307 research outputs found

    Associations of concomitant medications with immune-related adverse events and survival in advanced cancers treated with immune checkpoint inhibitors: a comprehensive pan-cancer analysis

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    Background: While concomitant medications can affect the efficacy of immune checkpoint inhibitors (ICIs), few studies have assessed associations of concomitant medications with the occurrence and profile of immune-related adverse events (irAEs). Methods: This study assessed associations of concomitant medication (antibiotics/proton pump inhibitors (PPIs)/corticosteroids)-based risk model termed the "drug score" with survival and the occurrence and profile of irAEs in 851 patients with advanced cancer treated with ICIs (with or without other agents). The study also assessed the survival impact of the occurrence of irAEs, using a landmark analysis to minimize immortal time bias. Multivariable Cox proportional hazard analyses were conducted for progression-free survival (PFS) and overall survival (OS). Results: The drug score classified patients into three risk groups, with significantly different PFS and OS. Notably, the score's predictive capability was better in patients treated with ICIs only than in those treated with ICIs plus other agents. The landmark analysis showed that patients who developed irAEs had significantly longer PFS and OS than those without irAEs. Generally, concomitant medications were negatively associated with the occurrence of irAEs, especially endocrine irAEs, whereas PPI use was positively associated with gastrointestinal irAEs, as an exception. Conclusions: Using a large pan-cancer cohort, the prognostic ability of the drug score was validated, as well as that of the occurrence of irAEs. The negative association between concomitant medications and irAE occurrence could be an indirect measure of the detrimental effect on the immune system induced by one or more concomitant drugs

    A Build of GIS Mthod in the Natural Environment of the Takada Castle Town

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    This study is, from the side of GIS, deals with the natural environment of the Takada castle town. The method of study is the considerations base on the maps of castle town, the investigations of the present condition and the geographical descriptions. In this paper, the author attempted, in the lay of the land, the geological features, the water and the vegetations of the Takada castle town, a trial to the application from the GIS mthod

    A Build of GIS Mthod in the Natural Environment of the Takada Castle Town

    No full text
    This study is, from the side of GIS, deals with the natural environment of the Takada castle town. The method of study is the considerations base on the maps of castle town, the investigations of the present condition and the geographical descriptions. In this paper, the author attempted, in the lay of the land, the geological features, the water and the vegetations of the Takada castle town, a trial to the application from the GIS mthod

    A Build of GIS Mthod in the Natural Environment of the Takada Castle Town

    No full text
    This study is, from the side of GIS, deals with the natural environment of the Takada castle town. The method of study is the considerations base on the maps of castle town, the investigations of the present condition and the geographical descriptions. In this paper, the author attempted, in the lay of the land, the geological features, the water and the vegetations of the Takada castle town, a trial to the application from the GIS mthod

    Publisher Correction: A genome-wide association analysis reveals new pathogenic pathways in gout.

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    In the version of the article originally published, there were errors in the consortium lists at the end of the paper. Maureen Rischmueller, Hyon K. Choi, Masahiro Nakatochi, Jeff N. Miner, Daniel H. Solomon, Kathleen M. Giacomini and Deanna J. Brackman were erroneously listed as members of the Japan Gout Genomics Consortium. Instead, Akiyoshi Nakayama, Tappei Takada, Masahiro Nakatochi, Seiko Shimizu, Yusuke Kawamura, Nariyoshi Shinomiya and Kimiyoshi Ichida should have been included in that consortium list. In addition, Lisa K. Stamp, Akiyoshi Nakayama and Yusuke Kawamura were omitted from the list for the GlobalGout Genetics Consortium. The lists have been corrected in the HTML and PDF versions of the articl

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    Na atualidade, uma das causas importantes de lesão encefálica em neonatos é a anóxia neonatal. Este é um problema grave nos serviços de perinatologia dos hospitais em todo o mundo sendo ainda pior em países subdesenvolvidos, devido à carência de precauções e cuidados requeridos. Modelos animais de anóxia vêm sendo empregados para avaliar seus efeitos, tanto em nível neurológico, como em nível comportamental. A anóxia neonatal tem sido estudada pelo laboratório de Neurociências do Instituto de Ciências Biomédicas da Universidade de São Paulo, com modelos de estudo já desenvolvidos, adaptados e validados. Para investigar se a anóxia neonatal afeta o desenvolvimento motor somático e sensorial, ratos foram submetidos a um modelo não invasivo de anóxia global (Takada et. al., 2011). Ratos Wistar com 30 h de idade (6-8 gramas), machos e fêmeas, foram expostos por 25 minutos a gás nitrogênio 100% num fluxo de 3L/min, pressão 101.7 kPa e temperatura de 37ºC em câmara semi-hermética de policarbonato. O grupo controle foi submetido às mesmas condições porem com o ar ambiente normal. Os animais foram avaliados durante o período de aleitamento (P2 a P21) quanto a parâmetros do desenvolvimento somático; desenvolvimento ontogenético e quanto a reflexos sensório motores. Os resultados indicaram que o grupo Anoxia macho(AM) apresentou aumento no peso corporal {AM(42.25±3.62);CM(38.76±5.60);AF(40.64±5.08);CF(41.33±5.45)}e diminuição do eixo longitudinal do corpo {AM(10.15±0.27);CM(10.39±0.50);AF(9.82±0.44);CF(10.82±0.46)} em relação ao grupo Controle macho(CM) e Anoxia fêmea(AF), AF foi menor em relacao ao Controle fêmea (CF). AM apresentou maior eixo látero-lateral do crânio em relação CM e AF {AM (3.18 ±0.10); CM (3.17 ±0.13); AF(3.06 ±0.16); CF(3.00 ±0.15)} No desenvolvimento ontogenético houve retardo na abertura do canal auditivo {AM (13.79± 0.58); CM (13.75±0.83); AF(14.21±1.01); CF(13.36±0.50)} e abertura dos olhos {AM (14.00± 0.88); CM (14.64±1.28); AF(15.14±0.86); CF(13.79±0.42)} no grupo AF em relação a CF e AM, mas no grupo AM não houve diferença significante. Na erupção dos incisivos superiores {AM (10.79± 0.43); CM(11.71±1.68); AF(11.43±0.65); CF(10.07±0.27)} o grupo AM adiantou enquanto o AF atrasou em relação ao grupo controle. A avaliação dos reflexos sensóriais mostrou que a anoxia adiantou a colocação pelas vibrissas {AM (8.80± 1.21); CM (9.50±1.56); AF (9.93±1.14); CF(10.14±1.28) no AF e AM. Apenas o AM adiantou {AM (10.93± 2.09); CM(13.43±0.94); AF(10.50±0.85); CF(9.57±0.76)} no reflexo de aversão ao precipício. Nos relfexos de geotaxia negativa {AM (14.87± 1.30); CM (13.57±2.34); AF(14.57±1.40);CF (12.00±2.11)} e sobressalto ao susto {AM (14.00±0.53); CM (13.21±1.31); AF (13.29±0.61); CF (11.93±0.27)} e preensão palmar {AM (6.60±0.83); CM (4.71±0.47); AF(10.14±0.83); CF(4.71±0.47)} a anóxia provocou atraso tanto em macho quanto em fêmeas motores. Houve atraso na ontogênese da maioria dos testes de reflexos dos filhotes do grupo Anóxia. Os resultados deste estudo demonstraram que a anóxia causa danos persistentes na maioria dos parâmetros avaliados em relação aos grupos controle, e diminuição no número de neurônios do córtex sensóriomotor {M2: AM (46.84±1.72); CM (52±1.66); AF (45.55±1.80); CF (52±1.55)M1: AM (23.70±1.33); CM (41.89±1.49); AF (25.69±0.83); CF (43.88±1.46) S1HL: AM (27.93±2.69); CM (30.19±1.31); AF(23.42±2.38); CF (38.88±1.48) S1FL: AM (31.85±1.09); CM (33.88±0.48); AF(27.66±1.36); CF(32.28±1.70)}, com diferença de gênero o que evidencia a importância de que estratégias e procedimentos para minimizar os efeitos desse estímulos sejam consideradas em relação ao gêneroAt present, one of the important causes of brain injury is the neonatal anoxia. This is a serious problem in the perinatology services of hospitals around the world being even worse in underdeveloped countries because of the lack of precautions and care required. Animal models of anoxia have been employed to assess their effects, both at the neurological level and at the behavioral level. Neonatal anoxia has been studied by the Neuroscience Laboratory of the Biomedical Sciences Institute of the University of São Paulo, with animal models already developed, adapted and validated. To investigate whether neonatal anoxia affects somatic and sensory motor development, rats were subjected to a non-invasive model of global anoxia (Takada et al., 2011). Male and female 30-h old (6-8 grams) Wistar rats were exposed for 25 minutes to 100% nitrogen gas in a flow of 3 L/min, pressure 101.7 kPa and temperature of 37ºC in a semi-hermetic chamber of polycarbonate. The control group was subjected to the same conditions but with normal ambient air. The animals were evaluated during the lactation period (P2 to P21) for parameters of somatic development; Ontogenetic development and for sensorimotor reflexes. The results indicated that the male Anoxia (AM) group presented increase in body weight (AM (42.25 ± 3.62), CM (38.76 ± 5.60), FA (40.64 ± 5.08), CF (41.33 ± 5.45)) and decrease in the longitudinal (10.82 ± 0.46), in relation to the male control group (CM) and the female Anoxia (AF), AF was lower in relation to the control group (AM) (10.15 ± 0.27), CM (10.39 ± 0.50), AF (9.82 ± 0.44) Female control (CF). AM increase in the cranio-lateral axis in relation to CM and AF (AM (3.18 ± 0.10); CM (3.17 ± 0.13); AF (3.06 ± 0.16); CF (3.00 ± 0.15). Concerning the ontogenetic development there was delay in opening the (13.79 ± 0.58), and the eyes {AM (14.00 ± 0.88); CM (14.64 ± 1.28), AF (15.14 ± 0.86), CF (13.79 ± 0.42)} in the AF group in relation to CF and AM, but in the AM group there was no significant difference. In the eruption of maxillary incisors (AM (10.79 ± 0.43), CM (11.71 ± 1.68), AF (11.43 ± 0.65), CF (10.07 ± 0.27), the AM group advanced while the AF delayed in control ration. The evaluation of the sensory reflexes showed that anoxia improved the placement of vibrissae (AM (8.80 ± 1.21), CM (9.50 ± 1.56), AF (9.93 ± 1.14), CF (10.14 ± 1.28) in AF and AM. Only AM advanced (AM (10.93 ± 2.09), CM (13.43 ± 0.94), AF (10.50 ± 0.85), CF (9.57 ± 0.76) in the reflex of aversion to the precipice. In negative geotaxia relays (AM (14.87 ± 1.30); CM (13.57 ± 2.34), AF (14.57 ± 1.40), CF (12.00 ± 2.11)} and startle reflex {AM (14.00 ± 0.53); CM (13.21 ± 1.31); AF (13.29 ± 0.61); CF (11.93 ± 0.27) and palmar grip (AM (6.60 ± 0.83); CM (4.71 ± 0.47), AF (10.14 ± 0.83), CF (4.71 ± 0.47)), anoxia caused delay in both male and female groups. There was a delay in the ontogenesis of most of the reflex tests of the puppies of the anoxia group. The results of this study demonstrated that anoxia causes persistent damage in most of the parameters evaluated in relation to the control groups, and a decrease in the number of sensory motor cortex neurons (M2: AM (46.84 ± 1.72), CM (52 ± 1.66), AF 1.80), CF (52 ± 1.55) M1: AM (23.70 ± 1.33), CM (41.89 ± 1.49), AF (25.69 ± 0.83), CF (43.88 ± 1.46) S1HL: AM (27.93 ± 2.69), CM (30.19 (31.88 ± 1.48), FA (27.66 ± 1.36), CF (32.28 ± 1.70), , which shows that strategies and procedures to minimize the effects of such stimuli should be considered in relation to gende

    Publisher Correction:A genome-wide association analysis reveals new pathogenic pathways in gout

    No full text
    Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-01921-5. Published online 15 October 2024.In the version of the article originally published, there were errors in the consortium lists at the end of the paper. Maureen Rischmueller, Hyon K. Choi, Masahiro Nakatochi, Jeff N. Miner, Daniel H. Solomon, Kathleen M. Giacomini and Deanna J. Brackman were erroneously listed as members of the Japan Gout Genomics Consortium. Instead, Akiyoshi Nakayama, Tappei Takada, Masahiro Nakatochi, Seiko Shimizu, Yusuke Kawamura, Nariyoshi Shinomiya and Kimiyoshi Ichida should have been included in that consortium list. In addition, Lisa K. Stamp, Akiyoshi Nakayama and Yusuke Kawamura were omitted from the list for the GlobalGout Genetics Consortium. The lists have been corrected in the HTML and PDF versions of the article

    Correction to: A genome-wide association analysis reveals new pathogenic pathways in gout (Nature Genetics, (2024), 10.1038/s41588-024-01921-5)

    No full text
    Correction to: Nature Geneticshttps://doi.org/10.1038/s41588-024-01921-5. Published online 15 October 2024. In the version of the article originally published, there were errors in the consortium lists at the end of the paper. Maureen Rischmueller, Hyon K. Choi, Masahiro Nakatochi, Jeff N. Miner, Daniel H. Solomon, Kathleen M. Giacomini and Deanna J. Brackman were erroneously listed as members of the Japan Gout Genomics Consortium. Instead, Akiyoshi Nakayama, Tappei Takada, Masahiro Nakatochi, Seiko Shimizu, Yusuke Kawamura, Nariyoshi Shinomiya and Kimiyoshi Ichida should have been included in that consortium list. In addition, Lisa K. Stamp, Akiyoshi Nakayama and Yusuke Kawamura were omitted from the list for the GlobalGout Genetics Consortium. The lists have been corrected in the HTML and PDF versions of the article
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