A Two-Stage Methodology Using K-NN and False-Positive Minimizing ELM for Nominal Data Classification

This paper focuses on the problem of making decisions in the context of nominal data under specific constraints. The underlying goal driving the methodology proposed here is to build a decision-making model capable of classifying as many samples as possible while avoiding false positives at all costs, all within the smallest possible computational time. Under such constraints, one of the best type of model is the cognitive-inspired extreme learning machine (ELM), for the final decision process. A two-stage decision methodology using two types of classifiers, a distance-based one, K-NN, and the cognitive-based one, ELM, provides a fast means of obtaining a classification decision on a sample, keeping false positives as low as possible while classifying as many samples as possible (high coverage). The methodology only has two parameters, which, respectively, set the precision of the distance approximation and the final trade-off between false-positive rate and coverage. Experimental results using a specific dataset provided by F-Secure Corporation show that this methodology provides a rapid decision on new samples, with a direct control over the false positives and thus on the decision capabilities of the model.     

Nursing homes and the elderly regarding the COVID-19 pandemic: situation report from Hungary

GeroScience - The global impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is significant in terms of public health effects and its long-term socio-economic...     

Ictal affective symptoms in temporal lobe epilepsy are related to gender and age

Purpose: We systematically analyzed the video‐recorded and patient‐reported, as well as positive and negative ictal affective symptoms (IAS) in temporal lobe epilepsy (TLE). Our aim was to assess (1) frequency, (2) gender effect, (3) lateralizing significance, (4) localizing value, and (5) prognostic significance in epilepsy surgery of IAS in patients with video‐registered seizures. Methods: We reviewed ictal video recordings of 184 patients (99 women, aged 16–63). All patients had surgery for intractable TLE with video‐recorded complex partial seizures (CPS) due to temporal lobe lesions visualized by high‐resolution magnetic resonance imaging (MRI). Affective auras (AAs) were categorized into two groups: positive or negative. Results: We registered AAs in 18% of patients: positive in 3%, negative in 15%. We saw ictal affective behavior (IAB) in 22% of patients; 10% had positive, whereas 14% had negative IAB. Two patients had both positive and negative IAB. AAs showed an association with IAB in case of fear expression versus fear auras (p = 0.018). IAB, especially negative IAB, occurred more often in women than in men. Patients with negative IAB were younger than others. We could not demonstrate an association between IAS and the localization, lateralization, or hemispheric dominance. Surgical outcome did not associate with IAS. Discussion: Patient‐reported and video‐recorded negative—but not positive—affective signs are related to each other. Video‐recorded negative AAs occur more often in women and young patients.     

Inhibition of proliferation of PC-3 human prostate cancer by antagonists of growth hormone-releasing hormone: lack of correlation with the levels of serum IGF-I and expression of tumoral IGF-II and vascular endothelial growth factor

BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) such as JV-1-38 can inhibit androgen-independent prostate cancer directly by several mechanisms and/or indirectly by suppressing growth hormone/insulin-like growth factor-I (GH/IGF-I) axis. To shed more light on the mechanisms involved, the effects of JV-1-38 on PC-3 human prostate cancer were compared with those of somatostatin analog RC-160 in vivo and in vitro. METHODS: Nude mice bearing PC-3 tumors received JV-1-38 (20 microg), RC-160 (50 microg) or a combination of JV-1-38 and RC-160. The concentration of IGF-I in serum and the expression of mRNA for IGF-II and vascular endothelial growth factor (VEGF) in tumor tissue were investigated. RESULTS: In vivo, the final volume of PC-3 tumors treated with JV-1-38 was significantly lowered by 49% (P < 0.01), whereas RC-160 exerted only 30% inhibition (NS), compared with controls. Combined use of both compounds augmented tumor inhibition to 63% (P < 0.001). Serum IGF-I levels were decreased only in mice treated with RC-160. JV-1-38 suppressed mRNA for IGF-II in PC-3 tumors by 42%, whereas RC-160 alone or in combination with JV-1-38 caused a 65% reduction. JV-1-38 and RC-160 used as single drugs decreased the expression of VEGF by 50%, and their combination caused a 63% reduction. In vitro, JV-1-38 inhibited the proliferation of PC-3 cells by 39%. This effect could be partially reversed by addition of IGF-I to the serum-free medium. RC-160 alone did not affect the PC-3 cell growth in vitro, but in combination with JV-1-38 it augmented the antiproliferative effect of the GH-RH antagonist to 72%. Exposure to JV-1-38 in vitro reduced the expression of mRNA for IGF-II in PC-3 cells by 55% but did not change VEGF mRNA levels, whereas RC-160 had no effect. CONCLUSIONS: The antiproliferative effect of JV-1-38 was not associated with the suppression of serum IGF-I and was only partially correlated with the expression of IGF-II and VEGF in PC-3 tumors, suggesting that other mechanisms play a role in the antitumor action of GHRH antagonists. Nevertheless, the stronger inhibition of tumor growth after combined treatment with JV-1-38 and RC-160 indicates that the interference with multiple local stimulatory factors leads to an enhanced inhibition of prostate cancer.     

Expression of Hsp70 in kidney cells exposed to ochratoxin A

Ochratoxin A (OTA) is a possible etiological agent of endemic nephropathy, a chronic renal disease with high prevalence in limited geographic areas. Ochratoxicosis has many characteristics of different pathological states in which heat shock proteins (Hsps) are usually induced. The most inducible heat shock proteins belong to the Hsp70 family. We determined the level of expression of Hsp70 by the Western blot analysis in kidneys of rats treated with low doses of OTA and in LLC-PK1 and MDCK cells exposed to OTA. Estimation of cell viability and release of lactate dehydrogenase (LDH) confirmed the toxic effects of OTA on cultured cells. OTA affects the relative distribution of two Hsp70 isoforms (68-kDa and 74-kDa isoforms), but does not change total amount of Hsp70 in rat kidney. No changes in the Hsp70 level were detected in LLC-PK1 and MDCK cells treated with OTA, although the cells were seriously injured, as was seen from the reduced cell viability and increased release of LDH. Both cell lines were capable of having Hsp70 induced following a heat shock. However, exposure of the cells to OTA before the heat shock challenge prevented Hsp70 induction. Results of the study show that OTA does not induce Hsp70 in rat kidney or in cultured kidney cells. The absence of Hsp70 protective effects in the cells and tissues might be a possible explanation for the cumulative destructive effects of OTA and a silent onset of endemic nephropathy in humans and of OTA-induced experimental nephrotoxicity in animals.     

Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity

Vasoactive intestinal peptide (VIP) stimulates the proliferation and invasiveness of malignant prostatic cells. Receptors for VIP and the closely related growth hormone-releasing hormone (GH-RH) show considerable homology and are found in prostatic and other carcinomas. Among various analogs of GH-RH synthesized, JV-1-52 is a non-selective VIP/GH-RH antagonist, whereas JV-1-53 is a VIP antagonist devoid of GH-RH antagonistic effect. In our study, nude mice bearing PC-3 human androgen-independent prostate carcinomas were treated with JV-1-52 or JV-1-53 (20 microg/day, s.c.) for 28 days. Both antagonists produced a similar reduction in tumor volume (62-67%, p < 0.01) and tumor weight (59-62%; p < 0.05) vs. controls and extended tumor doubling-time from 9.1 to about 16 days (p < 0.05). To investigate the mechanisms involved, in another study we compared the effects of JV-1-53 with those of somatostatin analog RC-160. VIP antagonist JV-1-53 reduced tumor weight by 67% (p < 0.01) and suppressed the expression of mRNA for c-fos and c-jun oncogenes by about 34% (p < 0.05), without affecting serum levels of insulin-like growth factor-I (IGF-I). In contrast, RC-160 (50 microg/day) reduced serum IGF-I by 19% (p < 0.05), but did not significantly decrease tumor weight. mRNA for VIP and high affinity receptors for VIP were detected on PC-3 tumors. Our results suggest that VIP/GH-RH antagonists can inhibit the growth of androgen-independent prostate cancer by abrogating the autocrine/paracrine mitogenic stimuli of VIP. The ability of GH-RH antagonists to block tumoral VIP receptors, in addition to GH-RH receptors, could be potentially beneficial for prostate cancer therapy.     

Effect of ketamine on dendritic arbor development and survival of immature GABAergic neurons in vitro.

Ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors, was reported to induce neuronal cell death when administered to produce anesthesia in young rodents and monkeys. Subanesthetic doses of ketamine, as adjuvant to postoperative sedation and pain control, are also frequently administered to young children. However, the effects of these low concentrations of ketamine on neuronal development remain unknown. The present study was designed to evaluate the effects of increasing concentrations (0.01-40 microg/ml) and durations (1-96 h) of ketamine exposure on the differentiation and survival of immature gamma-aminobutyric acidergic (GABAergic) interneurons in culture. In line with previous studies (Scallet et al., 2004), we found that a 1-h-long exposure to ketamine at concentrations > or = 10 microg/ml was sufficient to trigger cell death. At lower concentrations of ketamine, cell loss was only observed when this drug was chronically (> 48 h) present in the culture medium. Most importantly, we found that a single episode of 4-h-long treatment with 5 microg/ml ketamine induced long-term alterations in dendritic growth, including a significant (p < 0.05) reduction in total dendritic length and in the number of branching points compared to control groups. Finally, long-term exposure (> 24 h) of neurons to ketamine at concentrations as low as 0.01 microg/ml also severely impaired dendritic arbor development. These results suggest that, in addition to its dose-dependent ability to induce cell death, even very low concentrations of ketamine could interfere with dendritic arbor development of immature GABAergic neurons and thus could potentially interfere with the development neural networks.     

Wernicke-encephalopathy in children with cancer

In the last 4 years, 24 cases of neuroblastoma were treated in the Pediatric Hematology-Oncology Unit at the Chaim Sheba Medical Center, 8 of whom were under 1 year of age. Four of them were the product of a pregnancy-induced or preserved by gonadotropins, clomiphene citrate, or progestational hormones. These drugs are known to produce a higher than normal level of estradiol or progestrone in the early stages of pregnancy. Our observation led to the hypothesis that high levels of progestational hormones given during pregnancy are a risk factor for neuroblastoma in infancy. © 1994 Wiley-Liss, Inc.