Impact of health insurance coverage forHelicobacter pylorigastritis on the trends in eradication therapy in Japan: retrospective observational study and simulation study based on real-world data

Objectives: To explore the prevalence of Helicobacter pylori infection in Japan and the trends of its eradication therapy before and after the changes of the insurance coverage policy, first started in 2000, and expanded to cover H. pylori-positive gastritis in 2013. The impacts that the changes brought were estimated. Methods: In this retrospective observational study and simulation study based on health insurance claims data, product sales data and relevant studies, individuals who received triple therapy (amoxicillin, clarithromycin, proton-pump inhibitors or potassium-competitive acid blockers) were defined as the first-time patients for H. pylori eradication in two Japanese health insurance claims databases (from approximately 1.6 million and 10.5 million individuals). Each sales data of eradication packages and examination kits were used to estimate the number of H. pylori-eradicated individuals nationwide. The prevalence of H. pylori infection, including the future rate, was predicted using previous studies and the estimated population trend by a national institute. Cases completed prior to the policy change on insurance coverage were simulated to estimate what would have happened had there been no change in the policy. Results: The numbers of patients first received eradication therapy were 81 119 and 170 993 from two databases. The nationwide estimated number of patients successfully eradicated was approximately 650 000 per year between 2001 and 2012, whereas it rapidly rose to 1 380-000 per year in 2013. The estimated prevalence of infection in 2050 is 5%, this rate was estimated to be 28% and 22% if the policy changes had not occurred in 2000 and 2013, respectively. Conclusions: The impact of policy changes for H. pylori eradication therapy on the prevalence of infection was shown. The results suggest that insurance coverage expansion may also reduce the prevalence in other countries with a high prevalence of H. pylori infection if the reinfection is low

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis

Suppression of Sproutys Has a Therapeutic Effect for a Mouse Model of Ischemia by Enhancing Angiogenesis

Sprouty proteins (Sproutys) inhibit receptor tyrosine kinase signaling and control various aspects of branching morphogenesis. In this study, we examined the physiological function of Sproutys in angiogenesis, using gene targeting and short-hairpin RNA (shRNA) knockdown strategies. Sprouty2 and Sprouty4 double knockout (KO) (DKO) mice were embryonic-lethal around E12.5 due to cardiovascular defects. The number of peripheral blood vessels, but not that of lymphatic vessels, was increased in Sprouty4 KO mice compared with wild-type (WT) mice. Sprouty4 KO mice were more resistant to hind limb ischemia and soft tissue ischemia than WT mice were, because Sprouty4 deficiency causes accelerated neovascularization. Moreover, suppression of Sprouty2 and Sprouty4 expression in vivo by shRNA targeting accelerated angiogenesis and has a therapeutic effect in a mouse model of hind limb ischemia. These data suggest that Sproutys are physiologically important negative regulators of angiogenesis in vivo and novel therapeutic targets for treating peripheral ischemic diseases

Effect of crystallographic orientation on tensile fractures of (100) and (110) silicon microstructures fabricated from silicon-on-insulator wafers

This Letter investigates the effect of crystallographic orientation on tensile fractures of silicon microstructures. Specimens 5 μm wide and 5 μm thick were fabricated on (100) and (110) wafers with 〈100〉, 〈110〉, and 〈111〉 tensile axes. To explore the effects of different surface orientations and morphologies, these specimens were patterned from (100) and (110) silicon-on-insulator (SOI) wafers using the Bosch process under identical fabrication conditions, while other specimens were fabricated from (110) wafers under different conditions. Tensile tests of specimens prepared under the identical fabrication conditions showed that (100) specimens had lower strength than (110) specimens along the 〈100〉 and 〈110〉 axes; the average strength decreased from 3.62 to 3.14 GPa for 〈110〉. This decrease in strength is related to differences in damage that ultimately causes fractures. While (110) specimens fractured due to fabrication damage at top corners, fractures of (100) specimens were due to pit-like defects on bottom surfaces. Since these defects were introduced during SOI bonding processes, the fractures of (100) specimens were dominated by intrinsic SOI defects rather than damage introduced during specimen fabrication processes. To realise higher-strength structures on SOI wafers, both the damage caused during fabrication and the intrinsic defects need to be controlled

Analytical investigation of the feasibility of sacrificial microchannel sealing for Chip-Scale Atomic Magnetometers

An alkali metal vapor cell is a crucial component of the highly sensitive Chip Scale Atomic Magnetometers (CSAMs) that are increasingly deployed in a variety of electronic devices. Herein, we propose a novel microfabrication technique utilizing an array of microchannels at a bonded interface, to enable gas feedthrough for evacuation of unwanted gases from a vapor cell and subsequent introduction of an inert gas, followed by permanent sealing of the microchannels by reflow of a glass frit. The characteristics of glass frit reflow are analyzed to investigate the feasibility of using microchannels formed either on a silicon substrate, or embedded in a glass frit layer, with four different cross-sectional shapes considered. Prior to modeling the microchannels for simulation, the minimum cross-sectional size of a microchannel that fulfills gas feedthrough requirements was calculated and a value of 10 μm was determined based on a flow conductance model. The sealing of the microchannels was simulated using the finite element method (FEM) and the results revealed that flow resistance is a crucial design factor. Thus, embedded microchannel designs were more suitable for the proposed sealing technique than microchannel designs fabricated in silicon

Mixing speed-controlled gold nanoparticle synthesis with pulsed mixing microfluidic system

Gold nanoparticles with diameters of a few tens of nanometer and a narrow size distribution were synthesized using a pulsed mixing method with a microfluidic system which consists of a Y-shaped mixing microchannel and two piezoelectric valveless micropumps. This mixing method enables control of the mixing speed of gold salts and reducing agent by changing the switching frequency of the micropumps, which was our focus to improve the particle size distribution, which is an essential parameter in gold nanoparticle synthesis. In the proposed method, the mixing time was inversely proportional to the switching frequency and the minimum mixing time was 95 ms at a switching frequency of 200 Hz. During synthesis experiments, the mean diameter of the synthesized gold nanoparticles was found to increase, and the coefficient of variation of particle size was found to decrease with decreasing mixing time. We successfully improved the coefficient of variation to less than 10% for a mean diameter of around 40 nm