Positive Predictive Value of Tomosynthesis-guided Biopsies of Architectural Distortions Seen on Digital Breast Tomosynthesis and without an Ultrasound Correlate

Objective: The objective of the study was to determine the positive predictive value (PPV) of architectural distortions (AD) observed on digital breast tomosynthesis (DBT) and without an ultrasound (US) correlate. Materials and Methods: In this single-institution, retrospective study, patients who underwent DBT-guided biopsies of AD without any associated findings on digital mammography (DM) or DBT, and without a correlate on targeted US exam, over a 14-month period were included in this study. All patients had DM and DBT and targeted US exams. The PPV was computed along with the exact 95% confidence limits (CL) using simple binomial proportions, with histopathology as the reference standard. Results: A total of 45 ADs in 45 patients met the inclusion criteria. Histopathology indicated 6/45 (PPV: 13.3%, CL: 5.1-26.8%), ADs were malignant, including one high-risk lesion that was upgraded at surgery. ADs were appreciated only on DBT in 12/45 (26.7%) patients, and on both DBT and DM in 33/45 (73.3%) patients, and the corresponding PPV was 25% (3/12, CL: 5.5-57.2%) and 9.1% (3/33, CL: 1.9-24.3%), respectively. In all analyses, the observed PPV significantly exceeded the 2% probability of malignancy for Breast Imaging Reporting and Data System-3 diagnostic categories (P \u3c 0.004). Conclusions: The PPV of malignancy in DBT detected AD without an US correlate in our series of 45 cases was 6/45 (13.3%). In the absence of an US correlate, the PPV of AD is lower than that mentioned in prior literature but exceeds the 2% threshold to justify DBT-guided biopsy

Expression of 14-3-3 protein isoforms in mouse oocytes, eggs and ovarian follicular development

<p>Abstract</p> <p>Background</p> <p>The 14-3-3 (YWHA) proteins are a highly conserved, ubiquitously expressed family of proteins. Seven mammalian isoforms of 14-3-3 are known (β, γ, ε, ζ, η, τ and, σ). These proteins associate with many intracellular proteins involved in a variety of cellular processes including regulation of the cell cycle, metabolism and protein trafficking. We are particularly interested in the role of 14-3-3 in meiosis in mammalian eggs and the role 14-3-3 proteins may play in ovarian function. Therefore, we examined the expression of 14-3-3 proteins in mouse oocyte and egg extracts by Western blotting after polyacrylamide gel electrophoresis, viewed fixed cells by indirect immunofluorescence, and examined mouse ovarian cells by immunohistochemical staining to study the expression of the different 14-3-3 isoforms.</p> <p>Results</p> <p>We have determined that all of the mammalian 14-3-3 isoforms are expressed in mouse eggs and ovarian follicular cells including oocytes. Immunofluorescence confocal microscopy of isolated oocytes and eggs confirmed the presence of all of the isoforms with characteristic differences in some of their intracellular localizations. For example, some isoforms (β, ε, γ, and ζ) are expressed more prominently in peripheral cytoplasm compared to the germinal vesicles in oocytes, but are uniformly dispersed within eggs. On the other hand, 14-3-3η is diffusely dispersed in the oocyte, but attains a uniform punctate distribution in the egg with marked accumulation in the region of the meiotic spindle apparatus. Immunohistochemical staining detected all isoforms within ovarian follicles, with some similarities as well as notable differences in relative amounts, localizations and patterns of expression in multiple cell types at various stages of follicular development.</p> <p>Conclusions</p> <p>We found that mouse oocytes, eggs and follicular cells within the ovary express all seven isoforms of the 14-3-3 protein. Examination of the differential expression of these 14-3-3 isoforms in female germ cells and ovarian follicles provides the foundation for further investigating 14-3-3 isoform-specific interactions with key proteins involved in ovarian development, meiosis and oocyte maturation. This will lead to a better understanding of the individual functional roles of the 14-3-3 protein isoforms in mammalian oogenesis and female reproductive development.</p

Ultrasound Imaging Morphology is Associated with Biological Behavior in Invasive Ductal Carcinoma of the Breast

Objectives: Ultrasound (US) is commonly used for diagnostic evaluation of breast lesions. The objective of this study was to investigate the association between US imaging morphology from routine radiologists\u27 interpretation and biological behavior such as receptor status and tumor grade determined from histopathology in invasive ductal carcinoma (IDC). Material and Methods: This retrospective study included 453 patients with pathology-verified diagnosis of IDC who had undergone US imaging and had surgery over a 5-year period. US and surgical pathology reports were reviewed and compiled. Correlation analyses and age-adjusted multivariable models were used to determine the association between US imaging morphology and receptor status, tumor grade, and germ line mutation of the breast cancer genes (BRCA1 and BRCA2). The odds ratio (OR), area under receiver operating characteristic curve (AUC), and 95% confidence intervals (CI) were obtained. Results: The likelihood for high-grade cancer increased with size (OR: 1.066; CI: 1.042-1.091) and hypo-echogenicity (OR: 2.044; CI: 1.337-3.126), and decreased with angular or spiculated margins (OR: 0.605; CI: 0.393-0.931) and posterior acoustic shadowing (OR: 0.352; CI: 0.238-0.523). These features achieved an AUC of 0.799 (CI: 0.752-0.845) for predicting high-grade tumors. The likelihood for Estrogen Receptor-positive tumors increased with posterior acoustic shadowing (OR: 3.818; CI: 2.206-6.607), angulated or spiculated margins (OR: 2.596; CI: 1.159-5.815) and decreased with US measured tumor size (OR: 0.959; CI: 0.933-0.986) and hypoechoic features (OR: 0.399; CI: 0.198- 0.801), and achieved an AUC of 0.787 (CI: 0.733-0.841). The likelihood for Progesterone Receptor-positive tumors increased with posterior acoustic shadowing (OR: 2.732; CI: 1.744-4.28) and angulated or spiculated margins (OR: 2.618; CI: 1.412-4.852), and decreased with US measured tumor size (OR: 0.961; CI: 0.937-0.985) and hypoechoic features (OR: 0.571; CI: 0.335-0.975), and achieved an AUC of 0.739 (CI: 0.689-0.790). The likelihood for Human epidermal growth factor receptor 2-positive tumors increased with heterogeneous echo texture (OR: 2.141; CI: 1.17- 3.919) and decreased with angulated or spiculated margins (OR: 0.408; CI: 0.177-0.944), and was marginally associated with hypoechoic features (OR: 2.101; CI: 0.98-4.505) and circumscribed margins (OR: 4.225; CI: 0.919-19.4). The model with the aforementioned four US morphological features and achieved an AUC of 0.686 (CI: 0.614-0.758). The likelihood for triple-negative breast cancers increased with hypo-echogenicity (OR: 2.671; CI: 1.249-5.712) and decreased with posterior acoustic shadowing (OR: 0.287; CI: 0.161-0.513), and achieved an AUC of 0.739 (CI: 0.671- 0.806). No statistical association was observed between US imaging morphology and BRCA mutation. Conclusion: In this study of over 450 IDCs, significant statistical associations between tumor grade and receptor status with US imaging morphology were observed and could serve as a surrogate imaging marker for the biological behavior of the tumor

Sense3

Sense3, at its core, is a game in which the player has to collectively use the three senses of sight, touch and hearing to primarily dodge obstacles and collect audio samples, which are vertically remixed to form music. We chose EDM themed music, coupled with a futuristic outer space theme for the art style of the game, creating an immersive environment. The game is a pseudo-endless runner, where the player has to collect all the components to assemble their music. After each play through, the game allows the player to listen to the newly assembled music before reloading. We wanted to encourage replay value as each play through yields new and different music. The concept was decided upon after a series of prototyping sessions and iterations on a select few of them

YWHA (14-3-3) Protein Isoforms and Their Interactions with CDC25B Phosphatase in Mouse Oogenesis and Oocyte Maturation

Background Immature mammalian oocytes are held arrested at prophase I of meiosis by an inhibitory phosphorylation of cyclin-dependent kinase 1 (CDK1). Release from this meiotic arrest and germinal vesicle breakdown is dependent on dephosphorylation of CDK1 by the protein, cell cycle division 25B (CDC25B). Evidence suggests that phosphorylated CDC25B is bound to YWHA (14-3-3) proteins in the cytoplasm of immature oocytes and is thus maintained in an inactive form. The importance of YWHA in meiosis demands additional studies. Results Messenger RNA for multiple isoforms of the YWHA protein family was detected in mouse oocytes and eggs. All seven mammalian YWHA isoforms previously reported to be expressed in mouse oocytes, were found to interact with CDC25B as evidenced by in situ proximity ligation assays. Interaction of YWHAH with CDC25B was indicated by Förster Resonance Energy Transfer (FRET) microscopy. Intracytoplasmic microinjection of oocytes with R18, a known, synthetic, non-isoform-specific, YWHA-blocking peptide promoted germinal vesicle breakdown. This suggests that inhibiting the interactions between YWHA proteins and their binding partners releases the oocyte from meiotic arrest. Microinjection of isoform-specific, translation-blocking morpholino oligonucleotides to knockdown or downregulate YWHA protein synthesis in oocytes suggested a role for a specific YWHA isoform in maintaining the meiotic arrest. More definitively however, and in contrast to the knockdown experiments, oocyte-specific and global deletion of two isoforms of YWHA, YWHAH (14-3-3 eta) or YWHAE (14-3-3 epsilon) indicated that the complete absence of either or both isoforms does not alter oocyte development and release from the meiotic prophase I arrest. Conclusions Multiple isoforms of the YWHA protein are expressed in mouse oocytes and eggs and interact with the cell cycle protein CDC25B, but YWHAH and YWHAE isoforms are not essential for normal mouse oocyte maturation, fertilization and early embryonic development

Experimental investigation on no fines concrete by addition of natural fibres

No fines concrete is a type of lightweight concrete that is made without the use of fine aggregates. In this experimental investigation, the effect of adding bamboo and sugarcane fibres on the mechanical properties of no fines concrete was studied. The specimens were prepared by replacing a portion of the coarse aggregates with 1.5% of bamboo and sugarcane fibres by volume. The specimens were tested for compressive strength and splitting tensile strength at 7, 14, and 28 days of curing. The results showed that the addition of bamboo and sugarcane fibres improved the mechanical properties of no fines concrete. The optimal percentage of fibre content was found to be 1.5% by volume, which improved the compressive strength and splitting tensile strength by 23% and 18% respectively, compared to the control specimens. Additionally, the use o natural fibres in no-fine concrete can result in a more sustainable and eco-friendly construction material

Identification and characterization of two distinct PPP1R2 isoforms in human spermatozoa

Background: Protein Ser/Thr Phosphatase PPP1CC2 is an alternatively spliced isoform of PPP1C that is highly enriched in testis and selectively expressed in sperm. Addition of the phosphatase inhibitor toxins okadaic acid or calyculin A to caput and caudal sperm triggers and stimulates motility, respectively. Thus, the endogenous mechanisms of phosphatase inhibition are fundamental for controlling sperm function and should be characterized. Preliminary results have shown a protein phosphatase inhibitor activity resembling PPP1R2 in bovine and primate spermatozoa. Results: Here we show conclusively, for the first time, that PPP1R2 is present in sperm. In addition, we have also identified a novel protein, PPP1R2P3. The latter was previously thought to be an intron-less pseudogene. We show that the protein corresponding to the pseudogene is expressed. It has PPP1 inhibitory potency similar to PPP1R2. The potential phosphosites in PPP1R2 are substituted by non-phosphorylable residues, T73P and S87R, in PPP1R2P3. We also confirm that PPP1R2/PPP1R2P3 are phosphorylated at Ser121 and Ser122, and report a novel phosphorylation site, Ser127. Subfractionation of sperm structures show that PPP1CC2, PPP1R2/PPP1R2P3 are located in the head and tail structures. Conclusions: The conclusive identification and localization of sperm PPP1R2 and PPP1R2P3 lays the basis for future studies on their roles in acrosome reaction, sperm motility and hyperactivation. An intriguing possibility is that a switch in PPP1CC2 inhibitory subunits could be the trigger for sperm motility in the epididymis and/or sperm hyperactivation in the female reproductive tract.publishe

PP1γ2 and PPP1R11 Are Parts of a Multimeric Complex in Developing Testicular Germ Cells in which their Steady State Levels Are Reciprocally Related

Mice lacking the protein phosphatase 1 gamma isoforms, PP1γ1 and PP1γ2, are male-sterile due to defective germ cell morphogenesis and apoptosis. However, this deficiency causes no obvious abnormality in other tissues. A biochemical approach was employed to learn how expression versus deficiency of PP1γ2, the predominant PP1 isoform in male germ cells, affects spermatogenesis. Methods used in this study include column chromatography, western blot and northern blot analyses, GST pull-down assays, immunoprecipitation, non-denaturing gel electrophoresis, phosphatase enzyme assays, protein sequencing, and immunohistochemistry. We report for the first time that in wild-type testis, PP1γ2 forms an inactive complex with actin, protein phosphatase 1 regulatory subunit 7 (PPP1R7), and protein phosphatase 1 regulatory subunit 11 (PPP1R11), the latter, a potent PP1 inhibitor. Interestingly, PPP1R11 protein, but not its mRNA level, falls significantly in PP1γ-null testis where mature sperm are virtually absent. Conversely, both mature sperm numbers and the PPP1R11 level increase substantially in PP1γ-null testis expressing transgenic PP1γ2. PPP1R11 also appears to be ubiquitinated in PP1γ-null testis. The levels of PP1γ2 and PPP1R11 were increased in phenotypically normal PP1α-null testis. However, in PP1α-null spleen, where PP1γ2 normally is not expressed, PPP1R11 levels remained unchanged. Our data clearly show a direct reciprocal relationship between the levels of the protein phosphatase isoform PP1γ2 and its regulator PPP1R11, and suggest that complex formation between these polypeptides in testis may prevent proteolysis of PPP1R11 and thus, germ cell apoptosis