A genome-wide association study of contralateral breast cancer in the Women's Environmental Cancer and Radiation Epidemiology Study.

BACKGROUND: Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy. FINDINGS: We performed a genome-wide association analysis in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age < 55 years including 1161 with CBC who served as cases and 1668 with unilateral breast cancer (UBC) who served as controls. We observed two loci (rs59657211, 9q32, SLC31A2/FAM225A and rs3815096, 6p22.1, TRIM31) with suggestive genome-wide significant associations (P < 1 × 10-6). We also found an increased risk of CBC associated with a breast cancer-specific polygenic risk score (PRS) comprised of 239 known breast cancer susceptibility single nucleotide polymorphisms (SNPs) (rate ratio per 1-SD change: 1.25; 95% confidence interval 1.14-1.36, P < 0.0001). The protective effect of chemotherapy on CBC risk was statistically significant only among patients with an elevated PRS (Pheterogeneity = 0.04). The AUC that included the PRS and known breast cancer risk factors was significantly elevated. CONCLUSIONS: The present GWAS identified two previously unreported loci with suggestive genome-wide significance. We also confirm that an elevated risk of CBC is associated with a comprehensive breast cancer susceptibility PRS that is independent of known breast cancer risk factors. These findings advance our understanding of genetic risk factors involved in CBC etiology.

Agreement of medical record abstraction and self-report of breast cancer treatment with an extended recall window.

BACKGROUND: Medical record abstraction (MRA) and self-report questionnaires are two methods frequently used to ascertain cancer treatment information. Prior studies have shown excellent agreement between MRA and self-report, but it is unknown how a recall window longer than 3 years may affect this agreement. METHODS: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multicenter, population-based case-control study of controls with unilateral breast cancer individually matched to cases with contralateral breast cancer. Participants who were diagnosed with a first primary breast cancer from 1985 to 2008 before the age of 55 years completed a questionnaire that included questions on treatment. First primary breast cancer treatment information was abstracted from the medical record from radiation oncology clinic notes for radiation treatment and from systemic adjuvant treatment reports for hormone therapy and chemotherapy. Agreement between MRA and self-reported treatment was assessed with the kappa statistic and corresponding 95% confidence intervals (CIs). RESULTS: A total of 2808 participants with MRA and self-reported chemotherapy treatment information, 2733 participants with MRA and self-reported hormone therapy information, and 2905 participants with MRA and self-reported radiation treatment information were identified. The median recall window was 12.5 years (range, 2.8-22.2 years). MRA and self-reported treatment agreement was excellent across treatment modalities (kappachemo, 98.5; 95% CI, 97.9-99.2; kappahorm, 87.7; 95% CI, 85.9-89.5; kapparad, 97.9; 95% CI, 97.0-98.7). There was no heterogeneity across recall windows (pchemo = .46; phorm = .40; prad = .61). CONCLUSIONS: Agreement between self-reported and MRA primary breast cancer treatment modality information was excellent for young women diagnosed with breast cancer and was maintained even among women whose recall window was more than 20 years after diagnosis.

Long noncoding RNA PM maintains cerebellar synaptic integrity and Cbln1 activation via Pax6/Mll1-mediated H3K4me3.

Recent studies have shown that long noncoding RNAs (lncRNAs) are critical regulators in the central nervous system (CNS). However, their roles in the cerebellum are currently unclear. In this work, we identified the isoform 204 of lncRNA Gm2694 (designated as lncRNA-Promoting Methylation (lncRNA-PM)) is highly expressed in the cerebellum and derived from the antisense strand of the upstream region of Cerebellin-1 (Cbln1), a well-known critical cerebellar synaptic organizer. LncRNA-PM exhibits similar spatiotemporal expression pattern as Cbln1 in the postnatal mouse cerebellum and activates the transcription of Cbln1 through Pax6/Mll1-mediated H3K4me3. In mouse cerebellum, lncRNA-PM, Pax6/Mll1, and H3K4me3 are all associated with the regulatory regions of Cbln1. Knockdown of lncRNA-PM in cerebellum causes deficiencies in Cbln1 expression, cerebellar synaptic integrity, and motor function. Together, our work reveals an lncRNA-mediated transcriptional activation of Cbln1 through Pax6-Mll1-H3K4me3 and provides novel insights of the essential roles of lncRNA in the cerebellum.

Topiramate use in a pediatric patient with comorbid bipolar disorder and trichotillomania: A 3-year follow-up.

Trichotillomania (TTM) is an intractable and chronic mental disorder that causes significant distress or functional impairments in various life domains. Most individuals with trichotillomania have other comorbid diagnoses. Bipolar disorder (BD) is one of the most common comorbid conditions. Up to date, no FDA-approved drugs for TTM are available, not to mention children and adolescent patients with TTM and BD. Here, we present a case of an 8-year-old child with a long history of episodic TTM and bipolar disorder who was effectively treated with topiramate in a 3-year follow-up.

Gut Microbe-Metabolite Profiles Are Associated with Microbial Pathways of Longevity in Women: A Cross-Sectional Study Conducted in China.

INTRODUCTION: Recent research on the gut deepens people's understanding of the role of gut microbe-metabolites in longevity. However, most of the longevity population is female, and the gut microbe-metabolites associated with longevity in women remain unknown. Here, we hypothesize that the gut microbe-metabolite levels differed between the longevity women (LW, age ≥90) and the elderly women (EW, 60 < age <90). METHODS: We performed a cross-sectional study of 22 women in Guangxi longevity areas. 16S rRNA full-length sequencing, bioinformatic analysis, and nuclear magnetic resonance hydrogen spectra were determined to analyze the gut microbiota, microbial pathways, and fecal metabolites. We evaluated significant differences and relationships in gut microbe-metabolites and microbial pathways using the Mann-Whitney test and Spearman correlation, respectively. RESULTS: The EW experienced gut dysbiosis characterized by a higher Firmicutes/Bacteroidetes (F/B) value. The LW showed a higher abundance of Bacteroides and Alistipes, which might support health maintenance. Moreover, LW enriched alanine, aspartate, and glutamate metabolism, histidine metabolism, and pyruvate metabolism, leading to major changes in histidine, fumaric acid, acetate, valine, and aspartate. Interestingly, the most valuable metabolic pathway based on differential fecal metabolites confirmed the KEGG microbial pathway "alanine, aspartate, and glutamate metabolism" enriched in LW. Impressively, Bacteroides and Alistipes were positively correlated with alanine, aspartate, and glutamate metabolism, thus improving the level of aspartate, which could be a particular pathway related to longevity. CONCLUSION: The enriched gut genus and microbial pathways in LW showed a significant correlation, which might mediate the production of metabolites related to longevity.

The impact of comorbid premenstrual syndrome or premenstrual dysphoric disorder on the clinical characteristics of bipolar disorder among Han Chinese women.

Bipolar disorder (BD) is commonly comorbid with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). However, little is known about their relationship. This study aimed to assess the impact of comorbid PMS or PMDD on the clinical characteristics of BD. A cross-sectional study was conducted on 262 women with BD. PMS and PMDD were screened with the Premenstrual Symptoms Screening Tool (PSST). Symptomatic features were assessed with Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS), and atypical features by the depressive episode section of SCID-I/P. The rates of PMS and PMDD among BD were 57.6% and 20.6% according to PSST. No significant difference in the rates of PMS and PMDD was found between BD I, BD II, and BD-NOS. Compared to BD patients without PMS or PMDD, patients with comorbid BD and PMS or PMDD were younger, more educated, had a higher risk of OCD, had an earlier age of onset, scored higher on HAMD-17 and its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and were more likely to have increased appetite and leaden paralysis. In addition, patients with comorbid BD and PMDD were less likely to experience traumatic life events, more likely to have family history of mental disorders and have inflammatory or autoimmune disease, scored higher on HMAD-17, particularly in its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and sleep disturbance. Compared with BD without PMS or PMDD, BD with PMS or PMDD might be a specific subtype of BD characterized with earlier onset age, heavier genetic load, increased symptom severity, and atypical features.

Association of Breast Cancer Odds with Background Parenchymal Enhancement Quantified Using a Fully Automated Method at MRI: The IMAGINE Study.

Background Background parenchymal enhancement (BPE) at breast MRI has been associated with increased breast cancer risk in several independent studies. However, variability of subjective BPE assessments have precluded its use in clinical practice. Purpose To examine the association between fully objective measures of BPE at MRI and odds of breast cancer. Materials and Methods This prospective case-control study included patients who underwent a bilateral breast MRI examination and were receiving care at one of three centers in the United States from November 2010 to July 2017. Breast volume, fibroglandular tissue (FGT) volume, and BPE were quantified using fully automated software. Fat volume was defined as breast volume minus FGT volume. BPE extent was defined as the proportion of FGT voxels with enhancement of 20% or more. Spearman rank correlation between quantitative BPE extent and Breast Imaging Reporting and Data System (BI-RADS) BPE categories assigned by an experienced board-certified breast radiologist was estimated. With use of multivariable logistic regression, breast cancer case-control status was regressed on tertiles (low, moderate, and high) of BPE, FGT volume, and fat volume, with adjustment for covariates. Results In total, 536 case participants with breast cancer (median age, 48 years [IQR, 43-55 years]) and 940 cancer-free controls (median age, 46 years [IQR, 38-55 years]) were included. BPE extent was positively associated with BI-RADS BPE (rs = 0.54; P < .001). Compared with low BPE extent (range, 2.9%-34.2%), high BPE extent (range, 50.7%-97.3%) was associated with increased odds of breast cancer (odds ratio [OR], 1.74 [95% CI: 1.23, 2.46]; P for trend = .002) in a multivariable model also including FGT volume (OR, 1.39 [95% CI: 0.97, 1.98]) and fat volume (OR, 1.46 [95% CI: 1.04, 2.06]). The association of high BPE extent with increased odds of breast cancer was similar for premenopausal and postmenopausal women (ORs, 1.75 and 1.83, respectively; interaction P = .73). Conclusion Objectively measured BPE at breast MRI is associated with increased breast cancer odds for both premenopausal and postmenopausal women. Clinical trial registration no. NCT02301767 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bokacheva in this issue.

A simplified mid-infrared anti-resonant chalcogenide fiber with fewest resonant peaks.

High-power laser delivery in the mid-infrared via hollow-core fibers is attractive, but it is too difficult to be fabricated using chalcogenide glasses. Here, we designed a mid-infrared hollow-core anti-resonant chalcogenide fiber (HC-ARCF) with a simplified Kagome cladding micro-structure for the first time. Then, the fiber was firstly fabricated through a precision mechanical drilling and pressured fiber drawing method. Ultra-thin walls of 2µm in the fiber lead to the fewest resonance peaks in the 2-5µm among all reported HC-ARCFs. All the fundamental mode, the second-order mode, tube mode and node mode in the fiber were excited and observed at 1550 nm. The power and spectral properties of the core and cladding of HC-ARCF are studied for the first time. The fiber can deliver high-power of 4.84 W without damage with core-coupling, while the threshold of the node in the cladding is only 3.5 W. A broadening of the output spectrum from 1.96 to 2.41µm due to the high nonlinearity at the node was successfully observed under short-pulse laser pumping at 2µm. The potentials of the fiber used for mid-infrared high-power laser delivery via core, or nonlinear laser generation via node, were thus demonstrated.

Nonphthalate Plasticizers in House Dust from Multiple Countries: An Increasing Threat to Humans.

Along with the restrictions of phthalate esters (PAEs), a variety of nonphthalate plasticizers (NPPs) have been increasingly used for industrial needs. Knowledge remains limited on the environmental occurrences, fate, and human exposure risks of many emerging NPPs. In this study, we investigated a suite of 45 NPPs along with the major PAEs in house dust from five regions in the Asia-Pacific region and the United States. The findings clearly demonstrated ubiquitous occurrences of many NPPs in the home environment, particularly acetyl tributyl citrate (ATBC), tricapryl trimellitate (TCTM), trioctyl trimellitate (TOTM), glycerol monooleate (GMO), methyl oleate (MO), and diisobutyl adipate (DiBA). The median total concentrations of NPPs ranged from 17.8 to 252 µg/g in the study regions, while the mean ratios of ΣNPPs to ΣPAEs ranged from 0.19 (Hanoi) to 0.72 (Adelaide). Spatial differences were observed not only for the chemical abundances but also for the composition profiles and the hazard quotient (HQ) prioritization of individual chemicals. Although the current exposure may unlikely cause significant health risks according to the HQ estimation, potential exposure risks cannot be overlooked, due to the lack of appropriate toxic threshold data, the existence of additional exposure pathways, and possible cocktail effects from coexisting NPPs and PAEs.

Sorption of representative organic contaminants on microplastics: Effects of chemical physicochemical properties, particle size, and biofilm presence.

Microplastic pollution has attracted mounting concerns worldwide. Microplastics may concentrate organic and metallic contaminants; thus, affecting their transport, fate and organismal exposure. To better understand organic contaminant-microplastic interactions, our study explored the sorption of selected polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), α-hexabromocyclododecane (α-HBCDD), and organophosphate flame retardants (OPFRs) on high-density polyethylene (HDPE) and polyvinylchloride (PVC) microplastics under saline conditions. Sorption isotherms determined varied between chemicals and between HDPE and PVC microplastics. Log Freundlich sorption coefficients (Log KF) for the targeted chemicals ranged from 2.01 to 5.27 L kg-1 for HDPE, but were significantly lower for PVC, i.e., ranging from Log KF data (2.84 - 8.58 L kg-1). Significant correlations between chemicals' Log KF and Log Kow (octanol-water partition coefficient) indicate that chemical-dependent sorption was largely influenced by their hydrophobicity. Sorption was evaluated using three size classes (< 53, 53 - 300, and 300 - 1000 µm) of lab-fragmented microplastics. Particle size did not significantly affect sorption isotherms, but influenced the time to reach equilibrium and the predicted maximum sorption, likely related to microplastic surface areas. The presence of biofilms on HDPE particles significantly enhanced contaminant sorption capacity, indicating more complex sorption dynamics in the chemical-biofilm-microplastic system. Our findings offer new insights into the chemical-microplastic interactions in marine environment.

Association of contralateral breast cancer risk with mammographic density defined at higher-than-conventional intensity thresholds.

Mammographic dense area (MDA) is an established predictor of future breast cancer risk. Recent studies have found that risk prediction might be improved by redefining MDA in effect at higher-than-conventional intensity thresholds. We assessed whether such higher-intensity MDA measures gave stronger prediction of subsequent contralateral breast cancer (CBC) risk using the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population-based CBC case-control study of ≥1 year survivors of unilateral breast cancer diagnosed between 1990 and 2008. Three measures of MDA for the unaffected contralateral breast were made at the conventional intensity threshold ("Cumulus") and at two sequentially higher-intensity thresholds ("Altocumulus" and "Cirrocumulus") using the CUMULUS software and mammograms taken up to 3 years prior to the first breast cancer diagnosis. The measures were fitted separately and together in multivariable-adjusted logistic regression models of CBC (252 CBC cases and 271 unilateral breast cancer controls). The strongest association with CBC was MDA defined using the highest intensity threshold, Cirrocumulus (odds ratio per adjusted SD [OPERA] 1.40, 95% CI 1.13-1.73); and the weakest association was MDA defined at the conventional threshold, Cumulus (1.32, 95% CI 1.05-1.66). In a model fitting the three measures together, the association of CBC with Cirrocumulus was unchanged (1.40, 95% CI 0.97-2.05), and the lower brightness measures did not contribute to the CBC model fit. These results suggest that MDA defined at a high-intensity threshold is a better predictor of CBC risk and has the potential to improve CBC risk stratification beyond conventional MDA measures.

Single-mode suspended large-core chalcohalide fiber with a low zero-dispersion wavelength for supercontinuum generation.

Chalcogenide glass possesses outstanding advantages, such as supercontinuum generation, but its nonlinear applications were limited by large zero-dispersion wavelength (ZDW). Traditional suspended-core fibers can shift the ZDW to near IR with a tiny core size of less than 5 µm but a large evanescent wave loss exists in these fibers. In this paper, we prepared a novel suspended-core fiber (SCF) based on chalcohalide glasses for the first time via the extrusion method, in which the ZDW of the fundamental mode in the fiber with a core size of larger than 30 µm was successfully shifted to 2.6 µm. We also calculated confinement loss (CL) of propagation modes and fundamental mode energy ratio in the fiber. We found that the minimum CL ratio of the high order modes (LP11) to the CL of the fundamental mode is 124, indicating that the single-mode operation condition is satisfied when the wavelength is more than 4.6 µm. The lowest transmission loss is 1.2 dB/m at 6.5 µm. An ultra-broad supercontinuum spectrum, covering from 1.6 to 12 µm was generated in this suspended-core fiber pumped by a 5 µm femtosecond laser. Such a wide SC in the chalcogenide SCF is due to the large core size. All these results demonstrate the potential to use the large core SCF in the application of a mid-IR laser.

FLOW AND GEOMETRICAL ALTERATIONS IN RETINAL MICROVASCULATURE CORRELATED WITH THE OCCURRENCE OF DIABETIC RETINOPATHY: Evidence from a Longitudinal Study.

PURPOSE: To assess the relationship between flow and geometric parameters in optical coherence tomography angiography images and the risk of incident diabetic retinopathy (DR). METHODS: This prospective, observational cohort study recruited patients with Type 2 diabetes without DR in Guangzhou, China, and followed up annually. A commercially available optical coherence tomography angiography device (DRI OCT Triton; Topcon Inc, Tokyo, Japan) was used to obtain a variety of flow (foveal avascular zone area, vessel density, and vessel length density) and geometric (fractal dimension and blood vessel tortuosity) parameters in superficial capillary plexus (SCP) and deep capillary plexus. The odds ratio (OR) and its 95% confidence interval (CI) were calculated per 1-SD increase in each optical coherence tomography angiography parameter. RESULTS: Over a follow-up of 1 year, 182 of 1,698 participants (10.7%) developed incident DR. After adjusting for conventional risk factors and image quality score, the higher risk of DR onset was significantly associated with the reduced parafoveal vessel density of SCP (OR = 0.81; 95% CI: 0.69, 0.96; P = 0.016), reduced parafoveal vessel length density of SCP (OR = 0.73; 95% CI: 0.59, 0.90; P = 0.003), reduced fractal dimension of SCP (OR = 0.73; 95% CI: 0.61, 0.87; P < 0.001), increased blood vessel tortuosity of SCP (OR = 1.39; 95% CI: 1.18, 1.64; P < 0.001), and increased blood vessel tortuosity of deep capillary plexus (OR = 1.19; 95% CI: 1.01, 1.40; P = 0.033). CONCLUSION: Reduced vessel density and impaired vessel geometry posed higher susceptibility for DR onset in patients with Type 2 diabetes, supporting the adoption of optical coherence tomography angiography parameters as early monitoring indicators of the newly incident DR.

Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10-8 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

Rapid and sensitive electrochemical detection of microRNAs by gold nanoparticle-catalyzed silver enhancement.

MicroRNAs (miRNAs) have played a vital role in the regulation of gene expression and have been considered as potential biomarker candidates for early cancer diagnosis. Rapid and sensitive detection of microRNAs is highly desired. Here, we present a new method to rapidly and sensitively determine microRNAs based on the technology of gold nanoparticle catalyzed silver staining enhancement. The new method involves the sandwich hybridization of a capture probe immobilized on a magnetic bead, a reporter probe assembled on gold nanoparticles and a miRNA target, catalytic silver precipitation by gold nanoparticles, magnetic collection of the enhanced sandwich complex, dissolution of the silver precipitation and stripping detection. Using the proposed method the microRNA-7a assay was successfully carried out in less than 70 min and the detection limit was as low as 15 fM. The proposed biosensor may hold great promise in biological monitoring of microRNAs.

A long noncoding RNA cluster-based genomic locus maintains proper development and visual function.

Long noncoding RNAs (lncRNAs) represent a group of regulatory RNAs that play critical roles in numerous cellular events, but their functional importance in development remains largely unexplored. Here, we discovered a series of previously unidentified gene clusters harboring conserved lncRNAs at the nonimprinting regions in brain (CNIBs). Among the seven identified CNIBs, human CNIB1 locus is located at Chr 9q33.3 and conserved from Danio rerio to Homo sapiens. Chr 9q33.3-9q34.11 microdeletion has previously been linked to human nail-patella syndrome (NPS) which is frequently accompanied by developmental and visual deficiencies. By generating CNIB1 deletion alleles in zebrafish, we demonstrated the requirement of CNIB1 for proper growth and development, and visual activities. Furthermore, we found that the role of CNIB1 on visual activity is mediated through a regulator of ocular development-lmx1bb. Collectively, our study shows that CNIB1 lncRNAs are important for zebrafish development and provides an lncRNA cluster-mediated pathophysiological mechanism for human Chr 9q33.3-9q34.11 microdeletion syndrome.

Bronchial provocation test measured by using the forced oscillation technique to assess airway responsiveness.

Background: The bronchial provocation test (BPT) performed by using the forced oscillation technique (FOT) is cooperated without forced expiratory effort. However, a comparison of the application value and safety of BPTs measured by using the FOT and the standardized dosimeter method is lacking, which limits its clinical practice. Objective: We aimed to analyze the diagnostic value and safety of the BPT as measured by the FOT in patients with asthma and in healthy subjects. Methods: This was a randomized cross-over clinical study. Airway responsiveness was measured by using the FOT and the aerosol provocation system (APS) dosimeter method in all the participants. The between-test interval was 24 hours. The diagnostic value and safety of the two tests were analyzed. Results: Asthma control status was assessed based on ACT scores, and patients with asthma (including 27 uncontrolled, 34 partially controlled, and 32 controlled) were collected, and 69 healthy subjects were recruited. Receiver operating characteristic curves revealed slightly superior screening capability of cumulative dose of methacholine causing a 20% decrease (PD20)-forced expiratory volume in the first second of expiration when measured by using the APS-dosimeter method (area under the curve [AUC] 0.981 [95% confidence interval {CI}, 0.952-1.000]) over that of cumulative dose of inhaled methacholine at the inflection point when respiratory resistance began to increase continuously (Dmin) by using the FOT (AUC 0.959 [95% CI, 0.924-0.994]). The sensitivity and specificity were 98.9% and 98.6%, respectively, with the APS-dosimeter method, and 100% and 87.0%, respectively, with the FOT. It took an average of 9.0 minutes (range, 6.0-11.0 minutes) when using the FOT and an average of 17.0 minutes (range, 14.0-25.0 minutes) when using APS-dosimeter method (p < 0.01) in all the participants. The measurement time for the FOT was reduced by 47.1% than the APS-dosimeter. The incidence rate of the adverse events with the FOT was slightly higher than that with the APS-dosimeter method (p < 0.05). Both tests were well tolerated. No serious adverse event was found. Conclusion: The FOT, characterized as being simple, safe, and time saving, could be used to assess airway hyperresponsiveness in patients with asthma and worthy of clinical application.

Association of breast cancer with MRI background parenchymal enhancement: the IMAGINE case-control study.

BACKGROUND: Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may be associated with breast cancer risk, but previous studies of the association are equivocal and limited by incomplete blinding of BPE assessment. In this study, we evaluated the association between BPE and breast cancer based on fully blinded assessments of BPE in the unaffected breast. METHODS: The Imaging and Epidemiology (IMAGINE) study is a multicenter breast cancer case-control study of women receiving diagnostic, screening, or follow-up breast MRI, recruited from three comprehensive cancer centers in the USA. Cases had a first diagnosis of unilateral breast cancer and controls had no history of or current breast cancer. A single board-certified breast radiologist with 12 years' experience, blinded to case-control status and clinical information, assessed the unaffected breast for BPE without view of the affected breast of cases (or the corresponding breast laterality of controls). The association between BPE and breast cancer was estimated by multivariable logistic regression separately for premenopausal and postmenopausal women. RESULTS: The analytic dataset included 835 cases and 963 controls. Adjusting for fibroglandular tissue (breast density), age, race/ethnicity, BMI, parity, family history of breast cancer, BRCA1/BRCA2 mutations, and other confounders, moderate/marked BPE (vs minimal/mild BPE) was associated with breast cancer among premenopausal women [odds ratio (OR) 1.49, 95% CI 1.05-2.11; p = 0.02]. Among postmenopausal women, mild/moderate/marked vs minimal BPE had a similar, but statistically non-significant, association with breast cancer (OR 1.45, 95% CI 0.92-2.27; p = 0.1). CONCLUSIONS: BPE is associated with breast cancer in premenopausal women, and possibly postmenopausal women, after adjustment for breast density and confounders. Our results suggest that BPE should be evaluated alongside breast density for inclusion in models predicting breast cancer risk.

CYP2C19 is involved in the effect of Wuzhi tablet (Schisandra sphenanthera extract) and its constituents on the pharmacokinetics of intravenous voriconazole.

The co-administration of voriconazole (VCZ) and Wuzhi tablet (WZ) is frequently prescribed for solid organ transplantation patients in China. However, the pharmacokinetic interactions between VCZ and WZ as well as its bioactive constituents, such as schisandrin A and schisandrol B, remain unknown. Therefore, the effects of WZ and the two lignans on the metabolism of VCZ and the potential role of cytochromeP450 (CYP450), especially cytochrome P450 2C19 (CYP2C19), were investigated. The results showed that WZ extensively inhibited the activities of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Noteworthy, 2.5 mg/mL WZ almost completely inhibited the activity of 2C19, and the inhibition ratio reached 78.6±3% and 63.5±4.6% for schisandrin A and schisandrol B at concentrations 100 µM, respectively. In addition, rats were treated with a single or consecutive 14 day oral dose of WZ (250 mg/kg), schisandrol B (10 mg/kg) and schisandrin A (10 mg/ kg). In rats treated with WZ, the AUC0-∞ value for intravenous VCZ dosing was increased by 80.2% (single dose, p < 0.05) and 66.4% (dosage for 14 day, p < 0.05) and the Cmax was increased by 10.5% (p < 0.05) and (20.6%, p < 0.05), respectively, much greater than that when VCZ (28 mg/kg) was given alone. Unexpectedly, the AUC and Cmax values after schisandrol B and schisandrin A treatment were significantly increased. However, the mRNA expression of liver CYP2C19 and the protein expression of liver CYP2C19 were surprisingly increased after treatment with WZ, schisandrol B and schisandrin A in rats. Therefore, attention should be paid to when WZ and VCZ are administered concomitantly, as dosage adjustment might become necessary. Further clinical study is warranted to validate the interaction between WZ and VCZ.

An Improved Unauthorized Unmanned Aerial Vehicle Detection Algorithm Using Radiofrequency-Based Statistical Fingerprint Analysis.

Unmanned aerial vehicles (UAVs) are now readily available worldwide and users can easily fly them remotely using smart controllers. This has created the problem of keeping unauthorized UAVs away from private or sensitive areas where they can be a personal or public threat. This paper proposes an improved radio frequency (RF)-based method to detect UAVs. The clutter (interference) is eliminated using a background filtering method. Then singular value decomposition (SVD) and average filtering are used to reduce the noise and improve the signal to noise ratio (SNR). Spectrum accumulation (SA) and statistical fingerprint analysis (SFA) are employed to provide two frequency estimates. These estimates are used to determine if a UAV is present in the detection environment. The data size is reduced using a region of interest (ROI), and this improves the system efficiency and improves azimuth estimation accuracy. Detection results are obtained using real UAV RF signals obtained experimentally which show that the proposed method is more effective than other well-known detection algorithms. The recognition rate with this method is close to 100% within a distance of 2.4 km and greater than 90% within a distance of 3 km. Further, multiple UAVs can be detected accurately using the proposed method.