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关键词： Sickle cell disease   Primary prevention   Newborn screening   Ghana   Nigeria   COMMUNITY-HEALTH WORKERS   UNIVERSAL  

摘要： Sickle cell disease (SCD), an inherited blood disorder, impacts 2% of newborns in Nigeria and Ghana. Despite devastating health consequences, SCD prevention is not a priority in either country. This article describes our U.S. research team's feasibility assessment for adapting CHOICES, a computer-based SCD education program, for use in Ghana and Nigeria. We identified indigenous collaborators by reviewing published research and investigating advocacy organizations online. This led to a fact-finding trip to Africa to discuss SCD prevention with local boards of advisors. Three major recommendations emerged from the group discussions: design a culturally appropriate intervention; enlist community healthcare workers to deliver the CHOICES program; and collaborate with religious and community leaders and elders in public awareness campaigns. Based on extensive advisor input, we will modify the content and delivery of the CHOICES intervention to meet the needs of those impacted by SCD in Ghana and Nigeria.

关键词： RITUXIMAB   CHEMOTHERAPY   INVOLVEMENT   THERAPY   CHOP  

摘要： Highlights•PMLBCL rarely extends to extranodal subdiaphragmatic (ES) sites at diagnosis. •Among 455 patients, 32 (7%) had such localization at baseline. •Kidney, liver, and adrenals were most frequently involved. •ES site involvement had not independent prognostic impact beyond that of stage IV.

关键词： Augmentation   Bayesian optimization   Brain tumor   Convolutional neural networks   Deep learning   Image processing   IMAGES  

摘要： Detecting and classifying a brain tumor is a challenge that consumes a radiologist's time and effort while requiring professional expertise. To resolve this, deep learning techniques can be used to help automate the process. The aim of this paper is to enhance the accuracy of brain tumor classification using a new layered architecture of deep neural networks rather than the current state-of-the-art algorithms. In this paper, we propose automated tumor classification by concatenating two convolutional neural network structures of layers and tuning the hyperparameters by utilizing Bayesian optimization. The proposed solution focuses on enhancing the accuracy of classifying tumors to increase the level of trust in the technologies employed in the medical field. The work is tested and evaluated to predict the classification of magnetic resonance imaging inputs and achieving a higher accuracy (97.37%) than other similar works, with accuracies between 84.19% and 96.13%, for the same dataset.

关键词： Head and neck squamous cell carcinoma   Unknown primary   F-18-FDG PET   CT   Detection rate   LYMPH-NODE METASTASES   TOMOGRAPHY-COMPUTED-TOMOGRAPHY   FDG-PET/CT   CONTEMPORARY MANAGEMENT   DIAGNOSTIC EVALUATION   HUMAN-PAPILLOMAVIRUS   PRIMARY SITE   ORIGIN   IMPACT   CANCER  

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.

关键词： TUMOR-TISSUES   IFN-GAMMA   T-CELLS   IL-12   MICROENVIRONMENT   RESPONSIVENESS   SURVIVAL   IMMUNITY   ABILITY   FAMILY  

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： OVARIAN FAILURE   MEIOTIC ARREST   MUTATIONS   AZOOSPERMIA   SERVER   VISUALIZATION   INSTABILITY   INFERTILITY   GENERATION   SPARTAN  

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   NEURAL-NETWORKS   ART  

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： 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   DNA-DAMAGE   EXPRESSION  

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.