaths, making it still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Divergent trends for GC incidence were observed in the USA. Incidence rates, particularly for non‐cardia GC, were stable or increasing among persons aged <50 years. In an analysis of data from a public hospital database in Hong Kong, treatment of Helicobacter pylori infection was associated with a lower risk of GC, particularly in older subjects who received treatment ≥10 years before. Based on the results of a 16‐year endoscopy‐based follow‐up eradication trial, patients with incomplete‐type intestinal metaplasia (IM) should receive endoscopic surveillance upon H. pylori eradication therapy. Updated guidelines on the endoscopic surveillance of preneoplastic conditions of the stomach (MAPS II) have been published. In the RAINFALL trial, the addition of ramucirumab to a backbone chemotherapy as a first‐line regimen failed to improve overall survival (OS) of patients with metastatic disease. Also, pembrolizumab did not prolong OS when compared to paclitaxel in the second‐line treatment of patients with advanced GC or esophagogastric junction (EGJ) cancer. Trifluridine/tipiracil improved OS by 2.1 months in the third or further treatment line of patients with advanced GC. In a systematic investigation conducted on Chinese patients with GC, CLDN18‐ARHGAP26/6 fusion was associated with signet‐ring cell content and was prognostic for a worse outcome and predictive for no benefit from oxaliplatin/fluoropyrimidine‐based chemotherapy. Organoid cultures represent an appealing model that may be applied for therapy response testing in the near future.     

C-Terminal Fragment of Agrin (CAF): A Novel Marker for Progression of Kidney Disease in Type 2 Diabetics

Background

Diabetes is the leading cause of CKD in the developed world. C-terminal fragment of agrin (CAF) is a novel kidney function and injury biomarker. We investigated whether serum CAF predicts progression of kidney disease in type 2 diabetics.

Methods

Serum CAF levels were measured in 71 elderly patients with diabetic nephropathy using a newly developed commercial ELISA kit (Neurotune®). Estimated glomerular filtration rate (eGFR) and proteinuria in spot urine were assessed at baseline and after 12 months follow up. The presence of end stage renal disease (ESRD) was evaluated after 24 months follow-up. Correlation and logistic regression analyses were carried out to explore the associations of serum CAF levels with GFR, proteinuria, GFR loss and incident ESRD. Renal handling of CAF was tested in neurotrypsin-deficient mice injected with recombinant CAF.

Results

We found a strong association of serum CAF levels with eGFR and a direct association with proteinuria both at baseline (r = 0.698, p<0.001 and r = 0. 287, p = 0.02) as well as after 12 months follow-up (r = 0.677, p<0.001 and r = 0.449, p<0.001), respectively. Furthermore, in multivariate analysis, serum CAF levels predicted eGFR decline at 12 months follow-up after adjusting for known risk factors (eGFR, baseline proteinuria) [OR (95%CI) = 4.2 (1.2–14.5), p = 0.024]. In mice, injected CAF was detected in endocytic vesicles of the proximal tubule.

Conclusion

Serum CAF levels reflect renal function and are highly associated with eGFR and proteinuria at several time points. Serum CAF was able to predict subsequent loss of renal function irrespective of baseline proteinuria in diabetic nephropathy. CAF is likely removed from circulation by glomerular filtration and subsequent endocytosis in the proximal tubule. These findings may open new possibilities for clinical trial design, since serum CAF levels may be used as a selection tool to monitor kidney function in high-risk patients with diabetic nephropathy.     

Review: Prevention and management of gastric cancer

Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case‐control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5‐year survival. In an updated meta‐analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first‐degree relatives of GC patients as well. A meta‐analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy.     

Discussion on Spatial and Time Averaging Restrictions Within the Electromagnetic Exposure Safety Framework in the Frequency Range Above 6 GHz for Pulsed and Localized Exposures

Both the current and newly proposed safety guidelines for local human exposure to millimeter-wave frequencies aim at restricting the maximum local temperature increase in the skin to prevent tissue damage. In this study, we show that the application of the current and proposed limits for pulsed fields can lead to a temperature increase of 10°C for short pulses and frequencies between 6 and 30 GHz. We also show that the proposed averaging area of 4 cm², that is greatly reduced compared with the current limits, does not prevent high-temperature increases in the case of narrow beams. A realistic Gaussian beam profile with a 1 mm radius can result in a temperature increase about 10 times higher than the 0.4°C increase the same averaged power density would produce for a plane wave. In the case of pulsed narrow beams, the values for the time and spatial-averaged power density allowed by the proposed new guidelines could result in extreme temperature increases. Bioelectromagnetics. 2020;41:164–168. © 2019 Bioelectromagnetics Society.