A novel stepwise micro-TESE approach in non obstructive azoospermia

Background: The purpose of the study was to investigate whether micro-TESE can improve sperm retrieval rate (SRR) compared to conventional single TESE biopsy on the same testicle or to contralateral multiple TESE, by employing a novel stepwise micro-TESE approach in a population of poor prognosis patients with non-obstructive azoospermia (NOA). Methods: Sixty-four poor prognosis NOA men undergoing surgical testicular sperm retrieval for ICSI, from March 2007 to April 2013, were included in this study. Patients inclusion criteria were a) previous unsuccessful TESE, b) unfavorable histology (SCOS, MA, sclerahyalinosis), c) Klinefelter syndrome. We employed a stepwise micro-TESE consisting three-steps: 1) single conventional TESE biopsy; 2) micro-TESE on the same testis; 3) contralateral multiple TESE. Results: SRR was 28.1 % (18/64). Sperm was obtained in both the initial single conventional TESE and in the following micro-TESE. The positive or negative sperm retrieval was further confirmed by a contralateral multiple TESE, when performed. No significant pre-operative predictors of sperm retrieval, including patients’ age, previous negative TESE or serological markers (LH, FSH, inhibin B), were observed at univariate or multivariate analysis. Micro-TESE (step 2) did not improve sperm retrieval as compared to single TESE biopsy on the same testicle (step 1) or multiple contralateral TESE (step 3). Conclusions: Stepwise micro-TESE could represent an optimal approach for sperm retrieval in NOA men. In our view, it should be offered to NOA patients in order to gradually increase surgical invasiveness, when necessary. Stepwise micro-TESE might also reduce the costs, time and efforts involved in surgery

Testicular histopathology, semen analysis and FSH, predictive value of sperm retrieval: supportive counseling in case of reoperation after testicular sperm extraction (TESE)

Background: To provide indicators for the likelihood of sperm retrieval in patients undergoing testicular sperm extraction is a major issue in the management of male infertility by TESE. The aim of our study was to determine the impact of different parameters, including testicular histopathology, on sperm retrieval in case of reoperation in patients undergoing testicular sperm extraction. Methods: We retrospectively analyzed 486 patients who underwent sperm extraction for intracytoplasmic sperm injection and testicular biopsy. Histology was classified into: normal spermatogenesis; hypospermatogenesis (reduction in the number of normal spermatogenetic cells); maturation arrest (absence of the later stages of spermatogenesis); and Sertoli cell only (absence of germ cells). Semen analysis and serum FSH, LH and testosterone were measured. Results: Four hundred thirty patients had non obstructive azoospermia, 53 severe oligozoospermia and 3 necrozoospermia. There were 307 (63%) successful sperm retrieval. Higher testicular volume, lower levels of FSH, and better histological features were predictive for sperm retrieval. The same parameters and younger age were predictive factors for shorter time for sperm recovery. After multivariable analysis, younger age, better semen parameters, better histological features and lower values of FSH remained predictive for shorter time for sperm retrieval while better semen and histology remained predictive factors for successful sperm retrieval. The predictive capacity of a score obtained by summing the points assigned for selected predictors (1 point for Sertoli cell only, 0.33 points for azoospermia, 0.004 points for each FSH mIU/ml) gave an area under the ROC curve of 0.843. Conclusions: This model can help the practitioner with counseling infertile men by reliably predicting the chance of obtaining spermatozoa with testicular sperm extraction when a repeat attempt is planne

An 8 bit current steering DAC for offset compensation purposes in sensor arrays

Abstract. An 8 bit segmented current steering DAC is presented for the compensation of mismatch of sensors with current output arranged in a large arrays. The DAC is implemented in a 1.8 V supply voltage 180 nm standard CMOS technology. Post layout simulations reveal that the design target concerning a sampling frequency of 2.6 MHz is exceeded, worst-case settling time equals 60.6 ns. The output current range is 0–10 μA, which translates into an LSB of 40 nA. Good linearity is achieved, INL < 0.5 LSB and DNL < 0.4 LSB, respectively. Static power consumption with the outputs operated at a voltage of 0.9 V is approximately 10 μW. Dynamic power, mainly consumed by switching activity of the digital circuit parts, amounts to 100 μW at 2.6 MHz operation frequency. Total area is 38.6 × 2933.0 μm2

Applications of three-dimensional carbon nanotube

In this paper, we show that it is possible to synthesize carbon-based three-dimensional networks by adding sulfur, as growth enhancer, during the synthesis process. The obtained material is self-supporting and consists of curved and interconnected carbon nanotubes and to lesser extent of carbon fibers. Studies on the microstructure indicate that the assembly presents a marked variability in the tube external diameter and in the inner structure. We study the relationship between the observed microscopic properties and some potential applications. In particular, we show that the porous nature of the network is directly responsible for the hydrophobic and the lipophilic behavior. Moreover, we used a cut piece of the produced carbon material as working electrode in a standard electrochemical cell and, thus, demonstrating the capability of the system to respond to incident light in the visible and near-ultraviolet region and to generate a photocurrent

Multitask Learning on Graph Neural Networks: Learning Multiple Graph Centrality Measures with a Unified Network

The application of deep learning to symbolic domains remains an active research endeavour. Graph neural networks (GNN), consisting of trained neural modules which can be arranged in different topologies at run time, are sound alternatives to tackle relational problems which lend themselves to graph representations. In this paper, we show that GNNs are capable of multitask learning, which can be naturally enforced by training the model to refine a single set of multidimensional embeddings $\in \mathbb{R}^d$ and decode them into multiple outputs by connecting MLPs at the end of the pipeline. We demonstrate the multitask learning capability of the model in the relevant relational problem of estimating network centrality measures, focusing primarily on producing rankings based on these measures, i.e. is vertex $v_1$ more central than vertex $v_2$ given centrality $c$?. We then show that a GNN can be trained to develop a \emph{lingua franca} of vertex embeddings from which all relevant information about any of the trained centrality measures can be decoded. The proposed model achieves $89\%$ accuracy on a test dataset of random instances with up to 128 vertices and is shown to generalise to larger problem sizes. The model is also shown to obtain reasonable accuracy on a dataset of real world instances with up to 4k vertices, vastly surpassing the sizes of the largest instances with which the model was trained ($n=128$). Finally, we believe that our contributions attest to the potential of GNNs in symbolic domains in general and in relational learning in particular.Comment: Published at ICANN2019. 10 pages, 3 Figure

Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma

Canine malignant melanoma (MM) is a highly aggressive tumour with a low survival rate and represents an ideal spontaneous model for the human counterpart. Considerable progress has been recently obtained, but the therapeutic success for canine melanoma is still challenging. Little is known about the mechanisms beyond pathogenesis and melanoma development, and the molecular response to radiotherapy has never been explored before. A faster and deeper understanding of cancer mutational processes and developing mechanisms are now possible through next generation sequencing technologies. In this study, we matched whole exome and transcriptome sequencing in four dogs affected by MM at diagnosis and at disease progression to identify possible genetic mechanisms associated with therapy failure. According to previous studies, a genetic similarity between canine MM and its human counterpart was observed. Several somatic mutations were functionally related to MAPK, PI3K/AKT and p53 signalling pathways, but located in genes other than BRAF, RAS and KIT. At disease progression, several mutations were related to therapy effects. Natural killer cell-mediated cytotoxicity and several immune-system-related pathways resulted activated opening a new scenario on the microenvironment in this tumour. In conclusion, this study suggests a potential role of the immune system associated to radiotherapy in canine melanoma, but a larger sample size associated with functional studies are needed

Structural basis for cooperativity of human monoclonal antibodies to meningococcal factor H-binding protein

Monoclonal antibody (mAb) cooperativity is a phenomenon triggered when mAbs couples promote increased bactericidal killing compared to individual partners. Cooperativity has been deeply investigated among mAbs elicited by factor H-binding protein (fHbp), a Neisseria meningitidis surface-exposed lipoprotein and one of the key antigens included in both serogroup B meningococcus vaccine Bexsero and Trumenba. Here we report the structural and functional characterization of two cooperative mAbs pairs isolated from Bexsero vaccines. The 3D electron microscopy structures of the human mAb-fHbp-mAb cooperative complexes indicate that the angle formed between the antigen binding fragments (fAbs) assume regular angle and that fHbp is able to bind simultaneously and stably the cooperative mAbs pairs and human factor H (fH) in vitro. These findings shed light on molecular basis of the antibody-based mechanism of protection driven by simultaneous recognition of the different epitopes of the fHbp and underline that cooperativity is crucial in vaccine efficacy

Trend of incidence, subsite distribution and staging of colorectal neoplasms in the 15-year experience of a specialised cancer registry

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