Dynamic and subtype-specific interactions between tumour burden and prognosis in breast cancer.

We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR-/HER2-tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR-/HER2+ tumours among 131,178 patients with stage I-III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and < 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumours showed a persistent increase in mortality risk with an increase in tumour diameter, while the effect was modest in HER2+ tumours. Conversely, an increased number of metastatic nodes was accompanied by a persistently increased risk in HR-/HER2+ tumours, while the effect was minimal for HR-/HER2- tumours with > 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.

Distinctive patterns of pulmonary function change according to baseline lung volume and diffusing capacity.

SETTING: Multicentre retrospective study in South Korea.OBJECTIVE: To longitudinally evaluate changes in lung volume and diffusing capacity for carbon monoxide (DLCO) with forced expiratory volume in 1 sec (FEV1).DESIGN: A total of 155 patients with chronic obstructive pulmonary disease (COPD), whose pulmonary function parameters were measured annually for 5 years, were selected from a prospective cohort in South Korea. A random coefficients model was used to estimate mean annual FEV1, lung volume parameter and DLCO change rates.RESULTS: Patients were classified into four groups based on baseline DLCO and residual volume/total lung capacity (RV/TLC) measurements. The annual FEV1 decline rate was greater in patients with low DLCO than in those with normal DLCO, with the greatest decline occurring in patients with low DLCO and normal RV/TLC. RV and RV/TLC declined in patients with high RV/TLC, whereas these increased in patients with normal RV/TLC. DLCO decreased longitudinally in all four groups, with the greatest decline occurring in patients with normal DLCO and normal RV/TLC.CONCLUSIONS: Different subgroups of patients with COPD exhibited distinctive pulmonary function change patterns. Baseline DLCO and RV/TLC may be used as physiological markers to predict long-term changes in pulmonary function.

Effects of hydrochlorothiazide on drainage volume and seroma formation in deep inferior epigastric perforator flap breast reconstruction: Randomized controlled trial.

BACKGROUND: Seroma is a recognized complication encountered at the reconstructed breast and donor site after abdominal-based breast reconstruction. Seroma is caused by lymphatic channel disruption and the formation of a large space between the deep fascia during flap elevation. Surgical techniques to preserve the lymphatics and secure the closure of the donor site can reduce seroma formation. This study investigated the safety and effectiveness of the diuretic hydrochlorothiazide at reducing interstitial fluid accumulation and seroma formation during deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: Sixty patients with breast cancer who underwent skin- or nipple-sparing mastectomy and DIEP flap reconstruction were enrolled between August 2016 and June 2017. The patients were randomly assigned to receive either 25 mg per day of hydrochlorothiazide from the second to the twentieth day after surgery (treatment) or no diuretic (control). The clinicopathological characteristics, drainage time, and drainage volume were statistically compared between the two groups. RESULTS: The average total drainage volume at the donor site was 291 mL in the treatment group and 434 mL in the control group (p = 0.003). The differences in body mass index and flap weight between the two groups were not statistically significant (p = 0.879 and p = 0.963, respectively). No hypotension or electrolyte imbalance was noted during the follow-up. CONCLUSIONS: Intake of 25 mg per day of hydrochlorothiazide tablets effectively reduced the total abdominal drainage volume and removal time of indwelling drains. However, the adverse effects should be further investigated in a large population and multiracial cohort before using hydrochlorothiazide for seroma prevention.

Neutrophil-lymphocyte ratio predicts response to chemotherapy in triple-negative breast cancer.

Background: The neutrophil-lymphocyte ratio (nlr) has been reported to correlate with patient outcome in several cancers, including breast cancer. We evaluated whether the nlr can be a predictive factor for pathologic complete response (pcr) after neoadjuvant chemotherapy (nac) in patients with triple-negative breast cancer (tnbc). Methods: We analyzed the correlation between response to nac and various factors, including the nlr, in 87 patients with tnbc who underwent nac. In addition, we analyzed the association between the nlr and recurrence-free survival (rfs) in patients with tnbc. Results: Of the 87 patients, 25 (28.7%) achieved a pcr. A high Ki-67 index and a low nlr were significantly associated with pcr. The pcr rate was higher in patients having a high Ki-67 index (≥15%) than in those having a low Ki-67 index (35.7% vs. 0%, p = 0.002) and higher in patients having a low nlr (≤1.7) than in those having a high nlr (42.1% vs. 18.4%, p = 0.018). In multiple logistic analysis, a low nlr remained the only predictive factor for pcr (odds ratio: 4.274; p = 0.008). In the survival analysis, the rfs was significantly higher in the low nlr group than in the high nlr group (5-year rfs rate: 83.7% vs. 66.9%; log-rank p = 0.016). Conclusions: Our findings that the nlr is a predictor of pcr to nac and also a prognosticator of recurrence suggest an association between response to chemotherapy and inflammation in patients with tnbc. The pretreatment nlr can be a useful predictive and prognostic marker in patients with tnbc scheduled for nac.

Associations between fruits, vegetables, vitamin A, ß-carotene and flavonol dietary intake, and age-related macular degeneration in elderly women in Korea: the Fifth Korea National Health and Nutrition Examination Survey.

BACKGROUND/OBJECTIVES: Age-related macular degeneration (AMD) is one of the principal causes of blindness. This study investigated the association between diet and the prevalence of AMD in elderly Korean women. SUBJECTS/METHODS: Study subjects were women aged ⩾65 years (n=1008) from the Korea National Health and Nutrition Examination Survey (2010-2012). The presence of early- and late-onset AMD was determined on the basis of a fundus photograph from a health examination survey. Food intake was estimated using 24 h recall. RESULTS: The prevalence of AMD was 18.8% in elderly women in Korea. Multiple logistic regression analysis showed a significant negative association between vegetable intake and AMD (odds ratio (OR) 0.44, 95% confidence interval (CI) 0.25, 0.77, P for trend=0.002) after adjusting for age, body mass index, postmenopausal period, duration of hormone replacement therapy, residential area, education level, family income, smoking status, alcohol consumption, dietary supplement use and total energy intake. After adjusting for potential confounders, the ORs between extreme quartiles were 0.55 (95% CI 0.29, 1.05, P for trend=0.070) for fruit and vegetable intake, 0.38 (95% CI 0.21, 0.68, P for trend=0.001) for vitamin A, 0.36 (95% CI 0.19, 0.67, P for trend<0.001) for ß-carotene and 0.45 (95% CI 0.25, 0.82, P for trend=0.008) for flavonols. CONCLUSIONS: These results suggest that higher consumption of fruits and vegetables containing antioxidant nutrients and phytochemicals may provide some protection against AMD.

A study on setting of the fatigue limit of temporary dental implants.

A temporary dental implant is a medical device which is temporarily used to support a prosthesis such as an artificial tooth used for restoring patient's masticatory function during implant treatment. It is implanted in the oral cavity to substitute for the role of tooth. Due to the aging and westernization of current Korean society, the number of tooth extraction and implantation procedures is increasing, leading to an increase in the use and development of temporary dental implants. Because an implant performs a masticatory function in place of a tooth, a dynamic load is repeatedly put on the implant. Thus, the fatigue of implants is reported to be the most common causes of the fracture thereof. According to the investigation and analysis of the current domestic and international standards, the standard for fatigue of implant fixtures is not separately specified. Although a test method for measuring the fatigue is suggested in an ISO standard, it is a standard for permanent dental implants. Most of the test standards for Korean manufacturers and importers apply 250 N or more based on the guidance for the safety and performance evaluation of dental implants. Therefore, this study is intended to figure out the fatigue standard which can be applied to temporary dental implants when measuring the fatigue according to the test method suggested in the permanent dental implant standard. The results determined that suitable fatigue standards of temporary dental implants should be provided by each manufacturer rather than applying 250 N. This study will be useful for the establishment of the fatigue standards and fatigue test methods of the manufacturers and importers of temporary dental implants.

Anti-inflammatory effects of simvastatin in nonsteroidal anti-inflammatory drugs-induced small bowel injury.

Small bowel injury can occur as the result of a multifaceted process that includes increased acid secretion, generation of reactive oxygen species, and cyclooxygenase inhibition. However, no effective medication for small bowel ulceration is available. Simvastatin is an important lipid-lowering agent with anti-inflammatory activity. We aimed to validate the effects of simvastatin in vitro and in vivo. In presence or absence of simvastatin, IEC-6 small bowel cell line with 50 ng/ml of tumor nectosis factor α (TNF-α) was investigated by western blotting, qRT-PCR, and DCF-DA assay. In addition, an in vivo study of nonsteroidal anti-inflammatory drugs (NSAID)-induced small bowel inflammation was performed using 7-week-old specific-pathogen-free (SPF) male C57BL/6 mice. Simvastatin treatment reduced the mRNA levels of interleukin-6 and interleukin-8 by approximately 50% in TNF-α-stimulated IEC-6 cells. Treatment with a combination of 50 ng/ml TNF-α and µM simvastatin decreased activation of Akt, IκBα, and nuclear factor-κB p65 level in IEC-6 cells. By DCF-DA staining, intracellular reactive oxygen species (ROS) production was increased in TNF-α-stimulated cells, and treatment with simvastatin decreased the level of ROS. In addition, in vivo mouse model of NSAID-induced small bowel inflammation, the administration of simvastatin reduced the number of small bowel hemorrhagic lesions and the level of ROS production as determined by gross examination and 8-hydroxydeoxyguanosine immunohistochemistry of small bowel tissue, respectively. Simvastatin reduced NSAID-induced injuries by both suppression of ROS generation and modulation of inflammatory cytokines in vitro and in vivo. Therefore, simvastatin, an HMG-CoA reductase inhibitor, has potential as a prophylactic and therapeutic agent for NSAID-induced small bowel injury.

Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior.

Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1f/f; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.

Oncogenic BRAF fusions in mucosal melanomas activate the MAPK pathway and are sensitive to MEK/PI3K inhibition or MEK/CDK4/6 inhibition.

Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated. We biologically characterized a novel ZNF767-BRAF fusion found in a vemurafenib-refractory respiratory tract PMM, from which cell line harboring ZNF767-BRAF fusion were established for further molecular analyses. In an independent data set, NFIC-BRAF fusion was identified in an oral PMM case and TMEM178B-BRAF fusion and DGKI-BRAF fusion were identified in two malignant melanomas with a low mutational burden (number of mutation per megabase, 0.8 and 4, respectively). Subsequent analyses revealed that the ZNF767-BRAF fusion protein promotes RAF dimerization and activation of the MAPK pathway. We next tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in combination. Trametinib effectively inhibited tumor cell growth in vitro, but the combination of trametinib and BKM120 or LEE011 yielded more than additive anti-tumor effects both in vitro and in vivo in a melanoma cells harboring the BRAF fusion. In conclusion, BRAF fusions define a new molecular subset of PMM that can be targeted therapeutically by the combination of a MEK inhibitor with PI3K or cyclin-dependent kinase 4/6 inhibitors.

Whole-breast US following mammography and breast MRI in newly diagnosed breast cancer patients: can it be more than just a guidance tool for biopsy?

AIM: To evaluate the role of ultrasound (US) following magnetic resonance imaging (MRI) and mammography in patients with newly diagnosed breast cancers by assessing the additional cancer detection rate of US. MATERIAL AND METHODS: Two hundred and twenty-five women who had undergone 225 MRI examinations followed by US were included. An US-detected additional cancer was defined as a lesion detected using breast US that had not been detected by MRI, and which was shown to be malignant at histopathology. The rate of additional cancer detection, incidence of additional malignancies, positive predictive value (PPV), and false-positive (FP) rate were analysed. Factors associated with an increase in the additional cancer detection rate were analysed. RESULTS: The additional cancer detection rate was 0% (0/225) for the ipsilateral breast and 0.9% (2/225) for the contralateral breast, and the PPVs were 0% (0/5) and 100% (2/2), respectively. The overall TP:FP ratio was 0.4 (2:5). The additional cancer detection rate was higher for cases with moderate and severe background parenchymal enhancement than cases with minimal and mild background parenchymal enhancement (p=0.003). The additional cancer detection rate for cases with moderate and severe background parenchymal enhancement was 5.7% (2/35) for the contralateral breast (p=0.003). CONCLUSION: Preoperative breast US following MRI and mammography can help clinicians screen for contralateral cancers with an additional detection rate of 0.9%. Moreover, whole-breast US might be a useful contralateral screening modality in cases with moderate or marked parenchymal enhancement on breast MRI.

Association between basal-like phenotype and BRCA1/2 germline mutations in Korean breast cancer patients.

INTRODUCTION: BRCA mutation testing allows index patients and their families to be provided with appropriate cancer risk-reduction strategies. Because of the low prevalence of BRCA mutations in unselected breast cancer patients and the high cost of genetic testing, it is important to identify the subset of women who are likely to carry BRCA mutations. In the present study, we examined the association between BRCA1/2 germline mutations and the immunohistochemical features of breast cancer. METHODS: In a retrospective review of 498 breast cancer patients who had undergone BRCA testing at Seoul National University Bundang Hospital between July 2003 and September 2012, we gathered immunohistochemical information on estrogen receptor (er), progesterone receptor (pr), her2 (human epidermal growth factor receptor 2), cytokeratin 5/6, egfr (epidermal growth factor receptor), and p53 status. RESULTS: Among the 411 patients eligible for the study, 50 (12.2%) had germline mutations in BRCA1 or BRCA2. Of the 93 patients with triple-negative breast cancer (tnbc), 25 with BRCA1/2 mutations were identified (BRCA1, 20.4%; BRCA2, 6.5%). On univariate analysis, er, pr, cytokeratin 5/6, egfr, and tnbc were found to be related to BRCA1 mutations, but on multivariate analysis, only tnbc was significantly associated with BRCA1 mutations. Among patients with early-onset breast cancer or with a family history of breast or ovarian cancer, BRCA1 mutations were significantly more prevalent in the tnbc group than in the non-tnbc group. CONCLUSIONS: In the present study, tnbc was the only independent predictor of BRCA1 mutation in patients at high risk of hereditary breast and ovarian cancers. Other histologic features of basal-like breast cancer did not improve the estimate of BRCA1 mutation risk.

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

BACKGROUND: We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. PATIENTS AND METHODS: From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. RESULTS: The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. CONCLUSIONS: We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process.

Inhibition of TGFBIp expression reduces lymphangiogenesis and tumor metastasis.

Transforming growth factor-ß-induced protein (TGFBIp) is an extracellular matrix protein that has a role in a wide range of pathological conditions. However, the role of TGFBIp signaling in lymphangiogenesis is poorly understood. The purpose of this study was therefore to analyze the effects of TGFBIp on lymphangiogenesis and determine whether TGFBIp-related lymphangiogenesis is important for the metastasis of tumor cells. TGFBIp increased adhesion, migration, and morphologic differentiation of human lymphatic endothelial cells (LECs), consistent with an increase in lymphatic vessel sprouting in a three-dimensional lymphatic ring assay. TGFBIp also induced phosphorylation of intracellular signaling molecules SRC, FAK, AKT, JNK and ERK. TGFBIp-induced lymphatic vessel sprouting was inhibited by addition of anti-integrin ß3 antibody and pharmacologic inhibitors of FAK, AKT, JNK or ERK. TGFBIp increased both CCL21 expression in LECs, a chemokine that actively recruits tumor cells expressing the cognate chemokine receptors to lymphatic vessels and LEC permeability by inducing the dissociation of VE-cadherin junctions between LECs via the activation of SRC signaling. In vivo, inhibition of TGFBIp expression in SW620 cancer cells dramatically reduced tumor lymphangiogenesis and metastasis. Collectively, our findings demonstrate that TGFBIp is a lymphangiogenic factor contributing to tumor dissemination and represents a potential target to inhibit metastasis.

Overexpression of PI3K-p110α in the progression of uterine cervical neoplasia and its correlation with pAkt and DJ-1.

OBJECTIVE: To investigate the expression of PI3K-p110α, pAkt, PTEN, the signaling molecules from PI3K/Akt signaling pathway, DJ-1, an oncoprotein and HSP90a, a molecular chaperone, and their correlation in uterine cervical neoplasia, in order to elucidate their role in cervical carcinogenesis. MATERIALS AND METHODS: Using immunohistochemistry, the authors analyzed the expression of PI3K-p110α, pAkt, PTEN, DJ-1 and HSP90α, and their correlation in ten normal tissues, cervical intraepithelial neoplasia (CIN) including 30 CIN1 and 31 CIN3, and 33 cases of invasive squamous cell carcinoma (SCC). RESULTS: The expression of all proteins significantly increased in CIN3 compared to CIN1, and only the expression of PI3K-p110α significantly increased in invasive SCC compared to CIN3. There was a significant positive correlation between the expression of PI3K-p110α and DJ-1, as well as PI3K-p110α and pAkt in CIN3 and invasive SCC. CONCLUSION: Overexpression of PI3K-p110α is associated with progression of uterine cervical neoplasia, and the expression of pAkt and DJ-1 is positively correlated with PI3K-p110α expression in this process.

Expression of autotaxin and lysophosphatidic acid receptors 1 and 3 in the developing rat lung and in response to hyperoxia.

We sought to evaluate lysophosphatidic acid (LPA) signaling improvement in lung development by assessing the expression of autotaxin and LPA receptor 1 and 3 (LPAR1 and LPAR3) in the neonatal rat lung during normal perinatal development and in response to hyperoxia. In the developmental study, rats were sacrificed on days 17, 19, and 21 of gestation; on postnatal days 1, 4, and 7; and at adulthood (postnatal 9 weeks). In the hyperoxia study, 42 postnatal 4-day-old rat pups were divided into seven groups and exposed to either 85% O2 for 24, 72, or 120 h or room air for 0, 24, 72, or 120 h. The rats were then euthanized after 0, 24, 72, and 120 h of exposure. Immunofluorescence demonstrated that autotaxin, LPAR1, and LPAR3 proteins were broadly colocalized in airway epithelial cells, but mainly distributed in vascular endothelial and mesenchymal cells during the first postnatal week. The expression of autotaxin, LPAR1, and LPAR3 were increased during late gestation and then decreased after birth. Autotaxin expression and enzymatic activity were significantly increased at 72 and 120 h after exposure to hyperoxia. LPAR1 and LPAR3 expression was also increased after 120 h of hyperoxic exposure. These findings suggest that LPA-associated molecules were upregulated at birth and induced by hyperoxia in the developing rat lung. Therefore, the LPA pathway may be involved in normal lung development, including vascular development, as well as wound-healing processes of injured neonatal lung tissue, which is at risk of neonatal hyperoxic acute lung injury.

Adding MRI to ultrasound and ultrasound-guided fine-needle aspiration reduces the false-negative rate of axillary lymph node metastasis diagnosis in breast cancer patients.

AIM: To evaluate whether adding magnetic resonance imaging (MRI) to ultrasound (US) and US-guided fine-needle aspiration (US-FNA) can reduce the false-negative rate (FNR) in the diagnosis of axillary lymph node metastasis (ALNM) in breast cancer patients, and to assess false-negative diagnosis of N2 and N3 disease when adding MRI to US and US-FNA. MATERIALS AND METHODS: From March 2012 to February 2013, 497 breast cancer patients were included in the study. ALNM was evaluated according to US and US-FNA prior to MRI. Second-look US was performed when MRI showed positive findings of ALNM. If second-look US also revealed a positive finding, US-FNA was performed. Diagnostic performance, including FNR, was calculated for US and US-FNA with and without MRI. The negative predictive value (NPV) of N2 and N3 disease was evaluated in negative cases based on US and US-FNA with MRI. RESULTS: A total of 159 of 497 (32.0%) patients were found to have ALNM. Among them, 92 patients were diagnosed with metastasis on US and US-FNA. When adding MRI to US and US-FNA, an additional six patients were diagnosed with metastasis. The FNR of diagnosis of ALNM was improved by the addition of MRI (42.1% versus 38.4%, p = 0.0143). The NPV for N2 and N3 disease was 98% (391/399) based on US and US-FNA with MRI. CONCLUSION: Adding MRI to US and US-FNA could reduce the FNR of the diagnosis of ALNM. Furthermore, US and US-FNA with MRI may exclude 98% of N2 and N3 disease.

Three-dimensional efficient dispersive alternating-direction-implicit finite-difference time-domain algorithm using a quadratic complex rational function.

Efficient unconditionally stable FDTD method is developed for the electromagnetic analysis of dispersive media. Toward this purpose, a quadratic complex rational function (QCRF) dispersion model is applied to the alternating-direction-implicit finite-difference time-domain (ADI-FDTD) method. The 3-D update equations of QCRF-ADI-FDTD are derived using Maxwell's curl equations and the constitutive relation. The periodic boundary condition of QCRF-ADI-FDTD is discussed in detail. A 3-D numerical example shows that the time-step size can be increased by the proposed QCRF-ADI-FDTD beyond the Courant-Friedrich-Levy (CFL) number, without numerical instability. It is observed that, for refined computational cells, the computational time of QCRF-ADI-FDTD is reduced to 28.08 % of QCRF-FDTD, while the L2 relative error norm of a field distribution is 6.92 %.

Synthesis of orotidine by intramolecular nucleosidation.

An intramolecular nucleosidation approach provides easy access to orotidine in high yields. Notably, orotate itself is used as a leaving group at the anomeric position. This method has the potential for facile access to derivatives of orotidine of therapeutic interest, with implications for prebiotic formation of nucleosides.

Comparison of Cancer Yields and Diagnostic Performance of Screening Mammography vs. Supplemental Screening Ultrasound in 4394 Women with Average Risk for Breast Cancer.

PURPOSE: The effectiveness of supplemental screening ultrasound (US) was investigated in women ≥ 40 years at average risk for breast cancer regardless of breast parenchymal density. A total of 4394 women at average risk and having previously undergone screening mammography were classified as the mammography group.  MATERIALS AND METHODS: Of 4394 women, 2005 underwent screening US after a final assessment of category 1 or 2 on screening mammography, and were categorized as the US group. Category 0, 4, and 5 on mammography and 3, 4, and 5 on US were defined as positive. The cancer yields per 1000 women and diagnostic performance of two groups were compared. RESULTS: The total cancer and invasive cancer yields for the mammography group were 3.0 (95 % confidence interval 1.6, 5.1) and 2.0 (95 % CI, 0.9, 3.9) per 1000 women, higher than the US values of 2.0 (0.5, 5.1) and 1.0 (0.1, 3.6), not statistically significant. The specificity, accuracy, and positive predictive value (PPV) for mammography were 88.90 % (87.93, 89.81), 88.85 % (87.88, 89.76), and 2.61 % (1.39, 4.41), significantly higher than the US values of 69.07 % (66.99, 71.09), 69.13 % (67.05, 71.15), and 0.64 % (0.18, 1.64). The short-term follow-up rate of mammography was 5.51 % (4.85, 6.22), significantly lower than the rate of 26.58 (24.66, 28.58) for US.  CONCLUSION: Supplemental screening US in mammographically negative breasts can find additional carcinomas in women at average risk but is not as effective as screening mammography because of the lower cancer yield, invasive cancer yield, specificity, accuracy, PPV and a high short-term follow-up rate.