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008; FC = 2.1, p = .008, respectively), ii) similar dynamics at the protein level to what was observed at the RNA layer, and iii) to elicit significant specific cytotoxic immune responses detected by TFDP3 and DDX53 HLA-A*0201 tetramers. Our study addresses the unmet landscape of CTAs expression in MDS and CMML and revealed a previously unrecognized TFDP3 and DDX53 reactivation, detectable in plasma and able to elicit a specific immune response after one cycle of azacitidine.The prognostic potential of anti-tumor immune responses is becoming increasingly important in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S) especially regarding the use of immune checkpoint inhibitors. This study analyzes for the first time the prognostic impact of tumor-infiltrating lymphocytes (TILs) and checkpoint inhibitors in a large Caucasian cohort in patients with AGE/S. We screened tissue samples from 438 therapy-naïve patients with AGE/S undergoing surgery between 1992 and 2005, examined in a tissue microarray (TMA) and stained against human CD3, CD4, CD8, PD-1, and PD-L1. Out of 438 tissue samples, 210 were eligible for multivariate analysis. This revealed that high infiltration with CD3+, CD4+, or CD8+ TILs was associated with an increased overall survival in AGE/S patients, which could only be confirmed in multivariate analysis for CD3 (HR 0.326; p = .023). Independent improved survival was limited to gastric cancer patients and to early tumor stages as long as TILs did not express PD-1 (HR 1.522; p = .021). Subgroup analyses indicate that TIL-dependent anti-tumor immune response is only effective in gastric cancer patients in early stages of disease in PD-1 negative TILs. Combined analysis of PD-1 and CD3 could serve as a prognostic marker for the clinical outcome of gastric cancer patients and could also be of interest for immunotherapy.Adoptive T cell therapy has proven effective against hematologic malignancies and demonstrated efficacy against a variety of solid tumors in preclinical studies and clinical trials. Nonetheless, antitumor responses against solid tumors remain modest, highlighting the need to enhance the effectiveness of this therapy. Genetic modification of T cells with RNA has been explored to enhance T-cell antigen specificity, effector function, and migration to tumor sites, thereby potentiating antitumor immunity. This review describes the rationale for RNA-electroporated T cell modifications and provides an overview of their applications in preclinical and clinical investigations for the treatment of hematologic malignancies and solid tumors.Pancreatic cancer is one of the most common causes of cancer-related deaths worldwide. The two major histological subtypes of pancreatic cancer are pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of all cases, and pancreatic neuroendocrine neoplasm (PanNEN), which makes up 3-5% of all cases. PanNEN is classified into well-differentiated pancreatic neuroendocrine tumor and poorly-differentiated pancreatic neuroendocrine carcinoma (PanNEC). Although PDAC and PanNEN are commonly thought to be different diseases with distinct biology, cell of origin, and genomic abnormalities, the idea that PDAC and PanNEC share common cells of origin has been gaining support. This is substantiated by evidence that the molecular profiling of PanNEC is genetically and phenotypically related to PDAC. In the current review, we summarize published studies pointing to common potential cells of origin and speculate about how the distinct paths of differentiation are determined by the genomic patterns of each disease. We also discuss the overlap between PDAC and PanNEC, which has been noted in clinical observations.
HIV/AIDS transmission in Ecuador is considered a concentrated epidemic; therefore, there are some studies on high risk groups but there is limited published data regarding the HIV/AIDS risk factors among adolescents of African descent. In this study, we sought to explore the determinants of HIV/AIDS-related knowledge and behavior among afro-descendant youths attending schools in the city of Esmeraldas, Ecuador.
A cross-sectional survey among school-attending youths was conducted in Esmeraldas, Ecuador in 2010. Our target population was afro-descendant youths attending the last two years of high school. Thirty public high schools enrolling students in junior and senior years were identified. Outcome data were analyzed in the form of three composite variables. A multivariate linear regression model was built for each outcome.
A total of 213 school-attending afro-descendant youths aged 14 to 21 years old were enrolled in this study. Gender distribution was almost equal with a 11.17 male to female ratio. Overall, students in this population scored well in comprehensive knowledge of HIV with 88% having medium or higher knowledge.
Knowledge of HIV and its determinants was medium to high, but knowledge of sexually transmitted diseases was low among afro-descendant Ecuadorian adolescents in our study. Results of this study might be instrumental in facilitating decision-making processes related to the planning, implementation, and evaluation of HIV/AIDS prevention and control strategies in this specific population.
Knowledge of HIV and its determinants was medium to high, but knowledge of sexually transmitted diseases was low among afro-descendant Ecuadorian adolescents in our study. Results of this study might be instrumental in facilitating decision-making processes related to the planning, implementation, and evaluation of HIV/AIDS prevention and control strategies in this specific population.Deep neural networks have achieved remarkable success in various challenging tasks. However, the black-box nature of such networks is not acceptable to critical applications, such as healthcare. In particular, the existence of adversarial examples and their overgeneralization to irrelevant, out-of-distribution inputs with high confidence makes it difficult, if not impossible, to explain decisions by such networks. In this paper, we analyze the underlying mechanism of generalization of deep neural networks and propose an (n, k) consensus algorithm which is insensitive to adversarial examples and can reliably reject out-of-distribution samples. Furthermore, the consensus algorithm is able to improve classification accuracy by using multiple trained deep neural networks. To handle the complexity of deep neural networks, we cluster linear approximations of individual models and identify highly correlated clusters among different models to capture feature importance robustly, resulting in improved interpretability. Motivated by the importance of building accurate and interpretable prediction models for healthcare, our experimental results on an ICU dataset show the effectiveness of our algorithm in enhancing both the prediction accuracy and the interpretability of deep neural network models on one-year patient mortality prediction. In particular, while the proposed method maintains similar interpretability as conventional shallow models such as logistic regression, it improves the prediction accuracy significantly.
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder defined by motor and phonic tics. Sensory stimuli can trigger tics, which suggests that GTS is a disorder of perception-action processing rather than a pure motor disorder.
We describe a GTS patient that developed exacerbation of tics after transcutaneous electro-myo-stimulation (YGTSS pre-EMS 27/100, post-EMS 69/100).
If behaviorally irrelevant stimuli exacerbate tics, there might be a high readiness of the motor system to respond to any stimulus in these patients. In addition to tighter binding between previously established perception-action links, the likelihood for the formation of automatic perception-action links might also be higher in GTS.
If behaviorally irrelevant stimuli exacerbate tics, there might be a high readiness of the motor system to respond to any stimulus in these patients. In addition to tighter binding between previously established perception-action links, the likelihood for the formation of automatic perception-action links might also be higher in GTS.
Palatal tremor is involuntary, rhythmic and oscillatory movement of the soft palate. Palatal tremor can be classified into three subtypes; essential, symptomatic and palatal tremor associated with progressive ataxia.
A thorough Pubmed search was conducted to look for the original articles, reviews, letters to editor, case reports, and teaching neuroimages, with the keywords "essential", "symptomatic palatal tremor", "myoclonus", "ataxia", "hypertrophic", "olivary" and "degeneration".
Essential palatal tremor is due to contraction of the tensor veli palatini muscle, supplied by the 5
cranial nerve. Symptomatic palatal tremor occurs due to the contraction of the levator veli palatini muscle, supplied by the 9%
and 10%
cranial nerves. Essential palatal tremor is idiopathic, while symptomatic palatal tremor occurs due to infarction, bleed or tumor within the Guillain-Mollaret triangle. read more Progressive ataxia and palatal tremor can be familial or idiopathic. Symptomatic palatal tremor and sporadic progress debilitating than palatal tremor and needs new treatment approaches.
Ataxia with oculomotor apraxia (AOA1) is characterized by early-onset progressive cerebellar ataxia with peripheral neuropathy, oculomotor apraxia and hypoalbuminemia and hypercholesterolemia.
A 23-year-old previously healthy woman presented with slowly-progressive gait impairment since the age of six years. Neurological examination revealed profound areflexia, chorea, generalized dystonia and oculomotor apraxia. Brain MRI revealed mild cerebellar atrophy and needle EMG showed axonal sensorimotor neuropathy. Whole exome sequencing revealed a mutation in the aprataxin gene.
AOA1 can present with choreoathetosis mixed with dystonic features, resembling ataxia-telangiectasia. This case is instructive since mixed and complex movement disorders is not very common in AOA1.
Ataxia with oculomotor apraxia type 1 (AOA1) is characterized by early-onset ataxia and oculomotor apraxia caused by variants in the APTX gene.Ataxia is usually not the sole movement abnormality in AOA1.Hyperkinetic movement disorders, especially chorea and dystonia, may occur.Mixed and complex movement disorders is not very common in AOA1.Patients with early-onset ataxia associated with mixed movement disorders should also be investigated for AOA1.
Ataxia with oculomotor apraxia type 1 (AOA1) is characterized by early-onset ataxia and oculomotor apraxia caused by variants in the APTX gene.Ataxia is usually not the sole movement abnormality in AOA1.Hyperkinetic movement disorders, especially chorea and dystonia, may occur.Mixed and complex movement disorders is not very common in AOA1.Patients with early-onset ataxia associated with mixed movement disorders should also be investigated for AOA1.
Globus pallidus internus (GPi) deep brain stimulation (DBS) is widely used in patients with isolated dystonia; however, its use remains controversial in patients with acquired dystonia and cerebral palsy.
We report the first case of a cerebral palsy patient, who failed to recover 2 years after GPi DBS; DBS was administered on both superior cerebellar peduncles (SCPs) and dentate nuclei (DNs). The monopolar stimulation results suggested that DBS was better administered via the SCPs than via the DNs. At six months follow-up, the patient exhibited a significant improvement of dystonia and spasticity, as well as in her quality of life.
SCP DBS may be a potential treatment for cerebral palsy patients with dystonia and spasticity who do not respond well to GPi DBS.
SCP DBS may be a potential treatment for cerebral palsy patients with dystonia and spasticity who do not respond well to GPi DBS.
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