Search

A simplified filterless frequency octupling scheme by connecting an intensity modulator (IM) with a dual-parallel Mach–Zehnder (DPMZM) in series is proposed in this paper. The LO signal is distributed into two parts, and one part is used to drive the IM and the other part is applied to drive the DPMZM’s upper sub-modulator, both at the peak point. The lower sub-modulator is only driven by dc bias, and the parent modulator works at null point. By properly adjusting dc bias of the lower sub-modulator, only ±4th-order optical sidebands dominate at the output of the DPMZM. The approach is verified by experiments, and 32-GHz and 40-GHz millimetre waves (mm-waves) are generated using 4-GHz and 5-GHz LO signals, respectively. We acquire a 15-dB electrical spurious suppression ratio (ESSR) and a relatively good phase noise of the signal. Compared with other schemes, the scheme is simple in configuration because only an IM and a DPMZM are needed. What’s more, the scheme is tunable in frequency as no filter is used. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer, which is highly aggressive and incurable. Here, we proposed an ultrasound activatable bromodomain-containing protein 4 (BRD4) proteolysis targeting chimera (PROTAC) release strategy for the first time for precisely controlled protein degradation in preclinical TNBC model. Through combination of PROTAC and ultrasound-targeted microbubble destruction (UTMD) technology, the present strategy also aims to concurrently solve the major limitations of poor loading capacity of microbubbles and undesirable targeting and membrane permeability of PROTAC. PROTAC (ARV-825)-encapsulated microbubbles, ARV-MBs, were developed for the efficacious treatment of TNBC in vitro and in vivo. The microbubbles we synthesized showed ultrasound-responsive drug release ability, which could effectively promote the penetration of PROTAC into tumor site and tumor cell. Under ultrasound, ARV-MBs could play an effective antitumor effect by potentiating the ubiquitination and degradation of BRD4 in tumor. The current study may provide a new idea for promoting clinical translation of drug-loaded microbubbles and PROTAC, and offer a new efficacious therapeutic modality for TNBC., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Hongye He et al.)

Background: People who undergo sphincter-preserving surgery have high rates of anorectal functional disturbances, known as low anterior resection syndrome (LARS). LARS negatively affects patients' quality of life (QoL) and increases their need for self-management behaviors. Therefore, approaches to enhance self-management behavior and QoL are vital., Objective: This study aims to assess the effectiveness of a remote digital management intervention designed to enhance the QoL and self-management behavior of patients with LARS., Methods: From July 2022 to May 2023, we conducted a single-blinded randomized controlled trial and recruited 120 patients with LARS in a tertiary hospital in Hefei, China. All patients were randomly assigned to the intervention group (using the "e-bowel safety" applet and monthly motivational interviewing) or the control group (usual care and an information booklet). Our team provided a 3-month intervention and followed up with all patients for an additional 3 months. The primary outcome was patient QoL measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. The secondary outcomes were evaluated using the Bowel Symptoms Self-Management Behaviors Questionnaire, LARS score, and Perceived Social Support Scale. Data collection occurred at study enrollment, the end of the 3-month intervention, and the 3-month follow-up. Generalized estimating equations were used to analyze changes in all outcome variables., Results: In the end, 111 patients completed the study. In the intervention group, 5 patients withdrew; 4 patients withdrew in the control group. Patients in the intervention group had significantly larger improvements in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 total score (mean difference 11.51; 95% CI 10.68-12.35; Cohen d=1.73) and Bowel Symptoms Self-Management Behaviors Questionnaire total score (mean difference 8.80; 95% CI 8.28-9.32; Cohen d=1.94) than those in the control group. This improvement effect remained stable at 3-month follow-up (mean difference 14.47; 95% CI 13.65-15.30; Cohen d=1.58 and mean difference 8.85; 95% CI 8.25-9.42; Cohen d=2.23). The LARS score total score had significantly larger decreases after intervention (mean difference -3.28; 95% CI -4.03 to -2.54; Cohen d=-0.39) and at 3-month follow-up (mean difference -6.69; 95% CI -7.45 to -5.93; Cohen d=-0.69). The Perceived Social Support Scale total score had significantly larger improvements after intervention (mean difference 0.47; 95% CI 0.22-0.71; Cohen d=1.81)., Conclusions: Our preliminary findings suggest that the mobile health-based remote interaction management intervention significantly enhanced the self-management behaviors and QoL of patients with LARS, and the effect was sustained. Mobile health-based remote interventions become an effective method to improve health outcomes for many patients with LARS., Trial Registration: Chinese Clinical Trial Registry ChiCTR2200061317; https://tinyurl.com/tmmvpq3., (©Peng Zhou, Hui Li, Xueying Pang, Ting Wang, Yan Wang, Hongye He, Dongmei Zhuang, Furong Zhu, Rui Zhu, Shaohua Hu. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 13.08.2024.)

Background: Whether tumor mutation burden (TMB) correlated with improved survival outcomes or promotion of immunotherapies remained controversy in various malignancies. We aimed to explore the prognostic value of TMB and the relationship between TMB and immune infiltration in human epidermal growth factor receptor 2 -positive ( HER2 +) breast cancer (BC)., Methods: We downloaded somatic mutation data and clinical information for 216 HER2 + BC patients from the The Cancer Genome Atlas (TCGA) and cBioPortal databases. Patients were divided into high- and low-TMB groups through TMB calculation. Cox regression analysis was used to establish an immune- and mutant-related risk model based on 5-hub genes. The relationship between 5-hub genes mutants and the level of immune infiltration, as well as the relationship between the risk model and the immune microenvironment were analyzed by "TIMER" database., Results: TMB was negatively correlated with overall survival (OS) and disease-free survival (DFS), and high TMB may inhibit immune infiltration in HER2 + BC. Furthermore, risk score classified effectively patients into low- and high-risk groups in training and validation cohorts. The infiltration of CD4 + T cells and NK cells and the levels of immune checkpoint pathway genes were lower in the high-risk group, which indicated a poor prognosis., Conclusions: Higher TMB correlated with poor survival outcomes and might inhibit the immune infiltrates in HER2 + BC. The 5-hub TMB-related signature conferred lower immune cells infiltration which deserved further validation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-21-594/coif). All authors report that this work was supported by the Natural Science Foundation of the Hunan Province of China (2020JJ4828) and the Science and Technology Innovation Program of Hunan Province (2021SK2026). The authors have no other conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)