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Abstract Background Survivors of testicular cancer may experience long-term morbidity following treatment. There is an unmet need to investigate techniques that can differentiate individuals who need additional therapy from those who do not. 2-18fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with computerised tomography (CT) may be helpful in select settings and may be used outside of current evidence-based recommendations in real-world practice. Methods A institutional FDG-PET/CT database of scans performed between 2000 and 2020 for adults with testicular seminoma was interrogated. Endpoints of interest included the positive (PPV) and negative (NPV) predictive value of FDG-PET/CT for identifying active seminoma (defined by progressive radiology, response to treatment or biopsy); or no active seminoma within 24-months for patients with stage 1 and advanced seminoma. An exploratory analysis examining predictive role of SUVmax was also performed. Results 249 patients met eligibility criteria for the analysis, including 184 patients with stage 1 and 77 patients with advanced testicular seminoma. Of 193 FDG-PET/CT performed in stage 1 seminoma with available follow-up data, 79 were performed during active surveillance. 18 (23%) of these were positive, all of which had confirmed recurrent seminoma (PPV 100%). Of 45 negative FDG-PET/CT during active surveillance, 4 recurrences developed corresponding to a NPV 91%. When clinical suspicion precipitated FDG-PET/CT (n = 36): PPV 100%, NPV 86%. Of 145 FDG-PET/CT in advanced seminoma with available follow-up data, 25 (17%) were performed at baseline (within 2 months of diagnosis), 70 (48%) post-treatment for evaluation of treatment response and 50 (34%) during follow-up following prior curative treatment. 10 (14%) post-treatment FDG-PET/CT were positive corresponding to a PPV 60%. Of 46 negative FDG-PET/CT, 5 recurrences occurred (NPV 89%). During follow-up after prior curative treatment, 24 (50%) FDG-PET/CT were positive corresponding to a PPV 83%; of 20 negative FDG-PET/CT, 1 recurrence occurred, NPV 95%. When clinical suspicion indicated FDG-PET/CT (n = 36): PPV 100%, NPV 94%. Conclusion FDG-PET/CT offers high PPV for identifying seminoma and accurately predicts non-recurrence across a clinically relevant 24-months. Notably, FDG-PET/CT may prevent unnecessary treatment in 45% of patients undergoing investigation for clinical suspicion of recurrence during follow-up of advanced seminoma. The use of FDG-PET/CT in selected patients now, may help prevent unnecessary treatment of people with testicular seminoma.

Climate change is leading to habitat shifts that threaten species persistence throughout California's unique ecosystems. Baseline biodiversity data would provide opportunities for habitats to be managed under short-term and long-term environmental change. Aiming to provide biodiversity data, the UC Conservation Genomics Consortium launched the California Environmental DNA (CALeDNA) program to be a citizen and community science biomonitoring initiative that uses environmental DNA (eDNA, DNA shed from organisms such as from fur, feces, spores, pollen or leaves). Now with results from 1,000 samples shared online, California biodiversity patterns are discoverable. Soil, sediment and water collected by researchers, undergraduates and the public reveal a new catalog of thousands of organisms that only slightly overlap with traditional survey bioinventories. The CALeDNA website lets users explore the taxonomic diversity in different ways, and researchers have created tools to help people new to eDNA to analyze community ecology patterns. Although eDNA results are not always precise, the program team is making progress to fit it into California's biodiversity management toolbox, such as for monitoring ecosystem recovery after invasive species removal or wildfire.

The abyssomicins are a structurally intriguing family of bioactive natural products that include compounds with potent antibacterial, antitumour and antiviral activities. The biosynthesis of the characteristic abyssomicin spirotetronate core occurs via an enzyme-catalysed intramolecular Diels-Alder reaction, which proceeds via one of two distinct stereochemical pathways to generate products differing in configuration at the C15 spirocentre. Using the purified spirotetronate cyclases AbyU (from abyssomicin C/atrop-abyssomicin C biosynthesis) and AbmU (from abyssomicin 2/neoabyssomicin biosynthesis), in combination with synthetic substrate analogues, here we show that stereoselectivity in the spirotetronate-forming [4 + 2]-cycloaddition is controlled by a combination of factors attributable to both the enzyme and substrate. Furthermore, an achiral substrate was enzymatically cyclised to a single enantiomer of a spirocyclic product. X-ray crystal structures, molecular dynamics simulations, and assessment of substrate binding affinity and reactivity in both AbyU and AbmU establish the molecular determinants of stereochemical control in this important class of biocatalysts., Competing Interests: The authors declare there are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Rapid advances in biology demand new tools for more active research dissemination and engaged teaching. This paper presents Synteny Explorer, an interactive visualization application designed to let college students explore genome evolution of mammalian species. The tool visualizes synteny blocks: segments of homologous DNA shared between various extant species that can be traced back or reconstructed in extinct, ancestral species. We take a karyogram-based approach to create an interactive synteny visualization, leading to a more appealing and engaging design for undergraduate-level genome evolution education. For validation, we conduct three user studies: two focused studies on color and animation design choices and a larger study that performs overall system usability testing while comparing our karyogram-based designs with two more common genome mapping representations in an educational context. While existing views communicate the same information, study participants found the interactive, karyogram-based views much easier and likable to use. We additionally discuss feedback from biology and genomics faculty, who judge Synteny Explorer's fitness for use in classrooms.

Introduction: Alteration of expression of various genes including extracellular matrix components, have been suggested to play major role in the placental pathologies after somatic cloning in mammals. The objectives of the present study were to analyze pattern of expression (mRNA and protein) of the small leucine-rich proteoglycan, Decorin in association with Type I Collagen and Fibronectin in bovine placental tissues from normal and clone pregnancies., Methods: Genotyping and allelic expression of Decorin were determined by Sanger sequencing. The expression patterns of Decorin, Type I collagen and Fibronectin 1 were analyzed by quantitative RT-qPCR and combined in situ hybydization (ISH) and immunohistochemistry (IHC) in endometrial and placental tissues from D18 to term from artificially inseminated and somatic cloning pregnancies., Results: The expression levels of DCN increased in the AI endometrial stroma and chorionic mesenchyme during implantation and declined during placentome growth until term. Combined ISH and IHC revealed an unexpected discrepancy mRNA and protein tissue distribution. Moreover, Decorin was maintained in the placentome tissues from SCNT pregnancies while both mRNA and protein were absent in AI derived placenta., Discussion: In bovine, the pattern of expression of Decorin exhibits significant changes during placental formation. Downregulation of Decorin is associated with proliferation, remodeling and vascularization of placental tissues. These observations reinforces the putative role of Decorin in these processes., Conclusions: These observations suggest that Decorin is involved in placental growth and that dysregulation of its expression is associated with placental abnormalities in SCNT derived pregnancy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The mRNAs accumulated in oocytes provide support for embryo development until embryo genomic activation. We hypothesized that the maternal mRNA stock present in bovine oocytes is associated with embryo development until the blastocyst stage. To test our hypothesis, we analyzed the transcriptome of the oocyte and correlated the results with the embryo development. Our goal was to identify genes expressed in the oocyte that correlate with its ability to develop to the blastocyst stage. A fraction of oocyte cytoplasm was biopsied using micro-aspiration and stored for further expression analysis. Oocytes were activated chemically, cultured individually and classified according to their capacity to develop in vitro to the blastocyst stage. Microarray analysis was performed on mRNA extracted from the oocyte cytoplasm fractions and correlated with its ability to develop to the blastocyst stage (good quality oocyte) or arrest at the 8-16-cell stage (bad quality oocyte). The expression of 4320 annotated genes was detected in the fractions of cytoplasm that had been collected from oocytes matured in vitro. Gene ontology classification revealed that enriched gene expression of genes was associated with certain biological processes: 'RNA processing', 'translation' and 'mRNA metabolic process'. Genes that are important to the molecular functions of 'RNA binding' and 'translation factor activity, RNA binding' were also enriched in oocytes. We identified 29 genes with differential expression between the two groups of oocytes compared (good versus bad quality). The content of mRNAs expressed in metaphase II oocytes influences the activation of the embryonic genome and enables further develop to the blastocyst stage.

Background: Excessive fear of scrutiny is a defining feature of social anxiety disorder. Eye contact may trigger feelings of being scrutinized, and although eye contact is commonly feared in persons with social anxiety disorder, it has been studied little. The purpose of this study was to characterize fear and avoidance of eye contact in patients with social anxiety disorder and in nonpatient samples., Methods: Gaze fears and avoidance, social anxiety, and depression were assessed in 44 patients with generalized social anxiety disorder, 17 matched healthy comparison subjects, and 79 undergraduates. Patients were reassessed after 8 to 12 weeks of treatment with paroxetine. A new self-report instrument, the Gaze Anxiety Rating Scale (GARS), was used to assess fear and avoidance of eye contact, and its psychometric properties were analyzed., Results: Patients with generalized social anxiety disorder, in comparison with healthy control participants, reported significantly increased levels of fear and avoidance of eye contact, which decreased significantly after 8 to 12 weeks of treatment with paroxetine. Fear and avoidance of eye contact were significantly associated with severity of social anxiety in all 3 samples. The GARS demonstrated excellent internal consistency within each sample., Conclusions: Self-reported fear and avoidance of eye contact are associated with social anxiety in both nonpatient and social anxiety disorder samples. Preliminary psychometric analyses suggest that the GARS has utility in the assessment of gaze anxiety., (© 2011 Elsevier Inc. All rights reserved.)

Background: Observational studies have shown that hormone replacement therapy (HRT) is associated with lower coronary heart disease (CHD), and animal studies demonstrate potent antiatherosclerotic estrogen effects. Paradoxically, recent clinical trials have not demonstrated a protective effect. This paradox may be explained by a healthy woman effect bias. Women using HRT have improved health outcomes unrelated to underlying atherosclerotic burden. Examination of the association between coronary calcium (CC), a marker of atherosclerotic plaque burden, and the use of HRT in postmenopausal women may help address this paradox., Methods: The study population comprised 641 asymptomatic postmenopausal women, 425 (66%) of whom were taking HRT. Data obtained from a self-administered questionnaire and blood samples were analyzed. Electron beam tomography (EBT) for CC was performed on each subject. Analysis of variance (ANOVA) was used to evaluate adjusted means., Results: Independent t tests found that age, low-density lipoproteins (LDL), high-density lipoproteins (HDL), body mass index (BMI), vitamin use, coronary calcium score (CCS), coronary calcified volume (CCV), and the number of coronary calcium lesions (CCL) were significantly different between the HRT group and the non-HRT group. However, after controlling for potential confounders, no significant differences were observed in CCS, CCV, or the number of CCL between the HRT and non-HRT groups. Stratifying by BMI shows that obese/overweight women taking HRT have lower adjusted CCS and fewer CCL than the obese/overweight women not taking HRT., Conclusions: These findings demonstrate no association between HRT use and CCS, CCV, and CCL after adjusting for measurable confounders in postmenopausal women. Our failure to demonstrate an independent association between HRT use and a marker of atherosclerotic plaque burden suggests that a healthy woman effect may explain the beneficial association between HRT use and CHD in observational studies.

Background: Diabetics generally have more frequent and extensive silent myocardial ischemia than nondiabetics, increasing the importance of noninvasive detection of coronary artery disease (CAD) in this cohort. However, little is known regarding the diagnostic accuracy of myocardial perfusion single-photon emission computed tomography (SPECT) in patients with diabetes. This study was undertaken to compare the diagnostic value of rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion SPECT in patients with and without diabetes., Methods: Of the 203 patients with diabetes and 260 patients without diabetes who underwent dual-isotope myocardial perfusion SPECT with exercise or pharmacologic stress testing, 138 diabetics (12% type 1 diabetics) and 188 nondiabetics had coronary angiography within 6 months of the nuclear test, and 65 diabetics and 72 nondiabetics had a low likelihood (<10%, mean 6% +/- 3% and 6% +/- 3%) of CAD., Results: The angiographic data showed that patients with diabetes had less incidence of 1-vessel disease and a higher incidence of 3-vessel/left main artery disease than patients without diabetes (P <.05). The overall sensitivity and specificity, respectively, of SPECT for detecting CAD with the criterion of >/=50% diameter stenosis were 86% (95 of 111) and 56% (15 of 27) in diabetics, 86% (122 of 142) and 46% (21 of 46) in nondiabetics (P = not significant). With the criterion of >/=70% diameter stenosis the corresponding results were 90% (86 of 96) and 50% (21 of 42) in diabetics, and 91% (108 of 119) and 43% (30 of 69) in nondiabetics, respectively (P = not significant). The normalcy rate for low likelihood patients was 89% (58 of 65) in diabetics and 90% (65 of 72) in nondiabetics (P = not significant). The sensitivity and specificity for individual vessel detection were also similar in patients with and without diabetes (P = not significant) except for a lower sensitivity and a higher specificity for detecting left anterior descending coronary artery disease in the diabetic group (P <.05)., Conclusion: Dual-isotope myocardial perfusion SPECT has comparable accuracy for the diagnosis of CAD in diabetic and nondiabetic patients.

Background: We have previously described an automatic method for measuring left ventricular ejection fraction (LVEF) for myocardial perfusion single-photon emission computed tomography (SPECT). The repeatability of this method has not been previously described., Methods and Results: This study compares LVEF and relative end-systolic and end-diastolic volumes assessed from myocardial perfusion SPECT by our automatic method in 180 consecutive patients undergoing gated myocardial perfusion SPECT with injection of 99mTc-labeled sestamibi in whom the acquisitions were performed sequentially in supine and prone positions. The algorithm operated completely automatically in the prone and supine positions in 178 of the 180 patients. Very high correlations were observed for LVEF (r = 0.93), relative left ventricular end-systolic volume (r = 0.98), and relative left ventricular end-diastolic volume (r = 0.97). The mean paired absolute difference between LVEFs in the prone and supine position was 3.8+/-3.2, for left ventricular end-systolic volume was 4.9+/-4.8 ml, and for left ventricular end-diastolic volume was 7.4+/-6.7 ml. When patients were classified by the extent and severity of stress perfusion defect, there was no significant difference in repeatability for the measurements in any category., Conclusions: Our algorithm for automatic quantification of LVEF and relative end-systolic and end-diastolic volumes from gated 99mTc sestamibi myocardial perfusion SPECT is repeatable. When performed in the prone position, values of ejection fractions and ventricular volumes are essentially identical to those obtained in the supine position.

Objectives: We developed an automatic quantitative algorithm for the measurement of regional myocardial wall motion and wall thickening from three-dimensional gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomographic images., Background: The algorithm measures the motion of the three-dimensional endocardial surface using a modification of the centerline method, as well as wall thickening using both geometry (gaussian fit) and partial volume (counts)., Methods: The algorithm was tested using a "variable thickness" heart phantom, and the quantitative results were compared with visual segmental assessment of myocardial motion and thickening in 79 clinical patients with a wide range of ejection fractions (6% to 87%)., Results: Phantom measurements of simulated motion and thickening were accurate regardless of the camera used (dual or triple detector), the angular span of reconstructed data (180 degrees or 360 degrees), the amount of motion (3 or 6 mm) or the amount of thickening (33%, 50% or 100%). Quantitative measurements of segmental motion and thickening in the patients were correlated with visual scores (r = 0.668, exact agreement 72.6%, kappa 0.433 and r = 0.550, exact agreement 74.7%, kappa 0.408, respectively). Significant inverse linear relations exist between the global (summed) visual motion score and the average quantitative motion, and between the global (summed) visual thickening score and the average quantitative thickening. Automatic quantitative ejection fraction measurements correlated extremely well with average quantitative motion (r = 0.929) and thickening (r = 0.959)., Conclusions: Our algorithm is accurate and may be the first automatic technique for the quantitative three-dimensional assessment of regional ventricular function in cardiology.

We examined 1,159 consecutive patients who underwent adenosine stress dual isotope single-photon emission computed tomography (SPECT) and had follow-up performed at a mean of 27.5 +/- 9.1 months (94% complete) for hard events (cardiac death and myocardial infarction) and referral to cardiac catheterization after nuclear testing. During follow-up, 120 hard events occurred (11.0% hard event rate; 72 cardiac deaths [6.7% cardiac death rate] and 57 myocardial infarctions [5.3% myocardial infarction rate]). Cox proportional hazards analysis revealed that nuclear testing added incremental value after adjusting for clinical and historical variables (global chi-square increased 13 to 98 for cardiac death as the end point, global chi-square increased 19 to 105 for hard events as the end point; p <0.0001 for both). Kaplan-Meier analysis demonstrated that after clinical risk stratification of the patient population, the results of nuclear testing were further able to significantly stratify both low- and intermediate- to high-risk patients. Patients with both normal and mildly abnormal scans were at low risk of cardiac death (<1% cardiac death per year of follow-up) and the risk of events increased significantly with worsening scan result. Multivariable analysis revealed that the only predictor of referral to catheterization was the extent and severity of reversible defect present on the scan. Referral rates to early catheterization were very low in patients with normal scans and increased significantly as a function of worsening scan results. In patients who underwent myocardial perfusion SPECT using adenosine stress, the results of nuclear testing yielded incremental prognostic information and clinically relevant risk stratification. Referring physicians predominantly utilized nuclear information when referring patients to catheterization after nuclear testing and do so at rates comparable with those after exercise SPECT despite the higher risk of events in patients undergoing pharmacologic stress.

Noninvasive nuclear imaging techniques, including dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT), have been employed in the development of strategies for diagnosis and risk stratification of patients with suspected or known coronary artery disease. These risk-stratification strategies are based on studies in which known outcome has been linked to diagnostic and prognostic information provided by myocardial perfusion SPECT. This article describes a validated dual-isotope exercise protocol for assessment of perfusion and function and reviews the evidence on which a cost-effective risk management strategy is based.

Individual loci affecting economic traits can be located using genetic linkage. Application of either daughter or granddaughter design requires determination of allele origin in the progeny. If only the sires and their progeny are genotyped, the paternal allele origin of progeny having the same genotype as the sire cannot be determined. The expected frequency of informative sons can be predicted for each sire and genetic marker from the allele frequencies in the population. The accuracy of a predictor of the frequency of informative progeny was tested on 103 grandsire x microsatellite combinations. Number of sons per grandsire varied from 24 to 129. Allele frequencies in the population were estimated by genotyping seven sires. The regression of the frequency of informative sons on the predicted frequency was 1.04 with a zero intercept model. Thus, considering the large number of genetic markers available for analysis, predicted informative frequency is a useful criterion for selection of genetic markers.

On the basis of the "Lipschuetz-ovary" model the rat ovary is cystically altered. -- In such an ovary the effect of a spleen extract (Solcosplen) and FSH (Anternon) were compared with histological and histochemical methods. -- With bothe the substances could be observed a diminution of the cystic degeneration.