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The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs-which are usually more aggressive than natural compounds-with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with less side effects on human health. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. Moreover, the future directions in applications of various polyphenols in cancer therapy are emphasized.

Breast MRI offers high sensitivity for breast cancer detection, with preferential detection of high-grade invasive cancers when compared to mammography and ultrasound. Despite the clear benefits of breast MRI in cancer screening, its cost, patient tolerance, and low utilization remain key issues. Abbreviated breast MRI, in which only a select number of sequences and postcontrast imaging are acquired, exploits the high sensitivity of breast MRI while reducing table time and reading time to maximize availability, patient tolerance, and accessibility. Worldwide studies of varying patient populations have demonstrated that the comparable diagnostic accuracy of abbreviated breast MRI is comparable to a full diagnostic protocol, highlighting the emerging role of abbreviated MRI screening in patients with an intermediate and high lifetime risk of breast cancer. The purpose of this review is to summarize the background and current literature relating to abbreviated MRI, highlight various protocols utilized in current multicenter clinical trials, describe workflow and clinical implementation issues, and discuss the future of abbreviated protocols, including advanced MRI techniques., (© Society of Breast Imaging 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We present a deep convolutional neural network for breast cancer screening exam classification, trained, and evaluated on over 200000 exams (over 1000000 images). Our network achieves an AUC of 0.895 in predicting the presence of cancer in the breast, when tested on the screening population. We attribute the high accuracy to a few technical advances. 1) Our network's novel two-stage architecture and training procedure, which allows us to use a high-capacity patch-level network to learn from pixel-level labels alongside a network learning from macroscopic breast-level labels. 2) A custom ResNet-based network used as a building block of our model, whose balance of depth and width is optimized for high-resolution medical images. 3) Pretraining the network on screening BI-RADS classification, a related task with more noisy labels. 4) Combining multiple input views in an optimal way among a number of possible choices. To validate our model, we conducted a reader study with 14 readers, each reading 720 screening mammogram exams, and show that our model is as accurate as experienced radiologists when presented with the same data. We also show that a hybrid model, averaging the probability of malignancy predicted by a radiologist with a prediction of our neural network, is more accurate than either of the two separately. To further understand our results, we conduct a thorough analysis of our network's performance on different subpopulations of the screening population, the model's design, training procedure, errors, and properties of its internal representations. Our best models are publicly available at https://github.com/nyukat/breast_cancer_classifier.

We investigate the pressure-driven transport of particles 200 or 300 nm in diameter in shallow microfluidic channels ∼1 μm in height with a bottom wall characterized by a high roughness amplitude of ∼100 nm. This study starts with the description of an assay to generate cracks in hydrophilic thin polymer films together with a structural characterization of these corrugations. Microfluidic chips of variable height are then assembled on top of these rough surfaces, and the transport of particles is assessed by measuring the velocity distribution function for a set of pressure drops. We specifically detect anomalous transport properties for rough surfaces. The maximum particle velocity at the centerline of the channel is comparable to that obtained with smooth surfaces, but the average particle velocity increases nonlinearly with the flow rate. We suggest that the change in the boundary condition at the rough wall is not sufficient to account for our data and that the occurrence of contacts between the particle and the surface transports the particle away from the wall and speeds up its motion. We finally draw perspectives for the separation by field-flow fractionation.

Vascular lesions (VLs) of the breast present a diagnostic challenge on breast core biopsy (BCBx). We report on 27 VLs presenting on BCBx. The mean patient age was 60 years, and mean size was 7.5 mm (range, 1.6 to 16 mm). Presentation included palpable mass in 6 (22%), incidental in 6 (22%), and an imaging abnormality in 15 (56%) cases. Imaging impression included hematoma (24%), lymph node (10%), fat necrosis (10%), tortuous vessel (5%), and not provided in 52%. The lesions were classified on the basis of BCBx or BCBx and excision (available in 16 pts) as follows: 1 low-grade angiosarcoma, 8 angiolipomas, 6 capillary hemangiomas, 4 cavernous hemangiomas, 2 hemangiomas (not otherwise specified), 1 papillary endothelial hyperplasia, and 5 perilobular hemangiomas. The angiosarcoma was 9 mm, detected incidentally by magnetic resonance imaging, and showed dissection of stromal collagen, infiltration of glands, high cellularity, moderate cytologic atypia, scant mitotic activity, and Ki-67 reactivity of 10%. Among the 26 benign VLs, worrisome histologic features were noted in 14 on BCBx, including anastomosing vascular channels in 9, moderate cytologic atypia in 4, high cellularity in 2, Ki-67>10% in 2, mitotic activity in 1, and infiltration of glands in 1. Of the 12 VLs without worrisome features, the lesion extended to edge of core in 8, precluding complete evaluation. BCBx of VLs presents diagnostic challenges due to overlapping clinicopathologic and radiologic features with low-grade angiosarcoma. If completeness of removal is documented on BCBx, and cytoarchitectural changes are not worrisome, follow-up could be considered rather than excision. However, only 4 of these cases fulfilled those criteria.

Aims: To identify variables that can predict upgrade for magnetic resonance imaging (MRI)-detected atypical ductal hyperplasia (ADH)., Methods and Results: We reviewed 1655 MRI-guided core biopsies between 2005 and 2013, yielding 100 (6%) cases with ADH. The pathological features of ADH and MRI findings were recorded. An upgrade was considered when the subsequent surgical excision yielded invasive carcinoma (IC) or ductal carcinoma in situ (DCIS). The rate of ADH between institutions was 3.3-7.1%, with an average of 6%. A total of 15 (15%) cases had upgrade, 12 DCIS and three IC. When all cases were included, only increased number of involved cores was statistically significant (P = 0.02). When cases with concurrent lobular neoplasia (LN) were excluded (n = 14), increased number of ADH foci and increased number of involved cores were statistically significant (P = 0.002, P = 0.009). We analysed the data separately from a single institution (n = 61). Increased number of foci, increased number of total cores and involved cores and larger ADH size predicted upgrade with statistical significance., Conclusions: The incidence of ADH in MRI-guided core biopsy is rare. The rate of upgrade is comparable to mammographically detected ADH, warranting surgical excision. Similar to mammographically detected lesions, the volume of the ADH predicts the upgrade., (© 2015 John Wiley & Sons Ltd.)

Sonography is useful in the evaluation of axillary lymph nodes in patients with breast cancer. In this pictorial essay, we review the range of grayscale and Doppler appearances of abnormal axillary lymph nodes on 2-dimensional and 3-dimensional imaging., (© 2016 by the American Institute of Ultrasound in Medicine.)

There are certain criteria to recommend surgical excision for lobular neoplasia diagnosed in mammographically detected core biopsy. The aims of this study are to explore the rate of upgrade of lobular neoplasia detected in magnetic resonance imaging (MRI)-guided biopsy and to investigate the clinicopathological and radiological features that could predict upgrade. We reviewed 1655 MRI-guided core biopsies yielding 63 (4%) cases of lobular neoplasia. Key clinical features were recorded. MRI findings including mass vs non-mass enhancement and the reason for biopsy were also recorded. An upgrade was defined as the presence of invasive carcinoma or ductal carcinoma in situ in subsequent surgical excision. The overall rate of lobular neoplasia in MRI-guided core biopsy ranged from 2 to 7%, with an average of 4%. A total of 15 (24%) cases had an upgrade, including 5 cases of invasive carcinoma and 10 cases of ductal carcinoma in situ. Pure lobular neoplasia was identified in 34 cases, 11 (32%) of which had upgrade. In this group, an ipsilateral concurrent or past history of breast cancer was found to be associated with a higher risk of upgrade (6/11, 55%) than contralateral breast cancer (1 of 12, 8%; P=0.03). To our knowledge, this is the largest series of lobular neoplasia diagnosed in MRI-guided core biopsy. The incidence of lobular neoplasia is relatively low. Lobular neoplasia detected in MRI-guided biopsy carries a high risk for upgrade warranting surgical excision. However, more cases from different types of institutions are needed to verify our results.

Retrospective analysis of 99 male autosomal dominant polycystic kidney disease (ADPKD) patients compared to an age-matched control population showed seminal vesicle ectasia >10 mm (megavesicle) in 23% (23/99) of ADPKD patients that was not present in any controls (P<.0001). Median (range) seminal vesicle convoluted tubule diameter in ADPKD patients was 4.2 (1.7-30) mm compared to 3.1 (1.7-6.8) mm in controls (P<.0001). Discrete cysts were identified in four ADPKD patients but in none of the control population (P=.12). Seminal megavesicles may explain the infertility sometimes observed in male ADPKD patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: This study aims to estimate the prevalence of risk factors for osteoporotic vertebral fracture and analyze the possible associations between these factors and the presence of densitometric osteoporosis and prevalent morphometric vertebral fracture., Methods: Data from a population-based cross-sectional sample of 804 postmenopausal women over the age of 50 years old living in the city of Valencia (Spain) were used. The women were interviewed to identify the prevalence of osteoporotic fracture risk factors and underwent a densitometry and a dorsolumbar spine X-ray., Results: The most prevalent risk factors were densitometric osteoporosis (31.7%), history of parental hip fracture (19.4%), hypoestrogenism (19%), and body mass index (BMI) ≥ 30 kg/m(2) (35.2%). After adjusting for all covariables, densitometric osteoporosis was associated with increased age [odds ratio (OR)(65-69 years): 2.84, 95% confidence interval (CI): 1.75-4.61; OR(70-74 years): 4.01, 95% CI: 2.47-6.52; OR(75+years): 5.96, 95% CI: 3.27-10.87] and inversely associated with high BMI (OR(25.0-29.9): 0.51, 95% CI: 0.34-0.76; OR(≥ 30): 0.30, 95% CI: 0.19-0.46). Morphometric vertebral fracture was associated with age (OR(65-69 years): 2.04, 95% CI: 1.03-4.05; OR(70-74 years): 4.05, 95% CI: 2.11-7.77; OR(75+years): 8.43, 95% CI: 3.97-17.93), poor educational level (OR: 1.70, 95% CI: 1.06-2.72) and with densitometric osteoporosis and BMI ≥ 30 kg/m(2) (OR: 3.35, 95% CI: 1.85-6.07)., Conclusions: The most prevalent osteoporotic fracture risk factors were having a high BMI and the presence of densitometric osteoporosis. A higher risk of morphometric vertebral fracture in women with both low bone mineral density and high BMI was found. This association, if confirmed, has important implications for clinical practice and fracture risk tools. We also found a higher risk in women with a poor educational level. More attention should be addressed to these populations in order to control modifiable risk factors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Near infra-red (NIR) self-guided photo-polymerization is investigated in the context of micro-optics photo-fabrication on VCSELs (Vertical-Cavity Surface Emitting Lasers). We present the optimized process we have developed to allow for a collective fabrication on III-V devices wafers under real-time optical monitoring. The influence of photo-chemical parameters on final micro-elements dimensions is studied for two types of single mode 760 nm VCSELs. The difference of the resulting tip shape between the two lasers is due to the strong differences of their emissions, as they are nicely reproduced by the computed near-field profiles. The tip shapes are also compared to those produced by the light emitted by an optical fiber and differences with VCSEL tips are discussed. Also the VCSEL characteristics with fabricated tips are discussed and found in good agreement with optical modeling.

Purpose: To examine the feasibility of flow-independent T2-prepared inversion recovery (T2IR) black-blood (BB) magnetization preparation for three-dimensional (3D) balanced steady-state free precession (SSFP) vessel wall MRI of the popliteal artery, and to evaluate its performance relative to flow-dependent double inversion recovery (DIR), spatial presaturation (SPSAT), and motion-sensitizing magnetization preparation (MSPREP) BB techniques in healthy volunteers., Materials and Methods: Eleven subjects underwent 3D MRI at 1.5 Tesla with four techniques performed in a randomized order. Wall and lumen signal-to-noise ratio (SNR), wall-to-lumen contrast-to-noise ratio (CNR), vessel wall area, and lumen area were measured at proximal, middle, and distal locations of the imaged popliteal artery. Image quality scores based on wall visualization and degree of intraluminal artifacts were also obtained., Results: In the proximal region, DIR and SPSAT had higher wall SNR and wall-to-lumen CNR than both MSPREP and T2IR. In the middle and distal regions, DIR and SPSAT failed to provide effective blood suppression, whereas MSPREP and T2IR provided adequate black blood contrast with comparable wall-to-lumen CNR and image quality., Conclusion: The feasibility of 3D SSFP imaging of the popliteal vessel wall using flow-independent T2IR was demonstrated with effective blood suppression and good vessel wall visualization. Although DIR and SPSAT are effective for thin slab imaging, MSPREP and T2IR are better suited for 3D thick slab imaging., (Copyright © 2011 Wiley-Liss, Inc.)

Background: To describe the health related quality of life in a population sample of postmenopausal women over the age of 50 and resident in the city of Valencia (Spain), according to the presence/absence of osteoporosis and the severity of prevalent morphometric vertebral fractures., Methods: A cross-sectional age-stratified population-based sample of 804 postmenopausal women of 50 years of age and older were assessed with the SF-12 questionnaire. Information about demographic features, lifestyle, clinical features, educational level, anti-osteoporotic and other treatments, comorbidities and risk factors for osteoporosis were collected using an interviewer-administered questionnaire and densitometric evaluation of spine and hip and spine x-rays were carried out., Results: In the non-adjusted analysis, mild and moderate-severe vertebral fractures were associated with decreased scores in the SF-12 Physical Component Summary (PCS) but not in the Mental Component Summary (MCS), while densitometric osteoporosis with no accompanying fracture was not associated with a worse health related quality of life. In multivariate analysis worse PCS scores were associated to the age groups over 70 (-2.43 for 70-74 group and -2.97 for 75 and older), chronic conditions (-4.66, -6.79 and -11.8 according to the presence of 1, 2 or at least 3 conditions), obesity (-5.35), peripheral fracture antecedents (-3.28), hypoestrogenism antecedents (-2.61) and the presence of vertebral fracture (-2.05)., Conclusions: After adjusting for confounding factors, the physical components of health related quality of life were significantly lower in women with prevalent osteoporotic vertebral fractures than in women--osteoporotic or not--without vertebral fractures.

Purpose: To estimate the prevalence of vertebral fracture and densitometric osteoporosis in postmenopausal women over the age of 50 in Valencia, Spain., Methods: This cross-sectional study was conducted in 2006-2007. An age-stratified population-based random sample of 824 postmenopausal women over the age of 50 answered a questionnaire and received a densitometric examination of the lumbar spine and hip with dual-energy X-ray absorptiometry and a lateral X-ray of the thoracic spine and lumbar regions. Osteoporosis was defined as a T-score less than or equal to -2.5 compared to a population of young women, and the presence of vertebral fractures was classified according to Genant's semiquantitative method., Results: The average age of the women was 64 years (range 50-87 years). The prevalence for all vertebral fractures was 21.4% (95% CI: 17.7%-25.1%) and 9.7% (95% CI: 6.7%-12.7%) for moderate-severe fractures. In women over the age of 75, the respective values were 46.3% (95% CI: 34.2%-58.3%) and 23.9% (95% CI:13.6%-34.2%). Only 1.5% of the women with vertebral fractures were aware of their condition. The prevalence of osteoporosis was estimated as 27.0% (95% CI:23.1%-30.8%) for the lumbar spine, 15.1% (95% CI:11.7%-18.5%) in the femoral neck, and 31.8% (95% CI:27.8%-35.7%) at either sites., Conclusions: The study confirms that osteoporosis (1 in 3 women over the age of 50) and vertebral fracture (1 in 5 for all fractures and 1 in 10 for moderate-severe fractures) constitute a major public health and healthcare challenge; measuring their real impact will depend in part on the criteria used to define a fracture., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Among the various treatments for osteoporosis, calcium and/or vitamin D supplements are frequently included., Objective: The objective of the study was to analyse adherence to calcium and/or vitamin D treatment and to identify related predictors of non-adherence in a sample of postmenopausal women treated for osteoporosis in primary care., Methods: A cross-sectional, observational study was conducted in a sample of postmenopausal women receiving pharmaceutical treatment for osteoporosis with vitamin D and/or calcium. Sociodemographic, general and osteoporosis-related data were collected. Patient's perceptions of the adverse effects of treatment, their knowledge of osteoporosis (Batalla test), their attitude towards treatment (Morisky-Green test) and their self-reported therapeutic adherence (Haynes-Sackett test) were assessed., Results: Of 630 women (mean age +/- SD 64.1 +/- 8.7 years) evaluated, 36.2% (95% CI 32.4, 39.9) had problems with treatment tolerability, 63.5% (95% CI 59.7, 67.3) had good knowledge of osteoporosis, 20.5% (95% CI 17.3, 23.6) had a good attitude to treatment and 50.0% (95% CI 46.1, 53.9) had good self-reported adherence to treatment. Patients in the poor adherence group had higher mean body mass index (p = 0.014), more concurrent pathologies (p = 0.003), more tolerability problems (p < 0.001) and worse attitude to treatment (p < 0.001). The multivariate model showed a positive relationship between therapeutic adherence and good attitude to treatment (odds ratio [OR] = 11.7; p < 0.001), not having tolerability problems (OR = 3.3; p < 0.001) and no polymedication (OR = 0.80; p = 0.017)., Conclusions: Only one in two postmenopausal women with osteoporosis who take calcium and/or vitamin D have good self-reported therapeutic adherence to this treatment. Determinant factors of adherence to calcium and/or vitamin D treatment were patient's attitude to the treatment, tolerability problems with the treatment and number of concurrent treatments.

The 5' untranslated region (UTR) of the human cytoplasmic serine hydroxymethyltransferase (cSHMT) message is alternatively spliced, creating a full-length 5' UTR (LUTR) encoded within exons 1-3 and a shorter UTR (SUTR) that results from excision of exon 2. The role of the 5' UTRs in cSHMT expression was investigated by fusing the cSHMT 5' UTRs to the 5' end of the luciferase gene. Human cSHMT protein at 10 microM inhibits in vitro translation of cSHMT 5' UTR-luciferase fusion mRNA templates by more than 90%, but does not inhibit translation of the luciferase message lacking the UTR. Translation inhibition is independent of amino acid and folate substrate binding to the cSHMT enzyme. The cSHMT SUTR-luciferase mRNA binds to the cSHMT.glycine.5-formyltetrahydrofolate ternary complex with an apparent K(d) of 10 microM. Gel mobility shift assays demonstrate that the human cSHMT protein binds to the cSHMT LUTR-luciferase fusion mRNA in the presence and absence of glycine and 5-formyltetrahydrofolate pentaglutamate. The fusion cSHMT SUTR-luciferase message at 65 microM inhibits the cSHMT-catalyzed cleavage of allothreonine as a partial mixed type inhibitor, reducing both k(cat) and K(m) by 40 and 75%, respectively, while tRNA has no effect on cSHMT catalysis. These studies indicate that the cSHMT protein can bind mRNA, and displays increased affinity for the 5' untranslated region of its mRNA.