Spatial Control of Oxygen Vacancy Concentration in Monoclinic WO3 Photoanodes for Enhanced Solar Water Splitting

Oxygen vacancies (OVs) are a mixed blessing for the photoelectrochemical (PEC) water oxidation performance of monoclinic tungsten trioxide (m-WO3) photoanodes. Although it is widely accepted that a moderate concentration of OVs is beneficial for the PEC performance of the m-WO3 photoanodes, this argument assumes a uniform distribution of OVs throughout the m-WO3 crystal. In this case, only the overall concentration of OVs needs to be considered. However, the spatial non-uniformity of OV defects in m-WO3 photoanodes has not been thoroughly examined. In this study, by employing a m-WO3 nanorod array as a model photoanode, the aim is to show that a higher OV concentration near the surface of m-WO3 compared to that in the bulk is advantageous for the PEC performances of this material. In addition, a laser-assisted defect control (LADC) process is employed to manipulate the spatial distribution of OVs in the m-WO3 photoanodes to achieve enhanced PEC performances. Moreover, a one-step laser deposition process is introduced to obtain an ultrathin FeNi oxygen evolution catalyst overlayer on the defect-controlled m-WO3 photoanodes, further improving PEC performance, photostability, and Faradaic efficiency

Contributions and Limitations of National Cervical Cancer Screening Program in Korea: A Retrospective Observational Study

Summary: Purpose: The purpose of this study was to evaluate the contributions and limitations of the cervical cancer screening test with accuracy in Korea. Methods: This was a retrospective observational study. The study population consisted of all participants who underwent cervical cancer screening test from 2009 to 2014. The data were obtained from National Health Information Database (NHID) which represents medical use records of most Koreans. As the indices for contributions and limitations of the screening test, crude detection rate, incidence rate of interval cancer, sensitivity, specificity, and positive predictive value were used. Results: The crude detection rate of screening test per 100,000 participants increased from 100.7 in 2009 to 102.1 in 2014. The incidence rate of interval cancer per 100,000 negatives decreased from 13.0 in 2009 to 10.2 in 2014. The sensitivities of screening test were 88.7% in 2009 and 91.2% in 2014, and the specificities were 98.5% in 2009 and 97.7% in 2014. The positive predictive value of screening decreased from 6.2% in 2009 to 4.3% in 2014. Conclusion: The Korean national cervical cancer screening program has improved in accuracy and has contributed to detection of early stage of cervical cancer over the years. Along with efforts to promote participation in cancer screening programs, quality control over the screening program should be enhanced. Keywords: carcinoma in situ, early detection of cancer, Papanicolaou test, sensitivity and specificity, uterine cervical neoplasm

Clinicopathological Factors Associated with Oncotype DX Risk Group in Patients with ER+/HER2- Breast Cancer

Oncotype DX (ODX), a 21-gene assay, predicts the recurrence risk in early breast cancer; however, it has high costs and long testing times. We aimed to identify clinicopathological factors that can predict the ODX risk group and serve as alternatives to the ODX test. This retrospective study included 547 estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and lymph node-negative breast cancer patients who underwent ODX testing. Based on the recurrence scores, three ODX risk categories (low: 0–15, intermediate: 16–25, and high: 26–100) were established in patients aged ≤50 years (n = 379), whereas two ODX risk categories (low: 0–25 and high: 26–100) were established in patients aged >50 years (n = 168). Factors selected for analysis included body mass index, menopausal status, type of surgery, and pathological and immunohistochemical features. The ODX risk groups showed significant association with histologic grade (p = 0.0002), progesterone receptor expression (p p p = 0.023) in patients aged ≤50 years. In patients aged >50 years, tumor size (p = 0.022), Ki-67 (p = 0.001), and p53 expression (p = 0.001) were significantly associated with the risk group. Certain clinicopathological factors can predict the ODX risk group and enable decision-making on adjuvant chemotherapy; these factors differ according to age

Additional file 1: Figure S1. of Novel c-Met inhibitor suppresses the growth of c-Met-addicted gastric cancer cells

Inhibition Curve. The inhibition percentage was measured in c-Met enzyme assay. The detailed assay procedures are described in Methods. Figure S2. Phosphorylation of Akt and Erk is downregulated by c-Met inhibitors only in c-Met overexpressed cells. SNU-638 (A), SNU-620 (B), SNU-1 (C), or MKN-1 (D) cells were treated with KRC-00509 or crizotinib in dose dependent manner for 3 hr. Cell lysates were prepared for immunoblot with phospho antibodies of c-Met, Akt, and Erk. Tubulin band shows equal loading. Figure S3. Total tyrosine phosphorylations were reduced by c-Met inhibitors in c-Met overexpressed cells. Hs746T (A), or AGS (B) were treated with c-Met inhibitors or crizotinib in dose dependent manner for 3 hr. Cell lysates were prepared for immunoblot with phospho tyrosine antibody. (PPTX 6747 kb

Response Rate and Safety of a Neoadjuvant Pertuzumab, Atezolizumab, Docetaxel, and Trastuzumab Regimen for Patients With ERBB2-Positive Stage II/III Breast Cancer: The Neo-PATH Phase 2 Nonrandomized Clinical Trial

IMPORTANCE Addition of immune checkpoint inhibitors to anti-ERBB2 treatment has shown synergistic efficacy in preclinical studies and is thus worth investigating as a neoadjuvant treatment to maximize efficacy and to minimize toxic effects. OBJECTIVE To determine if neoadjuvant atezolizumab, docetaxel, trastuzumab, and pertuzumab therapy for ERBB2-positive early breast cancer warrants continuation to the next phase. DESIGN, SETTING, AND PARTICIPANTS This nonrandomized, open label, multicenter, phase 2 trial was conducted by the Korean Cancer Study Group and enrolled patients across 6 institutions in Korea from May 2019 to May 2020. Eligible patients were diagnosed with ERBB2-positive breast cancer (primary tumor size >2 cm or pathologically confirmed lymph node-positive cancer, without distant metastases) with a clinical stage of II or III. INTERVENTIONS Patients received 6 cycles of neoadjuvant pertuzumab (840 mg at first cycle, 420 mg during subsequent cycles), atezolizumab (1200 mg), docetaxel (75 mg/m(2)), and trastuzumab (600 mg via subcutaneous injection) every 3 weeks, followed by surgery. Patients with pathologic complete response (pCR) received 12 cycles of adjuvant atezolizumab, trastuzumab, and pertuzumab every 3 weeks after surgery. Patients without pCR were treated with 14 cycles of atezolizumab, 1200 mg, plus trastuzumab emtansine, 3.6 mg/kg, every 3 weeks. MAIN OUTCOMES AND MEASURES The primary end point was pCR rate, which was defined as the absence of invasive cancer cells in the primary tumor and regional lymph nodes (ypT0/isN0). Secondary end points included clinical objective response rate, 3-year event-free survival rate according to pCR achievement, disease-free survival, overall survival, toxic effects, and quality-of-life outcomes. RESULTS A total of 67 women (median [range] age, 52 [33-74] years) were enrolled. Hormone receptor expression was positive in 32 (48%) patients. Curative surgery was performed in 65 patients because 2 patients showed disease progression during neoadjuvant treatment and their tumors became unresectable. The overall pCR rate was 61% (41 of 67 patients). The pCR rate was higher in hormone receptor-negative disease vs hormone receptor-positive disease (27 of 35 [77%] patients vs 14 of 32 [44%] patients) and in programmed cell death 1-positive expression vs programmed cell death 1-negative expression (13 of 13 [100%] patients vs 28 of 53 [53%] patients). Grade 3 and 4 neutropenia and febrile neutropenia occurred in 8 (12%) patients and 5 (8%) patients, respectively. Grade 3 and 4 immune-related adverse events occurred in only 4 patients (grade 3 skin rash, encephalitis, hepatitis, and fever). No treatment-related death occurred during the neoadjuvant phase. CONCLUSIONS AND RELEVANCE In this nonrandomized clinical trial, treatment with the neoadjuvant atezolizumab, docetaxel, trastuzumab, and pertuzumab regimen in patients with stage II or III ERBB2-positive breast cancer appears to have had an acceptable pCR rate and modest toxic effects. Further investigation of this immunotherapy combination in ERBB2-positive early breast cancer is warranted.N

The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory

MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression in many tissues. Although a number of brain-enriched miRNAs have been identified, only a few specific miRNAs have been revealed as critical regulators of synaptic plasticity, learning, and memory. miR-9-5p/3p are brain-enriched miRNAs known to regulate development and their changes have been implicated in several neurological disorders, yet their role in mature neurons in mice is largely unknown. Here, we report that inhibition of miR-9-3p, but not miR-9-5p, impaired hippocampal long-term potentiation (LTP) without affecting basal synaptic transmission. Moreover, inhibition of miR-9-3p in the hippocampus resulted in learning and memory deficits. Furthermore, miR-9-3p inhibition increased the expression of the LTP-related genes Dmd and SAP97, the expression levels of which are negatively correlated with LTP. These results suggest that miR-9-3p-mediated gene regulation plays important roles in synaptic plasticity and hippocampus-dependent memory,close0