ATAC-clock: An aging clock based on chromatin accessibility.

The establishment of aging clocks highlighted the strong link between changes in DNA methylation and aging. Yet, it is not known if other epigenetic features could be used to predict age accurately. Furthermore, previous studies have observed a lack of effect of age-related changes in DNA methylation on gene expression, putting the interpretability of DNA methylation-based aging clocks into question. In this study, we explore the use of chromatin accessibility to construct aging clocks. We collected blood from 159 human donors and generated chromatin accessibility, transcriptomic, and cell composition data. We investigated how chromatin accessibility changes during aging and constructed a novel aging clock with a median absolute error of 5.27 years. The changes in chromatin accessibility used by the clock were strongly related to transcriptomic alterations, aiding clock interpretation. We additionally show that our chromatin accessibility clock performs significantly better than a transcriptomic clock trained on matched samples. In conclusion, we demonstrate that the clock relies on cell-intrinsic chromatin accessibility alterations rather than changes in cell composition. Further, we present a new approach to construct epigenetic aging clocks based on chromatin accessibility, which bear a direct link to age-related transcriptional alterations, but which allow for more accurate age predictions than transcriptomic clocks.

Explainable clinical coding with in-domain adapted transformers.

BACKGROUND AND OBJECTIVE: Automatic clinical coding is a crucial task in the process of extracting relevant information from unstructured medical documents contained in Electronic Health Records (EHR). However, most of the existing computer-based methods for clinical coding act as "black boxes", without giving a detailed description of the reasons for the clinical-coding assignments, which greatly limits their applicability to real-world medical scenarios. The objective of this study is to use transformer-based models to effectively tackle explainable clinical-coding. In this way, we require the models to perform the assignments of clinical codes to medical cases, but also to provide the reference in the text that justifies each coding assignment. METHODS: We examine the performance of 3 transformer-based architectures on 3 different explainable clinical-coding tasks. For each transformer, we compare the performance of the original general-domain version with an in-domain version of the model adapted to the specificities of the medical domain. We address the explainable clinical-coding problem as a dual medical named entity recognition (MER) and medical named entity normalization (MEN) task. For this purpose, we have developed two different approaches, namely a multi-task and a hierarchical-task strategy. RESULTS: For each analyzed transformer, the clinical-domain version significantly outperforms the corresponding general domain model across the 3 explainable clinical-coding tasks analyzed in this study. Furthermore, the hierarchical-task approach yields a significantly superior performance than the multi-task strategy. Specifically, the combination of the hierarchical-task strategy with an ensemble approach leveraging the predictive capabilities of the 3 distinct clinical-domain transformers, yields the best obtained results, with f1-score, precision and recall of 0.852, 0.847 and 0.849 on the Cantemist-Norm task and 0.718, 0.566 and 0.633 on the CodiEsp-X task, respectively. CONCLUSIONS: By separately addressing the MER and MEN tasks, as well as by following a context-aware text-classification approach to tackle the MEN task, the hierarchical-task approach effectively reduces the intrinsic complexity of explainable clinical-coding, leading the transformers to establish new SOTA performances for the predictive tasks considered in this study. In addition, the proposed methodology has the potential to be applied to other clinical tasks that require both the recognition and normalization of medical entities.

Description of the Third-Stage Larva and Puparium of Platycheirus (Carposcalis) chalconota (Philippi) (Diptera: Syrphidae) with New Information About the Trophic Interactions and Larval Habitats.

In this study, the third-stage larva and puparium of the copper-backed fly, Platycheirus (Carposcalis) chalconota (Philippi, 1865) are fully described using stereomicroscopy and scanning electron microscopy from material collected in peach orchards of central-west Argentina. The immature stages of P. chalconota were compared with the third-stage larva and puparium of the best-studied species in the genus Platycheirus scutatus (Meigen, 1822); as well as with the only known Carposcalis immature stages description available for the Neotropical region namely Platycheirus stegnus (Say, 1829). New data on trophic interactions and larval habitats are given: P. chalconota larvae were found feeding on the aphid's species Uroleucon sonchi (Linnaeus, 1767) (large sow thistle aphid) and Hyperomyzus lactucae (Linnaeus, 1758) (blackcurrant-sow thistle aphid) in low vegetation as Sonchus oleraceus (common sow thistle); the species was also found feeding on Myzus persicae (Sulzer, 1776) (green peach aphid) in high vegetation as Prunus persicae (L.) Stokes (Peach trees). The third larval stage and puparium of P. chalconota are described and illustrated for the first time improving substantially the knowledge about the immature stages and natural history of Neotropical Platycheirus, constituting also a baseline for future comparative morphological studies. Despite the efficiency of P. chalconota in the biological control of pests has not been assessed, we think that relevant data presented here can be used in pest management of peach orchards and suggest P. chalconota as an excellent candidate for future studies on the life cycle, prey consumption, efficiency, artificial rearing, and its potential importance as pollinators of Peach crops.

Unusual host selection in Amblycerus dispar larvae (Coleoptera: Chrysomelidae: Bruchinae) and its potential impact on stored almonds (Prunus dulcis).

We present the first report of Amblycerus dispar (Sharp) attacking stored almonds [Prunus dulcis (Mill.) D. A. Webb] in Argentina. A summarized diagnosis, illustrations, and photographs of the adult and mature larva are provided to facilitate identification. We performed species distribution models for A. dispar and its main host plant Geoffroea decorticans (Gillies ex Hook. & Arn.) Burkart. We include A. dispar into a previous morphological character matrix and conduct a phylogenetic analysis to infer its phylogenetic position. The evolution of host plant associations of the genus Amblycerus is herein re-analyzed. A. dispar and its main host shows high suitability areas especially in central-west Argentina and Chile, whereas for the USA, high suitability areas were found for the south-western which include the area of almond production in this country. Although the presence of A. dispar in the USA region is very unlikely, we recommend some awareness as other bruchines are present in the area. Although A. dispar is unlikely to become an economically important risk, monitoring for early detection is recommended to avoid productivity loss, especially when the native host is nearby cultivated areas. A. dispar is hypothesized to be the sister species of A. schwarzi Kingsolver. The colonization of a Rosaceae species is a novelty for this genus, being host shifts known as an important factor affecting both natural and agricultural systems.

Transfer learning with convolutional neural networks for cancer survival prediction using gene-expression data.

Precision medicine in oncology aims at obtaining data from heterogeneous sources to have a precise estimation of a given patient's state and prognosis. With the purpose of advancing to personalized medicine framework, accurate diagnoses allow prescription of more effective treatments adapted to the specificities of each individual case. In the last years, next-generation sequencing has impelled cancer research by providing physicians with an overwhelming amount of gene-expression data from RNA-seq high-throughput platforms. In this scenario, data mining and machine learning techniques have widely contribute to gene-expression data analysis by supplying computational models to supporting decision-making on real-world data. Nevertheless, existing public gene-expression databases are characterized by the unfavorable imbalance between the huge number of genes (in the order of tenths of thousands) and the small number of samples (in the order of a few hundreds) available. Despite diverse feature selection and extraction strategies have been traditionally applied to surpass derived over-fitting issues, the efficacy of standard machine learning pipelines is far from being satisfactory for the prediction of relevant clinical outcomes like follow-up end-points or patient's survival. Using the public Pan-Cancer dataset, in this study we pre-train convolutional neural network architectures for survival prediction on a subset composed of thousands of gene-expression samples from thirty-one tumor types. The resulting architectures are subsequently fine-tuned to predict lung cancer progression-free interval. The application of convolutional networks to gene-expression data has many limitations, derived from the unstructured nature of these data. In this work we propose a methodology to rearrange RNA-seq data by transforming RNA-seq samples into gene-expression images, from which convolutional networks can extract high-level features. As an additional objective, we investigate whether leveraging the information extracted from other tumor-type samples contributes to the extraction of high-level features that improve lung cancer progression prediction, compared to other machine learning approaches.

Testing the Insecticidal Activity of Nanostructured Alumina on Sitophilus oryzae (L.) (Coleoptera: Curculionidae) Under Laboratory Conditions Using Galvanized Steel Containers.

Most stored-grain pest insects increase their population within a relatively short time, causing serious damage to stored products. Sitophilus oryzae (L.) is one of the world's major stored-grain pest insects and was chosen as the model insect for our studies. This study compared the efficacy of three different dusts under laboratory conditions: aluminum dust (nanostructured alumina), DiatomiD®, and Protect-It® (commercial diatomaceous earth). Parental survival, grain damage, and progeny production were measured at 250 and 500 ppm in treated wheat. The tests were conducted in 400 mL galvanized steel jars, an experimental model used for the first time to measure the effectiveness of nanostructured alumina, since most studies have been typically performed in small petri dishes. Parental survival obtained was highest in the untreated controls, followed in decreasing order by DiatomiD®, Protect-It®, and nanostructured alumina (NSA). NSA caused the greatest mortality. All treatments significantly reduced grain weight loss and frass production in wheat infested by S. oryzae. The degree of progeny (F1) suppression was directly related to the product and treatment rate, progeny being significantly suppressed by NSA in wheat followed by Protect-It® and DiatomiD®. Therefore, NSA had a greater impact on insect population dynamics.

Emisores políticos, mediáticos y ciudadanos en internet: hacia un nuevo marco comunicativo en la jornada de reflexión en España / Political broadcasting, the media and citizens on the Internet: towards a new communication milestone for the day of reflection in Spain

Resumen La campaña electoral en España está regulada por la ley orgánica de régimen electoral general 5/1985, que no contempla ninguna medida específica para la cibercampaña. Este vacío legal motiva a los emisores a realizar una interpretación de la norma cuando se comunican en internet durante este periodo. Con el fin de explorar si el nuevo tempo y forma de comunicación en internet se corresponde con un nuevo espacio comunicativo, este estudio analiza los mensajes que políticos, periodistas y ciudadanos se intercambiaron en la jornada de reflexión de las últimas elecciones generales españolas (2011) y muestra cómo esta jornada, comprendida hasta la fecha como un día de reflexión silenciosa, cobra un nuevo sentido en internet.

Abstract Electoral campaigns in Spain are governed by Organic Law 5/1985 on the general election system, which does not include any specific measures on cybercampaigns. This legal vacuum has led the media to come up with their own interpretion of the regulations when engaging in Internet communications during this period. In order to explore whether the new speed and style of communicating by Internet is matched by a new communication space, this article analyzes the messages that politicians, journalists and citizens exchanged during the day of reflection in Spain’s last general election (2011), showing how what has, until now, been seen as a day of silent reflection takes on a new meaning with the Internet.

[Political broadcasting, the media and citizens on the Internet: towards a new communication milestone for the day of reflection in Spain]. / Emisores políticos, mediáticos y ciudadanos en internet: hacia un nuevo marco comunicativo en la jornada de reflexión en España.

Electoral campaigns in Spain are governed by Organic Law 5/1985 on the general election system, which does not include any specific measures on cybercampaigns. This legal vacuum has led the media to come up with their own interpretion of the regulations when engaging in Internet communications during this period. In order to explore whether the new speed and style of communicating by Internet is matched by a new communication space, this article analyzes the messages that politicians, journalists and citizens exchanged during the day of reflection in Spain's last general election (2011), showing how what has, until now, been seen as a day of silent reflection takes on a new meaning with the Internet.

Transvaginal color Doppler imaging in the detection of ovarian cancer in a large study population.

INTRODUCTION: The aim of the study was to compare the diagnostic accuracy of grayscale sonography and that of color Doppler imaging in the diagnosis of ovarian malignancy in a prospective study by the Sardinia-Navarra group. METHODS: The study was performed as a collaborative work at the 2 European university departments of obstetrics and gynecology between 1997 and 2007. A total of 2148 pelvic masses in 1997 women on whom transvaginal sonography were performed before surgical exploration were included in the study. An adnexal mass was first studied in grayscale sonography, and any cystic mass in which the echo architecture was not suggestive of benign tumor was categorized as malignant. Second, any solid excrescences or solid portions of the tumor were evaluated with color/power Doppler sonography. A mass was graded malignant if flow was shown within the excrescences or the solid areas and benign if there was no flow or if flow was only peripheral. RESULTS: Four hundred sixty-eight masses were malignant. Color Doppler evaluation was more accurate in the diagnosis of adnexal malignancies in comparison with grayscale sonography because of a significantly higher specificity (94% vs 89%, P = 0.001), with similar sensitivity (95% vs 98%, P = 0.44). The pretest probability of ovarian cancer was 22%, and this probability rose to 82% when the diagnosis was suggested by color Doppler evaluation. The diagnostic accuracy of the tests was also dependent on menopausal status. CONCLUSIONS: The evaluation of vessel distribution by color Doppler sonography in adnexal masses increases the diagnostic accuracy of grayscale sonography in the detection of adnexal malignancies in a large study population.

Tumor vascularization in cervical cancer by 3-dimensional power Doppler angiography: correlation with tumor characteristics.

OBJECTIVE: To evaluate whether tumor vascularity as assessed by 3-dimensional power Doppler angiography (3D-PDA) correlates with some tumor features in cervical cancer. METHODS: Clinical, sonographic, and histologic data on 56 women (mean age, 47.8 years; range, 27-81 years) with a diagnosis of carcinoma in the uterine cervix were analyzed. Tumor volume and 3D-PDA indexes (vascularization index, flow index, and vascularization flow index) were calculated in all cases. These data were correlated with some tumoral features such as histologic type, histologic grade, lymphovascular space involvement, lymph node metastases, and tumor stage. RESULTS: Intratumoral blood flow was found in all cases. No correlation was found between tumor volume and 3D-PDA indexes with histologic type, lymphovascular space involvement, and lymph node metastases. Moderately and poorly differentiated tumors and advanced-stage tumors had larger volume and 3D-PDA indexes (P < 0.05). CONCLUSIONS: Our data indicate that tumor vascularization as assessed by 3D-PDA correlates with some tumor features in cervical cancer.

The value of minilaparotomy for total hysterectomy for benign uterine disease: a comparative study with conventional Pfannenstiel and laparoscopic approaches.

BACKGROUND: The aim of this paper is to review and compare the results obtained using the Pfannenstiel, laparoscopy and minilaparotomy approaches for total hysterectomy procedure in relation to benign uterine diseases. METHODS: A retrospective data analysis was performed on 165 patients who underwent hysterectomy for benign uterine diseases at our centre during the period 2004 to 2006. FINDINGS: The minilaparotomy procedure was the fastest procedure with a mean time of 73.4 minutes (range: 67.85 to 78.94 minutes, p < 0.001). Hospital stay was shortest for laparosopic procedure (mean time: 3.24 days, range: 2.86 to 3.61 days) (p < 0.001). The rate of intraoperative and postoperative complications were not statistical different among three procedures. CONCLUSION: The minilaparotomy procedure offers a minimally invasive option for total hysterectomy due to benign uterine disease.

Assessing myometrial infiltration by endometrial cancer: uterine virtual navigation with three-dimensional US.

PURPOSE: To describe and analyze the diagnostic performance of uterine virtual navigation with three-dimensional (3D) ultrasonography (US) for the assessment of the depth of myometrial infiltration by endometrial cancer. MATERIALS AND METHODS: Institutional review board approval was obtained; patients gave oral informed consent. Women with endometrial cancer were evaluated by using 3D US prior to surgical staging. A 3D volume of the whole uterus was obtained and analyzed by using software. Virtual navigation through three orthogonal planes was performed to identify the shortest myometrial tumor-free distance to serosa (TDS) by analyzing the lateral, anterior, posterior, and fundal portions of the myometrium. Myometrial infiltration was also assessed by subjective impression of an examiner. Histologic findings of myometrial infiltration and TDS measured by a pathologist were used as the reference standard. A receiver operating characteristic curve was plotted to identify the best cutoff for TDS for identifying myometrial infiltration of 50% or more. RESULTS: Ninety-six women (mean age, 61.8 years; range, 31-86 years) with endometrial cancer were included in the study. At histologic analysis, myometrial invasion was found to be less than 50% in 69 (72%) cases and 50% or more in 27 (28%) cases. TDS measured with US was positively correlated with histologically measured TDS (r = 0.649; 95% confidence interval: 0.52, 0.76). The best cutoff for US-measured TDS was 9.0 mm (sensitivity, 100%; specificity, 61%; negative predictive value, 100%; positive predictive value, 50%). Subjective impression had a sensitivity of 92.6%, a specificity of 82.3%, a negative predictive value of 96.6%, and a positive predictive value of 67.7%. CONCLUSION: Uterine virtual navigation with 3D US is a reliable method for the assessment of myometrial infiltration in patients with endometrial cancer.

Diagnostic accuracy of FDG PET in the follow-up of platinum-sensitive epithelial ovarian carcinoma.

PURPOSE: This study was designed to retrospectively evaluate the diagnostic yield of FDG PET for the diagnosis of recurrent ovarian cancer. METHODS: Eighty FDG PET scans were performed on 55 patients owing to suspicion of relapse, and 45 FDG PET scans were performed on 31 patients who were clinically disease free. PET results were compared with the results of conventional radiological imaging (CIM) and serum CA 125 levels, and related to pathological findings in 54 cases or clinical follow-up in 71 cases. RESULTS: CIM correctly identified 49 cases with recurrence [sensitivity (SE) 53.3%] ,and there were 27 true negatives [specificity (SP) 81.8%] However, 43 cases were false negative and six were false positive. The positive predictive value (PPV), negative predictive value (NPV) and accuracy (ACC) of CIM were 89%, 38.6% and 60.8%, respectively. FDG PET correctly detected recurrent disease in 80/92 cases (SE 86.9%, p<0.05) and ruled out relapse in 26/33 cases (SP=78.8%). The PPV, NPV and ACC of PET were 91.9%, 68.4% and 84.8%, respectively. Standardised uptake values did not provide additional diagnostic accuracy compared with visual analysis. The CA 125 results showed an SE of 57.6%, an SP of 93.9% and an ACC of 67.2%. In 23 patients with positive serum CA 125 levels, but negative CIM, FDG PET was positive and relapse was confirmed. Furthermore, FDG PET was positive and relapse was confirmed in 11 patients with negative serum CA 125 levels and CIM. CONCLUSION: FDG PET may detect recurrent ovarian cancer earlier than CIM, with higher sensitivity and even higher diagnostic accuracy.

Endometrial volume and vascularity measurements by transvaginal 3-dimensional ultrasonography and power Doppler angiography in stimulated and tumoral endometria: an interobserver reproducibility study.

OBJECTIVE: The purpose of this study was to evaluate interobserver reproducibility of endometrial volume and vascular indices of the endometrium and subendometrial area estimated by 3-dimensional power Doppler angiography (3D-PDA) using the Virtual Organ Computer-Aided Analysis program, determining the influence of the endometrial growth etiology on measurements. METHODS: Forty women underwent 3D-PDA ultrasonography. Group A comprised 25 women scanned on the day after controlled ovarian stimulation with human chorionic gonadotropin. Group B comprised 15 patients who had uterine bleeding and questionable endometrial thickening. (Histologic evaluation revealed 10 endometrial cancers and 5 endometrial hyperplasias.) A single observer examined all patients and acquired all volume data sets. Forty volume data sets were then analyzed with the Virtual Organ Computer-Aided Analysis program by 2 different observers. Endometrial volume and vascularity indices (vascularization index [VI], flow index [FI], and vascularization flow index [VFI]) of the endometrium and subendometrium were manually calculated in the coronal plane with a 9 degrees rotation step. An intraclass correlation coefficient (ICC) was used to assess interobserver reliability. RESULTS: Endometrial volume was more reproducible in group A (ICC = 0.98) than in group B (ICC = 0.58) (P < .05). Endometrial and subendometrial VI, FI, and VFI also presented good reproducibility with ICC greater than 0.84. The ICC was not statistically different for endometrial and subendometrial VI, FI, and VFI according to patient group, although subendometrial VFI was less reproducible in group B (ICC = 0.53) than in group A (ICC = 0.88). CONCLUSIONS: Endometrial volume and endometrial and subendometrial 3D power Doppler indices have acceptable reproducibility. The interobserver reproducibility in tumoral endometrium was more similar than in stimulated endometrium. Our results indicate that 3D-PDA is a reliable method to evaluate physiologic and pathologic endometrial changes.

A new scoring system to differentiate benign from malignant adnexal masses.

OBJECTIVE: The purpose of this study was to develop and cross-validate a new sonographic scoring system for differentiation between benign and malignant adnexal masses. STUDY DESIGN: This study was conducted in a tertiary care university hospital. In the first part of the study, we used a multivariate logistic regression analysis to develop a scoring system that was based on morphologic and Doppler sonographic data for 705 adnexal masses in 665 patients who were diagnosed and treated at our institution from January 1995 to June 2001. The scoring system was designed to use only those parameters that are found to be independent predictors of malignancy. In the second part of the study, we prospectively cross-validated this scoring system in a series of 90 adnexal masses in 86 patients between July 2001 and March 2002. With the use of the area under the curve of the respective ROC curves, we compared the new scoring system with other scoring systems. RESULTS: Multivariate logistic regression analysis revealed that the only independent predictor parameters were thick papillary projections, solid areas, central flow, and velocimetric features of high velocity and low resistance. In the prospective cross-validation study, our scoring system had the best diagnostic performance (area under the curve, 0.98) compared with Sassone (area under the curve, 0.89; P =.017), De Priest (area under the curve, 0.92; P =.048), and Ferrazzi (area under the curve, 0.90; P =.013) scoring systems. CONCLUSION: Our new sonographic scoring system had a better diagnostic performance than three previously published scoring systems.

Intratumoral blood flow analysis in endometrial carcinoma: correlation with tumor characteristics and risk for recurrence.

OBJECTIVE: The aim of this study was to correlate intratumoral blood flow as assessed by transvaginal color Doppler ultrasound with tumor histopathologic characteristics, tumoral stage, and risk for recurrence in endometrial carcinoma. METHODS: Forty-five patients (mean age: 58.2 years, range: 30 to 83 years) with surgically treated endometrial carcinoma preoperatively evaluated with transvaginal color Doppler ultrasound were included in this retrospective study. The lowest arterial resistance index (RI) and highest peak systolic velocity (PSV) were used for intratumoral blood flow analysis. Individual tumor characteristics evaluated were tumor growth pattern, tumor size, histologic type, tumor grade, myometrial infiltration depth, cervical involvement, lymph node metastasis, and lymph-vascular space invasion (LVSI). Tumoral stage and risk for recurrence were also evaluated. RESULTS: Significantly lower RI was found in tumors with the following characteristics: infiltrative growth pattern (P = 0,013), grade 3 (P = 0.001), infiltrating >or=50% of the myometrium (P = 0.006), cervical involvement (P = 0.009), LVSI (P = 0.008), lymph-node metastasis (P = 0.049), stage >or=Ic (P = 0.004), and high risk for recurrence (P = 0.001). Significantly higher PSV was found in tumors that were grade 3 (P = 0.034), infiltrating >or=50% of the myometrium (P = 0.029), stage >or=Ic (P = 0.015), and with a high risk for recurrence (P = 0.002). CONCLUSIONS: Our data indicate that a correlation between intratumoral blood flow features and histopathological characteristics, tumor stage, and risk for recurrence exists in endometrial cancer. Further prospective studies are needed to determine the clinical usefulness of preoperative assessment of tumor vascularization in these carcinomas.