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1
Williams, Jason. "Evaluating Clean Water Act progress drivers for Idaho rivers and streams 2002–2022." PLOS Water 2, no. 8 (August 30, 2023): e0000112. http://dx.doi.org/10.1371/journal.pwat.0000112.
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In the United States, the Clean Water Act (CWA) is the primary legislation driving surface water quality management. Its goal is to “restore and maintain the chemical, physical, and biological integrity of the Nation’s waters.” Section 305(b) of the CWA requires states to document CWA progress by reporting whether applicable water quality standards are achieved for all state waters every two years. Developing strategies for increasing the proportion of waters achieving standards requires diagnosing factors driving 305(b) data temporal trends. This analysis demonstrates how systematically analyzing 305(b) data in new ways can help document CWA progress (or lack thereof) and associated drivers. Idaho 305(b) data were used to evaluate the relative contribution of assessment progress and restoration to 2002–2022 Idaho 305(b) temporal trends. Assessment progress was defined as assessing unassessed waters and correcting assessment errors. Restoration was defined as changes from not achieving one or more standards to achieving all assessed standards because water quality improved. From 2002–2022, the percentage of Idaho stream kilometers achieving all assessed standards increased from 24% to 32%. Systematically evaluating reasons for stream status changes revealed this trend was driven primarily by assessment progress, specifically progress monitoring previously unassessed waters in good condition and correcting prior assessment errors. More stream km changed from impaired to unimpaired because prior assessment errors were corrected than because water quality improved. In each biennial 305(b) report ≤ 5% of all stream km changing status resulted from water quality improvement. As of 2022, more state stream km were impaired (39%) than unassessed (29%) and restoration success rates will likely become the primary driver of 305(b) temporal trends in the future. Systematically analyzing 305(b) data in new ways may help develop new empirically driven strategies for accelerating CWA progress and merits further investigation.
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Kliegel, W., L. Preu, Steven J. Rettig, and James Trotter. "Structural studies of organoboron compounds. XXIV. 5-Methyl-5-nitro-2-phenyl-1,3-dioxa-2-boracyclohexane." Canadian Journal of Chemistry 64, no. 9 (September 1, 1986): 1855–58. http://dx.doi.org/10.1139/v86-305.
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The title compound was prepared according to the literature in order to determine whether it has a bicyclic cage structure resulting from intramolecular O → B coordination or a monocyclic boronate structure incorporating a trigonal planar boron atom. Crystals of 5-methyl-5-nitro-2-phenyl-1,3-dioxa-2-boracyclohexane are orthorhombic, a = 17.2358(4), b = 6.5007(2), c = 9.9225(3) Å, Z = 4, space group Pnam. The structure was solved by direct methods and was refined by full-matrix least-squares procedures to R = 0.064 and Rw = 0.070 for 798 reflections with I ≥ 3σ(I). The molecule actually has C1symmetry but, in the solid state, is located at a site of crystallographic Cs symmetry. In order to maintain the apparent mirror symmetry the nitro oxygen atoms are disordered over two mirror-related rotational positions around the C(2)—N bond. The molecule was found to have a monocyclic boronate structure, in agreement with earlier predictions. The six-membered heterocyclic ring has a "semi-planar" conformation. Bond distances and angles are normal.
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Mardenli, Omar R. "The Progeny test of Friesian sires for milk traits by using the contemporary comparison method." Revista Colombiana de Ciencia Animal - RECIA 13, no. 1 (March 11, 2021): e747. http://dx.doi.org/10.24188/recia.v13.n1.2021.747.
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In this study, the contemporary comparison method (CC) of half-sibs relation was used to estimate the breeding values of Holstein-Friesian sires for 305 -day milk yield (305-DMY) and basic components of milk traits, 409 records of cows that are daughters of ten sires in eight Syrian dairy farms where used. Result of the study showed differences in the estimated breeding values(ccEBVs), where the E Sire achieved the highest value of 305-DMY trait (254.47 kg), while the B Sire achieved the highest value of milk protein percentage (MPP), milk fat percentage (MFP)and milk lactose percentage (MLP) traits (0.822 %, 0.857 %and 1.09% respectively). According to their sires, daughters of E Sire outperformed the counterparts in the 305-DMY (p = 0.001), MPP (p = 0.001) and MFP (p = 0.04) traits (5701.44 kg, 3.55%, and 3.88% respectively). According to source of farm, daughters in Farm 5 achieved the highest value of 305-DMY trait (p=0.04) and daughters in the seventh farm achieved the highest value of MPP trait (p=0.007), the values were 5403.48 kg and 3.54 % respectively. Values of heritability (h2) for the traits of 305-DMY, MPP, MFP and MLP were 0.33,0.54,0.43 and 0.47 respectively. Most of genetic and phenotypic correlations coefficients were approaching to zero except the genetic relation between MLP and MPP and phenotypic relation between MFP and MPP (0.88 and 0.84 respectively).
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Huang, Wentao, Jie Luo, Yifan Li, Da Fei, Xia Qin, and Runsheng Li. "Abstract 6020: Preclinical activity of LM-305 targeting G-protein-coupled receptor class 5 member D (GPRC5D) antibody drug conjugate for the treatment of multiple myeloma." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6020. http://dx.doi.org/10.1158/1538-7445.am2022-6020.
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Abstract Emerging therapies including chimeric antigen receptor (CAR) T therapy targeting B cell maturation antigen (BCMA) have shown promising clinical outcomes in relapsed and refractory multiple myeloma (RRMM). However, majority of patients eventually develop progressive disease due to heterogeneity in BCMA expression or loss of antigen during treatment. Therefore, new targets are required to overcome the problem of resistance encountered with these agents. The expression of GPRC5D (G-protein-coupled receptor class 5 member D) is high on MM cells and low in normal tissues. Although high levels of GPRC5D and BCMA were found in similar proportions of MM patients, they are independently expressed by MM cells. GPRC5DxCD3 bispecific T-cell-redirecting antibody is currently under clinical investigation. Preliminary results have shown early evidence in efficacy with tolerable safety profile. These findings identified GPRC5D as an ideal therapeutic antibody drug conjugate (ADC) target for the treatment of patients with RRMM. Therefore, the present study was aimed at developing a novel anti-GPRC5D ADC drug LM-305 and evaluating its preliminary efficacy by performing preclinical activity using in vitro and in vivo mouse models. The binding affinity of LM-305 was evaluated by flow cytometry in engineered GPRC5D over-expressing MM tumor cells and endogenous GPRC5D-expressing MM tumor cells. The internalization of LM-305 was assessed with pH-dependent dye in NCI-H929 and MM.1R cell lines. The cytotoxicity of LM-305 was assessed by cell viability assay in MM tumor cell lines. In vivo anti-tumor activity of multiple doses of LM-305 (1mg/kg, 3mg/kg, 10mg/kg) was evaluated in NCI-H929 and MM.1R tumor cell line derived xenograft (CDX) models. In vitro studies revealed that LM-305 binds with high affinity to GPRC5D over-expressing cell lines and GPRC5D endogenously expressing MM cells in a dose-dependent manner. It can be efficiently internalized by GPRC5D expressing cells and further lysosomal lysis was detected by pHrodo dye. LM-305 displayed potent cytotoxicity when co-cultured with MM tumor cells (NCI-H929 and MM.1R) with IC50 values ranging from 0.1 to 0.3 nM. In vivo tumor xenograft models suggested that treatment with LM-305 resulted in dose-dependent inhibition of tumor growth in tumor bearing mice. Additionally, LM-305 exhibited complete response (CR) in the GPRC5D high-expressing MM CDX models at a dose of 3mg/kg. Moreover, LM-305 showed good safety profile in the animal studies. In conclusion, this preclinical data suggested that LM-305 is a novel GPRC5D targeting ADC with best-in-class potential, and therefore it can be a promising therapeutic candidate for the treatment of RRMM patients expressing GPRC5D. Citation Format: Wentao Huang, Jie Luo, Yifan Li, Da Fei, Xia Qin, Runsheng Li. Preclinical activity of LM-305 targeting G-protein-coupled receptor class 5 member D (GPRC5D) antibody drug conjugate for the treatment of multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6020.
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Gomez, Eliana B., Lippincott Isabel, Mary S. Rosendahal, Stephen M. Rothenberg, Steven W. Andrews, and Barb J. Brandhuber. "Loxo-305, a Highly Selective and Non-Covalent Next Generation BTK Inhibitor, Inhibits Diverse BTK C481 Substitution Mutations." Blood 134, Supplement_1 (November 13, 2019): 4644. http://dx.doi.org/10.1182/blood-2019-126114.
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Introduction: Bruton's Tyrosine Kinase (BTK) is an essential component of normal and malignant B-cell receptor signaling. Covalent BTK inhibitors have transformed the treatment of B-cell malignancies but are limited by off-target toxicity and acquired resistance, leading to eventual treatment discontinuation and disease progression. Emerging evidence suggests that acquired resistance is mediated predominantly by BTK C481 substitution mutations at the covalent BTK inhibitors' binding site. There is significant unmet clinical need for new treatment approaches that overcome acquired resistance and minimize toxicity. LOXO-305 is a highly selective, non-covalent, next generation BTK inhibitor. We previously showed that LOXO-305 potently inhibited both wild-type (WT) BTK and BTK C481S -mediated kinase activity in enzyme and cell-based assays with nanomolar potency, caused regression of BTK-dependent lymphoma mouse xenograft models, and was more than 300-fold selective for BTK over 98% of 370 other kinases tested and showed no significant inhibition of non-kinase off targets at 1 mM (Brandhuber et al. SOHO 2018). In addition, ADME and pharmacokinetic experiments in two preclinical species predicted that LOXO-305 will have high human exposure and sustained BTK C481S target coverage in patients at clinically achievable doses. Here we describe the activity of LOXO-305 against additional BTK C481 substitution mutations, including mutations identified in patients with acquired resistance to covalent BTK inhibitors. We further determine equilibrium-binding affinities for LOXO-305 for diverse mutant BTK enzymes in comparison to other clinically available BTK inhibitors. Methods: To assess cellular BTK inhibitor potency, HEK293T cell lines transiently expressing wild-type BTK and BTK C481 substitution mutations were serum starved and incubated with LOXO-305 overnight. Cells were next incubated with serum and orthovanadate for 5 min and the phosphorylated Y223 BTK was analyzed by immunoblot. Bands were quantified and the IC50 values calculated with GraphPad Prism. The equilibrium-binding affinities for targeted BTK inhibitors to BTK enzyme variants were determined by surface plasmon resonance (SPR) using the Biacore T200. Biotinylated BTK variants were immobilized on a docked streptavidin coated sensor chip. Five concentrations of each inhibitor plus blank controls were analyzed. Association/dissociation rate constants were calculated by global fitting of the data to a 1:1 binding interaction model. Results: While BTK C481S possessed similar levels of basal Y223 autophosphorylation as wild-type BTK in cells, BTK C481T autophosphorylation was reduced by ~50%, C481R by ~90%, and mutants C481F, and C481Y were inactive in HEK293T cells. LOXO-305 inhibited Y223 phosphorylation of all active mutants with similar nanomolar potency. In contrast, autophosphorylation of all BTK C481 mutants were resistant to both Ibrutinib and acalabrutinib. Equilibrium-binding affinities of LOXO-305 for select BTK C481 substitution mutations confirmed LOXO-305's superior potency versus commercially available BTK inhibitors (ibrutinib and acalabrutinib). Conclusions: The next generation, non-covalent, highly selective BTK inhibitor LOXO-305 potently inhibited the cellular activity of BTK C481S, T and R mutations and displayed strong equilibrium binding to WT BTK and several BTK C481 substitution mutations. Together with high selectivity and significant BTK target coverage in vivo, these results indicate that LOXO-305 may overcome acquired resistance to covalent BTK inhibitors in patients without significant off-target toxicity. A phase 1 clinical trial of LOXO-305 is currently underway. Disclosures Gomez: LOXO Oncology Inc.: Employment, Equity Ownership. Isabel:Loxo Oncology: Employment. Rosendahal:Loxo Oncology: Employment. Rothenberg:LOXO Oncology Inc.: Employment. Andrews:Loxo Oncology: Employment. Brandhuber:LOXO Oncology Inc.: Employment, Equity Ownership.
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Zohrabyan, Davit, Samvel Bardakhchyan, Sergo Mkhitaryan, Liana Safaryan, Jemma Arakelyan, Gevorg Tamamyan, Lilit Harutyunyan, et al. "Breast cancer pathology patterns in Armenia." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e12586-e12586. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e12586.
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e12586 Background: Breast cancer (BC) is the most common malignancy among the women in Armenia (AM). Currently there is a knowledge gap regarding the morphology distribution of the BC in AM. Methods: The data on patients with BC diagnosed in 2015-2016 in the pathology lab “Davidyants Labs” in AM were retrospectively reviewed. Pts with Her2+ results by IHC were excluded from the study, due to unavailability to perform FISH or CISH analyses. Overall 361 pathology reports were evaluated. Results: The median age was 54 years; range [19-82]. Histopathological subtypes were defined for 305 pts, from which lobular carcinoma 57.4% of cases (175/305), ductal carcinoma 26.9% (82/305), mucinous carcinoma 2.6% (8/305), mixed type carcinoma (lobular and ductal) 2.6% (8/305), DCIS 2% (n = 6/305), non specified carcinoma 2% (6/305), medullary carcinoma 1% (n = 3/305) and others 5.6% (17/305). Within the cohort 8.5% (23/270) were grade 1, 65.9% grade 2 (178/270); 25.6% grade 3 (n = 69/270). Vascular or lymphatic invasion was present in 59.5% (50/84) and 64.7% (55/85), respectively. Staging distribution, based on pT pN data for 92 pts who went to primary surgery, was: 0 stage 7.6% (7/92), I stage 22.8% (21/92), II stage 41.3% (38/92), III stage 28.3% (26/92). Staging distribution based on ypT ypN data for 27 pts who went to surgery after neoadjuvant chemo was 0 stage 25.9% (7/27), I stage 18.5% (5/27), II stage 29.6% (8/27), III stage 25.9% (7/27). ER and PR were defined for 244 patients. ER positive 89.8% (219/244) of cases, PR pos. 73% (178/244), ER/PR pos. 72.5% (177/244) cases. Her receptor was defined for 237 patients. Her3+ 16.9% (40/237); Her2+ 12.7% (30/237); Her1+ 38% (90/237); Her0 32.5% (n = 77/237). We could not evaluate Her2+ status by FISH or CISH, so these results were excluded from the analysis. Ki67 was low (≤20) in 42.1% (101/240) of cases and high ( > 20) in 57.9% (139/240). Within the group Luminal A type was 41.4% (84/203); Luminal B 32.5% (66/203); Her positive 19.7% (40/203) and triple negative 6.4% (13/203). p53 and perineural invasion (Pn) was present in 32% (16/50) and 52% (26/50), respectively. Tumor leukocyte infiltration was determined for 16 patients. Leukocyte infiltration was positive in 43.7% (7/16) cases, negative in 25% (4/16) cases, minimal in 31.3% cases (5/16). Conclusions: BC in Armenian women presents with different epidemiological characteristics in comparison with other ethnicities. Lobular type BC is the most frequent type among Armenian women, however, differential diagnosis between lobular/ductal carcinomas was done without IHC (E-Cadherin), which rises the need for further studies on that regard.
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LOLITA, MODANA, I. KOMANG GDE SUKARSA, and MADE SUSILAWATI. "ANALISIS STABILITAS HASIL GENOTIPE JAGUNG MENGGUNAKAN METODE FIXED AMMI." E-Jurnal Matematika 8, no. 1 (February 2, 2019): 9. http://dx.doi.org/10.24843/mtk.2019.v08.i01.p229.
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Additive Main Effect and Multiplicative Interaction (AMMI) is a method that is used in research to study interaction between genotype and location. The aim of this research is to apply fixed AMMI in examining the production of corn genotype data and to explore yield stability of its based on biplot picture and AMMI Stability Value (ASV). This research uses six corn genotypes, eight trial locations, and three repetitions. The Interaction Principal Component Analysis (IPCA) that are significant to entered in the model based on analysis of variance fixed AMMI are IPCA1, IPCA2, and IPCA3 with total diversity interaction as much as 92,16%. The biplot picture and ASV should the stable genotype in all location are genotype KUI Carotenoid Syn FS. 17-3-2-B-B T01 and genotype CML 305-B-B T01. In addition, corns that are able to adapt only in certain location is: genotype KUI Carotenoid Syn FS. 5-1-5-B-B T01, genotype KUI Carotenoid Syn FS. 25-3-2-B-B T01, genotype KUI Carotenoid Syn FS. 17-3-1-B T01, and genotype CML 130-B-B T01.
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Fabris, Sonia, Giovanna Cutrona, Massimo Gentile, Serena Matis, Emanuela Anna Pesce, Francesco Di Raimondo, Caterina Musolino, et al. "Incidence of Cytogenetic Abnormalities in Newly Diagnosed Binet Stage A B-CLL and Relationship with Prognostic Biomarkers: Preliminary Results On 305 Patients Included in the Prospective O-CLL1 GISL Study." Blood 114, no. 22 (November 20, 2009): 2341. http://dx.doi.org/10.1182/blood.v114.22.2341.2341.
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Abstract Abstract 2341 Poster Board II-318 Background. The clinical heterogeneity of chronic lymphocytic leukemia (CLL) requires parameters to stratify patients into prognostic subgroups to adapt treatment ranging from ‘watch and wait’ to allogeneic stem cell transplantation. To this end, several parameters such as lymphocyte doubling time, β-2 microglobulin, CD38 and ZAP-70 expression, immunoglobulin variable heavy chain (IgVH) mutation status and genetic abnormalities, as assessed by fluorescence in situ hybridization (FISH), have been integrated in clinical practice. Aims. In the present study, we investigated by FISH the incidence of the known major cytogenetic alterations (+12 and 13q14, 17p13, 11q23 deletions) in a series of Binet A B-CLL patients included in the prospective O-CLL1 GISL study started in April 2007. Methods. Molecular markers characterization and FISH analyses were performed as previously reported (Cutrona et al. Haematologica, 2008; Fabris et al. GCC, 2008). A cut-off value of 2% was used to distinguish mutated and unmutated patients. CD38 and ZAP-70 were determined by flow-cytometry and a 30% cut-off was used to distinguish between positive or negative cases. Results. Up to date, 326 patients have been enrolled in the trial and FISH data concerning trisomy 12 and 13q14, 17p13, 11q23 deletions were available in 305 patients. At least one abnormality was found in 197 (64%) cases. The most frequent was del(13)(q14) (150/305, 49%), followed by +12 (40/303, 13%) (in one and three cases accompanied by 17p13 and 13q14 deletions, respectively), del(17)(p13) (7/305, 2%) and del(11)(q23) (17/305, 5%). 13q14 deletion was found as a sole abnormality in 134 patients; in the remaining cases, it was combined with +12 (3 pts) and 17p13 (3 pts) or 11q23 (10 pts) deletions. Among patients with 13q14 deletions, 99 were monoallelic, 12 biallelic and 39 showed a combination of the two patterns. Biomarkers data were available in all of the patients: 95/305 (31%) cases had unmutated IgVH genes; ZAP-70 and CD38 were positive in 117/305 (38%) and 72/305 (23%) cases, respectively. Concerning the distribution of cytogenetic aberrations, the unmutated IgVH group included 29/150 (19%) 13q14 deleted cases, 23/40 (57%) cases with trisomy 12 and 4/7 (57%) and 16/17 (94%) with 17p13 and 11q23 deletions, respectively. ZAP-70-positive groups included 43/150 (28%) 13q14 deleted cases, 26/40 (65%) cases showing trisomy 12 and 5/7 (71%) and 12/17 (70%) with 17p13 and 11q23 deletions, respectively. Finally, CD38-positive cases included 18/150 (12%) 13q14 deleted cases, 26/40 (65%) cases carrying trisomy 12 and 5/7 (71%) and 7/17 (41%) with 17p13 and 11q23 deletions, respectively. The percentages of IgVH mutations significantly correlated with cytogenetic alterations; namely, 5.8±0.3 for cases with del(13)(q14), 4.6±0.4 for normal karyotype, 2.6±0.5 in +12, 0.3±0.2 in del(11)(q23), and 1.7±0.9 in del(17)(p13) cases (p for trend <0.0001). A significant correlation was also found for ZAP-70 expression: namely 32±1.8 for cases with del(13)(q14), 38.6±2.2 for normal karyotype, 47.6±3.7 for +12, 55.8±7.0 for del(11)(q22) and 42.4±11.7 for del(17)(p13) (p<0.0001). Similarly, CD38 percentages were (mean value ± sem) 9.3±1.7, 16.9±2.1, 52.9±5.7, 26.8±6.2, 37.0±12.7 for del(13)(q14), normal karyotype, +12, del(11)(q23) and del(17)(p13) alterations, respectively (p for trend <0.0001). Finally, cytogenetic abnormalities were clustered in 3 risk groups [i.e. low del(13)(q14) and normal; intermediate (+12); and high risk del(11)(q23) and del(17)(p13)] and significantly correlated (p<0.0001) with a scoring system in which cases were stratified in 4 different groups according to the absence (group 0) or presence of 1 (group 1), 2 (group 2) or 3 (group 3) biomarkers (Morabito et al., BJH, 2009, voce). Interestingly, 147/154 cases scoring 0, gathered in the low FISH group, whereas 17/22 high FISH risk cases clustered in scoring 2-3. Conclusions. Our preliminary results indicate that in Binet stage A B-CLL patients at diagnosis cytogenetic abnormalities with an expected negative clinical impact are relatively few (7.2%) but significantly associated with prognostic biomarkers which negatively predict the clinical outcome in B-CLL. Disclosures: No relevant conflicts of interest to declare.
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Arora, Sukeshi Patel, Jennifer L. Moseley, Laura LaNiel Tenner, Luisa Arellano, Mary Salazar, Qianqian Liu, Joel Michalek, and Devalingam Mahalingam. "Phase II study of modulation of sorafenib (SOR)-induced autophagy using hydroxychloroquine (HCQ) in advanced hepatocellular cancer (HCC): Planned interim efficacy and safety analysis." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 305. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.305.
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305 Background: SOR is the first systemic therapy approved for advanced HCC, but has shown only modest improvements in survival. Resistance to SOR in pre-clinical models has been attributed to autophagy induction. Autophagy inhibition with HCQ enhanced SOR-induced cell death and apoptosis in early pre-clinic and clinical studies. Data from the phase I study of SOR plus HCQ in advanced solid tumors at showed clinical safety and efficacy. Therefore, we conducted a prospective study to evaluate efficacy of SOR and HCQ in advanced HCC patients (pts) (NCT03037437) and report planned interim analysis for our first-line cohort. Methods: Prospective phase II study of SOR 400 mg po BID + HCQ 400 mg daily in pts with advanced HCC (CP A-B8 cirrhosis). Cohort 1: first-line SOR/HCQ. Cohort 2: add HCQ upon progressing on SOR. CP B pts started at 200 mg BID, with dose escalation as tolerated. Cycle = 4 weeks. Primary endpoint: mTTP. Secondary endpoints: mOS, response by RECIST; AEs (NCI-CTCAEv3.0); PD analysis for markers of autophagy and immunity. Pts evaluable for efficacy if completed C1. Planned interim efficacy and safety analysis approved by DSMB is reported here. Results: For cohort 1, n = 19. Median age 63.5 (51-80). 80% Male; 65% Hispanics. ECOG 0-1: 100%. CP B cirrhosis: 32%. Etiology of cirrhosis: HCV 84%, ETOH 26%, NASH 5%. BCLC B 21%, C 70%. AFP > 400: 47%, PVT: 32%, metastases: 64%, post-transplant: 21%. Reason off study: PD (n = 10), toxicity (n = 2), lost to f/u (n = 1), withdrew (n = 1). N = 16 completed C1, n = 2 remain on study. mTTP is 4.2 months (95% CI: 3.7-NA). mOS 13.8 months (95% CI: 13.8-NA). Response Rate (CR+PR): 25%. Best response: CR n = 1 (6%), PR n = 3 (19%), SD n = 7 (44%). 4+ cycles: n = 9 (56%). % alive. Median duration of response 7.6 months (3.67-20). Gr 1/2 AEs as expected from SOR. Gr 3: AST elevated (n = 1), diarrhea (n = 1) due to SOR. Gr 2 rash (n = 1) due to HCQ. No Gr 4/5. Dose reduction: 70% for SOR, 0% for HCQ. PD analysis on the 3 responders show favorable immune profile changes (increase in cytotoxic T cells and decrease T Regs). Conclusions: SOR/HCQ had a better response rate (25%) than historically SOR alone (2%) in pts with advanced HCC, predominantly BCLC C, with CP A and B cirrhosis. While immune checkpoint inhibitors (ICIs) are taking the forefront in advanced HCC, SOR/HCQ may have a role in patients with CP B cirrhosis, transplant or contraindications to ICIs. Further, analysis of predictive markers of response is ongoing. Clinical trial information: NCT03037437.
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Graulich, Jens, and Dietrich Babel. "Die Kristallstruktur von Bis-[methylammonium]-hexafluorosilikat, (MeNH3)2SiF6 / The Crystal Structure of Bis-[methylammonium]-hexafluorosilicate, (MeNH3)2SiF6." Zeitschrift für Naturforschung B 57, no. 9 (September 1, 2002): 1003–7. http://dx.doi.org/10.1515/znb-2002-0906.
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The results of a single crystal X-ray structure determination of monoclinic (MeNH3)2SiF6 are reported: a = 962.3(5), b = 964.4(1), c = 966.4(5) pm, " = 100.03(3)°; V = 883.2(7) Å3, Z = 4, space group C2/c; wR2 = 0.0999 based on F02 of 1291 independent reflections (including H refinement without restrictions). The structure is related to that of (NH4)2SiF6, but contains the dumb-bells of the cations well oriented along the greater cell diagonals and fixed by one nearly linear and two bi-furcated hydrogen bonds (N...F: 281 and 293 - 305 pm, resp.). The [SiF6]2- octahedron is nearly undistorted with average bond length Si-F: 167.7 pm (169.9 pm corrected for thermal motion)
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Chan, Yueh-Hsuan, Yu-Tzu Lee, Hung-Wen Chou, Pheidias Wu, Jiun-Bo Chen, Chau-Hong Li, Tien-Tien Cheng, Nien-Yi Chen, Tse-Wen Chang, and Ko-Haung Lue. "Developing an antibody targeting CεmX of mIgE for the treatment of IgE-mediated diseases (HYP4P.305)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 123.4. http://dx.doi.org/10.4049/jimmunol.194.supp.123.4.
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Abstract CεmX (also referred to as M1’) is a discrete domain of 52 a.a. residues, located between the CH4 domain and the C-terminal membrane anchor peptide of the ε heavy chain of membrane-bound IgE (mIgE) on human B lymphocytes. Antibodies that target CεmX are potentially useful in controlling IgE production for treating allergic and other IgE-mediated diseases. Herein we report that an anti-CεmX mAb, 4B12, was shown to be effective in reducing allergen-specific IgE and IL-5 production upon the challenge of the allergen in an asthma model employing CεmX gene knocked-in mice that express mIgE containing human CεmX domain on B cells. 4B12 could also alleviate airway hyper-responsiveness (AHR), allergen-induced eosinophil infiltration, and lung inflammation in those mice. Furthermore, we demonstrated that a humanized 4B12 mAb (referred to as FB825) could inhibit the production of human IgE in mice that had been reconstituted with human peripheral blood mononuclear cells. Based on the abilities of 4B12 to bind to mIgE and to lyse mIgE-expressing B cells by apoptosis, ADCC, and other cytolytic mechanisms and on the above results on animal models, a phase-I human clinical trial of FB825 to investigate its IgE-related biological effects is being performed.
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Podgonykh, S. M., and K. E. Bolotin. "Relationship between the Spontaneous Magnetization, Spontaneous Magnetostriction and Heat Capacity in the Compound Mn5Ge3." Solid State Phenomena 168-169 (December 2010): 153–56. http://dx.doi.org/10.4028/www.scientific.net/ssp.168-169.153.
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Spontaneous magnetization Ms of the ferromagnetic compound Mn5Ge3 with the Curie temperature TC=305 K has been studied in the temperature range from 2 to 400 K. The relationships between the magnetic part of the heat capacity (CMAG), the magnetic part of the volume thermal expansion coefficient (TEC) MAG, and the Ms for the compound Mn5Ge3 have been considered. It has been found that the magnetic part of the heat capacity can be well approximated by the dependence CMAG(T)=a×|dMs2/dT|–b×|dMs4/dT| with a>0 and b>0, and the magnetic part of the TEC, by the dependence MAG=C1×dMs2/dT+C2×dMs4/dT with C1<0 and C2>0 in the whole temperature. It is assumed that the main sources in the formation of the observed CMAG(T) and MAG(T) dependences are the changes in the elastic, magnetoelastic, magnetovolume, and magnetostatic energies of the sample that appear as a result of the spontaneous magnetostrictive deformation with temperature changing.
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Stillwell, Kyra, Noah Kramer, Bryan Birch, Brandon Reese, Arjun K. Pathak, and Mahmud Khan. "The magnetic and magnetocaloric properties of Al-rich Al0.85+xSi0.15Fe2B2 compounds prepared by drop-casting." AIP Advances 13, no. 2 (February 1, 2023): 025132. http://dx.doi.org/10.1063/9.0000538.
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Owing to the relative abundance of its constituent elements and large magnetocaloric properties observed near room temperature, the AlFe2B2 system has attracted much attention recently. Here, we have studied the magnetic and magnetocaloric properties of Al0.85+ xSi0.15Fe2B2 ( x = 0.2, 0.4) prepared by drop-casting followed by annealing and acid treatment. The second order ferromagnetic phase transitions were observed near room temperature (∼298–305 K) and peak magnetic entropy changes (−ΔSM) of more than −6 J kg−1 K−1 were observed for a field change of 5 T. The results are discussed in terms of the impurity phases formed in the compounds due to excess aluminum.
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Kaur, I., N. Chawla, A. S. Dhatt, and M. Kaur. "Evaluation of Physico-Chemical Composition in Bulbs of Red, Yellow, and White Onion (Allium Cepa L.) Genotypes of Sub-Tropical India." Acta Alimentaria 49, no. 4 (November 7, 2020): 483–90. http://dx.doi.org/10.1556/066.2020.49.4.14.
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In this study, thirty onion (Allium cepa L.) genotypes grown in sub-tropical region of India were analysed for different physico-chemical attributes. There were significant differences among genotypes, and the onion genotypes showed a tendency to be classified according to different colours. The cultivars of the same colour exhibited similar tendencies in terms of accumulating most of the analysed components. About 1.78 fold variation in dry matter (%) and 2 fold variation in fresh weight per bulb were recorded among coloured onions. Red genotype D-888-B possessed maximum contents of TS and NRS, while the yellow coloured genotype POH-5 accumulated highest RS and lowest NRS contents. Maximum values of fructans (3.68 g/100 g DW), AIS (6 g/100 g DW), protein (10.61 g/100 g DW), and FAA (4.24 g/100 g DW) were also found in red coloured genotypes D-715-B, D-97-B, PR-305, and D-PS-121-B, respectively. Proline content in different genotypes was found to vary about 6.9 fold. The correlation studies showed a positive relationship between most of the quality parameters. Our results suggested that red group genotypes were better than yellow and white groups for all the studied parameters except for RS, which makes red genotypes more suitable for processing purposes.
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Gaina, C., V. Gaina, and M. Sava. "New Poly(4-Dichloro)Maleimides: III. Synthesis and Characterization of Poly[Ether-Ester-Azomethine-(4-Chloro) Maleimides] and Poly(Azomethin Ester-Aspartimides)." High Performance Polymers 13, no. 4 (December 2001): 269–80. http://dx.doi.org/10.1088/0954-0083/13/4/305.
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New poly[(N-ester-azo)-3-ether-4-chloro)maleimides] and poly(azomethin-ester-aspartimides) were synthesized by the reaction of N-[4-(formylphenoxy carboxylphenyl)]-3-(4-formylphenoxy)-4-chloromaleimide (3 a) or N-[4-formylphenoxycarbonylphenyl)maleimide (3 b) with various diamines. IR and elemental analyses confirmed the structures of the resulting polymers. A series of model compounds were synthesized to facilitate confirmation of the polymer structures. The polymers possess inherent viscosities in the range 0.17–0.42 dl g−1, solubility in aprotic dipolar solvents and 5% weight loss at temperatures above 300 °C.
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Mato, Anthony R., Ian W. Flinn, John M. Pagel, Jennifer R. Brown, Chan Y. Cheah, Catherine C. Coombs, Manish R. Patel, et al. "Results from a First-in-Human, Proof-of-Concept Phase 1 Trial in Pretreated B-Cell Malignancies for Loxo-305, a Next-Generation, Highly Selective, Non-Covalent BTK Inhibitor." Blood 134, Supplement_1 (November 13, 2019): 501. http://dx.doi.org/10.1182/blood-2019-127509.
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Introduction: Bruton Tyrosine Kinase inhibitors (BTKis) have transformed the treatment of patients with chronic lymphocytic leukemia (CLL) and other B-cell malignancies by inducing durable responses, improving quality of life and prolonging overall survival. Prolonged use of BTKi in the real-world setting is limited by toxicity and acquired resistance. Discontinuation rates for BTKis may be as high as 40% in relapsed/refractory CLL, with BTK C481-mediated resistance evident in many progressing patients. Alternative therapies such as venetoclax are associated with on-target (BCL2) acquired resistance. We hypothesized that a selective, non-covalent BTKi would benefit patients with B-cell malignancies in the setting of acquired resistance and/ or unacceptable toxicities following an irreversible BTKi. LOXO-305 is a next-generation, highly selective, oral, non-covalent BTKi that inhibits wild-type and C481-mutated BTK preclinically. Here, we report results from a first-in-human, proof-of-concept phase 1 trial in patients with B-cell malignancies. Methods: This multicenter phase 1/2 trial (NCT 03740529) enrolled patients with advanced B-cell malignancies who had failed or were intolerant to > 2 prior therapies. LOXO-305 was dosed orally in 28-day cycles, using a standard 3+3 dose-escalation design with a primary endpoint of MTD/RP2D identification. Results: As of 26 July 2019, 13 patients (9 CLL and 4 MCL) were enrolled to 3 dose levels: 25mg (n=5), 50mg (n=5) and 100mg (n=3) QD. Median age was 65 (range 51-79) years and the median number of prior therapies was 3 (range 2-6). 12 patients (8 CLL, 4 MCL) received prior chemotherapy + anti-CD20 antibody; 2 MCL patients underwent prior autologous stem cell transplantation; 5 CLL patients received prior umbralisib; 10 patients (7 CLL, 3 MCL) received prior ibrutinib (5 intolerant, 5 relapsed), including 1 who had also received venetoclax. 6 CLL patients displayed high-risk genetic features, including unmutated IGHV (4), complex karyotype (4) and del17p (3). Molecular characterization was available in 7 patients (6 CLL, 1 MCL) and revealed: BTK C481S mutations (in 2 CLL patients post-ibrutinib), a BCL2 G101V mutation (in a CLL patient post-venetoclax), and a TP53 mutation (in an MCL patient post-ibrutinib). At doses ≥50 mg QD, LOXO-305 exposure exceeded the calculated IC90 for wild-type and C481S mutated BTK. No DLTs were reported and all TEAEs are grade 1-2. Clinical activity was noted within the first cycle of therapy and at the first dose level of 25mg QD. The first eight patients were evaluable for initial response and 7 tumor responses (87.5%) were observed (by disease-defined criteria): 5/5 CLL patients (1 PR and 4 PR-L including one with BTK C481S mutation after ibrutinib and one with BCL2 G101V mutation after venetoclax) and 2/3 MCL patients (2 PR and 1 PD with a preexisting TP53 mutation). 2 additional CLL patients were awaiting initial radiologic assessment but had already demonstrated treatment-induced lymphocytosis. 12/13 patients remain on therapy, the longest 5+ months. Conclusion: Phase 1 data with LOXO-305 demonstrate a favorable safety profile and provide proof-of-concept evidence of efficacy in heavily pretreated CLL and MCL patients, including patients with acquired resistance to available BTKis and venetoclax. Disclosures Mato: DTRM Biopharma: Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Gilead: Research Funding; Acerta: Consultancy; Janssen: Consultancy; TG Therapeutics: Consultancy, Other: DSMB member , Research Funding; Celgene: Consultancy; Sunesis: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; LOXO: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Research Funding. Flinn:F. Hoffmann-La Roche Ltd: Research Funding; Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Genentech, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Janssen, Karyopharm Therapeutics, Kite Pharma, Novartis, Pharmacyclics, Portola Pharmaceuticals: Research Funding; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; AbbVie, Seattle Genetics, TG Therapeutics, Verastem: Consultancy. Pagel:AstraZeneca: Consultancy; Gilead Sciences: Consultancy; Pharmacyclics: Consultancy. Brown:Teva: Honoraria; Janssen: Honoraria; Sunesis: Consultancy; Juno/Celgene: Consultancy; Gilead: Consultancy, Research Funding; Dynamo Therapeutics: Consultancy; Genentech/Roche: Consultancy; Pharmacyclics: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Loxo: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Sun Pharmaceuticals: Research Funding; Verastem: Consultancy, Research Funding; TG Therapeutics: Consultancy; Octapharma: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Catapult Therapeutics: Consultancy; Acerta Pharma: Consultancy; Invectys: Other: Data safety monitoring board; Morphosys: Other: Data safety monitoring board; AbbVie: Consultancy. Cheah:Roche, Janssen, MSD, Gilead, Loxo Oncology, Acerta, BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene, Roche, Abbvie: Research Funding; Roche: Other: Travel expenses. Coombs:Medscape: Honoraria; Covance: Consultancy; Cowen & Co.: Consultancy; H3 Biomedicine: Honoraria; Dedham Group: Consultancy; Loxo: Honoraria; Abbvie: Consultancy; Octopharma: Honoraria; Pharmacyclics: Honoraria. Rothenberg:LOXO Oncology Inc.: Employment. Tsai:Eli Lilly and Company: Employment. Ku:Eli Lilly and Company: Employment. Wang:BioInvent: Consultancy, Research Funding; VelosBio: Research Funding; Loxo Oncology: Research Funding; Guidepoint Global: Consultancy; Kite Pharma: Consultancy, Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Acerta Pharma: Consultancy, Research Funding; MoreHealth: Consultancy, Equity Ownership; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Juno Therapeutics: Research Funding; Dava Oncology: Honoraria; Aviara: Research Funding.
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ARTHUR, P. F., H. HEARNSHAW, R. BARLOW, P. J. WILLIAMSON, P. D. STEPHENSON, and K. DIBLEY. "Evaluation of Hereford and first-cross cows on three pasture systems. III. Milk yield and its influence on calf performance." Journal of Agricultural Science 129, no. 1 (August 1997): 91–98. http://dx.doi.org/10.1017/s0021859697004553.
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Milk yield was determined by the weigh-suckle-weigh method over 2 years (1983 and 1984 calvings), for a total of 305 purebred Hereford (H×H) and first-cross Brahman×Hereford (B×H), Simmental×Hereford (S×H) and Friesian×Hereford (F×H) cows grazing three pasture systems at Grafton, New South Wales, Australia. The age of the cows ranged from 6 to 11 years. The data were used to evaluate different estimates of milk yield and to examine the effects of milk yield on growth of calves up to weaning.Of all the cow traits studied, average lactation milk yield (average of early, mid and late-lactation milk yields) had the highest correlation coefficient with calf 210-day weight (r=0·73) and pre-weaning average daily gain (ADGtotal, r=0·73), and explained >50% of the variation in the calf traits. However, milk yield was also moderately correlated with other cow traits (liveweight and body condition score). Thus, to predict calf performance, milk yield data may not be required if detailed data on other cow traits are available. This is supported by the finding that differences in the coefficients of determination (R2) between models for calf 210-day weight and ADGtotal which included average lactation milk yield and other cow traits (highest R2=69%) and models which included other cow traits but no milk yield estimate (highest R2=57%) were <13%.Cow breed rankings for average lactation milk yield were similar to those for calf 210-day weight and ADGtotal. On high quality pasture, S×H and F×H cows produced the most milk (S×H, 7·5 kg/day; F×H, 8·3 kg/day; B×H, 5·7 kg/day; H×H, 5·5 kg/day) and weaned the heaviest calves (S×H, 255 kg; F×H, 252 kg; B×H, 215 kg; H×H, 217 kg), while on low quality pasture, B×H and F×H cows produced the most milk (B×H, 4·2 kg/day; F×H, 3·7 kg/day; S×H, 2·9 kg/day; H×H, 2·7 kg/day) but B×H cows weaned the heaviest calves (B×H, 180 kg; F×H, 168 kg; S×H, 159 kg; H×H, 124 kg).
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Nourbakhsh, Ali, Shashikant Patil, Prasad Vannemreddy, Alan Ogden, Debi Mukherjee, and Anil Nanda. "The use of bioabsorbable screws to fix Type II odontoid fractures: a biomechanical study." Journal of Neurosurgery: Spine 15, no. 4 (October 2011): 361–66. http://dx.doi.org/10.3171/2011.4.spine09656.
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Object Anterior screw fixation of the Type II odontoid fracture stabilizes the odontoid without restricting the motion of the cervical spine. The metal screw may limit bone remodeling because of stress shielding (if not placed properly) and limit imaging of the fracture. The use of bioabsorbable screws can overcome such shortcomings of the metal screws. The purpose of this study was to compare the strength of a 5-mm bioabsorbable screw with single 4-mm metal and double 3.5-mm lag screw fixation for Type II fractures of the odontoid process. Methods Three different modalities of anterior screw fixation were used in 19 C-2 vertebrae. These fixation methods consisted of a single 5-mm cannulated bioabsorbable lag screw (Group A), a single 4-mm cannulated titanium lag screw (Group B), and two 3.5-mm cannulated titanium lag screws (Group C). Anteroposterior (AP) stiffness and rotational stiffness were evaluated in all constructs. Results There was no statistical difference among the ages of the cadavers in each group (p = 0.52). The AP bending stiffness in Groups A, B, and C was 117 ± 86, 66 ± 43, and 305 ± 130 Nm/mm, respectively. The AP bending stiffness in Group C was significantly higher than that in Groups A and B (p = 0.01 and p = 0.001, respectively). The difference in AP bending stiffness values of bioabsorbable and 4-mm metal screws was not statistically significant (p = 0.23). The rotational stiffness of the double 3.5-mm metal screws was significantly greater than that of the 5-mm bioabsorbable and the 4-mm titanium screws. Conclusions Double screw fixation with 3.5-mm screws provides the stiffest construct in Type II odontoid fractures. Bioabsorbable lag screws (5 mm) have the same AP bending and rotational stiffness as the single titanium lag screw (4 mm) in odontoid fractures.
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Génova, R., J. E. Beckman, and J. Rodríguez Álamo. "Kinematical Structure of the Local Interstellar Medium." International Astronomical Union Colloquium 166 (1997): 195–98. http://dx.doi.org/10.1017/s0252921100070974.
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AbstractObservations of interstellar Na I in the spectra of 93 stars within 315 pc from the Sun show that it lies in a tunnel of gas moving away from Scorpio-Centaurus and is surrounded by gas moving toward the Galactic center.Gas approaches the Sun from Scorpio-Centaurus expanding from (r, l, b)=(160 pc, 313°7, +28°2) with LSR velocity 15.3 km s−1. The radius of this shell is 153 pc.We identify these clouds:D: velocity vector (υd, ld, bd)=(+7.2 km s−1, 305°1, −13°5), above and below the Galactic plane (GP) in the range of Galactic longitudes 357°–55°.C: velocity vector (υc, lc, bc)=(+11.5 km s−1, 349°0, −35°2), above and below the GP in the range 30°≤l≤110°.M: velocity vector (υm, lm, bm)=(+21.9 km s−1, 34°2, +1°5), above and below the GP in the range 100°≤l≤130°.P: velocity vector (υp, lp, bp)=(+13.8 km s−1, 244°9, +5°4), above and below the GP from l~120° to the limit of our data at l~210°.E: velocity vector (υe, le, be)=(+16.8 km s−1, 208°4, +6°2) in the range 160°≤l≤185° and −10°≤b≤–35°.A: velocity vector (υa, la, ba)=(+12.9 km s−1, 73°6, −5°6) towards the Galactic anti-center, below the GP.I: velocity vector (υi, li, bi)=(+37.7 km s−1, 132°8, −64°3) towards the Galactic anti-center, above the GP.
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Jasiurkowska-Delaporte, Małgorzata, Tomasz Rozwadowski, and Ewa Juszyńska-Gałązka. "Kinetics of Non-Isothermal and Isothermal Crystallization in a Liquid Crystal with Highly Ordered Smectic Phase as Reflected by Differential Scanning Calorimetry, Polarized Optical Microscopy and Broadband Dielectric Spectroscopy." Crystals 9, no. 4 (April 12, 2019): 205. http://dx.doi.org/10.3390/cryst9040205.
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The kinetics of the non-isothermal and isothermal crystallization of the crystalline smectic B phase (soft crystal B, SmBcr) in 4-n-butyloxybenzylidene-4′-n′-octylaniline (BBOA) was studied by a combination of differential scanning calorimetry (DSC), broadband dielectric spectroscopy (BDS) and polarized optical microscopy (POM). On cooling, part of the SmBcr phase undergoes conversion to a crystalline phase and the remainder forms a glassy state; after the glass softens, crystallization is completed during subsequent heating. By analyzing the area of the crystal growing in the texture of SmBcr as a function of time, the evolution of degree of crystallinity, D(t), was estimated. It was demonstrated that upon heating, D(t) follows the same Avrami curve as the crystallization during cooling. Non-isothermal crystallization observed during slow cooling rates (3K/min ≤ ϕ ≤ 5K/min) is a thermodynamically-controlled process with the energy barrier Ea ≈ 175 kJ/mol; however, the crystallization occurring during fast cooling (5 K/min > ϕ ≥ 30K/min) is driven by a diffusion mechanism, and is characterized by Ea ≈ 305 kJ/mol. The isothermal crystallization taking place in the temperature range 274 K and 281 K is determined by nucleus formation.
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Kito, Seiji, and Yuki Ohta. "In vitro fertilization in inbred BALB/c mice II: effects of lactate, osmolarity and calcium on in vitro capacitation." Zygote 16, no. 3 (August 2008): 259–70. http://dx.doi.org/10.1017/s0967199408004619.
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SummaryTo elucidate requirements for in vitro sperm capacitation in inbred BALB/c mice, osmolarity, calcium and lactate were optimized using modified simplex optimization medium (mKSOM). Modified human tubal fluid (mHTF), a capacitation-supporting medium, was used as a control. In the first series of experiments, the effects of calcium and osmolarity were studied in the presence of lactate. Although preincubation with ≥5 mM CaCl2 improved fertilization after insemination significantly, it was still significantly lower than incubation with mHTF. To obtain fertilization at the equivalent levels to that of mHTF, isotonic osmolarity (305 mOsmol) was required. Trehalose, an osmotic reagent, could substitute for NaCl partially. In the second series of experiments, the effects of lactate were examined using a concentration of 5 mM calcium and isotonic osmolarity. Preincubation with ≤2.5 mM lactate increased fertilization significantly (>75%), as well as the percentages of B (capacitated) pattern sperm (≥40%) in chlortetracycline (CTC) staining, as compared with incubation in mHTF (46% and 28%, respectively; p < 0.05). In the third series of experiments, the effects of osmolarity and calcium in the absence of lactate were examined. An increase in osmolarity during sperm preincubation increased both fertilization and B-pattern sperm significantly in a dose-dependent manner. Trehalose, sucrose and choline chloride could substitute for NaCl. An increase in CaCl2 concentration during preincubation had no effect on fertilization, but this increase reduced the percentages of B-pattern sperm. In vitro capacitation of inbred BALB/c mice is sensitive to lactate and osmolarity, but that sensitivity for calcium varies depending on the presence or absence of lactate.
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Zaytsev, E. M., M. V. Britsina, M. N. Ozeretskovskaya, N. U. Mertsalova, and I. G. Bazhanova. "Effect of antibodies to agglutinogens 1 and 2, filamentous hemagglutinin and pertussis toxin on formation of Bordetella pertussis biofilms on abiotic substrate." Journal of microbiology, epidemiology and immunobiology 98, no. 3 (July 3, 2021): 283–89. http://dx.doi.org/10.36233/0372-9311-110.
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Aim. Study of the effect of antibodies to agglutinogens 1 and 2, filamentous hemagglutinin (FHA) and pertussis toxin (PT) on the formation of biofilms by Bordetella pertussis strains on the abiotic substrate.Materials and methods. Vaccine-derived and freshly isolated strains of B. pertussis were used. Cultures of strains grown on a dense nutrient medium were used as an inoculum for obtaining biofilms. The intensity of biofilm formation in round-bottomed polystyrene 96-well plates in the presence of antisera to agglutinogens 1 and 2, antiserum to FHA, and monoclonal antibodies (MСА) to the S1, S2, and S3 subunits of PT was evaluated by staining with 0.1% gentian-violet solution.Results. Most of the studied strains were sensitive to antibodies, which was manifested in complete suppression of biofilm formation. All strains were sensitive to antiserum to agglutinogen 1, antiserum to FHA, and MCA to the S2 subunit of KT. Three out of 4 studied strains with this agglutinogen in their composition were sensitive to antiserum to agglutinogen 2: No. 475 (serotype 1.2.3), No. 317 (serotype 1.2.3) and No. 178 (serotype 1.2.0). Relative resistance to antiserum was detected only in serotype 1.2.0 strain No. 305, but with minimal dilution, the intensity of biofilm formation was 1.8 times lower than in the control group. Strains No. 703 (serotype 1.0.3) and No. 287 (serotype 1.0.3) that did not have agglutinogen 2 were resistant to antiserum. Four and 5 out of the 6 strains used were sensitive to the S1 and S3 subunits of PT, respectively. Strain No. 305 was resistant to MCA to the S1 and S3 subunits, and strain No. 287 to MCA to the S1 subunit. At the same time, the intensity of biofilm formation was 2 and 1.8 times lower than in the control at the minimum MCA dilution.Conclusion. These data indicate that the growth of biofilms of B. pertussis strains is suppressed by antibodies both to the surface structures of the microbial cell (agglutinogens 1 and 2, FHA) and to the S1, S2 and S3 subunits of PT.
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Wang, Jian-Rong, Yang-Yuan Li, Dan-Ni Liu, Jing-Shan Liu, Peng Li, Li-Zhi Chen, and Shu-De Xu. "Codon Optimization Significantly Improves the Expression Level ofα-Amylase Gene fromBacillus licheniformisinPichia pastoris." BioMed Research International 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/248680.
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α-Amylase as an important industrial enzyme has been widely used in starch processing, detergent, and paper industries. To improve expression efficiency of recombinantα-amylase fromBacillus licheniformis(B. licheniformis), theα-amylase gene fromB. licheniformiswas optimized according to the codon usage ofPichia pastoris(P. pastoris) and expressed inP. pastoris. Totally, the codons encoding 305 amino acids were optimized in which a total of 328 nucleotides were changed and the G+C content was increased from 47.6 to 49.2%. The recombinants were cultured in 96-deep-well microplates and screened by a new plate assay method. Compared with the wild-type gene, the optimized gene is expressed at a significantly higher level inP. pastorisafter methanol induction for 168 h in 5- and 50-L bioreactor with the maximum activity of 8100 and 11000 U/mL, which was 2.31- and 2.62-fold higher than that by wild-type gene. The improved expression level makes the enzyme a good candidate forα-amylase production in industrial use.
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Szymanska, Iwona, Anna Zbikowska, and Sylwia Onacik-Gür. "New Insight into Food-Grade Emulsions: Candelilla Wax-Based Oleogels as an Internal Phase of Novel Vegan Creams." Foods 13, no. 5 (February 28, 2024): 729. http://dx.doi.org/10.3390/foods13050729.
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Cream-type emulsions containing candelilla wax-based oleogels (EC) were analyzed for their physicochemical properties compared to palm oil-based creams (EP). The microstructure, rheological behavior, stability, and color of the creams were determined by means of non-invasive and invasive techniques. All the formulations exhibited similar color parameters in CIEL*a*b* space, unimodal-like size distribution of lipid particles, and shear-thinning properties. Oleogel-based formulations were characterized by higher viscosity (consistency index: 172–305 mPa·s, macroscopic viscosity index: 2.19–3.08 × 10−5 nm−2) and elasticity (elasticity index: 1.09–1.45 × 10−3 nm−2), as well as greater resistance to centrifugal force compared to EP. Creams with 3, 4, or 5% wax (EC3–5) showed the lowest polydispersity indexes (PDI: 0.80–0.85) 24 h after production and the lowest instability indexes after environmental temperature changes (heating at 90 °C, or freeze–thaw cycle). EC5 had particularly high microstructural stability. In turn, candelilla wax content ≥ 6% w/w accelerated the destabilization processes of the cream-type emulsions due to disintegration of the interfacial layer by larger lipid crystals. It was found that candelilla wax-based lipids had great potential for use as palm oil substitutes in the development of novel vegan cream analogues.
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Zhang, Feng JIN, JUN ZHI Shu, YI CHUN Xie, QI LI, Hong XI Jin, Wei GU, Jian FANG Jiang, and Quan CHANG Ling. "Prognosis of unresectable hepatocellular carcinoma: Comparison of seven staging systems (TNM, Okuda, BCLC, CLIP, CUPI, JIS, CIS) in a Chinese cohort." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 305. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.305.
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305 Background: Many liver staging systems that include the tumor stage and the extent of liver function have been developed. However, Prognosis assessment for hepatocellular carcinoma (HCC) remains controversial. In this study, the performances of 7 staging systems were compared in a cohort of patients with HCC who underwent non-surgical treatment. Methods: A total of 196 consecutive patients with HCC who underwent non-surgical treatment seen between January 1, 2004, and December 31, 2007, were included. Performances of TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and China integrated score (CIS) have been compared and ranked using concordance index (c-index). Predictors of survival were identified using univariate and multivariate Cox model analyses. Results: The median survival time for the cohort was 7.6 months (95% CI 5.6-9.7). The independent predictors of survival were performance status (P <.001), serum sodium (P <.001), alkaline phosphatase (P <.001), tumor diameter greater than 5 cm (P =.001), portal vein invasion (P <.001), lymph node metastasis (P =.025), distant metastasis (P =.004). CUPI staging system had the best independent predictive power for survival when compared with the other six prognostic systems. Performance status and serum sodium improved the discriminatory ability of CUPI. Conclusions: In our selected patient population whose main etiology is hepatitis B, CUPI was the most suitable staging systems in predicting survival in patients with unresectable HCC. BCLC was the second top-ranking staging system. CLIP, JIS, CIS, and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data. Clinical trial information: 1103-10.
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Van Wambeke, F., M. Tedetti, S. Duhamel, and R. Sempéré. "Diel variability of heterotrophic bacterial production and UV doses in the South East Pacific." Biogeosciences Discussions 5, no. 1 (January 31, 2008): 435–62. http://dx.doi.org/10.5194/bgd-5-435-2008.
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Abstract. Diel variability of heterotrophic bacterial production (BP) was investigated in the South East Pacific from October to December 2004 during the BIOSOPE cruise. Three sites differing by their trophic status were studied: Marquesas Islands (MAR; 08° S, 141° W), the centre of the South Pacific Gyre (SPG) (GYR; 26° S, 114° W) and the eastern part of the SPG (EGY; 32° S, 91° W). At the three sites, diel variability of BP ranged from 17 to 40% and from 13 to 22% for volumetric surface (5 m) and integrated (to Ze and Zm) data, respectively. The main feature we observed was at 5 m, an abrupt increase (×2 to ×4) in leucine activity during the afternoon-sunset period (12:00–18:00 at the site MAR and 15:00–21:00 at the site GYR) and lowest activities recorded between 10:00 and 14:00. To assess the potential influence of solar ultraviolet radiation (UVR: 280–400 nm) on this BP diel variability, we determined, from in situ optical measurements, the mean tri-hourly ultraviolet B (UVB, 305 nm) and ultraviolet A (UVA, 380 nm) doses (irradiances integrated over time) within the mixed layer (Hm(UVB) and Hm(UVA), respectively). The wavelengths 305 nm and 380 nm were used as biologically effective wavelengths for the induction of DNA damages (cyclobutane pyrimidine dimers: CPDs) and photoenzymatic repairs (PERs), respectively. In the SPG, daily Hm(UVB) and Hm(UVA) were 0.6 and 14 kJ m−2 nm−1, respectively. The latter were probably the highest daily doses ever measured in the marine environment. The Hm(UVB)/Hm(UVA) ratio (Q) increased by 58, 117 and 46% from 06:00–09:00 to 12:00–15:00, and decreased by 36, 26 and 16% from 12:00–15:00 to 15:00–18:00 at the sites MAR, GYR and EGY, respectively. The relationship between Q and BP suggested a significant influence of UVR on the diel variability of BP (BP decreased when Q increased) at the site GYR from the surface waters to Zm, likely in relation with its hyper-oligotrophic status. Therefore, possible alternance of CPD and PER periods attributed to Q ratio, as well as a strong lags between process of autotrophic production with their associated dissolved organic carbon (DOC) release and heterotrophic utilization of organic matter could explain such diel variations.
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Chapagai, M. K., Wan Rosli W.I., T. Karilla, and S. Pinkaew. "Variety difference of physicochemical and cooking properties of selected brown rice from Thailand and Malaysia." Food Research 4, no. 3 (December 29, 2019): 630–35. http://dx.doi.org/10.26656/fr.2017.4(3).305.
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Rice is a major staple food in Thailand and Malaysia. Although brown rice is a highly healthy substitute, preference is very low due to its texture and cooking quality. However, there are some brown rice varieties such as Sungyod (SY), Chiang (CH), Lepnok (LP) from Thailand and long grain specialty 1(LS1) and long grain specialty 2 (LS2) from Malaysian peninsula are commonly consumed in such areas. This study aimed to investigate the physicochemical and the cooking properties of these brown rice to understand the properties for better utilization. Therefore, Rapid visvo analyser (RVA), soaking characteristics, general cooking properties, textural properties and calorific values were measured and compared in 5 varieties of brown rice. Hydration kinetics indicated that LS1 and LS2 were faster in water absorption to reach plateau compared to the SY, LP, and CH. The cooking time of these brown rice was in the range from 29 to 35 min. The cooked brown rice had length/breadth (L/B) ratio (2.4 – 3.0), water uptake ratio (2.5 – 3.0), elongation ratio (1.1 –1.4) and gruel solid loss (3.2 – 5.2%). The hardness and the cohesiveness measured from texture analyzer were in the range of 6.75 – 15.5 N and 0.13 – 0.16. There was a significant variation in RVA pasting property of whole rice flour (p < 0.05). The variations of different properties of brown rice could be considered for the processing of brown rice and its application.
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CHOUDHARY, DEEKSHA. "Long term effect of STCR-based targeted yield application of fertilizers on productivity, profitability and nutrient uptake by wheat (Triticum aestivum L.) in an acid Alfisol." Annals of Plant and Soil Research 24, no. 3 (August 1, 2022): 373–77. http://dx.doi.org/10.47815/apsr.2022.10178.
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The present investigation was conducted during therabi season of 2017-18 at the research farm of CSK HPKV, Palampur (Himachal Pradesh). The effect of target yield based fertilizer application on productivity, profitability, and nutrient uptake by wheat were evaluated in a randomized block design with eight treatments. The results revealed that the continuous cropping for 10 years along with STCR based fertilizer application in target yield 35 q ha-1 + 5 t FYM ha-1 recorded the highest grain yield (34.9 q ha-1 ) followed by target 35 q ha-1 (31.6 q ha-1 ).The highest protein content (12.6 %) and protein yield (441.4 Kg ha-1 ) of wheat grains were observed with target yield of 35 q ha-1 + 5 t FYM ha-1 . Further, the maximum net profit of Rs.61401 ha-1 with a B: C ratio of 3.29 was obtained under target yield 35 q ha-1 . A significant increase in N, P, and K uptake by wheat grain and straw was observed in STCR based target yield plots as compared to soil test based, general recommended dose, farmers’ practice, and control. The available N, P, and K content in post-harvest soil were reduced in the control over their initial values. The higher values of available N (305 kg ha-1 ), P (70 Kg ha-1 ) and K (290 kg ha-1 ) were recorded with target yield of 35 q ha-1 + 5 t FYM ha-1 .
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CHOUDHARY, DEEKSHA. "Long term effect of STCR-based targeted yield application of fertilizers on productivity, profitability and nutrient uptake by wheat (Triticum aestivum L.) in an acid Alfisol." Annals of Plant and Soil Research 24, no. 3 (August 1, 2022): 373–77. http://dx.doi.org/10.47815/apsr.2021.10178.
Full textAbstract:
The present investigation was conducted during therabi season of 2017-18 at the research farm of CSK HPKV, Palampur (Himachal Pradesh). The effect of target yield based fertilizer application on productivity, profitability, and nutrient uptake by wheat were evaluated in a randomized block design with eight treatments. The results revealed that the continuous cropping for 10 years along with STCR based fertilizer application in target yield 35 q ha-1 + 5 t FYM ha-1 recorded the highest grain yield (34.9 q ha-1) followed by target 35 q ha-1 (31.6 q ha-1).The highest protein content (12.6 %) and protein yield (441.4 Kg ha-1) of wheat grains were observed with target yield of 35 q ha-1 + 5 t FYM ha-1. Further, the maximum net profit of Rs.61401 ha-1 with a B: C ratio of 3.29 was obtained under target yield 35 q ha-1. A significant increase in N, P, and K uptake by wheat grain and straw was observed in STCR based target yield plots as compared to soil test based, general recommended dose, farmers’ practice, and control. The available N, P, and K content in post-harvest soil were reduced in the control over their initial values. The higher values of available N (305 kg ha-1), P (70 Kg ha-1) and K (290 kg ha-1) were recorded with target yield of 35 q ha-1 + 5 t FYM ha-1.
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Bokemeyer, C., I. Bondarenko, A. Makhson, J. T. Hartmann, J. Aparicio, M. Zampino, S. Donea, H. Ludwig, A. Zubel, and P. Koralewski. "Cetuximab plus 5-FU/FA/oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colorectal cancer (mCRC): OPUS, a randomized phase II study." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 4035. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4035.
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4035 Background: FOLFOX-4 is a standard first-line treatment for patients (pts) with mCRC. The IgG1 monoclonal antibody cetuximab has proven activity in combination with cytotoxic chemotherapy. Excellent response rates (RRs) have been reported with first-line cetuximab and FOLFOX-4. This randomized, controlled study was conducted to compare RRs of FOLFOX-4 + cetuximab vs FOLFOX-4. Methods: Pts with previously untreated epidermal growth factor receptor (EGFR)-expressing mCRC not resectable with curative intent were eligible. They were randomized 1:1, stratified by ECOG performance status (PS) (0–1 vs 2), to either Group A (cetuximab 400 mg/m2 initial dose then 250 mg/m2/week plus FOLFOX-4 every 2 weeks [oxaliplatin 85 mg/m2 day (d) 1; FA 200 mg/m2 d1, 2; 5-FU 400 mg/m2 bolus + 600 mg/m2 infusion over 22 h, d1, 2]) or Group B (FOLFOX-4 only). The primary objective was the best confirmed RR assessed by independent review; secondary objectives were progression- free survival (PFS), overall survival (OS), the R0 resection rate after metastatic surgery of curative intent and safety. Results: Between July 2005 and March 2006, 337 pts were randomized and treated in more than 70 centers in Europe. 181 (53.7%) pts were male; the median age of all pts was 61.0 years [24–82]; 305 (90.5%) pts had an ECOG PS of 0 or 1, and 32 (9.5%) of 2. The best overall confirmed RR was 45.6% in A and 35.7% in B. For pts with ECOG PS 0–1, RR was 49.0% in A and 36.8% in B (Odds Ratio 1.648, 95%CI [1.043- 2.604]). PFS and OS results are not yet available. The most common grade 3/4 adverse events were neutropenia (27.6% in A; 31.5% in B), diarrhea (7.1 and 6.0%), leucopenia (7.1 and 5.4%) and rash (9.4%, in A only). Conclusions: The addition of cetuximab increased the RR of FOLFOX-4 in first-line treatment of mCRC. Grade 3/4 adverse events, with the exception of skin rash, were not significantly more frequent in the cetuximab arm. No significant financial relationships to disclose.
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Reis, A. M., M. Jankowski, S. Mukaddam-Daher, J. Tremblay, T.-V. Dam, and J. Gutkowska. "Regulation of the natriuretic peptide system in rat uterus during the estrous cycle." Journal of Endocrinology 153, no. 3 (June 1997): 345–55. http://dx.doi.org/10.1677/joe.0.1530345.
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Abstract Uterine natriuretic peptides may be involved in the alterations that occur in the uterus during the estrous cycle through its role in hydromineral balance. The following studies were performed to determine whether uterine natriuretic peptides and receptors follow a cyclic pattern during the estrous cycle. The results obtained show that atrial natriuretic peptide (ANP) content in rat uterine tissue was low in proestrus (8·5 ± 2·6 pg/g) and significantly increased (P<0·001) in estrus (71·5 ± 16·6 pg/g), metestrus (82·6 ± 19·7 pg/g) and diestrus (91·0 ± 19·4 pg/g), whereas plasma ANP was not altered during the cycle. Similarly, measurement of uterine ANP mRNA by reverse transcribed polymerase chain reaction (RT-PCR) indicated lowest levels of ANP mRNA at proestrus. Measurement of C-type natriuretic peptide (CNP) by a specific and sensitive radioimmunoassay revealed that uterine CNP also varies with the estrous cycle. Uterine CNP was low in diestrus (143·2 ± 22·4 pg/mg protein) as compared with proestrus, estrus and metestrus (305·3 ± 51·5, 267·5 ± 44·9, 291 ± 41·2 pg/mg protein respectively, P<0·05). Autoradiography performed on uterine tissue slices localized natriuretic peptide receptors to myometrial smooth muscle layers and to endometrial uterine glands. High binding of 125I-ANP was observed in proestrus and estrus with 60–75% decreases during metestrus and diestrus. Binding of 125I-tyr0CNP to uterine slices was also high during proestrus, but declined by 35% at estrus, metestrus and diestrus. The alterations in the receptors were also observed at the level of synthesis. RT-PCR detection of guanylyl cyclase A (GC-A) receptor mRNA and guanylyl cyclase B (GC-B) mRNA showed high signals at proestrus but 4- and 2-fold reductions respectively at metestrus and diestrus. In conclusion, variations in uterine ANP and CNP and their receptors during the rat estrous cycle imply the involvement of the natriuretic peptides in uterine hydromineral balance and myometrial motor activity. Journal of Endocrinology (1997) 153, 345–355
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Rodriguez, Nicolette J., C. Sloane Furniss, Matthew B. Yurgelun, Chinedu Ukaegbu, Pamela E. Constantinou, Ileana Fortes, Alyson Caruso, et al. "Abstract A029: A randomized study of two Strategies of remote Genetic Education, Risk Assessment, and Testing (GENERATE) for family members of patients with pancreatic cancer." Cancer Research 82, no. 22_Supplement (November 15, 2022): A029. http://dx.doi.org/10.1158/1538-7445.panca22-a029.
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Abstract Background: Uptake of genetic testing for cancer susceptibility in family members of cancer patients is suboptimal. The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated two strategies of remote genetic education and testing in relatives of pancreatic ductal adenocarcinoma (PDAC) patients. Methods: Eligible participants had: a first-degree relative with PDAC or had a known pathogenic germline variant (PGV) in one of thirteen PDAC predisposition genes (APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53) and a first- or second-degree relative with PDAC. Participants were cluster-randomized by family into one of two arms. Arm 1 included an interactive telemedicine session with a genetic counselor, followed by genetic testing at a commercial laboratory. Arm 2 involved remote online genetic education and testing at the commercial laboratory without the interactive session. The primary outcome was uptake of genetic testing across study arms, which was compared by permutation tests and mixed-effects logistic regression models. Results: Between 5/8/2019 and 6/1/2021, 424 families were randomized, including 601 participants (n=296 Arm 1; n=305 Arm 2). The uptake of genetic testing was 87% (257/296) in Arm 1 and 93% (284/305) in Arm 2 (p=0.014). Participants in Arm 1 were significantly less likely to obtain genetic testing compared to Arm 2 (Adjusted ratio [Arm1/Arm2] 0.90, 95% confidence interval 0.78-0.98). BRCA2, ATM, CDKN2A and PALB2 were the most common PDAC susceptibility genes in which PGVs were identified. Conclusions: Remote methods of genetic education and testing are successful alternatives to traditional germline susceptibility testing. Citation Format: Nicolette J. Rodriguez, C. Sloane Furniss, Matthew B. Yurgelun, Chinedu Ukaegbu, Pamela E. Constantinou, Ileana Fortes, Alyson Caruso, Alison N. Schwartz, Jill E. Stopfer, Meghan Underhill-Blazey, Barbara Kenner, Scott H. Nelson, Sydney Okumura, Alicia Y. Zhou, Tara B. Coffin, Hajime Uno, Miki Horiguchi, Allyson J. Ocean, Florencia McAllister, Andrew M. Lowy, Scott M. Lippman, Alison P. Klein, Lisa Madlensky, Gloria M. Petersen, Judy E. Garber, Michael G. Goggins, Anirban Maitra, Sapna Syngal. A randomized study of two Strategies of remote Genetic Education, Risk Assessment, and Testing (GENERATE) for family members of patients with pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A029.
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Ramaswamy, Anant, Prabhat Ghanshyam Bhargava, Biswajit Dubashi, Akhil Kapoor, Sujay Srinivas, Omshree Shetty, Rajiv Kumar Kaushal, et al. "A two-arm randomized open-label prospective design superiority phase III clinical trial to compare the efficacy of docetaxel-oxaliplatin-capecitabine/5 fluorouracil (DOC/F) followed by docetaxel versus CAPOX/mFOLFOX-7 in advanced gastric cancers (DOC-GC study)." Journal of Clinical Oncology 42, no. 3_suppl (January 20, 2024): LBA248. http://dx.doi.org/10.1200/jco.2024.42.3_suppl.lba248.
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LBA248 Background: The choice of optimal chemotherapy in advanced (unresectable/metastatic) gastroesophageal junction and gastric (GEJ/G) adenocarcinomas remains undecided with regard to the addition of docetaxel to a FOLFOX/CAPOX backbone in improving outcomes with equipoise with regard to the optimal duration of chemotherapy as well. Methods: The DOC GC study is a multicentric open-label, randomized controlled phase III trial, in adults ≥18 years with advanced GEJ/G adenocarcinoma and adequate end-organ function. Patients were randomized 1:1 to one of two arms: Arm A - modified CAPOX (3 weekly) or modified FOLFOX-7 (2 weekly) for a maximum of 6 months and then observation OR Arm B: modified FLOT (5-FU/leucovorin /Oxaliplatin/Docetaxel) or DOX (docetaxel/oxaliplatin/capecitabine) every 2 weeks for a maximum of four months followed by Docetaxel (60mg/m2) every 3 weeks till disease progression, unacceptable toxicity, or patient's decision to withdraw. The primary endpoint of the study is Overall survival (OS), as calculated by Kaplan-Meier method, while key secondary endpoints include Progression-free survival, and adverse event rates. Results: Of the 324 patients randomized between July 2020 and November 2022, 305 patients were evaluable for analysis (Arm A: 156; Arm B: 149). With a median follow-up time of 19.2 months (95% CI: 16.5 – 21.9) for the entire cohort, the median OS was 10.1 months (95%: 9.2-10.9) in Arm A and 8.9 months (95% CI: 7.3-10.5) in arm B and this difference was not statistically significant [p=0.70]. There were no statistical differences in median PFS between the two arms [Arm A: 7.1 months (95% CI: 6.1-8.1); Arm B: 6.2 months (95% CI: 5.7 – 6.8); p=0.39]. An increased proportion of grade 3/4 neutropenia (21% vs. 5.1%; p<0.001) was seen in patients in Arm B, with other treatment related side effects being comparable between the two arms. A greater proportion of patients in Arm A tended to receive second line therapy compared to Arm B (38% vs. 26%; p=0.07). Conclusions: The addition of docetaxel to a doublet regimen comprising 5-fluorouracil/capecitabine and oxaliplatin did not improve overall survival in patients with advanced GEJ/G cancers. Continuing chemotherapy beyond six months also does not appear to improve survival in this group of cancers. Clinical trial information: CTRI/2020/03/023944 .
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Diah, Chiquita Prahasanti, Retno Puji Rahayu, and Vani Rachmad Wijayanto. "Characterization of ultraviolet B light emitting diodes (UVB LED) irradiation device for Wistar rats as an experimental animal model." Bali Medical Journal 12, no. 3 (August 28, 2023): 2516–20. http://dx.doi.org/10.15562/bmj.v12i3.4639.
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Link of Video Abstract: https://youtu.be/-l5AY96hUI8 Background: Light emitting diodes (LED) lamps are used widely in daily because of their many benefits, including their low cost, extended lifespan, low energy consumption, and low environmental impact. The use of LEDs, especially ultraviolet B LED (UVB LEDs) is quite extensive and has been developed for the treatment of skin diseases, irradiating pet reptiles, and conducting research on experimental animals. The use of light for therapy must be done carefully so that unwanted side effects do not occur because light also harms tissue. The purpose of this characterization is to determine the stability of temperature and irradiation of the device we make and to determine the duration of light exposure based on the characterization. Methods: The irradiation device use UVB LEDs with a wavelength of 305-310 nm. The characterization carried out included temperature stability and irradiation stability, with observations every 30 minutes for 10 hours and no replication. Statistical analysis using the Kolmogorov-Smirnov (Asymptotic Approximation) testing technique. The test criteria state that if the probability value > level of significance (alpha (α) = 5%). Results: The characterization results from 10 hours of observation with sampling data taken every 30 minutes showed stable LED temperature and room temperature while unstable cage temperature and irradiance. Conclusion: This device can be considered to use in Wistar rat’ experimental studies using UVB and perhaps developed further. The duration of exposure can be adjusted according to the distance of the object and the dose required.
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COULON, J. B., P. D’HOUR, M. PETIT, E. ALBARET, and M. JAWOREK. "Niveau et répartition des apports de concentré hivernaux chez la vache laitière. Résultats sur primipares." INRAE Productions Animales 3, no. 5 (December 10, 1990): 319–28. http://dx.doi.org/10.20870/productions-animales.1990.3.5.4390.
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Cent dix neuf vaches laitières en première lactation ayant vêlé en moyenne le 6 décembre ont été utilisées au cours d’un essai conduit 3 années consécutives. Au cours de l’hiver, tous les animaux recevaient une ration de base composée d’ensilage d’herbe (à volonté) et de foin (4 kg/j). Chaque année 5 lots ont été constitues : 3 niveaux d’apport de concentré au cours de la période hivernale (haut H, moyen M et bas B), et pour chacun des 2 niveaux inférieurs, 2 modes de répartition du concentré (classique (C) ou uniforme (U)), ont été comparés. Au pâturage toutes les vaches ont été conduites ensemble. Au cours de la période expérimentale (semaine 4 à 18 de lactation), les vaches du lot H et des lots M et B ont ingéré respectivement 6,3, 4,8 et 3,5 kg MS/j de concentré et 9,2, 9,5 et 9,8 kg MS/j de fourrages. Les vaches du lot H ont produit en moyenne plus de lait (1,2 et 3,1 kg/j par rapport a celles des lots MC et BC), lait d’une teneur plus élevée en protéines (+ 0,6 et + 1,7 g/kg). Au cours de l’hiver, les variations de poids vifs ont été respectivement de + 1, - 26 et - 39 kg dans les lots H, M et B. A l’échelle de la lactation (305 j) les écarts de production atteignent 169 et 577 kg pour des écarts d’apport de concentré de 202 et 420 kg MS. Il n’y a pas eu d’effet significatif du mode de répartition du concentré sur les performances des animaux. Ces résultats sont discutes en fonction du niveau de production des animaux, et de leur conséquence sur leur carrière ultérieure.
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Savage, Kerry J., Mukesh Chhanabhai, Nicholas Voss, Shenkier Tamara, Randy D. Gascoyne, and Joseph M. Connors. "Survival of Limited Stage Peripheral T-Cell Lymphoma Is Similar To Diffuse Large B-Cell Lymphoma." Blood 106, no. 11 (November 16, 2005): 2817. http://dx.doi.org/10.1182/blood.v106.11.2817.2817.
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Abstract Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of diseases with an overall poor prognosis. Little information is available regarding the outcome of PTCL patients who present with limited stage disease. We sought to determine the outcome of PTCL patients presenting with limited disease in comparison with a cohort of patients with limited stage diffuse large B-cell lymphoma (DLBCL). Methods: In a retrospective analysis we identified all patients with limited stage (non-bulky (<10cm) stage I/II disease no symptoms) PTCL diagnosed at the British Columbia Cancer Agency (BCCA) between 1983 and 2004. Patients were excluded if they had cutaneous anaplastic large cell lymphoma (CutALCL) (n=13), NK/T-cell lymphoma nasal type (n=9) or primary CNS/ocular involvement (n=6). Results: Thirty-seven patients with PTCL were identified according to the World Health Organization Classification: ALK-neg ALCL 8 (22%); PTCL-unspecified (PTCLUS) 28 (78%); enteropathy associated TCL (EATL) 1 (3 %). The majority received CHOP-type chemotherapy (n=31, 86%), most with brief chemotherapy followed by involved-field radiation (n=19, 61%). The 5 y OS and PFS was similar between PTCLUS and ALK-neg ALCL. There was no difference in survival between extranodal and nodal cases. The outcome of PTCL patients (including ALK-neg ALCL and PTCLUS) was compared to a cohort of limited stage DLBCL patients (excluding CNS/ocular lymphoma) (n=305) diagnosed over the same time period and treated similarly. There was no difference in 5 y OS or PFS (Figure 1,2). Interestingly, there were no late relapses observed in PTCLUS, in marked contrast to DLBCL. Conclusions: Limited stage PTCL is rare, however outcomes appear to be comparable to early stage DLBCL, supporting that they should be treated in a similar manner. Unlike limited stage DLBCL where late relapses occur, a plateau in the progression-free survival curve is observed, highlighting a distinct natural history for limited stage PTCL. Overall Survival Limited Stage PTCL vs DLBCL p=.18 Overall Survival Limited Stage PTCL vs DLBCL p=.18 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07
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Rawofi, Lida, Melissa Edwards, S. Krithika, Phuong Le, David Cha, Zhaohui Yang, Yanyun Ma, et al. "Genome-wide association study of pigmentary traits (skin and iris color) in individuals of East Asian ancestry." PeerJ 5 (November 2, 2017): e3951. http://dx.doi.org/10.7717/peerj.3951.
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Background Currently, there is limited knowledge about the genetics underlying pigmentary traits in East Asian populations. Here, we report the results of the first genome-wide association study of pigmentary traits (skin and iris color) in individuals of East Asian ancestry. Methods We obtained quantitative skin pigmentation measures (M-index) in the inner upper arm of the participants using a portable reflectometer (N = 305). Quantitative measures of iris color (expressed as L*, a* and b* CIELab coordinates) were extracted from high-resolution iris pictures (N = 342). We also measured the color differences between the pupillary and ciliary regions of the iris (e.g., iris heterochromia). DNA samples were genotyped with Illumina’s Infinium Multi-Ethnic Global Array (MEGA) and imputed using the 1000 Genomes Phase 3 samples as reference haplotypes. Results For skin pigmentation, we did not observe any genome-wide significant signal. We followed-up in three independent Chinese samples the lead SNPs of five regions showing multiple common markers (minor allele frequency ≥ 5%) with good imputation scores and suggestive evidence of association (p-values < 10−5). One of these markers, rs2373391, which is located in an intron of the ZNF804B gene on chromosome 7, was replicated in one of the Chinese samples (p = 0.003). For iris color, we observed genome-wide signals in the OCA2 region on chromosome 15. This signal is driven by the non-synonymous rs1800414 variant, which explains 11.9%, 10.4% and 6% of the variation observed in the b*, a* and L* coordinates in our sample, respectively. However, the OCA2 region was not associated with iris heterochromia. Discussion Additional genome-wide association studies in East Asian samples will be necessary to further disentangle the genetic architecture of pigmentary traits in East Asian populations.
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Waanders, Esmee, Frank N. van Leeuwen, Eugene Verwiel, Simon V. van Reijmersdal, Marloes R. Levers, Joost C. van Galen, Edwin Sonneveld, Peter M. Hoogerbrugge, Ad Geurts van Kessel, and Roland P. Kuiper. "Pediatric Precursor-B ALL with BTG1 Deletions Show a Distinct Genomic Profile." Blood 114, no. 22 (November 20, 2009): 3244. http://dx.doi.org/10.1182/blood.v114.22.3244.3244.
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Abstract Abstract 3244 Poster Board III-181 Recent genome-wide profiling studies have revealed that childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent microdeletions, including the cell cycle regulator CDKN2A, the B-cell differentiation genes PAX5, EBF1 and IKZF1 (Ikaros) and the anti-proliferative gene B-cell translocation gene 1 (BTG1). In a previous study, we have shown that BTG1 is an important determinant of glucocorticoid sensitivity (Van Galen et al. Blood/ ASH Annual Meeting Abstracts, 2008). In the present study we have characterized these cases in more detail and elucidated the frequency of recurrent lesions in BTG1 deletion cases. Using locus-specific MLPA screening of an unselected cohort of 305 precursor B-ALL cases, we identified 26 microdeletions (8.5%). All deletions encompassed BTG1 only. We were able to genomically profile 22 diagnosis samples using Affimetrix SNP6.0 arrays. Of these, 12 did not develop a relapse during a minimal of 4,5 years of follow up. The mean number of CNVs was 29.6 of which 10.3 gains and 22.5 losses (median size 512 kb and 115 kb respectively). BTG1 deletions were generally focal, varying in size from 104 kb to 1,4 Mb. In all but one patient the breakpoints at the 5' end of the deletion tightly clustered and subsequent fine-mapping using qPCR revealed that this breakpoint cluster was located within intron 1 of the BTG1 gene. At the 3'end of the deletion, four breakpoint clusters could be identified. Analysis of the copy number variation (CNV) profiles showed that patients with a BTG1 deletion more often harbored a deletion in IKZF1 compared to an unselected cohort of pre-B ALL cases (27% vs 7%, chi-square p=0.042). In contrast, recurrent CNVs like PAX5, EBF1 and CDKN2A/B occur in similar frequencies (23%, 9% and 32% vs 17%, 0% and 23% respectively). In addition, the BTG1 deletion cases that developed into a relapse showed significantly more often a deletion in CDKN2A/B compared to the BTG1 deletion cases that did not develop a relapse (60% vs 8%, p=0.02). Together, these data indicate that pediatric precursor-B ALL carrying BTG1 deletions have distinct genomic profiles, showing increased frequencies of deletions in IKZF1 and CDKN2A. Disclosures No relevant conflicts of interest to declare.
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Amiri, A., A. I. Zuniga, and N. A. Peres. "Potential Impact of Populations Drift on Botrytis Occurrence and Resistance to Multi- and Single-Site Fungicides in Florida Southern Highbush Blueberry Fields." Plant Disease 102, no. 11 (November 2018): 2142–48. http://dx.doi.org/10.1094/pdis-11-17-1810-re.
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Incidence of blossom blight and Botrytis fruit rot (BFR), caused by Botrytis cinerea, on two southern highbush blueberry cultivars was evaluated in several blueberry fields grown in the vicinity (BB-Str(+)) or not (BB-Str(−)) of strawberry fields in central Florida. Blossom blight and BFR incidence were higher in BB-Str(+) fields in 2014 and significantly higher in 2015 compared to BB-Str(−) fields. In total, 613 B. cinerea isolates (i.e., 181 and 432 isolates from BB-Str(−) and BB-Str(+) fields, respectively) were collected. The isolates were evaluated for sensitivity to eight single-site and one multisite fungicides using a spore germination and a germ tube elongation assay. Overall, 5, 15, 24, 28, 54, and 93% of isolates collected from BB-Str(−) were resistant to penthiopyrad, cyprodinil, boscalid, fenhexamid, pyraclostrobin, and thiophanate-methyl, respectively. Respective resistance frequencies in BB-Str(+) isolates were 10, 30, 65, 66, 89, and 99%. Resistance frequencies for all fungicides were always higher in BB-Str(+) fields compared to BB-Str(−) fields. Isolates exhibiting resistance to six or five fungicides simultaneously were predominant (50 to 70%) in blueberry fields regardless if they were grown in the vicinity of strawberry fields or not. Among 308 and 305 B. cinerea isolates tested in 2014 and 2015, 41.8 and 47.1%, respectively, showed reduced sensitivity to the multisite fungicide captan. The lower label rate of captan applied preventively did not control isolates with reduced sensitivity on detached blueberry fruit. These findings suggest a potential population flow between strawberry and blueberry fields that may impact blossom blight and gray mold development in blueberry fields. The relatively lower fungicide input applied to blueberry fields compared with strawberry fields seems to be sufficient to select for resistance and multiple-resistant phenotypes in B. cinerea populations in blueberry.
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Ajčević, Miloš, Alex Buoite Stella, Giovanni Furlanis, Paola Caruso, Marcello Naccarato, Agostino Accardo, and Paolo Manganotti. "A Novel Non-Invasive Thermometer for Continuous Core Body Temperature: Comparison with Tympanic Temperature in an Acute Stroke Clinical Setting." Sensors 22, no. 13 (June 23, 2022): 4760. http://dx.doi.org/10.3390/s22134760.
Full textAbstract:
There is a growing research interest in wireless non-invasive solutions for core temperature estimation and their application in clinical settings. This study aimed to investigate the use of a novel wireless non-invasive heat flux-based thermometer in acute stroke patients admitted to a stroke unit and compare the measurements with the currently used infrared (IR) tympanic temperature readings. The study encompassed 30 acute ischemic stroke patients who underwent continuous measurement (Tcore) with the novel wearable non-invasive CORE device. Paired measurements of Tcore and tympanic temperature (Ttym) by using a standard IR-device were performed 3–5 times/day, yielding a total of 305 measurements. The predicted core temperatures (Tcore) were significantly correlated with Ttym (r = 0.89, p < 0.001). The comparison of the Tcore and Ttym measurements by Bland–Altman analysis showed a good agreement between them, with a low mean difference of 0.11 ± 0.34 °C, and no proportional bias was observed (B = −0.003, p = 0.923). The Tcore measurements correctly predicted the presence or absence of Ttym hyperthermia or fever in 94.1% and 97.4% of cases, respectively. Temperature monitoring with a novel wireless non-invasive heat flux-based thermometer could be a reliable alternative to the Ttym method for assessing core temperature in acute ischemic stroke patients.
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Spicer, D. B., and G. E. Sonenshein. "An antisense promoter of the murine c-myc gene is localized within intron 2." Molecular and Cellular Biology 12, no. 3 (March 1992): 1324–29. http://dx.doi.org/10.1128/mcb.12.3.1324-1329.1992.
Full textAbstract:
Previously we have demonstrated the existence of stable transcripts from the noncoding strand of a rearranged c-myc gene in murine plasmacytomas in which the oncogene has translocated to an immunoglobulin constant-region gene element (M. Dean, R. B. Kent, and G. E. Sonenshein, Nature [London] 305:443-446, 1983). The resulting RNAs are chimeric, containing c-myc antisense and immunoglobulin sense sequences. A normal unrearranged murine c-myc gene is transcribed in the antisense orientation throughout much of the gene; however, stable transcripts have not been detected. In this study, using Northern (RNA) blot, S1 nuclease, and primer extension analyses, we have mapped the 5' end of the stable chimeric transcripts to a site 175 bp from the start of exon 3, within intron 2 of the c-myc gene. In vitro transcription assays with constructs containing this site and 400 bp upstream, in the antisense orientation, and nuclear extracts from plasmacytoma cells, as well as a number of cell lines with normal unrearranged c-myc genes, indicated that this promoter was functional. This finding was confirmed in transient transfection assays using the antisense promoter linked to the chloramphenicol acetyltransferase reporter gene. These results suggest that a normal promoter of antisense transcription is used following c-myc gene translocation.
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Hidayat, Wahyu, Ema Utami, and Andi Sunyoto. "Selection of the Best K-Gram Value on Modified Rabin-Karp Algorithm." IJCCS (Indonesian Journal of Computing and Cybernetics Systems) 16, no. 1 (January 31, 2022): 11. http://dx.doi.org/10.22146/ijccs.63686.
Full textAbstract:
The Rabin-Karp algorithm is used to detect similarity using hashing techniques, from related studies modifications have been made in the hashing process but in previous studies have not been conducted research for the best k value in the K-Gram process. At the stage of stemming the Nazief & Adriani algorithm is used to transform the words into basic words. The researcher uses several variations of K-Gram values to determine the best K-Gram values. The analysis was performed using Ukara Enhanced public data obtained from the Kaggle with a total of 12215 data. The student essay answers data totaled to 258 data in the group A and 305 in the group B, every student essay answers data in each group will be compared with the answers of other fellow group member. Research results are the value of k = 3 has the best performance which has the highest some interpretations of 1-14% (Little degree of similarity) and 15-50% (Medium level of similarity) compared to values of k = 5, 7, and 9 which have the highest number of interpretation results 0%-0.99% (Document is different). However, if the students essay answers compared have 100% (Exactly the same) interpretations, the k value on K-Gram does not affect the results.
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Winiczenko, Radosław, Andrzej Sibicki, Paweł Skoczylas, and Jędrzej Trajer. "A genetic algorithm modelling of temperature distributions in the AZ31B magnesium alloys with 7075 aluminium alloy friction welded joints." E3S Web of Conferences 132 (2019): 01029. http://dx.doi.org/10.1051/e3sconf/201913201029.
Full textAbstract:
This paper presents a genetic algorithm modelling of temperature distribution during heating and cooling of AZ31B magnesium alloys with 7075 aluminium alloy friction welded joints. The temperature distributions estimated in the joints using K-type thermocouples with the accuracy of ±⚟0.1°C. The thermocouples were installed in 1.2 mm holes at the periphery joint - 5, 10, and 15 mm from the weld interface. Temperature reading was performed with a digital thermometer with the requisition frequency of 1000Hz during friction welding. Maximum temperature measurements in the half-radius of the analysed joints were equal to 305°C and 324°C, for the AZ31B magnesium alloy and 7075 aluminium alloy specimens, respectively. Both temperature and increasing temperature gradient at the axial specimens were higher than those at the half-radius and periphery of the joints. The empirical models for heating T=a/b+exp(ct) and cooling phases T=a-btc were formulated by the authors of this study. These models used to describe the temperature curves of welding process. The goodness of fit of tested mathematical models to the experimental data was evaluated with the coefficient of determination R2. A nonlinear regression analysis was conducted to fit the models by genetic algorithm (GA) using computer program MATLAB.
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Spicer, D. B., and G. E. Sonenshein. "An antisense promoter of the murine c-myc gene is localized within intron 2." Molecular and Cellular Biology 12, no. 3 (March 1992): 1324–29. http://dx.doi.org/10.1128/mcb.12.3.1324.
Full textAbstract:
Previously we have demonstrated the existence of stable transcripts from the noncoding strand of a rearranged c-myc gene in murine plasmacytomas in which the oncogene has translocated to an immunoglobulin constant-region gene element (M. Dean, R. B. Kent, and G. E. Sonenshein, Nature [London] 305:443-446, 1983). The resulting RNAs are chimeric, containing c-myc antisense and immunoglobulin sense sequences. A normal unrearranged murine c-myc gene is transcribed in the antisense orientation throughout much of the gene; however, stable transcripts have not been detected. In this study, using Northern (RNA) blot, S1 nuclease, and primer extension analyses, we have mapped the 5' end of the stable chimeric transcripts to a site 175 bp from the start of exon 3, within intron 2 of the c-myc gene. In vitro transcription assays with constructs containing this site and 400 bp upstream, in the antisense orientation, and nuclear extracts from plasmacytoma cells, as well as a number of cell lines with normal unrearranged c-myc genes, indicated that this promoter was functional. This finding was confirmed in transient transfection assays using the antisense promoter linked to the chloramphenicol acetyltransferase reporter gene. These results suggest that a normal promoter of antisense transcription is used following c-myc gene translocation.
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Pracella, Danae, Serena Bonin, Renzo Barbazza, Anna Sapino, Isabella Castellano, Sandro Sulfaro, and Giorgio Stanta. "Are Breast Cancer Molecular Classes Predictive of Survival in Patients with Long Follow-Up?" Disease Markers 35 (2013): 595–605. http://dx.doi.org/10.1155/2013/347073.
Full textAbstract:
In this study we investigate the clinical outcomes of 305 breast cancer (BC) patients, aged 55 years or younger, with long follow-up and according to intrinsic subtypes. The cohort included 151 lymph node negative (LN−) and 154 lymph node positive (LN+) patients. Luminal A tumors were mainly LN−, well differentiated, and of stage I; among them AR was an indicator of good prognosis. Luminal B and HER2 positive nonluminal cancers showed higher tumor grade and nodal metastases as well as higher proliferation status and stage. Among luminal tumors, those PR positive and vimentin negative showed a longer survival. HER2-positive nonluminal and TN patients showed a poorer outcome, with BC-specific death mostly occurring within 5 and 10 years. Only luminal tumor patients underwent BC death over 10 years. When patients were divided in to LN− and LN+ no differences in survival were observed in the luminal subgroups. LN− patients have good survival even after 20 years of follow-up (about 75%), while for LN+ patients survival at 20 years (around 40%) was comparable to HER2-positive nonluminal and TN groups. In conclusion, in our experience ER-positive breast tumors are better divided by classical clinical stage than molecular classification, and they need longer clinical follow-up especially in cases with lymph node involvement.
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Lee, Ning, Yingfu Li, Yong Mao, Guanfeng Liu, Jiang Li, and Qingchun Liu. "Abstract CT147: Phase I clinical study of Bruton’s tyrosine kinase inhibitor (BTKi) HBW-3220 capsules in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL)." Cancer Research 84, no. 7_Supplement (April 5, 2024): CT147. http://dx.doi.org/10.1158/1538-7445.am2024-ct147.
Full textAbstract:
Abstract Purpose: This clinical study is to evaluate HBW-3220, a novel reversible BTK inhibitor (BTKi) with an improved in vitro profile than the existing non-covalent drugs pirtobrutinib (LOXO-305, approved) and MK-1026 (Phase III). HBW-3220 shows superior inhibition against BTK wild-type and several common mutants, such as C481S, C481R, T474I, T316A, and L528W (the one predominantly enriched in patients resistant to the newer-generation BTKis), and hematopoietic cell kinase (HCK), a key contributor to the development of ibrutinib resistance associated with kinase-defective BTK. Methods: This phase I clinical study was conducted in R/R B-NHL patients who had received two or more prior lines of treatments. The dose escalation study adopts accelerated titration and a "3+3" design, with a daily single dose of 15, 30, 60, 90, 120, or 150 mg. During the dose escalation phase, the sponsor and investigators determined whether to expand the cohort of the previous dose based on the existing data. Adverse events (AEs) were assigned according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response assessment was based on the iwCLL 2018 guidelines, the IWWM-7 consensus, or the Lugano 2014 guidelines, according to the respective disease type. Results: 28 patients have been enrolled so far, and the dose escalation study has been completed. No dose-limiting toxicity (DLT) occurred in any patient, implicating good tolerability. Adverse events (AEs), similar to other BTKis, were mostly Grade 1 or 2, including fever (38%), diarrhea (35%), headache (19%), anemia (42%), infectious pneumonia (23%), decreased neutrophils (42%), decreased platelet count (27%), increased alanine aminotransferase (23%), etc. Drug-related Grade 3 AEs included neutrophil count decreased (n=3, 11%), increased lymphocyte count (n=2, 7%), and infectious pneumonia (n=2, 7%). 21 patients underwent at least 1 response assessment (4 chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); 4 marginal zone lymphoma (MZL); 5 mantle cell lymphoma (MCL); 3 diffuse large B-cell lymphoma (DLBCL); 5 other B-NHL), and the results are 1 complete response (CR), 6 partial response (PR), and 1 partial response with lymphocytosis (PR-L). The overall response rate (ORR) in CLL/SLL (all with prior irreversible BTKi treatment, and 2 of them with additional BCL2 inhibitor treatment), MZL, MCL, and DLBCL patients were 75% (3/4, including 1 PR-L), 50% (2/4), 40% (2/5) and 33% (1/3), respectively. Among the ORR (including CR, PR, and PR-L), 88% (7/8) were in the 90 mg and above dose group, regardless of previous BTKi treatment history or mutation status of p53 and BTK C481S. In the 90 mg and above dose group, the ORR is 47%. After oral administration, the drug exposures showed dose-dependent increases. The time to maximum plasma concentration (Tmax) was 2 hours, and the elimination half-life (T1/2) was 19 hours. Conclusions: The current data show that HBW-3220 is well tolerated, showing no DLT occurred at daily doses up to 150 mg, and has good efficacy in patients with CLL/SLL, MZL, and MCL. Citation Format: Ning Lee, Yingfu Li, Yong Mao, Guanfeng Liu, Jiang Li, Qingchun Liu. Phase I clinical study of Bruton’s tyrosine kinase inhibitor (BTKi) HBW-3220 capsules in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT147.
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Abu Bakar Ah, Siti Hajar, Haris Abd. Wahab, Noralina Omar, Mashitah Hamidi, Zaiton Azman, Al Azmi Bakar, Mohd Razman Achmadi Muhammad, and Azreen Rusnan. "TAHAP PENGAMALAN PRAKTIS KERJA SOSIAL DALAM KALANGAN PEGAWAI KEBAJIKAN DI MALAYSIA [THE LEVEL OF SOCIAL WORK PRACTICE AMONG MALAYSIAN SOCIAL WELFARE OFFICERS]." Journal of Nusantara Studies (JONUS) 5, no. 2 (June 25, 2020): 68–85. http://dx.doi.org/10.24200/jonus.vol5iss2pp68-85.
Full textAbstract:
Tujuan dan Latarbelakang: Kualiti penyampaian khidmat kerja sosial oleh pegawai kebajikan masyarakat dipengaruhi oleh latar belakang pengetahuan dan kemahiran kerja sosial yang mereka miliki. Kajian ini bertujuan untuk menilai tahap pengamalan praktis kerja sosial dalam kalangan pegawai kebajikan di Malaysia.
Metodologi: Pendekatan kuantitatif yang menggunakan reka bentuk tinjauan telah dilakukan ke atas 305 orang Penolong Pegawai dan Pembantu Pembangunan Masyarakat Gred 19 hingga Gred 38 terpilih yang berkhidmat di Jabatan Kebajikan Masyarakat di seluruh negara. Persampelan rawak mudah digunakan bagi mendapatkan responden. Tahap pengamalan terhadap praktis kerja sosial diukur berdasarkan Kerangka Kompetensi Kerja Sosial Nasional Singapura dan Piawaian Kompetensi Praktis Kerja Sosial Kebangsaan.
Dapatan: Tahap pengamalan terhadap praktis kerja sosial dalam kalangan responden menunjukkan skor yang tinggi.
Sumbangan: Bersandarkan dapatan kajian, tiga inisiatif bagi meningkatkan lagi kualiti pengamalan dan penyampaian praktis kerja sosial dalam kalangan pegawai kebajikan di negara ini telah dicadangkan iaitu i) pengukuhan program latihan; ii) penetapan semula maksud kecekapan dalam pengamalan; dan iii) penetapan pengamalan berdasarkan kod etika.
Kata kunci: Tahap pengamalan, praktis kerja sosial, penyampaian khidmat kerja sosial, pegawai kebajikan, Jabatan Kebajikan Masyarakat Malaysia (JKM).
ABSTRACT
Background and Purpose: The quality of social service delivery by welfare officers is influenced by the knowledge and social work skills they possess. This paper aims to study the level of social work practice among welfare officers in Malaysia.
Methodology: A quantitative approach using survey design was used to collect data from 305 Community Development Assistant Officers and Community Development Helper Grades 19 through 38 who served in the Social Welfare Department across Malaysia. The respondents were selected using simple random sampling. The level of social work practice was measured using the Singapore National Social Work Competency Framework and the National Social Work Practise Competency Standards.
Findings: The findings showed that the level of social work practice among the respondents is at high score.
Contribution: Based on the findings, three initiatives to improve the quality of social work practce among welfare officers are recommended: i) strengthening training programs; ii) redefining the meaning of practice; and iii) establishing practice based on ethical code.
Keywords: Level of practise, social work practise, welfare officer, delivery of social services, Department of Social Welfare Malaysia (JKM)
Cite As: Siti Hajar, A. B. A., Haris, A. W., Noralina, O., Mashitah, H., Zaiton, A., Al Azmi, B., ... Azreen, R. (2020). Tahap pengamalan praktis kerja sosial dalam kalangan pegawai kebajikan di Malaysia [The level of social work practice among Malaysian social welfare officers]. Journal of Nusantara Studies, 5(2), 68-85. http://dx.doi.org/10.24200/jonus.vol5iss2pp68-85
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Giudice, Ilaria Del, Barbara Anaclerico, Maria Stefania De Propris, Francesca Mancini, Edoardo Pescarmona, Luisa Bizzoni, Anna Levi, et al. "Diagnostic Approach to CD5+/CD23+ Leukemic Non-Hodgkin Lymphomas Lacking Lymphnode Histopathology." Blood 106, no. 11 (November 16, 2005): 4690. http://dx.doi.org/10.1182/blood.v106.11.4690.4690.
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Abstract Lymphoproliferative disorders (LPD) may be characterized at presentation by peripheral blood (PB) and/or bone marrow (BM) involvement. These may represent the unique diagnostic sources to subtype LPD in patients who lack nodal involvement or are not eligible for aggressive diagnostic procedures. Lymphocyte morphology and immunophenotype allow to distinguish typical chronic lymphocytic leukemia (CLL) from other leukemic B-cell LPD, though they cannot provide a specific classification of the latter. CD5+/CD23+ LPD are a heterogeneous group including typical/atypical CLL and leukemic B-cell non-Hodgkin lymphomas (B-NHL). Aim of this study was to define the value of BM and PB as the only tissue available for the differential diagnosis of B-LPD, focusing on CD5+/CD23+ subgroup. Between January 2003 and December 2004, we evaluated at our institution 305 consecutive patients characterized by clonal B-lymphocytosis. Among 205 CD5+/CD23+ cases, 135 (66%) had typical features of CLL, as for PB standard morphologic/immunophenotypic criteria, 70 (34%) were provisionally defined as B-NHL/atypical CLL. 36 of them underwent a lymphnode biopsy. In the remaining 34, diagnosis was approached only by BM biopsy in 27 cases (20 lacked superficial and/or internal adenopathies and 7 with superficial adenopathy could not undergo a lymphnode biopsy), while in 7 both a BM and node biopsy were performed. BM biopsy was analyzed by histopathology and immunocytochemistry (CD20, CD79a, Ig light chain, CD5, CD23, CD43, CD10, bcl-2, cyclinD1). Median age of patients (24 males and 10 females) was 68 years (range 39–78). Spleen enlargement was detected in 10 cases. Median WBC count was 17x109/l (range 8.5–90), lymphocyte count 9x109/l (range 4.3–69). In all cases, PB morphology was not typical of CLL: >10% of lymphocytes were large in 9 cases, cleaved in 15, nucleolated in 2, villous in 2 and with a mixed pattern in 6. Matutes’ immunophenotypic score was 5–4 in 25 cases and 3–2 in 9. BM infiltration was diffuse in 9 cases, interstitial in 21 or nodular +/− interstitial in 4. Distinctive lymphoma infiltrates, such as an intrasinusoidal pattern or proliferation centers, were recognized in 2 and 3 cases, respectively. CyclinD1 was negative in 5/5 evaluated cases. A final diagnosis was reached by PB/BM evaluation in 29 out of 34 cases (85%): small lymphocytic lymphoma (SLL/CLL) in 24 (70%), lymphoplasmacytic lymphoma in 2 (6%), marginal zone lymphoma in 2 (6%), follicular lymphoma in 1 (3%). Five cases (15%) remained unclassified. Among the 7 patients who underwent also a lymphnode biopsy, a discordant diagnosis between BM and lymphnode was observed only in 1 case that proved a Richter syndrome. In summary, CD5+/CD23+ clonal B-LPD not fulfilling criteria for CLL diagnosis, lacking node biopsy, can in most cases be adequately classified by PB/BM morphology/immunophenotype and BM immunohistochemistry. A small proportion of cases remain unclassified. Notably, 17% of CD5+/CD23+ “non-CLL” LPD are leukemic B-NHL. BM biopsy represents a valuable source to define as B-NHL with leukemic spillover cases not fulfilling a diagnosis of CLL, even in the absence of primary tissue histopathology.
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GILL, ALEXANDER, and DENISE OUDIT. "Enumeration of Escherichia coli O157 in Outbreak-Associated Gouda Cheese Made with Raw Milk." Journal of Food Protection 78, no. 9 (September 1, 2015): 1733–37. http://dx.doi.org/10.4315/0362-028x.jfp-15-036.
Full textAbstract:
In this article, we discuss the enumerative analysis for Escherichia coli O157 in two raw milk Gouda cheese products (A and B), implicated in an outbreak of 29 cases of E. coli O157:H7 illness that occurred across Canada in 2013. Samples were enumerated for E. coli O157 by most probable number (MPN) over a period of 30 to 60 days after the end of the outbreak. Samples (55.55 g) of product A (n = 14) were analyzed at 146 to 180 days postproduction. E. coli O157 was isolated from six samples at 19.9 to 44.6 MPN/kg. The E. coli O157 concentration of product A estimated from the results of all 14 samples was 9.5 MPN/kg. Samples (55.55 g) of product B (n = 20) were analyzed at 133 to 149 days postproduction. E. coli O157 was isolated from four samples at 19.9 MPN/kg. The E. coli O157 concentration of product B estimated from the results of all 20 samples was 3.7 MPN/kg. Analysis of a 305-g sample of product A (n = 1) stored at 4°C until 306 days postproduction revealed that the E. coli O157 concentration had declined to 3.6 MPN/kg. E. coli O157 could not be isolated from 555-g samples of product B (n = 5) after 280 days postproduction. The physicochemical parameters (pH, water activity, percent moisture, and percent salt) of both cheese products were found to be in the normal range for this type of product. The results of this study demonstrate that E. coli O157 could not replicate during storage at 4°C in the products tested but was capable of survival following aging and prolonged storage. This indicates that, if contaminated, the minimum 60-day aging period, which is required for raw milk Gouda cheeses, is not sufficient in all cases to ensure that the product does not contain viable cells of E. coli O157. The results also indicate that samples sizes greater than 100 g may be required to reliably detect E. coli O157 in cheese products associated with outbreaks.
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Abraham, Aby, Fouzia N., Anu Korula, Uday Prakash Kulkarni, Anup Devasia, Kavitha M. Lakshmi, Sandeep Albert, et al. "Ehl Factors at Lower Than Standard Dose Achieve Satisfactory Surgical Haemostatsis in Haemophilia." Blood 136, Supplement 1 (November 5, 2020): 25–26. http://dx.doi.org/10.1182/blood-2020-142222.
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Patients and methods All patients with haemophilia A or B who underwent major surgery, either as elective or as emergency, with rFVIIIFc or rFIXFc as the clotting factor concentrate (CFC) for hemostasis were included in this study. None of them were positive for inhibitors before. The factor was administered once daily or once every 36-48 hours depending on the product. The factor assays were done with a one stage APTT method. The CFC support was continued till suture removal, usually 10 days. Other supportive measures included tranexamic acid,at physician discretion. Results A total of 57 patients underwent surgery. There were 45 patients with haemophilia A and 12 with haemophilia B. Of those with haemophilia A, - 37 (82.2%) had severe, 3 (11.1%) moderate and 5 (6.7%) mild disease. Of those with haemophilia B, 7 (58.3%) had severe,3 (25 %) moderate and 2 (16.7%) mild disease. The median age was 30 years (range: 1-70). Among those with haemophilia A, there were 4 with inhibitor titre <5 BU, 3 more developed inhibitor 3-7 days following surgery, 1 of >5 BU, requiring bypassing agents. None with haemophilia B had inhibitor. The surgical procedures included 40 (70.1%) orthopaedic, 6 (10.5%) abdomino-perineal, 4(7%) urological and 3(5.2%) neurosurgical and 1(1.7%) each - venricular septal defect repair, skin graft, tympanoplasty and coronary angioplasty. The orthopaedic surgeries included pseudotumour excision (n=9), bilateral total knee replacement (bilateral n=4, unilateral n=1), total hip replacement (n=3), open reduction and internal fixation of fracture (n=11), corrective osteotomies/soft tissue release (n=6), amputation (n=1), arthrodesis (n=1), laminectomy (n=1), implant removal (n=1),intra articular repair(n=1)and curettage (n=1). For those with haemophilia A, the median recovery assay pre-op was 108% (range: 50-200).The median trough levels for post- operative days +1,+3,+5 ,+7 were 40% (11-138), 36.5% (13-94), 36.4% (1.4-118), and 27%(1.6-77) respectively. Among 35 patients with severe haemophilia undergoing major surgery, the median total factor used was 305 (125-563)IU/kg. The median recovery assay for those with haemophilia B prior to surgery was 70.1%(50-165).The median trough levels for post operative days+1,+3,+5 ,+7 were 49.8% (28-70.7), 40.7%(31.6-56.2), 42.3%(11.6-58.2), and 40.5%(24.5-59.4) respectively. The median total factor used was 400 (134-1000)IU/kg. Seventeen of those with haemophilia A (37.8%) required transfusion of at least 1 packed red cell each as per expected blood loss in those surgeries. Two patients required FFP and 1 patient required platelet transfusion as well for DIC. One patient had sustained injury to axillary artery during surgery and the other one had undergone resection of extensive pseudotumour. There was no unexpected post-operative bleeding. In those with haemophilia B, 2(16.7%) patients required transfusion of packed red cell as per expected blood loss in those surgeries. No other blood product was required. There was no excessive bleed during the perioperative period. Conclusions Modest doses of rFVIIIFc and rFIXFc can be used safely for major surgery in haemophilia with effective haemostasis and monitored with one stage APTT based assays. The less frequent administration makes these agents a more convenient option. Disclosures No relevant conflicts of interest to declare.