TiVo (United States)

Background: IL-12 exhibits potent anti-tumor properties, which enhance cytolytic activity and tumor infiltration of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) and activates Th-1-type immune responses [1-2]. However, systemic administration of recombinant IL-12 protein is still a challenge due to serious toxicity resulting from interferon (IFN)-γ overproduction [3-5]. Viral and non-viral vectors for IL-12 gene therapy represent an alternative therapeutic strategy, which can be combined with pro-drug activated cancer killing gene therapy approaches. Combined gene delivery of IL-12 and herpes simplex virus thymidine kinase (HSV-TK) significantly boosts anti-tumor efficacy in animal studies and has been shown to be safe in human clinical studies when administered intratumorally [6-12]. Here we present a novel gene therapy approach for in vivo gene delivery of IL-12 combined with an enhanced gain of function-variant of HSV-TK (v-eTK). Methods: Non-replicating retrovectors encoding murine IL-12 only (mGEN1018, encoding both p35 and p40 subunits, as described previously [13-14], or in combination with v-eTK (mGEN1013), were administered intratumorally or systemically to a subcutaneous tumor model of CT26 murine colorectal cancer in syngeneic BALB/c mice. Mice receiving mGEN1013 were subsequently treated with Ganciclovir (GCV) pro-drug. General health and body weight as well as tumor growth and survival were monitored over time, and immunophenotyping of peripheral blood, spleen, and tumor-infiltrating immune cells was performed. Results: Our data show that in subcutaneous CT26 tumor models, intratumoral and systemic gene delivery of IL-12 by the mGEN1018 vector induces both local and systemic anti-tumor immune responses primarily by stimulating production of IFN-γ from NK cells and CTLs. Gene delivery of IL-12 in combination with v-eTK by the mGEN1013 vector followed by GCV pro-drug showed enhanced tumor growth inhibition and increased survival compared to untreated controls. Systemic anti-tumor effects of IL-12 gene therapy were not associated with visible signs of toxicity or significant body weight loss. Conclusion: Gene delivery of v-eTK followed by GCV treatment results in tumor cell lysis and exposure of tumor antigens, while simultaneously, IL-12 gene delivery enhances anti-tumor immune responses though upregulation of inflammatory cytokines. These results show the potential of mGEN1013 as a novel RNA payload delivery platform for combined GCV pro-drug and more effective tumor-localized IL-12 immunotherapy without systemic toxicity. Citation Format: Laura Strauss, Carli Jones Burns, Akihito Inagaki, Stephanie Lees, Noriyuki Kasahara, Cecilia Roh, Robert G. Johnson. IL-12 immunotherapy using a novel gene delivery platform for RNA payloads achieves effective antitumor responses without systemic toxicity in an aggressive CT26 murine cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 474.

atravs da aplicao de um questionrio entregue aos participantes.Dos 38 profissionais, 27 profissionais responderam ao questionrio.Entre os profissionais, 20 eram do sexo feminino e sete do sexo masculino.Com relao a cor/raa, 20 trabalhadores se autodeclararam pardos, quatro brancos, dois pretos e um indgena.Sobre o estado civil, 17 trabalhadores disseram estar solteiros, quatro casados, dois amigados, dois separados e dois vivos.Em relao a escolaridade, 4% (1)dos trabalhadores possuem Ensino Fundamental, 31% (8) dos profissionais possuem Ensino Mdio completo, 23% (6) possuem curso tcnico, 15% (4) so universitrios, 4% (1) Ensino Superior e 23% (6) ps-graduao.Quanto a renda familiar dos profissionais, 22% (6) recebem at um salrio mnimo e 41% (11) recebem at dois salrios mnimos, 11% (3) recebem at quatro salrios mnimo, 7% (2) recebem at 10 salrios mnimos, 4% (1) at seis salrios mnimos, 15% (4) no responderam.Em relao ao tempo de servio, 22% (6) dos trabalhadores tinham menos de um ano, 26% (7) encontram-se na faixa de 1 a 5 anos, 19% (5) tinham entre 6 a 15 anos, 11%(3) entre 19 a 25 anos, 7% (2) de 37 a 46 anos e 15 % (4) no responderam.Observou-se que as equipes da UBS Planalto so formadas principalmente por profissionais oriundos de vnculos por contrato administrativo

BACKGROUND:Based on 6-month data from the InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold for Safety and Neurological Recovery in Patients with Complete Thoracic Spinal Cord Injury (INSPIRE) study (NCT02138110), acute implantation of an investigational bioresorbable polymer device (Neuro-Spinal Scaffold [NSS]) appeared to be safe in patients with complete thoracic spinal cord injury (SCI) and was associated with an ASIA Impairment Scale (AIS) conversion rate that exceeded historical controls.OBJECTIVE:To evaluate outcomes through 24 months postimplantation.METHODS:INSPIRE was a prospective, open-label, multicenter, single-arm study. Eligible patients had traumatic nonpenetrating SCI with a visible contusion on MRI, AIS A classification, neurological level of injury at T2-T12, and requirement for open spine surgery ≤96 hours postinjury.RESULTS:Nineteen patients underwent NSS implantation. Three patients had early death determined by investigators to be unrelated to the NSS or its implantation procedure. Seven of 16 evaluable patients (44%) had improvement of ≥1 AIS grade at 6 months (primary end point) to AIS B (n = 5) or AIS C (n = 2). Three patients with AIS B at 6 months had further neurological improvement to AIS C by 12 (n = 2) and 24 (n = 1) months, respectively; none have deteriorated per latest available follow-up. No unanticipated or serious adverse device effects were reported.CONCLUSIONIn this small group of patients with complete thoracic SCI, acute NSS implantation within the spinal cord appeared to be safe with no long-term neurological issues identified during the 24-month follow-up. Patients remain stable, with additional AIS conversions observed in some patients at 12 months and beyond. These data further support the safety and probable benefit of NSS implantation in this patient population.

Models of crop production play a key role in food security, predicting future agriculture challenges and supporting the establishment of public policies and sustainable management practices. However, due to the lack of reliable information, especially in developing countries, they have presented limited performance and restrictions for spatially explicit analyses. Thus, the objective of this study was to evaluate the DSM (Digital Soil Mapping) as an alternative to fill the gap of soil data. Our study site is in Southwest of Brazil in a 4,815 km area heterogeneous in geology and soil classes. The study were conducted with the following framework: (i) We used a soil survey data, containing 1,125 collected points with auger and 27 profiles and applied equal-spline equations to standardized the soil dataset into depth; (ii) A machine learning (ML) algorithm were used to predict soil attributes and their uncertainties (iii) Pedotransfer functions were performed to obtain soil hydrological properties (iv) DSSAT-Canegro was simulated in a 250m grid to sugarcane planted in October with harvest completing 12 months (v) We compared three levels of soil data source: a soil map (SM) (1:100,000 scale), SoilGrids (SG) and the map of attributes (MA) derived from our ML. Clay was the attribute that obtained the best performance to surface and subsurface (R=0.70 and 0.59, RMSE= 88.87 and 141 g kg -1 ) and low uncertainty (40 and 110%). In depth the attributes were reduced in their content and increased uncertainty. Therefore, the MA to be the most reliable source of data, being the one that most resembles field data, presents the best index of agreement (d= 0.8) and confidence coefficient (c=0.74). In addition, a 250m grid allowed the evaluation of the spatial variability of the attainable yield of sugarcane at a regional level. Nitisols achieved higher productivity and shallow soils did not exceed 100 t ha -1 . Thus, this work showed the applicability of digital mapping for application in crop modeling. This methodology can be replicated for decision-making at a regional level and also to improve management strategies for agriculture.

Objetivo: Avaliar os indicadores de cura e de abandono dos casos de tuberculose e de coinfecção tuberculose/HIV. Métodos: Estudo transversal, descritivo e quantitativo, realizado no estado da Paraíba-Brasil. A população estudada foi composta por dois grupos notificados no Sistema de Informação de Agravos de Notificação Compulsória da Secretaria de Saúde do Estado da Paraíba, durante 2013 a 2015, sendo eles: todos os casos de tuberculose e todos os casos de coinfecção tuberculose-HIV, em que ambos obtiveram cura ou abandono como situação de encerramento do tratamento. As frequências absolutas e relativas foram descritas, bem como, aplicou-se o teste de Odds Ratio. Resultados: Em relação aos doentes de tuberculose, 61% obtiveram cura e 13% abandonaram o tratamento. Quanto aos coinfectados tuberculose/HIV, 42% alcançaram a cura e 24% abandonaram o tratamento. Em ambos os grupos, o percentual de abandono foi maior para o tratamento autoadministrado em comparação com os que realizaram o Tratamento Diretamente Observado. Segundo teste de Odds Ratio, os sujeitos coinfectados apresentaram 2,6 mais chance de abandonar o tratamento da tuberculose comparados aos casos de tuberculose sem confirmação para o HIV. Considerações finais: O abandono do tratamento da tuberculose constitui o principal desafio dos órgãos de controle da doença, a adesão à terapêutica deve ser considerada como um fator imprescindível para a obtenção da cura. Portanto, os gestores e profissionais de saúde devem está atentos aos grupos populacionais em situação de maior vulnerabilidade, tanto para o adoecimento, quanto para a não adesão ao tratamento. Palavras chave: Tuberculose. HIV. Coinfecção. Saúde Pública.

We discuss the use of the preferential looking paradigm in eye tracking studies in order to study how infants develop, understand, and attend to the world around them. Eye tracking is a safe and non-invasive way to collect gaze data from infants, and the preferential looking paradigm is simple to design and only requires the infant to be attending to the screen. By simultaneously showing two visual stimuli that differ in one dimension, we can assess whether infants show different looking behavior for either stimulus, thus demonstrating sensitivity to that difference. The challenges in such experimental approaches are that experiments must be kept brief (no more than 10 min) and be carefully controlled such that the two stimuli differ in only one way. The interpretation of null results must also be carefully considered. In this paper, we illustrate a successful example of an infant eye tracking study with a preferential looking paradigm to discover that 6-month-olds are sensitive to linguistic cues in a signed language despite having no prior exposure to signed language, suggesting that infants possess intrinsic or innate sensitivities to these cues.

e18586 Background: A typical pathology report contains diagnoses of tissue types. Most pathology departments capture such information in free text, which makes it challenging to extract the information into a structured form. One application of such structured data is for Multi-Disciplinary Tumor Board (MDT) meetings, in which treatment options are discussed. A significant amount of time is usually spent prior to the meeting to manually summarize relevant information. In this paper, we propose a fully automatic solution for extracting information from free text prostate pathology reports. The proposed approach consists of several natural language processing modules that are developed with language-independence in mind. We store the data in a FHIR model specifically designed for prostate MDTs. Methods: Our solution uses a combination of ontologies, regular expressions and rules to detect the desired information. The FHIR data model is constructed for a typical prostate cancer MDT and based on guidelines available from multiple sites (English, Dutch, and Swedish). As an example, for anatomy detection, regular expressions were constructed to detect compound anatomical phrases. Each sub phrase corresponds to a set of prostate regions. To find the regions for to the compound phrase, the intersection of the regions corresponding to sub phrases were used. Results: Prostate pathology reports were available from multiple sites after ethics board approval and de-identification of the reports. Table 1 summarizes the performance of the proposed solution in terms of Recall, and Precision for three examples of information extraction modules. Conclusions: Structuring pathology reports is a challenging task currently performed manually. We presented a fully automatic solution to parse prostate pathology reports for MDT meetings and store them in a of FHIR model. English (291 reports from 3 sites) Dutch (73 reports from 3 sites) Swedish (40 reports from 1 site) Recall Precision Recall Precision Recall Precision Gleason score 99.7% 99.8% 100.0% 98.8% 99.4% 98.9% Vial 97.3% 99.4% 99.5% 98.9% 73.0% 97.5% Anatomy 97.6% 90.9% N/A N/A N/A N/A