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Lambert, G. D. "Book reviewsQuality Assurance in Radiotherapy. Guide prepared following a workshop at Schloss Reisensburg Federal Republic of Germany 3–7 December 1984, pp. 52, 1988 (World Health Organization, Geneva), SFr 11; US$6.60. ISBN 92–4–1–154224–1." British Journal of Radiology 62, no. 740 (August 1989): 780–81. http://dx.doi.org/10.1259/0007-1285-62-740-780-b.
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Kiewnick, S., G. Karssen, J. A. Brito, M. Oggenfuss, and J. E. Frey. "First Report of Root-Knot Nematode Meloidogyne enterolobii on Tomato and Cucumber in Switzerland." Plant Disease 92, no. 9 (September 2008): 1370. http://dx.doi.org/10.1094/pdis-92-9-1370a.
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Severe stunting and extensive root galling were observed on tomato rootstock (Solanum lycopersicum L. cv. Maxifort) resistant to Meloidogyne incognita (Kofoid & White, 1919) Chitwood, 1949, M. javanica (Treub, 1885), and M. arenaria (Neal, 1889) Chitwood, 1949 and cucumber (Cucumis sativus L. cv. Loustik) from two commercial greenhouses in the cantons Aargau and Lucerne in northern Switzerland. Examination of the roots of infected plants revealed the presence of root-knot nematodes in large numbers. Juveniles, males, and females were isolated, and the species was determined on the basis of morphological characteristics, including the female perineal pattern. Identification was confirmed by female esterase (Est) and malate dehydrogenase (MdH) electrophoresis (20 each for Est and MdH). All methods of identification were consistent with M. enterolobii Yang & Eisenback, 1983 (4). For further confirmation, type material of M. enterolobii (from the original host Enterolobium contortisiliquum (Vell.) Morong) from China (4) was used. Furthermore, comparison of the sequence data from 12 individuals of each of the two Swiss populations and the type material of a 310-bp fragment of cytochrome oxidase I (COI), a 723-bp fragment covering the internal transcribed spacer (ITS) region 1, 5.8s, ITS2, and part of the 26s, the mtDNA 63-bp repeat region, and a 780-bp fragment of the intergenic spacer region (1–3) showed 100% homology and confirmed the identification as M. enterolobii. The species M. enterolobii is of great importance because it is able to reproduce on resistant tobacco, pepper, watermelon, and tomato (4). To our knowledge, this is the first report of M. enterolobii in Switzerland. References: (1) M. A. M. Adam et al. Plant Pathol. 56:190, 2007. (2) V. C. Blok et al. Nematology 4:773, 2002. (3) T. C. Vrain et al. Fundam. Appl. Nematol. 15:565, 1992. (4) B. Yang and J. D. Eisenback. J. Nematol. 15:381, 1983.
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Gaudet, Charles E., Grant L. Iverson, Ross Zafonte, Paul Berkner, and Nathan E. Cook. "A-187 Prior Concussion History and Recovery Time Following Sport-Related Concussion in High School Athletes." Archives of Clinical Neuropsychology 37, no. 6 (August 17, 2022): 1342. http://dx.doi.org/10.1093/arclin/acac060.187.
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Abstract Objective: To examine whether adolescents with prior concussions take longer to return to school and/or sports following a subsequent sport-related concussion. Method: Injury surveillance data for 780 adolescents (M age=16.3, SD=1.3 years) were analyzed. Adolescents were divided into three groups: (a) no prior concussion history (69%; n=538), (b) history of one prior concussion (19.2%; n=150), and (c) history of two or more prior concussions (11.8%; n=92). We analyzed between-group differences in time to return to school and sports. Results: Groups did not differ in time to return to school (K-W: χ2(2)=0.95, p=.62; Log Rank: χ2 (2)=2.83, p=.24) or sports (K-W: χ2(2)=2.19, p=0.33; Log Rank: χ2 (2)=3.95, p=.14). However, a greater proportion of student athletes with two or more prior concussions had not returned to their sport at 28 days postinjury compared to those with no prior concussions (23.5% vs. 12.7%; OR=2.10, 95% CI 1.18-3.73). Of note, the two or more prior concussion group contained a higher proportion of adolescents with potential pre-injury risk factors for complicated recovery, namely, depression and migraines. Conclusions: Prior concussion history was not associated with longer time to return to school nor return to sport when examined as a continuous variable. However, at 28 days postinjury, a greater proportion of athletes with two or more prior concussions remained out of sports compared to those with no prior concussions.
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Jorge, Ahmed, Dylan A. Royston, Elizabeth C. Tyler-Kabara, Michael L. Boninger, and Jennifer L. Collinger. "Classification of Individual Finger Movements Using Intracortical Recordings in Human Motor Cortex." Neurosurgery 87, no. 4 (March 6, 2020): 630–38. http://dx.doi.org/10.1093/neuros/nyaa026.
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Abstract BACKGROUND Intracortical microelectrode arrays have enabled people with tetraplegia to use a brain–computer interface for reaching and grasping. In order to restore dexterous movements, it will be necessary to control individual fingers. OBJECTIVE To predict which finger a participant with hand paralysis was attempting to move using intracortical data recorded from the motor cortex. METHODS A 31-yr-old man with a C5/6 ASIA B spinal cord injury was implanted with 2 88-channel microelectrode arrays in left motor cortex. Across 3 d, the participant observed a virtual hand flex in each finger while neural firing rates were recorded. A 6-class linear discriminant analysis (LDA) classifier, with 10 × 10-fold cross-validation, was used to predict which finger movement was being performed (flexion/extension of all 5 digits and adduction/abduction of the thumb). RESULTS The mean overall classification accuracy was 67% (range: 65%-76%, chance: 17%), which occurred at an average of 560 ms (range: 420-780 ms) after movement onset. Individually, thumb flexion and thumb adduction were classified with the highest accuracies at 92% and 93%, respectively. The index, middle, ring, and little achieved an accuracy of 65%, 59%, 43%, and 56%, respectively, and, when incorrectly classified, were typically marked as an adjacent finger. The classification accuracies were reflected in a low-dimensional projection of the neural data into LDA space, where the thumb-related movements were most separable from the finger movements. CONCLUSION Classification of intention to move individual fingers was accurately predicted by intracortical recordings from a human participant with the thumb being particularly independent.
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Editorial, E. "Retraction: Pogacnik M, Znidarcic D, Strgar J. A school garden in biotechnical education. Arch biol sci. 2014; 66(2):785-92, DOI: 10.2298/ABS1402785P." Archives of Biological Sciences 67, no. 3 (2015): 1077. http://dx.doi.org/10.2298/abs150612076e.
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This is a notice of retraction of the article: A school garden in biotechnical education, published in the Archives of Biological Sciences in 2014, Vol. 66, Issue 2. Due to a printing error, caused by the journal, the same paper has already been published in the Archives of Biological Sciences, Vol. 66, Issue 1, 2014 (DOI: 10.2298/ABS1401393P). Therefore, the latter article is being retracted. The corresponding author has been informed of this error and retraction. We apologize to the authors and to the readers for this error. <br><br><font color="red"><b> Link to the retracted article <u><a href="http://dx.doi.org/10.2298/ABS1402785P">10.2298/ABS1402785P</a></b></u>
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Hultquist, G., M. Seo, Q. Lu, G. K. Chuah, and K. L. Tan. "Surface reactions at 300–750 K in the iron-oxygen-water system studied by SIMS." Applied Surface Science 59, no. 2 (January 1992): 135–45. http://dx.doi.org/10.1016/0169-4332(92)90297-b.
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Menter, Thomas, Stephan Dirnhofer, and Alexandar Tzankov. "LEF1: a highly specific marker for the diagnosis of chronic lymphocytic B cell leukaemia/small lymphocytic B cell lymphoma." Journal of Clinical Pathology 68, no. 6 (February 24, 2015): 473–78. http://dx.doi.org/10.1136/jclinpath-2015-202862.
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AimsChronic lymphocytic B cell leukaemia (CLL)/small lymphocytic B cell lymphoma (SLL) has proven to be not a uniform entity but to consist of various disease subtypes. CLL might also pose diagnostic challenges by demonstrating an uncommon immunohistochemical profile. Recently, the role of lymphocyte enhancer-binding factor 1 (LEF1) in CLL was elucidated being highly expressed and seeming to have a prognostic value. Our aim was to test the applicability of LEF1 as marker for CLL in a diagnostic setting.MethodsWe investigated LEF1 expression in lymphomas by immunohistochemistry on tissue microarrays containing several lymphoma entities (altogether 720 cases, including 61 CLL cases). We also separated CLL cases by zeta-chain-associated protein kinase 70 (ZAP70) and CD38 stainings and fluorescence in situ hybridisation analyses for TP53 deletions and trisomy 12 into respective groups and correlated data with LEF1 expression.ResultsThe area under the receiver operating characteristic curve for LEF1 as a diagnostic marker for CLL was 0.815 (95% CI 0.742 to 0.888). The relevant diagnostic cut-off value for LEF1 positivity determined by the Youden's index was 10% (specificity 92%, sensitivity 70%). The majority of CLL cases (70%) expressed LEF1. Eighteen per cent of (transformed) diffuse large B cell lymphoma cases also expressed LEF1. In most other lymphoma entities, LEF1 was negative. There was a positive correlation of LEF1 staining with ZAP70 expression (Spearman's rho: 0.438, p<0.001), but not with CD38 expression, TP53 deletions or trisomy 12.ConclusionsLEF1 is a useful marker in the differential diagnosis of CLL in difficult cases. It shows a high specificity (92%) and a reasonable sensitivity (70%) for this entity.
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Fry, F. A. "Book reviewsAssessment of Radioactive Contamination in Man 1984. International Atomic Energy Agency, pp. 565 + index, 1985 (IAEA, Vienna), 1140 Austrian Schillings. ISBN 92–0–020085–0." British Journal of Radiology 59, no. 700 (April 1986): 396. http://dx.doi.org/10.1259/0007-1285-59-700-396-b.
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Lopes, Kelvin Saldanha, Francisco Willyego Holanda Maciel, Roque Soares Martins Neto, Vilana Maria Adriano Araújo, Juscelino de Freitas Jardim, and Mardonio Rodrigues Pinto. "Aplicações e possibilidades terapêuticas do uso do biomaterial quitosana para a odontologia: revisão de literatura." ARCHIVES OF HEALTH INVESTIGATION 9, no. 6 (April 20, 2020): 587–91. http://dx.doi.org/10.21270/archi.v9i6.4782.
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A quitosana, polissacarídeo linear obtido a partir do exoesqueleto de crustáceos e artrópodes, tem sido pesquisada em Odontologia por suas diversas propriedades terapêuticas. O objetivo do presente estudo foi realizar uma revisão da literatura sobre as aplicações atuais e as possibilidades terapêuticas da quitosana na odontologia. A busca foi realizada através do banco de dados eletrônico do Pubmed, utilizando os descritores Quitosana, Odontologia e Biomateriais. Foram incluídas pesquisas científicas utilizando quitosana em diversas áreas da odontologia e excluídas revisões de literatura e estudos não odontológicos, sendo selecionados 13 artigos. A quitosana induz resposta transcricional e anti-inflamatória em fibroblastos gengivais sobre citocinas inflamatórias, fatores transformadores do crescimento (TGF -β) e fatores de crescimento tumoral (TNF-α) que estão diretamente relacionados à atividade patológica periodontal. Nas infecções endodônticas persistentes, a substância atua criando ligações de hidrogênio e liberação de íons cálcio, o que potencializa a ação dos irrigadores intracanal, além de causar menos estresse oxidativo. Para a odontologia restauradora, a quitosana demonstrou eficácia como auxiliar no condicionamento da dentina e mostrou potencial para induzir a migração de odontoblastos na proteção do complexo dentino-pulpar. A substância atua como uma cura de feridas orais devido à sua capacidade de estimular a formação de fibroblastos e novos vasos sanguíneos, além de células anti-inflamatórias.
Descritores: Biopolímeros; Biomateriais; Biotecnologia.
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Taukhid, Taukhid, Hambali Supriyadi, and Nenden Dalis Asmaeni. "PENGARUH PENAMBAHAN VITAMIN C (Ascorbic Acid) PADA PAKAN KOMERSIAL TERHADAP KETAHANAN BENIH LELE DUMBO (Clarias sp. Burchell) TERHADAP INFEKSI BAKTERI Aeromonas hydrophila Stainer." Jurnal Riset Akuakultur 1, no. 2 (November 16, 2016): 203. http://dx.doi.org/10.15578/jra.1.2.2006.203-209.
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Riset ini bertujuan untuk mengetahui jumlah optimal penambahan vitamin C ke dalam pakan ikan lele dumbo yang dapat memberikan ketahanan tubuh maksimal terhadap infeksi bakteri Aeromonas hydrophila. Perlakuan yang diterapkan terdiri atas (A) pakan komersial tanpa penambahan vitamin C sebagai kontrol, (B) penambahan vitamin C sebanyak 250 mg/kg pakan, (C) penambahan vitamin C sebanyak 500 mg/kg pakan, (D) penambahan vitamin C sebanyak 750 mg/kg pakan, dan (E) penambahan vitamin C sebanyak 1.000 mg/kg pakan. Pakan diberikan selama 62 hari, dan pada hari ke-56 dilakukan uji tantang terhadap bakteri A. hydrophila konsentrasi 1,0 x 106 cfu/mL yang diberikan melalui penyuntikan intra muskular (IM) sebanyak 0,1 mL/ekor ikan uji. Pengamatan dilakukan terhadap kadar titer antibodi spesifik, gejala klinis, dan sintasan setelah uji tantang serta kadar vitamin C dalam hati ikan. Hasil riset menunjukkan bahwa penambahan vitamin C pada pakan dapat meningkatkan ketahanan tubuh ikan uji terhadap infeksi bakteri A. hydrophila, dan nilai titer antibodi spesifik mengalami peningkatan yang mulai terlihat pada minggu ke-IV. Pada akhir pengamatan diperoleh sintasan ikan uji sebesar 68%, 78%, 92%, 96%, dan 92% masing-masing untuk kelompok kontrol, perlakuan B, perlakukan C, perlakuan D, dan perlakuan E. Berdasarkan analisis regresi dapat didekati bahwa jumlah optimal vitamin C untuk memperoleh level proteksi yang cukup tinggi dengan sintasan 98,86% adalah sebesar 893 mg/kg pakan.The experiment with the aim to know the amount of vitamin C added to commercial diet that could improved a maximum resistance of African catfish against Aeromonas hydrophila infection has been conducted. The treatments were (A) commercial diet without vitamin C as a control, (B) commercial diet with 250 mg/kg vitamin C, (C) 500 mg/kg, (D) 750 mg/kg, and (E) 1,000 mg/kg. The diet was given for 62 days, and at the 56th day the fish was challenged against A. hydrophila infection through intra muscular injection at the dose of 0.1 mL of 1.0 x 106 cfu bacterial suspensions. Specific antibody titer, clinical signs, survival rate, and vitamin C level on the liver of the fish were observed. The results indicated that addition of vitamin C to the diet was effective to increase the resistance of African catfish against A. hydrophila infection. Survival rates of fish test at the end of the experiment were 68%, 78%, 92%, 96%, and92% for the group of A, B, C, D, and E respectively. Based on regression analysis, the optimum amount of vitamin C add
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Holt, P. M. "The Īlkhān Aḥmad's embassies to Qalāwūn: two contemporary accounts." Bulletin of the School of Oriental and African Studies 49, no. 1 (February 1986): 128–32. http://dx.doi.org/10.1017/s0041977x00042543.
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With the accession of Tegüder, alias Ahmad, on the death of his brother Abaqa in 681/1282, the Īlkhānate was for the first time ruled by a Muslim. Consequently the possibility appeared of the establishment of peaceful relations with the rival Mamlūk sultanate under al-Manṣūr Qalāwūn (regn. 678–89/1279–90). Two successive embassies were in fact sent to the sultan during Ahmad's short reign, and accounts of these as seen in Mamlūk court circles are extant in the writings of two contemporaries. The first appears in the largely unpublished biography of Qalāwūn, al-Fadl al-ma'thūr min sīrat al-Malik al-Mansūr by Shāf‚’ b. ‘Alī (649–730/1252–1330), and the second in the published but incomplete biography, Tashrīf al-ayyām wa'l-‘usūr fi sīrat al-Malik al-Mansūr by the maternal uncle of Shāfi'b. ‘Alī, Muhyī al-Dīn Ibn ‘Abd al-Zāhir (620–92/1223–92). Both writers served in the chancery of the sultan in Cairo.
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Siu, Lillian L., Jeremy David Shapiro, Derek J. Jonker, Christos Stelios Karapetis, John Raymond Zalcberg, John Simes, Felix Couture, et al. "Final analysis of the phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with chemotherapy refractory, K-RAS wild-type (WT), metastatic colorectal carcinoma (mCRC): The NCIC Clinical Trials Group and AGITG CO.20 trial." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 3504. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.3504.
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3504 Background: The anti-EGFR monoclonal antibody CET has improved survival in pts with chemotherapy refractory, K-RAS WT mCRC. BRIV is a potent inhibitor of multiple receptor tyrosine kinases including both VEGFR and FGFR. The combination of CET and BRIV targets tumor growth and angiogenesis and demonstrated encouraging activity in an early phase clinical trial. Methods: Pts with mCRC previously treated with combination chemotherapy were randomized 1:1 to receive CET 400 mg/m2 IV loading dose followed by weekly maintenance of 250 mg/m2 plus either BRIV 800 mg PO daily (Arm A) or placebo (Arm B). Pts may have had 1 prior anti-VEGF, but no prior anti-EGFR therapy. Primary endpoint was overall survival (OS). Results: From 02/2008 to 02/2011, 750 pts were randomized (376 in Arm A and 374 in Arm B). Demographics: median age=64 (range 27-88); male=64%; ECOG 0:1:2 (%)=32:58:10; >3 prior chemotherapy regimens=92%; prior anti-VEGF therapy=41%; K-RAS WT=97%. Primary analysis was conducted per protocol after 536 deaths were observed, with median OS of 8.8 months in Arm A and 8.1 months in Arm B, hazard ratio (HR)=0.88; 95% CI=0.74 to 1.03; p=0.12. Median progression-free survival (PFS) was 5.0 months in Arm A and 3.4 months in Arm B, HR=0.72; 95% CI=0.62 to 0.84; p<0.0001. Incidence of any ≥grade 3 adverse event (AE) was 78% in Arm A and 53% in Arm B. Time to deterioration of physical function was shorter and global quality of life scores were lower in Arm A vs Arm B. Planned subgroup analyses revealed no statistically difference in treatment effects on OS based on pre-specified factors of age, gender, ECOG and race. Likewise, no difference was detected based on exploratory subgroup analyses of LDH and prior anti-VEGF therapy. Conclusions: Despite positive effects on PFS, the combination of CET+BRIV did not significantly improve OS in pts with chemotherapy refractory, K-RAS WT mCRC. Final updated results based on 20-25% additional events for a total of nearly 700 deaths, as well as further exploratory subgroup analyses, will be presented.
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Reimann, Timmy, and Jörg Töpfer. "Low-temperature sintered Ni–Zn–Co–Mn–O spinel oxide ceramics for multilayer NTC thermistors." Journal of Materials Science: Materials in Electronics 32, no. 8 (March 28, 2021): 10761–68. http://dx.doi.org/10.1007/s10854-021-05733-9.
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AbstractThe phase formation, sintering behavior and electrical properties of Ni–Co–Zn–Mn spinel NTC thermistor ceramics of the series Ni0.5ZnzCo0.5Mn2−zO4 with 0 ≤ z ≤ 1 were studied. In contrast to NiMn2O4, which exhibits limited stability in air below 730 °C and above 970 °C, the Zn–Co-substituted nickel manganite spinels are stable at T < 730 °C and decompose at Td > 900 °C, with Td increasing with decreasing Zn Content z. The samples were sintered at 900 °C with addition of 3 wt% Bi2O3 as sintering aid and densities of above 92% were achieved. The room temperature resistivity and thermistor B-constants are almost independent of composition at 0 ≤ z ≤ 0.6 and start to increase at higher Zn concentrations. A multilayer NTC thermistor was fabricated using green tapes of a spinel of composition z = 0.75, commercial Ag paste, and cofiring at 900 °C. The firing behavior, microstructure formation and electrical properties of the multilayer thermistor are reported.
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Shetty, Arusha, Gaurav Chatterjee, Sweta Rajpal, Tuhina Srivastava, Nilesh Gardi, Sumeet Mirgh, Anant Gokarn, et al. "Genomic Analysis of AZD1222 (ChAdOx1) Vaccine Breakthrough Infections in the City of Mumbai." International Journal of Clinical Practice 2022 (February 11, 2022): 1–9. http://dx.doi.org/10.1155/2022/2449068.
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Background. This manuscript describes the genetic features of SARS-CoV-2 mutations, prevalent phylogenetic lineages, and the disease severity amongst COVID-19-vaccinated individuals in a tertiary cancer hospital during the second wave of the pandemic in Mumbai, India. Methods. This observational study included 159 COVID-19 patients during the second wave of the pandemic from 17th March to 1st June 2021 at a tertiary cancer care centre in Mumbai. The cohort comprised of healthcare workers, staff relatives, cancer patients, and patient relatives. For comparison, 700 SARS-CoV-2 genomes sequenced during the first wave (23rd April to 25th September 2020) at the same centre were also analysed. Patients were assigned to nonvaccinated (no vaccination or <14 days from the 1st dose, n = 92), dose 1(≥14 days from the 1st dose to <14 days from the 2nd dose, n = 29), and dose 2 (≥14 days from the 2nd dose, n = 38) groups. Primary measure was the prevalence of SARS-CoV-2 genomic lineages among different groups. In addition, severity of COVID-19 was assessed according to clinical and genomic variables. Results. Kappa B.1.1671.1 and delta B.1.617.2 variants contributed to an overwhelming majority of sequenced genomes (unvaccinated: 40/92, 43.5% kappa, 46/92, 50% delta; dose 1: 14/29, 48.3% kappa, 15/29, 51.7% delta; and dose 2: 23/38, 60.5% kappa, 14/38 36.8% delta). The proportion of the kappa and delta variants did not differ significantly across the unvaccinated, dose 1, and dose 2 groups ( p = 0.27). There was no occurrence of severe COVID-19 in the dose 2 group (0/38, 0% vs. 14/121, 11.6%; p = 0.02). SARS-CoV-2 genomes from all three severe COVID-19 patients in the vaccinated group belonged to the delta lineage (3/28, 10.7% vs. 0/39, 0.0%, p = 0.04). Conclusions. Sequencing analysis of SARS-COV-2 genomes from Mumbai during the second wave of COVID-19 suggests the prevalence of the kappa B.1.617.1 and the delta B.1.627.2 variants among both vaccinated and unvaccinated individuals. Continued evaluation of genomic sequencing data from breakthrough COVID-19 is necessary for monitoring the properties of evolving variants of concern and formulating appropriate immune response boosting and therapeutic strategies.
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Zhang, Yingqiang, Guihua Huang, Hongfei Miao, Ze Song, Xiaoying Zhang, Wenzhe Fan, Yu Wang, Jiaping Li, and Yong Chen. "Apatinib treatment may improve survival outcomes of patients with hepatitis B virus-related sorafenib-resistant hepatocellular carcinoma." Therapeutic Advances in Medical Oncology 12 (January 2020): 175883592093742. http://dx.doi.org/10.1177/1758835920937422.
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Aims: This study aimed to (a) assess the effectiveness and safety of apatinib as a subsequent treatment for patients with sorafenib-resistant hepatocellular carcinoma (HCC), and (b) identify the clinical factors influencing their treatment outcomes. Methods: The electronic medical records of consecutive patients with newly diagnosed advanced HCC treated with first-line sorafenib from 2015 to 2017 were retrospectively reviewed. Patients who were confirmed to have primary resistance to sorafenib were enrolled in this study. The outcomes of patients treated with apatinib were compared with those of patients who received supportive care. The primary endpoint was overall survival (OS). Results: A total of 92 patients with sorafenib-resistant advanced HCC (84 men and 8 women; mean age, 51.9 years) were included. All patients had an etiology of hepatitis B. The median OS in the overall cohort was 5.0 months [95% confidence interval (CI): 3.9, 6.0]. Of 92 patients, 58 (63.0%) were treated with apatinib, and 34 (37.0%) received supportive care. Apatinib treatment was associated with longer survival times than supportive care for patients with sorafenib-resistant advanced HCC (median OS: 7.0 versus 4.0 months, p < 0.001). The results of the multivariate analysis demonstrated that liver tumor load [hazard ratio (HR): 3.653, 95% CI: 2.047, 5.965, p < 0.001] and extrahepatic spread (HR: 0.303, 95% CI: 0.231, 0.778, p = 0.003) were independent predictors of OS after apatinib treatment. Conclusion: This study showed that subsequent apatinib treatment may improve survival outcomes compared with supportive care for patients with sorafenib-resistant, advanced hepatitis B virus (HBV)-related HCC, especially for patients who have a lower liver tumor load and extrahepatic spread.
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Palmedo, Holger, Agnieska Manka-Waluch, Peter Albers, Ingo G. H. Schmidt-Wolf, Michael Reinhardt, Samer Ezziddin, Alexius Joe, et al. "Repeated Bone-Targeted Therapy for Hormone-Refractory Prostate Carcinoma: Randomized Phase II Trial With the New, High-Energy Radiopharmaceutical Rhenium-188 Hydroxyethylidenediphosphonate." Journal of Clinical Oncology 21, no. 15 (August 1, 2003): 2869–75. http://dx.doi.org/10.1200/jco.2003.12.060.
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Purpose: We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments. Patients and Methods: Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death. Results: In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P = .006 and P = .001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P = .0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P = .043). Conclusion: Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.
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Arrieta, Jesús María, Markus G. Weinbauer, and Gerhard J. Herndl. "Interspecific Variability in Sensitivity to UV Radiation and Subsequent Recovery in Selected Isolates of Marine Bacteria." Applied and Environmental Microbiology 66, no. 4 (April 1, 2000): 1468–73. http://dx.doi.org/10.1128/aem.66.4.1468-1473.2000.
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ABSTRACT The interspecific variability in the sensitivity of marine bacterial isolates to UV-B (295- to 320-nm) radiation and their ability to recover from previous UV-B stress were examined. Isolates originating from different microenvironments of the northern Adriatic Sea were transferred to aged seawater and exposed to artificial UV-B radiation for 4 h and subsequently to different radiation regimens excluding UV-B to determine the recovery from UV-B stress. Bacterial activity was assessed by thymidine and leucine incorporation measurements prior to and immediately after the exposure to UV-B and after the subsequent exposure to the different radiation regimens. Large interspecific differences among the 11 bacterial isolates were found in the sensitivity to UV-B, ranging from 21 to 92% inhibition of leucine incorporation compared to the bacterial activity measured in dark controls and from 14 to 84% for thymidine incorporation. Interspecific differences in the recovery from the UV stress were also large. An inverse relation was detectable between the ability to recover under dark conditions and the recovery under photosynthetic active radiation (400 to 700 nm). The observed large interspecific differences in the sensitivity to UV-B radiation and even more so in the subsequent recovery from UV-B stress are not related to the prevailing radiation conditions of the microhabitats from which the bacterial isolates originate. Based on our investigations on the 11 marine isolates, we conclude that there are large interspecific differences in the sensitivity to UV-B radiation and even larger differences in the mechanisms of recovery from previous UV stress. This might lead to UV-mediated shifts in the bacterioplankton community composition in marine surface waters.
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Galmiche, Simon, Timothée Bruel, Yoann Madec, Laura Tondeur, Ludivine Grzelak, Isabelle Staropoli, Isabelle Cailleau, et al. "Characteristics Associated with Olfactory and Taste Disorders in COVID-19." Neuroepidemiology 55, no. 5 (2021): 381–86. http://dx.doi.org/10.1159/000517066.
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<b><i>Introduction:</i></b> Olfactory and taste disorders (OTDs) have been reported in COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the mechanisms of which remain unclear. We conducted a detailed analysis of OTDs as part of 2 seroepidemiological investigations of COVID-19 outbreaks. <b><i>Methods:</i></b> Two retrospective cohort studies were conducted in a high school and primary schools of Northern France following a COVID-19 epidemic in February-March 2020. Students, their relatives, and school staff were included. Anti-SARS-CoV-2 antibodies were identified using a flow-cytometry-based assay detecting anti-S IgG. <b><i>Results:</i></b> Among 2,004 participants (median [IQR] age: 31 [11–43] years), 303 (15.2%) tested positive for SARS-CoV-2 antibodies. OTDs were present in 91 (30.0%) and 92 (30.3%) of them, respectively, and had 85.1 and 78.0% positive predictive values for SARS-CoV-2 infection, respectively. In seropositive participants, OTDs were independently associated with an age above 18 years, female gender, fatigue, and headache. <b><i>Conclusion:</i></b> This study confirms the higher frequency of OTDs in females than males and adults than children. Their high predictive value for the diagnosis of COVID-19 suggests that they should be systematically searched for in patients with respiratory symptoms, fever, or headache. The association of OTDs with headache, not previously reported, suggests that they share a common mechanism, which deserves further investigation.
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Cisak, Kamila Izabela, Amitoj Gill, Erin Faber, Rebecca A. Redman, Neal E. Dunlap, Shesh Rai, Xiaoyong Wu, and Cesar Augusto Perez. "Role of neutrophil to lymphocyte ratio in addition to revised international prognostic index (R-IPI) in patients with extranodal diffuse large B-cell lymphoma of head and neck." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e19032-e19032. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e19032.
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e19032 Background: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma (NHL). One third of DLBCLs cases have a primary extranodal origin and head and neck localization is second most common localization after gastrointestinal tract. The Revised-International Prognostic Index (r-IPI) is commonly used as prognostic tool, but there is growing evidence that neutrophil to lymphocyte ratio (NLR) also has prognostic significance in DLBCL. Methods: We retrospectively reviewed all cases of extranodal DLBCLs diagnosed between 2006 and 2016 at a single academic institution. Collected data included race, gender, primary site, baseline laboratory data, IPI score, pathology, treatment and survival. Results: A total of 33 patient were included, with 18 (54.5%) being females. Median age at diagnosis was 68 (range 28-92). 15% of patients had a r-IPI of 0, 30% a r-IPI of 1-2, 12% a rIPI of 3-5 and 36% a not evaluable (NE) r-IPI. Twelve (36%) patients had germinal center B cell subtype (GCB) and 17 (51%) patients had activated B cell subtype (ABC) by immunohistochemistry. Among all patients, 13 (39%) had pretreatment NLR equal or more than 3.5 and 11 (33%) patients had NLR less than 3.5 and 9 patients had a NE NLR. . Among deceased patients, 5 (56%) of them had NLR of more that 3.5 (p =0.011). Nine (27%) patients had pretreatment monocyte count less than 700/mm3 and 14 (42%) patients had monocyte count at least 700/mm3 (p=0.611). The 2-year overall survival was 77% (95% CI 0.61 - 0.93). Conclusions: (R-IPI) is the most common tool to predict outcome in DLBCL and our study showed that pretreatment NLR can be used as additional poor prognosis marker for patients with extranodal DLBCL of the head and neck. [Table: see text]
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TSUCHIYA, N., P. PATHIPVANICH, A. ROJANAWIWAT, N. WICHUKCHINDA, I. KOGA, M. KOGA, W. AUWANIT, P. E. KILGORE, K. ARIYOSHI, and P. SAWANPANYALERT. "Chronic hepatitis B and C co-infection increased all-cause mortality in HAART-naive HIV patients in northern Thailand." Epidemiology and Infection 141, no. 9 (November 1, 2012): 1840–48. http://dx.doi.org/10.1017/s0950268812002397.
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SUMMARYA total of 755 highly active antiretroviral therapy (HAART)-naive HIV-infected patients were enrolled at a government hospital in Thailand from 1 June 2000 to 15 October 2002. Census date of survival was on 31 October 2004 or the date of HAART initiation. Of 700 (92·6%) patients with complete data, the prevalence of hepatitis B virus (HBV) surface antigen and anti-hepatitis C virus (HCV) antibody positivity was 11·9% and 3·3%, respectively. Eight (9·6%) HBV co-infected patients did not have anti-HBV core antibody (anti-HBcAb). During 1166·7 person-years of observation (pyo), 258 (36·9%) patients died [22·1/100 pyo, 95% confidence interval (CI) 16·7–27·8]. HBV and probably HCV co-infection was associated with a higher mortality with adjusted hazard ratios (aHRs) of 1·81 (95% CI 1·30–2·53) and 1·90 (95% CI 0·98–3·69), respectively. Interestingly, HBV co-infection without anti-HBc Ab was strongly associated with death (aHR 6·34, 95% CI 3·99–10·3). The influence of hepatitis co-infection on the natural history of HAART-naive HIV patients requires greater attention.
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Moon, Jung Won, Ehwa Yang, Jae-Hun Kim, O. Jung Kwon, Minsu Park, and Chin A. Yi. "Predicting Non-Small-Cell Lung Cancer Survival after Curative Surgery via Deep Learning of Diffusion MRI." Diagnostics 13, no. 15 (August 1, 2023): 2555. http://dx.doi.org/10.3390/diagnostics13152555.
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Background: the objective of this study is to evaluate the predictive power of the survival model using deep learning of diffusion-weighted images (DWI) in patients with non-small-cell lung cancer (NSCLC). Methods: DWI at b-values of 0, 100, and 700 sec/mm2 (DWI0, DWI100, DWI700) were preoperatively obtained for 100 NSCLC patients who underwent curative surgery (57 men, 43 women; mean age, 62 years). The ADC0-100 (perfusion-sensitive ADC), ADC100-700 (perfusion-insensitive ADC), ADC0-100-700, and demographic features were collected as input data and 5-year survival was collected as output data. Our survival model adopted transfer learning from a pre-trained VGG-16 network, whereby the softmax layer was replaced with the binary classification layer for the prediction of 5-year survival. Three channels of input data were selected in combination out of DWIs and ADC images and their accuracies and AUCs were compared for the best performance during 10-fold cross validation. Results: 66 patients survived, and 34 patients died. The predictive performance was the best in the following combination: DWI0-ADC0-100-ADC0-100-700 (accuracy: 92%; AUC: 0.904). This was followed by DWI0-DWI700-ADC0-100-700, DWI0-DWI100-DWI700, and DWI0-DWI0-DWI0 (accuracy: 91%, 81%, 76%; AUC: 0.889, 0.763, 0.711, respectively). Survival prediction models trained with ADC performed significantly better than the one trained with DWI only (p-values < 0.05). The survival prediction was improved when demographic features were added to the model with only DWIs, but the benefit of clinical information was not prominent when added to the best performing model using both DWI and ADC. Conclusions: Deep learning may play a role in the survival prediction of lung cancer. The performance of learning can be enhanced by inputting precedented, proven functional parameters of the ADC instead of the original data of DWIs only.
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Cardin, L., and B. Moury. "First Report of Potato virus Y in Nicotiana mutabilis in France." Plant Disease 92, no. 2 (February 2008): 312. http://dx.doi.org/10.1094/pdis-92-2-0312b.
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Nicotiana mutabilis Stehmann & Semir is a recently described perennial plant species from southern Brazil that produces long floral stems with white to deep pink flowers and is used for its ornamental quality. In 2003, leaf mosaic symptoms were observed in all 30 N. mutabilis plants in a nursery in the south of France. Observation of crude sap preparations with the electron microscope revealed numerous flexuous particles, 700 to 730 nm long and approximately 11 nm wide, associated with “pinwheel”-like cytoplasmic inclusions, typical of the family Potyviridae. A range of plant species inoculated with extracts from five of the symptomatic plants showed reactions typical of Potato virus Y (PVY) (2), and the presence of the virus was confirmed by positive reactions in double-antibody sandwich (DAS)-ELISA with polyclonal antibodies raised against PVY. To test if PVY was responsible for the symptoms observed in N. mutabilis, an isolate was multiplied in N. tabacum cv. Xanthi plants after isolation from local lesions on Chenopodium amaranticolor and was then mechanically inoculated to 12 seedlings of N. mutabilis cv. Marshmallow. After 3 weeks, the 12 inoculated plants showed systemic vein clearing symptoms and PVY was detected by DAS-ELISA. Reverse transcription (RT)-PCR tests using PVY-polyvalent primers (5′-GATGGTTGCCTTGGATGATG and 5′-TAAAAGTAGTACAGGAAAAGCCA) covering the coat protein (CP) coding region amplified a single DNA fragment of the expected 900 bp from total RNA extracts from Xanthi plants inoculated with the five isolates. One of these DNA products was directly sequenced (GenBank Accession No. EU252529) and several accepted methods of phylogenetic analysis compared this sequence to 80 available PVY CP coding sequences and showed that the N. mutabilis PVY belonged to the C1 group (1). Similar to the other PVY strains in the C group, the N. mutabilis isolate was able to induce hypersensitive local lesions in leaves of potato genotypes carrying the Nc gene. However, contrary to the other characterized C1 isolates (1), it was unable to infect systemically cv. Yolo Wonder pepper plants. That peculiar behavior makes the N. mutabilis isolate a tool to identify the viral determinants controlling the host range of PVY. References: (1) B. Blanco-Urgoiti et al. J. Gen. Virol. 79:2037, 1998. (2) C. Kerlan. No. 414 in: Descriptions of Plant Viruses. CMI/AAB, Kew, Surrey, UK, 2006.
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Pardede, Sudung O., and Dimas K. Bonardo. "Rituximab: Apakah Efektif dalam Tata Laksana Sindrom Nefrotik?" Sari Pediatri 13, no. 4 (November 17, 2016): 285. http://dx.doi.org/10.14238/sp13.4.2011.285-92.
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Sebagian besar pasien sindrom nefrotik memberikan respons yang baik dengan steroid, tetapi terdapat pasien yang tidak responsif dengan steroid dan sulit mengalami remisi, disebut sindrom nefrotik refrakter. Berbagai regimen obat telah diberikan untuk menghindari atau mengurangi efek samping steroid, seperti siklofosfamid, klorambusil, siklosporin, vinkristin, mikofenolat mofetil, dan takrolimus dengan hasil yang bervariasi dan berbagai efek samping. Rituximab adalah antibodi monoklonal anti-CD20 yang menginduksi aktivitas imunologis yang dimediasi oleh komplemen dan mencetuskan aktivitas selular tergantung antibodi (antibody-dependent). Rituximab telah diberikan untuk mengobati sindrom nefrotik refrakter, dan pada sindrom nefrotik relaps sering, terjadi remisi dan tidak timbul relaps. Penelitian multisenter untuk sindrom nefrotik dependen steroid dan resisten steroid, memperlihatkan terjadi remisi pada sebagian besar pasien. Pemberian rituximab pada sindrom nefrotik dengan gambaran patologi anatomi kelainan minimal, nefropati membranosa, dan glomerulosklerosis fokal segmental menyebabkan remisi pada sebagian besar pasien. Keberhasilan rituximab dalam tata laksana sindrom nefrotik idiopatik merupakan bukti terdapatnya peran limfosit B dalam patogenesis sindrom nefrotik. Dosis yang sering digunakan 375 mg/m2LPB secara intravena diberikan 4 dosis dengan interval satu minggu atau dosis 750 mg/m2LPB diberikan dua dosis selang waktu dua minggu. Rituximab dapat mengurangi aktivitas penyakit dan memperbaiki sensitivitas terhadap obat imunsupresan. Efek samping yang sering terjadi berupa reaksi akut seperti demam, nyeri abdomen, diare, muntah, ruam kulit, bronkospasme, takikadia, dan hipertensi. Rituximab memberikan hasil yang baik dalam tata laksana sindrom nefrotik refrakter, namun diperlukan uji klinik dengan jumlah sampel yang cukup untuk menilai efikasi dan keamanan obat
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Готцева, Маріана. "A Neurocognitive Perspective on Language Acquisition in Ullman’s DP Model." East European Journal of Psycholinguistics 4, no. 2 (December 28, 2017): 24–33. http://dx.doi.org/10.29038/eejpl.2017.4.2.got.
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In the last few decades, the studies in second language acquisition have not answered the question what mechanisms a human’s brain uses to make acquisition of language(s) possible. A neurocognitive model which tries to address SLA from such a perspective was suggested by Ullman (2005; 2015), according to which, “both first and second languages are acquired and processed by well-studied brain systems that are known to subserve particular nonlanguage functions” (Ullman, 2005: 141). The brain systems in question have analogous roles in their language and nonlanguage functions. This article is meant to critically analyse the suggested DP model within the context of neurocognitive studies of L2; and evaluate its contribution to the field of SLA studies.
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Ullman, M.T. (2005). A cognitive neuroscience perspective on second language acquisition: the declarative/procedural model. In: Adult Second Language Acquisition, (pp. 141-178). C. Sanz, (ed.). Washington, DC: Georgetown University Press.
Ullman, M.T. & Pieport, E.I. (2005). Specific language impairment is not specific to language: the procedural deficit hypothesis. Cortex, 41, 399-433.
Ullman, M. (2006). Is Broca’s area part of a basal ganglia thalamocortical circuit? In: The Cortex: Integrative Models of Broca’s Area and the Ventral Premotor Cortex. (pp. 480-485). R. Schubotz & C. Fiebach, (Eds.). Milan: Masson.
Ullman, M. (2015) The declarative / procedural model: A neurobiologically motivated theory of first and second language. In: Theories in Second Language Acquisition: An Introduction, (pp. 135-158.) VanPatten, B. and J. Williams, (Eds.). 2nd ed. New York: Routledge.
Ullman, M. and Lovelett, J. (2016). Implications of the declarative / procedural model for improving second language learning: The role of memory enhancement techniques. Second Language Research, Special issue, 1-27.
Zurowski, B., Gostomzyk, J., Gron, G., Weller, R., Schirrmeister, H., Neumeier, B., Spitzer, M., Reske, S.N. & Walter, H. (2002). Dissociating a common working memory network from different neural substrates of phonological and spatial stimulus processing. Neuroimage, 15, 45-57.
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Miller, Langdon L., Edward L. Korn, Diane S. Stevens, John E. Janik, Barry L. Gause, William C. Kopp, Jon T. Holmlund, et al. "Abrogation of the Hematological and Biological Activities of the Interleukin-3/Granulocyte-Macrophage Colony-Stimulating Factor Fusion Protein PIXY321 by Neutralizing Anti-PIXY321 Antibodies in Cancer Patients Receiving High-Dose Carboplatin." Blood 93, no. 10 (May 15, 1999): 3250–58. http://dx.doi.org/10.1182/blood.v93.10.3250.410k35_3250_3258.
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This dose-escalation study was performed to evaluate the hematologic activity, biological effects, immunogenicity, and toxicity of PIXY321 (an interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein) administered after high-dose carboplatin (CBDCA) treatment. Patients with advanced cancers received CBDCA at 800 mg/m2 intravenously on day 0 of repeated 28-day cycles. In part A of the study, patients were treated with CBDCA alone during cycle 1 and then received PIXY321 on days 1 through 18 of cycle 2 and later cycles. In part B, patients received 18 days of PIXY321 beginning on day 1 of all CBDCA cycles, including cycle 1. PIXY321 was administered subcutaneously in 2 divided doses. Total doses of 135, 250, 500, 750, and 1,000 μg/m2/d were administered to successive cohorts of 3 to 6 patients in part A. In part B, patient groups received PIXY321 doses of 750, 1,000, and 1,250 μg/m2/d. The hematologic effects of PIXY321 were assessed in the first 2 cycles of therapy. Anti-PIXY321 antibody formation was assessed by enzyme-linked immunosorbent assay (ELISA) and neutralization assay. Of the 49 patients enrolled, 31 were fully evaluable for hematologic efficacy. When comparing the first B cycle (cycle B-1; with PIXY321) with the first A cycle (cycle A-1; without PIXY321), the fusion protein had no significant effect on platelet nadirs or duration of platelets less than 20,000/μL but was able to speed the time of recovery of platelet counts to 100,000/μL (15v 20 days; P = .01). Significant improvements in neutrophil nadir and duration of ANC less than 500 were observed in cycles A-2 and B-1 (with PIXY321) as compared with cycle A-1 (without PIXY321). Initial PIXY321 prophylaxis (cycle A-2 and cycle B-1), enhanced the recovery of ANC to greater than 1,500/μL by an average of at least 8 days as compared with cycle A-1 (without PIXY321;P ≤ .004). However, positive PIXY321 hematologic effects were lost in the second course of PIXY321 among patients treated in part B. ELISA analysis showed that 92% of patients had developed neutralizing anti-PIXY321 antibodies by the completion of 2 PIXY321-containing cycles. The incidental action of PIXY321 to depress serum cholesterol levels was also abrogated during cycle B-2. We conclude that PIXY321 was active in speeding hematologic recovery but that neutralizing anti-PIXY321 antibody formation suppressed the hematologic and biochemical effects by the second cycle of PIXY321 administration. The immunogenicity of this fusion protein provides a cautionary warning that clinical development of bioengineered human molecules requires thorough testing for immune neutralization.
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Lefebvre, Jean Louis, Yoann Pointreau, Frederic Rolland, Marc Alfonsi, Alain Baudoux, Christian Sire, Dominique de Raucourt, et al. "Induction Chemotherapy Followed by Either Chemoradiotherapy or Bioradiotherapy for Larynx Preservation: The TREMPLIN Randomized Phase II Study." Journal of Clinical Oncology 31, no. 7 (March 1, 2013): 853–59. http://dx.doi.org/10.1200/jco.2012.42.3988.
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Purpose To compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP). Patients and Methods Previously untreated patients with stage III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT—docetaxel and cisplatin 75 mg/m2 each on day 1 and fluorouracil 750 mg/m2 per day on days 1 through 5. Poor responders (< 50% response) underwent salvage surgery. Responders (≥ 50% response) were randomly assigned to conventional radiotherapy (RT; 70 Gy) with concurrent cisplatin 100 mg/m2 per day on days 1, 22, and 43 of RT (arm A) or concurrent cetuximab 400 mg/m2 loading dose and 250 mg/m2 per week during RT (arm B). Primary end point was LP at 3 months. Secondary end points were larynx function preservation (LFP) and overall survival (OS) at 18 months. Results Of the 153 enrolled patients, 116 were randomly assigned after ICT (60, arm A; 56, arm B). Overall toxicity of both CRT and BRT was substantial following ICT. However, treatment compliance was higher in the BRT arm. In an intent-to-treat analysis, there was no significant difference in LP at 3 months between arms A and B (95% and 93%, respectively), LFP (87% and 82%, respectively), and OS at 18 months (92% and 89%, respectively). There were fewer local treatment failures in arm A than in arm B; salvage surgery was feasible in arm B only. Conclusion There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou [GORTEC] 2000-01 trial [Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma]). The protocol that can best compare with RT alone after ICT is still to be determined.
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Sym, Sun-Jin, Sung Sook Lee, Min Kyoung Kim, Shin Kim, and Cheolwon Suh. "Ki-67 Expression Level Is Not a Significant Prognostic Factor in Korean Diffuse Large B-Cell Lymphoma." Blood 108, no. 11 (November 16, 2006): 4631. http://dx.doi.org/10.1182/blood.v108.11.4631.4631.
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Abstract The cell proliferation rate of tumors from patients with non-Hodgkin’s lymphomas has been shown to correlate with survival in previous studies. The aim of this study was to evaluate the independent prognostic value of Ki-67 expression level and the significance of cell proliferation rate as an outcome predictor. To this end, we reviewed the hospital case records and histopathological materials of 92 patients diagnosed with diffuse large B-cell lymphoma in a single center. The cell proliferative rate was expressed as percentage of Ki-67 positive cells (Ki-67 labeling index). All patients were available Ki-67 expression level. High Ki-67 labeling index was defined as nuclear Ki-67 expression in ≥ 70% of malignant cells. A cutoff point of 70% was used because this divided the group of cases into two subgroups of similar size (Ki-67 labeling index < 70, n = 46, Ki-67 labeling index ≥ 70, n = 46). The median age was 57 years (range, 15 to 83 years). The median follow-up time was 14 months. Sixty-nine (75%) patients were treated R-CHOP regimen initially and 13 (14%) patients were CHOP regimen. In a univariate analysis, age (p =.003), performance (p =.001), serum LDH (p =.020) were significant prognostic factors for overall survival. But Ki-67 had no statistical significance (p =.554). Multivariate analysis used Cox’s multivariate regression model revealed that serum LDH (relative risk estimate 6.7; 95% confidence interval, 1.5, 30.5), age (relative risk estimate 7.0; 95% confidence interval, 1.9, 26.4) were independent prognostic factors for overall survival. Taking all the results into consideration, it seems that Ki-67 expression level has no significance as outcome predictor in Korean diffuse large B-cell lymphoma.
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Siu, Lillian L., Jeremy D. Shapiro, Derek J. Jonker, Christos Stelios Karapetis, John Raymond Zalcberg, John Simes, Felix Couture, et al. "Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with metastatic (MET) chemotherapy refractory K-RAS wild-type (WT) colorectal carcinoma (CRC): The NCIC Clinical Trials Group and AGITG CO.20 trial." Journal of Clinical Oncology 30, no. 4_suppl (February 1, 2012): 386. http://dx.doi.org/10.1200/jco.2012.30.4_suppl.386.
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386 Background: The anti-EGFR monoclonal antibody CET has improved survival in pts with MET, chemotherapy refractory, K-RAS wild type (WT) CRC. The addition of BRIV, a tyrosine kinase inhibitor targeting vascular endothelial and fibroblast growth factor receptors (VEGFR/FGFR), to CET has shown encouraging activity in an early phase clinical trial. Methods: Pts with MET CRC previously treated with combination chemotherapy were randomized 1:1 to receive CET 400 mg/m2 IV loading dose followed by weekly maintenance of 250 mg/m2 plus either BRIV 800 mg PO daily (Arm A) or placebo (Arm B). Pts may have had 1 prior anti-VEGF, but no prior anti-EGFR therapy. The trial was amended shortly after opening to enrol K-RAS WT pts. Primary endpoint was overall survival (OS). Results: From 02/2008 to 02/2011, 750 pts were randomized (376 in Arm A and 374 in Arm B). Demographics: median age=64 (range 27-88); male=64%; ECOG 0:1:2 (%)=32:58:10; >3 prior chemotherapy regimens=92%; prior anti-VEGF therapy=41%; K-RAS WT=97%. Median OS in the intent-to-treat population was 8.8 months in Arm A and 8.1 months in Arm B, hazard ratio (HR)=0.88; 95% CI=0.74 to 1.03; p=0.12. Median progression-free survival (PFS) was 5.0 months in Arm A and 3.4 months in Arm B, HR=0.72; 95% CI=0.62 to 0.84; p<0.0001. Both partial responses (13.6% vs 7.2%, p=0.004) and stable disease (50% vs 44%) were higher in Arm A. Incidence of any ≥grade 3 adverse event (AE) was 78% in Arm A and 53% in Arm B. Most frequent ≥grade 3 AEs were fatigue (25%), hypertension (11%) and rash (10%) in Arm A, vs fatigue (11%), rash (5%) and dyspnea (5%) in Arm B. Time to deterioration of physical function was shorter and global quality of life scores were lower in Arm A vs Arm B. Pts received ≥90% dose intensity of CET=57% in Arm A vs 83% in Arm B; of BRIV/placebo=48% in Arm A vs 87% in Arm B. Conclusions: Despite positive effects on PFS and objective response, the combination of CET+BRIV did not significantly improve OS in pts with MET, chemotherapy refractory, K-RAS WT CRC. AEs were consistent with those reported for each drug given as monotherapy.
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Jaekel, Anika, Patrik Kehler, Timo Lischke, Lisa Weiß, Christoph Goletz, Evelyn Hartung, Anke Flechner, Sven Bahrke, Johanna Gellert, and Antje Danielczyk. "781 GT-001 - anti-Lewis Y antibody with superior fine-specificity and reduced off-target binding." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A816. http://dx.doi.org/10.1136/jitc-2021-sitc2021.781.
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BackgroundThe Lewis Y (CD174) carbohydrate antigen is widely expressed in primary and metastatic epithelial tumors like colon, lung, ovarian, and breast. Targeting Lewis Y for cancer therapy was pursued before, however, other anti-Lewis Y antibodies tested in clinical trials showed cross-reactivity to related carbohydrate structures expressed on blood cells and mostly failed for efficacy and/or safety reasons.1–4 We have developed a humanized antibody (GT-001) that shows superior fine-specificity and higher affinity compared to clinically tested anti-Lewis Y antibodies BR96 and h3S193.MethodsThe specificity and cross-reactivity of GT-001, BR96 and h3S193 were compared. Cross-reactivity binding to related carbohydrate PAA-conjugates was tested via ELISA and affinity towards Lewis Y-PAA was measured using switchSENSE® technology (DRX2, Dynamic Biosensors). Functional binding to several tumor cell lines and healthy human leukocytes was analyzed via flow cytometry. Binding of GT-001 to different cancer indications was analyzed by immunohistochemistry. Inhibition of tumor cell proliferation was tested using GT-001 coupled to ProtG-MMAE.ResultsGT-001 is strictly specific for Lewis Y and does not cross-react with >90 related carbohydrate structures tested. Our lead candidate shows superior fine-specificity compared to BR96, for which we could confirm the reported cross-reactivity towards Lewis X,5 and stronger binding of Lewis Y compared to h3S193 as shown by affinity measurement. Further, GT-001 shows no/weak binding to blood cells whereas BR96 and h3S193 significantly bind to different leukocyte subsets. IHC studies reveal that GT-001 stains tumor tissue of different cancer indications (breast cancer, colorectal cancer, head and neck cancer, (non) small cell lung cancer and ovarian cancer) at a high percentage of cases. In ADC surrogate assays, GT-001 potently inhibits the proliferation of several tumor cell lines indicating effective internalization.ConclusionsLewis Y is expressed on many epithelial tumor indications of high medical need. However, several approaches of targeting Lewis Y have failed in the past for efficacy and/or safety reasons. We have developed a humanized antibody that shows superior fine-specificity and higher affinity compared to clinically tested anti-Lewis Y antibodies BR96 and h3S193. Due to the superior fine-specificity, GT-001 shows no/reduced binding of healthy leukocytes potentially reducing side effects as observed for BR96 in the clinic. Its strong target binding and internalization properties make GT-001 an ideal candidate for ADC development.ReferencesAjani JA, Kelsen DP, Haller D, Hargraves K, Healey D. A multi-institutional phase II study of BMS-182248-01 (BR96-doxorubicin conjugate) administered every 21 days in patients with advanced gastric adenocarcinoma. Cancer J 2000;6(2):78–81.Saleh MN, Sugarman S, Murray J, Ostroff JB, Healey D, Jones D, Daniel CR, LeBherz D, Brewer H, Onetto N, LoBuglio AF. Phase I trial of the anti-Lewis Y drug immunoconjugate BR96-doxorubicin in patients with lewis Y-expressing epithelial tumors. J Clin Oncol 2000;18(11):2282–92.Scott AM, Tebbutt N, Lee FT, Cavicchiolo T, Liu Z, Gill S, Poon AM, Hopkins W, Smyth FE, Murone C, MacGregor D, Papenfuss AT, Chappell B, Saunder TH, Brechbiel MW, Davis ID, Murphy R, Chong G, Hoffman EW, Old LJ. A phase I biodistribution and pharmacokinetic trial of humanized monoclonal antibody Hu3s193 in patients with advanced epithelial cancers that express the Lewis-Y antigen. Clin Cancer Res 2007;13(11):3286–92.Smaletz O, Diz MD, do Carmo CC, Sabbaga J, Cunha-Junior GF, Azevedo SJ, Maluf FC, Barrios CH, Costa RL, Fontana AG, Madrigal V, Wainstein AJ, Yeda FP, Alves VA, Moro AM, Blasbalg R, Scott AM, Hoffman EW. A phase II trial with anti-Lewis-Y monoclonal antibody (hu3S193) for the treatment of platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Gynecol Oncol 2015;138(2):272–7.Zhang S, Zhang HS, Cordon-Cardo C, Reuter VE, Singhal AK, Lloyd KO, Livingston PO. Selection of tumor antigens as targets for immune attack using immunohistochemistry: II. Blood group-related antigens. Int J Cancer 1997;73(1):50–6.
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Leidy, Heather J., Mandi J. Bossingham, Richard D. Mattes, and Wayne W. Campbell. "Increased dietary protein consumed at breakfast leads to an initial and sustained feeling of fullness during energy restriction compared to other meal times." British Journal of Nutrition 101, no. 6 (September 2, 2008): 798–803. http://dx.doi.org/10.1017/s0007114508051532.
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The objective of the study was to assess whether the timing of increased dietary protein throughout the day influences the feelings of fullness during energy balance (EB) and restriction (ER). Nine men (age 48 (sem 6) years; BMI 32·7 (sem 0·7) kg/m2) randomly completed five controlled feeding trials, each consisting of 3 d of EB, followed by 3 d of ER of a 3138 kJ/d (750 kcal/d) reduction). The diet was composed of a normal amount of protein (NP) (0·8 g protein/kg per d), or an additional amount of protein (HP) (+0·6 g protein/kg per d) given at breakfast (HP-B), lunch (HP-L), dinner (HP-D) or equally divided among all meals (HP-E). Meal-related (3 h postprandial) and overall (15 h composite) feelings of fullness were assessed from thirteen-point, numbered, linear category scale questionnaires (reported as arbitrary units (au)). When comparing HP treatments, the data are presented as difference from NP. No differences in meal-related or overall fullness were observed among HP treatments during EB. During ER, the HP-B led to greater meal-related fullness (+137 (sem 44) au × 180 min) compared to HP-D ( − 1 (sem 37) au × 180 min; P = 0·003), but not for HP-L (+62 (sem 53) au × 180 min; P = 0·188) or HP-E-B (+92 (sem 85) au × 180 min; P = 0·587). HP-B also led to greater overall (15 h) fullness (+404 (sem 162) au × 900 min) v. HP-L (+33 (sem 162) au × 900 min; P = 0·009) and HP-D ( − 60 (sem 132) au × 900 min; P = 0·05), but not HP-E (+274 (sem 165) au × 900 min; P = 0·188). The initial and sustained feelings of fullness following protein consumption at breakfast suggests that the timing of protein intake differentially influences satiety during ER.
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Garibaldi, A., A. Minuto, and M. L. Gullino. "First Report of Powdery Mildew Caused by Golovinomyces cichoracearum on English Daisy (Bellis perennis) in Italy." Plant Disease 92, no. 3 (March 2008): 484. http://dx.doi.org/10.1094/pdis-92-3-0484a.
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Bellis perennis (English daisy) is a flowering plant belonging to the Asteraceae and is increasingly grown as a potted plant in Liguria (northern Italy). In February 2007, severe outbreaks of a previously unknown powdery mildew were observed on plants in commercial farms at Albenga (northern Italy). Both surfaces of leaves of affected plants were covered with white mycelia and conidia. As the disease progressed, infected leaves turned yellow. Mycelia and conidia also were observed on stems and flower calyxes. Conidia were hyaline, ellipsoid, borne in chains (as many as three conidia per chain), and measured 27.7 × 16.9 (15.0 to 45.0 × 10.0 to 30.0) μm. Conidiophores measured 114.0 × 12.0 (109.0 to 117.0 × 11.0 to 13.0) μm and showed a foot cell measuring 78.0 × 11.0 (72.0 to 80.0 × 11.0 to 12.0) μm followed by two shorter cells. Fibrosin bodies were absent. Chasmothecia were not observed in the collected samples. The internal transcribed spacer (ITS) region of rDNA was amplified using primers ITS4/ITS6 and sequenced. BLASTn analysis (1) of the 415 bp obtained showed an E-value of 7e–155 with Golovinomyces cichoracearum (3). The nucleotide sequence has been assigned the GenBank Accession No. AB077627.1 Pathogenicity was confirmed through inoculations by gently pressing diseased leaves onto leaves of healthy B. perennis plants. Twenty plants were inoculated. Fifteen noninoculated plants served as a control. Plants were maintained in a greenhouse at temperatures ranging from 10 to 30°C. Seven days after inoculation, typical symptoms of powdery mildew developed on inoculated plants. The fungus observed on inoculated plants was morphologically identical to that originally observed. Noninoculated plants did not show symptoms. The pathogenicity test was carried out twice. To our knowledge, this is the first report of powdery mildew on B. perennis in Italy. The disease was already reported in other European countries (2). Voucher specimens are available at the AGROINNOVA Collection, University of Torino. References: (1) S. F. Altschul et al. Nucleic Acids Res. 25:3389, 1997. (2) U. Braun The Powdery Mildews (Erysiphales) of Europe. Gustav Fischer Verlag, Jena, Germany, 1995. (3) U. Braun and S. Takamatsu. Schlechtendalia 4:1, 2000.
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Zain, J. M., F. Foss, W. K. Kelly, J. DeBono, D. Petrylak, A. Narwal, E. Neylon, G. Blumenschein, U. Lassen, and O. A. O'Connor. "Final results of a phase I study of oral belinostat (PXD101) in patients with lymphoma." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8580. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8580.
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8580 Background: Belinostat (Bel) is a histone deacetylase inhibitor with broad preclinical activity. A phase I of oral Bel in patients (pts) with solid tumors found a recommended dose for day (d) 1–14, q3w, of 750 mg QD, with option for intra-patient dose escalation if limited toxicity. The current study was initiated to assess if the same dose could be utilized in pts with lymphoma. Methods: Objectives included safety and efficacy of oral Bel in cohorts of 3–6 pts (A 750; B 1000; C 1250; mg QD) treated d 1–14, q3w. Pts with relapsed/refractory non-Hodgkin lymphoma (NHL) or Hodgkin's disease (HD) with evaluable disease and acceptable organ functions were eligible. Dose limiting toxicity (DLT) assessed in cycle 1 included: related non-hem grade (gr) 3/4 tox; gr 4 neutropenia > 5 d or with fever > 100.5 °F; gr 4 thrombocytopenia > 7 d. Results: 9 pts (3 per cohort), median age 51 (range 21–92), median 5 (range 2–7) prior regimens (83% had BM transplants, including 1 pt with allogeneic) have been enrolled. Diagnoses include mantle cell lymphoma (MCL; 4 pts), HD (3 pts), other NHL (2 pts). Most frequent adverse events (regardless of attribution or gr) in 7 pts fully evaluable for tox: anorexia (7 pts), fatigue, (6 pts), diarrhea (6 pts), and constipation, fever, and cough (each in 3 pts). Non-hem gr 3 events (no gr 4 noted): diarrhea (1 pt each in cohorts A and B, both in cycle 2), fatigue, anorexia, and leg DVT (each in 1 pt; all after cycle 1). One gr 3, and 1 gr 4 (from baseline gr 2; duration gr 4 <7 d) thrombocytopenia were seen in cohort C. In 6 pts evaluable for efficacy, stable disease have been noted in 5 pts for 3 to +7 cycles, including 3 of 3 pts (one refractory) with MCL and 2 of 2 pts (both refractory) with HD. Tumor shrinkage of 43 to 49% have been found in 1 HD and 2 MCL pts after cycle 2. Conclusions: Oral Bel can be delivered safely with a d 1–14, q3w schedule in pts with lymphoma at a daily dose higher than what has been established for pts with solid tumors. No protocol defined DLTs have yet been encountered in the dose range 750 to 1250 mg QD in pts with lymphoma. Final evaluation will include additional pts and possible dose escalation. The safety profile and early tumor shrinkage noted in MCL and HD warrants continued evaluation of Bel, especially in combination with other active compounds. [Table: see text]
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Tokarchuk, O. V. "Separate approaches to understanding human rights." TRANSFORMATION LEGISLATION OF UKRAINE IN MODERN CONDITIONS DOCTRINAL APPROACHES AND MEASUREMENTS, no. 14 (September 1, 2023): 134–38. http://dx.doi.org/10.33663/2524-017x-2023-14-134-138.
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1. Batanov O. V. Tendentsii rozvytku munitsypalnykh prav liudyny v umovakh hlobalizatsii. Chasopys Kyivskoho universytetu prava. 2016. № 4. S. 47–52. URL: http://nbuv.gov.ua/UJRN/Chkup_2016_4_12 2. Zahalna deklaratsiia prav liudyny: pryiniata ta proholoshena v rezoliutsii 217 A(III) Heneralnoi Asamblei vid 10.12.1948 r. URL: https://zakon.rada.gov.ua/laws/show/995_015?Lang =ru#Text 3. Kuchynska O. P., Ivanov M. S. Zahalnoteoretychne ta prakseolohichne rozuminnia prav liudyny. Visnyk kryminalnoho sudochynstva, 2017. № 1. S. 142–148. 4. Mahnovskyi I. Y. Zahalnoteoretychni aspekty kontseptu pryrodnykh prav liudyny v konteksti pryrodnoho prava. Prava liudyny v period zbroinykh konfliktiv: Zb. materialiv Mizhnarodnoi naukovo-praktychnoi konferentsii prysviach. 25-richchiu Natsionalnoho universytetu «Odeska yurydychna akademiia» (m. Odesa, 18 lystopada 2022 r.) / Nats. un-t «Odeska yurydychna akademiia»; kaf. mizhnarodnoho ta yevropeiskoho prava NU «OIuA»: u 2 t. Odesa, 2022. S. 37–41. 5. Rabinovych P. M. Prava liudyny i hromadianyna: navch. posib. Kyiv: Atika, 2004. 464 s. 6. Rabinovych P. Osnovopolozhni prava liudyny: termino-poniattievyi instrumentarii doslidzhennia ta vykladannia). Pravo Ukrainy. 2015. № 1. S. 9–23. 7. Sotsialno-pravovyi zakhyst ditei v Ukraini: monohrafiia / za red. B. I. Andrusyshyna. Kyiv: Vyd-vo NPU imeni M. P. Drahomanova, 2017. 264 s. 8. Khrystokin H. V. Ideia prav liudyny: poshuk novykh pidkhodiv obgruntuvannia v dobu hlobalnykh transformatsii. Filosofski ta metodolohichni problemy prava. 2021. № 1. S. 92–98. 9. Chetverte pokolinnia prav liudyny: osoblyvosti pravovoho rehuliuvannia, problemy ta perspektyvy rozvytku v sferi okhorony zdorovia: monohrafiia / za zah. red.: d.iu.n., prof. S. B. Buletsy; d.iu.n., dots. M. V. Mendzhul. Uzhhorod: Vyd-vo UzhNU «Hoverla», 2020. 444 s. 10. Yurydychna entsyklopediia: v 6 t. / Yu. S. Shemshuchenko (holova redkol.) ta in. Kyiv: Ukr. entsykl. T. 4: N‒P. 2002. 720 s
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Cetiner, Mustafa, Taflan Salepci, Elif Birtas Atesoglu, Mahmut Gumus, Aslihan Guven, Levent Undar, Tulin Firatli Tuglular, and Mahmut Bayik. "Rituximab-CHOP Versus CHOP Alone in Patients with Diffuse Large B Cell Lymphoma." Blood 108, no. 11 (November 16, 2006): 4708. http://dx.doi.org/10.1182/blood.v108.11.4708.4708.
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Abstract Recently, the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen plus rituximab (R-CHOP) have been used widely to treat patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) and it has also been reported to improve the outcome of DLBCL. We represent a retrospective analysis of newly diagnosed DLBCL patients between the years of 2003–2005 to evaluate the impact of R-CHOP therapy on response rates. Patients with DLBCL between 20–80 years of age (median: 46.0 and mean 56.2 ± 14.92) received 6 cycles of R-CHOP (n=28). For comparison, DLBCL patients between 15–76 years of age (median: 60.5 and mean 47.3 ± 16.6) who received 6 courses of CHOP therapy (n=30) were used as the control group. All patients received classical CHOP (cyclophosphamide 750 mg/m m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m m2 on day 1 and prednisone 40 mg/m m2 for 5 days) every 4 weeks. In R-CHOP group, rituximab 375 mg/m m2 was administered one day before CHOP chemotherapy. The median follow-up for R-CHOP and CHOP groups were 15.66 ± 5.90 (7–29) and 21.79 ± 9.20 (8–46) months, respectively. The International Prognostic Index (IPI) scores were not significantly different between these groups (median IPI of R-CHOP: 2.0 and mean IPI 2.01.27 ± 1.16 versus median IPI of CHOP: 1.0 and mean IPI 1.88 ± 1.26). Complete response (CR) and complete undetermined response (CuR) rate for R-CHOP was 92% (26 of 28 patients) which was statistically significantly higher than CHOP (24 of 30 patients, 80%) (p=0.004). Partial response (PR) rates for R-CHOP and CHOP groups were 7% (2 of 28 patients) and 10% (3 of 30 patients), respectively. While there were no unresponsive patients in the R-CHOP group, refractory disease rate was 10% (3 of 30 patients) in the CHOP group. Relapse rates during the follow up period were 13% (4 of 30 patients) for CHOP and 4% (1 of 28 patients) for R-CHOP group (p<.0001). No long-term toxicity appeared to be associated with the addition of rituximab to the CHOP combination. These results also confirmed the benefit of the addition of rituximab to standard CHOP chemotherapy in DLBCL even in young patients with low IPI scores.
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Ashouri, Karam, Brian Hom, Mollee Chu, Jennifer Hwang, Karen Resnick, Yekta Rahimi, Robert Ireland, et al. "B-Cell Acute Lymphoblastic Leukemia: Donor Matters in Allogeneic Stem Cell Transplant Outcomes of Hispanic Patients." Blood 142, Supplement 1 (November 28, 2023): 2241. http://dx.doi.org/10.1182/blood-2023-190541.
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Introduction: Hematopoietic stem cell transplantation (HSCT) improves long term overall survival (OS) and disease-free survival (DFS) in those with intermediate or high-risk B- cell ALL. Historically, matched related donors were the ideal choice, but with improved GVHD prophylactic regimens and supportive care, haploidentical donors are being increasingly used. Due to their increased graft-versus-leukemia (GVL) effect, they may be an option for Hispanic patients, for whom matched donation may be more challenging. Methods: This is a retrospective chart review of B- cell ALL patients that received allogeneic HSCT at Norris Comprehensive Cancer Center (NCCC) from 2012 to 2023. Mismatch-unrelated donors were excluded. For OS, DFS, and cumulative incidence of relapse (CIR), match sibling donors (MSD) and match unrelated donors (MUD) were grouped. However, for GVHD outcomes including graft-versus-host disease (GVHD)-free relapse-free survival (GRFS), incidence of grade 3-4 acute GVHD (aGVHD), and incidence of severe chronic GVHD (cGVHD) requiring immunosuppression MSD and MUD were separated. Incidence outcomes were evaluated using competing risk regression (Fine-Gray method), with death as a competing outcome, while survival outcomes were analyzed using Cox proportional hazards model. Results: One hundred eighteen B- cell ALL patients were included with a median age at transplant of 43 years (range: 21-69). Donor types included 46 (40.0%) MSD, 45 (38.1%) haploidentical, and 27 (22.9%) MUD. Most were Hispanic (N= 92, 78.0%) and our median follow-up time was 23.6 months. The majority of patients achieved CR1 (N=79, 66.9%) and MRD negativity by flow (N=106, 89.8%), pre-transplant. The 3-year OS and DFS for the cohort were 82.1% (95% CI 73.8-91.3%) and 66.2% (95% CI 57.2-76.6%), respectively, while the CR1 subgroup was 90.5% (95% CI 83.3-98.3%) and 77.1% (95% CI 67.8-87.7%) respectively. When compared to haploidentical HSCT, patients who received matched donors had significantly worse CIR (HR = 2.42; 95% CI 1.06-5.51; P = 0.036) and DFS (HR = 2.14; 95% CI 1.03-4.44; P = 0.041), along with a non-significant trend towards worse OS (HR = 2.54; 95% CI 0.83-7.80; P=0.10). Additionally, pretransplant minimal residual disease (MRD) positivity demonstrated worse OS (HR = 5.01; 95% CI 1.73-14.5; P = 0.003), DFS (HR = 3.25; 95% CI 1.48-7.16; P = 0.003), and CIR (HR = 2.05; 95% CI 0.78-5.39; P = 0.15). The 1-year GRFS, 1-year incidence of severe cGVHD, and 100-day incidence of grade 3-4 aGVHD was 52.6% (95% CI 43.5-63.6%), 29.5% (95% CI 20.9-38.6%), and 7.74% (95% CI 3.79-13.5%), respectively. Compared to haploidentical donors, GRFS was worse in the MUD (HR = 2.07; 95% CI 1.08-3.96; P = 0.028) but similar in MSD. This is likely driven by differences in survival and relapse, and there were no differences in the incidence of severe cGVHD or aGVHD between donor types. Multivariate analysis, which included age, MRD status pretransplant, and stage prior to transplant, demonstrated the improved predictive effect of haploidentical donors. Matched donors exhibited worse DFS (HR = 2.25; 95% CI 1.04-4.90; P = 0.04) and CIR (HR = 2.47; 95% CI 1.09-5.60; P = 0.03), with a trend towards worse OS (HR = 2.84; 95% CI 0.92-8.79; P = 0.07). Given the heterogeneity in donor-type outcomes, we conducted a subgroup analysis of the 45 haploidentical HSCT patients on the GRFS and DFS composite outcomes. After controlling for patient age, older donor age analyzed as a continuous variable was a significant predictor of worse GRFS (HR = 1.05; 95% CI 1.00-1.11; P = 0.039) but did not affect DFS. Conclusion: In a predominantly Hispanic population of ALL patients, haploidentical donors demonstrate improved OS and CIR. In those haploidentical patients, younger donor age confers improved GRFS.
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Bomben, Riccardo, Stefano Volinia, Stefania Gobessi, Daniela Marconi, Michele Dal Bo, Dania Benedetti, Giovanni Del Poeta, Luca Laurenti, Dimitar G. Efremov, and Valter Gattei. "The Mir-17~92 Cluster Family Determines the Responsiveness of CLL Cells with Unmutated IGHV Genes to Toll-Like Receptor 9 Triggering." Blood 116, no. 21 (November 19, 2010): 2407. http://dx.doi.org/10.1182/blood.v116.21.2407.2407.
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Abstract Abstract 2407 Introduction: The clinical course of chronic lymphocytic leukemia (CLL) is highly variable and prognosis is strongly associated with the mutational status of the IGHV genes. Recently, it has been observed that CLL cells expressing unmutated (UM) IGHV genes can be more efficiently induced to proliferate by stimulation of Toll-like Receptor 9 (TLR9) with unmethylated CpG oligonucleotides (CpG) than CLL cells expressing mutated (M) IGHV genes. MicroRNA (miRNAs) are 18- to 22-nucleotide-long RNA molecules that regulate gene expression and play a key role in several biological process including oncogenesis. Although the recognized pathogenetic relevance of miRNAs in CLL, their involvement in regulating activation/proliferation processes of CLL cells has still to be elucidated. Patients and Methods: Freshly-isolated negatively-selected CLL cells from 19 patients (9 UM and 10 M CLL) were stimulated with CpG or left unstimulated for 18 hours. MiRNA profiling and Gene expression profiling (GEP) were performed according to Agilent Technologies protocols. Bioinformatics analyses were performed integrating three different methods for supervised analysis (LIMMA algorithm, Agilent and Partek softwares). Results: The miRNA profile of CLL cells treated or not with CpG was separately evaluated in M and UM CLL. Consistent with the notion that M CLL cells are usually non-responsive to CpG stimulation, no miRNA was found to be differentially expressed between CpG-stimulated and unstimulated CLL cells belonging to this subgroup. In contrast, in UM CLL, as many as 28 miRNAs resulted differentially expressed, 24 up-regulated (miR-1260, miR-1274a, miR-1274b, miR-1280, miR-155, miR-155*, miR-17, miR-17*, miR-18a, miR-196a, miR-19b-1*, miR-20a, miR-20b, miR-221, miR-221*, miR-222, miR-29b-1*, miR-30b*, miR-30d*, miR-374b*, miR-720, miR-886-3p, miR-92a-1*, miR-939) and 4 down-regulated (miR-1226*, miR-125a-3p, miR-135a*, miR-150*) upon CpG stimulation. Data were confirmed by quantitative real time PCR. In order to identify the miRNAs actually involved in regulating activation/proliferation processes induced by TLR9 triggering, a concomitant GEP was performed comparing the same UM CLL cells exposed or not to CpG. Data analysis was carried out by taking advantage of the T-REX software that, by integrating four algorithms and six different target prediction programs, allows the identification of the regulated miRNAs on the basis of their repression activity on target mRNA. T-REX application selected four miRNAs whose mRNA targets resulted significantly down-regulated upon TLR9 triggering, namely miR-17, miR-20a, miR-20b and miR-93a. All these miRNAs belong to the miR-17~92 cluster family, known to be over-expressed in a variety of B-cell lymphomas, including diffuse large B-cell lymphoma, Burkitt lymphoma, follicular lymphoma and mantle cell lymphoma. Notably, three of these miRNAs and four additional miRNAs also belonging to the miR-17~92 cluster family (e.g. miR-17*, miR-18a, mir-19b-1* and mir-92a-1*) turned out to be among the 24 up-regulated miRNAs in CpG-stimulated UM CLL cells. In-silico analyses performed with the “Onto-Express” software, found that several differentially expressed genes were included in Gene Ontology (GO) categories related to regulation of cell proliferation, G1/S transition, apoptosis and NFkB signalling, in keeping with the typical proliferative response induced by CpG stimulation in UM CLL cells. The down-regulated genes included in these categories comprised CDKN1B/P27, CCNG2, NCOA3, E2F5, MAPK4, TRIM8, ZBTB4 and TP53INP1, all known target of miR-17~92 cluster family. Notably, the gene for the negative cell cycle regulator CDKN1B/P27 is also targeted by miR-221 and miR-222, two miRNAs both up-regulated in UM CLL cells upon CpG stimulation. Finally, transcripts for the proto-oncogene MYC also resulted over-expressed upon CpG stimulation. This observation may be relevant given the capacity of MYC to directly and positively regulate expression of miRNAs belonging to the miR-17~92 cluster family. Conclusion: Induction of the miR-17~92 family is a specific feature of UM CLL cells triggered through TLR9 and is associated with down-regulation of genes involved in cell cycle control and apoptosis regulation. MiRNAs belonging to the miR-17~92 family may represent promising novel targets for biological therapies of high risk CLL. Disclosures: No relevant conflicts of interest to declare.
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Khamidullaeva, G. A., N. Z. Srojidinova, G. J. Abdullaeva, N. Sh Shakirova, and L. Sh Khafizova. "IEFFICACY OF INDAPAMIDE AND VALSARTAN COMBINED THERAPY PATIENTS WITH ARTERIAL HYPERTENSION AND METABOLIC DISORDERS." Eurasian heart journal, no. 4 (December 30, 2014): 62–68. http://dx.doi.org/10.38109/2225-1685-2014-4-62-68.
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Aim of the study: to study antihypertensive and organ-protective efficacy of indapamide and valsartan combined therapy hypertensive patients with high cardiovascular risk and metabolic disorders. Methods: The studyincluded 37 patients with stage I-III hypertension (ESH 2007), with an average age of 47.67±10.02 years, 48.6% men and 51.4% woman. Blood pressure was measured by Korotkov method. All patients were performed by M- and B-mode echocardiography. Flow-mediated endothelium dependent vasodilatation was measured during reactive hyperaemia due to 5 minute brachial occlusion.A 7.5 MHz highresolution ultrasound was used to measure carotid artery intimaemedia thickness (IMT). Blood lipid and glucose level, serum creatinin and uric acid level were estimated by enzyme assay method on biochemical analyzer “Daytona TM”. Results: 12-weekly combined therapy with indapamide and valsartan were shown very good antihypertensive efficacy in average daily doses 2.5 mg and 80±40.6 mg respectively, with reducing average blood pressure on 19.7±7.0% and attained goal level of BP in 92% cases. During the treatment were found significantly regress of left ventricular hypertrophy by reducing left ventricular mass index on 16.2±11.3%, effective vasoprotection, without significantly changes of metabolic disorders, which characterized indapamide and valsartan combination like metabolic neutral drug combination. Conclusion: Indapamide and valsartan combined therapy characterize with high antihypertensive, cardio- and vasoprotective efficacy andmetabolic neutrality choosing for treatment hypertensive patients with high cardiovascular risk and metabolic disorders.
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Salvador, João Odemir, Adônis Moreira, Eurípedes Malavolta, and Cleusa Pereira Cabral. "Influência do boro e do manganês no crescimento e na composição mineral de mudas de goiabeira." Ciência e Agrotecnologia 27, no. 2 (April 2003): 325–31. http://dx.doi.org/10.1590/s1413-70542003000200011.
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Dois experimentos conduzidos em solução nutritiva tiveram como objetivo avaliar os efeitos de doses de boro e de manganês no crescimento e na composição mineral de folhas de mudas de goiabeira (Psidium guajava L.). No experimento com boro, foram testadas sete doses (0, 0,125, 0,25, 0,5, 1,0, 1,5 e 3,0 mg L-1). Pelos resultados, verificou-se que a necrose marginal e as manchas circulares púrpuras e esparsas no limbo foliar foram os principais sintomas de toxidez apresentados, sendo esses associados com a dose máxima e com um teor foliar de 146 mg kg-1. Análises de tecidos foliares sem e com necroses mostraram teores de 92 e 720 mg kg-1, respectivamente. Somente a produção de matéria seca de raízes e o teor foliar de fósforo e enxofre foram afetados significativamente pelas doses de B. Para o manganês, foram usadas sete doses (0, 0,5, 10, 20, 30, 40 e 50 mg L-1). A produção de matéria seca total e os teores foliares de Ca, Mg e Fe foram afetados pelas doses de Mn. Os sintomas foliares de toxidez evidenciaram-se em salpicos adensados de minúsculas pontuações escuras nas folhas velhas; folhas novas de dimensões menores, cloróticas e com reticulado verde das nervuras; formação de pontuações circulares castanhas espalhadas ou fundidas ao longo ou entre as nervuras.
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Yasenchak, Christopher A., Andres Forero-Torres, Vivian Jean Mikao Cline-Burkhardt, Rodolfo E. Bordoni, Dipti Patel-Donnelly, Patrick J. Flynn, Robert Chen, Abraham Fong, and Jonathan W. Friedberg. "Brentuximab Vedotin in Combination with Dacarbazine or Bendamustine for Frontline Treatment of Hodgkin Lymphoma in Patients Aged 60 Years and Above: Interim Results of a Multi-Cohort Phase 2 Study." Blood 126, no. 23 (December 3, 2015): 587. http://dx.doi.org/10.1182/blood.v126.23.587.587.
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Abstract Introduction Older patients (pts) with Hodgkin lymphoma (HL) have inferior outcomes compared to younger pts treated with standard chemotherapy regimens, and tolerate therapy poorly. New therapeutic options that improve both efficacy and tolerability are needed for these pts. Brentuximab vedotin (ADCETRIS®), an anti-CD30 antibody-drug conjugate, has durable activity as monotherapy in relapsed HL with a manageable safety profile. For frontline single agent treatment of HL pts aged ≥60 yrs, the objective response rate (ORR) was 92% (73% complete remission [CR]) and the median progression-free survival (PFS) was 10.5 months (mo) (Forero-Torres 2015). Brentuximab vedotin + dacarbazine (DTIC) demonstrated compelling activity in preclinical models (McEarchern 2010), and brentuximab vedotin + bendamustine (benda) provided an 82% CR rate in pts with relapsed HL (LaCasce 2014). This phase 2, frontline, open-label study examines the efficacy and durability of response of brentuximab vedotin as monotherapy and in combination with DTIC or benda in HL pts aged ≥60 yrs (NCT01716806). Methods Approximately 70 treatment-naïve pts aged ≥60 yrs with HL (30 monotherapy; 20 for each combination) are to be enrolled. Eligible pts have ECOG ≤3 and are ineligible for or have declined conventional treatment. Brentuximab vedotin 1.8 mg/kg is administered every 3 weeks for up to 12 cycles with DTIC (375 mg/m2) and up to 6 cycles with benda (90 or 70 mg/m2). Pts with clinical benefit may receive additional cycles of brentuximab vedotin. Response is assessed after Cycles 2, 4, 8, 12, 16 and every 6 cycles thereafter. The primary endpoint is ORR per the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Results Thus far, 60 pts have been treated (n=27 monotherapy; 22 DTIC combo; 11 benda combo). Median age for all pts was 76 yrs (range, 62-92), 55% were male, 65% had stage III-IV disease, 40% had B symptoms, 28% had ECOG 2-3, and 70% were deemed ineligible for conventional chemotherapy. To date, a median of 11.5 treatment cycles have been received by DTIC combo pts, compared to 8 cycles by monotherapy pts. Duration of treatment for the benda combo pts will be more clearly defined with additional follow-up time. A total of 45 pts have discontinued therapy. Discontinuations were due to adverse event (AE; n=18, including 15 for Grade 2 or 3 peripheral neuropathy), progressive disease (PD) after complete or partial remission (CR or PR; n=13), or other reasons (see table; n=14). Fifteen pts remain on therapy. For pts treated with the DTIC combo, the ORR was 100% (62% CR). The median PFS has not been reached (median observation time 9.8 mo) and 18/21 pts remain alive without PD. For pts treated with the benda combo, the starting dose of benda was reduced from 90 to 70 mg/m2 to improve tolerability after the first 10 pts were enrolled. The ORR was 100% (78% CR) in the first 9 pts; with limited observation time (median 3.6 mo), 8/9 pts remain alive without PD. Treatment-related AEs ≥ Grade 3 occurred in 43% of pts overall, SAEs were reported for 22% overall, and no pt died within 30 days of last dose. Conclusions This planned analysis demonstrated 100% ORRs for both the DTIC combo and benda combo with acceptable tolerability. Based upon these data, combinations including brentuximab vedotin appear to have promise as frontline therapy in this vulnerable patient population. Ongoing follow-up will define durability, and ultimately the potential role of these combinations as standard options for elderly patients with HL. Table. Monotherapy (N=27) DTIC Combo (N=22) Benda Combo a (N=11) Median treatment cycles (range) Brentuximab vedotin 8 (3, 23) b 11.5 (2, 16) 4 (2, 8) DTIC or benda - 11.5 (1, 12) 4 (1, 6) Pts remaining on therapy, n (%) 0 b 6 (27) 9 (82) Reason for treatment discontinuation, n (%) AE 11 (41) b 7 (32) 0 PD after CR or PR, n (%) 11 (41) b 2 (9) 0 Investigator decision 1 (4) b 4 (18) 1 (9) Pt decision 3 (11) b 2 (9) 1 (9) Completed treatment 0 b 1 (5) 0 Other non-AE reason 1 (4) b 0 0 Efficacy evaluable pts (N) 26 b 21 9 ORR, n (%) 24 (92) b 21 (100) 9 (100) CR rate, n (%) 19 (73) b 13 (62) 7 (78) PFS, median mo (range) 10.5 (2.6+, 22.3+) b - (4.2+, 14.3+) - (1.2+, 6.2+) Median observation time, mo (range) 20.4 (4.6, 30.4) 9.8 (4.9, 14.3) 3.6 (2.3, 7.0) Pts with progression or death, n (%) 16 (62) 3 (14) 1 (11) Treatment-related AE ≥ Grade 3, n (%) 13 (48) b 8 (36) 5 (45) Any SAE, n (%) 6 (22) b 2 (9) 5 (45) aEnrollment is ongoing bForero-Torres 2015 Disclosures Yasenchak: Seattle Genetics, Inc.: Research Funding. Off Label Use: Brentuximab vedotin is indicated in the US for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates. This study evaluates brentuximab vedotin as frontline treatment, both as monotherapy and in combination therapy, in older patients with HL.. Forero-Torres:Seattle Genetics, Inc.: Research Funding. Cline-Burkhardt:Seattle Genetics, Inc.: Research Funding. Bordoni:Seattle Genetics, Inc.: Research Funding. Patel-Donnelly:Seattle Genetics, Inc.: Research Funding. Flynn:Seattle Genetics, Inc.: Research Funding. Chen:Genentech: Consultancy, Speakers Bureau; Seattle Genetics, Inc.: Consultancy, Other: Travel expenses, Research Funding, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau. Fong:Seattle Genetics, Inc.: Employment, Equity Ownership.
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Tandoh, Kwesi Z., Kwadwo A. Kusi, Timothy N. Archampong, Isaac Boamah, and Osbourne Quaye. "Hepatitis B infection outcome is associated with novel human leukocyte antigen variants in Ghanaian cohort." Experimental Biology and Medicine 245, no. 9 (April 29, 2020): 815–22. http://dx.doi.org/10.1177/1535370220921118.
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Chronic hepatitis B infection is an important medical problem in sub-Saharan Africa. With increasing concerns of dwindling access to needed care, increasing cost of treatment, and rising prevalence of dire outcomes like liver cirrhosis and hepatocellular cancer, the need to determine the genetic associations underpinning hepatitis B virus persistence or clearance in a population comes to the fore. Genetic association studies have suggested a variation in human leukocyte antigen alleles associated with hepatitis B virus outcome along geo-ethnic lines. We investigated the association of human leukocyte antigen alleles to hepatitis B virus outcome against this backdrop. We used targeted next generation sequencing to type the human leukocyte antigen class I and II alleles of 173 study participants. These comprised of 92 cases with chronic hepatitis B infection and 81 healthy controls with serological evidence of naturally cleared hepatitis B virus infection. We have identified human leukocyte antigen alleles associated with hepatitis B virus clearance and persistence for the first time in a Ghanaian population. The class 1 allele C*16:01 (odds ratio (OR) = 3.4, confidence interval (CI) = 1.6–7.0, P-value = 0.01) was associated with hepatitis B virus persistence. Four class I alleles and one class II allele: A*34:02 (OR = 0.1, CI = 0.04–0.2, P-value = 3.4e-05), A*74:01 (OR = 0.3, CI = 0.2–0.7, P-value = 0.0135), B*13:02 (OR = 0.04, CI = 0.01–0.2, P-value = 0.000172), C*08:04 (OR = 0.06, CI = 0.01–0.2, P-value = 7.83e-05), and DRB1*08:04 (OR = 0.2, CI = 0.03–0.27, P-value = 0.000252) were associated with hepatitis B virus clearance. Our data show that previously reported human leukocyte antigen alleles associations to hepatitis B virus outcome are not found in this Ghanaian study. This study has therefore identified human leukocyte antigen types that are associated with either hepatitis B virus persistence or clearance and highlights the importance of geo-ethnic pivoted studies in determining the genetic associations to acute hepatitis B virus infection outcome. Impact statement Genetic association studies can determine the effect size of gene loci on disease outcomes. In the arena of HBV infections, HLA alleles that associate with HBV outcomes can be used in clinical management decisions. This potential translational utility can shape the future management of HBV infections by identifying at-risk individuals and tailoring medical interventions accordingly. This precision medicine motif is currently only a nascent idea. However, it has stakes that may well override the current “wait and see” approach of clinical management of HBV infections. Here, we have identified HLA alleles associated with HBV outcome in a Ghanaian cohort. Our findings support the motif that HLA alleles associate with HBV outcome along geo-ethnic lines. This buttresses the need for further population pivoted studies. In the long term, our findings add to efforts towards the development of an HLA molecular-based algorithm for predicting HBV infection outcomes.
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Kohns Vasconcelos, M., R. Santoro, M. Coslovsky, J. van den Anker, and JA Bielicki. "P54 KIDS-STEP: a swiss multi-centre RCT on effectiveness of adjunct betamethasone therapy in hospitalised children with community acquired pneumonia." Archives of Disease in Childhood 104, no. 6 (May 17, 2019): e39.2-e39. http://dx.doi.org/10.1136/archdischild-2019-esdppp.92.
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BackgroundThe incidence of community-acquired pneumonia (CAP) in young children is high (20- 30/1000 child-years) and is associated with a high rate of hospitalisation (around 10/1000 child-years). In adults, a benefit of adjunct corticosteroids on time to clinical stability and hospital discharge has been observed and confirmed in systematic reviews and meta-analyses. In contrast, only few small trials have addressed the potential impact of oral steroid treatment in CAP during childhood. The purpose of this study is to concurrently evaluate whether adjunct treatment with corticosteroids in children hospitalised with CAP is more effective in terms of the proportion of children reaching clinical stability and whether such adjunct treatment is no worse in terms of CAP relapse.MethodsChildren in KIDS-STEP1 receive either oral betamethasone or oral placebo dosed once daily for two consecutive days. We include 700 children from age 1 weighing at least 7 kilograms and up to a body weight of 35 kilograms and age below 10 years hospitalised for CAP using a clinical diagnosis.Co-primary outcomes are(a) The proportion of children clinically stable at 48 hours after randomisation. (b) The proportion of children with CAP-related readmission within 28 days after randomization. Secondary outcomes will be captured to further evaluate the efficacy and safety of adjunct oral steroids in the management of childhood CAP, including proportion of children experiencing solicited side effects of the trial treatment and/or serious adverse events, time to hospital discharge after index hospitalisation in days, time away from routine child care and away from work (for parents) in days up to 28 days after randomisation and total antibiotic exposure in days up to 28 days after randomisation.ResultsEnrolment started in November 2018 and is currently proceeding at approximately 1 participant per participating hospital per week.ReferencesStudy registration: BASEC - EKNZ 2018–00563Disclosure(s)Nothing to disclose
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Bang, Yung-Jue, Talia Golan, Chia-Chi Lin, Yoon-Koo Kang, Zev A. Wainberg, Heather Wasserstrom, Jin Jin, et al. "Interim safety and clinical activity in patients (pts) with locally advanced and unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase I study of ramucirumab (R) plus durvalumab (D)." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 92. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.92.
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92 Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This global phase 1 trial evaluates the combination of R (anti-VEGFR2) and D (anti-PD-L1) in pts with G/GEJ by simultaneously targeting these two processes. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02572687) enrolled pts with confirmed G/GEJ adenocarcinoma with prior progression on 1 or 2 lines of systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. PD-L1 expression was assessed using the SP-263 IHC; MSI status was determined using PCR. Enrolled pts received R (8 mg/kg IV) and D (750 mg IV) every two weeks on a 28-day cycle. Primary objective was to assess safety and tolerability of R+D; preliminary efficacy was also examined. Results: As of 26-May-2017, 29 G/GEJ adenocarcinoma pts were treated. The median age was 55 y; 69% were male; 66% had ECOG PS of 1; 48% had PD-L1 ≥25% expression in tumor or immune cells, 3.5% were MSI-high; and 72% received study treatment as second line for advanced disease. Median duration of treatment was 2.5 mo for R and 3.0 mo for D. Treatment-emergent adverse events (TEAEs) occurred in 29 (100%) pts and 21 (72%) pts experienced grade 3/4 TEAEs, while treatment-related AEs (TRAE) occurred in 24 (83%) pts; none resulted in treatment discontinuation. Ten (35%) pts had grade 3 TRAEs, and no grade 4 or 5. All grade TRAEs occurring in ≥10% of pts were hypertension (34%), fatigue (31%), headache (24%), diarrhea (21%), pyrexia (10%) and decreased appetite (10%). Five pts (17%) reported a serious adverse event related to study treatment. Preliminary efficacy data (RECIST v1.1) showed 5 of 29 pts (17%) achieved a confirmed PR. Only 1 responding pt was MSI high. The overall response rate for pts with PD-L1 ≥25% was 36%. Median PFS was 2.6 mo (95% CI, 1.45 to 6.28). As of data cut-off, 6 pts (21%) remain on treatment. Conclusions: R+D generated no unexpected toxicity, and demonstrated antitumor activity in pts with previously treated advanced G/GEJ adenocarcinoma. Clinical trial information: NCT02572687.
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Cerbaro, Kaueli Aline, and Raquel Dalla Costa da Rocha. "Tolerance and phytoremediation capacity of the Lemna minor in an aqueous medium contaminated by the Amoxicillin." Research, Society and Development 11, no. 7 (May 31, 2022): e45711730251. http://dx.doi.org/10.33448/rsd-v11i7.30251.
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This study aims to evaluate the behavior and the effectiveness of the aquatic plant Lemna minor as a phytoremediation potential about the antibiotic amoxicillin. Experiments were conducted through Central Composite Rotational Design (CCRD) and a kinetic study. The experiments taken by CCRD were performed in culture wells during a contact period of 5 days. The concentration of amoxicillin in the aqueous medium, the quantity of the plant mass, and the solution's pH were studied as independent variables. The dependent variables measured were the remaining amoxicillin in the solution, the plant's tolerance to mortality or fronds cloning and, for stress, chlorophyll-a/chlorophyll-b ratio. A kinetic study determined the rate of antibiotic removal in the aqueous medium. Because the only significant independent variable was the Amoxicillin concentration, the best experimental condition obtained through CCRD was considered the one with the higher level of Amoxicillin removal (92%) - the water medium with the drug concentration at 2.0 mg L-1 and pH 7.0. 5 g of wet mass from L. minor for each 10 mL of solution was chosen since this independent variable was not significant. There was no pH variation in the solution and the plant stress in the kinetics study. However, there was an amoxicillin removal of 80% after the seventh day. It is considered that, under conditions of low antibiotic load, the aquatic plant Lemna minor presents phytoremediation capacity to antibiotic amoxicillin.
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Marelli, Stefano Paolo, Luisa Zaniboni, Maria Giuseppina Strillacci, Manuela Madeddu, and Silvia Cerolini. "Morphological Characterization of Two Light Italian Turkey Breeds." Animals 12, no. 5 (February 24, 2022): 571. http://dx.doi.org/10.3390/ani12050571.
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We aimed to investigate the variability within turkeys’ phenotypical traits in two Italian heritage breeds: Brianzolo (BRZ) and Nero d’Italia (NIT), as analyzed through morphometry, morphometrical indexes, linear scoring, and colorimetric indexes. A total of 92 birds were measured, weighed, and scored (46 NIT: M/F = 19/27; 46 BRZ: M/F = 19/27). Live weight (LW), total body length (BL, excluding feathers), keel length (KL), chest circumference (BC), wingspan (WS), shank length (SL), shank diameter (SD), and shank circumference (SC). Massiveness (MASS), stockiness (STOCK), and long-leggedness (LLEG) indexes were also calculated. The body condition score (BCS) applied a linear evaluation to nutritional status and muscular development. Colorimetric indexes (L*, a*, b*) were recorded, sampling skin and shank. Data were analyzed using GLM procedures and PCA. NIT was the heaviest breed (4.89 vs. 4.07 kg; p ≤ 0.05). In both breeds, sexual dimorphism was visible in the LW trait with males (M) weighing significantly heavier than females (F) (p ≤ 0.05). NIT birds recorded the highest BL values: 58.44 vs. 57.15 cm (p ≤ 0.05). MASS was higher in NIT (8.26 vs. 7.0; p ≤ 0.05), and STOCK was higher in BRZ (82.62 vs. 85.37; p ≤ 0.05). Colorimetric indexes revealed significant differences in skin lightness (L*) and redness (a*). For shank color, the breed significantly affected differences in the indexes. This study characterizes these breeds at high risk of genetic erosion and extinction, which will help the morphological standardization of birds and the enhancement of genetic variability.
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Timila, R. D., J. C. Correll, and V. R. Duwadi. "Severe and Widespread Clubroot Epidemics in Nepal." Plant Disease 92, no. 2 (February 2008): 317. http://dx.doi.org/10.1094/pdis-92-2-0317b.
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Cultivation of brassica vegetables has the highest potential for generating income among more traditional rice and maize farmers in Nepal. Among brassica vegetables, the most important are cauliflower (Brassica oleracea var. botrytis L.) and cabbage (B. oleracea var. capitata L.). Although clubroot disease, caused by Plasmodiophora brassicae Woronin, has been observed in Nepal since 1993, severe and widespread epidemics have been observed since 2004 in the Bhaktapur, Kathmandu, Lalitpur, and Palung Valley production areas. Typical disease symptoms (1) are widespread, and disease severity has been particularly severe in the Kathmandu Valley and Palung/Daman area of the Makwanpur District. Many cauliflower fields in these areas have had as much as 100% yield loss between 2004 and 2006 with an estimated 40% overall loss from clubroot. Estimates from interviews with growers in the Palung production area during an intensive farmers' interaction program indicated that cauliflower production was reduced from 5 to 6 metric tons per household (1,500 m2) prior to 2004 to <300 kg per household in 2004 and beyond. The economic loss in this area alone was estimated at $1.4 million in 2004 and 2005. Examination of transplant nurseries indicated that frequently >80% of the seedlings have symptoms of clubroot at the time of transplanting. Soil samples from throughout the production areas indicated that the sandy loam soils were predominately acidic (pH range of 4.2 to 7.2 with >90% below 6.0). Several management practices are being employed to reduce disease severity, including the use of clubroot resistant cultivars, raising the soil pH to >7.0 by using dolomitic lime, testing of the fungicide flusulfamide (Nebijin) and biopesticide Sanjeevani (Trichoderma viride), and biofumigation and solarization of the nursery beds in an effort to reduce disease pressure on transplant material. References: (1) G. R. Dixon. Compendium of Brassica Diseases. S. R. Rimmer et al., eds. American Phytopathological Society, St. Paul, 2007.
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Wei, T., M. N. Pearson, D. Cohen, J. Z. Tang, and G. R. G. Clover. "First Report of Zantedeschia mosaic virus Infecting a Zantedeschia sp. in New Zealand." Plant Disease 92, no. 8 (August 2008): 1253. http://dx.doi.org/10.1094/pdis-92-8-1253a.
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In February 2004, leaf yellowing, mottling, and mosaics were observed on a few plants of a Zantedeschia sp. (calla lily) growing in Rangiora, Canterbury, New Zealand. Zantedeschia spp. are known to be susceptible to at least 13 virus species (1). No symptoms were observed on Chenopodium amaranticolor, C. quinoa, Cucumis sativus, Gomphrena globosa, Nicotiana benthamiana, N. clevelandii, N. occidentalis, or N. tabacum when inoculated with sap from symptomatic plants. However, electron microscopy of crude sap preparations from a symptomatic Zantedeschia sp. and inoculated N. clevelandii plants revealed the presence of flexuous, filamentous virus particles approximately 700 nm long and 12 nm wide. No virus particles were seen in the other inoculated indicator species. Nucleic acid was extracted from leaves of the infected Zantedeschia sp. and N. clevelandii plants and tested in reverse transcription (RT)-PCR using published potyvirus-specific primers (4). PCR amplicons of the expected size (327 bp) were obtained from both plant species and sequenced directly. The products were identical, and a BLAST search in GenBank showed 99% nucleotide identity with a Taiwanese isolate of the species Zantedeschia mosaic virus (ZaMV) (GenBank Accession No. AY026463). A product of 1,531 bp (GenBank Accession No. EU544542) was amplified from symptomatic Zantedeschia by RT-PCR using novel forward (5′-GCACGGCAGATAAACACGAC-3′) and reverse (5′-GTGGGCAACCTTCAACTGTG-3′) primers designed to amplify the 3′ untranslated region (3′UTR), coat protein (CP), and partial nuclear inclusion b protein (NIb) genes. The product was sequenced and had 94% nucleotide identity with a South Korean ZaMV isolate (GenBank Accession No. AB081519), with 95% nucleotide (97% amino acid) identity in the CP gene. A second crop of Zantedeschia spp. in Tauranga, New Zealand (approximately 700 km north of Rangiora) was observed to have similar disease symptoms. Symptomatic plants tested positive in ELISA using a potyvirus-specific monoclonal antibody (Agdia Inc., Elkhart, IN). Nucleic acid was extracted from leaves of symptomatic plants and tested in RT-PCR using potyvirus-specific primer pairs, PV2I/T7 and D335 and U335 and PV1/SP6, which amplify overlapping regions within the 3′UTR, CP, and NIb genes (2,3). The products were sequenced and a consensus sequence of 1,793 bp was generated (GenBank Accession No. EU532065). A BLAST search showed that the sequence had 78% nucleotide (88% amino acid) identity with Zantedeschia mild mosaic virus (ZaMMV) (GenBank Accession No. AY626825). However, the sequences had only 73% nucleotide (79% amino acid) identity in the CP gene, and therefore, this second virus may be a distinct species. To our knowledge, this is the first report of ZaMV in New Zealand. Cut flowers are an increasingly important commodity in New Zealand and Zantedeschia is one of the most important crops; in 2005, exports of rhizomes and cut flowers of the genus were worth NZ$10.9 million. These viral diseases may require management to ensure that the quality of production is maintained. References: (1) C. H. Huang et al. Plant Pathol. 56:183, 2007. (2) S. A. Langeveld et al. J. Gen. Virol. 72:1531, 1991. (3) A. M. Mackenzie et al. Arch. Virol. 143:903, 1998. (4) V. Marie-Jeanne et al. J. Phytopathol. 148:141, 2000.
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Popova, N. S., S. N. Novikov, P. I. Krzhivitskiy, L. A. Zhukova, P. V. Krivorotko, A. S. Artemyeva, A. E. Michnin, et al. "Diagnostic capabilities of breast scintigraphy and molecular imaging of the mammary glands in the detection of various biological subtypes of breast cancer." Tumors of female reproductive system 18, no. 3 (December 1, 2022): 14–23. http://dx.doi.org/10.17650/1994-4098-2022-18-3-14-23.
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Background. The accurate and early diagnosis of breast cancer can improve efficacy of the treatment. The standard diagnostic methods such as mammography, ultrasound, and magnetic resonance tomography have a pivotal role in the detection of breast tumors, however, in some cases, they have low diagnostic accuracy. Mammoscintigraphy (MSG) / molecular breast imaging (MBI) with tumor-specific radiopharmacy 99mTc-Technetril in patients with breast cancer can considerably increase the accuracy of diagnosis. However, the diagnostic performance of MSG / MBI in the detection of different biological subtypes of breast cancer is still under investigation.Aim. To evaluate the accuracy of MSG / MBI with 99mTc-Technetril in diagnosis of different biological subtypes of breast cancer.Materials and methods. The analysis included the results of MSG / MBI of 1080 patients (2154 mammary glands), who were examined for suspected breast cancer. MSG / MBI were performed 5–15 min after intravenous injection into the vein of one of the feet of 370–740 MBq of tumor-specific radiopharmacy 99mTc-Technetril. Examinations performed from 2007–2020 was carried out on the emission computed tomography Forte (Philips); since 2020 the molecular visualization has been providing on the special gamma-camera Discovery NM750b (General Electric). The obtained data were evaluated by 2 experienced radiologists. Verification of changes in breasts was provided by morphological examination (1060 cases) or dynamic observation.Results. The sensitivity, specificity and overall accuracy of MSG / MBI were 90 %, 98 %, 95 % correspondingly. When diagnosing tumors with a diameter of up to 10 mm, the sensitivity of MSG / MBI was decreased to 83 %. In patients with various biological subtypes, the sensitivity of MSG / MBI was as follows: luminal A – 88 %; luminal B– – 91 %; luminal B+ – 92 %; triple negative – 93 %; HER2-positive – 96 %. The intensity of tumor uptake depended on the biological subtype of breast cancer. The average values of the 99mTc-Technetril uptake coefficient were as follows: luminal A – 1.59; luminal B– – 1.71; luminal B+ – 1.95; triple negative – 1.93; HER2-positive – 2.22.Conclusion. Retrospective analysis indicate high diagnostic performance of MSG / MBI: sensitivity – 90 %, specificity – 98 %, accuracy – 95 %. There are significant differences in the intensity of 99mTc-Technetril accumulation in tumors in patients with different biological subtypes of breast cancer (p = 0.01–0.004). MSG / MBI characterized by significant differences in the sensitivity in the diagnosis of luminal A and HER2+ breast cancer subtypes: 88 % and 96 %, respectively (p = 0.02).
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Rodriguez, Maria Alma, Michelle Fanale, Fredrick Hagemeister, Peter McLaughlin, Barbara Pro, Jorge Romaguera, Larry Kwak, Luis Fayad, Xuelin Huang, and Jean Bernard Durand. "Phase II Study of RCHOP with Pegylated Liposomal Doxorubicin (DRCOP) for Patients > 60 Years Old with Untreated Diffuse Large B Cell Lymphoma (DLBCL)." Blood 110, no. 11 (November 16, 2007): 4468. http://dx.doi.org/10.1182/blood.v110.11.4468.4468.
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Abstract Background: DLBCL is a common lymphoma of older adults, and a potentially curable disorder with the regimen RCHOP (Coiffier, et.al. NEJM,2002). Doxorubicin, a key drug in the regimen, has risk for cardiotoxicity, and thus of concern in older patients (pts) with higher incidence of cardiovascular (CV) disease. In breast cancer pts pegylated liposomal doxorubicin (D) has shown greater cardiac safety and similar efficacy to doxorubicin. We thus replaced doxorubicin with D in RCHOP (DRCOP). Methods: The regimen is: Rituximab 375 mg/m2 IV day (d) 1; D 40 mg/m2 IV d 1; cyclophosphamide 750 mg/m2 IV d 1; vincristine 2 mg IV d 1 total dose; prednisone 100 mg/d p.o. d 1–5. Eligibility criteria are: > 60 years of age; untreated confirmed DLBCL (no discordant histology); Ann Arbor stage II-IV; baseline LVEF 50%. CV disease is permitted, if symptoms controlled, but consult at baseline by Cardiologist and at follow-up required. Growth factor support recommended (not required). Results: 34 pts are evaluable for toxicity; 30 evaluable for response (1 pt off study after 1 cycle; 3 too early for response). Characteristics of pts: age 62–92 (median 75); 18 female; IPI 1=1pt; IPI 2 = 2 pts; IPI 3 = 16 pts; IPI >3 = 15 pts. Responses are: 28/30 (93%) CR; 2/30 (7%) PR. At this time, 3/30 failed: 1 progression; 1 death due to non-neutropenic pneumonia; 1 death due to disease. Grade 3–4 adverse events were: 1 drop in LVEF; 8 atrial arrhythmias (reversed); 1 hypotension (reversed); 1 chest pain (reversed); 17 neutropenia (13 febrile, with 5 infections); 3 hand-foot syndrome; 4 fatigue; 2 DVT; 2 neuropathy. Conclusions: DRCOP has a high CR rate in this study of older pts with DLBCL, despite intermediate/high risk IPI. We’ve noted only one case of low LVEF ; more common are atrial arrythmias (8 pts), reversible. Neutropenia is the most common grade 3–4 adverse event (17 pts), and thus we strongly recommend growth factor support.
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de Précigout, Valérie, Christine Germain, Antoine Benard, Adeline Lacraz, Philippe Chauveau, Carole Deprele, Bruno Seigneuric, et al. "No Improvement of Hepatitis B Vaccination Response in Patients Dialysed with a Polymethylmethacrylate Membrane Compared to High-Flux Polysulfone: Results of the HEPADIAL Study." Blood Purification 49, no. 3 (November 13, 2019): 265–71. http://dx.doi.org/10.1159/000504035.
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Background: An altered immune response and decreased vaccine response are observed in patients with chronic renal failure. A preliminary study of 15 non-immunised patients, despite appropriate previous hepatitis B vaccination, showed a 60% seroconversion rate after 3 months of dialysis with a polymethylmethacrylate (PMMA) membrane. This response was associated with circulating soluble CD40 (CD40s) decrease, a natural inhibitor of the humoral immune response. The aim of the study is to confirm these results in a randomised study. Methods: We conducted a multicentre randomised intention-to-treat superiority clinical trial comparing polysulfone and a PMMA membrane in 2 parallel patient groups. The primary end point was the vaccine response rate, as defined by an anti-HBs antibodies titre of >10 IU/L, 1 month after the last vaccination with a double dose of Engerix B20®, performed at weeks 12, 16, 20, and 36. Results: Twenty-five patients were randomised and included in an intention-to-treat analysis. They were dialysed on polysulfone (n = 11) or PMMA (n = 14) for 40 weeks. Fifty percent of the PMMA patients versus 54.5% of the polysulfone patients achieved seroconversion (p = 1.00). The median anti-HBs antibody titre in responders at week 40 was 496 (92–750) versus 395 (43–572) UI/mL for PMMA and polysulfone, respectively (p = 0.46). The median CD40s titre at week 12 was 306 (193–448) versus 491 (281–515) pg/mL (p = 0.21). The CD40s median variation between week 0 and week 12 was 5 (–105 to 90) versus 64 (–63 to 123) pg/mL (p = 0.55). The CD40s level at week 12 in non-responders was slightly inferior to that of the responders: median 193 (168–331) versus 413 (281–512) pg/mL (p = 0.08). Conclusion: We did not observe a better vaccine response with the PMMA membrane compared to high-flux polysulfone. The PMMA membrane did not decrease the CD40s more than the polysulfone membrane probably because the titre was previously low in the 2 groups.
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Ogawa, Chitose, Akira Ohara, Atsushi Manabe, Ryoji Hanada, Hiroyuki Takahashi, Katsuyoshi Koh, Michiko Kajiwara, et al. "Treatment Outcome of Discontinued L-Asparaginase in Children with Standard-Risk Acute Lymphoblastic Leukemia: Tokyo Children’s Cancer Study Group (TCCSG) Study L99-15." Blood 106, no. 11 (November 16, 2005): 878. http://dx.doi.org/10.1182/blood.v106.11.878.878.
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Abstract BACKGROUND: L-asparaginase (L-asp) is one of the key drugs in the treatment of acute lymphoblastic leukemia (ALL) in children. However, L-asp often produces severe adverse effects including anaphylaxis resulting in its discontinuation. OBJECTIVE: To evaluate retrospectively the outcome of discontinuation of L-asp in patients with ALL. PATIENTS AND METHODS: Children newly diagnosed as ALL between 1999 and 2003 were consecutively enrolled on the TCCSG L99-15 study. Risk stratification was based on the age, initial white blood cell count, immunophenotype, cytogenetics and the response to prednisolone monotherapy. Totally, 267 (35%) out of 770 children were categorized into a standard-risk group (SR), 317 (41%) into a high-risk group (HR) and 186 (24%) into a very high-risk group (HEX). Allogeneic stem cell transplantation was indicated approximately in 50% of the HEX patients. L-asp was used 9 times in the induction phase in all the risk groups. The total number of L-asp administration all through the treatment was 19 in SR, 20 in HR and at least 10 in HEX. Patients were divided into two groups in the analysis: group A patients who received at least 50% of scheduled doses of L-asp and group B patients who received less than 50%. RESULTS: Remission was obtained in 259 (97%) patients in SR, 311 (98%) in HR and 171(92%) in HEX. In the patients who achieved remission and were analyzed, 195 (83.7%) in SR, 223 (78.8%) in HR and 123 (83.7%) in HEX received all the scheduled doses of L-asp. Event-free survival (EFS) (SE) and overall survival (OS) (SE) at 5 years for all the risk groups are shown in the table. Notably, EFS in group A (92.9%) and in group B (74.1%) in SR was significantly different (p=0.025). CONCLUSION: The outcome in patients who received less than 50% of scheduled dose of L-asp was inferior to that in the patients who received more than 50% of the scheduled dose. This suggests that modification or intensification of the treatment should be considered for the patients who discontinued L-asp in SR. EFS and OS in each group Risk group EFS ± SE(%) OS ± SE(%) (No. in A /B) group A group B p value group A group B p value SR (223 /10) 92.9±2.4 74.1±16.1 0.025 97.8±1.1 88.9±10.5 0.066 HR (269 /14) 78.5±3.2 66.7±19.2 0.969 88.9±2.6 50.0±25.0 0.158 HEX (142 /5) 58.2±5.5 75.5±21.7 0.514 75.6±4.3 80.0±17.9 0.873