课程文献中心 更多>>

关键词： Head and neck squamous cell carcinoma   Unknown primary   F-18-FDG PET   CT   Detection rate  

摘要： Purpose We performed a systemic review and meta-analysis to evaluate the performance of F-18-FDG-PET/CT as a next step in the search of occult primary tumors for patients with head and neck squamous cell carcinoma of unknown primary (HNSCC-UP). Methods PubMed and Embase databases were searched from the earliest available date of indexing through February 2021. Eligible studies were those using F-18-FDG-PET/CT to detect occult primary tumors for HNSCC-UP, of which the defining diagnostic workup had been limited to endoscopy with or without CT/MRI. The detection rates were meta-analytically pooled using a random-effects model. Subgroup analyses and meta-regression were performed to explore the source of heterogeneity. A pooled analysis evaluating the false-positive proportions was also performed. Results Sixteen studies with 724 patients were included in this meta-analysis. The pooled detection rate was 40% (95% CI 31-49%), with high heterogeneity (I-2 = 85.2%). No sources of heterogeneity were identified by analyzing multiple subgroups stratified by study design, sample size, ethnicity, use of contrast agent, defining diagnostic workup, image analysis, and reference standard (All P > 0.05). The most common sites of both true-positive cases and false-positive cases were tonsil and tongue base. The pooled false-positive proportion was 9% (95% CI 5-13%). Conclusions F-18-FDG PET/CT is useful as a next step in the search of occult primary tumors in HNSCC-UP patients defined by endoscopy with or without CT/MRI. However, in light of the high false-positive proportion, confirmatory histological investigations should be viewed as necessary practice upon positive PET/CT findings.

摘要： Background Peritoneal metastases portend poor prognosis in the setting of standard chemotherapy. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes, but relapse is common. We report a phase II trial evaluating the safety and efficacy of adjuvant alpha DC1 vaccination with chemokine modulation (CKM) after CRS/HIPEC. Methods Patients undergoing CRS/HIPEC for appendiceal cancer, colorectal cancer, or peritoneal mesothelioma were enrolled. In addition to standard adjuvant chemotherapy, patients received intranodal and intradermal injections of autologous tumor-loaded alpha DC1 vaccine. After each vaccine booster, patients received CKM over 4 days, consisting of celecoxib, interferon (IFN)-alpha, and rintatolimod. Results Forty-six patients underwent CRS/HIPEC followed by alpha DC1 treatment, including 24 appendiceal primaries, 20 colorectal, and 2 mesotheliomas. DC maturation was successful, with 97% expressing HLA-DR and CD86. Tumor cell recovery from peritoneal tumors was challenging, resulting in only 17% of patients receiving the target dose of alpha DC1. The alpha DC1 and CKM regimen was well tolerated. CKM successfully modulated serum inflammatory cytokine and chemokine levels. Median progression-free survival (PFS) for appendiceal primaries was 50.4, 34.2, and 8.9 months for grade 1, 2, and 3 tumors, respectively, while median PFS for colorectal cancer was 20.5 and 8.9 months for moderately and poorly differentiated tumors, respectively. Conclusions Adjuvant autologous tumor antigen-loaded alpha DC1 vaccine and CKM is well tolerated. The mucinous nature of peritoneal metastases limits the feasibility of obtaining adequate autologous tumor cells. The improvement in median PFS did not meet our predefined thresholds, leading us to conclude that alpha DC1 vaccination is not appropriate for patients undergoing CRS/HIPEC for peritoneal metastases.

关键词： Image recognition   Computer vision and image processing techniques   Neural nets  

摘要： The purpose of this study is to introduce efficient bio-inspired vision architectures, integrating human cognition capabilities, such as computation and memory emulating neurons and synapses, together with polarization of light properties, that would ultimately revolutionize and give rise to the next-generation highly efficient augmented intelligence vision systems. The system consists of a polarimetric dynamic vision sensor) and a spinning wheel, whose motion is externally modulated and controlled by means of a signal generator, varying its motion pattern and speed, respectively. A neural network has been designed to classify different object speeds and motion patterns. The neural network utilizes a limited number of events within a given time window, instead of full-frame images;as well as two classifiers, which practically take a single input and independently classify both its speed and motion pattern. As a result, both high computational efficiency and motion classification accuracy are achieved.

关键词： myotonic dystrophy type 1   human primary muscle cell culture   transcriptomics   splicing  

摘要： Myotonic dystrophy type 1 (DM1) is caused by CTG-repeat expansions leading to a complex pathology with a multisystemic phenotype that primarily affects the muscles and brain. Despite a multitude of information, especially on the alternative splicing of several genes involved in the pathology, information about additional factors contributing to the disease development is still lacking. We performed RNAseq and gene expression analyses on proliferating primary human myoblasts and differentiated myotubes. GO-term analysis indicates that in myoblasts and myotubes, different molecular pathologies are involved in the development of the muscular phenotype. Gene set enrichment for splicing reveals the likelihood of whole, differentiation stage specific, splicing complexes that are misregulated in DM1. These data add complexity to the alternative splicing phenotype and we predict that it will be of high importance for therapeutic interventions to target not only mature muscle, but also satellite cells.

摘要： Male infertility impacts millions of couples yet, the etiology of primary infertility remains largely unknown. A critical element of successful spermatogenesis is maintenance of genome integrity. Here, we present a genomic study of spermatogenic failure (SPGF). Our initial analysis (n = 176) did not reveal known gene-candidates but identified a potentially significant single-nucleotide variant (SNV) in X-linked germ-cell nuclear antigen (GCNA). Together with a larger follow-up study (n = 2049), 7 likely clinically relevant GCNA variants were identified. GCNA is critical for genome integrity in male meiosis and knockout models exhibit impaired spermatogenesis and infertility. Single-cell RNA-seq and immunohistochemistry confirm human GCNA expression from spermatogonia to elongated spermatids. Five identified SNVs were located in key functional regions, including N-terminal SUMO-interacting motif and C-terminal Spartan-like protease domain. Notably, variant ***115ProfsTer7 results in an early frameshift, while Spartan-like domain missense variants ***659Trp and ***664Cys change conserved residues, likely affecting 3D structure. For variants within GCNA's intrinsically disordered region, we performed computational modeling for consensus motifs. Two SNVs were predicted to impact the structure of these consensus motifs. All identified variants have an extremely low minor allele frequency in the general population and 6 of 7 were not detected in > 5000 biological fathers. Considering evidence from animal models, germ-cell-specific expression, 3D modeling, and computational predictions for SNVs, we propose that identified GCNA variants disrupt structure and function of the respective protein domains, ultimately arresting germ-cell division. To our knowledge, this is the first study implicating GCNA, a key genome integrity factor, in human male infertility.

关键词： Long-term cognitive networks   Recurrent neural networks   Backpropagation   Multi-label classification  

摘要： This paper presents a neural system to deal with multi-label classification problems that might involve sparse features. The architecture of this model involves three sequential blocks with well-defined functions. The first block consists of a multilayered feed-forward structure that extracts hidden features, thus reducing the problem dimensionality. This block is useful when dealing with sparse problems. The second block consists of a Long-term Cognitive Network-based model that operates on features extracted by the first block. The activation rule of this recurrent neural network is modified to prevent the vanishing of the input signal during the recurrent inference process. The modified activation rule combines the neurons' state in the previous abstract layer (iteration) with the initial state. Moreover, we add a bias component to shift the transfer functions as needed to obtain good approximations. Finally, the third block consists of an output layer that adapts the second block's outputs to the label space. We propose a backpropagation learning algorithm that uses a squared hinge loss function to maximize the margins between labels to train this network. The results show that our model outperforms the state-of-the-art algorithms in most datasets. (C) 2021 The Author(s). Published by Elsevier Ltd.

关键词： metastatic RCC   systemic targeted therapy   sunitinib   rechallenge   clinical outcomes   #uroonc   #kcsm   #KidneyCancer  

摘要： Objective To assess the efficacy and tolerability of rechallenge with sunitinib and other targeted therapies (TTs) in patitents with relapsed recurrent renal cell carcinoma (RCC) in the advanced setting. Methods In this multi-institutional retrospective study, patients with relapsed RCC were rechallenged with sunitinib or other systemic TTs as a first-line therapeutic approach after failed adjuvant sunitinib treatment. Patient characteristics, treatments and clinical outcomes were recorded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR) and overall survival (OS). Results A total of 34 patients with relapses were recorded, and 25 of these (73.5%) were men. Twenty-five patients were treated with systemic TT: 65% of patients received TT against the vascular endothelial growth factor pathway (including sunitinib), 21.7% received mammalian target of rapamycin inhibitors and 13% received immunotherapy. The median (interquartile range) time to relapse was 20.3 (5.2-20.4) months from diagnosis, and 7.5 months (1.0-8.5) from the end of adjuvant suntinib treatment. At a median follow-up of 23.5 months, 24 of the 25 patients had progressed on first-line systemic therapy. The median PFS was 12.0 months (95% confidence interval [CI] 5.78-18.2). There were no statistical differences in PFS between different treatments or sunitinib rechallenge. PFS was not statistically different in patients relapsing on or after adjuvant suntinib treatment (<= 6 or >6 months after adjuvant suntinib ending). The ORR was 20.5%. The median OS was 29.1 months (95% CI 16.4-41.8). Conclusions Rechallenge with sunitinib or other systemic therapies is still a feasible therapeutic option that provides patients with advanced or metastastic RCC with additional clinical benefits with regard to PFS and OS after failed response to adjuvant sunitinib.

关键词： Hypopituitarism   Autoimmunity   Anti-pituitary antibody   Cell mediated immune response  

摘要： Introduction Primary autoimmune hypophysitis (PAHs) is a rare inflammatory disease of the pituitary gland. Although largely investigated, the pathogenesis of PAH is not completely clarified. We aimed to investigate the immune response in PAHs. Material and methods Serum anti-pituitary and anti-hypothalamus antibodies (respectively APAs and AHAs) were investigated though an indirect immunofluorescence on monkey hypophysis and hypothalamus slides, serum cytokines though an array membrane and cell-mediated immunity though the white blood cells count. Results Nineteen PAH cases entered the study. APA or AHA were identified in all cases. APA were detected in 13 patients (68.4%) and AHA in 13 patients (68.4%). Ten patients (52.6%) were simultaneously positive for both APA and AHA. The prevalence of APAs and AHAs was higher as compared to those observed in 50 health controls (respectively 14% p < 0.001 and 24% p = 0.004) and in 100 not-secreting pituitary adenoma (NFPAs) (respectively 22% p = 0.002 and 8% p < 0.001). Similarly, the prevalence of simultaneous positivity for APA and AHA (52.9%) was higher as compared to the those detected in patients affected by NFPAs (0%;p < 0.001) and in health controls (16% p = 0.002). No differences were identified between PAHs and controls at qualitative and quantitative analysis of serum cytokines and white blood cells count. Conclusions This study suggest that APA and AHA may be detected in an high percentage of PAH cases and that their simultaneous identification may be useful for the differential diagnosis between PAH and NFPAs, in an appropriate clinical context.

关键词： Carcinogenesis   Colon cancer   Cytotoxicity   Genetic alterations   Heme iron  

摘要： Heme, a molecule abundant in red meat, is assumed to exert carcinogenic effects on normal colonic cells and tumour suppressive effects on cancer cells, though the hypothesis has not been explicitly proven yet. The present study aims to investigate hemin induced cytotoxic, genetic and biological alterations in both normal and cancerous colonic epithelial cells, which may imply its carcinogenic and anticarcinogenic properties. Normal colonic epithelial cells and colon carcinoma cells were treated with a 0-500 mu M concentration of hemin for 1-4 days following which cytotoxicity and wound healing assays, western blot, rt-PCR and cell cycle analysis were performed. Interestingly, hemin was cytotoxic to normal colonic cells, but carcinoma cells were more resistant. Cell migration potential of both normal colonic cells and colon carcinoma cells was impeded by hemin. Hemin caused upregulation of both P53 and beta-catenin gene and proteins expression in normal colonic cells with concomitant cell cycle arrest at G1(Gap 1) and G2/M (Gap 2/ Mitosis). G1 and G2 cell cycle arrests were also observed in colon carcinoma cells. In conclusion, the present study confirms that hemin, a main heme molecule present in red meat, facilitates behavioural, genetic and cell cycle kinetic alterations in both normal colonic epithelial and colon carcinoma cells.